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TCA yeast whole cell extracts from 5-10 ml aliquots of meiotic cultures were prepared as described previously 18 and proteins were resolved by SDS-PAGE and then transferred to PVDF membranes. To resolve the phosphorylated forms of Mek1, 10% SDS-PAGE gels with a 29:1 ratio of acrylamide:bisacrylamide containing 37,5 μM Phos-tag reagent (Wako) and 75 μM MnCl2 were prepared as described 1821, whereas normal 15% or 10% gels (acrylamide:bisacrylamide 37,5:1) were used for detection of H4K16ac, H3T11ph and H3K79me or Mek1, Hop1-T318ph, Cdc5 and Dot1-HA, respectively. Blots were probed with the following primary antibodies: rabbit polyclonal antibodies raised against Mek1 (1:1000) 13, Hop1-T318 (1:1000; kindly provided by J. Carballo), H3T11ph (1:2000; Abcam 5168), H4K16ac (1:2000; Millipore 07-329), H3K79-me1 (1:1000; Abcam ab2886), H3K79-me2 (1:2000; Abcam ab3594) and H3K79-me3 (1:2000; Abcam ab2621); goat polyclonal antibody against Cdc5 (1:1000; Santa Cruz Biotechnology sc-6733); mouse monoclonal antibody against the HA epitope (1:2000; Roche 12CA5). A mouse monoclonal antibody directed against 3-phosphoglycerate kinase (PGK) (1:10000; Molecular Probes A-6457) or a rabbit polyclonal antibody against histone H3 (1:5000; Abcam ab1791) were used as loading controls. HRP-conjugated secondary antibodies were from GE Healthcare (NA934 and NA931) or Santa Cruz Biotechnology (sc-2033). The Pierce ECL or ECL-2 reagents (Thermo Scientific) were used for detection and the signal was captured on film (Amersham Hyperfilm ECL; GE Healthcare) and/or with a ChemiDoc XRS (BioRad) system, using the Quantity One software (Bio-Rad). The same software was used to quantify protein levels.
| 4 | 0biomedical
| 0Study
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287,387 |
There may be a selection bias due to the differences in the proportion of basic characteristics between groups, which can be reasonably addressed by propensity score matching (PSM). The propensity score was defined as the probability of individuals with paclitaxel-coated devices being treated and was calculated with multiple logistic regression using variables that included age, sex, DM, HTN, warfarin, and NOAC. The paclitaxel-coated and non-paclitaxel-coated device groups were matched in a 1:1 proportion. Age and gender were perfectly matched between the two groups, and the other variables were matched by the Greedy nearest matching method. After PSM, Cox proportional hazards models were repeated to determine the association between usage of paclitaxel-coated devices and all-cause mortality and were reported in terms of hazard ratios (HRs) and 95% confidence intervals (CI).
| 4 | 0biomedical
| 0Study
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81,557 |
In the downstream part of the Danube, sulfamethoxazole levels were very similar in 2007 and 2013 (around 20 ng/L), and elevated levels were found in the tributaries Velika Morava (51 ng/L), Timok (40 ng/L), Iskar (65 ng/L), Russenski Lom (47 ng/L) and Arges (141 ng/L) (as for carbamazepine). In the downstream tributaries concentrations were higher in 2007 (Fig. 3).
| 3 | 0biomedical
| 0Study
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396,921 |
RPMI-8226-luc cells (8 × 106) were intravenously injected into NSG mice. After 4 weeks, mice were randomized into 2 groups [receiving vehicle (gray) and CM-272 (red); n = 6/group] and treated for additional 4 weeks with dosing and regimen schedules as specified in Supplementary Methods. Tumor dissemination was checked by A bioluminescence measurement and B serum levels of human Igλ secreted by RPMI-8226-luc cells at specified time points. Line plots represent mean and SEM. Box plots represent median ±IQR, with whiskers representing the minimum and maximum. Statistical significance was determined utilizing paired two-tailed Student’s t-test (*p < 0.05, **p < 0.01). C Representative microCT cross-sections at the metaphyses of distal femurs in a vehicle and CM-272-treated mice in transversal (upper) and sagittal (down) planes. D Transversal (left) and sagittal (right) planes of corresponding 3D renderings from microCT images at distal femurs (trabecular bone in red, cortical bone in gray). E Trabecular bone morphometric parameters from microCT images were quantitated for trabecular bone volume, occupancy, connectivity, and separation. F Serum levels of the bone formation marker P1NP were quantified by ELISA. Graphs represent mean values ± SEM with whiskers representing minimum and maximum values. CM-272-treated (red) mice were compared to the vehicle group (gray), where *p < 0.05; **p < 0.01 versus the vehicle control group. G Box plots showing DNA methylation levels of pooled MSCs obtained from healthy, vehicle- and CM-272-treated animals corresponding to hypermethylated CpGs between healthy and tumor-bearing animals. H GO enrichment analysis of CpG sites undergoing DNA hypermethylation changes in vehicle-treated MSCs versus MSCs from healthy mice. I Heatmap showing normalized DNA methylation levels of individual CpGs at selected Homeobox loci among animal groups. Data pooled from mice (n = 6) for each group with sufficient RRBS coverage (≥5 valid sequencing reads per CpG). <0.01 by paired two-tailed Student’s t-test. G Box plots showing mean ± SEM, with whiskers representing minimum and maximum values, of DNA methylation levels of pooled MSCs obtained from healthy (blue), vehicle- (gray), and CM-272-treated (red) animals corresponding to hypermethylated CpGs between healthy and tumor-bearing animals. A paired two-tailed Student’s t-test was performed to calculate statistical significance (****p < 0.001). H GO enrichment analysis of CpG sites undergoing DNA hypermethylation changes in vehicle-treated MSCs versus MSCs from healthy mice. p-values were calculated utilizing a binomial test. I Heatmap showing normalized DNA methylation levels of individual CpGs at selected Homeobox loci among animal groups. The color scale ranges from white to red, representing low to high levels of DNA methylation. Data pooled from mice (n = 6) for each group with sufficient RRBS coverage (≥5 valid sequencing reads per CpG).
| 4 | 0biomedical
| 0Study
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333,880 |
ME composite structures, which integrate FE and magnetic materials, have drawn intense interest due to the interesting physics of coupling of polarization and magnetization, as well as their applications in various novel room temperature multifunctional devices. ME composites possess large polarization, magnetization, and ME coupling at RT. For practical applications, this requires that the FE and magnetic ordering temperatures (TC) of ME composites occur well above RT. ME coupling and other physical properties in these composites can be suitably enhanced by the proper design of various types of connectivity of the FE and magnetic phases. Additionally, selecting appropriate FE and magnetic materials, suitable microstructural design, synthesis of phase pure structures, and good epitaxial growth are all critical for strong ME coupling. In ME composites, the coupling of FE and magnetic order parameters takes place via strain, charge coupling, and spin exchange (exchange bias) between the phases. Biquadratic (P2–M2) coupling typically dominates in these ME composite structures.
| 4 | 0biomedical
| 0Study
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61,040 |
Circulating bullous pemphigoid (BP)‐specific IgE is elevated in patients with BP and reacts with the same dominant epitopes as IgG. (a) α‐BP180 and (b) α‐BP230 IgE antibodies were measured in the peripheral blood of HCs (n = 18) or patients with BP (n = 19). (c) Normal and BP circulating IgG (blue) and IgE (yellow) were evaluated for reactivity against peptide stretches of BP180, spanning the NC16A or C‐terminal regions. An overlap in IgG and IgE reactivity towards the same peptide stretch is shown in red. The data represented in the graphs are mean ± SD. **P < 0·01, ****P < 0·0001. OD, optical density; NH, normal human; HC, healthy control.
| 4 | 0biomedical
| 0Study
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164,587 |
Thank you for submitting your article "Modelling spinal locomotor circuits for movements in developing zebrafish" for consideration by eLife. Your article has been reviewed by 3 peer reviewers, one of whom is a member of our Board of Reviewing Editors, and the evaluation has been overseen by Ronald Calabrese as the Senior Editor. The following individual involved in review of your submission has agreed to reveal their identity: Rishikesh Narayanan (Reviewer #2).
| 1 | 0biomedical
| 1Other
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374,885 |
By substituting natural with in vitro evolution, we explored a brand new application of DCA which overcomes the limitations that have so far hindered the generality and scalability of the method. As a proof of concept, we chose TEM-1 beta-lactamase (β-lactamase), a member of the β-lactamase family of enzymes that confer to bacteria the ability to destroy the beta lactam ring of penicillin and derivatives such as ampicillin (Abraham and Chain 1940). Resistance allows bacteria to grow in the presence of these antibiotics, a function that is easily amenable to a phenotypic selective pressure. TEM-1 is a golden standard for molecular evolution experiments (Bershtein et al. 2006; Salverda et al. 2010; Deng et al. 2012; Jacquier et al. 2013; Firnberg et al. 2014; Stiffler et al. 2015). Our data clearly demonstrate that proteins evolved by molecular evolution can be used to collect evolutionary and structural data and provide a new tool to all branching fields of evolutionary coupling and molecular evolution research.
| 4 | 0biomedical
| 0Study
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249,064 |
“I was one of the urban refugee,…living in a city back home, like an orange or an apple, it's very very expensive… but over here, oh my god, we buy all kind of fruit and you can afford it. It's like one dollar, a bunch of food. That makes me very happy as a Mama that I can provide healthy food to my kids.”
| 1 | 2other
| 1Other
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87,335 |
Recent studies suggest that protein aggregates are heterogeneous in composition. Some aggregates, such as oligomers and protofibrils, are highly toxic, while other species, including mature fibrils, lack toxicity.5 Assuming that both oligomers and protofibrils are precursors of mature fibrils,5 it is possible that anti-aggregation treatments may shift the equilibrium of protein aggregation from mature species to smaller toxic species, such as oligomers and protofibrils. As a result, suppression of protein aggregation might adversely enhance neurotoxicity, exacerbating synaptic dysfunction by disrupting LTP, axonal transport, and synaptic vesicle activity, eventually leading to cognitive, behavioral and motor deficits.10,30 Given such a paradoxical effect of immunotherapy, it is proposed that the toxic species, oligomers and protofibrils, rather than other forms, should be specifically targeted. Since oligomers and protofibrils have been examined most extensively using in vitro studies, further in vivo confirmation of this hypothesis is required. Similarly, the more toxic species of αS might be regarded as another specific target of immunotherapy.31
| 4 | 0biomedical
| 0Study
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155,523 |
Although NAOMi simulated many neurons in a volume, many of the simulated neurons were located out of the depth of focus and thus were not clearly visible at the principal imaging plane. We removed small or dim features at the simulation plane using the following steps. We binarized the spatial intensity profile of each neuron by using 0.2 times the maximum intensity of the spatial profile as the threshold. We calculated the area of each neuron as the number of pixels in the thresholded spatial profile, and removed neurons with areas smaller than half of the average neuron area. We calculated the integrated intensity over the spatial profile of each neuron, and removed neurons whose integrated intensity was lower than a threshold determined from the intensity distribution (∼60% neurons were removed in this step). We also removed neurons that did not have any action potentials after the 20 s transient period of the simulation (or 100 s for GCaMP7 series indicators). For each remaining neuron, we exported the thresholded spatial profile as the GT mask, and exported the clean trace as the GT trace. When using the default parameter set, each simulated video contained 18–55 GT neurons that met the above criteria, and the average neuron density was (4.3 ± 1.3) × 103 neurons/mm2.
