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We queried the scan results for markers previously reported to be associated with colorectal cancer. These variants were identified through previous genotyping in an independent sample of South Sulawesi colorectal cancer cases (R. Kusuma, I. Suriapranata, personal communication) and a recent catalog of colorectal cancer SNPs for a genome-wide association scan in Hispanics42. The source and annotation for these variants are provided in Supplementary Table 3. Variants with evidence of replication (p-value \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$<0.05$$\end{document}<0.05) were flagged for further investigation. Regional association plots were generated in LocusZoom43.
4
0biomedical
0Study
[ "Oncology", "Genetics" ]
39,297
Given the measured decreased Hsp10 to HSP60 protein ratio, we wondered what effects this could potentially have? The genes encoding HSP60 and HSP10, respectively, of eukaryotes from C. elegans to humans are organized in a head-to-head arrangement with a common bidirectional promoter (Ryan et al., 1997; Bross et al., 2013). Furthermore, in bacteria the corresponding genes encoding the large and small chaperonin subunits are typically organized in an operon under control of a common promoter (Lund, 2009). These architectures may provide transcription of both chaperonin genes at a fixed ratio suggesting that this ratio is crucial for correct function of chaperonin complexes. It has indeed been shown that the kinetics of in vitro refolding of malate dehydrogenase by the HSP60/HSP10 complex depended on the HSP10 to HSP60 ratio (Levy-Rimler et al., 2001). Maximum refolding rate was obtained at approximately 2:1 HSP10: HSP60 molar ratio and clearly lower refolding was observed at a ratio of to 1:1. Levy-Rimler et al. also presented evidence that HSP10 stabilizes the double-ring conformation of human HSP60. Thus, the observed almost 2-fold decrease of the HSP10/HSP60 ratio would be expected to compromise the function and capacity of the HSP60/HSP10 complex to assist folding and result in significant impairment of folding of those proteins that are most dependent on folding assistance by the HSP60/HSP10 complex.
4
0biomedical
0Study
[ "Molecular Biology", "Protein Biochemistry" ]
237,702
Whilst HA has been established as an osteoconductive material, its osteoinductive potential has also been investigated . This specifically refers to its ability to direct an undifferentiated cell down an osteogenic lineage rather than supporting the function of an already differentiated osteoblast. Lin et al., in 2008, using C3H101/2 cells, suggested that media conditioned by cells exposed to HA contained a secreted factor that could prime osteogenesis in cells. This cell–HA media was found to be 60% more effective than BMP supplemented media and 10x more effective than HA conditioned media alone . Whilst Lin determined that this response was not simply due to leached Ca and Pi ions, other studies have attributed the osteoinductive effect to them . Lin’s work adds to increasing research suggesting HA can act as a focal point for growth factors or potential extracellular vesicles (EVs) , forming an osteoinductive niche . We can infer that as a stem cell and osteoblast supporting material, HA would also serve to facilitate and support the activity of further differentiated osteocytes. This hypothesis is also supported by the observation that the MLO-A5 post-osteoblast cell line can express the Sost gene in the presence of hydroxyapatite mineral in 3D culture conditions after only 24 h, which would suggest the environment does indeed play an important role in its regulation . The expression of Sost by the IDG-SW3 cell in 2D culture is after approximately 10 days culture. This prolonged culture period may reflect the time required for the maturing osteocyte to lay a rudimentary mineralised matrix with which to interact. The significant role of osteocytes in remodelling and mineral homeostasis has been well described . Moreover, these data add to the growing evidence of HA as a bioactive molecule that has been shown to modulate expression of osteocyte proteins, such as Frizzled, Dickkopf, and Wnt, which are master regulators of the planar cell polarity and canonical pathways in osteocytes . Therefore, it is clear that the addition of endogenous bone macromolecules in the form of a more ‘bone-like’ mimetic ECM has a significant effect upon osteocyte gene expression, and that such culture conditions, in the form of Coll-HA, can improve the power of the MLO-Y4 osteocyte model in emulating the primary osteocyte.
4
0biomedical
0Study
[ "Other" ]
84,986
Chalcone-thio­phene derivatives have some mol­ecular structural features in common, namely the nearly planar geometry, as a result of the sp 2-hybridized C atoms of the main fragment, and the weak inter­molecular inter­actions, e.g. H⋯H, H⋯C or π–π contacts. One example for comparison with the title compound is the crystal structure of the compound 3-(4-methyl­phen­yl)-1-(3-thien­yl)-2-propen-1-one (Li & Su, 1993 ▸). In both of the structures, the mol­ecules are linked by weak inter­actions into centrosymmetric dimers and the crystal packing shows a herringbone motif: for the title compound this mol­ecular arrangement is clear when looking along the direction (Fig. 9 ▸ a) and for the above-mentioned 3-thienyl derivative, along (Fig. 9 ▸ b).
4
0biomedical
0Study
[ "Organic Chemistry" ]
175,534
Deletion strains were generated by standard gene replacement as previously described (33). Similarly, epitope tagged proteins were constructed by following the standard protocol (34). When required, the antibiotic cassette was removed by the expression of Flp recombinase from pCP20 as previously described (35). Oligonucleotides used for strains construction are listed in Supplementary Table S1.
3
0biomedical
0Study
[ "Molecular Biology" ]
345,457
At baseline, 210 caregivers consented to participate with their new-born baby, but due to insufficient sample collection or recent antibiotic exposure, only 206 infants were included. A flow chart for the children is shown in the Supplementary Fig. S1. All infants were healthy and had a birth weight above 2 500 grams. Due to family relocations or lack of time, the number of participating children decreased over time (see Supplementary Fig. S1). Additionally, 18 children had antibiotic use within 3 months before sampling and were excluded (Table 1). In total, 78 children participated at all sampling occasions, but 7 of these had antibiotics within 3 months before sampling, leaving 71 children for strict longitudinal analyses. 176 young adults consented to participate, but one subject was excluded due to failed sequencing. Summary characteristics of the included children and the 175 young adults are shown in Table 1 and additional information on participant inclusion is presented in the Supplementary information.Table 1Characteristics of the included children (2 days to 5 years of age) and of the included young adults (18 year of age).2 days3 months18 months3 years5 years18 yearsn = 207an = 159n = 141n = 141n = 119n = 175Boys, %53.154.157.955.151.351.4Age, mean (95% CI)—3.1 (2.8, 3.3)18.0 (17.9, 18.3)2.9 (2.7, 3.3)5.0 (4.8, 5.2)18.1 (18.0, 18.3)Caesarean section, %6.9—————Breastfedb, %98.582.45.02.00.0—Antibioticsc, n (%)1 (0.5)4 (2.5)9 (6.5)1 (0.7)3 (2.5)0 (0)Probiotic drops, %—17.54.7———Use of pacifier, %—69.065.543.20.8—Daily tooth brushingd, %———96.599.180.0Caries, %———8.810.069.7defs/DeFS, mean (95% CI)———1.2 (1.1, 2.0)2.7 (1.3, 5.0)4.7 (3.7, 5.8)Illumina analysise, n206155132140116175aAppropriate sampling was not possible for 3 infants.bExclusive or partial breast-feeding.cChildren receiving antibiotics within 3 months before sampling. For the 18-year-old subjects, antibiotic use within 6 months prior to sampling was an exclusion criterium.dDaily brushing refers to brushing 1–2 times per day.eNumbers after exclusion of participants that received antibiotics within 3 months prior to sampling.
4
0biomedical
0Study
[ "Epidemiology" ]
170,172
Publications identified in the searches were charted in Microsoft Excel for evaluation and eligibility assessment (54). The lead author (RQ) screened titles and abstracts using the inclusion/ exclusion criteria outlined in Table 1. Two authors (RQ, SR) independently read the full text of articles, applying the inclusion/exclusion criteria, and described the study characteristics. Where outcomes of eligibility assessment differed and remained unresolved after discussion, authors MRM or SL were consulted for a consensus agreement. Publication characteristics charted were source of article, year of publication, Indigenous population of study participants, aim or purpose of study, methodology including design and analysis of data, and study outcomes.
4
0biomedical
0Study
[ "Epidemiology", "Research Methodology" ]
298,601
COS was purchased from GlycoBio (GlycoBio, Dalian, China). NACOS was prepared in our lab in a previous study . HWCOS was purchased from Sigma (St. Louis, MO, USA). Table 1 lists the molecular weight range and deacetylation degree of COS, HWCOS, and NACOS.
2
0biomedical
0Study
[ "Biochemistry" ]
252,194
The multiple regressions with chlorophyll, temperature, and abundance values 2 years back (N P0+, N old, and N tot‐2) as independent factors explained about 80% of the variation in the population recruitment: R = 901–0.347·N P0+ + 332·Chl2 – 128·T 2 (R 2 = .769; p < .0004) R = 1011–0.767·N old + 366·Chl2 – 142·T 2 (R 2 = .806; p < .00014) R = 942–0.27·N tot‐2 + 343·Chl2 – 132·T 2 (R 2 = .784; p < .00027)
4
0biomedical
0Study
[ "Ecology", "Environmental Science" ]
374,176
The last three decades have seen an exponential growth in the number of studies evaluating where, when, why and how biodiversity could be affected by climate change and land degradation. Evidence for these effects comes from three distinct lines of research: (a) empirical and model‐based assessments of range shifts in species distributions linked to environmental changes (Chen, Hill, Ohlemuller, Roy, & Thomas, 2011); (b) compositional and richness changes (Blowes et al., 2019); and (c) links between life‐history, eco‐physiological or biogeographical attributes and the populations’ responses to environment changes (Angert et al., 2011). As the literature on environmental change impacts continues to grow, it is essential to translate the observed and expected patterns of biodiversity change to a metric that describes the threat to biodiversity from the adverse effects of environmental transformations. However, assessing biodiversity responses to observed or expected changes in environmental conditions is a multifaceted problem, where the point of view used to determine both the drivers and the degree of change matter. In this issue of Global Change Biology, Kling, Auer, Comer, Ackerly, and Hamilton (2020) tackle these problems by focusing on two of the facets (observed multivariate climate change and limiting environmental factors) defining how biodiversity may respond to climate change. Then they combine these facets to show how biodiversity could respond to novel climatic conditions under alternative paradigms of response.
