bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteomics-based prognostic signature and nomogram construction of hypoxia microenvironment on deteriorating glioblastoma (GBM) pathogenesis
Authors: Wen Ya-Dan , Zhu Xiao-San , Li Dong-Jie , Zhao Qing , Cheng Quan , Peng Yun 
Published: August 2021

AbstractThe present study aimed to construct and evaluate a novel experiment-based hypoxia signature to help evaluations of GBM patient status. First, the 426 proteins, which were previously found to be differentially expressed between normal and hypoxia groups in glioblastoma cells with statistical significance, were converted into the corresponding genes, among which 212 genes were found annotated in TCGA. Second, after evaluated by single-variable Cox analysis, 19 different expressed genes (DEGs) with prognostic value were identified. Based on λ value by LASSO, a gene-based survival risk score model, named RiskScore, was built by 7 genes with LASSO coefficient, which were FKBP2, GLO1, IGFBP5, NSUN5, RBMX, TAGLN2 and UBE2V2. Kaplan–Meier (K–M) survival curve analysis and the area under the curve (AUC) were plotted to further estimate the efficacy of this risk score model. Furthermore, the survival curve analysis was also plotted based on the subtypes of age, IDH, radiotherapy and chemotherapy. Meanwhile, immune infiltration, GSVA, GSEA and chemo drug sensitivity of this risk score model were evaluated. Third, the 7 genes expression were evaluated by AUC, overall survival (OS) and IDH subtype in datasets, importantly, also experimentally verified in GBM cell lines exposed to hypoxic or normal oxygen condition, which showed significant higher expression in hypoxia than in normal group. Last, combing the hypoxia RiskScore with clinical and molecular features, a prognostic composite nomogram was generated, showing the good sensitivity and specificity by AUC and OS. Meanwhile, univariate analysis and multivariate analysis were used for performed to identify variables in nomogram that were significant in independently predicting duration of survival. It is a first time that we successfully established and validated an independent prognostic risk model based on hypoxia microenvironment from glioblastoma cells and public database. The 7 key genes may provide potential directions for future biochemical and pharmaco-therapeutic research.
The differences of poor SRH among municipalities in Iwate after the Great East Japan Earthquake
Authors: Takahashi Shuko , Shimoda Haruki , Sakata Kiyomi , Ogawa Akira , Kobayashi Seiichiro , Kawachi Ichiro 
Published: August 2021

AbstractThe health of communities has been observed to recover at differential rates in the wake of disasters. In the present study, the 5-year trends in poor self-rated health (SRH) in three municipalities of Iwate Prefecture following the 2011 Great East Japan Earthquake and Tsunami were compared. Annual surveys were conducted from 2011 to 2015 in three municipalities (Otsuchi, Rikuzentakata, and Yamada) that were heavily damaged by the tsunami. We tracked the prevalence of poor SRH in 10,052 participants (mean age, 61.0 years; 39.0% men). Trends in the prevalence of poor SRH were analyzed using generalized linear mixed effect models with control for covariates. Immediately after the disaster (2011), all three municipalities reported similar prevalences of poor SRH (around 15%). Among people under the age of 65 years, there was a gradual improvement in health for residents of Rikuzentakata and Yamada, but the prevalence of poor SRH remained persistently high in Otsuchi. Among people over the age of 65 years, the prevalence of poor SRH remained constant in Rikuzentakata and Yamada but increased over a 5-year follow-up period in Otsuchi. The delayed health recovery in Otsuchi may be due to the characteristics of the local health system. Examination of the variations in health recovery may provide clues about the sources of disaster resilience.
Comprehensive polar metabolomics and lipidomics profiling discriminates the transformed from the non-transformed state in colon tissue and cell lines
Authors: Rombouts Caroline , De Spiegeleer Margot , Van Meulebroek Lieven , Vanhaecke Lynn , De Vos Winnok H. 
Published: August 2021

