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  • 1
    Publication Date: 2021-10-18
    Description: Background: Osteosarcoma is the most general bone malignancy that mostly affects children and adolescents. Numerous stem cell-related genes have been founded in distinct forms of cancer. This study aimed at identifying a stem cell-related gene model for the expected assessment of the prognosis of osteosarcoma patients.Methods: We obtained the genes expression data and relevant clinical materials from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases. We identified differentially expressed genes (DEGs) from the GEO dataset, whereas prognostic stem cell-related genes were obtained from the TARGET database. Subsequently, univariate, LASSO and multivariate Cox regression analyses were applied to establish the stem cell-related signature. Finally, the prognostic value of the signature was validated in the GEO dataset.Results: Twenty-five genes were prognostic ferroptosis-related DEGs. Consequently, we identified eight stem cell-related genes as a signature of prognosis of osteosarcoma patients. Then, the Kaplan–Meier (K-M) curve, the AUC value of ROC, and Cox regression analysis verified that the eight stem cell-related gene model were a new and substantial prognostic marker independent of other clinical traits. Moreover, the nomogram on the foundation of risk score and other clinical traits was established for predicting the survival rate of osteosarcoma patients. Biological function analyses displayed that tumor related pathways were affluent.Conclusion: The expression level of stem cell-related genes offers novel prognostic markers as well as underlying therapeutic targets for the therapy and prevention of osteosarcoma.
    Electronic ISSN: 2296-634X
    Topics: Biology
    Published by Frontiers Media
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  • 2
    Publication Date: 2021-10-18
    Description: Stimulus-responsive hydrogels are significantly programmable materials that show potential applications in the field of biomedicine and the environment. Ultrasound as a stimulus can induce the formation of hydrogels, which exhibit the superior performance of different structures. In this study, we reported an ultrasound-induced supramolecular hydrogel based on aspartic acid derivative N,N′-diaspartate-3,4,9,10-perylene tetracarboxylic acid imide, showing superior performance in drug release. The results show that the driving force of this ultrasonic induced hydrogel could be attributed to hydrogen bonding and π-π interaction. The rheological and cytotoxicity test illustrate excellent mechanical properties and biocompatibility of the hydrogel. The anti-Schistosoma japonicum cercariae (CC) drug release results show large drug loadings (500 mg/ml) and long-term release (15 days) of this hydrogel. This study demonstrates that this hydrogel may serve as a slow-release platform for anti-CC.
    Electronic ISSN: 2296-4185
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Published by Frontiers Media
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  • 3
    Publication Date: 2021-10-18
    Description: IntroductionPanton Valentine leukocidin (PVL) is a virulence factor which is associated with methicillin sensitive and resistant Staphylococcus aureus (MSSA/MRSA) causing skin and soft tissue infections (SSTI). This study aimed to evaluate a novel lateral flow immunoassay (LFI) for PVL detection in S. aureus cultures and to describe their genotypic characterization.MethodsThe study was carried out from January-August 2020 in Dubai, United Arab Emirates. S. aureus isolates associated with SSTI were tested for PVL detection using LFI. DNA microarray-based assays were used for molecular characterization including detection of pvl genes.ResultsOne-hundred thirty-five patients with a clinical diagnosis of SSTIs were recruited. Sixty-six patients received antibiotics, mostly beta lactams (n=36) and topical fusidic acid (n=15). One-hundred twenty-nine isolates (MRSA: n=43; MSSA: n=86) were tested by LFI and DNA microarrays. All 76 (58.9%) isolates which were unambiguously negative for the PVL in LFI were negative for pvl genes using the DNA microarray. All the LFI PVL positive isolates (n=53) had pvl genes detected. This translates into 100% each for sensitivity, specificity, positive and negative predictive values for the LFI. The LFI typically takes about 15 min inclusive of a 10 min incubation period. Predominant S. aureus clonal complexes (CC) were CC30 (n=18), CC22 (n=13), CC5 (n=12), CC1 (n=11), CC152 (n=8), CC15 (n=7); CC97 (n=7); CC8 and CC20 (n=6 each). Among MRSA, the proportion of pvl-positives (35/43; 81%) was higher than among MSSA (n/N=18/86; 21%). The fusidic acid resistance gene fusC was detected in 14 MRSA (33%) compared to 8 MSSA (9%). A co-carriage of fusC and pvl genes was present in 7 MRSA and in one MSSA.ConclusionLFI shows excellent diagnostic accuracy indices for rapid identification of PVL in MSSA/MRSA in a setting with high prevalence of pvl+ve strains. The high occurrence of pvl and fusC genes in MRSA strains causing SSTI is of concern and needs constant surveillance.
    Electronic ISSN: 2235-2988
    Topics: Biology , Medicine
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  • 4
    Publication Date: 2021-10-18
    Description: Cryptosporidium spp., the causative agent of cryptosporidiosis, can infect a variety of hosts. So far, there has been limited information regarding Cryptosporidium spp. infection in yaks (Bos grunniens). Here, we performed the first systematic review and meta-analysis for Cryptosporidium spp. infection in yaks in China. To perform the meta-analysis, five databases (Chinese National Knowledge Infrastructure (CNKI), VIP Chinese journal database, WanFang Data, PubMed, and ScienceDirect) were employed to search for studies related to the prevalence of Cryptosporidium spp. in yaks in China. The total number of samples was 8,212, and the pooled Cryptosporidium spp. prevalence in yaks was estimated to be 10.52% (1192/8012). The prevalence of Cryptosporidium spp. in yaks was 13.54% (1029/5277) and 4.49% (148/2132) in northwestern and southwestern China, respectively. In the sampling year subgroups, the prevalence before 2012 (19.79%; 650/2662) was significantly higher than that after 2012 (6.07%; 437/4476). The prevalence of Cryptosporidium spp. in cold seasons (20.55%; 188/794) was higher than that in warm seasons (4.83%; 41/1228). In the age subgroup, the yaks with age 〈 12 months had a higher prevalence (19.47%; 231/1761) than that in yaks with age ≥12 months (16.63%; 365/2268). Among 12 Cryptosporidium spp. species/genotypes, the C. bovis had the highest prevalence. Moreover, the effects of geography (latitude, longitude, precipitation, temperature, and altitude) and climate on Cryptosporidium spp. infection in yaks were evaluated. Through analyzing the risk factors correlated with the prevalence of Cryptosporidium spp., we recommend that effective management measures should be formulated according to the differences of different geographical factors, in order to prevent cryptosporidiosis and reduce economic losses in yaks in China.
    Electronic ISSN: 2235-2988
    Topics: Biology , Medicine
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  • 5
    Publication Date: 2021-10-18
    Description: Behavioral stability partially depends on the variability of net outcomes by means of the co-varied adjustment of individual elements such as multi-finger forces. The properties of cyclic actions affect stability and variability of the performance as well as the activation of the prefrontal cortex that is an origin of subcortical structure for the coordinative actions. Little research has been done on the issue of the relationship between stability and neuronal response. The purpose of the study was to investigate the changes in the neural response, particularly at the prefrontal cortex, to the frequencies of isometric cyclic finger force production. The main experimental task was to produce finger forces while matching the produced force to sine-wave templates as accurately as possible. Also, the hemodynamics responses of the prefrontal cortex, including oxy-hemoglobin concentration (ΔHbO) and the functional connectivity, were measured using functional near-infrared spectroscopy. The frequency conditions comprised 0.1, 1, and 2 Hz. The uncontrolled manifold (UCM) approach was applied to compute synergy indices in time-series. The relative phase (RP), the coefficient of variation (CV) of the peak and trough force values were computed as the indices of performance accuracy. The statistical parametric mapping (SPM) was implemented to compare the synergy indices of three frequency conditions in time-series. A less accurate performance in the high-frequency condition was caused not by the RP, but mainly by the inconsistent peak force values (CV; p 〈 0.01, ηp2 = 0.90). The SPM analysis revealed that the synergy indices were larger in the low-frequency than in high-frequency conditions. Further, the ΔHbO remained unchanged under all frequency conditions, while the functional connectivity decreased with an increase in the frequency of cyclic force production. The current results suggested that the concurrent activation of the prefrontal region mainly depends on the frequency of cyclic force production, which was associated with the strength of stability indices and performance errors. The current study is the first work to uncover the effect of frequency on the multi-finger synergies as to the hemodynamic response in the prefrontal cortex, which possibly provides a clue of the neural mechanism of synergy formation and its changes.
    Electronic ISSN: 1662-5161
    Topics: Medicine
    Published by Frontiers Media
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  • 6
    Publication Date: 2021-10-18
    Description: Cartilage tissue is comprised of extracellular matrix and chondrocytes, a cell type with very low cellular turnover in adults, providing limited capacity for regeneration. However, in development a significant number of chondrocytes actively proliferate and remodel the surrounding matrix. Uncoupling the microenvironmental influences that determine the balance between clonogenic potential and terminal differentiation of these cells is essential for the development of novel approaches for cartilage regeneration. Unfortunately, most of the existing methods are not applicable for the analysis of functional properties of chondrocytes at a single cell resolution. Here we demonstrate that a novel 3D culture method provides a long-term and permissive in vitro niche that selects for highly clonogenic, colony-forming chondrocytes which maintain cartilage-specific matrix production, thus recapitulating the in vivo niche. As a proof of concept, clonogenicity of Sox9IRES–EGFP mouse chondrocytes is almost exclusively found in the highest GFP+ fraction known to be enriched for chondrocyte progenitor cells. Although clonogenic chondrocytes are very rare in adult cartilage, we have optimized this system to support large, single cell-derived chondrogenic organoids with complex zonal architecture and robust chondrogenic phenotype from adult pig and human articular chondrocytes. Moreover, we have demonstrated that growth trajectory and matrix biosynthesis in these organoids respond to a pro-inflammatory environment. This culture method offers a robust, defined and controllable system that can be further used to interrogate the effects of various microenvironmental signals on chondrocytes, providing a high throughput platform to assess genetic and environmental factors in development and disease.
    Electronic ISSN: 2296-634X
    Topics: Biology
    Published by Frontiers Media
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  • 7
    Publication Date: 2021-10-18
    Description: A keratinase from Pseudomonas aeruginosa (KerPA), which belongs to the M4 family of metallopeptidases, was characterised in this study. This enzyme was engineered with non-canonical amino acids (ncAAs) using genetic code expansion. Several variants with enhanced activity and thermostability were identified and the most prominent, Y21pBpF/Y70pBpF/Y114pBpF, showed an increase in enzyme activity and half-life of approximately 1.3-fold and 8.2-fold, respectively. Considering that keratinases usually require reducing agents to efficiently degrade keratin, the Y21pBpF/Y70pBpF/Y114pBpF variant with enhanced activity and stability under reducing conditions may have great significance for practical applications. Molecular Dynamics (MD) was performed to identify the potential mechanisms underlying these improvements. The results showed that mutation with pBpF at specific sites of the enzyme could fill voids, form new interactions, and reshape the local structure of the active site of the enzyme.
    Electronic ISSN: 2296-4185
    Topics: Process Engineering, Biotechnology, Nutrition Technology
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  • 8
    Publication Date: 2021-10-18
    Description: BackgroundComparison of patterns of early hepatocellular carcinoma (HCC) recurrence beyond the Milan criteria (HRBM) and identification of the independent risk factors of time to recurrence beyond the Milan criteria (TRBM) after resection or ablation can develop an optimal first-line treatment and provide more opportunities and waiting time for salvage transplantation.MethodsThe patterns of HRBM after first-line resection or ablation in 384 patients with single-nodule HBV-associated HCC of 2–3 cm were retrospectively analyzed by one-to-one propensity score matching (PSM) between December 2008 and December 2017. The median TRBM between the resection group and the ablation group was estimated by Kaplan–Meier curves. The Cox regression analysis and binary logistic regression were used for the identification of the independent risk factors of TRBM and the occurrence of HRBM, respectively. The abilities of HRBM and the recurrence to predict overall survival (OS) were compared by the time-dependent receiver operating characteristic curves and estimated area under the curve.ResultsOf 384 patients enrolled in our study, 260 (67.7%) received resection (resection group) and 124 (32.3%) underwent ablation (ablation group). The median TRBM in the resection group was significantly longer than that in the ablation group before PSM (median, not available vs. 101.4 months, P 〈 0.001) and after PSM (median, not available vs. 85.7 months, P 〈 0.001). Cox regression showed ablation, older age, CRP ≥1.81 mg/L, and PLT ≤80 × 109/L were the independent risk factors of TRBM. Binary logistic regression also showed that ablation, CRP ≥1.81 mg/L, and PLT ≤80 × 109/L were the independent risk factors of the occurrence of HRBM. The incidences of various phenotypes of HRBM were not significantly different between the two groups, but the incidence of HRBM at the first recurrence in the ablation group was significantly higher than that in the resection group (P 〈 0.05). Besides, compared with recurrence, HRBM was a better predictor of OS (P 〈 0.05).ConclusionsCompared with ablation, resection should be considered as a more appropriate first-line option for patients with single-nodule HBV-associated HCC of 2–3 cm and a more promising bridge for liver transplantation in those patients.
    Electronic ISSN: 2234-943X
    Topics: Medicine
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  • 9
    Publication Date: 2021-10-18
    Description: mRNAs have been found to undergo substantial selective degradation during the late stages of spermiogenesis. However, the mechanisms regulating this biological process are unknown. In this report, we have identified Tex13a, a spermatid-specific gene that interacts with the CCR4–NOT complex and is implicated in the targeted degradation of mRNAs encoding particular structural components of sperm. Deletion of Tex13a led to a delayed decay of these mRNAs, lowered the levels of house-keeping genes, and ultimately lowered several key parameters associated with the control of sperm motility, such as the path velocity (VAP, average path velocity), track speed (VCL, velocity curvilinear), and rapid progression.