4
0biomedical
2Review
[ "Ecology" ]
294,601
An electronic search was conducted from the intersection up to January 2020 and updated in December 2020 in the following databases: MedLine through PubMed, Scopus (Elsevier), Web of Science, Latin American and Caribbean Health Sciences Literature (Lilacs) through Virtual Health Library (Bireme), Cochrane Central Register of Controlled Trials (CENTRAL) and Cochrane Database of Systematic Reviews. A manual search was conducted on the included studies and reviews. No restrictions were imposed on the year of publication. The research strategies used in each database are displayed in Table 1.
3
0biomedical
0Study
[ "Research methodology" ]
333,601
In this context, this study aimed to investigate the literature regarding the metallothionein (MT) mediated metal detoxification in Elasmobranchs, allowing for inferences concerning metal excretion capacity or lack thereof, and potential cellular contaminant accumulation.
4
0biomedical
0Study
[ "Toxicology" ]
121,981
We hypothesize that, if the Palv– loops provided by the plethysmograph are free from major artifacts, in expiration the loop should rotate CCW, both in healthy and COPD subjects, as in expiration all the factors potentially responsible for the genesis of the loop induce a CCW rotation. In contrast, in inspiration loops may rotate CW or CCW, because in inspiration the loop-generating factors have opposite effects on the sense of rotation. For the same reasons, we expect the expiratory loop to be bigger than the inspiratory one, especially in COPD patients who may show tidal expiratory flow-limitation at rest, a loop generating factor present only in expiration.
4
0biomedical
0Study
[ "Pulmonology" ]
28,112
In the coastal area of Finland, infectious pancreatic necrosis (IPN) was first reported in 1984 and has occurred annually since 1987 on fish farms without causing severe clinical disease. IPNV isolations were extremely rare in continental Finland until 2012, when the virus was detected at several inland farms . The inland IPNV isolates were demonstrated to belong to genogroup 2 based on partial VP2 sequences showing genetic properties associated with low pathogenicity, and the origin of the isolates appeared to be one or several coastal farms.
4
0biomedical
0Study
[ "Virology", "Aquatic Animal Health" ]
386,683
We chose the JSON Web Token (JWT) approach to save the user information temporally on the frontend. JWT is an encoded string used when the frontend communicates with the server. The benefits of JWT are (i) that it carries a server signature, which must match whenever the user tries to communicate with the server, and (ii) that an expiration date may be set, which implies token refreshing.
1
2other
1Other
[ "Computer Science" ]
16,762
Extensive alluvial fans form at the mouth of most gullies in the study area. Most valleys are covered by alluvial fans, and essentially all previous farmlands have been abandoned. However, some alluvial fans are used as farmland areas by local farmers due to a shortage of agricultural land. This study was conducted to investigate the expansion of seven collapsing gully areas in southern China, including TC, LH, GX, CT, AX, WH and CW. These regions are all experiencing an expansion in collapsing gullies, resulting in the accumulation of alluvial fan sediments. Additionally, four land-use patterns, including farmland, orchard, woodland and grassland, were chosen as areas of focus among the alluvial fans of the collapsing gullies in the study area. All soil types in the study area are granitic red soils (Ultisols). Soil samples were collected from the four different land-use patterns at a total of 28 sampling sites (i.e., 7 locations × 4 land uses). At each of these sites, we removed the litter and selected 10–20 points in the tillage layer in an S-pattern under different land-use patterns. Then, the soil collected from several points was combined into a single sample, and approximately 1–2 kg of soil samples was transferred to the laboratory after a four-way division of all samples. Additionally, bulk density, porosity and soil moisture were determined by using metal cylinders whose volumes were approximately 100 cm3 (5.02 cm diameter and 5.05 cm height).
1
2other
0Study
[ "Geology", "Environmental Science" ]
151,855
Free acidity and peroxide value were within the range normally found for refined oils . In OPOs, values for free acidity were 0.12–0.21% oleic acid and peroxide values were 2.4–3.0 meq O2/kg oil, below the limits established for OPOs, i.e., ≤1% and ≤15 meq O2/kg oil, respectively . In all sunflower oils, values for free acidity were 0.05–0.06% oleic acid and peroxide values were 3.2–6.7 meq O2/kg oil, likewise below the limits established, i.e., ≤0.2% and ≤10 meq O2/kg oil, respectively .
4
0biomedical
0Study
[ "Biochemistry" ]
300,212
miRNAs could inhibit the translation of specific genes by binding to their messenger RNA 3′UTR. Bioinformatics website predicted that there was a target relationship between miR-342-5p and Wnt3a (Fig. 1E). Dual luciferase reporter gene assay reported that in Wnt3a 3′UTR vector-transfected mouse aortic endothelial cells, the renilla/firefly value of luciferase was dose-dependently decreased by transfection with miR-342-5p agomir, with a significant decrease from 10 to 100 pM miR-342-5p agomir and a 64% decrease occurred at 100 pM miR-342-5p agomir group when compared with the NC group. This indicated the presence of a miR-342-5p target site in the Wnt3a 3′UTR. However, the renilla/firefly value of luciferase activity was not affected in the Wnt3a mutation group (Fig. 1F, G). Thus, it could be confirmed that Wnt3a was a direct target gene of miR-342-5p, and miR-342-5p/Wnt3a could regulate AS progression.
4
0biomedical
0Study
[ "Molecular biology" ]
48,643
Indeed the creation of image based segmentation models for surgical treatment planning, visualization of postoperative outcomes or for a further creation of 3D models, remains often an object of research projects without use in the practical routine or is outsourced from the clinical center to the industry as a monetary service because of e.g. personnel resources or employment reasons. This may be the reason because the algorithms presented in that field 1) do often not work stable enough, indeed fail too often or 2) are related to time consuming software processes, 3) complex user unfriendly interfaces, 4) less electronic computer powers and 5) especially to high financial costs if the software is licensed by its manufacturer. This may also be the reason that many of the major manufacturers of medical imaging equipment do not really offer sophisticated segmentation options within their workstation and software packages .
4
0biomedical
1Other
[ "Medical Imaging" ]
326,065
The mineral composition of sour safou, nonsour safou, safou‐fortified, and simple biscuits are presented in Table 6. Potassium is the most abundant mineral in safou (0.819 g/100 g) followed by magnesium, phosphorus, and calcium with sodium being the least. Iron was the most abundant trace mineral in safou (22.6 ppm) followed by copper, manganese, aluminum, and zinc. In rice biscuits, potassium was still the most abundant mineral (0.166 g/100 g) followed by phosphorus. Although trace minerals iron and zinc are higher in biscuits than in safou, there was a higher quantity of aluminum in biscuits (214.8 ppm) than in safou. The quantity of aluminum recorded in biscuits produced in this study was similar or lower to that recorded for other biscuits (Diet Grail, 2020). Aluminum in the food supply comes from natural sources including water, food additives, and contamination by aluminum utensils and containers. The daily intake of aluminum varies greatly from 0 to 0.095 g, and the real question is not the amount of aluminum in foods but the availability of the aluminum in foods and the sensitivity of some population groups to aluminum (Greger, 2007). Potassium is a mineral and an electrolyte that the body needs to work properly. Potassium is a very important mineral for the human body as it is needed to build proteins, break down and use carbohydrates, build muscle, maintain normal body growth, control the electrical activity of the heart, and control the acid–base balance. The required daily intake (RDI) is age depended—generally 0.4–0.8 g/day for infants, 2–2.3 g/day for adolescent, and 2.6–3.4 g/day for adult (United State Department of Agriculture (USDA), 2020). Iron is a mineral found in every cell of the body. Iron is considered an essential mineral because it is needed to make hemoglobin, a part of the blood cell. The human body needs iron to make the oxygen‐carrying proteins hemoglobin and myoglobin. Hemoglobin is found in red blood cells, and myoglobin is found in muscles. The RDI is age‐ and sex‐dependent—except for infants younger than 6 months whose recommended intake is 0.00027 g/day, the recommended intake is generally between 0.007 and 0.018g/day (USDA, 2020). Zinc is found in cells throughout the body. It is needed for the body's defensive (immune) system to properly work. It plays a role in cell division, cell growth, wound healing, and the breakdown of carbohydrates. Zinc is also needed for the senses of smell and taste. During pregnancy, infancy, and childhood, the body needs zinc to grow and develop properly (Jarosz, Olbert, Wyszogrodzka, Młyniec, & Librowski, 2017). Zinc also enhances the action of insulin and is a potent inhibitor of coronavirus and arterivirus replication (te Velthuis et al., 2010). The RDI is also age‐ and sex‐dependent—generally, 0.002–0.008 g/day for infant and children and 0.011–0.013 g/day for adolescent and adults (USDA, 2020). In cereals such as rice and wheat, zinc bioavailability is depressed by phytic acid. Thus, the biscuits produced can be a good source for potassium, phosphorus, iron, and Zn for different age and sex groups.
4
0biomedical
0Study
[ "Nutrition" ]
203,918
All patients, except one who refused, underwent brain MRI examinations, which revealed only mild subcortical white matter T2 hyperintensities, likely of vascular etiology. In one of the subjects, a swallow-tail sign at the level of substantia nigra was revealed. A DaT scan was performed on all 4 subjects with pathological findings.
4
0biomedical
0Study
[ "Neurology" ]
126,022
Chondrocytes are often chosen as seed cells, but the tissue sites for obtaining them are limited and vulnerable to injury. Chondrocytes used in cartilage tissue engineering have low immunogenicity, but isolation methods are complex and less well developed than those for MSCs (Francis et al., 2018a)—and considering their multi-directional differentiation potential, MSCs are often preferred (Aggarwal and Pittenger., 2005). In addition, MSCs can inhibit inflammation in scaffolds implanted in vivo, and reduce damage resulting from foreign body reactions (Ding et al., 2016).