AbstractColorectal cancer (CRC) is the fourth most lethal disease worldwide. Despite an urgent need for therapeutic advance, selective target identification in a preclinical phase is hampered by molecular and metabolic variations between cellular models. To foster optimal model selection from a translational perspective, we performed untargeted ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry-based polar metabolomics and lipidomics to non-transformed (CCD841-CON and FHC) and transformed (HCT116, HT29, Caco2, SW480 and SW948) colon cell lines as well as tissue samples from ten colorectal cancer patients. This unveiled metabolic signatures discriminating the transformed from the non-transformed state. Metabolites involved in glutaminolysis, tryptophan catabolism, pyrimidine, lipid and carnitine synthesis were elevated in transformed cells and cancerous tissue, whereas those involved in the glycerol-3-phosphate shuttle, urea cycle and redox reactions were lowered. The degree of glutaminolysis and lipid synthesis was specific to the colon cancer cell line at hand. Thus, our study exposed pathways that are specifically associated with the transformation state and revealed differences between colon cancer cell lines that should be considered when targeting cancer-associated pathways.
Misokinesia is a sensitivity to seeing others fidget that is prevalent in the general population
Authors: Jaswal Sumeet M. , De Bleser Andreas K. F. , Handy Todd C. 
Published: August 2021

AbstractMisokinesia––or the ‘hatred of movements’––is a psychological phenomenon that is defined by a strong negative affective or emotional response to the sight of someone else’s small and repetitive movements, such as seeing someone fidget with a hand or foot. Among those who regularly experience misokinesia sensitivity, there is a growing grass-roots recognition of the challenges that it presents as evidenced by on-line support groups. Yet surprisingly, scientific research on the topic is lacking. This article is novel in systematically examining whether misokinesia sensitivity actually exists in the general population, and if so, whether there is individual variability in the intensity or extent of what sensitivities are reported. Across three studies that included 4100 participants, we confirmed the existence of misokinesia sensitivity in both student and non-student populations, with approximately one-third of our participants self-reporting some degree of sensitivity to seeing the repetitive, fidgeting behaviors of others as encountered in their daily lives. Moreover, individual variability in the range and intensity of sensitivities reported suggest that the negative social-affective impacts associated with misokinesia sensitivities may grow with age. Our findings thus confirm that a large segment of the general population may have a visual-social sensitivity that has received little formal recognition.
Molecular dynamics study on the relationship between phase transition mechanism and loading direction of AZ31
Authors: Yang Qianhua , Xue Chun , Chu Zhibing , Li Yugui , Ma Lifeng , Gao Hong 
Published: August 2021

AbstractTo develop and design mg-based nanoalloys with excellent properties, it is necessary to explore the forming process. In this paper, to explore the effect of different loading directions on the phase transformation of magnesium alloy, the model of AZ31 magnesium alloy was established, the process of Uniaxial Compression (UC) of magnesium alloy in different directions was simulated, the changes of atomic position and phase structure were observed, and the phase transformation mechanism of AZ31 magnesium alloy under uniaxial compression under different loading directions was summarized. The conclusions are as follows: the stress and strain, potential energy and volume change, void evolution, phase structure change and dislocation evolution of magnesium alloy are consistent, and there is no significant difference. In the process of uniaxial compression, the phase transformation of hexagonal closely packed (HCP) → face-centered cubic (FCC) is the main, and its structure evolves into HCP → Other → FCC. Shockley partial dislocations always precede FCC stacking faults by about 4.5%, and Shockley partial dislocations surround FCC stacking faults. In this paper, the phase transformation mechanism of AZ31 magnesium alloy under uniaxial compression under different loading directions is summarized, which provides a theoretical basis for the processing and development of magnesium-based nanoalloys.
Differential responses of chicken monocyte-derived dendritic cells infected with Salmonella Gallinarum and Salmonella Typhimurium
Authors: Singh Degpal , Singh Mithilesh , Chander Vishal , Sharma Gaurav Kumar , Mahawar Manish , Teeli Aamir Salam , Goswami Tapas Kumar 
Published: August 2021

