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Fig. 5 Exo-Gel suppressed IL-1β-triggered chondrocyte apoptosis in vitro. A In vitro investigate the effect of Exo-Gel on apoptosis of chondrocytes treated with IL-1β (10 ng/ml) for 24 h. TUNEL (green) staining to analyze chondrocyte apoptosis, DAPI (blue) staining for cell nuclei (bar = 200 μm). B Quantitative assessment of the proportion of apoptotic cells in A. Data are expressed as means ± SEM (n = 6). C Annexin V/FITC/PI double-staining flow cytometry to detect the effect of Exo-Gel coincubated medium on IL-1β-triggered chondrocyte apoptosis. D Quantification of apoptotic cells (Annexin V-positive) in C. Data are expressed as means ± SEM (n = 4). E Representative Western blots of cleaved-Cas3, Bcl-2, and Bax expression in chondrocytes in different groups. F Quantification of cleaved-Cas3 protein expression and the ratio of Bcl-2 to Bax in chondrocyte in E. GAPDH was used as loading control. Data are expressed as means ± SEM (n = 3). *p < 0.05
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222,161
Zuboff’s findings exemplify conflicting interests between the puppet master orchestrating the uncontract dystopia, reifying Alford’s (1975: xiii) notion of “strategically structured interest” first applied to examine the conflicting interests in health system reforms. Alford contended there existed “a continuing struggle between major structural interests operating within the context of a market society – “professional monopolists” controlling the major . . . resources, “corporate rationalisers” challenging their power, and the community population seeking better . . . care” (ibid. : xiv). Based on the above, we interpret the current digital society in Fig. 1. Fig. 1Structured vested interests in the digital society (cf. Alford 1975)
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1Other
64,414
Establishment of the inactive X chromosome (Xi). Early in embryogenesis one of the two X chromosomes in female cells is inactivated by persistent expression of the X inactivation specific transcript RNA (XIST) from the X inactivation center (XIC). XIST RNA does not code for protein but remains in the nucleus and binds contiguous chromatin (i.e., the Xi, a.k.a. the Barr body), recruiting epigenetic silencing effectors (e.g., DNA methyltransferases). Approximately 95% of genes from the long arm (Xq) and 65% of genes from the short arm (Xp) are silenced. Silenced genes shown as dark blue, while genes that escape inactivation are shown as light blue [based on Ref. (89)]. The result is the Barr body which appears as a dense heterochromatic structure near the nuclear membrane. The bulk of the heterochromatic core contains Xq genes with some Xp genes, and the euchromatic-like surface layer has primarily Xp genes that are: actively expressed; potentiated for expression; or silenced but adjacent to expressed genes. Particularly interesting in the Xp is the pseudo-autosomal region 1 (PAR1) which has an abundance of Alu elements (46). In addition, Xp22 contains a “hot” LINE-1 sequence that can code for a fully functional reverse transcriptase. Xp22 also contains a fragile site (FRAXB). Fragile sites are preferential locations for viral insertions. And Xp22 on the Xi contains epigenetically silenced genes for spermine synthase (SMS) and spermidine/spermine N1 acetyltransferase (SAT1). Overexpression of SMS and/or SAT1 that could occur with disruption of epigenetic silencing on the Xi can impact cellular methylation and polyamine types and levels. This could also impact polyamine activity in the nucleoli.
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29,718
How to cite this article: Liu, X. et al. A general nonaqueous sol-gel route to g-C3N4-coupling photocatalysts: the case of Z-scheme g-C3N4/TiO2 with enhanced photodegradation toward RhB under visible-light. Sci. Rep. 6, 39531; doi: 10.1038/srep39531 (2016).
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200,984
Uncertainty was explored through one-way sensitivity analyses (Table 6). The Canadian publicly funded healthcare system is composed of federated healthcare structures, is siloed, and cost categories are accounted for in various budgets. As such, a scenario from a Canadian testing budget perspective was performed, in which only molecular genetic testing costs were considered.
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299,897
After the ultrasound-guided block, the anesthesia induction regimen was as follows: propofol (2 mg/kg), fentanyl (1 ug/kg), and rocuronium (0.9 mg/kg). All patients received endotracheal intubation. For anesthesia maintenance, sevoflurane and a mixture of O2/N2O were used to keep the bispectral index (BIS) within 40–60. Fentanyl was administered as needed to control the heart rate and blood pressure within baseline ± 20 %. All patients received 4 mg ondansetron and 5 mg dexamethasone for prophylactic antiemetic treatment. For postoperative analgesia, patients received intravenous parecoxib 40 mg iv as rescue analgesia in case of NRS between 3 and 4, and tramadol 100 mg iv as rescue analgesia if NRS > 4.
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52,709
The formation of charge‐transfer complexes of soluble molecules in supramolecular complexes based on cucurbituril has been reported previously.13, 15, 37 In the current system, formation of the host–guest system is based on extraction of the guests, which are essentially insoluble in water. The metal complexes that are co‐encapsulated by this metallocage make it possible to investigate the effect of the redox potential on the charge‐transfer complex. In this regard, various pairs of guests for the formation of ternary complexes were investigated. The donor in the charge‐transfer complex was expected to be the metal complex, hence various complexes with different steric and electronic properties were studied. The same steric structure was retained and only the electronic properties were changed by utilizing [(CpMe)Ir(cod)] (2) for the encapsulation studies. When 2 was co‐encapsulated with triphenylene, the charge‐transfer band was shifted to higher energy (513 nm, 2.42 eV; see Table 2) compared to that obtained with the rhodium complex (4). This blue‐shift of the charge‐transfer band was anticipated as the oxidation potential of 5 is higher than that of 3, as indicated by the redox potentials of the complexes in dichloromethane determined by cyclic voltammetry measurements (see Table 2 and Supporting Information S6). When the electronic properties of the rhodium complex were further changed by substituting it with four methyl groups (complex 5) as opposed to no methyl groups (complex 3), it became apparent that metal complexes with a higher oxidation potential yielded a charge‐transfer band with triphenylene at lower wavelength. To the best of our knowledge, this is the first time that metal complexes have been used to fine‐tune charge‐transfer bands through the formation of ternary complexes, based on their redox potentials. To ascertain whether similar trends could be observed, we co‐encapsulated other aromatic guests. For this purpose, pyrene (7) and perylene (8) were used to form the ternary complexes. With perylene (8) as aromatic co‐guest, the charge‐transfer bands shifted to higher energies. A recurring trend in the energies was observed, with the exception of 1 c⋅2⋅8, for which the energy was difficult to determine due to overlap with the UV band of perylene. The use of pyrene resulted in almost quantitative formation of the ternary complexes (see Table 1), including with the sterically demanding 5. However, the location of the charge‐transfer band was difficult to determine precisely as it partially overlapped with the absorption of pyrene (see Supporting Information S5). Although the estimated energies were therefore less accurate, all CT bands shifted to lower energies as a consequence of the lower‐lying LUMO of pyrene. This was consistent with the metal complex being the electron donor and the aromatic compound the acceptor. The resulting charge‐transfer complex may be stabilized by the electron‐poor cavity of the molecular container, but the dominant effect is the charge‐transfer complex formation between the two guests as variation of either component leads to changes in the bands. Based on these findings, we constructed a schematic energy diagram for the charge‐transfer interactions, as depicted in Figure 5.
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2,027
Cholinergic modulation can inhibit action potential firing of pyramidal neurons in superficial cortical layers by augmenting GABAergic inhibition through nAChRs and mAChRs (Kimura and Baughman, 1997; Disney et al., 2012; Alitto and Dan, 2013; Soma et al., 2013; Kimura et al., 2014). In rodents, application of ACh to non-fast spiking (non-FS) interneurons in layers 2/3 and 5 generates mixed responses mediated by muscarinic and nicotinic AChRs. Fast spiking (FS) interneurons in rodent neocortex generally do not show muscarinic responses (Gulledge et al., 2007), but species differences are large on this point. More than 75 percent of PV-immunoreactive visual cortical neurons in macaques, humans and guinea pigs express M1 mAChRs (Disney and Reynolds, 2014). In contrast, in rats only 25% of the visual cortex PV population is immunoreactive for M1 mAChRs. Similar to rodent cortex, non-PV interneurons in primate neocortex also express M1 mAChRs (Disney et al., 2014). M2 mAChRs are typically expressed at axons in neocortical interneurons (Disney et al., 2006).
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0Study
324,584
We conducted an observational study by retrieving data from the Medical Information Mart for Intensive Care (MIMIC III) open source clinical database, which contains de-identified health-related data of over forty thousand patients who received treatment in critical care units of the Beth Israel Deaconess Medical Center between June 2001 and October 2012 [8, 9]. The database is continuously updated, and the newest version (MIMIC-III v1.4) was released on 2 September 2016, which enhanced data quality and provided a large amount of additional data. We use the MIMIC-III v1.4 in our study, and all data in it was classified into 26 tables recording various individual information, such as demographic characteristics, treatment measures, nursing notes, and laboratory tests. Besides, it contains prognostic data obtained from the hospital and laboratory health record systems reporting the hospital mortality, or from the Social Security Administration Death Master File recording the out-of-hospital survival data. The MIMIC III database can be freely utilized after successful application and ethical approval from the Institutional Review Boards of both Beth Israel Deaconess Medical Center (Boston, MA, USA) and the Massachusetts Institute of Technology (Cambridge, MA, USA). Since all data are de-identified in this database to remove patients’ information, the requirement for individual patient consent is not indispensable.
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382,162
Socio-demographic factors including gender, age, education level, economic activity, marital status, household income level, and residential area; health behavioral factors including place-moving physical activity (PMPA), drinking, smoking, stress, sedentary time, and sleeping hours; and disease-related factors including hypertension, hypercholesterolemia, obesity, stroke, and heart disease, were controlled (Table 1). PMPA is the physical activity of walking or cycling for at least 10 min when moving between places, such as commuting to work, going to school, or going shopping.