4
0biomedical
0Study
[ "Tissue Engineering", "Cell Biology" ]
28,512
The SHTs are applied in every 3–4 years, depending on the specific crop-rotation scheme. This frequency is to reach the best cost-effective treatment that can be applied by farmers. Since the beginning of the experiment (2006), the Soil Health Treatments (SHTs) were applied two times until 2013, the year in which the soil sampling for this study was performed. From the end of July 2006 till May 2007, nine different SHTs were applied (Table 1). The SHTs were applied for the second time from the end of July 2009 till December 2009 as described for 2006.
1
2other
0Study
[ "Environmental Science", "Agriculture" ]
351,972
According to the analysis of the MF terms among the hub genes, MMP14, THBS2, CDH11, FBN1, LTBP1, MATN3, and VCAN were jointly involved in calcium ion binding, which is defined as selective and non-covalent interactions with calcium ions (Ca2+). Ca2+ is a ubiquitous and versatile second messenger involved in the regulation of numerous cellular functions, including gene transcription, vesicular trafficking, and cytoskeletal rearrangements (Nunes-Hasler, Kaba & Demaurex, 2020). Ca2+ and Ca2+-regulating proteins contribute to a large number of processes that are key to cancer cells, including proliferation, invasion, and cell death (Monteith, Prevarskaya & Roberts-Thomson, 2017; Prevarskaya, Skryma & Shuba, 2011). A high serum Ca2+ level is associated with a poor prognosis in PDAC (Dong et al., 2014), and cytosolic Ca2+ overload triggers apoptotic death pathways (Brini & Carafoli, 2009). It is thus reasonable that the seven abovementioned genes might regulate calcium ion binding and affect the development of PDAC. Furthermore, our study suggests that MMP14 is a promising biomarker for survival in PDAC. Considering that Ca2+ cannot be produced in cells but undergoes flux between intracellular calcium storage, cytosolic calcium signals, and the extracellular calcium pool (Yang et al., 2020), it would be reasonable to hypothesize that the overexpression of MMP14 influences calcium ion storage and thus might cause disorders of calcium homeostasis and hence contribute to an unfavorable prognosis in PDAC patients.
4
0biomedical
0Study
[ "Oncology" ]
337,621
Pyroptosis is an inflammatory form of programmed cell death that is triggered following infection with intracellular pathogens and may contribute to the innate immune response [1, 2]. At the molecular level, it begins with the recognition of the pathogen-associated molecular patterns (PAMP) or damage-associated molecular patterns (DAMP) by the pattern recognition receptor (PRR) on the host immune cells, which then induces the inflammasome pathway . The latter cleaves caspase-1, which in turn cleaves the downstream caspases (caspase-4/5 in humans and 11 in mice), as well as the prointerleukin-1 beta (IL-β) and IL-18 into their active forms. This eventually triggers the caspase-mediated pyroptotic cascade and releases high levels of the inflammatory cytokines IL-1β and IL-18 (Figure 1, the red arrow).
5
0biomedical
0Study
[ "Immunology" ]
293,112
The high-energy trauma includes MVC, pedestrian hit by a car and falling from height results in pelvic fracture of immature bone in children and is an indicator of the presence of associated injuries [18, 19]. The present study observed traffic accidents as the most common mechanism of injury which is similar to that of the adult pelvic fracture patients ; a finding that was reported by several earlier studies [4, 9, 10, 18, 19].
3
0biomedical
0Study
[ "Orthopedic Trauma" ]
341,417
M15 strain was grown in the presence of different carbon sources, in order to explore as them affect the RLs mixture composition. Moreover, the ability to produce RLs from petroleum derivate hydrocarbons, both aromatic and aliphatic, as sole carbon source was also explored in a bioremediation context.
3
0biomedical
0Study
[ "Microbiology", "Biotechnology" ]
149,659
The results shown in Table 4 are relatively different from the previous two tables. Text data representations from BERT could not outperform TFIDF, when used in both DEC and IDEC models. While in KM and EFCM, representation from BERT followed by mean pooling and layer normalization or standard normalization have the best performance with TFIDF still have a competitive performance.
2
2other
0Study
[ "Bioinformatics" ]
154,515
Due to the growth of streaming broadcasting via the Internet, it is standardized to perform streaming of movies by using the MPEG format. The format provides encoding methods with the frequency-based compression mentioned above and another method in the timeline direction. The key frame is introduced in the format, which is a compressed full frame image data. The format encodes multiple frames in the timeline direction by extracting the differences of pixel color information from the key frame. The method provides techniques to compliment the differences based on the visual nature that human eyes do not sense precisely the high-frequency parts of scenes. Therefore, the format reduces the color information between the key frames. The motion detection techniques (e.g., ) help to compliment the color and luminance information to chase changes of color pixels in video using vectors derived from the color changes. This technique results in a good compression ratio in the encoded movie data. Thus, the methods explained above can transfer the movie via an unstable communication data path by controlling throughput of the compressed data size.
1
2other
1Other
[ "Computer Science", "Information Technology" ]
290,550
To perform a clinical trial in patients with critical illness in the pre-hospital environment is challenging. The balance between patient safety and autonomy and the need to ensure the safety and efficacy of medical interventions prompts the need to conduct well designed randomised trials. The present study is designed to balance these concerns. Informed consent prior to randomisation is impossible in unconscious patients. REBOARREST have received ethical approval to include patients with deferred consent. Next-of-kin will be asked for deferred consent after a patient is admitted to hospital or declared dead at the scene. Patients who regain the capacity to provide informed consent within 3 months will be asked for renewed deferred consent. Patients may withdraw from the study at any time without the need for a rationale and without compromising their medical care. If the patient has not regained ability to provide consent, the next-of-kin can withdraw the patient from the study at any time. Data on adverse events registered for patients who withdraw from the study will be stored in the database in an anonymized form to ensure that no safety information is lost.
4
1clinical
1Other
[ "Emergency Medicine", "Critical Care" ]
171,447
Serum samples were pooled to a total volume of 140 µL (5 sera/pool; 28 µL per serum). Total RNA was extracted using the QIAamp Viral RNA Mini Kit (QIAGEN) according to the manufacturer’s instructions. RT-qPCRs were performed on a Rotor-Gene Q cycler (QIAGEN) using the Luna Universal Probe One-Step RT-qPCR Kit (NEB). LindaV as well as BungoV specific primers and probe were used as previously described . Sera of positive pools were extracted separately using 140 µL of each serum and again analyzed in RT-qPCR. The housekeeping gene beta-actin was used as an internal control for proof of successful RNA extraction and the absence of inhibitory factors in RT-qPCR. Amplification of beta-actin was conducted in a separate RT-qPCR run using the primers beta-actin-F1 (5′-CAGCACAATGAAGATCAAGATCATC-3′), beta-actin-R2 (5′-CGGACTCATCGTACTCCTGCTT-3′) and the probe beta-actin-HEX (5′-HEX-TCGCTGTCCACCTTCCAGCAGATGT-BHQ-1-3′) under the same cycling conditions used in the LindaV RT-qPCR.
4
0biomedical
0Study
[ "Virology", "Molecular Biology" ]
221,456
Nissl staining was performed to visualize the Nissl bodies to determine the morphological and pathological changes in the brain neuronal structure . In brief, the slides containing brain tissue were washed with water, to remove the salt’s residue, and stained for 8–10 min with the warm cresyl violet solution (0.5%), supplemented with a few drops of glacial acetic acid. The slides were quickly rinsed with MilliQ water to remove excess stain and then progressively dehydrated in 70, 95, and 100% ethyl alcohol for 15 min. The brain slices were then cleared twice in xylene, for 5 min each, before being mounted with a non-fluorescence permanent mounting medium and a coverslip. For morphological visualization, TIF images were acquired with a fluorescence optical light microscope, and the number of surviving neuronal cells in the hippocampi and cortices area was analyzed with ImageJ software.
4
0biomedical
0Study
[ "Neuroscience" ]
142,623
GLP-1RAs may exert beneficial actions on the kidneys through reductions in blood glucose, blood pressure, and weight, as well as via possible direct cardio-nephroprotective mechanisms, such as improved endothelial dysfunction, reduced oxidative stress, and reduced inflammation (62). The phase III FLOW trial (NCT03819153) is ongoing to determine the effect of once-weekly subcutaneous semaglutide 1.0 mg vs. placebo on the progression of renal impairment in over 3,000 patients with T2D and CKD (eGFR 50–75 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio [UACR] >300–<5,000 mg/g or eGFR 25–50 mL/min/1.73 m2 and UACR >100–<5,000 mg/g) (67). The primary endpoint is the time to the first occurrence of a composite primary outcome event, defined as persistent eGFR decline of ≥50% from trial start, reaching ESRD, death from kidney disease, or death from CVD for up to 5 years.
4
0biomedical
0Study
[ "Nephrology", "Endocrinology" ]
84,381
Data are expressed as the mean ± standard deviation. Differences between groups were analyzed using the Kruskal–Wallis test and analysis of variance (ANOVA). A P value less than 0.05 was considered significant. SPSS software (version 20.0) was used for all statistical procedures.
3
0biomedical
0Study
[ "Biostatistics" ]
361,525
Weighted prevalence of stunting and severe stunting among children by regions in Ethiopia, 2016. The map was created by the author(s) using ArcGIS version 10.3 (URL: https://www.esri.com/software/arcgis). The red color coded bars indicate the prevalence of severe stunting (< − 3 SD), the yellow color coded bars indicate the prevalence of stunting (< − 2 SD), while the green color coded bars indicate the non-stunted children.
