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BALB/c mice were injected with pVaxRT1.14opt-in, pVaxRT1.14oil, or pVax1 plasmids intradermally with subsequent electroporation. On day 22, mice were sacrificed; blood and spleens were collected. Splenocytes were isolated and tested for the ability to proliferate after in vitro stimulation with RT-derived antigens. Immune response was evaluated as the production of IFN-γ and IL-2 by Fluorospot and perforin and granzyme B by sandwich ELISA. RT1.14opt-in- and RT1.14oil-immunized mice demonstrated similar levels of cellular response against the recombinant RT1.14 protein (Figure 7(a)). Immunization with DNA encoding RT1.14opt-in and RT1.14oil induced a weak IFN-γ and IL-2 response against a CD4+ T cell epitope of RT localized at aa 528-543 , which tended to be stronger in mice DNA immunized with RT1.14oil (Figure 7(b), p < 0,1). Peptides representing other known epitopes of RT induced no specific IFN-γ or IL-2 production (data not shown). Interestingly, splenocytes of mice DNA immunized with RT1.14oil responded to stimulation with these peptides by a strong production of perforin (Figure 7(c)). Levels of perforin secretion significantly correlated to the levels of RT-specific production IFN-γ and IL-2 (Figure 7(e); R values >0,8; p < 0,0005). On contrary, mice DNA immunized with RT1.14opt-in responded to stimulation with RT-derived peptides by a high-level production of granzyme B which was not correlated to either IFN-γ or IL-2 levels (Figure 7(d), data not shown). IFN-γ/IL-2 responses have also been tested in splenocytes stimulated with a peptide encoding a leader sequence of NS1 (NS1 leader peptide). No specific cytokine secretion was detected (data not shown).
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131,592 |
Patient satisfaction generally reflected the quality and performance in hospitals as an essential improvement indicator . There are varied reasons identified by researchers for patients' dissatisfaction, and the functional value of medical treatment was believed as the key value which originated from the normalization and quality . Research studies based on structure-process-outcome analysis expanded the assessment of the medical service quality from patients' perspectives: “structure” indicated the environment and physical facility in hospitals, “process” implied the treatment experiences in interacting with hospital staffs, and “outcomes” meant the physical treatment consequence and psychological impression during the interactions . Medical incidents and disputes destroyed public trust and impaired hospitals' reputation. It implied nontransparent treatment details, or unclear treatment processes could result in untrustworthiness, which would largely enlarge the medical disputes and patient-doctors' conflicts in China.
| 2 | 0biomedical
| 1Other
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311,899 |
In the peer review (EFSA, 2010), two representative uses were evaluated, sugar beet and tomato. The PRAPeR Expert Meeting TC 29 considered the metabolism study on sugar beet as not acceptable due to significant concerns on the storage stability of hymexazol and uncertainty regarding the method of application. Only the use on tomato was thus peer reviewed. The residue definitions derived for the enforcement (hymexazol) and risk assessment (hymexazol and glucoside conjugates – hymexazol‐O‐monoglucoside, hymexazol‐O‐diglucoside and hymexazol‐N‐monoglucoside, expressed as hymexazol) of fruit crops are still considered valid. Nevertheless, no uses on fruits or fruiting vegetables are authorised at the time of this MRL review.
| 4 | 0biomedical
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369,624 |
A difference emerged in the rates of difficulty accessing surgery according to sex. Despite the majority of non-emergency surgery patients being female, males had a higher incidence of difficulty accessing surgical care than females (i.e., 16.5% versus 14.9%). Research has shown that females have greater healthcare consumption , and males delay in seeking medical care ; as a result, males may experience greater difficulty accessing care. Differences may also be related to biases in self-report. A recent study showed that males experience less satisfaction after surgery compared to females, which may also contribute to perceptions of increased difficulty . However, these hypotheses are speculative; future research should aim to understand factors that may be driving the emergent sex difference (e.g., healthcare utilization, type and complexity of surgery).
| 4 | 0biomedical
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362,536 |
The dosing details are also given in Table 1. The volume of oral (p.o.) and intraperitoneal (i.p.) administrations was 1 mL/100 g b.w of mice. The treatments were continued for 8 days. In the behavioural Y-maze and Novel object recognition tests, scopolamine (1 mg/kg, i.p.) was given to these groups only on day 8th, and according to the standard procedure, 1 h after the administration of drugs all the animals were subjected to Y-maze and Novel object recognition test.
| 4 | 0biomedical
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379,626 |
There was a 100% match between signs and syndromes of ASF, as described by the stakeholders and molecular diagnostics based on partial amplification of the ASFV VP72 gene by PCR and RT-PCR, indicating that the farmers’ knowledge of the syndromes and clinical signs associated with ASF is extremely good. Interestingly, samples of fetal tissues and fluids that were aseptically collected during sampling were positive for ASF, indicating transplacental transmission. All the nine samples tested positive by PCR and RT-PCR (Figure 6). All samples were found positive by PCR amplification of the VP72 gene, with the highest positives (lowest Ct values, close to 20), recorded for spleen, whole blood and serum.
| 4 | 0biomedical
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84,942 |
Consider, then, the key features of embodied cognition as envisioned by its radical proponents; a causally constitutive role for sensorimotor contingencies, an enactive coupling of the organism to its body and environment, an ecological account of perceptual affordances, and a quality of affect and social meaning that pervades perception at the lowest level of information processing. Can predictive processing pass this high bar?
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7,016 |
Meanwhile, TV programmes designed for children include (in their advertising slots) advertisements for foods likely to promote obesity; children, of all people, should be prevented from exposure to such material, so likely to be damaging to their longer term health as adults .
| 2 | 2other
| 1Other
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16,701 |
A two‐way ANOVA revealed a significant effect for artery (P < 0.01), as brachial anterograde flow decreased significantly (P < 0.01), while the carotid remained unchanged (P = 0.93). Retrograde flow significantly increased in the brachial artery (P = 0.05), whereas carotid retrograde did not change (P = 0.56) (Table 1). Vascular conductance was also calculated and revealed significant main effects for artery (P < 0.01) and time (P < 0.05, Fig. 1).
| 5 | 0biomedical
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312,014 |
The AUCs from the three mpMRI classification schemes were statistically compared with those from the two single sequence classifiers using the DeLong test28,29. Bonferroni–Holm corrections were used to account for multiple comparisons30, and a corrected P < 0.05 was considered to indicate a statistically significant difference in performance. Equivalence testing was performed to assess if image registration had any effect on the classification performances31. An equivalence margin of difference in AUC = 0.05 was chosen prima facie.
| 4 | 0biomedical
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342,765 |
In this section, we evaluate the correctness of the proposed model based on the formal specifications presented in Section 7. Also, based on the security framework, assumptions presented in Section 3, and the formal specification we evaluate the proposed framework against the threats and its conformance to the stated security goals.
| 1 | 2other
| 1Other
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217,082 |
The majority of ChREBP loss-of-function studies suggest that hepatic ChREBP activity is necessary for sugar and obesity-induced metabolic disease. Paradoxically, two hepatic ChREBP gain-of-function studies suggest that ChREBP can play a protective role (Fig. 3B) (87, 97). Adenovirus-mediated overexpression of an N-terminally truncated, constitutively active fragment of ChREBP similar to endogenous ChREBP-beta in the liver lowers circulating glucose, insulin, and triglyceride levels while increasing hepatic de novo lipogenesis and steatosis. The beneficial effects of ChREBP overexpression on hepatic insulin sensitivity may be mediated by insulin-sensitizing effects of an increased ratio of monounsaturated fat to saturated fat (87). Nevertheless, the observations that both knockout and overexpression of ChREBP can have positive effects on systemic metabolism has generated significant controversy. Given the translational significance to human health, defining specific mechanisms by which hepatic ChREBP activity may be beneficial or harmful will be essential to resolve this controversy and understand the role for ChREBP and its targets in metabolic health.
| 4 | 0biomedical
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210,906 |
Intensity normalization of all participants (n = 5038) was achieved by affine registration of individual bivariate histograms to the reference histogram. This normalization facilitates tissue classification and comparison. Figure 1 illustrates bivariate histograms in two example participants (1 control, 1 MS patient) before and after intensity normalization. Histogram alignment error in each individual was compared to a fixed criterion determined by visual inspection of a representative sample (Figure S1). Individuals with histogram alignment error above this threshold (n = 28, 0.6%) were excluded. Histogram normalization parameters obtained in each participant were applied voxelwise to the T1w and FLAIR data, thereby generating images whose bivariate histograms closely approximated the normative reference.
| 4 | 0biomedical
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35,223 |
In the present investigation it was found that STDP windows were required to be very brief. It has been shown that, in theory, learning is optimum when the time constant τ for the STDP window matched the time constant τ for the LIF synapse (Kennedy et al., 2014). Cortical neurons investigated in previous experimental work show long STDP windows roughly corresponding to their longer membrane time constants (Markram et al., 1997). In the present model, it is possible that this optimum is not selected by the genetic algorithm due to the unique spike-initiation mechanism of the octopus cell, which is dependent not on the value of V, but on the value of dV/dt (Ferragamo and Oertel, 2002). This is a topic for future investigation. Future experimental work should aim to discover whether STDP windows much shorter than previously found do exist in the auditory brainstem where membrane time-constants are also much faster.
| 4 | 0biomedical
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312,632 |
(A) H69 cleavage levels for Caenorhabditis elegans worms exposed 24 h to 4 PA14 mutants (lasR, rhlR, gacA, and PA14_27700). All mutants are required for virulence towards C. elegans and 3 of them regulate bacterial QS (lasR, rhlR, and gacA). (B) Relationship between the capability to induce H69 cleavage and Pseudomonas aeruginosa virulence. The virulence of P. aeruginosa wild isolates is represented by the median survival time (in days) of wt worms exposed to the isolate, as determined previously . H69 cleavage–inducing capacity (present or absent) was determined by analysis of total RNA from worms exposed to each isolate for 24 h, using capillary electrophoresis. The mean virulence of the 2 isolate sets is significantly different (Welch t test, p-value = 1.1 × 10−7). S3 Table contains source data for panel B. (C) H69 cleavage levels for worms exposed to a bacterial mutant of exotoxin A (toxA) or wt PA14 for 24 h. The cleavage levels are n.s. (Welch t test, p-value > 0.05). (D) H69 cleavage levels for worms exposed to E. coli expressing the toxA gene or v. control for 24 h. H69 cleavage for PA14-exposed worms is included as control. (E) H69 cleavage levels of C. elegans lf mutants in 3 host response pathways (pmk-1, fshr-1, and zip-2). The worms were exposed to PA14 for 24 h. (F) H69 cleavage levels, following exposure to PA14 for 24 h, for C. elegans worms with reduced dynamin (dyn-1) gene function. Two experimental conditions are shown: (1) a dyn-1 ts (restrictive at 25° C) is compared to wt worms; and (2) dyn-1 RNAi knockdown in the intestine (using strain VP303) is compared with e. vector RNAi condition. For all graphs, “*” indicates p-value < 0.05, and “**” represents p-value < 0.01 for Welch t test comparisons between the plotted conditions. S1 Data contains source data for panels A and C–F. e. vector, empty vector; H69, helix 69; lf, loss of function; n.s., not significantly different; QS, quorum sensing; RNAi, RNA-mediated interference; ts, temperature sensitive; v. control, vector control; wt, wild-type.
