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Malaria due to P. vivax results in considerable morbidity and mortality [2, 6, 11, 16]. P. vivax is currently the most widely distributed human malaria parasite with an estimated 2.5 billion people at risk . P. vivax accounts for more than half of all malaria cases in Latin America, the Middle East, Asia, and the Western Pacific. Outside sub-Saharan Africa, the proportions of P. vivax malaria are rising, a clear indication of the resilience of this parasite to control measures [10, 40]. P. vivax has long been considered a neglected parasite while its socio-economic burden in endemic areas is huge. P. vivax exist in a temperate form with a long latency period up to nine months and a tropical form with a short latency period [4, 5, 20, 28, 39]. The two forms can be separated by haplotype analysis [24, 38].
| 4 | 0biomedical
| 0Study
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352,773 |
Large-scale datasets should be made available via a public repository as described in the PLOS Computational Biology data availability policy, and numerical data that underlies graphs or summary statistics should be provided in spreadsheet form as supporting information.
| 1 | 0biomedical
| 1Other
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288,209 |
Cluster analysis was performed on each of the three result matrices of log-transformed band powers using K-means clustering on MATLAB to classify the 69 patients in each of the three segments into two distinct clusters, making six overall clusters. A cluster size of two was chosen for all three segments after silhouette analysis was performed. Across all three segments, the silhouette value for clusters of two (0.453, 0.422, and 0.406 respectively) were the utmost vs. clustering of any other size. Moreover, we performed the clustering 100 times and averaged them to yield the conclusions in order to improve the stability of the K-means results.
| 4 | 0biomedical
| 0Study
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257,246 |
Initially, the big five personality traits theory was developed and established by Fiske (1949). Later, this theory was expanded by some other researchers (Smith, 1967; Goldberg, 1981; McCrae and Costa, 1987). The five factors in the theory are extraversion, agreeableness, openness, conscientiousness, and neuroticism.
| 2 | 2other
| 1Other
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219,373 |
Compared with the NC group, a higher number of Ball‐1 and THP‐1 cells transfected with the miR‐99a‐3p agomir were observed to be in the G0/G1 phase. The opposite effect was observed in case of Ball‐1 and THP‐1 cells transfected with the miR‐99a‐3p antagomir, that is a lower number of Ball‐1 and THP‐1 cells transfected with the miR‐99a‐3p antagomir were observed to be in the G0/G1 phase, compared with the case in the NC group.
| 4 | 0biomedical
| 0Study
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188,427 |
A multicentric cross-sectional descriptive study was performed from March 2019 to February 2020 in three health districts of three provinces of Spain (Almería, Granada, and Málaga), which covered a total population of 1,741,888 people. The targeted study population was people with dementia, with an age of over 65, and concomitant treatment of drugs for dementia and antipsychotics, prescribed by primary health care doctors.
| 3 | 0biomedical
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193,045 |
In the liver cells, we noticed an upregulation of ATF3, a activating transcription factor 3, which is a suppressor of pro-inflammatory responses and has been considered a hub of the cellular adaptative response . Other transcription factors responsible for the pro-inflammatory response, such as TNFRSF9 and MXD1, were also found upregulated. Pathway enrichment analysis in the liver cells (Figure 1B; Supplementary Figures S3–S5) showed a downregulation of cell cycle pathways, an observation previously made . Hepatic manifestations may be the result of cell cycle arrest, which through the inhibition of cell death may allow immune evasion and/or help promote viral assembly. In the literature, it has been shown that HepG2 (liver) cells were significantly more permissive for both infection and virus production in the G(2) phase than Vero (kidney) cells .
| 4 | 0biomedical
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149,677 |
All full-length sequences were subjected to BlastSearch against the nucleotide database at NCBI . Multiple sequence alignments and phylogenetic trees were computed in MEGA software (v. 10.2.6) by the means of the Maximum likelihood method. Bootstrap values were computed with 500 replicates . SDT v1.2 was utilised for displaying pairwise genome identity scores of novel genomoviruses calculated from pairwise alignments generated by MUSCLE . Tandem repeats and inverted repeats upstream the rep-gene sequences were checked at Emboss explorer. Maximum size of tandem repeats was restricted to 30 nucleotides (nt) and the minimum size of inverted repeats was set to 4 nt. ORFfinder software (version 1.3.0) at NCBI served for in silico detection of potential open reading frames. Illustrations were plotted with SeqBuilder Pro of the DNASTAR software (Lasergene Inc., v. 17.1. DNASTAR. Madison, WI, USA) . ATG or TTG as alternative start codons were allowed. The minimum ORF size was limited to 75 amino acids (aa). Only ORFs ≥ 95 aa were included in further comparative and functional analyisis. Putative intron acceptor-/donor sites and conserved amino acid motifs were identified manually. All annotated genomes from this study were deposited in the GenBank database (Accession numbers OK148616-OK148630).
| 4 | 0biomedical
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221,226 |
Furthermore, we analyzed the microbial community in the ileum chyme at the phylum and genus levels, as shown in Figure 6. Firmicutes is the predominant phylum of ileum, accounting for more than 96% of the total sequences (Figure 6A). Furthermore, the main bacterial phyla among three groups were compared (Figure 6B). Compared with the ANT (97.25%) and CSB (96.80%), the relative abundance of Firmicutes was the highest (99.81%) in the CON (p < 0.05). However, the relative abundances of Verrucomicrobiota and other phyla in the CSB were the highest compared with the CON and ANT. In addition, the relative abundance of Actinobacteriota significantly increased in ANT (p < 0.05), from 0.06% in the CON and 0.32% in the CSB to 2.27% in the ANT.
| 4 | 0biomedical
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327,906 |
We describe the clinical history of C., female, 45 years old. Genetics: DF508/G178R. Pancreatic failure since June 2013. Normal liver and kidney function. On the waiting list since June 2015for bipulmonary transplantation. She has assumed Ivacaftor from September 2015. Patient has been followed up by clinical examination, instrumental and laboratory tests. Auxological parameters and respiratory function were monitored. She was subjected to a quality of life assessment questionnaire: CFQ-R.From the beginning of the therapy program, after about 3 years of treatment, an improvement of the auxometric parameters was observed, resulting in an increase in BMI from 19.9 to 25. Respiratory function has also improved (FEV1 from 19% to 25%). At the sweat test a decrease in chloride concentration from 127 mmol/l to 52 mmol/l has been recorded. Over the years, the patient's perception of the disease has improved with CFQ-R score increasing from 72 to 90. She performed eye and ECG examinations to assess possible toxicity of the drug. No adverse events were reported. In May 2019, the patient underwent a successful bipulmonary transplant. Today she has good general clinical conditions and continues follow-up.
| 4 | 1clinical
| 3Clinical case
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321,898 |
Different bacteria, such as Bacillus amyloliquefaciens, Paenibacillus curdlanolyticus, P. polymyxa, lactobacillus, and B. megaterium able to degrade cellulose, hemicellulose, xylans, and mannans molecules, thus significantly improve the natural quality of PKC . Lactiplantibacillus plantarum strains (especially; L. plantarum RG11, L. plantarum RI11, and L. plantarum RG14 (based on their total score of extracellular hydrolytic enzymes activates) can grow on PKC biomass. It performs synergistic secretions of various extracellular proteolytic, cellulolytic, and hemicellulolytic enzymes essential for the effective biodegradation of PKC . The latest findings showed the effects of L. plantarum RI11 on different renewable natural polymers, describing the L. plantarum RI11 can be a potential candidate as lignocellulosic biomass degrader. It can produce functional extracellular cellulolytic and hemicellulolytic enzymes in rice straw, molasses, PKC, and soybean pulp .
| 4 | 0biomedical
| 0Study
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58,683 |
From an evolutionary perspective, immune homeostasis is an important survival strategy, particularly for creatures such as bacterivorous nematodes that live in environments rich with microbes that must differentiate pathogens from potential food sources. Improper activation of immune responses in humans underlies many disorders, such as inflammatory bowel disease, cancer, and autoimmune diseases (3, 42). A mechanism of feedback control for a hyperactivated immune pathway has been discovered in flies and C. elegans (4, 7, 43). Here, we discovered that riok-1 is a novel immune suppresser of the infection-activated p38 MAPK pathway in C. elegans and plays an important role in achieving immune homeostasis.
| 4 | 0biomedical
| 0Study
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395,819 |
These interactions encompass regulatory effects on genes and SNPs with important functional roles. Specifically, 95 interaction eQTL variants overlap with variants previously identified in genome-wide association studies (GWAS, LD r2 > 0.8; Methods; Supplementary Data 11). For example, an eQTL for RNASET2 shows sensitivity to cellular respiratory metabolic state (Fig. 4a). This eQTL SNP is in LD (r2 = 0.86) with a GWAS risk variant for basal cell carcinoma19. Furthermore, an eQTL for SNRPC showed sensitivity to the G2/M state, and is in LD (r2 = 0.92) with a GWAS risk variant for prostate cancer20 (Fig. 4a). These cellular factors vary not only across cells in the experiments considered here, but also across cells in vivo, across individuals, and across environments. Thus, these examples illustrate the versatility of our single cell dataset and how it can provide regulatory information about variants in contexts beyond early human development.
| 4 | 0biomedical
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328,012 |
Until now 15 rounds have been completed and overall 90Italian laboratories have been monitored. Participants laboratories returned acceptable analytical results, in recent years compared to previous ones, but we still registered a number of reports with not complete or not accurate interpretation.
| 2 | 0biomedical
| 1Other
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343,484 |
The MSC have been isolated from different tissues, including bone marrow, fatty tissue, hair follicle, synovium, umbilical cord, placenta, and periodontal ligament, among others (Huang et al., 2011). Surprisingly, there is not a specific biochemical marker defining the MSC. Therefore, the scientific consensus, as we have previously described, is that they should not exhibit hematopoietic and endothelial markers, like CD-11b, CD-14, CD-31, CD-33, CD-34, CD-45, and CD-133 (Casado-Díaz et al., 2016). Thus, the International Society for Cellular Therapy (ISCT) has defined the minimum MSC features: (i) are plastic-adherent under standard culture conditions; (ii) express CD-73, CD-90, and CD-105, lacking the expression of CD-11b, CD-14, CD-19, CD-34, CD-45, CD-79a, and HLA-DR; and (iii) may differentiate into osteoblasts, adipocytes, or chondrocytes in vitro (Dominici et al., 2006). Likewise, it has been proposed that the MSC are involved in maintaining cellular homeostasis in the organism. That is accomplished through tissue regeneration and repair.
| 4 | 0biomedical
| 2Review
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385,462 |
We previously demonstrated that under physiological conditions conditional ablation of TNF in peripheral myeloid cells does not affect locomotor function, motor coordination, and neuromuscular function in male mice and found the same to be true in female mice (Supplemental Table S1), except for anxiety-related behavior in the EPM (Supplemental Figure S1A–C). Despite comparable locomotor performance (Supplemental Figure S1A), LysMCreTnffl/fl mice spent significantly more time in the open arm (Supplemental Figure S1B) and significantly less time in the closed arm (Supplemental Figure S1C) compared to Tnffl/fl mice.