2
0biomedical
1Other
[ "Nutrition", "Epidemiology" ]
81,301
(A) TIRF imaging of BFP-Sec61β and lyn-mCherry in WT U2OS cells and GRAMD2a KO cells. Total pixels of cortical ER were divided by total area of cells, judged by total staining of lyn-mCherry, to determine % cortical ER at PM. Standard Error shown. (B) PM PI(4,5)P2 distribution was examined using YFP-PH-PLCδ1 in U2OS wild type and GRAMD2a KO cells. Sample images are in shown in left panel. Line scans are shown in middle panel. Y-axis of line scans are arbitrary fluorescence units. % intensity of YFP-PH-PLCδ1 at PM is shown in right panel. (C) Distribution of cholesterol marker mCherry-D4H in wild type U2OS and GRAMD2a KO cells. Line scans are shown in bottom panel. Y-axis of line scans are arbitrary fluorescence units. (D) Distribution of cholesterol-binding protein Cav1-GFP in wild type U2OS and GRAMD2a KO cells. Both PM (cell surface) and internal (cross-section) planes are shown.
4
0biomedical
0Study
[ "Cell Biology" ]
125,344
PBL is an exceptional breast malignancy in the pediatric age; in literature, there are 11 case reports on this topic (Table 2) [9–19]. Although in other studies [20–25] some PBL patients aged from 15 years were reported, it was not possible to include these children in our review because no detailed information was presented. From the analysis of these 12 well-described pediatric patients (Table 3), it can be deduced that PBL mainly affects female adolescents (median and mean age 14.5 and 14.2 respectively) with only one 11-year-old boy; as in adulthood, there is a slight predominance of the right breast (6 out of 10 patients for whom the data are available), with only 1 girl showing bilateral involvement . Table 2Main features of pediatric PBL patients reported in the literature and our caseReferenceAge/SexSideSize (cm)StageHistologyTreatmentOutcome (from onset)Dixon et al. 1987 17y/FNA2NANHL unclassifiedSurgery + RTCR, 25 yearsBoothroyd et al. 1994 11y/FRightNANAB-cell NHLCTCR, 36 monthsRogers et al. 1994 14y/FNA8 x 7IIELBLCTCRAguilera et al. 2000 13y/FLeft6 x 6IEALCL ALK +SurgeryDeadBarista et al. 2000 17y/FRightNAIIEDLBCLCHOP + RTCR, 57 monthsAbdullah et al. 2004 15y/FLeft5IEALCL ALK +CT (cyclophosphamide, prednisolone)CR, 22 yearsLingohr et al. 2009 12y/FBilateralNANABLSurgeryDeadDaneshbod et al. 2010 16y/FRightNAIIEALCL ALK +CHOPDeadIshizuka et al. 2020 14y/FRight4IELBLCT (ALL, not specified trial)CR, 8 monthsCharfi et al. 2020 16y/FLeftNAIIEALCL ALK +CT (doxorubicin, bleomycin, vincristine, dacarbazine)CR, 24 monthsOral et al. 2021 11y/MRight3.5 x 1.7IELBLSurgeryNAOur case15y/FRight6.5IIEDLBCLCT (AIEOP LNH-97 trial)CR, 20 monthsAbbreviations: years; NA: not available; RT: radiotherapy; CR: complete remission; LBL: lymphoblastic lymphoma; CT: chemotherapy; ALCL: anaplastic large cell lymphoma; ALK: anaplastic lymphoma kinase; DLBCL; diffuse large B-cell lymphoma; CHOP: cyclophosphamide + doxorubicin + vincristine + prednisone; BL: Burkitt lymphoma; ALL: acute lymphoblastic leukemiaTable 3Main features of pediatric PBL patients sorted by frequencyN°12Frequency (%)Age (years)Median/Mean14.5/14.2-SexFemale1191.7Male18.3SideUnilateral975Bilateral18.3Unknown216.7Size≤ 5 cm433.3> 5 cm325Unknown541.7HistologyALCL433.3LBL325DLBCL216.7BL18.3B-cell NHL18.3NHL unclassified18.3StageIE433.3IIE541.7Unknown325Local treatmentSurgery only325Surgery + RT18.3ChemotherapyCT only758.3CT + RT18.3OutcomeCR866.6Dead325Unknown18.3Abbreviations: ALCL: anaplastic large cell lymphoma; DLBCL: diffuse large B-cell lymphoma; BL: Burkitt lymphoma; LBL: lymphoblastic lymphoma; LNH: non-Hodgkin lymphoma; CT: chemotherapy; RT: radiotherapy; CR: complete remission
5
0biomedical
2Review
[ "Oncology" ]
172,397
We tested neutralization of B.1.617.1 and B.1.617.2 using serum from individuals who had received 2 doses of the BNT162b2 Pfizer-BioNTech or ChAdOx1 nCoV-19 Oxford-AstraZeneca vaccine (Polack et al., 2020; Voysey et al., 2021). For Pfizer-BioNTech, serum was collected 4–14 days following the second dose of vaccine, administered 3 weeks after the first dose (n = 25). For the Oxford-AstraZeneca vaccine, serum was taken 14 or 28 days following the second dose, administered 8–14 weeks following the first dose (n = 25). Geometric mean neutralization titers against B.1.617.1 were reduced 2.7-fold (p < 0.0001) relative to the Victoria virus for the Pfizer-BioNTech vaccine serum (Figure 7A; Figure S5; Table S3) and 2.6-fold (p < 0.0001) for the Oxford-AstraZeneca vaccine (Figure 7B). For B.1.617.2, titers were reduced 2.5-fold (p < 0.0001) relative to the Victoria virus for the Pfizer-BioNTech vaccine serum (Figure 7C) and 4.3-fold (p < 0.0001) for the Oxford-AstraZeneca vaccine (Figure 7D). For B.1.617.2, reductions were comparable with those seen with B.1.1.7 and P.1 (Supasa et al., 2021; Dejnirattisai et al., 2021b), with only a small number of samples failing to reach FRNT50 titers at 1:20 serum dilution, in contrast to the results seen for neutralization of B.1.351 (Figure S4).Figure 7Neutralization by vaccine serum and mapping variants in antigenic spaceFor the Pfizer vaccine, serum (n = 25) was taken 7–17 days following the second dose of the Pfizer-BioNTech vaccine. For the AstraZenca vaccine, serum was taken 14 or 28 days following the second dose of the Oxford-AstraZeneca vaccine (n = 25).(A) NT50 titers of Pfizer-BioNTech serum against B.1.617.1-B pseudovirus.(B) FRNT50 titers of Oxford-AstraZeneca serum against B.1.617.1-B pseudovirus.(C) FRNT50 titers of Pfizer-BioNTech serum against B.1.617.2 virus.(D) FRNT50 against of Oxford-AstraZeneca serum against B.1.617.2 virus.(A–D) Comparison is made with Victoria pseudo virus (A and B) or wild-type Victoria, B.1.1.7, B.1.351, and P.1 (filled squares), reported previously (Supasa et al., 2021; Zhou et al., 2021; Dejnirattisai et al., 2021b) (C and D).Subsequent panels analyze responses following a single dose of Pfizer vaccine. Serum (n = 20) was taken 28 or 70 days following the first dose of the Pfizer-BioNTech vaccine.(E and F) Comparison of FRNT50 titers for individual samples obtained 28 or 70 days after the first dose against Victoria or B.1.617.2.(G and H) Comparison of percent virus neutralization at serum dilution of 1:20 against SARS-CoV-2 Victoria and B.1.617.2 strains. Mean values are indicated above each column.(E–H) Mann-Whitney unpaired test was used for the analysis in (E) and (G). Wilcoxon matched-pairs signed rank test was used for the analysis in (F) and (H).(I) Map of variants in antigenic space. Wall-eyed stereo pair plots show output of principal-component analysis converting serum/virus strain pair neutralization capacities to antigenic space. Circle size denotes depth along the axis connecting the reader’s nose to the origin. See also Video S1.(J) Positions and charge effects of RBD mutations found in variants of concern. Shown is an incoming ACE2 view of the surface of the RBD, with the footprint of ACE2 shown in green and mutations occurring in variants, including B.1.1.7, P.1, P.1.351, B.1.617.1, and B.1.617.2, shown in a range of other colors.Figure S5Neutralization curves against SARS-CoV-2 pseudotyped lentiviruses expressing full-length S of Victoria and B.1.617.1 strains by serum from 25 recipients of the Pfizer-BioNTech vaccine and Oxford-AstraZeneca vaccine, related to Figure 7FRNT50 titers given in Table S4.Figure S6Neutralization curves against authentic SARS-CoV-2-Victoria, B.1.1.7, B.1.351, P.1, and B.1.617.2 strains by serum from 25 recipients of the Pfizer-BioNTech vaccine and Oxford-AstraZeneca vaccine, related to Figure 7FRNT50 titers given in Table S4.
5
0biomedical
0Study
[ "Immunology", "Virology" ]
244,869
Since synapsis initiates at the ends of chromosomes and then “zippers-up” the remaining unpaired regions, it is not surprising that some chromosomal segments would become trapped between another set of homologs to form entanglements or interlocks as seen in many species (Zickler and Kleckner, 1999). Since it is not uncommon to see these structures at the late zygotene and early pachytene stages, it appears to be a distinct stage that has been termed the interlock stage. Nuclei in the interlock stage are distinguished from the late zygotene stage since they frequently contain individual pairs of chromosomes with extensive or even complete de-synapsis (Figure 2J; Blokhina et al., 2019). Since these de-synapsed chromosomes do not have evident crossovers, this stage is presumably distinct from the diplotene stage, though future work to definitively distinguish these stages is warranted. An interesting avenue of research will be to determine how interlocks and entanglements are removed and how synapsis is reestablished. Recent work in the plant Arabidopsis shows increased levels of entanglements in strains where expression of Topoisomerase II is knocked down using RNAi (Martinez-Garcia et al., 2018). In many species, including zebrafish, the zygotene stage is marked by substantial telomere-led movement via cytoskeletal motor proteins. It has been proposed that these movements may function in part to remove entanglements or interlocks (Koszul and Kleckner, 2009; Elkouby et al., 2016; Burke, 2018; Mytlis and Elkouby, 2021).
