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This manuscript is of interest to infectious disease specialists, biochemists and biophysicists working on SARS-CoV-2. It provides detailed and rigorous affinity and kinetics analyses of the effect of several biologically relevant amino acid substitutions in the SARS-CoV-2 receptor binding domain and ACE2 as measured by surface plasmon resonance with recombinant proteins. Although the study is limited to a binding analysis of monomeric protein domains, the data may contribute to understand the rapid emergence of SARS-CoV-2 variants with substitutions in the spike protein.
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249,227
Atrial fibrillation (AF) is the most commonly diagnosed arrhythmia in clinical practice . It is estimated that 2.3 million adults in the United States are burdened by AF, and as the population ages that number is expected to increase to 5.6 million by 2050 . The consequences of AF, including thromboembolic events, stroke, and heart failure, are well documented. These consequences of disease progression account for the significant impact on morbidity, mortality, and healthcare costs . Therefore, AF is not only a devastating clinical problem but also a public health and economic burden.
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2Review
312,060
In our earlier work, we described Erava heteroresistance in Staphylococcus aureus and Klebsiella pneumonia isolates with comparatively low Erava minimum inhibitory concentrations (MICs), which suggested that the resistance emerged as a result of antibiotic treatment failure (Zhang F. et al., 2018; Zheng J. X. et al., 2018). However, it is not known whether Erava heteroresistance is also found in E. faecalis. Recent evidence has attributed the development of resistance to the new class of Tet antibiotics including tigecycline (Tige) to genetic mutations in the Tet binding site of the 30S ribosomal subunit, which includes 16S rRNA and 30S ribosome protein S10 (Nguyen et al., 2014; Grossman, 2016). Regulators of several efflux pumps or membrane proteins, such as SoxS, MarA, RamA, and Rob, have also been implicated in Tige resistance (Nguyen et al., 2014; Grossman, 2016), although the mechanistic details are not well-understood. In addition, tet(X) orthologs, which encode Tet destructases and inactivate Tet antibiotics, represent a unique enzymatic Tet resistance mechanism (Grossman, 2016; He et al., 2019; Sun et al., 2019). Moreover, it is unclear whether Erava susceptibility is influenced by Tet binding site mutations or overexpression of the efflux pump and membrane proteins.
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20,741
We live in a 3D world. The ideal method to enable navigation in 3D space would be to have a 3D compass or global positioning system (GPS) that identifies direction and distance in relation to all 3 axes in an isotropic manner. Such a 3D compass system would seem to be essential for animals who fly or swim. Indeed, place cells and head direction cells found in flying bats were observed to be sensitive to all 3 axes (Yartsev and Ulanovsky 2013; Finkelstein et al. 2014). Behavioral experiments with fish also indicated a volumetric 3D representation of space (Burt de Perera et al. 2016). However, as suggested by Jeffery et al. (2015), extending spatial encoding from 2D to 3D space comes with complications such as the noncommutative property of 3D rotation, and a fully volumetric representation of 3D space might be costly and unnecessary for certain environments and species. When an animal’s movement is restricted on the earth’s surface due to gravity, its position can be identified by 2 coordinates on that surface and a quasiplanar representation could be more efficient than a volumetric 3D representation.
4
0biomedical
2Review
125,448
Feedback from tasks refers to the “degree to which carrying out the work activities required by the job results in the individual obtaining direct and clear information about the effectiveness of his or her performance” (p. 258). It can be considered as another important resource that contributes to the success of agile work . Agile work practices, for example, working in iterations and regular team reflection, are designed to provide regular opportunities to share knowledge, address difficulties, and exchange feedback on several perspectives . For example, in retrospective sessions, each team member gives feedback on what worked well, what did not work well, and how things could be changed in the next iteration . Some teams increase the visibility of the achieved performance by working with quantitative feedback using specific performance metrics, such as burndown charts. Furthermore, at the end of each work iteration, the agile team demonstrates the results in so-called review meetings to receive feedback from various internal and external stakeholders on the achieved product increment. Regarding the many different feedback opportunities, it can be assumed that members from agile teams perceive high levels of feedback from their work.
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2other
1Other
160,199
The Online Platform for Healthy Weight Loss (POEmaS, from the abbreviation in Portuguese) study was a 3-arm (1:1:1), parallel, RCT evaluating the efficacy of a coach-supported online platform for promoting weight loss . The protocol and main results are described in detail elsewhere. The RCT was registered at ClinicalTrials.gov (NCT03435445). This is a substudy of the POEmaS RCT that includes data from the two intervention arms only.
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Given that SBM1 encodes a plasma membrane‐localized oligopeptide transporter domain containing protein (Figure 1f), it may be involved in nitrogen utilization (Hu et al., 2015). We selected NPB, ko and OE plants to test the sensitivity of SBM1 to nitrogen treatment. Regardless of the presence of NH4NO3 or not, compared to NPB, both ko and OE lines showed significant difference in seedling biomass, with increase and decrease, respectively (Figure 1k). These indicated that SBM1 might respond to varied nitrogen application. Next, we tested this inference through a field experiment by using NPB and NIL‐SBM1Kasalath , with two different nitrogen application rates, that is high‐nitrogen (180kg/ha urea) and low‐nitrogen (90kg/ha urea) conditions. Compared to NPB, NIL‐SBM1Kasalath showed significant increase in plant height, grain number per panicle and grain yield per plot, but not in tiller number per plant under both conditions (Figure 1l). Given that significantly higher NUE was observed in NIL‐SBM1Kasalath (Figure 1l), we tried to test the difference in nitrogen uptake and transport activity between NPB and NIL‐SBM1Kasalath through a 15N‐NH4NO3 feeding experiment. NIL‐SBM1Kasalath showed significantly higher 15N uptake and transport activity than NPB (Figure 1m). Also, nitrate reductase activity, an important indicator of nitrogen utilization, was higher in NIL‐SBM1Kasalath than in NPB (Figure 1m). These confirmed the sensitivity of SBM1 to varied nitrogen application. Additionally, through phenotyping, rice accessions with Kasalath haplotype (HapB) at SBM1 tended to have a higher grain yield ratio (LN/HN) (Figure 1n), indicating this haplotype had great potential for improving nitrogen utilization in rice, as shown by desirable yield performance under low‐nitrogen conditions.
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Another SNP associated with PGII levels was rs8111742 in miR-Let-7e, an endogenous miRNA predicted to bind the 3′-UTR of PGC . This miRNA is a direct regulator of numerous genes involved in cell proliferation and differentiation, and it shows a tumor suppressor function for several oncogenes (e.g., RAS, MYC), which may explain why a reduction in its expression in a variety of cancers has been associated with poor prognosis and increased epithelial-mesenchymal transition . Due to its important role in both physiology and disease, miR-Let-7e is now considered a target for therapeutic drug development . Two studies have reported a reduction of miR-Let-7e expression in the tissue of GC patients , and lower levels in GC patients with H. pylori infection than controls . Thus, the miR-Let-7e reduction is a common event in GC. We found an association between lower serum PGII and the G/G genotype of rs8111742 in all GC patients and the subgroup of GC patients without H. pylori infection. These findings indirectly support a role in miR-Let-7e in GC pathogenesis H. pylori-mediated.
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Cardiac phenotype of pericardin alleles. (A-G′) Dissected third instar larvae were stained with anti-GFP (green channel) to visualise the GFP reporter expression in cardiac cells driven by hand-GFP (Sellin et al., 2006) and counterstained with Phalloidin-TRITC to label the actin fibres in cardiomyoblasts and somatic muscles (red channel). Pictures show the heart of dissected third instar larvae with the genotype handC-GFP (A,A′), handC-GFP; prc3-21/prc3-21 (B,B′), handC-GFP; prc3-548/prc3-548 (C,C′), handC-GFP; prcMB03017/prcMB03017 (D,D′), handC-GFP; prc3-21/prc3-548 (E,E′), handC-GFP; prc3-21/prcMB03017 (F,F′) and handC-GFP; prc3-548/prcMB03017 (G,G′). The higher magnifications (red channel) illustrate the orientation of F-actin fibres in the heart tube. (H) For quantification of the observed reduction of the heart diameter, five to 13 individual animals were used to measure the width along the heart chamber (with 10 µm distance between the individual reading points). The heart diameter is significantly reduced compared to wild type (***P≤0.0001, unpaired t-test). Higher-magnification images show representative areas of the dorsal vessel with the respective genotype, either taken from the same animal shown on the right side or a different animal with the same genotype. H shows box-and-whisker plots with lower and upper quartiles and the median. Whiskers indicate variability outside the upper and lower quartiles. In addition, scatter plots are shown.
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Standing height and bodyweight of the study participants were measured in a standardized manner, using digital weight and height scale (Detecto, Webb City, MO, USA) with the participants standing erect without shoes and wearing light clothes. BMI-for-age z-scores were calculated using WHO growth charts. Obesity was defined as BMI-for-age ≥ +3 Standard Deviation (SD), while overweight was defined as BMI-for-age > +2 SD and < +3 SD. Waist circumference (WC) was measured in the horizontal plane at the superior border of the right iliac crest to the nearest 0.1 cm with a non-stretchable tape by a trained data collector. Measurements were taken at the end of normal expiration; three readings were taken, and the average of the three was recorded. Care was taken to ensure that the tape was horizontal to the floor and touched the skin without compressing it. The ratio of waist circumference (cm) to height in centimeters (WC/Ht ratio) was calculated and the obesogenic waist was defined as a WC/Ht ratio of > 0.5 (37).
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TGF-β is a pleiotropic growth factor that has diverse roles in epithelial-mesenchymal transition (EMT), development, carcinogenesis, cancer metastasis and immune escape [8–11]. Although TGF-β may inhibit tumorigenesis at the early stage by inducing cell cycle arrest, it stimulates EMT and cancer metastasis at later stage . The canonical TGF-β singaling is mediated by SMADs. Upon TGF-β binding to its receptor complex including type I and type II TGF-β receptors (TGFBR1 and TGFBR2), TGFBR is phoshorylated and activated, and then induces SMAD2/3 phosphorylation. Subsequently, SMAD4 is recruited to the phosphorylated SMAD2/3 complex and translocated into the nucleus, where SMAD3 directly binds to DNA and regulates the transcription of many effector genes . Except for the canonical TGF-β signaling, TGF-β may promote the activation of other signaling pathways, such as phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signalling cascades . Notably, there is cross-talk between the canonical and non-canonical TGF-β signaling pathways. The mechanisms underpinning TGF-β signaling in cancer are quite complex. Given the importance of TGF-β signaling in tumorigenesis, it is crutial to identify the regulators of TGF-β signaling that are aberrantly expressed in human cancer.