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303,643
Stakeholders were asked about their perceptions regarding the inputs required to deliver cMDA with high coverage, including the number of CDDs and types of material resources needed to deliver MDA. There was a great deal of between-country and between-stakeholder variation in the perceived number of CDDs required to deliver MDA for a catchment area population of 5000 people, ranging from implementers in Malawi (average: 3) to mid-level managers in Benin (average: 59). When asked what materials were most important for delivering cMDA, participants identified community education materials as most important (25–26%), CDD incentives (22–24%), and well-trained staff (15–21%).
2
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0Study
128,413
The relationship of textural features of peritumoral breast AT with tumor size and molecular subtypes of breast cancer was also assessed. The size of the primary tumor revealed weak-to-moderate correlations with 33 peritumoral breast AT textural features (Table S4; p < 0.05; correlation coefficient, −0.434–0.549). Correlation analysis for peritumoral breast AT textural features and molecular subtypes (Table S5) showed significantly different values of 31 textural features according to the molecular subtypes of breast cancers (p < 0.05). On post hoc analysis, the patients with HER2-enriched and/or triple-negative breast cancers showed significantly different values of textural features from those with luminal A and/or luminal B breast cancers.
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44,655
STARs allow for control of multi-gene metabolic pathways. a Schematic of the four gene deoxyviolacein metabolic pathway (vioABCE) that converts L-tryptophan into the purple compound deoxyviolacein. b Schematic DNA template of a plasmid containing a STAR regulated vioABCE pathway. Characterization was performed on E. coli DH5 alpha pir cells transformed with this plasmid in the absence (-STAR) and presence (+STAR) of a plasmid encoding cognate STAR. Deoxyviolacein production was characterized by solvent extraction and spectral quantification of deoxyviolacein (measured in units of OD at 575 nm). Data represent mean values and error bars represent s.d. of n = 9 biological replicates
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285,688
Encouraged by these results, we aimed to study the impact of the insertion locus on transgene expression. RNA was extracted from GUS (+) CLOSITRA, purified, and subjected to reverse transcription. The generated cDNAs were used for absolute quantification by ddPCR. First, the mRNA levels of the two endogenous genes, RPS and TBP, in GUS (+) CLOSITRA were quantified (Figure 6). Overall, the concentration of TBP was similar in all clones, with values of 150–220 copies/µl. Although the concentration of RPS was also similar in our samples, it was at least 10-fold higher, with values of approximately 1,060 to 2,700 copies/µl. Thus, the RPS gene is much more highly expressed than the TBP gene (Supplementary Figure S10). This confirms the results obtained in a previous study, which showed that RPS shows transcript levels about 10 times higher than those of TBP by q-PCR analysis (Siaut et al., 2007). We used TBP as the reference gene for the subsequent experiments to avoid saturation. We next compared uidA and NAT transcript levels in all CLOSITRA (Figure 6). The concentration of the targeted gene was normalized according to the concentration of the TBP reference gene. As expected, clones 33, 72 and 78 show the highest uidA transcript levels compared to clones 36 and 40 (p-value <0.05, see exact p-value in the legend of the Figure 6). Intriguingly, clone 33 exhibits a reproducible discrepancy in the level of uidA and NAT transcripts.
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294,075
Recombinant PMAP-36 and PG-1 were produced using the GFP-scaffold system described previously . Briefly, DL4GFP-AMP-construct transformed BL21 (DE3) cells were grown in 1 L of Luria-Bertani (LB; BD Bioscience, Franklin Lakes, NJ, USA) medium at 37 °C, and the expression of GFP-AMP fusion protein was induced with 0.1 mM isopropyl β-D-1-thiogalactopyranoside at OD600 ranging from 0.8 to 1.0. The cells were harvested by centrifugation at 9900× g for 10 min at 4 °C after 5 h of induction. The cells were disrupted by sonication (Sonopuls HD 2070; Bandelin, Berlin, Germany) in lysis buffer (20 mM sodium phosphate buffer at pH 7.4 containing 150 mM sodium chloride, 0.1 mM phenylmethylsulfonyl fluoride, and 1 mM dithiothreitol). The insoluble fraction was separated by centrifugation at 20,000× g for 20 min at 4 °C. To remove cellular debris, nucleic acids, and cytosolic proteins, DNase (0.01 mg/mL), lysozyme (0.1 mg/mL), and 0.5% Triton-X 100 were added to the insoluble fractions and incubated at room temperature (24 °C) for 20 min. The pellet washes were repeated thrice without the addition of DNase and lysozyme. The insoluble fraction was dissolved in urea buffer (20 mM sodium phosphate buffer at pH 7.4 containing 8 M urea, 500 mM sodium chloride, and 30 mM imidazole), and the target proteins were purified using affinity chromatography using the His Trap HP column (GE Healthcare, Chicago, IL, USA). After dialysis and lyophilization, CNBr was added to the insoluble precipitates in 70% formic acid and incubated to cleave the N- and C-terminal GFPs flanking AMP. After removing CNBr by lyophilization, the target AMP was purified using a preparative RP-HPLC column (DeltaPak C18 Prep column 19, 300 mm; Waters, Tokyo, Japan) in a linear gradient of acetonitrile (5%–90%)/0.1% trifluoroacetic acid for 60 min at a flow rate of 12 mL/min. The target peptides were collected at optical densities of 214 nm and 280 nm. The samples collected before CNBr cleavage and after RP-HPLC were assessed using 12% SDS-PAGE and 16% Tris-Tricine PAGE, respectively, and quantified using the Bradford assay. Purified PG-1 were lyophilized and suspended in 20 mM sodium phosphate buffer pH 7.4 containing 8 M urea, 5 mM reduced glutathione and 0.5 mM oxidized glutathione to install two disulfide bonds within the molecule. The mixture was dialyzed against deionized water and purified peptides were lyophilized. PG-1 and PMAP-36 produced was aliquoted and stored at −20 °C. Chemicals without source information were purchased from Sigma Aldrich (Sigma Aldrich, St. Louis, MO, USA).
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178,480
Q3: The obvious candidate to leverage learning methods in this problem is to learn a drift model. In absence of reliable data to build predictive models of ocean currents, a simulator can take advantage of synthetic data derived from what is known of the physics of oceans.
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119,677
The bees experienced 6 CS+ and 6 CS− trials in a pseudorandom sequence (CS+, CS−, CS+, CS−, CS−, CS+, CS−, CS−, CS+, CS+, CS−, CS+), which was the same from bee to bee. Trials were separated by an intertrial interval of one minute. Such a short interval was chosen to diminish the impact of a possible decrease in the bee’s motivation to walk. If a bee did not respond with a proboscis extension to any sucrose-rewarding trial, or if it did not walk during the experiment, it was discarded from the analyses (<10% in each group).
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0Study
74,788
Although the soil carbon content was about 5% lower compared to the natural, it was still high (around 30%) at the drained site. On the other hand, the organic matter quality was different from the natural site (indicated by C/N ratio) and more suitable for the archaeal metabolic activity at the drained site (confirmed by the significant negative relationship between proportion of archaea in the microbial community and C/N in soil). The lower ammonia content and higher nitrate concentration refer to the higher nitrification activity that is conducted by autotrophic nitrifying archaea whose proportion was also higher in the prokaryotic community of the drained site. One factor that can be related to the differences in archaeal (including ammonium-oxidising archaea (AOA)) abundances between the studied sites can be the more pronounced effect of physical factors such as temperature in upper layer of drained soils. Almost 2 °C higher temperature was recorded at the sampling time in the drained peat. Studies have shown that bacteria and archaea expressing similar activity can have different temperature preferences. Wu et al.39 showed that AOA have higher temperature optimum than ammonium-oxidising bacteria (AOB) and proved autotrophic growth of AOA under warmer experimental conditions.
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37,844
Since small RNAs have regulatory functions, we focused our analysis on the identification of small RNAs. As expected miRNAs and tRNAs were widely and abundantly expressed. Then we performed a detailed quantification of annotated RNAs to functionally categorize the human small RNAs. The average across all three samples was calculated to obtain a representative profile of biological diversity between donors. Of total reads, the miRNAs were the most abundant small RNA species with 42.3%, followed by 34.79% of tRNAs, 8% piRNA, 7% Y RNA, 3.60% Metazoa Signal Recognition Particle (SRP) RNA, 2.17% U-RNA, 1.17% Vault RNA, 0.48% snoRNA and 0.14% pre-mature RNA (Fig. 2b). The reads map to all the human chromosomes in particular chromosome 1 and 3 (Fig. 2c). Since the chromosomes do not have the same size, we then normalized by size to look for specific enrichment. Since there are several copies of mitochondrial DNAs per cell, we excluded them from the analysis. After normalization, there was an enrichment in chromosome 18 and 22 (Fig. 2d).
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384,978
The setup is based on the principle of the three-point bending test performed on simply supported beams. In this test, one support point is fixed while the other can move in the direction perpendicular to the bending. The support that can move horizontally accommodates for the elongation of the bottom side of the specimen. Figure 1a shows a close-up of the support system. A schematic drawing is represented in Figure 1b as well.
2
2other
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15,903
Six trials [18, 20–22, 26, 27] reported data on major neurodevelopmental disabilities during follow-up. The number of major neurological disability in the monosialoganglioside and the usual therapy groups was 18 of 240 (7.5%) and 48 of 226 (21.2%), respectively. As shown in Fig 3A, monosialoganglioside treatment was associated with a significant reduction in the incidence of major neurodevelopmental disability compared with usual therapy care (RR = 0.35; 95% CI = 0.21–0.57) in a fixed-effect model, with no evidence of significant heterogeneity (I2 = 0%, p = 0.983). Subgroup analysis indicated that the effects of monosialoganglioside in reducing major neurodevelopmental disability were observed in each predefined subgroup (Table 2). Sensitivity analysis revealed that there were minimal changes in the pooling effect sizes with the omission of anyone trials.
