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277,036 |
All committee members therefore became more engaged and vocal as the process unfolded. However, this often meant that any need for different avenues of scientific inquiry or search terms for evidence review protocols only became apparent in later meetings. This became an issue when, during subsequent evidence discussions and recommendation writing meetings, committees requested evidence which differed from what had been originally agreed in the earlier evidence review protocols. Joan a lay member from GC1 was one of the committee members to describe her “difficult” experience of this:“We have asked for another review that has been rejected and I find that NICE can be quite inflexible and […] saying well those were your search terms (including outcomes), so that is the end of it.” Joan, GC1 (interview)
| 1 | 2other
| 1Other
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62,334 |
(A) Level of primary miRNA transcript as measured by RT-qPCR and normalized to 18S mRNA. (B) Levels of mature miRNAs measured using taqman assays and normalized to that of RNU43 miRNA. Error bars represent standard deviations from at least 3 independent experiments. Statistically significant differences between shScr and shHIF-1 cells are indicated. *P ≤0.05 (2-tailed t-test).
| 4 | 0biomedical
| 0Study
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304,409 |
Reactions were carried out with 1a (0.10 mmol), 2 (3.0 equiv.), NaOtBu (1.0 equiv.), C1 (20 mol%), EtOH (8.0 equiv.) and L/Yb(OTf)3 (1 : 1, 10 mol%) in EtOAc (0.17 M) at 35 °C for 48 hours. The isolated yield of 3 based on 1a. The dr value was detected by 1H NMR analysis, and the ee value was determined by HPLC on a chiral stationary phase.
| 4 | 0biomedical
| 0Study
|
186,900 |
It can be seen from Table 2 and Figure 2 that the most used acupuncture points for the treatment of constipation in modern acupuncture are Tianshu (526 times), followed by Shangjuxu (366 times), Dachangshu (334 times), Zusanli (328 times), and Zhigou (306 times). Among them, Tianshu acupoint is the most used acupoint and it has a large gap with the value of Shangjuxu in the second place. The values of the acupoints in the 2nd to the 5th place are more balanced, and the value of Qihai in the sixth place is different from Zhigou in the fifth place. Also, the difference between the 6th and 15th positions is more balanced. From the frequency of acupuncture treatment of constipation, the top 5 acupoints are Tianshu, Shangjuxu, Dachangshu, Zusanli, and Zhigou.
| 3 | 0biomedical
| 0Study
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139,153 |
This was also suggested by Reviewer 2. In response to both of them, we included Table 1. We included three variables that had a good rate of response (less than 10 missing cases): sex, age, and number of children. We had to exclude years of formal education because almost one third of participants did not answer to that question. This probably due to the access barriers to schools that that affects many communities living in rural areas in Peru.
| 2 | 0biomedical
| 0Study
|
333,952 |
The advantages of 2D HCPC-sensing devices mainly include (1) independent fabrication of 2D CPCs and hydrogels, as the monolayered colloid arrays could be either attached onto the hydrogel surfaces or embedded into the hydrogel during polymerization; (2) the response of the sensing device could be determined by measuring the Debye ring instead of using a fiber spectrometer; and (3) the readout of the 2D HCPC-sensing device is reliable since the diffracted light from the 2D structure is not affected by the change in refractive index during measurement .
| 4 | 0biomedical
| 0Study
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147,562 |
Cells were transfected with siRNAs for 48 h. Then 8 × 105 cells were plated on 6-well plates for 24 h and wounded by scratching with a pipette tip. Subsequently, the cells were incubated with OPTI MEM medium without FBS at 37 °C for up to 36 h. Three random fields under the microscope were photographed for calculating the percentage of wound closure. Assays were repeated at least three times. Data were shown as mean ± SD and p-value was calculated by Student’s t-test.
| 4 | 0biomedical
| 0Study
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104,060 |
Cytochrome c oxidation and TCP oxidative dehalogenation catalyzed by C45. a Representative changes to the UV/visible spectrum of equine cytochrome c during C45-catalyzed oxidation. b Michaelis–Menten plot of equine cytochrome c oxidation catalyzed by C45 in the presence of limiting H2O2 (100 μM). c Representative changes to the UV/visible spectrum of TCP during C45-catalyzed oxidative dehalogenation to the dichloroquinone product (DBQ). d Michaelis–Menten plot of 2,4,6-trichlorophenol oxidative dehalogenation catalyzed by C45 in the presence of limiting H2O2 (100 μM). All data were recorded in triplicate and error bars represent the standard deviation
| 4 | 0biomedical
| 0Study
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240,901 |
a Relationship between specific RNA abundance in biofilm and liquid for all MAGs. The black-coloured points indicate high-quality MAGs which were used for further analysis. The relative placement of the points with the red diagonal line reveals in which phase the specific RNA abundance is higher. The size reflects the percentage of identified genes with mapped mRNA. Note that MAG 9 occupies the highest specific RNA abundance in both phases followed by MAG 3. MAGs 1, 2, 5, 6, 8, 18 and 20 have a medium level of specific RNA abundance. b Functional landscape of the selected MAGs. The colours of the points indicate 8 functional clusters of MAGs, while the ellipses further gather them into three groups. The shape of the points indicates the ratio of the transcribed (T.) KOs (KEGG Orthologs) where the circular points are from the dominant members of the community (as defined in the text) and the rhombus points are from the non-dominant members of the community. The numbers next to the circular points indicate the dominant MAGs. For the dimensional reduction and clustering, we used Uniform Manifold Approximation and Projection (UMAP) and affinity propagation, respectively, on the binary (presence/absence) KO matrix. Note that the dominant MAGs are distributed across the functional groups.
| 4 | 0biomedical
| 0Study
|
343,836 |
Irrespective of the variability, the lung dose delivered by the MAD is large and therefore we asked whether concentration of influenza virus in a relatively small lung area affected the magnitude of immune responses. All MAD challenged animals generated strong immune responses and abundant local virus specific T cells in the BAL, that were multifunctional and resembled TRM phenotypically. BAL NP217-225 CD8 T cells were mainly of TEM phenotype as described in humans (40). For the first time we also characterized influenza specific trachea and nasal turbinate T cells in a large animal model. The proportion of tetramer specific cells in these sites was slightly lower than in BAL and their phenotype resembled CD8 T cells in human airways (40). Interestingly, URT T cells in mice have been shown to be long lived and the less differentiated phenotype of pig URT T cells may indicate that these too turn over more slowly than the differentiated TEM cells in BAL (41, 42). There was a smaller proportion of NP217-225 cells in the lung compared to BAL, probably due to the high vasculature of the organ and known difficulties in extracting TRM from tissues (43). The phenotype of the NP217-225 cells in the lung was very similar to that in humans, CD27+/- CCR7- (44, 45). Serum antibody responses correlate with protection against infection in humans and prevent influenza virus transmission in pigs (46). MAD delivery induced high mucosal and serum titers with higher IgA in BAL and nasal swabs. There was a low neutralising titer in BAL, but given the dilution factor when collecting it, it is likely there is significant neutralising activity in both lung and nasal swabs. We conclude that an effective delivery of a vaccine to the respiratory tract will be very effective in preventing transmission.
| 4 | 0biomedical
| 0Study
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335,366 |
It is worth noting that the children in our samples were on average older than the children in Reindl et al.'s study , meaning that greater cultural exposure prior to testing may have cemented children's tool use behaviours. Perhaps restricting our sample to a younger, more culturally ‘naive’ cohort could have reduced the group differences found. However, if we look at the performance seen between our youngest participants (2–3-year-olds), these differences are still apparent, and we found no interactions between cultural influence and age across our sample. This suggests that any indirect effects of cultural influence, previous social learning opportunities and/or material familiarity on spontaneous tool invention and associated cognitive abilities must emerge earlier than this age in children. The employment of alternative strategies to solve the puzzle boxes, such as using hands/fingers, applying brute force or disassembling, cannot explain our cultural differences, as an equally small percentage of children in each culture solved the tasks using such methods. Rather, it appears that the sociocultural niche of a child's environment, or the artefacts in it, might influence their perception of tool-like objects from an early age, and in doing so affect their potential to pick up a tool and use it in a certain way to solve a problem .
| 4 | 0biomedical
| 0Study
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260,432 |
The main hurdle is taking research results from the laboratory into the clinic, specifically the delivery of optogenetic tools in patients. As Shen et al. stated, the minimum requirements of an ideal clinical optogenetic therapy would be: (1) a safe and efficient gene delivery vehicle; (2) targeting of the gene delivery vehicle to the tissue of interest; (3) a delivery vehicle, transgene, and therapeutic protein gene-product, that is non-immunogenic and non-mutagenic; and (4) an optogenetic protein that is highly sensitive to light in the red to near-infrared wavelength range (to keep light doses low, maximize light penetration, and minimize photodamage) .
| 4 | 0biomedical
| 0Study
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161,911 |
Fragmentation by collision-induced dissociation of negative ions from N-linked glycans (those attached to proteins at asparagine in an Asn-Aaa-Ser(Thr) consensus sequence, where Aaa is any amino acid except proline) has been shown to provide a wealth of diagnostic cross-ring fragments. Each individual glycan spectrum is sufficient for determining most structural features without the use of derivatization such as permethylation or reducing end tagging . Specifically, for non-acidic glycans, the method provides the composition of the glycan in terms of its constituent isobaric and isomeric monosaccharide composition, its topology in terms of antenna branching (which type of triantennary glycan is present, for example), the location of fucose residues, and the presence or absence of bisecting GlcNAc. Some of these structural features are difficult to determine by traditional methods such as exoglycosidase sequencing as these enzymatic reactions are often incomplete plus they are often time-consuming and expensive. For acidic glycans, those with sialic acid can be converted to neutral compounds by methyl ester or amide formation and, depending on the method used, the resulting spectra provide information on sialic acid linkage by utilizing their different reactivities to the derivatizing reagents such that the linkage is revealed simply by mass difference [3, 4]. We have been systematically examining the negative ion fragmentation of different types of N-glycans [5–11] and in this report present negative ion collision-induced dissociation (CID) spectra and ion mobility properties of glycans containing N-acetylgalactosamine (GalNAc) terminating their antennae and their identification in the human immunodeficiency virus (HIV) envelope glycoprotein (Env) BG505 SOSIP.664 trimers expressed in HEK 293T cells.
| 5 | 0biomedical
| 0Study
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81,597 |
As defined by the ISCT29, our method allows the isolation of pluripotent mesenchymal muscle-derived stem cells from horse, human, dog and pig microbiopsies. Unfortunately, we were not allowed to use the entire panel of antibodies described by the ISCT for equine cells because the cross reactivity study showed us that CD73, CD19 and CD34 did not recognize the equine epitope. For humans, the results obtained were in accordance with the recommendations while for equine cells, only positivity for CD90, CD105 and CD44 and negativity for CD45 and MHCII was demonstrated. Even while it is known for human cells44, this is the first time that the expression of CD105 is described for equine skeletal muscle-derived stem cells. CD105, which is a component of the TGF beta-1 complex, has different important biological functions such as angiogenesis45 and growth induction at the joint/articular level. TGF beta-1 stimulates chondrocyte division as well as cartilage matrix synthesis but decreases the release of PGE2 by osteoarthritic synovial fibroblasts and hence decreases PGE2 stimulated matrix degradation in osteoarthritis46. CD105 expression thus appears to show excellent tissue regeneration characteristics to the obtained stem cells.
