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Several scores were developed in order to quantify atherosclerotic burden by CCTA but most of them do not include all those plaque features: the segment involvement score (SIS) uses the total number of segments with plaque, obstructive or non-obstructive (119); the segment stenosis score (SSS); and the CAD-RADS are based on degree of stenosis (119, 120). On the other hand, the Adapted Leaman Score (121) and, more recently, the Comprehensive CTA Score (122) assess all those plaque characteristics. Leaman Score is well-validated as a strong prognostic marker and demonstrated better cardiovascular event prediction when compared to SIS and SSS (123, 124). In a recent study, the Comprehensive CTA Score was superior to the CADS-RAD in predicting ACS (122).
| 4 | 0biomedical
| 2Review
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73,584 |
The studies were approved and performed in accordance with the institutional guidelines for the care and use of laboratory animals established by the Ethics Committee for Animal Experimentation of the University of Barcelona and the Catalonian Government (CEEA-UB Ref.493/12, DAAM: 6905).
| 1 | 0biomedical
| 1Other
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159,317 |
Secondary outcomes were changes in food insecurity, quality of life, physical function, and nutritional status after the intervention. Food insecurity was measured using the Household Food Insecurity Scale, a scale adapted and validated for the Portuguese population from the USDA Household Food Security Survey Module . The tool is applied at the individual level and collects data on food insecurity status for the whole household. Using a score ranging from 0 to 14, households were classified into different categories of food insecurity: food security (score of 0), low food insecurity (score between 1 and 5 for households with children and between 1 and 3 for households without children), moderate food insecurity (score between 6 and 9 for households with children and between 4 and 5 for households without children), and severe food insecurity (score between 10 and 14 for households with children and between 6 and 8 for households without children) .
| 4 | 0biomedical
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51,206 |
Phylogenetic analysis of these 48 putative LHCs in T. oceanica (CCMP 1005) led to their classification into the four previously described clades (Fig 5, Tables 1 and 2, S2 Table) [95–97]: the main Chl a/c Lhcf (26 predicted proteins), the red algal-like Lhcr (10 predicted proteins), the related clade Lhcz (three predicted proteins), and the LI818-like clade Lhcx (eight predicted proteins). The additional clade around Tp17531 has been added, given that at least 5 different diatoms have a protein that clusters here , including T. oceanica (this study). Furthermore, the Lhcf clade can be divided into three subclades: Lhcf- Group I-III.
| 4 | 0biomedical
| 0Study
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87,500 |
Underweight, overweight and obesity are known risk factors for NCDs [17, 18]. Raised BMI (overweight/obesity) is a major risk factor for cardiovascular diseases, diabetes, hypertension, musculoskeletal disorders and some cancers [11–13]. The overall impact of obesity/overweight on physical and mental health as well as health-related quality of life is significant . In countries where the economic impact of obesity has been studied, its direct (arising from preventive, diagnostic, and treatment services) and indirect (related to decreased productivity, increased absenteeism and restricted activity etc.) costs have been estimated to be enormous. In the UK, the direct and indirect costs of obesity have been estimated to be far in excess of 2 billion pounds sterling per year , while in the US, absenteeism arising from obesity alone has been estimated to cost as much as $4.3 billion annually .
| 4 | 0biomedical
| 2Review
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109,120 |
Perinexal width correlates with pre-existing atrial fibrillation. (A) Representative TEM image from the Right (RAA, n = 8) and Left (LAA, n = 4) atrial appendages from the same patient (top). Wp is wider in LAA relative to RAA independent of observer (bottom). (B) Representative TEM images from the RAA of a patient with a history of AF (MAZE procedure, n = 10) and without a history of AF (n = 29) (top). Both blinded observers found in 39 patients that mean Wp between 30 and 105 nm is significantly larger in patients with pre-existing AF relative to those without (∗p < 0.05, bottom).
| 4 | 0biomedical
| 0Study
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366,563 |
We also explored differences between the sets of affinities associated with distinct PDZ domains. Given the methodological differences described above, we performed a two-way ANOVA, taking both domain identity and methodological variation into account, and using a post-hoc Tukey’s HSD test in order to evaluate the hypothesis that higher affinity peptides may be available for some domains than for others. Assuming that the selected affinities are representative, of 1540 pairwise comparisons between affinity estimates for 56 single domains, 94 showed padj values <0.05. 95% confidence intervals are shown in Table S5 for the differences in estimated affinities for each of these comparisons. We then tabulated 200 affinities of engineered sequences for 12 different PDZ domains, giving greater depth of coverage to a smaller number of domains, (Table S6). We repeated the analysis and found 22 of the possible 66 pairwise comparisons of domain affinity ranges exhibited statistically significant differences, including 5 pairings seen using endogenous target affinities, and 17 new pairings (Table S7). For ease of visualization, we also performed a simplified analysis comparing peptide affinities for seven different domains, all obtained using ELISA-based assays (Fig. 7B). A one-way ANOVA with Tukey’s HSD test reveals multiple differences. For example, while the Erbin PDZ domain bound a number of peptides with affinities as low as 10 nM, the highest affinity peptide for the SCRIB PDZ3 domain was 1600 nM (padj < 0.005). We similarly find a statistically significant difference between CAL and PSD-95 PDZ2, both measured by FP (Fig. 7C). All of the phage display-derived experiments, measured with ELISA, were from the same group, whereas different labs, including ours, engineered the CAL and PSD-95 PDZ2 peptides for FP measurements (Amacher et al., 2013, Roberts et al., 2012, Runyon et al., 2007, Skelton et al., 2003, Tonikian et al., 2007, Vouilleme et al., 2010, You et al., 2006). Interestingly, even better targeting of PDZ proteins can be achieved by leveraging avidity effects and the presence of multiple domains, for example, Bach et al. reveal 10-100x stronger inhibitor binding to PSD-95 PDZs 1&2 by using a dimeric peptide, then when targeting each PDZ domain individually (Bach et al., 2012).
| 4 | 0biomedical
| 0Study
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157,868 |
A molecular dynamics trajectory for a 3 × 3 × 3 supercell of GB1 containing 108 monomers was computed using AMBER MD (Case et al., 2005; Doshi and Hamelberg, 2009; Maier et al., 2015; Tian et al., 2019). The coordinates of the X-ray structure of GB1 (PDB:2gi9 Franks et al., 2006b) were taken as a starting conformation. To the supercell, 108 PO4 3− counter ions were added. 12,852 explicit water molecules were added, followed by charge balancing with sodium ions giving an overall box size of 75.591 Å × 107.152 Å × 150.822 Å. The ff19SB (Tian et al., 2019) forcefield was used for the GB1 proteins, with OPC water (Izadi et al., 2014) and GAFF cocrystallites (Wang et al., 2004). After minimization, the system was replicated and heated to the temperatures indicated in the figures (280, 290, 300, 310 K). The systems were then simulated for full 400 ns runs. For each, a 2 fs timestep was used with a cut-off of 11 Å for non-bonded interactions. Temperatures were maintained using a Langevin thermostat, and the SHAKE algorithm (Ryckaert et al., 1977) was applied to all bond lengths involving a hydrogen atom. Anisotropic pressure scaling was used with periodic boundary conditions.
| 4 | 0biomedical
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20,969 |
We make a number of observations. First, levels of question reliability were unexpectedly low (Table 6). Mean question kappa for all modules was 0.447; question kappa for the adult module was 0.398.A kappa value >0.75 is generally accepted to reflect excellent agreement beyond chance; a value <0.4 represents poor agreement; and a value in the range 0.4–0.75 represents fair to good agreement . Question reliability in the long form of the VAI was fair at best.
| 2 | 0biomedical
| 0Study
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83,201 |
In microaerobic conditions (microtiter plates), Y128 grew more slowly than Y73 (t test, p value 2.379 × 10−06) (Fig. 2; Additional file 1), likely due to the disruption of key signaling pathways during the adaptation of Y128 to anaerobic growth in YPX media [25, 26] (Fig. 2). In general, hybrids isolated from fermented beverages grew more slowly than Y73 (t test, p value 1.551e−06) and the synthetic hybrids made with Y73 (t test, p value = 9.741e−05) (Fig. 2a). Thus, hybrid status itself does not enable better growth in ACSH; instead, the specific parents of the hybrids likely confer the relevant properties.Fig. 2Synthetic hybrids have intermediate kinetic parameters or display heterosis compared to their parents during ACSH microtiter growth. The kinetic parameter averages (n = 2) of normalized values (see “Methods”) of maximum growth rate (µ, defined as (ln(OD2) − ln(OD1))/(T 2 − T 1)) and maximum OD600 from Y73 hybrids (A, B) and Y128 (C, D) are represented. By definition the normalized value of the reference Y73 strain is 0, and values above this threshold are better than the reference. Normalized values for Y128 are represented by a dashed blue line. Synthetic hybrids generated from crosses with the haploid derivatives Y73 and Y128 are represented by red and blue dots, respectively. Previously isolated synthetic hybrids from other industrial applications are represented by black dots. The values of the non-S. cerevisiae parents are represented by colored lines according to the legend. Se: Saccharomyces eubayanus, Sk: Saccharomyces kudriavzevii, Sm: Saccharomyces mikatae, Su: Saccharomyces uvarum
| 4 | 0biomedical
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263,246 |
Our findings are congruent with previous studies focused on individuals at risk for psychosis (Tarbox et al., 2013) and around the onset of first psychosis. (Payá et al., 2013; Chang et al., 2013; Horton et al., 2015), suggesting that variation in cognitive and premorbid social features is associated with different early trajectories of premorbid adjustment.
| 4 | 0biomedical
| 0Study
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195,774 |
Quantitative real-time PCR was carried out using a SYBR Green Master Mix kit (GeNet BIO Inc., Daejeon, South Korea) in a real-time thermal cycler (Rotor-Gene Q, QIAGEN, Germany). The thermal profile for the reactions consists of 2 min at 94°C for initial denaturation; then 40 cycles for 30 s at 94°C, 30 s at 62°C, and 45 s at 72°C for annealing temperature; and one cycle for 5 min at 70°C for the final extension.
| 4 | 0biomedical
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152,598 |
All project partners support the dissemination of the recommendations following project completion. To promote the accessibility and long-term safeguarding of the research data and results for the scientific community, the consortium will report comprehensively and transparently on the project and, regardless of the results, prepare national and international publications (with open access, where possible). Furthermore, the project team will make electronic research data (protected by data protection and copyright) available for secondary use in response to verifiably justified requests.
| 1 | 2other
| 1Other
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194,797 |
Chemerin is a novel chemoattractant 14 kDa protein, described as retinoic acid receptor responder protein 2 (RARRES2), secreted as a prochemerin. This inactive precursor is changed into the active molecule by coagulation and inflammatory serine proteases . Chemerin and the receptor of chemerin, chemokine-like receptor 1 (CMKLR1, also known as ChemR23) are almost exclusively expressed and synthesized in white adipose tissue . Swensson et al. confirm that adipokines such as chemerin are also produced in several tissues apart from adipose tissue including human serum albumin .