| 4 | 0biomedical
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76,340 |
Many researchers have proposed countermeasures embedded in the sensor nodes to prevent most of the attacks shown in Table 1 . In this context, adequate embedded algorithms not only have to improve network security, but also have to consider the energetic constraints of the WSNs. Aware of this fact, researchers propose security and fault-tolerant mechanisms having energy efficiency as an additional requirement. For instance, proposes a low energy consuming mechanism to select the most trustworthy cluster head for cooperative spectrum sensing environments. In , the authors increase the reliability in mesh networks by reconstructing a reduced amount of broken links in order to recompute faulty paths. The authors claim that the proposed algorithms use less control packets and are more energy efficient than other comparable solutions. In , the authors propose a secure multipath routing scheme, which is tolerant to faults and intrusions, and it also preserves the energy of the sensors.
| 2 | 2other
| 0Study
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67,649 |
There were significant differences among treatments in the mean number of captured beetles (Kruskall-Wallis ANOVA H = 15.33, P < 0.01, Fig 7). Traps baited with the racemic synthetic pheromone (alone and in combination with host plant volatiles) consistently (i.e. at all three study sites and throughout the whole study period), captured more beetles (mean of 1.08 ± 0.22 beetles per 10 trap days; N = 77 beetles) than treatments without the pheromone compound (i.e. control traps, and traps baited with host plant volatiles; mean of 0.08 ± 0.04 beetles per 10 trap days; N = 6 beetles). The mean number of beetles attracted to the pheromone (1.03 ± 0.36 beetles per 10 trap days) was significantly different from the mean numbers attracted to host plant volatiles (0.13 ± 0.09 beetles per 10 trap days, Mann-Whitney U test, P < 0.01) or the control (0.03 ± 0.03 beetles per 10 trap days, Mann-Whitney U test, P < 0.01) (Fig 7). The host plant volatiles did not synergize attraction to the pheromone because there was no significant difference between the mean number of beetles attracted to the pheromone alone (1.03 ± 0.36 beetles per 10 trap days, Mann-Whitney U test, P = 0.89) compared to the pheromone in combination with host plant volatiles (mean of 1.14 ± 0.41 beetles per 10 trap days).
| 4 | 0biomedical
| 0Study
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114,332 |
An average of 48,194 cancer deaths occurred each year during 2011–2015 in nonmetropolitan rural counties, representing 8% of all cancer deaths reported in the United States (Table 2). The average annual age-adjusted death rate (death rate) for all cancer sites combined was higher in nonmetropolitan rural counties (180 deaths per 100,000 persons) than in nonmetropolitan urban counties (177 deaths per 100,000 persons), metropolitan counties with <1 million population (166 deaths per 100,000 persons), and metropolitan counties with ≥1 million population (158 deaths per 100,000 persons). By sex, overall cancer death rates among both men and women were higher in nonmetropolitan rural counties than in other counties. By age, overall cancer death rates in nonmetropolitan rural counties were generally similar to those in other counties among those aged <20 years but higher among those aged ≥20 years. Overall cancer death rates were higher in nonmetropolitan rural counties than in other counties among non-Hispanic whites and AI/ANs but lower among Hispanics and APIs; among non-Hispanic blacks, rates in nonmetropolitan rural counties were lower than in nonmetropolitan urban counties but higher than in metropolitan counties.
| 4 | 0biomedical
| 0Study
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82,822 |
The key to network-based predictions of potentially disease-related miRNA is the calculation of similarity network among disease and miRNA over networks. The construction of miRNA and disease similarity network significantly affects the prediction of miRNA-related disease. The network was derived from . The graph theory was used as a method for connecting different nodes and the walker to measure similarity nodes. Therefore, for all known disease-related miRNAs, if the miRNA mi (i=1, 2, 3… n) is related to any disease di, this relationship between miRNA and disease was set to be 1, otherwise 0. This helps us to obtain the number of miRNAs that is connected to disease (d). Then, we extract all unknown miRNAs for the prediction. We ranked all unknown miRNAs. The higher-ranked miRNAs were confirmed as potential candidates of a given disease (d).
| 3 | 0biomedical
| 0Study
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163,920 |
S. typhimurium is a facultative anaerobic pathogen that can colonize tumors. Besides its use as a delivery system for anti-tumor therapeutic agents, it also possesses an intrinsic anti-tumor effect, largely attributed to its immunomodulatory activity11. Systemic administration of S. typhimurium can effectively stimulate the immune system, resulting in the increased production of systemic proinflammatory cytokines, such as interleukin (IL)-1β, IL-18, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), as well as activation of both innate and adaptive immune cells11,12. These manipulated immune responses might lead to a hostile environment for tumor progression. For example, S. typhimurium treatment in mice bearing CT26 tumors was reported to suppress the growth of primary tumor through increased production of TNF-α and IL-1β by macrophages and dendritic cells13. Likewise, S. typhimurium treatments in other different contexts were reported to promote the recruitment of neutrophils, granulocytes, and macrophages, as well as activation of CD8+ T cells and natural killer (NK) cells14,15. However, the roles of these Salmonella-induced immune responses in metastasis suppression remains unclear.
| 4 | 0biomedical
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90,426 |
In situ measurements of dissolved Mn carried out with the METIS analyzer were presented. To our knowledge, these data were the first obtained by a multi-pumping flow-system using the PAN method for determining dissolved Mn concentrations at low micromolar levels and with high vertical resolution. We have conducted a hydrocast using a wet chemical analyzer deployed on a CTD-rosette frame. 1-(2-pyridylazo)-2-naphthol (PAN) was used as spectrophotometric reagent. During field experiments, high resolution data of dissolved Mn were obtained in near real-time. Ultimately, a detection limit of 77 nM was obtained. Analyzer results were verified by concurrent analyzes of discrete Mn samples by ICP-OES. In summary, METIS allows a detailed sampling of various study sites where natural Mn concentrations are within the working range of the analyzer, such as pelagic redoxclines , hydrothermal vent fields , and anoxic estauries .
| 4 | 0biomedical
| 0Study
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243,093 |
In the simulation of the biofilm in fluid flow, the flow is allowed to develop into a steady-state before allowing the biofilm to deform. This is accomplished by temporarily tethering each biofilm node \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\mathbf {X}}_{m}$$\end{document}Xm to its initial position \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\mathbf {X}}_{0m}$$\end{document}X0m with a stiff force12\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\begin{aligned} {\mathbf {F}}^*_{mm} = D\left( {\mathbf {X}}_{0m} - {\mathbf {X}}_{m} \right) . \end{aligned}$$\end{document}Fmm∗=DX0m-Xm.
| 4 | 0biomedical
| 0Study
|
99,540 |
Using complex sampling (e.g., longitudinal studies) or post-processing methods, detection of rare iSNVs is possible. To describe potentially significant remaining sample preparation error, we set criteria for preparation/sequencer error (“Prep”) as the mean errors of sites greater than 0.2% of population that were not found in in the plasmid (“Origin”), or post-transcription (“Transc”). Fig 4B provides a summary of mean errors /site/copy of iSNVs stratified by originating diversity present in “Origin”, “Transc” or “Prep”. “CIRSEQ,” using these criteria, performed substantially better in regards to sample preparation error than any other library (8.5−6 errors/site/copy), and the impact of transcription/reverse transcription errors was significantly (3–4 fold) lower than any other RNA-derived library. However, “CIRSEQ” resulted in a purifying effect on the originating diversity and eliminated both sites detected by all of the other methods, suggesting sensitivity limits in detecting rare variants. Shotgun sequencing residual error was determined to be 1.2−5 errors/site/copy from the mean of the “PLASMID” and “dsDNA” sample residual error. Amplicon amplification of both “P_AMP” and “DS_AMP” libraries resulted in comparable residual preparation errors 1.8−5 errors/site/copy and similar originating error. Under these conditions, “RNACC” demonstrated the best conservation of the originating diversity and lowest preparation errors/site/copy of 1.4−5 (a larger loading amount of 1 ng [rather than 50 pg] of viral RNA resulted in purification of the originating diversity likely due to exhaustion of the available probes), whereas, SISPA demonstrated the highest preparation error/site/copy of 4.4−5 (Fig 4B). The error profile expressed as the number of iSNV positions per percent of population (Fig 4C) demonstrates that the majority of the errors for all methods, except “SISPA”, occur in a narrow distribution around 0.09% of the population.
| 4 | 0biomedical
| 0Study
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3,468 |
FT-IR showed that there were three characteristic peaks for LCS at 3360 cm−1 for OH, 1380 cm−1 for C–O–C, and 1600 cm−1 for NH2 (Figure 3b). The oxygen bridge peaks of the skeletal vibrations involving the C–O stretching appeared between 1150 cm−1 and 1085 cm−1. As compared to LCS, the spectrum for inulin–LCS showed a weakened NH2-associated band near 1600 cm−1 for the N–H bending in the primary amine. Thus, the IR spectrum provided evidence for the reducing of the amino groups on the LCS chains by reaction with inulin.
| 4 | 0biomedical
| 0Study
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372,978 |
“For it requires only a small sample volume, our method can be used for pediatric studies where sample volume is limited, and it can be coupled with capillary tube sampling by a finger prick or more advanced microsampling techniques such as Seventh Sense Tap� to facilitate clinical studies. With the highly sensitive LC-MS/MS system, our method may be modified for dried blood spot samples.”
| 3 | 0biomedical
| 0Study
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34,793 |
HSP20/HSPB6 is a small HSP located in the cytoplasm that may translocate in part into the nucleus after a heart stress. Induced expression of HSP20/HSPB6 limits apoptosis and infarct size and improves cardiac contractility. HSP20 expression in I/R seems regulated, at least in part, by miR-320 (Ren et al., 2009). Inhibition of HSP20 phosphorylation may exacerbate cardiac I/R damage by suppressing autophagy and increasing other modalities of cell death (Qian et al., 2009; Edwards et al., 2011; Fan and Kranias, 2011). In ischemic conditions, HSP20 is associated to the sarcomeric structure in cardiac and skeletal muscle, as well as in cardiac myoblast cell line, H9C2 (van de Klundert and de Jong, 1999; Verschuure et al., 2002; Golenhofen et al., 2004). In cardiac cells, isoproterenol treatment induced a redistribution of HSP20 to the cytoskeleton and co-localization with actin. HSP20 can be phosphorylated in three phosphorylation sites: serine 16 by PKA/PKG; serine 59 through PKC; and serine 157 via insulin stimulation (Fan et al., 2005). Its phosphorylation at Ser16 may provide cardioprotection against β-agonist-induced apoptosis (Fan et al., 2004). Moreover, HSP20 may interact with the Bcl-2 family and the proapoptotic protein Bax. The anti-apoptotic effect of HSP20 is mediated by PKA pathway, and it prevents the translocation of Bax from the cytosol to the mitochondria, thus limiting cytochrome c release and caspase-3 activation (Fan et al., 2005).
| 5 | 0biomedical
| 0Study
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143,076 |
An interesting assay for diagnosis of acute lymphoblastic leukemia (ALL) was proposed by Mazloum-Ardakani et al. . They combined a genosensor detecting the BCR-ABL1 mutant gene and an aptasensor detecting the CEA cancer marker. The presence of Philadelphia chromosome (BCR-ABL1)-positive (Ph+) is a high risk for leukemia development in children. Only 20–30% of children with Ph+ and ALL survived . Carcinoembryonic antigens (CEA, CD66 family) were also considered as important cancer markers for early detection of ALL . In this approach the DNA genosensor was used first for evaluation of whether the BCR-ABL1 wsa present. A positive test indicated that the patient already had ALL or was at high risk to be affected by ALL. Subsequently, the second test performed by an aptasensor sensitive to CEA in blood could indicate the presence of ALL. For the development of the DNA sensor and aptasensors, the authors used nanocomposite materials consisting of carbon quantum dots (C-dots) and AuNPs. Both C-dots and AuNPs were immobilized at the surface of GCE. The thiolated ssDNA or aptamer probes were chemisorbed at the surface of the AuNPs. Both NPs enhanced the electrochemical signal. A DPV method was used for the detection of DNA hybridization with ssDNA probe as well as for CEA marker detection by DNA aptamers in the presence of electroactive probe—2 mM catechol. In both cases—DNA hybridization and binding of CEA to the aptamer—the current decreased, indicating the presence of either the BCR-ABL1 gene or CEA in the blood. The electrochemical sensors allowed detection of the BCR-ABL1 gene and CEA with a LOD of 1.5 pM and 0.26 pg/mL, respectively. The sensors were validated using blood from patients with various stage of ALL.