| 4 | 0biomedical
| 0Study
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286,856 |
After assessing the prognostic value of ATGs, as a next step; in order to increase the prognostic power of these individual markers out of these promising ones, we created an ATG based gene signature to predict prognosis of Tamoxifen treated breast cancer patients (Table 2 - see PDF). As indicated by the values: combined gene signature increased the statistical power of this signature with a highly significant p-value=8.3e-05 and HR=1.84 (1.35-2.51) (Figure 2A) to predict disease RFS or recurrence. ATG signature was found significantly predictive for distant metastasis free survival (DMFS) with a p-value= 0.0027 and HR= 2.03 (1.27-3.26) (Figure 2B). This ATG short signature may predict prognosis in ER positive breast cancer patients treated with anti estrogenic therapies.
| 4 | 0biomedical
| 0Study
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227,853 |
Variance in HPV vaccine uptake among Indigenous populations is well documented [20, 21, 37]. While quantitative research is essential for identifying health trends and disease spread, qualitative research is essential in exploring the stories and reasonings behind quantitative findings. Qualitative systematic reviews have the opportunity to uniquely inform policy decisions and to generate innovative solutions that successfully engage and directly benefit involved communities. Lack of knowledge is frequently correlated with lower vaccine uptake. While increased knowledge in communities would likely increase vaccine acceptance, the common sentiments expressed in this review of mistrust between individuals and healthcare systems [29, 32, 33] is deep-rooted in the colonial history of exploitation of Indigenous peoples. Educational programming will never have the capacity to resolve such profound issues. Addressing the aspects of health systems that currently function to preserve oppressive traditions is required to provide the fundamental human right of quality care to Indigenous peoples. Papers included in this review [29, 30] have highlighted various frameworks to consider when co-creating vaccine strategies with communities, such as the Ecological approach, that acknowledge the wider influences impacting vaccine-decisions and permit the development of more holistic and community-targeted initiatives.
| 4 | 0biomedical
| 2Review
|
119,513 |
Our studies revealed the central role of the DLX3 HD domain in mediating the DLX3-GCM1 physical and functional interactions. This is not surprising considering the HD domain also mediates the DLX3-MsxI and DLX3-Smad6 interactions60, 65. However, unlike in the latter cases where the DLX3-MsxI and DLX3-Smad6 associations interfere with the binding of the DLX3 HD to DNA and thus lead to loss of DLX3’s transcriptional activity60, 65, the DLX3-GCM1 interactions appear to have no effect on DLX3’s transcriptional activity32. Conversely, we speculate that the interaction with GCM1 might facilitate the association and binding specificity of DLX3 on the PGF promoter. The HD domain is known for promiscuous DNA binding with a general preference for motifs centered with the TAAT sequence62, 63, 66. Many HD proteins act in conjunctions with their binding partners to impart their DNA binding affinity and specificity63, 67. It is likely that interactions between DLX3 and its binding partners including GCM1 serve as a means to distinguish specific gene targets from other TAAT-rich sequences in the genome, depending on cellular contexts and physiological states. This is supported by the lack of DLX3 consensus binding sites on the PGF promoter region where both DLX3 and GCM1 localize in the proximal portion of the PGF promoter32. Notably, different binding partners would lead to variable regulatory outcomes in combination with DLX3. For example, DLX3 and ETS2 have been reported to synergistically transactivate the bovine Interferon-Tau and the CGA promoters in human trophoblast-derived cell lines in vitro 68, 69; and here we demonstrate that DLX3 and GCM1 antagonistically regulate PGF expression in human trophoblast-derived cells. Thus, we postulate that the DLX3-GCM1 interactions might affect specific functional activities of both factors from different aspects: while DLX3 inhibits GCM1’s transcriptional activity, GCM1 might facilitate the specificity of DLX3 binding on the PGF promoter.
| 4 | 0biomedical
| 0Study
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83,403 |
Besides the increase in oxidative stress, the excessive production of pro-inflammatory mediators is a key player to the intestinal damage progression in IBD. Concerning such mediators, both iNOS and COX-2 enzymes seem to play a synergistic role in inflammation onset and severity . Upregulation of these enzymes expression is known to be induced by activation of different signaling pathways, namely the nuclear factor κB (NF-κB) and the signal transducer and activator of transcription 1 (STAT1), whose expressions and activities have been reported to increase during intestinal inflammation . This work demonstrated that the treatment with anthocyanins could counteract drastically the strong overexpression of both iNOS and COX-2 enzymes induced by TNBS, while 5-ASA only counteracted COX-2 overexpression. Actually, the strong inhibition of COX-2 expression seems to be a crucial common mechanism underlying the anti-inflammatory actions of 5-ASA and ARF (Fig 7A). This observation is highly relevant given that this inducible form of COX is known to be upregulated in the inflamed gut of IBD patients , being a target for several drugs used in IBD, including 5-ASA . Regarding the effects on iNOS overexpression, the results obtained reinforced the much higher anti-inflammatory capacity of anthocyanins when compared to 5-ASA, as they inhibited almost completely the enzyme expression, in contrast with 5-ASA which did not show any significant effect (Fig 7B) despite being used in a much higher molar dose than that of anthocyanins.
| 4 | 0biomedical
| 0Study
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101,910 |
Surgical specimens of tumor tissues and paired normal adjacent tissues were obtained from LUAD patients who underwent surgery at the people's Hospital of Linyi City (Shandong Province, China) between April 2008 and Nov 2014. Informed written consents were obtained from all enrolled LUAD patients, and all LUAD patients had a complete five-year follow-up. All patients had never received any radiotherapy before surgery excision. All tissue samples were immediately frozen in liquid nitrogen after surgery.
| 4 | 0biomedical
| 0Study
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351,419 |
Reviewer #2: My major concern with the previous version of the manuscript has not been addressed. While the authors present an extremely detailed analysis of 14 bacteriophage genomes there doesn't appear to be any solid conclusion or impact from the study. The manuscript has been modified to make it clearer and easier to understand but the overall impact of the study remains unclear.
| 1 | 0biomedical
| 1Other
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291,222 |
In line with the general idea of sequential stages of development (Piaget, 2002), it was initially believed that children go through three stages of development in order to solve the task (Inhelder and Piaget, 1958). It was argued that around 5–8 years of age, children acquire an understanding that their actions can impact those of an object. Children thus begin to understand the impact of weight and distance on the scale. However, 5–8-year-olds do not seem to be able to successfully combine the values of weight and distance together. This coordination of information would be understood around adolescence (Inhelder and Piaget, 1958).
| 2 | 2other
| 1Other
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40,274 |
All patients were required to fulfill requirements according to WPATH Standards of Care prior to surgery . They had been receiving hormonal treatment for a mean period of 3 years (range: 18 months to 23 years). Testosterone treatment was discontinued two weeks before surgery in all patients.
| 4 | 0biomedical
| 0Study
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174,204 |
Nearly half of those who used the app said that they believed it increased their self-understanding. In particular, many believed that using the app enabled them to better understand their emotions and the individuals or situations that elicited those feelings. In doing so, some participants believed that the app made them more truthful about their emotions and what specifically they had accomplished that day:
| 2 | 2other
| 1Other
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330,660 |
Other women expressed concern about having the opportunity to follow some of the advice due to the conditions in which they were living:I have been in difficulties and to have a bath …you take your baby with you in your bathroom, bathroom is shared because we live in sharing house (BAME woman Int7).
| 1 | 2other
| 0Study
|
254,374 |
In this paper, the aerodynamic forces on conductors are numerically determined by means of computational fluid dynamics (CFD) and the aeolian vibration characteristics of conductor lines are investigated using the FE method. In addition, the stress distributions and fatigue lives of the transmission conductors under aeolian vibration are evaluated by a 3D refined FE model of the conductor segment and suspension clamp. The obtained results may provide foundation and instruction for the protection design of aeolian vibration and fatigue life estimation under aeolian vibration of transmission lines.
| 1 | 2other
| 0Study
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71,745 |
(A) Heatmap presentation indicates the fold-changes in expression of representative genes derived from microarray analysis. (B) Heatmap presentation indicates the fold-changes in expression of representative genes using qRT-PCR. Expression data were obtained from microarray analysis or qRT-PCR of 24-day-old Arabidopsis rosette leaf samples that were collected from 3 independent plants for microarray analysis (n = 3). UBQ10 was used as reference gene in qRT-PCR analysis. Relative expression levels are indicated by intensities of colors expressed in fold-change with saturation at 6. Red and blue colors indicate up- and downregulation, respectively. Note that not all data points shown in (a) passed the q-value < 0.05. M-C, kai2-2 well-watered control; M-D2, kai2-2 dehydrated 2 h; M-D4, kai2-2 dehydrated 4 h; W-C, WT well-watered control; W-D2, WT dehydrated 2 h; W-D4, WT dehydrated 4 h.
| 4 | 0biomedical
| 0Study
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375,890 |
Turland explained that the Glossary proposal would be automatically sent to the Editorial Committee if Art. 36 Prop. D was accepted. The Rapporteurs had commented that the proposed addition to Art. 36 Ex. 11 seemed to be beside the point because it concerned names published before 1953 and therefore Art. 36.2 did not apply. If Prop. D was accepted, the Editorial Committee should leave that Example unchanged and find a new one to illustrate the current proposal.
| 1 | 2other
| 1Other
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89,054 |
By combining the data of individual studies, we increased the statistical power to detect subtle associations, however,several limitations should be considered in our meta-analysis. Only studies published in the English and Chinese language were included in this meta-analysis; therefore, publication bias may have occurred. In addition, this meta-analysis was designed to analyze single polymorphism, a haplotype analysis may have been more powerful for finding significant associations with UC and CD. Finally, gene–environment interactions were not analyzed because of insufficient data.
| 4 | 0biomedical
| 0Study
|
112,121 |
With the gasoline vapours-induced toxicity protective role of vitamin A reported in this present work, it may be postulated that vitamin A can act as an antioxidant, preventing or reversing the toxic effects of the various reactive metabolites responsible for the hepatotoxicity, observed to be associated with exposure to gasoline vapors. The result of this work also indicated that the beneficial effect of vitamin A against gasoline vapors-induced hepatotoxicity was relatively higher in female than male rats. The specific mechanism of the observed relative sex-dependent hepatoprotective beneficial effect of the vitamin is a subject for further investigation. However, it may be concluded from the result of this study that vitamin A may be used to enhance recovery from, or prevent hepatotoxicity associated with exposure to gasoline vapors. Hence, this vitamin may be recommended at prophylactic dosages to those who are routinely occupationally exposed to gasoline vapors.
| 4 | 0biomedical
| 0Study
|
327,092 |
Yield 89%. Beige powder. Mp 92 °C, (methanol). 1H NMR (200 MHz, CDCl3) δ = 8.26 (d, J = 8.2 Hz, 1H), 8.09 (d, J = 8.2 Hz, 1H), 7.96–7.91 (m, 1H), 7.72–7.64 (m, 1H), 6.18 (qd, J = 8 Hz, J = 2 Hz, 1H), 2.52 (d, J = 2 Hz, 1H), 1.80 (d, J = 8 Hz, 3H). 13C NMR (50 MHz, CDCl3) δ = 166.4, 159.9, 150.5, 134.6, 128.8, 128.7, 123.7, 115.4, 97.0, 81.9, 73.7, 63.7, 21.2. LC-MS (ESI+) tR 4.73 min, m/z [M + H]+ 315.02/317.04/318.98. MW: 315.58 g/mol. Anal. Calcd for C13H9Cl3N2O: C, 49.48; H, 2.87; N, 8.88. Found: C, 48.96; H, 2.95; N, 8.93.
| 4 | 0biomedical
| 0Study
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337,569 |
AT9283 exhibits strong activity against several kinases . The ability of AT9283 to inhibit the growth and survival of tumor cells as well as xenografts has been demonstrated in imatinib-resistant BCR-ABL-positive leukemic cells , aggressive B-cell lymphoma and medulloblastoma . Several clinical studies have been completed on AT9283 as shown in Table 4 [107–111]. However, there have been no clinical or objective responses in patients in these trials because of the small numbers of patients.