| 4 | 0biomedical
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386,747 |
The intellectual property of this research is protected by the Brazilian patent number BR1020150308191. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
| 1 | 2other
| 1Other
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183,107 |
Another important distinction to be discussed, is the Virtual Reality approach – exergames and serious games. Exergames are the commercially available games designed primarily for general healthy population and accessible for anyone having the equipment at home or in clinic. Due to a wide variety of scenarios and intensity levels it can be successfully applied in the home-based telerehabilitation of neurological patients . Serious games however, are specifically designed for rehabilitative purposes for a particular limitation, are less entertaining and more task-oriented. The potential limitation of exergames is that their complex interfaces may not be compatible with postural or mobility constraints, or can be cognitively challenging for a person with a disability . Confusion and disappointment of being unable to use the system can result in non-compliancy. Flexibility and task-orientation of the virtual reality games is therefore imperative, based on a qualitative patient experience review of Lewis and Rosie . It was found that adult neurological patients are seeking more rehabilitative benefits of therapeutically principled design, rather than just playing games [43, 44]. On the other hand, exergames can be perceived as a more enjoyable, fun activity that is distracting from daily problems, since it does not distinguish the patient with special needs from otherwise healthy users. It is also easier to obtain cost- and availability-wise, to vary games and to use it together with caregiver or family members for some social interaction [28, 44].
| 4 | 0biomedical
| 2Review
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379,335 |
Carbon fibres (CFs) are used as reinforcement for polymer composites, being among prospective materials in an aerospace domain . An increased focus on carbon fibre-reinforced polymers (CFRPs) is specified by a unique set of their technically valuable properties, such as their high specific strength, low tensile strength at deformation, high thermal stability and conductivity. The main requirements to expand their applications are to enhance their mechanical properties while maintaining cost effectiveness of manufacturing process and final cost of the product.
| 2 | 2other
| 1Other
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335,418 |
After the network was inferred, we analysed characteristics of the transmission network, including the number of sequences (nodes), links (edges), and the degrees which each individual in the network was defined as the number of links with other individuals. Correlates of clustering were investigated using bivariate analyses and multivariable logistic regression models, and the groups analysed included both all individuals and clustering versus not clustering individuals . The topological properties and parameters of the CRF08_BC networks (e.g. nodes, edges, density, and clustering coefficients) were computed with the Cytoscape version 3.2.0 NetworkAnalyzer tool (https://med.bioinf.mpi-inf.mpg.de/netanalyzer/index.php) .
| 4 | 0biomedical
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165,095 |
For this reason, a modified MEX 3D printer will be presented, which, in addition to processing continuous carbon fibers, is also capable of processing natural fiber materials without conversion or other efforts. Furthermore, the printhead is designed in such a way that other fibers, such as glass fibers, can also be processed. With the help of this manufacturing system, specimens with a height of 4 mm are produced which are then subjected to tensile and flexural tests. In order to make the range of specimens as extensive as possible, both prepreg (flax and carbon) specimens and composites in which continuous flax or carbon fibers are combined with the matrix (PLA) in-situ are investigated in this paper. The flax fiber specimens are additionally varied in the fiber volume fraction in order to be able to investigate the influence of the fiber volume on composite properties. Finally, the tensile and flexural test results are discussed.
| 4 | 0biomedical
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141,261 |
Social control, in contrast, is understood as an ability to influence other agents’ behavior through the use of sanctions (Das and Teng 1998). It is well known in the game-theoretic literature that the implementation of effective sanctioning mechanisms is often difficult and impractical since sanctioning is often costly (a second-order dilemma). A form of sanctioning in the case of Hawala, which does not incur significant costs to the sanctioning player, is the exclusion of fraudulent players from further interactions. Such form of sanctioning is particularly effective if the exclusion is not only effected by the exploited agents, but turns into a social sanctioning mechanism applied by several agents. Such a mechanism requires some memory, monitoring, or communication on reputations. A similar operationalization is given by Sasaki and Uchida (2013) in a game-theoretic model in which they provide stability results for equilibria in which fraudulent players get successfully excluded from a cooperative population [related work can also be found in Stanley et al. (1994) and Hauk (2001)]. In Hawala, for instance, defectors may be expelled from the hawaladar community. The threat of ostracism should diminish the potential of opportunistic behavior.
| 1 | 2other
| 0Study
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333,063 |
164 renal tumor samples were studied. One hundred of these samples corresponded to clear-cell carcinomas (ccRCC), 16 to papillary tumors, and 21 chromophobe tumors. Subtype information was not available for 27 tumors. Of these 164 samples, clinical data were available for 142 patients. Twenty-three percent of the patients suffered a relapse and the median of follow-up was 54 months. The median overall survival was 57 months. Clinical characteristics of these patients were summarized in Table 1.
| 4 | 0biomedical
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378,214 |
The Podlesí granite crops out in the western part of the Erzgebirge and is composed of relatively older barren biotite granites followed by F-enriched Sn-bearing albite–topaz–biotite granites. The most fractionated residual melts of these magmas gave rise to small intrusions of extremely F-, P- and Li-rich granites making up the Podlesí stock (Fig. 2b, Breiter et al. 2005). The Podlesí granite suite forms a tongue-like intrusion of albite–topaz–protolithionite granite (stock granite) with the upper contact rimmed by a marginal pegmatite. At a depth of 40–100 m, the stock granite is intercalated with flat dykes of albite–topaz–zinnwaldite granite (dyke granite). Prominent layering and unidirectional solidification textures indicate extreme enrichment of fluxing elements and undercooling of the crystallised melt. Metasomatic greisens are subordinate.
| 1 | 2other
| 1Other
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317,488 |
QUE content in WML-P doubled after conditioning for 4 h, which can be explained by the breakdown of other flavonols containing QUE in their structure, that is, RUT, MAL, ISQ, ISR and was similar to those reported by Kim and Jang . It is speculated that up to 50% of the antidiabetic effect of WML extracts depends of the presence of chlorogenic acid and rutin. Chlorogenic acid can weaken glycogenolysis and reduce glucose uptake and has strong antioxidant properties . Rutin protects against cancer and inhibits the peroxidation of LDL cholesterol. The content of rutin in conditioned WML-P was close to those found in WML var. Yun711, Qiangsang1, 7946, Fengtian5 from eastern China . We found that CHL and RUT are present in WML-P in significant quantities. However, CHL can easily disintegrate during processing so that every technological process can change the ratio of caffeic acid to chlorogenic acid.
| 4 | 0biomedical
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269,346 |
Finally, when considering both supply and demand for meal access, measures from our 2SFCA analyses corroborate many of the previously mentioned trends. First, there was a considerable drop-off in accessibility in the regular school year during COVID-19; meal accessibility in spring 2020 was roughly one-third the accessibility in spring 2019 (Table 4).
| 1 | 2other
| 0Study
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352,165 |
Recordings of interviews were transcribed by the principal investigator and two data entry clerks. The transcripts were checked for content against the audio recordings by the research assistant. The transcripts were copied onto NVivo 10 (QSR International) software for coding.
| 2 | 0biomedical
| 0Study
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218,619 |
Wu et al. (2017a) reported that XIST is upregulated in ESCCs and performed an oncogenic progression through regulation of the miR-101/EZH2 signal pathway (Fig. 1A). Then, another group reported that XIST induced carcinogenesis through the miR-494/CDK6/JAK2/STAT3 signal pathway in EC, which provided a potential means for investigation of EC (Fig. 1B) (Chen et al. 2019a). Additionally, Wang et al. (2021) showed that downregulation of XIST suppressed the malignant behaviors in part by antagonizing the miR-129-5p/CCND1 signal pathway in EC (Fig. 1C).Fig. 1XIST mediates mechanisms involved in digestive system tumors. A XIST could promote the expression of EZH2 by targeting miR-101. B XIST could promote the expression of CDK6/JAK2/STAT3 by targeting miR-494. C XIST could promote the expression of CCND1 by targeting miR-129-5p. D XIST could promote the expression of MACC1 by targeting miR-497. E XIST could promote the expression of TGF-β1 by targeting miR-185. F XIST could promote the expression of JAK2 by targeting miR-337. G XIST could promote the expression of PXN by targeting miR-132. H XIST could promote the expression of MAPK1 by targeting miR-132-3p. I XIST could promote the expression of ZEB1 by targeting miR-200b-3p. J XIST could promote the expression of EZH2 by targeting miR-137. K XIST could promote the expression of WNT1 by targeting miR-34a. L XIST could promote the expression of NRP-2 by targeting miR-486b-5p. M XIST could promote the expression of HIF-1A by targeting miR-93-5p. N XIST could promote the expression of PAX5 by targeting miR-338-3p. O XIST could promote the expression of FOXK1 by targeting miR-497-5p. P XIST could promote the expression of SGK1 by targeting miR-124. Q XIST could promote the expression of ROR1 by targeting miR-30a-5p. R XIST could promote the expression of PKM2/PKM1 by targeting miR-137. S XIST could promote the expression of EGFR by targeting miR-133a. T XIST could promote the expression of iASPP by targeting miR-140/124. U XIST could promote the expression of YAP by targeting miR-34a. V XIST could promote the expression of ZEB1 by targeting miR-429. W XIST could promote the expression of TGF-β2 by targeting miR-141-3p. X XIST could promote the expression of Notch1 by targeting miR-137. Y XIST could promote the expression of PDK1 by targeting miR-139-5p. Z XIST could promote the expression of MAPK1 by targeting miR-194-5p
| 4 | 0biomedical
| 2Review
|
180,904 |
The aim of this pilot study was to assess if LC-OCT may non-invasively enhance the treatment monitoring of BCC. In general, the response of BCC to non-surgical treatment is assessed by clinical inspection which, however, cannot exclude the persistence of subclinical disease responsible for relapses. On the other hand, post-treatment biopsies for histopathology confirmation of resolution are rarely performed, as they only analyze partial samples. Additionally, multiple biopsies impair the advantages of a lack of invasiveness and good aesthetic results due to the use of non-invasive treatments . Based on this, the use of non-invasive techniques able to recognize sub-clinical signs of BCC persistence is advisable, and some experiences have been published utilizing dermoscopy, reflectance confocal microscopy, and optical coherence tomography .
| 4 | 0biomedical
| 0Study
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326,688 |
Frost tolerance of the collection was evaluated under field and controlled conditions. The field experiment was carried out at the INRAE (National Research Institute for Agriculture, Food and Environment) experimental station of Clermont-Ferrand Theix, France (45.72 °N latitude and 3.02 °E longitude at an altitude of 890 m) during the growing season of 2007–2008. Sowing date was 09 October 2007 and the date of emergence was 26 October 2007. Plots were sown in a randomized complete block design with three replicates. Weeds and diseases were controlled chemically.
| 2 | 0biomedical
| 0Study
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349,220 |
Effect of QiShen YiQi pill (QSYQ) on heart structure and function in rats. (A) Echocardiography of rat heart. (B) Left ventricular end-diastolic diameter in rats. (C) Interventricular septal thickness in rats. (D) Left ventricular posterior wall thickness in rats. Data are expressed as mean ± SD. *P<0.01, #P<0.05.
