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The impact of PDI on adhesion to polystyrene was tested in 0.25 × and 0.5 × MEC concentrations determined for each porphyrin in SW. TMPyP3-C17H35 in concentration 0.25 × MEC showed 100% inactivation of the adhesion in DEMI, while TMPyP3-CH3 showed ~30% decrease in comparison to control (Figure 9B,C). Negligible difference in DEMI was observed for TMPyP3 (Figure 9A). Additionally, somewhat “dark toxicity” was detected in DEMI for porphyrins TMPyP3-CH3 and TMPyP3-C17H35, with a decrease of 1 log10 CFU/mL in concentration 0.25 × MEC (Figure 9B,C). In SW and HW, a similar PDI effect was shown in both water samples for TMPyP3-C17H35, where the decrease was ~30%. A negligible decrease in comparison to the “light” control was observed for porphyrin TMPyP3-CH3 in SW and HW. In SW, porphyrin TMPyP3 showed complete inactivation of the adhesion, while in HW, ~50% decrease was observed (Figure 9A).
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92,531 |
Cells were either given low serum media containing 2% FCS, or control serum media containing 10% FCS and were incubated in T75cm2 flasks for 48 hours prior to plating at the required cell density. Cell culture media on all experiments was changed 30 minutes prior to the beginning of the experiment, with all transfections and experiments being performed in 10% FCS.
| 4 | 0biomedical
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244,581 |
She then had a broad patch-testing panel performed which showed a positive allergic reaction toward gold, specifically gold sodium thiosulfate (Figure 1). There were negative results to other common allergens and common environmental triggers like heavy metals and aromatic compounds.
| 3 | 0biomedical
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241,632 |
One possible explanation for the differences in action potential characteristics in our model compared to other DSG2-mutant models may be related to alterations in ion channel trafficking, which may be linked to desmoglein-2 and plakophilin-2 trafficking through the formation of macromolecular complexes, such as between Nav1.5 and plakophilin-2 , Nav1.5 and desmoglein-2 , and Kir2.1 and filamin . The different action potential behavior in our model as compared to other DSG2-mutant models, could be explained by variation in how different mutations affect the ability of DSG2 to form these complexes.
| 4 | 0biomedical
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67,910 |
The spatial distribution of CDOM during the dry season indicates that external input from adjacent wetland via surface waterways is prevalent, also suggesting that relatively high biomass of T. testudinum in the brackish inner bay during dry season might be explained by import of nutrients and organic material from neighboring ecosystems. Thus, T. testudinum beds growing landward may benefit seasonally from watershed organic material discharged into the system. The relevance of such loading is consistent with the dramatic drop of CDOM concentrations as a function of distance from the mangrove shoreline, with a sharp concentration drop crossing the channel towards the main bay (Fig 5d).
| 3 | 0biomedical
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362,722 |
Figure 2 shows an early version of the filter for use by ICGC-ARGO as part of its Expression of Interest (EOI) process. This shows the seven core research consent elements of participation in this consortium but also provides further steps that researchers can take to enable their dataset to be shared respecting research ethics requirements. Step 1 takes one through the six and if these points cannot be met, Step 2 asks if re-contact and re-consent are possible. If not, applying for a waiver from an appropriate body, such as a research ethics board, is suggested. This will be useful in cases when re-contact was not foreseen or for when it is may be impracticable to re-consent participants. Consent language would need to be interpreted to judge whether it fits with the items in the tool, so contact information of an ICGC-ARGO team member is available if guidance is needed. A possible further option would be to anonymize the dataset. This is not the preferred option as de-linked data would be of limited value in clinical care and may pre-empt projects from updating datasets longitudinally.
| 4 | 0biomedical
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96,187 |
The collected data were entered into Epi-Info version 3.5.2 and then transported to SPSS version 21 for further statistical analysis. Descriptive statistics were used for presenting the descriptive results. T-test with respective p value was used to show the mean differences in CGPA. The variables were checked for uniformity, outliers, and multicollinearity, and the variance was normally distributed. Pearson correlation was used to see the correlation of substances with students' grade point. Those variables with p value of less than 0.2 in univariate analysis were included and analyzed by multiple linear regression with 95% confidence interval. Standardized and unstandardized regression coefficients were used to indicate the associations. Variables with p values < 0.05 were considered as statistically significant.
| 3 | 0biomedical
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381,287 |
The use of biostimulants, which are kinds of natural or synthetic small bioactive molecules derived from human- or animal-related industrial processes, is considered an effective measure to ameliorate growth inhibition induced by salinity or to improve plant resistance to salinity stress [10, 23]. The tertiary amine bioregulator 2-(3,4-dichlorophenoxy) triethylamine (DCPTA) represents a class of highly bioactive, low-molecular-weight amine compounds that have a significant regulatory effect on crop growth and development . Previous studies have shown that DCPTA can improve the dry weight (DW) of tomato plants ; increase the root DW and leaf area of beet, radish , and maize ; and enhance ribulose-1,5-bisphosphate activity and increase the size of chloroplasts in the leaves of sugar beet (Beta vulgaris L.) . DCPTA can also enhance CO2 fixation in cotton, promote chlorophyll biosynthesis in guayule and stimulate carotenoid biosynthesis in citrus . Suitable concentrations of DCPTA can improve the net photosynthetic rate (Pn) in maize (Zea mays L.) and have anti-senescent properties, as demonstrated by the slowing of chlorophyll degradation in bean (Phaseolus vulgaris L.) leaf discs in darkness . Moreover, DCPTA can increase the ability of crops to adapt to stress and improve stress resistance [33–36]. Xie et al. showed that spraying DCPTA can increase the leaf relative water content (LRWC) and promote water uptake, as indicated by increased Lp, which may be due to improvements in root growth, increased photosynthetic capacity associated with the increased chlorophyll content, greater photosynthetic C4 enzyme activity and reduced damage to chloroplasts under drought stress, thereby increasing the drought tolerance of maize seedlings. DCPTA can also increase tolerance to low-temperature stress by increasing the maximum quantum efficiency of PSII photochemistry (Fv/Fm) and the chlorophyll content, which effectively was shown to protect the photosynthetic system of maize leaves under low-temperature stress .
| 4 | 0biomedical
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17,748 |
Bypass activation of tyrosine kinase receptors is a well described mechanism of resistance to EGFR TKIs in EGFR-mutated NSCLC. MET-driven resistance has been reported in up to 22% of patients with acquired resistance to EGFR TKIs . Still, although the biological basis of this mechanism of resistance has been extensively studied, there is very little data on the clinical characteristics and outcome of patients with MET-driven acquired resistance to EGFR TKIs. In this multicenter retrospective study, we report for the first time clinical features, response to MET inhibitors and outcome of 42 metastatic EGFR-mutated NSCLC patients with MET amplification or MET overexpression, as assessed on a post-progression re-biopsy. Because of the very low number of patients with MET-driven resistance to EGFR TKIs, we performed a multicentric retrospective study. Therefore, we could not perform a central analysis of RECIST responses, MET FISH, and MET IHC analysis. The absence of MET FISH and MET IHC analysis on the initial biopsy is also challenging. Indeed, we cannot exclude that some patients might have a MET overexpression or a MET amplification before EGFR TKI therapy. Most patients with EGFR exon 19 deletions in our study received a first generation EGFR TKI and were not treated with afatinib. There were no specific clinical characteristics of the patients included in our study but we observed a low rate of objective response to MET inhibitors when used as a monotherapy and a substantial rate of concomitant T790M mutations, which were still partially associated with efficacy of 3rd generation EGFR TKIs and favorable prognosis, even in association with MET overexpression or MET amplification.
| 4 | 0biomedical
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345,552 |
Summarized WSS scores for pregnancy microbiome dataset. A total of 24 species that had cut-off values were selected from the pregnancy microbiome dataset to compare the WSS scores between early gestational days (1–100 days) and every possible pair of later gestational days (101–150, 151–200 and 201–300 days) per individual. The summarized WSS scores of the 24 species per each individual were grouped into different colour boxes (colours described in the figure labels). Each column in the table represents an individual ID and matches the number shown in electronic supplementary material, table S1. WSS scores for all observed species are provided in electronic supplementary material, table S4. Bacteroides vulgatus was selected to conduct an additional strain profiling analysis (red outlined box) and the resultant data shown in figure 3.
| 4 | 0biomedical
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377,336 |
Illustration of the apical meristem of GM 971-2 as it shifts from vegetative to reproductive mode. The growing tip has a tear-shaped appearance through 56 days after planting (DAP), but assumed a globular shape by 76 DAP. For the photograph on the right, taken with a stereoscope, some young leaves have been removed to expose the inflorescence primordium.
| 3 | 2other
| 1Other
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302,284 |
Without the cooling option, only 150 mL of E8 full feed medium I required for the next 24 h of feeding should be deposited in the feed bottle at 20°C–22°C. Subsequently, the feed bottle needs to be refilled on a daily basis based on the applied feed rate (see Table 2).