| 4 | 0biomedical
| 0Study
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184,922 |
The isometric view of the 3D-printed microfilter chip and the interior structure’s schematic are shown in Fig. 5a, b. The device’s fundamental structure is a set of microchannels with decreased gap sizes in the cross-section working as a barrier in the flow direction (from 10 µm to 200 µm). The three weir-like, equally spaced barriers form gaps with the channel roof. Only particles smaller than the gap are permitted to pass over the obstruction, while larger particles will be captured and accommodated by the corresponding reservoir and collected later. The whole microparticle sorting system is shown in Fig. 5c. The system consists of three inlets for particle suspension (inlet 1), DI water (inlet 2 and 3), and four outlets for red particles (outlet 1), blue particles (outlet 2), green particles (outlet 3), and DI water (outlet 4). The working principle and sequences are shown in Supplementary Fig. 7 and Supplementary Movie 5. In phase 1, a certain particle mixture is introduced into the chip via inlet 1 with outlet 4 open. In phase 2, DI water flows in and out of the chip through inlet 2 and outlet 4, carrying particles to each corresponding reservoir. In phases 3–5, green, blue, and red particles are flushed by DI water coming from inlet 2 and 3 and recovered from outlets 3, 2, and 1 in order.Fig. 53D-printed microparticle sorting device.a Fabrication result of the microfilter chip (isometric view). b Schematic drawing illustrating the interior of the microfilter chip (not to scale, side sectional view). c Illustration of the working principle of the microparticle sorting system (top view). d–o Particle sorting behaviors with different doses. d, h, i Purity of the particles from each outlet. e–g, i–k, m–o Microscope images showing the sorted microparticles in each microfilter reservoir.
| 4 | 0biomedical
| 0Study
|
126,555 |
The NTZ-induced alteration in the S glycoprotein electrophoretic mobility pattern was mimicked by the NTZ active metabolite, tizoxanide (Fig. S3A), but not by other antiviral drugs, including chloroquine (10 µM), ribavirin (7.5 µM) and remdesivir (7.5 µM) (Fig. 2G).
| 4 | 0biomedical
| 0Study
|
89,191 |
Surveillance information for TB and TB/HIV is collated through the tuberculosis surveillance center and the Tuberculosis Registration Systems. Besides, CDC supplies all the case of TB, HIV diagnoses, with all tests following the principle of voluntariness. In the data set, it has covered the number of cases concerning HIV positive among TB people reported from 2007–2013 for each street in Urumqi. Therefore, the population data from Statistical Yearbook are able to be publicly available.
| 2 | 0biomedical
| 1Other
|
150,452 |
The utilization of wet fish, fish mince, by‐products, and weight loss due to washing is presented in Table 3. The study showed that meat utilization was higher in tuna than pangasius. The amount of by‐products produced was 55.45% and 45.38% for pangasius and tuna, respectively. Tuna produced 10% more yield of mince production than pangasius. The total mince was separated into two groups at 50:50 ratios to prepare fish ball from unwashed (UW) and washed mince (WM). The washing process showed significant weight loss, irrespective of the species. However, the washing process resulted in greater weight loss for pangasius mince (4.08%) than for tuna mince (3.66%) (Table 3). The individual characteristics of the fish muscles were a factor in weight loss: higher fat content in the white muscles of pangasius meat resulted in greater weight loss. On the other hand, the dark muscles and lower fat content in tuna resulted in less weight loss after washing. After the washing and dewatering process, 40%–50% of solids could be lost from the minced fish (Bakli et al., 2020). The result suggested that a significant amount (45%–55%) of by‐products are produced from inedible parts of the fish, which could be further utilized for preparation of other products, such as fish meal and fish silage. Ibrahim (2015) found that the fish‐processing industry produces more than 60% by‐products as waste, including head, skin, trimmings, fins, frames, viscera, and roes; the remaining 40% is edible fish muscle for human consumption. Department of Fisheries (DoF, 2013) reported that 25%–30% of fish comprises scales, guts, fins, bones, heads, and shells, which are discarded as waste during processing or preprocessing. On the other hand, in the washing process, there is a loss of valuable proteins, lipids, and minerals which are beneficial for consumer health. Losing such valuable nutrients in the name of improving textural quality is thought to be a serious waste of resources (Nowsad & Hoque, 2009). The by‐products and waste production varies based on fish species and size, the season, the postharvest or industrial preparation processes, and solid wastes generated from seafood factories (Ibrahim, 2015). In this study, efforts were made to utilize both the washed and unwashed mince from pangasius and tuna. By using the unwashed mince, unwanted loss of valuable nutrients could be minimized. Doing so, it would also substantially reduce the cost of production by increasing the weight of the final products, and the loss of materials would be low. However, the quality of unwashed minced‐based products and their shelf‐life in storage is a concern when compared with products from washed mince.
| 4 | 0biomedical
| 0Study
|
164,040 |
Antibody responses against viral pathogens are polyclonal and typically directed against several immunogenic structures including conformational and linear epitopes on these antigens. The choice, quality and conformation of an antigen highly influences specificity, sensitivity, and the overall performance of the serological assay. Here, we compared several SARS-CoV-2 antigens to identify the optimal antigens for a sensitive fluorescent bead-based multiplex assay, including two different RBD antigens. One was a synthetic, commercially available peptide. The second RBD antigen was expressed in mammalian cells, resulting in the closest homolog to expression of the natural viral protein after infection of a human host. The serological assay based on mammalian RBD antigen resulted in excellent sensitivity and specificity and a wide linear quantification range for antibodies in serum, while the assay based on the synthetic RBD peptide had a narrow quantification range and a poor ability to distinguish pre-COVID-19 sera without antibodies against SARS-CoV-2 from COVID-19 patient sera. The serological results suggest that the synthetic RBD peptide had a low structural homology to the natural viral RBD protein. In addition, the commercial peptide was truncated (74 aa) compared to the 210 aa mammalian expressed RBD antigen, possibly leading to missing antigenic epitopes of the synthetic peptide.
| 4 | 0biomedical
| 0Study
|
201,950 |
The chemical construction of the scaffolds was characterized by XRD and FTIR. As shown in Figure 1i, a wide diffraction peak can be observed at 21.4° in the 3D rGO/PPY spectra, which is attributed to graphene. This is because the GO had a low crystallinity for its irregular arrays of atoms in the three-dimensional structure. After being modified by Sr, several new peaks appeared, and the peaks at 2θ = 11.2°, 19.6°, 26.8°, 28.8° and 44.3°, corresponded to strontium salt . The characterization diffraction peaks of GO were not clearly shown in the 3D rGO/PPY/Sr; this is because the amount of GO is relatively low compared to that of strontium salt. In the FTIR spectra (Figure 1j), the peaks at 3438 cm−1, 1543 cm−1 and 1032 cm−1 indicate that -OH, C=C, and C-O bonds. Vibrational stretching at 2815 cm−1 indicates the C–H stretching of the aliphatic alkyl group. These are attributed to graphene oxide . The vibrational stretching at 1458 cm−1 indicated the presence of the carboxylate group. The peaks at 894cm−1, 660 cm−1 and 606 cm−1 corresponding to the carbonates (CO3−2) of the reacted SrCO3 were observed . It was indicated that Sr was successfully modified on the surface of the 3D rGO/PPY scaffold .
| 4 | 0biomedical
| 0Study
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252,324 |
In the public network of the Federal District and the surrounding region, all patients who require emergency ophthalmic surgery due to laceration of the eyeball are referred to the Base Hospital of the Federal District by the guidelines of the Urgency and Emergency Protocols of the Federal District Health Department since 2006 . Thus, the results obtained from sampling extracted from this hospital reflect the reality of the RIDE.
| 2 | 0biomedical
| 1Other
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236,167 |
One of the fast-growing alternative renewable energy forms that could serve as a replacement for fossil fuels is biomass energy. The suitability and quality of biogas to be produced by any selected biomass could be informed by ultimate analysis; hence, these factors necessitated the elemental, CHNSO, and investigative contents shown in Table 1. Carbon (39.98–43.08%), hydrogen (6.74–9.86%), nitrogen (1.34–1.53%), Sulfur (0.12–0.46%), and oxygen (46.69–51.82%) of cow dung, mango pulp, and Chromolaena odorata leaves are similar to those obtained for lignocellulose biomass investigated in past studies (Okolie et al.5; Kobra et al.13; Wannapokin et al.14; Dahunsi et al.34; Adegun and Yaru56: Fang et al.57). It is clear that all the biomass has low carbon contents and high oxygen contents, which are consistent with those reported for grasses and manure by Harpreet58 but inconsistent compared to coal by the same study. The results also indicated that the higher the oxygen concentration of typical biomass was, the lower the carbon content, which is observable in Table 1. Nitrogen and sulfur contents are reported not to be important in biofuel production because they tend to release harmful and toxic gases48. Therefore, negligible sulfur contents obtained for the selected biomass suggest their suitability for biogas production with a minute possibility of releasing voluminous toxic gases, which could negatively affect humans and the environment. Percentage contents of sulfur (0.46, 0.12, and 0.25) % and nitrogen (1.53, 1.34, and 1.51) % for cow dung, mango pulp, and Chromolaena odorata leaves, respectively, are considered acceptable because they imply low concentrations of oxides of sulfur and nitrogen present in biogas obtained as a result of their digestion53. Therefore, during biogas combustion, the possibility of releasing toxic gases that would otherwise cause undesirable environmental impacts is infinitesimal. These results match those obtained for similar lignocellulose biomass considered in the research conducted by Singh et al.53. Furthermore, the range of calorific values (13.77–16.16 MJ/kg) is indeed interesting and is found to be in accordance with the proximate and ultimate analyses that depict favourable levels of fixed carbon contents, i.e., above 13% and ash contents of less than 2%, respectively; with these results, the carbon contents promise to positively contribute to increasing the calorific values45. From Fig. 3, the calorific values of the selected biomass were all consistent with those obtained in previously studied lignocellulose biomass Jimoh et al.48; Rambo et al.59; Magdalena et al.60; Stelaski, et al.61. These results suggest the characteristic similarities of lignocellulosic biomass reported in the literature; however, slight variations observed in the calorific values presented in Fig. 3 could be ascribed to the locality of the biomass, climatic and environmental states, discrepancies in determination processes, nutrition, and chemical structure of the types of biomass investigated48,49,62. The predicted calorific values (using Eqs. 10–12, developed by Yin35, Sheng and Azevedo36, and Boie37, respectively) from those experimentally obtained in this study. This could be a result of inadequate data used for modeling on the part of the authors who developed the models because the greater the data point, the greater the coefficient of correlation (R-square value) tends towards unity and consequently enhancing the accuracy of the model.Figure 3Calorific values for previous and present studies.
| 4 | 2other
| 0Study
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102,491 |
Additional analysis of the expression profiling data found altered levels of molecules known to regulate the degradation, stability and activity of p53. We found significant increases in expression of MDM2 and MDM4, which target p53 for ubiquitination and degradation or inhibit its activity respectively. Higher levels of MDM2 and MDM4 would presumably result in less p53 and therefore reduced pathway activity. However, in contrast we found significantly reduced levels of the deubiquitinating enzymes encoded by USP2 and USP7 in cSCCHN with clinical PNI compared to tumors with incidental PNI or no neural involvement. Both USP2 and USP7/HAUSP target MDM2 and lead to its degradation25. It is also interesting to note that USP7 also protects p53 from degradation3031. Expression of RASSF1 was also significantly up-regulated in the clinical PNI samples. The RASSF1 protein disrupts the interaction between MDM2, DAXX and USP7/HAUSP32, which would promote MDM2 ubiquitination and therefore result in stabilization of p53 and increased activity. These results presented here may suggest the complex balance of molecules controlling degradation, stability and activity of p53 is disrupted in cSCCHN with clinical PNI.