| 4 | 0biomedical
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283,729 |
A further subdivision of the molecular function after the binding follows with 32.7% the catalytic activities (GO: 0003824), which are divided into the following groups: 47.1% hydrolysis activity (GO: 0016787), 16.8% oxidoreductase activity (GO: 0016491), 13.3% transferase activity (GO: 0016740), 7.8% lyase activity (GO: 0016829), 4.4% ligase activity (GO: 0016874), 18.3% protein activity on catalytic activities (GO: 0140096), 2.5% intramolecular transferase activity (GO: 0016866), and 1.7% further catalytic activity (GO: 0140098, GO: 0140097). This is followed by further molecular function with 10.1% structuring molecule activity (GO: 0005198), 5.3% molecular function regulator (GO: 0098772), 4.2% transporter activity (GO: 0005215), 2.1% molecular transducer activity (GO: 0060089), 1.8% transcriptional regulator activity (GO: 0140110), and 0.2% translational regulatory activity (GO: 0045182).
| 5 | 0biomedical
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85,769 |
The 143 Bacteria and Archaea genomes used in this work are the same dataset used in an earlier study 25, available at http://dx.doi.org/10.14264/uql.2016.908 35. The dynamic phylogenetic network of these genomes is available at http://bioinformatics.org.au/tools/AFnetwork, with the source code available at http://dx.doi.org/10.14264/uql.2016.952 36
| 3 | 0biomedical
| 1Other
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392,753 |
This study was based on data from a self-report questionnaire. Relying on a single data collection method may lead to common method bias and threaten construct validity (Donaldson and Grant-Vallone 2002) even if such a problem seems to be rarer than has been assumed (see for example Spector 2006). The tendency of an employee to bias his or her response may be evaluated based on four factors (a) the true state of affairs, (b) the sensitivity of constructs, (c) dispositional characteristics, and (d) situational characteristics (Donaldson and Grant-Vallone 2002). On this basis, we conclude that there is little risk that our participants’ responses were biased. For example, participants were not asked to self-report any socially undesirable behaviours among themselves and the constructs were not in itself sensitive for the respondents as we did not use self-definition of being exposed to bullying but the Negative acts questionnaire-revised (NAQ-R)—see Nielsen et al. (2011) for a discussion of the advantages and disadvantages of different workplace bullying measurement methods. Furthermore, the data were collected in the context of a regular work environment survey to which the participants were used to submitting information. This also indicates that data were collected in a context where there was little situational pressure to give socially desirable answers. Also, testing a common latent variable showed only 1.7% common variance among the variables in the study (Podsakoff et al. 2003).
| 4 | 2other
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30,698 |
Antimicrobial resistance decreased in more recent isolates, with a statistically significant difference for amikacin. Data for isolates of the present study were additionally analysed according to the same breakpoints used for isolates of Pellegrino et al. (2002); the difference increased for carbapenems and piperacillin-tazobactam. These results are consistent with the decline of SPM-positive isolates and the absence of the rmtD gene in the more recent isolates.
| 4 | 0biomedical
| 0Study
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223,399 |
To validate the effects of PEA in the development of NASH, PEA was administrated to MCD diet-induced NASH mice. The experimental scheme is shown in Figure 1A. MCD diet feeding caused a significant reduction of body weight, while PEA had no obvious impact on body weight compared with the MCD diet-fed mice during the experiment (Figure 1B). After sacrificing the mice, we first detected the role of PEA on MCD-induced NASH in mice through a histopathological evaluation, which is the gold standard for NASH assessment. HE staining showed that MCD diet-induced hepatic steatosis and ballooning compared to the mice who received a normal diet, while PEA treatment reduced both steatosis and ballooning (Figure 1C). Meanwhile, Oil Red O staining revealed that MCD diet feeding caused excessive lipid accumulation, while PEA significantly reduced the abundant lipid distribution in the liver (Figure 1D). Additionally, the high TG levels in the liver of MCD diet-treated mice were also obviously downregulated (Figure 1E). To further investigate the role of PEA on liver injury in MCD-treated mice, we determined the levels of ALT, AST, and LDH in plasma by a microplate-based method. MCD diet greatly induced the increase of plasma ALT, AST, and LDH levels, while PEA significantly decreased the levels of these biomarkers of liver function (Figures 1F–H). These results suggest that PEA significantly attenuated steatohepatitis in MCD diet-treated mice. In addition, we detected the levels of palmitic acid, palmitoleic acid, and oleic acid in the liver and found that palmitic acid levels were unchanged after being fed with a MCD diet, while hepatic palmitoleic acid and oleic acid levels were significantly decreased in mice fed MCD diet. Nevertheless, PEA treatment had no effect on all the above fatty acids compared with MCD-treated mice (Supplementary Figures S1A–C). Moreover, MCD diet feeding markedly elevated PEA levels, while PEA treatment enhanced this elevation compared to the Ctrl group (Supplementary Figure S1D). Meanwhile, we examined the expression of N-acylethanolamine-hydrolyzing acid amidase (NAAA) and fatty acid amide hydrolase (FAAH), both of which can hydrolyze endogenous PEA to palmitic acid and ethanolamine. The results showed that NAAA expression in the MCD group is higher than that in the Ctrl group and a reduced expression was observed in the PEA group, but these differences were not statistically significant (Supplementary Figure S1E). Notably, FAAH expression was obviously decreased with MCD feeding and unchanged after PEA treatment (Supplementary Figure S1F).
| 4 | 0biomedical
| 0Study
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256,580 |
Modification of STING. Post-translational modifications, trafficking degradation and binding affinities with cGAMP are involved. Phosphorylation by serine/threonine UNC-51-like kinase (ULK1) and TBK1 and ubiquitination by ubiquitin-binding protein p62 lead to the degradation of STING [73, 74]. Interestingly, the function of p62 is dependent on TBK1 and IRF3, which indicates negative feedback on the attenuation of signaling . Moreover, the tyrosine-protein phosphatase nonreceptor type (PTPN) 1 and 2 dephosphorylate STING at Y245 which promotes its 20S proteasomal degradation . Additionally, DNA virus infection triggered the ubiquitination of STING by upregulating TRIM29 .
| 4 | 0biomedical
| 0Study
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229,414 |
Research in the field of domestic violence against women and its relationship to the subsequent development of post-traumatic stress symptoms has focused mainly on studying factors external to the victim (e.g., intensity of violence or accumulation of traumatic incidents) that favor the clinical profile, ignoring factors internal to the victim herself, which has limited research in this field . Investigators might well have long avoided identifying the characteristics of the victim that may increase the risk of re-abuse in an attempt to avoid victim-blaming when the focus shifts away from the aggressors . Although this is a legitimate concern, it is important to collect information on the vulnerability of victims as it could guide patterns of action or treatment aimed at women’s empowerment and prevent revictimization by favoring the recovery of people subjected to intimate partner violence .
| 4 | 0biomedical
| 0Study
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354,605 |
While the total volume of brand-name OCP prescriptions filled declined steadily over time, the average prices of brand-name OCP increased by 90% from 2011 to 2014 (Fig 2). In 2011, market shares by each brand were more evenly distributed with prices of each brand spans narrowly differentiated; in contrast, in 2014, market shares by each brand were much more differentiated with an upward relationship between the price-prescription filled for those manufacturers with larger market shares. There was also a reduction of total number of brands from 22 in 2011 to 16 in 2014 (Fig 3). There was a steady increase of HHI from 1105 in 2011 to 2415 in 2014, and despite 37% fewer brand-name OCP prescriptions filled, there was an 18% increase in revenue from 2011 to 2014 for the industry (Table 3). The multiple regression analysis showed that for every 1 percentage point increase in the market share by an individual brand, its price increased by $3.12 (p<0.01) controlling calendar years, age, race, ethnicity, and insurance status. For the covariates, on average, compared to whites, African American had a price $4.78 lower (p<0.01) per Rx; compared to non-Hispanics, Hispanics had a price $4.87 higher per Rx; compared to those with private insurance, those with Medicare, uninsured had a price $7.02, $5.72 lower per Rx (p<0.01 respectively), while those with Medicaid, Tricare $1.26, $15.83 higher per Rx (p<0.01 respectively); each year of increase in age was associated with $0.32 higher in price (p<0.01); each year of increase in calendar year was associated with $7.57 higher per Rx (p<0.01).
| 4 | 0biomedical
| 0Study
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136,458 |
Third, we introduce an efficient MCTS playout policy for high-dimensional continuous action space. Traditional MCTS relies on a playout policy with random moves, but when the search space is intractable such a policy can make the learning process extremely difficult and inefficient22,23. For example, even with the tree-depth based scaling of action space, a random playout (assuming uniform probability distribution) will have a high chance of action selection which is far from the parent node; see Supplementary Methods (Section 3.2) for a discussion on how uniform or multivariate Gaussian probability distribution based playout policies systematically select actions that have large displacements from the parent node. To avoid this issue, we used a biased playout policy that selects action based on the probability distribution r−(d−1) where r is the distance from the parent node, and d is the dimensionality of the search space. Based on our experiments, we found this playout policy to provide significant improvement in the performance owing to better action selections.
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| 0Study
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227,664 |
The patient was referred to an ophthalmologist for evaluation of possible adverse effects of long-term systemic corticosteroid treatment. Best-corrected visual acuity was no light perception in the right eye and 5/20 in the left eye, with eccentric fixation and exotropia in the right eye. Anterior slit-lamp examination had no remarkable findings. A dilated fundus examination showed vascular attenuation, optic disc pallor, and retinal pigmentary changes in both eyes (Figures 1A, B). Macular optical coherence tomography (OCT) demonstrated marked disruption of the external limiting membrane with an ellipsoid zone in both eyes, and small foveal cysts in the left eye (Figures 1C, D). Scotopic and photopic electroretinograms showed no recordable responses in either eye (Figures 1E, F). Ultra-widefield fundus autofluorescence examination showed a subtle ring of excessive autofluorescence in the parafoveal regions in both eyes, and ultra-widefield OCT demonstrated diffuse thinning of both retinas with loss of outer retinal structures, as reported in a previous diagnostic image presentation (12). Serologic tests were positive for anti-recoverin antibody and negative for anti-alpha enolase antibody. Based on these ocular and serologic findings, the patient was additionally diagnosed with bilateral autoimmune retinopathy. Systemic evaluation including MRI, ultrasonography, and serum tumor marker determinations such as alpha-fetoprotein, carbohydrate antigen 19-9, carcinoembryonic antigen, and squamous cell carcinoma-related antigen disclosed no underlying malignancy at the age of 3 years.
| 4 | 0biomedical
| 3Clinical case
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298,622 |
The ionization states of the amino acid side chains were determined at pH7.0, using propKa implemented in the play molecule (Martínez-Rosell et al., 2017). The system was described using the ff14SB force field and further processed to run MD simulations with Desmond 3.6 (Bowers et al., 2006). The overall charge was neutralized by manual addition of 150 Na + ions to both systems that were subsequently solvated by adding TIP3P water molecules. In total, 77,896 (Deoxy) and 77,848 (Oxy) water molecules were present in a solvation box with edges set at least 12 Å from the solute atom.
