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Increasing numbers of reports have described elevated readouts of oxidative stress in plasma of A-T patients, in cultured A-T fibroblasts and lymphocytes, and in tissues and cultured cells from Atm-deficient mice (12, 13). Notably, the response of A-T fibroblasts to induced oxidative stress was found defective [reviewed in Ref. (14)].
| 4 | 0biomedical
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130,424 |
In the present work, we build upon the existing soRT-FDC technology to improve reliability of measurement, analysis, and sorting of enzymatically dissociated tissues. To develop and showcase the methods, we used dissociated retina cells originating from human retinal organoids (HROs) and mouse eyes (see Fig. 1A). HROs differentiated from a photoreceptor-specific reporter human induced pluripotent stem cell line (hiPSC-Crx mCherry14) were cultured for 125 days. Mice expressing GFP restricted to rod photoreceptors (Nrl-eGFP mouse15) were at postnatal day 4 (P04) when applying the dissociation protocol (see Materials and Methods). For flow cytometry measurement in RT-FDC or sorting using soRT-FDC, cells were resuspended in a measurement buffer with elevated viscosity (see Materials and Methods), as illustrated in Fig. 1A.Figure 1Cell preparation, soRT-FDC setup and chip design. (A) Retinae from reporter mice (Nrl-eGFP) or human retinal organoids (Crx-mCherry) are dissociated and resuspended in measurement buffer for soRT-FDC. (B) Sketch of the soRT-FDC setup. Two syringe pumps supply a microfluidic chip with sample and sheath fluid. Lasers excite fluorescence signal which is measured by avalanche photodetectors and the cell is imaged by a high-speed camera. A high-power LED illuminates the cell. Interdigital transducers (IDTs) excite surface acoustic waves, which push selected cells towards the target outlet. (C) Figure shows the 2D-CAD design of the entire sorting chip and zoomed in versions show specific parts. The red rectangles indicate filter assemblies, which consist of a cascade of pillars with decreasing distance. The orange rectangles indicate a unit of several serpentines, which helps to divide aggregates of cells and to increase the spacing between cells. The layout was designed using KLayout 0.25.3.
| 4 | 0biomedical
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109,820 |
Sub-project III explored how rehabilitation work was perceived and delivered by front-line services in two boroughs in Oslo. Norwegian municipalities are required to offer social, psychosocial, or medical rehabilitation to all inhabitants requiring such services and to establish a coordinating unit for rehabilitation. The results are summarised in two articles:
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| 1Other
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394,217 |
Comment 7: Underlying discourse: The term "inflated" used in the title, in Figure 2 and conclusion suggests manipulation or distortion of citations and an artificial advantage for authors of articles published in predatory journals before they are removed from Scopus. This is not demonstrated by the reasoning and data used in the article as a basis for comparison is missing.
| 1 | 2other
| 1Other
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277,152 |
The HRI fMRI task implemented in this study was already used and validated before (31). The combined task consists of Simon-, Go-/No-Go- and Stop-Signal trials that were integrated into one paradigm to assess interference inhibition, action withholding and action cancellation (Figure 1). A detailed description of the task can be found in the Supplementary Material.
| 3 | 0biomedical
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290,977 |
Traumatic brain injury (TBI) is a severe health problem affecting many people, contributing to a substantial amount of deaths and cases of disability. The view that neurological, behavioural and cognitive deficits are well‐known sequelae of TBI, leading to functional impairment and a worsening in quality of life, is widespread.1
| 4 | 0biomedical
| 2Review
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48,793 |
SIRT-1, H3K56ac, and p53ac protein expression in PBMCs recovered from T2DM patients submitted to resveratrol supplementation or placebo. a Cell extracts from T2DM patients’ PBMCs (subject 1–6) submitted to placebo were analyzed for SIRT-1, H3K56ac, and p53ac content at baseline (t0) and at the trial end (6 m). Protein levels were normalized to beta actin, H3 and p53 content, respectively. The values reported represent the relative amount (ra) of protein expression obtained by densitometric analysis. b Cell extracts from T2DM patients’ PBMCs (subject 7–12) submitted to resveratrol 40 mg/day supplementation (Resv40) were lysed and analyzed for SIRT-1, H3K56ac, and p53ac content at baseline (t0) and at the trial end (6 m). Protein levels were normalized to beta actin, H3 and p53 content, respectively. The values reported represent the relative amount (ra) of protein expression obtained by densitometric analysis. c Cell extracts from T2DM patients’ PBMCs (subject 13–18) submitted to resveratrol 500 mg/day supplementation (Resv500) were lysed and analyzed for SIRT-1, H3K56ac, and p53ac content at baseline (t0) and at the trial end (6 m). Protein levels were normalized to beta actin, H3, and p53 content, respectively. The values reported represent the relative amount (ra) of protein expression obtained by densitometric analysis
| 4 | 0biomedical
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304,672 |
Since the discovery of inosine by means of laborious purifications of specific RNA species, followed by selective RNA degradation and chromatographic studies , a number of techniques now exist for mapping inosine modifications. All these strategies have their strengths and limitations, and their preferential use is dependent on the RNA species of interest and the biological/biochemical question that needs to be addressed. Molecular inosine can be readily detected and quantified using standard biochemical methods that mostly rely on conversion of inosine into hypoxanthine. Detection of inosine within RNA species, on the other hand, is more challenging and will be the focus of this section.
| 5 | 0biomedical
| 2Review
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264,885 |
In almost all tissues, there is a resident population of mesenchymal stem/progenitor cells (MSPCs) . These cells exist inside stem-cell niches which maintain the state of quiescence, self-renewal or active differentiation of MSPCs . They could undergo directional migration under appropriate stimuli to maintain tissue homeostasis and repair injured tissues [21, 22]. A resident population of progenitor cells, also referred to as cartilage-derived progenitor cells (CPCs), has been found in the normal and degenerative AC . In addition, some tissue-specific MSPCs also have been found in other areas of the joint including synovium , synovial fluid (SF) , meniscus , infrapatellar fat pad , suprapatellar fat pad , and perichondrial groove , perichondrium . Some previous studies demonstrated that many injured-associated products (such as cell lysates, ECM fragments, high-mobility group box 1, HMGB1 and stromal cell derived factor-1, SDF-1) could stimulate in vitro migration of MSPCs [31, 32]. More importantly, an increased percentage of MSPCs-marker positive cells was observed in the injured cartilage tissue in comparison to the normal cartilage tissue [33, 34]. In addition, MSPCs were present in higher numbers in the SF after cartilage injury . All these findings indicate that when AC becomes injured, MSPCs in multiple stem-cell niches surrounding the injured sites would be activated in response to the stimulation of injured signals and migrate into the injured sites to produce replacement cells. Moreover, many in vitro and ex vivo studies have shown that chondrocytes are also able to migrate under different external stimuli, although in vivo chondrocyte migration remains to be further determined [36, 37]. To sum up, an endogenous self-repair attempt exists after AC injury. However, full recovery of the structure and function of the injured cartilage in human adults is rare or even considered to be absent. If cartilage tissue cannot regenerate itself, what are the limitations in injured cartilage self-repair?
| 5 | 0biomedical
| 2Review
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196,789 |
GMTF, GNNPS and GDQE results are shown graphically in Figures 4 and 5 for the frontal and lateral tube/detector combinations, respectively. The vertical direction is the one that the X‐ray tube moves during acquisition (scan direction) whereas horizontal is the direction of the detector slit (slit direction). The GMTF in the horizontal direction is influenced by signal scattering between pixels, as photoelectrons are able to travel in the horizontal direction and contribute to the signal in neighbouring channels. On the other hand, the line‐by‐line acquisition in the vertical direction prevents photoelectrons contributing to neighbouring channels in this plane. 16
| 4 | 0biomedical
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235,924 |
Participants imagined being happier, t (100) = 5.57, p < 0.001, d = 0.60, and calmer, t(100) = 4.05, p < 0.001, d = 0.37, when visiting the dentist without a toothache (respectively, M = 3.98; SD = 1.02 and M = 3.90; SD = 1.25) than when visiting the dentist with a toothache (respectively, M = 3.26; SD = 1.34 and M = 3.41; SD = 1.42).
| 3 | 0biomedical
| 0Study
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343,415 |
Trends in leaf epidermal flavonol index (Iflav) from five understorey species (A. podagraria, A. nemorosa, C. majalis, F. ulmaria, and O. acetosella) measured on five occasions during spring and summer 2015. The trend lines are given by loess fits to the cloud of points for each stand with 95% CI (grey band). The vertical grey dotted lines indicate the approximate beginning of summer with respective mean daily air temperatures continuously above +10°C degrees. Further details of weather during 2015 are provided in Table S3 .
| 2 | 2other
| 0Study
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226,294 |
Previous studies have shown the accumulation of readily detectable prion seeding activity in the skin of humans with Creutzfeldt–Jakob disease25,26, and rodents with scrapie, even early in the course of infection27. Given that the outer ear could serve as an accessible source of both skin and nervous tissue, we sought to investigate the utility of RT-QuIC to diagnose CWD in pre-clinical white-tailed and mule deer using ear pinna punches. Here, by coupling iron oxide magnetic extraction to a modified RT-QuIC assay, we were able to diagnose CWD by analyzing ear samples collected from both clinical and asymptomatic animals with an accuracy at least as good as previous assays of RAMALT tissue, with the advantage herein of using a more easily collectable specimen.
| 4 | 0biomedical
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301,456 |
21. P14 second paragraph: you state that other studies ‘[show] improvements in outcomes by the use of positive pressure’. Is there definitive evidence that outcomes are improved with CPAP? I can see reduced rates of transient hypoxia during apnea, as you have shown here, but I don’t believe there is evidence that meaningful case outcomes such as postop oxygen requirements, reintubation requirements, etc. are reduced. Thus I would recommend defining what outcomes, if any, are improved.
| 4 | 0biomedical
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341,675 |
Raw metagenomic data (available in https://www.ncbi.nlm.nih.gov/sra/PRJNA646106) were quality controlled and trimmed before de novo assembly with Megahit v1.1.2 . Prodigal v2.6.3 and MetaEuk were used to predict prokaryotic and eukaryotic protein-encoding genes for each metagenome, respectively. Taxonomic annotation of the predicted genes was conducted with DIAMOND v0.9.32.133 against the NCBI-nr database (Coordinators 2016, Database resources of the National Center for Biotechnology Information), (50% identity over at least 80% length). The top hits per predicted gene were retrieved with Megan v6.18.10 . GhostKOALA was also used for taxonomic annotation of predicted genes. Priority was given to the taxonomic assignation provided by DIAMOND+Megan, but for those not assigned, the assignations provided by GhostKOALA were considered. Functional annotation was conducted with KOFAMscan v1.3.0 and the KO+Pfam database released on May 2020. DNA-RPKM values (reads mapped to a gene per kilobase of the gene per total million mapped reads) were calculated for each predicted gene using BBMap . Quality-filtered metatranscriptomes were used after in-silico rRNA depletion of raw data using SortMeRNA v2.1 . The mRNA reads were mapped to the respective metagenome contigs with BBMap to calculate RNA-RPKM values.