| 4 | 0biomedical
| 0Study
|
285,457 |
Response: Thank you for your comment. The coding for histopathological class relied on the type of cervical lesion observed. For example, if one of the diagnosed cervical lesions was ‘benign’ it was coded ‘1’ and other respective classes i.e., precancerous and cancerous lesions were all coded ‘0’. This coding was done for all the 145 cervical biopsied samples except for all non-definitive diagnosis samples were all coded ‘0’. Moreover, correlation variables in Table 3 have been ordered in as follows: age, benign, precancerous, cancerous, TOP2A and p16.
| 2 | 0biomedical
| 0Study
|
374,734 |
As a cross-sectional study, our data revealed a potential relationship between disease progression and necrotic involvement. We found that at the time of diagnosis, 43 of 50 (86%) hips with type I necrosis and 32 of 61 (52%) with type II necrosis had already progressed to femoral head collapse, and there was no collapsed hip in type III, indicating that in the type I hips appear the higher risk of collapse compared with other two types. The influence of the location of the lesion is not demonstrated in the Ratliff classification. Therefore, we attempted to use the JIC classification as a complement to address the deficiency of Ratliff’s classification, principally as a result of setting a subclassification of Ratliff’s type II AVN. It is widely accepted that the JIC classification is a practical method for predicting the risk of femoral head collapse in adult necrosis of the femoral head with confirmed intra- and interobserver concordance . There is no doubt that all the cases of Ratliff’s type I AVN were classified as JIC stage C2 (Fig. 4); however, the definition of Ratliff’s type II AVN is vague. The partial involvement of necrosis can also be classified as JIC stage C1 or C2 (Figs. 5 and 6). Both of these conditions involve the lateral part of the femoral head; however, in the latter stage, AVN encroaches extensively beyond the lateral margin of the acetabulum and induces the highest risk of femoral head collapse. In the current study, at the time of AVN diagnosis, correlation analysis indicated a significant positive relationship between disease stage and JIC classification. In detail, 82.3% of type C2 hips and 57.5% of type C1 hips progressed to femoral head collapse. Further multivariate logistic analysis also demonstrated that the JIC classification showed a stronger correlation with femoral head collapse than did Ratliff’s classification. Fig. 4The anteroposterior radiographs of Ratliff type I avascular necrosis after pediatric femoral neck fracture. Femoral neck fracture occurred at age of 14 years (a) and avascular necrosis was diagnosed 16 months later (b), type C2 according JIC classification, presenting severe femoral head and hip subluxationFig. 5The anteroposterior radiographs of Ratliff type I avascular necrosis after pediatric femoral neck fracture. Femoral neck fracture occurred at age of 12 years (a) and avascular necrosis were diagnosed 8 months later (b), and JIC type C2, presenting collapsed femoral headFig. 6The anteroposterior radiographs of Ratliff type II avascular necrosis after pediatric femoral neck fracture. Femoral neck fracture occurred at age of 10 years (a) and avascular necrosis were diagnosed 5 months later (b), and JIC type C1, presenting non-collapsed femoral head
| 4 | 0biomedical
| 0Study
|
290,412 |
Scanning electron microscope (SEM) was used to observe the ultrastructural changes of the duodenum. Samples were rinsed twice in cold PBS and fixed with 2.5% glutaraldehyde solution overnight at 4°C. After being fixed, the tissues were trimmed into 3 mm3 and washed three times with precooled PBS, followed by successively dehydration using 30, 50, 70, 85, 95, and 100% alcohol, the tissue blocks were dried in the dryer and sprayed with gold. Then, Geminisem 300 Zeiss field emission scanning electron microscope system (GeminiSEM 300, Carl Zeiss, Germany) was applied to observe and photographing the changes in morphological structure of duodenum.
| 4 | 0biomedical
| 0Study
|
121,840 |
Finally, right-wing authoritarianism must not be conflated with political conservatism. For this reason, in addition to RWA, participants were also presented with three items to assess their degree of liberalism versus conservatism in the social, moral or fiscal domains. These items were adapted from Helzer & Pizarro (‘When it comes to social/moral/fiscal issues, how would you describe your political attitudes?’). Participants reported their responses on three separate seven-point scales ranging from 1 (very conservative) to 7 (very liberal). The responses were subsequently reverse-coded to make their interpretation coherent with the other scales (i.e. high scores = high level of conservatism).
| 1 | 2other
| 0Study
|
313,942 |
The goal of the pilot study was to select two subsets of six texts with two open-ended and two true-false questions per text that met the following criteria: First, text-question subsets that elicited ceiling or bottom effects in one of the open-ended questions or in more than one of the true-false questions were removed. We expected greater ceiling effects for true-false questions. Therefore, piloting three true-false questions allowed us to exclude one from each text-question set without removing the whole text-questions subset from the sample. Additionally, each sample of true-false questions at both measurement points included 6 true-false questions that were correct and 6 questions that were incorrect. Second, to ensure a suitable range of variance in question difficulty, we chose text-question sets that provided together a similar amount of easy (~ 30%), medium (~ 40%) and difficult (~ 30%) open-ended and true-false questions, for both age groups at both measurement points. And third, to make a comparison between the two age groups most reliable, for both age groups the same subsets of 12 texts (in a difficult and in an easier form) were chosen.
| 4 | 0biomedical
| 0Study
|
66,076 |
Hong Kong has one of the lowest smoking prevalence in developed regions as a result of strong tobacco control measures. The prevalence continues to decline, but appeared to be stable at about 11% in the last five years . Boosting quit rate to lower the burden of smoking-related illnesses is of public health concern, particularly in the nonusers of smoking cessation services. In our study, living with smoker(s) was significantly associated with lower odds of intention to quit and smoking cessation among ever smokers in the general population, where smoking cessation services are scarce. These associations were also observed, but became statistical non-significant in the prospective analysis, probably due to insufficient number (only seven baseline daily smokers who lived with smokers(s) had quit smoking during follow-up). Our study has provided the first evidence in a real life general population setting that living with smoker(s) is linked to lower odds of intention to quit and smoking cessation in Chinese adult smokers.
| 4 | 0biomedical
| 0Study
|
309,257 |
Before our study, there are two contrary reports regarding whether UL44 can be sumoylated (Sinigalia et al., 2012; Kim et al., 2014). Our studies confirmed that UL44 was a target for sumoylation and could be effectively conjugated with SUMO-1. We further determined 410lysine, located at the extreme carboxy terminus of UL44 and within a ψKxE consensus sumoylation motif, as the major sumoylation site of the protein. Mutation of 410lysine at UL44 carboxy-terminal strongly but not completely reduced the sumoylation capability of UL44, suggesting that the lysine within this ψKxE consensus motif is the major sumoylation site of UL44, and there are non-consensus lysines serving as sumoylation sites also. More importantly, although the mutation of 410lysine had no effects on subcellular localization or protein stability of UL44, we found that the removal of 410lysine sumoylation site enhanced both viral DNA synthesis in transfection-replication assays and viral progeny production in infected cells for HCMV, indicating a negative modulation of sumoylation on HCMV DNA replication and virus production.
| 4 | 0biomedical
| 0Study
|
296,994 |
The results are shown in Table 2. We test the selected 16 studies of SW technology with the ten criteria. Three of them obtain a score of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$9{-}10$$\end{document}9-10 within the good level, which the rate of the studies in all 16 studies is 18.75%. Seven of the 16 studies obtained medium levels scores (i.e., \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$6 {-}8$$\end{document}6-8), that is at a rate of 43.75%. Six of the 16 studies fall in the poor levels with \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$3{-}5$$\end{document}3-5 scores, that is in a rate of 37.5%. For the results of each criterion, 13 of the 16 studies match the first, second, and fourth, i.e., a rate of 81.25%. These three criteria are the best matched in the studies. By contrast, the third and eighth criteria are matched by 8 of the 16 studies, i.e., a rate of 50%. The other five criteria are matched by more than 50% but less than the best of 81.25%. These ten criteria in the SW technology index cover the mainstream criteria in these studies. However, many current studies only applied some of these ten criteria to the design of SW technology and therefore get low scores. We conclude that (1) the current situation of the work in SW technology is with casual even chaotic and non-standardized development and (2) the index is a useful standard to guide and evaluate the work of SW technology. We will further provide an in-depth discussion of the results in “Discussion” section.Table 2The validation of ten criteria in the Semantic Web technology index.StudiesAuthors, yearDataEvaluationKnowledge processAccessibilityScoreRate (%)1234567891025Auer et al., 2007++++++++++1018.7527Tanon et al., 2020++++++++++1029Liu et al., 2020++−+++++++948Dhandapani et al., 2021++−++−++++843.7549Bean et al., 2017++−++++−++850Shi et al., 2017++++−++−+−851Malas et al., 2019+++++−+−++852Xu et al., 2020−−+++++−++753Liu et al., 2020++−−+−++−+654Sosa et al., 2019++++++−−−−655Rotmensch et al., 2017++−+−−++−−537.533Yu et al., 2017+−−−++−+−−456Weng et al., 2017++−+−++−−−457Chen et al., 2020−+++−−−−+−458Hasan et al., 2016−+++−−−−−−359Rubio et al., 2021+−−−−−−+−+3Rate of +81.25%81.25%50%81.25%62.5%56.25%68.75%50.0%56.25%56.25%All 16 selected representative studies are evaluated with a quantified score of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$0{-}10$$\end{document}0-10. \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$+$$\end{document}+ (−) donates that the study matches (unmatches) the corresponding criterion.
| 4 | 0biomedical
| 0Study
|
112,927 |
We identified several new features of the auditory region that–contrary to the traditional morphological interpretation of relationships–ally Miocaperea with Caperea, cetotheriids and, in some cases, balaenopteroids, but not balaenids. Specifically, Miocaperea shares with (i) Caperea and the cetotheriid Herpetocetus the presence of an angled, medially projecting anteromedial corner of the pars cochlearis (Fig 1) ; with (ii) Caperea, Herpetocetus and certain (stem) balaenopteroids a lateral tuberosity of the periotic that extends anteriorly past the level of the anterior pedicle of the tympanic bulla ; with (iii) Caperea, the cetotheriids Herentalia, Metopocetus and Piscobalaena, and some balaenopteroids the extension of the lateral lamina of the pterygoid on to the anterior process of the periotic (Figs 1 and 3); and with (iv) cetotheriids, but not Caperea, the presence of an enlarged paroccipital concavity on both the anteroventral surface of the exoccipital and the posteroventral surface of the compound posterior process of the tympanoperiotic (hereafter, “posterior process”). The enlargement of the paroccipital concavity–previously misidentified as the facial sulcus –is particularly striking, and accompanied by the development of a posteroventral flange (sensu ) flooring the facial sulcus (Fig 1).
| 4 | 0biomedical
| 0Study
|
336,375 |
The results of GEPIA manifested that the expression of VIP was significantly positively related with pathological stage (P=0.027), while the expression of CLCA4, GUCA2A, GCG, SST, MS4A12, PLP1, CHGA, PYY, and GUCA2B was not as (Supplementary Figure S4B). Kaplan–Meier analysis showed that PCRC patients with low expression levels of CLCA4, and MS4A12 had poorer overall survival times than those with high expression levels (P<0.05; Figure 3A,E). PCRC patients with high expression levels of GCG, SST, PLP1, and CHGA had poorer overall survival times than those with low expression levels (P<0.05; Figure 3C,D,F; Supplementary Figure S5A). However, there was no statistically significant effect on OS associated with the expression of GUCA2A, PYY, VIP, and GUCA2B (P>0.05; Figure 3B, Supplementary Figure S5B–D).