| 4 | 0biomedical
| 0Study
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236,135 |
All chemicals were of analytical grade and were obtained from Sigma-Aldrich/Merck (Darmstadt, Germany) or Carbosynth (Berkshire, United Kingdom), except for psicose (Izumori Lab, Kagawa University, Kagawa, Japan), glycerol (Chem-Lab, Zedelgem, Belgium), tagatose (Nutrilab, Giessen, The Netherlands) and trehalose (Cargill, Vilvoorde, Belgium). Kojibiose, nigerose and βGlc1P were produced in-house according to the procedures of Beerens et al. , Franceus et al. and Van der Borght et al. , respectively.
| 2 | 0biomedical
| 0Study
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157,605 |
The biology of the tumor should cautiously guide surgeons in the planning of aggressive surgery with potential morbidity, especially when scheduling PD for well-differentiated tumours of the pancreatic head in the presence of LMs. In this high-risk situation with soft pancreas and/or obese patients, separating the entire sequence in multiple separate stages could be an option. Additionally, these patients should be referred to tertiary centres for the minimization of postoperative morbidity.
| 4 | 0biomedical
| 1Other
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41,625 |
We propose to segment prostate and surrounding structures in the wavelet domain. The major advantage of wavelets is the ability to perform local analysis, i.e. trends, breakdown points, discontinuities, etc. The Double Haar wavelet transform can make the image edge detection more effective. The moving window implementation can protect the details and smooth the noise . Therefore, we use a combination of these two—the Moving window-based Double Haar (MWDH) transformation for our prostate segmentation.
| 4 | 0biomedical
| 0Study
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33,219 |
Although local ablations including stereotactic body radiotherapy (SBRT) and cryoablation are relatively new, they have become alternative, minimally invasive local therapeutic options for several solid malignancies [23–28]. Advances in these novel ablations should be reevaluated in terms of possible immunological advantages [22, 29, 30]. In addition, recent studies have demonstrated the possible synergistic effect of these local ablations when combined with immunotherapy [31–33]. This raises the following questions: (1) whether combining local ablations with immunotherapy improves the survival outcomes of patients with solid tumors, (2) whether it is possible to differentiate the immunologic effect from abscopal effect of local ablations, and (3) which local ablation is the most likely to be effective when combined with immunotherapy. In answering these questions it would be ideal to focus on specific type(s) of cancer; however, there is a severe lack of data if our purview is limited to one specific type of solid tumor. To this end, we aim to review all published data available at PubMed on the immunological anti-tumor effects of local ablations and their possible additive effects when combined with immunotherapy.
| 4 | 0biomedical
| 2Review
|
155,802 |
Cavanagh proceeded to show images of the cornea obtained using CCM, which ‘blew me away’. I (N.E.) immediately saw the potential application of CCM to help understand the ocular response to contact lens wear. At great expense, I managed to obtain one of the first commercially available CCM instruments—the Tomey ConfoScan Confocal Microscope Model P4 (Tomey, Erlangen, Germany)—soon after it came onto the market in 1996.
| 2 | 0biomedical
| 1Other
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91,823 |
Number of relay nodes: Figure 12a illustrates the performance comparison in terms of the number of relay nodes required under varying R. The figure shows that for all compared algorithms, when R increases, the number of required relay nodes reduces such that for R = 350 m, each of RPSNC, FeSTA and MST_1TRNP requires five relay nodes, in contrast to QTA that requires six relay nodes. This can be attributed to the fact that fewer relay nodes are required to connect the partitions when R increases. Hence, depending on the topology, both QTA and FeSTA may be superior to one another, since QTA outperformed FeSTA for the tested case of random networks. RPSNC and FeSTA achieve the same results, since the optimal relay nodes for the Pentagram network are placed at the Steiner points of the triangles (see Figure 1c).
| 1 | 2other
| 0Study
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57,783 |
There are a few in vitro studies about the potential effects of PRP released GFs on stem cell and their cooperation in tissue regrowth. Wang et al. discovered that PRP could efficiently improve proliferation and differentiation of adipose derived stem cells with secretion of TGF-1 and PDGF-AB. And the effect of PRP was more long-lasting than platelet-rich fibrin (Wang et al., 2012).
| 4 | 0biomedical
| 0Study
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332,117 |
This study characterized S. Typhi isolated from cases of typhoid fever collected by the Sivigila National Surveillance System and laboratory from across Colombia between 2012–2015. Our work demonstrates that there is a substantial burden of typhoid fever in Colombia . The disease epidemiology in this Latin American country appears to be highly variable, with typhoid associated with sustained transmission in some regions and short-term outbreaks in other departments. We additionally found that typhoid is broadly distributed and caused by multiple genotypes, of which the majority may be constrained to Colombia and do not appear to circulate between other Latin American countries.
| 4 | 0biomedical
| 0Study
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184,467 |
In summary, commercial pharmacogenetic tests can be utilized to guide psychotropic medication prescribing for pediatric patients with psychiatric disorders while recognizing their limitations. In the context of pediatric pharmacogenetic testing, clinicians need to be aware of the ontologic effects of CYP450 drug metabolizing enzyme development in children. Clinicians should also use pharmacogenetic resources such as the CPIC and/or FDA guidelines to corroborate gene-drug(s) pairs that have strong evidence to support their use in the pediatric cohort. We anticipate that the debate surrounding the clinical utility of pharmacogenetic test for pediatric patients with psychiatric disorders continues as long as large randomized pharmacogenetic studies based on pediatric cohort remain unexplored, and that clinicians are not adequately trained in pharmacogenetics to effectively interpret test results. Ultimately, the results of commercial panel-based pharmacogenetic testing should not replace clinical experience and judgment for making the final medication choice.
| 4 | 0biomedical
| 2Review
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226,792 |
The results of the logit regression model demonstrated that age has a negative impact on food insecurity. Our study results are supported by a previous study, as Hofferth revealed that older people are more mature and may have better experiences obtaining the resources they require. In contrast, a study analyzed by Khan et al. reveals that work efficiency decreases as age increases and increases the chances of food insecurity.
| 2 | 2other
| 0Study
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250,331 |
KWC and KS conceived and designed the study. EK and SRu conducted the lifespan experiments. EK conducted IHC, MEA, electrophysiology and video analysis, with help from SRe. EK conceived and JB conducted the calcium and neuron experiments, with help from KF. IK and KI conducted the NAD+ measurements, with supervision by HH. PJM provided the Xrcc1 mouse model, and LJ managed the mouse colonies. KWC and KS wrote the manuscript, with editing from HH, EK and JB.
| 1 | 0biomedical
| 1Other
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117,084 |
Though IGF-2 levels were significantly modulated in HKCs and not HCFs, glycolytic flux was slightly reduced in HCFs with no change in the disparity between the elevated levels in HKCs even at basal conditions. These results suggest that though DHEA, prolactin, and E2 influence cellular bioenergetics, the inherent defects that drive elevated glycolytic flux in HKCs are unable to be overcome with hormone stimulation at the physiological levels utilized in this study. Furthermore, our study revealed a novel finding that exogenous DHEA may contribute to KC development or progression by reducing localized production of IGF-1 and autocrine or paracrine signaling contributing to altered metabolic function. The increase in carbamoyl phosphate and argininosuccinate, key metabolites involved in the urea cycle, suggests that arginine and polyamine flux in HKCs may be more sensitive to DHEA-induced modulation of collagen precursors, perhaps leading to ECM thinning, a trademark of KC. In contrast, HKCs showed less sensitivity to E2 treatment compared to HCFs with dramatic increases in glycolysis and PPP flux. These results highlight a hormone-specific response in healthy versus KC-derived cells which may be a factor related to the altered basal metabolism observed in HKCs. Further studies are needed to elucidate the effects of hormones in regulating genes associated with matrix deposition and mitochondrial function in KC in order to determine if the sex chromosomes regulate the cellular responses to exogenous hormones in vitro.
| 5 | 0biomedical
| 0Study
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14,667 |
There is long standing concern over coordination for patients requiring health and long-term care, in particular the delayed discharge of patients from hospital (Baumann et al. 2007; Bryan et al. 2006; House of Commons 2003; National Audit Office 2000).To improve integration policy makers need information about the effects of provision of one type of care on the other. In this paper we examine two questions where there is little quantitative evidence: the extent to which accessibility of long-term care affects the length of stay in hospital and the probability of a patient being discharged back to their homes rather than to a care home.
| 4 | 0biomedical
| 0Study
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248,078 |
Assessment of the target compounds as sPLA2 inhibitors was conducted by Ellman’s method-based assay (Table 3), dexamethasone was applied as a positive control. The target compounds exhibited promising sPLA2 inhibitory effect ranging from IC50 24.72 ± 1.59 (C7) to 2.01 ± 1.11 µM (C15). (Table 3, Figure 3)
| 3 | 0biomedical
| 0Study
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155,267 |
4) National core team. In line with guiding principle #4, both countries made efforts to form an ad hoc structure (a national core team) in which implementers and researchers could interact with policy makers to share emerging experiences, mobilize knowledge and perspectives from key stakeholders, and access the authority to address the identified bottlenecks. In Kenya this core team included actors from the Ministry of Health, KEMRI, and Nutrition International; in Uganda it included actors from the Ministry of Health, Office of the Prime Minister, and district offices. Several factors prevented these core teams from meeting and functioning as intended: competing time demands, the focus on the formal IR studies when they did meet, and the onset of COVD-19 which prevented the implementing teams from forming concrete bottleneck solutions for consideration by policy makers. Two strategies that provided a partial workaround were to schedule core team meetings during country visits by the SISN senior technical lead and having the country knowledge broker engage with individual members outside of formal meetings.
| 1 | 2other
| 1Other
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184,736 |
In our previous published report (Panthi and Leitch, 2019), we demonstrated that selective silencing of feed-forward inhibitory PV+ interneurons in the CTC network via regional injection of CNO into either the SScortex or the RTN thalamus of PVCre/Gi-DREADD mice, generated absence-like SWDs. In the current study, we further demonstrate that selectively activating these interneurons, during PTZ-induced seizures, prevents or suppresses the severity of absence seizures. Furthermore, PTZ-induced tonic-clonic seizures are also reduced in severity by activation of feed-forward inhibitory PV+ interneurons within the CTC network. PV+ interneurons account for ∼40% of the GABAergic population (Xu et al., 2010). Most PV+ neurons in the cortex are basket and chandelier cells; they are found throughout cortical layers 2–6. PV+ interneurons, typically have fast-spiking, low input resistance, and high-amplitude rapid after-hyperpolarization characteristics (Kawaguchi et al., 1987; Kawaguchi and Kubota, 1997), which enables them to fire a rapid train of action potentials unlike any other neuron in the cortex. They are therefore likely to have a profound impact on the spiking output of their targets (for review see Ferguson and Gao, 2018).
| 4 | 0biomedical
| 0Study
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94,150 |
Despite considerable combined evidence from coloration, morphometrics, and mtDNA data, comprehensive and accurate species limits for this group remain elusive, no matter what species concept one chooses to use. Using the biological species concept, I suggest that consideration of all of the available evidence indicates that we should recognize five species in the A. “prasinus” complex (A. wagleri, prasinus, caeruleogularis, albivitta, and atrogularis), each with any associated named subspecies (Appendix). Further study could raise this number (e.g., by splitting A. atrogularis cyanolaemus from atrogularis again). Under a phylogenetic species concept (PSC), one could probably raise every allopatric population in A. “prasinus” to the species level, resulting in at least 12 taxa using morphology alone. So how many species of toucanets are there in the A. “prasinus” complex?