4
0biomedical
0Study
[ "Genetics", "Cytogenetics" ]
306,065
To test if the rat model is successfully established, blood pressure was measured at different time points. Compared with the sham group, the blood pressure (SBP and DBP) (Table 1) was increased, and the difference was statistically significant (P < 0.05). LVMI was also calculated. As shown in Table 2, LVMI in the MH model group was significantly increased than that in sham group (P < 0.05). However, there was a significant decrease in LVMI of the MH+aspirin group than that of the MH model group (P < 0.05). These showed that the model rats with MH were successfully established.
4
0biomedical
0Study
[ "Cardiology", "Pharmacology" ]
271,951
The epipolymorphism score of 3′UTR CpGs 10–15 was positively correlated with age in the motor cortex of the controls (Fig. 6e, Supplementary Fig. 5), which is consistent with the age-related increase in the heterogeneity of DNA methylation36. In addition, the methylation-linkage diagram of the two youngest (middle-aged) and two oldest (elderly) individuals showed generally lower pairwise correlations in the elderly individuals (Fig. 6f, g), suggesting stochastic demethylation of the epialleles with aging37 rather than regulated demethylation by specific enzymes (Fig. 6h).
4
0biomedical
0Study
[ "Epigenetics" ]
311,512
Hysteresis and bistability. (a) Metal ball on a double-welled landscape driven by a magnet: analogy for a bistable system, see text for explanation. (b) Metal ball on a flat landscape driven by a magnet: analogy for system that has lost bistability, see text for explanation. (c) Example bistable plot with hysteresis, showing the response variable ball position (BP) as a function of the driving variable magnet position (MP). Of note is the ‘gap’ between the dynamics of BP as MP is moved left (blue line) and the dynamics of BP as MP is moved right (red line)—a typical characteristic of systems with hysteresis. (d) BP dynamics as a function of MP in an example scenario where there is no bistability or hysteresis. Note how the state variable BP linearly responds to the driving variable MP. (e) When this analogy is applied to Notch selection in ECs, the two stable valleys in the landscape correspond to the tip and stalk states, and the barrier between them is hypothesized to be caused by filopodial activity. The external magnetic driving force is analogous to the external Dll4 received by the cell from its neighbours. (f) In the case of normal filopodia, the landscape is hypothesized to have a double well. In this case, we expect the dynamics to resemble those in (c). (g) In the case of reduced filopodial activity (LOF), the landscape is hypothesized to flatten. In this case, we expect the dynamics to resemble those in (d). (Online version in colour.)
5
0biomedical
0Study
[ "Cell Biology" ]
65,984
A. Heatmap of the expression of genes altered > 2-fold (p < 0.05) by estrogen treatment, based on microarray analysis performed on estrogen-deprived MCF7 cells treated with either 10 nM estradiol (E2), 2.5 µM Senexin A (SNXA) or a combination of E2 and Senexin A (E2+SNXA) for 12hr. B. q-PCR validation of estrogen regulated genes in MCF7 cells treated with E2 (10 nM) and Senexin A (2.5 µM) for 12 hours. * denotes P < 0.05 and ** denotes P < 0.01.
4
0biomedical
0Study
[ "Molecular Biology" ]
37,371
Despite increasing number of digital health technologies for seizure management, we are not aware of development of mobile medical apps intended to reduce frequency of seizures in epilepsy patients. Our survey suggest that about two-thirds of PWE could see themselves using such mobile software for at least several months. Patients preferred automated features for different aspects of seizure and disease management, and were also interested in the relaxation features of the app. One interesting finding was that our subjects' interest was more in passively listening to music than actively using imagery. They were also more interested in playing games or puzzles, as compared to writing or drawing while listening to music. We concluded that in our subject population there was less interest in relaxation techniques that used mental creativity (drawing, writing or using imagery). There was more interest in relaxation techniques consisting of observation (practicing mindfulness) or immersing passively by listening to music, or engaging reactively in puzzles and games, as compared to those techniques involving mental creativity. The reasons for preferences toward more passive activities are not clear at this time, but it may be that such relaxation techniques might increase brain stem parasympathetic activity, which in turn may have some anti-seizure effects. Bodner and colleagues reported that antiseizure music was also effective in reducing seizures when delivered during sleeping (Bodner et al., 2012), suggesting that for PWE who favor less engagement there are opportunities to develop more passive strategies (like streaming antiseizure music during sleep).
4
0biomedical
0Study
[ "Neurology" ]
114,566
The doxorubicin-induced DCM rat model used in this study developed ventricular enlargement associated with impaired contractility and elevation in BNP and cTNI, consistent with the clinicopathological profiles of DCM. Echocardiography examination showed that intramuscular injection of hUCMSCs improved the myocardial contractility of the DCM rats as evidenced by elevated LVEF and LVFS. In addition, the markers for cardiac function (BNP and cTNI) were decreased in the DCM rats after hUCMSC treatments. These results suggest that intramuscular injection of hUCMSCs improved cardiac function of DCM and attenuated DCM-triggered heart failure. While intramyocardial injection of UCMSCs at similar dosages has been reported to promote tissue repair for heart attack-induced damage [18, 19], the current study using intramuscular injection has provided by far a more preferred choice due to its minimum invasiveness.
4
0biomedical
0Study
[ "Cardiology", "Stem Cell Biology" ]
126,746
As a preliminary conclusion, the DLPFC seems to be engaged in those aspects of language processing that exceed simple, rule-based, and highly automatized mechanisms of phonological, syntactic, and lexical–semantic processing. Such aspects come into play in case of certain stylistic features and in complex situations when language processing approaches its limits, for example, in case of ambiguity, novel, or nonliteral meanings, or garden path structures, when extra-linguistic cues have to be integrated, or when a speaker has to change into a different language. Thereby, the DLPFC seems to be important for controlling temporary functional connectivity patterns, for cognitive switching, and also for acting as part of an emergency brake if the ongoing process of language communication approaches a “dead end.” Maybe the key to an understanding of the role of the DLPFC in language processing can be found in the communication impairments in cases of frontal brain lesions and psychiatric disorders. In these cases, the major problem might be a disconnection syndrome in which various memory systems cannot be synchronized and mutually updated, resulting in lacking executive semantic functions that integrate extra-linguistic information and task demands into language processing.
5
0biomedical
0Study
[ "Neuroscience" ]
247,185
The following LUS findings were assessed: normal lung; thickness and appearance of the hyperechoic pleural line; presence/absence of B-lines; presence/absence of consolidations; presence/absence of subpleural nodules; and presence/absence of pleural effusion.
4
0biomedical
0Study
[ "Pulmonology" ]
204,231
There are several strengths that should be highlighted in the present study. One of the main strengths is the inclusion of device-based measures of PA and sedentary behavior through ActiGraph GT1M accelerometer devices, thus overcoming one of the most common limitations observed in this research . Apart from BMI, we reported additional adiposity indicators such as fat mass percentage and FMI, which have been less studied in longitudinal research with environmental and PA factors . Changes in adiposity were classified according to relevant changes (i.e., Cohen’s d), which avoids a substantial loss of information in comparison with traditional overweight/obese classifications and provides information about the interindividual variation in our sample . We provided a multidimensional perspective on this research topic by integrating a wide variety of intrapersonal, built environmental, and PA and sedentary behavior variables together that have been related to adiposity gain . Our homogeneous sample of older women allowed us to focus on a population that has received less attention in the literature and that is experiencing a worrying increase in adiposity .
4
0biomedical
0Study
[ "Epidemiology" ]
4,272
All the studies identified in this review were animal studies so we are cautious about drawing conclusions from different species using different methods on the potential of the solutions to cause damage in human subjects. In studies conducted on guinea pigs and chinchillas the main hypothesized method of inner ear penetration for solutions is through the round window. The Chinchilla round window membrane is 1/6 of the thickness of that of humans therefore this model is likely over estimating ototoxicity in humans .
4
0biomedical
2Review
[ "Otology" ]
139,454
Differentiation into mature moMΦ was induced using a modified protocol based on Carlson et al., 2016 and Carlson et al., 2020 . Briefly, one day after isolation, cells were washed three times with PBS before treatment with 5 ng/mL GM-CSF (KingFisher Biotech, Saint Paul, USA, #RP0940S) applied in fresh culture medium.
4
0biomedical
0Study
[ "Immunology" ]
144,333
Response: Information regarding the features of SETAF has been described in our Methods section under ‘Setting and sample’ (line 120-129) and summarised in Table 1. The patients were encouraged to explore all the features, however the research team did not dictate how they should do so in order to capture their actual usage behaviour. The patients’ actual usage behaviour was described in our Results section (line 382-405)
1
0biomedical
0Study
[ "Health Informatics" ]
32,914
Auxin is a phytohormone responsible for the regulation of tropic responses, cell division and elongation, root and shoot differentiation, development of the vascular system, abscission, senescence, and flowering in plants1. In addition, this hormone acts as a messenger for abiotic and biotic stimuli1. Indole-3-acetic acid (IAA) is the most abundant form of this phytohormone2. Gordon et al. showed the association of auxin with globulin and proteose seed proteins3. The level of free auxin in tissues is regulated via three basic mechanisms: synthesis, inactivation, and transportation4. IAA exists in a free state (active form) or in conjugated form with ester or amide forms, peptides, and proteins5. The auxin ester conjugates are the major inactive form of auxin found in seeds and storage organs of monocots, whereas amide conjugates are found in dicots6, 7. Auxin conjugated proteins have been identified in seeds of Phaseolus vulgaris, Arabidopsis thaliana, Pisum sativum and Fragaria ananassa 8. The conjugation of auxin and protein depends on the particular protein, as well as on the particular plant species9.