| 4 | 0biomedical
| 0Study
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383,500 |
In line with our hypothesis, we found the melanopsin-mediated pupil response, the PIPR, was greater after 4 weeks of additional daytime light exposure. This change in PIPR suggests that in patients with glaucoma, the melanopsin activity in viable ipRGCs can adapt to different light levels if sustained over a certain period. Why might we think that additional daytime light exposure over 4 weeks is an adaptation response of the melanopsin system? In a previous study, we had demonstrated that the PIPR to a bright narrow-bandwidth short wavelength light modulates with long-term changes in light timing, such as seasonal changes of daylight (36, 47). In the current study, we did not change the light exposure timing, but enhanced brightness of light exposure in the morning over 4 weeks. We found a greater PIPR at the end of 4 weeks without any substantial change in timing of rest-activity, sleep duration or 24-h amplitude as assessed from rest-activity recordings. The significant correlation with higher relative amplitude and inter-daily stability (both derived from rest-activity cycles over 4 weeks) with higher PIPR after LE weeks suggests that there may be a common mode of action conveyed by melanopsin, even though this correlation is not taken as evidence for causality.
| 4 | 0biomedical
| 0Study
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16,994 |
Linear measurements of both the C model and digital model were reproducible. Moreover, there was no significant difference in most linear measurements between the digital models and the C models. However, there were significant differences in the amount of crowding due to the accumulation of errors that occurred in single measurements. The differences in crowding were not dependent on the severity of crowding (>4.5 mm and <3.0 mm). In addition, the differences did not have a clinically meaningful effect (mean difference = −.02–.86 mm). Thus, as with C models, digital models can also be used for measuring crowding in severe crowding (>4.5 mm) cases. However, the use of digital models for cases of less crowding should be considered.
| 4 | 0biomedical
| 0Study
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24,175 |
Translational inhibition of inducible nitric oxide synthase (iNOS) is reversely correlated with miR-146a expression. RENCA, CT26, and TRAMP-C2 tumor cells lines (106 cells), and RAW 264.7 macrophage-like cells (106 cells) were incubated with or without the combined stimulation of IFNγ (100 U/ml) and LPS (1 µg/ml) for 24 h. (A) A representative western blot analysis for iNOS expression and (B) a representative histogram depicting EMMPRIN expression in RENCA cells (light gray, isotype control; blue, no stimulation; hatched yellow, with the combined stimulation). (C) Accumulation of nitrites, the stable product of nitric oxide (NO), reflecting inducible nitric oxide synthase (iNOS) activity; (D) densitometric analysis of western blots for iNOS protein expression; (E) iNOS mRNA accumulation; (F) accumulation of miR-146a-5p expression; (G) mean fluorescence of EMMPRIN protein expression; (H) accumulation of EMMPRIN mRNA (n = 5–6 in each group).
| 4 | 0biomedical
| 0Study
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356,985 |
We first assessed the nuclear translocation of GLI1 in H929 and OPM2 pre- and post-culture in the same well as that of the MSCs. We found that human H929 cells showed an increased nuclear localization of GLI1 and that the coculture with MSCs did not significantly alter the GLI1 translocation (Figure 5A,B). Importantly, OPM2 cells displayed a relatively low GLI1 activation (Figure 5C) that was observed upon same-well coculture with MSCs (Figure 5C,D). Concomitantly, we analyzed GLI1 activation on MSCs in control and post-cocultures with PCs. We found that both H929 and OPM2 cells (i.e., CD138 positive cells) were able to suppress the SHH signaling pathway on MSCs (i.e., CD90 positive cells, Figure 6A,B). These evidences support the hypothesis that myeloma cell lines reduce the SHH signaling pathway on MSCs, thus, inhibiting osteoblastogenic differentiation.
| 4 | 0biomedical
| 0Study
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152,833 |
Summary of OTUs identified at the species level in all groups. There were 2069 core species were present in all groups. The UC group had the most unique species (800). NG: normal group; UC: UC model group; UC + MOX: moxibustion group; UC + MES: mesalazine group; NG + MOX: normal rats with moxibustion group
| 3 | 0biomedical
| 0Study
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157,818 |
We assessed whether a bidirectional TW was traveling in one of its prominent directions versus the other based on frequency, amplitude gradients, or the topography of oscillation amplitude over the hippocampal surface. For each bidirectional TW (all instances except the predominantly unidirectional frequencies in Participant 2; see Supplementary Fig. 2), we took all valid timepoints in which the wave was traveling within 45° of either of its two preferred angles (again excluding timepoints with R2 values less than their own 99% CI), the direction being the binary class label (condition) for each data point. We utilized the entire baseline period to balance out adjacent timepoint similarities; total timepoints for each angle (note: resampled to 30 Hz sampling rate, see above) are provided in Supplementary Table 4. We compared the proportion of timepoints going toward/away from the temporal pole (ratio) by frequency using a Spearman correlation. We compared anterior-posterior amplitude gradients (mean z-scored amplitude across timepoints from the 16 electrodes in the anterior half of the grid minus the same from the posterior half) between the two direction conditions using a paired t-test (11 instances).
| 4 | 0biomedical
| 0Study
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369,622 |
The current study represents a descriptive examination of difficulty accessing non-emergency surgical care in Canada from 2005–2014. This study extends the work by the Fraser Institute through establishing the first Canadian population-based estimate of a wide variety of types of difficulties accessing surgical care over an extended duration and examining personal and surgery-related factors associated with difficulties accessing surgical care. Over 15% of individuals who required non-emergency surgery reported difficulty accessing that surgery, and rates of experiencing difficulty significantly increased across the study duration. Further, nearly 60% of individuals who experienced difficulty accessing surgical care cited a lengthy waiting time for their surgery. Those who endorsed difficulty waited on average 75 days longer for surgery than those who did not, in line with prior research indicating surgical patients commonly wait longer than is recommended . Finally, individuals who experienced difficulty were more likely to have their surgery cancelled or postponed by a surgeon or the hospital compared to those who did not experience difficulty.
| 4 | 0biomedical
| 0Study
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317,769 |
The disease can lead to increased mortality on account of large vessels, CNS, pulmonary and gastrointestinal systems involvement, particularly due to delayed diagnosis and treatment. In most patients with BD, arthritis can be managed with colchicine. IFNα, azathioprine and TNFα blockers may be tried in rare cases with resistant, longer lasting and disabling attacks. Therefore, the main target of treatment in BD is to prevent irreversible damage that mostly occurs early and active phase of the disease, and to prevent exacerbations of mucocutaneous and joint involvement, usually not causing damage but affecting QoL.39,40
| 4 | 0biomedical
| 2Review
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279,150 |
As indicated by the analysis of soil characteristics (pH, OM, HS and their fractions, ammonium nitrogen and available micro- and macronutrients), soil flushing affected the properties of the soil, but the magnitude and direction of the change depended on the WA that was used.
| 1 | 2other
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54,206 |
Post-run, the data was processed using Protein Discoverer (version 1.4., ThermoFisher). Briefly, all MS/MS data were converted to mgf files and the files were then submitted to the Mascot search algorithm (Matrix Science, London UK) and searched against a custom database containing the sequences of the C. subterraneum E1, E2, Ubq-FL (full length pro-ubiquitin including the CGEPIRRAA propeptide) and UBQ-GG (mature ubiquitin ending with the di-glycine motif) and the S. acidocaldarius Mre11/Rad50 proteins along with a number of contaminant sequences such as keratins and the digestion enzymes. The search settings employed were a fixed modification of carbamidomethyl and variable modifications of oxidation (M), deamidation (N/Q) and the ubiquitin modification TVGG (C/K). The peptide and fragment mass tolerances were set to 25 ppm and 0.8 Da, respectively. A significance threshold value of p < 0.05 and a peptide cut-off score of 20 were also applied.
| 4 | 0biomedical
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201,552 |
There was no significant difference in median OS (CIRT: 68.1 [95% CI, 44.0-102.6] months; en bloc resection: 58.6 [95% CI, 25.6-123.5] months; P = .57), median PFS (CIRT: 46.2 [95% CI, 33.3-75.7] months; en bloc resection: 40.7 [95% CI, 18.1-82.3] months; P = .55), local recurrence (CIRT: 9 of 47 [19.1%]; en bloc resection: 10 of 47 [21.3%]; P = .80), distant metastasis (CIRT: 14 of 47 [29.8%]; en bloc resection: 12 of 47 [25.5%]; P = .65), urinary retention (CIRT: no, 31 of 47; yes, 16 of 47; unknown, 0 of 47; en bloc resection: no, 20 of 47; yes, 16 of 47; unknown, 11 of 47; P = .34), or need for colostomy during or after treatment (CIRT: 9 of 47 [19.1%]; en bloc resection: 11 of 47 [23.4%]; P = .6) (eTable 2 in the Supplement). Most patients did not experience a change in their FMS scores from baseline to last follow-up or before recurrence; however, a higher percentage of patients had worse scores following treatment in the en bloc resection cohort, which was not statistically significant (34.0% vs 19.1%; P = .16). Patients who underwent en bloc resection had significantly higher rates of peripheral motor neuropathy and higher severity according to Common Terminology Criteria for Adverse Events, version 4.03 (CIRT: grade 0, 42 of 47; grade 1, 3 of 47; grade 2, 1 of 47; grade 3, 1 of 47; unknown, 0 of 47; en bloc resection: grade 0, 18 of 47, grade 1, 8 of 47; grade 2, 5 of 47; grade 3, 3 of 47; unknown, 13 of 47; P = .003). Additional outcomes are summarized in eTable 2 in the Supplement. The cumulative incidences of local recurrence and distant metastasis are shown in eFigure 1 in the Supplement.
| 4 | 0biomedical
| 0Study
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157,780 |
For each participant, a segment of the recording was selected as a baseline period for further analyses (40–190 s for each participant, selected to avoid signal artifacts and to overlap with behavioral task periods in awake participants). We calculated wavelet power spectra across this baseline recording period for each electrode (‘Methods’) and predominant individual (preferred) frequency peaks were identified from the adjusted spectral profiles for subsequent analyses (‘Methods’; Supplementary Fig. 1), similar to prior study approaches12,13. We explored a range of 1–15 Hz and found 13 unique preferred frequencies across all six participants (Supplementary Table 2).
| 4 | 0biomedical
| 0Study
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268,085 |
Figure 11 shows the results of MMPBSA calculations applied to the trajectory from molecular dynamics simulations. According to the results, the binding sites have similar binding energy (−58 ± 3 kJ·mol−1 and −49 ± 3 kJ·mol−1 for Site 1 and 2, respectively). Moreover, the results revealed the Van der Waals as the predominant interaction of the complex, which reinforced the result obtained from Van’t Hoff analyses.
| 4 | 0biomedical
| 0Study
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365,515 |
Thirdly, the experiment is done for the three algorithms over 1500 transactions. The execution time is presented in Table 8. We found that whatever the minimum support value the proposed ARM algorithm is the best. Table 8 is depicted as a graph in Figure 4.
| 1 | 2other
| 0Study
|
95,216 |
Data were obtained with three independent experiments in most cases. One-way ANOVA and post hoc Bonferroni Comparison Test were used to determine the differences between groups of the data obtained from PCR and western blot by using GraphPad Prism (V6.0) for all the studies except the mouse paw volume data where Two-way ANOVA and Bonferroni post hoc test were used. P-values < 0.05 were considered statistically significant.