| 4 | 0biomedical
| 0Study
|
85,852 |
We plotted individual baseline rSO2 and median rSO2 values to visually compare the range and central tendency for each device (Fig. 3). The median baseline rSO2 prior to desaturation trended higher for FORE-SIGHT by approximately 10 percentage points compared with INVOS, although the differences were not statistically significant. Median INVOS and EQUANOX baseline rSO2 values differed by less than 2 percentage points. INVOS reported a wider range of individual baseline rSO2 values (54–93%) compared to EQUANOX (58–84%). FORE-SIGHT reported a narrower range of baseline values (69–81%) than both INVOS and EQUANOX.Fig. 3Individual baseline and median rSO2 values prior to desaturation #1 (a) and #2 (b). INVOS demonstrated a wider spread of individual baseline values than both EQUANOX and FORE-SIGHT. Although the median FORE-SIGHT baseline rSO2 was consistently higher than INVOS by approximately 10%, the differences were not statistically significant (two-tailed Wilcoxon Signed-Rank test for paired samples)
| 4 | 0biomedical
| 0Study
|
148,871 |
If the FFR is to be used in clinical practice as a potential marker of future language impairment, it is necessary to establish reference values for each age range. This study is the first to provide reference values for latency, amplitude, and slope for infants using the Smart EP module. However, it will only be possible to identify normal and altered test results if there are standards with a strong scientific basis.
| 3 | 0biomedical
| 0Study
|
54,711 |
Mainstream services often reflect a feminist approach; women who are victims of violence are supported to leave their relationship, develop self-sufficiency and learn to take care of themselves and their children. First Nation's women believe they are married for life, therefore, do not envision an outcome where they leave their husbands. Their goal is to unite the family and put to rest the intergenerational trauma that has ruled their lives for centuries (Robertson, 2010).
| 1 | 2other
| 1Other
|
75,480 |
Great progress has been made on the biochemistry of elongation, although the exact composition of complexes is unclear due to biological context, biochemical complexity, and/or methodologies used in various studies. For the majority of genes, after transcription of about 20 to 50 nucleotides, RNAPII pauses when 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole (DRB) sensitivity inducing factor (DSIF, a heterodimer of Suppressor of Ty 4 and 5 (Spt4 and Spt5)) and negative elongation factor (NELF) protein complexes bind to the RNAPII and transcript [7–9], to form a DSIF-NELF complex promoting the pausing of RNAPII [10–12]. Paused RNAPII is released by the positive transcription elongation factor b complex (P-TEFb), which phosphorylates the DSIF and NELF complexes as well as the carboxy-terminal domain of RNAPII (CTD) [13–17]. The catalytic and regulatory components of P-TEFb are Cyclin-dependent kinase 9 (Cdk9) and Cyclin T respectively [18–20]. In addition to P-TEFb, Cdk9 can also form a complex with Cyclin K . Recruitment of P-TEFb kinase dissociates NELF, transforming DSIF into a positive elongation factor, triggering elongation .
| 5 | 0biomedical
| 0Study
|
1,518 |
Animals were weighted by a special electronic balance (YIY-OCS-1T, made by Shanghai YiYu Electronics Technology Co., Ltd., with a sensitivity of 100 g) before morning feeding and grazing activities, at the beginning and every 15 days of the 135-day experiment. The total live-weight gain was calculated as the difference between final live-weight and initial live-weight; average daily live-weight gain (ADG) was defined as total live-weight gain divided by experiment time (day); gain rate was calculated by ratio of total live-weight gain to initial live-weight; feed efficiency was defined as ratio of total DM consume to total live-weight gain; breeding profit was calculated by the difference between the benefit of live-weight gain and total feed cost. Net economic benefit (NEB) was determined by the following equation, NEB=(Gw×Pm)∕(Te×DMI×Pd)−1
| 4 | 0biomedical
| 0Study
|
78,015 |
The within-trial economic analysis (conducted by T. H. S. using Stata/SE 14.1) compared the costs and QALYs in the standard care and intervention groups from the perspective of the NHS. We attached published unit costs (2014–2015 UK pounds sterling) [29–31] to individual-level quantities of resource use (S1 Table) and estimated the mean cost per participant incorporating the cost of the intervention and wider healthcare resource use (primary care, secondary care, and medications).
| 4 | 0biomedical
| 0Study
|
300,966 |
Agreement on structural glaucomatous damage was evaluated in three studies . When performing slit-lamp examination, the optometrist’s cup/disc ratio was comparable to that of GEs and the optometrist’s ability to decide whether or not an optic disc was glaucomatous was also found to be good (sensitivity and specificity ~83.0%) . When evaluating fundus photographs on stability, the agreement between all HCP (GEs and optometrists) of the SC-MC was found to be good and comparable to the agreement between GEs alone. Banes et al. demonstrated the (dis)agreement rate to be independent of the cup/disc ratio values. Only Shah et al. examined the agreement on OCT interpretation between all HCPs, including GEs and optometrists, and found it to be “fair”. The study of Phu et al. evaluated the agreement between optometrists and ophthalmologists on gonioscopy. The agreement in the exact assessment of the angle was “fair to moderate”. Consistency with a final diagnosis, whether the angle was open or closed, was 93.4% .
| 4 | 0biomedical
| 0Study
|
366,759 |
Autophagy is important for proteins turnover and cell homeostasis, and participates in the maintenance of stem-like features and the remodeling of cells undergoing differentiation (Sotthibundhu et al., 2018). The role of autophagy in odontoblasts has recently been explored. Autophagy was detected in differentiated odontoblasts during embryonic and postnatal stages (Yang et al., 2013). In our studies, we found ATG5 and LC3 to be highly expressed in differentiated odontoblasts in incisors. Expression of LC3 and ATG5 also increased during odontoblast differentiation in vitro. Additionally, recent studies have also found the autophagic machinery to be involved in autophagy-dependent secretion of many proteins, such as TGF-beta, IL-1beta and some extracellular matrix components (New and Thomas, 2019). Many activities, such as protein transport, organelle recycling, and secretory activities, occur during odontoblast differentiation that are closely with autophagy activation. It is clear that autophagy is highly activated and required during odontoblast differentiation.
| 4 | 0biomedical
| 0Study
|
276,020 |
Looking for a possible effect of DHPS on the beta cell mass throughout the development of diabetes, Levasseur et al. generated a tissue-specific inducible deletion of dhps in pancreatic islets of mice. When fed a high fat diet (HFD) these mice developed diabetes with a lower level of glucose tolerance. In addition, unlike the HFD-fed controls, these mice were unable to gain beta cell mass (an indicator of obesity-induced diabetes) and this was due to a lack of cell proliferation rather than increased cell death. The cell proliferative phenotype in dhps-KO mice was attributed to a decrease in cyclin D2 expression, while the coding Ccnd2 mRNA (key mRNA which is crucial for beta cell proliferation) remained unchanged. The authors concluded that these results suggest a reduced translational initiation of Ccnd2 in DHPS deficient mice pancreatic islets. In addition, the pro-proliferative effect of c-Myc (a key regulator of cell proliferation) in mouse and human pancreatic islets is impaired when DHPS is inhibited. Finally, eIF5A hypusination links increased insulin demand caused by insulin resistance with beta cell proliferation to maintain glucose homeostasis . These data obtained from different teams revealed that opposite results could be obtained if we consider a genetic deletion of eIF5A versus a pharmacological inhibition using GC7. In the first case beta cell proliferation is impaired while in the second the beta cell mass is increased together with an improvement in glucose tolerance (Fig. 4).
| 4 | 0biomedical
| 0Study
|
392,383 |
Furthermore, half of the cross-sectional studies suffered on potential high risk of bias. Again, issues regarding the sample size definition, poor descriptions of non-respondent and lack of matching were the main shortcomings for these studies (Supplementary Table 4).
| 2 | 0biomedical
| 0Study
|
257,021 |
DH, GJ, and RB are employees of Unilever. FW is on secondment as Executive Chair, Medical Research Council. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
| 1 | 2other
| 1Other
|
190,681 |
The inclusion of inexpensive food and beverage industry co-products in animal diets has traditionally been used as a means of decreasing feed cost and as an alternative to disposal, which has an associated economic, as well as environmental impact . The use of industry co-products, however, requires careful management of diet formulation as co-products such as whey can be high in salt, and may also increase water requirements of pigs . Another challenge of co-product inclusion is the variability in microbial and nutritional composition between different products and indeed batches of the same co-product . Nonetheless, depending on availability, continuity and consistency in supply and proximity of co-products to a given farm, it can be a viable means of reducing feed costs. Another potential benefit of liquid co-product inclusion is that many sugar-rich food and beverage industry co-products have undergone fermentation by LAB and/or yeast and, therefore, have a pH of ~3.5–4.5 resulting from the formation of organic acids. The resultant lactic acid, and to a lesser extent acetic acid, are known to exhibit antimicrobial activity against pathogenic and spoilage microorganisms . In a survey of liquid feeding practices in the finisher section of commercial Irish pig units, O’Meara et al. found that 3 of the 8 units surveyed included either pot-ale syrup and/or liquid whey in their diets. The study found that on these pig units, Enterobacteriaceae counts in LF delivered freshly to troughs tended to be lower compared to units that did not use co-products. Additionally, E. coli counts were reduced in residual LF remaining in troughs just prior to the next feed-out on the units that used liquid co-products. Dietary co-product inclusion also reduced mould counts in the mixing tanks, as well as in fresh and residual LF in troughs, while also reducing the pH of the feed in the mixing tanks and of the fresh feed in the troughs .
| 4 | 0biomedical
| 0Study
|
210,787 |
Most publications mainly focus on the ionic conductivities and transport properties of electrolytes before implementing them in full systems (usually using LiFePO4 (LFP), LiMn2O4 (LMO) or LiNixMnyCozO2 (NMC) as a positive electrode and Li, Li-In or Li4Ti5O12 as a negative electrode). One of the current objectives for ASSLBs, and consequently the aim of the solid electrolyte, is to be able to operate at a high potential with high voltage cathode materials (NMC, NCA) working above 4.2/4.3 V vs. Li+/Li while being compatible with metallic lithium at the negative electrode. It is worth noting that there is a significant difference between being stable over one cycle (for example linear sweep voltammetry experiments), being stable for a few hundred cycles (what most of the publications report) and for thousands of cycles (industrial requirement). One way to predict the stability of the system during cycling is by analyzing the coulombic efficiency (CE). However, the fading of CE during cycling is rarely well understood and can be attributed to many factors such as the formation of dead Li, a bad cell assembly, and also to the degradation of the electrolyte. Thus, accurately assessing the stability of the electrolyte is one of the significant parameters that must be addressed due to the critical role of the ESW in the energy density and durability of the entire ASSLB. However, if the standardization of ionic conductivity measurements starts to appear , ESW, while recognized as a parameter of importance, comes almost secondary when compared to ionic conductivity. Thus, it is often inconsistently reported, determined, or evaluated.
| 4 | 0biomedical
| 0Study
|
29,327 |
Immune checkpoint inhibitors have demonstrated promising benefits for patients with GBM in several studies. In 2014, the first large phase III trial of nivolumab plus ipilimumab in recurrent glioblastoma (NCT02017717) was initiated. Besides, pidilizumab, as another PD-1 inhibitor is on clinical phase I and II testing the safety, toxicities, and efficacy in Relapsed GBM (NCT01952769). Representative clinical trials of checkpoint inhibitors in glioblastoma and brain metastases were summarized in Table 1.