| 4 | 0biomedical
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226,823 |
We treated U87 glioma cells with 100 µM PA, OA, and EPA, respectively, for the SRS spectral imaging. As shown in Fig. 3B, we measured all LDs with diameters above 1 μm in around 40 glioma cells and plotted their SRS spectra with the mean and the standard deviation (SD). We observed that the SRS spectra of LDs (Fig. 3B) exhibited the characteristic Raman spectral features of the FA (Fig. 3A) that was used to treat the cells in each experimental group, indicating that the supplied free FAs were largely incorporated into the neutral lipids stored in LDs. To quantitatively estimate the percent composition of each FA in LDs, we performed spectral linear unmixing using the multiple linear regression (MLR) method45. The data showed that FA-treated LDs contained ~ 23% of PA, ~ 20% of OA, and ~ 13% of EPA, respectively, relative to the innate LDs in the untreated glioma cells (Fig. 3C). This result demonstrates that using the SRS spectral imaging approach, the “flow” of FAs into LDs can be tracked and quantified in a label-free manner. In addition, the large SD values indicate that the chemical compositions of the LDs were heterogeneous even in cells treated with pure FA. This observation was consistent with the previous studies47,49–51.
| 5 | 0biomedical
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121,014 |
Increases in parental self-efficacy were seen in interventions ranging from one to 15 sessions. The finding that single session interventions can significantly increase parental self-efficacy has substantial potential clinical importance in terms of the ability to disseminate time and cost effective interventions to many parents. The four studies looking at single session interventions focussed on specific problem situations, such as mealtimes and shopping. All recruited volunteer samples of parents of children without a diagnosed behavioural difficulty so greater investigation with a range of difficulties and populations would be beneficial. Group-based interventions, regardless of the length, incorporate, and draw upon, the five factors Bandura (1977, 1997) identified as important for enhancing self-efficacy; previous experience, vicarious experience, verbal persuasion, and have been found to enhance physical and psychological wellbeing (Leahy-Warren 2005; McVeigh 1998). Additional, direct comparison of brief versus longer interventions would enable an exploration of the important elements of both interventions and whether these are the same in brief and longer interventions. The long-term sustainability of the impact of single session interventions requires further investigation as none of the reviewed studies reported control group comparison data at follow up. However, the maintenance of increased parental self-efficacy in the intervention groups after one session at 6 months is encouraging. This short, time-limited approach may fit well with the tiered model of early interventions recommended by the UK Government of universal support offered to all parents before more intensive support is focussed on “at risk” families (Allen 2011; Leadsom et al. 2014).
| 4 | 0biomedical
| 2Review
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394,099 |
Table 4 reports the mean values for a series of SPNP centrality-based patent variables computed for patents in each technology domain: the average centrality of the patents cited by patents in the domain, the centrality of the domain's patents measured after three years from filing and their centrality in 2015. All three are normalized in two different ways, one through the randomization of the entire USPTO patent citation network and the other by taking the rank percentile of the value for each patent, compared to other patents granted in the same year. These two normalization methods and their advantages and disadvantages are discussed at length in Triulzi et al. (2020) . Data in Table 4, as it is presented, is available in the file “DF_means_centrality.xlsx”. The file “DF_means_all_variables.xlsx” makes available means by domains for each variable described in Table 3. It has 30 rows, one per domain, and 48 columns including the mean values for each of the variables in the rows of Table 3.Table 4Average normalized centrality variables for each domain.Table 4DomainmeanSPNPcited_1year_before_randomized_zscore_RPbyYearmeanSPNPcited_1year_before_RankPerc_by_yearSPNP_count_t3_randomized_zscore_RPbyYearSPNP_count_t3_RankPerc_by_yearSPNP_count_2015_randomized_zscore_RPbyYearSPNP_count_2015_RankPerc_by_year3D printing0.6750.6620.6180.6090.5010.593aircraft0.3210.2400.3560.3280.4240.355batteries0.4410.3940.4310.4000.4620.408camera0.6090.6330.5840.6310.5200.625capacitor0.3880.4150.3730.4550.3950.500comb engine0.4440.5230.4900.5620.4980.543ct0.5400.4870.5250.4930.5120.530electric computation0.7820.8260.7630.7540.6240.721electric motor0.3650.3590.3810.4130.4010.432electric telecom0.5030.4930.4860.5150.5040.579electro powertrans0.5270.5510.4980.5500.5240.609flywheel0.4360.4350.4430.5050.3910.452fuelcell0.5340.4390.4990.3980.5210.403genome0.4450.3150.3800.3050.4280.298hybrid corn0.2860.0780.1730.1540.1860.164ic0.6480.6920.6390.6600.5900.660incandescent0.4100.3310.4430.3800.4970.377led0.5780.5390.5390.5160.5360.531magnetic info storage0.5490.5990.5060.6010.4970.620magnetic mat0.5040.4660.4780.4520.4690.433milling0.2650.2460.2860.3160.3580.330mri0.6100.6560.5890.6510.4950.671optical info storage0.6360.6680.6330.6230.5720.571optical telecom0.6240.7140.6430.6850.5890.677photolithography0.5110.5010.5010.4950.5120.483semiconductor info storage0.6550.6590.6320.6390.5710.668solar pv0.4880.5270.5020.5020.4920.532superconductor0.4290.3860.4460.4170.4910.394wind0.3390.3490.3640.4610.3710.467wireless telecom0.6440.7130.6290.6800.6140.700
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| 1Other
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163,938 |
In the present study, we defined CD3-NKp46+ cells as classical NK cells, but CD3-NKp46+ cells also include ILC1s, a rare non-cytotoxic innate lymphoid cell type that is capable of producing IFN-γ and shares many markers with classical NK cells across tissues37. In addition to the cytotoxicity, expression of Eomes can also be used to distinguish NK cells from ILC1s38. However, we found more than 96% of Lin-NKp46+ cells (CD3-NKp46+ cells included) are Eomes+, indicating they are classical cytotoxic NK cells. Moreover, the Lin-NKp46+ Eomes− cells (defined as ILC1s) did not show a higher ability to produce IFN-γ (Supplementary Fig. 8a–c). We further examined the levels of granzyme B and perforin in lung-infiltrating CD3-NKp46+ immune cells from mice treated with Salmonella YB1 and found that CD3-NKp46+ cells from YB1-treated mice have significantly higher levels of granzyme B and perforin (Supplementary Fig. 8d, e). These results together indicate that most CD3-NKp46+ cells after YB1 treatment, if not all, are conventional cytotoxic NK cells. Although we cannot fully rule out the possibility of ILC1s in Salmonella-provoked metastasis suppression, the current data have not provided strong support for it. Using flow cytometry, we identified an obvious phenotypic change in lung-infiltrating NK cells from mice with Salmonella YB1 treatment. Lung-infiltrating NK cells from mice treated with PBS or YB1 were isolated and analyzed for surface markers. We performed a t-SNE analysis and found that NK cells from PBS and YB1 groups formed two distinct populations (Fig. 6f). We found NK cells isolated from YB1-treated mice were larger in size (higher FSC (forward scatter), and SSC (side scatter)) and had higher expression levels of CD38 and NKG2D, suggesting an activated status. The YB1-activated NK cells also had high expression levels of CD11b and CD11c, consistent with NK cell clusters 13 and 14 identified by CyTOF in NOD SCID mice (Figs. 5c–e and 6f). Next, we compared the activity of NK cells isolated from mice treated with PBS or YB1. Production of IFN-γ and expression of CD107a are commonly regarded as functional markers for assessing cytokine production and degranulation of NK cells39. Indeed, NK cells from YB1-treated mice produced more IFN-γ and showed higher CD107a expression ex vivo (Fig. 6g, h). Cytotoxicity assay was performed on the isolated NK cells against YAC-1 cancer cells as previously described34. We assayed effector/target ratios of 3 : 1, 2 : 1, and 1 : 1, and found NK cells from YB1-treated mice had higher cytotoxicity against YAC-1 at all ratios (Fig. 6i), which is consistent with higher levels of granzyme B and perforin after YB1 treatment (Supplementary Fig. 8d, e). Altogether, the results showed YB1-provoked NK cells were larger, had greater cytotoxicity to tumor cells, and had higher expression levels of CD11b, CD11c, NKG2D, and CD38 compared to the NK cells from PBS-treated mice.
| 4 | 0biomedical
| 0Study
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166,793 |
Adherence from the self-report measure was higher than from MPR, but there was substantial agreement between the scales. It is therefore recommended that for practice, self-report or medication possession ratio could be used for adherence measurement as there is substantial agreement between them. However, this should be complemented with laboratory markers like viral load counts. A further study can also be done to ascertain the situation in adults as the study was limited to adolescents whose adherence pathways might be different from those in adults.
| 4 | 0biomedical
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161,796 |
LH: supervision, conceptualization, methodology, software, writing—original draft, resources, formal analysis, data curation, resources and visualization and review and editing. RR: data curation, resources, and visualization. YB: data modeling, software, and data inspection. All authors contributed to the article and approved the submitted version.
| 1 | 2other
| 1Other
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239,382 |
Symmetric conditions are enforced on both spanwise boundaries for the finite foil simulation. The domains extend from the pivot point to 4C at the front, 11C at the rear, 5.5C at the top and bottom. Meanwhile, the tip distance to the maximum spanwise domain is 3.2C. The grid convergence study provided in using an infinite foil with a span length of 6C in Re = 5300 as a comparison of time-averaged thrust coefficient for different resolutions. The force coefficient converges to within 7% of the finer simulations (for two- and three-dimensional simulations) using a resolution of C/Δx = 128. As a balance between the grid resolution and the number of simulations, this resolution is deemed sufficient to capture the dynamics of the flow.
| 1 | 2other
| 0Study
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316,521 |
In the current study, curcumin (Cur) encapsulated into sodium alginate- gum Arabic nanoparticles was characterized, and the antioxidant activity against DPPH was assessed with different time intervals and concentrations of nanoparticles. This is the first time reporting the effectiveness of using sodium alginate/gum arabic-curcumin nanoparticles as an improved delivery tool of curcumin in number of cancer cell lines including MCF7, HepG2, HT29, and A549 cancer cells demonstrating an increased antioxidant and anti-proliferative properties. Therefore, this study supports the use of both polymers in nanomedicine applications.
| 4 | 0biomedical
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196,270 |
Additional file 1: Figure S1. The planar structure of BBSKE. Figure S2. Effects of BBSKE on cellular proliferation. Figure S3. Pretreatment with GSH markedly attenuated the combined treatment-induced cell growth inhibition in gastric cancer cells. Figure S4. The inhibiting efficiencies of p-p38 and p-JNK by BMS-582949 and SP600125 respectively. Figure S5. Molecular docking of BBSKE with TrxR1 protein was carried out with the docking software. Figure S6. BBSKE reduced the toxicity of cisplatin in vivo. Figure S7. The morphology of 3 cases of successful established human gastric cancer organoids (hGCO1-3) under white field microscope.