| 3 | 0biomedical
| 0Study
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153,290 |
One of the hot topics of research in radar, sonar, and communication engineering like cognitive radios is detection . Detectors are the hub of radar systems and have extensively been addressed in the past . The most commonly used detection method is cross-correlation. However, there are several other methods in the research as well. Singular vector-based methods have gained quite a popularity in the recent past . SSVD is one of the recent contributions, where singular value decomposition (SVD) is used to decompose the received data matrices. The resulting singular vectors are formulated to form a detection test statistics, comprising all the singular vectors obtained from every channel in the system.
| 1 | 2other
| 1Other
|
38,578 |
This analytic strategy is ideal in cases where the dependent variable is a characteristic of alters or ties since aggregation to the ego level results in a loss of information. In all multivariate models, we prevent cluster confounding (Seaman et al. 2014) by including contextual variables (i.e. aggregated versions of alter characteristics) for all level-1 measures that vary within egos (e.g. alter gender and percent of alters who are female are both included). Interactions are detected using pooled regression models with an interaction term. Significance of interactions is determined using Chow-type tests of the equality of coefficients and is confirmed using the Delta method for differences in predicted probabilities. All significant interactions are presented as figures of predicted probabilities rather than in tables to facilitate interpretation. All regressions control for ego characteristics and level-1 and -2 versions of constitutive terms in the interaction model.
| 4 | 2other
| 0Study
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18,990 |
In the prognosis analysis, the rs80112640 and rs72855279 polymorphisms could both improve OS for GC patients after adjustments by several clinicopathological parameters. No significance was observed in univariate model, which was consistent with the results of analysis for OS-related factors. The two SNPs were located in the exon of lnc-C6orf132-1, of which the structural motifs might be affected and display a protective role for GC. However, the other SNPs in lnc-C6orf132-1, rs7747696 and rs7749023 were both associated with an increased AG risk, seemingly conflicting for the polymorphisms in the same lncRNA gene. Considering the results in function analysis of lnc-C6orf132-1, we believe this phenomenon could be explained to some extent. A number of co-expressing genes for lnc-C6orf132-1 were revealed in our lncRNA expression profile, shown to have bidirectional regulation effects on DNA transcription. That indicates lnc-C6orf132-1 has the ability to simultaneously upregulate and downregulate the expression of some relevant oncogenes or tumor suppressor genes when affected by different SNPs. As a result, the expression level of the same gene may vary from different stages during the progression of gastric diseases. Besides, the components associated with cancer outcome are quite complex, in which diverse factors might interact with each other. Therefore, it is comprehensible that the SNPs in lnc-C6orf132-1 cause contrary effects on AG risk and GC prognosis, while the specific mechanism still needs to be further investigated.
| 4 | 0biomedical
| 0Study
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201,306 |
GST fusion proteins were expressed in the E. coli strain BL21. To purify the GST fusion proteins, cells were lysed by sonication in lysis buffer (phosphate-buffered saline [PBS], 1% Triton X-100, 2% β-mercaptoethanol, and 0.1 mM phenylmethylsulfonyl fluoride [PMSF]), and the resulting lysates were incubated for 1 h at 4 °C with glutathione-Sepharose beads. The beads were pelleted by centrifugation and washed with dialysis buffer for subsequent experiments. Nuclear extracts were then incubated with resin-bound proteins at 4 °C for 3 h with rotation, washed four times in washing buffer (20 mM HEPES (pH 7.9), 0.2 mM EDTA (pH 8.0), 20% glycerol, 0.15 M KCl, and 0.2% NP-40) and analyzed by Western blotting using the appropriate antibodies. Western blotting was performed according to standard procedures.
| 4 | 0biomedical
| 0Study
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304,923 |
The SI of the village cadres can eventually arouse IB of villagers. There is also an essential moderating mechanism factor, personal resilience of villagers (such as perseverance, firmness, etc.). Gao and Bi (2009) pointed out that village cadres play an essential role in promoting “agricultural efficiency, income of farmers and rural development,” which is mainly reflected in guidance and mobilization of village cadres through SI. Eventually, this is transformed into the IB of the villagers (Li and Xiang, 2010). What is the internal influence mechanism of encouragement of village cadres on IB of villagers? Few studies have discussed this. Theoretically speaking, innovation behavior of individuals at the micro level is related to their innovation consciousness and their resilience (Hao et al., 2020). According to human ethology and social psychology, resilience is the dynamic ability to overcome setbacks and adapt to changes (Martin, 2012; Eicher et al., 2015), and it is also regarded as inspiring confidence of people in their careers. It is only when villagers are optimistic about their jobs that the SI of the village cadres can be transformed effectively into IB of villagers. According to organizational behavior theory, resilience is a more appropriate moderating variable (Gong et al., 2019). This paper argues that the impact of SI of village cadres on innovation behavior of villagers is strengthened or weakened by resilience of the villagers. Therefore, the following hypothesis is obtained.
| 1 | 2other
| 0Study
|
129,942 |
To better correlate the three time series, we calculated for each sensor the average values of VRP on a weekly scale (VRPw), as shown in Figure 6a, on a logarithmic scale. The three weekly datasets have been correlated by calculating the best-fit linear coefficient (m) and the Pearson correlation coefficient (r). From these analyses, it results that the MIROVAVIIRS vs. MIROVAMODIS and MIROVAVIIRS vs. FIRMSVIIRS are characterized by coefficient r equal to ~0.82 and ~0.87, respectively (Figure 6b,c). Data are slightly dispersed around the 1:1 ratio line, with a linear best-fit coefficient m of ~0.90 for MIROVAVIIRS vs. FIRMSVIIRS correlation, suggesting that MIROVA-derived weekly mean are slightly lower than FIRMS-derived FRP (Figure 6b). On the contrary, the coefficient m = 1.05 found for MIROVA-derived VRP (VIIRS vs. MODIS) indicates that the weekly mean for VIIRS is slightly higher than those obtained with MODIS (Figure 6c).
| 4 | 0biomedical
| 0Study
|
397,917 |
We incubated mESCs cultured on irradiated feeder MEFs together in ESC dissociation buffer (500ul of 0.5M EDTA and 0.9g of NaCl in 500ml Calcium/Magnesium free PBS) for 20 minutes at 37°C. We next detached mESC colonies from MEFs by gentle pipetting and dissociated ESCs to single cells by incubating with Accumax for 5 minutes at 37°C. To ensure removal of MEFs, we incubated single cell suspensions of ESCs on a 100mm tissue culture dish for 40 minutes at 37°C. We then collected the supernatant which contained mESCs only. We seeded a 1,200 well micro-well plate (STEMCELL Technologies, 27945) with 1.2 million ESCs in EB media (mESC media without LIF), to obtain a density of ~1000 cells per well. This approach allowed us to obtain morphologically consistent EBs controlling for spontaneous differentiation which can be altered by EB size and shape (Koike et al., 2007). For EB differentiation with inducible barcoding experiments, we seeded FACS sorted RFP+/GFP−/BFPmid cells to ensure Cre expression and remove unwanted recombination by un-controlled CreERT2 activation.
| 4 | 0biomedical
| 0Study
|
242,001 |
Science continues to improve the design and function of nonpharmaceutical technologies such as face masks, air filtration, and germicidal UV for cleaning of air in commercial markets, sparked by the COVID-19 pandemic4,5. Adoption and integration, of these and other simple technologies, each a beneficial response to the air quality challenges of climate change, has accelerated over the last two years among high- and middle-income populations through a combination of public discourse and mandates, commercial markets, and charitable giving.
| 2 | 0biomedical
| 1Other
|
48,120 |
Pressure myography was used to construct pressure–diameter relationships to assess uterine artery properties from GD 18 WKY, SHRSP, and SHRSP treated with etanercept. Etanercept treatment did not significantly alter the diameter or wall thickness of the SHRSP uterine arteries (Figure S5). Investigation of uterine artery vasomotor function using wire myography showed that uterine arteries from pregnant SHRSP had a significantly increased contractile response to noradrenaline and a blunted endothelium-dependent vasorelaxation relative to the WKY (Figure 3A and 3B). In contrast, uterine arteries from pregnant SHRSP treated with etanercept exhibited a marked reduction in contractile response that was not significantly different from WKY and a significant increase in vasorelaxation to carbachol (Figure 3A and 3B). Etanercept treatment did not have a significant effect on mesenteric artery function in SHRSP (Figure S6).
| 4 | 0biomedical
| 0Study
|
117,177 |
The outputs provided by different RGC types can be divided into two major classes: On and Off type RGCs . At cone-driven (photopic) light levels, signals in the vertebrate retina diverge into parallel On and Off pathways already at the first synapse. On bipolar cells depolarize in response to light increments, whereas Off bipolar cells hyperpolarize . The contributions of 14 different bipolar cell types driving RGC signals can vary depending on the background light levels: some RGC types can turn from On to Off or vice versa as the light levels increase owing to changes in the relative contributions of On and Off type bipolar cells . At mesopic, and even at rod-driven (scotopic) light levels higher than visual threshold, multiple pathways mediating rod and/or cone signals through the retina can be active at the same time . However, near the dark-adapted visual threshold, rod-driven signals propagate through the mammalian retina via the so-called rod bipolar pathway [33–36] (figure 1a): rod → rod bipolar cell → AII amacrine cell → On and/or Off cone bipolar cell → RGC. In these conditions, On and Off RGCs share the same pathway up to the AII amacrine cells, so that signals from rod SPRs diverge into depolarizing (On) and hyperpolarizing (Off) responses only at the AII output in the inner retina. This is the case of interest here: what are the functional consequences of the On and Off pathway asymmetries at the lowest light levels, where sparse rod-driven signals traverse the mammalian retina via the rod bipolar pathway? Figure 1.Nonlinearity in the On but not in the Off pathway near the absolute threshold. (a) Top: schematics of the rod bipolar pathway in the primate retina. Near the absolute threshold, the primary Off and On pathways (rod bipolar pathway) share the circuitry up to the AII amacrine cell (highlighted in blue). The synapse between On cone bipolar cells and ganglion cells not only operates as a thresholding nonlinearity to reduce noise, but also limits information about single photons. The numbers shown in the diagram indicate the number of rods converging on a particular cell type. Spike responses to dim flashes are shown for an Off (left) and On parasol cell (right) at the bottom. (b) The stimulus–response relationship for primate Off and On parasol cells near absolute threshold. At very low light levels (a few R* per RGC), both the spiking responses (black squares) and excitatory input currents (black circles) of On cells show supralinearity, while the spiking responses of Off cells (green squares) show a linear relationship. The dashed line shows a linear relationship as a reference. Inset: the slopes of the stimulus-response relationship measured at low-light intensities for the excitatory synaptic current to On (left), spike response of On (middle) and spike response of Off (right) parasol cells. (c) Dim-flash detection performance predicted by a nonlinear (black) and linear (green) model. The nonlinear model is in line with the On parasol responses while the linear model predicts Off cell responses. (d) The false-positive rates predicted by the model in (c). Adapted with permission from Ala-Laurila & Rieke .