4
0biomedical
0Study
[ "Plant physiology" ]
394,763
Low-resolution 3C methods, such as Hi-C3 and its derivatives, use a 6-bp cutting enzyme to generate genome-wide interaction maps, with the standard experiment generating 10–50 kb resolution2. Higher-quality profiles can be achieved through combinations of massively increased sequencing, use of a 4-bp cutter, targeted enrichment (e.g., Capture Hi-C4 [CHi-C], often called Promoter Capture Hi-C), and increased cell numbers. The prohibitive costs mean that such datasets rarely include sufficient number of replicates for robust statistical analysis and are not applicable to rare primary cell types due to the requirement for high cell numbers. Conversely, sub-kilobase resolution can be achieved by methods which enrich for target loci in 4-base cutter libraries; e.g., Capture-C5, 4C-seq6,7, and their derivatives. The current best high-resolution 3C method for sensitivity is NG Capture-C, with 10,000–100,000+ unique interacting reporter reads per viewpoint2,8. NG Capture-C achieves its high resolution and sensitivity using biotinylated oligonucleotide pull-down of target loci from 3C material. The use of sequential enrichment, or double capture, results in 30–50% on-target sequencing, an 160-fold increase over the initial Capture-C method5,8.
5
0biomedical
0Study
[ "Genomics" ]
58,803
We also confirmed an association between the duration of neutropenia (lasting >30 days) and risk of IFI. Neutrophils play an important role in the control of fungal infection. With an increased proliferation of leukemia cells in the bone marrow, production of normal neutrophils declines. Lack of neutrophil recovery usually indicates refractory acute leukemia. Brazilian researchers have developed an index (the D-index) that combines duration and severity of neutropenia and successfully predicts different risks for invasive mold infection in febrile neutropenic patients (33). This index was not available for us to apply at the start of induction therapy. Moreover, baseline neutrophil counts could not predict the onset of IFI in our analysis.
4
0biomedical
0Study
[ "Hematology", "Oncology" ]
299,333
The distinctive cell lineage fates of both MSC populations are clearly reflected by the transcriptome. In pMSCs, enriched genes are linked to a function in cytoskeleton, cell growth, and particularly in negative regulation of BMP signaling and fibroblast proliferation, indicating their elevated fibrogenic cell fate. In fact, our in vitro studies showed the differentiation of pMSCs to fibrogenic cells which might indicate that pMSCs play a role in fibrosis of the pancreas, e.g., in the development of pancreatitis. Due to the expression of genes related to a positive regulation of fat cell differentiation, pMSCs are principally able to become adipocytes. The IPA (Ingenuity Pathway Analysis) detected 8 genes which are more abundant in pMSCs than in iwatMSCs, and which are organized in an adipocyte-specific network. These genes include the transcription factor Isl1 (insulin gene enhancer binding protein 1) which was shown to be markedly but transiently upregulated in 3T3-L1 cells shortly after the initiation of differentiation. Its overexpression during early differentiation suppressed Pparg expression and inhibited adipogenesis . Tcf4 (transcription factor 4) is involved in Wnt signaling and forms a complex with β-catenin . Interestingly, treatment of cardiac stem cells with high glucose concentrations inhibited the β-catenin/TCF4 pathway and promoted adipogenesis . Therefore, it is conceivable that hyperglycaemia of NZO mice inhibits the expression of Tcf4 in pMSCs, which could ultimately induce their differentiation to adipocytes. Transcripts of two fibroblast growth factors, Fgf1 and Fgf2, are higher expressed in pMSCs than in iwatMSCs and both are involved in the regulation of fat cell differentiation. FGF1 promotes adipogenesis in preadipocytes by increasing the expression of Pparg . In contrast, FGF2 rather inhibits adipogenesis because treatment of proliferating preadipocytes with FGF1 reduced the Fgf2 expression markedly, leading to decreased proliferation and increased expression of adipogenic marker genes . Thus, the fact that both Fgf1 and Fgf2 are expressed at higher levels in pMSCs might explain why their adipogenic cell fate is lower than that of iwatMSCs.
4
0biomedical
0Study
[ "Stem cell biology" ]
198,794
The BC clinical tissues and their corresponding normal adjacent tissues (N = 30) were collected in the 3rd Affiliated Teaching Hospital of Xinjiang Medical University (Affiliated Cancer Hospital) from 2014 to 2018, and the above tissues were stored at – 70 ℃ conditions immediately. The participates did not accept any treatments before surgical resection. All the clinical experiments were approved by the Ethics Committee of the 3rd Affiliated Teaching Hospital of Xinjiang Medical University (Affiliated Cancer Hospital), and the informed consent had been obtained from all the participants.
3
0biomedical
0Study
[ "Oncology" ]
84,616
Functional analyses conducted on LRR-RLK genes over the last twenty years raveled the role of the domains located in the ECD of these receptors. The LRR domains are highly versatile in number allowing a whole range of protein-protein interactions. These include homo- or hetero-dimerization of receptors, in addition to ligand binding. Furthermore, some LRR-RLK receptors possess island domains – devoid of LRRs – located between LRR motifs (Li and Chory, 1997). They were identified in the BRI1 receptor as the binding site for the brassinosteroid (BR) hormone (Kinoshita et al., 2005; Hothorn et al., 2011; She et al., 2011). Few studies have also described the functions of other ECD domains. For example, two Cys-pair have been reported. The first one is located in the N-terminal part of the LRR-RLKs, approximately 60 AA from the start codon between the SP and the first LRRs. The second one – if present – can be found between the last LRR and the TM domain (Dievart and Clark, 2003). Mutations in the Cys-pairs have been shown to affect the function of some LRR-RLKs, e.g., FLAGELLIN SENSING 2 (FLS2), a gene participating in the perception of the bacterial elicitor flagellin. However, there is also an example of a LRR receptor like protein (CLAVATA 2) for which mutations in Cys-pairs had no effect on the function of protein - at least in the meristem and roots (Noguchi et al., 1999; Song et al., 2010; Sun et al., 2012). In BRI1, a mutant harboring a mutation in Cys-pairs appears to be functional but seems to be retained in the endoplasmic reticulum and degraded. This suggests that this mutant protein does not pass the endoplasmic reticulum quality control (Hong et al., 2008). Although no general conclusions can be drawn so far on the importance of this motif, all the variations observed in Cys-pairs likely play a role in the folding, trafficking and/or the binding to other proteins. It was therefore suggested that this motif influences the signaling pathways activated downstream of the LRR-RLKs (Su et al., 2012). Another ECD, the MLD lying in between the SP and the LRRs, has also been described in one LRR-RLK SG (Hok et al., 2011). In legumes and actinorhizal plants, the SYMBIOSIS RECEPTOR LIKE KINASE (SYMRK, also known as NORK or DMI2) receptor, involved in phosphate-acquiring arbuscular mycorrhiza and in nitrogen-fixing root nodule symbiosis, possesses a malectin domain but the exact function of this receptor is still unclear (Antolin-Llovera et al., 2014a). It has been recently demonstrated that the SYMRK receptor is likely cleaved at the plasma membrane to release the N-glycosylated MLD (Antolin-Llovera et al., 2014b). Moreover, this cleavage would permit a physical interaction between the SYMRK and the LysM-type RLK NOD FACTOR RECEPTOR 5 and induces a rapid degradation of the SYMRK protein lacking its MLD. Thus, all the domains lying in the ECD with the LRRs play essential and complementary roles for specific LRR-RLK receptor functions.
4
0biomedical
0Study
[ "Molecular Biology", "Plant Biology" ]
25,399
The calculations of the local Fano factors η*(M) and η*(S) around a stable fixed point (m*, s*) are carried out in detail in the S1 File, Section 2.3. The obtained formula read: η*(M)=1+fg−1−f(ν1+ν+11+ν·rfg)(16) η*(S)=1+fg−1−f(11+ν+ν1+ν·1rfg)iff≠0,(17) η*(S)=1+ν1+νg2riff=0.(18) Here, f≔dℱ(cs)dcs|cs=cs* and g≔dG(cm)dcm|cm=cm*incaseofmodel(3),(19) g≔dG¯(cm)dcm|cm=cm*=∑n=0∞(G(n+1)−G(n))(m*)nn!e−m*incaseofmodel(4).(20) According to these formula, the Fano factors depend on a local derivative of G if the classical LNA is used. The derivative can vary considerably with the chosen interpolating function and is therefore quite arbitrary. In contrast, if the novel hLNA approach is applied, g is an average difference quotient (Eq (20)) that only uses the original discrete function values of G. Besides the values of g, the values of r and f might differ between the two LNA approaches, since the fixed points of the underlying deterministic models are not necessarily identical, as we have just seen.
4
0biomedical
0Study
[ "Mathematical Biology" ]
7,316
The first successful surgical was operated by Bjork and Crafoord in 1947, and the first therapeutic embolization was performed by Zuberbuhler et al. in 1974. Previous study showed that a very low morbidity and mortality rate (0–4 %) when fistulas are operated on in infancy and childhood (Schumacher et al. 1997). Although repair of coronary artery fistula is relatively mature, postoperative complications may happen occasionally, including thrombosis, angina with coronary thrombosis, myocardial infarction and rupture of aneurysm. The incidence of each is less than 2 % (Mangukia 2012). There are also 20–30 % of patients with residual shunting using coronary angiography after CAF repair. Meanwhile, 10 % had demonstrable recurrence of fistula without hemodynamic disturbance (Cheung et al. 2001; Valente et al. 2010). Although postoperative coronary angiography should be done, some parents refused to perform it because of invasion and radiation. So we use TTE to evaluate the effect of surgery and to follow up just like Case 3.
4
0biomedical
0Study
[ "Cardiology" ]
230,723
The pole placement method described earlier requires knowledge of the system states at all times. In practice, this is very demanding due to unavailable or expensive sensors often driven by high noise as well. Moreover, some types of application require the system to operate as a sensor rather than as an actuator. Given the proven observability of the studied system, a state observer is designed to overcome the issue. A state observer is capable of estimating and observing the system states regardless of whether some state variables are available for direct measurement or not. The only measurable output for the hereby-described electromechanical oscillator is the inductance voltage. The observer mimics the model of the plant, except for an additional term, introduced to compensate for inaccuracies in the matrices A and B. This new term, called estimation error, is equal to the difference between the estimated output value and the measured value.
