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Hamsters infected with SARS-CoV-2 develop severe respiratory disease, and yet the changes in gene and protein expression following infection are poorly defined. To further interrogate host responses in the development of severe COVID-19-like disease, we characterized global changes in the expression of lung mRNA, protein, and phosphoproteins during the development of severe COVID-19-like disease in the hamster.
| 4 | 0biomedical
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118,417 |
This study was aimed at the discovery of novel industrially relevant strains that harbour saccharolytic enzymes to degrade cellulose and xylan have lactic acid as their main fermentation product and are genetically accessible. We describe the isolation of 94 facultative anaerobic Geobacillus strains that were capable of fermentation of both C6 and C5 sugars under micro-aerobic and anaerobic conditions. For isolate G. thermodenitrificans T12 direct conversion of beech wood xylan to lactic acid was demonstrated. The selection methods yielded several isolates that were capable of degrading xylan and cellulose. All strains described in this study were isolated from compost at both moderate and high temperature by repetitive growth on both CMC and xylan. It has been previously shown that Geobacillus was the dominant genus in “mature” compost [35–37]. However, it cannot be concluded if the ratio of Geobacillus species found in this study represents the composition of the Geobacillus community in the compost heap sampled, or results from selection by the sampling and isolation methods. In prior studies , compost heaps on the same site were sampled and screened for thermophilic organisms. The TMM media used in the study of Bosma et al. contained 0.9 g NaNO3 which led, at 65 °C, to the isolation of mainly G. thermodenitrificans strains. When both vitamins and metals were added, a larger diversity in Geobacillus species was found. In isolations done at 60 °C without nitrate in the medium approximately half the isolates belonged to Geobacillus but no G. thermodenitrificans isolates were found (E F Bosma, unpublished data). With the selection criteria used in this study, it was anticipated that geobacilli would be isolated. The overrepresentation of G. thermodenitrificans (79 % of isolates) in this isolation procedure, however, was surprising since nitrate was excluded from the isolation media to prevent this species benefiting over other species.
| 5 | 0biomedical
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207,082 |
After 2,000 steps of steepest descent energy minimization, the membrane patch was equilibrated first for 1 ns of MD simulation in an NVT ensemble with a 1-fs time step and then in an NPT ensemble (7.5 ns) with a 2-fs time step using a Berendsen thermostat and barostat (35). Three production simulations (one 1 µs and two 480 ns long) were run with a 2-fs time step at a temperature of 310 K and a pressure of 1 bar in an NPT ensemble using a Nosé-Hoover thermostat (36) and a semi-isotropic Parrinello-Rahman barostat (37) with a characteristic time of 5 ps and a compressibility of 4.5 × 10−5 bar−1.
| 4 | 0biomedical
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352,207 |
In this study, we extended our previous approach to examine how integrated information changes under different timescales by adding new parameter settings as the global parameter settings. By applying these metrics, we succeeded in classifying the different sizes of schools as qualitatively different autonomous systems (e.g., chasing, fission–fusion, leadership, and interactive). We also succeeded in defining these classifications based on the system’s group integrity while using minimal information partition (see Section 2.1), and related our class to the actual behaviours. This is a novel type of classification of collective animal behaviour. Finally, we discussed the heap paradox on collective behaviour, for which we showed that our IIT 3.0 analysis can provide two kinds of tentative answers.
| 4 | 0biomedical
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264,052 |
An insulinoma (INS) is a functioning NEN originating from the neuroendocrine islet cells or multipotent stem cells of the pancreas, that produces insulin independently of glucose level’s stimuli. Insulinomas are therefore responsible for the HH syndrome and, differently from CS that is usually associated with malignant NENs, are associated with a benign neoplasm with a 97% 5-year overall survival (OS) rate . Indeed, malignant INSs represent less than 10% of all INSs with an estimated incidence of 1–3 per million/year . The diagnosis can be challenging and is generally delayed up to 5 years in approximately 20% of patients due to the fact that symptoms are often misrecognized. In fact, despite the pathognomonic clinical presentation known as the “Whipple’s triad” ; due to its possible insidious symptoms often confused with other diseases, these patients are mistaken quite often as “mentally ill”. Once again, awareness and a prompt diagnosis represent the rate-limiting step of the whole therapeutic strategy in patients with F-NENs. Therefore, management by an experienced and dedicated multi-specialistic team is mandatory to offer patients the best therapeutic approach.
| 4 | 0biomedical
| 2Review
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83,132 |
In this work, we introduce a tool to predict protein–protein interactions from transcript sequences using sequence alignments and a reference Human interactome. This tool was then used to predict 11 different protein interactions networks from 11 S.mediterranea transcript datasets. As a result, we provide PlanNET, a web application that allows researchers to explore these networks in different ways, as well as to access to all sequence annotations performed in order to predict the interactions.
| 4 | 0biomedical
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103,197 |
Cannabinoids are molecules interacting with cannabinoid receptors, or with similar chemical structure to tetrahydrocannabinol, the major constituent of Cannabis sativa. Thus, cannabinoid agonists comprise molecules derived from the plant, synthetic molecules, with higher potency, and the endocannabinoids, present in living animals. Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are the major endocannabinoids, which along with their synthetic and degrading enzymes, and specific cannabinoid receptors constitute the endocannabinoid system (Di Marzo and De Petrocellis, 2012; Pertwee, 2012), which has a modulatory role with pleiotropic actions. Cannabinoid agonists have shown neuroprotective and anti-inflammatory effects of interest for the treatment of different neurodegenerative (Baker et al., 2000; Glass et al., 2000; Arévalo-Martín et al., 2008; Fernández-Ruiz et al., 2011) and mental disorders (Marsicano et al., 2002; de Bitencourt et al., 2013; Leweke et al., 2016). We (Ramírez et al., 2005; Martín-Moreno et al., 2012) and others (Wu et al., 2013; Aso and Ferrer, 2014; Cheng et al., 2014) have described beneficial effects relevant for AD treatment. Indeed, cannabinoid agonists rescue the cognitive impairment in AD animal models, affording neuroprotection by decreasing neuroinflammation and Aβ levels. On the other hand, cannabinoid agonists are hypotensive agents. Their cardiovascular actions are complex (Randall et al., 2004; López-Miranda et al., 2008). They cause vasorelaxation of isolated vessels in vitro, and in vivo they induce multiphasic responses that lead to sustained hypotension. For instance, anandamide, the endocannabinoid, caused a triphasic response in anaesthesized rats: first, there is a hypotensive response, vagally mediated, followed by a pressor response and by a sustained hypotension (Varga et al., 1996). Moreover, WIN 55,212-2 and HU-210 in conscious rats induced pressor, and renal and mesenteric vasoconstrictor effects, but hindquarters vasodilator actions (Gardiner et al., 2001). Although in some instances the classical cannabinoid receptors, the well characterized CB1 and CB2 receptors, are involved in such responses, in other occasions different receptors are activated, the release of endothelial mediators may be implicated, or even direct effects on transduction mechanisms have been invoked.
| 4 | 0biomedical
| 2Review
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139,219 |
For Group 2, the 120 stimuli were assigned to 6 different sets of 20 stimuli (A-F), with 8 stimuli in set G. Each task, except auditory object naming, presented 2 different stimulus sets. In Experiment 1, the first task presented two novel sets (A and C), and the second to fifth presented one novel set (not presented in a previous task) and one repeated set (E and A, B and C, F and E, and D and F for tasks 2–5). In Experiment 2, visual object naming presented sets D and F. The pictures in set D were novel but their names had been presented during auditory semantic matching in Experiment 1. The pictures in set F were not novel as they had previously been presented for sentence production. For auditory object naming, participants were presented with 8 new stimuli from set G and 12 stimuli that had previously been seen or heard in Sets A to E.
| 4 | 0biomedical
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35,711 |
Index values of physical performance were determined as those of the timed-up-and-go (TUG) test, one-leg standing time (OLST), and maximum gait speed (MGS). All values were collected by trained investigators based on standard procedures. The TUG test of static and dynamic balance uses the time that a person takes to rise from a chair, walk 3 m, turn around, walk back to the chair, and sit down. The TUG test is used frequently in the elderly population . The time (sec) to complete the TUG was recorded based on the average of two separate trials .
| 4 | 0biomedical
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193,830 |
A: stress at the transition point; B: strain at the transition point; C: elastic modulus; D: maximum tensile strength; and E: maximum stress. The asterisks indicate P<0.05. If the plots are connected by a line, they are stifle joints of the same dog. The stress at the transition point is significantly lower in the GC group than in the control group. GC, glucocorticoid.
| 3 | 0biomedical
| 0Study
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370,978 |
The importance of landscape perception and public participation is thus only fostered in European-level policy, whilst a broader range of objectives on health and wellbeing and the importance of life on land are recognized in the 2030 Sustainable Development Agenda, specifically through sustainable development goals 3 and 15 . Even though scientific literature has identified the strong links between landscape and health , the importance of landscape regarding community health and community building seems to have been disregarded in international recommendations and sustainability agendas, which explains the focus on the ELC as the main reference for this research. Understanding that not all communities are cohesive and not all individuals have the same levels of awareness towards their landscapes, the ELC promotes a new culture of participatory and collaborative landscape analysis, management, and design, focusing on ordinary landscapes as opposed to previous concerns over highly valued or protected landscapes.
| 2 | 2other
| 1Other
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320,877 |
Notably, clustering of nuclear INsfGFP puncta reached a near completion by ~36 hpi, as indicated by the plateau in the kinetic curve (Figure 5B), whereas the EdU signal that was associated with these IN complexes continuously increased over time (Figure 5D). This signal, as expected, was significantly increased by Vpx treatment and abrogated by NVP treatment (Figure 5D). Thus, consistent with the recent findings , vDNA synthesis can continue beyond HIV-1 nuclear import and VRC clustering. The kinetics of infection (onset of Gag-expression) closely followed that of vDNA synthesis and reached ~20% and ~80% by day 4 in untreated and Vpx(+) MDMs, respectively (Figure 5A,D,E). These results collectively suggest that the robust infection of SAMHD1-depleted MDMs is likely due to a more efficient vDNA synthesis in the nucleus.
| 4 | 0biomedical
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109,967 |
Although only three FA cell lines (fancc, fancl, and fanci) were sensitive to metformin, they were also highly sensitive to CDDP. Collectively, these results suggest that although metformin induces DNA damage that is repaired by the FA pathway, this DNA damage may not be canonical ICLs such as those induced by CDDP. Alternatively, the efficacy of ICL introduction by metformin under glucose-depleted conditions was less than that by CDDP, obviating the apparent need for some FA factors.
