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360,094 |
The storage tanks, whose layout axis was nearly perpendicular to the direction of the sliding mass movement, were easily hit and hence damaged by the blocks. Accordingly, the blocks were also found to accumulate on the ground between the storage tanks and the slope. Because the structure of the storage tanks provided sufficient resistance to the impact, they were beneficial for the protection of the pipelines. For example, the root valve was protected by the storage tanks from being impacted by the blocks.
| 1 | 2other
| 1Other
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38,395 |
Patient positioning for radiotherapy is one of the most important components of the entire planning and treatment process. Carbon fiber couches are often used in external beam radiotherapy as a means of providing patient positioning. In addition to being strong, rigid, and light,1 carbon fiber has also been described as radiotranslucent.2, 3 Recent years the external photon beam radiotherapy delivery techniques and modalities have been undergone a rapid development, the method of radiation treatment has switched from the use of a single treatment beam to the utilization of multiple beams or rotation treatment. With the introduction of intensity modulated radiation therapy (IMRT) the number of fields used for patient treatment increases, the effect of treatment couches becomes more significant.4, 5, 6, 7, 8 Especially as the advanced volumetric modulated arc therapy (VMAT) delivery systems become a main role of treatment ways, which places even greater demands on delivering accuracy.
| 4 | 0biomedical
| 0Study
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12,238 |
Samples were processed similarly at each collaborating laboratories14,21,27,28; for example, at the MEEI each virus was grown in either A549 cells, a human alveolar carcinoma cell line or HEp-2, a human laryngeal carcinoma cell line, and purified by CsCl gradient ultra-centrifugation. DNA was extracted either using a phenol–chloroform method or with a QIAmp MinElute Virus Spin Kit (Qiagen GmbH; Hilden, Germany). Most eye specimens were unpassaged and directly used for DNA extraction. The MEEI Human Studies Committee exempted this study from requiring informed consent as the samples were de-identified and would otherwise have been discarded.
| 4 | 0biomedical
| 0Study
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101,750 |
Time course profiles of TTX urinary excretion (from the basolateral to the apical side of the LLC-PK1 cell monolayers) are shown in Figure 1A. At an incubation temperature of 37 °C, the amount of TTX transported was 0.087 ± 0.015 nmol/mL/cm2 5 min after incubation, which significantly increased to 1.237 ± 0.229 nmol/mL/cm2 60 min after incubation (p < 0.05). When the incubation temperature was 4 °C, the amount of TTX transported was 0.034 ± 0.008 nmol/mL/cm2 5 min after incubation, which significantly increased to 0.247 ± 0.032 nmol/mL/cm2 60 min after incubation (p < 0.05). At 60 min, the amount of TTX transported at 4 °C was significantly lower (0.20 fold) than the value at 37 °C (p < 0.05), indicating that the urinary excretion of TTX is temperature-dependent.
| 4 | 0biomedical
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155,852 |
To determine the statistical significance of each latent variable in the PLSC, a permutation test was used (p < 0.001; 5000 permutation iterations). Five-thousand bootstrap samples were also created to assess the reliability of the effect at each node of the functional brain network. Brain and design saliences were recalculated for every bootstrap sample, yielding bootstrap ratios (BSRs; original saliences/bootstrap standard errors). We used a BSR threshold of ±3.3, which is equivalent to a p value of approximately 0.001.
| 4 | 0biomedical
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259,571 |
The novel coronavirus disease 2019 (COVID-19) has become a challenge for all countries across the globe. Amidst the COVID-19 pandemic, an international effort has been concerted to identify the factors associated with more adverse outcomes to better allocate resources and perform more effective targeted preventive measures. One important factor is known to be smoking and hookah use1,2. Generally, it has been shown that smoking and hookah use increases the risk of respiratory system infection due to several reasons, including cardiopulmonary comorbidities associated with smoking, impaired mucociliary system, altered immune system, and different healthcare seeking behavior3. Additionally, the risk of COVID-19 infection increases among hookah users due to social gathering in crowded places and having close contact with each other, sharing the same pipes, difficult-to-clean pipes and cold water reservoirs4. Consequently, due to the increased viral load, increased COVID-19 severity and adverse outcomes could be anticipated. In this regard, this study aims to describe the risk of COVID-19 adverse outcomes among individuals with a history of being ever cigarette smokers and being ever hookah users. To the best of our knowledge, no studies have evaluated the association between hookah use and COVID-19 adverse outcomes in Iran.
| 4 | 0biomedical
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329,629 |
As reported by previous studies (10,15,35), the present study reported no significant difference in the PD-L1 expression rate between the different sampling types (cytology, biopsy or surgical specimen) in all patients combined. This result was confirmed by very good agreements between sample pairs from the same patient, as similarly described by Cho et al (25). Comparison of the present results with results from the Blueprint Phase 2B study, which compares the PD-L1 status between various samples types from the same lung tumor (16), is not yet possible.
| 4 | 0biomedical
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72,535 |
The proportion of women that had ever used any form of contraception was highest in urban areas (92.8%), among women that had completed higher education (87.2%), were aged above 25 years (87.1%), with two or more children (77.1%), and of high socioeconomic status (79.2%) (Table 3). In the logistic regression, after adjusting for confounding variable (education), only urban residence (AOR: 3.7; CI: 2.2–6.0), peri-urban residence (AOR:2.3; 95% CI:1.4–3.1), and high socioeconomic status (AOR:2.1; CI: 1.01–4.3) were the independent predictors of ever use of contraception. In reference to women who had one child, women with two or more children had higher odds of reporting ever used of any contraceptive methods.Table 3Factors associated with use of contraceptiveVariablesEver use any methods (n = 645)Ever used any modern methods (355)Current use of any contraception methods (538)Current use of any modern contraceptive methods (281)Frequency (%)AOR (CI)Frequency (%)AOR (CI)Frequency (%)AOR (CI)Frequency (%)AOR (CI)Age 30 and below305 (79.2)Ref174 (43.0)Ref251 (65.2)Ref138 (34.1)Ref Above 30339 (87.1)1.3 (0.8–2.0)181 (44.9)287 (73.8)1.0 (0.7–1.5)143 (35.5)0.8 (0.6–1.1)Level of education No formal education4 (50.0)–1 (12.5)–3 (37.5)0 (0.0)– Primary86 (79.6)–50 (43.9)–70 (64.8)39 (34.2)– Secondary344(82.5)–193 (44.4)–286 (68.6)150 (34.5)– Higher degree211 (87.2)–111 (44.0)–180 (74.4)92 (36.5)–Place of residence Urban270 (92.8)3.7 (2.2–6.0)***130 (42.3)1.6 (1.1–2.2)*248 (85.2)4.5 (3.0–6.8)***122 (39.7)2.1 (1.4–3.0)*** Peri-urban167 (83.9)2.3 (1.4–3.8)**100 (48.3)1.7 (1.2–2.5)*137 (68.8)2.2 (1.5–3.3)***77 (37.2)1.9 (1.3–2.9)*** Rural208 (73.0)125 (42.4)154 (54.0)Ref82 (27.8)RefSocioeconomic status Low33 (64.7)Ref26 (50.0)Ref24 (47.1)Ref19 (36.5)Ref Middle361 (82.6)1.8 (0.9–3.5)199 (43.2)1.0 (0.5–1.8)301 (68.9)1.7 (0.9–3.2)152 (33.0)0.9 (0.5–1.7) High248 (87.3)2.1 (1.01–4.3)*130 (44.4)1.2 (0.6–2.3)212 (74.6)1.9 (1.0–3.6)110 (37.5)1.0 (0.5–2.0)Parity 1128 (73.1)Ref64 (33.9)Ref102 (58.3)Ref52 (27.5)Ref 2177 (91.7)3.9 (2.2–7.1)***99 (49.5)1.9 (1.2–2.9)*150 (77.7)2.9 (1.8–4.8)***78 (39.0)1.6 (1.1–2.5)* 3165 (82.5)1.9 (1.1–3.3)*89 (43.2)1.4 (0.9–2.2)142 (71.0)2.1 (1.3–3.4)***71 (34.5)1.4 (0.9–2.2) 4 and above175 (84.5)2.7 (1.5–4.8)***103 (48.9)1.9 (1.2–3.0)*145 (70.0)2.4 (1.5–4.1)***80 (37.4)1.7 (1.03–2.7)*Models adjusted for level of education; Ref reference, AOR adjusted odd ratio, CI confidence interval*** Means p < 001, ** Means P < 0.005, * Means P < 0.05
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161,649 |
Conserved Sequence & MHC-I HLA Analysis of Peptide 2. (A) The sequence of Peptide 2 was highly conserved in the 11 virus variants that have been identified as the variants of interest and the variants of concern, as published by WHO. (B) Position of Peptide 2 (yellow marked segment) in the stereoscopic structure of the spike protein. (C) The global distribution of HLA alleles. (D) Analysis of Peptide 2 by integration of MHC-I binding prediction, MHC-I immunogenicity, and MHC-NP prediction from the HLA alleles.
| 4 | 0biomedical
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234,732 |
The aims of this research were to recognize the response of cuttings Rosa “Hurdal” in anatomical structure to the plant origin preparations during the process of rhizogenesis. Moreover, we hypothesized that the response of cuttings prepared from shoots in four phenological stages may be different. Consistently, the various anatomical changes occurring in stock plants during the flowering period can affect rooting effectiveness and the quality of rooted cuttings. Analysis of changes in anatomical structure before and after the rooting process could reveal the reason for difficulties in the rooting of some rose cuttings.
| 1 | 2other
| 0Study
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227,826 |
Any disagreements between the two reviewers were resolved in consultation with a third reviewer (L.J.). While efforts were made to decrease publication bias, the reviewers recognize that limiting the search to the English language could result in loss of data in other Native languages. Additionally, the inclusion of all grey literature could have provided additional findings for the study and decreased possible impacts of publication bias.
| 2 | 0biomedical
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248,142 |
If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.
| 2 | 0biomedical
| 1Other
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356,331 |
(A) Pilot studies used in Gagliano et al. Top row shows maze fan and light configuration for training period, bottom row shows configuration during testing day and the maze arm into which plants grew. (B) Additional controls used in this study to address the same questions as the pilot studies in Gagliano et al. (C) Main experimental conditions.Results shown are from gagliano et al. in Gagliano et al., 2016. Results here are simplified, for more detailed results from both studies see Figures 2 and 3. (D) Conditioning regimen. Horizontal bars indicate time periods for which fans and lights were active, the x-axis indicates time of day.
| 3 | 0biomedical
| 0Study
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303,064 |
More studies are required to evaluate further the contributing factors for the high stability of BLMPLFE. Upon proper optimization, it is possible to fabricate BLMPLFE (or BLM made of BTL with structures similar to PLFE) with a membrane lifetime even longer than that currently reported (11 days). For example, we could optimize the critical factors in lipid–substrate interactions, which include the solvent used for painting lipids, the pretreatment of the torus with lipids, the shape of the micro-pore, and the pore size. In the study of Ren et al. , the solvent used was a mixture of chloroform/methanol/water, the edge of the pore was flat on both sides of the thin film, and there was no lipid pretreatment on the torus. In the present study, the final solvent used was n-decane, the edge of the pore was irregular and rough, and the torus was pre-treated with PLFE lipids. Stability of BLM is known to increase with decreasing the size of the pore over which the BLM is formed . In the present study, the pore size was ~400 μm, which could be reduced to 20–100 μm in the future studies using photolithography or laser micromachining to further increase stability of BLMPLFE. Such stable BLMPLFE can be installed on microchips for various applications such as biosensing, drug screening, and artificial photosynthesis, to name a few .