| 4 | 0biomedical
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243,778 |
3. The authors are recommended to use another phrase instead of “bridge to heaven” as the subthemes does not fit with the title. In addition, it is not “death”, it is “life” which the health staff aims from the beginning to the end. As a last point, the authors are recommended to use a more objective description for the themes.
| 1 | 2other
| 1Other
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190,695 |
Although backslopping is a commonly used fermentation strategy, in practice, many farms feeding LF backslop unintentionally due to the impracticality of sanitising the liquid feeding system before a new batch of feed (see Section 5). Moran et al. found that for wheat fermentation, there was no advantage to increasing the backslopping proportion above 20% (up to 42% was trialed), in agreement with the findings of Dujardin et al. . The 20% backslopping treatment reduced coliforms to the greatest extent, and yielded the highest lactate concentrations and the lowest pH. The authors also agreed with the consensus that high lactic acid concentrations and low pH are the key factors in coliform exclusion in LF. However, they noted that the time of exposure to these conditions is critical for coliform exclusion suggesting a minimum period of 24 h with a pH <4.0, coupled with high lactic acid concentrations , while Dujardin et al. reported that coliforms were still not eliminated after 48 h under similar experimental conditions.
| 4 | 0biomedical
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315,832 |
We exploit the consistency in object motion to establish reliable point correspondences between the sequences, and combine this with edge features to align them with great accuracy (Fig. 1). We model the transformation between the two sequences using a series of TPSs (Wahba 1990). TPS are an expressive non-rigid mapping that can accommodate for the deformations of complex articulated objects. TPS have been used before mostly for registration (Chui and Rangarajan 2003) and shape matching (Ferrari et al. 2010) in still images. We extend these ideas to video by fitting TPS that vary smoothly in time.
| 4 | 0biomedical
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21,033 |
We collected pupillary traces in a total of 20 subjects. An example raw data recording for four single epochs is shown in Figure 1B. We observed that the pupil size started to change after 200 ms following image presentation. Typically, the pupil shows a fast contraction, followed by a slower dilatation. Figure 2A shows the average pupil signals obtained for each condition for the NM group. For neutral images, maximal pupil contraction peaked at 810 ms from the stimulus onset. This initial contraction was followed by a dilatation that did not reach baseline level by the end of the image presentation. This suggests that these images can establish a different pupillary tone as reflected by the prolongation of the under-baseline pupil response. Later, when the natural image was replaced by the pink-noise image, another contraction took place, and despite its greater magnitude, the pupil size returned rapidly to baseline levels. The difference between the steady state reached by the pupillary response after 2 s in the natural images and the pink-noise images cannot be explained by luminance alone since the luminance of the images were comparable among these categories. Indeed, we found no significant difference in luminance between these images (F(2,87) = 2.89, p = 0.06). In the same experimental group, the pupillary response associated to the positive category displayed a similar contraction and dilation profile. As before, dilation reached a steady state level below the baseline. However, this steady state (between 2 s and 4 s) reached a greater magnitude at peak compared to neutral images. We calculated windowed statistics to detect latency differences, but we found a continuous overlap in these intervals (see shaded areas in Figure 2A). As with neutral images, pink-noise images after positive images resulted in a pupillary contraction followed by a dilatation with a rapid tendency to return to baseline.
| 4 | 0biomedical
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271,565 |
Ongoing analysis of genomes from Madagascar and Papua New Guinea ([PNG] to be described in detail elsewhere) have also identified localized variants. The Madagascar group belongs to clade 2.5, is distantly related to other 2.5 sequences from India (separated by ~122 SNVs), and has been designated 2.5.2. The PNG genotype 2.1.7 population is subdivided into 2 distinct sublineages designated genotypes, 2.1.7.1 and 2.1.7.2, with 2.1.7.1 observed more frequently.
| 4 | 0biomedical
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263,705 |
A total of 101 patients were assessed; the 27 patients excluded were from 20 families lost to follow-up and 7 who did not wish to participate (3 for distance issues and 4 for inability or non-desire to participate). The remaining 74 patient families agreed to enrol their adolescents in the study. Of these, one patient was unable to undergo the complete speech evaluation and another was retroactively re-qualified as a case of isolated CP. Thus, the present study included 72 cases.
| 3 | 0biomedical
| 0Study
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42,358 |
The innate immune system could be activated via recognition of specific pathogen-associated molecular patterns (PAMPs) by toll-like receptors which sequentially trigger the cascade of inflammatory responses against the invasion of pathogenic microorganisms1, 2. Most TLRs, upon recognition of PAMPs in microbial components, bind adaptor proteins (e.g. MyD88) which in turn recruit the interleukin-1 receptor-associated kinase (IRAK) complex, including IRAK1, IRAK2, IRAK4 and IRAKM3. Once IRAK1 phosphorylated, IRAKs associate with TNF receptor-associated factor 6 (TRAF6) and lead to the activation of NF-κB and MAPKs signaling4–6. The IRAK-TRAF6 complex induces the phosphorylation and degradation of IκB through the IKK complex, and then activates the nuclear translocation of NF-κB that promotes the expression of various inflammatory genes, including IL-1β, IL-6 for defending against invaders6. However, excessive TLR signaling activation and overproduction of inflammatory cytokines will disrupt immune homeostasis, further may induce the autoimmune and inflammatory diseases7. As such, it is essential to study the mechanisms for the negative regulation of TLR signaling.
| 4 | 0biomedical
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166,081 |
The hydroxamic groups of the MMP-12 inhibitors shown in Scheme 1 are weak acids with predicted pKa values of 8–9. However, previous QM/MM calculations on MMP/inhibitor complexes have shown that the mode of binding of ligands bearing zinc-binding groups, such as hydroxamic, is consistent with a negatively charged ZBG and a neutral carboxylic group for the conserved Glu side chain,50,51 which is largely favored by the solvent and enzyme environment. Thus, the Glu219 residue was modeled in its neutral protonation state, while the hydroxamic group of the ligands was negatively charged.
| 4 | 0biomedical
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249,837 |
The chick CAM assay is an important model in cancer research. The main advantages of this assay pertain to economy and reliability. The use of this model supports a considerable replacement of animal experiments. A disadvantage is the high mortality rate of the embryos and the rejection of tumours after transplantation into the CAM. Moreover, not all tumour cells can produce macroscopically visible colonies over the short time of the experiment. However, we were able to improve the viability rate of the embryos by up to 80% by using a standardised protocol. We established strategies to raise the stability of the spheroids in the CAM, improved the vascularisation of the spheroid, and achieved a threefold increase of the transplanted spheroid volume. The optimisation of the chicken CAM in UM research may expedite preclinical tests and facilitate the development of personalised methods in oncology.
| 4 | 0biomedical
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5,793 |
(A) The genotype-specific rates of food intake are depicted as percentages (%) relative to the intake in control specimens (mef2-Gal4 x w1118) after 40 min of feeding, which was set to 100%. While nep4 knockdown animals (mef2-Gal4 x UAS-nep4 RNAi) exhibited reduced food intake after 10 and 20 min of feeding, Nep4A overexpression animals (mef2-Gal4 x UAS-Nep4A) were characterized by reduced intake throughout the whole measurement (up to 40 min). Animals overexpressing catalytically inactive Nep4A (mef2-Gal4 x UAS-Nep4Ainact) did not exhibit any significant changes in food intake, when compared to controls. Values represent the mean (± s.d.) of at least six independent biological replicates. Asterisks indicate statistically significant deviations from controls (*p<0.05, one-way ANOVA with pairwise comparisons). The lower panel depicts representative images of the genotype-specific food intake at the indicated time points. (B) Changes in the expression of selected dilp genes are presented as percentages (%) relative to expression in control specimens (mef2-Gal4 x w1118), which was set to 100%. Muscle-specific overexpression of Nep4A (mef2 x UAS-Nep4A) reduced the expression of every dilp gene analyzed, while nep4 knockdown in the same tissue (mef2 x nep4-RNAi) resulted in upregulation of dilp2. Animals overexpressing catalytically inactive Nep4A (mef2 x UAS-Nep4Ainact) did not exhibit any significant changes in dilp expression, when compared to controls. Values represent the mean (+ s.d.) of at least three independent biological replicates, each consisting of at least three technical replicates. Asterisks indicate statistical significance (*p<0.1; **p<0.05, one-way ANOVA with pairwise comparisons); n.s. indicates ‘not significant’.
| 4 | 0biomedical
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131,385 |
Plasma protein profile in SAA patients and HD is distinct and shows a good intra-group consistency by PCA and Pearson’s correlation analysis (Figure 1B; correlation coefficient >95%, Figure 1C). Of the 239 identified proteins, 49 had missingness and were removed from further analyses. Among the remaining proteins, 6 decreased and 15 increased proteins in SAA patients were observed (p < 0.05) (Figure 1D; Supplemental Material S1).
| 4 | 0biomedical
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306,112 |
In summary, USP rHuEPO-RS, along with EPO Chemical Reference Substance (CRS) developed by the European Pharmacopoeia, helps to underpin the global framework of quality of methods and equipment used to manufacture rHuEPO products. (35, 36) Each is validated against a separate yet overlapping set of physicochemical methods, thereby providing biosimilar manufacturers with validated standards that satisfy both US and European regulators. (36) Combining these standards with USP’s Erythropoietin Bioassay reference standard for measuring potency gives manufacturers tools for maintaining the quality of their EPO products, which can help reduce the barriers that block access to more EPO products and stimulate competition among manufacturers.
| 4 | 0biomedical
| 1Other
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271,293 |
Clinically, management strategies could be available by stratifying the risk of future attack based on both age-adjusted cut-off values and intraindividual changes in blood GFAP levels. Based on an individual's different strata of attack risk, clinicians could decide treatment initiation, continuation, and escalation/de-escalation of NMOSD patients. For example, it could be possible to set a serum GFAP range for the treatment response of patients and classify patients into treatment-responsive and treatment-resistant groups. This classification would enable precision treatment strategies that quickly change from one option to another suitable before it is too late (e.g., the advent of clinical relapses).
| 4 | 0biomedical
| 1Other
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25,541 |
A 2016 fMRI study (Klucken et al.) compared two groups of heterosexual males: subjects with compulsive sexual behaviors (CSB) and healthy controls. The mean time typically spent watching sexually explicit material weekly was 1187 min for the CSB group and 29 min for the control group. Researchers exposed all subjects to a conditioning procedure in which previously neutral stimuli (colored squares) predicted the presentation of an erotic picture. Compared to controls the subjects with CSB displayed increased activation of the amygdala during presentation of the conditioned cue predicting the erotic picture. This finding aligns with studies reporting increased amygdala activation when substance abusers are exposed to cues related to drug use . Voon et al. also reported that explicit videos induced greater amygdala activation in CSB subjects than in healthy controls. This research converges with animal research linking the amygdala to appetitive conditioning. For example, stimulating opioid circuitry in the amygdala magnifies incentive salience intensity towards a conditioned cue, accompanied by a simultaneous reduction of the attractiveness of an alternative salient target . While the CSB group in Klucken et al. had greater amygdala activation to a cue predicting a sexual image, their subjective sexual arousal was no higher than controls. Interestingly, three of the twenty CSB subjects reported “orgasmic-erection disorder” when interviewed to screen for Axis I and Axis II diagnoses, while none of the control subjects reported sexual problems. This finding recalls Voon et al., in which CSB subjects had greater amygdala-ventral striatum-dACC activation to explicit sexual videos, yet 11 of 19 reported erectile or arousal difficulties with sexual partners. Klucken et al. also found decreased coupling between the ventral striatum and the prefrontal cortex in subjects with CSB compared with controls. Decreased ventral striatal-PFC coupling has been reported in substance disorders and is believed to be related to impaired impulse control .