AbstractSalmonella enterica serovar Gallinarum is a host-restricted bacterial pathogen that causes a serious systemic disease exclusively in birds of all ages. Salmonella enterica serovar Typhimurium is a host-generalist serovar. Dendritic cells (DCs) are key antigen-presenting cells that play an important part in Salmonella host-restriction. We evaluated the differential response of chicken blood monocyte-derived dendritic cells (chMoDCs) exposed to S. Gallinarum or S. Typhimurium. S. Typhimurium was found to be more invasive while S. Gallinarum was more cytotoxic at the early phase of infection and later showed higher resistance against chMoDCs killing. S. Typhimurium promoted relatively higher upregulation of costimulatory and other immune function genes on chMoDCs in comparison to S. Gallinarum during early phase of infection (6 h) as analyzed by real-time PCR. Both Salmonella serovars strongly upregulated the proinflammatory transcripts, however, quantum was relatively narrower with S. Gallinarum. S. Typhimurium-infected chMoDCs promoted relatively higher proliferation of naïve T-cells in comparison to S. Gallinarum as assessed by mixed lymphocyte reaction. Our findings indicated that host restriction of S. Gallinarum to chicken is linked with its profound ability to interfere the DCs function. Present findings provide a valuable roadmap for future work aimed at improved vaccine strategies against this pathogen.
Causes of admission, length of stay and outcomes for common kestrels in rehabilitation centres in the Czech Republic
Authors: Lukesova Gabriela , Voslarova Eva , Vecerek Vladimir , Vucinic Marijana 
Published: August 2021

AbstractRehabilitation centres help injured animals to recover and return back to the wild. This study aimed to analyse trends in intake and outcomes for the common kestrels (Falco tinnunculus) admitted into rehabilitation centres in the Czech Republic. From 2010 to 2019, a total of 12,923 kestrels were admitted to 34 rehabilitation centres with an increasing trend (rSp = 0.7697, P < 0.01) being found during the monitored period. Subadult kestrels (34.70%) and kestrels injured by power lines (26.57%) were most often admitted. Most kestrels in the rehabilitation centres died or had to be euthanized (81.66%), only 15.90% of the birds could be released back into the wild. The median length of stay in rehabilitation centres for kestrels that were subsequently released was 35 days. Considering survival rates, the most critical threat to kestrels was poisoning (100% of the cases resulted in death) but mortality of the kestrels admitted for most other reasons also exceeded 80%. Given the low success rate of the care of kestrels in rehabilitation centres and the relatively small proportion returned to the wild, it is essential to eliminate the causes leading to their admission, that is, to protect their natural habitats and to prevent unnecessary capture.
TP53 isoform junction reads based analysis in malignant and normal contexts
Authors: Vural Suleyman , Chang Lun-Ching , Yee Laura M. , Sonkin Dmitriy 
Published: August 2021

AbstractTP53 is one of the most frequently altered genes in cancer; it can be inactivated by a number of different mechanisms. NM_000546.6 (ENST00000269305.9) is by far the predominant TP53 isoform, however a few other alternative isoforms have been described to be expressed at much lower levels. To better understand patterns of TP53 alternative isoforms expression in cancer and normal samples we performed exon-exon junction reads based analysis of TP53 isoforms using RNA-seq data from The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), and Genotype-Tissue Expression (GTEx) project. TP53 C-terminal alternative isoforms have abolished or severely decreased tumor suppressor activity, and therefore, an increase in fraction of TP53 C-terminal alternative isoforms may be expected in tumors with wild type TP53. Despite our expectation that there would be increase of fraction of TP53 C-terminal alternative isoforms, we observed no substantial increase in fraction of TP53 C-terminal alternative isoforms in TCGA tumors and CCLE cancer cell lines with wild type TP53, likely indicating that TP53 C-terminal alternative isoforms expression cannot be reliably selected for during tumor progression.
Patient-specific effects of soluble factors from Staphylococcus aureus and Staphylococcus epidermidis biofilms on osteogenic differentiation of primary human osteoblasts
Authors: Tübel Jutta , Maier Elisabeth , Jegen Magdalena , Marthen Carmen , Obermeier Andreas , Haug Alexander T. , Schneider Jochen , Burgkart Rainer 
Published: August 2021

