bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simulation ermöglicht soziale und interaktive Lernprozesse
Authors: Lang Markus , Pfeilstecher Manuel 
Published: May 2021

Was ist zu diesem Thema bekannt? Über die Anwendung von Simulationstraining in der psychiatrischen Pflegeausbildung wird im deutschsprachigen Raum kaum publiziert. Wie wird eine neue Perspektive eingebracht? Simulationstraining ermöglicht für die psychiatrische Pflegeausbildung soziale und interaktive Lernprozesse sowie das Sichtbarmachen von möglichen Krankheitsverläufen. Was sind die Auswirkungen für die Praxis? Studierende erleben in der Simulation realitätsnahe Situationen und erfahren dadurch bereits in der Ausbildung die eigene Reaktion auf mitunter sehr herausfordernde psychiatrische Pflegesituationen.
Assessment of FY‐2G Atmospheric Motion Vector Data and Assimilating Impacts on Typhoon Forecasts
Authors: Liang Jiahao , Chen Keyi , Xian Zhipeng 
Published: May 2021

AbstractAtmospheric motion vectors (AMVs) have produced positive impacts on global weather forecasts, but few studies have evaluated the impacts of AMV data from the Fengyun (FY) geostationary satellite series, especially from FY‐2G and FY‐4, on typhoon forecasts in a regional model. In this study, the qualities of FY‐2G and Himawari‐8 AMV data are comparatively evaluated with several preprocesses (e.g., height assignment, quality control, channel merging, thinning, and observation error assignment) employed, and a super typhoon (Typhoon Hato, which occurred in 2017) is selected to assess the forecasting performances with the AMV data assimilated in the Weather Research and Forecasting data assimilation (WRFDA) system. The results show that the AMV data from Himawari‐8 are better overall than those from FY‐2G, with smaller RMSEs and biases for full wind speeds, and the preprocesses improve the qualities of these two geostationary satellite AMV data sets, as they both depict the same general atmospheric circulations. On the other hand, assimilation of AMV data improves the forecasts of environmental fields, resulting in the simulated track and intensity being closer to the observations. Generally, assimilating FY‐2G AMV data has comparably positive impacts with Himawari‐8 AMVs, and the AMV data retrieved from multiple channels provide even better forecasts. Experiments involving another typhoon case are also performed to further provide evidence that the derived AMV data from the Fengyun geostationary satellite series have value in the operational applications.
Platycodin D, a natural component of Platycodon grandiflorum, prevents both lysosome- and TMPRSS2-driven SARS-CoV-2 infection by hindering membrane fusion
Authors: Kim Tai Young , Jeon Sangeun , Jang Youngho , Gotina Lizaveta , Won Joungha , Ju Yeon Ha , Kim Sunpil , Jang Minwoo Wendy , Won Woojin , Park Mingu Gordon , Pae Ae Nim , Han Sunkyu , Kim Seungtaek , Lee C. Justin 
Published: May 2021

AbstractAn ongoing pandemic of coronavirus disease 2019 (COVID-19) is now the greatest threat to global public health. Herbal medicines and their derived natural products have drawn much attention in the treatment of COVID-19, but the detailed mechanisms by which natural products inhibit SARS-CoV-2 have not been elucidated. Here, we show that platycodin D (PD), a triterpenoid saponin abundant in Platycodon grandiflorum (PG), a dietary and medicinal herb commonly used in East Asia, effectively blocks the two main SARS-CoV-2 infection routes via lysosome- and transmembrane protease serine 2 (TMPRSS2)-driven entry. Mechanistically, PD prevents host entry of SARS-CoV-2 by redistributing membrane cholesterol to prevent membrane fusion, which can be reinstated by treatment with a PD-encapsulating agent. Furthermore, the inhibitory effects of PD are recapitulated by the pharmacological inhibition or gene silencing of NPC1, which is mutated in patients with Niemann–Pick type C (NPC) displaying disrupted membrane cholesterol distribution. Finally, readily available local foods or herbal medicines containing PG root show similar inhibitory effects against SARS-CoV-2 infection. Our study proposes that PD is a potent natural product for preventing or treating COVID-19 and that briefly disrupting the distribution of membrane cholesterol is a potential novel therapeutic strategy for SARS-CoV-2 infection.
miR-19b enhances osteogenic differentiation of mesenchymal stem cells and promotes fracture healing through the WWP1/Smurf2-mediated KLF5/β-catenin signaling pathway
Authors: Huang Yan , Xu Yongqiang , Feng Siyin , He Pan , Sheng Bing , Ni Jiangdong 
Published: May 2021