    Electronic ISSN: 2296-634X
    Topics: Biology
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  • 10
    Publication Date: 2021-10-18
    Description: This study explored the fatigue effect on postural control (PC) across menstrual cycle phases (MCPs) in female athletes. Isometric maximal voluntary contraction (IMVC), the center of pressure sway area (CoParea), CoP length in the medio-lateral (CoPLX) and antero-posterior (CoPLY) directions, and Y-balance test (YBT) were assessed before and after a fatiguing exercise during the follicular phase (FP), mid-luteal phase (LP), and premenstrual phase (PMP). Baseline normalized reach distances (NRDs) for the YBT were lower (p = 0.00) in the PMP compared to others MCPs, but the IMVC, CoParea, CoPLX, and CoPLY remained unchanged. After exercise, the IMVC and the NRD decrease was higher at PMP compared to FP (p = 0.00) and LP (p = 0.00). The CoParea, CoPLX, and CoPLY increase was higher in the PMP compared to FP (p = 0.00) and LP (p = 0.00). It was concluded that there is an accentuated PC impairment after exercise observed at PMP.
    Electronic ISSN: 1664-042X
    Topics: Biology
    Published by Frontiers Media
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  • 11
    Publication Date: 2021-10-18
    Description: Background:BRCA1/2 mutations are closely related to high lifetime risk of breast cancer (BC). The objective of this study was to identify the genes, regulators, and immune-associated patterns underlying disease pathology in BC with BRCA1/2 somatic mutations and their associations with clinical traits.Methods: RNA sequencing data and clinical information from The Cancer Genome Atlas (TCGA; N = 36 BRCA1-mutant BC; N = 49 BRCA2-mutant BC; and N = 117 BRCA1/2-wild-type BC samples) were used for discovery, which included consensus network analysis, function enrichment, and analysis of hub genes; other TCGA data (N = 117 triple-negative BC) and two Gene Expression Omnibus database expression profiles were used as validation cohorts.Results: Consensus network analysis helped to identify specific co-expressed modules that showed positive correlations with tumor stage, number of positive lymph nodes, and margin status in BRCA1/2-mutant BC but lacking correlations in BRCA1/2-wild-type BC. Functional enrichment suggested potential mechanisms in BRCA1/2 carriers that could regulate the cell cycle, immune response, cellular metabolic processes, and cell migration, via enriched pathways including p53 and JAK–STAT signaling. Consensus network analysis identified the specific and common carcinogenic mechanisms involving BRCA mutations. Regulators cross-linking these modules include E2F or IRF transcription factor family, associated with cell cycle or immune response regulation module, respectively. Eight hub genes, including ISG15, BUB1, and TTK, were upregulated in several BRCA1/2-mutant BC datasets and showed prognostic value in BC. Furthermore, their genetic expression was related to higher levels of immune infiltration in BRCA1/2-mutant BC, which manifested as recruitment of T helper cells (Th1 cells), follicular helper T cells, and regulatory T cells, and T cell exhaustion. Moreover, important indicators for evaluation of BC immunotherapy, tumor mutational burden and neoantigen load also positively correlated with expression of some hub genes.Conclusion: We constructed a BRCA1/2 mutation-type-specific co-expressed gene network with related transcription factors and immune-associated patterns that could regulate and influence tumor metastasis and immune microenvironment, providing novel insights into the pathological process of this disease and the corresponding BRCA mutations.
    Electronic ISSN: 2296-634X
    Topics: Biology
    Published by Frontiers Media
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  • 12
    Publication Date: 2021-10-18
    Description: Depression is one very common mental health disorder which can cause morbidity and mortality if not addressed. Recent studies have provided strong evidence that depression may be accompanied by immune activation, secondary inflammatory reaction, and hyperactivity of the Hypothalamic Pituitary Adrenal (HPA) axis. It is well-known that it takes at least 2 weeks for conventional antidepressants, especially SSRIs (Selective serotonin reuptake inhibitors) to produce effects. To better understand the mechanism of antidepressant effects on depression and subsequently further elucidate the pathogenesis of depression, we selected phytestrogen daidzein (DD) to observe its effects on the depression-like and anxiety-like behavior in two different rodent models of depression which were induced by learned helplessness and chronic mild stress (CMS) and then simultaneous evaluation of the depression-like behavior, the activity of HPA axis, and circulatory cytokines. Our results showed that daidzein attenuated depression-like behaviors through alleviating HPA axis hyperactivity, decreasing the levels of stress-related hormones, and partly rectifying some inflammatory cytokines imbalance in both the rodent models of depression.
    Electronic ISSN: 1662-5153
    Topics: Medicine
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  • 13
    Publication Date: 2021-10-18
    Description: Congestive heart failure (CHF) often leads to progressive cardiac hypertrophy and salt/water retention. However, its pathogenesis remains largely unclarified. Corin, a cardiac serine protease, is responsible for converting proANP and proBNP to biologically active peptides. Although the involvement of corin in cardiac hypertrophy and heart failure was extensively studied, the alterations in corin and proprotein convertase subtilisin/kexin-6 (PCSK6), a key enzyme in the conversion of procorin to corin, has not been studied simultaneously in the cardiac and renal tissues in cardiorenal syndrome. Thus, this study aims to examine the status of PCSK6/corin in the cardiac and renal tissues of rats with CHF induced by the creation of aorto-caval fistula (ACF). We divided rats with ACF into two subgroups based on the pattern of their urinary sodium excretion, namely, compensated and decompensated. Placement of ACF led to cardiac hypertrophy, pulmonary congestion, and renal dysfunction, which were more profound in the decompensated subgroup. Corin immunoreactive peptides were detected in all heart chambers at the myocyte membranal and cytosolic localization and in the renal tissue, especially in the apical membrane of the proximal tubule, mTAL, and the collecting duct. Interestingly, the expression and abundance of corin in both the cardiac ventricles and renal tissues were significantly increased in compensated animals as compared with the decompensated state. Noteworthy, the abundance of PCSK6 in these tissues followed a similar pattern as corin. In contrast, furin expression was upregulated in the cardiac and renal tissues in correlation with CHF severity. We hypothesize that the obtained upregulation of cardiac and renal PCSK6/corin in rats with compensated CHF may represent a compensatory response aiming at maintaining normal Na+ balance, whereas the decline in these two enzymes may contribute to the pathogenesis of avid sodium retention, cardiac hypertrophy, and blunted atrial natriuretic peptide/brain natriuretic peptide actions in decompensated CHF.
    Electronic ISSN: 1664-042X
    Topics: Biology
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  • 14
    Publication Date: 2021-10-19
    Description: Autism spectrum disorder (ASD) is a severe brain development disorder that is characterized by deficits in social communication and restricted, repetitive and stereotyped behaviors. Accumulating evidence has suggested that gut microbiota disorders play important roles in gastrointestinal symptoms and neurodevelopmental dysfunction in ASD patients. Manipulation of the gut microbiota by fecal microbiota transplantation (FMT) was recently shown to be a promising therapy for the treatment of various diseases. Here, we performed a clinical trial to evaluate the effect of FMT on gastrointestinal (GI) and ASD symptoms and gut microbiota alterations in children with ASD. We found that there was a large difference in baseline characteristics of behavior, GI symptoms, and gut microbiota between children with ASD and typically developing (TD) control children. FMT could improve GI symptoms and ASD symptoms without inducing any severe complications. Similarly, FMT significantly changed the serum levels of neurotransmitters. We further observed that FMT could promote the colonization of donor microbes and shift the bacterial community of children with ASD toward that of TD controls. The abundance of Eubacterium coprostanoligenes pre-FMT was positively correlated with high GSRS scores, whereas a decrease in Eubacterium coprostanoligenes abundance induced by FMT was associated with the FMT response. Our data suggest that FMT might be a promising therapeutic strategy to improve the GI and behavioral symptoms of patients with ASD, possibly due to its ability to alter gut microbiota and highlight a specific microbiota intervention that targets Eubacterium coprostanoligenes that can enhance the FMT response. This trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn) (trial registration number ChiCTR1800014745).
    Electronic ISSN: 2235-2988
    Topics: Biology , Medicine
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  • 15
    Publication Date: 2021-10-19
    Description: Since their discovery, antibodies capable of broad neutralisation have been at the forefront of HIV-1 research and are of particular interest due to in vivo passive transfer studies demonstrating their potential to provide protection. Currently an exact definition of what is required for a monoclonal antibody to be classed as a broadly neutralising antibody (bnAb) has not yet been established. This has led to hundreds of antibodies with varying neutralisation breadth being studied and has given insight into antibody maturation pathways and epitopes targeted. However, even with this knowledge, immunisation studies and vaccination trials to date have had limited success in eliciting antibodies with neutralisation breadth. For this reason there is a growing need to identify factors specifically associated with bnAb development, yet to do this a set of criteria is necessary to distinguish bnAbs from non-bnAbs. This review aims to define what it means to be a HIV-1 bnAb by comparing neutralisation breadth, genetic features and epitopes of bnAbs, and in the process highlights the challenges of comparing the array of antibodies that have been isolated over the years.
    Electronic ISSN: 1664-3224
    Topics: Medicine
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  • 16
    Publication Date: 2021-10-20
    Description: Many factors have been described to contribute to voriconazole (VCZ) interpatient variability in plasma concentrations, especially CYP2C19 genetic variability. In 2014, Hicks et al. presented data describing the correlation between VCZ plasma concentrations and CYP2C19 diplotypes in immunocompromised pediatric patients and utilized pharmacokinetic modeling to extrapolate a more suitable VCZ dose for each CYP2C19 diplotype. In 2017, in our hospital, a clinical protocol was developed for individualization of VCZ in immunocompromised patients based on preemptive genotyping of CYP2C19 and dosing proposed by Hicks et al., Clinical Pharmacogenetics Implementation Consortium (CPIC) clinical guidelines, and routine therapeutic drug monitoring (TDM). We made a retrospective review of a cohort of 28 immunocompromised pediatric patients receiving VCZ according to our protocol. CYP2C19 gene molecular analysis was preemptively performed using PharmArray®. Plasma trough concentrations were measured by immunoassay analysis until target concentrations (1–5.5 μg/ml) were reached. Sixteen patients (57.14%) achieved VCZ trough target concentrations in the first measure after the initial dose based on PGx. This figure is similar to estimations made by Hicks et al. in their simulation (60%). Subdividing by phenotype, our genotyping and TDM-combined strategy allow us to achieve target concentrations during treatment/prophylaxis in 90% of the CYP2C19 Normal Metabolizers (NM)/Intermediate Metabolizers (IM) and 100% of the Rapid Metabolizers (RM) and Ultrarapid Metabolizers (UM) of our cohort. We recommended modifications of the initial dose in 29% (n = 8) of the patients. In RM ≥12 years old, an increase of the initial dose resulted in 50% of these patients achieving target concentrations in the first measure after initial dose adjustment based only on PGx information. Our experience highlights the need to improve VCZ dose predictions in children and the potential of preemptive genotyping and TDM to this aim. We are conducting a multicenter, randomized clinical trial in patients with risk of aspergillosis in order to evaluate the effectiveness and efficiency of VCZ individualization: VORIGENIPHARM (EudraCT: 2019-000376-41).
    Electronic ISSN: 1663-9812
    Topics: Medicine
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  • 17
    Publication Date: 2021-10-19
    Description: Background: Big data and real-world data (RWD) have been increasingly used to measure the effectiveness and costs in cost-effectiveness analysis (CEA). However, the characteristics and methodologies of CEA based on big data and RWD remain unknown. The objectives of this study were to review the characteristics and methodologies of the CEA studies based on big data and RWD and to compare the characteristics and methodologies between the CEA studies with or without decision-analytic models. Methods: The literature search was conducted in Medline (Pubmed), Embase, Web of Science, and Cochrane Library (as of June 2020). Full CEA studies with an incremental analysis that used big data and RWD for both effectiveness and costs written in English were included. There were no restrictions regarding publication date. Results: 70 studies on CEA using RWD (37 with decision-analytic models and 33 without) were included. The majority of the studies were published between 2011 and 2020, and the number of CEA based on RWD has been increasing over the years. Few CEA studies used big data. Pharmacological interventions were the most frequently studied intervention, and they were more frequently evaluated by the studies without decision-analytic models, while those with the model focused on treatment regimen. Compared to CEA studies using decision-analytic models, both effectiveness and costs of those using the model were more likely to be obtained from literature review. All the studies using decision-analytic models included sensitivity analyses, while four studies no using the model neither used sensitivity analysis nor controlled for confounders. Conclusion: The review shows that RWD has been increasingly applied in conducting the cost-effectiveness analysis. However, few CEA studies are based on big data. In future CEA studies using big data and RWD, it is encouraged to control confounders and to discount in long-term research when decision-analytic models are not used.