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191,854
The incidence of irritable bowel syndrome (IBS) was reported to improve when supplements combining isoflavone and active vitamin D were taken. Since periodic changes in the levels of estrogen affect female IBS patients and activated vitamin D is involved in the activity of estrogen receptors in intestinal smooth muscles, it was thought that ingestion of isoflavones and vitamin D could alleviate IBS symptoms. Thus, 40 mg of isoflavone and 50,000 international unit (IU) of activated vitamin D supplement, either separately or in combination, were given to 100 female IBS patients for 6 weeks, and indicators such as TNF-α, NF-κB, and fecal serine protease were measured. NF-κB (a transcription factor) is an important factor in triggering mucosal inflammation, and high levels of TNF-α (an inflammatory cytokine) induces the production and release of other inflammatory cytokines that induce NF-κB activation and increase intestinal permeability. Fecal serine protease is also an indicator of intestinal epithelial tissue permeability. If intestinal permeability is increased, it can cause an inflammatory reaction due to the invasion of pathogens. In the study, after 6 weeks, all indices increased in the placebo group; however, in the groups that received at least one type of supplement, there were significant decreases in all indices. The group that took both supplements showed the greatest decrease in these indices, with NF-κB being significantly reduced by half (Table S3) . These results indicate that the combined intake of isoflavone and active vitamin D can help improve gastrointestinal disorders such as IBS by lowering the levels of cytokines that cause inflammation in the intestine, thus reducing intestinal permeability.
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Several population-based experiments confirmed that elevated baseline Hcy levels are positively associated with cSVD incidence and the subsequent severity and disease progression, independent of vascular risk factors and severity of the atherosclerotic disease. The relevance of the presence and number of lacunar infarcts, WMH volume, and progression to high baseline Hcy levels (32, 69–71) provides a more intuitive view of the correlation between HHcy and cSVD. In patients with dementia caused by small vessel lesions, higher tHcy levels were used to predict WMH progression, and the level was associated with deep CMBs and lacunes (32). In cSVD-related stroke, serum Hcy levels were significantly higher in patients with large WMH volumes than those with small WMH volumes (69, 70). The association between Hcy and WMH burden suggested that the degree of ED may be greater in patients with increased WMH volume and may, in part, explain that ED acts as a bridge between HHcy and cSVD (72). Similar results were obtained in recent observational studies, where WMH volume and EPVS number were positively correlated with plasma Hcy concentrations. EPVS may be specifically associated with BBB leakage led by injured ECs and is considered as an important marker of BBB disruption (68, 73, 74).
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The injectable nature of drug delivery was perceived by healthcare professionals to be a barrier to recruitment. One suggested that having had an injection pen available for potential participants to see and hold when approached about the trial could have improved recruitment. A common misconception was that the injections would be similar to depot injections, with a much larger needle. This was, understandably, off-putting for many. Participants reported being pleasantly surprised by the injection device and only one participant expressed concern regarding injections, namely that the needle may bend. They did not experience such an event. The results show that participants did not find the injections to be burdensome and easily accommodated them within their usual daily routine.
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TO03’s purified peptides were analyzed on the linear-trapping quadrupole—Orbitrap mass spectrometer (LTQ-Orbitrap Velos; ThermoFisher Scientific) on-line coupled to an Agilent 1290 Series HPLC using a nanospray ionization source (ThermoFisher Scientific) including a 2 cm long, 100 μm-inner diameter fused silica trap column, 50 μm-inner diameter fused silica fritted analytical column and a 20 μm-inner diameter fused silica gold coated spray tip (6 μm-diameter opening, pulled on a P-2000 laser puller from Sutter Instruments, coated on Leica EM SCD005 Super Cool Sputtering Device). The trap column was packed with 5 μm-diameter Aqua C-18 beads (Phenomenex, www.phenomenex.com) while the analytical column was packed with 3 μm-diameter Reprosil-Pur C-18-AQ beads (Dr. Maisch, www.Dr-Maisch.com). Buffer A consisted of 0.5% aqueous acetic acid, and buffer B consisted of 0.5% acetic acid and 80% acetonitrile in water. Samples were run on a gradient method where buffer B was from 10% to 25% over 120 min, from 25% to 60% over 20 min, from 60% to 100% B over 7 min, kept at 100% for 2.5 min and then the column was reconditioned for 20 min with buffer A. The HPLC system included Agilent 1290 series Pump and Autosampler with Thermostat set at 6°C. The sample was loaded on the trap column at 5 μL min-1 and the analysis was performed at 0.1 μL min-1. The LTQ-Orbitrap was set to acquire a full-range scan at 60,000 resolution from 350 to 1600 Th in the Orbitrap to simultaneously fragment the top fifteen peptide ions by CID in each cycle in the LTQ (minimum intensity 200 counts). Parent ions were then excluded from MS/MS for the next 30 sec. Singly charged ions were excluded since in ESI mode peptides usually carry multiple charges. The Orbitrap was continuously recalibrated using lock-mass function. The mass error measurement was typically within 5 ppm and was not allowed to exceed 10 ppm.
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Next, we evaluated the effect of MAGL inhibition on neuronal survival using KML29, a second-generation MAGL inhibitor that shows higher potency (IC50 = 43 nM) than JZL184 (IC50 = 262 nM) for the rat enzyme inhibition . Starting at DIV6, GFP-transfected neurons from mixed and enriched cultures were treated with 250 nM KML29 every 48 h and subjected to longitudinal survival analysis (Figure 3A). MAGL inhibition significantly increased the risk of death in neurons from enriched primary cultures, but neurons in mixed cultures were not affected. This result strongly suggests that the presence of glial cells counteract the neurotoxic effect of MAGL inhibition with KML29 (Figure 3B). CB1 and CB2 receptors are potential candidates through which this glial-dependent counteractive effect could be mediated. In particular, CB2 receptors that are preferentially expressed in glial cells.
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All these data collectively strongly indicate that inhibition of the NF-κB signal pathway may be a promising target to control SARS-CoV-2 induced excessive immune activation associated with systemic cytokine and chemokine release, capillary leakage, and multi-organ tissue damage ( Figure 1 ).
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273,636
The emergence, transmission, and persistence of highly infectious diseases in healthy populations are often facilitated by climate change and exacerbated in areas with intense anthropogenic activity (McKnight et al., 2017; Rizzoli et al., 2019). The introduction and re‐introduction of infectious diseases often result in rapid local population declines, reducing species’ adaptive potential and generating substantial economic losses (Belant & Deese, 2010; Escobar et al., 2019). In Ontario deer, however, we observed an excess of rare alleles with no evidence of strong population structure, including in southern Ontario where an environmental cline exists around lake systems. An excess of rare alleles and high N e and absent population structure might provide the means for effective adaptation to selective pressures, including climate change, infectious disease, and human activity.
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385,105
Even if its effects on birth outcomes and child growth remain unclear, aflatoxin exposure is still a substantial public health threat due to its carcinogenic properties. In our study sample, the 99% prevalence of aflatoxin exposure at relatively low levels highlighted critical research gaps that need to be filled. Researchers should investigate potentially safe levels of exposure in utero, methods and timing of exposure measurement, the complex and interacting pathophysiology of multiple mycotoxins, and exposure management at the population and individual levels. In parts of Africa, South Asia, and Southeast Asia, chronic, low levels of aflatoxin exposure have been shown to be widespread. Although these health effects could be less obvious compared with higher exposure levels, the public health implications for such a large population could be substantial. The growing knowledge surrounding the extent of aflatoxin exposure and its health effects should be used to demonstrate the necessity of both improved food safety measures and expanded research into less understood areas.
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32,135
The SOM was evaluated for all individuals that were followed up and did not have anemia at baseline (Figure 1F) and was trained with a subset of individuals that were lost to follow-up and did not have anemia at baseline (Figure 1L). This training subset closely matched the ones that were followed-up. Matching was based on the first two principal components for each network module (Figure S1) as these components summarise the aggregate information from the network modules . We selected the closest matching pairs that showed no significant difference (p > 0.05) in age, sex, baseline hemoglobin and ferritin levels, and baseline daily calories and iron intake. To eliminate confounding effects from gender, the SOM training data were first split by sex, all continuous variables were then converted into ranks within the genders, respectively, and finally, the two groups were pooled back together before applying the SOM algorithm. The pattern for incident anemia at the five-year follow-up suggested four subgroups (Figure 2). The mean values for each subgroup, together with 95% confidence intervals, were estimated by bootstrapping with 10,000 simulations.
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Even though neurophysiological measures have potential to provide insight into learning, the question remains how research on this topic should move forward to ensure valid applications. The nature of this current overview does not allow to go into the details of methodological issues inherent to the studies reviewed, but will instead assume the importance of these peer-reviewed articles and focus on how to best move the field forward.
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0biomedical
2Review
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Probiotics do not give significant effect to the egg mass. The factors that cause variations in egg mass are the natural pattern of egg production, feed, management, and also other factors related to genetics. Egg mass is genetically inherited. Environmental influences such as pen environment, parent body size, the maturity stage, age, medications, type of feed, the amount of feed, and food substances in the diet such as the adequacy of protein and linoleic acid greatly affect the of the egg mass . Egg production in a relationship with genetic selection makes today’s egg production quails quite different from reviews those of a decade ago .
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0biomedical
1Other
52,390
Adult onset Still’s disease (AOSD) is a rare chronic inflammatory disorder that usually accompanied with high spiking fever, arthritis and salmon pink skin rash . The wide range of disease manifestations and course suggest heterogeneity of the disease entity . Macrophage activation and subsequent overproduction of cytokines are involved in the pathogenesis of AOSD . Therefore, cytokine-directed therapies have the potential to target macrophage-activation seen in AOSD . Also, recent insights into autoinflammatory disorders have indicated that interleukin (IL)-1 blockers may be effective against steroid-refractory or immunosuppressant-refractory AOSD . To treat steroid-resistant AOSD, previous reports have suggested the use of immunosuppressants such as methotrexate and cyclosporine A . Additionally, anti-cytokine treatments including TNF or IL-6 blockers appear to be an efficient well-tolerated, steroid-sparing treatment against immunosuppressants-refractory AOSD . The application of these biologics may provide clinicians with useful tools for the management of refractory AOSD. While targeting these cytokines has shown promising effects , there remain AOSD patients who do not respond to these biologics and they are associated with potential severe side effects. This is the first report on the successful induction of remission with colchicine in biologics-refractory AOSD.