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40,006
The established ARIMA (2,1,3) model was compared with GM (1,1) from two aspects of fitting and prediction. The comparison in fitting was shown in Table 2. While the average MAE and MAPE of GM (1,1) were 4.81% and 7.34%; the average MAE and MAPE of ARIMA (2,1,3) were 3.63% and 5.74%. Therefore, ARIMA was better than GM in fitting performance.Table 2Fitting results of two models.YearActual (%)ARIMA (2,1,3)GM (1,1)Fitted (%)MAE (%)MAPE (%)Fitted (%)MAE (%)MAPE (%)198881.2NANANANANANA198974.2NANANA78.54.35.8199073.4NANANA77.33.95.3199183.085.72.73.376.16.98.3199276.271.34.96.474.91.31.7199374.269.74.56.173.70.50.7199482.281.40.81.072.69.611.7199566.368.42.13.271.45.17.7199668.168.60.50.770.32.23.2199779.575.34.25.369.210.313199871.166.15.07.068.13.04.2199956.468.211.820.967.010.618.8200069.470.71.31.966.03.44.9200155.160.65.510.064.99.817.8200260.967.56.610.863.93.04.9200356.864.98.114.362.96.110.7200455.358.83.56.361.96.611.9200566.463.52.94.460.95.58.3200663.661.71.93.060.03.65.7200762.058.23.86.159.03.04.8200861.060.30.71.158.12.94.8200960.158.61.52.557.22.94.8201055.155.40.30.556.31.22.2Average3.635.744.87.4
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(A) Binding of MOG-IgG to the human MOGα1 mutants N31Q, P42S, E64K, A75S, R86Q, and H103A + S104E (103/104) and to mouse and rat MOG according to their MOG isoform binding patterns (α1β1, n = 64; α1-3β1, n = 43; α1-3β1-3, n = 46). The median differences compared to wild-type MOGα1 are shown as symbols with interquartile ranges (error bars). (B) Competition of binding to MOGα1 in a CBA-FACS assay by soluble MOG-ecIgD added in increasing concentrations (0, 1.6, 3.2, and 9.6 μM) for the 3 MOG isoform binding patterns (α1β1, n = 10; α1-3β1, n = 5; α1-3β1-3, n = 8) and for monoclonal antibody 8-18-C5 (dashed line). Squares indicate the median percentage bound, error bars indicate the interquartile ranges, and the value used for the calculation of IC50 (50% binding) is indicated by the dotted line. Groups were statistically compared using repeated measures 2-way analysis of variance. (C) IC50 values for the competition of binding to MOGα1 in a CBA-FACS assay by soluble MOG-ecIgD according to MOG isoform binding patterns (α1β1, n = 10; α1-3β1, n = 5; α1-3β1-3, n = 8). Individual data points are shown by scatter dots, and medians and interquartile ranges are indicated by lines and error bars. The IC50 value for monoclonal antibody 8-18-C5 is indicated by the dashed line. (D) Binding of human MOG-IgG according to the 3 MOG isoform binding patterns to human, mouse, and rat myelin in brain sections, as well as in ELISA (human MOG Ig domain), CBA-FACS (human MOGα1), and a commercial fixed CBA-IF (human MOGX11). The percentages of myelin/MOG-IgG–positive samples are shown as bars with 95% CI (error bars). CBA = cell-based assay; FACS = fluorescence-activated cell sorting; IF = immunofluorescence; MOG = myelin oligodendrocyte glycoprotein; MOGAD = MOG-IgG–associated disorders; MOG-ecIgD = extracellular MOG immunoglobulin domain; MOG-IgG = serum IgG antibodies against MOG.
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0biomedical
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263,022
Electrophysiological assays using T. metuendus venom on seven sub-types of human voltage gated sodium channels (hNav1.1 to 1.7) revealed that it presents α- and β-scorpion toxins . In vivo assays showed that T. metuendus venom was lethal to mice strain CD1 (25 g body weight) intraperitoneally injected with 200 μg and 300 μg of venom, respectively, within 80 min and 38 min after injection .
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129,005
For our particular use-case, we exploit the existing technique of to use K-means clustering for image compression, i.e., by reducing the number of colors of an image to the most commonly occurring colors of an image. The number of k colors could be set as desired by the programmer or it could also be optimised to a minimum K that would output an image to a reasonable quality. It should be noted here that this method of compression gives significant reductions in terms of size of an image and leads to significant reductions in the number of radio transmissions.
1
2other
1Other
273,059
Participants distinguished between what they were expecting from the procedure and what they hoped the outcome would be. As an experimental trial, some held no expectations at all or considered their probability of remission in light of outcomes from other trials. With extensive histories of non-response to standard depression treatments, some were inclined to consider “no benefit” the most likely outcome and entertained few hopes to avoid later disappointment. In contrast, one patient described their expectations in positive, absolute terms (“I expect to recover”), explaining optimism was necessary to give them determination to proceed. This affirming mindset appeared balanced by a realistic understanding of the trial’s experimental nature. One patient and caregiver had held initially high expectations after seeing a positive case study in the media; however, these were tempered after discussions with the clinical trial team and receiving further information. Many emphasized how meaningful even a small or partial improvement would be for their quality of life.
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50,791
A multivariate logistic regression analysis was performed to assess the predictive role of the OPG and DKK-1 levels on radiological progression, controlling for potential confounders such as age, sex, disease activity, mean corticosteroid dose, and DMARD treatment duration. The construction of the regression models was perfomed by backward stepwise using both statistical and clinical judgment. The interaction effect of gender was tested by stratified analysis.
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396,755
There was a significant level of edema in the inoculated bulls (IN group) in their subscapular axillary and popliteal lymph nodes, except in bull IN-6 – this animal exhibited edema in its dewlap area and joints, accompanied by lesions on its muzzle, and general weakness (Figs. 2 and 3). In the C1 group, edema appeared late, between days 28–30 p.i., in the areas under the jaw, corresponding with the detectable viremia and elevated body temperatures in all the bulls in this group (up to 40.6 °C, in C1-5) (Figs. 5 and 6). In the C2 group, elevated temperatures were recorded in all animals within a week following their inclusion in the trial (day 33 p.i.), found to be associated with slightly enlarged lymph nodes and edema in the jaw (for C2-3), and the C2-1 bull displayed a mild edema in its dewlap.Figure 2Lesions in the muzzle (red arrows) of IN-6 at day 21 p.i.Figure 3Edematous joints in IN-6 bull at day 21 p.i.Figure 4In-contact bull C1-9 with swollen submandibular space (red arrow) at day 28 p.i.Figure 5C1-5 bull with hyperaemic muzzle epithelium at day 28 p.i.Figure 6Viremia dynamics (averaged per group) (blue – IN, pink – C1, orange – C2).
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44,259
In this study, specific genomic islands could not be exclusively associated with a particular stress tolerance phenotype. This is to be expected as genomic islands often contain virulence factors, and in general these are overrepresented in genomic islands as compared to the chromosome (Sui et al., 2009). In L. monocytogenes in particular, genomic islands have been associated with virulence, heavy metal resistance, and benzalkonium chloride efflux (Gilmour et al., 2010; Kuenne et al., 2010; Kovacevic et al., 2015). SSI-1 as described above, has been previously associated with L. monocytogenes' stress response, but was not significantly correlated with the stress tolerance phenotypes examined in the present study.
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354,480
In the classroom instruction group, the estimated marginal means of the perceived vital signs increased from 3.3 (95% CI 2.9-3.8) with conventional monitoring to 6.2 (95% CI 5.6-6.8) with the Visual Patient. In the individual instruction group, the estimated marginal means of the perceived vital signs increased from 4.1 (95% CI 3.4-4.9) with conventional monitoring to 8.5 (95% CI 7.5-9.5) with the Visual Patient. As shown in Figure 5, this resulted in a mean difference of 2.3 between the number of vital signs perceived with the Visual Patient in the 2 instruction groups (95% CI 1.1-3.5; P<.001).
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95,214
Cells were treated with kaempferol and IL-6 as stated earlier. After incubation, cells were washed with PBS and fixed with 4% paraformaldehyde for 15 min at room temperature. Fixed cells were permeabilized using 0.1% TritonX-100 (Sigma-Aldrich, USA) in PBS for 15 min followed by further washing. The cells were then incubated in blocking solution (PBS containing 0.1% Tween 20, 22.52 mg/mL glycine and 1% bovine serum albumin) for 1 h at room temperature. This was followed by incubation of the respective cell samples with phospho-STAT3 and NF-κB p65 antibody (at 1:100 and 1:400 dilution respectively), overnight at 4 °C. The cells were then washed and incubated with secondary antibody tagged with Alexa Fluor 488, for an hour at room temperature in dark. The cells were mounted with Prolong gold antifade mounting solution with DAPI (Thermo Fisher Scientific, USA) and observed with fluorescence microscope (Olympus model IX83, Japan).
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163,650
Consumption of the supplement chilled was also preferred by the majority of participants; however, for those taking the supplement to work and not having a fridge to store it, this provided a barrier to adherence. As such, it was suggested that consumption of the supplement twice per day, morning and evening, would help to overcome this barrier and facilitate longer-term adherence. “Although you could have them room temperature, it was nice to have them chilled……. But at room temperature, they weren’t as palatable, if you know what I mean.”. (P6, male, aged 47)
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0Study
19,877
Jet energy resolution (JER): After correcting for the mismatch between the data and simulation for the energy resolution, the uncertainty is determined by varying the corrected JER within its \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\eta $$\end{document}η-dependent ±1 standard deviation uncertainties. These changes are then propagated to the calculation of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p_{\mathrm {T}} ^\text {miss}$$\end{document}pTmiss.
2
2other
0Study
384,157
All evaluated data were exported to Microsoft Excel spreadsheets (Microsoft Excel 2010; Microsoft, Redmond, WA, USA) for descriptive statistical analysis. Continuous variables are presented as mean and standard deviation (SD), minimum and maximum, categorical data as frequencies and percentages.
2
0biomedical
0Study
383,507
Colorectal cancer (CRC) ranks third in terms of incidence, but second in terms of cancer-related death worldwide.1 Treatment decision and prognosis assessment mainly depend on the pathological stage of the tumour.2 However, about 20% patients of stage II CRC will relapse after curative surgery.3 Therefore, some other factors were proposed for therapy decisions. For example, stage II patients with high-risk factors, such as T4 stage and high tumour grade, have a greater chance of relapse and should be treated with chemotherapy after surgery.4 But these clinicopathological risk factors do not adequately distinguish between patients who have high or low risk of relapse, and lead to over- or under-diagnosis.5
4
0biomedical
0Study
102,143
Although literature scarcely addresses the correlation of therapeutic vancomycin trough concentrations with improvements in mortality due to infection, there is evidence among the general population that suggests that patients with trough concentrations ≥10 mcg/mL during the presence of an infection were more likely to become afebrile . Additionally, little is known regarding vancomycin dosing in oncology patients who have developed decreased renal function due to concomitant nephrotoxic agents and underlying malignancies.