| 4 | 0biomedical
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241,203 |
Barret corroborates this idea and states that our brain acts as a completely integrated network that contributes to the interpretation and elaboration of different mental states, considering the idea that most neurons are multipurpose, that is, there is no region of the brain related to a single emotion. According to the author, emotions arise from the firing of neurons, but no neuron is dedicated exclusively to emotion. This idea reinforces the importance of a balanced interoception to contribute to the construction of balanced emotional responses .
| 4 | 0biomedical
| 1Other
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200,577 |
We noticed that the VD11-4-2 influence on cell migration was dependent on the initial EGF concentration (Figure 7C). VD11-4-2 reduced cell velocity by almost 2 µm/h (p < 0.05) when the starting EGF concentration was from 0 to 50 ng/mL but had no significant effect when the starting EGF concentration was between 50 and 100 ng/mL. No changes in the speed of control group cells under different EGF concentrations were observed.
| 4 | 0biomedical
| 0Study
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381,614 |
Figure 13a–c shows that κ1 and κ2 of the gas–oil interface have opposite signs, resulting in a very negative Gaussian curvature between gas and oil during GI. This indicates that oil is well connected in the pore space when in contact with gas, in wetting and spreading layers. Similarly, κ1 and κ2 of the oil–water interface have opposite signs (figure 13d–f), indicating that oil and water are well connected, especially that water remains highly connected in the larger pores surrounded by oil layers during GI (see section ‘Oil layers’ and electronic supplementary material, figure S5).
| 4 | 0biomedical
| 0Study
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7,389 |
Parameters controlling the variation of the number of thymic progenitors: β, b0, and τb. It should be noted that the parameter β arising in Eq. (4) is computed on the basis of the estimated values of b0 and τb such that the number of progenitors at t0 is 1.
| 1 | 0biomedical
| 0Study
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116,308 |
Despite similarities between the CCHCR1-HEK293 cell lines, some isoform- and haplotype-specific effects on the gene expression were apparent, which is observable from the Venn diagram (Fig. 1a) and the heatmaps. For instance Wnt signaling (heatmap in Fig. 3a) was mainly upregulated only in the Iso3Non-risk cells when compared with controls (Additional file 3: Table S3). While several pathways were mainly downregulated in the Iso3Risk cells, these including regulation of actin cytoskeleton (heatmap Fig. 2a) and RIG-I-like receptor signaling (heatmap in Fig. 3b; Additional file 3: Table S3). As CXCL8 (alias IL8) is involved in several signaling pathways that were highlighted in our expression data, as well as related to psoriasis, we validated its expression in the CCHCR1-HEK293 cell lines by qPCR; IL8 showed reduced expression in the Iso3 cell lines and upregulation in the Iso1cells, especially in Iso1Non-risk (Fig. 3c), as observed in RNAseq.Fig. 3Gene expression profiles of Wnt and RIG-I-like signaling in the CCHCR1-HEK293 cell lines. Both pathways were highlighted in the CCHCR1 cell lines. Heatmaps of Wnt (a) and RIG-I-like (RLR) (b) signaling in the Iso1Non-risk (IN), Iso1Risk (1R), Iso3Non-risk (3 N), and Iso3Risk (3R) CCHCR1 cell lines, vector transfected cells (v), and wild type HEK293 (wt) demonstrated that there were differences between cell lines. Wnt signaling is mainly upregulated only in the Iso3Non-risk cells while RLR signaling shows more downregulation in Iso3Risk than in other cell lines. Color key: red represents upregulated and blue downregulated expression (row Z-score). c The expression of CXCL8 in the CCHCR1-HEK293 cell lines was validated with qPCR, and compared with the gene expression in the wild type cells. Here shown normalization with HPRT1. Error bars: standard deviation
| 4 | 0biomedical
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88,427 |
Consumers’ demand for high-quality, minimally processed or fresh food has increased in developed countries. While consumption of these kinds of foods has increased, the incidence of foodborne illnesses linked to them has grown as well. One of the most important foodborne pathogens is Salmonella spp., which can cause gastroenteritis infection. In fact, there are 94 million cases of gastroenteritis and 155,000 deaths globally because of Salmonella each year, and nearly 85% of these cases are directly related to food . Salmonella Senftenberg is one of the serovars causing salmonellosis, and it is isolated from a range of different foods (seafood, eggs, etc.) . It is considered one of the most heat-resistant serovars within the Salmonella genus .
| 3 | 0biomedical
| 0Study
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300,727 |
Limited whole-lesion histogram analysis has been used to evaluate PCa therapeutic responses . Kyriazi et al. proved that the 25th percentiles of ADC were the best predictor of chemotherapeutic responses in patients with metastatic ovarian cancer and primary peritoneal cancers . Xie et al. used the histogram and texture analyses of ADCs to differentiate triple-negative breast cancers from other subtypes . Another group used DCE MRI and texture analysis to differentiate malignant glioma from glioblastoma . Texture analysis parameters, extracted from T2W images of rectal cancer patients, were also found to be useful imaging biomarkers to assess tumor responses to neoadjuvant chemotherapies . Meng et al. revealed possible T2W and ADC texture parameters that could be used as noninvasive imaging biomarkers for the early detection of recurrence in patients with advanced cervical cancer after radiotherapy. These parameters could help clinicians adjust therapeutic strategies and offer more personalized anticancer therapies .
| 4 | 0biomedical
| 2Review
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255,813 |
Cuticles were washed and stained in 0.05% Saponin in PBS (PBSS), while tumours were washed and stained in PBS containing 0.1% Triton X-100 (PBST). Cuticles were stained overnight at 4 °C with DAPI, Phalloidin-488 (Invitrogen, Waltham, MA, USA) at 1:100, and LipidTOX Deep Red (Thermofisher Scientific, Waltham, MA, USA) at 1:500. Cuticles were washed 3 times in PBSS before mounting on glass slides in Vectashield mounting media without DAPI (Vector Laboratories, Inc., San Francisco, CA, USA). Tumours were stained overnight at 4 °C with DAPI, washed three times in PBST and mounted on glass slides with a spacer in Vectashield mounting media without DAPI.
| 3 | 0biomedical
| 0Study
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392,436 |
The chromosomes were analyzed with Axio Scope.A1 microscope coupled to an image capturing system AxioCam Cm1 (Carl Zeiss, Germany) using a 100 × oil objective. The number of chromosomes in 100 G-banded metaphase spreads was determined. At least 35 C- and Ag-stained metaphase spreads per each technique were examined using a 100 × oil objective. Karyotyping of 112 cells was performed on Axio Imager A2 microscope (Carl Zeiss, Germany) equipped with the Ikaros4 Karyotyping System (MetaSystems, Germany) using a 63 × oil objective. Percent of polyploid cells was estimated by viewing of 1000 metaphase plates. The nomenclature for Chinese hamster (Cricetulus griseus) chromosomes at 325-band and 575-band levels of resolution was employed for chromosome identification. Karyotype and structurally rearranged chromosomes described according to the International System for Human Cytogenetic Nomenclature ISCN, 2016 . The frequency of chromosome involvement in clonal and nonclonal ASR was calculated as the ratio of the number of structural rearrangements of each chromosome to the number of the corresponding chromosome in 112 karyotypes. To compare frequencies, Fisher’s exact test was used. For calculations, a p value < 0.05 was considered statistically significant.
| 5 | 0biomedical
| 0Study
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89,062 |
Cancer is a malignant tumor with a high mortality rate, and many people die from various types of cancers every year in the world. In 2015, the World Health Organization report ranked the top five most common cancer deaths across the world, including lung cancer, liver cancer, colorectal cancer, stomach cancer, and breast cancer (Figure 1). In 2015, 1.69 million people died of lung cancer in the world. Breast cancer is more common in women, and 571,000 people, including men, died of breast cancer in 2015. Furthermore, lung cancer, liver cancer, and breast cancer are highly fatal and easily overlooked.
| 2 | 0biomedical
| 1Other
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1,792 |
The time of expansion for one population of Pinus caribaea in Central America was obtained using LSWH, MPH and ABC (Table 1). We found that the only method where homoplasy is not taken into account, LSWH, produces lower estimates of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ \widehat{\tau} $$\end{document}τ^ compared to ABC and MPH, suggesting that homoplasy may cause the expansion time to be underestimated by approximately 100,000 years in this case. The 95% confidence intervals of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ \widehat{\tau} $$\end{document}τ^ for all methods is large however (Table 1). ABC-based estimates of homoplasy are 0.11 and 0.246 for MSH and DH respectively, which agrees with the theoretical estimates of 0.106 and 0.269 obtained for those homoplasy measures using equations (24, Appendix) and (17, Appendix) given the demographic parameters estimated using ABC.Table 1Estimates of homoplasy and times of expansion in the population of Pinus caribaea analyzed \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ \widehat{\tau_{LSWH}} $$\end{document}τLSWH^ \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ \widehat{\tau_{MPH}} $$\end{document}τMPH^ \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ \widehat{\tau_{ABC}} $$\end{document}τABC^ MSHDHTheoretical estimate of MSHTheoretical estimate of DH4.074 (1.359 – 6.086)5.994 (1.732 – 10.297)5.591 (2.645 – 11.005)0.115 (0.026 – 0.244)0.246 (0.106 – 0.415)0.1060.269Time of expansion in years (LSWH)Time of expansion in years (MPH)Time of expansion in years (ABC)224,900 (75,000 – 335,900)330,800 (95,600 – 568,400)308,600 (146,000 – 607,400)The estimated values of the time of expansion were obtained using three different methods (LSWH, MPH and ABC). The estimated values of MSH and DH were obtained using ABC. The numbers inside the parentheses denote the upper and lower limits of the 95% confidence interval for the parameter or homoplasy measure. The theoretical estimates of MSH and DH were estimated using the values of τ and θ 1 obtained using ABC and the Eqs. (24) and (17)
| 4 | 0biomedical
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20,443 |
The study had some limitations. Firstly, the inclusion of patients in the analysis depended on the clinicians’ diagnosis of malaria, and further analysis relied on their documentation of testing and laboratory records. Similarly, the study relied on documentation in the case record of symptoms, signs and treatments to examine practices. The potential challenges of using such routine information that often has missing data were minimised through use of standardized record forms to record clinical information, timing data collection during discharge, data quality checks implemented within CIN, feedback to and development of partnerships with hospitals in the CIN all of which improved data availability and quality . The study only captures data from five hospitals, hence generalizing results to other facilities in Kenya should be done with caution. Lastly, data on treatment preceding hospitalization were not available. Conceivably these information may have influenced some clinical decisions and practices which we assessed. The potential threat to reported findings posed by preadmission investigations not recorded in the CIN data is minimal because from our experience clinicians rarely use investigations conducted outside their facility as a basis for treatment for acute medical illnesses because these investigations are often perceived as unreliable, and also the essential investigations are readily available within facilities at minimal costs or for diseases like malaria these investigations are provided at no cost to patients. Despite these limitations, the findings from this study can provide an insight into the quality of routine inpatient malaria case management and the extent to which national and international policies are influencing practice.