| 4 | 0biomedical
| 0Study
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366,919 |
Our findings are generally in agreement with former studies. Smoking was associated with higher MSI-high compared to MSS CRC risk in five previous studies6–10 and in a meta-analysis published in 2018.34 Stronger associations were also previously reported for BRAF-mut compared to BRAF-wt CRC,8,10,11 for KRAS-wt compared to KRAS-mut CRC12–14 and for CIMP-high compared to CIMP-low/negative CRC.10,11 Smoking has also been found to be associated with the serrated-polyps pathway, defined by CIMP-high and BRAF-mut status.35–37 Further, in accordance with previous studies, no major or statistically significant differences were found in the associations between alcohol consumption and CRC risk by molecular pathological subtypes,9,17–19,22 although the observed associations with CRC pathways pointed to potential differences in our study.
| 4 | 0biomedical
| 0Study
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261,118 |
In our present study, the phenotype of the frozen-thawed AT-MSCs did not differ from that of the non-frozen, control cells, irrespectively of the cryoprotectant or cell passage used. Variation in the homogeneity of our cell populations with respect to the expression of hematopoietic markers did not exceed 1% and was similar to or better than that reported by others (Mitchell et al., 2006; Baer et al., 2013). Moreover, our present findings, in accord with those of others’ (Luetzkendorf et al., 2015; Oja et al., 2019), indicate that freezing of MSCs does not affect the phenotype of these cells. In fact, although expression of CD105 which was low just after thawing returned to normal during passages 4 and 5.
| 4 | 0biomedical
| 0Study
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359,589 |
In contrast to only seven subjects owning a tablet (36.8%), 17 subjects owned a smartphone (89.5%) (Table 3). All subjects had access to the internet through a wireless network, and the majority had additional internet access through a cellular network (75.0%). Most subjects had experience accessing the internet or their email account(s) (85.0%) and researching information about heart failure (60.0%). Fewer subjects had previously used apps on their smartphones to achieve health-related goals (52.6%), to make decisions about treatment (44.4%), and to ask a doctor new questions or to get a second opinion (47.4%).
| 2 | 0biomedical
| 0Study
|
200,217 |
A series of agents with the specific aim of raising HDL are the CETP antagonists, still today the drugs with the best activity on HDL-C raising, in general by over 50%. Depending on their chemical structure, CETP inhibitors that have reached late-stage clinical development are categorized into CETP inhibitors (torcetrapib, anacetrapib, and evacetrapib) and modulators (dalcetrapib). While inhibition of CETP potently raises plasma HDL-C levels, the clinical outcome trials reported generally negative results calling into question the benefit of raising HDL-C . The only exception was with anacetrapib, providing a significant, albeit limited −9% reduction in CV events in a secondary prevention after a median 4.1-year follow-up. Interestingly, the extended follow-up (median 2.2 years) the REVEAL (Randomized Evaluation of the Effects of Anacetrapib through Lipid Modification) study showed an overall 12% RR risk reduction (95%CI 7–17%) corresponding to an absolute 1.8% reduction in major coronary events during the combined median overall follow-up period of 6.3 years [85••]. These findings highlight the need of a sufficient follow-up duration of the RCTs aiming at assessing the CV benefit of lipid-modifying agents.
| 4 | 0biomedical
| 2Review
|
93,843 |
Pixel-wise statistical map showing the number of fixations in the stimulus space of the intuitive group as revealed by the iMap3 analysis. (A) The statistical pattern of distribution of fixations. The colors of the map correspond to fixation counts on that particular area (see color scale on the right). (B) The same pattern mapped onto an example stimulus. A one-tailed Pixel test (Chauvin et al., 2005) was applied for the group fixation map (p < 1,0). Finally, for each condition average Z-score values were extracted for each observer individually, within the regions showing significance in the differential fixation maps.
| 4 | 0biomedical
| 0Study
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149,810 |
The statistical analyses were performed using JMP software (versionPro14, SAS institute, Cary, CA) and prism (GraphPad Prism9, GraphPad Software inc). Data are expressed as the mean ± SD for parametric data and a comparison of the means between the groups was performed using an independent samples T‐test. The categorical data were compared by a chi‐square test. Two‐sided p‐values < .05 were considered statistically significant.
| 4 | 0biomedical
| 0Study
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279,954 |
The gRNAs and pre-crRNAs were synthesized by in vitro transcription with the T7 RiboMAX™ Express Large Scale RNA Production System (Promega, Madison, WI, USA) and purified by ethanol precipitation, or LiCl precipitation when specified. The pre-crRNA and gRNA target sequences are listed in Tables S2 and S3, and the primer information for template synthesis is listed in Table S4.
| 4 | 0biomedical
| 0Study
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137,821 |
Bacteria of the genus Bacillus have been used extensively in industrial biotechnology as cell factories for protein production, which relates to their high protein secretion capacities and the fact that they are nonpathogenic to humans, animals, and plants (14, 15). Among these bacilli, the Bacillus subtilis strain 168 gained popularity not only because of its application potential but also because it has been an important model organism for studies on Gram-positive bacteria in general. Accordingly, B. subtilis 168 was one of the first organisms with a completely sequenced genome (16). Subsequently, this bacterium became the starting point for extensive genome-wide studies on gene function, involving the individual deletion of all nonessential genes (5). Based on the gathered knowledge, and taking advantage of the excellent genetic amenability of B. subtilis, extensive genome minimization studies were undertaken. This culminated in the engineering of B. subtilis strains that have the largest genome reductions thus far described for any living species (4, 17). One of these massively genome-minimized strains is the so-called ‘miniBacillus’, which lacks ∼35% of the genome of its parental strain 168 (17, 18). However, since minimization of the B. subtilis genome was based on a sequential stepwise process, a host of intermediate genome-reduced strains was created, such as the landmark strains IIG-Bs27-24 and IIG-Bs24-47-24 (17).
| 4 | 0biomedical
| 0Study
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389,248 |
Predation on CoTS by coral reef fish reported in the literature. Review of studies in the primary and grey literature on the predation on different life stages of Crown-of-Thorns Starfish (CoTS, Acanthaster spp.) by coral reef fish species. (F) and (L) indicate field and laboratory-based observations, respectively.
| 3 | 0biomedical
| 2Review
|
239,223 |
An ultrasonic transducer in the array system must generate a widespread beam pattern so that the furthest transducer pair in the array device receives a distinguishable ultrasonic signal among the noise. In order for the transducer to have the widespread beam pattern, the diameter of the transducer should be as small as a point. This point-like transducer called DPC (Dry Point Contact) transducer does not require a couplant . The MIRA device, therefore, can scan quickly without applying the couplant to scan surfaces every time.
| 3 | 0biomedical
| 1Other
|
292,401 |
Our goal was to test the relative contributions of daylength, nest cavity temperature, and position within the nest to diapause status in M. rotundata. We hypothesized that the daylength the mother experienced while laying an egg would influence diapause initiation in the offspring. We also hypothesized nest cavity temperature during larval development would influence diapause initiation. We measured the effect of temperature on diapause incidence by monitoring cavity temperature in the field. The date a nest was completed was used to calculate the daylength on the day each egg was laid, and nests were x-rayed to determine diapause status and brood cell position. We also investigated whether high nest temperatures increased mortality. Our results indicate that daylength, not temperature, influences diapause incidence in M. rotundata under our field conditions.
| 4 | 0biomedical
| 0Study
|
104,942 |
When considering plane waves v(t,x)=V(λt+βx), the argument s=λt+βx is set up with λ and β satisfying the equation P(η)=0 given in (3.7). The roots of (3.7) are η=0,0,α,−α with η=α denoting the root defined in (3.8). In particular, exponential waves are plane waves for which λ and β satisfy the dispersion equation Q(λ,β)=b0+b2=0 given in (3.25). This implies that α=1.
| 2 | 2other
| 1Other
|
2,058 |
Unlike KLF2 and 4, endothelial KLF5 and 6 are associated with vascular inflammation and remodeling that is largely deleterious. While KLF5 is largely considered to be a major effector of VSMC function (see below), there is evidence that it mediates endothelial chemotactic function. Specifically, knockdown of endothelial KLF5 in vitro reduces TNF-α-induced expression of key monocyte chemoattractant protein, MCP-1 (51). While the in vivo implications of this phenomenon are unclear, there is ample evidence implicating MCP-1 in many forms of vascular inflammation including atherogenesis, diabetic vascular disease, and vascular occlusion (52–54).
| 4 | 0biomedical
| 0Study
|
217,616 |
Moreover the quality of signals obtained for these materials is generally very sensitive to heating inhomogeneities, local changes in material density, and proximity to the material edges. Therefore, it is extremely important to define the limits of defect sizes that can be detected and, further, to introduce algorithms for processing measurement data, enable to extract even extremely fine anomalies observed in the temperature distribution at the sample surface. To process the thermographic data obtained during the material quality assessment, numerous techniques are applicable.
| 3 | 0biomedical
| 0Study
|
232,389 |
Exposed to metastasis and recurrence, patients with breast cancer bear unsatisfied therapy efficacy and survival. Mechanism for invasion and proliferation is therefore urgently warranted for depiction. ADAMTS9-AS1 was noticeably inactivated in breast cancer cells here. ADAMTS9-AS1 is a dysregulated antisense lncRNA in many tumors and is involved in the pathogenesis of a variety of human malignancies (Wang et al., 2016; Xing et al., 2018). For example, in colorectal cancer, lncRNA ADAMTS9-AS1 constrains invasion and migration of colorectal cancer (Li et al., 2020). ADAMTS9-AS1 also represses tumor-relevant prostate cancer behaviors (Zhou et al., 2021). The present paper found that ADAMTS9-AS1 could repress cancer proliferation and invasion through in vitro functional experiments. Nevertheless, there are reports that are contrary to our research results. For instance, overexpression of ADAMTS9-AS1 aggravates hepatocellular carcinoma (Zhang et al., 2020) and colorectal cancer development (Chen et al., 2020). We speculated that the different roles of ADAMTS9-A1 may be attributed to different cancer types.
| 4 | 0biomedical
| 0Study
|
63,055 |
Plasmid constructs were cotransfected into HEK293 cells and 48 hours later washed twice with PBS and lysed in ice-cold lysis buffer containing 50mM Tris-HCl pH 8.0, 150mM NaCl, 1mM EDTA, 1% NP-40, and 10% Glycerol supplemented with Protease Inhibitor Cocktail (Sigma). Cell lysates were cleared by centrifugation (15,000×g, 15 min.) and incubated with antibodies or control IgG overnight at 4°C. Antibody bound complexes were purified using Dynabeads Protein G beads (Life Technologies) at 4°C and washed three times with lysis buffer. For immunoprecipation from tissues, lysates were pre-cleared using Protein G beads prior to the addition of antibodies or control IgG. Following purification immunocomplexes were eluted by boiling in SDS sample buffer prior to Western Blot.