AbstractDue to the frequency of biofilm-forming Staphylococcus aureus and Staphylococcus epidermidis in orthopedics, it is crucial to understand the interaction between the soluble factors produced by prokaryotes and their effects on eukaryotes. Our knowledge concerning the effect of soluble biofilm factors (SBF) and their virulence potential on osteogenic differentiation is limited to few studies, particularly when there is no direct contact between prokaryotic and eukaryotic cells. SBF were produced by incubating biofilm from S. aureus and S. epidermidis in osteogenic media. Osteoblasts of seven donors were included in this study. Our results demonstrate that the detrimental effects of these pathogens do not require direct contact between prokaryotic and eukaryotic cells. SBF produced by S. aureus and S. epidermidis affect the metabolic activity of osteoblasts. However, the effect of SBF derived from S. aureus seems to be more pronounced compared to that of S. epidermidis. The influence of SBF of S. aureus and S. epidermidis on gene expression of COL1A1, ALPL, BGLAP, SPP1, RUNX2 is bacteria-, patient-, concentration-, and incubation time dependent. Mineralization was monitored by staining the calcium and phosphate deposition and revealed that the SBF of S. epidermidis markedly inhibits calcium deposition; however, S. aureus shows a less inhibitory effect. Therefore, these new findings support the hypotheses that soluble biofilm factors affect the osteogenic processes substantially, particularly when there is no direct interaction between bacteria and osteoblast.
Explainable machine-learning predictions for complications after pediatric congenital heart surgery
Authors: Zeng Xian , Hu Yaoqin , Shu Liqi , Li Jianhua , Duan Huilong , Shu Qiang , Li Haomin 
Published: August 2021

AbstractThe quality of treatment and prognosis after pediatric congenital heart surgery remains unsatisfactory. A reliable prediction model for postoperative complications of congenital heart surgery patients is essential to enable prompt initiation of therapy and improve the quality of prognosis. Here, we develop an interpretable machine-learning-based model that integrates patient demographics, surgery-specific features and intraoperative blood pressure data for accurately predicting complications after pediatric congenital heart surgery. We used blood pressure variability and the k-means algorithm combined with a smoothed formulation of dynamic time wrapping to extract features from time-series data. In addition, SHAP framework was used to provide explanations of the prediction. Our model achieved the best performance both in binary and multi-label classification compared with other consensus-based risk models. In addition, this explainable model explains why a prediction was made to help improve the clinical understanding of complication risk and generate actionable knowledge in practice. The combination of model performance and interpretability is easy for clinicians to trust and provide insight into how they should respond before the condition worsens after pediatric congenital heart surgery.
Increased retinal venular calibre in acute infections
Authors: Fitt Cara , Luong Thao Vi , Cresp Damian , Hutchinson Anastasia , Lim Karen , Hodgson Lauren , Colville Deb , Savige Judy 
Published: August 2021

AbstractPopulation-based studies have demonstrated that increased retinal venular calibre is a risk factor for cardiac disease, cardiac events and stroke. Venular dilatation also occurs with diabetes, obesity, dyslipidemia and autoimmune disease where it is attributed to inflammation. This study examined whether the inflammation associated with infections also affected microvascular calibre. Participants with infections and CRP levels >  100 mg/L were recruited from the medical wards of a teaching hospital and assisted to complete a demographic and vascular risk factor questionnaire, and to undergo non-mydriatic retinal photography (Canon CR5-45NM, Japan). They were then treated with appropriate antibiotics, and underwent repeat retinal imaging when their CRP levels had fallen to less than 100 mg/L. Retinal images were examined for arteriole and venular calibre using validated semi-automated software based on Knudtson’s modification of the Parr-Hubbard formula (IVAN, U Wisconsin). Differences in inflammatory markers and calibre were examined using the paired t-test for continuous variables. Determinants of calibre were calculated from multiple linear regression analysis. Forty-one participants with respiratory (27, 66%), urinary (6, 15%), skin (5, 12%), or miscellaneous (3, 7%) infections were studied. After antibiotic treatment, participants’ mean CRP levels fell from 172.9 ± 68.4 mg/L to 42.2 ± 28.2 mg/L (p < 0.0001) and mean neutrophil counts fell from 9 ± 4 × 109/L to 6 ± 3 × 109/L (p < 0.0001). The participants’ mean venular calibre (CRVE) decreased from 240.9 ± 26.9 MU to 233.4 ± 23.5 MU (p = 0.0017) but arteriolar calibre (CRAE) was unchanged (156.9 ± 15.2 MU and 156.2 ± 16.0 MU, p = 0.84). Thirteen additional participants with infections had a CRP > 100 mg/L that persisted at review (199.2 ± 59.0 and 159.4 ± 40.7 mg/L, p = 0.055). Their CRAE and CRVE were not different before and after antibiotic treatment (p = 0.96, p = 0.78). Hospital inpatients with severe infections had retinal venular calibre that decreased as their infections resolved and CRP levels fell after antibiotic treatment. The changes in venular calibre with intercurrent infections may confound retinal vascular assessments of, for example, blood pressure control and cardiac risk.
Downregulation of CD40L–CD40 attenuates seizure susceptibility and severity of seizures
Authors: Pototskiy Esther , Vinokuroff Katherine , Ojeda Andrew , Major C. Kendall , Sharma Deepak , Anderson Taylor , Howard Kendall , Borenstein Ronen , Musto Alberto E. 
Published: August 2021