4
0biomedical
0Study
331,008
Participants were familiarised with the visual cue displayed on a computer monitor that was customised in MATLAB software 7.13 (MathWorks, Inc., Natick, MA, USA, 2010. The visual cue prompted participants to (1) focus on the screen, (2) prepare for the ankle movement by watching a moving cursor, (3) execute either a ballistic voluntary or imagined dorsiflexion movement with their right ankle at a specified time-point and hold for 1 s, and (4) rest. The length of focus and rest periods varied (2–3 s and 6–8 s, respectively). Participants completed two sets of 25 repetitions for both voluntary and imagined movement conditions, while continuous EEG was recorded via a 40-channel EEG amplifier (NuAmps, Compumedics Neuroscan, Dresden, Germany) and sampled at 500 Hz with 32-bit accuracy (SCAN software, Compumedics Neuroscan, Dresden, Germany).
4
0biomedical
0Study
34,714
PSi chip arrays are produced on monocrystalline silicon by lithography technology and electrochemical etching. The diameter of each circular cell on the chip array is approximately 500 μm, and every circular cell has a microcavity structure . By careful design of the parameters of the microcavity structure, when a He-Ne laser with a wavelength of 633 nm produces vertical incidence (0°), the minimum reflectivity is obtained. The laser incident angle starts from 0°, as the incident angle increases, the reflectivity will increase, as shown in Figure 1. This process is equivalent to the increase of the refractive index of the PSi microcavity when the laser produces vertical incidence . Calculation and experimentation have proved that the average gray value of the array cells is directly proportional to the change of the refractive index . Therefore, the change of the refractive index can be obtained by the change of the gray value of the cell in the image. This method has high detection sensitivity and can detect refractive index changes of less than 10−3 .
4
0biomedical
0Study
383,029
Despite the type, portosystemic shunts are typically found incidentally. However, they may be associated with other congenital abnormalities such as duodenal atresia, absence of the ductus venosus, shunts associated with other organs, etc. Clinical presentation depends on the degree and the type of shunt, ranging from an incidental finding on imaging to hepatic encephalopathy .
3
0biomedical
1Other
208,124
Human spaceflight is associated with several cardiovascular risk factors such as changes in normal exercise routine, increased psychological stressors, and elevated exposure to ionising radiation. Upon entering ug, cephalad fluid shift is the most notable adjustment to space and results in an increase in SV (35–46%) and CO (18–41%). Despite these increases, astronauts enter a state of hypovolemia (10–15% decrease in blood volume) during spaceflight. The absence of orthostatic pressure and a decrease in AP reduces the workload of the heart to provide the body with oxygen and nutrient-rich blood. This is believed to be the underlying mechanism for the development of cardiac atrophy in space (10–20% decrease in ventricular size). There are also important cellular and molecular changes. Exposure to µg is associated with changes in cell shape and endothelial dysfunction through suppressed cellular proliferation, increased cell apoptosis, and oxidative stress. The µg platforms have allowed studying multiple physiological changes and have also been necessary for the development of appropriate tools and countermeasures for future human spaceflight missions to LEO and beyond.
4
0biomedical
0Study
115,615
These women otherwise show a full-blown phobic avoidance picture, to all extents and purposes indistinguishable from the phobic pattern as described above in vaginismus. In the clinical setting they tend to be younger women, single or living in a couple relationship as described above. Presentation to the clinical service for help may be, as for vaginismus, related to the desire for full sexual intercourse, or the desire for pregnancy in a couple with a formally unconsummated relationship. A less obvious component of the motivation for help lies in the experience of what may be termed “anticipatory anxiety,” inasmuch as these patients live with a subliminal background fear of the next intimate encounter and are unable fully to relax in approaching intimacy. Anticipatory anxiety (the fear of another panic attack) is in fact a well described feature of panic disorder and plays an important role in the disruption of the quality of life.1
4
0biomedical
1Other
97,042
Plasmodium vivax parasites were collected from patients with malaria in Thailand and spotted onto eight-well glass slides. The slides were fixed in ice-cold acetone for 10 min, dried, and blocked in 5% BSA in PBS-T at 37 °C for 30 min. Then the slides were incubated (dual-labelled) with rabbit anti-PvMSP1-19 (1:50 dilution), rabbit anti-PvDBP (1:50 dilution), rabbit anti-PvRAMA (1:50 dilution), and mouse anti-PvMSA180 (1:100) as primary antibodies at 37 °C for 1 h. Next, the slides were stained with Alexa Fluor 568-conjugated anti-rabbit IgG or Alexa Fluor 488-conjugated goat anti-mouse IgG as secondary antibodies (Invitrogen), and nuclei were stained with 4′,6-diamidino-2-phenylindole (DAPI, Invitrogen) at 37 °C for 30 min. The slides were mounted in ProLong Gold antifade reagent (Invitrogen) and visualized under oil immersion using a confocal laser scanning microscope (FV200Olympus, Tokyo, Japan) equipped with 20× dry and 60× oil objectives. Images were captured using the FV10-ASW 3.0 viewer software.
4
0biomedical
0Study
105,888
Many of these important biological transport processes are modeled as the movement of particles along an ordered chain of sites. In the context of intracellular transport, the particles are motor proteins and the chain models actin filaments or microtubules. In transcription, the particles are RNAPs moving along the DNA molecule, and in translation the particles are ribosomes moving along the mRNA molecule (see Fig 1).
4
0biomedical
0Study
111,598
Considering the gain G(f) of the matching network, the noise floor of the setup is used to estimate the CSMN SNR, such that:(2)SNR(f)=es(f)G(f)/en(f) where es(f) is the output signal induced in the coil, and en(f) denotes the total equivalent voltage noise at the input of the preamplifier. This total noise is calculated from all the individual noise sources depicted in Figure 10 and consists of three components (i.e., input voltage noise eni, input current noise ini, and Nyquist noise et = (4kTRtot)1/2 of all resistors in Figure 10) . We assume these three noise components to be uncorrelated. All these noise contributions can be combined to obtain en as expressed below. (3)en=eni2+(iniZi)2+(4kTRtot)2 where Zi is the impedance of all resistors that input current noise flows through, T is the environmental temperature of resistance Rtot, and k is the Boltzmann factor (1.38⋅10−23 W⋅s/K). eni and ini represent the input voltage noise and the input current noise of the preamplifier, respectively.
4
0biomedical
0Study
238,925
PAR2 deficiency is associated with improved survival after IAV infection. Par2+/+ and Par2-/- mice were infected with 0.04 HAU IAV and changes in body weights were recorded daily for 14 days (A). Overall survival (B) was observed as well as calculated from body weights for 14 days. A weight loss of ≥25% of the initial body weight was set as compassionate humane endpoint as specified in the animal protocol. Body weights before infection (day 0) was set to 100%. Data (mean ± SEM) and calculated survival were analyzed by two-way ANOVA (A) and log-rank test (B). *P < 0.05.
4
0biomedical
0Study
21,896
The greatest contribution to propofol’s individual response is seen in the variants of the CYP2C9, CYP2B6, UGT1A9, SULT1A1, NQO1 genes, involved in the biotransformation pathway of the anaesthestic and also of transporting proteins: especially P-glycoprotein and serum albumin, encoded by the ABCB1 and ALB genes, as well as the receptor genes GABRA1 and ADRA1A 4,9,10. The crucial role can be probably played by three of the genes mentioned above: CYP2B6 (OMIM123930), CYP2C9 (OMIM601130) and UGT1A9 (OMIM606434), coding for metabolizing enzymes: cytochromes P-450 2B6 and 2C9, and UDP-glucuronosyltransferase 1A9, acting mainly in the liver.
4
0biomedical
0Study
178,546
Abbreviations: TPL, threatened premature labor; BMI, body mass index; APH, antepartum premature hemorrhage; CS, caesarian section; HC, head circumference; ACB, arterial cord blood; BE, base excess; *, less asthma admissions in excluded group (mean included = 0.37, mean excluded = 0.26).
3
0biomedical
1Other
144,521
To define the factors, we further examined the EFA results and analysed the scales’ coefficients of internal consistency by calculating Cronbach’s α and McDonald’s ω (scale and scale if item deleted), as well as item-rest correlations. The content of all the items composing factor no. 1 reflects the same latent construct, namely Attitudes Towards People With Mental Health Problems. Deleting any of the items in factor no. 1 would not result in higher α or ω. The item-rest correlations range from .51 (item no. 33) to .72 (item no. 31). Item no. 33, namely ‘Willingness to vote for a politician if you knew they had suffered a mental illness’, has the lowest item-rest correlation and factor loading; however, its deletion does not change the reliability values (Cronbach’s α or McDonald’s ω). Moreover, item no. 33 does not appear to theoretically diverge from other items included in this factor, measuring attitudes towards people with mental health problems. Therefore, we propose to retain this item. The content of the items included in factor no. 2 reflects a latent construct General Attitudes Towards Mental Problems and Help-Seeking. For this factor, item-rest correlations range from .44 (item no. 25) to .61 (item no. 21), with the exception of item no. 20, namely ‘People with mental illness could snap out of it if they wanted’ (rest-item correlation of .25). Deleting this item would result in higher α and ω of .83 (for both measures). Although the item is theoretically more associated with factor no. 2, it also loads factor no. 4 (−.31). This item could be problematic partially due to translation issues. Upon closer inspection, we noticed that the Slovenian translation of the item lacks the negative connotation that is present in the original; it could have a double meaning and thus be understood differently by participants than in the original. Therefore, we propose to exclude this item when applying the instrument. The content of all the items included in factor no. 3 reflects the same latent construct, namely Recognition of Mental Health Disorders. For factor no. 3, deleting any of the items would not result in a higher α or ω. The corrected item-total correlations range from .39 (item no. 5) to .49 (item no. 4). The content of the items included in factor no. 4 refers to the factor named Knowledge About Seeking Mental Health Information. The item-rest correlations for this factor range from .25 (item no. 17) to .54 (item no. 19). Item no. 17, namely ‘Information seeking – using a computer or a telephone’, has the lowest item-rest correlation. Deleting this item would result in higher α of .63 and ω of .64. The item could be problematic because it refers to the usage of phones and computers when seeking mental health information, which may not be equally available to people from certain socio-demographic backgrounds. However, the factor loading value for this item is acceptable 20 and the content of this item reflects the same latent construct as the remaining items in factor no. 4. In addition, factor no. 4 consists of only four items, thus deleting one item would result in a lack of items in the factor, jeopardising the adequate representation of the construct. Therefore, we suggest retaining item no. 17.