| 4 | 0biomedical
| 0Study
|
386,984 |
We classified species in terms of the predominant lifespan observed in wild populations from their native range. In some cases, this differed from lifespan assignment in the USDA accession description, in which case it was confirmed by extensive literature review; this occurred for P. coccineus, P. dumosus, and P. filiformis. Wild P. coccineus is a vigorous, perennial, indeterminate vine with an extensive root system; perenniality is also maintained in many cultivated forms (Delgado-Salinas, 1988; Smartt, 1988; Debouck, 1992; Freytag and Debouck, 2002 ). P. dumosus, a hybrid of P. coccineus and P. vulgaris, is also perennial, although it is less frost tolerant than P. coccineus (Smartt, 1988; Schmit and Debouck, 1991; Debouck, 1992; Freytag and Debouck, 2002; Mina-Vargas et al., 2016). Lastly, P. filiformis is an ephemeral, annual vine primarily found in the Sonoran Desert, which can survive up to seven months in favorable conditions (Buhrow, 1983; Nabhan and Felger, 1985; Freytag and Debouck, 2002). In addition, one accession of P. maculatus (PI 494138) was labeled as annual, although the species in general and and other accessions of this species are classified as perennial (Freytag and Debouck, 2002).
| 4 | 0biomedical
| 0Study
|
326,544 |
Additionally, TCF1 appears to be multifunctional, being implicated in both exhausted and memory CD8+ T cells. While the effects of TCF1 on either exhausted or memory CD8+ T cells may have been somewhat elucidated, the relationship between TCF1+ TEX and memory CD8+ T cells is less clear. Whether TCF1+PD-1+CD8+ TEX cells are to be considered as MPECs capable of differentiating into TCM cells has yet to be determined.
| 4 | 0biomedical
| 0Study
|
22,702 |
The distribution of cells and ECM (collagen and fibronectin) throughout microtissue thickness was quantified as follows. For each tissue, the tissue core was defined by all Z-stack slices from the collagen channel that had a normalized fluorescent intensity of 0.5 or higher (S2A Fig, vertical dashed line intersecting with the green line: representing collagen), thereby defining 3 regions in the tissue, i.e. bottom, core and top. Intensity values belonging to the three different regions, were summed and normalized to the total sum of intensity values, thus normalizing to 100%. Since high intensity values for the collagen channel are taken as a reference, the tissue core contains the majority of the collagen. Tissue bottom and top of the microtissues thus have limited amount of collagen and represent the basal and apical side, respectively. Subsequently, the sum of intensity values for the Dapi and fibronectin channels were calculated in the same way, but always based on the ‘bottom, core, top’-distribution of the collagen channel. The visual representation of these distributions thus represent the fraction of cells or fibronectin that overlap with the collagen core, and the top and bottom surface of the microtissues. To determine significant differences between bottom, core and top, One-Way-ANOVA, Bonferroni post hoc test was applied to the Dapi and fibronectin distributions.
| 4 | 0biomedical
| 0Study
|
194,484 |
One of the key molecules controlling the production of IL-17A and related cytokines is the transcription factor retinoic acid receptor-related orphan receptor RORγt (murine) or RORC (the human homologue). RORC is involved in the production and regulation of IL-17A by different cell types including Th17 cells (8), γδ T cells (9), innate lymphoid cells (10). In animal models a distinctive group of RORγt+ Tregs that is vital to maintain gastrointestinal homeostasis and avoid colitis (11–13). Moreover, it is crucial in orchestrating the differentiation of naïve CD4 T cells to Th17 cells (8). Enhanced gene transcription of RORC increases IL-17A production in a T cell line and human primary cells (14–16), whereas blockade of RORC in human CD4 T cells suppresses IL-17A and other inflammatory cytokines, including IL-17F and IL-22 (17, 18). Expression of IL-23R, CCR6, and IL-26 were also decreased upon RORC inhibition in Th17 cells, without affecting the gene signature of other T helper cell types (18, 19). Genetic lack of RORγt protected mice against experimental autoimmune encephalomyelitis (EAE), induced defects in Th17 differentiation and prevented T-cell-transfer-mediated colitis (8, 20). Pre-clinical studies in animal models, including imiquimod-induced psoriasis (21), spontaneous colonic inflammation (22), antigen induced arthritis (17), EAE (23), and experimental autoimmune uveitis (EAU) (24), confirmed that RORC inhibition markedly reduces local and systemic IL-17A levels and decreases tissue inflammation. Moreover, expression of IL-17F and IL-22 was also reduced upon in vivo RORC inhibition (21, 23). These findings indicate that RORC could be an interesting therapeutic target in IL-17A dependent pathology, blocking not only IL-17A but also related pro-inflammatory cytokines.
| 5 | 0biomedical
| 0Study
|
16,589 |
However, once the clinical decision was made to consider antihypertensive medication, providers were concerned that medication initiation would promote continued unhealthy behaviors.Provider 005: “If I start the medication, does that mean that they then disregard all their other factors… So okay, I’ll take a blood pressure pill and then I’m going to you know, eat all the salt I want and eat all the fat and gain weight and sit around and do nothing.”Provider 008: “Do they kind of view it as a crutch, you know? Get their blood pressure down in a normal range and then kind of go back to eating whatever they want or not exercising at all.”
| 2 | 1clinical
| 1Other
|
303,778 |
The simulations were performed with two concentrations of ambient agonist: 10 µM and 1 µM. With both concentrations of glycine, the implementation of TBS induced the NMDAR responses, which resembled the ones observed in the experiment. Each burst caused a single peak of open state probability, resulting in five responses, each having five peaks (Figure 11). When the higher concentration of glycine was present, the individual peaks displayed a slight decrease within each set of five bursts. In the low concentration of glycine, the amplitude of the probability peaks showed a more substantial reduction during the train (Figure 11), comparable to the experimental observations of NMDAR currents during the TBS. Thus, the simulation demonstrates that glycine in low concentration promotes the use-dependent downregulation of NMDAR during the TBS, similar to that observed in the experiments.
| 4 | 0biomedical
| 0Study
|
316,871 |
A key role of the retina is to convert light stimuli to neural impulses, which are then transmitted through the optic nerve to the occipital lobe . The retina is made of the retinal pigment epithelium (RPE), Bruch's membrane, and a sensorineural layer which is also known as the sensory retina. Within this sensory retina are photoreceptors that convert the light signal to action potentials that are sent to the brain for processing . Within the center of the retina lies the macula and in its center is the fovea. The fovea is a specialized region of the eye that has the highest visual acuity due to the absence of rods and a maximum cone density. The center of the fovea, which is the fovea pit, is also thinner as a result of the outward displacements of inner retinal neurons . RPE is also crucial to the normal functioning of the retina due to its support towards the photoreceptors. RPE cells are hexanocuboidal neuroectodermal origin monolayer cells located in-between Bruch's membrane and the photoreceptor cells [4, 5]. The apical side of the RPE membrane faces the photoreceptor's outer segments of rods and cones, while the basolateral side faces Bruch's membrane, forming the blood-retinal barrier . Key features of the RPE cells are their tight junctions between neighboring cells which functions to tightly control the transportation of fluids and solutes across the blood-retinal barrier. It also prevents plasma components and toxic molecules from entering the retina. The main function of the RPE is to (1) maintain the blood-retinal barrier (BRB) between the choroidal blood circulation and photoreceptors; (2) transport nutrients, ions, and water; (3) protect the outer retina against photooxidative damage by absorbing light; (4) perform phagocytosis and degrade detached distal portions of photoreceptors; (5) reisomerize all-trans-retinal to 11-cis-retinal; and finally (6) act as a vascular and neural protector by secreting cytokines and growth factors . Figure 1 depicts an illustrated anatomy of the eye and the arrangements of cells within the retina.
| 5 | 0biomedical
| 0Study
|
201,043 |
The literature for submaximal fatiguing tasks is varied, including measures such as EMG measurements and torque, as well as objective activity measures such as assessment of fatigue in functional tasks in laboratory environment and during the execution of daily living activities.
| 2 | 0biomedical
| 1Other
|
141,334 |
For all musicians, the median inter-injection interval was 4.1 months (Q1–Q3: 3.6–4.9 months). There was a correlation between the inter-injection interval and treatment duration (r = 0.27; p = 8.7 × 10−4) (Figure 2, Table 2, for a boxplot with individual data see Supplementary Figure S1).
| 2 | 0biomedical
| 0Study
|
12,868 |
The characteristics of obese patients experienced anesthesia induction and supraglottic airway device Blockbuster™ insertion are also summarized in Table 2. Four patients developed apnea and two of them experienced apnea after receiving propofol. The incidence of apnea was 13.3%, and the longest time of apnea was 47.9 s. The lowest SpO2 during the procedure was 94% in one patient. No patient experienced oxygen desaturation (defined as SpO2 less than 92%) during this study. The respiratory rates and tidal volume were significantly different at different measure point (P < 0.001).Table 2Characteristics of anesthesia induction and postoperative interview in obese patientsObese patients(n = 30)Anesthesia induction period Laryngospasm0 Coughing4 (13.3%) Purposeful limb movement9 (30.3%) Muzi score > 215 (50.0%) Number of patients with apnea4 (13.3%) Apnea time (s)38.2 (7.37) Longest apnea time (s)47.9 Lowest SpO2 during tracheal intubation (%)97.5 (97–98.3 [94–99]) Successful insertion at first attempt15 (50%) Successful insertion at second attempt13 (43.3%) Successful insertion at third attempt2 (6.67%)Respiratory rate* Before induction14 (12–15 [10–22]) 1 min after induction14 (11–15 [9–16]) 1 min before supraglottic airway device insertion16 (14–18 [10–21]) immediately before supraglottic airway device insertion17 (16–18 [12–22]) 1 min after supraglottic airway device insertion16 (14–18 [10–22])Tidal volumes† Before induction605 (101) 1 min after induction412 (93.6) 1 min before supraglottic airway device insertion361 (90.1) immediately before supraglottic airway device insertion339 (79.2) 1 min after supraglottic airway device insertion366 (82.3)Postoperative interview Pleasant induction30 Repeat same anesthetic technique30Values are expressed as mean (SD), numbers (proportion), or median (IQR [range])*P < 0.001; † P < 0.001
| 4 | 0biomedical
| 0Study
|
315,303 |
Food items were classified as energy dense if >225 kcal/100 g (WCRF/AICR, 2007). We classified foods based on their nutrient composition by assigning each food with a nutrient density score to reflect its nutrient quality based on previously validated approaches (e.g. Drewnowski, 2005; 2010; Drewnowski and Fulgoni, 2014). The score incorporated 11 nutrients to encourage (protein, fibre, vitamins A, C, E and iron, calcium, potassium and magnesium, folate and zinc) and three nutrients to limit (total fat, total sugars, sodium) based on balancing the public health nutrition context with the availability of food composition data for the selected nutrients in Ghana (Abdul-Haq et al., 2018) and in Kenya. For each food item consumed, nutritional information per 100 kcal for the 11 nutrients and energy density were extracted from a combination of food composition tables based on their rigour and local relevance. Nutritional content (both macro- and micro-nutrient information) for each of these unique food items was then identified using a combination of food composition tables) (6 for Ghana and 4 for Kenya). The primary tables used were: The West African Food Composition Table (Ghana) and the Kenyan Food Composition Table (Supplementary file 3: Food composition tables and nutrient profiling method). Where food composition data were unavailable for nutrients and/or energy density in any of these tables (38 foods in Ghana; 2 in Kenya), they were substituted with similar food items agreed by co-authors (AT, SK, MG, MH, MW, NB, RP). Using USDA dietary recommendations, the % daily value of all nutrients was calculated per 100 kcal. Nutrient density scores were generated by subtracting the sum of the nutrients to limit from the sum of the positive nutrients to encourage. Each food item was categorised as nutrient dense if the nutrient density score was ≥10% and nutrient poor if <10% applying widely used cut-offs (U.S. Department of Health and Human Services, 2013).