| 4 | 0biomedical
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59,501 |
The pathophysiology of depressive disorders is complex and not adequately understood. At present, there is substantial evidence implicating neurogenic processes and neurotrophic regulation in key limbic structures of the depressive brain.1, 2, 3, 4 The timeframe for the therapeutic effects of antidepressants, particularly selective serotonin reuptake inhibitors, coincides with that required for the maturation of nascent granule cells in the dentate gyrus.1, 4, 5 Disrupting neurogenesis (for example, via irradiation) blocks the behavioural effects of serotonin reuptake inhibitors in animal models.1, 3 In addition to hippocampal neurogenesis, antidepressants upregulate brain-derived neurotrophic factor (BDNF) in various brain regions.2, 6
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193,888 |
The rat insulinoma cell line, INS1E, was a gift from Dr. Dawn Kilkenny, University of Toronto, ON, Canada. The cells were maintained in RMPI 1640 medium (Sigma) supplemented with 2 g/L sodium bicarbonate, 10 mM Hepes, 11.2 mM D-glucose, 1 mM sodium pyruvate, 2 mM L-glutamine, 50 µM beta-mercaptoethanol, 100U/ml penicillin/streptomycin and 10% heat-inactivated fetal bovine serum (FBS). Cells were cultured in a humidified incubator at 37°C and 5% CO2 and passaged when cultures reached 80% confluency. For all in vitro experiments, cells were plated at a density of 5x105 cells/well in 6-well multiwell tissue culture plates (Falcon, VWR International, Mississauga, ON, Canada).
| 4 | 0biomedical
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158,799 |
Thank you for the opportunity to resubmit a revised version of our manuscript now entitled ‘Dietary risk factors for hip fracture in adults: An umbrella review of meta-analyses of prospective cohort studies’. We thank all reviewers for their constructive comments and suggestions, and present point-by-point responses below. References to changes made refer to the revised manuscript with track changes. All responses below are also presented in the 'response to reviewers' letter.
| 1 | 2other
| 1Other
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147,332 |
After showing that Cyp4a14 was an important player in liver fibrosis after BDL, we then addressed the question whether overexpression could rescue this effect. HSC activation is the center process in BDL-induced fibrosis. We hypothesized that Cyp4a14 may play an important role in the HSC activation. To explore the exact role of Cyp4a14 in HSC activation, we constructed a GFAP-promoter driven AAV9-Cyp4a14. We overexpressed Cyp4a14 in the HSCs of WT mice via tail vein injection 2 weeks before BDL surgery. Cyp4a14 overexpression was succeeded and validated by mRNA and protein levels by four- to seven-fold (Figures 4A,B). The body weight was also obviously decreased while liver weight was increased in the AAV-control + BDL group compared with the sham group (Figure 4C). There was no difference between the AAV-control + BDL group and the AAV-Cyp4a14 group (Figure 4C). Masson and Sirius Red staining revealed a significant decrease in fibrotic area in the AAV-Cyp4a14 + BDL group compared with the AAV-control + BDL group (Figure 4D). In line with the histological analysis, liver Hyp content is also improved in the AAV-Cyp4a14 + BDL group compared with the AAV-control + BDL group (Figure 4E). In addition, serum ALT and AST were significantly lower in the AAV-Cyp4a14 + BDL group compared with the AAV-control + BDL group (Figures 4F,G). These together confirmed that BDL-induced liver damage was alleviated after HSC Cypa14 overexpression.
| 4 | 0biomedical
| 0Study
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373,926 |
Recent literature suggests that the host microbiome is a modifier of disease outcome and parasite development. The microbiota serves as an immune response trainer , processor of carbon sources unavailable to the parasite , sustenance to the parasite via phagocytosis , can produce metabolites that inhibit encystation , and together with a healthy mucus barrier, is the first line of defense against parasite infection (reviewed in ). Moreover, the microbiota is required for E. histolytica pathogenicity, as germ-free mice have an attenuated response to parasite infection . The importance of the microbiome is also observed in human cohorts and case studies, demonstrating a correlation between dysbiotic state, a well-known niche for opportunistic pathogens, and E. histolytica infection outcome . Recently, the microbiome has been shown to have an effect on disease severity via the recruitment of neutrophils . Additionally, halting of encystation has been observed in E. invadens via microbiome metabolites . The oral infection route is a modulator of disease progression and host immunological response, based on the impact pathogen delivery has in other parasites. For Toxoplasma gondii, immune murine knockout strains only displayed an increased susceptibility to infection when parasites were delivered through the natural route of infection . For Trypanosoma cruzi, oral versus gastrointestinal delivery of trypomastigotes displays distinct patterns of disease progression in BALB/c mice . Lastly, vaccine administration factors are evidence of how the route of delivery of antigens can lead to distinct immune responses, for example, mucosal inoculation leading to immunoglobulin A (IgA) production . While bacterial microbiome changes have been correlated with various parasitic infections in numerous cohort studies (reviewed in ), it is unclear if the parasitic infection causes a state of dysbiosis or vice versa. Animals colonized with fixed microbial communities and orally challenged with either parasite stage will provide insight regarding the effect of the microbiome on parasite development.
| 5 | 0biomedical
| 2Review
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196,017 |
T2D is not only attributed to beta-cell dysfunction but also alpha-cell dysfunction.141,142 Pathologically high plasma concentrations of glucagon are observed in T1D, advanced T2D, and diabetic ketoacidosis.142 It is well established that islet alpha-cell populations increase in T1D, whereas in T2D, patients can have alpha-cell numbers increased or unaltered.141 Paradoxically, T2D patients have increased levels of glucagon during the postprandial period, leading to augmentation of postprandial hyperglycaemia associated with impaired insulin secretion.142,143 Hence, it is correct to state that the behaviour of diabetic islet alpha-cells is different for healthy individuals, as an abundance of nutrients during the postprandial period prevents glucagon secretion in healthy individuals by raising ATP levels (as discussed earlier in this review).144 Therefore, in T2D, the islet alpha-cells must have altered biochemical pathways inducing altered mechanisms of glucagon secretion. Studies have estimated that postprandial hyperglucagonemia may contribute to ~50% of the pathological increase in plasma glucose levels after glucose ingestion.145–147 Interestingly, fasting hyperglucagonemia has been reported in some T2D patients with moderate glycaemic control, and glucagon levels are ~50% higher in diabetic subjects.146,148 The dysfunctional glucagon secretion in T2D could be due to the decreased insulin levels, as insulin suppresses alpha-cell function.105,149 However, islet alpha-cells should have their exocytotic function suppressed during the fed state, as intracellular ATP levels should be high as a result.144 However, studies have demonstrated that blocking insulin signalling in islet alpha-cells in mice results in defective suppression of the fed state on glucagon secretion, highlighting the pivotal role of insulin in the regulation of the alpha-cell.105,149
| 4 | 0biomedical
| 2Review
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75,755 |
Studies showed that the Egr-1 promoter containing CArG regulatory sequences can control the expression of downstream genes spatially and temporally [28–33]. Our previous studies found that a chimeric promoter containing six tandem CArG boxes can sense radiation treatment and activate the expression of the target gene P53 . Therefore, a certain number of tandem CArG boxes can be used as a radiosensitive regulatory element to regulate the expression of the therapeutic gene . A chimeric promoter composed of nine tandem CArG boxes coupled with the CMV basic promoter has better radiosensitivity and lower normal background than the wild-type Egr-1 promoter [14, 36]. Based on the preliminary work, we used the lentiviral vector pLVX-AcGFP1-N1 as backbone vector, replacing the original CMV promoter with a chimeric C9BC promoter containing nine tandem CArG boxes coupled with the CMV basic promoter and constructed the radiation-inducible reporter vector pLVX-C9BC-AcGFP1-N1 and therapeutic vector pLVX-C9BC-SOD2-T2A-AcGFP1.
| 4 | 0biomedical
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31,266 |
The tryptic peptides from both control and DMOG-treated cells were analyzed by LCMS as previously described. The precursor ions with the mass-to-charge ratios of 668.3604 and 663.0288, corresponding to hydroxylated and unmodified Brd4 peptides, respectively, were targeted for fragmentation. The mass spectrometry data were acquired with Orbitrap in high resolution for both MS and MS/MS analysis. Specific HPLC elution peaks for each peptide were determined with Parallel Reaction Monitoring (PRM) of multiple product ions . The peak areas of the precursor ions were calculated to determine the abundance of modified and unmodified peptide isoforms. The stoichiometry was estimated with the following formula: Hyp% = (Peak area of Hyp peptide) / (Peak area of Hyp peptide + Peak area of Pro peptide).
| 4 | 0biomedical
| 0Study
|
354,438 |
There is a widespread need to improve the functioning and alleviate the symptoms of patients with NSCLC. Symptom monitoring allows earlier detection of symptoms, adverse events, and their recurrence, so that interventions can be used to improve HRQOL and possibly prolong survival .
| 2 | 0biomedical
| 1Other
|
83,914 |
Other potential approaches to suppress TGF-β signaling include gene transfer of inhibitory Smad7, which has been tested in animal models for vascular remodeling, diabetic kidney disease, and colonic and hepatic fibrosis.571,572 The major concern that limits the clinical translation of this approach is the barriers that face all gene therapies.573 TGF-β activation may also be blocked by small peptides. An LSKL (Leu-Ser-Lys-Leu) peptide, which specifically binds to a conserved sequence in the LAP region of the TGF-β latent complex has shown effectiveness in suppressing TGF-β signaling in vitro.71 However, its TGF-β blockade efficacy has not been demonstrated in vivo yet.
| 4 | 0biomedical
| 0Study
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391,522 |
The EcoKMcrA N-terminal domain (NEco) engages in base-specific interactions with the DNA primarily via two loops (residues 29–37 and 107–123), as well as an α-helical region (residues 64–71) (Figure 1). All three regions of NEco approach the DNA predominantly from the major groove side. The loop 29–37 is closer to the distal strand, but nevertheless interacts with both DNA strands. The other two regions are closer to the proximal strand and interact only with it. NEco-DNA interactions are discussed below following the proximal strand in the 5′ to 3′ direction. The relatively scarce distal strand contacts are discussed together with interactions to the paired proximal strand base (Figure 3 and Supplementary Figure S3).
| 4 | 0biomedical
| 0Study
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363,516 |
As described in Section 3.3.2.2, field trials were performed in the US in the 2010 growing season to assess the agronomic/phenotypic characteristics of the five‐event stack maize in comparison with the non‐GM comparator. The data showed no changes in agronomic and phenotypic plant characteristics that would indicate altered fitness, persistence and invasiveness of the five‐event stack maize.
| 2 | 0biomedical
| 0Study
|
381,394 |
At the beginning the source phase was an aqueous solution (2 mL) of acetic acid salts of various amines in 1 mol/L concentration, while the receiving phase was 6 mL of distilled water. The bulk liquid membrane was a solution of the crown ether in 12 mL of dichloromethane, which proved to be an appropriate solvent due to its high apolarity and density. Using an apolar membrane solvent prevents membrane leakage and allows only the carrier-mediated transport of the amines. The concentration of crown ethers in the membrane was 1 mmol/L, and thus the amines were present in more than a hundredfold excess during the transport. The transported weight-percentage value of the ammonium salt content in the receiving phase was chosen as output parameter as well as flux, since it includes information about both the transport time and the geometry of the applied apparatus. The structural preference of the crown ethers toward the amine model compounds was investigated from various aspects (Figure 3A–D). The results are summarized in Figure 3.