4
0biomedical
0Study
107,612
Importantly, patients with HNSS had good survival rates. Similar OS rates have been reported for 167 HNSS patients in a recent Surveillance, Epidemiology, and End Results Program database analysis . A prior study from our institution, which included 42 patients with not only primary tumors but also recurrent and metastatic tumors, reported a similar 5-year OS rate (72%) . Several other studies have also reported 5-year OS rates ranging from 40% to 70% [7, 15, 17, 19] (Table 4).
4
0biomedical
0Study
139,204
Specifically, we compared how consistently four different object naming tasks activated sensory, motor and language regions in neurotypical individuals at the voxel/region level. Three of the object naming tasks involved visual (picture) naming, the third involved auditory object naming (from the non-verbal sounds of objects and animals). For all four tasks, the number of stimuli presented and the fMRI acquisition time was controlled but, for two of the visual naming tasks, we presented objects in pairs every 5 s for a duration of 2.5 s, whereas in the other two tasks we presented one object at a time every 2.5 s for a duration of 1.5 s (Figure 1).
4
0biomedical
0Study
105,626
In the present study, multivariate analyses revealed that tumor size, mitotic count, and histologic subtype were associated with recurrence after curative resection for gastric GISTs. Most studies have shown that the most important prognostic factors for GISTs are tumor size and mitotic count [14, 18, 19]. In the case of histologic subtype, some studies have reported that recurrence is not associated with histologic subtype [20, 21]. On the other hand, another study showed that patients with spindle cell type GIST show significantly higher 5-year RFS than those with epithelioid or mixed type, which is similar to our results .
4
0biomedical
0Study
252,450
In the VABS-II, we found significant differences among the three groups across all domains and combined scores: Communication (χ2 = 84.932; p < 0.001), Daily living skills (χ2 = 106.643; p < 0.001), Socialization (χ2 = 143.458; p < 0.001), Motor skills (χ2 = 50.009; p < 0.001), and the Composite scale (χ2 = 114.885; p < 0.001) (Table 1). The post-hoc analyses showed that, in all subscales, the scores of the ASD + ADHD group were significantly lower than those of the ASD group, and the scores of the ASD group were significantly lower than those of the TD group (Supplementary Table 1; Figure 2A).
4
0biomedical
0Study
56,207
Microscopic changes in the lungs on days 1 (A), 3 (B), 5 (C), 7 (D), 14 (E) and 21 (F) post infection in IBV infected group; A and B: Bronchial Hyperemia, C: Degeneration and necrosis of bronchial epithelium, lymphoid nodules in bronchial wall, D: Lymphoid aggregation in bronchial wall, mild infiltration of mononuclear cells in interstitium, E: Mononuclear cell infiltration, epithelial degeneration and F: Hyperemia and mild inflammatory cell infiltration (H & E; 40×).
4
0biomedical
0Study
369,141
In the present study, mammary tissues from S. aureus-infected rats lasted only 24 h, during which time, the host's defense against S. aureus was mainly regulated by the innate immune response. Through innate immune recognition, inflammatory cascades, including the aggregation of leukocytes to the site of infection, induction of the adaptive immune response and activation of antimicrobial mechanisms, were initiated. These signaling pathways are coordinated through complex mechanisms. The results of the functional enrichment of KEGG pathways in this experiment showed that 82 of the upregulated DSEPs participated in the immune system pathway, involving the complement and coagulation cascades pathway (rno04610), Fc gamma R-mediated phagocytosis pathway (rno04666) and leukocyte transendothelial migration pathway (rno04670).
4
0biomedical
0Study
225,141
Δ(SNP-index) of 12 F2 populations. The female parents of the 12 F2 populations were: 79 (Pop1), Bamla Suffaid 32 (Pop2), M 136–20 (Pop3), Cash (Pop4), Balam 2 (Pop5), Kalasu (Pop6), Black 28–573 (Pop7), Bhahuri Kalasu (Pop8), Changai Kalasu (Pop9), Basmati 385 Kalasu (Pop10), IR 64 Kalasu (Pop11), and BR 11 Kalasu (Pop12).
2
0biomedical
0Study
342,962
The poor quality of care perceived by the population was also reported as a major barrier to access to healthcare services [30, 35]. Poor quality of care was described as a lack of medicines, supplies, and skilled staff and poor attitudes towards patients among health staff [35, 43].
2
0biomedical
0Study
80,803
Nowadays, due to higher levels of pollution, violence and poverty, cities can no longer ensure a good quality of life for everyone and have become unhealthy environments for a great many local inhabitants . An unprecedented urbanization, along with physical, social and economic developments, is having a significant impact on the health of the population .
2
0biomedical
1Other
385,413
Figure 3 and Figure 4 show the particle size distribution and microscopic morphology of different walnut shell powder particle sizes. In the Figure 3a,b and Figure 4a,b, type I presented most walnut shell powder particle sizes gathered in 45 μm, and type II showed sizes gathered in 75 μm. These kinds of powder particle shapes were very diverse, like dendritic, flake, and clavate. As shown in Figure 3c–e and Figure 4c–e, type III presented most walnut shell powder particle sizes gathered in 114 μm, type IV showed sizes gathered in 148 μm and type V showed sizes gathered in 290 μm. These kinds of powder particle shapes were relatively simple, only like dendritic and clavate. In Figure 3f and Figure 4f, type VI presents most walnut shell powder particle sizes gathered in 439 μm, powder particle shape is the simplest, only like clavate. Therefore, it can be concluded that the smaller the walnut shell powder particles sizes were, the more the particle shape types were, and the more complex the particle system was. However, with increasing the walnut shell powder particles sizes, the particle shape types decreased, and the particle system became simple. In the process of SLS, flake and dendritic powder particles were inconvenient for spreading powder, but clavate-shaped particles closer to spherical particles, which was advantageous to spread powder. Importantly, the walnut shell powder particles should not be too big, and in type VI, large powder particle size led to big dimension deviation of sintered parts under process parameters in Table 2. Hence, type VI was ignored in the follow-up study.
4
0biomedical
0Study
18,226
(A-D) Ishikawa cells transfected with siPrx3 or siCont, and treated with doxorubicin for 24 hours. The mitochondrial ROS levels (A), calcium level (B), and mitochondrial membrane potential (C) as measured in CD133+ and CD133− cells. The CD133+ population, analyzed using a flow cytometer, in the siPxr3-transfected Ishikawa cells (D). (E) Doxorubicin-treated CD133+ cells, isolated from the Prx3-depleted and control Ishikawa cells, respectively. Western blots with antibodies against PARP, caspase-3, Prx3, and tubulin are shown.
4
0biomedical
0Study
171,438
SK-6 cells were grown in Dulbecco’s modified Eagle’s medium (DMEM, Biowest, Nuaillé, France) supplemented with 10% heat-inactivated fetal calf serum (FCS, Corning, Tewksbury, MA, USA; negatively tested for pestiviruses), 100 U/mL penicillin and 100 µg/mL streptomycin. Cells were maintained at 37 °C and a CO2 concentration of 5%.
4
0biomedical
0Study
227,173
The area quantification module (v2.1.3), which is a default module available as part of the basic HALO software package, was used to calculate the pix H-score with the number of phenotypes set to 1 (see Supporting information for the settings files). The algorithm deconvolves the IHC image into hematoxylin and DAB channels and can detect and classify hematoxylin and DAB positive pixels as high, medium, and low based on a user defined threshold. For the calculation of pix H-score, a single threshold was used to detect all hematoxylin positive pixels and three separate thresholds were used to detect and classify the DAB positive pixels. In HALO, these thresholds take values between 0 and 1. In order to keep the thresholds implemented in Visiopharm and HALO identical, the threshold values used in Visiopharm, which take values between 1–255, were rescaled to take values between 0 and 1 and these were then used in HALO. Unlike Visiopharm, HALO keeps track of the detected pixels in the DAB and hematoxylin channels separately. Consequently, pixels that contain both DAB and hematoxylin signal that are above the thresholds will be accounted for in both the hematoxylin and DAB channels. In order to mimic the Visiopharm implementation of pix H-score, we define a third channel, which is denoted as phenotype 1 channel in HALO that pertains to pixels that are positive for hematoxylin but negative for DAB. This phenotype 1 channel will contain pixels that are analogous to the hematoxylin positive pixels detected in the Visiopharm implementation of pix H-score algorithm. The algorithm outputs the area of high, medium, and low pixels in the DAB channel, and the area of positive pixels in the phenotype 1 channel, which is used as an estimate of the total area of pixels containing only the hematoxylin signal. These values are then used in Eq 3 to calculate the pix H-score.
5
0biomedical
0Study
78,995
Using PS, 32 (59%) of 54 resection samples had at least one EGFR mutation (35 mutations total), with an additional 8 identified by NGS (Table 4). One PS mutation was not confirmed with NGS. By PS/NGS, 33 resections (61%) were RAS mutated. Twenty-six resections had a single, 7 a double and one a triple mutation (Supplementary Online Material Table 3).