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To assess the potential of the PEDOT-based films to act as instructive coatings for biomaterials, we investigated four different systems: cells seeded on PEDOT-PSS-based multilayer films without electrical stimulation; cells seeded on PEDOT-PSS-based multilayer films with electrical stimulation; cells seeded on PEDOT-S-based multilayer films without electrical stimulation; and cells seeded on PEDOT-S-based multilayer films with electrical stimulation using a custom built setup (Figure 3A). Those samples without electrical stimulation were cultured for 3 days, whereas those that were electrically stimulated were cultured for 1 day without stimulation, followed by one period of stimulation at 10 mV mm−1 for 4 h, then 44 h without stimulation.
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Used alongside the results of exploratory factor analysis and confirmatory factor analysis in the two research stages (Table 2, Table 4 and Table 5), the compiled safety perception scale had good construct validity, convergent validity, and discriminant validity. The three dimensions of safety perception in an urban forest environment (safety environmental perception, control perception, and safety emotion) could be properly distinguished in people’s cognition and were consistent with the theoretical conception of personal safety perception.
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To screen for polymorphic molecular markers, we first extracted the genomic DNA of a representative fruiting body of A. exitialis, using the CTAB-based method that was slightly modified for fungi as described previously . The genomic DNA was digested by the HaeIII endonuclease and run on 1% agarose gel . The DNA fragments between 1kb to 1.5kb were excised from the agarose gel and purified with the QIAquick PCR purification Kit. The obtained DNA fragments were subcloned into pPCR-Script Amp predigested cloning vector with a PCR-Script Amp Cloning Kit (Stratagene, La Jolla, CA, USA). The recombinant molecules were transformed into the XL10-Gold® Kan Ultracompetent cells. The transformed cells were grown and screened for E. coli colonies containing recombinant molecules. The A. exitialis genomic DNA fragments inserted into the cloning vector were individually amplified by PCR and sequenced.
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32,961
The present meta-analysis was carried out using the Comprehensive Meta-Analysis (version 2.0) software package (Borenstein et al., 2005). Since we only included studies using the 21-item BDI, the mean difference (the mean BDI score in the male sample minus the mean BDI score in the female sample) was also available as an effect size, together with the widely used Cohen’s d. For both measures, a negative difference score indicates a higher BDI depression score in females than in males. The random model was used for calculating the effect sizes due to expected heterogeneity. A funnel plot was used to illustrate potential publication bias and quality of individual studies. In addition, the fail-safe-N, the number of additional unpublished studies with negative effect that would be needed to increase the p value for the meta-analysis to above 0.05, was also calculated to estimate publication bias (Rosenberg, 2005).
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Following on the previous perspectives on the macro-archaeological scale, this section explores alternative research avenues to past stone artefact technologies prompted by materiality thinking. Rather than offering a complete survey of the analytical and interpretive possibilities of materiality theory, deviating from or disrupting common apprehensions of the archaeological record, this section probes into a small selection of promising themes and issues profiting from materiality-oriented inquiry. We focus on three interrelated dimensions or aspects of the Palaeolithic record: (1) Geospatial, (2) technical and (3) evolutionary. The objective is to showcase the large bandwidth of ideas, concepts and perspectives supplied by object-theoretical renderings of lithic technology and their capacity to further, re-direct and, if necessary, subvert palaeoarchaeological discourses and narratives.
1
2other
1Other
396,851
Attainment target 1 (Scientific enquiry) has not been a success. It did not promote the kind of practical enquiry of those who first proposed it intended. Rather, it led to a routinisation of practical activity, and a reduction in the kind of illustrative practical work that can help students gain knowledge of natural phenomena and understanding of concepts and principles. (p. 180)
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1Other
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Lastly, the antimicrobial activity of a prepared composite of BC/SA at different concentrations of GM was evaluated using the disk diffusion method. As shown in Table 5 and Fig. 8, the SA and BC/SA composites have activity on of the model pathogens applied. The addition of GM to BC/SA composites enhanced the antimicrobial activity against all of the model microbes except for P. aeruginosa and C. albicans. These results indicated increasing the GM concentration was correlated with increased antibacterial activity of BC/SA composites against E. coli, S. mutans, S. aureus, and K. pneumoniae. Based on the diameters of inhibition zones (Table 2), the highest antimicrobial activities were against S. mutant, S. aureus, E. coli, and K. pneumoniae, in order. The varied antimicrobial activity (Different halo zones) may be attributed to differences in the susceptibility of different microbes to prepared composites72. GM exerts its action through inhibiting the protein synthesis, nucleic acid reproduction, formation of vital metabolites, and DNA destruction of bacteria that lead to the cell membrane rupture and subsequent death of cells69,73. Hence, the antimicrobial activity of the BC membrane is neglected74,75; several studies reported its fabrication with other materials to enhance this activity including BC/SA/silver sulfadiazine72, BC/SA/PHMB76, BC/SA/silver nanoparticles77, and BC/SA/chitosan/copper sulfate78. Combining all beneficial qualities would make prepared BC/SA/GM composites good antibacterial wound dressing materials as well as for other biomedical applications.Table 5The antimicrobial activity of the prepared BC/SA/GM composite at four concentrations against six pathogenic microorganisms.OrganismDiameter of halo-zone (mm)SamplesSABC/SABC/SA/GM1BC/SA/GM2BC/SA/GM3BC/SA/GM4E. coli009 ± 0.851415 ± 0.2316 ± 0.84P. aeruginosa000000K. pneumoniae00089 ± 0.4610 ± 0.78S. aureus0020 ± 0.5128 ± 0.4729 ± 0.5831 ± 0.12S. mutant0029 ± 0.1235 ± 0.763840 ± 1.49C. albicans000000Figure 8Disk diffusion method for antimicrobial activity expressed as halo zones of the prepared BC/SA/GM composite at four GM concentrations 1 (0.025), 2 (0.050), 3 (0.075), and 4 (0.100) against six pathogenic microorganisms.
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Comparison of experimental (blue) and theoretical (red) curves of the relationships between the flowing time and flowing distance of different samples treated with laser fluence: (a) 11.63 J/cm2, (b) 18.49 J/cm2, (c) 27.71 J/cm2, (d) 35.55 J/cm2, (e) 44.05 J/cm2, (f) 52.67 J/cm2, (g) 61.56 J/cm2, (h) 68.42 J/cm2. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
3
0biomedical
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274,731
Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), aggravates morbidity and mortality and increases economic burden in patients with cancer1–3. Although a predisposition to hypercoagulability in patients with cancer induces VTE, VTE can also be caused by a combination of acquired factors, including age, immobility, surgery, trauma, smoking, obesity, medical comorbidity, history of VTE, chemotherapy, and hormone therapy1,4,5.
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More research is clearly needed to explain the distribution of these reefs. Ideally we would use species distribution modeling to analyze the factors most correlated with the distribution of these species as well as to determine the locations of possible areas of suitable habitat14, 15, 31, but we currently do not have high enough resolution data for key parameters that would go into such modeling, in particular backscatter, in situ currents, and other important factors.
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Another benchmark dataset, popularly known as the FEP dataset, was selected from the work of Wang et al. . This dataset was used to predict the relative binding potency using a modern free-energy calculation protocol and forcefield. This dataset was comprised of ligands from BACE, MCL1, PTP1B, thrombin, and Tyk2 targets. Notably, except for thrombin, all prediction performances from SMPLIP-Score were positive, and the prediction ranking was PTP1B > Tyk2 > BACE > MCL1 > thrombin. Comparison of the prediction results with those of other methods (i.e., KDEEP and Res4HTMD) revealed that for all of the FEP targets, SMPLIP-Score performed better than the KDEEP model, while for BACE and PTP1B targets, Res4HTMD performed better [24, 29].
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C57BL/6J (both male and female 8–10 weeks old) and DBA/1 male mice were from Guangzhou Southern Medical University Laboratory Animal Technology Development Co., Ltd. (Guangzhou, China) and Guangdong Medical Laboratory Animal Center (Guangzhou, China), respectively. All the animals were kept and bred under the same environment with a 12-h light/dark cycle. Food and water were given ad libitum. Animal experiments were performed by following the rules from the National Institutes of Health Guide for the Care and Use of Laboratory Animals, which were approved by the Southern Medical University Animal Ethics Board.
3
0biomedical
1Other
386,868
For the analysis of the data, the vaccination report of the mother was used. Age was categorized in four groups: 18–24, 25–30, 31–35, ≥36. Patients were classified as high obstetric risk if they reported having diagnosis of bronchitis, asthma, chronic obstructive pulmonary disease, cystic fibrosis, diabetes, HIV, cardiovascular disease, chronic kidney disease or stroke. We calculated the percentage of women that were vaccinated against influenza by provider recommendation and the offer of influenza vaccination. Among unvaccinated persons, we categorized the main reasons reported for not being vaccinated into 4 main groups: access issues, not wanting or needing the vaccine, concern with safety, lack of offer / recommendation of the vaccine. We also assessed the categorized main reported reasons for not being vaccinated by demographic characteristics, education, number of children, antenatal care, and high-risk conditions. Finally, we analyzed the relationship of receipt of influenza vaccination with predictors for vaccination (age, educational level, marital status, employment, antenatal care, number of children, high-risk conditions, gestational age at birth, recommendation or offer of vaccination by health care provider, and knowledge and attitudes about vaccination) by bivariate and multivariate analysis (log-binomial regression). We present unadjusted and adjusted prevalence ratios (PRs) with 95% confidence intervals. Data were analyzed using STATA® software (version 14.0).
4
0biomedical
0Study
263,846
Mutant C shows the highest succinate production with 7.9015 mmol gDW−1 h−1 and 0.2761 h−1 of growth rate. Mutant C involved the removal of gnd gene, genes that encode pdh (aceE, aceF, and lpdA), and sdh genes (same as Mutant B). Tang et al. stated that knockout of the gnd gene that catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate affects the pentose phosphate cycle . It leads to a large amount of glucose is utilized in the glycolysis and citric cycles to produce more succinate. The removal of pdh genes that catalyzes the overall conversion of pyruvate to acetyl-CoA, inhibits pyruvate to be used to produce acetyl-coA. Its removal hence inhibits the formation of competing products such as ethanol and acetate that leads to an increase of succinate production . It acts as the primary link between glycolysis and the tricarboxylic acid (TCA) cycle . By inhibiting the production of competing products, the production of succinate is notably increased. Figure 4 illustrates the succinate pathway of mutant A, B, and C where the genes are being knocked out.
4
0biomedical
0Study
77,505
Alcohol group. Inclusion criteria included the following: age ≥ 18 years up to 65 years of age, lifetime AUD diagnosis and at least 4 weeks of abstinence. The exclusion criteria of the alcohol group were as follows: the presence of infectious diseases, personal history of cancer, incapacitating cognitive alterations and pregnancy. Four abstinent AUD patients were excluded from the initial cohort according to the exclusion criteria.