| 4 | 0biomedical
| 0Study
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277,899 |
Blue bars denote clear positive correlation, red for negative correlation, and gray bars have no clear correlation. Land area and population are the top two features that determine model predictions. Among amenities, Leisure, Civic/Amenity, and Sustenance are the top 3 predictive features.
| 1 | 2other
| 1Other
|
176,847 |
While time-correlated single-photon counting (TCSPC) allows probing the dynamics of fluorescent photoexcited species, it is too slow for fast picosecond transitions along the S1 PES and cannot monitor any dark states that may form. Therefore, we resorted to pump-probe transient-absorption TA spectroscopy to elucidate further the excited-state dynamics of these DPPs.
| 4 | 0biomedical
| 0Study
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242,654 |
Six-week-old female NSG (NOD.Cg-Prkdcscid ll2rgtm1Wjl/SzJ) mice were purchased from the Centrale Dienst Proefdieren (CDP) breeding facility within the University Medical Center Groningen. Mouse experiments were performed in accordance with national and institutional guidelines, and all experiments were approved by the Institutional Animal Care and Use Committee of the University of Groningen (IACUC-RuG). Ten female NSG mice were injected subcutaneously with U2932 cells in matrigel (Basement Membrane Matrix, 354234, Corning, 50/50, 1 million cells) in each flank and randomly divided into two groups of five. The treatment group received a 50 mg 60-day release tamoxifen pellet (Innovative Research of America) on day zero, which has been shown to raise levels of tamoxifen in serum to 0.07 µM and was effective in a xenograft mouse model . Tumor size was measured with caliper up to three times a week.
| 4 | 0biomedical
| 0Study
|
86,279 |
Reverse osmosis (RO) technology is being used worldwide for full-scale municipal wastewater reclamation to produce high-quality recycled water to meet the increasing water supply demand . However, this technology generates highly saline RO concentrate (ROC) streams, which contain almost all of the contaminants and nutrients derived from the secondary effluent at elevated levels (4–6 times higher) . With commercial scale capacities up to 3 million m3/day of clean water, generation of ROC at large scale creates a significant ecological problem. Consequently, there is a growing need to explore cost-effective treatment options for the ROC for reducing its environmental and health risks on disposal or reuse.
| 2 | 2other
| 1Other
|
253,593 |
The mechanisms underlying the pathogenesis of tendinopathy in diabetes remain unclear . The novel finding in this study is that MIF can alter the tendon differentiation function of TdSCs in hyperglycemic conditions. Under hyperglycemic conditions, expression of osteochondrogenic differentiation markers in TdSCs was upregulated following treatment with recombinant MIF and downregulated upon knockdown of the MIF gene. In contrast, treatment with recombinant MIF did not affect the expression of tenogenic differentiation markers, and knockdown of the MIF gene upregulated the mRNA expression level of only some of the tenogenic differentiation markers. To the best of our knowledge, this is the first study on the effects of hyperglycemic conditions and MIF on the differentiation function of TdSCs.
| 4 | 0biomedical
| 0Study
|
171,649 |
Each line represents seroprevalence rates (summarized in table below) derived from four analytical methods bi-monthly between April and September 2020 (during the first COVID-19 Wave). > = 2 proteins (positivity was determined by a reactive sample from two or more assays), BLCA-Bayesian latent class analysis with informative priors, results are posterior means and error bars are 95% CrI and Abbott-NP is a single commercial assay.
| 4 | 0biomedical
| 0Study
|
27,504 |
We found that it took less time to perform rigid URSL than PCNL. It should be indicated that most studies didn’t state the definition of operation time clearly and each study might calculate the operation time in different criteria, which was also the most important reason for high heterogeneity. Moreover, operation time mainly depends on patient characteristics and surgeon’s experience. The shortest and longest operation time for rigid URSL in included studies was 30.6±7.8min and 92.0±32.5min respectively, while 38.5±8.2min and 115.4±49.5min for PCNL, which showed a great difference.
| 4 | 0biomedical
| 0Study
|
133,563 |
Titanium alloys are commonly used in aerospace industries, where their high strength and relatively low weight allow for significant weight savings. The additional high corrosion resistance makes them favourable for applications where good performance under high frequencies and at high numbers of load cycles regime is required. HCF-related gas turbine engine failures observed by the US Air Force led to increased interest in fatigue of Ti6Al4V in the early 1990s, resulting in the “High Cycle Fatigue Science And Technology Program” by the US Air Force, starting in 1994 (e.g., ). Today, the interest in titanium alloys extends to additively manufactured (AM) applications, where a methodology for the rapid characterisation of fatigue properties for the many different processes, build conditions and post-processing procedures could greatly speed up material development.
| 2 | 2other
| 1Other
|
321,099 |
The distribution by professional categories has emphasized that the poorly managed situations refer to the following issue groups: while medical nurses complain especially about issues regarding perspective, work diversity, trust, and cooperation, communication, information and competence, the lack of appreciation for their work, physicians complain especially about issues regarding contradictory provisions and the work tasks. All categories complain to the same extent about issues related to hygiene, security, retribution, and work fractioning.
| 2 | 0biomedical
| 0Study
|
102,653 |
Finally, qPCR assay allowed M. bovis detection in sterile soils A and B incubated at 22°C over a longer period of time than the culture-based assay. Indeed, M. bovis DNA was detected by qPCR for up to 150 days in the two sterile soil samples, while bacterial culture detected viable M. bovis cells up to 60 days in soil B and 90 days in soil A.
| 4 | 0biomedical
| 0Study
|
350,405 |
In literature, there is no consensus on the relationship between trust and credibility in the realm of health-related information seeking (Sbaffi and Rowley, 2017). Though correlation has been proposed, the distinctions made in the literature are unclear. In the present research, we thus focused on both. We specifically stressed the perceived credibility of information sources related to the COVID-19 pandemic, as well as the general trust in institutions that were involved in spreading information about COVID-19 in Slovenia and abroad. We proposed and tested two structural models linking each of the constructs to self-protective behavior, which was mediated by the effect of negative emotions and subjective knowledge about the disease.
| 4 | 0biomedical
| 0Study
|
386,336 |
In addition to analyzing patients’ prosthetic maintenance measures, the present study also investigated OHRQoL. Analysis of the results of the OHIP-G14 questionnaire revealed that the study patients’ OHRQoL was less impaired than that of most patients who are edentulous or wear complete dentures . A possible explanation for the findings could be that wearing implant-supported prostheses results in an increase in oral function. In general, an improvement in speech quality after prosthetic rehabilitation was observed by Knipfer et al. . Furthermore, Müller et al. described a positive effect on chewing efficiency for implant-supported overdentures .
| 4 | 0biomedical
| 0Study
|
245,319 |
In the nearly seventy years since the discovery of the DNA double helix, technologies have advanced for determining, analyzing and altering genome sequences and gene expression patterns in cells and organisms. These molecular tools are the foundation of molecular biology, fueling the therapeutic industry by enabling profound advances in understanding the genetics of normal and disease traits. The ability to diagnose genetic diseases has developed rapidly with reductions in genome sequencing costs, extensive comparative analyses of human genome sequences and applications of high-throughput genomic screening. However, the dearth of therapies, much less cures, for genetic diseases has created a growing disconnect between diagnostics and treatments, underscoring the urgent need to develop therapeutic options. Mitigation or correction of disease-causing mutations is a tantalizing goal with tremendous potential to save and improve lives, representing a convergence of technical and medical advances that could eventually eradicate many genetic diseases.
| 4 | 0biomedical
| 2Review
|
341,906 |
This study includes limitations. First, data on childhood illness and related care-seeking behavior during the previous two weeks were collected during participant interviews and may be subject to a combination of recall and social desirability bias. A recent study of the validity of maternally-reported care-seeking for childhood illness found that the indicator had both high sensitivity and specificity, resulting in only a minor overestimation of care-seeking relative to true levels . Previous experience within this study area noted the potential for underreporting of sensitive health behaviors (eg, abortion services), especially when solicited through a survey-based approach , though this bias is likely reduced when asking about less sensitive behaviors. Second, the high levels of sociodemographic indicators (eg, mother’s education, access to care) observed within our study population limit the generalizability of our findings to the state of Maharashtra and similar contexts . The study area represents a community in transition, historically based in agriculture but subject to the urbanizing influence of the nearby metropolitan area. As large urban centers continue to expand throughout India and elsewhere, the number of such communities will continue to grow. Third, distance to the nearest health facility was estimated as the shortest path along the road network and did not account for other factors potentially affecting travel time, such as road type or the transportation mode used, as the inputs required for such an approach were unavailable in this study. Furthermore, a comparison of methods to calculate geographic access to care found similar results across methods of varying levels of sophistication, suggesting that a less sophisticated approach may provide a reasonable measurement of geographic access in the context of low- and middle-income countries . Finally, one fifth of illness records included at least one variable with a missing response with illness severity missing most frequently. Excluding these records from analysis may have reduced statistical efficiency and yielded null results where a significant association might otherwise be detected. Similarly, excluding records with missing values may have resulted in biased estimates if these data were systematically different from those that were not missing. Our sensitivity analysis comparing completed cases alone with the multiply imputed data set yielded similar results, suggesting no significant bias in our results due to missing data.
| 4 | 0biomedical
| 0Study
|
240,555 |
In both 2′-dG-II riboswitches, the critical nucleotide U22 was essential for communication between P1 and P2, with approximately 0.97 degeneracy. Therefore, the preferred communication pathway involved the aptamer’s P1–J1/2–P2 regions (Figure 8C,D). In class I, the equivalent nucleotide (C31) resulted in a degeneration of 0.64 and 0.18 for rG and dG, respectively. Here, the key nucleotide C80, from the J1/3 region, presented a degeneration of 0.72 and 0.33 for dG and rG, respectively. Moreover, the preferred communication path of the dG-bound system involved the P1–J3/1–P3–L2–P2 regions (Figure 8A,B).
| 4 | 0biomedical
| 0Study
|
137,067 |
Stripe rust is one of the most devastating diseases of wheat worldwide (Chen, 2020) and is especially destructive in the western United States (Chen et al., 1995b; Rutkoski et al., 2014; González-Camacho et al., 2018; Liu et al., 2019) causing more than 90% yield losses in fields planted with susceptible cultivars (Liu et al., 2020). The use of resistant varieties and fungicide applications are the primary methods to control stripe rust (Chen et al., 1995b; Liu et al., 2020). Quantitative stripe rust resistance, also known as adult-plant resistance (APR) or HTAP resistance, is usually a non-race specific resistance associated with durable resistance with some genes being effective for more than 60 years (Klarquist et al., 2016). APR is conferred by different numbers of loci with varying effects and often displays partial resistance, which makes it difficult to incorporate into new cultivars (Liu et al., 2019). Therefore, APR must be improved over multiple cycles of selection and can be approached similarly to other agronomic traits (Rutkoski et al., 2014; Poland and Rutkoski, 2016; González-Camacho et al., 2018). GS approaches would be able to capture the additive effects of APR and are therefore relevant for accumulating favorable alleles for rust resistance (Rutkoski et al., 2014; Michel et al., 2017).