| 3 | 0biomedical
| 1Other
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23,960 |
The resulting magnetic phase diagram of BiCr1−xGaxO3 is given in figure 11. The TN gradually decreases with increasing x, as one would expect because of the dilution of the magnetic sublattice by a nonmagnetic ion, while TSR increases. By the extrapolation, the TN and TSR should merge near x = 0.15. There is almost linear dependence of TN on x in the compositional ranges of 0.0 ≤ x ≤ 0.3 and 0.4 ≤ x ≤ 0.7. In both ranges, TN vanishes near x = 0.7 by the extrapolation, that is, near the percolation threshold. From the extrapolation, we can also estimate that TN should be about 130 K for a hypothetical R3c phase of BiCrO3, which was studied theoretically in some papers [16, 25]; the theoretically estimated TN is about 80–120 K . The G-type AFM structure should realize in BiCrO3-based perovskites as predicted in many theoretical papers [15, 16, 25] and found experimentally [11–13]. However, spin canting mechanisms might be different depending on the symmetry; this is why different regions are marked as c-AFM1, c-AFM2 and c-AFM3 in figure 11. Spin canting is allowed by the symmetry in the C2/c and R3c structures and G-type magnetic arrangements.
| 4 | 0biomedical
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352,180 |
Partial breastfeeding with breastmilk substitutes was related to feeding and medical problems in two babies which were resolved in the first 2 months. A third mother returned to school and the caretaker supplemented with cow’s milk from when the baby was 2 months old.
| 2 | 0biomedical
| 1Other
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309,204 |
In conclusion, we investigated the performance of multivariate statistical methods in the discovery of diagnostic biomarker panels for OSCC from transcriptomic data. The novel classifying gene expression signatures derived here will contribute to the ongoing development of diagnostic and prognostic biomarker panels for OSCC. In addition, many of the classifying genes have not been previously reported for OSCC and represent promising putative targets for further molecular analysis.
| 4 | 0biomedical
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110,226 |
RNAi was performed on nematode growth media (NGM) plates supplemented with either 25 μg/ml carbenicillin or 100 μg/ml ampicillin, 1 mm IPTG, and 12.5 μg/ml tetracycline and seeded with appropriate HT115 RNAi bacteria. The RNAi clones were from the Ahringer (Source BioScience) or Vidal library except those listed in Table S14.
| 4 | 0biomedical
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336,628 |
Stimulatory activities are present in HeLa WCE that enhance incision of THF-in mononucleosome substrate by recombinant APE1. (A) Purification scheme for the isolation of stimulatory activities from HeLa WCE using column chromatography, finishing with mass spectrometry (MS) analysis of active protein fractions. (B) Immunoblotting analysis of APE1 within WCE and fractions (10 μg) generated by low salt (PC150) and high salt (PC1000) elution of proteins from Phosphocellulose chromatography. Fractions were also immunodepleted using APE1-specific antibodies (APE1 ID), although this was only partially effective using the PC1000 fraction. (C, D) Incision of the THF-in mononucleosome substrate (50 fmol) by WCE, PC150 and PC1000 (0.16 μg) in the absence and presence of recombinant APE1 (60 fmol). (D) Shown is the mean percent substrate incision from two independent experiments, along with the difference in THF incision by the extracts in the absence and presence of recombinant APE1. (E, F) Stimulation of APE1-dependent incision of the THF-in mononucleosome substrate by fractionated proteins generated from Mono-Q chromatography. (E) Shown is the mean percent substrate incision from two independent experiments in the absence (red line) or presence (blue line) of recombinant APE1, normalized to 0 after subtraction of the incision observed with recombinant APE1 only (∼20%). (F) A representative image from the respective gels is shown highlighting the majority of the stimulatory activities present in fractions 34–38 and 44–54. The respective control reactions performed in the absence of any fraction (Control) and with APE1 only are indicated.
| 4 | 0biomedical
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115,296 |
Many proteins interact with both normal and polyQ-expanded Htt. These include proteins implicated in 14-3-3 signaling, microtubule-based transport, proteostasis, and fission of mitochondria . Several of these interactions have been mapped to the N-terminal segment of Htt and are influenced by polyQ expansion . Large amounts of polyQ-expanded forms of Htt accumulate in the cytoplasm, where they form dynamic “aggregates” [5, 28]. However, it remains controversial as to whether aggregation of Htt accounts for its toxicity. Studies of cultured cells as well as the mouse brain show that N-terminal fragments of polyQ-Htt are especially toxic. Moreover, the N-terminal fragment derived from cleavage at D586 is required for the pathogenesis of HD in a mouse model . Administration of an inhibitory peptide containing the sequence around D586 protects a HD mouse model from pathogenesis .
| 4 | 0biomedical
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32,471 |
Restenosis in the target vessel may affect treatment success. In some studies, restenosis has been defined as stenosis of 50% or greater, and in some others, 70% or greater.25,28,29 Not every stenosis leads to new neurological problems; studies have reported restenosis rates varying between 6% and 14%, although only 1-5% of these cases have reported to suffer a new neurological event.30 In a randomized controlled multicenter study, the restenosis rates of CEA 6.3% and CAS 6% have been reported.28 In the same study, being symptomatic did not affect restenosis rate, while female gender, DM, and HL were independent predictors of restenosis.28 Another study found significantly greater restenosis rate in the endovascular treatment group compared with the surgery group.25 We found a higher, albeit non-significant, restenosis rate in CEA group than the CAS group. Unlike literature data, we found a significantly higher restenosis rate in symptomatic cases in the CEA group than the CAS group.
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177,691 |
A numerical fear rating scale (NFRS) was used to measure the level of fear in the study which has been reported to have good reliability and validity . It is a segmented numeric version of the visual analogue scale (VAS) in which a respondent selects a whole number (0–10 integers) that best reflects the intensity of their fear. Higher scores indicate greater fear as follows: 0 for no fear, 1–3 for mild fear, 4–6 for moderate fear, 7–9 for severe fear, 10 for extreme fear.
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262,636 |
We next sought to confirm our GRO-seq analysis using qRT-PCR across the breast cancer cell lines. We chose representative cells from each subtype and combined them into groups based on their classification as normal immortalized epithelial cell lines (MCF10A), non-TNBC cell lines (MCF7, HCC1954, and UACC812), or TNBC-specific cell lines (MDA-MB-436 and HCC1937). Our results confirmed that we could detect significantly more CSF1 mRNA and eRNA in the TNBC cell lines when compared to normal or non-TNBC (Figure 1C,D). To determine if these transcripts could also be detected in human tumors, we procured nine samples collected from TNBC patients and six from non-TNBC patients for analysis of CSF1 expression. We performed reverse transcriptase PCR (RT-PCR) with primers specific to either eRNA or mRNA transcripts, demonstrating that both could be detected in human tumors (Figure 1B). However, variations in RNA quality, time of storage for samples, and the quality of each tumor specimen obtained made it challenging to quantitatively measure the differences in eRNA expression levels across this small sample size of human tumors. Instead, we leveraged much larger datasets to examine the quantitative changes in the expression of CSF1 mRNA across BC patients. We found that CSF1 is most highly expressed in TNBC Claudin-low patients and is significantly higher than the next highest subtype, Luminal A (p-value = 9.436 × 10−6, Welch two sample t-test) (Figure 1E) . To determine if the activity of the enhancer might be contributing to the increased CSF1 expression in TNBC tumors, we analyzed The Cancer Genome Atlas (TCGA) ATAC-seq data to compare the chromatin accessibility landscape of this enhancer across 133 breast cancer samples . Patients were separated into groups based on BC subtype (PAM50 classification), and accessibility scores were calculated based on the mean ATAC-seq score for the five bins overlapping the enhancer region. We found that the CSF1 enhancer is significantly more accessible in TNBC patients as compared to the HER2, LumA, and LumB groups (p-values of 2.25 × 10−9, 3.02 × 10−7, and 8.59 × 10−10, respectively) (Figure 1F). This demonstrates that enhancer accessibility, which is required for enhancer function, is greater in the TNBC group. Interestingly, the CSF1 mRNA transcription start site (TSS) showed similar chromatin accessibility in the TNBC group compared to LumA and LumB groups and while exhibiting more accessibility compared to the HER2 group (p-values of 2.28 × 10−3, 0.23, and 0.46, respectively). This suggests that the CSF1 mRNA promoter is viable in all subtypes and the enhancer may be responsible for amplifying the expression in TNBC patients (Figure 1G). Taken together, these results suggest that a novel regulatory element ~30 kb upstream of the CSF1 gene is more highly transcribed in triple-negative breast cancer patients and is associated with increased expression of CSF1 mRNA.