3
0biomedical
0Study
31,948
Formation of compatibility stresses at the interface of a bicrystal under external loading (schematic figure modified and adapted from ). (a) Interface of two crystals (e.g. twin variants) 1 and 2 in the unloaded condition, and relative orientation of twinning elements K1 and η1 for the special case of a twin boundary. (b) Free deformation of the two crystals due to their orientation and elastic anisotropy under external loading leads to strain incompatibility at the interface. (c) Compatibility at the interface requires that additional compatibility stresses (with different signs on both sides of the interface) occur.
4
2other
1Other
153,705
Stereotactic RT is usually proposed for early-stage NSCLC in medically inoperable patients. Owing to the technical properties and characteristics of dose gradient, SRT is associated with low-dose bath to ensure a high conformal dose distribution around the target; however considering the small size of the lesions treated with SRT, this low-dose spread is usually limited. This could prompt to develop approaches of SRT-based sub-volume radiation boost following a conventionally fractionated course of RT for the treatment of locally advanced disease; this approach is currently being explored in stage III NSCLC (136).
4
0biomedical
0Study
94,908
All reactions were carried out in three technical replicates using the Applied Biosystems 7500 fast Real-Time PCR System . Amplification plots were examined for adequate amplification and successful polymerase chain reaction. A ΔRn threshold value of 0.2 (within the exponential phase of amplification) was set to ensure comparability across plates. Ct values were recorded for both samples and controls and compared using the ΔΔCt method.
4
0biomedical
0Study
205,780
Tumor length >4 cm is the only strong predictive factor correlated with decreased rate of pCR in our study. There were few previous studies reported that tumor length was the predictor for pCR. Ren et al in 2019 showed that tumor length ≤3 cm and well differentiation tumor were the significant factors associated with pCR. Ouyang et al reported in 2021 that tumor length may be an early predictor of pCR and high sensitivity to total neoadjuvant treatment. However, this study did not give the cut-off point of tumor length. The major limitation in this study is 43% of patients received mFOLFOX6 which is not standard regimen for CRT. The major advantage of tumor length as a predictive factor for pCR is it can be obtained in preoperative period, thus helping surgeons for preoperative decision making before treatment. Regarding to our results, we can establish some recommendations. First, low rectal cancer patients who had preoperative tumor length ≤4 cm may has a chance to be the potential candidate of watch and wait strategy due to high rate of pCR, these might be benefit if they refused to proceed with abdominoperineal resection. Second, locally advanced rectal cancer patients who had preoperative tumor length >4 cm may require additional treatment in order to improve pCR rate and oncological outcome. Longer waiting time between 11 and 12 weeks and more intense neoadjuvant therapy may be considered as the potential options. Futuremore, large scale randomized controlled trial will be the next step to answer this question.
4
0biomedical
0Study
108,575
Activin βA immunofluorescence staining (Fig. 7) revealed that the βA subunit was localised mainly in the cytoplasm of Sertoli cells as well as in some interstitial cells in untreated and adjuvant control testes at 30 (Fig. 7a,b), 50 (Fig. 7e,f) and 80 (Fig. 7i,j) days. A similar pattern of activin βA expression was also observed in low grade EAEO at 30 (Fig. 7c), 50 (Fig. 7g) and 80 (Fig. 7k) days. In contrast, in severe EAEO testis at 30 (Fig. 7d), 50 (Fig. 7h) and 80 (Fig. 7l) days after the first immunisation a strong staining of activin βA was detectable in cells within the inflammatory infiltrates and in Sertoli cells.
4
0biomedical
0Study
64,740
Several previous reports demonstrated the interaction of CaMKII and Cx36 in neurons (Alev et al., 2008; Kothmann et al., 2012; Turecek et al., 2014). In the inferior olive, electrical coupling is strengthened by activation of NMDA receptors and CaMKII-mediated phosphorylation of Cx36 (Turecek et al., 2014). In the retina, a similar pathway is active in AII amacrine cells, the key interneurons of the most sensitive rod pathway. Kothmann et al. (2012) localized activated CaMKII at Cx36-containing gap junctions in AII amacrine cells and demonstrated that Ca2+ influx via NMDA receptors leads to CaMKII-mediated phosphorylation of Cx36 and to an increase in gap junctional coupling between AII cells. However, for both brain regions, it remained unclear which CaMKII isoform mediates the synaptic potentiation. Our data indicate now that in AII cells, activity-dependent phosphorylation of Cx36 is predominantly mediated by CaMKII-δ. Immunolabeling in sections and intracellular dye injections into individual AII cells showed considerable overlap between CaMKII-δ and Cx36. Although CaMKII-α and -β are well characterized for their function in synaptic plasticity and interaction with NMDA receptors (Sanhueza et al., 2011), only CaMKII-β was weakly expressed at AII gap junctions (Figure 7, Supplementary Figure S3). As NMDA receptor/Cx36 complexes may exist in many other brain regions (Kothmann et al., 2012), it will be interesting to see whether it is always CaMKII-δ and maybe -β that link glutamate-mediated excitation to potentiation of electrical coupling.
5
0biomedical
0Study
80,164
The question arises to which extent the calculated sensitivities vary for different parameter sets of the model. To address this question we employed a random sampling approach to obtain multiple parameter sets and combined it with sensitivity analyses. Specifically, we applied a bottom-up sampling in which the steady state concentrations and reaction flows are sampled directly over seven orders of magnitude. The rate coefficients are then calculated from the sampled values. Details are provided in the Methods section. For each model, parameter sets are sampled until the period and amplitude sensitivities for 2 500 different parameter sets yielding sustained oscillations for each parameter perturbation could be analyzed. Depending on the specific model between 5.9·104 and 2.4·107 parameter sets had to be sampled (numbers given in the S1 File).
4
0biomedical
0Study
110,777
The vascular endothelial growth factor (VEGF) is an important angiogenic mediator in breast cancer . VEGF-A is a multifunctional cytokine widely expressed by tumor cells that acts through receptors (VEGFR-1, VEGFR-2, and neuropilin) expressed on vascular endothelium and on some other cells. It increases microvascular permeability, induces endothelial cell migration and division, reprograms gene expression, promotes endothelial cell survival, prevents senescence, and induces angiogenesis . VEGF targeted therapy with the monoclonal antibody against VEGF-A, bevacizumab; seem to have modest clinical efficacy in patients with metastatic breast cancer [73, 74]. IBC is known to have high rates of endothelial cell proliferation and vascular density when compared to non-IBC, which could suggest potentially greater sensitivity to antiangiogenic therapies . Wedam et al. reported results of a small cohort of 21 patients with both IBC (n=20) and (n=1) non-IBC treated with bevacizumab for cycle 1 (15 mg/kg on day 1) followed by six cycles of bevacizumab with doxorubicin (50 mg/m2) and docetaxel (75 mg/m2) every 3 weeks in the neoadjuvant setting . Tumor biopsies were collected on cycles 1, 4, and 7; a median decrease of 66.7% in phosphorylated VEGFR2 in tumor cells and median increase of 128.9% in tumor apoptosis were seen after bevacizumab alone. These changes persisted with the addition of chemotherapy. One patient had a complete pathological had a complete pCR and 14 have partial clinical response overall response rate (ORR) of 67% (95% CI, 43% to 85.4%). The ORR results are comparable with historical controls treated with anthracycline/taxane combination without bevacizumab in the neoadjuvant setting (ORR 81%) .
5
0biomedical
0Study
47,670
In this study, we target MTHFR and COMT to investigate the function of these two genes in lignification and their potential synergetic effects on morphology in switchgrass. Our results showed that strong downregulation of MTHFR in a COMT-deficient background led to reduced plant growth. However, lignin content of the MTHFR/COMT-RNAi plants was similar to that of the single COMT downregulated plant. To our surprise, a novel lesion-mimic leaf phenotype was observed. Molecular analyses revealed that the lesion-mimic phenotype was regulated by both MTHFR and COMT, with MTHFR playing a predominant role. Microarray analysis demonstrated significant induction of genes related to oxidative and defense responses. This research not only demonstrated the synergistic effects of MTHFR and COMT on plant performance, but also revealed an unexpected role of the two genes in the modulation of lesion-mimic cell death.
4
0biomedical
0Study
87,708
Percutaneous coronary intervention(PCI) [10, 11] is one of the important methods for the treatment of coronary heart disease. In particular, the extensive use of drug eluting stents significantly reduces the incidence of restenosis after PCI and cardiovascular events. In the United States, approximately 1 million 500 thousand people receive PCI treatment annually, and approximately 5–30% of patients exhibit perioperative myocardial infarction (PMI). It was found that the incidence of PMI was approximately the same as spontaneous myocardial infarction . An increasing number of experiments have confirmed that during PCI operation, in addition to mechanical damage, some substances that act on blood vessels and have biological activities are also released. They enter the microcirculation via the blood vessels, resulting in vascular contraction and inflammation, endothelial dysfunction, myocardial ischemia and necrosis. All of these factors can cause the heart muscle to be damaged within a short time period, which can lead to complications such as myocardial injury and infarction in the perioperative period.
4
0biomedical
0Study
43,741
We first identified genes specifically involved in the response to Nosema infection in abdominal tissues: midgut, fat body, or complete abdomen (Additional file 2: Tables ST4 and ST5). The functional analysis of 104 genes with increased expression upon Nosema infection revealed overrepresentation of genes encoding enzymes and proteins involved in metabolic processes, catalytic activities, and transporter activity (Additional file 2: Table ST6), while genes related to cell components were overrepresented among 88 down-regulated genes after Nosema infection (Additional file 2: Table ST7).
4
0biomedical
0Study
357,751
Outward emotional reactions were used as a dependent variable to investigate their antecedents, and as an independent variable to investigate their consequences. Based on the video footage, two coders independently classified the players’ reactions after each point into (1) a positive outward emotional reaction, (2) a negative outward emotional reaction, or a (3) neutral outward emotional reaction. The first coder was a researcher with expertise in emotion literature and the second one a former Greek professional table tennis player and currently a coach. The coding was based on different body signals such as postures, gestures, facial expressions, and verbalizations, indicating the players’ emotional state (Mauss and Robinson, 2009). Since research suggests that conclusions about an individual’s emotional state cannot be drawn from physical features alone, but rather depend on context (Kayyal et al., 2015), the outcome of the point was taken as relevant context information. The coders were instructed to code outward emotional reactions as positive when the players’ behavior indicated that something emotionally positive occurred, and as negative if the players’ behavior indicated that something emotionally negative happened. Considering that individuals are always in some kind of emotional state (Russell, 2009), if the coders could not tell from the behavior of the players that something emotionally positive or negative occurred, these outward emotional reactions were coded as neutral.