| 4 | 0biomedical
| 0Study
|
378,589 |
All participants were able to complete the tasks. Ten of 12 surgeons (83.3%) had a higher rate of movement hesitations and corrections in monitor-based performance. Monitor-to-site angles > 45° caused high discomfort. In monitor-to-site angles < 45°, we observed a linear increase of hesitations, corrections, and monitor-to-site checks (angle 0–10°: mean CHECS 14.6; angle > 10°: mean CHECS 20.7). Furthermore, we saw differences between more paramedian (frontoparietal) and more lateral (pterional) approaches (see Fig. 2) including a positive correlation between more lateral camera inclination and impact on hand-eye coordination (rs = 0.756, P = .01).Fig. 2Synopsis of effects on hand-eye coordination in cranial task performance compared for frontoparietal (light gray) and pterional (dark gray) approaches (participants n = 9); plotted on the horizontal axis are numbers of hesitations, corrections, and direct sight control plus overtime needed for task completion in minutes
| 4 | 0biomedical
| 0Study
|
248,016 |
As part of the standardisation of life courses in the post-war period, a relatively early marriage was incentivised leading to a spike in marriage rates. Although marriage rates have since declined with cohabitation and divorce common, a stable first marriage is still associated with a range of wealth-enhancing mechanisms for both men and women (Lersch, 2017). This marriage wealth premium is shaped, firstly, by greater economies of scale and institutional benefits (i.e. tax, pension, or insurance benefits) that enable higher saving rates. Secondly, social norms around marriage explicitly emphasise saving for a joint future, highlighting long-term commitment, and increasing intergenerational transfers. High levels of commitment and perceived longevity of the marital institution additionally provide an environment in which sharing, and resource integration are perceived as low risk. This increases the likelihood of investing in assets that may provide higher returns in the long-term and over time compounded interest effects may exponentially increase wealth as a form of cumulative advantage. Thus, the duration of marriage matters with marriage at a normative age (i.e. after completion of education and not too late in the life course) associated with an optimal time to maximize wealth benefits associated with marriage.
| 1 | 2other
| 1Other
|
378,691 |
A single human participant (male, age 27.5) watched 30 episodes from seasons 2 to 4 of the 2005 relaunch of Doctor Who. This comprised the training set which was used for model estimation. Episodes were split into 12 min chunks (with each last one having varying length) and presented with a short break after every two runs. The participant additionally watched repeated presentations of the short movies Pond Life (five movies of 1 min, 26 repetitions) and Space / Time (two movies of 3 min, 22 repetitions), in random permutations and after most episodes. They were taken from the series’ next iteration to avoid overlap with the training data. This comprised the test set which was used for model validation.
| 2 | 2other
| 0Study
|
332,252 |
The body varies from 4.8 to 5.6 mm long. The head may be almost entirely pale, with only a small brown marking on the posteromedial area of the vertex. This varies to an almost entirely black head, with only parts of the antennal calli and anterofrontal region pale. In some specimens, the region below the eyes and the antennal fossae are pale, while the frontal ridge and anterofrontal ridge are brownish black. In others, the frontal ridge is pale, the antennal calli and the entire area beyond the eyes and antennal fossae are brown, while the rest of the head is black. In some specimens, the dorsal surface of basal antennomere is distally or entirely brown. Rather than entirely pale, the pronotum may have a brownish black, irregularly shaped macula (Fig. 4C). The ventral areas of prothorax may be partially black (Fig. 4D). The venter of some specimens is entirely pale yellow, while that of others is largely brownish but with the area immediately anterior to each mesocoxa and the posterior margin of the abdominal ventrites paler (Figs 1B, 4D). Apparently, the elytral setae are easily abraded, and they are therefore not abundantly present in some specimens.
| 3 | 0biomedical
| 0Study
|
230,236 |
Here, we found that SAMHD1 expression was significantly associated with poorer prognostic clinical outcomes, including DFS and OSCD in all tumor types analyzed, including advanced disease cases of breast, ovarian, and NSCLC cancer. Interestingly, SAMHD1 positivity was an independent prognostic factor of worst DFS in breast and NSCLC cancer. Collectively, our data confirm the key role of SAMHD1 in cancer progression but also indicates that its function might depend on the specific tumor type, being able to act as a tumor suppressor, as reported previously mainly for hematological tumors or alternatively as a promoter of cancer progression. Indeed, data derived from TCGA or ICGC databases show similar results, pointing towards SAMHD1 tumor promoter function in ovarian carcinoma, but not in lung and breast carcinoma , in contrast with the data presented here. Differences in methods for determining SAMHD1 status, the heterogeneity of the clinical series evaluated, and the possible different treatments that patients receive may explain the apparent contradictory results between data from databases and our data, which rely on rather small but homogenous cohorts evaluated using the same criteria across tumor types and samples. Overall, our results, and that of others, point toward a tumor type-dependent function of SAMHD1 in cancer onset and/or progression, reflecting once more the great heterogeneity of cancer biology, which deeply challenges the drive for personalized treatment.
| 4 | 0biomedical
| 0Study
|
4,088 |
Confocal imaging was performed on a Zeiss LSM 780 upright confocal microscope (Carl Zeiss, Jena, Germany) with a W-Plan Apochromat × 20 objective, NA 1.0. The calcein staining was excited at 488 nm and the emission was collected at 492/577 nm. Z-stacks were acquired at 1.5 μm increments, every 1 min. Pictures were processed off-line using ImageJ (NIH) and Avizo (FEI).
| 4 | 0biomedical
| 0Study
|
196,249 |
To determine whether BBSKE can synergize with oxaliplatin to kill cancer cells, we first tested the effect of BBSKE or oxaliplatin alone or their combination on the viability of SGC-7901 and MGC-803 cells. Using a CCK8 assay, we found BBSKE treatment suppressed the growth of gastric cancer cells in a dose-dependent manner (Additional file 1: Figure S2A). In addition, we found 5 µM BBSKE significantly increased the cytotoxicity of oxaliplatin in SGC-7901 and MGC-803 cells (Fig. 1a-b) but showed no cytotoxic effect on GES-1 cell (Additional file 1: Figure S2B). The interaction of BBSKE and oxaliplatin was calculated by using combination index values (Fig. 1c-d), which demonstrated that BBSKE in combination with oxaliplatin exhibited a synergistic effect in gastric cancer cells. Furthermore, compared with BBSKE or oxaliplatin treatment alone, the combined treatment dramatically increased the apoptotic cell death in both SGC-7901 and MGC-803 cells (Fig. 1e-f). These results suggested that BBSKE synergized the chemotherapeutic effect of oxaliplatin in gastric cancer cells. Fig. 1BBSKE synergistically increased the cytotoxicity of oxaliplatin in gastric cancer cells. a-b SGC-7901 and MGC-803 cells were treated with BBSKE and oxaliplatin alone or in combination with the indicated concentrations. At 24 h after treatment, the cell viability was determined by CCK8 assay. c-d The combination index (CI) values of BBSKE combined with oxaliplatin were calculated using the calcusyn software. e-g SGC-7901 and MGC-803 cells were treated with BBSKE and oxaliplatin alone or in combination with the indicated concentrations. At 24 h after treatment, the percentage of cell apoptosis was determined by Annexin-V/PI staining and flow cytometry, and the percentage of apoptotic cells in the treatment groups was calculated. (* p < 0.05, ** p < 0.01)
| 4 | 0biomedical
| 0Study
|
33,773 |
To further investigate the role of USP13 in antiviral signalling, we generated USP13-deficient mice by CRISPR/Cas9-mediated genome editing (Supplementary Fig. 3a). Results from sequencing showed that a single cytosine was inserted into the first exon of Usp13 gene at the 97 position of the Usp13 open reading frame, which caused a frame shift and led to an early translational termination of USP13 (aa1–57) (Supplementary Fig. 3b). Immunoblot analysis further demonstrated a complete loss of USP13 protein in the Usp13m/m mice (Supplementary Fig. 3c). The Usp13+/m mice bred normally with the Mendelian inheritance ratio and the Usp13m/m mice did not show any developmental defect until 12-week old compared to the wild-type littermates (Supplementary Fig. 4a,b). The differentiation of Usp13m/m bone marrow cells into BMDC, BMDM or pDCs was similar to that of wild-type counterparts in the presence of GM-CSF, M-CSF or Flt3L, respectively (Supplementary Fig. 4c). The numbers and percentages of various immune cells in thymus, spleen or peripheral lymph nodes were comparable between the wild-type and Usp13m/m mice (Supplementary Fig. 4d–f), indicating that USP13 is dispensable for development and homoeostasis of immune cells.
| 4 | 0biomedical
| 0Study
|
260,295 |
Several common issues affect the speed, complexity and reliability of specific downstream analyses but are not addressed by these existing tools. Clean and Interpret Alignments (CIAlign) is primarily intended to address four such issues and to be used (where appropriate) in combination with existing tools which remove unreliable alignment columns. Researchers in many fields regularly edit MSAs by hand to address these issues, however, as well as being extremely time consuming, ensuring reproducibility with this approach is almost impossible and it cannot be incorporated into an automated analysis pipeline. CIAlign automatically removes full columns and full or partial rows from user generated MSAs to address these issues in a fast, reproducible manner and can be easily added to an automated pipeline. The downstream applications of alignments cleaned with CIAlign are not limited to phylogenetic analysis and are too numerous to list, but CIAlign as an alignment cleaning tool is particularly targetted towards users working with complex or highly divergent alignments, partial sequences and problematic assemblies and towards those developing complex pipelines requiring fine-tuning of parameters to meet specific criteria.
| 4 | 0biomedical
| 1Other
|
76,669 |
Responses to 2 subthreshold vFh (T − 1 and T − 2) and the threshold hair (T) and a suprathreshold hair (T + 1) were recorded and the same 4 hairs used in all subsequent stimulation conditions for data analysis. Thresholds were determined as the vFh that produced an EMG response more than 10% greater than the resting EMG activity. Each hair was then applied 3 times, and the mean reading for each of the 3 presentations recorded. Different hairs were used in each age group as mechanical withdrawal thresholds increase with age. A stimulus-response curve of EMG magnitude vs mechanical stimulus intensity was plotted, and the area under the curve was calculated to provide an integrated measure of spinal reflex excitability. Specific hairs used in each age were (P10: 15, 26, 60, and 100 g; P21: 26, 60, 100, and 180 g; and P40: 60, 100, 180, and 300 g).
| 4 | 0biomedical
| 0Study
|
237,418 |
Another point raised by Singer et al. (2021) is that “the Generation R Study (El Marroun et al., 2009) was inexplicably not included” in our review. It is true that we excluded these papers from our review. But the reason for this is not inexplicable, rather it's quite simple: papers from the Generation R study did not assess cognitive functioning. Our review focused on the empirical literature assessing the cognitive outcomes of children prenatally exposed to cannabis. Granted, one study from the Generation R cohort was initially considered for inclusion (El Marroun et al., 2011). But after careful review of the study's Methods section, we determined that it was inappropriate. The methodology consisted of asking mothers about their children's behavior (using The Child Behavior Checklist for toddlers) as a means of assessing “attention.” So we excluded this study from our analysis because a checklist is not a cognitive test.