4
0biomedical
0Study
[ "Biomedical Engineering" ]
124,974
As shown in Table 2, among the common features of DE-MRI images listed, morphological features and texture features are commonly used in image processing, while hemodynamic and pharmacokinetic features are DE-MRI images' unique characteristics . Compared with morphological and texture characteristics, hemodynamic characteristics and pharmacokinetic characteristics can reflect the change characteristics of the DE-MRI image sequence. Therefore, the classifier trained as a feature has a better classification and recognition effect. It should be pointed out that the features listed in Table 2 are only part of the feature information contained in DE-MRI images. Therefore, the focus of future research is to find more and better features to characterize the characteristics of DE-MRI images.
4
0biomedical
0Study
[ "Biomedical Imaging" ]
385,744
The pan-FGFR inhibitor erdafitinib recently received regulatory approval based on a 40% response rate in advanced patients with FGFR alterations detected by tissue profiling3. We detected somatic FGFR3 mutations in ctDNA from eight patients with mUC (Fig. 4c). Importantly, these mutations were independently detected in all ctDNA-positive samples and patient-matched tissue. All FGFR3 mutations had VAFs suggestive of truncal status (Supplementary Data 8). FGFR3 mutations are enriched in non-muscle-invasive lesions relative to adjacent muscle-invasive disease26, and consistent with this, in three patients we observed FGFR3 p.S249C mutations in non-muscle-invasive tissue that were not detected in later muscle-invasive tissue or mUC ctDNA samples (Fig. 4c). In a further three patients, breakpoints in ctDNA indicated the presence of activating FGFR3 gene fusions (Fig. 4c, Supplementary Data 9, and Supplementary Fig. 14b). In total, 13.8% of the ctDNA-evaluable mUC cohort (11/80) exhibited FGFR3 alterations likely to sensitize their tumors to erdafitinib. Tissue samples with activating FGFR3 alterations demonstrated elevated FGFR3 expression (Fig. 4d). Surprisingly, one FGFR3-TACC3 fusion identified in ctDNA was not identified in earlier TURBT tissue (despite other shared genomic alterations); consistent with this, tissue FGFR3 RNA expression was below the 25th percentile. In an exploratory subgroup analysis, we observed a modest association between FGFR3 alteration and shorter progression-free survival (PFS) for patients receiving immunotherapy (n = 58; PD-1/PD-L1/CTLA-4, single agent or in combination) (Fig. 4e).
4
0biomedical
0Study
[ "Oncology" ]
269,911
A 60 µm thick epoxy coating was used as a primer coat in the two-coat systems. The topcoat in the 1- and 2-coat systems is a TGIC-free (triglycidyl isocyanurate) polyester coating. According to the requirements of Qualisteelcoat, the way of galvanizing the test panels (continuous hot-dip galvanizing) and the chemical pretreatment of the substrate before painting (phosphating) allow to achieve high durability (H) for the 1-layer system up to the maximum corrosion class C3–H and for the 2-layer system up to the corrosion class C4–H according to ISO 12944-2.
2
2other
1Other
[ "Materials Science" ]
165,788
This cross-sectional study recruited 19 patients with ESRD (including nine men) who received PD for at least 1 year and 24 age- and sex-matched controls (including nine men) with normal renal functions. All participants were right-handed. The causes of ESRD in the 19 patients included diabetic nephropathy in six patients, hypertensive nephropathy in five, chronic glomerulonephritis in four, renal artery stenosis in one, kidney graft failure in one, and unknown etiology in two patients. We excluded patients with known neurological disorders and psychiatric diseases, and those taking any medication involving the central nervous system (e.g., sleeping pills). Each subject underwent pain assessment with the numeric scales and depression screening based on Patient Health Questionnaire-2 (PHQ-2) by a neurologist (T.Y.C.) at the outpatient clinic before the enrollment. Baseline mini-mental status examination (MMSE) score was evaluated by a licensed psychologist. Subjects with any evidence of pain, depressive mood, or with an MMSE score below 24 were also excluded (24, 25). A routine laboratory test for the patients was done within 1 week prior to performing the MRI scan. For the controls, basic biochemistry data was recorded upon enrollment. Each participant received compensation of ~US $20.
4
0biomedical
0Study
[ "Nephrology" ]
191,206
A variant of FRET, i.e., FRET competition experiments, can be very helpful to evaluate the G-quadruplex over duplex or the G-quadruplex over G-quadruplex selectivity.45 In these experiments, the affinity for the sequence of interest (DNA G-quadruplex) is evaluated in the presence of increasing concentrations of a competing sequence (duplex or G-quadruplex DNA). The G-quadruplex vs duplex selectivity of the ligands was assessed for disubstituted 1, 2, 9, and 11; trisubstituted 40, 41, 44, 48, 50, 55, 61, 62, 63, 64, 65, 66, 82, 87, 88, 89, 90, and 91; tetrasubstituted 102, 103, 106, 107, 109, 110, 116, 117, 118, 119, 123, 124, 137, 145, 146, 148, 152, 153, 154, 160, and 161; core-extended 179; and cyclic 209.22,31,33,34,36,37,46−48 On the other hand, a preference for a telomeric G-quadruplex forming sequence over other DNA G-quadruplexes was well established for cyclic 203.30 Moreover, for trisubstituted 52, 60–66 and tetrasubstituted 116–119, c-myc and bcl-2 G-quadruplexes proved to efficiently compete with telomeric G-quadruplex for binding to the NDIs, whereas c-kit1 and c-kit2 G-quadruplexes were less effective competitors.46,49
4
0biomedical
0Study
[ "Biochemistry", "Molecular Biology" ]
60,010
We have overcome the limitation of these former assays by using an unique functional assay in which effector production is spatially separated from its action, and in which no wounding is involved. Our grafting experiment shows that although Avr2 is present in the xylem sap of the I-2 graft, and hence is translocated from the Avr2 rootstock, it is unable to trigger I-2-mediated immune responses in the I-2 scion. These data suggest that I-2-expressing cells do not autonomously take up the effector protein from the xylem sap in the absence of Fol. Crosses between either Avr2 or ΔspAvr2 plants with I-2 tomato substantiate this conclusion, as an autoimmune response was only observed in the ΔspAvr2/I-2 crosses. Furthermore, the lack of an immune response in the Avr2/I-2 plants implies that secretion of Avr2 is a very efficient process. So although Avr2 is abundantly present in the extracellular spaces of Avr2/I-2 progeny, the secreted Avr2 is not perceived by intracellular I-2 again implying that plant cells do not autonomously take up the Avr2 effector.
5
0biomedical
0Study
[ "Plant Pathology" ]
350,348
This study was performed in accordance with the Helsinki Declaration of the World Medical Association. Our hospital introduced the use of an artificial pancreas in hepato‐biliary‐pancreatic surgeries in 2019. This retrospective study enrolled 52 patients who underwent pancreatectomy at Tokushima University Hospital from 2015 to 2019. All patients provided written informed consent, and the study protocol was approved by the institutional review board of Tokushima University Hospital (approval number from the Tokushima Clinical Trial Management System [ToCMS]: 3215). Of the 52 patients, perioperative blood glucose control using an artificial pancreas was performed in 26 patients since 2019 (artificial pancreas group). Postoperative blood glucose control with manual insulin injections based on commonly used sliding scales was performed in the previous 26 patients (control group).
4
0biomedical
0Study
[ "Endocrinology", "Surgery" ]
211,256
Diagram of study design and processing steps, highlighting probes and samples remaining in the primary (PREG) and replication (GAPPS) cohorts after performing quality control for DNA methylation microarrays. BA = Horvath-derived biological age estimates, GAAD = gestational age at delivery.
3
0biomedical
0Study
[ "Epigenetics", "Molecular Biology" ]
283,913
Finally, we study the stability of the f-Li6Si5 structure inside both zigzag (15,0) and armchair (9,9) CNTs by performing BO-AIMD simulations. Figure 9A shows the equilibrium geometry of the f-Si5Li6 structure inside the (15,0) CNT. We find that the structure remains almost unchanged with respect to f-Si5Li6 in the free space, showing that the CNT would have a small influence in the Li6Si5 NW stability. We only note a small displacement of the Li ions at the extreme of the f-Li6Si5 structure which move toward the CNT wall. The integrity of the f-Li6Si5 structure inside the (15,0) and (9,9) CNTs was investigated by BO-AIMD simulations at 300 K. We find that the f-Si5Li6 structure preserves its stability where the Li ions move around the Si5 ring without detaching. Similar results are found for the f-Li6Si5 structure inside the armchair (9,9) CNT, indicating that the formation and stability of the Li6Si5 NW inside the CNTs is independent of its chirality. This result suggests that Li6 Si5-NW are likely to form inside CNTs in a compact form, which would allow efficient storage of Li ions into CNTs mediated by Si5 rings. Supplementary Figure S2 shows the variation of the total energy for the BO-AIMD simulation of f-Li6Si5 inside the (15,0) and (9,9) CNTs at 300 K. We observe energy fluctuation of around 5 eV in both CNTs, preserving the stability of the f-Li6Si5 structure.