| 4 | 0biomedical
| 0Study
|
108,971 |
(2) DXA cannot measure individual spinal muscles such as paravertebral muscle and psoas. The trunk SMI defined in this study includes the internal organs so it is not an accurate measure of actual trunk muscle volume but merely a relative evaluation. However, trunk muscle accounts for approximately 15% of the lumboabdominal region and is second only to the 30% representing the femoral muscles, and so it cannot be ignored in terms of assessing whole-body skeletal muscle mass . A new device has recently been introduced to evaluate the total and regional body composition—bioelectrical impedance analyzer (BIA). BIA estimates body composition using the difference of conductivity of the various tissues due to the difference of their biological characteristics. High agreement between DXA and BIA was high for lean mass trunk (95%IC 0.82) . In the future, results should be compared to measure the trunk muscle with BIA and MRI evaluations. (3) The study is a cross-sectional analysis, not a longitudinal one. (4) This study was only compared to patient with spinal stenosis but not compared to a normal population without back problems and not compared to younger populations.
| 4 | 0biomedical
| 0Study
|
78,269 |
(A, B) Comet assay demonstrating elevated DNA damage in cells treated with PHEN and/or APR-246. UMSCC14 cells were treated with 10 μM PHEN and/or 40 μM APR-246 for 24 h. The cells were then trypsinized and washed with PBS. Two thousand cells were mixed with 100 μl low melting agarose for alkaline comet assay. Cells in the gel were stained and visualized with epifluorescence microscopy (A). (B) Percentage of DNAs in the tail (damaged DNA) was calculated. * P < 0.01, n = 3. (C) DNA damages were markedly escalated in PHEN- and APR-246-treated cells. Antioxidant NAC and over-expression of TrxR1 reduce above agents-induced DNA damage. The indicated UMSCC14 cells were exposed to 10 μM PHEN and/or 40 μM APR-246 for 24 h. Cell lysates were collected for western blot analysis. GAPDH serves as loading control. (D, E) NAC pretreatment and over-expression of TrxR1 reduce PHEN- and APR-246- induced apoptosis. UMSCC14 cells were pretreated with 5 mM NAC for 6 h (D) or transfected with pcDNA3/TrxR1 as described in Figure 6C and 6D (E). The cells were then exposed to 10 μM PHEN and/or 40 μM APR-246 for 48 h. After the treatment, cell apoptosis was quantified using a cell death ELISA kit (Roche Diagnostics) showing enrichment of nucleosomes in the cytoplasmic fraction of the cells. Data represent the mean ± S.D. * P < 0.01, n = 3.
| 4 | 0biomedical
| 0Study
|
109,643 |
In summary, a very high risk at all the measurement points (K1–K4) located in the surroundings of coking plants was noted for the following elements found in PM1: As, Cd, Mn, Pb and Sb, as well as Se (except measurement points K1 and K2), and Co, as well as Ni at point K1. A low threat in all the analyzed points in the vicinity of coking plants was posed by Cr (without taking into consideration a particular degree of oxidation), Hg only at points K3 and K4 and Ni only at point K4. It is worth emphasizing that based on the risk assessment code (RAC), a very high risk has been revealed due to the presence of carcinogenic (As and Cd) and potentially carcinogenic elements (Pb and Sb) in PM1 subjected to analysis at the points located in the surrounding coking plants (Fig. 6).
| 4 | 0biomedical
| 0Study
|
211,623 |
In the present study, the M398T mutant exhibited a 1.4-fold increase in basal cAMP response, consistent with the suggestion that the hLHR mutant exhibited a 3.5-fold increase in basal cAMP response in COS-7 cells and a similar increase in HEK 293 cells . However, another study demonstrated a dramatic increase in basal cAMP response of 25-fold in HEK 293 cells . Thus, we suggest that the eLH/CGR-M398T mutant displays a constitutive activation of cAMP response without agonist treatment, and the basal cAMP response differs from that in the cells expressing those mutants, despite the small increase observed in this study. In agreement with previous studies on the equivalent mutation of the hLHR and rLHR , our results showed that the eLH/CGR-D540G and eLH/CGR-D578Y mutations induce a marked increase in cAMP production without agonist treatment. Compared to the wild-type eLH/CGR, the two mutants resulted in a 16.4- and 11.2-fold increase in basal cAMP production in CHO-K1 cells, indicating that such mutants are constitutively activating, as previously reported for other mammalian hLHR , and rLHR . The maximal responses of these two mutants exhibit a 6–17% increase, relative to the cAMP level detected in cells expressing the wild-type eLH/CGR. A previous study on transgenic rat LHR-D556H (equivalent to D578Y in eLH/CGR) under control of the inhibin α−subunit promoter demonstrated that the level of constitutive activity was similar to the results obtained in vitro .
| 4 | 0biomedical
| 0Study
|
222,229 |
Room temperature carrier concentration (p) and mobility (μH) were examined using a direct-current (dc) Hall effect measurement system (model 8404; Lakeshore Cryotronics, USA) at the excitation current up to 100 mA and magnetic field of 1.5 T. Electrical resistivity (ρ) and Seebeck coefficient (S) were measured by a static dc method (LSR-3, Germany) under a helium (99.999%) atmosphere. The thermal conductivity (κ) is calculated by κ = D d Cp, where D is the thermal diffusivity, Cp is the specific heat, and d is the volume density. The thermal diffusivity (D) was measured by a laser flash method (LFA 457; Netzsch, Germany); the specific heat (Cp) was estimated based on Dulong–Petit law, which is approximate to the measurement result; and the volume density (d) was determined by the Archimedes method.
| 4 | 0biomedical
| 0Study
|
48,386 |
Microstructural, EDS and EBSD analyses were performed using a FEG SEM JEOL 6500 F field-emission scanning electron microscope with energy-dispersive spectroscopy (an INCA X-SIGHT LH2-type detector, INCA ENERGY 450 software) and EBSD (HKL Nordlys II EBSD camera using Channel5 software). The instrument was operated at 15 kV and a 1.2-nA current for the EBSD analysis, with a tilting angle of 70 degrees. The aluminium IPF phase orientation map was observed using cross-section and top view. The detection was set to 5–7 bands, 4 × 4 binning. Minimal post-processing was performed in the case of the mappings, which was limited to removing the so-called “wild spikes”. The laser-remelted structure was also characterised in a JEOL 2011FX TEM at 200 kV. TEM samples, 100 nm thick, were prepared using an xT Nova NanoLab 200 Dualbeam focused-ion-beam miller at 30 kV.
| 4 | 0biomedical
| 0Study
|
187,642 |
One advantage of our method is the elimination of residual SeV by transient exposure to the cultivation at a treatment temperature of 38℃, as the SeV vector in this study carries a temperature‐sensitive mutation. 11 Interestingly, treatment at 38℃ increased both the differentiation efficiency and the number of cells with spindle‐like elongated muscle cell morphology. We speculate that this could be due to increased expressions of specific heat shock proteins. A previous study reported that heat shock proteins (HSPs), including MKBP/HSPB2 and HSPB3, are induced during muscle differentiation under the control of Myod1, suggesting that these HSP oligomers might have an additional system closely related to muscle functions. 25 Others showed that the levels of HSPs, namely HSP25, HSP40, HSP90 and HSP110, were highly elevated in 50% confluent proliferating myoblasts. 26 , 27 It has also been shown that HSPs play a crucial role in myogenesis. McArdle et al. showed that HSP70 overexpression facilitates muscle regeneration. 28 Barone et al. found increased skeletal muscle HSP60 after endurance training. 29 Taken together, it is suggested that transient exposure at a temperature of 38℃ might act like heat shock and improve myogenic differentiation. For further disease modelling of motor neuron diseases, we previously reported the generation of motor neurons using SeV encoding three transcription factors: LIM/homeobox protein 3, neurogenin 2 and islet‐1. 12 By combining the SeV‐based differentiation system into motor neurons or SkM cells from patient iPSCs with various disorders in the neuro‐skeletal muscle system, we can open the way for disease modelling and drug discovery in the future.
| 4 | 0biomedical
| 0Study
|
173,741 |
DON is a mycotoxin produced in crop grains infected with F. graminearum and F. culmorum. It is found mostly in wheat, barley, rye, and corn. DON is the most commonly found type B trichothecene, and its structure is shown in Figure 1 . DON has two secondary and one primary hydroxyl groups present along with an epoxide and a conjugated ketone, either of which may be associated with toxicity . The epoxide on the C12/13 position of DON is considered to be essential for toxicity and has a key role in the inhibition of cellular protein synthesis . It has been shown that the opening of the epoxide results in a loss of DON toxicity . Other studies that point to a role for this group have shown that the de-epoxy metabolites of DON are less toxic than DON itself . In one study, the cytotoxicity of DON and another trichothecene, Nivalenol, and its de-epoxy metabolite were compared using a Bromodeoxyuridine based cell proliferation assay. The results illustrated that the de-epoxy metabolites of DON and Nivalenol were 54 and 55 times less toxic, respectively, than the toxins with the epoxide ring . Similar results were obtained in another study in which the cytotoxicity of DON and deepoxy-deoxynivalenol were compared, and in which the relative lack of deepoxy-deoxynivalenol toxicity was confirmed using six different cytotoxicity assays . These studies clearly show that the 12, 13-epoxide ring plays an important role in DON toxicity.
| 5 | 0biomedical
| 0Study
|
347,752 |
Primary end point was the mean change in MmsHD between the 30‐day pretreatment period compared to 12 months. Data were also reported at 3, 6, and 9 months. A moderate/severe headache day was defined as a day with moderate or severe pain that last at least 4 hours or those requiring the use of abortive therapy. 28
| 4 | 0biomedical
| 0Study
|
81,773 |
Taking together, the demographic landscape of Europe, with a particularly and striking case in Portugal, urges the need of defining new strategies and implementing actions to deliver innovative and disruptive solutions. These solutions are expected to have impact at the individual, family, labor, societal, and economic dimensions to support individual health and well-being, at all ages, and deliver solutions to support health and social care sustainability. As we will elaborate bellow, the EIP on AHA movement, and the particular case of Ageing@Coimbra (as a Community Case Study), may be inspiring for the required change management processes, delivering solutions for the challenges of aging and opening new opportunities for economic growth.
| 2 | 2other
| 1Other
|
306,443 |
PRT measurement was done in the same sitting position as previously described for the MVIC measurement. The knee joint was passively moved for five cycles at an angular velocity of 5°/s from 90° to 60°. According to previous studies (Kubo et al. 2002; Mahieu et al. 2009), the velocity of the dynamometer was set to 5°/s to exclude any reflexive muscle activity. Participants were asked to relax completely. The lowest torque value of the last three circles in the extension phase was taken for further analysis.
| 4 | 0biomedical
| 0Study
|
263,086 |
The use of valid and trustworthy instruments to measure suicidal behavior is capable of providing reliable results regarding this phenomenon, which, in turn, will support the implementation of interventions for the prevention of suicide. Knowledge of the applicability and validity of these instruments in the Brazilian context can be relevant.