| 5 | 0biomedical
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105,946 |
We next evaluated the reduction due to drop off over: 1) all 6310 protein-encoding S. cerevisiae genes; 2) most expressed S. cerevisiae genes (top 20%); and 3) least expressed S. cerevisiae genes (bottom 20%). The average reduction in R and ρ over these three sets of genes are depicted in Figs 9 and 10, respectively. It may be noticed that the average reduction over the highly expressed genes is lower than the average reduction over the lowly expressed genes. It is possible that this is related to stronger evolutionary selection for lower drop off rates in genes with higher mRNA levels. Indeed, highly expressed genes “consume” more ribosomes (due to higher mRNA levels), so a given (per-mRNA) drop off rate is expected to be more deleterious to the cell, and a mutation which decreases the drop off rate in such genes has a higher probability of fixation.
| 4 | 0biomedical
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273,155 |
Although highly reproducible, the tension created by the suture lines and the high technical failure associated to severe TA dilatation have limited the use of the suture annuloplasty toward alternative strategies such as the implantation of prosthetic ring or band (54).
| 2 | 0biomedical
| 1Other
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47,120 |
A very interesting study. It highlights the increasing use of WES in diagnosing rare diseases. The authors confirm the findings of ES with Sangers and sequence both the parent and the proband. The manuscript needs editing and rearrangement of text. The paragraph on SME and AME needs/can probably be put together as the introduction. Minor grammar corrections.
| 2 | 0biomedical
| 1Other
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314,648 |
Although diagnostic ICA utilization was reduced using the coronary CTA/FFRCT strategy, among those with obstructive CAD, the proportion of ICA patients who underwent revascularization was 62% (34 of 55). Multiple other studies in various clinical settings, including Emergency Departments, the Veterans Affairs health system, and in various countries, have reported lower diagnostic yield and revascularization rates with a standard of care practice not incorporating FFRCT in the diagnostic pathway . We observed a higher diagnostic yield of cardiac catheterization through improved patient selection combining anatomic with functional data in one platform using FFRCT. This strategy enriched the catheterization-laboratory experience for our patients by sending those individuals to the laboratory who would benefit most from revascularization.
| 4 | 0biomedical
| 0Study
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294,900 |
To date, 13 travel grants have been awarded; 11 for Australian conference attendance and two for travel overseas. When travel was prohibited by the COVID-19 pandemic, funding which had been allocated for travel was re-purposed for collaboration grants which are described below.
| 1 | 2other
| 1Other
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122,763 |
(A) Average g-ratio of myelin sheath thickness was comparable in control and Tgm2-/- mice. p=0.728, unpaired t-test, N = 3 per genotype. (B) The distribution of myelinated axons with respect to the axon diameter in the CC of control and Tgm2-/- mice. p=0.8291, two-way ANOVA, p=0.2524, Gaussian non-linear curve fit, N = 3 per genotype. (C) Axon diameter in the CC is comparable in control and Tgm2-/- mice. Mean ± s.d.; p=0.8771; unpaired t-test; N = 3 per genotype. (D) Number of total axons (myelinated and unmyelinated) is comparable in the CC of in control and Tgm2-/- mice at P28. p=0.7947, unpaired t-test, N = 3 per genotype. Error bars are means ± s.e.m (A–D).
| 4 | 0biomedical
| 0Study
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353,668 |
Given the above, we can conclude that our exercise protocol accentuated LPS-induced AKI, increasing the expression of TLR-4. The positive regulation of TNF-α, NGAL, and TLR-4 observed in trained + LPS compared to sedentary + LPS animals may be due to the decreased AOAH in the liver, the main LPS detoxification enzyme. Considering this decrease in hepatic AOAH, the amount of active LPS in the bloodstream may be higher in trained animals submitted to LPS injection. Further investigation is required to confirm this suggestion and to investigate the impact of different exercise protocols on liver enzymes involved in LPS clearance.
| 4 | 0biomedical
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123,928 |
Total RNA was isolated from colonic tissue (or Caco-2 cells), using TRIzol Reagent (Invitrogen, Carlsbad, CA, USA), according to the manufacturer’s instructions. RNA samples were then standardized and reverse transcribed using a Transcriptor First Strand cDNA Synthesis Kit (Roche, Basel, Switzerland) with an oligo-dT/random nonamer primer mixture. RT-qPCR was carried out using a ‘Roche FS Universal SYBR Green Master’ mixture (Roche), according to the manufacturer’s instructions, and a ‘Viia7’ system (Applied Biosystems, Shanghai, China).
| 4 | 0biomedical
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22,684 |
To further understand why Fn-/- MEFs continued to reside within the collagen scaffold in the absence of fibronectin, we asked whether exposure to fibronectin versus collagen directly affects cell migration speed and persistence. Therefore, cell migration speed and persistence was quantified in single cell assays where fibroblast-populated beads were seeded on manually pulled plasma fibronectin fibers (Fig 3A), since we know that the conformation of fibrillar fibronectin, which is often stretched by the cells, is far more extended compared to that of fibronectin adsorbed to flat glass substrates or directly to collagen gels and that the fibronectin conformational distribution within these single fibers closely resembled those observed in a native 3D extracellular environment . The fibers were either left uncoated or were decorated with rat tail collagen type I (matching that of the 3D scaffolds in this study). The aim here was thus to construct fibers that are similar in their physical properties (diameter, rigidity, etc.), but present either fibrillar fibronectin versus collagen 1-decorated fibronectin fibers. To assess solely how cell migration is affected by the presence of different ECM components presented by single fibers, the migration speed and persistence of individual MEFs was tracked using fibronectin-depleted growth medium. Two major observations can be made: First, while the Fnf/f MEFs and the Fn-/- MEFs were highly persistent walkers on the single plasma fibronectin fibers, collagen I decoration increased the turn-around events for both (Fig 3B and 3D). Almost half of both Fnf/f and Fn-/- MEFs changed migration direction over the course of the observation (Fig 3B and 3C, magenta-colored circles). Second and perhaps surprising, the migration speed of Fn-/- MEFs on plasma fibronectin fibers was significantly higher compared to Fnf/f MEFs (Fig 3B and 3D), but decorating the plasma fibronectin fibers with collagen significantly reduced the migration speed of the Fn-/- MEFs to levels approaching those of Fnf/f MEFs (Fig 3B), while collagen coating had little effect on the migration speed of the Fnf/f MEFs. However, persistently migrating cells on collagen decorated fibers did not show a significantly different average speed when compared to non-persistent cells (assessed for both Fnf/f and Fn-/- MEFs individually using Student’s T tests). The efficacy of the collagen coating covering the Fn-fibers was verified by staining for the different components after having tracked the cells in real-time (Fig 3C).
| 4 | 0biomedical
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124,286 |
The first endoscopic papillectomy (EP) for papillary adenoma (n = 2) was described in 1983, and the first substantial cohort (n = 25) was published 10 years later.1,2 A number of predominantly retrospective case and cohort studies have been published subsequently.3–7 Despite the lack of randomized controlled trials and prospective series, EP for papillary adenoma is considered a relatively safe, minimally invasive treatment for lesions without significant intraductal extension or invasive disease.5 It has proven difficult to generate high-level scientific knowledge on the best treatment algorithm primarily because of low incidence and therefore difficult to conduct large prospective or randomized controlled studies. Subsequently, a consensus for EP practices has not been established. In 2015 the Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy attempted to develop an evidence-based guideline on the role of endoscopy in papillary and duodenal adenomas.8 However, based on the current literature only limited recommendations regarding the optimal diagnostic workup, treatment, and follow-up protocol could be made. Unsurprisingly, at present there remains a wide variety in daily practice, mostly based on individual preferences.9,10
| 4 | 0biomedical
| 2Review
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129,604 |
Eggs laid from 40-week-old Arbor Acres breeder hens were obtained from a local breeder farm (Hapcheon, Korea). A total of 252 eggs were weighed (61.0 ± 0.2 g), labeled individually, and incubated in an incubator (Rcom Co., Ltd., Kimhae, Korea) with standard conditions (37.8 °C and 56% relative humidity) from embryonic days (EDs) 1 to 17, and then 36.8 °C and 70% from EDs 18 to 21. On ED 10, eggs were candled, and a total of 210 remained (61.3 ± 0.3 g) for the trial. Thereafter, the eggs were assigned to one of five treatment groups: 1) un-injected control (CON); 2) distilled water (DW)-injected control (DDW); 3) 5% GABA (G05); 4) 10% GABA (G10); and 5) 20% GABA (G20). DW was used as a diluent-injected control according to a previous study . Within 3 h before the injection, GABA (#A2129 Sigma-Aldrich Inc., St. Louis, MO, USA) was dissolved in DW to obtain 0%, 5%, 10%, and 20% solutions for injection. The solutions were then stored at 30 °C until the injection was complete. The selected injection day was ED 17.5 because in ovo vaccination is usually executed between ED 17.5 to 19.25 , and the target of our injection was the amniotic sac of the embryo. Briefly, on ED 17.5, individual eggs received 0.6 mL of each solution at the blunt end using a 1 mL syringe with a 23-G and 1-inch needle. Therefore, the total amount of GABA injected into each egg was 0, 30, 60, and 120 mg for DDW, G05, G10, and G20 treatments, respectively. Before injection, the blunt end of each egg was disinfected with a 70% ethanol solution and a small hole was drilled using a dental drill (Saeshin, Daegu, Korea). After the injection, the egg hole made was sealed with surgical tape (3M Micropore, Saint Paul, Mn, USA) and placed back in its own incubator. In the case of CON, the eggs were taken out of the incubator and left for the same time without injection, and then returned to the incubator. Each treatment group consisted of 42 eggs (7 replicates of 6 eggs each). The eggs were turned every hour until ED 18.