| 4 | 0biomedical
| 0Study
|
5,840 |
We repeated the experiments depicted in Figure 1 with the respective UAS-controls and did not observe any significant effects on viability, body size or mass. Thus, if there is a small background activity of the UAS-constructs, it is of no distinct physiological relevance. The respective UAS-controls were included in Figure 1.
| 2 | 0biomedical
| 0Study
|
182,196 |
Novel physio-pathological brain tumor mechanisms are targeted with new PET radiotracers. Tumor perfusion, angiogenesis and neuroinflammation pathways have attracted particular interest . However, results are very preliminary, and validation studies are required.
| 2 | 0biomedical
| 1Other
|
108,456 |
We performed a comparative analysis of yeast and human RAS amino acid sequences and confirmed the high similarity in sequence and structure between human and yeast RAS proteins (Figure 3). Specifically, the N-terminal region is strongly conserved, especially in the first half of the sequence. This reflects the important functional constraints involved in the recognition of guanine nucleotide and phosphate, for which the N-terminal is responsible (Figure 3a). In this segment, 58% of residues are identical between any of the yeast RAS proteins and any of the mammalian RAS sequences. As expected, G12 and G13 residues, which are frequently found mutated in cancer, are among those invariant positions (Figure 3a). The human KRAS structure (PDB ID 3GFT) was used to infer the structure of the yeast RAS (Figure 3b) through homology modeling, as previously documented . This comparative analysis evidences the similarity between human KRAS and both yeast RAS proteins (Figure 3c) and suggests that the differences in amino acid sequence would still result in a similar fold in humans and yeast proteins (Figure 3c). The main difference between the three mammalian RAS isoforms (KRAS, HRAS and NRAS) and yeast homologues lies at the C-terminal domain, in the HVR, which is critical to membrane localization and function (Figure 3a). Interestingly, yeast RAS proteins contain an extra C-terminal portion not present in RAS protein from other organisms (Figure 3a). The extended C-terminal accounts for 120 aa in the case of Ras1 and 131 aa for Ras2, making yeast RAS HVR around 140 aa . It has not been established yet if this part can form a secondary structure, however its function has been identified. The extended C-terminal was reported to serve as a negative regulatory domain for RAS, promoting its interaction with GDP and therefore the permanence in the inactive status . Accordingly, it was shown that yeast cells expressing truncated RAS proteins lacking the C-terminal domain (or mammalian RAS proteins, without the extra 120 aa) do not require a functional GEF to be viable, while they do when expressing normal RAS proteins .
| 4 | 0biomedical
| 0Study
|
310,149 |
We next established another three tumor-seeded mouse models with preexisting primary tumors at different sites to observe whether the primary tumors would affect the therapeutic effect of HFD consumption. We found that HFD consumption did not affect the growth of primary tumors in s.c., in situ or Apcmin+/− tumor-seeded models (Fig. S3a, c, e). However, HFD consumption markedly suppressed the metastatic seeding of MC-38 cells in these models (Fig. S3b, d, f). These results indicated that the preexisting primary tumors did not affect the therapeutic effect of HFD consumption on the metastatic seeding of CRC cells. Thus we did not need to pre-establish primary tumors in subsequent studies.
| 4 | 0biomedical
| 0Study
|
367,032 |
We performed a nested case control study to evaluate potential risk factors for maternal infections (Table 3). Travelling during the epidemic [crude OR 46.4, 95% CI 7.0–1916.5] and travelling to the Caribbean islands compared to other regions [crude OR 5.0, 95% CI 2.0–12.6] were associated with an increased risk of maternal infection. Similarly, a duration of stay >2 weeks [crude OR 12.8, 95% CI 1.9–541.3] and a duration of stay > 3 weeks [crude OR 2.9, 95% CI 1.0–8.9] compared to those ≤ 2 weeks or ≤ 3 weeks, respectively, were both associated with an increased risk for maternal infection. Similar findings were also observed when considering all possible ZIKV infections or active ZIKV infections, except that a duration of stay > 4 weeks compared to those ≤ 4 weeks was also associated with an increased risk of possible ZIKV infections.
| 4 | 0biomedical
| 0Study
|
168,635 |
We also agree with the reviewer’s assessment that there is no standardization of secretome MSCs. Secretome MSCs contain exosome and soluble molecule active. This is a potential limitation of the study because we have not standardized the secretome MSCs. Therefore, further studies of secretome MSCs standardization need to be carried out.
| 2 | 0biomedical
| 0Study
|
150,662 |
In comparison to the molecular weights of lipids in liposomes, polymersomes can have their component copolymers of higher molecular weights, thus can demonstrate better physical and chemical stability.[ 177 ] The molecular weights of copolymers can be up to 100 kDa, while that of lipid is usually less than 1 kDa. A schematic presentation of liposome and polymer vesicle is presented in Figure 6a showing their structural similarities. Physicochemical properties of polymersomes can be altered by the judicial choice of appropriate polymer, correct molecular weights, and ratio of hydrophobic to hydrophilic segments.
| 4 | 0biomedical
| 0Study
|
209,527 |
The many immunoregulatory roles described for itaconate have uncovered its potential as a therapeutic for numerous diseases. In support of this, many of the studies discussed above have included relevant murine disease models demonstrating therapeutic effects of itaconate (summarized in Table 1). Therapeutically, lessons from natural properties of itaconate may also inform us of novel drug targets that may be worth pursuing. For instance, there is currently much interest in modulating NLRP3, Nrf2, and GAPDH in inflammatory diseases. While itaconate derivatives continue to show success in disease models, alternative approaches could aim to increase endogenous itaconate through the upregulation of Irg1 or through the development of enzymatic activators of ACOD1.
| 4 | 0biomedical
| 2Review
|
95,930 |
All trials were performed in triplicate replication and error bars represent the standard deviation of the mean. For most experiments, the results were analyzed using a one-way analysis of variance (ANOVA). A pairwise multiple comparison was then completed for each using the Holm-Sidak method. All statistical analyses were performed using Sigma Plot (Systat Software Inc, San Jose, CA, USA) at a p-value < 0.05.
| 3 | 0biomedical
| 0Study
|
299,994 |
Conversion 2: We aggregate the 39 normalized layers at infrastructure asset level into ten normalized layers at subsystem level. An infrastructure type t belongs to a specific subsystem g. Accordingly, the normalized layers for infrastructure types within a given subsystem are combined into an aggregated layer at subsystem level \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\bar{S}\left({I}_{g}\right)$$\end{document}S¯Ig, which represents the spatial intensity of that specific subsystem. The number of infrastructure types T within a subsystem g is denoted as \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${T}^{g}$$\end{document}Tg. To continue with the example provided in Fig. 5, the solid waste subsystem is represented by two infrastructure types \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${T}^{g}$$\end{document}Tg, namely landfill and waste transfer station. The normalized layers for these infrastructure types are combined into an aggregated layer representing the solid waste subsystem. We use an equal weighting, which means that each infrastructure type is considered equally as important. We denote the weighting of a given infrastructure type as \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$w({I}_{t})$$\end{document}w(It). The product of the summation, denoted as \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\sum }_{t=1}^{\left|{T}^{g}\right|}\bar{S}\left({I}_{t}\right)\ast w\left({I}_{t}\right)$$\end{document}∑t=1TgS¯It∗wIt, is normalized using the same method as in the first conversion. The second conversion is expressed by Eq. 2:2\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\bar{S}({I}_{g})=\frac{{\sum }_{t=1}^{| {T}^{g}| }\bar{S}({I}_{t})\ast w({I}_{t})}{{\rm{\max }}({\sum }_{t=1}^{| {T}^{g}| }\bar{S}({I}_{t})\ast w({I}_{t}))}\quad {\rm{with}}\;t\in g$$\end{document}S¯(Ig)=∑t=1∣Tg∣S¯(It)∗w(It)max(∑t=1∣Tg∣S¯(It)∗w(It))witht∈g
| 4 | 2other
| 0Study
|
13,088 |
To investigate the potential association between the identified SNPs and SM, a cohort of 461 CKCS including 187 unaffected and 274 SM-affected (that included the original 65 dogs) were genotyped with two TagSNPs from each of the associated regions on CFA22 and CFA26. While the 2 selected TagSNPs on CFA26 at position 32,797,595 bp and 32,757,080 bp did not show any significant association to SM (P value = 0.7637 and 0.7614), the 2 selected TagSNPs on CFA22 at position 13,933,606 bp and 13,804,718 bp reached significance (P value = 0.0104 and 0.02309). Bonferroni corrected P value of the TagSNP at position 13,933,606 bp on CFA22, was still significant at a P value of 0.0104. Hence, we successfully identified a region on CFA22 associated to ratio F-d/BC and SM in the CKCS dogs.
| 4 | 0biomedical
| 0Study
|
82,062 |
In addition, neutrophils also contain a full-length cationic antimicrobial protein, bactericidal/permeability-increasing protein (BPI) in azurophil granules . BPI possesses three types of anti-infective activities: direct antimicrobial activity, neutralizing endotoxin activity through direct binding of LPS, and opsonic activity. BPI binding to LPS results in increased bacterial permeability, hydrolysis of bacterial phospholipids, and death of the bacterium. In addition to its well-documented anti-infective properties, BPI has also been shown to possess additional bioactivities, such as accelerating apoptosis, binding the vascular endothelial growth factor (VEGF), and inhibiting migration of human umbilical vein endothelial cells.
| 4 | 0biomedical
| 0Study
|
247,947 |
Fig. 3 Exo-Gel enhanced chondrogenic differentiation mBMSCs in vitro. A In vitro estimate the ability of Exo-Gel by coculture in chondrogenic differentiation of mBMSCs. B RT-PCR analysis for COL II, ACAN and SOX9 mRNA in mBMSCs treated as described in (A) at different time-points. Data are represented as means ± SEM (n = 3). C AB staining of mBMSCs in different treatment groups under light microscopy on the 14th day of induction of differentiation (bar = 100 μm). D Immunofluorescent assay of mBMSCs for COL II (red) and DAPI (Blue) in different treatment groups at the same time-point in C (bar = 100 μm). E Western blot assay to detect the protein expression levels of COL II, ACAN and SOX9 at the same time-point in C. F Quantification of protein expression in E. GAPDH was used as loading control. Data are expressed as means ± SEM (n = 3). G Representative Western blot showing the levels of total protein and phosphorylated protein for the indicated molecules (Smad2/3, ERK1/2, and p38) in mBMSCs with or without TGFβ1 neutralizing antibody at the same time-point in C. H Quantification of protein expression and the level of signaling activation in G. GAPDH was used as loading control. Data are expressed as means ± SEM (n = 3). I AB staining of mBMSCs with or without TGFβ1 neutralizing antibody under light microscopy on the 14th day of differentiation (bar = 100 μm). J Immunofluorescent assay of mBMSCs for COL II (red) and DAPI (blue) under the same condition as (I) (bar = 100 μm). *p < 0.05
| 4 | 0biomedical
| 0Study
|
318,584 |
An overall key feature of attention is that it works through gain changes [30, 44]. Such gain changes have been extensively investigated and modeled in the context of gain control mechanisms prevalent in the cortex [5, 10, 25, 27, 36, 44]. Much less focus has been put on the question whether such multiplicative changes to cellular responsiveness reflect specific neurotransmitter changes (see for a review). Nevertheless, there is ample evidence in favor of an involvement of the cholinergic system in attentional modulation, primarily gained from rodent studies ([17, 32, 40]; reviewed in ). A study performed in macaque primary visual cortex (V1) was the first in non-human primates to shed light on the underlying cellular mechanisms of the effects of spatial attention on firing rates . A cholinergic agonist (acetylcholine) or antagonist (scopolamine or mecamylamine) was iontophoretically injected in the direct vicinity of the recording electrode while the monkey performed a spatial attention task. Injecting acetylcholine caused an increase in the attentional modulation of neuronal responses, while blocking the action of muscarinic, but not nicotinic, cholinergic receptors reduced attentional modulation. However, it is unclear whether V1 can serve as a model for the extrastriate cortex, as it has specific anatomical characteristics that distinguish it from other visual areas, such as a reduced amount of inhibitory neurons as well as a difference in quantity of cholinergic receptor subtypes [9, 14].