| 4 | 0biomedical
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265,340 |
The presence of immune cells in tumours capable of recognising mutated cancer cells raises several important questions, which until now remain a significant challenge in oncology: How do cancer cells avoid destruction by the immune system? How is immune control lost? And when during tumorigenesis is this control lost?
| 4 | 0biomedical
| 2Review
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109,495 |
COD crystals with different shapes were prepared by altering reactant concentration, reaction temperature, stirring speed, and additive. Table 1 shows the additives during the preparation process and physicochemical characteristics of COD crystals. Figure 1a–d illustrate the SEM images of the COD crystals (~5 µm in size) with different shapes, including cross-shaped (COD-CS), flower-like (COD-FL), bipyramid (COD-BD), and elongated–bipyramid (COD-EBD). Both COD-CS and COD-FL presented a similar dendrite structure, of which COD-CS comprised four sharp branches, whereas COD-FL had eight blunt branches. COD-BD and COD-EBD crystals showed the most common morphology of bipyramid structure, but the (100) face was gradually extended. Figure 1e shows the XRD patterns of the as-prepared COD crystals of varying shapes and the standard XRD pattern (PDF card number: 17-0541)14. All crystals were detected at diffraction peaks d = 0.618, 0.442, 0.277, 0.241, and 0.224 nm, which were assigned to the (200), (211), (411), (103), and (213) planes of COD crystals, respectively. No other impurity peaks in the XRD spectra were found. The intensity ratio of the main (100) and (211) planes (I100/I211) of the COD crystals with varying shapes was COD-EBD > COD-BD > COD-FL > COD-CS (Table 1).Table 1Characterization of the physical and chemical properties of COD crystals with various shapes.Crystal morphology and abbreviationCrystal size/μmAdditiveI100/I211 Specific surface area SBET /m2/gZeta potential in culture medium/mVConductivity/μS/cmCOD-flower-like (COD-FL)4.8 ± 0.3Na2EDTA1.462.79−6.01 ± 1.3243.3 ± 0.92COD-cross-shaped (COD-CS)5.2 ± 0.5Na2EDTA1.333.04−5.75 ± 1.1948.2 ± 1.17COD-bipyramid (COD-BD)4.9 ± 0.2SDS3.435.33−12.6 ± 1.6835.7 ± 0.74COD-elongated-bipyramid (COD-EBD)4.7 ± 0.4SDS4.105.81−10.9 ± 2.6233.6 ± 1.85 Figure 1SEM images (a–d) of COD crystals with various shapes and the XRD patterns (e) of as-prepared COD crystals and the standard XRD pattern of COD (PDF card number: 17-0541)14. (a) COD-FL; (b) COD-CS; (c) COD-BD; (d) COD-EBD; (e) XRD spectra. Scale bars: 5 μm.
| 4 | 0biomedical
| 0Study
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385,099 |
However, several other studies have found significant adverse effects of aflatoxin exposure in utero and birth outcomes and/or child growth. Four of the five studies reviewed by Shuaib, Ehiri, et al. (2010) found that aflatoxin exposure was inversely associated with birth weight, but for two of these studies, the association only held for female infants, and all of the study designs were cross‐sectional (Shuaib, Ehiri, et al., 2010). The study by Turner et al. of 107 infants in The Gambia linked aflatoxin exposure in utero, as measured through maternal, cord, and infant blood, to growth faltering in children based on anthropometry at 1 year of follow‐up (Paul C. Turner et al., 2007). The authors find that aflatoxin albumin levels in maternal blood were a strong predictor of both the infant's height and weight, estimating that a reduction in AF‐alb levels from 110 to 10 pg/mg would lead to an increase of 0.8 kg in weight and 2 cm in height within the first year of infancy. Placental weight and gestational duration were included among the confounders, and these could be important mediators of the effect of aflatoxin on growth. The study by Shuaib, Jolly, et al. found a statistically significant increase in the odds of low birth weight in the highest compared with the lowest quartiles of AFB1‐lysine levels (adjusted OR: 2.09; 95% CI: 1.19–3.68), but no significant association was observed for the outcomes SGA, preterm, or stillbirth. Although the sample size was higher than that of our study (785 pregnant women) and the higher exposure levels might have made effects more detectable, the design was cross‐sectional, such that blood samples were taken at delivery (Shuaib, Jolly, et al., 2010).
| 4 | 0biomedical
| 0Study
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16,015 |
An ultra-compact PSR has been proposed and numerically demonstrated by utilizing an ADC consisting of a RSW and a GERSW. The ERI of the GERSW for the TE mode can be significantly changed by tuning the chemical potential of graphene. As a result, the phase-matching condition between the TM mode in the RSW and the TE mode in the GERSW can be well satisfied over a broad spectral band. The PSR embedded with seven layers of graphene and with a 11.1-μm coupling length and a 150-nm gap separation enables a high TM-to-TE conversion efficiency (>−0.5 dB) within a broad bandwidth (1516–1602 nm). Overall, this designed PSR presents a strong ability to address the issue of polarization dependence at 1550 nm with the TE-to-TE thru loss (>−0.01 dB), TM-to-TE polarization conversion loss (>−0.26 dB), and extinction ratio at the thru port (>14 dB).
| 4 | 0biomedical
| 0Study
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282,702 |
In the cluster of treatment management, survival analysis, chemotherapy, and hepatectomy were the top three research topics. Endeavors were also put on stent placement and risk factors. In the cluster of diagnosis research, differential diagnosis, positron emission tomography (PET), and contrast-enhanced computed tomography (CT) were the top three research topics. The cluster of basic research covered the largest proportion of these topics, with microRNA expression, gene expression profile, and proliferation & apoptosis as the top three focused topics in this cluster. Notably, the basic research cluster showed a poor connection with other clusters, while the strongest connections appeared between survival analysis and expression profiles of microRNA and gene, indicating that a large amount of basic researches failed to translate to clinical therapies.
| 4 | 0biomedical
| 2Review
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323,921 |
Caspase-3 activity was measured with a caspase-3 assay kit according to the manufacturer’s protocol. Rin-m5f cells were lysed following a 24 h PA stimulation and were centrifuged at 12,000 rpm for 15 min at 4 °C. Then, cell lysates were incubated in reaction buffer containing the caspase-3 fluorogenic substrate Ac-DEVD-pNA at 37 °C for 2 h. Then, the absorbance of p-nitroanilide (pNA) cleaved by caspase-3 was measured at 405 nm with a microplate reader (Bio-Tek, Winooski, VT, USA).
| 4 | 0biomedical
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100,778 |
In the binary classification problem one is trying to deduce the answers to new questions, rather than just recall the answers to old ones. In order to do that we need to train the classifier from question-answer pairs (the training set). This is called supervised learning, because it requires a teacher, knowing the rule, which gives the correct answer to the example questions. In the case here, the author consider score-based binary classifiers, which does not need such learning stage. Could the author put the problem in the context supervised vs. no-supervised?
| 1 | 2other
| 1Other
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381,506 |
Intravitreal anti-VEGF therapy has shown to be safe and effective for the treatment of macular edema secondary to RVO.10,11 The anti-VEGF medications aflibercept and bevacizumab are commonly used for the treatment of macular edema secondary to CRVO.12,13 The Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2) recently showed that, with regard to visual acuity letter score (VALS), intravitreal bevacizumab was noninferior to aflibercept in patients with CRVO and HRVO.14 Although studies have demonstrated that visualization of EZ integrity improves in eyes with macular edema secondary to RVO receiving anti-VEGF therapy, and EZ integrity may predict visual outcomes,15,16 there is a paucity of large clinical trial data with long-term follow-up. In addition, assessment of EZ is mostly based on integrity of EZ and not a quantitative assessment of area or thickness. Accurate surrogate parameters improve the selection of eyes for clinical trials, establish therapeutic outcomes, and influence clinical management. Therefore, we sought to evaluate the EZ integrity assessed by SD-OCT–generated en face thickness maps and its association with VALS in eyes with macular edema secondary to CRVO or HRVO in the SCORE2 trial using a semiautomated, machine learning approach.
| 4 | 0biomedical
| 0Study
|
136,309 |
This was a retrospective study conducted in a single center and approved by the Clinical Research Ethics Committee of Takeda General Hospital and registered with the University Hospital Medical Information Network (registration number UMIN000044040). Written informed consent was obtained from each patient included in the study, which was performed in accordance with the Declaration of Helsinki. The primary endpoint of the study was hierarchical cluster analysis based on the scores obtained by c-Myc staining to clarify the characteristics of each group. The secondary endpoints of the study were the c-Myc expression rates in early gastric neoplasia based on the WHO classification.
| 4 | 0biomedical
| 0Study
|
365,755 |
Page 14 line 248. If the same matrix A used for computation which is reported in this study, then the whole computation may be revised because the results may be affected by changing the value in A reported in 2. For instance, “ ① All elements of each row of the matrix A were multiplied and the nth root was taken.”
| 2 | 0biomedical
| 0Study
|
310,569 |
Subjects comprised a total of 564 females of Korean ethnicity. Sixty patients with POF and 182 controls in the discovery set, and 120 patients with POF and 218 controls in the replication set. Patient genomic DNA samples were genotyped using an PMRA. Kinship analysis detected 30,876 associations among 242 individuals in the discovery set, and there were no first and second degree relationships. Kinship analysis was also conducted in the replication set and a total of 322 individuals were left. Our results indicated that none of the study participants were related.
| 4 | 0biomedical
| 0Study
|
193,382 |
In support of the safety of the active substance, the applicant performed a literature search. The search was done via three meta‐search sites: LIVIVO, Ovid, and ToxNet sixteen single databases (incl. PubMed and Web of Science), and eight publishers search facilities (incl. Elsevier, Ingenta, Springer, Wiley). A detailed description of the iterations used and the inclusion/exclusion criteria applied for the selection were provided.24 The search resulted in 713 papers retrieved, 28 publications were considered relevant. The list of papers was provided as RIS. File.25 None of the papers identified a safety concern for the target species, the consumer, the user and the environment.