| 4 | 0biomedical
| 0Study
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100,158 |
In total, 300 patients, enrolled between March 2013 and December 2015, received riociguat treatment in the CTEPH EAS and were included in the full analysis set. Study treatment was completed by 262 patients (87%) (Fig. 1). Thirty-eight patients discontinued riociguat treatment during either the dose-adjustment or maintenance phase. The most frequent reason for discontinuation was an AE (n = 14). A further four patients discontinued during the safety follow-up phase, resulting in 258 patients (86%) completing the entire study. Baseline demographic and disease characteristics are shown in Table 1; most patients were female (62%), in WHO FC II/III (96%), and had inoperable CTEPH (72%). The median treatment duration was 47 weeks (range 0–121 weeks).Fig. 1Patient disposition. *Patients who discontinued treatment prematurely were to enter the safety follow-up phase Table 1Patient characteristics at baselineCharacteristicFull analysis set(n = 300)Switched patients(n = 84)a Treatment-naïvepatients (n = 216)Sex, n (%) Female185 (62)55 (65)130 (60) Male115 (38)29 (35)86 (40)Age (mean ± SD), years63.9 ± 12.565.5 ± 11.663.3 ± 12.7Type of CTEPH, n (%) Inoperable216 (72)64 (76)152 (70) Persistent/recurrent84 (28)20 (24)64 (30)WHO FC, n (%) I5 (2)05 (2) II112 (37)31 (37)81 (38) III175 (58)51 (61)124 (57) IV8 (3)2 (2)6 (3)6MWD (mean ± SD), m374 ± 117b 389 ± 87c 369 ± 125d 6MWD 6-min walking distance, CTEPH chronic thromboembolic pulmonary hypertension, ERA endothelin receptor antagonist, PDE5 phosphodiesterase type 5, SD standard deviation, WHO FC World Health Organization functional class aPatients who previously received an ERA, prostacyclin, and/or PDE5 inhibitor, and who stopped this treatment before starting riociguat b n = 213; last observed value prior to start of study treatment c n = 52 d n = 161
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224,529 |
This study investigated how the candidate biomarker metabolites identified in the block study behaved in the entire data set (SAS/STAT; Version 9.2; SAS Institute Inc. Cary, NC, USA). Generalized Linear Models were applied, and Bonferroni correction (p < 0.10) was used as a false discovery rate post hoc test. The variable endpoints analyzed were P40, P62, birth, miscarriage after Day-40, and metabolic differences between Day-8 and Day-7 embryos.
| 4 | 0biomedical
| 0Study
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290,653 |
Figure 5a displays the comparison of the Raman spectra of R6G (5 × 10−5 M) probe molecules on MoS2/graphene nanohybride substrates that were synthesized with different precursor solution concentrations from 0.06 wt% to 0.32 wt%, measured using the same excitation of 532 nm wavelength. Most of the R6G Raman peaks are visible on all spectra. Especially, the spectra include the R6G fundamental peaks at 613 cm−1 allocated to the C–C–C ring in-plane vibration mode, 773 cm−1 assigned to aromatic C–H bending mode, 1190 cm−1 and 1648 cm−1 allocated to C–O–C stretching mode and the C–C stretching mode, respectively . Among the five spectra, the R6G spectra on the lowest precursor concentration of 0.06 wt% (green) have the lowest R6G peak intensity, indicative of the lowest SERS enhancement. It should be mentioned that MoS2 N-discs are predominant in this sample. In contrast, the highest SERS enhancement is observed on the spectrum for MoS2/graphene nanohybride made with 0.26 wt% precursor concentration (black) on which MoS2 N-donuts are predominant. Quantitatively, the enhancement factor can be estimated using the ratio of the intensity of the R6G Raman peaks on the MoS2/graphene samples made using different precursor concentrations at 613 cm−1 and 773 cm−1 to the ones on the MoS2 (0.06 wt%)/graphene). Figure 5b exhibits the estimated enhancement factor as a function of precursor concentration of the five samples shown in Figure 5a. The maximum enhancement factor of 8.2 was obtained on the MoS2/graphene sample at 0.26 wt% precursor concentration, suggesting that the SERS enhancement is a compromise of the shape, dimension, and density of MoS2 NPs. Interestingly, MoS2 N-donuts are predominant in MoS2/graphene nanohybrides when the precursor concentration is exceeding ~0.20 wt%. The higher SERS sensitivity in this precursor concentration range, especially the peak SERS sensitivity in MoS2/graphene nanohybride made from 0.26 wt% precursor concentration, suggests that MoS2 N-donuts may support LSPR in a more preferable way than other N-discs or other shapes of MoS2 nanostructures.
| 4 | 0biomedical
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157,551 |
Other key differences with E. coli includes the lack of identifiable SQ mutarotase and SQase encoding genes. Interestingly, the isolated strains could grow on the simple SQ glycoside, methyl α-sulfoquinovoside. This suggests that they may harbor an unidentified SQase without homology to known SQases. Finally, both organisms contained a gene encoding an IolG homologue, of unknown function. IolG proteins are NAD(P)-dependent oxidoreductases of the Gfo/Idh/MocA family, and catalyze oxidation of the hydroxyl groups of pyranose and inositol rings (Taberman et al. 2016). Members of this family include inositol dehydrogenase (Idh), which forms 2-keto-myo-inositol (2-inosose) from myo-inositol (Ramaley et al. 1979; Yoshida et al. 2006), glucose-6-phosphate dehydrogenase (G6PD), which forms 6-phosphogluconolactone from glucose-6-phosphate (Rowland et al. 1994), and levoglucosan dehydrogenase, which forms 3-keto-levoglucosan from levoglucosan (1,6-anhydro-β-d-glucose) (Sugiura et al. 2018; Kuritani et al. 2020). Inositol dehydrogenase IolG from Bacillus subtilis has maximal activity on myo-inositol and possesses activity on d-glucose and d-xylose, and produces d-gluconolactone from the former (Ramaley et al. 1979). Possibly, the Arthobacter spp. IolG homologues may convert SQ to SGL, which coincidentally is an intermediate in the sulfo-ED pathway (Felux et al. 2015), although the downstream sulfo-ED genes are missing in these organisms. An alternative possibility is suggested by the Gfo/Idh/MocA family member DgpA from the intestinal bacterium PUE. DgpA catalyzes the oxidation of the 3-hydroxyl group of the C-glycoside puerarin, facilitating the elimination of the aglycon and formation of 3-keto-2-hydroxyglucal (1,5-anhydro-d-erythro-hex-1-en-3-ulose) (Nakamura et al. 2020). A similar process applied to an SQ glycoside could facilitate the cleavage of the glycoside in the absence of an SQase and would give rise to the corresponding 6-sulfo-3-keto-2-hydroxyglucal, the fate of which is uncertain. However, we were unable to identify possible companion genes encoding proteins that would be required to enable the elimination/isomerization/reduction to SQ.
| 4 | 0biomedical
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333,292 |
Another common issue concerning layered lithium- and sodium-containing oxides is their poor cycling stability at elevated temperatures (Wright et al., 2018; Zhou et al., 2020). From structural point of view, the high operating temperatures accelerate the structural evolution of lithium–manganese-rich layered oxides into core–shell structure during cycling along with lattice oxygen extraction and lattice densification, transition-metal migration, and aggregation on the crystal surface (Yu et al., 2018). The transition metal migration during cycling is also responsible for the voltage decay observed at lithium-rich oxides (Pham et al., 2016). The cationic redistribution process between layers has also been established for Mg-substituted P3-NaxNi1/2Mn1/2O2 when used as an electrode in Na-ion cells (Kalapsazova et al., 2020). This process occurring during Na+ extraction is intensified at elevated temperatures and, contrary to the lithium-containing oxides, has a positive impact on the cycling stability (Kalapsazova et al., 2020).
| 4 | 0biomedical
| 0Study
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43,307 |
The MAGNETOM Skyra 3T MRI System (Siemens, Erlangen, Germany) and the standard head coil at DGMIF (Daegu-Gyeongbuk Medical Innovation Foundation) were used to perform blood oxygenation level-dependent (BOLD) fMRI. BOLD-weighted Echo Planar Imaging (EPI) parameters were as follows: Repetition Time (TR)/ Echo Time (TE) = 2 sec/30 msec, field of view (FOV) =210 mm, flip angle = 90°, matrix size = 64 × 64, and slice thickness = 4 mm. For anatomical reference images, 28 axial, 4 mm slice thick, T1-weighted, spin echo images were obtained with a matrix size of 128 × 128 and FOV of 210 mm. Total images were acquired parallel to the bicommissural line of the anterior commissure-posterior commissure.
| 4 | 0biomedical
| 0Study
|
291,406 |
As described above, non-adherence in this patient group tends to be due to forgetting. Many participants described easy and practical solutions that help them to remember their treatment, such as visual reminders (e.g. putting the bright yellow sharps bin on the breakfast bar); linking treatment to particular activities (such as having breakfast); and digital reminders (alerts on a mobile phone, tablet or computer).
| 2 | 0biomedical
| 0Study
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85,245 |
(A-B) rDNA instability for the indicated WT and mutant strains was measured by the ADE2 marker-loss assay. (C) ChIP-qPCR experiments in strains expressing Fob1-TAP or Sir2-TAP proteins. The location of the rDNA primers is indicated on the schematic above the graphs. Data are presented as mean +/- SEM and a t-test was used to compare the means of WT and mutant cultures. (*) P < 0.05. See also S4 Fig.
| 4 | 0biomedical
| 0Study
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187,433 |
SLex immunostaining was assessed through light microscopy by 2 independent experienced pathologists (Li Fu and Fangfang Liu). Both pathologists reevaluated the staining and reached a conclusion by consensus. The antibody staining patterns were scored and calculated as the average of I × P, where I is the intensity of staining (0, 1, 2, or 3), and P is the percentage of positive tumor cells (0%–100%). The intensity of staining was scored as no staining (0), low intensity (1), moderate intensity (2), or high intensity (3). The sLex expression was categorized as negative when the score was below 2.5 or as high when the score was above 6017.
| 4 | 0biomedical
| 0Study
|
116,602 |
Thirty healthy 18–32 year olds (17 female; mean age = 21.87± 3.74) took part in the study. Participants were all right handed, native English speakers, free from psychiatric, neurological, and substance use disorders, and reported a regular sleep schedule of going to bed between 10pm and 1am and waking between 6am and 9am. Participants self-reported that they obtained, on average, 6 hours and 45 minutes (SD = 49 minutes) of sleep the night preceding the day of testing.
| 4 | 0biomedical
| 0Study
|
334,264 |
Linear mixed models were developed following the approach described above for number of radii, absolute web area, number of mooring threads, web asymmetry, web shape, relative mean mesh height (mesh height divided by cephalothorax width) and relative web area (web area divided by cephalothorax width squared) with species as a fixed factor and location as a random factor. To ensure normality, the relative web area was logarithmic transformed. We used the same posthoc test described above for pairwise species comparisons, where the full model showed species was a significant variable. All models were built with the lmer() function from the lme4 package80 in R81. P values were found with the Type II Wald F-test.