4
0biomedical
0Study
95,041
Drug susceptibility testing of field isolates is logically assumed to be the most useful method to predict treatment outcome, as has been established for antibiotics in bacterial infections (Boothe, 2010) and for malaria (Duru et al. 2015). However, treatment failure is a complex interplay between various factors (Table 3) related to either drug, parasite or host, and is thus not necessarily exclusively linked to drug susceptibility (Vanaerschot et al. 2014). For example for SbV, a correlation was found between treatment outcome and the in vitro amastigote susceptibility profile of field isolates ranging from susceptible (S/S) over intermediate (R/S) to resistant (R/R). Actually, R/R cases could be linked to non-responders or relapse cases while S/S strains were linked to cure. The intermediate R/S profile was linked to an increased risk for R/R development (Inocencio da Luz et al. 2009). On the other hand for MIL, in vitro susceptibility data could not be used to predict treatment failure (Hendrickx et al. 2015a) even though some studies do suggest a weak link between in vitro susceptibility and treatment outcome (Bhandari et al. 2012; Rijal et al. 2013). Also the promastigote back-transformation assay, initially proposed as an alternative to assess treatment outcome (Hendrickx et al. 2014) could not differentiate between responder and relapse patients when evaluated on a larger set of clinical isolates (Hendrickx et al. 2015a). Table 3.Overview of factors involved in VL disease progression and treatment failureFactorReferencesHostImmunological factors(Jarvis & Lockwood, 2013; Ostyn et al. 2014)Pharmacokinetics(Ostyn et al. 2014)Genetics(Blackwell, 1996; Castellucci et al. 2014)Reinfection(Rijal et al. 2013)Environment(Perry et al. 2013)DrugDrug quality(Dorlo et al. 2012a, b )Intrinsic drug properties (e.g. T1/2)(Hastings et al. 2002)Treatment duration(Geli et al. 2012)Non-compliance(Rijal et al. 2013)ParasiteLower intrinsic susceptibility to the drug(Singh et al. 2006; Rijal et al. 2013)– gene amplification of drug target enzymes– structural and functional modifications of drug target enzymes(Mondelaers et al. 2016)– decrease in intracellular drug concentration due to extrusion by specific transportersHigher parasite fitness(Vanaerschot et al. 2014; Hendrickx et al. 2015b; Hendrickx et al. 2016)
4
0biomedical
2Review
68,684
Box plots comparing patients with probable PTSD and those without symptomatic PTSD for (A) pain severity (z [N = 430] = 8.48, P < 0.0001, r = 0.41), pain interference (z [N = 431] = 9.07, P < 0.0001, r = 0.44), and pain disability (z [N = 431] = 8.72, P < 0.0001, r = 0.42); (B) pain catastrophizing (z [N = 430] = 9.74, P < 0.0001, r = 0.47), kinesiophobia (z [N = 428] = 8.25, P < 0.0001, r = 0.40), and self-efficacy (z [N = 422] = 9.20, P < 0.0001, r = 0.45); and (C) anxiety (z [N = 430] = 11.58, P < 0.0001, r = 0.56), and depression (z [N = 431] = 10.80, P < 0.0001, r = 0.52). PTSD, posttraumatic stress disorder.
4
0biomedical
0Study
274,748
In our study, we assume that patients with low SES receive adequate cancer management under the Korean national health insurance system because low SES was not a risk factor for VTE. The risk of VTE increased in patients diagnosed with cervical cancer more recently, which might be attributed to developments in diagnostic techniques for VTE and improved accessibility under the Korean national health insurance system.
2
0biomedical
0Study
148,810
The NSF was used to assess anxiety-like behaviors in mice. Before the test, mice were deprived of water and food for 24 hours. In the NSF, a high-fat chow was placed in the middle of the 50 × 50 cm arena; then, mice were placed into one side of the arena. The mice were videotaped for 5 minutes, and the latency time to the first eat was automatically recorded by Intelligent Systems Inc.
4
0biomedical
0Study
295,873
The tissues were lysed (1:10, w/v) in RIPA (Solarbio Life Sciences; Beijing, China) containing protease inhibitors to quantify the protein production of IFN-α, IFN-β, IL-6, and TNF-α from mouse organs. The supernatants from these tissue lysates were examined by ELISA, using a VeriKine Mouse IFN Alpha ELISA Kit (PBL Interferon Source), Legend Max Mouse IFN-β ELISA kit (BioLegend; CA, United States), Legend Max Mouse IL-6 ELISA kit (BioLegend), or Legend Max Mouse TNF-α ELISA kit (BioLegend). To further quantify the protein production of the major inflammatory cytokines, the supernatants from tissues lysates (brain, spleen, and liver) and serum were examined by flow cytometry, using a LEGENDplex™ Mouse Inflammation Panel (13-plex) with a filter plate (BioLegend), following the manufacturer’s instructions.
4
0biomedical
0Study
44,907
ChIP assay was carried out according to the manufacturer's protocol (ChIP assay Kit, Millipore). The precleared lysates were immunoprecipitated with Sox9 antibody and normal rabbit IgG (sc-2027, Santa Cruz). The pull-down purified DNA was quantified using qPCR, with the primers indicated in Supplementary Table S4.
3
0biomedical
0Study
218,550
Systematic data analysis in Marín-Franch et al.14 consisted of fitting a sine wave to the accommodative response, r, to a moving stimulus over time t, with frequency f, amplitude a, and temporal phase p. Thus,1\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\begin{aligned} r = a\, \text {sin}\, 2\pi f \left( t-p\right) , \end{aligned}$$\end{document}r=asin2πft-p,where the frequency f was 0.05 Hz, 0.1 Hz, 0.2 Hz or 0.4 Hz. Amplitude a and phase p were estimated using ordinary least squares. Note that this calculation is equivalent to performing a Fourier transform and collecting amplitude and phase at the frequency of interest22. As we previously published, only three observers could follow the stimulus at 0.4 Hz (Figure 5 in Marin-Franch et al.14) and thus, data from this frequency was removed from the analysis. Therefore, data for 24 trials for each of the 9 observers were selected for analysis: 6 preliminary trials and 6 trials for the optical-blur condition with temporal frequencies 0.05 Hz, 0.1 Hz, 0.2 Hz.
4
0biomedical
0Study
166,846
Galectin-3 was also broadly studied in grown-ups with congenital heart diseases, and the results could serve as a direction for future research in younger cohorts. In the study by Frogoudaki et al. of galectin-3 as a risk factor for major cardiovascular events defined as death, hospitalization, worsening functional class or cardiac intervention did not produce optimistic results; however, the concentration of the marker correlated with arrhythmias and was significantly higher in the case of patients presenting supraventricular or ventricular tachycardia. Moreover, the authors found a correlation between galectin-3 and global longitudinal strain in adults with congenital heart diseases. Galectin-3, as a marker of ventricular function, was also assessed in a cohort of adults with a systemic right ventricle by Geenen et al. and only weak correlations were found in relation to right ventricle global longitudinal strain; however, again, higher galectin-3 levels were associated with an increased risk of arrhythmias. An interesting study in adult patients with arrhythmogenic right ventricular cardiomyopathy by Oz et al. and implanted defibrillators adds to the evidence for galectin-3 being useful in the risk stratification of arrhythmias. Emphasizing fibrosis as the source of the disease, the authors found galectin-3 to be predictive of ventricular tachycardia and ventricular fibrillation in this cohort. An interesting report by Geenen et al. assumed that we have a significant decrease of galectin-3 one day post-atrial septal defect closure in adults, suggesting that it could reflect shunt cessation and subsequently volume overload of the right ventricle. Moreover, in 2020, the results delivered by Kowalik et al. showed galectin-3 to be useful in patients with an overloaded right ventricle; however, only in those with congenitally corrected transposition of the great arteries. No significant correlation was found in adults with Eisenmenger syndrome.
4
0biomedical
2Review
59,291
For each sex, past year substance use problem was modeled as a function of age and syndemic profile (Table 4). Among women, older age (OR = 1.02; 95% CI: 1.00–1.03) and membership in either the Low Resources and Support (OR = 8.50; 95% CI: 3.85–18.74) or Historical Risk/Assets (OR = 2.81; 95% CI: 1.29–6.12) syndemic classes increased the odds of a past year substance use problem relative to the Assets and Few Historical Risks class.
4
0biomedical
0Study
300,232
Additional file 1: Fig. S1 Expression levels of β-catenin under the treatment of different concentrations of miR-342-5p agomir, miR-342-5p antagomir and oe-Wnt3a in aortic tissues of AS mice. A. Comparison of β-catenin mRNA expression under treatment with different concentrations of miR-342-5p agomir; B. comparison of β-catenin mRNA expression under treatment with different concentrations of miR-342-5p antagomir; C. comparison of β-catenin mRNA expression under treatment with different concentrations of oe-Wnt3a vectors; n = 6; # P < 0.05 vs. the NC group; measurement data were indicated as mean ± standard deviation. Comparisons among multiple groups were assessed by one-way ANOVA followed by Tukey’s multiple comparisons test. NC, negative control.
4
0biomedical
0Study
328,241
Furthermore, the binding mode of the active compound 21a was evaluated by molecular docking studies, where the negatively charged carboxylate moiety at the position 3 of the pyrazole compound was shown to be anchored in the active site through ionic interaction with the positively charged non-heme iron. Through hydrophobic interaction, the aryl substituent at position 5 interacts with the hydrophobic side-chains of the amino acids Leu368, Leu414, Ile415 and Phe421. In addition, the aryl substituent and the benzenesulfonamide moieties are involved in Van der Waals interactions with the amino acid Phe421. Through hydrogen bonding, the sulfonamide moiety interacts with Tyr181 and Asn425 residues in 5-LOX enzyme.
5
0biomedical
0Study
264,535
Some teachers reported on children who, before the introduction of the robot, would not be willing to talk to the teacher, or did not want to learn. However, after the robot was introduced in the classroom, these children started to talk. First to the robot, and thereafter to the teacher. Teachers said that they expected that children would more easily express certain things to robots than to their teachers. “I think that a robot could definitely be used for that [emotional support] as well […] because it is something that is a bit further away from you and a bit less personal, so I think it is easier to discuss more difficult things […] and certainly in the social, emotional area,” as voiced by one of the teachers. Some teachers used the robot as a means to let children talk about their feelings by letting the robot express emotions. This has led to the opportunity to talk about emotional feelings. One teacher compared this to hand puppets that are currently used in the Dutch educational system to start confirmations on difficult subjects, which the teacher considered a similar tool.