AbstractUnregulated neuro-inflammation mediates seizures in temporal lobe epilepsy (TLE). Our aim was to determine the effect of CD40–CD40L activation in experimental seizures. CD40 deficient mice (CD40KO) and control mice (wild type, WT) received pentenyltetrazole (PTZ) or pilocarpine to evaluate seizures and status epilepticus (SE) respectively. In mice, anti-CD40L antibody was administered intranasally before PTZ. Brain samples from human TLE and post-seizure mice were processed to determine CD40–CD40L expression using histological and molecular techniques. CD40 expression was higher in hippocampus from human TLE and in cortical neurons and hippocampal neural terminals after experimental seizures. CD40–CD40L levels increased after seizures in the hippocampus and in the cortex. After SE, CD40L/CD40 levels increased in cortex and showed an upward trend in the hippocampus. CD40KO mice demonstrated reduction in seizure severity and in latency compared to WT mice. Anti-CD40L antibody limited seizure susceptibility and seizure severity. CD40L–CD40 interaction can serve as a target for an immuno-therapy for TLE.
Non-toxic polymer nanovectors for improved delivery of dexamethasone
Authors: Ede Benjamin C. , Diamanti Paraskevi , Williams David S. , Blair Allison 
Published: August 2021

AbstractDexamethasone (Dex) is a highly insoluble front-line drug used in cancer therapy. Data from clinical trials indicates that the pharmacokinetics of Dex vary considerably between patients and prolonging drug exposure rather than increasing absolute dose may improve efficacy. Non-toxic, fully biodegradable Dex loaded nanovectors (NV) were formulated, via simple direct hydration within 10 min, as a vehicle to extend exposure and distribution in vivo. Dex-NV were just as effective as the free drug against primary human leukemia cells in vitro and in vivo. Importantly, high levels of DMSO solvent were not required in the NV formulations. Broad distribution of NV was seen rapidly following inoculation into mice. NV accumulated in major organs, including bone marrow and brain, known sanctuary sites for ALL. The study describes a non-toxic, more easily scalable system for improving Dex solubility for use in cancer and can be applied to other medical conditions associated with inflammation.
Difference in electron microscopic findings among interstitial cystitis/bladder pain syndrome with distinct clinical and cystoscopic characteristics
Authors: Lee Yu Khun , Jhang Jia-Fong , Jiang Yuan-Hong , Hsu Yung-Hsiang , Ho Han-Chen , Kuo Hann-Chorng 
Published: August 2021

AbstractUrothelial dysfunction may be a key pathomechanism underlying interstitial cystitis/bladder pain syndrome (IC/BPS). We therefore examined if clinical severity is associated with the extent of urothelial damage as revealed by electron microscopic (EM) analysis of biopsy tissue. One hundred IC/BPS patients were enrolled and 24 patients with stress urinary incontinence served as controls. Clinical symptoms were evaluated by visual analog scale pain score and O’Leary-Sant Symptom score. Bladder biopsies were obtained following cystoscopic hydrodistention. The presence of Hunner’s lesions and glomerulation grade after hydrodistention were recorded and patients classified as Hunner-type IC (HIC) or non-Hunner-type IC (NHIC). HIC patients exhibited more severe defects in urothelium cell layers, including greater loss of umbrella cells, umbrella cell surface uroplakin plaque, and tight junctions between adjacent umbrella cells, compared to control and NHIC groups (all p < 0.05). Both NHIC and HIC groups demonstrated more severe lamina propria inflammatory cell infiltration than controls (p = 0.011, p < 0.001, respectively). O’Leary-Sant Symptom scores were significantly higher among patients with more severe urothelial defects (p = 0.030). Thus, urothelium cell layer defects on EM are associated with greater clinical symptom severity.