3
0biomedical
0Study
358,597
Besides, evidence suggested that control of S. schenckii is Th1/Th17 dependent (27) and optimal fungal clearance depends on an intact Th17 response during the S. schenckii systemic infection in mice (16). Similarly, in our study, we found that the frequency of CD4+IL-17A+ Th17 cells was greatly elevated in whole patients (P < 0.0001, n = 18) and remained high level in both patients with SD (P < 0.0001, n = 7) and LD (P < 0.0001, n = 11) ( Figures S1B, C ). However, CD4+RORγt+ Th17 cells had no change in whole patients and in patients with different duration or clinical types ( Figures 1B–D ).
4
0biomedical
0Study
119,138
Body weight (BW; kg), height (cm) and waist circumference (WC; cm) measurements were measured on a voluntary basis by trained interviewers using digital scales, a stadiometer and a metal tape respectively. Pregnant women were not measured. Subjects were encouraged to remove their shoes and any heavy clothing prior to having measurements taken. Body mass index (BMI) was derived using Quetelet’s metric (kg/m2). Standard cut offs for BMI and WC were applied: underweight/normal weight: BMI < 25 kg/m2; overweight: BMI ≥ 25 kg/m2 and <30 kg/m2; obese: BMI ≥ 30 kg/m2; and central adiposity: WC > 102 cm (men) and >88 cm (women) .
4
0biomedical
0Study
253,848
Then, despite marked improvements in all peri-implantitis symptoms (e.g., BOP, PPD, GI, and PI) in the group treated with L/T antibiotics, the evidence failed to reveal any remarkable differences between the control and test groups for all microbiological and clinical parameters.
2
0biomedical
0Study
17,902
BgTEP-positive cells do not phagocyte. Phagocytosis of green fluorescent zymosan particles in hemocytes observed by confocal microscopy. On picture 1, Alexa-594 phalloidin was used to label actin of all hemocytes (red). Phagocytosis assay was monitored using green fluorescent yeasts. On picture 2, BgTEP-positive cells were detected by immunolocalization using the antibody anti-BgTEP-PEP and an Alexa Fluor 594 dye conjugated to the secondary antibody (red).
4
0biomedical
0Study
287,976
In addition to glucose and glycolysis mentioned above, some other metabolic pathways were also found involved in regulating the activity of Hippo signaling, such as lipids, hormones, and other metabolites . As reviewed, alterations on lipid metabolism contribute to the activation of several important oncogenic signaling pathways, including Hippo signaling . Research findings have indicated that YAP/TAZ activity is regulated by the SREBP/mevalonate pathway in many cancer cells . Oncogenic mutant p53, acting as a positive transcriptional cofactor for SREBPs, leads to increased mevalonic acid and promotes YAP activity in tumor cells . The mevalonate pathway, involved in the synthesis of cholesterol, bile acids, steroid hormones, and statins used to inhibit this pathway, was found to efficiently suppress YAP/TAZ nuclear translocation . Palmitic acid is a common saturated fatty acid in organisms. It has been reported that palmitic acid inhibits YAP by upregulating MST1, thereby inhibiting endothelial cell proliferation, migration, and angiogenesis . These results reveal a tight connection between YAP/TAZ activity and metabolic substances and pathways.
4
0biomedical
2Review
314,566
At the end of the treatment period, cystometry experiments were performed. Finally, the rats were anesthetized with isoflurane (2.0–2.5%, Centravet, France) and then euthanized by intraperitoneal injection of pentobarbital at 0.1 ml/100 g of body weight (Centravet, France) in accordance with Animal Care Regulations in force in France. The bladder was then harvested, weighed and paraffin-embedded for histological examination and measure of the bladder wall thickness. The prostate was also harvested and weighed.
4
0biomedical
0Study
186,060
Based on the type of analysis and separate arsenic, antimony, chromium, and selenium forms, different analytical columns were tested. The main element for this research was arsenic, so the analysis was optimized in all conditions to separate the As(III), As(V), DMA, MMA, and AsB forms. After finding the optimal conditions and separating all of the arsenic forms, further elements were added, and the effectiveness of the analysis was checked. Out of the various types of columns, the following were tested:-PRP-X100 (250 mm × 4.1 mm, 10 μm), packing material type: PS-DVB/Trimethyl ammonium exchanger (Hamilton, Reno, NV, USA);-PRPX-200 PEEK (250 mm × 4.6 mm, 10 µm), packing material type: PSDVB/Sulfonic Acid (Hamilton, USA);-BioWAX (50 mm × 2.1 mm, 5 µm), packing material type: nonporous/dietyloamine (Agilent, Santa Clara, CA, USA);-Supelco SAX (250 mm × 4.6 mm, 5 µm), packing material type: silica gel, spherical particle platform/propyltrimethylammonium phase (Sigma–Aldrich, USA);-Waters SAX (250 mm × 4.6 mm, 5 µm), packing material type: silica-based quaternary ammonium bonded sorbent (Waters, Milford, MA, USA);-Dionex CS5A (250 mm × 4 mm, 9 µm), packing material type: latex, DVB/Cation: Sulfonic Acid/Anion: Quaternary Ammonium (Thermo, Waltham, MA, USA);-Dionex CG5A (50 mm × 4 mm, 9 µm), packing material type: latex, DVB/Cation: Sulfonic Acid/Anion: Quaternary Ammonium (Thermo, USA);-Dionex AS22 (250 mm × 4 mm, 6 µm), packing material type: DVB/Alkanol Quaternary Ammonium Ion (Thermo, USA);-Dionex AG22 (250 mm × 4 mm, 6 µm), packing material type: DVB/Alkanol Quaternary Ammonium Ion (Thermo, USA).
4
0biomedical
0Study
58,449
Direct comparison of the simulated total radial distribution function (RDF) and H-H pRDF (Inset) for a-SiH (black lines) to the experimental results (green lines) for the 2.44/0.46 fs cell. These simulations give a better overall description of the observed H–H pRDF.
4
0biomedical
0Study
369,670
We next examined the effects of AC220 combined with DAPT on primary AML cells. Peripheral blood samples from 12 AML patients were collected. Mononuclear cells were isolated and cultured with AC220 (250 nM) and/or DAPT (25 µM) for 48 h. Although these primary cells showed different sensitivities to AC220 and DAPT, stronger inhibition of cell proliferation by the combined treatment was more likely to be observed in specimens from FLT3/ITD+ patients (Fig. 2i). Consistent with the cell lines results, a significant increase in Annexin V+ binding was detected following combined treatment with DAPT and AC220 in FLT3/ITD+ primary samples compared to either DAPT or AC220 alone (Fig. 2j, Supplemental Fig. S9).
4
0biomedical
0Study
334,073
Because the severity of the infant’s medical condition, especially during the first months of life, is suspected to generate stress for parents and babies, we created a score to take it into account by attributing 1 point for the presence of each of the following four events during the first year of life: tracheotomy, tube feeding for more than 6 months, more than 6 months spent at the hospital, and at least one surgical intervention. The total medical severity score during the first year of life ranges from 0 to 4.
4
0biomedical
0Study
250,733
Despite advances in chemotherapy, the overall five-year survival rate for SOC is just roughly 20%, mainly due to chemoresistance, which leads to cancer recurrence and treatment failure for SOC patients [3, 4]. Previous studies indicated that cancer chemoresistance is underlined by multiple mechanisms, including DNA repair, autophagy, drug efflux, metabolism reprogramming, epithelial-mesenchymal transition (EMT), mitochondrial alteration, etc. [5, 6]. Molecules involved in those processes may play roles in regulating chemoresistance, and could provide potential targets for drug treatment or diagnosis, in order to improve survival rates for ovarian cancer patients.
4
0biomedical
0Study
180,051
A common next step in aptamer generation is minimizing sequence length. Structural studies of aptamers have shown that a full length (~80 nt) aptamer is usually unnecessary to retain strong binding affinity. Minimization, or truncation, can reduce synthesis cost, complexity, and potential for non-specific interaction all while increasing the maximum attainable concentrations (surface or volumetric)45. Traditionally this is achieved via brute force experimental approaches46 or by researchers’ biological insight coupled with manual curation to investigate enriched motifs47 and secondary structures48,49.
4
0biomedical
0Study
250,832
Other DEMs in C. pisiformis-infected rabbit serum, such as let-7-5p, miR-7, miR-9-5p and miR-125-5p_4, were also significantly differentially expressed in the Hymenolepis microstoma larvae , showing their important roles in the interactions between host and metacestode of tapeworms. The most abundant miR-10-5p and let-7-5p in Taenia solium and Taenia crassiceps characterized immunosuppressive effects on murine peritoneal macrophages, which strongly decreased the expression of interleukin 6 (IL-6), tumor necrosis factor (TNF) and interleukin (IL-12) secretion. They also moderately decreased nitric oxide synthase inducible (NOS2) and Il1b expression (pro-inflammatory cytokines) in M (IFN-γ) macrophages, expression of Tgf1b, and the secretion of IL-10 (anti-inflammatory cytokines) in M (IL-4) macrophages . miRNA let-7-5p from C. pisiformis exosomes has been reported to decrease M1 phenotype expression while promoting polarization to the M2 phenotype through inhibition of the expression of transcription factor CCAAT/enhancer-binding protein (C/EBP)-δ. However, let-7-5p was also detected in rabbit serum at 2 months post infection, and may be released into rabbit serum through C. pisiformis exosomes .
4
0biomedical
0Study
176,209
We identified four major themes about the participant experience of the journey to receive cancer care and how these experiences may impact opportunities to participate in decisions. We report the four themes in relation to the map of the journey to receive cancer care to explain the events around three main events as follows: at the initial entry into the cancer care system, travel, and arrival to receive cancer care services. (Fig. 1) Fig. 1Map: The journey to receive cancer care(see Additional files, Details on themes).
4
0biomedical
0Study
170,266
To evaluate plot‐level forest structural attributes, we calculated the total forest structural attributes per plot; we counted numbers of trees with DBH more than 1cm and summed basal area, crown area and crown length per plot. To assess the horizontal variation in each of these structural attributes, we calculated for every one of the 16 subplots the mean value and SD of each attribute, and then the coefficient of variation as 100 × SD/mean. We used the coefficient of variation rather than the absolute standard deviation, as relative variation is less sensitive to differences in the mean value of each structural attribute among different plots, and hence can be a more precise predictor of the horizontal forest structural heterogeneity among different‐aged stands.