| 4 | 0biomedical
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235,517 |
Notably, when Eq 3 was applied to predict breathability of WP036, excluded from the calibration, it generated a very high estimate for this material at 19.24 mmH2O/cm2. A slightly underestimated value was predicted for WP047 (predicted value = 10.2 compared to measured value of 11.55 mmH2O/cm2). The linearized goodness of fit test between measured and predicted material differential pressures is provided in Fig 4. Eq 3 was subsequently used to predict material differential pressures for all characterized fabrics as identified in S1 Table. When fabrics were grouped into consumer fabric categories, only high quality batik fabrics had a mean fabric category pressure differential expected to significantly (p<0.05; one sample t-test) exceed the Level 1 medical mask criteria of 5 mmH2O/cm2. Bed sheets were predicted to achieve the highest average differential pressures, but were also among the most variable fabric types for breathability across samples tested. Thus, even though 2/6 characterized bed sheets had predicted differential pressures as high as 9 and 19 mmH2O/cm2, four other samples had breathability lower than guideline limits.
| 4 | 0biomedical
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94,710 |
Isopentenyl pyrophosphate (IPP) is the direct precursor for rubber biosynthesis and mainly derived from the mevalonic acid (MVA) pathway17. HMG-CoA reductase (HMGR) is a rate-controlling enzyme that catalyzes the reduction of HMG-CoA to MVA31. Post-IPP processes include initiation and elongation of rubber macromolecules. Farnesyl diphosphate synthase (FPS) catalyzes the biosynthesis of farnesyl diphosphate. The farnesyl diphosphate acts as the prime which is essential for initiating prenyl chain whereas Hevea rubber transferase (HRT), rubber elongation factor (REF) and small rubber particle protein (SRPP) are crucial for integrating IPP units into prenyl chain1731. To examine the expression patterns of the genes involved in rubber biosynthesis in response to ABA, the rubber tree shoots were treated by ABA, respectively. As shown in Fig. 7, ABA markedly up-regulated HbFPS1, HbHRT1, HbHRT2, HbSRPP and HbREF expression, except HbHMGR expression.
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355,136 |
Researchers at Google designed the GoogleNet architecture in 2014. Its construction is much deeper than AlexNet and consists of 22 layers. GoogleNet architecture is based on the inception block, which considers dropping the number of parameters in a CNN. Therefore, it contains a lower number of parameters, almost 12 times lower than AlexNet, which leads to faster convergence. The GoogleNet structure won the ImageNet Large-Scale Visual Recognition Challenge (ILSVRC14) in 2014, for achieving the best performance (Szegedy et al., 2015). The main module of this structure is nine inception blocks that occur at every layer of the GoogleNet. These blocks are scaled upon each other with a maximum pooling layer. Lastly, an fc layer exists just before the output layer.
| 2 | 2other
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198,674 |
Before user authentication, we performed user identification based on individual keystroke dynamics. For the four‐digit password, the keystroke features of those four keys were sent to the ANN model to identify the user's individual behavioral information. For each user (User 1, User 2, User 3, User 4), we performed the user identification with the EMG sensor, TENG sensor, and hybrid sensor data, as shown in Figures S10 and S11, Supporting Information. The confusion matrices show that, during user identification, our ANN algorithm achieves an accuracy of 98–99% for hybrid sensors, while it varies from 93–97% for a single EMG or TENG sensor. Then we trained our AI model with multiple user keystroke information for the common password “1356” for user authentication. Figure 5b–d shows the confusion matrix for user authentication based on the EMG sensor, TENG sensor, and hybrid sensor, respectively. While testing with “User 2” data, with only EMG sensor, the system achieved an accuracy of 96%, with TENG 97%, and with hybrid, 99% accuracy was achieved. These results show a clear benefit of using a hybrid sensor for increased accuracy in biometric authentication. We also performed user authentication with different user dataset, and the result is shown in Figure 5e, in which hybrid sensor plays better than the single sensor‐based user authentication. These excellent results exhibit a promising addition of a security layer in computing where password leakage might be no more things to be concerned about. Most of the state‐of‐the‐art works used support vector based machine learning (SVM) instead of a deep neural network.[ 5 , 6 ] We compared the user authentication with the same dataset for EMG, TENG, and hybrid sensors, as shown in Figure 5f. The comparative analysis shows that, for EMG sensors, there is no significant difference between SVM and ANN, however, ANN performed better for TENG and hybrid sensors with more accuracy. Also, ANN has the capability to learn the user's time‐variant keystroke behavioral information and update the algorithm, which is not possible in machine learning. Therefore, an ANN‐based neural network is implemented in this work. Figure 5g shows a photograph of the fabricated hybrid sensors installed on a commercial keyboard and analog circuit for signal processing.
| 4 | 0biomedical
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108,072 |
During mold filling, the powder covering the liquid steel inside the mold forms a slag layer that floats on top of the rising molten steel . An excessive turbulence at the powder–metal interface can cause reoxidation and exogenous inclusions. To evaluate the tendency for powder entrapment, the Weber number was calculated according to the modified equation reported by Erikson et al. : (6)We= usteel2·ρsteelγg(ρsteel−ρslag) where usteel is the tangential steel velocity on the free surface of the molten steel; ρsteel and ρslag are the density of the steel and of the powder, respectively; g is the gravity; and γ is the slag-steel interfacial tension. According to the finding of Xiao et al. , no problems occur when Weber number is lower than 12.3.
| 4 | 2other
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394,344 |
To identify important stepping‐stone sites, we calculated network metrics related to node centrality: betweenness, weighted degree, and node resistance. For each pair of sites in the migration network, we identified the shortest path (i.e., minimum weighted path length between the 2 nodes) via the Dijkstra algorithm (Dijkstra 1959). Node betweenness was quantified by the number of shortest paths passing through that node (Freeman 1979; Brandes 2001) and was calculated using the second‐generation weighted betweenness measure (Opsahl et al. 2010). Node betweenness was normalized by dividing it by the highest betweenness value. Node degree indicates the connection strength between the focal site and other sites in the network and was measured as the sum of weights of the connections to and from the focal node, again calculated with the Dijkstra algorithm (Dijkstra 1959). Node resistance was the effective resistance (McRae et al. 2008) between the focal node (i.e., a stopover site) and the breeding site and between the focal node and the nonbreeding site. Node resistance indicates the resistance for traveling between the focal stopover site to the breeding site and the nonbreeding site. We also calculated the degree of habitat loss at each stopover site as the ratio of habitat loss to gain from 1992 to 2015. We selected 1992 as a baseline due to the rapid urbanization and socioeconomic development in East Asian countries since 1992 (Seto & Fragkias 2005; Xu et al. 2019b). The 1992 data are the earliest land‐cover map in the analyzed data set.
| 4 | 0biomedical
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253,955 |
To find new and novel classes of E6 PPI inhibitors, it will also be necessary to explore new strategies for studying and probing PPIs. Most known E6 PPI inhibitors were discovered using HTS techniques and, to a lesser extent, virtual screening. HTS has certainly been successful at identifying PPI inhibitors. However, other techniques have been found to be better. Fragment-based drug discovery (FBDD) is one such technique, with a higher hit rate and ligand efficiency for PPIs that are especially difficult to target . In FBDD, simple low-molecular fragments from a fragment library are screened using biophysical or biochemical methods for molecules that bind to regions most critical for PPIs. Once the fragment hits (often of low affinity) have been identified, sensitive biophysical methods are often used to determine the binding mode of ligands. Using this information, a structure-based drug design can then be used to rationally and systematically grow the fragment . A similar approach has also been used for PPI inhibitors specifically aimed at creating chemotypes that mimic the critical residues in the interface. In this approach, an anchor residue has to be established (none has been found yet for E6) from the hot spot amino acids, and this then is used for substructure search and bioisosteric design. Once initial leads are available, crystal structures of the protein–ligand complexes are created and systematic optimization through medicinal chemistry is carried out . Such methodical, rational, and repetitive efforts to optimize identified hit compounds into leads with favorable physicochemical, PK, and in vivo properties have not yet been done in the context of inhibitors of E6 PPIs. For most inhibitors found through HTS, there is often no follow-up work to analyze the binding mode and how substituents are interacting with residues in the pocket so as to leverage this information for structure-guided design and reiterative hit-to-lead optimization. Evidence in the field shows that a lack of such a collaborative approach in studying PPIs is likely detrimental to the hopes of effectively inhibiting PPIs, as discovery of the leads that have been approved or are in clinical trials has historically come through multidisciplinary work. One case in point is provided by a recent study by Dawidowski et al., which illustrates the type of work needed to improve the affinity and potency (by severalfold) of an initial hit into the final lead that inhibits the PEX5–PEX14 interaction. This study shows an interplay of structure-based virtual screening, NMR analyses, AlphaScreen-based competition assays, biochemical assays, X-ray cocrystals, and cycles of medicinal chemistry optimization . It remains to be seen whether similar approaches will be utilized for studying E6 PPIs in the future. Importantly, it is crucial to keep in mind that barriers to utilizing some of the biophysical methods used to study PPIs are huge; not only is the equipment utilized in structural biology studies expensive, but also the techniques themselves and the data analysis require special expertise with steep learning curves. Additionally, the lack of anchor hot residues, the huge flexibility of residues such as rim arginines, and the biological degeneracy of E6 may present challenges that some of these proposed strategies cannot overcome. Nevertheless, it will be worthwhile to see how some of these novel approaches can change the fortunes of E6 PPI inhibition.
| 4 | 0biomedical
| 2Review
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106,637 |
PolyPhen-2, SIFT, Provean and Mutation assessor mutational impact (upper table) and ranking analysis of TGFBR1 mutations isolated from all samples (lower left table). The nature of the base change and its characteristic of a UV signature (C-T or G-A transitions) or a T-C or A-G signature are shown. Variant allele frequencies (% read) are shown, as is the ranking of the mutation according to variant allele frequency of NOTCH1, NOTCH2, TP53, CDKN2A, HRAS, NRAS, KRAS, TGFBR1 and TGFBR2 mutations identified in each tumour with rank 1 indicating the highest variant allele frequency. The total number of mutations in the 9 genes is also shown. Right hand lower table shows average (AV) read %, average rank and average number of mutations for total samples and samples separated by damaging or non-damaging prediction. The % of mutations exhibiting a UV signature or a T-C + A-G signature and ranked 1 or 2, ranked > median are also shown. The total number of TGFb receptor mutations ranked 1 is also indicated.
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181,753 |
According to current legislation, the cultivation of selected hemp varieties with low levels of THC has been permitted for food use in the EU . However, not all products derived from fiber hemp are directly approved as food. According to the Novel Food Regulation (EU) 2015/2283, foods and food ingredients that have not been consumed by humans to a significant extent in the EU before 15 May 1997, are to be classified as novel and therefore require an approval . With respect to the hemp plant Cannabis sativa L., according to the EU Novel Food catalog, extracts derived from the hemp plant and the cannabinoid-containing products made from them, and CBD, are classified as novel foods because the consumption of such products has not been demonstrated before 1997 . According to this classification, CBD products are not authorized and therefore are not legally available as foods . Cannabis leaves and flowers are also questionable as food business operators were unable to provide proof of consumption before 1997.