    Electronic ISSN: 1663-9812
    Topics: Medicine
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  • 18
    Publication Date: 2021-10-20
    Description: Euphausiids are abundant micronekton and important links between higher and lower trophic levels in marine ecosystems; however, their detailed diets cannot be fully understood by conventional microscopy, especially in subtropical areas. Here, we report the euphausiid community structure in the California Current (CC) area and the eastern/western North Pacific subtropical gyre (ESG and WSG) and detail the feeding ecology of the dominant species (Euphausia pacifica, E. brevis, and E. hemigibba) in each region using a combined approach of gut content analysis via 18S V9 metabarcoding and stable carbon and nitrogen isotope analysis. A pronounced omnivorous feeding of all studied euphausiid species was supported by both methods: phytoplanktonic taxonomic groups (Dinophyta, Stramenopiles, and Archaeplastida), Copepoda, and Hydrozoa were detected in the gut contents; all the three euphausiid species displayed an intermediate trophic position between the net plankton (0.2–1.0 mm) and the myctophid fish (15.2–85.5 mm). However, Hydrozoa found in euphausiid gut contents likely derived from a potential cod-end feeding, based on isotope analysis. E. pacifica in the CC province ingested more autotrophic prey, including pelagophyte and green algae, due to a greater abundance of Stramenopiles and Archaeplastida in shallow layers of CC water. On the other hand, non-autotrophic prey such as mixotrophic Kareniaceae dinoflagellates, Pontellidae and Clausocalanidae copepods, and Sphaerozoidae rhizarian contributed more to the diets of E. brevis and E. hemigibba because of a lower chlorophyll a concentration or potentially a scarcity of autotrophic prey availability in ESG and WSG. The feeding patterns of dominant euphausiid species conducting filter feeding were thus largely determined by phytoplankton prey availability in the environments. Dietary difference across three species was also indicated by stable isotope analysis, with a lower mean trophic level of E. pacifica (2.32) than E. brevis (2.48) and E. hemigibba (2.57). These results verify direct trophic interactions between euphausiids and primary production and suggest that the omnivorous feeding habit is a favorable character for dominant Euphausia species.
    Electronic ISSN: 2296-7745
    Topics: Biology
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  • 19
    Publication Date: 2021-10-18
    Description: Establishing personalized medication plans for patients to maximize therapeutic efficacy and minimize the toxicity of vancomycin (VAN) requires rapid, simple, and accurate monitoring of VAN concentration in body fluid. In this study, we have developed a simple and rapid analytical method by integrating Eu (III) chelate nanoparticles (CN-EUs) and lateral flow immunoassay (LFIA) to achieve the real-time monitoring of VAN concentration in serum within 15 min. This approach was performed on nitrocellulose (NC) membrane assembled LFIA strips via indirect competitive immunoassay and exhibited a wide linear range of detection (0.1–80 μg*ml−1) with a low limit of detection (69.2 ng*ml−1). The coefficients of variation (CV) of the intra- and inter-assay in the detection of VAN were 7.12–8.53% and 8.46–11.82%, respectively. The dilution test and specificity indicated this method had a stability that was not affected by the serum matrix and some other antibiotics. Furthermore, the applicability of the proposed method was assessed by comparing the determined results with those measured by LC-MS/MS, showing a satisfactory correlation (R2 = 0.9713). The proposed CN-EUs-based LFIA manifested promising analytical performance, which showed potential value in the real-time monitoring of VAN and could help optimize the clinical use of more antibiotics.
    Electronic ISSN: 2296-2646
    Topics: Chemistry and Pharmacology
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  • 20
    Publication Date: 2021-10-18
    Description: A series of new complexes, [Ln (2,4-DMBA)3(5,5′-DM-2,2′-bipy)]2 (Ln = Sm(1), Eu (2)), [Pr (2,4-DMBA)3 (5,5′-DM-2,2′-bipy)]2·0.5(C2H5OH) (3), [Ln (2,4-DMBA)3 (5,5′-DM-2,2′-bipy)]2·0.5(2,4-DMBAH)·0.25(5,5′-DM-2,2′-bipy) (Ln = Tb (4), Dy (5)) (2,4-DMBA = 2,4-dimethylbenzoate, 5,5′-DM-2,2′-bipy = 5,5′-dimethy-2,2′-bipyridine) were synthesized via hydrothermal reaction conditions. The complexes were characterized through elemental analysis, Infrared spectra (IR), Raman (R) spectra, UV-Vis spectra, single X-ray diffraction. Single crystal data show that complexes 1–5 are binuclear complexes, but they can be divided into three different crystal structures. The thermal decomposition mechanism of complexes 1–5 were investigated by the technology of simultaneous TG/DSC-FTIR. What’s more, the luminescent properties of complexes 1–2 and 4 were discussed, and the luminescence lifetime (τ) of complexes 2 and 4 were calculated.
    Electronic ISSN: 2296-2646
    Topics: Chemistry and Pharmacology
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  • 21
    Publication Date: 2021-10-20
    Description: The increased life expectancy for patients with Down Syndrome (DS) has elicited the need to improve their quality of life by enhancing functional outcomes and identifying the factors that contribute to their long-term cognitive decline. Although the majority of individuals with DS have issues with hearing impairment (HI) since early childhood, to our knowledge no study has investigated whether HI represents a potential modulator of cognitive decline over time. The present explorative cohort study, albeit very preliminary due to the limited cohort (17 children), highlights the significant relation of a significant HI not only with receptive language abilities, but also with mental age in young patients with DS. Additional studies are required to confirm the link between HI and mental age and to assess the impact of audiological treatment on the enhancement of functional outcomes and of cognitive decline in individuals with DS.
    Electronic ISSN: 2296-2360
    Topics: Medicine
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  • 22
    Publication Date: 2021-10-18
    Description: Acute Kidney Injury (AKI) is an independent risk factor for mortality in hospitalized patients. AKI syndrome leads to fluid overload, electrolyte and acid-base disturbances, immunoparalysis, and propagates multiple organ dysfunction through organ “crosstalk”. Preclinical models suggest AKI causes acute lung injury (ALI), and conversely, mechanical ventilation and ALI cause AKI. In the clinical setting, respiratory complications are a key driver of increased mortality in patients with AKI, highlighting the bidirectional relationship. This article highlights the challenging and complex interactions between the lung and kidney in critically ill patients with AKI and acute respiratory distress syndrome (ARDS) and global implications of AKI. We discuss disease-specific molecular mediators and inflammatory pathways involved in organ crosstalk in the AKI-ARDS construct, and highlight the reciprocal hemodynamic effects of elevated pulmonary vascular resistance and central venous pressure (CVP) leading to renal hypoperfusion and pulmonary edema associated with fluid overload and increased right ventricular afterload. Finally, we discuss the notion of different ARDS “phenotypes” and the response to fluid overload, suggesting differential organ crosstalk in specific pathological states. While the directionality of effect remains challenging to distinguish at the bedside due to lag in diagnosis with conventional renal function markers and lack of tangible damage markers, this review provides a paradigm for understanding kidney-lung interactions in the critically ill patient.
    Electronic ISSN: 2296-2360
    Topics: Medicine
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  • 23
    Publication Date: 2021-10-18
    Description: Leptospira weilii belongs to the pathogenic Leptospira group and is a causal agent of human and animal leptospirosis in many world regions. L. weilii can produce varied clinical presentations from asymptomatic through acute to chronic infections and occupy several ecological niches. Nevertheless, the genomic feature and genetic basis behind the host adaptability of L. weilii remain elusive due to limited information. Therefore, this study aimed to examine the complete circular genomes of two new L. weilii serogroup Mini strains (CUDO6 and CUD13) recovered from the urine of asymptomatic dogs in Thailand and then compared with the 17 genomes available for L. weilii. Variant calling analysis (VCA) was also undertaken to gain potential insight into the missense mutations, focusing on the known pathogenesis-related genes. Whole genome sequences revealed that the CUDO6 and CUD13 strains each contained two chromosomes and one plasmid, with average genome size and G+C content of 4.37 Mbp and 40.7%, respectively. Both strains harbored almost all the confirmed pathogenesis-related genes in Leptospira. Two novel plasmid sequences, pDO6 and pD13, were identified in the strains CUDO6 and CUD13. Both plasmids contained genes responsible for stress response that may play important roles in bacterial adaptation during persistence in the kidneys. The core-single nucleotide polymorphisms phylogeny demonstrated that both strains had a close genetic relationship. Amongst the 19 L. weilii strains analyzed, the pan-genome analysis showed an open pan-genome structure, correlated with their high genetic diversity. VCA identified missense mutations in genes involved in endoflagella, lipopolysaccharide (LPS) structure, mammalian cell entry protein, and hemolytic activities, and may be associated with host-adaptation in the strains. Missense mutations of the endoflagella genes of CUDO6 and CUD13 were associated with loss of motility. These findings extend the knowledge about the pathogenic molecular mechanisms and genomic evolution of this important zoonotic pathogen.
    Electronic ISSN: 1664-302X
    Topics: Biology
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  • 24
    Publication Date: 2021-10-18
    Description: Electroanatomic mapping is the gold standard for the assessment of ventricular tachycardia. Acquiring high resolution electroanatomic maps is technically challenging and may require interpolation methods to obtain dense measurements. These methods, however, cannot recover activation times in the entire biventricular domain. This work investigates the use of graph convolutional neural networks to estimate biventricular activation times from sparse measurements. Our method is trained on more than 15,000 synthetic examples of realistic ventricular depolarization patterns generated by a computational electrophysiology model. Using geometries sampled from a statistical shape model of biventricular anatomy, diverse wave dynamics are induced by randomly sampling scar and border zone distributions, locations of initial activation, and tissue conduction velocities. Once trained, the method accurately reconstructs biventricular activation times in left-out synthetic simulations with a mean absolute error of 3.9 ms ± 4.2 ms at a sampling density of one measurement sample per cm2. The total activation time is matched with a mean error of 1.4 ms ± 1.4 ms. A significant decrease in errors is observed in all heart zones with an increased number of samples. Without re-training, the network is further evaluated on two datasets: (1) an in-house dataset comprising four ischemic porcine hearts with dense endocardial activation maps; (2) the CRT-EPIGGY19 challenge data comprising endo- and epicardial measurements of 5 infarcted and 6 non-infarcted swines. In both setups the neural network recovers biventricular activation times with a mean absolute error of less than 10 ms even when providing only a subset of endocardial measurements as input. Furthermore, we present a simple approach to suggest new measurement locations in real-time based on the estimated uncertainty of the graph network predictions. The model-guided selection of measurement locations allows to reduce by 40% the number of measurements required in a random sampling strategy, while achieving the same prediction error. In all the tested scenarios, the proposed approach estimates biventricular activation times with comparable or better performance than a personalized computational model and significant runtime advantages.
    Electronic ISSN: 1664-042X
    Topics: Biology
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  • 25
    Publication Date: 2021-10-18
    Description: ObjectiveTo develop and validate a new strategy based on radiomics features extracted from intra- and peritumoral regions on CT images for the prediction of atypical responses to the immune checkpoint inhibitor (ICI) in cancer patients.MethodsIn total, 135 patients derived from five hospitals with pathologically confirmed malignancies receiving ICI were included in this retrospective study. Atypical responses including pseudoprogression (PsP) and hyperprogression disease (HPD) were identified as their definitions. A subgroup of standard progression disease (sPD) in 2018 was also involved in this study. Based on pretreatment CT imaging, a total of 107 features were extracted from intra- and peri-tumoral regions, respectively. The least absolute shrinkage and selection operator (Lasso) algorithm was used for feature selection, and multivariate logistic analysis was used to develop radiomics signature (RS). Finally, a total of nine RSs, derived from intra-tumoral, peri-tumoral, and combination of both regions, were built respectively to distinguish PsP vs. HPD, PsP vs. sPD, and HPD vs. sPD. The performance of the RSs was evaluated with discrimination, calibration, and clinical usefulness.ResultsNo significant difference was found when compared in terms of clinical characteristics of PsP, HPD, and sPD. RS based on combined regions outperformed those from either intra-tumoral or peri-tumoral alone, yielding an AUC (accuracy) of 0.834 (0.827) for PsP vs. HPD, 0.923 (0.868) for PsP vs. sPD, and 0.959 (0.894) for HPD vs. sPD in the training datasets, and 0.835 (0.794) for PsP vs. HPD, 0.919 (0.867) for PsP vs. sPD, and 0.933 (0.842) for HPD vs. sPD in the testing datasets. The combined RS showed good fitness (Hosmer–Lemeshow test p 〉 0.05) and provided more net benefit than the treat-none or treat-all scheme by decision curve analysis in both training and testing datasets.ConclusionPretreatment radiomics are helpful to predict atypical responses to ICI across tumor types. The combined RS outperformed those from either intra- or peri-tumoral alone which may provide a more comprehensive characterization of atypical responses to ICI.
    Electronic ISSN: 2234-943X
    Topics: Medicine
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  • 26
    Publication Date: 2021-10-18
    Description: We report an ongoing regional outbreak of an emerging porcine reproductive and respiratory syndrome virus (PRRSV2) variant within Lineage 1C affecting 154 breeding and grow-finishing sites in the Midwestern U.S. Transmission seemed to have occurred in two waves, with the first peak of weekly cases occurring between October and December 2020 and the second starting in April 2021. Most of cases occurred within a 120 km radius. Both orf5 and whole genome sequencing results suggest that this represents the emergence of a new variant within Lineage 1C distinct from what has been previously circulating. A case-control study was conducted with 50 cases (sites affected with the newly emerged variant) and 58 controls (sites affected with other PRRSV variants) between October and December 2020. Sites that had a market vehicle that was not exclusive to the production system had 0.04 times the odds of being a case than a control. A spatial cluster (81.42 km radius) with 1.68 times higher the number of cases than controls was found. The average finishing mortality within the first 4 weeks after detection was higher amongst cases (4.50%) than controls (0.01%). The transmission of a highly similar virus between different farms carrying on trough spring rises concerns for the next high transmission season of PRRS.