| 4 | 0biomedical
| 2Review
|
190,755 |
High self‐stigma tends to be associated with depression and low self‐esteem; reducing self‐stigma can improve depressive symptoms and low self‐esteem in patients, and ultimately improve their QOL. 10 , 17 Because self‐stigma is associated with QOL, evaluation of self‐stigma and interventions to reduce it are important in the treatment of epilepsy.
| 4 | 0biomedical
| 2Review
|
393,798 |
Adult, 14 day old (from egg) flies were knocked out with CO2 gas and placed into individual plastic straws about 4 inches in length and capped with plastic pipette tips on both ends (Fig 1). During anesthetization, a steady supply of CO2 was flowing through a semi-porous plate. The flies were placed on the plate and separated by gender and each fly was gently swept into the plastic straw using a fine painters brush. An equal number of females and males were used per population. Food was provided to each fly at one end of the straw. Each fly was transferred to a new straw with new food and new pipette tips every 3 days to maintain a clean environment. The straw length and girth permitted individuals to fly from one end to the other.
| 4 | 0biomedical
| 0Study
|
391,041 |
Significant clusters identified via ClusterONE is shown in Figure 6. Three of 5 significant clusters comes from the 1 large community with 20 nodes and 27 edges (Community 5) while other 2 comes from Communities 1 and 3 (Supplementary Figure 11). Enrichment results of this community show significant association with metal-ion sequestering, G2/M cycle, organelle localization and phagosome. Neurodegeneration associated terms (Huntington’s disease and Alzheimer’s disease) are also found in the results. These results indicate that a wide range of processes are affected from the infection, or perhaps multifunctional genes which take part in above mentioned processes also respond to viral infections.
| 4 | 0biomedical
| 0Study
|
95,242 |
When static inhomogeneous broadening is included in the simulations, the sub-peak contrast gradually decreases with increasing inhomogeneity (Supplementary Fig. 8). Remarkably, when choosing a Gaussian broadening of ∼90 meV, similar to the strength of the electronic coupling, the linear absorption spectrum predicted by our phenomenological coupling model is in very good agreement with the experimentally measured spectrum (Fig. 3f). In contrast to the incoherent exciton model39 (Fig. 1a, black), not only the low-energy region, but basically the lineshape of the complete spectrum is matched by assuming strongly-coupled exciton and polaron pair excitations and their interaction with one dominant underdamped vibrational mode. For this magnitude of the inhomogeneous broadening, the sub-peak splitting of 2DES peaks is still visible (Supplementary Fig. 8), but slightly less pronounced than in the experiment.
| 4 | 0biomedical
| 0Study
|
211,272 |
To our knowledge, this study is the largest study to investigate maternal BA during pregnancy and is the first to examine the stability of prenatal BA and its relationship across time with GAAD. Major strengths of this study include the use of both a primary and replication cohort both containing longitudinal measurements during pregnancy. The inclusion of a diverse cohort allowed for the investigation of BA differences by self-reported race. Finally, all analyses and hypotheses examined in this study were preregistered on the Open Science Framework47 using the AsPredicted format.
| 4 | 0biomedical
| 0Study
|
130,811 |
Consequently, the atherogenic index or the triglyceride- to-HDL ratio and the triglyceride-glucose index have emerged as powerful predictors of ASCVD and, implicitly, of PAD. The triglyceride-glucose index is obtained via the formula Ln (fasting triglycerides (mg/dL) × fasting blood glucose (mg/dL)/2) and was used initially as a marker of insulin resistance in healthy individuals . However, da Silva et al. underscored that this parameter is positively linked to a higher rate of symptomatic CHD and metabolic and behavioral risk factors . Later on, the usability of the triglyceride-glucose index in clinical practice as a cost-effective marker of ASCVD was endorsed by the results of a large retrospective observational cohort study of 55,593,134 subjects aged 40 years and above included in the National Health Information Database of South Korea, where higher values of this index were connected to an increased risk of major complications of atherosclerosis .
| 4 | 0biomedical
| 0Study
|
112,746 |
Figure 1e (3D model) and Fig. 1f (cross section z = 0) show the bi-layer spherical cloak, the outer layer is CAM, and the inner layer is conductor, Q is a point electric charge. The electric potential in the four regions is (See Supplementary Information) \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\varphi }_{e1}=\sum (-(Q/4\pi {\varepsilon }_{0})({r}^{n}/{L}^{n+1})+{A}_{n}/{r}^{n+1}){P}_{n}(\cos \,\theta )$$\end{document}φe1=∑(−(Q/4πε0)(rn/Ln+1)+An/rn+1)Pn(cosθ), \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\varphi }_{e2}=\sum ({B}_{n}{r}^{n}+{C}_{n}/{r}^{n+1}){P}_{n}(\cos \,\theta )$$\end{document}φe2=∑(Bnrn+Cn/rn+1)Pn(cosθ), \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\varphi }_{e3}=\sum ({D}_{n}{r}^{n}+{E}_{n}/{r}^{n+1})$$\end{document}φe3=∑(Dnrn+En/rn+1) \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${P}_{n}(\cos \,\theta )$$\end{document}Pn(cosθ), \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\varphi }_{e4}=\sum ({F}_{n}{r}^{n}){P}_{n}(\cos \,\theta )$$\end{document}φe4=∑(Fnrn)Pn(cosθ), where A n, B n, C n, D n, E n and F n are unknown coefficients, it should be pointed out that φ e2, φ e3 and φ e4 are the electric potential superposition of the point electric charge and spherical cloak. The relation between the electric field and electric potential is \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\overrightarrow{E}=-\nabla {\varphi }_{e}$$\end{document}E→=−∇φe, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\nabla =\partial /\partial r\overrightarrow{{e}_{r}}+(1/r)\partial /\partial \theta \overrightarrow{{e}_{\theta }}+(1/r\,\sin \,\theta )\partial /\partial \varphi \overrightarrow{{e}_{\varphi }}$$\end{document}∇=∂/∂rer→+(1/r)∂/∂θeθ→+(1/rsinθ)∂/∂φeφ→, the electric field in the four regions can be obtained (See Supplementary Information). Due to the magneto-electric response of the CAM, the magnetic scalar potential is induced in the four regions, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\varphi }_{m1}=\sum ({A}^{{\rm{01}}}{r}^{n}+{A}_{n}^{1}/{r}^{n+1}){P}_{n}(\cos \,\theta )$$\end{document}φm1=∑(A01rn+An1/rn+1)Pn(cosθ), \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\varphi }_{m2}=\sum ({B}_{n}^{1}{r}^{n}+{C}_{n}^{1}/{r}^{n+1}){P}_{n}(\cos \,\theta )$$\end{document}φm2=∑(Bn1rn+Cn1/rn+1)Pn(cosθ), \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\varphi }_{m3}=\sum ({D}_{n}^{1}{r}^{n}+{E}_{n}^{1}/{r}^{n+1}){P}_{n}(\cos \,\theta )$$\end{document}φm3=∑(Dn1rn+En1/rn+1)Pn(cosθ), \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\varphi }_{m4}=\sum {F}_{n}{r}^{n}{P}_{n}(\cos \,\theta )$$\end{document}φm4=∑FnrnPn(cosθ), where A 01, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\rm{A}}}_{{\rm{n}}}^{{\rm{1}}}$$\end{document}An1, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\rm{B}}}_{{\rm{n}}}^{{\rm{1}}}$$\end{document}Bn1, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\rm{C}}}_{{\rm{n}}}^{{\rm{1}}}$$\end{document}Cn1, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\rm{D}}}_{{\rm{n}}}^{{\rm{1}}}$$\end{document}Dn1, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\rm{E}}}_{{\rm{n}}}^{{\rm{1}}}$$\end{document}En1 and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\rm{F}}}_{{\rm{n}}}^{{\rm{1}}}$$\end{document}Fn1 are unknown coefficients. Because of no physics magnetic field in region I, so A 01 = 0. We can obtain the magnetic field in the four regions (See Supplementary Information). When An = 0, only the electric field of the point electric charge is in region I; when F n = 0, the electric field vanishes in region IV, namely, the device is an electric cloak. When \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\rm{A}}}_{{\rm{n}}}^{{\rm{1}}}$$\end{document}An1, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\rm{B}}}_{{\rm{n}}}^{{\rm{1}}}$$\end{document}Bn1, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\rm{C}}}_{{\rm{n}}}^{{\rm{1}}}$$\end{document}Cn1, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\rm{D}}}_{{\rm{n}}}^{{\rm{1}}}$$\end{document}Dn1, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\rm{E}}}_{{\rm{n}}}^{{\rm{1}}}$$\end{document}En1 and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\rm{F}}}_{{\rm{n}}}^{{\rm{1}}}$$\end{document}Fn1 are non-zero, the magnetic field is induced by the point electric charge. That is to say, we can cloak the electric field and induce magnetic field. Supposed that the inner layer is a conductor, setting A n = 0, F n = 0, solving the boundary conditions, we can obtain \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\rm{A}}}_{{\rm{n}}}^{{\rm{1}}}$$\end{document}An1, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\rm{B}}}_{{\rm{n}}}^{{\rm{1}}}$$\end{document}Bn1, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\rm{C}}}_{{\rm{n}}}^{{\rm{1}}}$$\end{document}Cn1, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\rm{D}}}_{{\rm{n}}}^{{\rm{1}}}$$\end{document}Dn1, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\rm{E}}}_{{\rm{n}}}^{{\rm{1}}}$$\end{document}En1 and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\rm{F}}}_{{\rm{n}}}^{{\rm{1}}}$$\end{document}Fn1, according to magnetic charge formulation63, the interesting thing take places, namely, many monopoles are induced in the four regions. For example, neglecting infinitesimal of the higher order (See Supplementary Information), we obtain coefficient \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${A}_{n}^{1}=-(\alpha {\varepsilon }_{1}/{\varepsilon }_{2}){({\varepsilon }_{0}/{\mu }_{0})}^{1/2}(Q/4\pi {\varepsilon }_{0})n/(2n+1){a}^{2n+1}/{L}^{n+1}$$\end{document}An1=−(αε1/ε2)(ε0/μ0)1/2(Q/4πε0)n/(2n+1)a2n+1/Ln+1, and the magnetic scalar potential in region I,4\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\varphi }_{m{\rm{1}}}=-\frac{\alpha {\varepsilon }_{1}}{{\varepsilon }_{2}}\sqrt{\frac{{\varepsilon }_{0}}{{\mu }_{0}}}\frac{Q}{4\pi {\varepsilon }_{0}}\sum (\frac{n}{2n+1}\frac{{a}^{2n+1}}{{L}^{n+1}{r}^{n+1}}){P}_{n}(\cos \,\theta )$$\end{document}φm1=−αε1ε2ε0μ0Q4πε0∑(n2n+1a2n+1Ln+1rn+1)Pn(cosθ)
| 5 | 0biomedical
| 0Study
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13,127 |
Twenty-four of the states require the use of specific language. Twenty-one states notify women with dense breasts; ten of the states choose to notify everyone, while Oregon only notifies women with “extreme density” (BI-RADS d). Most states (27) inform a woman if she has dense breasts, although in a majority of cases her personal density category is not specified. Twenty-four states mention the masking effect of density and a majority specify it is a risk factor for breast cancer. Unfortunately, less than half (15) mention supplemental screening. Of the 31 states with notification legislation, only 5 states (CT, IL, NJ, NY, IN) have enacted legislation mandating some form of insurance coverage for supplemental screening for women with dense breasts. In cases where “dense breasts” has been defined in the legislation, it is the BI-RADS density categories that have been cited. Therefore, to comply, visual BI-RADS or commercial software that provides density categories must be used i.e., Volpara, Quantra, Philips Spectral Density or iReveal. Providing accurate MBD assessments for communicating masking risk to lay women is becoming increasingly important as more and more states implement density notification laws and the use of objective methods have been shown to improve consistency across radiologist visual readings .