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244,957 |
Linear regression analysis of the R2* values measured using 2D cardiac and 3D liver CSE-MRI demonstrates strong Pearson’s correlation coefficient (r = 0.98) and strong Lin’s concordance correlation (ρ = 0.98) for the retrospective clinical study, for the prospective research study (r = 0.99 and ρ = 0.99), and for both studies combined (r = 0.99 and ρ = 0.98) (Table 2). The linear regression analysis all study groups together is shown in Fig. 3.Table 2Correlation results for the retrospective study, prospective study, and combined dataRetrospective clinical studyProspective research studyTotalNumber of acquisitions233154Linear regression Pearson’s correlation coefficient (95% CI)0.98 (0.95–0.99)0.99 (0.98–1.00)0.99 (0.97–0.99) Lin’s concordance coefficient (95% CI)0.98 (0.95–0.99)0.99 (0.98–1.00)0.98 (0.97–0.99) Slope (95% CI)0.92 (0.84–1.01)0.96 (0.91–1.01)0.94 (0.89–0.98) Intercept (95% CI)15.9 (− 7.1–38.9)7.5 (− 3–17.9)11.3 (0.5–22.2)Bland–Altman Mean of differences (95% CI of mean differences)lower and upper limit of agreement0.9 (− 13.8–15.6)− 69.6–71.4− 0.4 (− 7–6.3)− 37.2–36.50.2 (− 7.1–7.4)− 53.0–53.4Shown are correlation coefficients, Lin’s correlation coefficient for all study groups, the slope and interception as well as the mean of differences and the limit of agreement from the Bland–Altman analysis with their 95% confidence intervals (CI)Fig. 3Very strong correlation between R2* measurements made in the liver using 2D CSE-MRI and 3D CSE-MRI was observed. Further, excellent agreement between these methods was observed for R2* values up to 400 s−1 (severe iron overload). Results of the linear regression analysis for both the retrospective clinical and prospective research studies together are shown in this diagram. The values closely are located near to y = x (dashed line) indicating low variability of R2* measurements
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179,343 |
Central to the pathogenesis of severe falciparum malaria is the sequestration of parasitised red blood cells, leading to microcirculatory obstruction, endothelial dysfunction and impaired tissue perfusion [2, 3]. Accordingly, metabolic (i.e. lactic) acidosis and renal impairment are among the strongest predictors of death in malaria patients across age groups [4, 5].
| 5 | 0biomedical
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295,374 |
The optimum cut-off values for lactate and PI of MCA in the asphyxiated infants who received therapeutic hypothermia were identified by drawing ROC curves (Figure 1). The area under ROC curves (AUC) and cut-off values were shown in Table 5. Within 6 h of age, the cut-off value of lactate was 14 mmol/L (p = 0.015) and PI of MCA was 1.15 (p = 0.015). At the 4th day old, the cut-off value of lactate was 2.8 mmol/L and PI of MCA was 1.05. The sensitivity and specificity of either lactate (p = 0.011) or PI of MCA (p = 0.011) at the 4th day old were better than that within 6 h of age (Table 5).
| 4 | 0biomedical
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234,131 |
At baseline, APOEε4 carriers had higher CBF in the proximal and middle branches of the ACA and MCA vascular territories and the proximal PCA (Table 2, Supplementary Figure 1). Following FDR correction, the differences remained significant for the proximal and middle ACA and MCA, these regions are shown as an overlay to the generated baseline study-specific GM template in Figure 1. Reduced CVRi in APOEε4 carriers was observed in the proximal ACA and MCA regions, although these differences did not survive FDR correction (Table 2, Supplementary Figure 2).
| 4 | 0biomedical
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46,369 |
Figure 2a shows that the positive prediction value (PPV) for DCA predictions on the protein expression data is as high as 72% for top 100 pairs, among which 28% PPIs are physically interacting, which are classified as binary interactions or experimentally scored with highest confidence in STRING. As a comparison, we also computed and ranked MI values for all possible protein pairs. The predictive performance of MI is lower compared to DCA, with PPV of 65%, including 21% physically interacting PPIs. The ratios of direct interactions to all positively predicted interactions for DI are higher than MI (Supplementary Fig. S2). When further looking into the top 10 pairs, the performance of DI on predicting physically interacting PPIs is as high as 50%, while MI only reached 30% of the accuracy. Moreover, MI is not able to identify physically interacting PPIs until the fifth pair. We observe that DI is better than MI in capturing interactions, especially in capturing pairs with highest confidence combined scores in the STRING database (Supplementary Fig. S3). Moreover, the area under precision-recall (P–R) curve (AUPR) for DI is higher than MI under both verification methods (Supplementary Fig. S4). The nominal p-value range for top 100 DI pairs is from 9.521E-35 to 1. 271E-13 (false discovery rate: FDR < 1.8E-11) (Supplementary Table S4, Supplementary Fig. S5). Figure 2b shows a comparison between the pairs uncovered by MI and DI and then verified in the literature. The DI group shares 51% of the top 100 pairs with MI set, resulting in 49 distinct PPIs respectively. A number of 33 pairs out of 49 pairs in DI set are predicted correctly with 8 binary interactions, while the PPV of MI is 23 out of 49. When comparing the distinct PPIs ranked among top 25 in each group, we find 5 non-overlapping pairs in each group. In the DI group, 3 pairs are physically coupled and 2 pairs are strongly related. However, 3 out of 5 pairs in the MI group are predicted, and none of the 5 PPIs are physically interacting.Figure 2Protein-protein interaction pairs predicted from pan cancer protein expression levels with DCA. (a) Positive prediction values comparison between the direct information and mutual information. Solid line plots indicate number of protein-protein pairs verified with a curated literature review and STRING pairs with a combined scored at medium confidence (y-axis) against total number of pairs (x-axis) ranked by DI values (red) or MI (blue) values. Dash line plots indicate coupling pairs identified as binary interactions classified from a literature review and STRING pairs with experimental scores at highest confidence. The ratios of direct interactions to the all verified interactions for top 100 pairs are shown in the inset table. (b) Comparison of top 100 DI ranked and MI ranked predicted pairs. The pie charts on the right panel represent the distinct protein pairs in both groups with different colors indicating different categories. The digits near the pie charts are the number of protein pairs included into according category. Two lists named Ranked Top 25 show the detailed protein pairs that appear distinctly in the top 25 pairs by DI and MI methods.
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197,987 |
Secondly, the current study also highlights the importance of an ethical leader for a hospital. In this regard, it is important to mention here that only the CSR engagement of an organization is not enough. The presence of responsible management is a necessary precondition to achieve the expected outcomes for a hospital. Moreover, an ethical leader further highlights the importance of the individual to improve nature and the environment. Especially in the context of sustainability management, the presence of an ethical leader makes their role toward environmental improvement clear to every employee. There is a dire need to promote such an ethical leadership style in the healthcare sector to address environmental dilapidation effectively.
| 2 | 2other
| 1Other
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384,363 |
L-2 hydroxyglutarate dehydrogenase is a FAD-dependent enzyme that catalyzes the conversion of L-2-hydroxygluratic acid to 2-ketoglutarate. L-2-hydroxyglutaric acid elevation in urine, cerebrospinal fluid, and plasma is pathognomonic for L2HGDH-induced disease. Patients with biallelic L2HGDH variants have exclusive neurological findings of psychomotor retardation, cerebellar ataxia, macrocephaly, and epilepsy. Recessive and rare dominant D2HGDH variants in the chiral configuration enzyme, D-2-hydroxyglutarate dehydrogenase induce D-2-hydroglutaric acid to 2-ketoglutarate, and patients present with epilepsy, hypotonia, and psychomotor retardation.
| 5 | 0biomedical
| 0Study
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46,273 |
In the above analysis, the loaded stress is parallel to Y-axis, as shown in Figure 6. If the stress is parallel to X-axis, the output Δλ of FBG 1 will be much smaller, as shown in Figure 26. Δλ caused by stress parallel to Y-axis and X-axis are represented by Δλ1y and Δλ1x, respectively. With the same loaded stress, Δλx/Δλy = 0.26. It shows that the designed sensor is more sensitive to the stress parallel to Y-axis. So the Y-axis of the sensor is suggested to be used to sense the stress of measuring object.
| 2 | 2other
| 0Study
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52,923 |
Of course, the most efficient route to unprotected allenylboronic acids is using the above synthesis with application of unprotected diboronic acid 5a (Tables 1 and 2). However, in order to extend the scope of the synthesis of allenylboronic acids, we studied the possibilities of hydrolysis of protected allenyl-Bpin compounds, such as 1a-Bpin. The Santos method14 can be used for deprotection of various alkyl-Bpin derivatives, even aryl-Bpin compounds affording the corresponding organoboronic acids. However, the reaction of 1a-Bpin with diethanolamine did not result in any formation of 1a-ean at 40 °C in 48 h (Fig. 3c), and thus this method cannot be used for accessing allenylboronic acids from pinacol esters.
| 4 | 0biomedical
| 0Study
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227,787 |
In recent years, with the in-depth development of molecular biology research technology, it has become clear that lung tissue is not always in a balanced state. Studies have shown that inhaled upper respiratory tract secretions can bring part of the oropharyngeal microbial community into the lung tissue; at the same time, the host activates the defense mechanism, which can effectively eliminate microbes and achieve the purpose of blocking infection. The manifestations of changes in the respiratory microecosystem are complex and diverse, and may eventually lead to local or systemic bacterial infections. However, in the course of lung cancer, the changes in the respiratory tract microflora have not been clearly understood.
| 4 | 0biomedical
| 0Study
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262,113 |
Yield 45%, m.p. 53.3-56.4°C, a,b isomers, 1HNMR (400MHz, CDCl3) δ: 14.94 (s,1H, NH (a,b)), 7.03-7.09 (m, 3H, Ar C3,4,5-H (a,b)), 4.38 (q, J = 7.2 Hz, 2H, ethyl (b)), 4.28 (q, J = 7.2 Hz, 2H, ethyl (a)), 2.62 (s, 3H, methyl (a,b)), 2.44 and 2.43 (each s, 6H, Ar C2,6-CH3 (a,b)), 1.41(t, J = 7.2 Hz, 3H, ethyl (b)), 1.35 (t, J = 7.2 Hz, 3H, ethyl (a)); IR (cm-1): 1689, 1506, 1361, 1187, 780. ESI-MS m/z: 263 (M-H+).
| 3 | 0biomedical
| 0Study
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168,858 |
The role of elbow flexion in changing the nerve distances to bony landmarks has been extensively investigated in relation to portal placement for elbow arthroscopy. Hackl et al. demonstrated that the distance of the median nerve to the anterior tip of the coronoid and to the anterior border of the trochlea significantly increases from extension to 90° flexion . These findings were supported by a recent review of cadaveric studies, which concluded that the distended elbow in a 90° flexed position minimizes the risk for neurovascular injury with the arthroscope .
| 4 | 0biomedical
| 2Review
|
72,300 |
In April 2017, we then searched the electronic databases at the Hanoi Medical University Library, the Hanoi University of Public Health Library, the Vietnam Oncology Journal (K Hospital) and the Institute for Preventive Medicine and Public Health Library in Vietnam using the keyword equivalent of ‘Breast Cancer’ in Vietnamese and the same inclusion criteria noted above. We charted and synthesised the data in Vietnamese before translating the results into English and combining them with our initial findings.