    Electronic ISSN: 2297-1769
    Topics: Medicine
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  • 27
    Publication Date: 2021-10-20
    Description: Background: Anorexia nervosa (AN) is a serious and life-threatening psychiatric condition. With a paucity of approved treatments, there is a desperate need for novel treatment avenues to be explored. Here, we present (1) an overview of the ways through which Public Patient Involvement (PPI) has informed a trial of psilocybin-assisted therapy for AN and (2) a protocol for a pilot study of psilocybin-assisted therapy in AN currently underway at Imperial College London. The study aims to assess the feasibility, brain mechanisms and preliminary outcomes of treating anorexia nervosa with psilocybin.Methods: (1) PPI: Across two online focus groups, eleven individuals with lived experience of AN were presented with an overview of the protocol. Their feedback not only identified solutions to possible barriers for future participants, but also helped the research team to better understand the concept of “recovery” from the perspective of those with lived experience. (2) Protocol: Twenty female participants [21–65 years old, body mass index (BMI) 15 kg/m2 or above] will receive three oral doses of psilocybin (up to 25 mg) over a 6-week period delivered in a therapeutic environment and enveloped by psychological preparation and integration. We will work with participant support networks (care teams and an identified support person) throughout and there will be an extended remote follow-up period of 12 months. Our two-fold primary outcomes are (1) psychopathology (Eating Disorder Examination) across the 6-month follow-up and (2) readiness and motivation to engage in recovery (Readiness and Motivation Questionnaire) across the 6-week trial period. Neurophysiological outcome measures will be: (1) functional magnetic resonance imaging (fMRI) brain changes from baseline to 6-week endpoint and (2) post-acute changes in electroencephalography (EEG) activity, including an electrophysiological marker of neuronal plasticity.Discussion: The results of this pilot study will not only shed light on the acceptability, brain mechanisms, and impression of the potential efficacy of psilocybin as an adjunct treatment for AN but will be essential in shaping a subsequent Randomised Control Trial (RCT) that would test this treatment against a suitable control condition.Clinical Trial Registration: identifier: NCT04505189.
    Electronic ISSN: 1664-0640
    Topics: Medicine
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  • 28
    Publication Date: 2021-10-18
    Description: Odor hedonic evaluation (pleasant/unpleasant) is considered as the first and one of the most prominent dimension in odor perception. While sex differences in human olfaction have been extensively explored, gender effect in hedonic perception appears to be less considered. However, a number of studies have included comparisons between men and women, using different types of measurements (psychophysical, psychophysiological,…). This overview presents experimental works with non-specific and body odors separately presented as well as experimental studies comparing healthy participants vs patients with psychiatric disorders. Contrary to sensitivity, identification or discrimination, the overall literature tends to prove that no so clear differences occur in odor hedonic judgment between men and women. On the whole, gender effect appears more marked for body than non-specific odors and is almost never reported in psychiatric diseases. These findings are discussed in relation to the processes classically implied in pleasantness rating and emotional processes.
    Print ISSN: 1662-4548
    Electronic ISSN: 1662-453X
    Topics: Medicine
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  • 29
    Publication Date: 2021-10-18
    Description: Incidence of brain metastases has increased in patients with colorectal cancer (CRC) as their survival has improved. CD3 T-cells and, lately, DGMate (DiGital tuMor pArameTErs) score, have been identified as prognostic factors in locally advanced CRC. Until now, there is no data concerning the prognostic value of these markers in patients with CRC-derived brain metastases. All consecutive patients with CRC-derived brain metastases diagnosed between 2000 and 2017 were retrospectively included. Staining for CD3, CD8, PD-1, PD-L1 and DGMate analyses were performed using tissue micro-array from primary tumors and, if available, brain metastases. All in all, 83 patients were included with 80 primary tumor samples and 37 brain metastases samples available. CD3 and CD8 T-cell infiltration was higher in primary tumors compared to brain metastases. We observed a significant higher DGMate score in rectal tumors compared to colon tumors (p=0.03). We also noted a trend of higher CD3 T-cell infiltration in primary tumors when brain metastases were both supra and subtentorial compared to brain metastases that were only subtentorial or supratentorial (p=0.36 and p=0.03, respectively). No correlation was found between CD3 or CD8 infiltration or DGMate score in primary tumors or brain metastases and overall survival (OS) in the overall population. In patients with rectal tumors, a high DGMate score in brain metastases was associated with longer OS (13.4 ± 6.1 months versus 6.1 ± 1.4 months, p=0.02). High CD3 T-cell infiltration in brain metastases was associated with lower OS in patients with supratentorial brain metastases (9.8 ± 3.3 months versus 16.7 ± 5.9 months, p=0.03). PD-L1 overexpression was rare, both in primary tumors and brain metastases, but PD-L1 positive primary tumors were associated with worse OS (p=0.01). In contrast to breast and lung cancer derived brain metastases, CD3 and CD8 infiltration and DGMate score are not major prognostic factors in patients with CRC-derived brain metastases.
    Electronic ISSN: 1664-3224
    Topics: Medicine
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  • 30
    Publication Date: 2021-10-20
    Description: We present the case of a severely symptomatic patient with a malfunctioning aortic bioprosthesis and severe multidistrict atherosclerosis that was addressed to our unit for transcatheter valve-in-valve implantation. The imaging and clinical assessment that led to the selection of the access route is discussed.
    Electronic ISSN: 2297-055X
    Topics: Medicine
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  • 31
    Publication Date: 2021-10-19
    Description: Andean uplift and the concomitant formation of the Diagonal Arid of South America is expected to have promoted species diversification through range expansions into this novel environment. We evaluate the evolution of Argylia, a genus belonging to the Bignoniaceae family whose oldest fossil record dates back to 49.4 Ma. Today, Argylia is distributed along the Andean Cordillera, from 15°S to 38.5°S and from sea level up to 4,000 m.a.s.l. We ask whether Argylia’s current distribution is a result of a range expansion along the Andes Cordillera (biological corridor) modulated by climatic niche conservatism, considering the timing of Andean uplift (30 Ma – 5 Ma). To answer this question, we reconstructed the phylogenetic relationships of Argylia species, estimated divergence times, estimated the realized climatic niche of the genus, reconstructed the ancestral climatic niche, evaluated its evolution, and finally, performed an ancestral range reconstruction. We found strong evidence for climatic niche conservatism for moisture variables, and an absence of niche conservatism for most of the temperature variables considered. Exceptions were temperature seasonality and winter temperature. Results imply that Argylia had the capacity to adapt to extreme temperature conditions associated with the Andean uplift and the new climatic corridor produced by uplift. Ancestral range reconstruction for the genus showed that Argylia first diversified in a region where subtropical conditions were already established, and that later episodes of diversification were coeval with the of Andean uplift. We detected a second climatic corridor along the coastal range of Chile-Peru, the coastal lomas, which allowed a northward range expansion of Argylia into the hyperarid Atacama Desert. Dating suggests the current distribution and diversity of Argylia would have been reached during the Late Neogene and Pleistocene.
    Electronic ISSN: 1664-462X
    Topics: Biology
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  • 32
    Publication Date: 2021-10-20
    Description: We introduce for the first time a new product line able to make high accuracy measurements of a number of water chemistry parameters in situ: i.e., submerged in the environment including in the deep sea (to 6,000 m). This product is based on the developments of in situ lab on chip technology at the National Oceanography Centre (NOC), and the University of Southampton and is produced under license by Clearwater Sensors Ltd., a start-up and industrial partner in bringing this technology to global availability and further developing its potential. The technology has already been deployed by the NOC, and with their partners worldwide over 200 times including to depths of ∼4,800 m, in turbid estuaries and rivers, and for up to a year in seasonally ice-covered regions of the arctic. The technology is capable of making accurate determinations of chemical and biological parameters that require reagents and which produce an electrical, absorbance, fluorescence, or luminescence signal. As such it is suitable for a wide range of environmental measurements. Whilst further parameters are in development across this partnership, Nitrate, Nitrite, Phosphate, Silicate, Iron, and pH sensors are currently available commercially. Theses sensors use microfluidics and optics combined in an optofluidic chip with electromechanical valves and pumps mounted upon it to mix water samples with reagents and measure the optical response. An overview of the sensors and the underlying components and technologies is given together with examples of deployments and integrations with observing platforms such as gliders, autonomous underwater vehicles and moorings.
    Electronic ISSN: 2296-7745
    Topics: Biology
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  • 33
    Publication Date: 2021-10-20
    Description: ObjectivesThe roles played by β-III-spectrin, also known as spectrin beta, non-erythrocytic 2 (SPTBN2), in the occurrence and development of lung adenocarcinoma (LUAD) have not been previously examined. Our study aimed to reveal the relationship between the SPTBN2 expression and LUAD.Materials and MethodsTwenty pairs of LUAD tissues and adjacent tissues were collected from patients diagnosed and treated at the Thoracic Surgery Department of The First Affiliated Hospital of Zhengzhou University from July 2019 to September 2020. RNA sequencing (RNA-seq) analysis determined that the expression of SPTBN2 was higher in LUAD samples than in adjacent normal tissues. The expression levels of SPTBN2 were examined in various databases, including the Cancer Cell Line Encyclopedia (CCLE), Gene Expression Omnibus (GEO), and Human Protein Atlas (HPA). The Search Tool for the Retrieval of Interacting Genes (STRING) online website was used to examine protein–protein interactions involving SPTBN2, and the results were visualized by Cytoscape software. The Molecular Complex Detection (MCODE) plug-in for Cytoscape software was used to identify functional modules of the obtained protein–protein interaction (PPI) network. Gene enrichment analysis was performed, and survival analysis was conducted using the Kaplan–Meier plotter. The online prediction website TargetScan was used to predict SPTBN2-targeted miRNA sequences by searching for SPTBN2 sequences. Finally, we verified the expression of SPTBN2 in the obtained tissue samples using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The human lung cancer cell lines A549 and H1299 were selected for the transfection of small interfering RNA (siRNA) targeting SPTBN2 (si-SPTBN2), and the knockdown efficiency was evaluated by RT-qPCR. The cellular proliferation, migration, and invasion capacities of A549 and H1299 cells were determined using the cell counting kit-8 (CCK-8) proliferation assay; the wound-healing assay and the Transwell migration assay; and the Matrigel invasion assay, respectively.ResultsThe expression of SPTBN2 in non–small cell lung cancer (NSCLC) ranked 13th among cancer cell lines based on the CCLE database. At the mRNA and protein levels, the expression levels of SPTBN2 were higher in LUAD tissues than in normal lung tissues. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that proteins related to SPTBN2 were enriched in apoptotic and phagosomal pathways. Kaplan–Meier survival analysis revealed that SPTBN2 expression was significantly related to the prognosis of patients with LUAD. The TargetScan database verified that miR-16 was a negative regulator of SPTBN2 mRNA expression. The results of the CCK-8 cell proliferation assay revealed that SPTBN2 knockdown significantly inhibited the cell proliferation abilities of A549 and H1299 cells. The wound-healing assay indicated that SPTBN2 knockdown resulted in reduced migration after 48 h compared with the control group. The Transwell migration and invasion test revealed that the migration and invasion abilities were greatly decreased by SPTBN2 knockdown compared with control conditions.ConclusionWe uncovered a novel gene, SPTBN2, that was significantly upregulated in LUAD tissues relative to normal tissue expression. SPTBN2 is highly expressed in LUAD, positively correlated with poor prognosis, and can promote the proliferation, migration, and invasion of LUAD cells.
    Electronic ISSN: 2234-943X
    Topics: Medicine
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  • 34
    Publication Date: 2021-10-18
    Description: Rationale: Maternal obstructive sleep apnea-hypopnea (OSAH) is associated with hypertensive disorders of pregnancy (HDP). Attenuation of the normal nocturnal blood pressure (BP) decline (non-dipping) is associated with adverse pregnancy outcomes. OSAH is associated with nocturnal non-dipping in the general population, but this has not been studied in pregnancy. We therefore analyzed baseline data from an ongoing RCT (NCT03309826) assessing the impact of OSAH treatment on HDP outcomes, to evaluate the relationship of OSAH to 24-h BP profile, in particular nocturnal BP dipping, and measures of arterial stiffness.Methods: Women with a singleton pregnancy and HDP underwent level II polysomnography. Patients with OSAH (apnea-hypopnea index (AHI) ≥ 5 events/h) then underwent 24-h ambulatory BP monitoring and arterial stiffness measurements (applanation tonometry, SphygmoCor). Positive dipping was defined as nocturnal systolic blood pressure (SBP) dip ≥ 10%. The relationships between measures of OSAH severity, measures of BP and arterial stiffness were evaluated using linear regression analyses.Results: We studied 51 HDP participants (36.5 ± 4.9 years, BMI 36.9 ± 8.6 kg/m2) with OSAH with mean AHI 27.7 ± 26.4 events/h at 25.0 ± 4.9 weeks’ gestation. We found no significant relationships between AHI or other OSA severity measures and mean 24-h BP values, although BP was generally well-controlled. Most women were SBP non-dippers (78.4%). AHI showed a significant inverse correlation with % SBP dipping following adjustment for age, BMI, parity, gestational age, and BP medications (β = −0.11, p = 0.02). Significant inverse correlations were also observed between AHI and DBP (β = −0.16, p = 0.01) and MAP (β = −0.13, p = 0.02) % dipping. Oxygen desaturation index and sleep time below SaO2 90% were also inversely correlated with % dipping. Moreover, a significant positive correlation was observed between carotid-femoral pulse wave velocity (cfPWV) and REM AHI (β = 0.02, p = 0.04) in unadjusted but not adjusted analysis.Conclusion: Blood pressure non-dipping was observed in a majority of women with HDP and OSAH. There were significant inverse relationships between OSAH severity measures and nocturnal % dipping. Increased arterial stiffness was associated with increasing severity of OSAH during REM sleep in unadjusted although not adjusted analysis. These findings suggest that OSAH may represent a therapeutic target to improve BP profile and vascular risk in HDP.