| 4 | 0biomedical
| 0Study
|
204,646 |
The time to diuretic administration influenced hospital mortality rate. A study by Matsue et al. and Maisel reported that ED arrivals who received an intravenous diuretic agent within 60 minutes in AHF patients had a lower hospital mortality rate (11, 12). The results of this study showed that a door-to-diuretic time >60 minutes predicted 30-day adverse events (adj. OR = 3.89; 95%CI: 2.16-7.00) (p < 0.001). Therefore, the EP should give early administration of intravenous diuretic agents within 60 minutes in AHF patients to decrease the occurrence of adverse events.
| 4 | 0biomedical
| 0Study
|
146,294 |
This study for the first time reported the mutations of sCT that significantly enhanced sCT(22–32) affinity for the CTR ECD. The N26D and S29P mutations of sCT(22–32) markedly increased affinity for the CTR ECD by 6-fold and the additional P32HYP mutation further increased sCT(22–32) affinity by over 2-fold compared to the wild-type sCT(22–32). Accordingly, the sCT(22–32) with the combined mutations (N26D, S29P, and P32HYP) increased affinity for the CTR ECD by 21-fold compared to wild-type sCT(22–32) and this affinity enhancement was conserved for all three types of the AMY receptor ECDs. This peptide analog fragment with improved affinity for the CTR and the AMY receptor ECDs could be considered for developing next-generation peptide drugs targeting CTR and AMY receptors.
| 4 | 0biomedical
| 0Study
|
46,898 |
Figure 4A shows grand average ERPs for the SM task at electrode P3 for Hit trials where the source was correctly remembered (HSC), Hit trials where the source was not correctly remembered (HSI) and CR responses (mean number of HSC/HSI/CR trials = 64/35/114; minimum trials = 30/16/74; maximum = 108/88/143; mean percentage of trials rejected = 17%/16%/21%). Topographic maps (Figure 4B) show old/new effect distributions between 500 and 800 ms post-stimulus. As expected both HSC and HSI responses are more positive going than CRs, with the difference appearing maximal over left parietal electrodes. The HSC-CR difference appears slightly more widespread in distribution; nonetheless the difference is once again clearly maximal over left posterior electrodes. HSC responses are more positive than HSI responses, however, this difference appears to have a central maximum. As per Experiment 1, an average left parietal old/new effect was calculated (average of electrodes P5, P3, P1). As illustrated in Figure 4C (left), mean old/new effect magnitude across these electrodes were larger for HSC than HSI responses.
| 4 | 0biomedical
| 0Study
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219,318 |
Our results show that supplementation with a combination of β‐alanine, L‐arginine, and Nigella sativa reduced TNF‐α and h‐CRP following military training. Military training increased the levels of pro‐inflammatory mediators such as IL‐6 and TNF‐α which have a detrimental impact on muscle functions and immune responses to infection (Gomez‐Merino et al., 2003). Nigella sativa oil extract contains a considerable amount of aromatic organic compounds with anti‐inflammatory and anti‐oxidative properties such as thymoquinone, dihydrothymoquinon, p‐cymene, carvacrol, and thymol. In a study on treadmill‐exercised rats, the administration of Nigella sativa significantly reduced TNF‐α concentrations and TNFα/IL‐10 and IL‐6/IL‐10 ratio and increased IL‐10 (anti‐inflammatory cytokine) concentrations immediately after intense training (Gholamnezhad et al., 2014). Recent systematic review and meta‐analysis revealed that supplementation with Nigella sativa (1–3 g) reduced hs‐CRP by 0.5 mg/L among subjects with an inflammatory condition (Tavakoly et al., 2019). Nigella sativa has been shown to inhibit the activation of NF‐KB, a crucial transcription factor for the inflammatory gene expression, and the degradation of I‐KB as an inhibitor of the NF‐KB (Chehl et al., 2009). Recent systematic review and meta‐analysis revealed that L‐arginine supplementation did not affect CRP, IL‐6, and TNF‐α (Nazarian et al., 2019). However, there is evidence suggesting that L‐arginine can reduce inflammatory mediators (TNF‐α, IL‐1β, and IL‐6) and enhance muscle regeneration in Mdx mouse muscles through down‐regulation of the NF‐KB gene expression and inhibition of NF‐KB/metalloproteinase cascade (Hnia et al., 2008). In addition to L‐arginine, a randomized trial revealed the administration of 12 g/day β‐alanine for 7 days can increase IL‐10 concentrations during intense military training (Hoffman et al., 2018). Regarding inflammation, it can be concluded the anti‐inflammatory properties of our enriched ration bars can be due to the individual or cumulative effects of its active components.
| 4 | 0biomedical
| 0Study
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97,942 |
3) InFigure 5—figure supplement 2 and other measurements, state whether the multiple measurements were made on a single pore or on different pores, and report on the reproducibility of measurements made on separately fabricated pores with the same grafting material (e.g. FG domain of Nsp1)?
| 3 | 0biomedical
| 1Other
|
67,556 |
In this study, a household was defined as all persons who shared a cooking pot . The questionnaire had 10 and 11 question items on knowledge and attitude variables. Prior to analysis, correct responses were coded as ‘1’ while incorrect responses were coded ‘0’ for knowledge questions. The respondents’ attitude was measured by 5 point Likert scale: “Strongly agree”, “agree”, “undecided”, “disagree” and “strongly disagree” and scored 5, 4, 3, 2 and 1, respectively. For knowledge and attitude variables, the aggregate scores were dichotomized into good and poor for knowledge, positive and negative for attitude scales, respectively. In this regard, the median (inter-quartile range) for attained knowledge score were 7 (6–8). So, a score below 7 was recoded as low and a score equal to or greater than 7 was considered high [20, 21]. Similarly, a score of 42 (39–45) was used to stratify the sum of attitude scores on child faeces management into positive and negative categories, respectively. In constructing the wealth categories, variables such as ownership of the house, and household items such as fridge, Television/video, paid satellite television, care/motorcycle, laptop, separate room for kitchen contributed towards the measuring scale. The presence of the household items was rated ‘1’ while the lack of these was rated ‘0’. To stratify into categories, 1–39%, 40–69% and ≥ 70% were rated poor, average and rich, respectively. For bivariate analysis, chi-square (Pearson) statistics was used to assess the type of relationship among pairs of under five child defecation practice indices, except otherwise stated, with the level of significance at <5%.
| 4 | 0biomedical
| 0Study
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92,329 |
The specifics of the proposed pipeline for personalisation of full-cycle LV mechanics models are described below. First, we present the cardiac mechanics model, including the governing equations, the passive and active constitutive laws, and the boundary conditions. A minimal clinical dataset required is outlined next, and the procedure for personalisation of the model based on this dataset is described. We also present the steps involved in generating the in silico datasets.
| 4 | 0biomedical
| 0Study
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210,663 |
We showed previously that IL-12 selectively induced activation of STAT1 and STAT3 in Ba/F3 cells (24), because Ba/F3 cells have very low STAT4 protein levels and cannot be used for analysis of IL-12-induced STAT4 activation (25). HIL-12D36K/W37K/T38K was biologically inactive on Ba/F3-gp130-mIL-12Rβ1-mIL-12Rβ2 cells (Fig. 5, C and D). Coimmunoprecipitation revealed interaction of HIL-12D36K/W37K/T38K with IL-12Rβ2 but not with IL-12Rβ1, whereas HIL-12 precipitated both IL-12Rβ1 and IL-12Rβ2 (Figs. 5E and S6C). As a control, we used site 3 variant HIL-12Y185R, which interacts with IL-12Rβ1 and not IL-12Rβ2 (13). In summary, our data indicate that D36/W37/T38 is mandatory in p40 for interaction with IL-12Rβ1.
| 4 | 0biomedical
| 0Study
|
367,741 |
The diet nutrients showed obvious seasonal changes (Fig. 2A). Pandas preferred one-year-old WB leaves (protein/fibre %, 22.59 ± 3.90) than multi-year-old WB leaves during the first several months after they move back to the low elevations, usually from September to November (Table 2). As the consumption of one-year WB leaves gradually increased, multi-year WB leaves increased gradually in their daily diet items (protein/fibre %, 17.87 ± 3.08) from December to April of the next year (Table 2). We found that pandas would also feed on a small part of WB culms (protein/fibre %, 2.59 ± 0.35) and AB culms (protein/fibre %, 2.09 ± 0.41) in March (12.3% WB culms and 4.1% AB culms) and April (12.5% WB culms and 7.5% AB culms). In May, the WB shoots were the main food of giant pandas when they were available, and the percent of protein/fibre in the WB shoots (69.23 ± 9.93) was significantly higher than that in the WB leaves. When the WB shoots matured, the percent of protein/fibre decreased, and pandas migrated to the high-elevation site and switched to AB shoots (protein/fibre %, 47.51 ± 7.51) and one-year-old AB leaves (protein/fibre %, 29.92 ± 2.38) from June to August.
| 4 | 0biomedical
| 0Study
|
36,084 |
The HFOs in different frequency ranges are usually responsible for different brain behaviours such as normal information processing and spontaneous seizures. The third step of our procedure is to calculate the frequencies of various HFOs, which is done by locating the starting and ending times of an HFO, finding the number n of oscillating periods within it and dividing by its duration: f=n/THFO. When necessary, we combine overlapping HFOs across different IMFs, as shown in figure 6c. When various HFOs have been identified, we can classify them into distinct frequency ranges: low-frequency range (less than 80 Hz), ripples (80–200 Hz, between pairs of solid blue triangles in figure 6c) and fast ripples (greater than 200 Hz, between pairs of open magenta triangles in figure 6c). HFOs of frequencies lower than 80 Hz are identified as population spikes. An example of identifying and classifying HFOs is shown in figure 7. Figure 7.Example of successful HFO and PS detection. (a) Original EEG data plot of about 3 s. (b) IMF 5 plot with solid blue triangles marking the ripples and open magenta triangles marking the fast ripples. (c) The amplitude of IMF 5. The horizontal blue line is the threshold for separating on/off intervals of HFOs. The threshold is calculated from the amplitude data segment of about 1 h. The computational parameters are aμ=1 and aσ=1. (a ′)–(c ′) The original data, IMF 6, and its amplitude function, respectively. The black diamonds mark the position of the population spikes.