| 2 | 0biomedical
| 1Other
|
355,655 |
The heritability estimates for RH in the current study were moderate in all scenarios (Table 2). These results suggest that the response to direct selection for this trait will yield satisfactory gains regardless of the inclusion of genomic information. In sheep, direct heritability estimates for body conformation traits, such as height, usually range from moderate to high . Thus, the genetic improvement of these traits can be efficiently achieved through the classical methods. Nevertheless, studies using data derived from molecular markers can generate information that may be incorporated into genetic evaluations and selection indexes in the future . Furthermore, the inclusion of genomic information allows the detection of higher proportion of additive genetic variance, as mentioned above, and consequently provides more accurate estimates of breeding value, even for traits with moderate or high heritability.
| 4 | 0biomedical
| 0Study
|
316,898 |
Besides that, studies have also addressed the involvement of p53 in UVB-induced cell death [33, 109, 110]. After irradiating the ARPE-19 cells with 30-90 mJ/cm2 UVB, the degree of elevation of phosphorylated p53 was obtained . Likewise, the p53 mRNA level was also reported to increase almost 5-fold higher than the unexposed control in DrRPE cells . In the study by He et al. , they also measured the expression of phosphorylated ataxia telangiectasia mutated (p-ATM), phosphorylated histone H2A (p-H2A), and phosphatase and tensin homolog (PTEN). Both p-ATM and p-H2A were found to be upregulated by UVB while PTEN was negatively regulated. He et al. then proceeded to overexpress PTEN which resulted in a decrease in p-H2A and an increase in cell viability. On the other hand, when PTEN was silenced, not only was p-H2A increased but even the phosphorylation of p53 was increased together with cell apoptosis. Treatment with p53 inhibitor, however, was able to decrease the apoptosis of ARPE-19 cells even with PTEN was silenced, indicating a positive involvement of p53 with UVB-induced cell death. Research by Yan et al. showed not only an increase in p53 but also an increase in p21 and a decrease in the inhibitor of apoptosis-stimulating p53 protein (iASPP) protein expression. The DNA synthesis of the ARPE-19 cells was also decreased after UVB exposure. When iASPP protein was induced to overexpress, the cell viability and DNA synthesis were increased, whereas p53, p21, and apoptotic cells were decreased. Hence, it can be said that iASPP plays a role in the regulation of p53, p21, and the survival rate of the UVB-damaged RPE cells.
| 5 | 0biomedical
| 0Study
|
234,527 |
Literature review shows that space robots suffer from singularities, depending on the mode of operation. It is also known that dynamic singularities affect free-floating space robots, whereas kinematic singularities affect free-flying space robots. As the CFSR can control its base’s motion, only kinematic singularities occur during the arm’s movement. It is possible to avoid kinematic singularities using the extra degrees of freedom offered by the spacecraft base. In short, the controlled-floating mode offers the benefits of both free-flying and free-floating modes of operation, and an accurate model of a CFSR will be highly beneficial to the end-users.
| 1 | 2other
| 1Other
|
146,366 |
Next, the predictive ability of the ARLnc prognostic signature was further validated in the validation cohort. Consistently, 319 patients were divided into two groups with the same cutoff used in the training cohort (Fig. 2F), and the survival duration of 319 patients was determined (Fig. 2G). The expression profiles plotted by the risk heatmap in the validation cohort showed that compared to the low-risk group, the expression level of risk-type lncRNAs (AC245041.1 and AC037198.1) in the high-risk group was elevated, while the expression level of protective-type lncRNAs (PVT1 and LINC01315) was decreased (Fig. 2H). Kaplan–Meier survival curves indicated that patients with high-risk scores had a significantly poorer OS than those with low-risk scores in the validation cohort (p = 2.555e-06, Fig. 2I). Moreover, in the validation cohort, the AUCs for 1-, 3-, and 5-year OS were 0.671, 0.646, and 0.680, respectively, showing the good prognostic prediction of the ARLnc-related gene signature (Fig. 2J).
| 4 | 0biomedical
| 0Study
|
71,123 |
Pain, sore throat, laryngeal edema and airway obstruction may occur after adenotonsillectomies and are the probable etiological factors of emergence agitation. In the present study, dexamethasone and fentanyl were administered to all patients for the prevention of laryngeal edema and pain. Fentanyl administrated at induction to all the patients and planed as intraoperative rescue analgesic but none of our patients needed intraoperative rescue analgesic and dexamethasone was the drug chosen for the prevention edema for both groups. Evidently both groups benefited from the decrease in incidence of the emergence agitation but this did not affect the comparison of the groups because all the patients in both groups received the equivalent dosage of dexamethasone and fentanyl.
| 4 | 0biomedical
| 0Study
|
290,496 |
Taste responsiveness was determined using the Burghart filter paper method . The tastes were sweet (sucrose, 0.2 g/mL), sour (citric acid, 0.165 g/mL), salty (NaCl, 1.0 mol/L), and bitter (quinine hydrochloride, 0.0024 g/mL). Participants were tested in a dedicated room without odors or visual or auditory distractions; they were instructed by an expert administrator and were asked not to eat or brush their teeth beforehand. Specifically, each participant placed the paper on his/her tongue and had to recognize the correct taste among a list of four descriptors: sweet, bitter, salt, and sour. A possible choice was also “I do not perceive any taste”. After tasting each paper, the participant rinsed his/her mouth with 10 mL of bottled mineral water (room temperature). The number of errors was counted, including as an error the answer “I do not perceive any taste”. Reduced taste capacity was defined as the number of errors ≥ 1, in agreement with other studies .
| 4 | 0biomedical
| 0Study
|
224,951 |
We further advocate its role in the CNS by discussing published genetic studies, which showed association of specific Np gene polymorphisms with cortical thickness and intellectual ability in adolescents, susceptibility to schizophrenia, and occurrence of neurodevelopmental disorders, e.g., autism [1–3]. We argue for its key role in the memory, by summarizing all available immunohistochemical data, which demonstrates specific immunolocalization of Np in adult human brain and in the trisynaptic hippocampal pathway [4, 5]. Role of Np in neurodegeneration is also suggested by demonstrating its involvement in tissue reorganization in Alzheimer’s disease (AD) , whereas its role in neurodevelopment and brain maturation is further argued by data analysis showing that the Np gene expression (NPTN) steadily increases from the prenatal period to adulthood when the expression is highest . Finally, we hypothesize housekeeping role of Np in neuroplasticity, given its high level of expression in the CNS compared to other human brain genes in general.
| 4 | 0biomedical
| 2Review
|
58,182 |
The polled phenotype of cattle is inherited as an autosomal dominant trait, for which the POLLED locus was genetically mapped to Chromosome 1 [5–8]. During the past years, many efforts have been devoted to explore causative mutation(s) for polled phenotype in cattle [9–14] as well as the related bovine species of yak [15, 16]. Two heterogeneous mutations were first observed to perfectly segregate with polled phenotype, including the complex duplication-insertion of 202 bp fragment (P202ID) in beef or dual-purpose breeds and 80 kb fragment (P80kbID) in Holstein [10, 17]. More recently, a novel duplication-insertion event of a 219 bp fragment (P219ID) was also revealed to be responsible for polled phenotype in Mongolian Turano cattle . Therefore, a total of three causative mutations have been confidently proposed to be associated with polled phenotype in cattle so far.
| 4 | 0biomedical
| 0Study
|
207,391 |
Regardless of the above-mentioned limitations, our study provides the first hints towards a role of cancer-associated EVs in organotropic metastasis in urological malignancies, which will be further elucidated future studies. In addition, a better understanding of the role of EVs in metastasis could pave the way for novel EV-associated therapeutic strategies .
| 4 | 0biomedical
| 0Study
|
76,700 |
As described elsewhere, the EC signalling system is essential for normal brain maturation and pain processing.36 In our studies, we report postnatal alternations in the expression of EC-related targets in the midbrain of humans and the brainstem nuclei of rats, and these changes have significant functional consequences on pain modulation. Interestingly, our data also reveal a novel role for GPR55 receptors in pain modulation during the early postnatal period, as the expression of GPR55 receptor mRNA was highest in the early adolescent period of the rat, and supraspinal activation of GPR55 receptors strongly inhibited nociceptive reflexes in early infancy and adolescence of the rat. Altogether, our research provides further insights into our understanding in the maturation of pain signalling systems during postnatal development.
| 4 | 0biomedical
| 0Study
|
394,856 |
GTPase activity was measured by using a colorimetric malachite green assay that monitors the amount of free phosphate released over time79. To measure the basal GTPase activity of TgMcrBAAA, 0.4 μM TgMcrBAAA was incubated with 1 mM GTP at 65 °C in reaction buffer (20 mM Tris-HCl, pH 8.0, 150 mM KCl, and 5 mM MgCl2). To measure the GTPase activity of TgMcrBAAA stimulated by TgMcrC, the same conditions were used but 0.1 μM TgMcrC was added. At time points of 0, 5, 10, 20, 30, 45, 60, 80, 100, and 120 min, 20-μL aliquots were taken and quenched with 5 μL of 0.5 M EDTA, pH 8.0. For colorimetric reactions, 150 μL of filtered malachite green solution were added to each sample and incubated for 5 min. The absorbance at 650 nm of the samples was measured with a Multiskan GO Microplate Spectrophotometer (Thermo Scientific). The amount of phosphate released was determined using a standard curve. To account for the spontaneous hydrolysis of GTP at 65 °C, a protein-free sample containing GTP and magnesium was incubated in parallel, and the measured amount of phosphate released at each time point was subtracted from the corresponding measurements of protein-containing samples. The specific activity is reported for all wild-type and mutant proteins. Quantified data represent the average of three independent experiments using multiple independently purified batches of protein with error bars indicating the standard deviation from the mean (n = 3, mean ± standard deviation). GraphPad Prism and Microsoft Excel were used for statistical analysis and to plot the data.
| 5 | 0biomedical
| 0Study
|
99,876 |
Pooled data in A and data from individual subjects in B. Triangles in B indicate time at which performance reaches 80% of baseline (see 'Materials and methods'); the values of this time are 28, 35, 30, and 26 ms for subjects JV, JS, LV and MK respectively. All other conventions as in Figure 2A. Related to Figure 2A.
| 3 | 0biomedical
| 0Study
|
94,685 |
Maternal age, husbands' education, marital status, seasonal availability of food, access to all food groups, source of health information, and knowledge of mother had a statistically significant association with outcome variable. Those mothers who belong to the age group of 25–34 years were 1.82 times more likely to practice good dietary diversity for their 6–23-month-old children as compared with those who belong to the age group of 15–24 years (AOR = 1.82, 95% CI = (1.05, 3.17)). Mothers who were married and living with their husbands were 88% times less likely to practice good dietary diversity as compared with single mothers (AOR = 0.22, 95% CI = (0.08, 0.59)). And those mothers who were divorced were 91% times less likely to practice good dietary diversity compared to single mothers (AOR = 0.09, 95% CI= (0.02, 0.53)). Mothers' dietary diversity practice was also affected by seasonal availability of food groups to diversify meal for their 6–23-month-old children. Mothers who can have access to all food groups in winter were 1.78 times more likely to practice good dietary diversity as compared with those mothers who can have access to all food groups in summer (AOR = 1.78, 95% CI = (1.01, 3.15)).