1
2other
1Other
269,743
Plates with the library of 433 FDA-approved compounds from Selleckchem’s anticancer drug library (Supplementary Table S1). HuT78 cells were seeded into plates (2 × 104 cells/well), and were treated or not with 10 μM of histamine for 72 h. To determine the cell viability, we used the homogeneous method CellTiter-Glo® Luminescent Cell Viability Assay (Promega, USA) following manufacturer’s instructions. It is based on quantification of the ATP present, which signals the presence of metabolically active cells. Luminescence was measured using the Synergy4 microplate reader (BioTek).
4
0biomedical
0Study
31,621
Our in vitro studies showed that PRK efficiently inhibits the activity of MtArgJ, a crucial enzyme in the arginine biosynthesis pathway of the pathogen. So, we hypothesized that the in vivo (cell‐based) effect is due to the reduction in arginine levels within the pathogen. Therefore, we aimed to confirm the mechanism of action of PRK‐mediated killing of Mtb H37Rv. To examine this, we supplemented the Mtb minimal media cultures with arginine alongside PRK treatment and calculated the CFU post‐treatment. As shown in Fig 7A, the Mtb cultures treated with PRK (1 μg/ml) had significant decrease in the cell survival. However, upon supplementation with arginine (1 mM), the effect of PRK‐mediated cell death is rescued. In the samples treated with rifampicin (0.4 μg/ml), arginine supplementation had no effect on the cell death. This shows that PRK induces its bactericidal effect on Mtb by reducing the arginine levels in the pathogen, while no such effect was observed when a totally different antibiotic (the one against bacterial RNA pol) was used instead. The inability of Mtb to survive under arginine deficit created by PRK is also consistent with the suitability of MtArgJ as a target against Mtb survival.
5
0biomedical
0Study
278,199
(a–e) MD simulations of 5HT2AR in complex with TM5-Tat and Tat-TM6 peptides. The previously published computational model of the CB1R–5HT2AR heteromer18,20 (panel a) was used as the starting point for MD simulations (see Experimental Section) of a membrane-embedded (yellow spheres) 5HT2AR (green ribbons) in complex with peptides where the TM5 (blue ribbon, panel b) or TM6 (red ribbon, panel c) sequences are fused to HIV-Tat(48–57) (orange). These TM5-Tat and Tat-TM6 peptides (Table 1) were stable in the three replicas of 1 μs unbiased MD, as shown by root-mean-square deviations (Figure S1). Panels (d,e) show detailed views of the interactions between TM5-Tat and Tat-TM6, respectively, with TM helices 5 and 6 of 5HT2AR. Snapshots along the trajectories are shown as transparent ribbons, whereas representative structures are solid ribbons. Side chain residues involved in stable interactions of TM5-Tat and Tat-TM6 with 5HT2AR (Ballesteros–Weinstein notation) during the MD simulations are labeled. Interaction frequency maps for frequencies above 50% in at least one of the three replicas (r1, r2, and r3) are depicted. TM5-Tat and Tat-TM6 residues involved in stable interactions with two or more 5HT2AR residues are highlighted in bold.
4
0biomedical
0Study
120,728
Two other issues related to physician online contribution can be investigated in future work. First, patients with chronic or acute conditions would come with quite different symptoms and receive different treatment processes . In particular, most people with acute illnesses (eg, flu) will soon recover, but chronic health conditions (eg, diabetes) usually cannot be cured, only controlled. The chronic or acute condition might lead to dissimilar physicians’ online contribution behavior. Second, and perhaps more importantly, the physician online contribution must meet different types of social support needs including informational and emotional support . The former can be specified into experience-based information, unconventional information, and medical facts . By contrast, emotional support involves a patient’s emotions or feelings; for instance, physicians need to listen and talk about patients’ concerns in a way that is helpful and reassuring. In terms of mental health, the emotional support may be more important than the informational support. Therefore, it is also worthwhile to explore the type of social support that the physician online contribution provides for patients.
2
2other
1Other
1,523
Feed efficiency was an important index reflecting digestion and absorption efficiency of a given dietary . In this study, feed efficiency of Tibetan sheep fed TMR and OS maintained a relative efficient level after 45th day of the experiment (Fig 3), OH was the least efficient in feed conversion among three given diets. There was a trend that dietary with higher CP level was better in feed efficiency in Tibetan sheep. Feed efficiency of yaks fed TMR and OH maintained a relative efficient level after 60th day of the experiment, OS was the least efficient among three given diets. Overall results indicated that feed efficiency of TMR (7.65 for Tibetan sheep and 8.50 for yaks) was better as compared to OH and OS (Table 3).
4
0biomedical
0Study
395,733
38 patients (23 female, 15 male) underwent a pre-operative CT kidney-ureter-bladder (CTKUB), because right sided renal colic was initially suspected at presentation. A radiological diagnosis of acute appendicitis was made in 26 patients of which 25 (96.15%) had the diagnosis confirmed histologically. Of the nine patients whose appendix was reported as “Normal” on CTKUB, 2 (22.22%) had histologically proven appendicitis.
4
0biomedical
0Study
332,967
The stimuli consisted of six patterns superimposed on four surfaces. Each pattern–surface pair was used to create a tetrad of stimuli as depicted in Fig. 4e. The full stimulus set consisted of 24 tetrads, which were a subset of those tested in our previous study25.
2
0biomedical
0Study
383,522
Then, we applied the signature to independent datasets to validate the prognostic value. In the validation cohort with 89 stage II CRC patients treated with surgery only from the GSE33113, 52 patients were predicted to be in the low-risk cluster, whose DFS was significantly higher than the other 37 patients who were predicted to be in the high-risk cluster (Fig. 2b, HR = 3.32, CI: 1.24–8.88, log-rank p = 0.0112). A similar result was shown in GSE14333 and GSE17538 cohorts (Fig. 2c, d). Since different datasets could be directly integrated based on the within-sample REOs, we combined datasets with small samples (sample size < 50) according to the individual platforms and defined Com_570 and Com_96, respectively. As expected, patients in the Com_570, combined from the GSE26906, GSE31595, GSE39084 and GSE92921 cohorts, were significantly stratified in terms of DFS (Fig. 2e). However, only 39 gene pairs (Supplementary Table S3b) of 51-GPS were detected by Com_96 from the HG-U133A Array, we recalculated the optimal vote threshold in the training dataset as described above and a sample was classified as a high-risk cluster if at least 20 gene pairs voted for the high-risk, otherwise, low-risk cluster. Patients in the Com_96, combined from the GSE12945 and GSE41258 cohorts, were also stratified into two risk clusters with significant DFS differences by the signature (Fig. 2f).
4
0biomedical
0Study
106,199
The sites were established in October 2005 as plots that were 1.4 m by 1.2 m by 1.0 m. Maize or corn was grown in triplicate plots every year since the spring of 2006, with subtypes of Haiyu 6 at the N site, Zhengdan 958 at the C site, and Denghai 11 at the S site. Maize cropping, together with fertilizers of CO(NH2)2, (NH4)2HPO4, and KCl at the level of 150 kg N, 75 kg P2O5 and 60 kg K2O per ha, was administered to another triplicate plots. The P and K fertilizers and half of the amount of the N fertilizers were applied before maize cropping (growing maize). The other half of the N fertilizer was applied at the maize bell stage. Bare fallow plots were used as a control for maize cropping and NPK fertilization.
3
0biomedical
0Study
390,077
Health centers began implementation by identifying adult patients, 18 to 85 years of age who might benefit from SMBP. Health center care teams recommended patients with uncontrolled primary/essential hypertension (defined as a systolic blood pressure ≥ 140 mmHg or a diastolic blood pressure ≥ 90 mmHg) for SMBP based on individual health center protocols, typically through health information technology registry identification and a recommendation or referral from medical providers. From July 2017 to June 2018, identified patients were offered training on SMBP. Patients were given or loaned a monitor and educated on how to use it. The education included proper preparation and positioning to obtain an accurate measurement and how to communicate blood pressure measurements back to the care team. For those using Bluetooth-enabled monitors, patients received training on an associated app that sent measurements to an online portal accessible to their care team. Patients were supported via follow-up phone calls, patient portal messages, and/or text messages.
4
0biomedical
0Study
235,449
It is known, however, that FSH only has a moderate sensitivity and specificity in predicting ovarian response to gonadotrophins, as its serum levels rise only when the ovarian reserve is severely compromised . In the past, various cut-off values of serum FSH ranging from 10 to 15 IU/L have been recommended for predicting POR in IVF , but a generally accepted cut-off value above which one would expect POR has not yet been determined. As ovarian aging begins several years before FSH’s rise, normal FSH values do not exclude POR to OS . Therefore, we can only predict POR to OS in women with extremely high levels of FSH.
4
0biomedical
0Study
391,969
One erroneous argument made for ear cropping is to prevent illnesses and injuries in spaniels, terriers, other hunting dogs, and dogs with pendulous ears; however, there is no evidence to back up these claims (101). The etiology of otitis is related to many factors, including allergies, and breeds historically shown with cropped ears are no more likely to be diagnosed otitis (102–104). There should be no argument that this surgical procedure causes pain. As with tail docking, people will provide the argument in favor of “tradition” to support the continued practice of ear cropping. Given these weak arguments, there is little evidence to support ear cropping.
4
0biomedical
2Review
152,161
The main purpose of this article is to explore the effect of BPs on fracture healing. The main parameters include bone mineral density (BMD) changes, healing time, and bone metabolism indicators. The goal is to clarify if BPs can be used to promote fracture healing after fractures.
4
0biomedical
0Study
199,219
Cells seeded in 24-well plates were fixed with 4% formaldehyde in phosphate-buffered salt solution (PBS; pH 7.4) at the desired times postinfection. Staining for viral proteins was performed with conditioned 4G2 hybridome (anti-flavivirus mouse antibody) media at a 1:10 dilution or ZIKV NS2B protein antibody (rabbit polyclonal IgG; Genetex, catalog no. GTX133308) at a 1:100 dilution. Myofibers were stained using a polyclonal antibody against myosin heavy chain (MF20) at a 1:50 dilution. They were then stained with goat anti-mouse Alexa Fluor 488 (Invitrogen) at a 1:500 dilution. Cells in each field were visualized with the nuclear stain DAPI (GIBCO/Life Technologies) at a 1:10,000 dilution. Images were acquired using an inverted fluorescence microscope (IX81; Olympus) at a magnification of ×20. Images of 4G2-positive cells for at least 10 fields were used to determine the percentages of infected HSMM cells. The cell fusion index in cultured mock-treated or ZIKV-infected myotubes was determined by quantification of MF20-positive cells as the percentage of the total number of nuclei (DAPI), and the fiber area was obtained by measuring the MF20 fluorescence normalized by the cell number per field. Image quantification was performed for at least 10 fields using ImageJ software (version 1.51 j.8).