AbstractBone marrow mesenchymal stem cell (BMSC)-derived exosomes have been found to enhance fracture healing. In addition, microRNAs contributing to the healing of various bone fractures have attracted widespread attention in recent years, but knowledge of the mechanisms by which they act is still very limited. In this study, we clarified the function of altered microRNA-19b (miR-19b) expression in BMSCs in fracture healing. We modulated miR-19b expression via mimics/inhibitors in BMSCs and via agomirs in mice to explore the effects of these changes on osteogenic factors, bone cell mineralization and the healing status of modeled fractures. Through gain- and loss-of function assays, the binding affinity between miR-19b and WWP1/Smurf2 was identified and characterized to explain the underlying mechanism involving the KLF5/β-catenin signaling pathway. miR-19b promoted the differentiation of human BMSCs into osteoblasts by targeting WWP1 and Smurf2. Overexpression of WWP1 or Smurf2 degraded the target protein KLF5 in BMSCs through ubiquitination to inhibit fracture healing. KLF5 knockdown delayed fracture healing by modulating the Wnt/β-catenin signaling pathway. Furthermore, miR-19b enhanced fracture healing via the KLF5/β-catenin signaling pathway by targeting WWP1 or Smurf2. Moreover, miR-19b was found to be enriched in BMSC-derived exosomes, and treatment with exosomes promoted fracture healing in vivo. Collectively, these results indicate that mesenchymal stem cell-derived exosomal miR-19b represses the expression of WWP1 or Smurf2 and elevates KLF5 expression through the Wnt/β-catenin signaling pathway, thereby facilitating fracture healing.
Invasive mechanical ventilation at 36 weeks post-menstrual age, adverse outcomes with a comparison of recent definitions of bronchopulmonary dysplasia
Authors: Guaman Milenka Cuevas , Pishevar Nikou , Abman Steven H. , Keszler Martin , Truog William E. , Panitch Howard , Nelin Leif D. 
Published: May 2021

Abstract
Objectives
To determine whether the need for invasive mechanical ventilation (iMV) at 36 weeks PMA in patients with severe bronchopulmonary dysplasia (sBPD) identifies those patients at highest risk for tracheostomy or gastrostomy, and to compare sBPD with recent definitions of BPD.

Study design
Observational study from Jan 2015 to Sept 2019 using data from the BPD Collaborative Registry.

Results
Five hundred and sixty-four patients with sBPD of whom 24% were on iMV at 36 weeks PMA. Those on iMV had significantly (p < 0.0001) increased risk for tracheostomy or gastrostomy. The overall mortality rate was 3% and the risk for mortality was substantially greater in those on iMV than in those on noninvasive support at 36 weeks PMA (RR 13.8, 95% CI 4.3–44.5, p < 0.0001). When applying the NICHD definition (2016) 44% had Grade III BPD. When applying the NRN definition, 6% had Grade 1 BPD, 70% had Grade 2 BPD, and 24% had Grade 3 BPD.

Conclusions
Patients with sBPD who were on iMV at 36 weeks had a significantly greater risk of inhospital mortality and survivors had a significantly greater risk of undergoing tracheostomy and/or gastrostomy. The use of type 2 sBPD or Grade 3 BPD would enhance the ability to target future studies to those infants with sBPD at the highest risk of adverse long-term outcomes.
Intermittent fasting enhances long-term memory consolidation, adult hippocampal neurogenesis, and expression of longevity gene Klotho
Authors: Dias Gisele Pereira , Murphy Tytus , Stangl Doris , Ahmet Selda , Morisse Benjamin , Nix Alina , Aimone Lindsey J. , Aimone James B. , Kuro-O Makoto , Gage Fred H. , Thuret Sandrine 
Published: May 2021

AbstractDaily calorie restriction (CR) and intermittent fasting (IF) enhance longevity and cognition but the effects and mechanisms that differentiate these two paradigms are unknown. We examined whether IF in the form of every-other-day feeding enhances cognition and adult hippocampal neurogenesis (AHN) when compared to a matched 10% daily CR intake and ad libitum conditions. After 3 months under IF, female C57BL6 mice exhibited improved long-term memory retention. IF increased the number of BrdU-labeled cells and neuroblasts in the hippocampus, and microarray analysis revealed that the longevity gene Klotho (Kl) was upregulated in the hippocampus by IF only. Furthermore, we found that downregulating Kl in human hippocampal progenitor cells led to decreased neurogenesis, whereas Kl overexpression increased neurogenesis. Finally, histological analysis of Kl knockout mice brains revealed that Kl is required for AHN, particularly in the dorsal hippocampus. These data suggest that IF is superior to 10% CR in enhancing memory and identifies Kl as a novel candidate molecule that regulates the effects of IF on cognition likely via AHN enhancement.
The chosen few—variations in common and rare soil bacteria across biomes
Authors: Bickel Samuel , Or Dani 
Published: May 2021