| 2 | 2other
| 0Study
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85,763 |
Figure 2 shows the network of phylogenetic relatedness of the same 143 genomes; a dynamic view of this network is available at http://bioinformatics.org.au/tools/AFnetwork/. As in our tree ( Figure 1), Archaea and Bacteria form two separate paracliques; even at t = 0, we found only one archaean isolate (the euryarchaeote Methanocaldococcus jannaschii DSM 2661) linked to the bacterial groups Thermotogales and Aquificales 25. Upon reaching t = 3, most of the 14 phyla have formed distinct densely connected subgraphs in our network, i.e. Cyanobacteria and Chlamydiales form cliques at t = 1.5 and all subgroups of Proteobacteria form a large paraclique with the Firmicutes at t = 2. Four Escherichia coli and two Shigella isolates, known to be closely related, form a clique up to t = 8.5. Interestingly, this network also showcases the extent that genomic regions are shared among diverse phyla, e.g. the high extent of genetic similarity among Proteobacteria versus the low extent between Chlamydiales and Cyanobacteria. Our observations largely agree with published studies 10, 25, but also highlight the inadequacy of representing microbial phylogeny as a tree. For instance, in the tree Coxiella burnetii, a member of the gamma-Proteobacteria, is grouped with Nitrosomonas europaea of the alpha-Proteobacteria (marked with an asterisk in Figure 1); in the network, the strongest connection of C. burnetii is with Wigglesworthia glossinidia, a member of the gamma-Proteobacteria (marked with an asterisk in Figure 2) at t = 2. Both W. glossinidia and C. burnetii are parasites; the W. glossinidia genome (0.7 Mbp) is highly reduced 31 and the C. burnetii genome (2 Mbp) is proposed to be undergoing reduction 32. As both the tree ( Figure 1) and network presented here were generated using the same alignment-free method, the contradictory position of C. burnetii is likely caused by the neighbour-joining algorithm used for tree inference 25. In this scenario, the C. burnetii genome connects with N. europaea because it shares high similarity with N. europaea and Neisseria genomes of the beta-Proteobacteria ( S between 1.43 and 1.68), second only to W. glossinidia ( S = 2.05), and because it shares little or no similarity with other genomes of gamma-Proteobacteria that are closely related to W. glossinidia, i.e. Buchnera aphidicola isolates (average S = 0.63) and “ Candidatus Blochmannia floridanus” ( S = 0).
| 4 | 0biomedical
| 0Study
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388,931 |
To assess the direct cytotoxicity of CME in breast cancer cells, MCF-7, and MDA-MB-231 were treated with CME and analyzed using the MTT assay. We found that CME exerted dose- and time-dependent cytotoxic effects on both cell lines. In MCF-7 cells, the half inhibitory concentrations (IC50) of CME were 27.17, 8.90, and 5.23 μg/ml for 24, 48, and 72 h treatments, respectively (Figure 1A). The IC50 values of CME in MDA-MB-231 were 19.96, 12.01, and 5.55 μg/ml, respectively for 24, 48, and 72 h treatments (Figure 1B). Notably, the inhibitory effect of CME in MDA-MB-231 was comparable to or greater than that in MCF-7, indicating that CME may be an effective cytotoxic agent against TNBC.
| 4 | 0biomedical
| 0Study
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237,444 |
There are two histological subtypes of craniopharyngioma: adamantinomatous and papillary. While adamantinomatous craniopharyngiomas can occur in children and adults, the papillary subtype is mainly observed in adults . The adamantinomatous subtype is thought to arise from neoplastic transformation of epithelial cell remnants within the craniopharyngeal duct. Histologically, they exhibit palisading a columnar epithelium surrounding well-differentiated squamous epithelium, wet keratin, and stellate reticulum associated with adjacent gliosis and Rosenthal fibers . Activating mutations of the WNT pathway gene, CTNNB1, characterize the majority of cases while rare downstream WNT pathway mutations in APC have also been described . Papillary craniopharyngiomas are thought to arise from transformed epithelial cells within the pituitary stalk. Histologically, they exhibit papillary architecture, characterized by solid sheets of well-differentiated non-keratinizing squamous epithelium and fibrovascular cores surrounded by crude papillae . Nearly all cases of papillary craniopharyngioma demonstrate BRAF V600E mutations , which may be amenable to treatment with anti-BRAF agents and can lead to dramatic tumor response .
| 5 | 0biomedical
| 2Review
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157,496 |
In addition to Itpr1 mRNA, at least several hundred mRNAs, packaged into RNA granules, are transported into dendritic spines . From mouse brain extracts and hippocampal lysates, a subset of these transcripts immunoprecipitate with full-length DISC1 protein when using a C-terminal antibody. These transcripts were at least two-fold enriched in the DISC1 immunoprecipitate compared with an IgG immunoprecipitate. Those identified included the pore-forming subunit of the VGCC CaV1.2 (Cacna1c), and its accessory subunit α2δ1 (Cacna2d1); KV3.1, a delayed rectifier K+ channel (Kcnc1), expressed in fast spiking GABA interneurons; and KV3.4, a second K+ channel family member (Kcnc4). The interactions appear direct since in vitro RNA binding assays confirmed GST–hDISC1–N1 interaction with biotin-labeled 3′UTR mRNA of each gene but not with GST alone or to 3′UTR of other transcripts such as the sodium channel NaV2.1 (Scn2a), or to the coding sequence of Cacna2d1 . Taken together, these findings indicate that DISC1 binds to a subset of mRNAs encoding proteins that regulate membrane excitability and Ca2+ influx. Decreased functional DISC1 would be predicted to lower transport of mRNA to critical sites, consequently decreasing expression and compromising the normal complement of proteins regulating Ca2+-dependent events.
| 4 | 0biomedical
| 0Study
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57,609 |
The limiting branching process may be described by a continuous-time multitype Markov branching process, with the type of an infective corresponding to its effective degree. Let \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\tilde{D}}$$\end{document}D~ denote the (size-biased) degree of a typical neighbour of a typical individual in the network and let \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\tilde{p}}_k=\mathbb {P}({\tilde{D}}=k)$$\end{document}p~k=P(D~=k) \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$(k=1,2,\ldots )$$\end{document}(k=1,2,…). Then \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\tilde{p}}_k=\mu _D^{-1} k p_k$$\end{document}p~k=μD-1kpk, where \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mu _D=\mathbb {E}\left[ D\right] $$\end{document}μD=ED, since when a stub is paired it is k times as likely to be paired with a stub from a given individual having degree k than it is with a stub from a given individual having degree 1. Under the branching process approximation, the effective degree of a newly infected individual is distributed according to \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\tilde{D}}-1$$\end{document}D~-1, since one of that individual’s stubs is ‘used up’ when it is infected. Note for future reference that \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mu _{{\tilde{D}}}=\mu _D^{-1}\mu _{D^2}$$\end{document}μD~=μD-1μD2 and, more generally, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mu _{f({\tilde{D}})}=\mu _D^{-1} \mu _{Df(D)}$$\end{document}μf(D~)=μD-1μDf(D) for any real-valued function f. (For a random variable, X say, we use \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mu _X$$\end{document}μX to denote its expectation \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathbb {E}\left[ X\right] $$\end{document}EX. Thus, for example, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mu _{Df(D)}=\mathbb {E}\left[ Df(D)\right] $$\end{document}μDf(D)=EDf(D).)
| 4 | 0biomedical
| 0Study
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295,556 |
The mixture of 0.100 mmol Cd(NO3)2 · 4H2O, 0.100 mmol Ca(NO3)2 · 4H2O, 0.1 mmol H4L, 3.0 mL DMF and 1.0 mL H2O was stored into a small glass vial (20 mL), and after that, at 110 °C in an oven the glass vial was sealed and heated for 2 days. The compound’s colorless massive crystals were gathered with 38% yield in the light of Cd(NO3)2 · 4H2O after the temperature of oven was cooled to RT. Elemental analysis calcd. for the C57H67Ca2Cd2N5O28 (1575.08): C, 43.46; H, 4.29; N, 4.45%. Found: C, 43.42, N, 4.43, and H, 4.27%.
| 3 | 0biomedical
| 0Study
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21,601 |
Shannon entropy was used as an estimate of how uniform the distribution is across the whole range of possible phenotypes. The range of possible phenotypes was defined by the minimum and the maximum fluorescence measurement in the entire dataset, across all measured mutant library DMEs. Entropy was calculated as:S=-∑kPklogPk+logΔx
| 4 | 0biomedical
| 0Study
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369,423 |
Bai J. et al. developed FA-containing transdermal HG patches to treat skin damage induced by UV radiation . The authors used a partially neutralized polyacrylate (NP700) as gelling base, and different combinations of dihydroxyaluminum aminoacetate, tartaric acid, glycerine, FA and water to obtain the HG with the best release rate and skin penetration performance. Dihydroxyaluminum aminoacetate acted as a cross-linking agent for the polymeric backbone by releasing aluminum ions in acidic conditions, promoted by tartaric acid in the presence of water. The antioxidant potential of FA, in relation to the development of effective delivery systems, has also been taken into consideration for the treatment of corneal wound healing, as low ocular bioavailability and short residence time are usually limiting factors associated with (poly)phenolic antioxidants topically administrated.
| 4 | 0biomedical
| 0Study
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311,752 |
With the advancement of deep learning, network-embedding techniques are developed to identify the same users in different platforms. For example, Liu et al. proposed IONE algorithm, which embeds users into a low-dimensional space for anchor link prediction. Man et al. proposed an embedding and matching-based model PALE. However, different from our approach, the network embedding in PALE is purely unsupervised and does not leverage observed anchor links when encoding the network structure into embeddings. Moreover, the two approaches cannot make use of network attributes. Recently, Zhang et al. proposed an attributed network alignment algorithm, called FINAL. The method leverages the node attribute information to guide the topology-based alignment. In FINAL, a nice alignment consistency principle is designed and developed, i.e., the alignments between two pairs of nodes across the networks should be “similar/consistent” with each other. However, this algorithm works in an unsupervised manner and cannot leverage the observed anchor links.
| 1 | 2other
| 0Study
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134,014 |
In the non-canonical branch (Figure 3, right), the cascade works through a Smad-independent manner via at least three signaling cascades, namely the extracellular signal-regulated kinase (ERK) (also known as mitogen-activated protein kinase (MAPK)), phosphatidylinositol-3 kinase (PI3K), and RhoA kinase cascades . These three cascades can act independently or interact with each other to regulate gene transcription. In ERK signaling, for example (Figure 3, Ras-ERK), the cascade is initiated by a GTPase known as Ras, which is phosphorylated in response to the activation of the type I/II receptor complex formation. This results in a conformational change of Ras, allowing it to activate RAF, which in turn phosphorylates MEK and activates it. MEK finally phosphorylates ERK, also known as MAPK, which then directly activates or inhibits transcription factors such as PAX6, a key transcription factor essential for the development of the early brain and eye . The kinase pathways involved in non-canonical signaling interact closely with each other, with Ras also activating the PI3K-Akt signaling pathway (Figure 3, PI3K-mTOR) . The activated protein kinase Akt is involved in many different processes, depending on its downstream target. Frequently, Akt inactivates GSK-3 through phosphorylation .