3
2other
0Study
76,469
We identify eighteen bottleneck metabolites in iPfa, whose intracellular concentrations determine the directionality of a set of reactions and render eight genes essential (Table 2). The bottleneck metabolites are phosphorylated nucleotides, sugar nucleotides, and intermediates in the production of phospholipids. The concentrations of the bottleneck metabolites play a critical role on the directionality of reactions in the cytosol and ER that are mainly involved in the production of phospholipids. Specifically, the genes identified as essential were required to maintain the redox and energy balance in the ER. Additional analysis using the TFA framework helped us quantify the effect of the metabolite concentrations on the reaction directionalities and can guide future metabolomics studies on the malaria parasites (S1 Methods, S1 Dataset). The results of these studies further suggest that there exists in P. falciparum a thermodynamic dependency between the production of phospholipids, phosphorylated nucleotides, and sugar nucleotides through the concentrations of the bottleneck metabolites. The knowledge of metabolic subsystems that are thermodynamically dependent can be used to design drugs that synergistically target these parts of the metabolism and prevent their metabolic regulation and rise of drug-resistant parasites.
4
0biomedical
0Study
309,465
Central phenomena comprise participants’ behaviors, statements, experiences, or repeated patterns in response to a problem or situation that occurred due to the impact of the causal condition . The central phenomena in nurses’ adaptation process when caring for COVID-19 patients were “complexed emotions”. The subcategories of “complexed emotions” were “anxiety over the lack of medical supplies and equipment”, “fear of something that has not been experienced before”, “the burden of new tasks”, “frustration with the endless situation”, “anxiety over unpredictable patient prognoses”, and “feelings of shame, faced with their own limitations”. At the beginning of the pandemic, nurses were not provided with enough personal protective equipment (PPE), such as masks and protective gowns. Additionally, as patient conditions worsened, mid-career nurses with little experience in caring for severe patients essentially became novices, as they were attempting to use unfamiliar machines. It was difficult for them to determine and predict the status of patients with whom they had no previous experience. COVID-19 patients have diverse symptoms, and the guidelines for symptomatic therapy are unclear and can be confusing. As experienced nurses suddenly became novices, they felt ashamed and helpless, viewing all the experience they had accumulated as useless. Instead of improving, this situation persisted: Because we are not ICU (intensive care unit) nurses, we didn’t know how to prepare when we heard that a CV (central venous) catheter should be inserted. We didn’t even know what Prolene and silk were. I am a charge nurse and yet I did not know how to cope with such a situation, like acting nurses. I didn’t know how to keep a nursing record in the current situation and I didn’t even know what nursing instructions I should give. It was very hard and so I cried a few times during work hours. Every day I was afraid of work. (Participant 18)
4
0biomedical
0Study
391,193
From the early days of discovery, BCMV strains were shown to be transmitted through infected seeds (Morales and Castaño, 1987). The rates of transmission of BCMV and BCMNV strains depend on common bean genotypes (Morales and Castaño, 1987) and can be as high as 83% (Bos, 1971). Transmission of BCMNV, however, is not possible in common bean plants that have the dominant I gene because of the black root symptom, which results in plant death and thus no seeds for the next cropping season (Grogan and Walker, 1948). There are few published studies on seed transmission of BCMV and BCMNV in Tanzania. A comprehensive study was conducted about 17 years ago and aimed at determining the incidence of BCMV and BCMNV in seeds collected from farmers, public markets and Agricultural Research Institutes (ARIs) and wild legumes (Njau and Lyimo, 2000). There were 10,300 seeds collected in this study, representing 341 and 30 seed lots of common bean and wild legumes, respectively (Njau and Lyimo, 2000). The seeds were grown in an insect proof screen-house and the incidence of BCMV and BCMNV determined using ELISA. The two viruses were detected only in bean seed samples collected from northern and eastern Tanzania (Njau and Lyimo, 2000) and were not detected in wild legume seeds. The virus infections were more common in bean seeds collected from ARIs (in 20 out of 59 seed lots) and rare in bean seeds collected from farmers and public markets (in four out of 282 seed lots). The highest incidence for BCMNV was 36.6%, whereas it was only 12.4% for BCMV. The average incidences for both viruses were less than 8% (Njau and Lyimo, 2000).
4
0biomedical
0Study
57,682
A popPK model was developed from nine clinical studies, comprised of 1534 subjects. The detailed method for the popPK model development is described in a separate manuscript . Individual exposures for subjects in the METEOR study were predicted from this popPK model for use as the exposure metrics for the present ER analysis.
4
0biomedical
0Study
216,587
The efficiency of studied markers in the early diagnosis of primary tumors was evaluated. Five apparently healthy (H; n = 5) cats showed positive AAbs values of 1.11 ± 0.10 for PCNA, 1.08 ± 0.12 for P53, 1.15 ± 0.10 for MUC-1, and 1.04 ± 0.07 for C-MYC. By following two of them for 11 months, they did not show any clinical manifestation of mammary carcinoma. Therefore, we could not validate AAbs’ efficiency in the early diagnosis of feline mammary carcinoma as in human breast cancer (Fig. 6).Figure 6Measured and predicted values of P53 in a cat with a mammary tumor. The intersection between measured and predicted values marks the end of the PPTT treatment course. Figure was prepared using SigmaPlot v14.0 (Systat Software, San Jose, CA, USA).
4
0biomedical
0Study
286,132
The results of the literature search were transferred to the literature management program, Citavi, which was used to remove duplicates. Via a search of titles and abstracts, potentially relevant studies were extracted. Studies published in English or German between January 2008 and January 2020 that focused on technologies in DM therapy were included. Furthermore, to be included, the studies had to make remarks or comments on the clinical effectiveness, for example, effect on glycemic control, of the type of technology that was presented. There were no limitations to the study design. Studies that focused only on the comorbidities of DM were excluded. As this paper is a scoping review, we selected those studies from our presorted studies that seemed to give great overviews and explanations but still reported on clinical effectiveness.
4
0biomedical
2Review
397,972
Several things are noteworthy. First, the linear regressions show very significant correlations between calculated ii and measured pKa values: His (R2 = 0.9978), Asp (R2 = 0.9869), Glu (R2 = 0.9802) and Cys (R2 = 0.9670). Second, removal of the positive charge in the α-amino group by N-acetylation results in the greatest side-chain pKa in all amino acids, and removal of the negative charge in the α-carboxyl group in the lowest, with the zwitterion and the doubly modified amino acids giving intermediate values, with the zwitterion giving consistently a slightly lower pKa than the doubly-modified amino acid. Third, the effect of the modifications is variable, that is, the change in pKa with ii value (the slope) varies for each amino acid side-chain. Fourth, there is a difference in slope between the β-carboxyl group of Asp and the γ-carboxyl group of Glu (see Discussion). Finally, in the case of His, where two different modifications of the α-carboxyl group were available (amidation and methyl esterification), the calculation of Inductive Index discriminates between the two values of measured pKa. These points will be taken up in more detail in the Discussion.
4
0biomedical
0Study
280,560
Sperm traits across sites sampled in previous studies, and the ancestral sites sampled for this study, were compared using linear models. Since test salinities between studies differed slightly, velocity and motility responses were grouped according to four salinity categories as follows: freshwater: sperm tested in 0–1 PSU; brackish: sperm tested in 15–16 PSU; marine: sperm tested in 30–32 PSU; local: the test salinity closest to the salinity at the males’ site of capture. Differences between groups were tested using linear models for each salinity category, with site as predictor variable and sperm velocity or sperm motility as response variable using the lm function in R. For the freshwater and brackish categories, the sites of the Danube (ancestral freshwater) and Sozopol (ancestral brackish) were chosen as ‘controls’, respectively, with the a priori expectation that fish from these sites were most likely to be locally adapted. For the marine and local categories, differences were simply tested between groups.
4
0biomedical
0Study
36,642
The participants with higher completed education were more often co-living, whereas those with less completed education were more often single (2-sample “t” tests, both with p = 0.01). Education and Specific Knowledge Scale score were directly correlated (Spearman ρ = 0.22, p = 0.000); the women with lower completed education had lower specific knowledge about HPV, CIN and cervical cancer. The women who did not know that HPV can lead to other cancers had a lower educational level (post-hoc Bonferroni p = 0.03) compared to those who endorsed this statement (one-way analysis of variance (ANOVA), F = 3.16, p = 0.02).
4
0biomedical
0Study
133,634
EBV‐positive DLBCL patients following AITL have been reported in some case reports. 3 , 4 , 5 , 6 EBV infection may reduce the immune function of AITL patients and lead to B‐cell dysfunction. The occurrence of secondary DLBCL seems to be triggered by EBV infection. Some studies 7 , 8 have reported that AITL patients composite with DLBCL.
4
0biomedical
0Study
247,019
The ASTRA phase III study (NCT01843062) in high-risk DTC patients failed to demonstrate an improved disease-free survival with selumetinib (a MEK inhibitor)-enhanced adjuvant RAI administration compared with placebo and adjuvant RAI. This may be due to the low inhibitory efficacy of selumetinib. As already pointed out, in patients with a BRAF V600E mutation, in particular if a TERT mutation is also present, the RAI uptake in the neoplastic tissue is frequently absent, and these patients might benefit from a redifferentiation program before being treated with RAI, but further trials are needed (see Section 7).
4
0biomedical
0Study
11,099
Taken together, the results of these control analyses support the interpretation of our effect being specific to an absolute directional code independent of locations and distances in Donderstown. The sections of the manuscript describing these analyses are shown below.
3
0biomedical
0Study
60,270
The morphology of the WO3 (WO3-HW; WO3-HW5) crystals synthesized from tungstic acid was rod-like, accompanied sometimes by nanosheets (Figure 5). The crystal size was ≈1 μm, which were built from very small polycrystalline nanoparticles with d ≈ 20 nm. This material “construction” was also observed by Liang Zhou and coworkers . Using sodium tungstate as the precursor, the morphology of the tungsten trioxide (WO3-NWH) crystals were fiber-like . Their individual length was ≈3–4 μm. Taking a closer look, it was observed that these fibers were, in fact, fiber bundles (“built” from ≈12–14 smaller nanofibers) composed from much smaller d = 40–50 nm fibers. Finally, the morphology of the microcrystals (WO3-AMT) obtained from ammonium metatungstate (AMT) was star-like . These stars’ mean diameter was ≈3–4 μm and were composed from microfibers of ≈3–4 μm length. These were built from several smaller nanowires with a diameter =10–15 nm (Figure 5).
4
0biomedical
0Study
5,595
We estimated cost to develop a highly complex multiplex assay based on a new biomarker(s) concept ready for technology transfer to an ISO 13485‐certified diagnostic company for full development at $3.2 million (Table S3). The estimate considered four phases of development (technical feasibility, development, manufacturing transfer, and external evaluation) and the parties involved (manufacturer, academic partner, and external evaluator). For each phase, full‐time equivalent labour required (valued at $225,000 annually) for 11.4 person‐years of work over a 36‐month period was estimated along with additional costs for development and quality assurance specimens, equipment, and specimens and kits for external validation. These cost estimates (details in Table S7) are based on the diagnostic industry experience of one of the authors (PD) and were verified with two additional diagnostic industry experts. If substantial research and development work were still needed at technology transfer, the development phase would be 1.5 to 2.0 times longer with a corresponding increase in development phase costs.