| 4 | 0biomedical
| 0Study
|
131,663 |
To increase the chance of survival, some viruses appear to have adopted the strategy of damaging the host cell mitochondrial DNA. Since mitochondria function as a source of energy and play an important role in antiviral immunity, it is possible that damage to mitochondrial DNA may help in evading mitochondrial antiviral immune responses (1). Some viruses have found different ways to degrade cytosolic mtDNA. Indeed, dengue fever virus induces mitochondrial elongation through the viral protein NS4B, and mitochondrial hyperfusion appears to have a proviral role in reducing IFN response (52). In the same vein, influenza virus-encoded NS1 protein, which interacts with the cytosolic mtDNA, leads to a reduction in the induction of IFN (5). As A3 DNA mutators are downstream of IFN induction, another viral strategy could be to exclude A3 from replication and transcription sites. Recent studies reported the relocation of A3A from the nuclear to cytoplasmic compartment, as is the case during HSV-1 infection (53, 54). This was observed for a variety of viral proteins, in particular with HSV-1 and ICP6, EBV and BORF-2, and KSHV and ORF61 (53, 54).
| 5 | 0biomedical
| 0Study
|
49,010 |
Our research was conducted as a large project called the Adachi Child Health Impact of Living Difficulty (A-CHILD) study, which examined the health and living environment of children in the first grade in all elementary schools (69 schools) in Adachi City, Tokyo. Adachi City, known as a deprived area in Tokyo (e.g., the unemployment rate was 7.1% in 2010 (30), which is higher than Japan's average of 3.1% in 2016 (31) is keen on tackling with child poverty, which made the current study feasible. Participants were young Japanese children, and the present study has gathered more data than that in a previous study conducted in the United States (11). In the present study, we aimed to examine the association between leaving young children aged 6 or 7 years at home alone and their mental health, focusing on both positive and negative aspects; that is, resilience, difficult behavior, and prosocial behavior, adjusting for the effects of social capital, status of household, and caregiver's mental health.
| 4 | 0biomedical
| 0Study
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234,236 |
The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.
| 1 | 0biomedical
| 1Other
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310,597 |
Myofibroblasts play a key role in tissue fibrosis, and α-SMA expression is a significant marker of myofibroblast activation . The proportion of myofibroblasts in the overall fibroblast population is closely associated with the severity of fibrosis-related diseases . For an example, a recent study indicated that α-SMA expression was increased in fibroblasts cultured from SSc skin biopsies, which is consistent with the transforming growth factor-β (TGF-β)-induced increase in α-SMA levels observed in vitro. Furthermore, a recent single-cell RNA-sequencing analysis identified different subgroups of fibroblasts in human skin samples . In this study, we found that α-SMA levels were elevated both in antagomiR-16-5p-treated and NOTCH2 overexpression plasmid-treated HSFs, suggesting that both miR-16-5p inhibition and NOTCH2 overexpression can activate myofibroblasts in HSFs.
| 4 | 0biomedical
| 0Study
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97,789 |
Biosphere 87Sr/86Sr values higher than 0.7165, such as those this individual exhibits, have been recorded in regions further afield, in areas such as the Cairngorm mountains in north‐east Scotland, over 500 km from Penywyrlod (Evans et al., 2010). However, current Bayesian modelling suggests that Neolithic material culture and practices may only recently have become established within this region of Scotland at this time, beginning to appear in this area from the decades around 3800 cal BC (Bayliss et al., 2011a). Biosphere 87Sr/86Sr values close to 0.7170 have similarly been recorded in Northern Ireland (Snoeck et al., 2016). However, the attribution of this individual to this area may also be problematic on archaeological grounds as at present there is limited evidence to suggest that Neolithic material culture and practices were established in Ireland any earlier than the 38th century BC (Bayliss et al., 2011a, pp. 805–808; Cooney et al., 2011, pp. 663–668; Schulting et al., 2012, pp. 31; Whitehouse et al., 2014).
| 4 | 0biomedical
| 0Study
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306,620 |
Some of these benefits have also been highlighted by others. 5 Through our participation in the research project, some of us fulfilled an obligation to participate in extracurricular activity required as part of our secondary school degree. Moreover, participation in the project was beneficial to some of us who applied to be accepted as university students abroad, two of us were invited to participate in a reference group in another research project, and one member got a position as a research assistant at another university.
| 1 | 2other
| 1Other
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120,355 |
Ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO, EC 4.1.1.39) is believed to be the most abundant enzyme on Earth (Ellis, 1979; Raven, 2009). It is the key enzyme of the autotrophic Calvin-Benson-Bassham (CBB) cycle and catalyzes the carboxylation of ribulose-1,5-bisphosphate (RuBP) to 3-phosphoglycerate (3-PGA) (Berg, 2011). Since the CBB cycle is estimated to account for most of Earth’s net primary production (>99.5% of 105 × 109 tons/year) (Field et al., 1998; Raven, 2013), it is important to understand RubisCO expression and its activation in many different organisms.
| 4 | 0biomedical
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49,998 |
Infection of IECs with the AToCC strain BAA-1457 significantly affected the expression of 6810 transcripts, of which 1394 were differentially expressed at levels greater than 1.5-fold or less than 0.75-fold (Fig. 1A, Supplementary Data 1). A range of pathways and processes were found to be significantly enriched in each of the upregulated and downregulated datasets (Figs 2A,B and 3A,B, Supplementary Data 2). Pathways and processes related to epithelial-to-mesenchymal transition (EMT) were enriched in the upregulated dataset, in particular NOTCH signaling and Hedgehog signaling (Figs 2A and 3A). Processes related to cytoskeletal remodeling and cellular junctions, as well as inflammatory responses (IL-2, IL-5, IL-18, CCL2, TNF, IFN, and TGF-β signaling) were also upregulated following infection with C. concisus BAA-1457 (Figs 2A and 3A). In contrast, cystic fibrosis transmembrane conductance regulator (CFTR)-associated pathways, cell cycle processes (S-phase and others), and DNA damage processes were all downregulated following infection (Figs 2B and 3B).
| 4 | 0biomedical
| 0Study
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388,974 |
The pandemic that is most often mentioned in the context of COVID-19 is the 1918–1919 influenza pandemic (see also the 1976–1977 swine flu epidemic in the USA (Neustadt and Fineberg 1978)). It has been estimated that about 500 million people became infected with the influenza virus (one-third of the then world’s population) and about 50 million people died (a mortality rate of about 10%). Like COVID-19, the disease was another example of a zoonosis (a disease transmitted to humans from non-human animals), being caused by an H1N1 virus with genes of avian origin (Jordan et al. 2019), but, unlike COVID-19, mortality seems to have been highest in people younger than 5 years old, 20–40 years old and 65 years and older (Fig. 1).Fig. 1Camp Funston, at Fort Riley, Kansas, during the 1918 influenza pandemic. Taken from https://upload.wikimedia.org/wikipedia/commons/b/bc/Camp_Funston%2C_at_Fort_Riley%2C_Kansas%2C_during_the_1918_Spanish_flu_pandemic.jpg
| 4 | 0biomedical
| 2Review
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38,245 |
The process of routing to the sink is shown in Figure 3b. When the source node generates data, it uses the shortest routing algorithm to send data to the sink according to the routing hop count to the sink, forming a routing path as shown in Figure 3b. Then, the routing hop count in the routing path is set to 0 and the routing hop count to the sink is broadcasted. Affected nodes near the routing path update their routing hop counts to reach the sink. As shown in Figure 3b, the gray nodes indicate that their routing hop counts to the sink have been updated.
| 1 | 2other
| 1Other
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188,783 |
The datasets and analyses presented in this paper also have limitations. We analyzed shapes from just one database (Carlier et al., 2016) and, for each dataset, we selected only ten shapes for analysis, and only conducted two-sample tests. While we do not expect analysis of datasets from other databases to appreciably affect this paper’s messages, we acknowledge that analyses of relatively small samples, and just one simple experimental design, fully exposes neither the advantages nor disadvantages of the proposed analysis framework. We selected just ten shapes for each dataset primarily to emphasize that the proposed parametric procedure is sufficiently sensitive to detect morphological effects for small sample sizes. The specific ten shapes were selected in an ad hoc manner to emphasize particular concepts including, for example: interpretation agreement between the proposed and landmark methods’ results, and the opposite: interpretation disagreement. Since these datasets were selected in an ad hoc manner, from a single database, and with only two-sample analyses, the reader is left to judge the relevance of these results to other datasets and experimental designs.
| 3 | 0biomedical
| 0Study
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395,999 |
The combined activity and interactions between peptides, pexiganan, purine and pyrimidine analogs against S. aureus in MHB were determined using isobolographic combinations, also called the checkerboard assay method, (8 × 8 matrix of concentrations combinations) (35). In a 96-well plate, 50 μl of pexiganan at 4x MIC concentration was 2-fold serially diluted ranging from 32 to 0.25 μg/ml in the direction of the columns from 1 to 8. In another 96-well plate, 100 μl of nucleoside analogs at 8x MIC concentrations were prepared identically to the previous plate, but diluted in the direction of the rows from A to H. Half of the content (50 μl) of each well from the analog drug plate was transferred to the corresponding well of the plate containing pexiganan in an equal 1:1 mix fashion, halving the concentration of both compounds. In the same plate, the columns 9 and 10 were used to serially dilute both the peptide and the analog drug in the same concentrations that were present in the combination to compare single compounds vs. combination. Columns 11 and 12 were used as a control, by inoculating column 11 wells with bacteria without any drug and leaving columns 12 only with the same volume of MHB as a media contamination control. Each plate was prepared in triplicates to check for consistency. The bacterial suspension was prepared by growing S. aureus SH1000 to mid-exponential phase (2.5 h, with moderate shaking at 37°C) in MHB to an OD600 between 0.3 and 0.5. The bacterial suspension was diluted in MHB and ~1 × 106 bacteria were inoculated in each well. After 24 h of incubation at 37°C in a humid chamber, the plates were visually examined for growth. The Fractional inhibitory concentration (FIC index) for a combination of pexiganan and each antimetabolite drug was calculated as [(MIC of the peptide in combination with a given analog)/(MIC of peptide alone)] + [(MIC of analog in combination with peptide)/(MIC of analog alone)]. The interpretation of the results was as follow: FIC ≤ 0.5, synergistic; 0.5 < FIC ≤ 1, additive; 1 < FIC ≤ 4, indifferent; FIC > 4, antagonistic (36). To ensure that bacteria lost viability while reading MIC values for pexiganan-analog combinations, we used the resazurin colorimetric assay as described previously with minor modifications (37). Resazurin (THK, Germany) was prepared at 0.015 % in distilled water and sterilized by filtration. It was stored at 4°C for a maximum of 1 week after preparation. Resazurin (0.015%) was added to each well (10 μl per well, 1/3 of the original described quantity) and further incubated for 3 h for the observation of color change. Columns with no color change (blue resazurin) were scored as dead culture. In contrast, color change to purple (reduced resazurin) was considered as a sign of viability.
| 4 | 0biomedical
| 0Study
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269,358 |
Although extant research has provided evidence of selection and social influence of peers for a variety of behaviors, most prior research has considered the networks of friends, and there has been limited research examining different types of peer relations. However, adolescents have peer social interactions in diverse ways, and different peer relations could have important implications for individuals’ behavioral tendencies. For example, adolescents hang around with a group of peers, cooperate on a task with a few friends, and often build close and intimate relationships with friends. Also, adolescents may admire, respect, and want to be like certain peers , or they could also want to be different from certain friends. Such different peer relations can play distinct roles in individuals’ behavior development, and the features of social interaction can vary by the types of individual’s social relations. Thus, specifying and examining selection and influence of peers beyond friend networks are important to advance our understanding of different peer relations’ implications for adolescents’ adjustment.
| 2 | 2other
| 1Other
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360,758 |
The micromorphologies of cross-section and worn surface of this coating were measured by field emission scanning electron microscopy (FE-SEM, Tescan Mira 3, Bron, Kohoutovice, Czech Republic). A Philips X’Pert-MRD X-ray diffractometer (XRD; Cu-Ka radiation, current 150 mA, potential 40 kV, Philips, Eindhoven, The Netherlands) was utilized to analyzed phase composition. The phase compositions on the worn surface were analyzed by Czemy-Tumer Labram HR800 Raman spectrometer (Horiba, Paris, France).