Abstract
Soil bacterial communities are dominated by a few abundant species, while their richness is associated with rare species with largely unknown ecological roles and biogeography. Analyses of previously published soil bacterial community data using a novel classification of common and rare bacteria indicate that only 0.4% of bacterial species can be considered common and are prevalent across biomes. The remaining bacterial species designated as rare are endemic with low relative abundances. Observations coupled with mechanistic models highlight the central role of soil wetness in shaping bacterial rarity. An individual-based model reveals systematic shifts in community composition induced by low carbon inputs in drier soils that deprive common species of exhibiting physiological advantages relative to other species. We find that only a “chosen few” common species shape bacterial communities across biomes; however, their contributions are curtailed in resource-limited environments where a larger number of rare species constitutes the soil microbiome.
Novel strain-level resolution of Crohn’s disease mucosa-associated microbiota via an ex vivo combination of microbe culture and metagenomic sequencing
Authors: Teh J J , Berendsen E M , Hoedt E C , Kang S , Zhang J , Zhang F , Liu Q , Hamilton A L , Wilson-O’Brien A , Ching J , Sung J J Y , Yu J , Ng S C , Kamm M A , Morrison M 
Published: May 2021

Abstract
The mucosa-associated microbiota is widely recognized as a potential trigger for Crohn’s disease pathophysiology but remains largely uncharacterised beyond its taxonomic composition. Unlike stool microbiota, the functional characterisation of these communities using current DNA/RNA sequencing approaches remains constrained by the relatively small microbial density on tissue, and the overwhelming amount of human DNA recovered during sample preparation. Here, we have used a novel ex vivo approach that combines microbe culture from anaerobically preserved tissue with metagenome sequencing (MC-MGS) to reveal patient-specific and strain-level differences among these communities in post-operative Crohn’s disease patients. The 16 S rRNA gene amplicon profiles showed these cultures provide a representative and holistic representation of the mucosa-associated microbiota, and MC-MGS produced both high quality metagenome-assembled genomes of recovered novel bacterial lineages. The MC-MGS approach also produced a strain-level resolution of key Enterobacteriacea and their associated virulence factors and revealed that urease activity underpins a key and diverse metabolic guild in these communities, which was confirmed by culture-based studies with axenic cultures. Collectively, these findings using MC-MGS show that the Crohn’s disease mucosa-associated microbiota possesses taxonomic and functional attributes that are highly individualistic, borne at least in part by novel bacterial lineages not readily isolated or characterised from stool samples using current sequencing approaches.
In-depth analysis of N2O fluxes in tropical forest soils of the Congo Basin combining isotope and functional gene analysis
Authors: Gallarotti Nora , Barthel Matti , Verhoeven Elizabeth , Pereira Engil Isadora Pujol , Bauters Marijn , Baumgartner Simon , Drake Travis W , Boeckx Pascal , Mohn Joachim , Longepierre Manon , Mugula John Kalume , Makelele Isaac Ahanamungu , Ntaboba Landry Cizungu , Six Johan 
Published: May 2021

Abstract
Primary tropical forests generally exhibit large gaseous nitrogen (N) losses, occurring as nitric oxide (NO), nitrous oxide (N2O) or elemental nitrogen (N2). The release of N2O is of particular concern due to its high global warming potential and destruction of stratospheric ozone. Tropical forest soils are predicted to be among the largest natural sources of N2O; however, despite being the world’s second-largest rainforest, measurements of gaseous N-losses from forest soils of the Congo Basin are scarce. In addition, long-term studies investigating N2O fluxes from different forest ecosystem types (lowland and montane forests) are scarce. In this study we show that fluxes measured in the Congo Basin were lower than fluxes measured in the Neotropics, and in the tropical forests of Australia and South East Asia. In addition, we show that despite different climatic conditions, average annual N2O fluxes in the Congo Basin’s lowland forests (0.97 ± 0.53 kg N ha−1 year−1) were comparable to those in its montane forest (0.88 ± 0.97 kg N ha−1 year−1). Measurements of soil pore air N2O isotope data at multiple depths suggests that a microbial reduction of N2O to N2 within the soil may account for the observed low surface N2O fluxes and low soil pore N2O concentrations. The potential for microbial reduction is corroborated by a significant abundance and expression of the gene nosZ in soil samples from both study sites. Although isotopic and functional gene analyses indicate an enzymatic potential for complete denitrification, combined gaseous N-losses (N2O, N2) are unlikely to account for the missing N-sink in these forests. Other N-losses such as NO, N2 via Feammox or hydrological particulate organic nitrogen export could play an important role in soils of the Congo Basin and should be the focus of future research.
OTUD7B stabilizes estrogen receptor α and promotes breast cancer cell proliferation
Authors: Tang Jianing , Wu Zeyu , Tian Zelin , Chen Wei , Wu Gaosong 
Published: May 2021