| 2 | 0biomedical
| 0Study
|
177,345 |
Reverse Transcription (RT): As a result of the large sample number and the automated process, RNA concentration was not taken into account for each individual reaction. Fourteen µL of each RNA sample was reverse transcribed in a total volume of 20 µL using the High capacity cDNA reverse transcription kit (without RNase inhibitor, Applied Biosystems, Thermo Fisher, Loughborough, UK). The average RNA concentration across the 142 samples was 32.4 ng·µL−1 equating to an average of 453 ng RNA/reverse transcription reaction. Reactions were performed in 96 well PCR plates on a PTC-225 Peltier thermal cycler (MJ Research, St. Bruno, Quebec, Canada) using the following profile: 25 °C for 10-min, 37 °C for 60-min, 85 °C for 5-min, 4 °C hold. Minus RT control reactions were set up for 14 samples, in which the RNA component was replaced with nuclease free water (Ambion, Fisher Scientific, Loughborough, UK).
| 4 | 0biomedical
| 0Study
|
150,409 |
In CRF– neurons (n = 7 CrfCre;chr2-yfp mice, 12 cells), we failed to observe either light-induced EPSCs or IPSCs while voltage clamping the neurons at −60 or −35 mV (not shown). Perfusion with 4AP (30 μM) increased the frequency of sEPSCs that was accompanied by occasional bursting (Supplementary Figure 3B left). Light activation of BRN in the presence of 4AP produced an increase in small EPSCs only in one CRF– neuron (Supplementary Figure 3B, middle) and IPSCs in another neuron (Supplementary Figure 3B, right) out of 10.
| 4 | 0biomedical
| 0Study
|
83,239 |
To assess performance of key strains in a more industrially relevant condition, anaerobic fermentations were performed in ACSH at 30 °C for Y73, two synthetic hybrids, and two evolved hybrids. Media and cultures were degassed in an anaerobic chamber where O2 levels remained below 30 ppm. In this case, we sampled each day during the 7 days of fermentation.
| 4 | 0biomedical
| 0Study
|
169,423 |
A multisectoral group of representatives from civil society, academia, and funding organizations organized a workshop titled “From ‘learning from the field’ to addressing power imbalances and jointly driving change.” We aim to provide an alternative voice at the GHF, raising questions about power, rights, and ownership of the processes, management, and dissemination of public health research and policymaking. First we highlight the deficiencies in the relationship between health authorities, donors, service providers, research institutions, and the people that they intend, and are expected, to serve. We examine language and its use to explore people’s participation and power in health policymaking and research. Next we review global, regional, and national level case studies provided by working group members that may contribute to overcoming power imbalances and achieving a new agenda for ‘people’s participation.’ Our ultimate aim is to prompt reflection among participants in the GHF and to help the conference evolve from an approach of learning from the field to one focused on jointly driving change. That is, to move from taking lessons back from ‘from the field’ to actively promoting equity-affirming public health advocacy, research, policy, and practice.
| 2 | 2other
| 1Other
|
377,008 |
We assessed students’ well-being at school through two scales, the SRW scale and the SWQ . We developed an Italian version of the SRW scale by means of a back-translation procedure, from English to Italian and back from Italian to English. The SRW is a 6-item unidimensional scale assessing well-being at school (see Table 1 for the English and the Italian versions). The instruction used in this study were: “The following sentences refer to how you feel at school. For each sentence, put a cross on the number which corresponds to how much the sentence is true for you. You can choose among the following alternatives: 1 = not at all, 2 = slightly, 3 = moderately, 4 = very, and 5 = extremely”. The students evaluated how much each item was true for them (e.g., I feel good at school) on a 5-point scale (1 = not at all and 5 = extremely).
| 2 | 2other
| 0Study
|
346,936 |
Globally, protected areas designated for the conservation of biodiversity account for a very small percentage of landcover, only about 3.48% . Consequently, wildlife and humans, sharing the same landscape, are often forced to interact with one another and this may lead to conflict situations, wherein one or both species may face tremendous losses. It is, therefore, important to understand the ecology of nonhuman species to explain the persistence of these animals in anthropogenic habitats. It then becomes crucial to examine the behavioural changes displayed by individual animals, as these are often amongst the first responses that a species demonstrates to a changing environment .
| 2 | 2other
| 1Other
|
324,923 |
The biocidal polymers can be obtained either by the polymerization of cationic monomers not necessarily active and frequently without antibacterial activity or by functionalizing an inactive polymeric scaffold with inactive cationic groups to form a cationic macromolecule with antimicrobial activity due to its high density of positive charge. Biocidal polymers are active because they are positively charged macromolecules that, miming CAMPs, are able to kill bacteria on contact, by a disruptive action on their anionic cell membranes .
| 4 | 0biomedical
| 1Other
|
54,433 |
It is in the profound differences in metabolic activity and organization between the two microbial systems that the explanations for the differences in corrosion rates are likely rooted. Aspects of the metabolic conditions in the HC systems that would seem to be particularly relevant to aggressive corrosion include the accumulation of sulfides and/or H2S, greater biomass, the presence of fermentation products, and the generation of a unique chemical environment.
| 4 | 0biomedical
| 0Study
|
69,243 |
To assess the correct estimation of the target position in monkey and human trials, neuron-dropping curves were computed for each neuron of monkey-only and human-only cells, separately, in the delay period. The computation started from one neuron randomly selected from each cells’ category. For the selected neuron and for a given condition, one test trial corresponding to one correct target position among the 4 possible positions was randomly chosen and temporarily removed. The mean firing rates of all remaining trials were assembled in a look-up table. The look-up table was a matrix of mean firing rates for the 4 target positions. The difference in firing rate between the test trial and the average rate for each remaining trial type was calculated and then ranked between 1 and 4, 1 indicating the closest match. The selected test trial was then classified as being of the trial type with the smallest sum of ranks across the selected neurons. If the classified trial type and the test trial type shared the same location, then the classification of the target position was correct. We computed neuron-dropping curves for one neuron to the total number of neurons, considering different ensembles for the population estimation.
| 4 | 0biomedical
| 0Study
|
239,578 |
Existing relationships and cross-talks between SSC have been excellently reviewed in several important papers , and interested readers can find comprehensive information. However, a detailed survey on the interactions of the four compounds taking place during heavy metal exposure is still missing. In this compact review, the results of applications of the respective compounds are presented in Table 2, with studies focusing on the interplays between at least two of them particularly highlighted. Small signaling compounds are the most versatile priming agents used for metallic stress tolerance induction, and the basics of their priming features are summarized below. Methodological details concerning pretreatments with small regulatory compounds in heavy metal-focused studies are summarized in Table 2.
| 4 | 0biomedical
| 2Review
|
165,155 |
Further, when the study was initiated, the Veggie Meter® device was accompanied by a protocol developed by the manufacturer. While this protocol outlined the basic steps for usage, it did not take into account the logistics of implementing the device in school settings, in which additional steps may be required to ensure data collection proceeds smoothly. As this was the first time the device was used by this research group, it became evident that it would be necessary to supplement the Veggie Meter® manufacturer protocol to render it feasible to administer in schools efficiently and minimize the amount of classroom time diverted for data collection.
| 3 | 0biomedical
| 0Study
|
30,300 |
Many gastrointestinal disorders are directly or indirectly associated with the malfunction of intestinal disaccharidases. In this study, we aimed to provide a measure for the amount and activity of the disaccharidases from intestine of a healthy human subject, and characterize the effects of environmental factors, such as pH and temperature, on their function. Our results showed that SI and MGAM in combination comprise about 11% of total BBM proteins, which indicates that a high proportion of mucosal proteins are dedicated to carbohydrate digestion. In previous studies, the activities of intestinal disaccharidases have been normalized to the wet weight of the intestinal biopsies or the total protein content of the sample , which results in a wide range of normal disaccharidase activities based on expression levels in different individuals . Here, the activities are determined based on the mean disaccharidase content, and provides a more confined reference unit, which is independent of the expression level. This method can be used as a tool for specifying the rationale of disaccharidase insufficiency towards either loss of function or lowered intestinal expression of the enzymes. We identified that extraction of the disaccharidases from the membrane affects their functional capacity; this point should be considered when comparing activity values from different studies. SI, MGAM and LPH have their optimum activity at pH 6, and preserve more than 50% of their activity up to pH 7, which is consistent with the intraluminal pH in the small intestine. Accordingly, slight pH variations in the intestinal lumen caused by chronic disorders are not expected to substantially affect the function of the intestinal disaccharidases per se. The activity of the intestinal disaccharidases increased with an increase in temperature up to 45 °C, with an acceptable stability. This effect could enhance the functional efficiency of these disaccharidases when physical exercise increases the core body temperature. The novel data provided in this study expand the current knowledge on the function of intestinal disaccharidases, and could provide a scale for functional characterization of these enzymes under pathological conditions.
| 5 | 0biomedical
| 0Study
|
186,020 |
Cytotoxicity was evaluated after 72 h of cell culture, using a live and dead cell assay kit (ab115347, Abcam). Briefly, media were aspirated from each well and replaced with live and dead cell assay solution diluted in RPE1 cell culture media to a final concentration of 1X as per the manufacturer’s instructions and incubated in the dark for 10 min at room temperature. Subsequently, the live and dead cell assay solution was aspirated and replaced with Hoechst 33342 (B2261, Sigma-Aldrich) diluted at 1:10 000 in cell culture media. Cells were further incubated for 5 min, after which the solution was aspirated from each well. Wells were washed three times with PBS before being replaced with culture media for the duration of the imaging. Plates were immediately imaged with an ImageXpress Micro Confocal High-Content Imaging System (Molecular Devices). Overall, 16 fields of view repeated in triplicate were used for subsequent quantification, with each image set, equivalent to one field of view/site composed of three fluorescent channels. Obtained images were quantified using open source CellProfiler software using a variety of image processing protocols developed in house. Numeric image analysis outputs were statistically analyzed applying one-way ANOVA with Bonferroni’s multiple comparison test; a significance of p < 0.05 was reported. Data generated are shown in Figure 5A,C.
| 4 | 0biomedical
| 0Study
|
36,873 |
Pediatric patients that received benzodiazepines were three times more likely to experience anterograde amnesia than those who received a placebo. The likelihood of experiencing anterograde amnesia was higher when the sedatives were used as agent for procedural sedation than when used as premedication. In fact, it is widely believed that benzodiazepines impair the retention of memories of information acquired after the administration of a benzodiapine drug . According to the present results, the benzodiazepine-related amnesia is independent of the method employed to evaluate it, including whether the means of recall involved pictures or events. It has been shown that memory impairments remain even when a task that mimics a real world situation is used . Hence, benzodiazepines impair memories of study items in addition to personally relevant events .