    Electronic ISSN: 1664-042X
    Topics: Biology
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  • 35
    Publication Date: 2021-10-20
    Description: Intracranial atherosclerotic disease (ICAD) is a dynamic process that leads to ischemic stroke. Symptomatic ICAD patients still suffer a high recurrent rate even under standard treatment. In this case report, to better understand the response of intracranial atherosclerotic plaques to medication, serial MR imaging was added to standard clinical workup in a 47-year-old male patient with acute occipital lobe infarction at baseline, 3-month, 6-month, and 12-month post index stroke to directly visualize the morphology and signal change of plaques. We noticed that one of the plaques showed dramatic worsening at 3-month imaging follow-up despite a decrease in low-density lipoprotein level. Early identification of patients who do not respond well to medication is critical to prevent the recurrence of cardiovascular events in ICAD patients.
    Print ISSN: 1662-4548
    Electronic ISSN: 1662-453X
    Topics: Medicine
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  • 36
    Publication Date: 2021-10-18
    Description: As a main component of the tumor microenvironment, the stroma is critical in development, progression, and metastasis of pancreatic ductal adenocarcinoma (PDAC). The genomic status and its relationship of neoplastic and stromal components remain unclear in PDAC. We performed targeted sequencing for 1,021 cancer-suspected genes on parallel microdissected stromal and neoplastic components from 50 operable PDAC patients. Clonality analysis of mutations was conducted to reconstruct the evolutionary trajectory, and then molecular subtypes were established. Multi-lineage differentiation potential and mesenchymal transformation of KRAS-mutant cell line Panc1 were evaluated using RT-PCR and immunofluorescence staining. In this study, 39 (78.0%) were genomically altered in stroma, with KRAS (71.8%), TP53 (61.5%), and CDKN2A (23.1%) as the most commonly mutated genes. The majority of stromal mutations (89.8%) were detected in matched neoplastic components. Patients with KRAS/TP53-mut stroma demonstrated a higher tumor cell fraction (TCF) than did those with wild-type (WT) stroma (p = 0.0371, p = 0.0014). In both components, mutants KRAS and TP53 often occurred as clonal events, and the allele frequencies presented linear correlation in the same specimen. All neoplasm-like stroma (characterized with all or initial neoplastic clones and driver events in stroma) harbored KRAS or TP53 mutations. Neoplasm-like and KRAS-mutant stroma was associated with shorter disease-free survival. It is a new finding for the existence of driver gene mutations in PDAC stroma. These data suggest that genomic features of stromal components may serve as prognostic biomarkers in resectable PDAC and might help to guide a more precise treatment paradigm in therapeutic options.
    Electronic ISSN: 2234-943X
    Topics: Medicine
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  • 37
    Publication Date: 2021-10-19
    Description: Due to its immunomodulatory potential, the intestinal microbiota has been implicated as a contributing factor in the development of the meta-inflammatory state that drives obesity-associated insulin resistance and type 2 diabetes. A better understanding of this link would facilitate the development of targeted treatments and therapies to treat the metabolic complications of obesity. To this end, we validated and utilized a novel swine model of obesity, the Mangalica pig, to characterize changes in the gut microbiota during the development of an obese phenotype, and in response to dietary differences. In the first study, we characterized the metabolic phenotype and gut microbiota in lean and obese adult Mangalica pigs. Obese or lean groups were created by allowing either ad libitum (obese) or restricted (lean) access to a standard diet for 54 weeks. Mature obese pigs were significantly heavier and exhibited 170% greater subcutaneous adipose tissue mass, with no differences in muscle mass compared to their lean counterparts. Obese pigs displayed impaired glucose tolerance and hyperinsulinemia following oral glucose challenge, indicating that a metabolic phenotype also manifested with changes in body composition. Consistent with observations in human obesity, the gut microbiota of obese pigs displayed altered bacterial composition. In the second study, we characterized the longitudinal changes in the gut microbiota in response to diet and aging in growing Mangalica pigs that were either limit fed a standard diet, allowed ad libitum access to a standard diet, or allowed ad libitum access to a high fat-supplemented diet over an 18-week period. As expected, weight gain was highest in pigs fed the high fat diet compared to ad libitum and limit fed groups. Furthermore, the ad libitum and high fat groups displayed significantly greater adiposity consistent with the development of obesity relative to the limit fed pigs. The intestinal microbiota was generally resilient to differences in dietary intake (limit fed vs ad libitum), though changes in the microbiota of pigs fed the high fat diet mirrored changes observed in mature obese pigs during the first study. This is consistent with the link observed between the microbiota and adiposity. In contrast to intestinal bacterial populations, bacteriophage populations within the gut microbiota responded rapidly to differences in diet, with significant compositional changes in bacteriophage genera observed between the dietary treatment groups as pigs aged. These studies are the first to describe the development of the intestinal microbiota in the Mangalica pig, and are the first to provide evidence that changes in body composition and dietary conditions are associated with changes in the microbiome of this novel porcine model of obesity.
    Electronic ISSN: 2235-2988
    Topics: Biology , Medicine
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  • 38
    Publication Date: 2021-10-19
    Description: Intracerebral hemorrhage (ICH) has one of the worst prognoses among patients with stroke. Surgical measures have been adopted to relieve the mass effect of the hematoma, and developing targeted therapy against secondary brain injury (SBI) after ICH is equally essential. Numerous preclinical and clinical studies have demonstrated that perihematomal edema (PHE) is a quantifiable marker of SBI after ICH and is associated with a poor prognosis. Thus, PHE has been considered a promising therapeutic target for ICH. However, the findings derived from existing studies on PHE are disparate and unclear. Therefore, it is necessary to classify, compare, and summarize the existing studies on PHE. In this review, we describe the growth characteristics and relevant underlying mechanism of PHE, analyze the contributions of different risk factors to PHE, present the potential impact of PHE on patient outcomes, and discuss the currently available therapeutic strategies.
    Electronic ISSN: 1664-3224
    Topics: Medicine
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  • 39
    Publication Date: 2021-10-20
    Description: Objectives: Endothelial dysfunction (ED) has been linked to the pathogenesis of cerebral small vessel disease (SVD). We aimed to assess ED and cerebrovascular reactivity (CVR) in the patients with a diverse manifestation of SVD, with similar and extensive white matter lesions (WMLs, modified Fazekas scale grade ≥2), compared with a control group (CG) without the MRI markers of SVD, matched for age, gender, hypertension, diabetes, and to evaluate the change of CVR following 24 months.Methods: We repeatedly measured the vasomotor reactivity reserve (VMRr) and breath-holding index (BHI) of the middle cerebral artery (MCA) by the transcranial Doppler ultrasound (TCD) techniques in 60 subjects above 60 years with a history of lacunar stroke (LS), vascular dementia (VaD), or parkinsonism (VaP) (20 in each group), and in 20 individuals from a CG.Results: The mean age, frequency of the main vascular risk factors, and sex distribution were similar in the patients with the SVD groups and a CG. The VMRr and the BHI were more severely impaired at baseline (respectively, 56.7 ± 18% and 0.82 ± 0.39) and at follow-up (respectively, 52.3 ± 16.7% and 0.71 ± 0.38) in the patients with SVD regardless of the clinical manifestations (ANOVA, p 〉 0.1) than in the CG (respectively, baseline VMRr 77.2 ± 15.6%, BHI 1.15 ± 0.47, p 〈 0.001; follow-up VMRr 74.3 ± 17.6%, BHI 1.11 ± 0.4, p 〈 0.001). All the assessed CVR measures (VMRr and BHI) significantly decreased over time in the subjects with SVD (Wilcoxon's signed-rank test p = 0.01), but this was not observed in the CG (p 〉 0.1) and the decrease of CVR measures was not related to the SVD radiological progression (p 〉 0.1).Conclusions: This study provided evidence that the change in CVR measures is detectable over a 24-month period in patients with different clinical manifestations of SVD. Compared with the patients in CG with similar atherothrombotic risk factors, all the CVR measures (BMRr and BHI) significantly declined over time in the subjects with SVD. The reduction in CVR was not related to the SVD radiological progression.
    Electronic ISSN: 1663-4365
    Topics: Medicine
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  • 40
    Publication Date: 2021-10-20
    Electronic ISSN: 2296-875X
    Topics: Medicine
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  • 41
    Publication Date: 2021-10-18
    Description: Neonatal metabolic acidosis (NMA) is a common problem, particularly in critically ill patients in neonatal intensive care units (NICUs). Complex etiologies and atypical clinical signs make diagnosis difficult; thus, it is crucial to investigate the underlying causes of NMA rapidly and provide disorder-specific therapies. Our study aims to provide an overview of the genetic causes of NMA in patients from NICUs. We performed next-generation sequencing (NGS) on neonates with NMA from January 2016 to December 2019. Clinical features, genetic diagnoses, and their effects on clinical interventions were collected for analysis. In the 354 enrolled patients, 131 (37%) received genetic diagnoses; 95 (72.5%) of them were autosomal recessively inherited diseases. Two hundred and fifteen variants spanning 57 genes were classified as pathogenic (P) or likely pathogenic (LP) in 131 patients. The leading cause was metabolic disorders due to 35 genes found in 89 patients (68%). The other 42 NMA patients (32%) with 22 genes had malformations and renal, neuromuscular, and immune-hematological disorders. Seven genes (MMUT, MMACHC, CHD7, NPHS1, OTC, IVD, and PHOX2B) were noted in more than four patients, accounting for 48.9% (64/131) of the identified P/LP variants. Forty-six diagnosed patients with uncorrected NMA died or gave up. In conclusion, 37% of neonates with metabolic acidosis had genetic disorders. Next-generation sequencing should be considered when investigating the etiology of NMA in NICUs. Based on early molecular diagnoses, valuable treatment options can be provided for some genetic diseases to achieve better outcomes.
    Electronic ISSN: 2296-2360
    Topics: Medicine
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  • 42
    Publication Date: 2021-10-20
    Electronic ISSN: 2673-253X
    Topics: Medicine
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  • 43
    Publication Date: 2021-10-18
    Description: Objectives: Methylation of the neuronal nitric oxide synthase (NOS1/nNOS) gene has recently been identified as a promising biomarker of psychiatric disorders. NOS1 plays an essential role in neurite outgrowth and may thus affect the microstructure development of white matter (WM) in the corpus callosum (CC), which is known to be altered in panic disorder (PD). We examined the relationship between NOS1 methylation, WM tracts in the CC, and symptoms based on this finding.Methods: Thirty-two patients with PD and 22 healthy controls (HCs) were recruited after age, gender, and the education level were matched. The cell type used was whole-blood DNA, and DNA methylation of NOS1 was measured at 20 CpG sites in the promoter region. Although 25 patients with PD were assessed with the Panic Disorder Severity Scale (PDSS), diffusion tensor imaging (DTI) scans were only collected from 16 participants with PD.Results: We observed that the PD group showed lower methylation than did the HCs group and positive correlations between the symptom severity of PD and methylation at CpG4 and CpG9. In addition, CpG9 methylation was significantly correlated with the fractional anisotropy (FA) and mean diffusivity (MD) values of the CC and its major components (the genu and the splenium) in the PD group. Furthermore, path analyses showed that CpG9 methylation offers a mediating effect for the association between the MD values of the genu of the CC and PD symptom severity (95% CI = −1.731 to −0.034).Conclusions: The results suggest that CpG9 methylation leads to atypical development of the genu of the CC, resulting in higher PD symptom severity, adding support for the methylation of NOS1 as a future prognostic indicator of PD.
    Electronic ISSN: 1664-2295
    Topics: Medicine
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  • 44
    Publication Date: 2021-10-19
    Description: The dense accumulation of α-Synuclein fibrils in neurons is considered to be strongly associated with Parkinson’s disease. These intracellular inclusions, called Lewy bodies, also contain significant amounts of lipids. To better understand such accumulations, it should be important to study α-Synuclein fibril formation under conditions where the fibrils lump together, mimicking what is observed in Lewy bodies. In the present study, we have therefore investigated the overall structural arrangements of α-synuclein fibrils, formed under mildly acidic conditions, pH = 5.5, in pure buffer or in the presence of various model membrane systems, by means of small-angle neutron scattering (SANS). At this pH, α-synuclein fibrils are colloidally unstable and aggregate further into dense clusters. SANS intensities show a power law dependence on the scattering vector, q, indicating that the clusters can be described as mass fractal aggregates. The experimentally observed fractal dimension was d = 2.6 ± 0.3. We further show that this fractal dimension can be reproduced using a simple model of rigid-rod clusters. The effect of dominatingly attractive fibril-fibril interactions is discussed within the context of fibril clustering in Lewy body formation.