| 4 | 0biomedical
| 1Other
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69,362 |
Since SAL has been reported to inhibit CSC in several cancer models we investigated its activity in a model of breast CSC. Two sublines derived from the cell line HMLER and differing in their stem cell properties have been recently described . We first observed that the subline HMLER CD24low, carrying CSC properties has an increased sensitivity to autophagy inhibition mediated by Lys-01 and SAL with respect to the non-CSC subline HMLER CD24+, confirming that autophagy plays a crucial role in maintaining survival and proliferation of CSC [41, 70, 71]. Interestingly, exposure to acidic medium increased the sensitivity of CD24+ cells by 5-fold whereas a 15-fold increase in sensitivity was observed in CD24low cells. In line with this, SAL was more effective at inhibiting autophagic flux in CD24low cells and as low as 200 nM SAL was sufficient to block autophagic flux in CD24low cells cultured in acidic conditions. CD24low cells were described to have CSC features among which the ability to form mammospheres in vitro . We found that SAL inhibits mammosphere formation from CD24low cells in standard culture conditions and such inhibition is greatly amplified during acidosis. This indicates that cells with stem-like properties are more susceptible to autophagy inhibition. Moreover it also supports new findings suggesting that inhibition of lysosomal function may specifically target CSC in different cancer types [72, 73]. To further investigate the potential clinical relevance of our observation, we analysed the pH-dependent effects of SAL on CSC derived from patients with breast carcinoma. Breast CSC obtained from cancer patients showed a much greater sensitivity to SAL when cultured in acidic medium.
| 4 | 0biomedical
| 0Study
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164,607 |
The bursting in the ICs (formerly PMs) is not essential to single coiling. In response to this question, we created a model with ICs firing a single spike per burst. With an increase in the synaptic weight from IC to MNs, this generated single coiling as well. However, we modelled ICs as bursting to resemble the recordings of ICs from Tong and McDearmid (2012), which show sustained bursts of short spikelets. To address this question, we have clarified the reason why our IC models display bursting. We can add the result of the one-spike bursting ICs as a figure supplement to Figure 2 if desired.
| 4 | 0biomedical
| 0Study
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76,919 |
The operating mechanism under the condition of x-axis vibration is presented in Figure 2. Due to the limit of the separation plate and the membranes, the electrolyte solution flows as shown in Figure 2, resulting in an opposite change of liquid flow in channel A and channel B. but due to the opposite cathode-anode layout, the active ions both moved from the cathode to the anode in each channel in A and B, producing comparable current outputs.
| 3 | 0biomedical
| 0Study
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49,942 |
The proposed DNN-driven e-skin sensor outperformed present sensors in terms of pressure sensitivity and spatial resolution when the number of probe terminals was set at 16. The test accuracy for position recognition was exactly 100% for all the virtual lattice designs (4 × 4, 6 × 6, and 10 × 10). A regression-typed DNN gave a brilliant spatial resolution (0.78 ± 0.44 mm) for position recognition. Also, a high precision of pressure sensing (%RMSE ~3) was secured.
| 4 | 0biomedical
| 0Study
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25,713 |
The DRC was one of the first countries to adopt the second edition of the World Health Organization’s malaria treatment guidelines , for which a cornerstone of these guidelines was the recommendation to provide confirmatory diagnostic testing for all febrile patients, even in children under the age of five. Results from the 2013 outlet survey in Kinshasa demonstrate that nearly 90% of public facilities in Kinshasa have confirmatory testing available, primarily through malaria microscopy as opposed to RDTs. However, significant gaps persist in availability of quality-assured ACT, with fewer than one-third of public sector outlets stocking quality-assured ACT. Overall, only one in four public sector outlets have both confirmatory testing and quality-assured ACT available. Only one in five public outlets had SP available for IPTp during antenatal care visits.
| 4 | 0biomedical
| 0Study
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165,830 |
The fact that propiolamide substrates afford the E-alkenylated oxindoles 3s–u as main coupling products reveals that in those cases the alkenyl-Pd(II) intermediate, arising from the syn carbopalladation step, could undergo an isomerization process. There are several precedents in the literature of related Pd-catalyzed cascade reactions involving the syn carbopalladation of alkynes and subsequent isomerization prior to the final C–Pd bond functionalization.14,22,25,63−67 Generally, the isomerization of the alkenyl-Pd intermediates is driven by steric factors. Nevertheless, α-alkyl-substituted alkynyl substrates, such as 1a, require the use of bulky phosphine ligands (Q-Phos, X-Phos, or PtBu3 among others) to increase the steric hindrance around the Pd center and therefore promote the isomerization.25,63,64 In the case of α-acyl-substituted alkynyl substrates, such as propiolamides 1m–o, the isomerization is a frequent feature in a range of different conditions, probably due to the conjugation of the alkenyl-Pd moiety and the carbonyl group, which might lower the energy barrier for the C–C rotation process (Scheme 6).28,62,68,69 Likely the coordination of the carbonyl moiety might facilitate such processes. Nevertheless, the opposite isomerization has been observed in related systems (that is, the steric factors seemed to predominate over the possible coordination of the carbonyl group in intermediates such as E).68,69
| 4 | 0biomedical
| 0Study
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269,985 |
The study was supported by grants from the Region H (to HBM), the Novo Nordisk Foundation (to FP), The Beckett Foundation (to LBN), Aase og Ejnar Danielsens Fond (to AHM), The Sehested Hansen Foundation (to CF), Dronning Louises Børnehospitals Forskningsfond (to CF) and Frimodt-Heineke Fonden (to CF). Part of the research is supported by IMI2-EU under grant agreement No 115797 (INNODIA) and No 945268 (INNODIA HARVEST) (to FP). This Joint Undertaking receives support from the Union’s Horizon 2020 research and innovation program and “EFPIA”, “JDRF” and “The Leona M. and Harry B. Helmsley Charitable Trust”.
| 1 | 2other
| 1Other
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154,554 |
The graphs depicted in Figure 6 show the PSNRs after decoding by a line and the compression ratios by bars. The vertical axis on the left side is the compression ratio. The one on the right side is the PSNR. Regarding Evaluation Image (a), the PSNRs when varying the encoding bit length M from 4 to 8 show about 50. As M is decreasing from 3 to 1, the PSNRs are decreasing. However, we confirmed any M maintains adequate image quality because all PSNRs in this experiment show values greater than 30. Here, let us focus on the visual qualities between the bit lengths M of 1 and 2, as shown in Figure 7. When M=1, as shown on the left in Figure 7, the image becomes blurry in the horizontal direction. This is caused by the low flexibility because the predicted offset is decided by only a single bit. When M=2, as shown on the right in Figure 7, it is sharper than the image of M=1. However, it still has blurry parts in edges of colors such as the one between a leaf and the sky in the image. This is a typical encoding characteristic because ADPCM cannot follow such large changes of color values when the encoding bit length is small. On the other hand, Evaluation Image (b) also maintains the same relationship as Evaluation Image (a) between the image quality and M, as shown in Figure 8. Thus, we confirmed that we should avoid M=1 to maintain adequate image quality as well as restrict the condition 2≤M≤N in applications of ADPCM-VBL.
| 1 | 2other
| 0Study
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360,835 |
Following a 2‐year treatment period, T2* liver MR imaging showed an average hepatic T2* value of 6.1 ms indicative of moderate liver iron loading. However, as this was a different modality to the pre‐treatment Ferriscan, we cannot comment on whether there had been a radiological improvement. Cardiac T2* MR imaging before and at 3‐year follow up did not detect any cardiac iron deposition. His neurological examination at 12‐month follow up was unremarkable.
| 4 | 0biomedical
| 0Study
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202,981 |
To date, it is merited to answer why the toxic levels of H2S are used in physiological studies. The rationality of using high levels (i.e., micro-moles or even milli-moles) of H2S to study and predict its physiological effects depends on the initial reports, where the concentration of H2S in blood or tissue is at high micromolar in the blood or tissues (Furne et al., 2008). Philippe Haouzi has reviewed that two main reasons could explain why high micro-moles of “endogenous” H2S are found in the blood and tissues (Haouzi, 2016). The first reason is related to the nature of the pools of sulfide present in the blood and in tissues, and the second reason for this error is linked with the methodology of measurement of the pool of diffusible/dissolved H2S in a biological milieu (Van de Louw and Haouzi, 2012). The subsequent studies have found that low levels of H2S donors in vivo are unlikely to increase the concentrations of H2S in tissues because of a fact that the majority of H2S in the blood after intravenous or intraperitoneal injections in vivo is immediately oxidized or combined with metallo-proteins (hemoglobin), dropping the level of free H2S to almost zero, unless the lethal levels are applied (Insko et al., 2009; Wintner et al., 2010; Haouzi and Klingerman, 2013; Klingerman et al., 2013). There is a very small margin between the concentration that does not produce an effect and the concentration that can kill. As reviewed by Szabo et al. (2011), the variable concentrations of H2S donors might result in the toxic levels or without chaging H2S concentrations in blood and tissues (Szabó, 2007). A growing number of studies support the “physiological” and protective roles of H2S by using solution of free H2S in the high micro-moles levels that are only found during a lethal in toxication in vivo (Haouzi and Klingerman, 2013). As such, high micro-moles or milli-moles levels of H2S donors are still used to elucidate the properties of endogenous H2S in those ongoing studies. In all, H2S donors regulate a multitude of biological processes at the typically used doses (so-called physiological effect), which should belong to the field of toxicology in many cases (Haouzi and Klingerman, 2013). Future studies are necessary to quantify the actual H2S concentration of each exogenous H2S donor used in the tissues and determine what effects are expected to be produced in keeping with sulfide toxicity and its rapid disappearance in the body or solutions.
| 4 | 0biomedical
| 2Review
|
313,246 |
GGBS, as a by-product material obtained during the manufacture of pig-iron, is produced in large amount around the world. The main chemical components of GGBS are CaO, SiO2, and Al2O3 . Numerous studies show that alkali-activated GGBS (AAS) cementitious materials have excellent properties such as high strength, corrosion resistance, low porosity, frost resistance, low permeability, fire resistance, solidification of heavy metals, and are considered as low carbon environmental friendly cementitious materials .