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268,296 |
In accordance with the research conducted in couples with a neurodegenerative disease (e.g., Wawrziczny et al., 2016a,b, 2019), the aim of this study was to explore the experience of couples confronted with advanced PD and to put into perspective the patient and his or her partner meaning-making regarding their couple functioning. Therefore, the data were analyzed qualitatively using IPA (Smith and Osborn, 2003). This method is well suited for this analysis because it captures the individual’s lived experience and the meaning-making associated with a given phenomenon (Eatough and Smith, 2008). To study the mechanisms through a multiperspective design (Larkin et al., 2019) in the context of couples that underlie the functioning of couples (e.g., Antoine et al., 2013, 2018), it is important to assess the experience of each of the partners, patient and assisting partner. The analyses were related to the divergences and convergences in the discourses of partners to account for the singularity and the complexity of the individual functioning intertwined in the dyadic functioning. We met with the afflicted partner and the assisting partner individually to allow partners to explore their experience as a couple without introducing bias due to the presence of the other partner.
| 4 | 0biomedical
| 0Study
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313,673 |
Separate analyses of the overall association between PA and LADA/type 2 diabetes using genetic controls as reference (ESM Table 5) (19) indicated similar results as those based on controls sampled within the ESTRID study (ESM Table 1) (19). When we used a more detailed assessment of PA, including duration and intensity of the activity, that was available for a subset of the HUNT population, the association between PA and LADA/type 2 diabetes was similar to that seen in the overall analyses (ESM Table 6) (19). Separate analysis of the HUNT data with a stricter LADA definition, that is, no insulin treatment, also indicated similar results regarding the association with PA as the main analyses (ESM Table 7) (19).
| 4 | 0biomedical
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193,863 |
Response: This study collected ligaments from model dogs euthanized for cardiovascular studies, dogs euthanized for non-orthopedic studies, and dogs used on one side for surgical training in veterinary students. For the histological and biomechanical studies, specimens collected at close time points were used as controls. Only one side was available in the biomechanical study as four of the five dogs were used for surgical training. (Lines 76-77, 366-376)
| 3 | 0biomedical
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166,835 |
Management of patients with cardiovascular diseases usually requires risk stratification for complications and further clinical course of the disease. Therefore, reliable prognostic biomarkers that help to improve the accuracy of the diagnosis and the way of the treatment are still desirable. The understanding of the mechanisms of galectin-3 activity gave rise to the consideration of this biomarker as a valuable tool in clinical practice, either in the initial phase of the disease or during follow up in various circulatory system pathologies, including those seen in children. For these reasons, we reviewed the literature on galectin-3 as a cardiac biomarker in the pediatric population.
| 4 | 0biomedical
| 2Review
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255,552 |
Fisher’s (1998, 2000, see also Fisher et al., 2002) evolutionary theory of independent emotions systems delineates sex drive (lust), attraction (romantic love), and attachment (pair-bonds). Sex drive is primarily associated with estrogens and androgens and serves to motivate individuals to engage in sexual activity, generally. Attraction is primarily associated with the catecholamines (i.e., dopamine and norepinephrine), phenylethylamine, and serotonin and serves to focus efforts on preferred mating partners. Attachment is primarily associated with oxytocin and vasopressin and serves to enable individuals to engage in positive social behaviors and connections of a sufficient length of time to satisfy species-specific parenting approaches (Fisher, 1998). Sex drive relates most to the sex function of romantic love, attraction to the mate choice and courtship functions, and attachment to the pair-bonding function. Romantic love shares similarities with the ‘courtship attraction system’ found in many mammals (Fisher et al., 2006).
| 4 | 0biomedical
| 2Review
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180,691 |
Nosti et al. found that patients with cervical elongation were more likely to be older . In our study, patient age older than 65 years was a predictor of cervical elongation, which was similar to the previous study. In contrast, other studies did not find the same association. Ibeanu et al. reported that age was not a risk factor for cervical elongation and Berger et al. reported that age was inversely related to cervical elongation . The difference among studies may be explained by the different definitions of cervical elongation and study populations. Ibeanu and colleagues clinically defined cervical elongation as cervical length measure by POP-Q C-D ≥ 8 cm . Berger et al. use MRI study to define a uterine corpus length of 63 mm and cervical length of 33.8 mm (CCR = 1.9) or cervix to corpus ratio ≤ 0.79 (CCR = 1.26) as normal . Our definition of uterine cervical elongation was based on a CCR ≤ 1.5, which was measured by the post-hysterectomy uterine specimen.
| 4 | 0biomedical
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298,207 |
While investigating the frequency of suspected common SNPs of F2, F5 and PAI-1 genes in this study, there were no statistically significant differences between the severe patient group and the healthy population in SNPs. Given these findings, there is a need for research focused on other thrombophilia-related genetic factors that contribute to severe NCP.
| 2 | 0biomedical
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241,339 |
From this, it can be deduced that the interaction energies of the protein in aqueous glycerol solution depend on the glycerol concentrations. The peptide stabilization propensity increases as the number of water molecules increase in the solvent. The large fluctuations in the energies of systems with higher glycerol concentrations can be attributed to the mobility of the few water molecules in the neighborhood of the peptide. This mobility results in frequent changes in the solution surrounding the solute, and register as larger fluctuations.
| 4 | 0biomedical
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251,031 |
To avoid the influence of confounding factors, 8 significant factors from the univariate analysis were included in the LASSO regression, and variables were re-evaluated. Finally, 6 non-zero coefficient variables were included in the multivariate analysis. These factors were vascular lymphatic invasion, histological grade, imaging results, preoperative CEA, submucosal invasion depth, and tumor type (Figures 1A,B). In addition, the random forest algorithm was used to analyze the 8 factors that were of great significance in the single factor analysis, and the importance of the variables was ranked. The greater the Gini coefficient, the greater the importance of the factor. The imaging results ranked first, followed by histological grade, vascular and lymphatic invasion, preoperative CEA, and submucosal invasion depth (Figure 1C).
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263,170 |
When available, research must be carried out for N. gonorrhoeae and C. trachomatis through molecular biology in a first prenatal medical appointment. The treatment is recommended for non-complicated urogenital infection by C. trachomatis during pregnancy and breastfeeding. The test for control of cure must also be conducted if it is available. Azithromycin was considered safe and efficient according to clinical experience, and WHO also recommended it during pregnancy 33 .
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356,445 |
Unlike the special cases of real and complex-valued SISO channels (i.e., nt=nr=1), the structure of the capacity-achieving input distribution, denoted as FX⋆, is in general not known. To motivate why in this paper we are seeking for novel upper and lower bounds on the capacity (Equation (2)) instead of trying to solve the optimization problem directly, in this section we first summarize properties optimal input distributions must posses, which demonstrate how complicated the optimization problem actually is. Note that, whereas an optimal input distribution always exists, it does not necessarily need to be unique.
| 1 | 2other
| 0Study
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162,011 |
Motives for suicide attempts were more related to mental problems after COVID-19 for all ages. In adolescents, interpersonal relationships and job-related motivation (school) decreased, while in the elderly, the motives for physical illness or loss of people around them had a statistically significant increase (p < 0.001) (Table 2).
| 2 | 0biomedical
| 0Study
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66,802 |
The inactivation of DAPk in cancer is usually a result of hypermethylation at the promoter of the DAPk gene rather than mutation . The 5′-UTR of DAPk1 gene contains a CpG island in which hypermethylation leads to gene silencing and loss of expression . The hypermethylation of DAPk1 and DAPk2 genes has been detected in several human tumors, albeit at varying methylation rates (Figure 3) . Besides hypermethylation, microRNA (miRNA) which are noncoding RNA molecules can also downregulate DAPk levels by a miRNA-dependent mechanism. Chen et al., in a recent publication demonstrated that two miRNA (miR-103 and miR-107) can inhibit DAPk1 translation by targeting its 3′-UTR . This was confirmed by a correlation between the increased expression of miR-103/107 and downregulation of DAPk1 in colorectal cancer (CRC) cell lines and CRC patients . Additionally, downregulation of the transcriptional mediator complex subunit 1 (Med1) which interacts with transcriptional factor C/EBP-b to participate in the transcriptional activation of DAPk has been found to correlate with DAPk1 downregulation . Futhermore, hypermethylation and transcriptional regulation, DAPk1 expression loss can also result from heterozygosity and homozygous deletion of DAPk1 as found in certain types of cancers . In addition, the expression of DAPk1 in some tumors have shown that posttranslational mechanism may also inactivate DAPk1 . For example, the tumor suppressor functions of DAPk1 can be inactivated by phosphorylation of DAPk1 by tyrosine kinase Src at Tyr491 and Tyr492 .
| 5 | 0biomedical
| 0Study
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246,025 |
Obviously, from the comprehensively consideration of accuracy and speed, the multilabel model based on binary relevance and improved MobilesNet-v2 with spatial attention mechanism has the best performance. Also, it was selected as the final model called NMLNet to classify the navigation mark's lights.
| 2 | 0biomedical
| 0Study
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106,804 |
The decomposition algorithm is shown in Algorithm 2, where the time complexity of selecting two solutions randomly from the mating pool is O(1), region replacement is O(1), and re-labelling new solution is O(N). So the time complexity of this algorithm is O(N).
| 1 | 2other
| 1Other
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193,175 |
In summary, emphasizing high-contrast edges while suppressing the interior of salient regions is a major obstacle of the pixel or patch-based methods. Region-based image abstractions are considered superior to pixel- or patch-based methods because they can employ a richer feature representation for saliency detection. Superpixel-based methods have gained popularity in recent years because of their computational efficiency. However, finding an optimum superpixels granularity is a challenging task for the superpixel-based image abstraction process. This is because the efficiency and robustness hallmarks of saliency detection methods are highly dependent on the granularity of superpixels. This empathizes the significance of constructing an efficient method that can automatically detect the number of regions for image abstraction. The proposed color histogram-based image abstraction can automatically detect the appropriate image region granularity based on the color distribution of an image as explicated in the subsequent section.
| 3 | 2other
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228,602 |
The five companies were selected for the following reasons: (a) they were mid-/large-sized ethical pharmaceutical companies and top performers in their industry; (b) all companies had established processes and allocated teams for packaging development; (c) each company had developed at least one patient-centered packaging for which they could disclose to the researchers the history of the development process, and provide additional data from different sources; (d) participants had several years of experience in pharmaceutical packaging projects, many of them with strategic and managerial positions in the company. They were also responsible for the development of the patient-centered package and could join in an online workshop with team members and report their experiences from that development.