    Electronic ISSN: 2296-889X
    Topics: Biology
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  • 45
    Publication Date: 2021-10-20
    Description: Melon (Cucumis melo) is one of the top 10 fruits in the world, and its production often suffers due to soil-borne diseases. Grafting is an effective way to solve this problem. However, graft incompatibility between scion and rootstock limits the application of melon grafting. In this study, the melon was grafted onto eight Cucurbitaceae species (cucumber, pumpkin, melon, luffa, wax gourd, bottle gourd, bitter gourd, and watermelon), and graft compatibility evaluation and anatomical observation were conducted. Taking melon homo-grafted plants as control, melon grafted onto cucumber and pumpkin rootstocks was compatible, while melon grafted onto luffa, wax gourd, bottle gourd, bitter gourd, and watermelon rootstocks was incompatible based on the scion dry weight on day 42 after grafting. Meanwhile, we found that starch–iodine staining of scion stem base is an index to predict graft compatibility earlier, on day 14 after grafting. Further, microsection observations showed that there was more cell proliferation at graft junction of melon hetero-grafted combinations; vascular reconnection occurred in all graft combinations. However, excess callose deposited at graft junction resulted in the blockage of photosynthate transport, thus, leading to starch accumulation in scion stem base, and finally graft incompatibility. In addition, undegraded necrotic layer fragments were observed at graft junctions of melon grafted onto incompatible bitter gourd and watermelon rootstocks. The above results provide clues for the selection and breeding of compatible Cucurbitaceae rootstocks of melon and demonstrate that starch accumulation in scion base and callose deposition at graft junction is associated with melon graft compatibility.
    Electronic ISSN: 1664-462X
    Topics: Biology
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  • 46
    Publication Date: 2021-10-20
    Description: Increasing evidence shows that polycystic ovary syndrome (PCOS) patients are particularly vulnerable to anxiety/depression-like behaviors. This study sought to determine the prevalence of anxiety/depression-like behaviors among women with PCOS and to identify factors associated with these behaviors. This study was a secondary analysis of three studies performed on Chinese women who were aged 18 to 40 and diagnosed with PCOS according to the modified Rotterdam criteria. We obtained 802 useable responses for the self-rating anxiety scale and 798 responses for the self-rating depression scale. The prevalence of anxiety-like and depression-like behaviors among women with PCOS was 26.1% (209/802) and 52.0% (415/798), respectively. Anxiety-like behaviors were associated with age, body image-related factors (including body mass index and waist-to-hip ratio), and hyperandrogenism-related factors (including free androgen index and hirsutism). Depression-like behaviors were associated with age, body image-related factors, hyperandrogenism-related factors, and metabolic factors (including fasting insulin, fasting plasma glucose, and homeostatic model assessment of insulin resistance). Body image-related factors and hyperandrogenism-related factors were related to both anxiety-like behaviors and depression-like behaviors in both infertile and fertile PCOS patients.
    Electronic ISSN: 1664-0640
    Topics: Medicine
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  • 47
    Publication Date: 2021-10-18
    Description: Horsegram is a grain legume with excellent nutritional and remedial properties and good climate resilience, able to adapt to harsh environmental conditions. Here, we used a combination of short- and long-read sequencing technologies to generate a genome sequence of 279.12Mb, covering 83.53% of the estimated total size of the horsegram genome, and we annotated 24,521 genes. De novo prediction of DNA repeats showed that approximately 25.04% of the horsegram genome was made up of repetitive sequences, the lowest among the legume genomes sequenced so far. The major transcription factors identified in the horsegram genome were bHLH, ERF, C2H2, WRKY, NAC, MYB, and bZIP, suggesting that horsegram is resistant to drought. Interestingly, the genome is abundant in Bowman–Birk protease inhibitors (BBIs), which can be used as a functional food ingredient. The results of maximum likelihood phylogenetic and estimated synonymous substitution analyses suggested that horsegram is closely related to the common bean and diverged approximately 10.17 million years ago. The double-digested restriction associated DNA (ddRAD) sequencing of 40 germplasms allowed us to identify 3,942 high-quality SNPs in the horsegram genome. A genome-wide association study with powdery mildew identified 10 significant associations similar to the MLO and RPW8.2 genes. The reference genome and other genomic information presented in this study will be of great value to horsegram breeding programs. In addition, keeping the increasing demand for food with nutraceutical values in view, these genomic data provide opportunities to explore the possibility of horsegram for use as a source of food and nutraceuticals.
    Electronic ISSN: 1664-462X
    Topics: Biology
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  • 48
    Publication Date: 2021-10-18
    Description: Blue lasers are becoming more widely used in the diagnosis and treatment of bladder cancer; however, their photobiomodulation effects on bladder cancer cells remains unclear. The purpose of the current study was to explore the photobiomodulation effect of blue laser irradiation on bladder cancer progression and the associated mechanisms. The human uroepithelial cell line SV-HUC-1 and human bladder cancer cell lines T24 and EJ were exposed to blue laser irradiation (450 nm) at various energy densities, and cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and the levels of the proteins associated with the MAPK pathway proteins were determined. A significant decrease in cell viability was observed in a density-dependent manner after blue laser irradiation at 〉 4 J/cm2 in both bladder cancer cell lines. However, the blue laser did not reduce cell viability in SV-HUC-1 cells until the energy density exceeded 16 J/cm2. Meanwhile, Ki67 levels, reflecting cell proliferation and senescence, were also significantly decreased after blue laser irradiation at 4 J/cm2 and 8 J/cm2 in the absence of cell cycle arrest. Moreover, blue laser irradiation at 4 J/cm2 and 8 J/cm2 caused a reduction in cell migration and invasion and also reduced the expression levels of MMP-2, MMP-9, Snail, N-cadherin, phospho-MEK and phospho-ERK, and elevated the expression levels of E-cadherin. Meanwhile ERK activator(tBHQ) significantly reversed the irradiation-induced suppression of proliferation, migration and invasion in T24 and EJ cell lines. The present study showed that blue laser irradiation inhibited bladder cancer proliferation in a density-dependent manner and inhibited bladder cancer progression by suppressing migration, invasion, and the EMT process in T24 and EJ cell lines. This inhibition was possibly mediated via suppression of the MAPK/MEK/ERK pathway. Thus, the use of a low-energy blue laser in the diagnosis and treatment of bladder cancer is possibly safe and may have an anti-tumor effect.
    Electronic ISSN: 2234-943X
    Topics: Medicine
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  • 49
    Publication Date: 2021-10-18
    Description: Primary familial brain calcification (PFBC) is a progressive neurological disorder manifesting as bilateral brain calcifications in CT scan with symptoms as parkinsonism, dystonia, ataxia, psychiatric symptoms, etc. Recently, pathogenic variants in MYORG have been linked to autosomal recessive PFBC. This study aims to elucidate the mutational and clinical spectrum of MYORG mutations in a large cohort of Chinese PFBC patients with possible autosomal recessive or absent family history. Mutational analyses of MYORG were performed by Sanger sequencing in a cohort of 245 PFBC patients including 21 subjects from 10 families compatible with a possibly autosomal-recessive trait and 224 apparently sporadic cases. In-depth phenotyping and neuroimaging features were investigated in all patients with novel MYORG variants. Two nonsense variants (c.442C 〉 T, p. Q148*; c.972C 〉 A, p. Y324*) and two missense variants (c.1969G〉C, p. G657R; c.2033C 〉 G, p. P678R) of MYORG were identified in four sporadic PFBC patients, respectively. These four novel variants were absent in gnomAD, and their amino acid were highly conserved, suggesting these variants have a pathogenic impact. Patients with MYORG variants tend to display a homogeneous clinical spectrum, showing extensive brain calcification and parkinsonism, dysarthria, ataxia, or vertigo. Our findings supported the pathogenic role of MYORG variants in PFBC and identified two pathogenic variants (c.442C 〉 T, c.972C 〉 A), one likely pathogenic variant (c.2033C 〉 G), and one variant of uncertain significance (c.1969G〉C), further expanding the genetic and phenotypic spectrum of PFBC-MYORG.
    Electronic ISSN: 1664-8021
    Topics: Biology , Medicine
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  • 50
    Publication Date: 2021-10-18
    Description: Background and PurposeRecent studies have shown that several proteins, including Axl, are related to hemorrhagic transformation (HT) following intravenous thrombolysis by affecting blood-brain barrier (BBB) function. However, the effects of these proteins on BBB function have been studied primarily in animal models. In this study, we aimed to identify serum protein markers that predict HT following intravenous thrombolysis in patients with acute ischemic stroke (AIS) and verify whether these serum proteins regulate BBB function and HT in animal stroke models.MethodsFirst, 118 AIS patients were enrolled in this study, including 52 HT patients and 66 non-HT patients. In Step 1, baseline serum levels of Axl, angiopoietin-like 4, C-reactive protein, ferritin, hypoxia-inducible factor-1 alpha, HTRA2, Lipocalin2, matrix metallopeptidase 9, platelet-derived growth factor-BB, and tumor necrosis factor alpha were measured using a quantitative cytokine chip. Next, sequence mutations and variations in genes encoding the differentially expressed proteins identified in Step 1 and subsequent function-related proteins were detected. Finally, we verified whether manipulation of differentially expressed proteins affected BBB function and HT in a hyperglycemia-induced rat stroke model.ResultsSerum Axl levels were significantly lower in the HT group than in the non-HT group; none of the other protein markers differed significantly between the two groups. Genetic testing revealed that sequence variations of GAS6 (the gene encoding the Axl ligand)-derived long non-coding RNA, GAS6-AS1, were significantly correlated with an increased risk of HT after intravenous thrombolysis. In animal studies, administration of recombinant GAS6 significantly reduced brain infarction and neurological deficits and attenuated BBB disruption and HT.ConclusionsLower serum Axl levels, which may result from sequence variations in GAS6-AS1, are correlated with an increased risk of HT after intravenous thrombolysis in stroke patients. Activation of the Axl signaling pathway by the GAS6 protein may serve as a therapeutic strategy to reduce HT in AIS patients.
    Electronic ISSN: 1664-3224
    Topics: Medicine
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  • 51
    Publication Date: 2021-10-14
    Description: Objective: Given the ever-changing flow of obstetric patients in the hospital, how the government and hospital management plan and allocate medical resources has become an important problem that needs to be urgently solved. In this study a prediction method for calculating the monthly and daily flow of patients based on time series is proposed to provide decision support for government and hospital management.Methods: The historical patient flow data from the Department of Obstetrics and Gynecology of the First Hospital of Jilin University, China, from January 1, 2018, to February 29, 2020, were used as the training set. Seven models such as XGBoost, SVM, RF, and NNAR were used to predict the daily patient flow in the next 14 days. The HoltWinters model is then used to predict the monthly flow of patients over the next year.Results: The results of this analysis and prediction model showed that the obstetric inpatient flow was not a purely random process, and that patient flow was not only accompanied by the random patient flow but also showed a trend change and seasonal change rule. ACF,PACF,Ljung_box, and residual histogram were then used to verify the accuracy of the prediction model, and the results show that the Holtwiners model was optimal. R2, MAPE, and other indicators were used to measure the accuracy of the 14 day prediction model, and the results showed that HoltWinters and STL prediction models achieved high accuracy.Conclusion: In this paper, the time series model was used to analyze the trend and seasonal changes of obstetric patient flow and predict the patient flow in the next 14 days and 12 months. On this basis, combined with the trend and seasonal changes of obstetric patient flow, a more reasonable and fair horizontal allocation scheme of medical resources is proposed, combined with the prediction of patient flow.
    Electronic ISSN: 2296-2565
    Topics: Medicine
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  • 52
    Publication Date: 2021-10-19
    Description: The vertical root distribution and rooting depth are the main belowground plant functional traits used to indicate drought resistance in arid and semiarid regions. The effects of the slope aspect on the aboveground traits are visible but not the belowground deep root traits. We aimed to investigate the fine root traits of the locust tree (Robinia pseudoacacia L.) planted on southerly and northerly aspects, and the variations in the rooting depth in regions with different rainfall, as well as assessing how deep rooting, might affect the response to drought in a loess region. We selected three study sites with different rainfall amounts, with six sampling plots at each site (three each with southerly and northerly aspects). Soil core samples were collected down to the depth where no roots were present. The locust trees tended to develop deeper fine roots rather than greater heights. The tree height and diameter were greater for locust trees on northerly aspects, whereas trees on southerly aspects had significantly deeper rooting depths. Fine root traits (root length, root area, and root dry weight density) were higher in the southerly aspect for both Changwu and Ansai, but lower in Suide. The ratio of the root front depth tree height ranged from 1.04 to 3.17, which was higher on southerly than northerly aspects, and it increased as the rainfall decreased. Locust tree growth traits (belowground fine root and aboveground tree height) were positively correlated with the mean annual rainfall. The soil moisture content of the topsoil decreased as the rainfall decreased, but the pattern varied in the deep layer. Our results suggest that the variations in the belowground rooting depth under different slope aspects may be related to plant survival strategies. The vertical extension of the rooting depth and tree height may be key functional traits that determine plant growth in drought-prone regions.