| 2 | 0biomedical
| 0Study
|
339,645 |
In cells, amino acid transport across the plasma membrane is mediated by distinct transport systems . Based on their substrate specificity, regulatory properties, and transport mechanism, amino acid transporters can be classified as sodium (Na+)-dependent neutral amino acid transporters, including systems A, ASC, where ASCT2 is included, B, and N; Na+-independent neutral amino acid transporters, gathering system L, that includes LAT1, and system T; Na+-dependent and -independent anionic amino acid transporters; and Na+-dependent and -independent cationic amino acid transporters . Additionally, based on their sequence homology, these transporters can be included in different family groups . Indeed, system ASC proteins belong to the solute carrier family 1 (SLC1) . On the other hand, system L proteins are divided between two families, with LAT1 and LAT2 belonging to the SLC7 family, and LAT3 and LAT4 belonging to the SLC43 family .
| 4 | 0biomedical
| 0Study
|
57,822 |
The mechanisms through which Mtb infection induces HO-1 expression in vivo or for that matter in infected cells are not completely understood. In the case of cultured macrophages, we and others have demonstrated a role for the Mtb virulence factor ESAT-6 in HO-1 induction. While our previous experiments with primary human macrophages indicated a requirement for live infection with ESAT-6 expressing bacteria and cytosolic delivery of the protein (10), Kumar et al. studying both murine BMDMs and RAW264.7 cells found that exposure to soluble recombinant ESAT-6 protein alone was sufficient to trigger HO-1 expression (50). Analyzing the mechanism responsible for HO-1 induction, the latter authors identified a major role for the micro RNA miR-155 and Bach-1 in the transcriptional regulation of HO-1. In other studies, soluble ESAT-6 has been shown to stimulate miR-155 through a TLR2, MyD88-dependent pathway (63).
| 4 | 0biomedical
| 0Study
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195,617 |
This study aimed to investigate the influence of knee OA on postural balance and investigate the differences in the measures of the trunk, pelvic, lower extremity kinematics, and lower extremity muscle activity between the knee OA group and the control group during the stand-to-sit task. We found that individuals with knee OA showed greater postural sway and prolonged duration of the stand-to-sit task, reduced ankle dorsiflexion RoM, quadriceps femoris, and TA activation level during the stand-to-sit task in comparison with the control group. At the same time, individuals with knee OA may increase pelvic anterior tilt RoM and BF muscle activity to functional compensation than the control group during the task.
| 4 | 0biomedical
| 0Study
|
204,487 |
In this study, we bring forward a novel combination of a new generation SINE compound, KPT-8602, with different PARP inhibitors for the first time. Importantly, KPT-8602 showed synergy with PARPi olaparib, veliparib and rucaparib at pharmacologically relevant concentrations in growth inhibition assay. KPT-8602-PARPi combinations triggered apoptosis. Mechanistically, KPT-8602-PARPi suppressed AR, ARv7 and the ARv7 downstream targets SAM68, FOXA1 and UBE2C. Excitingly, KPT-8602 with or without olaparib was able to reduce expression of DDR genes including BRCA1, XRCC3, CHEK1 and RAD51 that may play an important role in sensitizing mCRPC to the synthetic lethal action of PARPi.
| 4 | 0biomedical
| 0Study
|
287,804 |
Diego de Trujillo, Spanish chronicler and conqueror, in 1530-1533, observed guavas at several places along the Ecuadorian coast during the expedition that ended with the conquest of the Inca Empire (Patiño, 2002). Around the same time, guava crops were reported near the city of Cuzco in 1534 and north coast of Peru (1535 and 1630) (Patiño, 2002). Different kinds of guava with various colors, shapes, and sizes were found during expeditions through Peru and Ecuador in the mid and end of the 16th century (Patiño, 2002).
| 1 | 2other
| 1Other
|
54,180 |
The overall similarity in structural arrangement of the eukaryotic and archaeal E2 enzymes extended to the conservation of key amino-acid residues that mediate the interaction with E3 ligases21, 22, 41 (Fig. 3b and Supplementary Figs 3 and 4). We therefore also compared the C. subterraneum E3-like srfp protein with known structural homologues to search for the reciprocal conserved regions on the archaeal ligase that might mediate these interactions. It has been established that eukaryotic RING-domain proteins fold with a cross-brace arrangement by coordinating Zn2+ ions, forming an interface for E2 binding21, 22, 45. The PHYRE2 protein fold recognition server46 identified the zinc finger domain of the Homo sapiens E3 ubiquitin-protein ligase Praja-1 (PDB code: 2L0B) as a top structural homologue (Fig. 5a and Supplementary Table 1). Furthermore, the I-TASSER structural prediction software generated a model for the C. subterraneum homologue, which revealed that the key residues and surfaces involved in the interaction with the E2 conjugating enzyme were also conserved (Fig. 5a–c and Supplementary Figs 3 and 4). The conserved zinc-coordinating cysteine and histidine residues indicated that the C. subterraneum srfp protein belongs to the RING-H2 class of proteins, defined by a C3H2C3 sequence of zinc-binding residues (Fig. 5a)21. However, it should be noted that the position of the C. subterraneum C3 and H4 residues are out of alignment by two residues and an additional cysteine residue (denoted C3B) may be involved in the coordination of the second zinc ion, as predicted in the I-TASSER model (Fig. 5a–c). As suggested in previous studies in eukaryotic systems45, 47–49, it seems plausible that the conserved residues P67/Y68 and P103/S104 on the C. subterraneum E2-enzyme on loops L4 and L7, respectively, are critical for the interaction with the E3 components (Figs. 5b, c and Supplementary Figs 3 and 4). These residues associate either with conserved hydrophobic residues that are located on two loops on the E3 protein, or with an invariant tryptophan on the intervening α-helix, which contributes to the E2 interaction surface (Fig. 5a–c)22. In eukaryotic systems it had previously been demonstrated that the docking of the E3 RING domain onto the cognate E2-conjugating enzyme is able to dramatically stimulate the activity of the E2-enzyme by restricting movement of the ubiquitin-E2 thioester intermediate, inducing a conformationally constrained or ‘closed’ state in which it is positioned ideally for the catalytic transfer to a lysine on the substrate50, 51. The conservation of the key residues and structural features on the reciprocal binding surfaces of the C. subterraneum E2 and srfp-E3 proteins predicted in the I-TASSER models suggested that the archaeal ubiquitylation system also operates by an equivalent mechanism. We sought to verify these bioinformatics predictions experimentally by attempting to biochemically reconstitute the E1/E2/srfp(E3) ubiquitylation cascade and then probe the system using site-directed mutations of the key residues.Fig. 5Structural prediction of the canonical RING-domain crossbrace arrangement of the C. subterraneum srfp (E3) protein. a (left top) schematic representation of the RING-domain cross-brace structure with the zinc-coordinating residues circled in red; (left bottom) consensus sequence of the RING-domain (RING-H2 family) with zinc-binding residues highlighted in red (‘X’ any residue); (middle top): RING-domain of the Homo sapiens RING-E3 ubiquitin ligase praja-1 (PDB: 2L0B); (right top): I-TASSER model of the C. subterraneum srfp (E3-like) homologue. Zinc-binding residues are coloured pink (with carbon and sulphur atoms in blue and yellow, respectively) and a conserved tryptophan coloured blue. Green spheres denote Zn2+ ions. Loops that interact with conserved residues in the E2-enzymes are coloured blue. b Schematic predicting contacts between residues in the C. subterraneum RING domain and the E2-like enzyme loops 4 and 7 based upon conservation of residues in eukaryotic components21, 22, 41, 44. Zinc-coordinating residues are coloured red; the conserved tryptophan and the hydrophobic residues presented on loops in the RING domain are coloured blue. Key conserved hydrophobic residues on the E2-like enzyme (PY or PS on loops 4 or 7, respectively) are indicated. c Multiple sequence alignments of the C. subterraneum E2-like and E3-like protein amino-acid sequences with the closest eukaryotic homologues also indicating the specific E2/E3 interactions shown in b. E2-ubiquitin-conjugating homologues: (Paramecium tetraurelia [Alveolata ciliate], Musa acuminata [banana], Aureococcus anophagefferens [alga], Tarenaya hassleriana [spider flower], Theileria orientalis [Apicomplexan parasite]). E3-RING homologues: (Elaeis guineensis [oil-palm], Vigna radiata [mung bean], Beta vulgaris [sugar beet], Arabidopsis lyrata [rockcress], Prunus persica [peach]). The conserved motifs on loops 4 and 7 of the E2-like enzymes are represented by green and red bars, respectively. The catalytic cysteine is denoted by a green circle. The E3-like zinc-binding cysteines and histidines are highlighted by purple circles. Note that the position of the C. subterraneum C3 and H4 are out of alignment by 2 residues (red box). The conserved tryptophan (blue circle) and hydrophobic interaction interfaces between cysteines C1 and C2 and C7 and C8 (blue bars) are also highlighted. The position of residues I30, W58 and R69 are also indicated. Structural figures were prepared using PyMOL
| 4 | 0biomedical
| 0Study
|
187,666 |
Post-progression management after TKI therapy. —Patients managed with TKIs can also develop isolated intracranial progression while on therapy. It is unclear whether this is due to acquired resistance versus the brain being a “sanctuary” site. This underscores the need for brain-penetrable TKI therapies that not only effectively treat existing intracranial metastases but also lower the cumulative incidence of subsequent metastases. For patients who develop new or progressing intracranial metastases on TKI therapy, radiotherapy at the time of progression remains an effective option enabling continued use of post-progression TKI therapy.78 Alternatively, the systemic therapies described above for patients without a driver mutation (see “Non-Targeted Systemic Therapy: Chemotherapy, Immunotherapy & Bevacizumab”) can also be considered in the later-line setting following TKI therapy especially if there is concurrent extracranial progression as well. Some TKI therapies such as osimertinib have also been safely used in combination with carboplatin-doublet chemotherapy.79 The choice to continue TKI therapy while also adding chemotherapy may be particularly advantageous in patients who experience extracranial progression but are considered to have ongoing control of intracranial disease from their TKI therapy.
| 4 | 0biomedical
| 2Review
|
121,348 |
Despite these advances, there are several limitations of our approach as currently implemented. One challenge is in how peptides are partitioned into likely co-regulated sites. On the one hand, co-regulated targets may be inappropriately split into multiple submodules due to overfitting. For example, PKA can phosphorylate both RKxS and RRxS sequences , yet motif-X partitions peptides containing these motifs into separate modules. Such overfitting may hinder the subsequent identification of SIs due to small numbers of constituents in each submodule. On the other hand, sites recognized by different kinases can in theory be incorporated into the same submodules, if those kinases share the same specificity and mutant dependencies. Proline-directed Hog1 and Cdc28 both recognize SP motifs while PKA and Sch9 regulate basophilic sequences . This is a key consideration when formulating hypotheses for subsequent testing. Finally, some kinases do not have strong sequence recognition motifs , and consequently their targets may not share a phospho-motif. Our method primarily uses phospho-motifs to partition peptides into likely co-regulated groups; while we visually represent edges where known SI kinase specificity matches the submodule motif, motif-match edges were not prioritized in the ILP because of the potential for kinases to recognize other sequences. We note that other methods could be used to identify co-regulated peptide groups, including shared docking motifs .