| 4 | 0biomedical
| 0Study
|
273,735 |
In conclusion, this is the first case report to focus on adult DMG-H3K27a of pediatric-type diffuses high-grade gliomas in the spinal cord from a clinico-histopathologico-radiographical aspect. Although under the microscope the tumors had aggressive behavior, their radiographical appearances were more like low-grade tumors, and the prognosis was more favorable than expected. Lastly, when encountering adult patients with suspected glioma arising at midline sites, an immunohistochemical examination for H3K27 alterations should be applied despite the seemingly less aggressive radiographical manifestations. The prolonged survival time could be the result of the comprehensive treatment according to NCCN recommendations and adjuvant TCM therapy.
| 4 | 0biomedical
| 3Clinical case
|
210,243 |
Indications for valproate for these 330 individuals is shown in Table 3. The most common indication for women prescribed valproate, at both the start and end of the study period, was epilepsy (65%; n = 139 and n = 88, respectively) followed by bipolar disorder (14% and 15%; n = 31 and n = 20, respectively). The distribution of indications was largely unchanged at the end of the study period despite an overall reduction in the number of women prescribed valproate.
| 4 | 0biomedical
| 0Study
|
56,853 |
Bamboo miRNAs are present in the breast milk of giant panda. (A) The color of the breast milk of the giant panda during distinct lactation periods. (B) Equal amounts of synthetic plant (dla-miR-172d-3p) and giant panda (ame-let-7b-5p) small RNAs (with or without 2′-O-methylated 3′ ends) were treated with/without sodium periodate. Subsequently, the endogenous and plant miRNAs levels were detected via a qRT-PCR assay. (C) The expression correlation of bamboo miRNAs in bamboo leaves and giant panda breast milk. (D) The expression levels of plant miRNAs in the breast milk of the giant panda during distinct lactation periods, detected using small RNA-seq and (E) stem-loop qRT-PCR. (F) The functional enrichment analysis of exosome-loaded exogenous bamboo miRNAs. All data are expressed as mean ± SD. *P < 0.05, **P < 0.01.
| 4 | 0biomedical
| 0Study
|
367,224 |
if \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$T=P_e$$\end{document}T=Pe then pick the least pair u, v as in the definition of requiring attention; define, for any \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$x,y\in [u]_{R[s]} \cup [v]_{R[s]}$$\end{document}x,y∈[u]R[s]∪[v]R[s], \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$f(\langle x, y\rangle , s+1):=1$$\end{document}f(⟨x,y⟩,s+1):=1 and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\gamma (\langle x, y\rangle , s+1):=1$$\end{document}γ(⟨x,y⟩,s+1):=1;
| 4 | 0biomedical
| 0Study
|
38,059 |
In our model, individuals reproduce and die according to density-dependent fecundity (b(N)=b0−b1N) and density-independent mortality (d0), where the overall density of individuals N is equal to the susceptible individuals S plus the infected individuals I. Susceptible individuals give birth and die according to these fecundity and mortality functions, where b0 and d0 represent the maximum birth and minimum death rates, respectively. Reduced fecundity at high host density constrains the population dynamics according to a logistic fashion, where the carrying capacity is given by (b0−d0)/b1.
| 4 | 0biomedical
| 0Study
|
69,755 |
Additionally, as noted previously, Hill and colleagues demonstrated significant disparities between labelling guarantees of nutritional content and actual nutritional contents of pet food brands in five of the United States. When using calculation methods recommended by the National Research Council, ME density was found to be significantly greater than advertised. Given that dietary variation is minimal for companion animals, when compared to human diets, and that chronic feeding is the norm, such an error constitutes a significant dietary hazard. It could partly explain the concerning rates of obesity and its sequelae in companion animals . Within the UK, for example, a recent survey of 572 veterinary professionals reported that 81% believed they had observed increased pet obesity in the preceding two years, and 80% believed there would be more overweight than healthy pets within the next five years .
| 4 | 0biomedical
| 0Study
|
121,376 |
The FP‐IMRT planning technique was developed and used in our clinic between 1995 and 2003. The details of this planning technique have been described elsewhere. (9) Beam‐split FP‐IMRT plans were used to treat the primary and upper‐neck nodal regions. The lower‐neck and supraclavicular nodes were treated with a split‐beam anterior field matched to the inferior border of the FP‐IMRT plan at the isocenter.
| 4 | 0biomedical
| 0Study
|
176,509 |
Self-monitoring of BP was well received and accepted by preeclampsia pregnant women who participated in the study. It is therefore recommended that the Department of Health introduces the use of BP machines for preeclampsia patients. Due to the unaffordability and unavailability of the BP machine, it is recommended that hospitals and clinics rendering ANC provide patients with preeclampsia and those who are at high risk, with reliable and affordable BP equipment to do self-monitoring at home. Healthcare institutions and practitioners, especially midwifery specialists, should provide health education programmes that will be monitored and measured for compliance to ensure that quality outcomes can be accurately reported.
| 3 | 0biomedical
| 1Other
|
226,397 |
Previous researches have revealed that chronic Aβ accumulation around astrocytes accompanies with not only BBB damage but delayed neuronal death (DND) within six months after cerebral I/R and even deposits to plaques with the further extension of time [43, 44], which provide experimental evidence for the occurrence of sporadic AD induced by ischemic stroke. Furthermore, a clinical study by Liu et al. demonstrated that patients with Aβ deposition experienced a more severe and rapid cognitive decline over 3 years after stroke/transient ischemic attack compared with subjects without AD-like Aβ deposition, and Aβ was associated with changes in multiple cognitive domains. Recently, Martins et al. have reported the acute accumulation of Aβ oligomers within 24 h in blood vessel walls including small capillaries and nearby brain tissues after cerebral I/R, and that such accumulation acts as a detrimental factor promoting brain damage. Additionally, the accumulation of toxic Aβ can produce swelling in astrocytes and their endfeet and also cause dysregulation of capillaries by acting on pericytes, influencing energy supply for neurons [45, 46]. Our study revealed that pyroptosis accounts for dysfunctions of the BBB-glymphatic system and the accumulation of toxic Aβ and thus destroys the CNS homeostasis on which neurons survival depend, aggravating the damage of neurons and neurological deficits after cerebral I/R. However, inhibiting pyroptosis could markedly abate these pathological changes. On the other hand, toxic Aβ has been identified as a trigger of pyroptosis and neuroinflammation [47, 48], which suggests a magnified effect of Aβ accumulation after cerebral I/R.
| 4 | 0biomedical
| 0Study
|
233,265 |
p62 and NBR1 translocate into the nucleus of brown adipocytes upon adrenergic stimulation and form a multi-protein complex with the nuclear receptor PPARγ and its obligate co-activator RXRα. p62 separately interacts with PPARγ and RXRα, increasing their nuclear proximity and facilitates their heterodimerization to drive thermogenic gene expression. NBR1 emerges as an opposite player that impairs PPARγ:RXRα complex formation and decreases PPARγ activity through direct interaction with PPARγ. The fact that p62 and NBR1 synergistically bind to PPARγ allows p62 to restrain NBR1 from its inhibitory binding to PPARγ. Nuclear p62 serves as a thermogenic promoter contributing to PPARγ activation in brown adipocytes.
| 4 | 0biomedical
| 0Study
|
149,947 |
Male athymic NCR nude mice (14–16 g, age 4–5 weeks) were used for the tumor xenograft model. The project was conducted following the Animal Welfare Act and other federal statutes. The maintenance of the mice and all the in vivo studies were conducted in the Animal Care Center of St. John’s University. The animal study was reviewed and approved by the Institutional Animal Care and Use Committee of St. John’s University (Protocol #1925).
| 2 | 0biomedical
| 0Study
|
102,447 |
The analysis within ENL group has revealed that the median percentage of CD4+ T-cells was significantly decreased during and after prednisolone treatment in each ENL patient. On the other hand, the median percentage of CD8+ T-cells was significantly increased following prednisolone treatment unlike CD4+ T-cells. Interestingly, the CD4+/CD8+ T-cell ratio was significantly deceased after prednisolone treatment implying the role of prednisolone in re-establishing the immune homeostasis by downregulating excessive CD4+ T-cell activation. Studies have shown that prednisolone reduces CD4+ T-cells [14, 48]. A reduction of CD4+ to CD8+ T cells ratio in patients with rheumatoid arthritis when as little as 2.5mg of prednisolone was administered every 6hrs has been reported . Mshana et al. were the first to hypothesize that ENL is precipitated by an imbalance of T-lymphocyte subpopulations . According to this hypothesis, ENL has two phases: initiation, due to an imbalance in T-cell subpopulations with decreased suppressor cells (now called Tregs) and perpetuation. Hence, the finding of the imbalance of T-lymphocyte subpopulations (CD4+/ CD8+ ratio) in this study would support the initiation of ENL reaction in patients with lepromatous leprosy. The initiation of ENL reaction by hyper activation of T-cells further explained by the association of viable bacterial load with the release of soluble antigenic material at the site of bacterial degranulation in ENL patients compared to the intact bacteria observed in non-reactional LL patients [51, 52]. Hence, it seems that unlike in the LL patients, macrophages in ENL patients may be activated and processes the bacteria and hence fragmented and granular bacterial deposits seen in these patients. The activation of macrophages by T-cells (most likely through IFN-γ secretion) may produce inflammatory cytokines such as TNF-α and IL-1β which could amplify the immune hyperactivation and hence tissue damage in ENL patients.
| 5 | 0biomedical
| 0Study
|
323,431 |
While protection from the primary tumor challenge is an important assessment of vaccine efficacy, the establishment of protective immune memory is also very important. Accordingly, mice that survived the primary challenge for 100 days with no sign of ascites development were rechallenged to assess their ability to reject tumors months after vaccination, providing an indication of immune memory. The rechallenge data for each experiment and subsequent survival are shown in Figure 1a–d. We selected survival for at least 60 days following rechallenge as an indication of established, protective immune memory. Only mice treated with the combination of CPMV and irradiated cells survived 60 days following rechallenge (Figure 1 and Figure 2b). This study of longer-term protection clearly established the combination of CPMV and irradiated cells as superior to any other vaccine, including the combination of freeze–thawed cells and CPMV. Additionally, two mice vaccinated with CPMV and irradiated cells that survived 100 days after rechallenge (200 days after primary challenge) were rechallenged a second time at that 200 day mark, after which they survived to 300 days, when they were rechallenged for the third time. Both animals survived until 450 days after the primary challenge and had no ascites when the experiment was concluded (data not shown). Overall, these data show the unique ability of the vaccine combining CPMV and irradiated cells to establish long-term, protective memory against a mouse model of ovarian cancer.