| 4 | 0biomedical
| 0Study
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12,145 |
At variance with typical CJDMM1, however, all five cases also displayed a variable number of PrPSc plaque-like deposits in the white matter, not correlating, overall, with the degree of white matter damage (Tables 2 and 3), in virtually all brain regions analyzed (Fig. 2 c,d and Table 2). Furthermore, with the only exception of the case carrying the E200K PRNP mutation (case #4), PAS staining revealed the presence of PrP-amyloid plaques (Fig. 2 e,f), quantitatively reflecting the number of PrPSc plaque-like deposits. While in three cases the plaques were immediately noticed given their number and the typical kuru-type morphology, they were much rarer and limited to a small core in the case with the longest duration and the most severe pathology (case #3). Notably, the three cases with the highest number of PrP plaques also showed numerous coarse focal PrP deposits and tract-like PrP deposits in gray matter areas delimiting the white matter (data not shown). These types of deposits were seen in the striatum in proximity of the internal capsule and in the lateral thalamus. Besides plaques, no other PrP deposits were seen in the white matter either intra- or extracellularly.Table 2Distribution of PrPSc plaque-like deposits (3F4-immunopositive) in the cerebral white matterfrontal cortextemporal cortexparietal cortexoccipital cortexhippocampusneostriatumthalamusmidbrainmedulla oblongatacerebellumcase #1++++++++++++++++++++++++++++++case #2+++++++++++++++++case #3++++++++NA0case #4++++++++++++case #5+++++++++++++The semi-quantitative evaluation was carried out by averaging the number of plaques among three 200× microscopic fields (1–10 +, 11–20 ++, >21 +++) after selecting the areas with the highest density of PrP deposits. NA: not available Table 3Assessment of white matter lesions in 4 representative areasLesionAREACase #1Case #2Case #3Case #4Case #5DemyelinationFrontal cortex+++++++++0Temporal cortex++++++++++Occipital cortex++++++++++0Cerebellum++++++++Axonal damageFrontal cortex+++++++0Temporal cortex++++++++0Occipital cortex++++++0Cerebellum+++++++0AstrocytosisFrontal cortex+++++++++0Temporal cortex+++++++++Occipital cortex+++++++++Cerebellum+++++MicrogliosisFrontal cortex++++++++++++Temporal cortex++++++++++++Occipital cortex++++++++++++Cerebellum+++++++Each lesion was scored semiquantitatively using a 0–3 scale (0, absence of significant abnormalities: + mild, ++ moderate, and +++ severe changes). The list of staining used for the assessment are listed in the materials and methods
| 4 | 0biomedical
| 0Study
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89,870 |
Figure 4 illustrates the average received and harvesting powers from different RF sources operating at [700 900 1800 2100] MHz, respectively. The variations in received and harvesting powers are plotted by varying the distance of nodes from 0∼500 m. The rest of the simulation parameters are the same as that mentioned for Figure 3. In this simulation result, we try to depict the heterogeneity of RF sources in terms of operating frequency bands and transmission powers. In Figure 4a, we use the same power of 46 dBm, whereas in Figure 4b, we use the power of [46 40 35 30] dBm for [700 900 1800 2100] MHz sources, respectively. It is clear from the two results that the highest energy can be harvested from that primary source for at 700 MHz source with 46 dBm of power and harvesting energy decreases as we move to the higher spectrum. Furthermore, the overall harvesting energy decreases with a decrease in the transmission power or an increase in the distance. One important thing is the difference (i.e., the difference between solid and dashed or dotted lines) between the received power and the harvesting power. This is due to the lower harvesting efficiency η of the receiver.
| 4 | 0biomedical
| 0Study
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339,860 |
For the evaluation of academic competencies, the PAIB-1 (Test of basic instrumental aspects: Reading, writing and numeric concepts; Galve-Manzano et al., 2009) was used in its pencil and paper version. This test allowed for the assessment of literacy and mathematics competencies, obtaining the following: (1) one score referred to Basic Aspects of Reading and Writing; (2) another score referred to Basic Aspects of Mathematics; (3) a total score for all academic competencies (Global Basic Aspects), sum of the 2 previous scores. Therefore, the PAIB-1 permitted the assessment of the most important academic competencies for academic success (Organization for Economic Co-Operation and Development [OECD], 2016), justifying its use as opposed to the use of other standardized instruments that only offer a global score. (Although PAIB-1 also permits the obtaining of other scores, they were not used in this study, given the objective of the same). The reliability of the PAIB-1 has been demonstrated (Galve-Manzano et al., 2009).
| 2 | 2other
| 0Study
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392,981 |
The density distribution inside the model was assigned based on the CT-value contrast shown in Fig. 3. The total porosity was computed from density and using the mass-balance law by assuming that the mineral is pure calcite with density 2.71 g/cc. Finally, this porosity contrast was translated into the elastic-moduli contrast by assuming the stiff-rock effective-medium model described in, e.g.,10. This model accurately describes the velocity–porosity wireline data from the well where the samples were extracted from (see11).
| 2 | 0biomedical
| 0Study
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274,378 |
Our findings indicated that low-dose Cu exposure exacerbates depressive actions in the ApoE4 mice, showing the potential underlying causes of depression. ApoE is a polymorph protein involved in the transformation and metabolism of lipoproteins, and its gene can regulate many biological functions that have been existed as a risk factor in mental diseases, such as depression . Additionally, the disturbance of Cu metabolism can cause neuropsychiatric symptoms, such as depression . Therefore, ApoE4 mice showed aggravation of depression-like behavior under Cu exposure. However, the mice showed no cognitive impairment on the Morris water maze test, possibly related to age.
| 4 | 0biomedical
| 0Study
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393,640 |
a Comparison of the σ1.2/σNCR and βlobe/Si1 conformations in apo-RNAP (middle), RPc (left), and RNAP-DksA/ppGpp (R-DksA, right, DNA is removed from the RP1-DksA/ppGpp to model this complex). RNAP (subunits and domains), DksA and DNA are indicated. Close-up views of the RNAP cleft are shown below. The DNA loading gate is closed in the apo-RNAP due to the βgate loop (βGL) contacts with σ1.1/σ1.2 (white dashed oval). The opening of the DNA loading gate in RPc and RP1-DksA/ppGpp is indicated by blue and red arrows, respectively. b A proposed model of σ1.1 ejection in the RPc. The RPc is depicted as a transparent surface with cartoon models of the clamp (purple) and the lobe/Si1 (blue). The clamp in the apo-form RNAP and the lobe/Si1 in RP1-DksA/ppGpp are colored gray and white, respectively. In the RPc, the σNCR rotation (black arrow) contacts the β’CT, resulting in clamp movement toward σ1.1 (red arrow) and a steric clash with σ1.1 (white oval).
| 4 | 0biomedical
| 0Study
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192,123 |
The 11 fragments in the hexon monomer sequence fold into the ordered three-dimensional structure of the hexon (Figure 3). Figure 3 is divided into 12 sub-pictures from the upper left corner, and the corresponding segment number is marked in the upper left corner of each sub-picture. The first to the eleventh subgraphs corresponded to 11 segments, respectively. The twelfth subgraph in the lower right corner is the overall folded shape of all 11 segments of the monomer in the hexon trimer. The red area is the base region, namely segments 1, 5, 9, and 11. The green area is the neck, containing segments 2, 4, 6, 8, and 10; the blue area is the tower region, containing segments 3 and 7.
| 4 | 0biomedical
| 0Study
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153,758 |
Validation of the DKK1 RNAscope CISH assay was conducted to assess specificity, sensitivity, accuracy, and precision in G/GEJ tumor resections according to CLIA guidelines. Briefly, 40 G/GEJ tumor resections were assessed, and the CISH assay passed the pre-defined acceptance criteria for specificity, sensitivity, accuracy, and precision (Table 1). The same lot of probes were used during the course of the study. The details of the validation are summarized below.Table 1DKK1 RNAscope assay validation results.Performance parameteraTumor resections evaluated (n)Percentage passParameter pass/failAnalytical specificityb40100% (40/40)PassAnalytical sensitivityc40100% (40/40)PassAccuracyd20rho = 0.629, p value = 0.003PassPrecisione1292% (11/12)PassaDetails of the pre-defined acceptance criteria are described in the methods.bSignal was predominantly localized to tumor cells.cSignal was detected above background.dSpearman correlation (p value < 0.05) with DKK1 qPCR results.eResults across 3 separate staining days within the same binned category of expression (negative bin: H-score = 0, low bin: H-score < 34, and high bin: H-score ≥ 35). In cases of discordant binning of negative, low or high categories, a ± 20 point H-score discrepancy was still considered acceptable.
| 4 | 0biomedical
| 0Study
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176,388 |
Lest I be misunderstood, I am not suggesting that contemporary European states should adopt the kind of qualified face-covering ban just outlined as opposed to having no ban at all. While I have identified some morally important reasons for doing so, my claim in this article has been more modest, namely that it is morally permissible for them to do so. As I have argued, even if the social costs of public face-covering are ordinarily fairly low within these societies because of the small shares of inhabitants who wear non-medical face-coverings, or who would do so if this were allowed, this is not a decisive reason against banning this type of face-covering given that its social costs would be substantial if larger shares were to publicly cover their face, which seems enough to justify a ban in the same way that various other behaviours that produce significant harm only at an aggregate level seem to be permissibly restricted (e.g. walking on lawns, driving diesel cars in city centres). However, if this is correct, then it looks like France and several other European countries are justified in banning non-medical face-coverings from public spaces even if they are wrong not to allow exemptions from these bans.
| 1 | 2other
| 1Other
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302,674 |
To benchmark hypertension prevalence, awareness, treatment, and control in the UAE, pooled estimates from this study were compared to country-specific estimates of the NCD-RisC study published in Lancet 2021 . Country-specific data from the Arabian Gulf countries showed that the 31% prevalence of hypertension in the UAE is lower than that in Saudi Arabia (33.3%), Bahrain (37.7%), Kuwait (39.4%), Qatar (39.7%), and Oman (43.6%) . However, the UAE data presented in the Non-Communicable Disease NCD Risk Factor Collaboration (NCD-RisC) study reported that the prevalence of hypertension in the UAE was 39.2% , which is higher than our pooled estimates (31%). Differences in the health survey data, diagnoses and treatments of hypertension using questionnaires, BP measurement errors, validation of the BP devices, and several other residual factors may contribute to the differences in estimating the prevalence of hypertension.
| 4 | 0biomedical
| 0Study
|
13,923 |
To determine the impact of the presence of normal AMs in the control of M. avium in SCID mice, AMs from BALB/c mice were instilled into the lungs of recipient SCID mice followed 10 min later by airway delivery of M. avium. Four weeks later, there was a slight, but not significant, decrease in M. avium numbers in the lungs of the AM‐treated SCID mice relative to untreated control (Fig. 2A).
| 4 | 0biomedical
| 0Study
|
287,175 |
This analysis included 316 patients (age, mean ± SD, 38.8 ± 18.2; males, 153 [48.3%]; females, 163 [51.7%]). The median follow-up period (interquartile range) was 939 (473–1279) days. The tumors were located in the lower extremities, upper extremities, trunk, and head/neck in 160 (50.5%), 56 (17.7%), 93 (29.3%), and 7 (2.2%) patients, respectively. Furthermore, the tumor subtypes were monophasic, biphasic, and unclassified/undifferentiated in 153 (48.3%), 89 (28.2%), and 74 (23.4%) patients, respectively. The median (interquartile range) tumor size was 5.4 (3.4–9.0) cm. The tumor stages were Ia-b, IIa-b, and III in 12 (3.8%), 157 (49.5%), and 147 (46.4%) patients, respectively.