| 4 | 0biomedical
| 0Study
|
126,841 |
Some natural compounds from plants, such as piperine , curcumin , or baicalin , extracted by the conventional extraction methods showed low solubility, poor stability, low adsorption in the gastrointestinal tract and poor bioavailability , which may affect their pharmacological activities. The pharmacological effects of the compounds are often due to their pharmacokinetic behavior, i.e., absorption, bioavailability, distribution, metabolism, and excretion . NADES as an extracting solvent can increase the solubility and bioactivity of these compounds compared to that of conventional solvents . The use of NADES can also increase the stability and shelf life of compounds in extracts. In addition, the bioavailability of compounds dissolved in NADES was also reported to increase .
| 4 | 0biomedical
| 0Study
|
394,587 |
The highest solubility of 89.41 mg/mL for EFV was observed for flaxseed oil and the solubility data are summarized in Table 3. Flaxseed oil was therefore used as the oil phase for constructing pseudo-ternary phase diagrams for the self-emulsifying nanoemulsions. In addition to the physicochemical properties of the EFV the molecular volume, polarity of the oil, chain length and saturation or unsaturation of triglyceride chains of the vegetable oils also influence solubility (MCT) have due to their higher fluidity, better solubility properties . Medium chain triglycerides (MCT) containing oils are best for LBDDS as they are resistant to oxidation and possess high solvent capacity when compared to long-chain triglycerides (LCT) oils because of the high effective concentration of ester functional groups in the oil . However, most of the vegetable oils selected for this study (Table 3) are predominantly and commonly composed of LCT and C18 chains. It was observed that as the proportion of the unsaturated component C18:3 component of the vegetable oils increases the solubility of EFV increased. Flaxseed oil has approximately 50% C18:3, soybean oil approximately 9.5% C18:3, grapeseed, sunflower and olive oil contain C18:3 of <2% .
| 4 | 0biomedical
| 0Study
|
213,190 |
Loa-LAMP assay: DBS samples with their corresponding number assigned in the laboratory. The WarmStart Colorimetric LAMP 2x Master Mixes contains the pH-sensitive dye Phenol Red that changes color from bright pink (negative amplification for L. loa) to yellow (positive amplification for L. loa) as shown here after amplification for 30 minutes of. PC: positive control (positive for L. loa by microscopy and F-RT-PCR). NC: negative control (negative for any filarial parasite); NTC: non-template control.
| 3 | 0biomedical
| 1Other
|
199,405 |
PMX tools such as non-linear mixed effects modeling (NONMEM) , through Pearl-Speaks-NONMEM (PsN) [13, 14] modules, and Monolix provide a wide range of selection-based methods for covariate assessment, including stepwise covariate modeling (SCM) , linearization-based methods , least absolute shrinkage and selection operator (LASSO) , and conditional sampling for stepwise approach based on correlation tests (COSSAC) . However, these methods are not designed to handle multi-dimensional problems involving a variety and a large number of covariates, which is becoming a common situation in the new digital age of medicine in which a vast amount of various types of data are collected. This raises the challenge of finding appropriate and efficient approaches to allow fast screening of large sets of covariates for next-generation PMX and MID3. When supported by a question-driven rationale, the integration of existing methods from other fields can offer unprecedented opportunities to advance methodological frameworks and enhance scientific understanding [20, 21].
| 4 | 0biomedical
| 0Study
|
383,076 |
Co-expression networks facilitate methods on network-based gene screening that can be used to identify candidate biomarkers and therapeutic targets. In our study, the gene expression data profiles of TCGA-HNSCC and GSE6631 were constructed to gene co-expression networks using the WGCNA package in R (8). WGCNA was used to explore the modules of highly correlated genes among samples for relating modules to external sample traits. To build a scale-free network, soft powers β = 3 and 20 were selected using the function pickSoftThreshold. Next, the adjacency matrix was created by the following formula: aij = |Sij|β (aij: adjacency matrix between gene i and gene j, Sij: similarity matrix which is done by Pearson correlation of all gene pairs, β: softpower value), and was transformed into a topological overlap matrix (TOM) as well as the corresponding dissimilarity (1-TOM). Afterwards, a hierarchical clustering dendrogram of the 1-TOM matrix was constructed to classify the similar gene expressions into different gene co-expression modules. To further identify functional modules in a co-expression network, the module-trait associations between modules, and clinical trait information were calculated according to the previous study (17). Therefore, modules with high correlation coefficient were considered candidates relevant to clinical traits, and were selected for subsequent analysis. A more detailed description of the WGCNA method was reported in our previous study (17).
| 4 | 0biomedical
| 0Study
|
123,568 |
The immunoreactivity of phospho Thr231 (pTau231), AT-100 and Alz-50 was quantified as follows: For each subject, two brain slices (at least 800 μm apart) were imaged. Thereafter, from each slice we obtained the following images: 14 images from dorsal hippocampus (four from each CA1, CA2, and CA3, and four from dentate gyrus), eight images from entorhinal cortex (layers VI-III), 14 images from parietal (layers VI-III), and 14 images from temporal cortex (layers VI-III). The total area covered from each region was calculated as the total number of images multiplied by 276360 μm2 (area of a single image). We used ImageJ software (NIH, Bethesda, MD, USA) to determine the area occupied by tau aggregates. To determine the percentage of area in a determined region, the sum of the areas covered by tau aggregates was divided by the total area, and then, multiplied by 100.
| 4 | 0biomedical
| 0Study
|
19,841 |
The measurement reported here is performed using the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sqrt{s}=$$\end{document}s=8 TeV proton-proton collision data sample collected in 2012 with the CMS detector, corresponding to an integrated luminosity of 19.7 fb\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{-1}$$\end{document}-1.
| 2 | 2other
| 0Study
|
268,421 |
We also tested the within-trial dynamics of dogs’ gaze at the screen by creating looking-time curves for both patterns within each trial, separately for the two groups. A single point of a curve represents the proportions of time spent looking at the chasing and independent patterns by subjects in the specific group, for every three consecutive frames. Considering that at the beginning of the trials subjects did not look at the stimuli, we only included data points after the proportion values reached 80% of the average proportion of looking time at the stimuli during the specific trial. Linear regression was applied to the data to capture overall trends and estimate slopes (β ± SE) (see Supplementary Data S2 for the notebook; data used for this analysis is attached as Supplementary Data S3/Chasers/and Supplementary Data S4/Retrievers/).
| 4 | 0biomedical
| 0Study
|
122,617 |
In 1990, the LPI metric peaked at the urban center, fell swiftly in the urban fringe (−6 km and 6 km), and rose again in the outer region, with the increasing distance being a result of the full-coverage class gradually becoming dominant. Because of urban expansion, the remaining green space in the urban fringe was occupied, and more and larger patches of built-up area were formed, as indicated by the increased LPI in the urban area in 2002. However, with the new urban greening strategy in the latter decade, greatly increasing low- and medium-coverage green space fragmented the large built-up patches. Consequently, the vegetation landscape became more diverse, as evidenced by the significant decrease of LPI in most of the region in the 2013 transect.
| 3 | 2other
| 0Study
|
52,308 |
Manufacturing multilayer films by dip coating is very attractive as it is simple and industrially scalable. Moreover, the properties of the films could be easily tuned by altering the contents of the dipping baths. For example, using water soluble CPs with molecular weights below the renal filtration limit of approximately 50 kDa allows the preparation of bioerodible conductive films, and it is likely that adhesion could be improved by coating with mixtures of extracellular matrix-derived proteins (e.g., collagen, fibronectin, laminin). We believe the simplicity of our approach enables us to tailor the properties of the films to specific niche applications (and potentially specific patients).
| 4 | 0biomedical
| 0Study
|
144,244 |
For each droplet, the video was read into a MATLAB script, which processed individual frames, identifying and measuring the drop radius by utilising the Hough Transform. For each processed frame, the time and radius were plotted. An example size profile of a drop is given in Figure S2. In each case, the profile was used to extract the rate of dissolution and from this, the diffusion coefficient of the dispersed-phase solvent (ethyl acetate) into the continuous (aqueous) phase determined. Since the diffusion coefficient was found to be approximately constant across the polymer concentrations and drop sizes, an average value was taken. The Epstein–Plesset model was applied , using the averaged diffusion coefficient, to calculate the theoretical estimate of the time taken for solvent to be removed from drops of increasing radii from 1 to 100 µm for 1%, 5% and 10% (w/v) of PDLLA.
| 4 | 0biomedical
| 0Study
|
370,052 |
Based on this study, we will pursue our efforts to evaluate the use of TLR2eF as a serological tool, more particularly to determine its potential for identifying NTM infections in CF patients in the context of microbiological diagnosis during epidemiological studies.
| 3 | 0biomedical
| 0Study
|
2,430 |
To further characterize the function of PhCESA3, cellulose content was analyzed in plants treated with TRV and TRV-PhCESA3 treatment plant. PhCESA3-silenced plants showed a significant decrease in total cellulose content of the stems and leaves (Fig. 5a and b). In 5-week-old plants, mature stems in PhCESA3-silenced plants had about 80% and mature leaves had about 70% of the control level of cellulose (Fig. 5a and b).
| 4 | 0biomedical
| 0Study
|
177,044 |
(A–I) Correlations between baseline PET/CT metabolic parameters and peak serum cytokines during CRS. All these values were given as lg. Linear regression was used for statistical analysis. (A–C) lg (Baseline SUV) were significantly correlated with lg (peak IL-6) (R = 0.40, p = 0.02), lg (peak IFN-γ) (R = 0.43, p = 0.01), and lg (peak Ferritin) (R = 0.59, p = 0.001). (D–F) lg (Baseline MTV) were significantly correlated with lg (peak IL-6) (R = 0.45, p = 0.008), lg (peak IFN-γ) (R = 0.57, p < 0.001), and lg (peak Ferritin) (R = 0.48, p = 0.01). (G–I) lg (Baseline TLG) were significantly correlated with lg (peak IL-6) (R = 0.46, p = 0.007), lg (peak IFN-γ) (R = 0.57, p = 0.001), and lg (peak Ferritin) (R = 0.51, p = 0.005). (J) Spearman correlation between baseline PET/CT metabolic parameters and prognostic factors of NHL. *0.01 ≤ P < 0.05, **0.001 ≤ P< 0.01.
| 4 | 0biomedical
| 0Study
|
194,959 |
Of the three putative box C’/D’ motifs tested, only snR51-kl1 bound to L7Ae (Fig. 1D). Similar to the positive control sR26-kl, the snR51-kl1 RNA was completely displaced at a 1:1 ratio of the total concentrations of RNA and protein. This demonstrates that the KD of the complex is at least one order of magnitude smaller than the total RNA concentration, corresponding to a KD ≤ 100–200 nM). According to its annotation, the snR51-kl1 box C’/D’ motif contains the 1n−1b A•G base-pair of the consensus sequence, as well as base-pairs –1 and –2 of stem I. By contrast, the predicted snR41-kl1 box C’/D’ motif lacks the 1n−1b A•G base-pair, and snR54-kl1 lacks both base-pair –1 of stem I and the 2n−2b G•A base-pair of stem II. The positive control sR26-kl has the consensus box C/D sequence but lacks stem I.
| 5 | 0biomedical
| 0Study
|
54,500 |
To maintain high levels of TAG molecules, the rate of TAG catabolism should be low . The gene triacylglycerol lipase (EC:3.1.1.3) is highly expressed under nitrogen-replete fresh water conditions (FPKM: 1734). The expression is down regulated under nitrogen-deplete and salt water conditions, LFC -0.3, LFC -0.9, and LFC -0.6 for fresh water nitrogen-depleted, salt water nitrogen-replete and depleted conditions respectively (S1 Table).