4
0biomedical
0Study
282,502
Locality: NW Atlantic (Newfoundland and Labrador 4), NE Atlantic (England and Wales9, Firth of Forth7), North Sea (Belgium5, Denmark6, Netherland1), North Sea/Baltic Sea (Denmark1, German5,11), Baltic Sea (Poland12), Black Sea2,8 (Crimea10), not mentioned2
1
2other
1Other
200,095
Data were missing for one or more of the pain, ASD, MMHC, or CNC variables for 3,588 total individuals (7.0% of the available dataset), resulting in a final study sample of 47,568 individuals (Figure 1, Table 1). The reference group (group 1: no ASD; no MMHCs) had more white, non-Hispanic children than other groups (Table 1). As expected, males accounted for approximately 80% of ASD children (groups 3 and 4, Table 1), who also had higher prevalence of CNCs than the non-ASD groups. The outcome of pain was prevalent in 7.4% (95% CI = 6.9–7.8) of children in the control − no MMHCs group, 22.8% (95% CI = 18.7–26.8) of the control + MMHCs group, 16.1% (95% CI = 9.8–22.4) of the ASD + no MMHCs group, and 25.4% (95% CI = 12.3–35.8) of the ASD + MMHCs group. Maternal health status of fair or poor was reported in 3.9% of individuals without ASD and 10.3% of those with ASD.
4
0biomedical
0Study
339,917
Efforts are now addressed to develop a direct reprogramming method which is safe and free from ethical and technical concerns associated with genetic manipulation of cells. The use of microRNAs (miRNAs) may represent one valid strategy to induce direct reprogramming of human fibroblasts into iCMs, satisfying such requirements. miRNAs are short non-coding RNAs (of approximately 22 nucleotides) that regulate gene expression post-transcriptionally (He and Hannon, 2004). As cardiac tissue-specific miRNAs play pivotal role in cardiac development and functions, the regulation of their expression would aid in generating functional iCMs starting from human fibroblasts (Tian et al., 2017). Endogenous miRNAs can be easily overexpressed or downregulated through the administration of miRNA mimics or miRNA inhibitors, respectively (Peng et al., 2015). MiRNA mimics and inhibitors hold a great potential as therapeutic agents because of their cytoplasmic activity, relatively small size and ability to be administered systemically or locally by nanoparticle-based delivery systems, avoiding the use of viral vectors (Lee et al., 2019). Modulation of miRNAs for direct reprogramming was first proposed by Jayawardena et al. (2012), who demonstrated that a combination of four miRNA mimics (referred to as “miRcombo”: miR-1, 133, 208 and 499) promotes the direct reprogramming of mouse fibroblasts into iCMs both in vitro and in vivo. The selected miRNAs are highly conserved in cardiac and skeletal tissue and have been found to regulate developmental and physiological processes in the heart (van Rooij et al., 2009; Xu et al., 2011). Furthermore, this specific set of microRNAs was found to be expressed in human embryonic stem cells-derived CMs, whereas their expression was nearly undetectable in fibroblasts (Kitchener et al., 2010).
5
0biomedical
0Study
155,908
To investigate the phylogenetic relationship between the CsABF and CsbZIP gene families in tea plant, 78 bZIP in Arabidopsis were applied to construct the phylogenetic tree with 76 bZIP in C. sinensis. The phylogenetic tree was generated and displayed by the Mega 7.0 program with the following parameters: neighbor-joining (NJ) method, P-distance model, pairwise deletion, and 1000 bootstrap replicates. Multiple sequence alignments of CsABF were performed by DNAMAN. The Multiple Em for Motif Elicitation (MEME) suite (version 4.10.1)6 was used to identify the conserved motifs in all CsABFs. The parameters were as follows: maximum number of motifs: 6; number of repeats: any; maximum number of motifs: 50; optimal motif width: 6–200 amino acid residues.
4
0biomedical
0Study
117,107
Despite these clinically important findings, to our knowledge, there is no population-based study that has examined the relationship between BMD and alcohol consumption in Korean PMP women. The aim of this study was to evaluate the association between alcohol intake and PMP women’s bone health by using data from the Korean National Health and Nutrition Examination Survey (KNHANES).
4
0biomedical
0Study
304,313
In this article, we have taken the figure of the monster as a theoretical tool in analyzing and discussing the emancipatory significance of women’s representations on infertility reality TV. Monstrosity has come to be seen as a way to question and challenge normative identities through offering an alternative. This monster’s subversiveness, however, is ambiguous: it breaks the norm but at the same time reinforces it. As such, the question arises whether the representation of women as in/fertile monsters is just subject to such reinforcement, or whether they may actually challenge the norm, and thereby, help an emancipatory process of freeing women from restrictive norms related to infertility.
1
2other
1Other
82,772
The molecular mass of heteropolysaccharides may range from 4.0 ∗ 104 and 6.0 ∗ 106 ; Streptococcus thermophilus SY2 produced two EPS fraction of 2 ∗ 106 and 5 ∗ 104 . Lactobacillus paracasei produces two eps fractions of 4 ∗ 104 Da and 1.36 ∗ 104 Da . Lactobacillus plantarum was reported to have a molecular weight of 2.68 ∗ 105 Da , while Streptococcus thermophilus produces EPS with the molecular weight of 1 ∗ 106 Da . Other strains of Streptococcus thermophilus have been reported to produce high molecular weight EPS with glucose and galactose as the monosaccharide units [1, 29, 30].
4
0biomedical
0Study
262,973
The specific treatment for moderate and severe scorpion stings, in Brazil, consists of antivenoms produced against T. serrulatus venom, species that does not belong to the Brazilian Amazon region . A case report showing that severe symptoms caused by T. silvestris sting were refractory to anti-Tityus antivenom illustrates the need to develop new antivenoms or improve the effectiveness of those available. Despite the territorial extension of the North region, the specific clinical care and professional support to taxonomically distinguish venomous animals that are life-threatening is usually carried out in the capitals of the Brazilian states of Amazonas and Pará, respectively, Manaus (03°05′S 60°02′W) and Belém (1°26′S 48°29′W) [9, 50]. The severity of the systemic effects caused by Tityus species depends on the venom composition and the patient's clinical condition . Therefore, it is essential to identify and characterize the components within the scorpion venom to produce more effective antivenoms.
4
0biomedical
0Study
274,778
We found that patients with type 2 diabetes with greater BMI level tended to be at risk for poor glycemic control. Similarly, one related study in the US reported positive associations between being overweight or obese and having uncontrolled type 2 diabetes29. Additionally, strong evidence was found that obesity management could be beneficial in treating type 2 diabetes30,31. Related studies have reported that the sustained weight loss has been illustrated to improve glycemic control32,33. Thus, the dietary therapy and weight management should be encouraged for patients with type 2 diabetes to better glycemic control.
4
0biomedical
2Review
117,646
The selection of biomaterials for artificial joints is heavily constrained by conventional concepts of mechanical engineering, mainly underlying their fracture strength, reliability, and tribological response. During the last decade, however, the requirements from patient side appear to have undergone a quite radical evolution towards additional and more demanding tasks. In other words, as extended lifetime expectations for arthroplastic patients represent nowadays the new main target, a fundamental process of revalidation becomes needed for establishing the new criteria upon which joint design and biomaterial choices should be based. Specifically, in relation to surface engineering concepts in joint arthroplasty, a paradigmatic shift is required to establish new evaluation criteria taking into account the pivotal role of surface reactivity and related off-stoichiometry (evolutional) characteristics of the joint bearing surfaces during service operation. While the most recent studies of advanced polyethylene liners have brought revitalized attention to the pivotal role of oxidation chemistry on the expected lifetime of the implanted joints, the “chemistry” approach is yet conspicuously missing for ceramic components, as they are erroneously considered to be completely bioinert. In reality, the situation is not quite so straightforward. If the bearing surfaces of hip joints should preserve their mechanical and physical characteristics for quite a long-term span of time despite the interference from an extreme (i.e., cumulatively in terms of mechanical, thermal, and chemical loading) physiological environment, a finer tuning of their molecular structure should be mandatorily required. We shall show in the remainder of this paper how fundamental features related to the inherently ionic structure of ceramic oxides and to the complex nature of the biochemical environment of hip joints could severely exacerbate surface degradation processes. In other words, as far as hip implants are concerned, the definition of bioinertness should mandatorily encompass not only a macroscopic view of retaining the bulk integrity of the biomedical implant, but also the resistance to degradation of its surface at the molecular level. This latter is indeed a property extremely difficult to achieve. Even very stable materials as oxide ceramics interact at their surface to some extent with the biological environment, such interaction locally altering their inherent properties in terms of hardness, wear resistance and toughness. We shall thus start our discussion from first accepting the concept of “impossibility of inertness”, as already stated by Williams , and extending it to the molecular scale. Accepting such impossibility is perhaps the most appropriate starting point for studying the bearing surfaces of artificial hip joints.
5
0biomedical
0Study
15,743
For the current survey, samples of individual products were sampled from separate retail outlets, to give duplicate or triplicate samples. Date of sample purchase, location and formulation details are (S.I. S1 File). The sampling strategy was to go to major (ASDA, Boots, Dunne’s, Holland & Barrett, Marks & Spencer, Sainsbury’s) and minor retailers to purchase 3 (in a minority of cases only 2 were available, see S.I. S1 File “product averages” tab for N) replicates of each individual rice based product available in baby food sections. In total, 24 stores across the province of Northern Ireland were sampled (located in Enniskillen Craigavon, Lisburn and Belfast), see S.I. S1 File “all sample details” tab for a breakdown. The bulk of the data were labelled as being from the EU or produced in UK or Belgium as their source of origin, only 4 products actually stated the country of origin of the rice (one Italian, 2 Japanese, 1 Thai), reported in “product averages” tab of S.I. S1 File. Details of the UK 2016 and 2014 survey are given in Signes-Pastor et al. .
3
0biomedical
0Study
283,437
Behavior in populations is known to be influenced by and change because of the population’s knowledge, beliefs, and opinions about a disease . In the case of COVID-19, public opinion was also found to be influenced by the spread of dis- and misinformation about the disease . As one of several key elements, the course of the COVID-19 epidemic in Germany depended on the population’s behavior during the lockdown. However, in Germany the “unorthodox thinker” (“Querdenker”) movement and conspiracy theorists started to have an increasing influence on public opinion during the protests against government measures and restrictions. As cases in Germany started to increase again in July and August 2020 to numbers that in mid-October 2020 exceeded those of the first wave in March and April 2020, controlling the spread of the virus became even more important, and after further increases, the government started to discuss a second shutdown or lockdown . This second wave increased the need to obtain a picture of the population’s knowledge and opinions about COVID-19 as a basis for understanding and influencing their behavior.