| 4 | 0biomedical
| 0Study
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209,880 |
Induced sputum was collected using inhaled hypertonic saline and established protocols that have been previously described [13, 14]. A portion of subjects (33 RA, 21 controls, and 31 at-risk) provided an unstimulated saliva sample prior to sputum induction. Saliva samples with volume remaining after anti-PAD4 antibody testing were also tested for ACPA, and this included 28 RA, 19 controls, and 28 at-risk subjects (see below for a description of antibody testing methodologies). All samples were stored at −80°C.
| 3 | 0biomedical
| 0Study
|
165,169 |
Many of the tools used to assess dietary behaviors among youth, such as 24-h recall and food frequency questionnaires, rely on recall, which is subject to memory, social desirability bias, and respondent burden . An issue that may be encountered in low-income populations is low response rate for lengthy food frequency questionnaires, speculated to be due to the time involved and complexity of the forms, causing insurmountable burden for youth and their parents . An unexpected benefit of the Veggie Meter® was that researchers noted youth, as well as classroom teachers in some cases, were very enthusiastic and engaged when the Veggie Meter® was introduced, which may have increased participation. While this observation is anecdotal, a similar phenomenon was noted with wearable activity monitors that displayed user feedback in response to physical activity, which may have resulted in increased activity during the assessment period independent of the intervention .
| 4 | 0biomedical
| 0Study
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214,144 |
In patients with Crohn´s disease, it was demonstrated that steroid-sensitive and -resistant patients show different cell type-specific patterns of activation of pro-inflammatory pathways. GC response correlated with activation of p38, JNK1, and NF-κB mainly in lamina propria macrophages while GC-resistance was associated to activation of these mediators mostly in epithelial cells . In line with these studies, treatment of patients with p38 and JNK inhibitor CNI-1493 achieved significant improvement of Crohn’s disease patients .
| 4 | 0biomedical
| 0Study
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236,160 |
Various bacterial cultures were then purified using the streak plate method on nutrient agar medium40. Using a sterilized inoculating loop, a slightly picked colony from the spread plate was made to drag the loop over the face of another plate in a haphazard motion. The loop was sterilized over the flame, and the plate rotated to 90°, drag the loop over the area initially streaked before. Then, the plate was incubated for 24 h. Isolated colonies and their growths were observed. This procedure was repeated several times until purified colonies were ensured. The purified bacterial culture was kept over nutrient agar slant.
| 5 | 0biomedical
| 0Study
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209,328 |
The results showed that the sperm deformity index was significantly increased in the D and the D-Ex groups compared with the C group (P<0.001). Voluntary exercise significantly improved the sperm deformity index in the D-Ex group in comparison with the D group (P<0.001, Figure 1).
| 4 | 0biomedical
| 0Study
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65,952 |
The cDNA sequence of EgCaM had an open reading frame of 450 bp (GenBank: KR153481) encoding a protein of 149 amino acids with a theoretical molecular weight of 16.8 kDa (isoelectric point, pI = 4.09). The instability index was calculated as 33.43. No signal peptide or transmembrane regions were found in the deduced amino acid sequence. BLASTp showed that the amino acid sequence of EgCaM shared 84.9–100% identity with CaMs from E. multilocularis, Hymenolepis microstoma, Fasciola hepatica, Schistosoma japonicum, Caenorhabditis elegans, Toxocara canis, Plasmodium falciparum, Trypanosoma cruzi, Homo sapiens and Mus musculus (Fig. 1). Four Ca2+-binding domains were located at residues 21–32, 57–68, 94–106 and 130–142 in EgCaM. A phylogenetic tree showed the relationship of EgCaM with calmodulin from other parasites and hosts; EgCaM clustered with the calmodulins from E. multilocularis and H. microstoma, but not with the other calmodulins (Fig. 2).Fig. 1Multiple alignment of the deduced amino acid sequence of Echinococcus granulosus calmodulin with sequences of related proteins from other parasites and hosts. Echinococcus multilocularis (CDS37648.1), Hymenolepis microstoma (CDS28106.1), Fasciola hepatica (CAL91032.1), Schistosoma japonicum (AAW27335.1), Caenorhabditis elegans (NP_503386.1), Toxocara canis (KHN73369.1), Plasmodium falciparum (AAA29509.1), Trypanosoma cruzi (XP_808093.1), Homo sapiens (NP_001734.1), and Mus musculus (NP_033920.1) Fig. 2Phylogenetic tree of calmodulin. The tree was built using the neighbor-joining method in MEGA v. 5. The bootstrap values are shown at the branching points (1000 replications)
| 5 | 0biomedical
| 0Study
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292,452 |
Similar to ST-1901, penA-2 and 10 of ST-7363 exhibited identical nucleotide sequence from nucleotide 1 to 293, followed by the mosaic region from nucleotide 294 to 390 bp downstream of the end of penA (region 2′, indicated by the red line in Fig. 3b and between red arrows in Additional file 5: Figure S6). This is most parsimoniously explained by a recombination event, although the source of this DNA segment is unknown (Fig. 4). Comparison of the length of the recombined regions between ST-1901 and ST-7363 indicated that penA-10 in ST-7363 was unlikely to be the origin of penA-10 in ST-1901, as the recombined fragment was shorter than that of ST-1901 (Fig. 4).
| 4 | 0biomedical
| 0Study
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183,352 |
Uncertainty about the exact mechanisms involved in SI-PGP limits advanced uses of this otherwise simple and robust polymerization method. The monomers excited by UV irradiation form radicals with enough energy to initiate free-radical polymerization. Wang et al. suggested that the self-initiation mechanism occurs via excitation of monomers with sufficient energy to abstract hydrogen from an organic substrate and to initiate the grafting.28 However, this does not exclude the possibility of the formation of radicals on the already existing polymer chains. Wang et al. also observed an initial acceleration in the grafting rate (or, to be accurate, of the grafting conversion) with time, suggesting that this depended on the grafting of either monomers or chains onto already grafted chains and that this was facilitated by the high solubility of chains and/or monomers with each other.28 Since this is an uncontrolled polymerization reaction where polymerization proceeds in the bulk, and where monomers, oligomers, or polymers are grafted, while possibly also cross-linking and branching of grafted chains occur, the resulting polymer is expected to be heterogeneous. However, our results are consistent with a model where the grafting of solution-polymerized chains to the substrate surface is a dominating process and has some similarities to the grafting-through process63 (see further comments below). Grafting to existing chains cannot be excluded, but the extent of this is not possible to estimate from our data.
| 4 | 0biomedical
| 0Study
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131,911 |
This paper uses Python to obtain the task completion rate and on-time rate information and to return it to the user. According to the task data and the design requirements of the model, the task completion rate and return information are calculated as a whole, and then, the job functions in the system are classified and sorted to finally obtain initial calibration data.
| 1 | 2other
| 1Other
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277,679 |
The other compounds indicated in Table 4 provide less effective inhibition and mainly lose the pan-inhibitor profile. TCMDC-143191 shows an interesting activity only towards TbPTR1 and assumes an orientation different from both the antifolate- and substrate-like ones, in which the pyrimidine nitrogen H-bonds Tyr174 and the ribose, the tricyclic system forms a hydrophobic interaction with Trp221 and the carbonyl contacts Cys168 (Figure S4a). Compound TCMDC-143459 behaves similarly, showing an effect only towards TbPTR1 and being able to profitably locate only in PDB ID 4CLO, where it H-binds to NADPH ribose and phosphates through the triazole and imidazole rings, and it forms a π–π sandwich with the cofactor and Phe97, and an additional π–π stacking with Trp204 through the terminal benzyl ring (Figure S4b). Compounds TCMDC-143518 and TCMDC-143386 present, on the contrary, better inhibition towards LmPTR1 than TbPTR1. TCMDC-143518 difficultly fits in both PTR1 binding sites and finds a suitable pose only in the Lm enzyme, in PDB IDs 2BFA and 1W0C. Here, the standard connections with the cofactor and Tyr194 are mainly lost, apart from the weak H-bonds that can be formed by acidic pyrimidine hydrogens. However, the pyrimidine still forms a π–π sandwich with the cofactor and Phe113, one of the two pyrimidine nitrogen becomes closer to Arg17, the protonated amine interacts with the cofactor and a possible contact is formed by the benzimidazole with Arg287 (Figure S4c). TCMDC-143386 assumes quite different poses according to the protonation state and to the X-ray structure of the protein. A particularly interesting pose of the compound is generated in LmPTR1 (PDB ID 2BFA) and shown in Figure S4d. H-bonds are formed by the cyclic amide with Arg17 and the cofactor phosphate, and by the aniline nitrogen with the cofactor nicotinamide. The π–π sandwich is maintained, and an additional H-bond is formed by the terminal hydroxyl with Tyr283. Hydrophobic contacts are formed with Tyr191, Leu229 and Val230.
| 4 | 0biomedical
| 0Study
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216,963 |
CD22 is a transmembrane glycoprotein that is widely expressed across malignant B-cell histologies . In contrast to Zevalin® and Bexxar®, the anti-CD22 90Y-epratuzumab tetraxetan can be administered without a loading dose of cold antibody. A phase I/II trial assessed 90Y-epratuzumab in patients with relapsing B lymphoma . Patients had imaging studies one week prior to treatment with 111In-epratuzumab. The trial enrolled patients in two cohorts: patients who had prior high-dose chemotherapy (Group 2) and patients who did not have a prior stem-cell transplantation (SCT) (Group 1) . Irrespective of tumor targeting and tumor size, antitumor responses were seen in both indolent and aggressive NHL. Similarly, antitumor responses have also been seen from using fractionated dosing of 90Y-epratuzumab with toxicities that were primarily hematological and dose dependent . The efficacy of fractionated 90Y-epratuzumab as consolidation therapy after rituximab-based therapy was investigated in elderly (age>60 years) patients presenting with stage I/II bulky or stage III/IV diffuse large B-cell lymphoma (DLBCL). The estimated 2-year event-free survival was 75%, and grade 3/4 thrombocytopenia and neutropenia were seen in 84% and 79% patients, respectively. One patient each developed myelodysplastic syndrome and acute myeloid leukemia post-RIT .
| 4 | 0biomedical
| 0Study
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196,791 |
Technical evaluation of the EOS System can be performed by following the proposed methodology and the data presented can be used for comparative purposes or baselining. The system performed well within acceptable performance criteria. There were differences in image‐quality specific results, depending on the imaging direction studied, but these results were anticipated from the system design. Results also showed that it was appropriate to adopt performance tolerance criteria of existing evaluation guidelines, even though an alternative test protocol was implemented. The proposed methodology requires set‐up time on the system and off‐line data processing which may not always be readily available. Therefore, it is recommended that subjective image‐quality tests tailored to the needs of each clinical site are performed as an adjunct to the proposed methodology, in order to establish local baselines for quick, periodic quality control of the system.
| 3 | 0biomedical
| 0Study
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178,771 |
For example, if a datum unit with a certain IDENTIFIER is parsed to indicate the left turn signal, then there is a high probability that the right turn signal is also with this IDENTIFIER. As another example, if we already parse that the left door related state is represented by 2 bytes and presented in certain manner, then it is much likely to that relevant state corresponding to the right door is also represented by 2 bytes and presented in the same manner.
| 1 | 2other
| 1Other
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329,089 |
The studies involving human participants were reviewed and approved by the Institutional Review Board of The First Affiliated Hospital of Sun Yat-sen University. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.
| 1 | 0biomedical
| 1Other
|
224,925 |
Alternate conformations generated with qFit-ligand paint a similar picture to that obtained from ER. The geometries of the three ligands are shown in Figs. 10 ▸(a)–10 ▸(c) and R factors are shown in Table 1 ▸. Two conformations each were found for the M and P ligands, but they are rather similar and could be considered to be a single conformation, confirming the low flexibility that they show in the ER. The summed occupancies of the M and P conformations from qFit-ligand are 0.92 and 0.93, respectively. Unrestrained occupancy refinement in phenix.refine, starting from the deposited crystal structure, gives occupancies of 0.80 for both ligands.