AbstractBreast cancer is the most common malignancy in women worldwide. Estrogen receptor α (ERα) is expressed in ∼70% of breast cancer cases and promotes estrogen-dependent cancer progression. In the present study, we identified OTU domain-containing 7B (OTUD7B), a deubiquitylase belonging to A20 subgroup of ovarian tumor protein superfamily, as a bona fide deubiquitylase of ERα in breast cancer. OTUD7B expression was found to be positively correlated with ERα in breast cancer and associated with poor prognosis. OTUD7B could interact with, deubiquitylate, and stabilize ERα in a deubiquitylation activity-dependent manner. Depletion of OTUD7B decreased ERα protein level, the expression of ERα target genes, and the activity of estrogen response element in breast cancer cells. In addition, OTUD7B depletion significantly decreased ERα-positive breast cancer cell proliferation and migration. Finally, overexpression of ERα could rescue the suppressive effect induced by OTUD7B depletion, suggesting that the ERα status was essential to the function of OTUD7B in breast carcinogenesis. In conclusion, our study revealed an interesting post-translational mechanism between ERα and OTUD7B in ERα-positive breast cancer. Targeting the OTUD7B–ERα complex may prove to be a potential approach to treat patients with ERα-positive breast cancer.
Colorectal cancer cell intrinsic fibroblast activation protein alpha binds to Enolase1 and activates NF-κB pathway to promote metastasis
Authors: Yuan Ziming , Hu Hanqing , Zhu Yihao , Zhang Weiyuan , Fang Qingxiao , Qiao Tianyu , Ma Tianyi , Wang Meng , Huang Rui , Tang Qingchao , Gao Feng , Zou Chaoxia , Gao Xu , Wang Guiyu , Wang Xishan 
Published: May 2021

AbstractFibroblast activation protein alpha (FAP) is a marker of cancer-associated fibroblast, which is also expressed in cancer epithelial cells. However, the role of FAP in colorectal cancer (CRC) cells remains to be elucidated. Here we investigate the expression pattern of FAP in CRC tissues and cells to prove that FAP is upregulated in CRC cells. Loss- of and gain-of-function assays identified FAP promotes migration and invasion instead of an effect on cell proliferation. Microarray assays are adopted to identify the different expressed genes after FAP knockdown and gene set enrichment analysis (GSEA) is used to exploit the involved signaling pathway. Our works reveal FAP exerts a function dependent on NF-κB signaling pathway and FAP expression is associated with NF-κB signaling pathway in clinical samples. Our work shows FAP is secreted by CRC cells and soluble FAP could promote metastasis. To investigate the mechanism of FAP influencing the NF-κB signaling pathway, LC/MS is performed to identify the proteins interacting with FAP. We find that FAP binds to ENO1 and activates NF-κB signaling pathway dependent on ENO1. Blocking ENO1 could partially reverse the pro-metastatic effect mediated by FAP. We also provide evidences that both FAP and ENO1 are associated with CRC stages, and high levels of FAP and ENO1 predict a poor survival in CRC patients. In summary, our work could provide a novel mechanism of FAP in CRC cells and a potential strategy for treatment of metastatic CRC.
Circ_0001367 inhibits glioma proliferation, migration and invasion by sponging miR-431 and thus regulating NRXN3
Authors: Liu Liang , Zhang Peng , Dong Xuchen , Li Haoran , Li Suwen , Cheng Shan , Yuan Jiaqi , Yang Xuejun , Qian Zhiyuan , Dong Jun 
Published: May 2021