| 4 | 0biomedical
| 0Study
|
154,167 |
Multiple studies explored selectivity for CDK4 or CDK6 degradation by building focused sets of analogs with palbociclib, ribociclib and abemaciclib as the POI ligand, varying linker compositions, and E3-ligase ligands . For the most part, PROTACs with shorter hydrophilic linker lengths and ribociclib as the POI ligand favored CDK4 degradation while those with longer hydrophobic linkers and palbociclib as the POI ligand resulted in selectivity for CDK6.
| 4 | 0biomedical
| 0Study
|
266,281 |
Data on multiple procedural and hospital discharge variables were collected, including implant success, cross-clamp time, length of stay in the intensive care unit, and total length of hospitalization. Clinical success was defined as a successful valve implantation without the occurrence of major adverse events by the time of discharge. Major adverse events (investigator reported) were defined as death (all-cause, non-cardiovascular, and cardiovascular [including deaths of unknown cause]), stroke, and reintervention (surgery or other cardiac invasive therapy). Serious valve-related adverse events included bleeding, thromboembolism, valve thrombosis, endocarditis, non-structural dysfunction, and structural valve deterioration. All adverse events are defined according to the Valve Academic Research Consortium-2 criteria . Severity of valve dysfunction was classified as mild (grade 1+), moderate (2+), moderate to severe (3+) or severe (4+). Improvement in clinical status was defined as an improvement of ≥1 in the New York Heart Association (NYHA) classification from baseline (before the procedure), measured annually throughout the study. Echocardiographic and haemodynamic data were collected. Early outcomes were defined as those occurring up to 30 days after the procedure and late outcomes as those occurring > 30 days after the procedure.
| 4 | 0biomedical
| 0Study
|
237,091 |
In this work, we employed a system effective energy modeling a volume constraint for each cell, adhesion at all interfaces, and chemotaxis, 38\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ \mathcal{H}(t)=\sum_s{\lambda}_v\left(\tau \left(s,t\right)\right){\left(v\left(s,t\right)-{v}_c\left(\tau \left(s,t\right)\right)\right)}^2+\sum_{x\in \mathcal{U}}\sum_{x^{\prime}\in \mathcal{N}(x)}\left(1-{\delta}_{\sigma \left(x,t\right),\sigma \left({x}^{\prime },t\right)}\right)J\left(\tau \left(\sigma \left(x,t\right),t\right),\tau \left(\sigma \left({x}^{\prime },t\right),t\right)\right)+\sum_{x\in \mathcal{U}}\sum_c\frac{\lambda_c\left(\tau \left(\sigma \left(x,t\right),t\right)\right)c\left(x,t\right)}{1+{c}_{CM}\left(\sigma \left(x,t\right),t\right)} $$\end{document}Ht=∑sλvτstvst−vcτst2+∑x∈U∑x′∈Nx1−δσxt,σx′tJτσxttτσx′tt+∑x∈U∑cλcτσxttcxt1+cCMσxtt
| 4 | 0biomedical
| 0Study
|
267,826 |
Research-based learning mode relying on network technology is subject-oriented, which changes the teaching process from traditional inheritance to inquiry. Students use the Internet to do a lot of online reading and online audio-visual, get “information input”, accumulate materials, and then refine their own views, transfer the perceived information to oral, form materials for oral expression, and provide “speaking” with the contents and ways of oral communication through logical transformation of thinking.
| 1 | 2other
| 1Other
|
51,100 |
Typical characteristics of cancers are self-sufficiency in growth signals, enhanced proliferative signaling, invasion, metastasis, angiogenesis, replicative immortality, and resistance to cell death . Pancreatic ductal adenocarcinoma (PDAC) harbors all of these classical hallmarks. Reduced response to conventional cytotoxic therapies is the culprit responsible for tumor development and progression despite therapy . A less conventional therapeutic approach for PDAC arises from the stimulation of extrinsic apoptosis by death ligands. Accordingly, appropriate expression of respective death receptors (DR) on the plasma membrane and a functional downstream signaling apparatus is required to successfully stimulate the extrinsic apoptosis cascade reviewed in . tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/Apo2L) and its pro-apoptotic receptors TRAIL receptor 1 (TRAIL-R1) and 2 (TRAIL-R2) represent such a death ligand/receptor system. On the one hand, the TRAIL-TRAIL-R system is expressed by PDAC cells and, on the other hand, capable of activating apoptosis selectively in tumor cells by binding to its death receptors reviewed in .
| 4 | 0biomedical
| 0Study
|
70,535 |
Anesthetized mice were intracardially perfused with 4% paraformaldehyde in phosphate buffer, and the brains and spinal cord were post-fixed overnight at 4 °C in the same buffer, and embedded in paraffin. The brain sections (6 μm) were deparaffinised, autoclaved at 120 °C for 2 min and blocked with 3% donkey serum and 1% bovine serum albumin in Tris-buffered saline containing 0.1% TritonX-100. The brain sections were then probed with the following primary antibodies: FLAG (Sigma-Aldrich, M2, ×500), TDP-43 (ProteinTech, #10782-2-AP, ×500), ChAT (Millipore, #AB144P, ×100), IbaI (Wako, #019–19741, ×500), GFAP (Sigma, #G3893), Myelin Basic Protein (Millipore, #AB980), NeuN (Millipore, #MAB377), GAD-67 (Millipore, #MAB5406, ×500), Parvalbumin (Millipore, #MAB1572, ×1000), Calretinin (Millipore, #MAB1568, ×1000), p62 (MBL, #PM045, ×500), multi-Ubiquitin (MBL, #D058-3, ×300), MAP2 (Abcam, #AB7756, ×600), Tau1 (Millipore, #MAB3420, ×200), Rfk (Abgent, #AP7183a, ×50), RIPK-1 (Novus Biogenesis, #NBP1-77077, ×400), and Cleaved Caspase-3 (Cell Signalling, #9661 S, ×400); and with the following secondary antibodies: fluorescently conjugated anti-rabbit, anti-rat, anti-mouse, and anti-goat antibodies (Alexa Flour, Life Technologies). For the DAB staining, the sections were blocked using the avidin-biotin blocking kit (Vector Lab, #SP-2001), probed with primary antibodies and biotinylated secondary antibodies. The staining was visualised by the avidin-biotin complex immunoperoxidase technique using the VECSTATIN Elite ABC system (Vector Lab). The images were obtained using a Zeiss LSM 5 exciter confocal microscope (Carl Zeiss) and the Fluorescence Microscope system BioVio BZ-9000 (KEYENCE, Japan)
| 4 | 0biomedical
| 0Study
|
312,058 |
Enterococcus faecalis is a Gram-positive facultative anaerobe that normally exists as a commensal microbe colonizing the gastrointestinal or urinary tract of humans and animals (Arias and Murray, 2012). E. faecalis is an important nosocomial pathogen that is linked to various infections, including urinary tract infection, sepsis, endocarditis, and peritonitis (Arias and Murray, 2012; Mercuro et al., 2018). E. faecalis exhibits both intrinsic and acquired resistance to several commonly used antibiotics, such as aminoglycosides and macrolides, and can serve as a model for the emergence of antibiotic resistance (Arias and Murray, 2012). Given the increasing number of reports of multidrug resistant E. faecalis strains, including those resistant to vancomycin (VAN) and linezolid (LZD), there is an urgent need to develop effective measures to treat infections caused by E. faecalis (Van Harten et al., 2017; Sparo et al., 2018; Fiore et al., 2019; García-Solache and Rice, 2019).
| 5 | 0biomedical
| 0Study
|
43,669 |
— Treeness ϕ is used to measure the hierarchical organization on network topologies . A tree graph can be described as a set of connected nodes without closed paths. The treeness covers the ranges from non-hierarchical, ϕ=0 (the graph displays all closed paths), to hierarchical, ϕ=1 (the graph displays a tree-like structure) which is defined by the following equation: 2.6ϕ=LTree⟨L⟩,where LTree is the sum of the average path length of the graph without closed circuits and 〈L〉 is the average path length of the entire graph.
| 3 | 2other
| 1Other
|
395,310 |
Micromasses were obtained as previously described . Briefly, adherent cells were treated with trypsin-EDTA (Corning, Corning, NY, USA) and washed. 2.5 × 105 hOAC were resuspended in culture media and centrifuged at low speeds (2000× g) for 5 min to form aggregates. After 24 h, cell aggregates were detached from the bottom of the tube and the media were changed to begin the treatments. Micromasses were treated either with DPBS (Euroclone, Pero, Italy) (Ctrl) or r-irisin (Sigma, St. Louis, MO, USA) for 7 days at a concentration of 25, 50, 75, and 100 ng/mL, which is the range between intraarticular and blood concentrations in humans . Media were changed three times during the week of culture. At the end of the experiment, micromasses were directly used to assess GAG content normalized to DNA as following. Micromasses were washed with PBS and digested with 100 µL of papain (Sigma, St. Louis, MO, USA) solution (0.25 mg/mL in 50 mM phosphate buffer, pH 6.5 containing 5 mM cysteine–hydrochloride and 5 mM ethylenediaminetetraacetic acid) overnight with gentle shaking at 65 °C. GAGs were measured by reaction with 1,9-dimethylmethylene blue (DMMB; Polysciences, Warrington, PA, USA) using chondroitin sulfate (Sigma, St. Louis, MO, USA) as a standard. Measurements of absorption were performed at a wavelength of 530 nm (Tecan Infinite M200 PRO).
| 4 | 0biomedical
| 0Study
|
80,195 |
The model for circadian oscillations in D. melanogaster relies on a negative feedback (Fig 6B) and frequently employs Michaelis-Menten kinetics in both conversion as well as degradation reactions (gray arrows in Fig 6B). Thus, the model is comparable to the chain model with negative feedback applying Michaelis-Menten kinetics in all reactions (compare Fig 5B to the dark red dots in Fig 3I). From these model structure properties one would expect considerably larger median period and amplitude sensitivity values and ranges for the D. melanogaster model compared to the mammalian circadian model which are in fact obtained (compare Fig 5B to Fig 5A, p-values <10−5, Tables J, K in the S1 File). The circadian model for A. thaliana encompasses positive and negative regulations which result in only negative feedbacks (Fig 6C), and all degradation reactions obey Michaelis-Menten kinetics (gray arrows in Fig 6C). Thus, it resembles the negative feedback chain model with Michaelis-Menten kinetics in the degradation reactions (Fig 3A, 3G and 3H). One would expect enlarged median period sensitivities and distribution ranges and slightly decreased amplitude sensitivities compared to the mammalian circadian model. We observe the former, but also increased amplitude sensitivities (compare Fig 5C to Fig 5A, p-values <10−5, Tables J, K in the S1 File), which could result from the overall different structures of the two models (Fig 6A and 6C). Taken together, in most cases we can explain the sensitivity distributions of the examined circadian models using insights gained from the analyses of the chain models. Like in the prototype oscillator models the use of Michaelis-Menten kinetics influences the sensitivity distributions of circadian oscillation models.
| 4 | 0biomedical
| 0Study
|
311,911 |
The metabolism of hymexazol in plant was investigated in primary crops. According to the results of the metabolism studies after seed treatment of sugar beet, the residue definition for enforcement and risk assessment can be proposed as hymexazol. The residue definition is restricted to seed pelleting of root and tuber vegetables. It is also applicable to rotational crops and processed commodities. For fruit crops, the residue definitions for enforcement and risk assessment derived in the peer review are still considered valid.