| 4 | 0biomedical
| 0Study
|
299,621 |
Kenaf fiber (KF) and particulate snail shell (PSS) were added to polypropylene (PP) matrix with the view of improving the mechanical properties for engineering application, the following conclusions were arrived at;the blend of 2 wt% PSS and 5, 10, 20, and 30 wt% KF ensued progressive enhancement of hardness, impact, compressive and flexural strength with 2 wt% PSS/30 wt% yielding 14.9, 46.4, 27.5, and 53.4% for each property respectively. For flexural strength, optimum improvement was attained when 2 wt% PSS was combined with 30 wt% KF. Meanwhile, tensile strength achieved an optimum improvement of 72.9% when 2 wt% PSS was combined with 20 wt% KF.presence of 4 wt.% PSS, 5, 10, 20, and 30 wt% KF engendered progressive enhancement of hardness, 4 wt% KF yielded 29.5 optimum improvements for impact strength while the same dosage yielded optimum enhancement of 36.9% over neat PP for compressive strength. Flexural strength was enhanced by admix of 5 and 10 wt% KF even as further addition of 20 and 30 wt% KF led to a depreciation in strength. Tensile strength showed progressive enhancement up to 20 wt% KF before a further decline.the blend of 10 wt% PSS and 5, 10, 20 and 30 wt% KF triggered enhancement of hardness, the same proportion spawned downward trend in impact, compressive, flexural, and tensile strength as proportion KF increased from 5 to 30%. Hence, intermix of 10 wt% PSS and kenaf fiber from 5 to 30 wt% are detrimental to properties of PP matrix.Taguchi optimization revealed an optimum mix proportion of 4 wt% PSS/10 wt% KF. Conclusively, particulate snail shell derived from African giant snail and kenaf bast fiber are good reinforcement in polypropylene in the development of a cost effective but stronger biocomposites which can find applications in automobile and aerospace application.developed composite in this study showed better performance than their counterpart reinforced with hydroxylapatite and chitosan which are mostly used in reinforcement of biopolymers.
| 4 | 0biomedical
| 0Study
|
126,543 |
Like other enveloped viruses, SARS-CoV-2 infection causes the display of newly synthesized fusogenic S protein on the host cell plasma membrane, which, as discussed later, allows ACE2-expressing neighboring cells to fuse into giant multi-nucleated cells (syncytia) [15, 16].
| 4 | 0biomedical
| 0Study
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17,668 |
Cells were plated at 2 × 105 cells per ml in a 24-well plate and treated as indicated in the figure legends. Cells were then trypsinized and plated at limiting dilution to form colonies and grown on for 10–14 days. Colonies were stained using 0.5% crystal violet (BDH Chemicals) in 50% methanol and counted. Each individual experiment contained three technical repeats and is normalized to untreated controls. Graphs shown are combined data from a minimum of three independent experiments and error bars show SE.
| 4 | 0biomedical
| 0Study
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128,588 |
All participants arrived at the laboratory at the Space Institute of Southern China 3 days before the experiment started. In these 3 days, participants received detailed information about the experimental aims, procedure, time schedule, and laboratory settings.
| 2 | 0biomedical
| 0Study
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126,539 |
Similarly to other viral fusion glycoproteins, including influenza hemagglutinin (HA) and parainfluenza fusion (F) proteins, the SARS-CoV-2 spike is a trimeric class-I fusion protein; each monomer is synthesized as a fusogenically inactive precursor of about 180 kDa containing an N-terminal signal peptide (SP) (Fig. 1B) that primes the nascent polyprotein for import into the endoplasmic reticulum (ER), where the protein is extensively modified with N-linked glycans (each protomer comprises 22 N-linked glycosylation sequons) [10, 11]. The spike protein assembles into an inactive homotrimer, which is endoproteolytically cleaved by cellular proteases giving rise to a metastable complex of two functional subunits: S1 (bulb) containing the receptor-binding domain (RBD) responsible for recognition and attachment to the host hACE2 receptor, and the membrane-anchored S2 (stalk) that contains the fusion machinery (Fig. 1B). S2 harbors the fusion peptide (FP), a short segment of 15–20 conserved mainly hydrophobic amino acids, which anchors to target membranes and plays an essential role in mediating membrane fusion by disrupting and connecting lipid bilayers of host cells. The FP is followed by two heptapeptide repeat sequences HR1 and HR2, the transmembrane anchor domain (TM), and a short cytoplasmic tail (CT) (Fig. 1B) .
| 5 | 0biomedical
| 0Study
|
297,147 |
Although our review identified relevant articles systematically, it was difficult to draw conclusive inferences due to variability in study designs and assessment tools. There were numerous limitations related to the studies, including minimal detail of sampling strategies, allocation concealment, blinding of participants and assessors, small sample sizes, and lack of clarity on study and analytic methods. Therefore, it was difficult to evaluate the validity and rigour of the findings. Furthermore, due to the nature of the methodology of surveys, audits and case reports, no comparators were included; thus rendering their data as inconclusive. In addition, the discrepancy in the different sample sizes reported from the same RCT could not be resolved despite attempts in contacting the authors. Consequently, we believe that the evidence published at different time points represent findings from preparatory work that includes single feasibility (Edwards et al., 2005a) and pilot (Edwards et al., 2005b) testing stages, as well as data from the later full RCT (Edwards et al., 2009).
| 4 | 0biomedical
| 2Review
|
296,116 |
The analysis of NucS enzymatic activity initially showed that NucS was a structure-specific endonuclease able to cut ssDNA/dsDNA junctions on branched substrates (flapped and sprayed DNAs) in archaeal P. abyssi . However, further characterization in Actinobacteria (C. glutamicum) and Archaea (P. furiosus and T. kodakaerensis) revealed that NucS acts as an endonuclease able to recognize and cut a mismatched DNA substrate .
| 4 | 0biomedical
| 0Study
|
5,451 |
Abbreviation: HR hazard ratio, CIs confidence intervals, BMI body mass index, pTNM pathologic tumor–node–metastasis, ALP alkaline phosphatase, LDH lactate dehydrogenase, CRE, serum creatinine, UA, uric acid, LDH lactate dehydrogenase, NLR neutrophil count to lymphocyte count, PLR platelet count to lymphocyte count, CRP/Alb the serum CRP level to the serum Alb level
| 3 | 0biomedical
| 1Other
|
158,996 |
Excessive emotional resonance with others and arising difficulties with self-other distinction could have a broader effect on conscious experience of cognitive mental states including judgments about the origin of these. Difficulty knowing whether a thought or intention arose from the self explains many symptoms of psychosis [e.g., (155)] including delusions relating to thought transfer and telepathy. Incorrect assumptions that one is aware of the cognitive mental state of another could also reduce mentalizing leading to egocentric errors (289). Projection of negative emotions or intentions onto others, as seen in disorders such as BPD and schizophrenia (including on social cognitive tasks: Table 2), is likely to prompt social anxiety and paranoia. If a projected thought is positive, it could encourage grandiosity. Doubts about whether thoughts are internally generated may also underlie magical thinking as seen in Obsessive-compulsive Disorder (OCD), explaining the association between negative sense of agency and likelihood thought action fusion (287) i.e., the belief that thinking about events makes those events more likely to happen.
| 4 | 0biomedical
| 0Study
|
318,920 |
One particularly important strategy used by viruses is to enter the PNS and travel in a retrograde manner in the axons to the CNS. The PNS consists of nerve fibers and ganglia that connect the CNS to peripheral tissues, which are protected from infection by peripheral innate and adaptive immune cells . Another critical point of viral entry is through sensory and motor neurons that extend beyond the CNS barriers into the periphery. The differential expression of viral receptors on either sensory or motor neurons can dictate the type of peripheral nerve ending that a particular neurotropic virus will target. Poliovirus, adenoviruses and rabies virus bind to neurons at the neuromuscular junction owing to the neuronal expression of specific receptors. In this context, oxidative stress seems to be implicated in neuromuscular junction impairment, with mitochondrial dysfunction and inflammation being prominent features; related to this, melatonin has been reported to reverse age-related neuromuscular transmission dysfunction and improve muscle physiology .
| 5 | 0biomedical
| 0Study
|
389,154 |
Like IL-1R, IL-18R contains a Toll/IL-1 receptor (TIR) domain in the intracellular region that is shared with TLRs, and signaling into the cell is mediated by myeloid differentiation factor 88 (MyD88) (33–35). MyD88 is a well-known adaptor molecule for TLRs and IL-1R. The activation of IL-18R results in the recruitment of MyD88 to the TIR and anchors IL-1 receptor-associated kinase (IRAK) (36). Phosphorylated IRAK dissociates from the complex and binds to tumor necrosis factor receptor-associated factor 6 (TRAF6), which in turn phosphorylates nuclear factor kappa B (NF-κB)-induced kinase (NIK) (37). This results in the activation of I kappa B (IκB) kinase (IKK). The phosphorylation of IκB by IKK leads to the ubiquitination and degradation of IκB (38). NF-κB is then able to migrate into the nucleus and initiate the transcription of target genes such as IFN-γ (39).
| 5 | 0biomedical
| 0Study
|
69,298 |
Wild-type cryptogein was purified from P. cryptogea culture according to the method of Ricci (1989) and prepared in distilled water (stock solution 0.5mg ml−1). Recombinant wild-type cryptogein (Cry X24) and its variants (Cry V84F, Cry L41F, and Cry V84F/L41F) were expressed using the vector pPIC9 with the inserted cryptogein gene (wild type or mutated forms) from P. cryptogea with an additional N-terminal glycine residue to improve the processing ability of the KEX2 protease (α-secretion factor cleavage). The constructed vectors were expressed into Pichia pastoris strain GS115. Screening for optimal protein production was performed and the most suitable strain was cultivated in a Biostat B-DCU bioreactor (Sartorius) using a previously described protocol (Wood and Komives, 1999). After cultivation, the expressed protein was concentrated by ultrafiltration (cut off 3kDa) and purified by fast protein liquid chromatography using a Source S15 ion-exchange column (GE Healthcare). Molecular weights of isolated proteins were confirmed by MALDI-MS spectroscopy (Supplementary Fig. S1 at JXB online). Proteins were quantified by Bradford assay and conserved in distilled water (stock solution 0.5mg ml−1).