| 4 | 0biomedical
| 0Study
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380,949 |
Resistance to platinum-class agents has been shown to be mediated by intracellular levels of GSH, an antioxidant demonstrated to thwart platinum agent efficacy and toxicities in vitro and in vivo3. Conversely, GSH pool depletion has been shown to sensitize cancer cells to cisplatin and carboplatin18. We therefore hypothesized that ATQ-induced mROS production depletes GSH pools in a concentration-dependent manner and posited that this effect could underpin the sensitization. Accordingly, we measured intracellular GSH levels in H460 cells at 1, 4, and 24 h post-treatment using 10 or 30 μM ATQ (Fig. 3A). A significant decrease in GSH was observed using 30 μM ATQ but not 10 μM ATQ at 4 and at 24 h. We then used the specific inhibitor of GSH synthesis, buthionine sulfoximine (BSO), to validate that GSH pool depletion induces sensitization to cisplatin or carboplatin in our hands (Fig. S7). Indeed, the effect of both platinum agents was potentiated by BSO.Fig. 3ATQ-mediated GSH pool depletion underpins platinum sensitization.A H460 cells were allowed to attach overnight then assayed for glutathione (GSH) using a colorimetric assay (Promega) at 1, 4, or 24 h post-ATQ treatment. B PI-exclusion time-course rescue flow assays. Attached H460 cells were preincubated for 2 h with 0–10 mM n-Acetyl cysteine (NAC), then 2 h co-incubation with 0–30 μM ATQ or DMSO, and then a further 24 h incubation with carboplatin 5 μM (left), 10 μM (middle) or 20 μM (right). C Representative histograms from (B). D, E Colony-forming assays using H460 cells. Cells were plated and allowed to attach for 4 h, pre-treated with 0–10 mM NAC for 2 h, then co-incubated for 2 h with 0–30 μM ATQ or DMSO, and then a further 24 h co-incubation with (D) carboplatin or (E) cisplatin. Data representative of N = 3 experiments and shown with mean ± SD. Significance determined using one-way ANOVA according to: *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.
| 4 | 0biomedical
| 0Study
|
126 |
We now zoom in on a more detailed analysis and comparison of the results of the different experiments and exploit the differences in masker configurations to search for the presence of possible MOCR effects. With tonal ON-frequency maskers, cochlear gain changes due to the MOCR can affect both the probe and masker response. Tonal OFF-frequency maskers, of a frequency lower than the probe, perform masking in the tail of the masker's excitation pattern. Of course, with an OFF-frequency masker, higher masker levels are required to reach masking threshold. OFF-frequency maskers are of interest because they behave linearly with masker level, and, at the tonotopic location of the probe, are believed to be unaffected by the MOCR (Kawase et al., 2000; Cooper and Guinan, 2006). If the precursor indeed triggers the MOCR, this activation will cause a gain reduction for both ON-frequency masker and probe. However, with an OFF-frequency masker a gain reduction due to MOCR activation would only affect the probe and not the masker, effectively making the masker more potent. Thus, the expectation is that, when preceded by a precursor, ON-frequency maskers show a smaller response reduction than OFF-frequency maskers.
| 4 | 0biomedical
| 0Study
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157,776 |
Yet, other reports in rats suggest that intrinsic hippocampal neural activity may not flow in only one direction17,18. Recent methods applying two-dimensional models to electrode grid recordings over the cortical surface have revealed oscillations traveling in multiple directions supporting versatile inter-regional communication and timing13,19–23. We hypothesized that analogous grid recordings over the extensive human hippocampal surface24,25 may reveal other versatile wave properties relevant for the flexible assimilation of its topographical connections. We also sought to understand whether wave propagation extends to low frequencies in delta (1–4 Hz) and alpha (10–15 Hz) ranges, since they may herald distinct cortico-hippocampal communications26–28.
| 4 | 0biomedical
| 0Study
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88,734 |
Blood was obtained from healthy human donors. Informed consent was obtained from all donors and this work was carried out in compliance with the ethical committee guidelines of Shoolini University, Solan. Peripheral blood mononuclear cells (PBMCs) were isolated from the blood using a Ficoll-Paque Plus system according the instructions of the manufacturer. The blood sample was diluted with the same volume of PBS. Afterward, the diluted blood sample was carefully layered on the Ficoll-Paque Plus (Amersham Biosciences, Piscataway, NJ, USA). The mixture was centrifuged at 400× g for 40 min at 18–20 °C. The undisturbed lymphocyte layer was cautiously transferred out. The lymphocyte was washed and pelleted down with three volumes of PBS twice and resuspended in RPMI-1640 media supplied with 10% fetal bovine serum (FBS), 2 mM l-glutamine and antibiotics (100 µg/mL penicillin and streptomycin). Cell counting was accomplished to determine the PBMC cell number with an equal volume of trypan blue .
| 4 | 0biomedical
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|
287,393 |
Univariate analysis and adjusted mortality analysis on all-cause mortality and amputation after PSM are presented in Tables 2 and 3. From the univariate analysis, all-cause mortality was not associated with paclitaxel-coated device use (HR 0.99; 95% CI 0.90–1.1; P = 0.8431). The adjusted analyses did not differ from the previous results (Table 2). After PSM, the rate of amputation event was higher in patients with a drug-coated device than a non-drug-coated device from the univariate analysis (HR 1.614; 95% CI 1.26–1.58; P ≤ 0.001) and the multivariable adjustment (HR 1.614; 95% CI 1.46–1.78; P ≥ 0.001) (Table 3).Table 2Univariate and multivariate analysis of all-cause mortality after propensity score matching.ReferenceCrudeAdjustedHR95% CIP-valueHR95% CIP-valueNon-drug coated device0.990.90–1.10.84310.9920.91–1.080.8464SexMale1.3111.19–1.45 < 0.00011.0591.05–1.06 < 0.0001Age1.0031–1.010.23711.11–1.220.0613DMNo1.2731.16–1.4 < 0.00011.3521.23–1.49 < 0.0001HTNNo1.2911.15–1.44 < 0.00011.1080.99–1.24.0811CHDNo1.0250.95–1.110.5416WarfarinNo0.7080.61–0.82 < 0.00010.8360.72–0.970.0193AntiplateletNo0.270.25–0.29 < 0.0001NOACNo0.520.44–0.61 < 0.00010.460.39–0.54 < 0.0001CCI1.051.02–1.080.001Devices on procedureNo1.0791.03–1.130.0007ER visitNo1.341.01–1.780.0446DM diabetes mellitus, HTN hypertension, CHD coronary heart disease, NOAC new oral anticoagulants, CCI Charlson comorbidity index, HR hazard ratio, ER emergency room.Table 3Univariate and multivariate analysis of amputation free survival after propensity score matching.ReferenceCrudeAdjustedHR95% CIP-valueHR95% CIP-valueNon-drug coated device1.6141.26–1.58 < 0.00011.6141.46–1.78 < 0.0001SexMale1.3291.18–1.49 < 0.00011.0061–1.010.0187Age1.0071–1.010.00611.2751.13–1.43 < 0.0001DMNo2.4982.19–2.85 < 0.00012.4532.14–2.81 < 0.0001HTNNo1.191.04–1.360.00990.9310.81–1.070.2973CHDNo0.7360.67–0.81 < 0.0001WarfarinNo0.7240.6–0.870.00050.8410.7–1.010.064AntiplateletNo0.5240.48–0.58 < 0.0001NOACNo0.5770.48–0.7 < 0.00010.6310.52–0.77 < 0.0001CCI1.0981.07–1.13 < 0.0001Devices on procedureNo1.0851.04–1.13.0003ER visitNo2.281.73–3 < 0.0001DM diabetes mellitus, HTN hypertension, CHD coronary heart disease, NOAC new oral anticoagulants, CCI charlson comorbidity index, HR hazard ratio, ER emergency room.
| 4 | 0biomedical
| 0Study
|
195,238 |
Based on the above findings, the CRISPR system is related to bacterial virulence; thus, analysis of the CRISPR sequence is helpful in studies of the mechanisms of bacterial virulence changes. The role of these systems in regulating virulence is undoubtedly a new and exciting research field. However, due to the limitation of the number of strains, isolation area, and time, there is no unified assessment of the relationship between bacterial CRISPR and virulence, indicating that bacterial CRISPR and virulence should be further studied. Understanding the mechanism of virulence control exerted through the CRISPR-Cas system will provide a deeper perspective on gene regulation. Future studies should explain how these systems promote the pathogenesis of bacteria, which will help identify bacteria and provide defence strategies during infection.
| 4 | 0biomedical
| 0Study
|
356,318 |
Limited literature is available indicating the association of SH3RF3, PAXIP1, and CD3E, targeted by blv-miR-B1-5p. As part of a panel of 6 genes, SH3RF3 is used to establish the prognosis of patients affected with ALL. When SH3RF3 is expressed, in conjunction with CAMSAP1 and PCGF6, the outcome of ALL is favorable; however, when this genes is not expressed in ALL patients, the outcome of the disease is less than desirable (48). Blv-miR-B1-5p, may have a role in inhibiting expression of SH3RF3 to establish leukemia in cattle. The hematopoietic stem cells (HSC) are responsible in providing the organism with mature blood cells. The HSC reside in bone marrow pockets in the interphase of the bone and bone marrow. The PAXIP1 or PTIP genes are epigenetic regulators responsible for maintaining the bone marrow pockets. Downregulation of PAXIP1 results in downregulation of HSC. Downregulation of PAXIP1 has also been associated with downregulation of leukemia cells (49). The role of blv-miR-B1-5p in the regulation of PAXIP1 is unclear given that downregulation of PAXIP1 would result in a downregulation of leukemia cells. It has been established that CD3E is overexpressed in patients with T-cell ALL (50), and that patients with this condition and that a remission of the disease can be obtained with an anti-CD3E recombinant immunotoxin (51). Potentially, blv-miR-B1-5p has a role in the overexpression of CD3E in T-cell ALL patients; however, further studies would be needed to establish this effect. A similar process could be occurring for BLV infection in cattle.
| 4 | 0biomedical
| 0Study
|
157,194 |
Due to SF’s great characteristics, it has been shown that it is a promising biomaterial as a coating agent in terms of drug delivery . In a recent study, SF was used by Kwon et al. (2021) for coating probiotic strains. The aim of this study was to improve the stability of probiotics in the human body. By performing this experiment, the authors observed that the survival rate of the target probiotics that were SF coated was improved. Furthermore, by using SF as a biomaterial, cell adhesion was significantly increased .
| 4 | 0biomedical
| 0Study
|
247,290 |
Curcumin showed to be 2-fold less toxic for the monogenean compared to cedrol, a potent anti-Vibrio anguillarum agent (but ineffective against V. harveyi), and lacked negative effects on the sea bream cell line. This well-known polyphenolic compound of turmeric (Curcuma longa Linn.) has been previously tested in fish feed as an immunostimulator and booster in the antioxidant status and protein content . Although it has been employed against many protozoan and few trematode infections in humans over the years , it has been recently introduced in aquaculture as an experimental and efficient treatment of the ciliates Ichthyophthirius multifiliis infecting carp and Philasterides dicentrarchi infecting turbot .