| 4 | 0biomedical
| 0Study
|
195,264 |
In the description of maternal–fetal genotypes deduced using the MLE, major (maternal) alleles detected in the cfDNA were denoted with the capital letters “A” (wild type) and “B” (mutant), while minor (fetal) alleles were denoted with the small letters “a” (wild type) and “b” (mutant) (Table 1). The cutoff for quality control (QC) to call a valid maternal–fetal genotype was set as FF ≥ 5%, total sequencing reads ≥500, and P value ≥70%, according to our previous study (Lv et al., 2021).
| 4 | 0biomedical
| 0Study
|
133,149 |
The antifungal therapy currently available in clinical practice does not fully cover the sharp rise in morbidity and mortality caused in recent decades by invasive fungi. This represents a serious concern for public health that mainly affects the immunocompromised population . In spite of the arsenal of approved compounds (namely polyenes, azoles, echinocandins, allylamines, and pyrimidine analogues) that can be used for the treatment of fungal infections in humans, there are a growing number of isolated nosocomial outbreaks of fungi habitually considered as non-pathogenic recorded in hospitals and a harmful rise in strains resistant to the usual chemotherapeutics. These and other factors increasingly complicate the standardization of effective treatments against invasive mycosis .
| 4 | 0biomedical
| 2Review
|
45,583 |
It has been reported that AQP8 is expressed in the salivary glands, although there are discrepancies between the reports. Koyama et al. 35 demonstrated the expression and localization of AQP8 mRNA in the acinar cells of rat salivary glands by in situ hybridization. In the present study, we were able to detect AQP8 mRNA in rat SMGs by RT‐PCR analysis with specific primers for this. However, exercise did not affect the expression of AQP8 mRNA in the SMG, as it did the AQP1 mRNA levels (data not shown).
| 4 | 0biomedical
| 0Study
|
205,513 |
The WHO/ILO Joint Estimates may include estimates of the burden of cardiovascular disease (CVD) attributable to occupational exposure to noise, if feasible, as one additional prioritized risk factor-outcome pair. To optimize parameters used in estimation models, the present systematic review and meta-analysis is required of studies with estimates of the effect of occupational exposure to noise on cardiovascular disease (CVD), here defined as comprising prevalence, incidence and mortality of ischaemic heart disease (IHD), stroke, and hypertension (Teixeira et al., 2019). WHO and ILO, supported by a large number of experts, have in parallel also produced a systematic review of studies estimating the prevalence of occupational exposure to noise (Teixeira et al., 2021), applying novel systematic review methods (Pega et al., 2020a). The organizations have conducted or are conducting several other systematic reviews and meta-analyses on other risk factor-outcome pairs (Descatha et al., 2018, Descatha et al., 2020, Godderis et al., 2018, Hulshof et al., 2019, Hulshof et al., 2021b, Li et al., 2018, Li et al., 2020, Mandrioli et al., 2018, Pachito et al., 2020, Paulo et al., 2019, Pega et al., 2020b, Rugulies et al., 2019, Tenkate et al., 2019). To our knowledge, these are the first systematic reviews and meta-analyses (with a pre-published protocol) conducted specifically for an occupational burden of disease study. The WHO/ILO joint estimation methodology and the WHO/ILO Joint Estimates are separate from these systematic reviews, and they will be described and reported elsewhere.
| 4 | 0biomedical
| 2Review
|
317,029 |
Tissues were fixed in 10% buffered formalin and embedded in paraffin. Sections of 4–5 microns in thickness were cut and placed on electromagnetically charged slides (Fisher Scientific, Fair Lawn, NJ, USA) to prevent detachment. Hematoxylin and Eosin was performed for routine histopathological examination. Tumors were diagnosed according to the latest World Health Organization Classification of Tumors of the Nervous System . Immunohistochemistry was performed using the avidin-biotin-peroxidase methodology, according to the manufacturer’s instructions (Vectastain ABC Elite Kit, Vector Laboratories, Burlingame, CA, USA). Our modified protocol includes deparaffination in xylenes, rehydration through descending grades of ethanol up to water, non-enzymatic antigen retrieval with 0.01 M sodium citrate buffer pH 6.0 at 95 °C for 25 min, endogenous peroxidase quenching with 3% H2O2 in methanol, blocking with normal horse serum (for mouse monoclonal antibodies) or normal goat serum (for rabbit polyclonal or recombinant rabbit monoclonal antibodies) and incubation with primary antibodies overnight at room temperature in a humidified chamber. Antibodies for viral proteins included a mouse monoclonal anti-SV40 T-Antigen, which cross reacts with the T-Antigen of JCPyV (clone PAb416, 1:100 dilution, Millipore/Sigma, Burlington, MA, USA); p53 was detected with a mouse monoclonal antibody (Clone DO-7, DAKO/Agilent, Santa Clara, CA, USA); antibodies for cellular markers included mouse monoclonals against Class III-beta Tubulin (Clone TuJ1, 1:500 dilution, Novus Biologicals Centennial, CO, USA), Chromogranin A (Clone DAK-A3, 1:200 dilution, DAKO/Agilent), S-100 (Clone B32.1, 1:500 dilution, abcam, Cambridge, MA, USA), Neuron-Specific Enolase (Clone BBS/NC/VI-H14, 1:500 dilution, DAKO/Agilent), Glial Fibrillary Acidic Protein (GFAP) (Clone SMI25, 1:1000 dilution, Sternberger/Biolegend, San Diego, CA, USA), and a recombinant rabbit monoclonal antibody against Prolactin (EPR18018-31, 1:16,000 dilution, abcam). After rinsing in PBS, sections were incubated with biotinylated secondary antibodies for 1 h, followed by incubation with avidin-biotin-peroxidase complexes for 1 h, both at room temperature in a humidified chamber. Finally, the peroxidase was developed with diaminobenzidine (Boehringer, Mannheim, Germany) for 3 min, and the sections were counterstained with Hematoxylin and mounted with Permount (Fisher Scientific). Photomicrographs were taken with an Olympus DP72 Digital Camera using an Olympus BX70 microscope (Olympus, Center Valley, PA, USA).
| 4 | 0biomedical
| 0Study
|
129,034 |
The consensus statement for histological diagnosis of IgG4-RD allows the distinction between lesions that are “histologically highly suggestive” and those that show “probable histological features”. In both cases, the presence of at least one between dense lymphoplasmacytic infiltrate, storiform fibrosis and obliterative phlebitis must be present. The IgG4/IgG ratio has to be at least 40%, and the number of plasma cells for HPF has to be specified.
| 4 | 0biomedical
| 1Other
|
169,918 |
Further results of Kaplan–Meier analysis suggested that the all-cause and CVD survival rates decreased with increasing urinary DEHP concentration. The subjects in the highest quartile of urinary DEHP concentration exhibited only increased CVD mortality, and the log-rank p values of all-cause and CVD mortality were 0.63 and 0.045, respectively (Fig. 1). Since there was a significant difference in the association of MECPP with CVD mortality in Cox regression, we further assessed the Kaplan–Meier results of MECPP for all-cause and CVD mortality (Figure S1). The results show that the log-rank p values were 0.39 and 0.0043, respectively.Fig. 1Kaplan–Meier survival curves for DEHP and all-cause and cardiovascular disease mortality. DEHP quartiles were used, in which 4 DEHP concentration groups were assessed for all-cause (A) and cardiovascular disease mortality (B): lowest (< 27.3 ng/mL), lower (>=27.3 to <45.5 ng/mL), higher (>=45.5 to 83.4 ng/mL) and highest (>=83.4 ng/mL)
| 4 | 0biomedical
| 0Study
|
263,814 |
(A) Each top ten enrichment pathways for BP, CC, MF of target genes. The x-axis displays enrichment, and the y-axis represents the GO terms. The filled colored circles display each statistically significant GO term. The size of circles represents gene number. (B) Top sixty pathways of target genes. The x-axis displays rich factor of target genes, and the y-axis represents the KEGG pathway. The filled colored circles represent each statistically significant KEGG pathway. The filled colored circles display each statistically significant KEGG term. The size of circles represents gene number.
| 2 | 0biomedical
| 0Study
|
393 |
Mice carrying an allele of Satb2 in which exon 4 is flanked by loxP sites (Satb2flox/flox) were generated by microinjection of ES cells carrying a Satb2tm1a(KOMP)Wtsi Knockout First (Promoter driven) allele (clone Satb2_G07, JM8.N4 subline; KOMP repository) into blastocysts from albino C57BL/6J donor mice. The germline-positive mice were further crossed with FLPo deleter mice (RRID:MMRRC-032247-UCD) (Kranz et al., 2010) to excise the FRT cassette and to establish a conditional allele. To generate Satb2 conditional mutants Satb2flox/flox mice were crossed with Camk2a-Cre mice (Minichiello et al., 1999) on a C57BL/6 background. In all experiments, mice that carry the floxed exon 4 but do not express the Cre transgene (Satb2flox/flox) were used as littermate controls. Unless otherwise stated, adult male mice at the age of 3–4 months were used for behavioral and molecular analyses. All experimental procedures were approved by the Austrian Animal Experimentation Ethics Board (Bundesministerium für Wissenschaft und Verkehr, Kommission für Tierversuchsangelegenheiten).
| 5 | 0biomedical
| 0Study
|
262,926 |
Herein, we show that Notch1 activation induces glutamine addiction in T‐ALL cells both in vitro and in vivo. We observed that Notch1 upregulation leads to proteosomal degradation of GS, responsible for glutamine addiction in Notch1‐activated leukemic cells. Concomitantly, Notch1 also induces the upregulation of GLS and the subsequent activation of mTORC1 signaling pathway, leading to mTORC1 dependency in Notch‐driven T‐ALL. Beyond confirming the model by which Notch1 induces glutaminolysis, our results propose that Notch1 executes a program leading to the upregulation of glutamine catabolism and cell growth signaling, and blocking glutamine anabolism, which ultimately leads to glutamine addiction in Notch1‐driven leukemia. Our results also pointed at the potential therapeutic benefits of targeting glutamine availability and mTORC1 signaling specifically in Notch1‐positive T‐ALL patients.
| 4 | 0biomedical
| 0Study
|
252,221 |
A similar tendency for variation in the number of water molecules was also observed in the modified C3deOAmBEr channel model, as shown in Figure 4. However, compared with the results using a common AmBEr channel with the same diameter, d = 12 Å shown in Figure 3, a somewhat shorter variation period was seen for the modified C3deOAmB (d = 12 Å) channel shown in the inserted enlarged figure in Figure 4. As mentioned in our previous study , the C3deOAmB channel became more hydrophobic when modified by hydrogen atoms. This modification to enhance the hydrophobicity at the middle of the channel was considered one of the methods that could be used to improve the ability of reject ion/leakage . In order to compare the water permeation performance of two different simulation models, the same calculation method was followed, and the slope was adopted to predict the value of the water permeability. In the case of the C3deOAmB channel, a steady state was observed at a simulation time of around 2 ns. Therefore, a mean slope of 3 ns was adopted, and the value of water permeability was calculated at approximately 2.2 × 10−11 (mole m s−1 m−2 Pa−1).