| 4 | 0biomedical
| 0Study
|
324,734 |
To identify the DEGs of the two different genotypes under alkaline stress, the expression patterns of DEGs were analysed by comparing 6-h and 24-h libraries with the control library for Alamo and AM-314/MS-155. A total of 10,219 DEGs with up- or downregulated expression between samples (fold change ≥2 and false discovery rate (FDR) < 0.01) at any pair of alkaline salt-treated points were identified (Additional file 6: Table S5). In the early stage of alkaline salt stress (0–6 h), 4483 genes (58.02% of the DEGs) were upregulated in AM-314/MS-155, and 867 genes (61.36% of the DEGs) were upregulated in Alamo (Table 1). In the late stage of alkaline salt stress (24 h), 2942 genes (56.17% of the DEGs) were upregulated in AM-314/MS-155, while Alamo had 2732 upregulated genes (61.61% of the DEGs). The proportion of upregulated genes in the tolerant genotype (Alamo) was higher than that in the sensitive genotype (AM-314/MS-155) in both the early and late stages of stress. In addition, the DEGs of AM-314/MS-155 were mainly concentrated in the early stage, while Alamo showed greater advantages in the late stage. Table 1Comparison of DEGs between two genotypes at different time pointsItemsAM-314/MS-155 (sensitive)Alamo (tolerant)0 h vs 6 h0 h vs 24 h6 h vs 24 h0 h vs 6 h0 h vs 24 h6 h vs 24 hTotal77,57883,25534,65878,34977,79933,172DEGs772752381150141344341255Up-regulated448329423618672732675Down-regulated324422967895461702580
| 4 | 0biomedical
| 0Study
|
47,868 |
The interaction between individual and organizational prevention enhanced the amount of explained variance in procedural justice perceptions by 3%, F(1, 293)= 11.51, p < 0.001. Again, we have analyzed the moderation using the J-N procedure (Johnson and Fay, 1950). The results of the analysis are depicted in Figure 2. It demonstrates the strength of the relationship between the prevention of the organization's climate and procedural justice perceptions depending on the employee's prevention level. The J-N point (marked with a vertical red line) is at 3.36 points of the employee's prevention. The results indicate that, in line with Hypothesis 2, only for employees who have scored relatively high on prevention focus (above 3.36 on a 1–5 scale), there is a positive link between the organization's prevention and its justice perceptions. Meanwhile, for people who scored lower, the relation ceases to exist.
| 2 | 2other
| 0Study
|
335,132 |
On the other hand, the conductivity of the CSPPSU-vinylon electrolyte membrane increased with increases in the temperature and humidity. The conductivity of the CSPPSU-vinylon membrane was higher than that of the CSPPSU membrane. In particular, the CSPPSU-10vinylon membrane had a higher conductivity than the other membranes. The diffusion of protons in the electrolyte membrane depended on the concentration and proton mobility of the sulfonic acid groups (-SO3H) in the electrolyte membrane, and became faster as the temperature and humidity were increased. In addition, the nanostructure (conduction path) of the electrolyte membrane was greatly affected. The homogeneity of the CSPPSU-10vinylon membrane was better than that of the other membranes (Figure 4). As shown in Table 5, changes in the IEC values of the CSPPSU-vinylon membrane due to the difference in the amount of PVA added, was small and slightly higher than those of the CSPPSU membrane. However, the water content and the number of water molecules per sulfonic acid group (λ) of the CSPPSU-10vinylon membrane, were higher than those of the other crosslinked membranes. These differences contributed to the high proton conductivity of the CSPPSU-10vinylon membrane. The degree of crosslinking of the CSPPSU-vinylon membrane was 42%–45%. It is possible that the hydroxy groups (-OH) of vinylon in the CSPPSU-vinylon membrane contributed to the proton transfer. From the above, it is clear that the conduction mechanism of the SPPSU-vinylon composite membrane is very complicated.
| 4 | 0biomedical
| 0Study
|
313,349 |
The average age of the patients was 22 years. Patients did not differ regarding demographic or surgical factors, such as the eventual extraction difficulties, dental position, or quantity of anesthetic used (Table 1). RT-PCR showed no difference in COX-1 expression in the placebo group from T0 to T30; however, in the groups treated with ibuprofen (p=0.004) and etoricoxib (p=0.010) showed a significant increase in the COX-1 expression from the first (T0) to the second moment (T30) (Fig. 1A). The increase in the COX-1 expression was significantly greater in the groups treated with ibuprofen (0.9±0.3) and etoricoxib (1.1±0.2) than in the placebo group (0.1±0.2) (p=0.020).
| 4 | 0biomedical
| 0Study
|
226,628 |
The higher values of RCP%, obtained with the fully automated method compared to our previous one, were confirmed with both radio-TLC and Radio-UV-HPLC CQs. The developed Radio-UV-HPLC led us to verify exactly the presence of free Ga-68 (1.450 min) and the radiopharmaceutical product (6.955 min), but also to detect other radioactive impurities at 5.647 and 11.517 min (Figure 3). We have integrated both these peaks and they did not affect the RCP% of the product that resulted more than 95% in all the three validation batches (97.05%, 95.75%, and 96.15%). Therefore, being that the impurity peak areas were very low, we considered it unnecessary and not essential to isolate and characterize them. The higher RCP% of the radiopharmaceutical was also confirmed with Radio-TLC method (Figure 5) that is able to detect Ga-68 colloids at Rf < 0.2 and [68Ga]Ga-NODAGA-exendin-4 at Rf > 0.4 (Supplementary Figure S1).
| 4 | 0biomedical
| 0Study
|
231,535 |
Returning to the birthday problem analogy, considering the number of isolate pairs (equivalent to people with the same birthday) obtained from the original genome dataset can provide clues about the extent of lineage diversity in the natural population. Using total NC rates, we were able to assess the nature of coalescence across the sample time frame for each species. The coalescence we refer to here is equivalent to the number of ancestral strains at a particular time point (effective lineages) in the natural environment from which contemporary strains emerged. Effective population size (Ne) is commonly used to reflect the number of individuals in a population that contribute to subsequent generations . This has been used to investigate bacteria but contrasting approaches can provide different estimates depending on the method used [53, 60]. The idea of effective lineages, described in this study, is related to Ne but is more specific for organisms that reproduce clonally. Rather than typical Ne estimates for sexual populations, where the mating of two individuals is largely independent of what happened in previous generations, the number of effective lineages in a bacterial population reflects the number of distinct lineages that will survive and therefore contribute to future generations. This provides information on the genetic inertia of the population, i.e. the limitations for future evolutionary pathways based on the number of successful ancestors at a particular point in time.
| 4 | 0biomedical
| 0Study
|
376,805 |
To be assigned a classification, athletes are observed during one or more games by classifiers, who are trained to recognize the unique features of a functional class in athletes’ play. The functional potential of a team consists of the sum of classification points of the five players on the court, and at any given time in a game, this sum of points must not exceed 14.0. In this way the functional potential of teams is equalized and the result of competition is directly related to performance and not to disability.
| 1 | 2other
| 1Other
|
102,993 |
A hallmark of this curricular design was the formation of an inter-institutional, interdisciplinary faculty learning community (FLC) who, through a backwards design process, worked together to delineate the desired student learning outcomes and core curriculum for the Research Methods course as well as the second-semester RCN courses (Table 3). Although common learning outcomes were mutually agreed upon, each institution had the flexibility to instill their mark in the courses based on the institutional context. For example, at UDM, faculty decided that separate research methods courses, dedicated to each discipline-based RCN course would be most beneficial. Marygrove College and Wayne State University created a universal Research Methods course that was open to ReBUILDetroit Scholars as well as other freshman STEM majors interested in advanced degrees in biomedical sciences.Table 3ReBUILDetroit Interdisciplinary Research Methods Common Course Student Learning Outcomes1.Identify unsafe research practices2. Describe the ethical responsibilities of scientific researchers3. Identify and articulate a scientific question that has impact and relevance to society 4. Apply the scientific method in various sub-disciplines to posed challenges5. Describe methods to collect, compare, contrast, analyze and interpret different types of data6. Communicate effectively in a variety of written and oral formats7. Use databases to search and access the scientific literature8. Work collaboratively with peers and develop a personal sense of accountability when working with teams9. Explain the role of the IRB in research oversight
| 4 | 0biomedical
| 1Other
|
146,015 |
Following the LPA, the subgroups were compared regarding the discrete behaviors identified through the micro-analytic coding system. The moderate to large effect size results revealed that positive discrete behaviors (praise, instructions, question, and social attention) were more frequent in the higher quality subgroup, whereas negative discrete behaviors (aversive vague instructions and performs side-by-side with the child) were more frequent in the lower quality subgroup. None of the children’s behaviors were different between subgroups, which is a somewhat different finding from that of other studies, in which negative parental behavior may lead to more externalizing problems in children . Although child misbehaviors are a common topic of study in the area of child maltreatment, often these behaviors are more related to a parent’s perceptions and, indeed, do not represent their child’s behaviors displayed in the interaction . Nevertheless, the lack of differences in the children’s behaviors between the subgroups can also be a consequence of the type of activity and method chosen, in which the nature of the observational structured activity does not allow for the variability of the child’s behavior over the interaction .
| 4 | 0biomedical
| 0Study
|
75,413 |
PIK3CA mRNA expression increased from primary tumors to their corresponding metastasis (p = 0.031; Fig. 4a), also seen as a tendency of increased PI3K signature score (although only borderline significant p = 0.055; Fig. 4c). Previously, PIK3CA mRNA expression has been found to increase from normal control tissue to endometrial cancer tissues and from endometrioid to non-endometrioid histologic type47. Interestingly, in our study PIK3CA mutations seemed most likely to affect PIK3CA expression negatively (Fig. 4b and Supplementary Fig. S3a). We also found that high PIK3CA mRNA expression associated with poor prognosis and showed increased expression in metastases, suggesting independence of PIK3CA mutation status.
| 4 | 0biomedical
| 0Study
|
224,526 |
We used the discriminant analysis (DA) algorithms sparse Partial Least Square (sPLS-DA) and Orthogonal Partial Least Square (OPLS-DA) for supervised sample separation. Multivariate analysis started by analyzing the entire feature dataset (6111 retained features) as a function of pregnancy at the gestational endpoints D40, D62 and Birth. Subsequently, sample separation was explored by combinations of breed and/or embryonic stages, or their combinations with culture condition and cryopreservation. The effect of each single bull as a random factor was also analyzed.
| 4 | 0biomedical
| 0Study
|
317,765 |
Articular involvement is the initial symptom in one-third of patients and attacks can be precipitated by mild traumas, physical and emotional stress, exposure to cold, fat-rich meals, and infections. Patients with recurrent arthritis carry three-times higher risk for amyloidosis as compared to patients without articular involvement. Generally, attacks tend to decrease with aging.24 The attacks, that are often associated with increased levels of erythrocyte sedimentation rate, C-reactive protein, fibrinogen, and leukocytes, usually last for 1 to 3 days and resolve spontaneously; however, they may remain up to 1 month or rarely longer, and the interval between attacks is clinically relatively symptom-free.30–31 Colchicine is very efficacious in preventing FMF attacks and associated amyloidosis. Symptoms during attacks may be alleviated by non-steroidal anti-inflammatory drugs (NSAIDs), whereas usual dose of colchicine administration should be continued. Glucocorticoids may decrease the duration of attacks, but may also increase their frequency. Alternative biological treatments should be considered in cases that are resistant to, or intolerant of, colchicine.24,32 Certainly, the most significant goals should be to achieve appropriate treatment in order to prevent subclinical inflammation and the development of ‘silent’ amyloidosis, eventually to improve quality of life (QoL) in FMF as in other chronic diseases.
| 4 | 0biomedical
| 2Review
|
19,968 |
The task was filmed and the numbers of treats eaten by the child and shared with his or her older sibling were counted. Treats shared with or by the parent were not counted; when a child took treats back from the older sibling, these were subtracted from the total number of shared treats. Two groups of 15 undergraduate students in total (six at the 3-year wave and nine at the 4-year wave) rated the 964 videos (two home visits at two waves for 241 families) on sharing. After being trained on a set of 16 videos, each student in each group completed a reliability set (n = 30) with 50 % overlap between the two sets (coders who rated the 4-year wave completed a reliability set including 15 videos of that particular wave and 15 videos that were also in the reliability set of the coders who rated the 3-year wave). Interobserver reliability based on the reliability set was adequate; the intraclass correlations (single rater, absolute agreement) between all pairs of coders were equal to or above .70. Children’s sharing during the father and the mother home visit were coded by different coders to guarantee independency among ratings. No coder rated a child twice either within or across waves. In addition, sharing was rated by a group of coders who did not code parental emotion talk of either parent in either wave.
