Recording of Chronic Diseases and Adverse Obstetric Outcomes during Hospitalizations for a Delivery in the National Swiss Hospital Medical Statistics Dataset between 2012 and 2018: An Observational Cross-Sectional Study.

The prevalence of chronic diseases during pregnancy and adverse maternal obstetric outcomes in Switzerland has been insufficiently studied. Data sources, which reliably capture these events, are scarce. We conducted a nationwide observational cross-sectional study (2012-2018) using data from the Swiss Hospital Medical Statistics (MS) dataset. To quantify the recording of chronic diseases and adverse maternal obstetric outcomes during delivery in hospitals or birthing centers (delivery hospitalization), we identified women who delivered a singleton live-born infant. We quantified the prevalence of 23 maternal chronic diseases (ICD-10-GM) and compared results to a nationwide Danish registry study. We further quantified the prevalence of adverse maternal obstetric outcomes (ICD-10-GM/CHOP) during the delivery hospitalization and compared the results to existing literature from Western Europe. We identified 577,220 delivery hospitalizations, of which 4.99% had a record for ≥1 diagnosis of a chronic disease (versus 15.49% in Denmark). Moreover, 13 of 23 chronic diseases seemed to be substantially under-recorded (8 of those were >10-fold more frequent in the Danish study). The prevalence of three of the chronic diseases was similar in the two studies. The prevalence of adverse maternal obstetric outcomes was comparable to other European countries. Our results suggest that chronic diseases are under-recorded during delivery hospitalizations in the MS dataset, which may be due to specific coding guidelines and aspects regarding whether a disease generates billable effort for a hospital. Adverse maternal obstetric outcomes seemed to be more completely captured

Production and characterization of anti-human interferon γ receptor antibody fragments that inhibit cytokine binding to the receptor

Three single-chain antibody fragments that recognize the extracellular human interferon γ receptor α-chain (IFNγR), and inhibit the binding of human IFNγ, have been produced in Escherichia coli. These fragments are derived from murine anti-receptor monoclonal antibodies, and comprise the variable heavy (VH) domain linked to the variable light (VL) chain through a 15 amino acid linker [(GGGGS)3]. Using surface plasmon resonance technology (BIAcore), the soluble proteins were shown to retain a high affinity for recombinant IFNγR, and by radioimmunoassay to possess high inhibitory activity towards IFNγ-binding to human Raji cells. The antibody fragments most likely recognize epitopes that overlap the cytokine binding site on the receptor surface. Attempts to dissect further the antibodies to isolated VH- and VL-chains and to synthetic linear and cyclic peptides derived from the individual complementarity determining regions failed to afford fragments with significant IFNγR binding affinity. Nevertheless, these native-like variable region fragments and petidomimetics derived from them are of interest in the design of novel IFNγR antagonist

Stromal upregulation of lateral epithelial adhesions: Gene expression analysis of signalling pathways in prostate epithelium

BACKGROUND: Stromal signalling increases the lateral cell adhesions of prostate epithelial cells grown in 3D culture. The aim of this study was to use microarray analysis to identify significant epithelial signalling pathways and genes in this process. METHODS: Microarray analysis was used to identify genes that were differentially expressed when epithelial cells were grown in 3D Matrigel culture with stromal co-culture compared to without stroma. Two culture models were employed: primary epithelial cells (ten samples) and an epithelial cell line (three experiments). A separate microarray analysis was performed on each model system and then compared to identify tissue-relevant genes in a cell line model. RESULTS: TGF beta signalling was significantly ranked for both model systems and in both models the TGF beta signalling gene SOX4 was significantly down regulated. Analysis of all differentially expressed genes to identify genes that were common to both models found several morphology related gene clusters; actin binding (DIAPH2, FHOD3, ABLIM1, TMOD4, MYH10), GTPase activator activity (BCR, MYH10), cytoskeleton (MAP2, MYH10, TMOD4, FHOD3), protein binding (ITGA6, CD44), proteinaceous extracellular matrix (NID2, CILP2), ion channel/ ion transporter activity (CACNA1C, CACNB2, KCNH2, SLC8A1, SLC39A9) and genes associated with developmental pathways (POFUT1, FZD2, HOXA5, IRX2, FGF11, SOX4, SMARCC1). CONCLUSIONS: In 3D prostate cultures, stromal cells increase lateral epithelial cell adhesions. We show that this morphological effect is associated with gene expression changes to TGF beta signalling, cytoskeleton and anion activity

Spontaneous regeneration of keratinized tissue at implants and teeth.