| 2 | 2other
| 1Other
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288,524 |
CPNE1 activated the MET signaling pathway in NSCLC. A, B Western blot analysis of RACK1, p-MET, MET, p-AKT, AKT, p-Erk, and Erk protein levels in CPNE1-overexpressing cells compared to control cells, with quantification on the right. C, D Western blot analysis of relevant protein levels in CPNE1 knockdown cells compared to control cells, with quantification on the right. E A human RTK phosphorylation array analysis demonstrated that the p-MET level is increased in CPNE1-overexpressing cells. F Western blot analysis of p-MET in CPNE1 knockdown cell lines treated with HGF (20 ng/mL) for 24 h. *P < 0.05; **P < 0.01; ***P < 0.001
| 5 | 0biomedical
| 0Study
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32,176 |
At last, Nec-1 unable to further inhibit necroptosis during H/R injury in hiPSC-MSCs-EVs-treated HK-2 cells (Fig. 7c). Meanwhile, both SP1 and SKI-II inhibition completely abolished the anti-necroptosis effect of hiPSC-MSCs-EVs (Fig. 7c). After SP1 knockout in hiPSC-MSCs, the secreted EVs can no longer decrease the H/R-induced necroptosis in HK-2 cells unless restoring the level of SP1 by Ad-SP1 (Fig. 7c). These data prove that hiPSC-MSCs-EVs deliver SP1 to the target HK-2 cells and result in intracellular activation of SK1 expression and generation of S1P, which inhibit H/R-induced necroptosis.
| 4 | 0biomedical
| 0Study
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140,378 |
2) a mean difference (at 18m) between study arms of a) 0.24 serve/day in fruit [SD=1.7, ICC=0.071]; b) 0.25 serve/day in vegetables [SD=2.0, ICC=0.000]; c) 0.06 serve/day in non-core drinks [SD=0.44, ICC=0.034]; d) 0.06 serve/day in non-core sweet [SD=0.39, ICC=0.064]; e) 0.05 serve/day in non-core savoury [SD=0.33, ICC=0.047]; f) 6.7 min/day of screen use [SD=44, ICC=0.11]; and g) 18.4 min/day of physical activity [SD=143, ICC=0.018]. While individual energy-balance behaviour changes appear small, modest increments in energy consumption (126-189kJ/day (30-45 calories)) are estimated to promote population weight gain over time. Collectively these changes have capacity to influence weight gain trajectories at a population level (47, 48);
| 4 | 0biomedical
| 0Study
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384,135 |
DSBs are one of the most lethal DNA lesions induced by IR, as well as endogenous reactive oxygen species (ROS) , which are mainly repaired through non-homologous end joining (NHEJ) repair pathway in circulating lymphocytes. Ku proteins (Ku70 and Ku80) proteins play crucial role in NHEJ repair. Ku is a heterodimer composed of 69kD and 83 kD polypeptides, which initiates DSB repair process by binding to the broken DNA ends and recruits the DNA-PK catalytic subunit (DNA-PKcs) to form the active DNA-PK enzyme. The active DNA-PK enzyme, through its kinase activity recruit other enzymes, such as Artemis, that process and join the broken ends . Ku proteins also take part in DNA replication, apoptotic signaling and telomere maintenance . Ku70 and Ku80 genes are very active during G0/G1 and early S-phase of the cell cycle [37–39].
| 4 | 0biomedical
| 0Study
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165,689 |
Histograms depicting SUMO conjugation rates to Rfa1 for different RPA–DNA complexes. Siz2 and DNA are both present in the reaction at a concentration of 1 µM while RPA concentration is varied from 1 to 3 µM and the length of single‐stranded DNA is varied from 27 to 80 nucleotides. Representative gels are shown in Appendix Fig S7.A model for SUMO signal amplification. (i) Siz2 binds dsDNA and modifies with SUMO the RPA that is closest to the dsDNA/ssDNA junction. (ii) SUMO‐modified RPA is exchanged with an unmodified RPA. (iii) Siz2 modifies the RPA that is closest to the dsDNA/ssDNA junction. (iv) SUMO‐modified RPA is exchanged with an unmodified RPA.
| 4 | 0biomedical
| 0Study
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93,268 |
Various terms have been used to refer to the involvement of multiple disciplines in health research and practice. Choi and Pak use the terms multidisciplinarity, interdisciplinarity, and transdisciplinarity to refer to a continuum of increasing involvement of multiple disciplines. They suggest the more general term “multiple disciplinary” for when the nature of involvement of multiple disciplines is unspecified. The involvement of various disciplines is a defining characteristic of behavioral medicine, but the strength of the involvement of various disciplines may vary. Although this would suggest “multiple disciplinary” as the most appropriate term, we prefer the more traditional term “multidisciplinary” to define behavioral medicine.
| 3 | 0biomedical
| 1Other
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245,505 |
Older adults were classified as having the well-being paradox if they reported high self-reported health (excellent or very good) and a high level of multimorbidity (four or more chronic conditions). Four or more chronic conditions was selected based on a clinical understanding of the burden of these conditions. This is because while some of the conditions could be described as risk factors (e.g., hypertension, obesity) or symptoms (e.g., incontinence, colon disorder) , those older adults with four or more chronic conditions are likely to experience greater challenges with their health than those with fewer than four conditions.
| 3 | 0biomedical
| 0Study
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71,065 |
The monophyly of the Madagascan species clade is very well supported with a bootstrap value of 99 encompassing two distinct groups. The first group contains A. mangelsdorffii + A. antsingyensis with a support of 90. Bogner (2003) suggested these two species to be more closely related to each other although their gross morphology does not support this. Amorphophallus antsingyensis actually looks quite like species from the other clade by its narrow spathe (Figure 4a), long rhizomatous offsets, lanceolate leaflets, distinct style, stigma shape (Figure 4b), etc. It is generally smaller in all its dimensions and almost uniformly green in all its parts but clearly the results presented here show such differences are not indicative of phylogenetic distance. Amorphophallus mangelsdorffii is in fact the oddity of all Madagascan species, owing to its deviating growth cycle, short, coiling spathe (Figure 3c), lack of differentiated style, and very small stigmas. The one character that does unite A. mangelsdorffii and A. antsingyensis is their spiny pollen (Bogner 2003, Figure 1; Hetterscheid et al. 1999, Figure 2). (Van der Ham et al. 2005), and as such may be regarded as a strong morphological synapomorphy between the two.
| 4 | 0biomedical
| 0Study
|
269,332 |
We estimated accessibility to free, school-sponsored meals before and during the COVID-19 pandemic in three ways. First, using the average number of meal access points, we demonstrated how meal accessibility before and during COVID-19 relates to both family poverty and supermarket access. Second, using Euclidean (or straight-line) distances, we demonstrated how meal accessibility relates to free and reduced-price lunch status. Finally, using a gravity-based model that considers both family poverty and the number of meal access points, we demonstrated how meal accessibility changed during COVID-19 and how this change relates to urbanicity and racial/ethnic composition.
| 2 | 2other
| 0Study
|
209,075 |
Our goal was to select rural counties with wide representation across the state in terms of geographic location, cancer prevalence, social economic status, and ethnicity. We identified six rural counties using the rural-urban commuting area (RUCA) codes that classify US census tracts based on population density, urbanization, and daily commuting. The NM Tumor Registry provided estimates of the average annual cancer counts per county. We selected counties that had at least one town with population of 10,000–49,999 people (RUCA codes 4–6). See Table 1 for details about selected counties (for anonymity, we are not including the names of the counties and towns).
| 2 | 0biomedical
| 0Study
|
353,527 |
The nuclear factor kappa B (NFκB) family consists of dimeric transcription factors central to the regulation of genes related to inflammation, the immune response, cell differentiation, proliferation, and survival . Many inflammatory cascades enhance NFκB-dependent transcription, which in turn promotes inflammatory programs. In brief, activation of these cascades leads to increased inhibitory kappa kinase activity and phosphorylation, ubiquitination and degradation of the inhibitory proteins IκBα and IκBβ, eliciting NFκB-p65 translocation to the nucleus and transcription of proinflammatory genes . Regarding tumorigenesis, NFκB has context-dependent effects that lead to elevated tumorigenic inflammation and stimulate tumor initiation and progression . TNFAIP3 and PLAU have been proven to be the target genes of NFκB . TNFAIP3 was originally identified as a protector of cells from TNF-induced cytotoxicity and, most notably, a repressor of excessive inflammation . However, some recent studies implied a paradoxical role for TNFAIP3 outside the immune system, suggesting its contributory effects to the proliferation and metastasis of a variety of cancer cells . The evaluation of genes differentially expressed in normal esophageal mucosa and ESCC also identified TNFAIP3 as a candidate biomarker of dysplasia or invasive ESCC . uPA encoded by PLAU is produced by cancer cells and/or surrounding stromal cells as a proenzyme and converted to an active form when secreted into the tumor microenvironment by binding to the uPA receptor. uPA is involved in cell invasion and metastasis and is correlated with a poor prognosis of patients with one of various malignant tumors, including colon, breast, and stomach tumors .
| 5 | 0biomedical
| 0Study
|
319,662 |
Cervical cancer is the fourth most common malignancy in women with an estimated 260,000 deaths every year worldwide (1). Human papilloma virus (HPV) types 16 and 18 account for roughly 70% of all cervical cancer cases (2, 3). The HPV early proteins E6 and E7 are the main mediators for the induction of HPV-associated cervical cancer as both the proteins are consistently expressed in HPV-associated cervical cancer cells (4, 5). E6 inactivates the tumor suppressor p53 by binding to the ubiquitin ligase E6AP and inhibits the p53-mediated signaling pathway (6–9), whereas E7 binds with pRb and promotes its proteasomal degradation (10–12). Since E6 and E7 proteins are constitutively expressed in HPV-associated cervical cancer cells, these tumor-specific antigens serve as an attractive therapeutic strategy to target HPV-associated cervical cancer cells.
| 5 | 0biomedical
| 0Study
|
85,428 |
Indeed, a human error was detected during the manual review process. For evaluation purposes, the Physical Quantity (PQ) had been transcribed a second time from the XML-snippets to a spreadsheet. In one case, there was a discrepancy of a value, which occurred during the transcription of the PQ on the spreadsheet. Consequently, the manual review process has to be automated for preventing human errors during the transcription of the values. This issue can be solved by pattern recognition, ontology extraction and SPARQL, which is a complex topic and could be described in another paper in the future.
| 2 | 0biomedical
| 1Other
|
230,704 |
Let us now consider the electromechanical system shown in Figure 1a. In specific, the system’s circuit consists of an electric current source, a conductance, a capacitor and the electromagnet’s coil all connected in parallel. The Lagrangian of the system can then be written as:(3)ℒ=Ke+Km−(Te+Tm), (4)Ke=12CV2=12Cψ˙2 (5)Te=12L(x)iL2−isψ=12L(x)ψ2−isψ (6)Km=12mx˙2, (7)Tm=12kx2−xf(t) (8)Pe=−ψ˙22R ,Pm=−bx˙22
| 3 | 0biomedical
| 0Study
|
261,052 |
Despite describing clinic attendance as satisfactory (n = 3), two participants found the journey to appointments problematic because of the additional stress of not being in control over timing while waiting for their taxi. One participant suggested booking the taxi 20-30 min earlier to reduce this burden.
| 2 | 1clinical
| 1Other
|
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