| 4 | 0biomedical
| 0Study
|
314,970 |
Figure 13 shows that as the bevel angle is increased to the same diameter, the force of the application increases. The same figure also shows that for the same bevel angle, the application force increases as the diameter increases. The best option, in the case studied, was the needle with 6 mm in diameter and bevel angle of 15. The worst option was the needle with 1.4 mm in diameter with bevel angle of 90.
| 3 | 0biomedical
| 0Study
|
88,618 |
The potential impact of dynamic equilibria is particularly obvious for the composition of non-membrane-enclosed compartments such as nuclear bodies and cytoplasmic granules. Proteins arrive there by diffusion and stay as a result of a preference for the environment of the respective compartment. However, it is highly unlikely that concentration gradients and local affinity will generate a binary sorting result, placing only proteins in those compartments that the cell needs to have there for functional reasons. For example, proteins appear not to exclusively localize to nucleoli, despite their enrichment there .
| 4 | 0biomedical
| 0Study
|
209,193 |
One convention is for the less frequently occurring allele (minor allele) to be considered the effect allele, since it is a change from the population norm—under this labelling, an effect allele could be inversely associated with the condition of interest. An alternative approach is to label the alleles that increase risk of a condition as the effect alleles. Where two datasets have taken different approaches to this labelling, or when the less frequent allele changes between populations, the labels could be inverted between our data sets (see Row 2, Table 4).
| 4 | 0biomedical
| 0Study
|
86,063 |
A variety of structural, histopathological and biochemical pathologies take place in the white matter of AD patients (summarized in Fig. 3). In this review, we have tried to answer two questions: What changes occur in white matter in the course of AD and what is the relationship between these changes and the pathological hallmarks of the disease? Fig. 3This figure summarizes the pathological cascades, and their relation with each other, occurring during the development of Alzheimer’s disease in white matter and cortex. While ischemia, excitotoxicity, oxidative stress, and iron overload in white matter damage oligodendrocytes, on one hand, and amyloid toxicity affects them, on the other hand, the iron released from damaged oligodendrocytes promotes amyloid polymerization and deposition in grey matter. The consequent demyelination and axonal loss result in further white matter damage and neuronal dysfunction. Neuronal dysfunction is also a result of amyloid deposition in cortex and a proposed cause for white matter abnormalities in AD patients. White matter hyperintensities are labelled with red in the MRI (FLAIR) scan of an AD patient. Blue arrows: direction of the damages originating in grey matter. Maroon arrows: direction of the damages originating in white matter. LV lateral ventricle
| 4 | 0biomedical
| 2Review
|
216,942 |
When a radiolabeled mAb binds to its target antigen, the emitting radionuclide results in DNA-strand breaks through the generation of free radicals, resulting in apoptosis and programmed necrosis. In contrast to other anticancer therapies, radioimmunoconjugates may not require internalization (with the exception of alpha-particle therapy) and do not target specific signaling pathways to exert their antitumor effects. Compared to naked mAbs, treatment with radiolabeled mAbs can result in high response rates with lower toxicities, particularly when compared to many other systemic cancer treatments . However, toxicity due to red marrow exposure related to the circulating half-life of intact mAbs is generally dose limiting. For therapeutic purposes, most radioimmunoconjugates contain either alpha-particle- or beta-particle-emitting radionuclides. The β-emitters are light energetic electrons that travel over a relatively long path length (0.5–12 mm) and have a low LET (approximately 0.2 keV/μm). They induce the formation of free radicals, causing DNA damage . Examples of β-emitting radionuclides include iodine-131, copper-67, lutetium-177, or yttrium-90; iodine-131 and yttrium-90 have been used in most clinical RIT trials and are considered the current standard to which all other therapeutic radionuclides are compared . In contrast, α emitters are positively charged heavy particles with a short-range path length of (20–100 μm) and high LET (approximately 100 keV/μm) .
| 5 | 0biomedical
| 0Study
|
386,898 |
Atom-based symmetric functions describe the chemical environment of atom i in terms of radial and angular terms. Therefore, each atom's Cartesian coordinate Ri = (xi, yi, zi) needs to be converted into the so-called symmetric function form of Equation (3):
| 4 | 0biomedical
| 0Study
|
22,236 |
The study was performed by Eurofins Cerep (France) using standardized Diversity Profile - P9 panel, comprising 53 receptors, 14 ion channels, 5 transporters and 27 enzymes (results from enzyme assays are not disclosed in this article). Binding of BP-Cx-1 to receptors, ion channels and transporters was examined with radioligand binding assays. Assay parameters are presented in the Supplementary File 4.
| 3 | 0biomedical
| 0Study
|
144,042 |
There has been a continuous increase in populations, development, urbanization, and industrialization in the world1. These human-derived factors impact the availability of fresh water resources2. A well-established method for providing fresh water is seawater desalination, which is a process that produces potable water from seawater. Many countries, like Qatar, invest substantial amounts annually of their technological and financial resources in desalination research, training, and implementation to overcome their water scarcity problems3–5. Zheng and coworkers reported that during the last two decades, a major worldwide trend in employing desalination technologies to overcome the water availability issues has been noticed6. The number of countries relying on desalination to a great extent remained to increase continuously after that. For example, it was estimated that in the year 2011, more than 30 million m3/d of desalinated potable water was produced globally. In addition, the economic trends of the world’s spending on desalination technologies revealed that by the year 2015 the desalination industry would reach 30 billion US dollars5,7. In the year 2015, it was reported that around 18,426 desalination plants existed around the world, which provided more than 150 countries with more than 86.8 million m3 of fresh water. Interestingly, the North African and Middle Eastern countries compromised around 45% of the desalination freshwater capacity provided then8. Specifically, seawater desalination accounts for 99% of Qatar’s accessible water, whereas groundwater meets the remaining 1%. The water per capita consumption rates in Qatar are among the highest in the world at about 500 Liters per day4. These consumption rates are met by increasing the number of desalination plants and capacities throughout the years. For example, in 2014, the production of desalinated potable water in Qatar was around 493 million m3. In 2017, the amount of desalinated water in Qatar was estimated to be 540 million m33,9. In the year 2017, the number of countries that applied desalination technologies increased to reach 231 countries. One of the most important driving forces to this trend is the fact that water demand is also increasing6.
| 4 | 2other
| 2Review
|
231,433 |
Thirdly, ample supplementation of vitamins is obligatory for better broiler production, especially amid harsh environment (10, 116, 117). Vitamin supplementation through drinking water is common practice in some poultry farms that have proved helpful to boost immunity and enhance heat-stressed broilers' performance. Diets containing vitamin A help broilers to fight against oxidative injuries induced by high environmental temperature (118). Kucuk et al. (118) also reported that vitamin A fortification has positive effects on production status as it enhances body weight gain, feed efficiency and reduces oxidative damage. Poultry birds can synthesize Vitamin C by itself and does not seek an external supply of vitamin C during normal conditions. However, under stress conditions, the additional supplementation of vitamin C might be fruitful for broilers' better performance as it promotes fatty acid oxidation instead of protein breakdown and reduces respiratory quotient (119). Studies reported increased hunger of birds for vitamin C during HS as vitamin C promotes fatty acid oxidation instead of protein breakdown and reduces respiratory quotient (119, 120). Moreover, it enhances meat quality by producing meat with high protein and low-fat contents and maintains redox status during high temperature because of its ability to be one of the best antioxidants. A study based on vitamin E diet supplementation reported that vitamin E supplementation promotes the phagocytic activity of macrophages and increases serum antibodies (IgM and IgG) levels in broiler under HS (121).
| 4 | 0biomedical
| 0Study
|
150,773 |
Studies regarding access of immigrants to healthcare services in Spain have concluded that they utilize them to a lesser extent than natives. In general, the immigrant population used less specialised, primary, and mental healthcare services in comparison to natives, even if they used the emergency services more [6–8]. Among the reasons for immigrants having difficulties accessing healthcare services, are legal restrictions, health systems’ excessive bureaucracy, professionals’ negative attitudes towards immigrants and racism . Restrictive legislation is often represented as the greatest barrier for accessing healthcare services for certain groups of immigrants, namely undocumented ones and asylum-seekers . However, access to healthcare is dependent on many individual and systemic factors, as different subgroups of populations may have a very different healthcare access experience, even under the same level of entitlement.
| 2 | 2other
| 1Other
|
236,375 |
We show that inhibition of γ‐secretase by L‐685458 or knockdown of Notch2 via CRISPR/Cas9 leads to reduced branching morphogenesis in vitro and abrogates transcriptional activation of HES1. Furthermore, we find that EGF stimulation during branching morphogenesis is correlated with increased Notch signal transduction, evidenced by the upregulation of HES1. We find that this transcriptional regulation of Notch activity is specific to 3D culture conditions. Whether this phenotype is regulated by ECM stiffness has yet to be elucidated, but mechanical forces have been demonstrated to regulate YAP/TAZ control of Notch activation in epidermal stem cells.[ 45 ] Additionally, bi‐potent mouse hepatoblasts have been shown to preferentially differentiate into cholangiocytes at the periphery of circular micropatterned domains. Compared to central areas, these regions elicit increased actomyosin stress and elevate NOTCH2 and JAG1 transcriptional activity.[ 46 ] Applying these principles to our system, we stipulate that rheological characterization of our optimized matrices will provide additional insight into the role of scaffold mechanics on Notch‐mediated morphogenesis.
| 4 | 0biomedical
| 0Study
|
215,383 |
A 66-year-old female patient was hospitalized, in a tertiary hospital in Hangzhou, Zhejiang province, China, in 2019, with symptoms of pyosepticemia, pancreatic malignancy, leukopenia, thrombocytopenic purpura, hepatic failure, and renal insufficiency. Initially, the patient received tigecycline by intravenous injection. Isolates were cultured from the inpatient during her hospitalization. The first isolate KP1-1, cultured form the blood sample of the inpatient within 24 h after admission, displayed extensively antibiotic resistance (including tigecycline) but susceptible only to colistin. The antibiotic therapeutic strategy was then adjusted to that of intravenous colistin (500,000 Unit every 8 h for the first 4 days and every 12 h for the following days). After received colistin treatment for 9 days, the second isolate KP1-2 was cultured from the stool sample with a colistin MIC of 32 mg/L. At the end of the treatment period, the inpatient expired from pyosepticemia and pancreatic malignancy. The isolates were identified by VITEK 2 (bioMérieux, Marcy-l’Étoile, France) and Matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS, Bruker, Billerica, MA, United States).