AIM To investigate the spontaneous regeneration of the implanto-mucosal and dento-gingival unit after complete removal of keratinized tissue (KT). MATERIALS AND METHODS One hemi-mandible per dog (n = 4) was allocated to receive three dental implants (test sites, premolar region), whereas three premolars on the contralateral side were controls. After osseointegration, the entire KT (buccal + lingual) was surgically excised on all test and control sites, leaving the bone exposed. Clinical measurements were performed before excision (T0 ) and after 12 weeks (T1 ). Following healing, the animals were euthanized, and the specimens were histologically processed. Descriptive statistical analyses were performed. RESULTS Clinical measurements revealed that at T1 , on all teeth, a band of KT was spontaneously regenerated (mean width: 2.60 ± 0.66 mm), whereas on implants, KT was detected only occasionally at mesial or distal but not at buccal sites (mean total: 0.35 ± 0.53 mm; p < .0001). Histologically, spontaneous regeneration of the dento-gingival unit was evident, displaying masticatory mucosa. At the implant sites, on the other hand, the implanto-mucosal unit was characterized by a non-keratinized epithelium and elastic fibres, indicating the characteristics encountered in alveolar mucosa. CONCLUSION After excision of KT at implant sites, the spontaneous regeneration of the soft tissue is characterized by a non-keratinized epithelium typical for alveolar mucosa, while at tooth sites the spontaneous regeneration was characterized by soft tissue resembling gingiva

Clinical and histologic evaluation of heterotopic mucosa transpositioning at teeth and dental implants.

AIM To investigate the healing after heterotopic mucosa transpositioning at dental implants and teeth. MATERIALS AND METHODS One hemimandible per dog (n = 4) was allocated to receive 3 implants (test), whereby 3 premolars on the contralateral side served as controls. After osseointegration, a Z-plasty was performed on the buccal aspect of the test and control sites to heterotopically move the zone of keratinized tissue (KT) into a region with non-keratinized tissue (nKT) and vice versa. Clinical measurements were performed before (T0) and at 12 weeks following heterotopic transposition (T1). Thereafter, specimens were processed for histological analysis. RESULTS Clinical measurements revealed that at T1, a band of KT was reestablished at teeth (mean: 2.944 ± 1.866 mm), whereas at implants, the transpositioned nKT resulted in a mucosa without any signs of keratinization (mean: 0 mm; p < .0001). At implant sites, the probing attachment level loss was more pronounced compared to tooth sites (-1.667 ± 1.195 mm and -1.028 ± 0.878 mm, respectively; p = .0076). Histologically, the transpositioned nKT, was accompanied by the formation of KT at the tooth but not at implant sites. The supracrestal soft tissues were statistically significantly higher at tooth compared to implant sites (2.978 ± 0.483 mm and 2.497 ± 0.455 mm, p = .0083). The transpositioned KT remained mostly unaltered in its morphological characteristics. CONCLUSIONS The findings of this study indicate that: (a) transpositioned KT may retain its morphological characteristics; and (b) transpositioned nKM was accompanied by the formation of KT at the tooth but not at implant sites