| 4 | 0biomedical
| 0Study
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118,319 |
The main goal of the medical proteomics is to find disease biomarkers including proteins or peptides that are specific to a disease. This goal has not been reached yet. However, Human Proteome Project and other independent studies are inspiring concerning medical proteomics (30–35).
| 3 | 0biomedical
| 1Other
|
328,654 |
Detection of non-viable pneumococci may arguably be advantageous, but in any case was relatively uncommon in our study, where there were 2,456 swabs that were lytA positive, and of these, 2,395 (97.5%) were culture-positive. The paper by Messaoudi et al. is informative for the field, but its implications for our study are less obvious. The authors developed serotype-specific real-time multiplex PCRs and found that the nasopharyngeal density in hospitalised/pneumonia patients was around 3-fold higher for serotypes that were also isolates from the blood of the patients tested. They also reported that some serotype-specific qPCRs had different sensitivity, but the reason was unclear. The authors presented some reasons, including primer-probe interactions in the multiplex PCR, as well as differences in extraction efficacy between serotypes. Of note, our focus is on risk factors with overall, vaccine-type, and non-vaccine type carriage and density, rather than serotype specific carriage and density. We agree that there are likely some differences in the cell lysis between serotypes of pneumococci, but we are not aware of evidence that this characteristic differs between vaccine vs non-vaccine serotypes more generally.
| 4 | 0biomedical
| 0Study
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390,352 |
The study was conducted at the beginning of August 2016 on the M. rubra metapopulation system occurring in grasslands near the city of Kraków (50°01′N/19°53′E) in a meadow complex occupying the flat-bed of the Vistula River valley, at an altitude of 200–240 m above sea level. Recently, many meadows have been invaded by goldenrod (Solidago spp.). Three seminatural meadows and three meadows invaded by goldenrod were randomly selected on the study site with a minimum distance of 1 km and a maximum distance of 5 km among meadows. Meadows were separated from each other by a watercourse, forest, and a human settlement. Seminatural meadows were those that had a surface covered 100% by native plants, mainly Molinion caeruleae, but also with a high abundance of Sanguisorba officinalis and some rare plant species, such as Gentiana pneumonanthe, Gladiolus imbricatus, Iris sibirica, or Trollius europaeus. Meadows invaded by goldenrods were nearly pure stands (covered 90–100%) of Solidago plants, with only a few other plant species (Moroń et al. 2009).
| 4 | 0biomedical
| 0Study
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108,207 |
Soil samples were collected at the depth of 5–20 cm from a field, which had never been treated with D-phenothrin or fertilizers, in South China Agricultural University, Guangzhou, China. Physicochemical properties of the soils were as (g/kg of dry weight): organic matter, 10.5; total N, 0.5; total P, 0.4; total K, 18.2; and pH, 6.9 and has sandy loam texture (sand, 65.0%; silt, 28.0%; clay, 7.0%). Soil samples were air-dried in the laboratory to the suitable moisture level, sieved (2 mm), and used for bioremediation studies (Chen et al., 2012, 2014).
| 2 | 2other
| 0Study
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297,418 |
The COVID pandemic has become one of the most severe pandemics since the 1918–1920 Spanish influenza. Our findings demonstrate that individuals with greater PTS and SOC reported more positive relationships between severity judgment at the outbreak peak and domains of PTG subsequently. Also, PTG was related to greater flexibility in severity judgments between the peak and the trough of the outbreak. These findings illustrate both the ingredients and the salutary impacts of PTG.
| 2 | 0biomedical
| 0Study
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285,961 |
Following one week of acclimatisation, AOM was injected intraperitoneally for two consecutive weeks (10 mg/kg/week) in all groups, except the negative control mice, to induce CRC without exceeding the tumour size/burden to ensure the welfare of animals, as previously reported . The animals were then observed for another 20 weeks with no intervention and received standard laboratory chow with water ad libitum. All treatment protocols were initiated at week 21 post-AOM and continued for 4 weeks. Freshly prepared calcitriol (0.07 µg/kg/day; five times/week) and metformin (430 mg/kg/day; five times/week) were administrated orally to the designated groups, and the delivered amounts were equivalent to the highest daily recommended doses for a 60 kg body weight adult human for calcitriol (0.25 µg/day; 0.0042 µg/kg/day) and metformin (1500 mg/day; 25 mg/kg/day) as per the dose conversion formula between humans and mice . 5-FU was administrated to the designated groups for four successive cycles as a single weekly intraperitoneal injection (50 mg/kg/week) as previously described . The study design is summarised in Figure S1. Euthanasia was performed on the first day of week 25 post-AOM by cervical dislocation under anaesthesia, as described earlier . Blood samples were collected from each animal, and serum was stored at −20 °C until use to measure liver and renal biochemical parameters. The colon from each animal was removed, flushed with cold phosphate-buffered saline (PBS), cut longitudinally, and soaked in 10% formalin overnight between layers of filter paper .
| 4 | 0biomedical
| 0Study
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264,468 |
All models used the full exposure distribution of PM2.5 (1.72-15.90 μg/m3). For interpretability and quantification of associations, percent changes in outcomes associated with 4-μg/m3 increments of PM2.5 exposure were calculated using model-estimated predictions and SEs (eMethods in the Supplement). An increase in PM2.5 exposure from 4 to 8 μg/m3 was associated with percent increases that ranged from 0.25% (95% CI, −3.08% to 3.58%) to 1.44% (95% CI, −0.22% to 3.10%) in the 6 tracts evaluated (plus the all fiber summary), whereas an increase in PM2.5 exposure from 8 to 12 μg/m3 was associated with larger rN0 percent increases that ranged from 0.93% (95% CI, −0.10% to 1.97%) to 3.01% (95% CI, −0.39% to 6.40%) (eTable 5 in the Supplement). In tracts with strong positive associations, a PM2.5 increase from 8 to 12 μg/m3 was associated with increases of 2.16% (95% CI, 0.49%-3.84%) in the left cingulum, 1.95% (95% CI, 0.43%-3.47%) in the left uncinate, and 1.68% (95% CI, 0.01%-3.34%) in the right uncinate. Percent changes in rN0 according to household income and 6-month increases in age were estimated to contextualize the observed air pollution associations. In all models, age was included as a continuous variable with 1-month units, but for percent change calculations, 6-month increments were chosen as a reasonable time frame to capture developmental changes in white matter microstructure, given the 2-year age range of the study population. Increases in household income categories were not associated with rN0; percent changes ranged from −0.76% (95% CI, −2.4% to 0.61%) to 0.20% (95% CI, −1.17% to 1.60%); a 6-month increase in age was associated with percent changes in rN0 that ranged from 0.57% (95% CI, −2.44% to 3.58%) to 1.26% (95% CI, 0.11 to 2.41%) (eTable 5 in the Supplement).
| 4 | 0biomedical
| 0Study
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122,544 |
MRI of a patient with siderosis showing hemosiderin deposition along the vestibulocochlear nerves. The image on the left is an axial gradient-echo (GRE) T2*-weighted sequence. The image on the right is an axial T2-weighted image. Both figures are through the internal auditory canals. The study was performed on a 1.5-Tesla strength MR.
| 3 | 0biomedical
| 1Other
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396,607 |
To assess how frequent low-intensity signals were in our cohort, 500 NP samples were randomly selected and tested from our catalog of over 9,000 maternal samples, none of which yielded detecting results. Applying the binomial theorem for an expected frequency of just under 1/500 (i.e., assuming that the next sample would have been detecting), the probability that seven of eight mothers of infected infants also had one or more detecting assays occurring by chance was <0.0001. We conclude that random chance is unlikely to account for the high concordance within these pairs, or for their evident tendency to coincide in time.
| 4 | 0biomedical
| 0Study
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352,356 |
Where patients’ data can be anonymized, Ipsen will share all individual participant’s data that underlie the results reported in this article with qualified researchers who provide a valid research question. Study documents, such as the study protocol and clinical study report, are not always available. Proposals should be submitted to DataSharing@Ipsen.com and will be assessed by a scientific review board. Data are available beginning 6 months and ending 5 years after publication; after this time, only raw data may be available.
| 2 | 0biomedical
| 1Other
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138,846 |
SIS protocols also have several advantages over other (chronic) stress models. SIS protocols can be easily and successfully applied in males and females. In addition, the recurring changes in home-cage hierarchy continue to produce unpredictable social stress, which should maintain sensitivity to the social stress. SIS protocols are also easy to upscale, making it potentially high-throughput, and are relatively low in labor intensity. A SIS protocol works with a minimal cage density of two, but cage density can be increased to upscale the number of experimental animals. One should however note that the number of cage mates, as well as cage area size, will likely impact the aggressiveness of the animals and will thus impact the intensity of the social stress. A SIS protocol can last multiple weeks to months, making it a bonafide chronic stress model. Because of the easiness to apply SIS protocols for a longer duration, social stress can be applied to adolescent animals and last into adulthood. This allows for the possibility to study the effects of social stress spanning multiple ages. When started during adulthood compared to adolescence, SIS is often associated with more aggression. Males also demonstrate more aggression during SIS, especially during adulthood, compared to females. Although one should always carefully monitor the health of each individual experimental animal, this is especially true for SIS cohorts of (adult) males.
| 4 | 0biomedical
| 0Study
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98,579 |
Genetic studies in animal models provide important opportunities for identifying the genes and mechanisms underlying disease traits. Experimental crosses in rats and mice, including mapping studies in congenic strains, have been used to identify hundreds of physiological and pathophysiological quantitative trait loci (QTLs) for complex traits such as blood pressure, left ventricular (LV) mass and type 2 diabetes (Aitman et al., 2008). Whilst genes underlying these QTLs have in some cases been identified and translated to mice and humans (Aitman et al., 2008; McDermott-Roe et al., 2011; Nabika et al., 2012; Petretto et al., 2008), the overwhelming majority of rodent QTL genes remain unidentified.
| 4 | 0biomedical
| 0Study
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173,586 |
Using the biological variation frequencies generated as true positives for each dataset, we evaluated the amount of isomiRs detected for each software and type of read. For paired-end reads, we also used a different percentage difference cutoff. For each isomiR, the detected counts were classified as: True positives (TP) when observed counts matched the expected counts; false positives (FP) when observed counts exceeded the expected counts and were wrongly assigned; and false negatives (FN) when observed counts did not get to the minimum expected counts. We calculated the sensitivity or recall as TP/(TP + FN) and the precision or specificity as TP/(TP + FP). We also reported True Negatives (TN) when expected counts were not observed and new generation isomiRs when new variants or miRNA appeared and were not expected. We plotted results using ggplot2 for each software and type of read respectively.
| 4 | 0biomedical
| 0Study
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341,895 |
†Public sector facility sources include: rural hospital, primary health center, and sub-centre/auxiliary nurse midwife. Private health facility sources include: private hospital, private doctor/clinic, and non-governmental organization or trust hospital/clinic.
| 2 | 2other
| 1Other
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336,822 |
With the orthogonal demodulation and the phase unwrap, the phase can be extracted from the in-phase and the quadrature components of the beat signals . Then we use differential methods to reconstruct vibration signals . Figure 1 shows how an external vibration that induces extra stress on the fiber and results in a change in optical path length (OPL), where two segments of fiber A and B with a length of L are selected as the reference regions. The change in length ΔL is directly related to the change in relative phase difference Δφ between the two regions. Any external perturbation within two specific points changes the phase of the backscattered light wave. Therefore, the reconstruction of external vibration signal can be realized by demodulating the phase difference Δφ. (1)Δφ=4πnλΔL where n is the refractive index of fiber; λ is the wavelength of probe light; ΔL is fluctuation of fiber length results from external perturbation.