| 2 | 0biomedical
| 0Study
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127,752 |
We tested cleaners in their house aquaria individually. To do so, we divided the house aquaria into two compartments: holding compartment and testing compartment. We allowed fish to acclimatize for at least 10 min after introducing the opaque divider in the aquaria before the start of trials. During the trials, we used two partitions (i.e. one opaque and one transparent) to confine the focal individual to one side of the test compartment. Meanwhile, we placed the test plate(s) on the other side of the test compartment that was inaccessible by the cleaner. Once the test plate(s) were ready, we removed the opaque partition followed by the transparent one. This allowed the fish to see the test plate(s) before granting it access (figure 1). It is important to note here that in all the cognitive tasks we perform in this study, we used Plexiglas plates with food as surrogates for client fish. The tasks did not involve ‘real’ clients at any stage.
| 4 | 0biomedical
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127,991 |
Histopathologically, Sjögren syndrome mainly features extensive CD4+ T cells and antibody-secreting B cell infiltration, which together cause the destruction of salivary glands (Fox, 1996). Dendritic cells are also found near the ductal epithelium, where they secrete inflammatory cytokines such as TNF-α and IL-6 (O'Dell, 2020). TNF-α induces apoptosis of salivary-gland cells (Jin and Yu, 2013), while IL-6 participates in the generation of Th17 cells (Youinou and Pers, 2011). T cells that secrete IL-17 have been widely detected in diseased salivary glands, suggesting that the pathogenesis of SS may in part be Th17 development (Brito-Zeron et al., 2016). In the presence of IL-6, Th17 cells also orchestrate the development of germinal centers (GCs) (Hsu et al., 2008), which facilitate antigen-driven B cell responses in the salivary glands (O'Dell, 2020).
| 4 | 0biomedical
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100,484 |
Inspired by AC , we select the optimal value of lag from 1 to 30. We can get 30×6=180 dimensional vector. We also compute the frequency of 20 amino acids appearing on this sequence. As a result, a protein sequence is represented as 30×6+20=200 features. Finally, we combine descriptors of two proteins, and build a 400-dimensional vector to represent each pair of proteins by NMBAC.
| 3 | 0biomedical
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294,776 |
Colonoscopy localized the lesions throughout the eight colonic segments, with most lesions located in the sigmoid (26.6%), ascending colon (21.1%) and caecum (15.1%). Comparing intraoperative and colonoscopic localization, there were small differences in all the colonic segments, but the differences were not significant.
| 4 | 0biomedical
| 0Study
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72,443 |
Growth effect of B. bifidum ATCC 15696 on HMO or Neu5Ac as a carbon source. (A) Growth profiles of wild-type and Δsiabb2 B. bifidum ATCC 15696 strains cultured in mMRSCS containing 0.5% (wt/vol) HMO. (Right panel) Single-culture model. (Left panel) Coculture model. (B) Growth profiles of wild-type B. bifidum ATCC 15696 in mMRSCS containing 0.5% (wt/vol) Neu5Ac. Data are presented as means ± standard deviations (n = 3). Significant differences were determined by analysis of variance with the Tukey test. *, P < 0.05 versus wild-type and Δsiabb2 strains. ns, nonsignificant. Download FIG S2, TIF file, 0.6 MB.
| 4 | 0biomedical
| 0Study
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277,577 |
In response to BEZ235 proliferation decreased in a dose-dependent manner in OV-90 aggregates, with statistically significant reductions relative to the control at concentrations of 0.5 μM and above (Figure 6A). A similar response was seen in OV-90 spheroids although these were less sensitive with statistically significant reductions at 5 and 50 μM. There was no significant difference between the response of OV-90 aggregates and spheroids to BEZ235. At the concentrations tested BEZ235 had no significant effect on proliferation in OVCAR8 suspension aggregates or spheroids (Figure 6C) suggesting that these may be resistant to the inhibitor. A statistically significant difference was found between the response of OVCAR8 aggregates to BEZ235 in comparison to OVCAR8 spheroids ( p = 0.0248).
| 5 | 0biomedical
| 0Study
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201,640 |
The surface elements of PSVII@MCP-CaP were determined by X-ray photoelectron spectrometer (ESCALAB250Xi, Thermo Fisher Scientific, USA). The scanning times were 10. The excitation source was Al Ka X-ray, and the analysis point area was 650 µm. The analyzer mode was CAE. The band pass energy was 20.0 eV, and the analysis energy step was 0.05 eV.
| 4 | 0biomedical
| 0Study
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2,333 |
The E3 ligase RNF44 is implicated in UPS of AMPK‐α1 degradation in BR cells. (A) Parental cell and BR cells were incubated with MG‐132 (10 μm) and CHX (80 μg·mL−1), respectively. Cell lysates were collected at different time intervals, and subsequently, AMPK‐α1 was assayed by immunoblotting. The levels of AMPK‐α1 were quantitated by ImageJ and presented as curves. (B) Parental and BR cells were incubated with or without ADI‐PEG20 in the presence of MG‐132 (10 μm) for 4 h. Ubiquitin (Ub) and AMPK‐α1 were separately detected by immunoblotting following immunoprecipitation of AMPK‐α1. (C) The precipitated proteins from A2058 cells and A2058BR cells were, respectively, labeled with Cy3 and Cy5 and then were subjected to 2D gel. Thereafter, the Cy5‐positive spot was identified as RNF44 (Q7L0R7) by MALDI‐TOF MS based on UniProtKB/Swiss‐Prot database. (D) The levels of different E3 ligases (RNF44, Cidea, MAGE‐A3, and MuRF1) in precipitated proteins (D) or total cell lysates (E) were detected by immunoblotting. (F) A2058 cells were constantly treated with vemurafenib (5 μm), and its cell lysates were collected at different time points. The levels of AMPK‐α1, RNF44, or actin were detected by immunoblotting.
| 4 | 0biomedical
| 0Study
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11,602 |
It was hypothesized that ENL is an IC-mediated disorder because it has some clinical features in common with the Arthus reaction, a type III hypersensitivity reaction that involves the deposition of ICs mainly in the vascular walls, serosa, and glomeruli and is characterized histologically by vasculitis with a polymorphonuclear cell infiltrate (37). The multisystem involvement of ENL resembling autoimmune diseases associated with ICs such as systemic lupus erythematosus (SLE), also lends credence to this theory.
| 4 | 0biomedical
| 0Study
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249,101 |
Numerous biologically active metabolites secreted by the human gut microbiome continuously interact with the host, modulate host immunity, and participate in maintaining immune homeostasis. Previous research has mainly focused mainly on short-chain fatty acids (SCFAs) (112). SCFAs are water-soluble and diffusible fermentation products of dietary fiber produced by anaerobic bacteria. They comprise one to seven carbons, with acetate, propionate, and butyrate accounting for 90%–95% of total colonic SCFAs (112). SCFAs reach a peak concentration in the cecum and decrease from the proximal to the distal colon (113). SCFAs regulate adaptive immune cell functions mainly by combining G protein-coupled receptors (GPCRs) (37, 41) and inhibiting histone deacetylase and metabolic disturbances (32, 35, 36, 39). Among GPCRs, GPR43 recognizes a wide range of SCFAs (41), including acetate, propionate, and butyrate. Among these, acetate promoted intestinal IgA responses depending on the GPR43 pathway, which induced DCs to express Aldh1a2 and then converted vitamin A into its metabolite retinoic acid. In turn, blockade of retinoic acid signaling inhibited the acetate-induced IgA production (41). Takeda et al. showed that the bacterial metabolites, pyruvic acid and lactic acid, could induce dendrite protrusion via GPR31 in CX3CR1+ cells in mice, which enhanced immune response and high resistance to intestinal Salmonella infection (38). In addition, SCFAs are able to regulate the colonic Treg pool through Ffar2 (the gene encoding the receptor GPCR43 of SCFAs) expressed on colonic Tregs (114). Moreover, SCFAs inhibit the production of histone deacetylase, causing increased acetylation and expression of Foxp3, which is the core transcription factor that drives Treg differentiation (35, 112). Arpaia et al. found that butyrate and propionate simultaneously increase CNS1-dependent extrathymic Tregs and peripheral Tregs (32).
| 5 | 0biomedical
| 0Study
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146,219 |
Item analysis is essentially a t-test, which will check whether high and low subgroups are different. In this study, the dimensional items of social attachment were ranked from high to low. The data for all items were then divided into high, low, and medium clusters. Research has shown that there should be a significant difference between the mean of the data for the high and low scoring groups. If there is no significant difference, it means that the scores for the high scoring group are too close to the low scoring group, which means that this is an invalid questionnaire as there is no gap in the scores for all the questions. The results of the items analysis show that this is an invalid item, so it should be removed from this study (Liden and Maslyn, 1998; Babbie, 2004).
| 4 | 0biomedical
| 0Study
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78,276 |
Wild-type and mutation p53 constructs (R280K, R249S, R273H, and R175H) were purchased from Addgene and sub-cloned into lentivirus vector . UMSCC1 cells were transduced with lentiviruses expressing these mutations and selected with puromycin. Scramble siRNA and siRNA duplexes to human TrxR1 were ordered from Thermo Scientific (Lafayette, CO) and transfected to the cells with siRNA transfectant #2 (Thermo Scientific).
| 4 | 0biomedical
| 0Study
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148,535 |
Furthermore, strength variables explained 42%, 36% and 59% of the variance in CoD180 in basketball players, long-distance runners and tennis players, respectively. In the basketball model (R2 = 0.42), two peak torques (Hip ADD, Knee FLX) and two RTD variables (Ankle FLEX RTD100, Knee EXT RTD50) were included. The model for runners (R2 = 0.36) included Knee FLX peak torque, Hip ABD RTD50 and Hip IR RTD100. Finally, the model for tennis players (R2 = 0.59), included 4 peak torque values (Hip ADD, Hip ABD, Trunk LFLEX, Ankle FLX) in addition to Knee EXT RTD50.