| 4 | 0biomedical
| 0Study
|
388,403 |
Following appropriate institutional board review approval, all patients who underwent an open reduction and internal fixation (ORIF) for a proximal fifth metatarsal fracture at our institution between November 2013 and November 2016 were reviewed. Patients were excluded if they had history of prior proximal fifth metatarsal fracture surgery or injury to the fifth metatarsal, Charcot arthropathy, or any midfoot/forefoot conditions that disrupted the normative anatomy of the fifth metatarsal in relation to the rest of the foot. All patients underwent operative fixation using fully threaded cannulated screws. A query of our institutional data warehouse yielded 24 patients who met inclusion criteria. Twenty-three patients were included in the study following one exclusion due to concurrent bilateral procedures. All included patient records were qualitatively reviewed to confirm diagnosis of a fracture of the proximal fifth metatarsal of zones 2 or 3. There were 21 zone 2 fractures and two zone 3 fractures in our cohort. Twenty-one patients had baseline PROMIS Physical Function data and 20 have baseline PROMIS Pain Interference data; 18 had postoperative follow-up PROMIS data.
| 4 | 0biomedical
| 0Study
|
233,072 |
We constructed an optogenetic differentiation system consisting of a blue light-inducible Cre recombinase under the control of a constitutively expressed optogenetic transcription factor, EL222 (refs. 39,40). In order to test the functionality of the system, we designed a recombination cassette composed of a floxed coding sequence (CDS), coding for a fluorescent reporter (mCerulean) that is transcribed constitutively via a pTDH3 promoter upstream of the first LoxP site. Another CDS, coding for a different fluorescent reporter (mNeonGreen), was added downstream of the second LoxP site (Fig. 1a, top and Supplementary Fig. 7).Fig. 1Design and functional characterization of the differentiation system in liquid and 2D cultures.a Design and experimental setup. Cells constitutively express EL222 optogenetic transcription factor. Blue light triggers expression of Cre and recombination, and a change in fluorescence from mCerulean to mNeonGreen. Cells carrying the differentiation system were cultured to exponential phase in batch and induced via LEDs. Cytometry measurements were made by sampling at regular intervals. b Quantification of differentiation. Cells are classified as differentiated if cellular mNeonGreen fluorescence exceeds 200 arb. units (red line). The plot shows the evolution of population mNeonGreen fluorescence as a function of time. The threshold was set such that only cells that have expressed detectable amounts of mNeonGreen are classified as differentiated. c Efficiency and background differentiation. Twenty colonies were picked and cultured in batch for 72 h in dark or induced at t = 0 for 4 h. Measurements were taken at t = 0, t = 24 h and t = 72 h. Bars represent means from a single experiment. Error bars signify standard deviation. Individual data points from colonies are depicted in a scatter plot overlaid on the bar plot (blue and grey insets). Increase in differentiated fraction was not significant (n.s.) after 24 h (p = 0.41) but became significant at 72 h (p = 5.3e−08; two-sided paired t-test) (black horizontal lines). d Snapshots of cell growth and differentiation under the microscope. Images during induction from a representative field of view. Cellular fluorescence changes from mCerulean (cyan) to mNeonGreen (yellow) (Supplementary Movie 1). e Differentiation dynamics under the microscope. Images were segmented and analysed. To be deemed differentiated, median cellular fluorescence had to exceed 300 arb. units mNeonGreen fluorescence. Circles represent mean differentiated fraction over eight fields of view from two independent experiments. Shaded region shows standard error of mean. The total number of cells at t = 0 summed over all fields of view are given by n (n = 817). f Imprinting patterns in the population. Cells were allowed to form a monolayer inside a µIbidi slide. A user-defined pattern was illuminated over the monolayer using a digital mirror device (DMD). Merge consists of mCerulean fluorescence (cyan), mNeonGreen fluorescence (yellow), and the pattern (magenta).
| 4 | 0biomedical
| 0Study
|
131,771 |
We used two datasets (DFKZ 2018 and GSE70770), as described in the “Data preparation” section, to validate the RS model. We transformed the data into the TPM format to ensure consistency with the training dataset. We applied the RS model to the validation datasets and divided them into two groups according to their respective medians. We then performed corresponding survival and ROC analyses for comparison with the results of the training cohort.
| 4 | 0biomedical
| 0Study
|
238,693 |
A primary function of the UPR is to promote adaptive remodeling of ER proteostasis pathways to mitigate ER stress and restore ER proteostasis. This is primarily achieved through the adaptive remodeling of ER quality control pathways involved in protein folding, trafficking, and degradation by the UPR-associated transcription factors XBP1s and ATF6 (Fig. 2). These transcription factors induce overlapping, but distinct, sets of ER proteostasis genes, indicating that they can differentially influence ER quality control and overall ER function (Shoulders et al., 2013). Consistent with this, genetic activation of XBP1s or ATF6 differentially impacts ER quality control of destabilized, aggregation-prone proteins. For example, selective ATF6 activation preferentially reduces secretion of destabilized, aggregation-prone variants of TTR, LC, and α-1-antitrypsin, without significantly impacting secretion of more stable, non–aggregation-prone variants of the same proteins (Smith et al., 2011; Chen et al., 2014; Cooley et al., 2014). In contrast, XBP1s overexpression reduces secretion of amyloidogenic Aβ through increased targeting of destabilized amyloid precursor protein (APP) variants to ER degradation pathways (Kaneko et al., 2010). These ATF6- and XBP1s-dependent alterations in the secretion of destabilized, aggregation-prone protein are likely attributed to the remodeling of ER quality control pathways afforded by these transcription factors. For example, ATF6-dependent reductions in amyloidogenic LC secretion correspond to increased interactions with ATF6-regulated ER chaperones (Plate et al., 2019). Alternatively, XBP1s-dependent expression of ERAD factors such as HRD1 is associated with increased APP degradation that limits secretion of amyloidogenic Aβ (Kaneko et al., 2010).
| 4 | 0biomedical
| 0Study
|
373,983 |
Moreover, analyses revealed only insignificant changes in bacterial sputum composition when assessing alpha and beta diversity with no changes of Shannon diversity and bacterial richness after initiation of prophylaxis. This is important to note, as pneumonia and respiratory infections are common among patients with liver cirrhosis, especially with ACLF [1, 2]. Thus, future studies may focus on gut/stool microbiome analysis when assessing the impact of long-term quinolone prophylaxis in these patients. Here, a special focus should also include the prevalence of resistance mechanisms in quinolone prophylaxis up to the complete resistome analyses using e.g. long read sequencing.
| 4 | 0biomedical
| 0Study
|
91,404 |
Risk factors associated with infection due to resistant pathogens (vs. susceptible pathogens) have been identified in the literature [31, 32]. Information regarding a portion of these risk factors for cIAI was available for patients in the PACTS dataset, including (a) nosocomial infection, (b) age ≥ 65 years, and (c) ICU stay.
| 4 | 0biomedical
| 0Study
|
331,555 |
It makes intuitive sense that there exists a means by which the innate immune system directs its resources to the most likely source of infection upon detecting microbial components that are presented as an acute threat. We propose this organ-specific microbial recognition reflects a more sophisticated level of immunological education than the non-specific training that initially occurs in the bone marrow. It is reminiscent of a similar phenomenon observed in invertebrates, which lack adaptive immunity, yet show a stronger immune response to bacterial strains previously encountered compared to strains to which they are naïve27. It was previously demonstrated that a Klebsiella-based immunotherapy was effective in reducing lung cancer burden in Rag2 deficient mice that are largely devoid of classical adaptive immune function8. The contribution of adaptive immunity to the observed microbial mediated organ-specificity cannot be ruled out; however, we believe it is unlikely the primary driver of this organ specific memory and recruitment. Cells not conventionally considered to be part of the immune system, such as epithelial and endothelial cells that function as the interface between the host and its microbiota, are also capable of forming long-term memories. Acute inflammation was elegantly shown to functionally change epithelial stem cells to respond to such subsequent assaults with improved barrier restoration31. On the other hand, barrier dysfunction can also develop through reprogramming of epithelial cells in response to allergic inflammation32. This epithelial inflammatory memory, similar to innate immune training5, is mediated at the level of epigenetic programming31. In our study, the presence of pathology in the targeted tissue further potentiated this organ specific immune response to the microbial stimulus, and the nature of the pathology dictated the effector functions executed by the recruited primed innate immune cells.
| 4 | 0biomedical
| 0Study
|
47,581 |
The method proposed in this paper is closely related to [12, 13] in the sense that in all three cases, based on a validation data set, the ensemble combines directly the various models’ prediction outputs without entailing any training or interfering with the constituent models’ structure and background. This is particularly useful when wishing to combine models emerging from very different theories. Moreover, it ensures scalability of the method particularly when dealing with such large data. For instance, we tried to employ stacked BR as well to our problem but without any success due to scalability issues. Regarding these three methods ([12, 13] and ours), it should be noted that proposes an ensemble limited to combine only models with probabilistic outputs (i.e. outputs ranging between 0 and 1) and thus it is not appropriate for our case where models with diverse outputs need to be combined. Therefore, in the experiments presented in “Experiments” section our method is compared only to the one by along with a more simplistic version of MULE.
| 4 | 0biomedical
| 0Study
|
396,174 |
Despite health facilities and governments trying to ‘normalize’ HIV by the routinization of testing, diagnosis and treatment, through the ‘test and treat policy’ of patient-centred care, for ALHIV, the disease remains exceptional [64, 65]. Chiletso’s, Timve’s and Chifuno’s accounts illustrate SRH-related challenges including negative emotional outcomes such as regret and physical health outcomes—STIs and pregnancy [11, 66, 67]. We see the responsibility of institutions to meet adolescents’ needs. ALHIV become involved in casual sex to gain a sense of affection and belonging, and for some, as a means of survival. To avoid unwanted disclosure, they do not request or insist on protection during sex. This is in line with findings from a systematic review of being on ART in Africa, which indicated that competition for relationships, material and marital responsibilities lead adolescents to difficulties to access support . There is need to balance adolescents’ sexual interests and the rules defining sexual relationships to enable a negotiation space that allows for choices (delayed sex, less unsafe sex, contraception use, sexual knowledge) and informed consent.
| 4 | 0biomedical
| 0Study
|
77,732 |
The sample included home healthcare services in two municipalities (A and B) located in rural northern Norway. Municipality A has a total land area of 405.58 km2 (156.60 mile2), and Municipality B has a total land area of 698.22 km2 (269.58 mile2). Although the two municipalities have a similar number of inhabitants, the settlement patterns differ due to geography. In addition to rural and remote areas, Municipality A has four smaller centers, and Municipality B has one (Fig. 1). In 2012, Municipality A had a population of approximately 10,800, and Municipality B had a population of approximately 10,100. That year, 16% of residents in Municipality A and 13% of those in Municipality B were 67 years or older (retirement age in Norway). In both municipalities, home healthcare services are divided into five sectors. Municipality A has three smaller centers, including a sector office and a community center with two sector offices; in Municipality B, all sector offices are located at the community center. The smaller centers in Municipality A have a grocery store and a postal service. In Municipality B, citizens must travel to the municipal center to food shop in a grocery store. In both municipalities, home healthcare recipients live within a 30-min drive of the home care sector offices .Fig. 1Location of home care recipients, showing the number of individual decisions each recipient has
| 1 | 2other
| 0Study
|
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