| 4 | 0biomedical
| 0Study
|
170,583 |
In terms of reflection, less than half of the students describing a critical incident reflected upon it. This indicates that students who experience challenging or conflicting situations in a clinical setting do not process them at a cognitive level, which is important in order to achieve academic or personal benefits from the experience. Critical reflection has been linked with better professional development (Andersen, Hansen, Søndergaard, & Bro, 2008; Boenink, Oderwald, De Jonge, Van Tilburg, & Smal, 2004; Mann, Gordon, & MacLeod, 2009; Plack, Driscoll, Marquez, & Greenberg, 2010). If medical students do not engage in reflection to the level of integrating the learning from the reflection into future practice, then it is likely they are not progressing to the reconstructive phase of the clinical learning, where behavior change occurs. Through reflection medical students can gain new insights regarding clinical practice through self-awareness and critical, reflective evaluation (Carr & Carmody, 2006). As a result, many educational institutions have incorporated the ability to reflect as an objective of their curricula, premised on a belief that reflective thinking is something that can be developed rather than a stable personality trait (Sandars, 2009). In addition, the fact that reflection at different levels can be assessed means that it can be potentially improved (Boenink et al., 2004).
| 4 | 0biomedical
| 0Study
|
341,300 |
It should be considered that the use of a turbine pocket spirometer to measure VC during expiration is less meaningful than the use of a pneumotachograph. Since the measurement is not a purely mechanical determination of the measured values, neither a respiratory curve nor detailed measurement results are recorded digitally. The determination of the coarse value can only be read off visually by the measuring personnel on the spirometer scale at 100 ml intervals.
| 4 | 0biomedical
| 1Other
|
13,473 |
In this section, we reported accuracies of all patients based on the classification of EEG signals from all 12 electrodes (see Tables 3A,B). For the reported accuracies (online) we distinguished the cardboard presentation (Table 3A) from the standard presentation mode (Table 3B). In Table 3A, reached performances when using a re-trained classifier (ReC, offline) not considering occipital electrodes were added. Performances improved over sessions when using the cardboard paradigm (Table 3A).
| 4 | 0biomedical
| 0Study
|
41,909 |
Although there is only one exposure indicating unequivocal glaciotectonic activity associated with the ridges in the central Fenland, comparison of the form and distribution of the ‘island’ ridges strongly suggests that they all represent ‘hill-hole pair’ (ice-pushed ridge) glaciotectonic landforms (cf. ). The Fenland ridges are characterized by an arcuate-shaped plan morphology on the proximal sides, steep marginal slopes on the distal sides, subparallel ridge-alignment, their internal geology and the occurrence of basinal depressions on the potential (concave) up-glacier side of the ridges. Finally, the occurrence of meltwater deposits on the tops of the ridges has been recorded from comparable landforms by Bluemle & Clayton and implies that the gravels and sands, and the lacustrine deposits on the ‘islands’ can also be explained by local glacial meltwater release.
| 3 | 2other
| 0Study
|
329,760 |
Sex differences in TARGET-OS gene expression. a Heatmap of all differentially expressed genes (adj. p value < 0.05) identified between male and female TARGET-OS samples. Top color bars indicate the sex (male = black, red = female), if metastasis was detected at diagnosis (light blue = metastatic, dark blue = non-metastatic), and age at diagnosis in years (darker green = older patients). Sample and gene order of the heatmap was dictated by unsupervised hierarchal clustering using Euclidean distance and complete clustering. Side color bars indicate the chromosomal location of the gene. b Overlap between enriched pathways in differentially expressed genes between male and female mouse-OS and TARGET-OS. c Overlap between differentially expressed genes between healthy male and female osteoblasts and TARGET-OS
| 5 | 0biomedical
| 0Study
|
160,814 |
Histology of the kidneys, testes, salivary glands (serous and mucinous glands), liver, spleen and femur did not reveal any morphological abnormalities for the treated mice (Figure 5 and Figure 6, results not shown for the lowest activity). No histological alterations of glomeruli (capillaries and Bowman’s capsule), tubules (proximal/distal convoluted tubules and collecting ducts), interstitium (no inflammation or fibrosis) or blood vessels (no congestion and haemorrhage) of the kidneys were observed (Figure 5).
| 4 | 0biomedical
| 0Study
|
58,692 |
Legend: Nature - invasiveness of the technique employed; Embryo stage – range of stages where the embryo was suitable or was used in the study; Compared to what traditional technique – when it was the case - that a new proposed technique had its efficacy compared to a traditional and well established one; On what parameters – when there was such comparison, did it occur, if not the case, in what primary parameters the authors evaluated the embryos; Sample size – the quantity of embryos used on the study; NA – not available; ND – not determined.
| 4 | 0biomedical
| 0Study
|
188,455 |
Permutation test was used to investigate whether the performance of the fusion model was statistically significantly improved compared with those before fusion. The test was performed between: (1) the model trained on MRI before fusion versus the fusion model, and (2) the model trained on blood parameters before fusion versus the fusion model. For both models, we calculated the errors between the chronological ages and the predicted ages, and obtained two sets of errors. We first calculated the mean values of the two sets, and obtained the true difference of the two mean values. These two sets of error values were then combined into one set and randomly divided equally into two groups, and the difference of the two mean values was calculated as well. We permutated for 999 times and plotted the distribution of the 1,000 (999 fake difference and the true difference) values to test if the true difference was within top 5% (p <.05), which indicated that the improvement of fusion model was statistically significant. We completed this permutation test based on the R‐package (https://www.r-project.org/).
| 4 | 0biomedical
| 0Study
|
79,055 |
Cells were washed in ice-cold 1 x PBS (phosphate-buffered saline) and lysed in lysis buffer containing 25 mM Tris-HCl, pH 8.0, 137 mM NaCl, 2.7 mM KCl, and 1% Triton X-100 supplemented with a commercial protease inhibitor mixture (Sigma, St. Louis, MO, USA). Equivalent amounts of protein (50 μg) were separated on 10% SDS-polyacrylamide gel electrophoresis and then electro-transferred onto a polyvinylidene difluoride membrane (Immobilon; Merck Millipore, Amsterdam, Netherlands). The membrane was probed with mouse monoclonal anti-p53 (DO-1; Santa Cruz Biotechnology, Santa Cruz, CA, USA), rabbit polyclonal anti-TAp73 (GeneTex, Irvine, CA, USA), rabbit polyclonal anti-TAp63 (GeneTex), rabbit polyclonal anti-p21WAF1 (Cell Signaling Technologies, Beverly, MA, USA), rabbit polyclonal anti-BAX (Cell Signaling Technologies), rabbit polyclonal anti-RUNX2 (Cell Signaling Technologies), rabbit polyclonal anti-PARP (Cell Signaling Technologies), mouse monoclonal anti-γH2AX (2F3; BioLegend, San Diego, CA, USA) or with rabbit polyclonal anti-actin antibody (20–33, Sigma) at room temperature for 1 h. After extensive washing in Tris-buffered saline containing 0.1% Tween 20 (TBS-T), the membrane was incubated with horseradish peroxidase-conjugated goat anti-mouse or anti-rabbit IgG (Invitrogen) at room temperature for 1 h. Visualization of horseradish peroxidase was achieved by using an enhanced chemiluminescence detection system (ECL; GE Healthcare Life Science, Piscataway, NJ, USA).
| 4 | 0biomedical
| 0Study
|
215,444 |
Next, WT mice were intranasally instilled with either r-venestatin (50 μg) in PBS (25 μL) or PBS alone, followed by 2% carrageenan or Gla-BSA (50 μg) in saline (50 μL) after 1 h. The lungs of saline-instilled mice were used as negative controls. Mice were euthanized after 48 h, and the lungs were collected and fixed.
| 4 | 0biomedical
| 0Study
|
89,946 |
Another deduction from the model is that by comparing a set of reference molecules with known RH the RH-dependent barrier specificity can be calculated. As an example, if the Q(B) of two molecules with RH of 3 and 4 nm is greater than the Q(B) of two proteins with RH of 4 and 5 nm, then the conclusion is that the barrier is more discriminative between 3 to 4 nm than between 4 and 5 nm. This allows conclusions on the physiological properties of the barrier to be made.
| 4 | 0biomedical
| 0Study
|
354,838 |
In summary, our study reinforces new evidence about the association between periodontal diseases and asthma, and it reveals a novel and close association between gingivitis and otitis media/externa. However, additional studies are needed to verify these findings and to clarify the mechanism underlying the associations.
| 4 | 0biomedical
| 0Study
|
105,228 |
Mortality data for Carteriospongia foliascens was fitted to nonlinear regression curves to calculate the lethal concentration (LC) at which 50% (LC50) and 10% (LC10) of the population died. Nonlinear regression of the dose−response curve (R2 = 0.8675, AICc = 85.23) met assumptions of normality and homoscedasticity and there was no evidence for a lack of fit in the replicates test (P = 0.694). After the 28 d exposure period, the LC50 (and 95% confidence intervals range) for mortality in Carteriospongia foliascens was 40.6 mg L−1 (range: 28.9–57.0 mg L−1) and the LC10 was 21.5 mg L−1 (range: 13.1–35.2 mg L−1). Mortality data from Coscinoderma matthewsi did not meet model assumptions and LC values could not be calculated.
| 4 | 0biomedical
| 0Study
|
30,418 |
Knowledge and perception of the referral system: Only 34.7% of the participants demonstrated good knowledge of what a referral system is and its operationalization (Figure 2). Likewise, the proportion of respondents with good perception of a referral system was 30.0% (Figure 2). The most common reasons provided for engaging in self-referrals to higher levels of health care include desire for quality of services (35.7%) and availability of competent staff (35.2%) (Table 2). Other reasons were reputation of hospital (33.8%), location of the hospital (33.3%), past experiences (31.9%), attitude and friendliness of hospital staff members (30.9%) and proximity to place of residence (29.1 %) (Table 2). Malaria was the commonest health problem (39.7%) for which respondents engaged in self-referrals to higher level of health care. Other common health problems reported as reasons for self-referral included upper-respiratory tract infection (URTI) (12.7%), medical and follow-up checks (11.3%), eye problems (5.0%), birth deliveries (4.0%) and dental procedure (3.7%). Less common health reasons for self-referral include gynecological problems (3.3%), accident/injury (3.0%), surgery (2.7%), sexually transmitted diseases (2.0%) and heart/respiratory complications (1.0%) and ear problems (0.7%) (Figure 3). More female respondents (76.0%) compared to male respondents (64.0%) significantly engaged in self-referral (p=0.02, X2 = 5.14). Less respondents with a tertiary education would self-refer compared to those with a secondary education; however, this is not a significant finding (p=0.54, X2 = 0.37). Likewise, respondents who were ever married (p=0.19, X2 = 1.69), currently enrolled in the National Health Insurance Scheme (NHIS) (p=0.60, X2 = 0.28), on income grade levels 1-6 (p=0.44, X2 = 1.66) and got health information with regards to referrals from colleagues (p=0.12, X2 = 5.90) would not engage in self-referrals compared to their counterparts; though these were not significant associations (Table 3). Respondents with good knowledge would not self-refer compared to the respondents with poor knowledge. (p=0.02, X2 = 5.43) (Table 3).