| 4 | 0biomedical
| 0Study
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308,973 |
Using the distribution (5) it is possible to calculate \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\varepsilon _k$$\end{document}εk, the expected number of choices from category k, as well as \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\chi _k$$\end{document}χk, the expected number of choices with costs larger than or equal to that of category k. The latter is what in the literature of ego-networks is referred to as a social “circles”20. It is straightforward to obtain the expression128\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\begin{aligned} \varepsilon _k\equiv \frac{{\mathbb {E}}(\ell _k)}{L}=\frac{e^{k\mu }-e^{(k-1)\mu }}{e^{r\mu }-1}, \qquad \chi _k\equiv \sum _{j=1}^k\varepsilon _k=\frac{e^{k\mu }-1}{e^{r\mu }-1}. \end{aligned}$$\end{document}εk≡E(ℓk)L=ekμ-e(k-1)μerμ-1,χk≡∑j=1kεk=ekμ-1erμ-1.
| 4 | 0biomedical
| 0Study
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313,457 |
Since patients with ASPPC usually receive prompt antimicrobial treatment after serologic results, little is known about the natural course of the disease. To the best of our knowledge, only 5 cases of ASPPC with spontaneous improvement have been reported , , , . We report the natural course and the multimodal retinal imaging features of an additional case, and discuss the pathogenetic implications and the importance of early recognition of this rare clinical entity.
| 3 | 0biomedical
| 3Clinical case
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55,139 |
Figure 3 shows the histogram of two significant features namely dissimilarity and inverse difference normalized. This figure also illustrates the distribution of survival across the features values.Fig. 3Histograms of significant features a) dissimilarity and b) inverse difference normalized. The figure also illustrates the distribution of survival across the features values
| 2 | 0biomedical
| 0Study
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358,663 |
‘I decided to use my skip queue letter because the line now I can pass people then whenever I stand in the queue or whatever I do not feel like talking to people I do not feel like seeing people I don’t like being around people so I found myself being with people, and I was in a bad space so I decided to take out the skip queue letter for myself and I went and stood in the line towards the side to the third table, I went there and I showed the lady in front that I had this letter and then I stood. The person finished from the desk and then I proceeded forward; I don’t even remember what she said, but hurt me in such a way that I just broke down there and now it was seen and everything and yeah’. (Participant 21, 21 years old, Male)
| 1 | 2other
| 1Other
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171,145 |
Surprisingly, a weak antioxidant activity was measured in both extracts, while the content of phenolic compounds was high mainly in the latex. However, the phytochemical analysis showed a high level of methylation of chromones, and it is known that the antioxidant activity is different depending on these specialized metabolites.
| 2 | 0biomedical
| 0Study
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369,916 |
The fast, iterative, tv-regularized, statistical reconstruction technique (FIRST22) was also used for sparse-view image reconstruction. This algorithm is an ultra-fast variant of the adaptive steepest descent-projection on to convex sets (ASD-POCS72) and has been shown to suppress additional artifacts on the periphery of the object. The performance of FIRST was compared to MS-RDN using one small-size breast, one medium-size breast, and one large-size breast.
| 4 | 0biomedical
| 0Study
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116,091 |
Research on bulk-DDIF measurement of bovine trabecular samples (Figure 3 and Figure 9) shows higher spectral weights in short-decay regions of bone samples with high surface-to-volume ratios. For the full range of samples examined in that study, it was shown that the integrated weight of the short-decay region (20 ms < TDDIF < 500 ms) of the DDIF spectra of each sample correlates well with the projected surface-to-volume ratio (PSVR) that was determined using both independent PFG-NMR measurements as well as the mean intercept length (MIL) of the trabecular bone samples obtained using μCT image analysis, as shown in Figure 9. MIL was found by averaging the lengths of the line segments between trabeculae across the whole structure. MIL and other related metrics, such as trabecular density, are well-known measures of the integrity of trabecular bone structures.
| 4 | 0biomedical
| 0Study
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95,860 |
Other platforms have been considered. For example, some authors have suggested the liver as an alternative site . Unlike muscle, it is designed to secrete circulating proteins. It is also thought to be less immunogenic. However, transduction would require systemic administration of the vector, and there would be no simple means of eliminating expression in the event of a complication. Another potential site could be the salivary glands. While it is well-know that the salivary glands secrete proteins into the oral cavity, it may be less well appreciated that they have also been used as a platform to deliver therapeutic proteins, including the IgG Fc fragment and a host of other proteins, into the systemic circulation [36, 37]. Transgenes delivered to the salivary gland tend to favor being sorted either into the saliva or the blood, though it is currently a challenge to predict which direction a particular protein will sort . The major paired salivary glands are also easily accessible, and the parotid glands are encapsulated, which minimizes vector spillage into the general circulation. Futhermore, in the event of complications, the transfected glands could be removed without creating major disability.
| 4 | 0biomedical
| 0Study
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249,881 |
Previous studies have suggested the use of GLP-1 as a possible treatment of chemotherapy-induced mucositis (13, 18). Administration of GLP-1 analogs in mice treated with chemotherapy ameliorated mucositis and accelerated healing of the intestinal injury (13, 14). In patients with diabetes, obesity and psoriasis, treatment with GLP-1 analogs has been found to cause reduction in chronic low-grade inflammation (40–43). Although the mechanism is debated and probably confounded by the metabolic-improving effects of GLP-1 treatment (43), amelioration of the putative dysfunctional intestinal barrier might play a role in these conditions (44).
| 4 | 0biomedical
| 0Study
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355,611 |
Christiane Katharina Sonntag: Conceptualization, Investigation, Visualization, Writing - original draft, Writing - review & editing. Lion Konstantin Flachbart: Conceptualization, Verification. Celine Maass: Investigation. Michael Vogt: Investigation. Jan Marienhagen: Conceptualization, Funding acquisition, Supervision, Resources, Writing - original draft, Writing - review & editing.
| 1 | 0biomedical
| 1Other
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258,669 |
Effects of carbachol, 2-APB and BAPTA-AM on HTV-induced pathological lung injury and inflammation. (A) H&E staining the histology of lung tissues from group CON, HTV, HTV+Carbachol, HTV+2-APB mice, and the HTV-treated mice pretreated with Ca2+ chelator BAPTA-AM (HTV+BAPTA-AM group). Scale bar: 200μm. An inset picture was employed to show the indicated area at 4X magnification. (B) Pathological scores were assessed by results of H&E staining. (C) Lung edema was assessed by determining the weight ratio between wet and dry lungs. (D) Total protein concentration in BALF. (E) Infiltrated cell counts in BALF. (F–H) Levels of IL-1β (F), IL-6 (G) and TNF-α (H) in BALF. Data are expressed as means ± SD (n = 8 per group except for group HTV+ Carbachol (n=7), which has 1 mouse died unexpectedly and was removed from analysis). *P < 0.05 vs. CON group; # P < 0.05 vs. HTV group.
| 4 | 0biomedical
| 0Study
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116,024 |
Since we observed significant G2 or M phase arrest and H3 pSer10 staining during flow cytometry cell cycle analysis, we explored whether scoulerine affects the microtubule structures of cells. To visualize this, lung carcinoma A549 cells were chosen as a model for indirect immunofluorescence with a monoclonal anti-β-tubulin antibody due to a lower nuclear-cytoplasmic ratio compared to leukemic cells. Additionally, A549 cells were sensitive to scoulerine and displayed strongly diminished proliferation during xCELLigence analysis at concentrations exceeding 10 µM. Epi-fluorescence microscopy performed with fixed A549 cells labeled with a monoclonal anti-β-tubulin antibody and DAPI counter stain revealed that the intact microtubules extended continuously through the cytoplasm in control cells. In contrast, scoulerine applied for 24 h at 10 and 20 µM obviously disrupted microtubule structure with a dense aggregation of microtubules around cell nuclei, being less dense at the cell periphery. Besides, A549 cells treated with scoulerine at 5 µM resisted the treatment with almost intact organized tubulin networks as seen in 0.1% DMSO exposed control cells. Nocodazole, the microtubule depolymerizer, was used as a positive control for the study. As is apparent from the microscopic images presented in Fig. 8, treatment with nocodazole at 5 µM resulted in the observation of expected disorganized and disassembled microtubule structures as compared to 0.1% DMSO control cells.Figure 8Microscopic images of A549 cells stained with an anti-β-tubulin antibody (red) and counterstained with DAPI (blue). The cells were treated for 24 h with scoulerine or a solvent (0.1% DMSO) as vehicle control. Nocodazole, an antineoplastic agent that disrupts microtubule function by binding to tubulin was used as a reference compound in this assay. Scale bar: 10 µm. Experiments were performed in triplicate using epi-fluorescence microscopy. Photographs from representative chambers are shown. Compared with controls, thicker and denser microtubule bundles were evident in scoulerine-treated cells.
| 4 | 0biomedical
| 0Study
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169,984 |
The expression levels of NPY5R in BC tissues. (A) NPY5R mRNA expression in BC and normal breast tissues from TCGA database (*p < 0.05). (B) Analysis of NPY5R expression in BC and normal breast tissues using the GEO database. Statistical significance was evaluated using Wilcoxon rank sum test. (C) Immunohistochemical staining of NPY5R in BC tissues and adjacent non-tumor tissues. Typical images are shown at 200× and 400× magnifications. Scale bars, 50 μm. (D) H-SCORE of the two groups (p < 0.001). (E) 8 pairs of primary BRCA and adjacent tissues are tested by q-PCR (p < 0.001).