| 4 | 0biomedical
| 0Study
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388,759 |
Boxplots representing percentage changes in net profit on (A) dairy and (B) beef farms under “disease” and “disease + cc” scenarios compared to the baseline scenario; (line is the median and cross is the average value for each farm groups; y-axis represents percentage).
| 1 | 2other
| 1Other
|
388,053 |
Challenges associated with liver segmentation, i.e., inhomogeneity of intensity in the liver region (a), fuzzy separation between liver and heart (b) and the multi-segments geometry within single slide (c). In addition, these cases exhibit different intensity ranges of liver tissue.
| 3 | 0biomedical
| 1Other
|
279,252 |
Distribution of the intra‐household DBM by household wealth quintile, maternal education level and area of residence across WHO regions and overall: (a) households with overweight/obesity among mothers and anaemia among children and (b) households with anaemia among mothers and overweight/obesity among children. Wealth quintiles: Q1 (poorest), Q2 (poorer), Q3 (middle), Q4 (richer), Q5 (richest). Maternal education levels: E1 (no education), E2 (primary education), E3 (secondary education), E4 (higher education). The EMRO and EURO regions are missing for maternal education level, as 1/2 and 5/6 countries, respectively, had sample sizes below 25 observations for one or two education levels; and thus, the regional pooled prevalence could not be calculated. All countries with sample sizes above 25 observations for the five wealth quintiles, four maternal education levels and urban/rural areas were included in the calculation of the overall pooled prevalence estimates. AFRO, African region; EMRO, Eastern Mediterranean region; EURO, European region; OWOB, overweight/obesity; PAHO, Americas region; SEARO, Southeast Asian region
| 4 | 0biomedical
| 0Study
|
385,484 |
The finding that conditional ablation of TNF in microglia resulted in an impairment in functional outcome that approached statistical significance suggests that microglial TNF may confer some protection after SCI. In our experimental stroke model, we previously demonstrated that microglial-derived TNF is protective after focal cerebral ischemia , that Tnf−/− mice displayed increased lesion size but that ablation of solTNF reduceed lesion size . Macrophage-derived TNF had no effect on lesion size . From our stroke models, we conclude that microglial-derived tmTNF is neuroprotective. In stroke, the lesion develops quickly, prior to leukocyte infiltration, which may explain the importance of microglial-derived TNF on the final lesion size. In SCI, genetic ablation of solTNF had no effect , whereas central—not systemic—inhibition of solTNF was protective . In line with previous findings , we also in the present study observed that conventional deletion of TNF in Tnf−/− mice had no effect on functional recovery. This suggests that central and peripheral myeloid TNF may have opposing effects. We previously demonstrated opposing functions of microglial and macrophagic TNF-TNFR2 signaling in an animal model of multiple sclerosis—experimental autoimmune encephalomyelitis (EAE) . We showed that TNFR2 ablation in microglia resulted in early onset EAE with increased leukocyte infiltration, T cell activation, and demyelination. Conversely, TNFR2 ablation in macrophages resulted in EAE suppression with impaired peripheral T cell activation and reduced CNS T cell infiltration and demyelination. This supports a detrimental role of TNFR2 signaling in macrophages and a protective role of TNFR2 signaling in microglia. Whether such differences in microglia and macrophage function also occur after SCI is not fully known at present. In addition to the present study, more work into the kinetics of microglia and macrophage responses are needed in order to pave the way to effectively target these cells to improve outcome in SCI.
| 4 | 0biomedical
| 0Study
|
194,247 |
The purpose of the present study was to investigate the effect of serial passaging on intracellular AGE formation and osteoclastogenesis. This study shows some evidence of intracellular AGE formation and accumulation, as well as removal under in vitro culture conditions and a dramatic fall of osteoclastogenesis after a few passaging cycles.
| 3 | 0biomedical
| 0Study
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276,412 |
We performed ID conversion on transcriptomics and proteomics data taken as example matrices using Ensembl ID and uniport ID, respectively. OMnalysis is built to assign the most updated IDs. To the transcriptomic data matrix, the OMnalysis assigned 11,357 updated Ensembl IDs from a total of 11,398 uploaded Ensembl ID (Table S7). Next, to those updated IDs, OMnalysis was successful in assigning 10,951 human gene names, 10,932 HGNC symbols, 11,354 gene descriptions, and 7,463 UniProtKB/Swiss-prot ID (Table S7). In the case of proteomic data, 731 UniProt IDs were submitted to OMnalysis. Please note that, these 731 IDs include several repeated UniProt IDs from 4 treatments. From this list, 281 UniProt IDs were mapped to Ensembl gene ID, 277 to the gene name, 0 to HGNC symbol, 273 to gene description and 273 to UniProtKB/Swiss-Prot ID (Table S8).
| 4 | 0biomedical
| 0Study
|
270,989 |
Diffusion strategy is an effective tool to optimize the global utility in a locally distributed manner . The diffusion strategy updates local parameters by not only the local information but also neighbor nodes’ parameter variation trend. In this way, the coupling between nodes in the optimization process is considered. A typical Combine-then-Adapt (CTA) diffusion model consists of two steps: (1) neighbor nodes’ parameter combination, (2) local parameter update. For more details about the CTA diffusion model, please refer to .
| 1 | 2other
| 1Other
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47,799 |
Basic descriptive statistics, including coverage of interventions at household level were calculated with adjustment for survey design. To explore associations with PCR-confirmed parasitaemia and categorical variables, the χ2 test was employed; where cells had an expected frequency below five, Fisher’s exact test was used. Associations for continuous variables were examined using the Kruskal–Wallis or Wilcoxon rank-sum test. For each variable, the odds ratio (OR) for malaria infection was calculated using univariate logistic regression. All exploratory variables with biological plausibility as identified in similar studies and p-values ≤ 0.2 were included in multivariable models . A wealth index for households was constructed from household assets using principle components analysis .
| 4 | 0biomedical
| 0Study
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218,078 |
2) In the methods, the authors stated that they "conducted sensitivity analyses that excluded pharmacological interventions that do not have legal approval to be prescribed in the United States, use alternative outcome data reported in included studies, and are based on risk of bias assessments". Could the authors reword the sentence and clarify how these analyses were conducted? However, the results of these analyses are not described, except for the sensitivity analysis regarding remission from alcohol use after excluding studies with high risk from the pharmacologic network (p8 l184: please change 0.9998 by 1.00).
| 2 | 0biomedical
| 0Study
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265,606 |
The questionnaire design was guided by participatory cocreation processes with people with diabetes and HCPs, using qualitative research and extensive literature review to take into account empirical research related to diabetes self-efficacy , self-determination , empowerment , social ecological and biopsychosocial care , behavioral and health psychological diabetes research , and person-centered diabetes care .
| 2 | 0biomedical
| 0Study
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234,167 |
The NICOLE study (NCT04123925) is the first study to examine the effect of neoadjuvant nivolumab for treatment of early-stage colon cancer without selection for MMR status. This study enrolled 44 patients with cT3/T4 resectable colon cancer. The experimental cohort (86% with MSS) received 2 cycles of nivolumab, and then surgery, and the control cohort (77% with MSS) received surgery. The primary end points were the feasibility of preoperative nIT, the degree of pathological response, and molecular and immunophenotypic changes in the tumor and peripheral blood. The results showed that more than 70% of the patients in nivolumab group experienced significant tumor regression ( Table 1 ). The nivolumab group also had significantly higher levels of CD8− and CD8+ non-inhibitory T cells.
| 4 | 0biomedical
| 0Study
|
58,908 |
DUBs also play vital roles in spermatogenesis (e.g. during gonocyte and spermatogonia development and meiosis regulation ), as well as in oogenesis (e.g. oocyte maturation and fertilization ). USP2-knockout mice display abnormal aggregation of elongated spermatids, resulting in fertility defects . Histological data have shown that USP14-deficient testes display abnormal spermatogenesis . USP26 regulates androgen receptor hormone-mediated spermatogenesis and steroid production , suggesting that the DUBs stabilizing USP2, USP14, USP26 and UCHL1 ultimately regulate the processes of spermatogenesis and oogenesis.
| 4 | 0biomedical
| 0Study
|
93,997 |
Sera were obtained from venous blood and stored at −20 °C until tested. Sandwich ELISA test kits EIA Toxoplasma IgG (Test-Line Clinical Diagnostics Ltd., Brno, Czech Republic) were used to evaluate serum samples for the presence of specific IgG antibodies to T. gondii. The index of positivity (IP) was calculated for each sample according to the formula: “IP = sample OD (optical density)/average cut-off OD”. Samples with IP >1.1 were considered positive.
| 4 | 0biomedical
| 0Study
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383,852 |
Next, we investigated the role in PM repair of the tubular endocytic pathway upregulated in the absence of caveolae. To this end, we used siRNA in both WT and Cav1 KO MEFs to inhibit the expression of proteins previously reported to participate in tubular endocytosis, such as galectin-3 (Lakshminarayan et al., 2014) and endophilins (Ambroso et al., 2014; Renard et al., 2015). After confirming that siRNA treatment decreased expression of these proteins (Fig. 3A; Fig. S1B,D,F), we determined the ability of WT and Cav1 KO MEFs to reseal their PM after permeabilization with SLO for 2 min. RNAi-mediated knockdown of galectin-3, endophilin-A1 and endophilin-A3 had no effect on the typical PI-staining pattern of each cell type in the flow cytometry assay, reflecting their PM repair capacity (Fig. S1A,C,E). We also tested the involvement of clathrin-dependent endocytosis by reducing levels of clathrin heavy chain expression, which inhibited endocytosis of biotinylated surface proteins but had no impact on PM repair (data not shown). Fig. 3.EndoA2 promotes fission of tubular endosomes and PM repair in Cav1 KO MEFs. (A) Western blot using antibodies against EndoA2 and tubulin (loading control) of WT and Cav1 KO MEF lysates treated with control (−) or EndoA2 (+) siRNA. (B) Flow cytometry of WT (blue) and Cav1 KO MEFs (red) treated with control (dashed lines) or EndoA2 (full lines) siRNA for 48 h, exposed to increasing concentrations of SLO (50–100 ng/ml) in the presence of Ca2+ at 37°C for 2 min, and stained with PI to detect permeabilized cells. The vertical dashed lines represent the gate utilized to calculate cell population percentages (light color, control siRNA; dark color, EndoA2 siRNA). The results are representative of six independent experiments. (C) TEM images of tubular endosomes in WT and Cav1 KO MEFs treated with control or EndoA2 siRNA for 48 h and incubated with CTxB–gold for 1 min at 37°C. Arrowheads: CTxB–gold. Arrows: open tubular endosomes. Scale bars: 100 nm. (D) Quantification of total, apparently closed and open tubular endosomes containing CTxB–gold in WT and Cav1 KO MEFs treated as in C. All tubular endosomes containing CTxB–gold were counted in 20 individual cell sections/sample. The data represent the mean±s.e.m. of CTxB–gold-containing tubular endosomes/cell section, and are representative of two independent experiments. *P=0.015–0.02; **P<0.01; ***P<0.001 (unpaired two-tailed Student's t-test comparing each sample with the WT control siRNA condition). (E) Flow cytometry of WT (blue) and Cav1 KO MEFs (red) treated with control (dashed lines) or EndoA2 (full lines) siRNA for 48 h and exposed to SLO (25 and 100 ng/ml) or not (no SLO) in the presence of Alexa Fluor 488–CTxB for 10 min at 37°C, followed by quenching with anti-Alexa Fluor 488 antibodies and Trypan Blue for 20 min at 4°C. Negative controls (gray dashed lines) represent WT or Cav1 KO MEFs incubated with Alexa Fluor 488–CTxB at 4°C followed by quenching at 4°C, without stimulating endocytosis at 37°C. The results are representative of three independent experiments.