    Electronic ISSN: 1664-462X
    Topics: Biology
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  • 53
    Publication Date: 2021-10-20
    Description: Tuberculosis (TB) is the global health problem with the second highest number of deaths from a communicable disease after COVID-19. Although TB is curable, poor health infrastructure, long and grueling TB treatments have led to the spread of TB pandemic with alarmingly increasing multidrug-resistant (MDR)-TB prevalence. Alternative host modulating therapies can be employed to improve TB drug efficacies or dampen the exaggerated inflammatory responses to improve lung function. Here, we investigated the adjunct therapy of natural immune-modulatory compound berberine in C57BL/6 mouse model of pulmonary TB. Berberine treatment did not affect Mtb growth in axenic cultures; however, it showed increased bacterial killing in primary murine bone marrow-derived macrophages and human monocyte-derived macrophages. Ad libitum berberine administration was beneficial to the host in combination with rifampicin and isoniazid. Berberine adjunctive treatment resulted in decreased lung pathology with no additive or synergistic effects on bacterial burdens in mice. Lung immune cell flow cytometry analysis showed that adjunctive berberine treatment decreased neutrophil, CD11b+ dendritic cell and recruited interstitial macrophage numbers. Late onset of adjunctive berberine treatment resulted in a similar phenotype with consistently reduced numbers of neutrophils both in lungs and the spleen. Together, our results suggest that berberine can be supplemented as an immunomodulatory agent depending on the disease stage and inflammatory status of the host.
    Electronic ISSN: 1664-3224
    Topics: Medicine
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  • 54
    Publication Date: 2021-10-20
    Description: Coastal wetlands such as salt marshes have been increasingly valued for their capacity to buffer global climate change effects, yet their long-term persistence is threatened by environmental changes. Whereas, previous studies largely focused on lateral erosion risk induced by stressors like sea level rise, it remains poorly understood of the response of lateral expansion to changing environments. Seedling establishment is a key process governing lateral marsh expansion as seen in many coastal regions such as Europe and East Asia. Here, we evaluate mechanistically the response of seed bank dynamics to changing physical disturbance at tidal flats, using the globally common coastal foundation plant, cordgrass as a model. We conducted a large-scale field study in an estuary in Northwest Europe, where seed bank dynamics of cordgrass in the tidal flats was determined and linked to in situ hydrodynamics and sediment dynamics. The results revealed that wave disturbance reduced the persistence of seeds on the surface, whereas amplified sediment disturbance lowered the persistence of both surface and buried seeds. Overall, this indicates that increasing storminess and associated sediment variability under climate change threatens seed bank persistence in tidal flats, and hence need urgently be incorporated into models for long-term bio-geomorphological development of vegetated coastal ecosystems. The knowledge gained here provides a basis for more accurate predictions on how climatically driven environmental changes may alter the fitness, resilience and persistence of coastal foundation plants, with significant implications for nature-based solutions with coastal vegetation to mitigate climate change effects.
    Electronic ISSN: 2296-7745
    Topics: Biology
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  • 55
    Publication Date: 2021-10-20
    Description: Safflower (Carthamus tinctorius L.) is a herbal plant with a long history of clinical application worldwide, such as coronary heart disease, hypertension, dysmenorrhea and amenorrhea. It is also extensively used as an important oilseed plant for hundreds of years in some countries, like China, India, Mexico and the United States. Therefore, safflower is believed as a crop with dual values of medicine and economy as well. Safflower polysaccharides (SPS), from the plant, are believed as one of the most important biologically active components with multiple pharmacological properties, including anti-tumor, immune regulation, anti-oxidation, and anti-cerebral ischemia reperfusion injury effects. The polysaccharides, from bee pollen of safflower, named PBPC, also attract the attention of researchers because of their particular origin and bioactivities. Although the extraction, purification, structure and biological activities of SPS and PBPC have been studied for decades, there is not any available review both concerning SPS and PBPC. In this condition, this paper aims to systematically review the research progress in extraction, purification, structural characteristics, and bioactivities of SPS and PBPC, and provide basis for the in-depth study about their structure-bioactivity relationship. It will serve as a methodological outline for further research in fields of new drug discovery and clinical application of SPS or PBPC, and simultaneously remind us of unresolved problems noted in the polysaccharide research.
    Electronic ISSN: 1663-9812
    Topics: Medicine
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  • 56
    Publication Date: 2021-10-19
    Description: Sphingolipids are an extensive class of lipids with different functions in the cell, ranging from proliferation to cell death. Sphingolipids are modified in multiple cancers and are responsible for tumor proliferation, progression, and metastasis. Several inhibitors or activators of sphingolipid signaling, such as fenretinide, safingol, ABC294640, ceramide nanoliposomes (CNLs), SKI-II, α-galactosylceramide, fingolimod, and sonepcizumab, have been described. The objective of this review was to analyze the results from preclinical and clinical trials of these drugs for the treatment of cancer. Sphingolipid-targeting drugs have been tested alone or in combination with chemotherapy, exhibiting antitumor activity alone and in synergism with chemotherapy in vitro and in vivo. As a consequence of treatments, the most frequent mechanism of cell death is apoptosis, followed by autophagy. Aslthough all these drugs have produced good results in preclinical studies of multiple cancers, the outcomes of clinical trials have not been similar. The most effective drugs are fenretinide and α-galactosylceramide (α-GalCer). In contrast, minor adverse effects restricted to a few subjects and hepatic toxicity have been observed in clinical trials of ABC294640 and safingol, respectively. In the case of CNLs, SKI-II, fingolimod and sonepcizumab there are some limitations and absence of enough clinical studies to demonstrate a benefit. The effectiveness or lack of a major therapeutic effect of sphingolipid modulation by some drugs as a cancer therapy and other aspects related to their mechanism of action are discussed in this review.
    Electronic ISSN: 2234-943X
    Topics: Medicine
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  • 57
    Publication Date: 2021-10-20
    Description: Background: Due to the survival of preterm neonates being continually improved, the modifiable prognostic factors of necrotizing enterocolitis (NEC) are essential to be investigated and considered in making a suitable treatment to decrease the prevalence and effect of NEC. Many prognostic factors have been associated with the survival of neonates with NEC; however, the studies show conflicting results. Moreover, the study from developing countries regarding NEC outcomes is minimal. Here, we aimed to determine the survival of neonates with NEC and associate it with the prognostic factors.Methods: A retrospective study was conducted using medical records of neonates with NEC at our institution from January 2014 to December 2019.Results: Fifty-two neonates with NEC were involved with the overall survival of 44.2%. Log-rank analysis showed that NEC staging and birth weight were significantly associated with the survival of neonates with NEC with a p-value of 0.010 and 0.002, respectively, while sex, APGAR score, platelet count, and type of treatment were not (p = 0.068, 0.752, 0.087, and 0.343, respectively). Multivariate analysis revealed that sex and NEC staging were strongly associated with the survival of neonates with NEC with a p-value of 0.018 [HR = 3.10 (95% CI = 1.21–7.93)] and 0.019 [HR = 0.44 (0.22–0.87)], respectively.Conclusions: Our study shows that sex and NEC staging might affect the survival of neonates with NEC. It implies that NEC staging should be closely monitored and intervened as early as necessary to prevent further morbidity and mortality.
    Electronic ISSN: 2296-2360
    Topics: Medicine
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  • 58
    Publication Date: 2021-10-18
    Description: In Se-deficient populations, Selenium- (Se-) enriched wheat is a source of Se supplementation, and Se content can be improved by agronomic biofortification. Thus, black-grained wheat (BGW) and white-grained wheat (WGW) (as the control) were grown in Se naturally contained soils at different concentrations (11.02, 2.21, 2.02, and 0.20 mg·kg−1). Then, a field experiment was conducted to assess agronomic performance, the concentration of microelements and heavy metals, and the uptake and distribution of Se in the BGW under the application of Se ore powder. The results showed that the grain yield and grain Se concentration of wheat respectively show a significant increase and decrease from high Se to low Se areas. Higher grain yield and crude protein content were observed in Se-rich areas. The soil application of Se ore powder increased wheat grain yield and its components (biomass, harvest index, grain number, and 1,000 kernels weight). The concentrations of Zn, Fe, Mn, total Se, and organic Se in the grains of wheat were also increased, but Cu concentration was decreased. The concentrations of Pb, As, Hg, and Cr in wheat grains were below the China food regulation limits following the soil application of Se ore powder. Compared with the control, Se ore powder treatment increased the uptake of Se in various parts of wheat plants. More Se accumulation was observed in roots following Se ore powder application, with a smaller amount in grains. In addition, compared with the control, BGW had significantly higher concentrations of Zn, Fe, and Mn and accumulated more Se in grains and shoots and less Se in roots. The results indicate that wheat grown in Se-rich areas increases its grain yield and crude protein content. The soil application of Se ore powder promotes wheat growth and grain yield. Compared with WGW, BGW accumulated more Se in grains and had a higher concentration of organic Se in grains. In conclusion, the application of Se ore powder from Ziyang as Se-enriched fertilizer could be a promising strategy for Se biofortification in the case of wheat, and BGW is the most Se-rich potential genotype.
    Electronic ISSN: 1664-462X
    Topics: Biology
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  • 59
    Publication Date: 2021-10-27
    Description: Liuweiwuling Tablet (LWWL) is a licensed Chinese patent medicine (approval number: Z20060238) included in the national health insurance for anti-inflammation of chronic HBV infection, whereas its anti-HBV effect remains clarification. The study aimed to clarify its antiviral effect and related mechanisms. HepG2.2.15 cells (wild-type HBV-replicating cells) and HepG2. A64 cells (entecavir-resistant HBV-replicating cells) were used for in vitro test. Hydrodynamic injection-mediated HBV-replicating mouse model was used for in vivo test. Active compounds and related mechanisms for antiviral effect of LWWL were analyzed using network pharmacology and transcriptomics. The inhibition rates of LWWL (0.8 mg/ml) on HBV DNA, HBsAg, and pgRNA were 57.06, 38.55, and 62.49% in HepG2.2.15 cells, and 51.57, 17.57, and 53.88% in HepG2. A64 cells, respectively. LWWL (2 g kg−1 d−1 for 4 weeks)-treated mice had 1.16 log10 IU/mL decrease of serum HBV DNA, and more than 50% decrease of serum HBsAg/HBeAg and hepatic HBsAg/HBcAg. Compared to tenofovir control, LWWL was less effective in suppressing HBV DNA but more effective in suppressing HBV antigens. Thirteen differentially-expressed genes were found in relation to HBV-host interaction and some of them were enriched in interferon (IFN)-β pathway in LWWL-treated HepG2.2.15 cells. CD3+CD4+ T-cell frequency and serum IFN-γ were significantly increased in LWWL-treated mice compared to LWWL-untreated mice. Among 26 compounds with potential anti-HBV effects that were predicted by network pharmacology, four compounds (quercetin, luteolin, wogonin, and kaempferol) were experimentally confirmed to have antiviral potency. In conclusion, LWWL had potent inhibitory effect on both wild-type and entecavir-resistant HBV, which might be associated with increasing IFN-β and IFN-γ production.
    Electronic ISSN: 1663-9812
    Topics: Medicine
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  • 60
    Publication Date: 2021-10-27
    Description: A new easy-to-use online bioinformatic tool analyzing whole genome sequences of healthcare associated bacteria was used by a local infection control unit to retrospectively map genetic relationship of isolates of E. faecium carrying resistance genes to vancomycin in a hospital. Three clusters of isolates were detected over a period of 5 years, suggesting transmission between patients. Individual relatedness between isolates within each cluster was established by SNP analyses provided by the system. Genetic antimicrobial resistance mechanisms to antibiotics other than vancomycin were identified. The results suggest that the system is suited for hospital surveillance of E. faecium carrying resistance genes to vancomycin in settings with access to next Generation Sequencing without bioinformatic expertise for interpretation of the genome sequences.
    Electronic ISSN: 2296-858X
    Topics: Medicine
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  • 61
    Publication Date: 2021-07-15
    Description: Global HIV-1 genetic diversity forms a major obstacle to the development of an HIV vaccine. It may be necessary to employ subtype-specific HIV-1 vaccines in individual countries according to their HIV-1 subtype distribution. We estimated the global and regional need for subtype-specific HIV-1 vaccines. We took into account the proportions of different HIV-1 variants circulating in each country, the genetic composition of HIV-1 recombinants, and the different genome segments (gag, pol, env) that may be incorporated into vaccines. We modeled different scenarios according to whether countries would employ subtype-specific HIV-1 vaccines against (1) the most common subtype; (2) subtypes contributing more than 5% of HIV infections; or (3) all circulating subtypes. For therapeutic vaccines targeting the most common HIV-1 subtype in each country, 16.5 million doses of subtype C vaccine were estimated globally, followed by subtypes A (14.3 million) and B (4.2 million). A vaccine based on env required 2.6 million subtype E doses, and a vaccine based on pol required 4.8 million subtype G doses. For prophylactic vaccines targeting the most common HIV-1 subtype in each country, 1.9 billion doses of subtype A vaccine were estimated globally, followed by subtype C (1.1 billion) and subtype B (1.0 billion). A vaccine based on env required 1.2 billion subtype E doses, and a vaccine based on pol required 0.3 billion subtype G doses. If subtype-specific HIV-1 vaccines are also directed against less common subtypes in each country, vaccines targeting subtypes D, F, H, and K are also needed and would require up to five times more vaccine doses in total. We conclude that to provide global coverage, subtype-specific HIV-1 vaccines need to be directed against subtypes A, B, and C. Vaccines targeting env also need to include subtype E and those targeting pol need to include subtype G.