| 4 | 0biomedical
| 0Study
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227,136 |
Looking at the correct answers throughout all four conducted studies, we observed that in Studies 2 and 3, participants in the conformity condition provided significantly more correct answers on the task when engaging in MCII (vs. other conditions), though these results need to be taken with caution as the interaction effects between conformity and self-regulation condition were not significant; in Study 1 and 4, however, the planned contrasts results were only marginally significant. Interestingly, in Study 4, in which participants were permitted to find their own idiosyncratic if-then plan, the interaction effect between conformity and the self-regulation condition was significant.
| 1 | 2other
| 0Study
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88,511 |
The abnormal collagen metabolism plays an important role in the pathogenesis of recurring incisional hernias. Surgically, it is equally likely for these pathological changes to cause the reduction of abdominal wall compliance and to contribute to the difficulty of achieving durable incisional hernia repairs.
| 3 | 0biomedical
| 1Other
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320,322 |
Combining power readings with video data captured from multiple angles could allow for more accurate avatar modeling, thereby increasing the realistic nature of in-game performance. Photographs or video of riders in their preferred riding positions on the bicycle could be beneficial to those with certain body shapes or greater flexibility.
| 1 | 2other
| 1Other
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84,940 |
While the intermixing of b-representations and predictive coding motivates unique behavioural and neuroscientific hypotheses, we should also ask if something is lost in the appeal to B-predictions. Philosopher Shaun Gallagher provides a compelling critique,18 describing ‘moderate embodied cognition’ as an ‘invasion of the body-snatchers’:... The body snatchers ...devise a version of embodied cognition that leaves the body out of it... Rather, the real action, all the essential action, occurs in the brain. Indeed, the body, in this version of embodied cognition, is the “body in the brain”. In effect, body snatchers have invaded theories of embodied cognition and have replaced bodies with “sanitised” body-formatted (or B-formatted) representations in the brain. (Gallagher 2015, pp. 97–98)By appealing solely to the representational mixing of bodily and cognitive information, Gallagher suggests that proponents of ‘moderate’ embodied cognition actually argue for something that is not particularly embodied at all. Indeed, according to moderate (or weak) embodied cognition, such an agent could easily be simulated from within a vat, provided reasonable simulacra of bodily signals were provided. According to the moderate view, the body is just “a better designed container that delivers information to the brain in its own peculiar way”, rather than a constitutive element of information processing. What then should a radical theory of embodied prediction provide? Gallagher suggests that (bodily) anatomy, affect, sensory-motor contingencies, and environmental couplings—all of the things that weak EC reduces to neural representations—should be considered relevant to cognition.
| 5 | 0biomedical
| 0Study
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384,240 |
We employed an information theoretic model for the inference of microbial species interaction networks based on RSA interdependence. The model was used to infer microbial networks associated to different health states and is suitable for predicting selected biodiversity patterns characterizing the space-time organization of bacteria α-, β-, and γ-diversity. Thus, the primary purpose of the model is not to infer causal (or “true”) species–species interactions among bacteria. The computational inference of “real” interactions is always very hard—provided that there is a complete knowledge of the reality on which results can be validated—and any inferred interaction is always dependent on the analytics and data used. For instance, RSA profile may not necessarily contain the information about all species–species interactions aimed to be assessed but still the question remains about what is truly an interaction (aimed to be measured) since any physical or functional interaction may not necessarily reflect any change in RSA, or other biomarker. Additionally, any change in RSA or other biomarkers may be related to other external factors, such as environmental fluctuations, which alter species simultaneously. What is certainly true, however, is that, if the inference model detects strikingly different patterns for different population groups, then those patterns likely tell something meaningful about different dynamics and collective environmentally driven changes . In this perspective the entropy-based model is focused on the predictability of patterns vs. causal investigation of mechanisms. The proposed model can be applied to both abundance and RSA, or other biomarkers, without any special modification. Theoretically, the pdf of abundance and relative abundance is the same leaving aside numerical artifacts; independently of this, RSA seems better suited for this type of ecological analyses because it informs about changes of species abundance with respect to the whole community. Abundance and/or RSA seems also the most likely to detect species functional roles and interactions as highlighted by recent studies . Constructing a network for each health group is the purpose of studies such as ours that try to identify common group dynamics in populations independently of individual variability (see, e.g., Bashan et al. , where universal group dynamics in microbiome is the core quest). The identified network topologies have a correspondence with the dynamics of RSA, that is a critical dynamics for the scale-free information network associated to the healthy state, and exponential dynamics for the random network associated to the unhealthy state. The total network entropy is the lowest for the healthy microbiome for any threshold of the information flow TE (Figure 2). This implies higher free energy available to the healthy microbiome and lower information needed to function where information entropy in the physical space can be thought of as the average interspecies communication/interdependence. The lower entropy in species collective interactions has certain implications for data collection, potentially implying fewer data are needed for characterizing healthy microbiomes. This is because one single globally stable state was identified for the healthy microbiome (in the entropy pattern in Figure 2) vs. multiple stable states for the unhealthy microbiome (one globally and two locally stable state for high, medium and low value of network entropy, respectively). These states correspond to different biodiversity states in terms of α, β and γ. The existence of multiple dysbiotic states seems to confirm the previously observed “Anna Karenina effect” where “all healthy microbiome look alike, instead each unhealthy microbiome is diverse in its own way”. More theoretically speaking, the lowest entropy across the system’s landscape of potential states is a sign of criticality that is the state toward which any ecosystem tends to ; the critical state is where there is a balance of system’s self-organization and environmental influence .
| 5 | 0biomedical
| 0Study
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107,840 |
Phylogenetic trees and molecular evolutionary analysis were made using the MEGA version 6.0 . The phylogenetic tree was constructed according to the neighbor-joining, maximum parsimony, and maximum likelihood algorithms [43, 44]. In order to evaluate the consensus of the branching, the bootstrap of phylogenetic tree analysis was employed with 1000 replicates of the data set. A suite of SPSS 11.5 software (IBM) was used for the statistical analysis to find the relation between culture depentent Trichoderma spp., counts (CFU) and other sediment properties (Sediment depths, sites or seasons) by ANOVA followed by post hoc test (Tukey’s) and correlation analysis using Pearson’s correlation method. In addition to this, PRIMER (Plymouth Routines in Multivariate Ecological Research (version 6.1.10) was used to analyze the diversity indices.
| 4 | 0biomedical
| 0Study
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134,835 |
We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.
| 1 | 2other
| 1Other
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36,408 |
The present study showed favorable results for metabolic control of diabetes mellitus from the empowerment program applied over 12 months. As for the socio-demographic data, our study had young participants, that is, with a lower age for diabetes when compared to other studies [5, 12, 27]. Educational levels were predominantly low, which may reflect the reality of the adult Brazilian population. There was also a lesser presence of men, perhaps because women value self-care more and consequently were more willing to participate in the program . Most of the participants lived with a companion and some studies show that family support is a favorable factor for health care [11, 29].
| 3 | 0biomedical
| 0Study
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265,633 |
These outcome data were obtained from the multi-item and single-item scores for each PRO visit in the study using the HCP evaluations on the Post-Visit PRO Tool Evaluation Questionnaire immediately after or within a few days of the visit. The HCPs will complete informed consent and are informed that the collected data are only used in an anonymized manner. In addition, the HCPs will complete evaluation questionnaires at the end of the study, which evaluate their overall views and attitudes regarding the use of PRO, impact of use of PRO, and requirements for use of PRO.
| 2 | 0biomedical
| 0Study
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28,170 |
We then evaluate whether each region in the resulting segmentation contains a local maximum points and we delete the regions lacking local maximum points. On this basis, we compute some statistical characteristics including the eccentricity, major axis, and minor axis. Then we reserve the regions that exhibit statistical characteristics similar to a disk. Finally, we record the location of the reserved regions and determine whether the peak intensity of each region is more than three times brighter than its axon shaft in the original image . The final result of axonal boutons analysis is shown in Fig. 3 e.
| 4 | 0biomedical
| 0Study
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231,227 |
Based on the role of redox imbalance in the pathogenesis of melanoma and nonmelanoma skin cancer, Kuo et al. were interested in flavonoids (anthocyanidins), which have been shown to activate Nrf2 antioxidant responsive element (ARE) pathway as an intrinsic defense mechanism against oxidative stress. Delphinidin, one of the most powerful and abundant anthocyanidins found in berries, suppressed 12-O-tetradecanoylphorbol13-acetate (TPA)–induced neoplastic cell transformation in mouse epidermal JB6 P+ cells by 69.4 to 99.4%. The demethylation of 15 CpG sites in the mouse Nrf2 promoter region between nt 1226 and 863 from the transcription start site was linked to the activation of the Nrf2-ARE pathway. The reduction in protein expression of DNMT1, DNMT3a, and class I/II histone deacetylases was consistent with the lower CpG methylation ratio in the Nrf2 promoter area (HDACs). Overall, these findings demonstrate that delphinidin, an epigenetic demethylating agent of the Nrf2 promoter, may activate the Nrf2-ARE pathway, suggesting that it might be used as a skin cancer chemopreventive agent.