4
0biomedical
0Study
113,769
This study provides additional evidence that the universal, non-specific VTE assessment model known as the KRS is not suitable for all types of malignancies, particularly lymphoid malignancies. Both DLBCL and HL require prompt initial systemic chemotherapy, and, as they are both lymphomas, they are categorized as intermediate groups according to the KRS. Consistent with the literature, our data show that the overall incidence rate of VTE in patients with lymphoid malignancies is high, reaching 15% within the observation time [15–18]. In addition, we demonstrated a difference in the VTE incidence between DLBCL and HL patients (19 vs. 10%) and in the clinical presentation.
4
0biomedical
0Study
146,811
Our results also confirm the effectiveness of the proposed clinical pathway in significantly decreasing the LOS for several categories of patients with different clinical conditions as shown (Table 3). Such an impact of the clinical pathways is widely recognized in the literature. Indeed, as outlined in the European Quality of Care Pathways (EQCP)-study on proximal femur fracture performed by the European Pathway Association, an international not-for profit association, they demonstrated not only that care pathways can significantly reduce the LOS in hospital settings, thus having a positive impact on different healthcare outcomes, but also that the LOS, with particular regard to the preoperative LOS, is a crucial indicator that needs to be monitored and taken into great account when designing a quality improvement study and this has been proven not only in the case in the elderly population, but also in the case of the pediatric population .
4
0biomedical
0Study
37,458
Oligonucleotide primer pairs were designed for bb0017 and for the constitutively-expressed flaB gene (S7 Table). The primer pairs were tested to confirm the amplification of a single product with a known size using genomic B. burgdorferi DNA as the template. Reverse transcription reactions were performed by combining Invitrogen’s SuperScript II Reverse Transcriptase (ThermoFisher Scientific, Waltham, MA) with purified RNA from the appropriate B. burgdorferi strain according to manufacturer’s instructions. The gene-specific primers bb0017R or flaBF (S7 Table) were used to synthesize cDNA. Detection of flaB was done to control for the isolation of RNA. A control reaction lacking reverse transcriptase was performed in all cases to test for the presence of residual DNA. Subsequently, the cDNA from the reverse transcription reactions was used as template and subjected to PCR using Takara EmeraldAmp Max PCR Master Mix (Clontech Laboratories, Mountain View, CA). To amplify the B. burgdorferi targets, the amplification program was modified as follows: (1) 94°C for 2 min; (2) 98°C for 10 sec; (3) 45°C for 30 sec; and (4) 72°C for 2 min. Steps two through four were repeated 30 times followed by a final extension step at 72°C for 10 min. The resulting samples were then resolved by agarose gel electrophoresis.
4
0biomedical
0Study
255,734
In this experiment, specific primers HygF1 and HygR1 (Supplementary Table 1) of the transgenic vector hygromycin resistance gene were used to detect different lines of transgenic wheat in the T1 generation and to screen the seeds of the transgenic wheat with a resistance: sensitivity ratio of 3:1 to identify single-copy transgenic lines. Genomic DNA was isolated from transgenic wheat leaves using the cetyltrimethylammonium bromide method (Porebski et al., 1997). The DNA was then used for polymerase chain reaction (PCR) assays, and PCR-amplified products were separated by 1.0% agarose gel electrophoresis. The T2 generation of the transgenic wheat was detected by PCR, and the T3 generation was detected by PCR and RT-qPCR.
4
0biomedical
0Study
61,474
The VEGF/VEGFR-2 signaling axis represents an essential and attractive target to manipulate pathological angiogenesis in vivo. Ramucirumab is a monoclonal antibody developed from a human Fab antibody fragment targeting VEGFR-2 , and approved for the treatment of advanced gastric cancer, gastroesophageal junction adenocarcinoma cancer, non-small cell lung cancer, and metastatic colorectal cancer . Furthermore, promising studies with antibodies and DARPins targeting VEGFR-2 have been previously published . We set out to generate novel VEGF/VEGFR-2 inhibitors based on VEGFR-2 specific antibody fragments that allosterically block receptor activation.
4
0biomedical
0Study
375,682
Knapp confirmed that this was the procedure that would be followed: someone would have to propose to send something to the Editorial Committee. The Section would then vote on sending it to the Editorial Committee with the proviso that the Editorial Committee could accept it or reject it as they saw fit. A vote counter to that would mean that Section would not want a proposal to go to the Editorial Committee.
1
2other
1Other
180,036
We aimed to create ML training data with minimal false positives and multiple, sharply-defined affinity levels (Fig. 2a; Methods). We synthesized aptamer particles from a DNA library containing a 40-mer random region flanked by primer sites and performed two rounds of PD with a total of three affinity thresholds. To perform a round of PD, the pool of aptamer particles was first incubated with fluorescently-labeled target at a given concentration. Next, the pool was screened via fluorescence-activated cell sorting (FACS) to partition the particles based on a gating fluorescence value as the threshold (see Methods for details). The affinity thresholds were separated by fourfold each by lowering the target concentration fourfold while keeping the same sorting gate value at Fmax/3 (Supplementary Table ST1). The approximate affinity thresholds for the increasing stringencies (<128 nM, <512 nM, and <2 µM) were estimated via KD curves on a subset of the observed aptamers (Supplementary Fig. S1, Supplementary Table ST1). In Round 1 the relatively low-affinity thresholds (<512 nM, and <2 µM) created a large pool of initial candidates. Under these conditions, we observed that a fraction of the library was able to pass the Fmax/3 thresholds (Supplementary Fig. S2). At each concentration, we collected the positive aptamer particles as well as ~105 negative aptamer particles (F < Fmax/3), for use as negative examples in ML training. Primer particles exhibiting no aptamer sequences were excluded from this analysis.Fig. 2Design of particle display training data and concordance across experimental affinity thresholds.a Two rounds (denoted R1 or R2, respectively) of particle display (PD) experiments were run with increasing stringency (decreasing protein concentrations) such that the lowest stringency (light green) should contain all aptamers observed at higher stringencies. At each stringency level, we obtained positive pools of aptamers each with affinities that pass the affinity threshold (green shades) and negative pools that do not pass the affinity threshold. R1 positive pools were amplified then mixed as the template for the R2 particle display experiment. All pools were NGS sequenced. b, c Venn diagram of unique aptamer clusters in (b) the original particle display experiment and (c) the machine learning guided particle display (MLPD) positive pools. Green-colored sections indicate sequences observed at a particular stringency and all lower stringencies. The dotted line and pie chart in (c) show the concordance (dark green) of the fourth and highest stringency run in the MLPD experiment (< 8 nM).
4
0biomedical
0Study
126,054
PCL and PLGA encapsulated cell-laden hydrogel was used to make a meniscus scaffold by 3D printing technology. (A) Schematic diagram of the design of a bioprinted composite material study for regeneration of a goat meniscus. (B) PLGA-encapsulated hydrogels containing MSCs cells exhibited good printability. (C) CAD model of the meniscus for 3D printing. The cell hydrogel and PCL were printed into 3D meniscus by 3D printing technology. (D) Zone-specific matrix phenotype analysis in engineered versus native tissue (Sun et al., 2020).
4
0biomedical
0Study
329,415
Gender-based violence reduces engagement for women living with HIV at multiple care continuum levels . It might be a particularly salient issue for the Latin American region, where high rates of intimate partner violence, sexual assaults, and femicide have been documented [13, 14].
2
0biomedical
1Other
353,994
Lastly, we evaluated the opinion of scientific societies on the possible future effects of the SARS-Cov-2 pandemia in pediatric medical assistance. Most scientific societies believe that they will treat COVID-19 related diseases, primarily deriving from the indirect action of the virus, mostly psychosomatic disorders. In fact, during a severe pandemic like COVID-19, community-based mitigation programs, such as closing of schools, parks, and playgrounds will disrupt children’s usual lifestyle and can potentially promote distress, confusion, anxiety and hostility .
2
0biomedical
1Other
122,798
Microglia were isolated as previously described (Cardona et al., 2006). Briefly, male and female P7 pups were perfused with ice-cold HBSS, before isolating and mincing the brains. The tissue was homogenized with a dounce homogenizer containing RPMI media before being mixed with stock isotonic percoll (SIP) creating a 30% SIP solution. This cell/SIP mixture was layered on top of a 70% SIP solution before being centrifuged. The resulting interphase containing the microglia was collected and washed with HBSS and cells were counted before being lysed for western blot analysis.
3
0biomedical
0Study
370,935
The almost complete absence of Cripto expression in adult tissues under physiological conditions highlights its potential role as a biomarker for multiple diseases. Genetic imbalance of the TDGF1 locus is per se a risk factor of tumorigenesis, as demonstrated by data from transgenic mouse models with a heterozygous loss of TDGF1. When challenged with a colon-specific carcinogen, Cripto heterozygous mice exhibited a higher incidence of colon cancer compared to Cripto wild-type mice . Polymorphisms and mutations in the TDGF1 locus have been linked to different medical conditions and assessing the TDGF1 genetic status was shown to improve cancer patients’ risk stratification, as well as produce information about potential genetic disorders . For instance, Cripto promoter methylation was shown to discriminate among different subtypes of testicular germ cell tumors . The potential use of Cripto as a biomarker also showed promising results in breast and colon cancer, with higher levels in the serum of cancer patients compared to healthy individuals . However, its use as a pan-cancer serological marker should be further investigated in order to establish a definite threshold for baseline levels of circulating Cripto. In this regard, a few polymorphisms in the TDGF1 promoter have been linked to a significantly reduced level of circulating Cripto in a genome-wide association study of about 1500 individuals .
4
0biomedical
0Study