| 2 | 0biomedical
| 0Study
|
313,484 |
Immunofluorescence staining was performed with the brain section containing the striatum area to examine the expression and morphology related to activation of astrocyte (GFAP) and microglia (Iba1). Briefly, 40 µm coronal brain sections containing striatum were incubated with proteinase K (5 µg/µL) for 30 min at 25 °C to allow the penetration of the antibody. After washing with PBS, the sections were incubated with blocking reagent (10% normal goat serum in PBS containing 0.3% Triton-X 100). The sections were then incubated with the primary antibodies such as anti-GFAP (1:1000) and anti-Iba-1 (1:1000) overnight at 4 °C. The sections were then briefly washed three times with PBS and incubated for 1 h with a fluorescent secondary antibody (Alexa Flour 488 goat antirabbit) at room temperature. Sections were then washed thoroughly and mounted on a slide. The sections were then cover slipped using Fluoroshield mounting media (Sigma-Aldrich, St. Louis, MO, USA). Images were taken randomly, selecting 3–5 files per sample with a Leica fluorescent microscope at 20× (Leica DFC 3000G). Images were used to count activated astrocyte (GFAP) and microglia (Iba-1) per field using NIH image J software.
| 4 | 0biomedical
| 0Study
|
231,063 |
In detection and diagnosis, the emergence of single-cell transcriptomics has brought us many new opportunities, especially in vitro diagnosis. The rise of in vitro diagnosis is mainly due to cancer and rare diseases, for which the diagnosis is complex. If the diagnosis is unclear, we cannot develop a stable treatment plan, as one scholar said: “you can't stop it if you can't see it.” Based on single-cell transcriptomics, we can map the development track of human embryos; Tang (82–84) did a lot of meaningful work in this area, depicting the picture of embryo development. The diagnostic significance of single-cell level is undoubtedly huge for cancer and rare diseases (85–87), because they have heterogeneity, and single-cell transcriptomics is a powerful weapon to reveal heterogeneity. This is an important supplement to the previously accumulated bulk data; after a period of time, bulk data will become a supplement to single-cell data.
| 4 | 0biomedical
| 2Review
|
202,747 |
Current oncological drug development, in the view of precision medicine, is focused on the identification of molecular drug targets to improve pharmacological activity and reduce systemic toxic effects. Thus, analysis of drug target gene expression in individual patients is a mandatory requirement. CLIC1, highly expressed in most GBMs, acts as a main regulator of growth rate (see [1, 8], and this study). Here, we describe for the first time the distribution of CLIC1 in discrete human GBM cells. The presence of intense staining in cells localized near vessels, resembling infiltrating cells, supports not only the well-known role of this ion channel in cell division and motility , but also the importance to develop a pharmacological strategy to inhibit CLIC1, as proposed in this study. However, we identified few human GBMs (namely, GBM39, GBM44, and GBM50) natively expressing this channel at low levels, which could represent a subset of tumors in which CLIC1 activity is bypassed by different intracellular signaling. Interestingly, these tumors in patients, and the relative GSCs isolated in vitro, display similar features than CLIC1 high-expressing counterparts. In fact, the analysis of the expression of several stem-related markers (CD44, CD133, CD15, ITAG6, Olig2, Sox2, nestin and S100), while showing the expected heterogeneity in different GBMs, did not detect a specific pattern for low CLIC1 expressing GBMs. Moreover, in 2D and 3D cultures these cells behave similarly to GSCs with high CLIC1 activity (for example as far as spherogenesis, differentiation ability, organoid development). Thus, while CLIC1 functional expression enhances GSC proliferation and tumorigenesis, its activity can be circumvented in some GBMs through the activation of alternative intracellular pathways allowing tumor development and progression also when the channel activity is negligible, as also shown by the lack of differences in patients’ survival according to CLIC1 expression (see Fig. S12). However, in these tumors antitumor activity of metformin and novel biguanides is significantly impaired. Conversely, in tumors which express CLIC1 and display high ion channel activity, its blockade is deleterious for GSC growth and invasiveness, highlighting that, in the majority of GBMs, CLIC1 targeting might represent a powerful therapeutic option.
| 5 | 0biomedical
| 0Study
|
365,253 |
Software tools such as BioTransformer can help to predict in silico metabolism of a metabolite/environmental chemical by following human metabolic pathway reactions that are gut, tissue or environment specific (Djoumbou-Feunang et al., 2019). Competitive Fragmentation Modeling (CFM)-ID can aid in annotation of spectral peaks, in prediction of spectra of a given chemical structure, and in putative identification of metabolites from unknown spectra (Allen et al., 2014). ChemDistiller can help annotate metabolites using tandem MS data against a compiled DB of millions of compounds (Laponogov et al., 2018). CSI (Compound Structure Identification): FingerID combined fragmentation tree computation and machine learning to help resolve unknown compound identification challenges (Dührkop et al., 2015). InterpretMSSpectrum is a tool suitable for annotating and evaluating in source full-scan mass spectra from gas chromatography-atmospheric pressure chemical ionization-mass spectrometry (GC/APCI-MS) data (Jaeger et al., 2016). MetFrag can perform compound DB searching and fragmentation prediction for metabolite identification of tandem MS spectral data (Ruttkies et al., 2016). MS2LDA uses tandem MS data for inferencing sets of fragment and neutral loss features that co-occur in spectral data for aiding in unknown interpretation (Wandy et al., 2018). Using tools such as MS-FINDER one can determine molecular formulas of precursor ions from accurate mass, isotope ratio etc. where the predicted formulae are retrieved from metabolome DBs and follow the nine hydrogen rearrangement (HR) rules (Tsugawa et al., 2016). mzCloud is a curated DB of HR tandem MS data arranged as spectral trees, where tandem MS and multistage MSn data were acquired at various collision energies. SIRIUS 4 is another computational approach for molecular structure identification (Dührkop et al., 2019).
| 5 | 0biomedical
| 2Review
|
156,349 |
This disadvantage (or advantage) does not have to have occurred because of atypical (or typical) linguistic development. For example, Gundel and Johnson, 2013 found that typically-developing 3 year-olds observed in their home environment demonstrate spontaneous production of sentences encapsulating ToM, even though this age group tends to fail on more formal “tests” of ToM such as via false-belief (Wellman et al., 2001; Wright and Mahfoud, 2014). Along somewhat similar lines, a deaf sub-group of children having a linguistic advantage over a second sub-group (e.g., bilingual vs. monolingual or early bilingual signers vs. late bilingual signers) tends to as a consequence demonstrate higher ToM abilities on false-belief tasks (Meristo et al., 2007).
| 2 | 2other
| 0Study
|
58,121 |
P4 is widely known for its role in sexual reproduction, but during the last decade, increasing evidence of the neuroprotective role of neurosteroids has been obtained. P4 has been successfully used in different clinical trials for the treatment of traumatic brain injury (Wright et al., 2007). These P4 neuroprotective effects may be due to its action on numerous processes and signaling pathways, such as the decreased release of inflammatory cytokines, decreased cellular apoptosis, positive regulation of the γ-aminobutyric acid neurotransmitter (GABA), and decreased lipid peroxidation and oxidative stress (Stein, 2008).
| 4 | 0biomedical
| 0Study
|
207,198 |
Chemotherapy-exposed MSC and nerve infiltration in tumor xenografts. (A) Two different polyclonal antibodies identifying nerve tissue (against S100 protein and PGP9.5 protein) stained nerve structures cross-section area in the tumor (indicated by arrows) and in the adjacent adipose tissue up to 2 mm from the tumor surface. (B) Nerve infiltration was expressed as percentage of the tumor section area in each experimental group. Increased nerve infiltration of tumors was observed in co-cultures with DOX-/PAC-MSC. (C) DOX-MSC co-injection also increased nerve diameter of detected tumors. For statistical analysis, one-way ANOVA with Tukey’s multiple comparisons test was used. Statistically significant results are highlighted with asterisks at p < 0.05 (*), p < 0.01 (**)
| 4 | 0biomedical
| 0Study
|
87,303 |
There were no significant differences between the four stimulus groups (familiar with increased yellow, familiar with decreased yellow, unfamiliar with increased yellow and unfamiliar with decreased yellow) in body mass, tarsus and wing length of males in female mate choice (ANOVA, all P > 0.59, all ω 2 < −0.03, n = 36) and female social choice (ANOVA, all P > 0.16, all ω 2 < 0.06, n = 40) or females in male mate choice (ANOVA, all P > 0.24, all ω 2 < 0.04, n = 31) and male social choice (ANOVA, all P > 0.19, all ω 2 < 0.06, n = 30). Thus body size differences between stimulus birds are unlikely to affect choice of focal bird in our experiment.
| 3 | 0biomedical
| 0Study
|
88,585 |
Ndiuzaani is expressing complicity with the hegemonic norm, in that he might be teased by others if he helps with child care. Attending under-five clinics was reported as one of the activities of childcare that men typically do not like to do, again related to hegemonic masculinity norms of maintaining respect and keeping separate from domestic spaces and subjects. The study participants gave several reasons why men do not like the idea of attending these clinics, particularly the discussion topics at the under-five clinics, including domestic work, child spacing and family planning. As one female participant explained:I know the type of food to feed my children because I learn this at under-5 clinics. Men don’t attend these lessons because domestic work is mostly discussed over there, and men feel that these discussions do not concern them [Judith, Female, 28 years].
| 1 | 2other
| 0Study
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344,393 |
Regarding the effect of emotion on BIC, the present study found that the P3 amplitude in response to happy faces was smaller than that in response to angry faces in the SI group, whereas the NSI group had no significant differences in BIC between the two emotions. In light of the P3 amplitude decreases in the condition of cognitive control (Chen et al., 2008), individuals with SI require more cognitive control to eliminate the interference of unrelated information to complete the process of inhibitory control under the condition of happy faces. In contrast to a previous study of healthy individuals showing that BIC was weaker in response to negative emotions (Yuan et al., 2007, 2012), the current study found that BIC decreased in response to positive emotions among the SI group. The Broaden-and-Build Model of Positive Emotions suggests that positive emotions significantly expand the scope and increase the flexibility of attention (Fredrickson, 1998; Schmitz et al., 2009), which makes individuals pay attention to the integrity of information and ignore the details of the information, thus making them unable to concentrate on the completion of the control task and hindering their BIC. Moreover, the reduced P3 amplitude that reflects impulsivity is usually interpreted as indicating a reduction in attentional resources that are available for information processing because these resources are not allocated effectively or because of decreased physiological arousal (Russo et al., 2008). In this way, the reason for this result may be that individuals with SI pay less attention to positive stimuli (Jollant et al., 2008), and they require more effort to exhibit BIC in response to happy (vs. angry) faces. Individuals with SI have acceptable BIC in response to angry faces, which could be explained by the model of cognitive control of emotion (MCCE). MCCE suggests that there are four steps involved in generating emotional responses (Ochsner et al., 2012): perceiving stimuli in the environment, deploying attention to these stimuli, appraising the significance of stimuli, and responding to the stimuli, including automatic physiological responses. P3 component shows differences in the process of appraising stimuli, which represent the cognitive evaluation of the meaning of stimuli (Ito et al., 1998; Huang and Luo, 2006). Specifically, angry faces indicate more threatening information, and individuals tend to employ more attention to these faces and evaluate it as negative information, which would recruit more physiological and psychological resources and elicit a higher P3 amplitude. This result shows that different emotions have an effect on the BIC of the SI group but not the NSI group, which is helpful for understanding the relationship between impulsivity and SI from the role of emotion.
| 4 | 0biomedical
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