| 4 | 0biomedical
| 0Study
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219,490 |
When 0 < H < 0.5, it shows that the time series of vibration signal presents the characteristics of inverse long-term correlation and independence, and the future overall trend is contrary to the past, which is to say, the past is increasing, and the future is decreasing. The vibration signal, therefore, has strong variability and mutability due to the ongoing reversion.
| 2 | 2other
| 1Other
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163,457 |
The host plants for A. pomi were seedlings of Chaenomeles japonica, for M. rosae, the host plants were seedlings of Rosa rugosa and for C. cupressi the host plants were Juniperus scopulorum. The plants were free of pathogens, were set in 30 cm × 30 cm × 30 cm pots (Ch. japonica and R. rugosa) or 20 cm × 20 cm × 20 cm (J. scopulorum), and were grown for two weeks at 20 °C to acclimatise before the experiment.
| 3 | 0biomedical
| 0Study
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351,595 |
To evaluate the effect of YM101 on the components of the TME, we calculated the scores of multiple immune signatures. The scores of the signatures of T cell, NK, DC, macrophage, IFN-α response, and IFN-γ response were markedly increased in the YM101 group (Fig. 9c–h).
| 4 | 0biomedical
| 0Study
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52,572 |
The synergy port developed permits the bilateral teleoperation of the SoftHand from monitoring the user’s finger posture using a hand exoskeleton. However, a grasp is completely defined by the combination of the hand’s intrinsic and extrinsic DOFs, as underlined in Ciocarlie and Allen (2009). Indeed, the stable grasp of an object located in its environment requires the control of the wrist position and orientation during the reaching phase so as to place the robotic hand in an adequate configuration with respect to the object such that the further closure of the hand during the pre-shaping and grasping stages leads to a force closure grasp.
| 4 | 0biomedical
| 0Study
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324,967 |
In this regard, acrylate monomers with pendant biguanide groups were successfully synthesized and their homopolymers and copolymers with acrylamide were prepared by radical polymerization using AIBN as initiator. Evaluated in a clean system, these CAPs showed to be higher effective against Gram-positive bacteria, rather than on Gram-negative strains, but to be much more active than the monomeric species .
| 4 | 0biomedical
| 0Study
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89,726 |
Interestingly, yeast two-hybrid and BiFC assays revealed that both FT2α and FT1, but not FT2β, could form homodimers (Fig. 4a–c; Supplementary Fig. 9). Thus we propose that the negative effect of FT2β on flowering time results from the binding of FT2β to FT2α and FT1, which prevents them from interacting with FD and 14-3-3s, thereby reducing the number of functional flowering initiation complexes.
| 4 | 0biomedical
| 0Study
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72,219 |
After silibinin treatment, cells were harvested in RIPA lysis buffer containing protease inhibitors (thermo scientifical) according to the manufacturer’s instructions. The protein concentration was determined using the BCA assay (Beyotime). Equal amounts of protein (20 ug) were separated by SDS-PAGE gels and electrophoretically transferred to PVDF membrane (Bio-Rad, USA). After blocking with 5% BSA for 2 h at room temperature, the membranes were probed with primary antibodies for 12–16 h at 4 °C. Then membranes were incubated with appropriate HRP (horseradish peroxidase)–labeled secondary antibodies for 2 h at room temperature. Immunoreactive protein bands were visualized by enhanced chemiluminescence (ECL, Amersham Pharmacia Biotech, USA), and GAPDH was used as a protein loading control. The density of the specific bands was quantified using imageJ software. Antibodies for SIRT1, NF-κB were purchased from Abcam (Cambridge, MA, USA). Antibodies for Bcl2, Bax, cytochrome c, Cleaved-Caspase3, GAPDH, HRP-conjugated secondary antibodies were purchased from Cell Signaling Technology (Beverly, MA, USA). Antibodies for Beclin and LC3 were from Novus (Littleton, CO, USA).
| 4 | 0biomedical
| 0Study
|
79,477 |
In Poland, the assessment of the ecological status of water bodies based on the quantity of phytoplankton is performed by calculating the multimetric phytoplankton index (IFPL) which is the arithmetic mean of the trophic index (TI) and the chlorophyll index (CH) (Błachuta and Picińska-Fałtynowicz 2012; Rimet and Bouchez 2012).
| 2 | 2other
| 1Other
|
269,345 |
Similarly, average distances to the closest meal access points from schools increased from spring 2019 to spring 2020 yet decreased from summer 2019 to summer 2020. We also saw much shorter distances in schools with higher proportions of students qualifying for FRPL. For example, the distance to the closest meal access point in spring 2020 was 0.71 miles in schools where over 62.5% of the students qualify for FRPL, compared to 4.64 miles in schools where less than 40% of the students qualify for FRPL.
| 1 | 2other
| 0Study
|
130,746 |
In the case of a convex loss function, Jensen’s inequality lower bounds the risk of the randomised function by its Q-aggregate: ℓ(FQ(x),y)≤Ef∼Qℓ(f(x),y). The equality is achieved by the linear loss, a fact we will exploit to obtain an easier PAC–Bayesian optimisation objective in Section 5.
| 4 | 0biomedical
| 0Study
|
386,145 |
A popular method for inferring the physiological relevance of M1 TEPs has been to investigate how these TEPs and their features covary with MEPs, primarily due to the wealth of prior MEP research. A key finding from the present study is that noise can be introduced to the TEP signal with increasing stimulus intensities, which makes inferences based on MEPs more difficult. Going forward, we recommend that the intensity of preconditioning stimuli should be minimized when attempting to measure ppTMS TEPs using TMS-EEG for two primary reasons: (1) increasing stimulus intensity activates neurons not relevant to the FDI axis, and (2) increasing stimulus intensity activates neurons not relevant to intracortical inhibition.
| 4 | 0biomedical
| 0Study
|
24,094 |
The characterization of the calcium carbonate crystals was carried out using powder X-ray diffraction. Figure 5 shows the X-ray diffraction patterns of CaCO3 obtained in the absence and in the presence of proteins, such as ovalbumin, lysozyme, and a mixture of both proteins. The X-ray diffraction (XRD) data indicated that calcite was the precipitate obtained after 24 h both in the absence and in the presence of the proteins. The peak characteristic of calcite at 2Θ = 34.04° corresponded to the (104) crystallographic plane of the calcite observed in all the samples . The analysis of the XRD patterns of calcium carbonate precipitate after 10 min revealed that small peaks corresponding to vaterite appeared in the samples with 0.1% of ovalbumin and the protein mixture.
| 4 | 0biomedical
| 0Study
|
110,931 |
Immunofluorescent localization within the hippocampal strata radiale (sr), pyramidale (sp), and oriens (so), indicated that the majority of parvalbumin (abbreviated PV) positive interneurons within CA3 express nuclear SLM2 protein (arrowheads in Figure 6A). Nearly all of the larger, excitatory glutamatergic pyramidal cells in the CA3 fields of the hippocampus also strongly express SLM2 protein, identified by their large nuclei, and by their location in the stratum pyramidale. SLM2/NPNF (non-phosphorylated neurofilament) positive pyramidal cells are indicated by arrowheads in Figure 6B. Very few large nuclei, identified by DAPI counterstaining, were completely SLM2 protein negative (a SLM2 negative/NPNF positive pyramidal cell is indicated by an asterisk in Figure 6B). Instead, negatively staining nuclei were generally small and mostly belonged to glial cells, but could also be interneuronal or small pyramidal cell nuclei. These data are also consistent with results from within the CA1 subfield (Iijima et al., 2014).
| 5 | 0biomedical
| 0Study
|
118,421 |
Strain T12 was found to have an optimum pH between 6.5 and 7.5, and temperature of 65 °C, identical to that of isolation. When T12 is grown on pure glucose or xylose the sugar consumption rate was almost equal, whereas during co-fermentation the glucose consumption rate was approximately two to three times as high compared to the xylose consumption rate. This indicates that the presence of glucose partially inhibits xylose uptake and/or metabolism. Reduced xylose consumption by Geobacillus in a glucose/xylose mixture has been reported before . On average, hemicellulose makes up 25–35 % of lignocellulosic biomass, which makes simultaneous sugar uptake advantageous for the CBP economy . There are many microbes capable of xylose consumption, however, most of these organisms suppress the uptake of xylose when glucose is present. This negative feedback results in sequential consumption of available sugars, leading to elongated fermentation times or accumulation of xylose in the reactor during fed-batch.
| 4 | 0biomedical
| 0Study
|
332,557 |
Altogether, we have revealed both the extent of mutations in the MAPK pathway genes across more than 100 human cancer types and the subset of these mutations that are most likely to impact disease outcomes. Our integrative analysis of the CRISPR-derived gene dependencies of cancer cell lines, together with the drug responses of these same cell lines, indicates that the mutations in, and expression signatures of, MAPK pathway genes are associated with the responses of the cell lines to various MAPK pathway inhibitors. It is apparent; therefore, that it should be relatively straightforward to extend such an integrative analysis approach to identify high-confidence drug targets for a broad array of human cancers.
| 4 | 0biomedical
| 0Study
|
365,957 |
We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.
| 1 | 2other
| 1Other
|
48,838 |
Isometric head rotation to the right or left in comparison to rest also produced overall patterns of activation in subjects with CD that were similar to those in controls (Figure 3; Table 4). Both groups showed activation of the precentral gyrus, SMA, basal ganglia, anterior/mid-insula, frontal and parietal operculum, and ipsilateral cerebellum.