| 4 | 0biomedical
| 0Study
|
270,167 |
The qualified samples were enrolled into the group, and the total RNA was extracted after DNA and protein removal. RNA concentrations extracted from samples were measured using a Nano Drop 1000ND analyzer (Thermofisher Scientific, Waltham, MA, USA). The ratio of OD260/OD280 was used as the index of RNA purity. Only samples with OD260/OD280 ratio between 1.8 and 2.1 were considered for downstream processing. A circRNA sequencing library was prepared according to the following steps.. RNA pretreatment. 5 μg of total RNA was used as starting material, and the circRNA enrichment kit (Cloud-SEQ Inc, Shanghai, China) was used for the enrichment of circRNA to obtain the expression profile of circRNAs.RNA library construction. RNA was pretreated by TruSeq stranded total RNA library prep kit (Illumina, USA). RNA sequencing library was prepared according to the manufacturer's recommendations.RNA integrity quality control: We have assessed RNA and library quality and quantification using a BioAnalyzer 2100 instrument (Agilent Technologies, USA). In brief, 10 pM library was transformed into single-stranded DNA molecules, which were sequenced using an Illumina 4000 HiSeq sequencer and paired end mode.
| 4 | 0biomedical
| 0Study
|
395,008 |
LN LECs derive from specialized angioblasts and, due to their draining functions in LVs, play a key role in immune cell trafficking (entry and exit from LNs). Similar to FRCs, LECs release CCL21 to promote lymphocyte homing into LNs. Moreover, single-cell mRNA sequencing of LN cells identified four LN LEC subsets in mouse samples, while up to six subsets were defined in human LNs . LN LEC subsets are so far less characterized compared to FRC subsets. Two LN LEC subsets—the floor LECs (fLECs) and ceiling LECs (cLECs)—localized in the subcapsular parts of LNs and in close proximity to afferent LVs, seem implicated in immune cell entry into LNs (Figure 1) . Another subset is localized in the medullar part of LNs (MedLECs), where immune cells exit from LNs (Figure 1). Finally, a fourth subset localized in the paracortical sinus, adjacent to the medulla, expresses high levels of Spns2 (spinster homolog 2), the transporter required to release sphingosine-1-phosphate (S1P) in lymph (Figure 1) . LEC-derived S1P has been previously shown to play a crucial role in lymphocyte egress from LNs . Together with its paracortical sinus localization, it is tempting to speculate that the LN LEC subset expressing high levels of Spns2 generates a gradient of S1P and therefore regulates (T) lymphocyte egress from LNs. LEC-derived S1P does not only control lymphocyte egress from LNs. A study further revealed that Spns2 expression, and therefore S1P release by LECs, inhibits naïve T cell apoptosis by promoting T cell mitochondrial functions, hence playing an important role in naïve T cell homeostasis and survival . Moreover, the type II receptor of S1P (S1PR2) is highly express by Tfh cells, and genetical deletion of S1PR2 impairs their localization in GCs . However, as S1P is also important for T cell survival, it is still unclear whether this observation is a consequence of a direct impact on Tfh retention in GCs or an alteration of Tfh viability.
| 5 | 0biomedical
| 0Study
|
357,465 |
A meningococcal antigen typing system (MATS) was developed and standardized across public health laboratories worldwide (14, 15) to predict the potential coverage of 4CMenB (14) in different countries. The MATS combines a sandwich enzyme-linked immunosorbent assay (ELISA) for detection of qualitative and quantitative differences in fHbp, NadA, and NHBA expression together with PorA genotyping (14). The MATS results correlate with killing of strains in hSBA (14). The MATS serves as a conservative predictor of strain coverage by 4CMenB in infants and adolescents (16) and has been employed to predict 4CMenB strain coverage in many countries (17–21). It has recently been shown that MATS can be complemented by genetic MATS (gMATS) through association of antigen genotyping and phenotypic MATS results (22). The gMATS is emerging as a cost-effective tool which has the added benefit of not requiring cultivable isolates, thus allowing prediction across MenB-caused IMD cases identified by PCR only.
| 4 | 0biomedical
| 0Study
|
51,478 |
The results presented above undoubtedly show that phagocytosis is stimulated by a rise in the free Ca2+ content of erythrocytes. This ion is a well-known modulator of PS externalization in human RBCs (Bitbol et al., 1987; Williamson et al., 1992), which in turn constitutes an important signal for macrophage recognition and erythrocyte removal (Schroit et al., 1985). To investigate if the Ca2+ action is related to PS exposure, macrophages were preincubated with PS-containing liposomes in RPMI medium. As control, macrophages were similarly exposed to PC liposomes. After washing, macrophages were challenged with 7 μM Ca2+-loaded RBCs, in the presence and absence of 40% AS.
| 4 | 0biomedical
| 0Study
|
203,035 |
In order to precisely regulate the inflammatory stage, which mainly take place in the initial 5 days as reported,[ 10 ] the dosage and release rate of Dex were carefully tailored. With rhBMP‐2/MBG (B/M) as a matrix, various doses of Dex were incorporated according to the efficient performance of modulating macrophage infiltration and phenotypes (Figure S2, the Supporting Information), and Dex was initially and quickly released in 2 days. We thought that the BD/M scaffolds with various Dex amounts mainly regulated inflammatory microenvironment at different levels in the early stage, and thus exerted an effect on B/M‐induced bone regeneration. Meanwhile, given the complexity of the orthotopic bone formation in vivo, and higher cost and larger defect area of the surgery, we selected an ectopic model to study the effects of the early‐stage inflammatory response on late‐stage endochondral ossification. Ectopic models are known to exhibit similar endochondral ossification in the early stages with orthotopic bone formation. As anticipated, ectopic bone formation visualized with digital images and histology was significantly improved by B6D/M scaffolds at 2 weeks (Figure 2E,F; Figure S4, the Supporting Information). Because an obvious difference was shown in groups with and without Dex, and 90% Dex was released in 2 days (Figure 1H), we hypothesized an important function of early inflammation responses occurring in 7 days in EO.
| 4 | 0biomedical
| 0Study
|
138,189 |
We next asked whether prior COVID-19 may impact an individual’s response to non-SARS-CoV-2 immunological challenges. The seasonal influenza quadrivalent vaccine was administered to study participants, who were subsequently followed longitudinally for up to 100 days, including days 1, 7, and 28, to evaluate the immune response to the vaccine at the serological, molecular, and cellular levels (Fig. 1a, 1b, 2a). This vaccine was selected in part due to its public health importance: the 2020–21 influenza season was approaching at the start of our study and it was not clear whether prior COVID-19 infection would impact responses to the influenza vaccine. In addition, the cellular and molecular responses to seasonal influenza vaccination and the associated kinetics have been well characterized in healthy adults, including early innate/inflammatory and interferon (IFN) responses on day 1 (D1) after vaccination and a strong but transient plasmablast peak around day 7 (D7) culminating in the generation of influenza-specific antibodies26–29. Thus, influenza vaccination provides an excellent perturbation to elicit coordinated immune activity that can be sampled at specific times after vaccination to probe the potential functional impacts of prior mild SARS-CoV-2 infection.
| 4 | 0biomedical
| 0Study
|
78,487 |
Cells were washed with PBS and lysed in ice-cold 30 mM Tris buffer (pH 7.5), containing 100 mM NaCl, 1% Triton X-100, 10 mM NaF, 1 mM EGTA, 1 mM Na3VO4, 2 mM p-nitrophenyl-phosphate, 10 mM benzamidine, 1 mM phenylmethylsulphonyl fluoride (PMSF), 25 μg/ml each of Pepstatin A, trypsin inhibitor and aprotinin. Lysates were clarified by centrifugation at 14000 rpm for 10 min at 4°C. Sample buffer (4x, 0.2 M Tris, 0.277 M SDS, 40% (V/V) glycerol, 0.588 M β-mercaptoethanol, 0.05 M EDTA, 1.19 mM bromophenol blue in distilled water) was then added to the supernatants, and the samples were boiled for 3 min. Equal amounts of samples were subjected to SDS-PAGE using 7.5, 10 or 12.5% running gels, respectively. In case of testing for the presence of Tks4, proteins were transferred to nitrocellulose membranes while in the other cases, PDVF membranes were used. Membranes were blocked and incubated for 60 min with the appropriate primary antibodies at room temperature. Polyclonal anti-SH3PXD2B specific antibody was generated earlier7. Anti-α-tubulin (DM1A) was obtained from Sigma-Aldrich, St. Louis, MO, USA, PPARγ (81B8), adiponectin (C45B10) from Cell Signaling Technology, Danvers, MA, USA and anti-RunX2 (ab76956), anti-Osterix (ab22552) from Abcam, Cambridge, UK. After several washing steps, membranes were incubated for 30 min with a horseradish peroxidase-conjugated secondary antibody (GE Healthcare, Little Chalfont, Buckinghamshire, UK) and washed again. Reacting antigens were visualized with the enhanced chemiluminescence (ECL) detection reagents (Amersham Life Sciences Limited, Buckinghamshire, UK).
| 4 | 0biomedical
| 0Study
|
84,041 |
The aims of the present study were: (1) to look at the changes in physical fitness, expressed as maximal oxygen consumption (VO2max), flexibility, strength and balance, in untrained adults with different circadian preferences (chronotypes) who live at 70°N when they train during the polar night (in this study, this was from 26 November to 17 January); and (2) to evaluate the adherence to the experimental protocol in M-, N- and E-types.
| 4 | 0biomedical
| 0Study
|
121,591 |
The relative configuration of the 5,3,6-tricyclic unit in 1 was deduced by NOESY experiments (Fig. 3). In the NOESY spectrum of 1, H-8 was found to show NOESY correlations with H-5, H3-19 and H3-20, and the NOESY correlation could be observed between H-4 and H-5, indicated that these protons should be on the same face of 1. On the opposite face of 1, the key NOESY cross-peaks between H-6 and H-10 suggested that these two protones should be cofacial. To determine the absolute configuration of 1, we applied modified Mosher’s method using (R)-( + )- and (S)-(−)-MTPA-Cl to give the (S)- and (R)-MTPA esters of 1 (1 s and 1r), respectively. The absolute configuration at C-8 in 1 was assigned as S deduced from the Δδ H values between the two MTPA esters (Fig. 4) following the MTPA rules16. Thus, the configuration of tricyclic nucleus for compound 1 was determined as 1 S, 4 R, 5 R, 8 S, 9 R, 10 S.Figure 3Selected NOESY correlations of 1. Figure 4Values of Δδ H(S-R) (measured in CD3OD) of the MTPA esters of 1.
| 4 | 0biomedical
| 0Study
|
199,738 |
We identified 267 records by database searches and 624 records by searching other sources (eFigure in Supplement 1). From 790 unique search results, we identified 20 guidelines,3,34,35,36,37,38,39,40,41,42 including 10 in English,4,5,25,43,44,45,46,47,48,49 issued by academic societies or health agencies in 15 countries between 2010 and 2020 (eTable 3 in Supplement 1). There were 11 guidelines3,4,5,25,36,41,42,46,47,48,49 (55%) that reported their development process, and they were developed by multidisciplinary groups; 5 guidelines4,41,42,46,47 reported a literature review, 2 guidelines5,48 reported a systematic review, and 4 guidelines3,25,36,49 provided a grading or a rating of the level of proof or the strength of recommendations.