| 4 | 0biomedical
| 0Study
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33,933 |
To gain further insights into cellular mechanisms, we focused on cells that were loosely associated or in close proximity but not yet clustered. As in the naturally occurring endocrine cells, induced endocrine cells showed filopodia, shape changes, and narrow cell-cell connections as they moved closer together (Fig. 2A-C, Fig. 3A-C). Particularly striking was the appearance of long, flexible and highly dynamic protrusions revealed by the membrane-targeted mnx1:memGFP transgene, which are barely detectable by cytoplasmic dsRed expression (Fig. 2A, Fig. 3). By collecting image sequences at shorter (minutes) and longer (hours) time intervals, we captured movements of single cells and groups of cells along axes demarcated by narrow cell-cell connections (Fig. 2A-C, Fig. S3B; n=7/11 samples tracked over time). We further observed that as cells coalesce, narrow filopodia transform into broader connections with progressive shifting of cytoplasm (Fig. 3A,B, Fig. S4, Movie 1). Fig. 2.Clustering endocrine cells extend dynamic protrusions. (A-C) Image series acquired by confocal microscopy showing pancreatic endocrine cells in pax6b:dsRed;mnx1:memGFP transgenics at 7 dpf, following Notch inhibitor treatment from 4 dpf to 5 dpf. Shown are maximum intensity projections (A,B, left) and 3D representations of tracked cells (colored spheres), rotated to best visualize individual cells (A,B, right, C). mnx1:memGFP transgene expression delineates dynamic protrusions (arrowheads). Arrows indicate fine cell-cell connections. (D) Progression of cell clustering over time. Clustering is quantitated as the volume of a convex 3D polygon enclosing the cell centers (see Fig. S3A), plotted against time for the samples shown in A-C. Volume decreases over time as cells come into closer proximity (for details see the supplementary Materials and Methods). Scale bars: 10 μm. Fig. 3.Dynamics of cell coalescence. (A) Confocal time-lapse series of Notch inhibitor-treated pax6b:dsRed; mnx1:memGFP transgenic at 7 dpf showing coalescence of two cells (orange and green spheres). Three additional cells are tracked. (B) z-projections corresponding to the images in A, with RFP rendered in gray. (C) Two-channel, close-up view of the GFP+ cell outlined in B (green). A subset of images from a series collected at 18 min intervals are shown. Scale bars: 10 µm. (D) Quantitation of clustering (as in Fig. 2D) for the tracked cells indicated in A.
| 4 | 0biomedical
| 0Study
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117,692 |
Optical images at the locations of elliptical scars on the pins made of Composites A and B after self-mating tests lasting 2 × 103 m in a pin-on-ball configuration (in (a) and (b), respectively); In (c) and (d), high magnification electron micrographs are shown from the damage scar regions (from ball side) in Composites A and B, respectively.
| 2 | 2other
| 0Study
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106,606 |
Given this potential aetiological loss of TGFβ signalling, we sought to identify sites of active TGFβ signalling in normal skin, to gain insight into the cellular origin of cSCC RAF inhibitor-induced lesions. PO4-SMAD3 activity was barely detectable by IHC analysis in normal human epidermis (Supplementary Fig. 8) but showed strong immunoreactivity in the hair matrix zone of anagen hair follicles (Fig. 5a and Supplementary Fig. 8). PO4-SMAD3 positivity was also detected in the hair matrix of anagen hair follicles in mouse back skin (Fig. 5a). In anagen, the hair follicle transit-amplifying (TA) cells are localized in the matrix and are positive for Sonic hedgehog (SHH)11. Elegant studies by Blanpain and colleagues11 have demonstrated these cells are unable to act as a cell of origin for papilloma formation, even when both oncogenic Kras and Tp53 were targeted. This suggests that these PO4-SMAD3+ve hair matrix cells are unlikely to be the cell of origin for the rapid cSCC observed in humans following RAF inhibitor treatment. To investigate this in the mouse, we tested whether Tgfbr1 deletion could permit the transformation of TA cells. RAF inhibitors stimulate paradoxical activation of the MAPK pathway in cells with wild-type BRAF harbouring upstream pathway activation, via mechanisms such as the following: upregulated receptor tyrosine kinases, oncogenic RAS via RAF dimer formation333435 or relief of inhibitory auto-phosphorylation36. Circumventing pharmacological enhancement of MAPK signalling in the presence of mutated RAS, we modelled hyperactivation of the MAPK pathway in the SHH+ve compartment by targeting downstream oncogenic BrafV600E and oncogenic activation of KrasG12D. We crossed our previously described LSL-BrafV600E mice37, which allow inducible expression of BrafV600E from the endogenous Braf gene, with the ShhCREER strain38. This permits tamoxifen-inducible activation of the Cre recombinase in SHH+ve cells. To assess the role of TGFβ signalling in the SHH+ve cells, we then crossed these animals with Tgfbr1fl mice30 (Supplementary Fig. 9a,b). No tumours formed in the skin of ShhCREER BrafV600E and ShhCREER BrafV600E Tgfbr1fl/+ mice (Fig. 5b and Supplementary Fig. 10a,b). A small percentage of ShhCREER BrafV600E Tgfbr1fl/fl mice developed minimally proliferative papillomatous lesions (as evidenced by low level 5-bromodeoxyuridine (BrdU) staining) mainly in the lips, but only at long latency (Fig. 5b and Supplementary Fig. 10c). No mice developed cSCC. Mice failed to develop any skin lesions following oncogenic activation of KrasG12D with or without deletion of Tgfbr1 in this cell compartment (Fig. 5c). Together, these studies indicate that the SHH+ve cells are unlikely to be the cell of origin for either rapid onset vemurafenib-induced cSCC or sporadic cSCC.
| 4 | 0biomedical
| 0Study
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22,867 |
Although the test uses a simple and basic vocabulary, it was decided to check, previously, the subtest of vocabulary, to ensure that the words used by the Peruvian children to name the elements of the test were the same as those used by Spanish children. In this group, it was found that when the child knew the word, he always used the same word as the one supposedly correct by the test. No child responded to any item with a synonym or specific word to their region. Based on these results, it was not considered necessary to revise the test or its correction criteria. Alongside these lexical varieties we reviewed all items of the test and found that two items of the alphabetical knowledge test and one item of the phonological awareness test could be affected by the phonological differences between the two dialectal variances. The most important differences are found in some phonological varieties of Spanish spoken in Peru: the /s/, /c/ and /z/ are pronounced the similar way; the /rr/ and /r/ are pronounced without fricativization; the "s" is predorsal and aspired before consonant (not at the end of syllable); the final /d/ becomes /t/ or is omitted; the sound /ll/ is pronounced as /y/; and tendency to eliminate hiatus in words with the suffix ‘–ear’.
| 2 | 2other
| 0Study
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387,732 |
Autaptic cultures provide the ultimate in synaptic simplicity: a one-neuron circuit. Despite a current tendency to study complex and preferably in vivo neural networks, autaptic cultures still have an important place in the toolbox of cellular neuroscientists because they enable straightforward, elegant experiments that address fundamental questions about synaptic transmission. The examples of applications given in this review provide a taste of the diversity of experiments that are possible with autaptic cultures, and will hopefully inspire novel applications, perhaps involving new-generation optical technologies. Of course, like all model systems, autaptic cultures have advantages and disadvantages, and these must be carefully weighed up when deciding whether autapses are the right tool for the job. It is hoped that this review has provided enough information to make that decision easier, and will assist in the implementation of autaptic culture experiments with the minimum pain and maximum prospect of success.
| 4 | 0biomedical
| 2Review
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259,681 |
This work was supported by the National Natural Science Foundation of China (81773527, 81973138), the China-Australia International Collaborative Grant (NHMRC APP1112767, NSFC 81561128020) and the European Commission Horizon 2020 Framework Programme (PRODEMOS-779238).
| 1 | 2other
| 1Other
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365,687 |
A second concept we realized is that testicular sperm retrieval procedures not only can fail but also can do permanent damage to the testicle and lead to hypogonadism or lower testosterone levels5,6. Given that many couples might need multiple in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) cycles and sperm retrievals for a successful conception, there is an onus on clinicians to develop (a) efficient sperm retrieval techniques that, (b) maximize yield, (c) minimize procedure extent and morbidity, and (d) allow sperm cryopreservation to avoid repeated procedures (Figure 1). A Cochrane review of the literature on techniques of sperm retrieval found a lack of randomized controlled trials on which to base a recommendation for one sperm retrieval technique over another7. The only hard and fast recommendation was to select the least invasive and simplest technique for sperm retrieval whenever possible. Surely reproductive urologists, like other physicians, should be guided by the Hippocratic oath to “First, do no harm”. Indeed, this had led to several creative strategies that seek to optimize the safety and success of surgical sperm retrieval.
| 4 | 0biomedical
| 2Review
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78,433 |
Intra-tumor heterogeneity contributes to tumor evolution, progression, metastasis, and resistance to chemotherapy and radiation in head and neck cancer . RPPA analysis was performed to define active signaling pathways and treatment-induced changes in mEERL and MLMs. Whole-cell lysates were harvested 24 hours after 1) no treatment, 2) CRT, 3) rapamycin, or 4) CRT and rapamycin (CRT/rapamycin). Protein expression was significantly different across cell lines (Supplementary Figure 1); however, mTOR signaling was consistently activated in each (Figure 1). mTOR signaling proteins demonstrating activation (red color) included P-Rictor (rapamycin insensitive companion of mTOR, a component of the mTORC2 complex), P-Akt s473 (mTORC2 phosphorylation site on Akt), P-S6K and P-S6 (direct downstream targets of mTOR), and P-NDRG1 (N-myc downstream regulated gene 1, a downstream target of mTOR induced by radiation and a key determinant in resistance to alkylating chemotherapeutic agents ). The full-length array for mEERL is shown as an example in Figure 1 alongside enlargements of these protein clusters for each cell line. Full-length arrays are included in Supplementary Figure 1. These results suggest mTOR signaling may be implicated in this murine model of HPV+ OPSCC and its recurrent/metastatic derivatives. Importantly, rapamycin inhibits activated mTOR-related phospho-proteins in all cell lines even in the context of CRT (Figure 1, green color). These data support emerging evidence that mTOR activation contributes to HPV+ OPSCC [13, 16], and correlates increased mTOR signaling with recurrent/metastatic disease. These data also suggest that mTOR remains targetable in resistant, recurrent/metastatic cells and that its inhibition is a feasible adjuvant to CRT.
| 5 | 0biomedical
| 0Study
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190,401 |
The OVCAR-5 cell line was cultured on coverslips until reaching 70% confluency. Cells were then treated with MSN_CurNQ for 24 h, thereby allowing for cellular uptake to occur. After this, Phalloidin-Atto 488 was added, and staining occurred over 30 min. Cells were then washed and fixed through incubation in 5% formaldehyde in PBS for 20 min. After fixation, DAPI stain was added at a concentration of 1 μg/mL and samples were left to incubate for 15 min in the dark. Hereafter, samples were washed thoroughly with PBS to remove unstained DAPI. Coverslips were stored in the dark in PBS. Coverslips were viewed on the Zeiss Laser Scanning Confocal Microscope (LSM) 780 (Oberkochen, Germany). Super resolution microscopy was performed using Airyscan technology as an added on feature to the LSM confocal microscope.
| 4 | 0biomedical
| 0Study
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177,665 |
Furthermore, we performed rescue experiments to separately overexpress tRNA LysCTT or EGFR. We found that forced expression of tRNA LysCTT or EGFR could partially rescue cancer progression in siMETTL1 MHCC97H and Huh7 cells (Figure 5A–J and Figure S8A–D). In addition, tRNA LysCTT overexpression also partially rescued EGFR and Cyclin A2 expression in siMETTL1 MHCC97H and Huh7 cells (Figure 5A). Overall, we demonstrated that reduced m7G tRNA modification impairs the translation of certain oncogenic mRNAs, resulting in the suppression of the HCC progression.