AbstractMany studies have reported that circular RNAs play a vital role in the malignant progression of human cancers. However, the role and underlying mechanism of circRNAs in the development of gliomas have not been fully clarified. In this study, we found that circ_0001367 was downregulated in glioma tissues and showed a close correlation with glioma patient survival. Functional assays demonstrated that upregulation of circ_0001367 could suppress the proliferation, migration and invasion of glioma cells in vitro and inhibit glioma growth in vivo. Furthermore, bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation assay indicated that circ_0001367 can serve as a sponge for miR-431 and that miR-431 acts as an oncogene by regulating neurexin 3 (NRXN3). In addition, rescue experiments verified that circ_0001367 could regulate both the expression and function of NRXN3 in a miR-431-dependent manner. In conclusion, circ_0001367 functions as an suppressor in glioma by targeting the miR-431/NRXN3 axis and may be a promising therapeutic target against gliomas.
A Japanese hereditary spastic paraplegia family with a rare nonsynonymous variant in the SPAST gene
Authors: Morikawa Takuya , Miura Shiroh , Tateishi Takahisa , Noda Kazuhito , Shibata Hiroki 
Published: May 2021

AbstractSpastic paraplegia (SPG) type 4 is an autosomal dominant SPG caused by functional variants in the SPAST gene. We examined a Japanese family with three autosomal dominant SPG patients. These patients presented with typical symptoms of SPG, such as spasticity of the lower limbs. We identified a rare nonsynonymous variant, NM_014946.4:c.1252G>A [p.Glu418Lys], in all three family members. This variant has previously been reported in a Russian SPG family as a “likely pathogenic” variant.5 Ascertainment of additional patients carrying this variant in an unrelated Japanese SPG family further supports its pathogenicity. Molecular diagnosis of SPG4 in this family with hereditary spastic paraplegia is confirmed.
Decreased GLUT2 and glucose uptake contribute to insulin secretion defects in MODY3/HNF1A hiPSC-derived mutant β cells
Authors: Low Blaise Su Jun , Lim Chang Siang , Ding Shirley Suet Lee , Tan Yaw Sing , Ng Natasha Hui Jin , Krishnan Vidhya Gomathi , Ang Su Fen , Neo Claire Wen Ying , Verma Chandra S. , Hoon Shawn , Lim Su Chi , Tai E. Shyong , Teo Adrian Kee Keong 
Published: May 2021

AbstractHeterozygous HNF1A gene mutations can cause maturity onset diabetes of the young 3 (MODY3), characterized by insulin secretion defects. However, specific mechanisms of MODY3 in humans remain unclear due to lack of access to diseased human pancreatic cells. Here, we utilize MODY3 patient-derived human induced pluripotent stem cells (hiPSCs) to study the effect(s) of a causal HNF1A+/H126D mutation on pancreatic function. Molecular dynamics simulations predict that the H126D mutation could compromise DNA binding and gene target transcription. Genome-wide RNA-Seq and ChIP-Seq analyses on MODY3 hiPSC-derived endocrine progenitors reveal numerous HNF1A gene targets affected by the mutation. We find decreased glucose transporter GLUT2 expression, which is associated with reduced glucose uptake and ATP production in the MODY3 hiPSC-derived β-like cells. Overall, our findings reveal the importance of HNF1A in regulating GLUT2 and several genes involved in insulin secretion that can account for the insulin secretory defect clinically observed in MODY3 patients.
Longitudinal analysis of blood markers reveals progressive loss of resilience and predicts human lifespan limit
Authors: Pyrkov Timothy V. , Avchaciov Konstantin , Tarkhov Andrei E. , Menshikov Leonid I. , Gudkov Andrei V. , Fedichev Peter O. 
Published: May 2021

AbstractWe investigated the dynamic properties of the organism state fluctuations along individual aging trajectories in a large longitudinal database of CBC measurements from a consumer diagnostics laboratory. To simplify the analysis, we used a log-linear mortality estimate from the CBC variables as a single quantitative measure of the aging process, henceforth referred to as dynamic organism state indicator (DOSI). We observed, that the age-dependent population DOSI distribution broadening could be explained by a progressive loss of physiological resilience measured by the DOSI auto-correlation time. Extrapolation of this trend suggested that DOSI recovery time and variance would simultaneously diverge at a critical point of 120 − 150 years of age corresponding to a complete loss of resilience. The observation was immediately confirmed by the independent analysis of correlation properties of intraday physical activity levels fluctuations collected by wearable devices. We conclude that the criticality resulting in the end of life is an intrinsic biological property of an organism that is independent of stress factors and signifies a fundamental or absolute limit of human lifespan.