Cyclic triterpenoid production with tailored Saccharomyces cerevisiae

Triterpenoids are secondary plant metabolites derived from squalene and consist of six isoprene units (C30). Many of them or their synthetic derivatives are currently being investigated as medicinal products for various diseases. The cyclic triterpenoid betulinic acid is of special interest for the pharmaceutical and nutritional industry as it has antiretroviral, antimalarial, and anti-inflammatory properties and has potential as an anticancer agent (Muffler et al. 2011, Mullauer et al. 2010). Despite their obvious industrial potential, the application is often hindered by their low abundance in natural plant sources. This poses challenges in a biosustainable production of such compounds due to wasteful and costly product purification. Here, we present a novel biotechnological process for the production of betulinic acid using tailored Saccharomyces cerevisiae strains. The multi-scale optimization of this microbial process included: - pathway engineering by determination of optimal gene combination and dosage, - compartment engineering to increase the reaction space of the betulinic acid pathway, and - strain engineering by implementation of different push, pull and block strategies. In parallel we developed the fermentation process and were able to boost the performance of the engineered yeast by optimization of medium composition, cultivation conditions, carbon source and mode of fermentation operation in lab scale bioreactors. Product purification was achieved by a one-step extraction with acetone. The final process was evaluated in terms of economic and ecological efficiency and rated to be competitive with existing plant extraction procedures with potential for further performance improvement. Please click Additional Files below to see the full abstract

Greater Greenland Ice Sheet contribution to global sea level rise in CMIP6

Future climate projections show a marked increase in Greenland Ice Sheet (GrIS) runoff during the 21st century, a direct consequence of the Polar Amplification signal. Regional climate models (RCMs) are a widely used tool to downscale ensembles of projections from global climate models (GCMs) to assess the impact of global warming on GrIS melt and sea level rise contribution. Initial results of the CMIP6 GCM model intercomparison project have revealed a greater 21st century temperature rise than in CMIP5 models. However, so far very little is known about the subsequent impacts on the future GrIS surface melt and therefore sea level rise contribution. Here, we show that the total GrIS sea level rise contribution from surface mass loss in our high-resolution (15 km) regional climate projections is 17.8 ± 7.8 cm in SSP585, 7.9 cm more than in our RCP8.5 simulations using CMIP5 input. We identify a +1.3 °C greater Arctic Amplification and associated cloud and sea ice feedbacks in the CMIP6 SSP585 scenario as the main drivers. Additionally, an assessment of the GrIS sea level contribution across all emission scenarios highlights, that the GrIS mass loss in CMIP6 is equivalent to a CMIP5 scenario with twice the global radiative forcing.Peer reviewe

DNA methylation transcriptionally regulates the putative tumor cell growth suppressor ZNF677 in non-small cell lung cancers

In our study, we investigated the role of ZNF677 in non-small cell lung cancers (NSCLC). By comparing ZNF677 expression in primary tumor (TU) and in the majority of cases also of corresponding non-malignant lung tissue (NL) samples from > 1,000 NSCLC patients, we found tumor-specific downregulation of ZNF677 expression (adjusted p-values < 0.001). We identified methylation as main mechanism for ZNF677 downregulation in NSCLC cells and we observed tumor-specific ZNF677 methylation in NSCLC patients (p < 0.0001). In the majority of TUs, ZNF677 methylation was associated with loss of ZNF677 expression. Moreover, ZNF677 overexpression in NSCLC cells was associated with reduced cell proliferation and cell migration. ZNF677 was identified to regulate expression of many genes mainly involved in growth hormone regulation and interferon signalling. Finally, patients with ZNF677 methylated TUs had a shorter overall survival compared to patients with ZNF677 not methylated TUs (p = 0.013). Overall, our results demonstrate that ZNF677 is trancriptionally regulated by methylation in NSCLCs, suggest that ZNF677 has tumor cell growth suppressing properties in NSCLCs and that ZNF677 methylation might serve as prognostic parameter in these patients

Adaptive main-memory indexing for high-performance point-polygon joins

Connected mobility applications rely heavily on geospatial joins that associate point data, such as locations of Uber cars, to static polygonal regions, such as city neighborhoods. These joins typically involve expensive geometric computations, which makes it hard to provide an interactive user experience. In this paper, we propose an adaptive polygon index that leverages true hit fltering to avoid expensive geometric computations in most cases. In particular, our approach closely approximates polygons by combining quadtrees with true hit filtering, and stores these approximations in a query-effcient radix tree. Based on this index, we introduce two geospatial join algorithms: an approximate one that guarantees a user-defined precision, and an exact one that adapts to the expected point distribution. In summary, our technique outperforms existing CPU-based joins by up to two orders of magnitude and is competitive with state-of-the-art GPU implementations