    Electronic ISSN: 1664-302X
    Topics: Biology
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  • 62
    Publication Date: 2021-10-27
    Description: Objective: To evaluate whether the combined measurement of pelvic organ mobility and levator hiatus area improves the sensitivity of transperineal ultrasound (the index test) for diagnosing pelvic organ prolapse (POP).Methods: We retrospectively recruited women who had been examined in a tertiary gynecological center for symptoms of lower urinary tract incontinence and/or POP between January 2017 and June 2018. We excluded patients who had undergone hysterectomy previously or those who had received corrective surgery. All subjects underwent a standardized interview, POP quantification (POP-Q) examination (a reference standard for patients and controls), and ultrasound measurements of the levator hiatus area at rest (rHA), on contraction (cHA), and on Valsalva (vHA). We also determined the mobility of the bladder neck (BNM), cervix (CM), and rectum ampulla (RAM). Receiver operating characteristic (ROC) curve analyses were performed to determine cut-off values for diagnosis. Diagnostic performance was assessed by sensitivity, specificity, and area under curve (AUC).Results: A total of 343 women were eligible for analysis, including 247 POP patients (stage 2–3 by POP-Q) and 96 controls. Compared with controls, POP cases had significantly higher values for rHA, vHA, cHA, BNM, CM, and RAM. Each parameter was identified as a significant discriminator for POP and controls, as determined by ROC curve analysis, although the cut-off value varied slightly between different parameters. The combination of rHA, vHA, and cHA (with any HA that was ≥ the cut-off) improved the sensitivity from 64–89 to 89–93%. The combination of pelvic organ mobility with rHA, vHA, and cHA, further increased the sensitivity from 89–93 to 95–97%.Conclusion: The combination of levator hiatus area and pelvic organ mobility improved the sensitivity of transperineal ultrasound in the diagnosis of POP, whether used as a frontline test to assist POP-Q grading or to monitor the effect of pelvic floor exercise programs.
    Electronic ISSN: 2296-858X
    Topics: Medicine
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  • 63
    Publication Date: 2021-10-27
    Description: Detecting early signs of cognitive decline is crucial for early detection and treatment of Alzheimer's Disease. Most of the current screening tools for Alzheimer's Disease represent a significant burden, requiring invasive procedures, or intensive and costly clinical testing. Recent findings have highlighted changes to speech and language patterns that occur in Alzheimer's Disease, and may be detectable prior to diagnosis. Automated tools to assess speech have been developed that can be used on a smartphone or tablet, from one's home, in under 10 min. In this study, we present the results of a study of older adults who completed a digital speech assessment task over a 6-month period. Participants were grouped according to those who scored above (N = 18) or below (N = 18) the recommended threshold for detecting cognitive impairment on the Montreal Cognitive Assessment (MoCA) and those with diagnoses of mild cognitive impairment (MCI) or early Alzheimer's Disease (AD) (N = 14). Older adults who scored above the MoCA threshold had better performance on speech composites reflecting language coherence, information richness, syntactic complexity, and word finding abilities. Those with MCI and AD showed more rapid decline in the coherence of language from baseline to 6-month follow-up, suggesting that this score may be useful both for detecting cognitive decline and monitoring change over time. This study demonstrates that automated speech assessments have potential as sensitive tools to detect early signs of cognitive impairment and monitor progression over time.
    Electronic ISSN: 2673-253X
    Topics: Medicine
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  • 64
    Publication Date: 2021-10-27
    Description: The world's population is aging. With this comes an increase in the prevalence of age-associated diseases, which amplifies the need for novel treatments to counteract cognitive decline in the elderly. One of the recently discussed non-pharmacological approaches is transcranial direct current stimulation (tDCS). TDCS delivers weak electric currents to the brain, thereby modulating cortical excitability and activity. Recent evidence suggests that tDCS, mainly with anodal currents, can be a powerful means to non-invasively enhance cognitive functions in elderly people with age-related cognitive decline. Here, we screened a recently developed tDCS database (http://tdcsdatabase.com) that is an open access source of published tDCS papers and reviewed 16 studies that applied tDCS to healthy older subjects or patients suffering from Alzheimer's Disease or pre-stages. Evaluating potential changes in cognitive abilities we focus on declarative and working memory. Aiming for more standardized protocols, repeated tDCS applications (2 mA, 30 min) over the left dorso-lateral prefrontal cortex (LDLPFC) of elderly people seem to be one of the most efficient non-invasive brain stimulation (NIBS) approaches to slow progressive cognitive deterioration. However, inter-subject variability and brain state differences in health and disease restrict the possibility to generalize stimulation methodology and increase the necessity of personalized protocol adjustment by means of improved neuroimaging techniques and electrical field modeling.
    Electronic ISSN: 1662-5161
    Topics: Medicine
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  • 65
    Publication Date: 2021-10-27
    Description: Introduction: Hypopituitarism is a rare, often underdiagnosed, complex hormonal disease caused by the decreased secretion of one or more hormones in the pituitary gland. The present study was designed to assess left ventricular (LV) rotational mechanics in patients with treated hypopituitarism. It was also aimed to find possible differences in these parameters according to the origin of hypopituitarism (congenital vs. acquired).Methods: The present prospective study involved 35 treated patients with hypopituitarism; however, 4 patients had to be excluded due to inferior image quality. The mean age of the remaining 31 cases was 56.3 ± 13.2 years (18 males). The control group consisted of 29 age- and sex-matched healthy volunteers (mean age: 55.3 ± 4.8 years, 14 males). In all cases a complete two-dimensional echocardiography examination was performed followed by three-dimensional speckle-tracking echocardiography.Results: No significant differences could be found in LV volumes between the controls and patients with hypopituitarism and hypopituitary subgroups. LV apical rotation (8.1 ± 5.1° vs. 10.6 ± 3.5°, p 〈 0.05) and LV twist (11.9 ± 5.3° vs. 15.1 ± 3.8°, p 〈 0.05) were impaired in the hypopituitary group with normally directed LV rotational mechanics as compared to the healthy controls. However, 13% of patients showed a near absence of LV twist called LV “rigid body rotation” (LV-RBR). There were no significant differences regarding LV apical and basal rotations and twist between acquired and congenital hypopituitary subgroups.Conclusions: Impaired LV apical rotation and twist could be demonstrated in hypopituitarism regardless of its origin. In the present study with small number of patients with hypopituitarism, LV-RBR was present in 13% of cases.
    Electronic ISSN: 2297-055X
    Topics: Medicine
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  • 66
    Publication Date: 2021-10-27
    Description: Adipose tissue-derived microvascular fragments (MVF) represent effective vascularization units for tissue engineering. Most experimental studies exclusively use epididymal fat tissue of male donor mice as a source for MVF isolation. However, in future clinical practice, MVF-based approaches may be applied in both male and female patients. Therefore, we herein compared the vascularization capacity of MVF isolated from the epididymal and peri-ovarian fat tissue of male and female donor mice. Freshly isolated MVF from male and female donors did not differ in their number, length distribution, viability and cellular composition. After their assembly into spheroids, they also exhibited a comparable in vitro sprouting activity. Moreover, they could be seeded onto collagen-glycosaminoglycan matrices, which were implanted into full-thickness skin defects within mouse dorsal skinfold chambers. Repetitive intravital fluorescence microscopy as well as histological and immunohistochemical analyses revealed a comparable vascularization and incorporation of implants seeded with MVF of male and female origin. Taken together, these findings demonstrate that the vascularization capacity of MVF is not gender-specific.
    Electronic ISSN: 2296-4185
    Topics: Process Engineering, Biotechnology, Nutrition Technology
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  • 67
    Publication Date: 2021-10-27
    Description: Sphaeranthus indicus L. is a medicinal herb having widespread traditional uses for treating common ailments. The present research work aims to explore the in-depth phytochemical composition and in vitro reactivity of six different polarity solvents (methanol, n-hexane, benzene, chloroform, ethyl acetate, and n-butanol) extracts/fractions of S. indicus flowers. The phytochemical composition was accomplished by determining total bioactive contents, HPLC-PDA polyphenolic quantification, and UHPLC-MS secondary metabolomics. The reactivity of the phenolic compounds was tested through the following biochemical assays: antioxidant (DPPH, ABTS, FRAP, CUPRAC, phosphomolybdenum, and metal chelation) and enzyme inhibition (AChE, BChE, α-glucosidase, α-amylase, urease, and tyrosinase) assays were performed. The methanol extract showed the highest values for phenolic (94.07 mg GAE/g extract) and flavonoid (78.7 mg QE/g extract) contents and was also the most active for α-glucosidase inhibition as well as radical scavenging and reducing power potential. HPLC-PDA analysis quantified rutin, naringenin, chlorogenic acid, 3-hydroxybenzoic acid, gallic acid, and epicatechin in a significant amount. UHPLC-MS analysis of methanol and ethyl acetate extracts revealed the presence of well-known phytocompounds; most of these were phenolic, flavonoid, and glycoside derivatives. The ethyl acetate fraction exhibited the highest inhibition against tyrosinase and urease, while the n-hexane fraction was most active for α-amylase. Moreover, principal component analysis highlighted the positive correlation between bioactive compounds and the tested extracts. Overall, S. indicus flower extracts were found to contain important phytochemicals, hence could be further explored to discover novel bioactive compounds that could be a valid starting point for future pharmaceutical and nutraceuticals applications.
    Electronic ISSN: 1663-9812
    Topics: Medicine
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  • 68
    Publication Date: 2021-10-27
    Description: Several studies have been conducted and published on medicinal plants used to manage Diabetes Mellitus worldwide. It is of great interest to review available studies from a country or a region to resort to similarities/discrepancies and data quality. Here, we examined data related to ethnopharmacology and bioactivity of antidiabetic plants used in the Democratic Republic of Congo. Data were extracted from Google Scholar, Medline/PubMed, Scopus, ScienceDirect, the Wiley Online Library, Web of Science, and other documents focusing on ethnopharmacology, pharmacology, and phytochemistry antidiabetic plants used in the Democratic Republic of Congo from 2005 to September 2021. The Kew Botanic Royal Garden and Plants of the World Online web databases were consulted to verify the taxonomic information. CAMARADES checklist was used to assess the quality of animal studies and Jadad scores for clinical trials. In total, 213 plant species belonging to 72 botanical families were reported. Only one plant, Droogmansia munamensis, is typically native to the DRC flora; 117 species are growing in the DRC and neighboring countries; 31 species are either introduced from other regions, and 64 are not specified. Alongside the treatment of Diabetes, about 78.13% of plants have multiple therapeutic uses, depending on the study sites. Experimental studies explored the antidiabetic activity of 133 plants, mainly in mice, rats, guinea pigs, and rabbits. Several chemical classes of antidiabetic compounds isolated from 67 plant species have been documented. Rare phase II clinical trials have been conducted. Critical issues included poor quality methodological protocols, author name incorrectly written (16.16%) or absent (14.25%) or confused with a synonym (4.69%), family name revised (17.26%) or missing (1.10%), voucher number not available 336(92.05%), ecological information not reported (49.59%). Most plant species have been identified and authenticated (89.32%). Hundreds of plants are used to treat Diabetes by traditional healers in DRC. However, most plants are not exclusively native to the local flora and have multiple therapeutic uses. The analysis showed the scarcity or absence of high-quality, in-depth pharmacological studies. There is a need to conduct further studies of locally specific species to fill the gap before their introduction into the national pharmacopeia.
    Electronic ISSN: 1663-9812
    Topics: Medicine
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  • 69
    Publication Date: 2021-10-27
    Electronic ISSN: 1664-3224
    Topics: Medicine
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  • 70
    Publication Date: 2021-10-27
    Description: Background: Serum carcinoembryonic antigen (CEA), a classic tumour marker, is widely used in lung cancer in clinical practice. Nevertheless, few studies have elucidated the influence of dynamic changes in CEA in the perioperative phases, as a prognostic indicator, on lung cancer prognosis.Methods: This retrospective cohort analysis included consecutive patients with stage I-III lung cancer who underwent curative resection between December 2010 and December 2014. The patients were grouped into three cohorts: group A included patients with normal preoperative CEA, group B included patients with elevated preoperative CEA but normal postoperative CEA, and group C included patients with elevated preoperative and postoperative CEA. Five-year overall survival (OS) was estimated by Kaplan-Meier analysis (log-rank test). Multivariate analyses were performed with Cox proportional hazard regression.Results: A total of 1662 patients with stage I-III lung cancer were enrolled in our study. Patients with normal preoperative CEA had 15.9 and 20.1% better 3- and 5-year OS rates than the cohort with elevated preoperative CEA (p 〈 0.001). Furthermore, group C had 36.0 and 26.6% lower 5-year OS rates (n = 74, 32.4%) than group A (n = 1188, 68.4%) and group B (n = 139, 59.0%) (p 〈 0.001). Group B had poorer OS than group A (p = 0.016). For patients with different pathological TNM stages, subgroup analyses showed that group C had the shortest OS in stages I and II (p 〈 0.05), and patients with a post-preoperative CEA increment had poorer OS than those without an increment (p = 0.029). Multivariate analyses suggested that group C (HR = 2.0, 95% CI, 1.5–2.7, p 〈 0.001) rather than the group with normalized postoperative CEA (HR = 1.2, 95% CI, 0.9–1.5, p = 0.270) was an independent prognostic factor. In subgroup analysis of adenocarcinoma (ADC), survival analyses suggested that group C predicted a worse prognosis. Multivariate analysis of ADC indicated that group C was an independent adverse prognostic factor (HR = 1.9, 95% CI, 1.4–2.7, p 〈 0.001).Conclusions: Combined elevated preoperative and postoperative CEA is an independent adverse prognostic factor for stage I-III lung adenocarcinoma. Additionally, routine perioperative detection of serum CEA can yield valuable prognostic information for patients after lung cancer surgery.
    Electronic ISSN: 2296-889X
    Topics: Biology
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  • 71