| 4 | 0biomedical
| 0Study
|
358,469 |
The IBT method was used to visualize specific transcripts using the single-molecule FISH (smFISH) strategy48. Previously, FISH was implemented in the SIMS field for abundant transcripts49–52, but not for the detection of single RNA molecules. Instead of using fluorescent tags, the oligonucleotide probes were conjugated to biotin and streptavidin-conjugated 5 nm 197Au nanoparticles were used to detect biotin. The nanoparticles allowed the detection of single RNA molecules without the need for amplification. As a proof of concept, 24 biotinylated oligonucleotides of 20 nucleotides in length were designed to hybridize to the highly expressed ActB mRNA (Supplementary Fig. 43a). Use of multiple oligonucleotides that target the single mRNA result in significant signal enhancement relative to a single probe.
| 4 | 0biomedical
| 0Study
|
192,153 |
Being able to appreciate the emotional experience of other people is a foundational building block for cooperation and for building long-lasting relationships (Zaki and Ochsner, 2012). The ability to feel happy for other people’s positive experiences is called vicarious joy (Batson et al., 1991; Royzman and Rozin, 2006). Prior studies using neuroimaging measures demonstrated that reward processing for self and others (i.e., vicarious reward processing) has partly overlapping neural correlates but also dissociable patterns. Reward processing for self is associated with increased activity in a network of brain regions, including the ventral striatum, a region in the basal ganglia (Apicella et al., 1991, 1992; Kawagoe et al., 1998). Similar to what was previously observed in animal studies (Montague and Berns, 2002; Schultz, 2016), human studies have repeatedly found the Nucleus Accumbens (NAcc), a subregion of the ventral striatum, to be involved in reward processing (Berridge and Kringelbach, 2015; Delgado, 2007; Liu et al., 2011). The NAcc responds to a wide range of rewards, including food, social interactions, and monetary rewards (Delgado, 2007; Knutson et al., 2001; Sescousse et al., 2013) and peaks in activity in mid-adolescence (Braams et al., 2015; Schreuders et al., 2018). While the neural mechanisms underlying personal reward processing have been well studied, the neural processes for vicarious reward are less clear.
| 4 | 0biomedical
| 0Study
|
348,978 |
Eighty-two percent (n = 1325) of all patients with suspected sepsis met at least 2 SIRS criteria (SIR > 2), and 70% (n = 934) did not meet the primary outcome (false positive). Only 35% (n = 568) met at least 2 qSOFA criteria (qSOFA ≥ 2), and about 64% (n = 361) were false positive. NEWS ≥ 8 and REMS ≥ 9 could detect similar proportions of patients (about 56%), but REMS ≥ 9 had the highest absolute risk difference compared to the other three EWSs. Similarly, REMS 10 could also provide the highest absolute risk difference in predicting mortality within 7 days of admission (Table 4). Table 4Classification according to sepsis criteriaOutcomesAll patients, no (%)SIRS, no (%)Absolute difference, % (95%CI)qSOFA, no (%)Absolute difference, % (95%CI)NEWS, no (%)Absolute difference, % (95%CI)REMS, no (%)Absolute difference, % (95%CI)< 2 (n = 297)≥ 2 (n = 1325)< 2 (n = 1054)≥ 2 (n = 568)< 8 (n = 702)≥ 8 (n = 920)< 9 (n = 713)≥ 9 (n = 909)In-hospital death457 (28.2)66 (22.2)391 (29.5)7.3 (2.0–12.6)250 (23.7)207 (36.4)12.7 (8.0–26.3)146 (20.8)311 (33.8)13.0 (8.7–17.3)145 (20.3)312 (34.3)14.0 (9.7–18.3)All patients, no (%)< 2 (n = 297)≥ 2 (n = 1325)Absolute difference, % (95%CI)< 2 (n = 1054)≥ 2 (n = 568)Absolute difference, % (95%CI)< 8 (n = 702)≥ 8 (n = 920)Absolute difference, % (95%CI)< 10 (n = 935)≥ 10 (n = 687)Absolute difference, % (95%CI)Death within 7 days280 (17.3)32 (10.8)248 (18.7)8.0 (3.8–12.1)142 (13.5)138 (24.3)10.8 (6.7–14.9)84 (12.0)196 (21.3)9.3 (5.8–12.9)119 (12.7)161 (23.4)12.7 (10.7–15.0)Abbreviations: CI confidence interval, SIRS systemic inflammatory response score, qSOFA quick sequential organ failure assessment score, NEWS national early warning score, REMS rapid emergency medicine scores
| 4 | 0biomedical
| 0Study
|
169,149 |
To clarify how AKDS001 MS increases new bone formation in the xenograft model, histomorphometric analysis on the area of newly formed bone was performed. Osteoblasts were more numerous and widely distributed in the AKDS001 MS group (Figures 4A,B). In the Blank MS group, most of the new bone formation was observed on scalloping cement lines created by osteoclastic bone resorption. In contrast, in the AKDS001 MS group, new bone was formed on smooth cement lines (Figure 4C). New bone formation on smooth cement lines is characteristic of bone minimodeling, in contrast to bone remodeling in which bone resorption by osteoclasts precedes bone formation by osteoblasts (Jee et al., 2007). Thus, the mode of osteogenesis caused by AKDS001 MS was shown to be minimodeling rather than remodeling.
| 5 | 0biomedical
| 0Study
|
143,674 |
Scoring of TILs was performed on 37 HE-stained tissue sections derived from tumors of 12 treatment-naive female patients. The histopathological and molecular subtypes as well as the Nottingham grade of the tumors are shown in Supplementary Table S1 . TILs were defined within the tumor border as mononuclear cells and the TIL-HE, i.e., TIL score determined on HE-stained sections, was defined as the area occupied by TILs in the area of stromal compartment (percentage). Tissue sections representative for lymphocyte predominant breast cancer (LPBC) versus non-LPBC are shown in Figure 1A .
| 4 | 0biomedical
| 0Study
|
1,192 |
To validate the antitumor activity of chrysin against HCC, the efficacy of chrysin was assessed in HCC-LM3 xenograft model. As shown in Fig. 6a-d, comparing with the vehicle group, tumor growth in chrysin group was significantly suppressed. In the end of experiment, the tumor volume of vehicle group had reached about 500 mm3, while the average tumor volume of chrysin group was around 200 mm3. Meanwhile, no obvious toxicity was observed as evaluating the change of body weight. Immunohistochemistry analysis of chrysin-treated tumor tissue demonstrated the expression of HK-2 in tumor tissue was substantially decreased after chrysin treatment, which confirmed the effect of chrysin on HK-2 in vivo (Fig. 6e). Ki-67 is a well-known marker to represent the potential of cell proliferation, Ki67 in chrysin group was substantially decreased in contrast with the vehicle group. With the suppression of glycolysis by reducing HK-2 in tumor tissue, energy supply to sustain tumor growth was blocked, and the proliferative capability of tumor cell was weakened.Fig. 6Chrysin inhibited HCC-LM3 xenograft growth in vivo. Nude mice with HCC-LM3 xenograft were randomly divided to groups when tumor volume reached 50 to 100 mm3. 30 mg/kg chrysin was administrated three times weekly by intraperitoneal injection. a, photograph of tumors in vehicle and chrysin-treated group; b, the change of body weight of tumor bearing mice; c, tumor growth curve in vehicle and treated group; d, tumor weight in vehicle and chrysin group; e, tumor tissues were subjected to immunohistochemistry staining with indicated antibodies to detect the change of HK-2, Ki67 after chrysin treatment
| 4 | 0biomedical
| 0Study
|
53,844 |
Wealth was represented in our models by income and asset measures. A higher gross household income was associated with a decrease in first-time utilization of LTC services. For the first-time utilization of any type of LTC-service, an increase of 10,000 euro is associated with an OR = 0.91 (95% CI: 0.90–0.92) for the 20+ population and an OR = 0.94 (95% CI: 0.92–0.96) for the 65+ population. For LTC domestic home-care services the income effect is somewhat stronger for both the 20+ (OR = 0.87, 95% CI: 0.85–0.89) and 65+ population (OR = 0.88, 95% CI: 0.85–0.92). The best performing asset measure proved to be a classification of home-ownership into three groups: ‘homeowners’ (reference category), ‘social rent’ and ‘private rent’. Subjects classified under ‘social rent’ pay lower rents, because they have a low income compared to the market rates and get a tax break to remedy this. Subjects classified under ‘private rent’ pay rents at market prices.
| 3 | 0biomedical
| 0Study
|
12,909 |
The W12 system was developed from a polyclonal culture of cervical squamous cells (keratinocytes) naturally infected with HPV16, which were derived by explant culture of a cervical LSIL.7 At early passages, these ‘parental' W12 cells are phenotypically and genetically stable. They allow maintenance of HPV16 episomes at ~100 copies per cell and recapitulate an LSIL in three-dimensional organotypic culture. Following long-term culture of W12, however, the cells lose these properties and closely mirror the virus and host events associated with cervical carcinogenesis in vivo, with phenotypic progression of the reformed epithelia to high-grade SIL and then SCC.4 These events may be associated with deregulation of episome numbers and transcriptional control (e.g. W12 series 4 and W12E cells).2, 6 More typically, however, there is a change in the virus physical state from episomal to integrated, due to loss of trans-repressive episomes and emergence of a clonal population containing the HPV16 integration event that confers the greatest growth advantage.16 In different W12 series, different integration sites are seen in the selected cells.16
| 5 | 0biomedical
| 0Study
|
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