| 4 | 0biomedical
| 0Study
|
119,917 |
Caspar et al. reported that gwd leaves accumulate higher levels of starch than WT leaves when plants were cultured under CL conditions. This phenomenon can be ascribed to either one of the following reasons: (i) starch degradation operates in WT illuminated leaves (but not in gwd leaves), or (ii) starch phosphorylation by GWD exerts a negative effect on starch biosynthesis during illumination. To differentiate between these possibilities we measured the starch content in leaves of gwd, sex4, bam1/bam3, bam4 and amy3/isa3/lda starch breakdown mutants germinated and permanently cultured under CL conditions. The rationale behind this experimental approach was that, if starch breakdown solely occurs during the dark period, leaves of starch breakdown mutants other than gwd should accumulate WT levels of starch when cultured in the absence of a dark period. Conversely, if starch degradation also occurs during the day, leaves of the above starch breakdown mutants should accumulate higher levels of starch than WT leaves. As shown in Fig 1, both iodine staining and quantitative starch content measurement analyses revealed that leaves of all the above starch breakdown mutants accumulate higher levels of starch than those of WT plants cultured under CL conditions. The overall data thus provide strong evidence for the occurrence of starch breakdown in Arabidopsis leaves during illumination.
| 4 | 0biomedical
| 0Study
|
376,690 |
The resulting text files were filtered to exclude reverse database hits, potential contaminants and proteins only identified by site. A statistical data analysis was performed using Perseus software (v 1.4.0.20). Biological replicates for each condition were defined as groups and the LFQ intensity values were filtered for a “minimum value of 3” per group. After log2 transformation, the missing values were imputed with random noise simulating the detection limit of the mass spectrometer. The imputed values are taken from a log normal distribution with 0.25× the standard deviation of the measured, logarithmized values, down-shifted by 1.8 standard deviations. The differences in protein abundance between the groups were calculated using a two-sample Student´s t-test. Proteins passing the FDR significance cut-off (0.05) were considered differentially expressed.
| 4 | 0biomedical
| 0Study
|
368,523 |
Total protein was extracted from kidney tissue samples using a total protein extraction kit (Signalway Antibody; College Park, MD, USA). Proteins were separated using SDS/PAGE and then transferred to membranes. Western blotting was performed using the following primary antibodies: anti‐STAT1 (Cell Signaling Technology Inc.) and anti‐GAPDH (Cell Signaling Technology Inc.). Next, the membrane was incubated with HRP‐conjugated antibodies (Signalway Antibody). The ChemiDoc™ MP Imaging System (Bio‐Rad Laboratories, Hercules, CA, USA) was used.
| 4 | 0biomedical
| 0Study
|
375,882 |
Greuter wanted to stress the point raised by Gereau that the proposal looked fine. In fact, he thought it looked appetizing. [Laughter] However, when voting on a retroactive change in an Article concerning the valid publication of names, he was wary of possible consequences. He wondered if the consequences of accepting the proposal had been assessed and found to be irrelevant or minor?
| 1 | 2other
| 1Other
|
112,027 |
As regards gender, studies in Brazil also show that the nursing workforce is composed mainly of women, 100% 11 ) and 97.3% 13 , in the United States 78.4% 2 , Colombia 91.6% 14 , China 95.2% 15 and in Portugal 66.7% 16 . This composition shows the historical insertion of women into society and the Nightingale heritage as a female profession 11 , reproducing a role of nurse and educator 5 . As for the age range, 85% 15 ) are aged from 20 to 40 years, like in a study carried out in China, but unlike other studies conducted in Brazil, in which most professors were middle-aged adults, 66.7% 11 . This shows that the School’s workforce is mainly young, partly due to the hiring of new staff in 2010, when new professors were hired, as well as the implementation of a competency-based curriculum in 2013, which caused an increase of teaching staff numbers.
| 2 | 2other
| 0Study
|
181,170 |
All faculty benefit from supportive communities for satisfaction and advancement.35, 45 Local and national peer mentorship communities enable clinician educators to discuss best practices, share resources, promote equity, and prevent burnout.41, 46, 47 Local medical educator academies can support educator development and fund education innovations. Membership in educator academies can signal achievement and open doors to tangible support.48, 49 Within a division, leaders can include clinician educators along with research faculty in works-in-progress discussions, celebrations of teaching awards and successful curricula, and sharing of opportunities. Chairs and chiefs play a critical role in breaking down silos and creating supportive and inclusive academic communities across missions and institutions.
| 2 | 2other
| 1Other
|
180,348 |
Sea turtle nesting activity was recorded on CPDK, Baa Atoll, Maldives throughout the year (in agreement with the guidelines of the Environmental Protection Agency of the Maldives, research permits EPA/2018/PSR-T03 and EPA/2020/PSR-T06). Nesting attempts and true nests were recorded, and nests were monitored throughout the incubation period until hatching occurred. Nests were excavated, and the nests’ contents were analysed at least 2 days after the emergence of the first hatchling, to allow for natural hatching of any stragglers. Variation in excavation times resulted from coronavirus disease 2019 (COVID-19)related safety measures and organisational restrictions. Any unhatched eggs were opened by hand, pinching the eggshell between two fingers and pulling apart to reveal the egg contents, which were then classified according to the criteria specified in Table 1 and reburied at the site of the nest.
| 2 | 2other
| 0Study
|
296,406 |
The measurements of fluorescently labeled DNA were conducted on Nikon® Eclipse Ti inverted epifluorescence Microscope (lens ApoTIRF × 100, NA 1.49) equipped with Andor® iXon 897 EMCCD camera and filters providing excitation for SYBR® Green at 465–495 nm and emission at 515–555 nm. DNA was stained by SYBR® Green I Sigma-Aldrich®.
| 4 | 0biomedical
| 0Study
|
144,098 |
Study concept and design: XX and YY. Data acquisition and data analysis: QG. Draft and revision of important content: XX and XD. Final draft approval: XS and XG. Literature research: ZL and XD. All authors contributed to the article and approved the submitted version.
| 1 | 2other
| 1Other
|
233,273 |
For preparation of primary BA, BAT was excised from neonates of WT, Sqstm1–/–, Nbr1–/–, and Sqstm1–/–Nbr1–/– mice regardless of gender, and minced in 2 ml PBS, then added with collagenase D (1.5 U/ml), dispase II (2.4 U/ml), and CaCl2 (10 mM) and the tissues were incubated at 37 °C with gentle shaking (30 min). Larger particles were removed using a 100 μm cell strainer, and the filtrates were centrifuged at 500 g for 5 min three times to pellet SVF and remove collagenase residue. Isolated SVF were seeded in culture dish for 4 days to eliminate the unattached dead cell/white blood cell populations. SVF including adipogenic precursors were passed into 6-well plate for in vitro differentiation. Two days post confluence, differentiation was initiated by induction cocktail (DMEM/F-12 containing 10% FBS, 2 μg/ml dexamethasone, 0.5 mM isobutylmethylxanthine, 125 µM indomethacine, 1 nM T3, 0.5 μg/ml insulin, and 1 µM rosiglitazone) for 2 days, followed by maintenance cocktail (DMEM/F-12 containing 1 nM T3, 0.5 μg/ml insulin, and 1 µM rosiglitazone and 10% FBS) for another 5 days to become fully differentiated. To generate iBAs, BAT SVF were immortalized by retroviral pBabe-zeo-LT-ST (SV40) and selected by Zeocin. Single cell clone was selected and tested for differentiation capacity. All selected clones used in this study maintain efficient differentiation potential and express the BA marker UCP1. Immortalized SVF are cultured in DMEM supplemented with 10% FBS (without pyruvate). For differentiation of iBAs, the induction cocktail contains dexamethasone (2 µg/ml), isobutylmethylxanthine (0.5 mM), indomethacine (125 µM), rosiglitazone (0.5 µM), T3 (1 nM), and insulin (5 µg/ml) in growth medium. After 2 days, cells were maintained in growth medium supplemented only with rosiglitazone, T3, and insulin till day 7 for experiments. For transfection assay, differentiating cells at day 5 were transfected with indicated vectors using X-tremeGENE HP transfection reagent (Roche). To stimulate thermogenesis, cells were treated with ISO (Sigma-Aldrich) for indicated times when cells were fully differentiated.
| 5 | 0biomedical
| 0Study
|
162,556 |
As the most direct method of reshaping gut microbiota, FMT had been applied to patients with severe diarrhea in the 4th century, according to the Chinese scientist Ge Hong.[ 171 ] The development of modern medicine has greatly improved the safety and patient compliance of FMT. Fecal donor selection and screening, fecal matter storage and biobanking, prudent clinical administration and data monitoring are all crucial steps in successful FMT.[ 173a,b ] As of yet, the most successful case of FMT application was about recurrent Clostridium difficile infection (RCDI).[ 178 ] The cure rate reached 90% with acceptable side effects.[ 173 , 178 ] As a biological therapeutic regimen, FMT was approved by FDA in 2013 for treating RCDI.[ 173a ] Subsequently, the executive discretion of FDA removed the restriction from Investigational New Drug on application of FMT to treat RCDI by qualified professionals.[ 173a ] The issued guideline for FMT from FDA requests the joint society recommendation to standardize the collection and analysis of fecal materials.[ 173a ] Moreover, to reduce the risk of FMT procedures, non‐profit “Netherlands Donor Feces Bank” is recommended as a fine example, for it runs an effective and credible system to optimize the safety of every step of FMT.[ 173b ] Not only for RCDI, several studies have provided evidence for the potential of FMT to treat IBD, colitis, and digestive system cancer.[ 42 , 179 ] Significant differences in gut microbiota have been observed in healthy and CRC patients based on 16 sRNA and OTU analysis. Generally, Fusobacterium, Escherichia–Shigella, and Peptostreptococcusten are enriched in CRC patients, which can be potential markers for diagnostics.[ 24 , 115 , 180 ] FMT to colitis‐associated colon cancer mice model decreased the tumor size by exerting protective anti‐inflammatory functions through the induction of CD4+ CD25+ Foxp3+ Tregs.[ 179 ] Furthermore, several seminal studies demonstrated that microbiota from anti‐PD‐1 therapy responders enhanced tumor‐infiltrating T cells and efficacy of immunotherapy.[ 154 , 155 ] A clinical trial utilizing FMT to ameliorate the outcome of anti‐PD‐1 therapy on melanoma cancer patients who failed to respond to immunotherapy has started in Israel (NCT03353402). In addition, a pilot study on the possibility of applying FMT on CRE has shown satisfactory outcomes, although large randomized controlled trials are still needed.[ 168 ] Recently, a project to investigate the safety of FMT for alleviating the toxicity of ipilimumab and nivolumab combination therapy on renal cell carcinoma patients was approved by FDA (NCT04163289). As the application of FMT in cancer therapy is in its infancy, more detailed mechanisms are supposed to be elucidated. The various adverse effects caused by FMT limit its clinical application. The mechanisms of FMT‐related adverse effects and treatment regime have not been established.[ 173 , 181 ] Since cancer patients usually suffer from compromised immune functions, stringent donor selection and screening are necessary for protecting patients from severe infections.[ 181 ]
| 4 | 0biomedical
| 2Review
|
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