| 4 | 0biomedical
| 0Study
|
89,743 |
Plants contain complex regulatory machineries to optimize the seasonal timing of flowering. Our present discovery of AS-mediated FT2 regulation in temperate grasses not only extends the manner of flowering control by FT but also reveals florigen control at both the transcriptional and posttranscriptional levels during the process of floral transition (Fig. 7c). In respect that multiple alternatively spliced forms of FT orthologous genes have been detected in Platanus acerifolia53, it will be interesting to determine whether the blocking flowering complex formation by splice variants is the same FT regulatory mechanism in trees.
| 4 | 0biomedical
| 0Study
|
134,563 |
A clinical diagnosis was OLP in reticular lesions in the bilateral buccal mucosa, lateral border, and inferior tongue face. The warty plaque was clinically diagnosed as leukoplakia. An incisional biopsy was performed on the buccal mucosa on both sides; in the left side, the biopsy involved both the reticular lesion and the warty plaque.
| 4 | 0biomedical
| 3Clinical case
|
296,313 |
The overall prevalence of urinary tract infection was 23.7% (100/422) (95% CI: 19.3–27.5). Out of 259 community-acquired UTI symptomatic patients, 19.3% (50/259) (95% CI:16.0–24.7) were culture-positive and 30.7% (50/163) (95% CI:23.3–38) were culture-positive for hospitalized patients (Table 2). Of the total 422 urine specimens processed, 74.2% (313/422) showed no bacteriuria growth and 2.13% (9/422) showed insignificant bacterial growth. Significant growth was present in 23.7% (100/422) samples with 22.99% (97/422) single growth and 0.71% (3/422) in mixed growth with two organisms in hospitalized patients (Figure 1). Three out of four hundred twenty-two (0.71%) samples with two bacteria each were isolated, making the number of bacteria isolated to be 103 with the isolation rate of (24.4%). From a total of 103 different uropathies bacterial isolated, 53 (51.46%) were hospital-acquired setting isolates, and 50(48.54% were community-acquired setting isolates (Table 3). Sixty-one (59.22%) were Gram-negative bacilli and 42(40.78%) were Gram-positive cocci (Figure 2).
| 5 | 0biomedical
| 0Study
|
390,511 |
The 11 LFs used to determine whether a given EEG clip contains seizure onset were written collaboratively by a clinical neurologist and a postdoctoral computer scientist over the course of less than 8 cumulative hours of dedicated time using a labeled development set of 200 reports. These LFs simultaneously leverage the structure of the EEG report along with unstructured information contained in the raw text, which can often cover several paragraphs. The Snorkel software package is then used to create probabilistic labels for each report.30 Due to the length of these reports and their highly variable structure, the LFs for this application represent a particularly compelling example of how domain-specific knowledge can be used to inform heuristic development.
| 4 | 0biomedical
| 0Study
|
395,329 |
Our results indicate that irisin may be one of the mediators by which physical exercise and muscle tissues modulate cartilage metabolism, demonstrating the existence of a biological cross-talk mechanism between muscle and cartilage. Taken together, our data demonstrate the role of irisin in osteoarthritic chondrocyte metabolism and suggest that irisin can be used as a cartilage-regulating factor, which directly targets chondrocytes and enhances cell anabolism while decreasing catabolism, suggesting a potential therapeutic role in treating OA.
| 4 | 0biomedical
| 0Study
|
199,609 |
Successful amplification was verified on a 1% agarose gel, and a second nested PCR was performed to attach sequencing adaptors and sample barcodes with 2.5 μl of the sample from the first PCR with a total of 11 cycles and an annealing temperature of 55 °C (OG125/OG126).
| 3 | 0biomedical
| 1Other
|
76,964 |
In the sensitivity analysis, larger number of CAG repeats is associated with a faster decline over time, in all domains except behavior. Met/Val HD gene carriers decline faster than Val/Val HD gene carriers in motor domain. Met/Met HD gene carriers decline faster than Val/Val and Met/Val HD gene carriers in cognitive domain, but the associated P-value is no longer significant after Bonferroni correction (see S2 Table).
| 4 | 0biomedical
| 0Study
|
241,441 |
Displacements from isocenter occurring during isocentric robotic rotations of the treatment couch have been recently reported in a study on the 3D surface imaging system AlignRT to verify patient positioning following couch rotations . During isocentric rotations, the mean displacement AlignRT vectors for the phantom, immobilized, and non-immobilized volunteers were found to be 0.1 ± 0.1 mm, 0.8 ± 0.1 mm, and 1.1 ± 0.2 mm respectively.
| 4 | 0biomedical
| 0Study
|
33,282 |
In this study we did not investigate the duration of the antibody response, although one of our HBV responders had an HbSAb concentration of less than 10 mIU/mL approximately a year after completion of vaccination. This is an area of further investigation, although it is unclear whether maintenance of an adequate HbSAb concentration, once achieved, is associated with breakthrough HIV infection in treated individuals [5, 35]. Furthermore, the small sample size, given the characteristics of the subjects identified for study and the availability of archived specimens for testing, did not allow for further analysis of T-cell populations that could have an impact on the development of B-cell responses. However, our study points to possible mechanisms for the responsiveness to HBV vaccination in HIV infected individuals [4, 5] even after cART treatment [4, 6] and provides a rational base for future studies focusing on the germinal center dynamics that could direct HBV vaccine efficacy.
| 4 | 0biomedical
| 0Study
|
31,341 |
To our knowledge nobody has analyzed human metabolic changes upon intense light therapy yet. The effects of intense light therapy in humans are recognized and already widely used. As such intense light therapy is used to treat winter depression [59, 60], but also might have effects on preventing delirium or might improve sleep in general [62, 63]. Our findings show that intense light significantly increased miR-21 in human plasma samples which was associated with increased phosphofructokinase activity, the key enzyme of glycolysis. These findings indicate that our in vitro and murine in vivo findings are translatable into a human system. More detailed studies on intense light therapy in humans will hopefully help us to further dissect those mechanisms. However, it needs to be pointed out that it is unclear if light activated glycolysis in humans would be indeed cardioprotective as seen in murine studies .
| 4 | 0biomedical
| 0Study
|
48,565 |
The PI was specifically referring to the development of community action plans for adaptation to climate change, collection of weather data on indicators of droughts or floods and identification of intermediate host snails for Schistosomiasis and malaria vector mosquitos in their water sources.
| 2 | 0biomedical
| 1Other
|
24,530 |
A prior study showed that expression of either lamin B receptor (encoded by Lbr) or lamin A/C (encoded by Lmna) is required to maintain a conventional nuclear architecture in non-rod cell types13. To determine whether expression of these two genes is associated with selective chromatin closure in rods, we examined the open chromatin and transcriptional profiles of these loci in detail (Fig. 4). The Lbr locus harbors a single open chromatin peak overlapping the TSS, with comparable ATAC-seq signal in rods, green cones and blue cones (Fig. 4A). It was previously shown by antibody staining that that lamin B receptor is downregulated in both rods and cones as they differentiate13. Nevertheless, we detected modest levels of Lbr transcript in both rods and blue cones (Fig. 4C), suggesting that either the level of lamin B receptor in adult photoreceptors is regulated post-transcriptionally, or that it is below the limit of detection by antibody staining. While the open chromatin profile surrounding Lbr is similar in rods and cones, two peaks at the Lmna locus are selectively closed in rods—one overlapping the gene promoter and another ~6.5 kb upstream (Fig. 4B, red boxes). The rod-specific closure of these peaks is correlated with a marked reduction in the level of Lmna transcript in rods (Fig. 4D), consistent with the rod-specific reduction in Lamin A/C protein levels reported previously13. Taken together, these data indicate that rods selectively downregulate Lmna at the transcript level, and this downregulation may be mediated by the selective closure of two upstream open chromatin regions. Furthermore, these findings indicate that NRL mediates chromatin closure at the Lmna locus, either directly or indirectly, offering a mechanistic link between the expression of a key rod cell fate determinant and the cell’s inverted nuclear architecture.
| 5 | 0biomedical
| 0Study
|
294,893 |
The CREATE Program has been developed across multiple platforms, including provision of funding opportunities, professional development activities and network building. Key to its success has been the wide-ranging collaborative support of the peak bodies in respiratory health, Lung Foundation Australia (LFA) and Thoracic Society of Australia and New Zealand (TSANZ). All aspects are overseen by the Program Advisory Committee (PAC) which ensures the CREATE program objectives are met, reviews the budget to determine activities we are able to support, and considers ways to leverage additional funding. The PAC has evolved to comprise key opinion leaders (two CRE-PF steering committee members, two ECR representatives (one clinical and one scientist), two mentor representatives with special interest in academic development (at different career stages), and management/administrative support. The PAC meets at least quarterly with ad hoc meetings as required.
| 1 | 2other
| 1Other
|
167,726 |
Between February 2014 and June 2016, 287 patients at our hospital underwent a combination strategy of therapeutic TACE and RFA to treat HCC. The diagnosis of HCC was made according to the diagnostic criteria used by the European Association for the Study of the Liver . These diagnostic criteria are defined as either two imaging techniques showing typical features of HCC, positive findings on one imaging study together with an α-fetoprotein level of more than 400 ng/mL, or a histologic diagnosis of HCC. All patients signed an informed consent and gave permission to use their clinical data for our research. Our research protocol conformed to the ethical guidelines of the World Medical Association Declaration of Helsinki and was approved by our Institutional Review Board.
| 4 | 0biomedical
| 0Study
|
50,554 |
In the current form, VGC-KiMo1 source code includes two Markov formulations for the Kv11.1, best known as the hERG K+ channel. Any other channel can be added to the source code in addition to the current one, as well as different Markov models and other voltage protocols. The experimental data chosen for the model validation was not used for the development of the model's parameters and belongs to a different cell line than the one used to originally derive the parameters for the M-model (HEK cells), see SM (Section 2: Validation). The performance of the original parameters is fairly good but corrections were needed to reproduce the data from CHO cell line, suggesting that the published set of parameters is robust and reliable. A preliminary version of VGC-KiMo has also been used recently to simulate WT hERG and a variant using experimental data from HEK cell line (Guo et al., 2015; Perissinotti et al., 2015).
| 4 | 0biomedical
| 0Study
|
280,910 |
To test this hypothesis, we sequenced the genomes of (n = 33–39) randomly chosen diploid lines from VL_B (1 and 2), VL_C, M, and H crosses, as well as (n = 34) diploid and (n = 36) triploid lines from L crosses soon after mating and at the end of the experiment. We measured the rates of aneuploidy (chromosome gain and loss) and loss of heterozygosity (LOH) resulting from mitotic recombination within chromosomes, two typical GIN hallmarks64,65. We looked at the diploid lines of these crosses, reasoning that crosses with more intense GIN would also have more unstable diploid lines.
| 4 | 0biomedical
| 0Study
|
165,178 |
Legionella pneumophila is a Gram-negative bacterium and a member of the class of opportunistic premise plumbing pathogens (OPPPs), a group of pathogens with common features that include the formation of biofilms and resistance to commonly used disinfection approaches such as the use of thermal treatment, chlorination, and biocides. Other OPPPs that pose a danger to human health include Mycobacterium spp. and Pseudomonas aeruginosa .
| 4 | 0biomedical
| 1Other
|
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