| 4 | 0biomedical
| 0Study
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193,120 |
In addition, many positive or neutral representations of tobacco, alcohol, and drug use can be seen in contemporary film productions . In earlier film adaptations of drug use scenes, such as the aforementioned Requiem for a Dream or Trainspotting, the message was relatively unambiguous and could inform future physicians about drug behavior and medical methods ; however, in these productions, some scenes, due to the attractive depiction of the moment of drug intake and colorful experiences, can also arouse interest in this mysterious and interestingly depicted activity.
| 2 | 0biomedical
| 1Other
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39,612 |
Male Nkx2.1-Bmal1−/− (Nkx2.1-Cre;Bmal1fl/−; n = 11) and control (Bmal1fl/− and Nkx2.1-Cre;Bmal1+/fl; n = 8 and 6, respectively) mice, aged 9–15 weeks, were housed individually in cages placed in a light-tight chamber with a light intensity of ~50 lux. Spontaneous locomotor activity and food intake were recorded by infrared motion sensors and food intake monitor (O'Hara) in 10-min bins. Actogram, activity profile, and χ2 periodogram analyses were performed using ClockLab (Actimetrics). The free-running period was measured by periodogram for Days 5–21 in constant darkness (DD).
| 4 | 0biomedical
| 0Study
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381,845 |
The effect of Sphingomonas SaMR12 on (a) GSH content and (b) proline content in both shoots and roots. The solid line, non-inoculated plants; the dashed line, SaMR12-inoculated plants. Plant samples were harvested after 7 d of treatment. The vertical line on each bar shows the standard deviation (n = 3). The different letters on the error bars indicate significant differences among treatments at p < 0.05 in the shoot and the root, respectively. The same letters above the bars indicate no difference between the treatments at p < 0.05. Asterisk (*) and double asterisks (**) indicate p < 0.05 and p < 0.01, respectively, for Student’s t-test carried out between SaMR12 non-inoculated and SaMR12-inoculated samples
| 4 | 0biomedical
| 0Study
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202,525 |
The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.
| 2 | 0biomedical
| 1Other
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305,045 |
The purpose of the study was to estimate what kinds of pain symptoms as a possible precursor of injuries are directly related to CrossFit, how often those pain symptoms occur within a population of recreational CrossFit athletes, and which factors are influencing the frequency of pain while CrossFit training.
| 2 | 0biomedical
| 0Study
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194,064 |
Within neuro-otology, radiomics is a very new concept. This study pioneered in developing a computer-aided diagnostic tool for MD by using a radiomic approach. Research on the role of imaging within MD’s diagnosis mainly focuses on the in-vivo visualization of EH on delayed gadolinium-enhanced MRI. One of the main benefits of radiomics is that it can also be applied to MRI scans acquired with no contrast agent. Within the diagnostic workup of MD, these scans are often readily available since MRI is indicated to exclude other causes of asymmetrical hearing loss. Radiomics is not just reserved for centers with specialized radiological expertise on EH. Instead, it could be performed in any center with a (1.5 T or 3 T) MRI scanner, without a delayed scanning protocol, and also in case of allergic reaction to contrast media.
| 4 | 0biomedical
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134,054 |
We initially compared the RT-PCR data from this manuscript with RNA-seq data we previously published generating retinal organoids from H1 embryonic stem cells. In general, we found that the appearance of retinal genes in the control condition in our pilot experiment described in this manuscript matched the control retinal organoid differentiation RNA-seq data we previously published (Figure 11A): NANOG was present on days 0 and 4 before losing its expression. PAX6 was the first neural developmental gene to be expressed, followed by the retinal marker RAX, with VSX2 being expressed last. MITF expression seemed to peak at day 25 before decreasing, as seen in our pilot control condition. ATOH7 was expressed from day 25 onwards. Dataset GSE119274 , presented in Figure 11B, originated from a study that also used the embryonic stem cell line H1 to generate retinal organoids, taking samples from day 15, 1 month, 3 months, 6.5 months and 9 months in culture. We observed that PAX6 is also the first retinal developmental marker to appear in this method, peaking after 1 month of culture, with RAX and VSX2 being similarly expressed at this time point, similarly to our RT-PCR and RNA-seq data. We also observed a significant increase in the expression of ATOH7 between 15 days and 1 month of culture, mirroring our RT-PCR analysis of ATOH7 in our cultures. Another group, Kaewkhaw et al. (2015), cultured organoids and generated the dataset GSE67645 . Their RNA-seq for the relevant data is presented in Figure 11C. These authors generated retinal organoids using another embryonic stem cell line, H9, and analyzed samples taken throughout the culture at days 0, 37, 47, 67 and 90. They showed higher levels of PAX6, RAX and VSX2 expression at day 37 compared to the cell-specific marker MITF, something we also observed in our cultures. Similarly, the expression of ATOH7 increased significantly between day 0 and 37, in line with our findings. Finally, we analyzed the transcriptomic dataset GSE104827 of the developing fetal human retina (presented here in Figure 11D). Extensive data from samples were available throughout development (day 52 or 54, 53, 57, 67, 80, 94, 94 (second sample), 105, 107, 115, 125, 132, 136). Ideally, in vitro retinal development should be as close to fetal expression as possible. However, it is often difficult to compare these due to the hugely different environments and timelines. The most striking difference was the large increase in total expression when compared to the data of our retinal organoids (Figure 11A), with some genes expressed 100-fold more. Although it was difficult to compare all of the different organoid datasets with the fetal retina, we did observe some interesting similarities. In dataset GSE104827, PAX6 expression was at its highest after around 50 days of development, before decreasing over time to day 136. In our retinal organoid RNAseq data, we also observed a peak in PAX6 expression after around 60 days of development, before decreasing over the course of the differentiation to day 160. The fetal expression of RAX slightly increased and decreased throughout development, but remained somewhat constant between day 52 and 136. This was mirrored in our organoid development, varying slightly but keeping relatively stable over time. Interestingly, we observed that VSX2 expression in fetal retina increased over time from day 53 to 136, whereas in all three organoid datasets, VSX2 expression was at its peak within the first month of development, before decreasing over time during the culture. Finally, we found that although ATOH7 expression in the fetal retina did mirror the expression found in our dataset, the peak of expression was shifted to an earlier time point. In our RNAseq dataset, ATOH7 expression increased gradually until day 63, where it peaked before decreasing over time. However, in the fetal retina, ATOH7 expression peaked by day 53, and by day 67 was already reduced by around half, decreasing further throughout development. When comparing these similarities in gene expression, it is important to consider the relative timeline, as retinal organoid maturation and fetal eye maturation do not occur within the same timeframe. Taken together, these data highlight important similarities and differences between in vitro and in vivo retinal development.
| 4 | 0biomedical
| 0Study
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94,476 |
Abbreviations: QS = quality score; PT = preterms; NC = normal controls; TSFI = Test of Sensory Functions in Infants; BSID (II/III) = Bailey Scales of Infant Development (II/III); ITSP = Infant/Toddler Sensory Profile; GA = gestational age; CA = corrected age; SRS = Sensory Responsiveness Scale; SP = Sensory Profile; RCT = randomized controlled trial; WPPSI = Wechsler Preschool and Primary Scale of Intelligence; WISC = Wechsler Intelligence Scales for Children; WMA = white matter abnormalities; NICU = neonatal intensive care unit; MDI = mental development index M-CHAT = Modified Checklist for Autism in Toddlers; CSBS-DP-ITC = Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist; ASD = autism spectrum disorder; SSP = Short Sensory Profile; BRIEF-P = Behavior Rating Inventory of Executive Function- Preschool Version; EF = executive functioning; IRQ = inter quartile range; SPD = sensory processing disorder; TBAQ = Toddler Behavioral Assessment Questionnaire (Sensory overresponsivity scale; similar to SSP).
| 2 | 0biomedical
| 1Other
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283,888 |
The composition of ZPPs was confirmed by TGA thermograms in Figure 4D. The weight residues of crosslinked ZPPs were 26.9, 19.5, and 21.9 for 1, 5, and 10% DVB, respectively, and were significantly higher than that of the non-crosslinked ZPPs (12.8%). The higher ZnO content are attributed to the higher polymerization rate caused by DVB (reactivity ratios of DVB = 1.3 and of St = 0.55) and the miscibility between OA-ZnO and DVB, as already mentioned.
| 4 | 0biomedical
| 0Study
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251,686 |
Rad51 (RecA homolog, Escherichia coli) protein is a component of the HR repair pathway of DNA DSBs and inter-strand cross-links. Genetic variants of Rad51 influence mRNA stability and translational efficiency and have been linked to carcinogenesis and radiosensitivity (30–32).
| 4 | 0biomedical
| 0Study
|
42,649 |
It is well established that some lymphatic structures, including the thoracic dermal lymphatic capillaries studied here, originate from venous-derived progenitors [12,58–60]. The evidence for a venous origin of many lymphatic vessels is extensive and includes analysis defining the molecular mechanisms required and showing that this developmental pathway is conserved [61–63]. However, recent analysis has also provided evidence, based on lineage marking, for non-venous sources of lymphatic progenitors (reviewed in in the lumbar region dermal capillaries and in the heart . In the current study, we have assessed developmental mechanisms in the thoracic region lymphatic capillaries that are of venous origin. In the future, it will be interesting to determine whether the myeloid-Wnt mechanisms defined here apply equally to lymphatic precursors of all lineages.
| 5 | 0biomedical
| 0Study
|
324,554 |
Given that blood urea N levels can fluctuate throughout the day, with the highest levels normally detected 4 to 6 h after feeding, the time of sampling can influence BUN concentrations. However, this pattern is influenced by dietary CP: for example, Kauffman and St. Pierre reported PUN to be unaffected by the time of sampling when cows were offered a diet with a content of 13% but a downward trend in PUN concentrations over time when offered a 17% CP diet. This may reflect increased urea clearance from blood with higher CP levels in the diet. Fluctuations in BUN prior to and following a meal may also be influenced by the Labile N pool . Labile N is primarily found as urea in the blood plasma, but also in organs with a high protein turnover rate, such as the liver, kidneys, and intestine. These ‘protein’ pools are then available when protein is low, for example, prior to feeding. Therefore peaks in BUN following a meal may be lower than expected due to the buffering effect of the protein absorbed and stored in these tissues . Blood urea N levels are also sensitive to water intake, with BUN concentrations in dairy cows observed to increase from 8.5 mg/dL to 15.6 mg/dL with a 50% reduction in water intake , as a consequence of low water intakes reducing urine production. Thus season can impact BUN levels as it has been estimated that each one degree Celsius increase in ambient temperature can increase water intake by 1.5 kg/day . In addition to ambient temperature, the water intake of a dairy cow can be influenced by factors such as milk production, sodium intake, and body weight . Despite diurnal variations, BUN is routinely measured on some farms as part of a herd metabolic profile to identify nutritional constraints before they impair herd performance . A plasma urea concentration >1.7 mmol/L was identified as satisfactory for dairy cows under United Kingdom (UK) conditions . In an analysis of data from 35,000 dairy cows in the UK, 16% of cows in early lactation had plasma urea concentrations <1.7 mmol/L, suggesting the ration either to be deficient in effective rumen degradable protein (ERDP), or to be adequate in ERDP but the cows having low intakes . While 21.9% of cows in this same study had a ‘high’ plasma urea concentration (>3 mmol/L), the authors highlighted this due to potential concerns about cow fertility, rather than concerns about cows being offered diets with increased environmental risk .
| 5 | 0biomedical
| 0Study
|
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