| 4 | 0biomedical
| 3Clinical case
|
385,735 |
a Gene mutation frequency and mutation type in metastatic urothelial carcinoma (mUC) ctDNA versus The Cancer Genome Atlas (TCGA) localized muscle-invasive bladder cancer (MIBC) cohort, across 50 driver genes on our targeted panel. TCGA information was obtained via cBioPortal. b Detection of protein-altering somatic mutations in ctDNA and patient-matched tumor tissue from 46 patients. Variant allele fractions (VAFs) for 265 mutations detected via targeted DNA-sequencing are normalized to tumor fraction estimates. c Correlation of gene copy number between ctDNA and tissue for seven commonly amplified oncogenes. Linear regression p value calculated for 38 amplification events across 27 patients (remaining 19/46 patients lacked amplifications in selected oncogenes). Data are presented as the exact gene copy number estimate (dot), +/− the 95% confidence interval (error bar) as calculated per gene from the coverage log ratio in samples with no evidence of cancer (tumor fraction = 0). Source data for (a) and (c) are provided as a Source Data file.
| 4 | 0biomedical
| 0Study
|
193,044 |
The spleen tissue of the infected patients showed upregulation of the AVPR2 gene (vasopressin receptor), which increases retention of water by increasing cyclic AMP , and the TYRO3 gene, which activates the AKT survival pathway and mediates the clearance of apoptotic cells . Pathway enrichment analysis for the spleen tissue (Figure 1A; Supplementary Figures S3–S5) revealed a downregulation of immune components related with the phosphorylation of the STAT protein, type I interferon, autophagy and RIG-I-like receptor signaling pathway; the latter is a target of DENV that regulates RIG-I-directed IFN induction to successfully replicate and spread . Dimerization of STATs is essential for the establishment of classical JAK-STAT signaling pathways, which have an important role in the control of immune responses. A downregulation of signaling pathways related to the response to angiotensin was also detected. On the other hand, the upregulation of insulin and cholesterol metabolic pathways could also be distinguished.
| 5 | 0biomedical
| 0Study
|
136,567 |
We assessed the impact of fluorescamine amount on the fluorescence intensity by recording the fluorescence intensity of solutions containing a fixed CFM concentration and different reagent volumes. We found that 1 ml of fluorescamine 0.02% (w/v) produced maximum fluorescence. At higher volumes, we observed a slight fluorescence intensity decrease (figure 6a). Figure 6. (a) Effect of volume of fluorescamine on the relative fluorescence intensity of the reaction product of cefepime (100 ng ml−1) with fluorescamine at pH 8.0. (b) Effect of volume of acriflavine (2 × 10−6 M) on the relative fluorescence intensity of the reaction product of acriflavine with cefazolin (5 µg ml−1) at pH 8.0.
| 4 | 0biomedical
| 0Study
|
56,232 |
By choosing different fluorescent markers for the particles and lipid membranes, we are able to visualize the effect of a single particle on a lipid membrane (see Fig. 2). We find that particles exist in either a completely wrapped state or a completely non-wrapped state: partial wrapping is only observed as a transient situation. Non-wrapped particles are located on the outside of the vesicle without deforming the membrane (Fig. 2a–c), while wrapped particles are protruding into the interior of the vesicle (Fig. 2d–f). Co-localization of the membrane fluorescence with the particle fluorescence further corroborates the fully wrapped state.
| 4 | 0biomedical
| 0Study
|
279,588 |
The SWAN Sleep Study protocol was conducted across an entire menstrual cycle or 35 days, whichever was shorter. Unattended PSG sleep studies were conducted in participants’ homes on the first three nights of the protocol. Study staff arrived at participants’ homes approximately 3 h before the participants’ bedtime to apply electrodes and calibrate monitors. Participants slept in their own beds and went to bed and awoke according to their habitual sleep and wake times, which were determined by self-report. Participants turned off the PSG recorder and removed study equipment themselves upon awakening in the morning. Wrist actigraphy and sleep diary data were collected throughout the protocol. Other measures pertinent to the current analyses were collected in conjunction with the Sleep Study or core SWAN protocol, as described below.
| 4 | 0biomedical
| 0Study
|
209,621 |
AKR1C3 promoted sorafenib resistance through AKT phosphorylation in liver cancer cells. (A) The mRNA expression level of AKT in sorafenib‐sensitive (n = 21) and sorafenib‐resistant (n = 46) patients. (B) The protein levels of AKR1C3, AKT, and p-AKT in HepG2 cells (control group and AKR1C3 overexpression group) treated with or without sorafenib (10 μM). (C) Immunostaining images of p-AKT in HepG2 cells (AKR1C3 overexpression group and control group) treated with sorafenib (10 μM) or without sorafenib; scale bars, 50 μm. (D) The efficiency of the p-AKT inhibitor was detected by Western blot. (E) The MTT assay of HepG2 cells (control, overexpressing AKR1C3) with or without 5 nM AZD5363 for 72 h. Data are presented as mean ± SD and are representative of three independent experiments. *P < 0.05.
| 4 | 0biomedical
| 0Study
|
196,373 |
Two aortic tissue culturing methods were tested for tissue viability: (1) aorta en face, fixed with acupuncture needles on a Petri dish, and (2) aorta en face in our microfluidic device. Ethidium homodimer (EthD-1, L3224, Thermo Fisher) was used as an indicator of cell death. Tissue media consisted of DMEM/F12 with 2% pen/strep. After dissection in fresh tissue media, the tissue was directly exposed for 10 min to media with EthD-1 at 37 °C and 5% CO2 followed by micrograph acquisition. Next, the tissue was cultured in tissue media for 7 h. Every hour, the tissue was exposed to EthD-1, and micrographs were acquired. As a positive cell death control, the tissue was exposed to DMEM with 0.05% Tween 20 (P9416, Sigma-Aldrich) for 10 min.
| 4 | 0biomedical
| 0Study
|
4,283 |
Table 1 details other covariate and outcome measures. Pre-existing perception measures were asked prior to experimental manipulations. Cronbach’s alpha was calculated for related sets of survey items that were grouped as one variable (i.e., attitudes, risk of addiction, and risk of health problems); all showed sufficiently high reliability (Table 1). Additionally, the following sociodemographic characteristics were assessed: age, gender (male, female, other), race (white, black or African-American, Asian, other), ethnicity (Hispanic, non-Hispanic), sexual orientation (heterosexual, lesbian/gay/bisexual, other), education, and parental education (high school or less, some college or associate’s degree, bachelor’s degree or more). As younger participants may not have completed their education yet, highest parental education was used as the education value for participants aged 18–22; own education was used for participants aged 23–26. Past 30-day use of tobacco products other than LCCs (e.g., cigarettes, cigars, hookah, e-cigarettes) was also assessed. Pre-existing perceptions of LCCs, sociodemographic characteristics, and other tobacco use were included as control covariates in all models due to their clinical [20–22] and statistical significance (see S2 Table for unadjusted analyses).
| 4 | 0biomedical
| 0Study
|
340,974 |
We also performed RNA-seq in singlet on three primary FSHD myoblast cell lines described previously (24), namely FSHD3 (FSHD1, 7RU, female), FSHD6 (FSHD1, 8RU, female) and FSHD9 (FSHD1, 7RU, male) alongside age and sex-matched controls, both in proliferation and after 3 days of differentiation into multinucleated myotubes. These new RNA-seq data were considered with our previously published datasets of immortalized FSHD myoblasts and myotubes in triplicate (32,45) that describes three pathological FSHD cell lines (54-12, 54-A5 and 54-2, all FSHD1, 3RU, male) alongside two control lines (54-A10, 54-6, 11RU) from a mosaic patient (46) and two further FSHD cell lines (16Abic, FSHD1, 7RU, female and 12Abic, FSHD1, 6RU, female) alongside sibling and sex-matched controls (16Ubic and 12Ubic, respectively). This totals 27 immortalized myoblasts and 27 immortalized myotube RNA-seq samples. None of the primary or immortalized FSHD myoblast or control myoblast samples contained DUX4 transcripts detectable by RNA-seq (Fig. 1B). Considering the myotube transcriptomes, three FSHD myotube samples contained DUX4 transcripts, namely primary line FSHD3 and 2/3 replicates of the immortalized 54-2 FSHD cell line (Fig. 1B). No control myotube samples expressed DUX4 (Fig. 1B). In a recent single cell RNA-seq of FSHD1 and FSHD2 unfused myocytes, DUX4 transcripts were found in 27/5133 (0.5%) FSHD cells (40) (Fig. 1B).
| 4 | 0biomedical
| 0Study
|
4,221 |
A Kaplan–Meier survival analysis will be done for the primary outcome which is time to recover following hysterectomy. The end-point is the actual time to recover. It will be assessed and documented at the 6-week clinic visit. Patients who have not recovered by 6-weeks will be followed-up beyond 6-weeks to detect complications and the actual time to recover. Post hoc pairwise analysis between TAH, NDVH and TLH will be done using COX regression.
| 4 | 0biomedical
| 0Study
|
370,336 |
An important issue for intervention studies is the growing randomized controlled trial (RCT) evidence that health benefits of vitamin D supplementation are greatest in vitamin D‐deficient people.( 67 ) This may also apply to cancer as a recent meta‐analysis of cohort studies revealed that 25OHD was inversely associated with cancer incidence at approximately <30 nmol/L only, and had an inverse relationship with cancer mortality that was strongest at low 25OHD levels (especially at approximately <50 nmol/L).( 13 ) Thus, any cancer‐related benefits of vitamin D supplementation may be greatest in vitamin D‐deficient individuals. However, trials have not contained large numbers of such people. For example, the average baseline 25OHD of 10 trials examined in the recent meta‐analysis by Keum and colleagues( 20 ) we reviewed was approximately 60 nmol/L.
| 4 | 0biomedical
| 0Study
|
365,092 |
The study was executed at the outpatient clinic at Department of Oncology, Odense University Hospital. The (a) group with individual information was included in the period 1/1 2016 – 31/3 2016, and the (b) group having group information was included from 1/4–30/6 2016.
| 2 | 0biomedical
| 0Study
|
27,305 |
The Figure presents the compliance of the BCG, tetravalent, MMR, and PCV-10 vaccines. The latter presented the lowest percentage in the adequacy of vaccination compliance, being less than 85%; the other vaccines showed a percentage of adequacy higher than 97%.
| 2 | 0biomedical
| 1Other
|
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