2
0biomedical
0Study
42,938
As I will turn to demonstrate in the next section, ‘The gift of sound and vision: designing the exercise’, exercises work to assess pre-existing protocol and develop new forms of protocol. Both the assessment and development of protocol is achieved in exercises by pushing the limit of pre-scribed protocol. To do so, exercises stage and imagine types of fire emergencies yet to be addressed by pre-existing protocol. In relation to the assessment of protocol, exercises present new emergency scenarios in order to gauge the applicability of protocol beyond the type of fire incident it was formulated around. If assessment of protocol is about gauging the applicability of protocol, the development of protocol is actualised by recording the action of participants which exceeds pre-established protocol. Observations of participants’ actions in exercises are then fed back to generate wholly new forms of response protocol altogether.
1
2other
1Other
38,162
The thickness of individual S-Mo-S layer in the pristine crystalline MoS2 was approximated to be equal to ≈0.63 nm16. In pristine crystals, the hexagonal 2H-type arrangement of atoms is more stable and dominant. As a result, rhombohedral 3R-type MoS2 phase transforms into 2H-type upon heating17. A pure 2 H phase can transform to a metastable metallic 1T phase upon Li-intercalation and exfoliation of S-Mo-S layers weakly interacting with each other by van der Walls forces18. In contrast to the 2 H structure, the MoS2 nanocrystals often exhibit a triangular morphology19. As reported, the triangular and hexagonal forms can be changed by varying the sulphiding and MoS2 formation conditions20. In the case of amorphous MoS2 materials, they usually have many defect sites and coordinately unsaturated S atoms21. As reported by Xie group9, the basal planes of MoS2 containing abundant defects can readily crack exposing additional active edge sites.
5
0biomedical
0Study
309,023
A five-step process (see McLeod and Weisz 2005) was employed to systematically develop the observational rating system in this study.Step 1.Rating system focus. The GenPMTO literature delineates specific components that characterize the model (e.g., Forgatch and Gewirtz 2017; Forgatch and Patterson 2010), allowing us to identify focal components for fidelity assessment (see Schoenwald et al. 2011). Specifically, this rating system was developed to measure eight GenPMTO components: (a) clear directions, (b) skill encouragement, (c) emotion regulation, (d) limit setting, (e) effective communication, (f) problem solving, (g) monitoring, and (h) positive involvement. Guided by the conceptual framework for implementation fidelity, which identifies adherence as the central construct in fidelity measurement (Carroll et al. 2007), we focused our measurement efforts on assessing adherence to each component. A critical feature of this rating system is that, in contrast to fidelity tools meant to evaluate adherence to prescribed session content, the current measure is able to quantify the extent to which each intervention component was delivered with fidelity across the course of the intervention. As a result, this rating system can be used to advance current research by determining how much exposure to each intervention component a participant received and how exposure to each component is linked to outcomes.Step 2.Scale and item development. In accordance with standard psychometric procedures (see Lambert and Hill 1994) and following the work of McLeod and Weisz (2005), we began by reviewing the GenPMTO literature to establish a strong basis for validity. This included program manuals, the GenPMTO fidelity protocol, empirical studies, and other sources describing the intervention components (e.g., Dishion et al. 2016; Forgatch 1994; Knutson et al. 2019). From this review, we established a preliminary set of items describing the content of each intervention component. Each item was then operationalized via a set of indicators that described how the item could be observed during a session (e.g., see Nelson et al. 2012). Next, we distributed the items for review to the intervention developer and a group of GenPMTO experts to obtain systematic feedback. After subsequent refinements to the items and component scales, the resulting product was reviewed and confirmed by the intervention developer.Step 3.Scoring strategy. We determined ratings would occur at the macroprocess level (McLeod et al. 2013) with the intervention session as the unit of measurement. In line with other fidelity scholars (e.g., Breitenstein et al. 2010), we believe rating entire sessions will allow for the most comprehensive measurement of intervention adherence. Therefore, each item is rated on a 7-point Likert scale (0 = not at all to 6 = extensively) according to the extent that behavior was present during session. This rating accounts for both thoroughness and frequency of delivery (Hogue et al. 1994, 1996). Thoroughness attends to the breadth and comprehensiveness of delivery, whereas frequency considers the duration and number of times an item was addressed. Together these complementary dimensions combine to form an extensiveness rating for each item (Hogue et al. 1994, 1996). Extensiveness ratings have a well-established history in treatment integrity research and confer advantages over rating systems that only assess for presence or absence of an item (Waltz et al. 1993). Extensiveness ratings have been used successfully in prior studies (e.g., McLeod and Weisz 2010; Southam-Gerow et al. 2016) and are a proven design feature for observational assessments of treatment (McLeod et al. 2009).Step 4.Pilot testing and refinement. Next, the principal investigator and a graduate research assistant used the measure to independently rate approximately 10% (n = 18) of the sessions. During pilot testing, the researchers discussed the clarity and utility of the items and their indicators to inform further refinements to the rating system. Intraclass correlation coefficients (ICC) were calculated at both the component and item levels using IBM SPSS Statistics version 24 based on a single measures, absolute agreement, two-way random effects model. These ICC(2,1) values were moderate to excellent (r = .55 to .92; Koo and Li 2016) for each of the eight component scales, providing initial support for their reliability. At the item level, 15 items demonstrated poor reliability (ICC < .50; Koo and Li 2016) and were re-evaluated and revised when necessary. This process resulted in the initial version of the Component Level Implementation Fidelity Rating System (CLIFRS), a 76-item measure that assesses adherence to eight GenPMTO components. The CLIFRS is included as Supplemental File A. A rating manual was also completed to accompany the CLIFRS (Holtrop et al. 2019).Step 5.Research application. We subsequently evaluated the initial psychometric properties of the CLIFRS using video data from the prior GenPMTO prevention trial. All study procedures were approved by the Michigan State University institutional review board.
4
0biomedical
0Study
60,237
The central prediction of the ‘mismatch hypothesis’ is that childhood food allergies will increase as violations of Rule 3 increase. There are many potential avenues for testing this prediction but they are not equally feasible or definitive. For example, it is straightforward to predict an increase in childhood food allergies at the boundary of the Pleistocene-Holocene transition in regions where farming and long-distance trade were first adopted. However, since there are no prehistorical accounts of food allergies, and only anecdotal accounts in the distant historical record, this specific prediction cannot be tested directly. It might be possible, however, to get a glimpse of what happened in the past by looking at extant foragers and determining whether childhood food allergies increase when formerly isolated groups come into contact with the world at large, and thereby are exposed to novel foods. Some such groups have been extensively studied (e.g. Kung, Ache and Hadza) but I am unaware of any published relevant data.
4
0biomedical
0Study
250,530
Mental disorders are common in individuals suffering from chronical physical conditions, with symptoms of depression being most prevalent (Deschênes et al., 2015). Particularly psychosomatic diagnoses have been found to be the most common cause of disability pensions in the past years (Dannenberg et al., 2010). As a result, early retirement or extensive psychosocial and vocational rehabilitation programs may be necessary in order to restore work capacity and well-being (Köllner, 2014; Linden, 2014).
3
0biomedical
1Other
262,598
(A) Plasma neutrophil gelatinase-associated lipocalin (NGAL) concentrations at baseline, and at 4 and 24 h after the start of 36 h a continuous intravenous infusion of either 0.9% NaCl solution (6 ml/kg/h, sham, n = 1) or 0.9% NaCl solution (6 ml/kg/h) in combination with LPS (0.75; 2.0 and 5.0 μg/kg/h, n = 2/group). (B) NGAL concentrations in voided urine, collected after 4 h after the start of the respective infusions.
4
0biomedical
0Study
226,370
Several points of deviation from the national and international guidelines for rabies PEP were noted. Wound washing is considered an important component of effective rabies PEP as it serves to physically remove the virus from the point of entry into the body.6 Wound treatment with wound washing was reported for only one-third of the cases. It is however likely that this form of treatment was performed but not recorded on the patient files. Tetanus vaccination and antibiotics, which are general components of animal bite wound care, were also often provided. For the administration of RIG, the guidelines hinge on the categorisation of exposures.6 Category 1 exposures include interactions with rabid or potentially rabid animals, but did not include contact with infectious saliva of the animal (e.g. petting such an animal).6 For category 2 exposures, which imply wounds that do not break the skin, only vaccination is required, whilst for category 3 exposures, both the vaccine and RIG therapy are recommended. For the cases investigated, rabies vaccine and RIG were provided regardless of the category of exposures noted on the patient records. For example, nearly 20% of cases were categorised as category 1 exposures, which would require no intervention, yet rabies PEP was provided fully. Most cases were reported as category 2 (73.58%) which would only require the administration of vaccine, yet RIG was provided in most cases. A review of the description of the exposures allowed for the re-categorisation of the exposures for 19 of the cases under investigation. Most of the exposures could be re-categorised as category 3, which would require the full rabies PEP provided.
4
0biomedical
0Study
212,252
The pace at which climatic threats may be altering biotic interactions urges intensifying novel experimental and analytical approaches to better comprehend the effect on the plant disease triangle (PDT). PDT postulates that any plant disease is the result of the interaction between a host’s genotype, the biotic stress, and their environment . Genomic prediction, machine learning, and gene editing strategies, although usually disentangled, offer powerful opportunities for trans-disciplinary and emergent inferences at the interface among the fields of forest genomics, pathology, and ecology .
4
0biomedical
0Study
21,285
Risk perception was strongest among families who had a previous non-cephalic delivery and had a related complication. Those with previous negative experiences sought care and had a pervasive sense of fear in their rhetoric and behavior. One spent a significant amount of money on a traditional healer to “prevent the umbilical cord from coming out first again,” while others sought facility care immediately upon discovering at the start of labor that the fetus was in non-cephalic position. Similarly, participants who had heard of negative consequences of non-cephalic birth from neighbors or from other sources generally sought care, and this was described in the FGDs as well. One woman said, “Everyone in my family got scared seeing the breech delivery. One of the people in our village also had a breech delivery and her child died. My family members were very concerned so they kept calling the doctors.” Those who had a complicated home delivery indicated that they would deliver at a facility the subsequent time. In contrast, a few women in both IDIs and FGDs who had a previous non-cephalic delivery but had no complications did not convey a strong sense of concern regarding non-cephalic deliveries.
3
0biomedical
0Study