| 5 | 0biomedical
| 0Study
|
334,456 |
In quantum mechanics, the maximal eigenvalue of a self-adjoint linear operator can be identified with the maximal value of an observation. Therefore, the spectral theorem supplies even the state associated with this maximal eigenvalue λ1: it is the eigenvector (linear subspace) |e1〉 associated with the orthogonal projector Ei=|e1〉〈e1| occurring in the (re)ordered spectral sum of T.
| 1 | 2other
| 1Other
|
108,733 |
In summary, our analysis of thermal history at global coral reef locations revealed warming at almost all reefs in recent decades; summertime temperature increased through the record at the great majority of reefs. One-third of the world’s reefs were exposed to bleaching-level thermal stress less than once per decade, with one-third of reefs exposed between once and twice per decade, and the remaining one-third exposed more than twice per decade. The global percentage of reefs impacted by bleaching stress tripled through the 28-year record, explaining the increase in observed bleaching. While the onset of thermal stress mostly coincided with the warmest part of the year, we found that at nearly one-quarter of reefs it did not. The following key points were identified from each set of thermal history parameters.
| 4 | 0biomedical
| 0Study
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242,897 |
Significant attempts have been done to target DCs using polymeric NPs. DCs are optimal candidates since they hold a key role in the modulation of immune system and possess high phagocytic capacity. Although it has been demonstrated that the physicochemical features of NPs (e.g., size, surface charge) could enhance the interaction with DCs , the most effective approach to precisely target DCs would be providing NPs with specific targeting ligand. For example, Cruz et al. built PEGylated PLGA NPs decorated with distinct antibodies against TNF-α family (CD40), integrin (CD11c) and c-type (DEC-205) and loaded with ovalbumin and Toll-like receptor (TLR)-3 and- 7 ligands. Results demonstrated that all targeted NPs induced CD8+ T cell responses both in vitro and in vivo . Another strategy to enhance the uptake of polymeric NPs by DCs is the functionalization with mannan (mannose receptor) as carriers to deliver therapeutic oligonucleotides . Mannosylation could be also a target of macrophages. Thus, Deng et al. showed that mannose-modified chitosan NPs loaded with micro (mi)RNA-146b are taken up selectively by intestinal macrophages in the treatment of colitis, resulting in a localized suppression of pro-inflammatory cytokines . Notably, dextran and its derivate act as ligands for macrophages due to the expression of dextran-binding proteins and scavenger receptors on macrophages surface. For this reason, they have received increasing attention in biomedical application as well as they possess remarkable biocompatibility and biodegradability . In a murine model of RA, dextran sulfate NPs showed a higher accumulation in inflamed joints due to an active uptake by macrophages responsible for the inflammation. Moreover, the combination of targeting with the encapsulation of an anti-rheumatic drug significantly improved the therapeutic efficacy compared with free drug . Polymeric NPs with a semi-solid shell can be a reservoir to encapsulate molecules easily degradable if administered alone (e.g., drugs or antigens). Maldonado et al. synthesized PLGA NPs containing a peptide antigen and the immunosuppressive drug, rapamycin. The nanocarrier administration induced the inhibition of T cell activation and generation of T regulatory cells (Treg), inducing the antigen specific tolerance in autoimmune encephalomyelitis (EAE) mouse model . In a model of T1D, a diabetogenic peptide was either entrapped or conjugated to PLGA NPs. In vivo results showed that functionalized NPs were really taken-up by APCs and upregulated the expression of anti-inflammatory cytokines IL-10 and TGF-β. More interestingly, the treatment induced amplification of Treg and restored tolerance in both CD4+ and CD8+ T cells . In another work, Cappellano et al. reported that polymeric NPs co-loaded with IL-10 and myelin oligodendrocyte glycoprotein (MOG) peptide decreased inflammatory cytokine secretion by T cells in mice with EAE without any cytotoxicity effect . Finally, in our own laboratory, we showed that NPs containing hyaluronic acid (HA) and a 21-mer therapeutic peptide called P140, which is currently evaluated in phase-III clinical trial in lupus patients, were efficient when given via the intra-duodenal route to Murphy Roths large/lymphoproliferative (MRL/lpr) lupus-prone mice . Proteinuria, that appear in these mice with age was delayed and remained less frequent all along the course of the disease. The intra-duodenal administration of HA-P140, a first step for the future design of oral administration of peptide, was also shown to be beneficial on the mortality rate of treated mice. In the control group, the first mice died at 15 weeks of age while in the treated group, the first mouse died at 22 weeks only. At 37 weeks, 100% of non-treated mice and only 50% of mice having received the HA-P140 were dead. These results led us to conclude that intra-duodenal administration of HA-P140 NPs to MRL/lpr lupus mice allows their life expectancy to be lengthened in a significant way.
| 5 | 0biomedical
| 0Study
|
157,042 |
To evaluate the impact of a pre-vaccination screening intervention in Puerto Rico, we modified an agent-based model of dengue transmission with humans and mosquitoes represented as agents. This model has been described in previous publications . While our model has been calibrated to demographic and geographic data from Iquitos, Peru , the model can represent DENV transmission in a generic setting and has been modified in this study to simulate DENV transmission dynamics in Puerto Rico. Our model compares two strategies, an intervention strategy and the status quo. The intervention strategy is the routine pre-vaccination screening and subsequent vaccination of seropositive of 9-year-olds in Puerto Rico. Nine-year-olds is the lowest age approved for vaccination, and has been used as a default age of vaccination in other studies . For each of the strategies, the model population was followed for 10 years, keeping track of dengue-related health events defined as dengue virus infections, hospitalizations, and deaths.
| 4 | 0biomedical
| 0Study
|
175,594 |
Many plant species produce pollen that is poor in proteins, e.g., protein-poor pollens are produced by conifers and grasses, which are non-nectar-yielding plants . The protein content in the pollen of various plants is highly variable, ranging from 2.5% to 61%, with an average of 25–45% . The lowest protein content is found in Cactaceae and Onagraceae plants (15–25% of protein), while Melastomataceae, Cochlospermataceae and Solanaceae are the richest in protein (over 51%) .
| 4 | 0biomedical
| 0Study
|
107,069 |
Targeted NGS of the 10 SCLC-associated genes (KRAS, TP53, RB1, PIK3CA, PTEN, BRAF, NRAS, ALK, NOTCH1, EGFR) for the CDX3 tumour DNA samples was carried out using custom xGen Lockdown Probes (Integrated DNA technologies). In brief, 500 ng adaptor-ligated DNA libraries from 6 FACS-sorted CDX3 tumour samples were pooled together and combined with 5 μg of Cot-I DNA (Invitrogen) and 1 nmol each of blocking oligonucleotides (TS-p5 and TS-p7). The mixture was lyophilized and then re-suspended in 1.8 μl water, 8.5 μl 2 × xGen hybridization buffer and 2.7 μl xGen hybridization buffer enhancer. The mixture was heated to 95 °C for 10 min. Subsequently, 3 pmol of cuxtom xGen lockdown probes were added and allowed to hybridize for 4 h at 65 °C. After hybridization, M-270 streptavidin beads (Life Technologies) were added and washes were performed according to the manufacturer's recommendations. The enriched DNA libraries were re-amplified using the KAPA HiFi PCR Kits and Illumina sequencing primers for 30 cycles. The amplified enriched libraries were then sequenced on the Illumina MiSeq (Illumina) benchtop sequencer using MiSeq Reagent Kit v2 (Illumina).
| 4 | 0biomedical
| 0Study
|
346,823 |
The bands of quinonoid and benzenoid structures shifted from 1582 cm−1 to 1567 cm−1 and from 1509 cm−1 to 1489 cm−1, respectively (Figure 1), with increasing acidity of the reaction system. These prominent redshifts may be due to enhanced conjugation interactions and doping of the PANI chains with HCl. The intensity ratio of the quinonoid/benzenoid peaks (IQ/IB) could be used to determine the proportion of chain structures to some extent. The calculation results (the values of IQ/IB for PANI-0.1H, PANI-0.3H and PANI-1H are 0.814, 0.875, and 0.914 respectively) revealed that the ratio of quinonoid to benzenoid structures increases with increasing HCl concentration, possibly due to enhanced conjugation interactions.
| 4 | 0biomedical
| 0Study
|
84,843 |
SQR protein levels in brain were almost undetectable in wild‐type mice (Fig 8A), while Pdss2 kd/kd mice exhibited a trend toward increase in SQR protein levels in brain (154% of controls; P = 0.211; Fig 9A), which was in stark contrast to the situation in the kidney. Importantly, levels of the other enzymes of the pathway were comparable with those of control wild‐type animals (Fig 9B–D).
| 5 | 0biomedical
| 0Study
|
230,677 |
The obstacle model can provide some suggestions for the formulation and adjustment of sports development policy by analyzing and diagnosing the obstacle factors that affect the resilience level of sports development in each province (Pan et al., 2019). The factor contribution degree is represented by the weight wj of a single index. Index deviation degree Ij refers to the difference between a single index and the target expressed as the difference between the standardized value of each indicator and 1, and xj′ is standardized data. Obstacle degree Oj means the degree to which each indicator or criterion layer factors affect the development of regional sports resilience in China (Huang et al., 2020). The obstacle degree is calculated as follows:
| 2 | 2other
| 0Study
|
198,131 |
As shown in Figure 3, the TDPDP flow model presumes linear flow in three separate regions, which are coupled by the continuous flow rate and identical pressure system at the interface between contiguous regions. The necessary parameters and assumptions are listed as follows.(1)Closed outer boundary (x = xe).(2)Virtual impermeable interface (y = ye).(3)Slightly compressible fluids and rock frame.(4)Pseudo-interporosity flow between the matrix and fracture systems.(5)Symmetric and equidistant identical transverse hydraulic fractures.(6)Impermeable hydraulic fracture tips/end (x = xF).(7)Half-length of the hydraulic fracture xF, constant.(8)Width of the fracture wF, constant.(9)Hydraulic fracture height h, constant.(10)Permeability of the inner and outer reservoir regions, kI and ko, respectively.(11)Porosity and total system compressibility,ϕ and Ct, respectively.
| 4 | 0biomedical
| 0Study
|
78,799 |
Recent work indicates that birds, like insects, have strongly developed brain areas that are tuned for processing optic flow (revs. Frost, 2010; Wylie, 2013). Does this provide birds with equally adept visual flight control? What visual strategies do birds use while navigating through the environment, and how do these strategies compare with those known to be key for visual flight control in insects (Figure 1)? Until the past decade, relatively little research has been carried out to address these questions. Zebra finches hold their heads at a constant orientation -interspersed by brief saccadic rotations—while flying past an obstacle (Eckmeier et al., 2008). This suggests that optic flow could provide a reliable estimate of obstacle distance. How the information derived from optic flow is used to control the various phases of bird flight—such as takeoff, cruise, obstacle avoidance, and landing—remains to be uncovered, although some clues have begun to emerge, as will be described in this review.
| 4 | 0biomedical
| 2Review
|
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