4
0biomedical
0Study
[ "Nanotechnology", "Materials Science" ]
95,086
TEMP174azF was accessible to Click modification, but efficiency was lower (estimated ∼33% using the absorbance properties of 2) compared to TEMY105azF. It is unknown how local protein microenvironment dictates SPAAC efficiency but dynamics, relative exposure to aqueous solvent and the character of shallow “pockets” have been suggested as possible determinants.23 The molecular model suggests that interaction of the azide moiety with other residues, which may play a role through, for example, altering the relative populations of resonance structures sampled by the azide moiety (R–N <svg xmlns="http://www.w3.org/2000/svg" version="1.0" width="16.000000pt" height="16.000000pt" viewBox="0 0 16.000000 16.000000" preserveAspectRatio="xMidYMid meet"><metadata> Created by potrace 1.16, written by Peter Selinger 2001-2019 </metadata><g transform="translate(1.000000,15.000000) scale(0.005147,-0.005147)" fill="currentColor" stroke="none"><path d="M0 1440 l0 -80 1360 0 1360 0 0 80 0 80 -1360 0 -1360 0 0 -80z M0 960 l0 -80 1360 0 1360 0 0 80 0 80 -1360 0 -1360 0 0 -80z"/></g></svg> N+ N–/R–N––N+ <svg xmlns="http://www.w3.org/2000/svg" version="1.0" width="16.000000pt" height="16.000000pt" viewBox="0 0 16.000000 16.000000" preserveAspectRatio="xMidYMid meet"><metadata> Created by potrace 1.16, written by Peter Selinger 2001-2019 </metadata><g transform="translate(1.000000,15.000000) scale(0.005147,-0.005147)" fill="currentColor" stroke="none"><path d="M0 1760 l0 -80 1360 0 1360 0 0 80 0 80 -1360 0 -1360 0 0 -80z M0 1280 l0 -80 1360 0 1360 0 0 80 0 80 -1360 0 -1360 0 0 -80z M0 800 l0 -80 1360 0 1360 0 0 80 0 80 -1360 0 -1360 0 0 -80z"/></g></svg> N), and/or its accessibility and available orientations to the incoming DBCO. The effect of the SPAAC nnPTM on the ability of TEMP174azF to hydrolyse ampicillin varied depending on the DBCO adduct. Modification with 2 exerted a similar but somewhat smaller inhibitory effect (∼40% drop) as observed for TEMT105azF (Fig. 3 and ESI Table 1†). Modification with 1 resulted in a significant increase in overall activity restoring apparent catalytic efficiency essentially to wild-type levels (Fig. 3). This should be considered as a lower estimate of activation as ∼70% of the protein may be unmodified (vide supra). With both adducts, the most significant contribution was the change in k cat of TEMP174azF compared to unmodified protein (ESI Table 1†); modification with 1 increased k cat by 210% while addition of 2 reduced k cat by almost half.
5
0biomedical
0Study
[ "Biochemistry" ]
31,398
Our present study suggested that dietary menthol leads to an elevation of the thermogenic gene program in cultured white adipocytes and sWAT, which could provide therapeutic benefits for obesity and metabolic diseases. Moreover, in vivo data revealed that dietary menthol prevented HFD-induced obesity and ameliorated insulin resistance. Previous study has reported that TRPM8 is widely expressed in many tissues, such as BAT , dorsal root ganglia neurons , and bladder . Therefore, we could not exclude the contribution of other tissues in the effects of dietary menthol on HFD-induced obesity and insulin resistance. On the other hand, the size of the therapeutic window of menthol in metabolic diseases may depend on the expression of TRPM8 in those tissues.
4
0biomedical
0Study
[ "Endocrinology", "Metabolism" ]
44,769
In the third theme “perceived characteristics of a nurse”, participants shared their passion and belief about the personal qualities of a nurse. Historic and personal influences (DH (Department of Health), 2012) were evident:work hard, be determined, dedicated and courageous [81M1N] I am very passionate about being a nurse and due to lots of personal experience as a patient I feel I can put myself in their shoes [82F1N]
2
0biomedical
0Study
[ "Nursing" ]
301,313
To make the untagged peptides immunogenic, they were conjugated to BSA using glutaraldehyde. After dialysis to remove unbound peptide, the average carrier:peptide ratios between BSA and mutant peptide were determined by amino acid analysis to be: BSA:STh-A14T, 1:18 (±4.1); BSA:STh-L9A/A14T, 1:17 (±4.3); BSA:STh-L9N/A14T, 1:13 (±3.2); and BSA:STh-L9K/A14T, 1:11 (±4).
4
0biomedical
0Study
[ "Immunology", "Biochemistry" ]
20,511
Over the past decades, the prevalence of food allergies has increased in Western countries (1, 2). Harmless food proteins are recognized as being immunogenic by the immune cells of food-allergic patients, resulting in allergic sensitization. In sen-sitized individuals, these allergens can provoke a variety of symptoms when ingested, ranging from itching and swelling in the mouth to anaphylaxis. Next to eliminating these food proteins from the diet, there are currently no therapies available for treating food allergies that induce sustained oral tolerance. Several studies were able to induce desensitization in patients undergoing oral immunotherapy (OIT), hereby increasing the eliciting dose (ED) (3–5). However, inducing sustained non-responsiveness or tolerance remains difficult and is often combined with severe side effects (1, 4). Combining OIT with additional immunomodulatory agents, such as prebiotics as dietary adjuvant, may enhance safety and efficacy of immunotherapy, and support clinical tolerance induction (6).
4
0biomedical
0Study
[ "Immunology", "Allergology" ]
48,904
Acupuncture, first mentioned in the 5th century BC, is part of traditional Chinese medicine and its effects, especially in pain control, have been confirmed in clinical trials, which led to the usage of acupuncture also in many other countries. A questionnaire of 180 patients with peripheral neuropathy showed that 30% of them choose acupuncture as an alternative method of pain control .
2
0biomedical
1Other
[ "Pain management", "Alternative medicine" ]
12,275
Viruses represent a highly tractable model system for studying evolutionary biology. The HAdV genome is largely conserved, but interrupted in stereotypical fashion by hypervariability at four major regions of the genome, specifically the three major capsid genes and the E3 transcription unit. By comparison of genomic differences between HAdV major capsid regions, marked differences across species were noted. For example, the penton base genes of HADV-C types are relatively conserved. In contrast, HAdV-A and -B penton base genes are largely hypervariable across their entire open-reading frames. HAdV-D penton base genes show overall conservation interrupted by two distinct hypervariable regions, accounting for two distinct hypervariable loops on the external capsid surface, HVL1 and HVL2. We previously showed that these two hypervariable regions of the penton base gene often undergo homologous recombination, and at times, independent of one another50. HAdV-D72 was typed as a novel genotype on the basis of differential recombination within the penton base gene, specifically involving RGD loop (HVL2). Thus, it appears that viruses within HAdV-D may more frequently utilize penton base gene recombination for their evolution than other HAdV species. Also notable was the fiber gene. Viruses within HADV-B and -D had shorter fiber genes than HAdV-A or -C, but for all the four species, the fiber sequences showed a similar degree of diversity. A short trimeric fiber protein is thought to be more rigid, perhaps with more strict receptor interactions and cellular specificity. However, a short fiber may permit docking of penton base proteins to host cell integrins independent of fiber knob binding to a primary adenovirus receptor, and allow for fiber-independent cell entry51. These data suggest that fiber length matters, but in a complex fashion. Furthermore, we and others have shown a correlation between fiber knob amino acids and corneal tropism42,52. Altogether, these data are consistent with an important role for variations in fiber length and nucleotide content in infectivity and cellular tropism.
5
0biomedical
0Study
[ "Virology" ]
293,927
The right inferior frontal gyrus (rIFG) is considered a key node for the inhibition of premature or no longer appropriate motor responses, which is one of the core aspects of behavioral flexibility and control (Swann et al., 2012; Aron et al., 2014, 2016). The IFG represents a structurally diverse area in the prefrontal cortex that usually is divided into three sub-regions based on its cytoarchitecture: the pars opercularis, pars triangularis, and pars orbitalis. Given that variability in the structural architecture of the brain often relates to specific aspects of behavior (Johansen-Berg, 2010), it is likely that the rIFG exhibits a richer functional diversity than often posited. A recent meta-analysis identified different functional clusters of the rIFG to be involved in distinct large-scale networks; only the posterior part (roughly corresponding to the pars opercularis) seemed to be involved in motor control, and was further divided into dorsal and ventral regions associated with response initiation and general inhibition, respectively (Hartwigsen et al., 2019). However, a structural connectivity map of rIFG subregions that would support this functional parcelation is lacking.
5
0biomedical
0Study
[ "Neuroscience" ]
306,691
Among the 105 patients enrolled in this study, 7 patients were excluded due to incomplete medical data. The data from 98 patients receiving TNF-α inhibitors were analyzed. The mean age of the included patients was 53 years (range: 20–82 years), and there were 79 (80.6%) females. The mean duration of RA was 9 years, and 29 patients reached remission. To determine the possible effect of disease status on response to TNF-α inhibitors, baseline DAS-28 and its subcomponents were examined. Baseline DAS-28 and its subcomponents were not statistically significant between the remission and non-remission groups (Table 1). Marginal significance was found according to sex (p = 0.059) and hypertension (p = 0.060).Table 1Patient characteristics according to the response at 6 months treatment of TNF inhibitors.Characteristics, n (%)Remission (n = 29)No remission (n = 69)p-valueSex0.059Male9 (31.0)10 (14.5)Female20 (69.0)59 (85.5)Age51.4 ± 13.453.6 ± 13.90.399 < 6526 (89.7)53 (76.8)0.142 ≥ 653 (10.3)16 (23.2)BMI, kg/m223.4 ± 3.022.3 ± 3.80.220 < 2313 (44.8)42 (60.9)0.144 ≥ 2316 (55.2)27 (39.1)Duration of rheumatoid arthritis, months103.9 ± 87.8111.0 ± 69.20.666Rheumatoid factor0.329Positive20 (69.0)54 (78.3)Negative9 (31.0)15 (21.7)ACPA0.177Positive17 (34.6)49 (79.0)Negative9 (65.4)13 (21.0)Concomitant drugHydroxychloroquine0.902 Yes16 (55.2)39 (56.5) No13 (44.8)30 (43.5)Leflunomide0.665 Yes10 (34.5)27 (39.1) No19 (65.5)42 (60.9)Methotrexate0.319 Yes19 (65.5)52 (75.4) No10 (34.5)17 (24.6)Sulfasalazine0.111 Yes7 (24.1)7 (10.1) No22 (75.9)62 (89.9)Tacrolimus0.986 Yes5 (17.2)12 (17.4) No24 (82.8)57 (82.6)ComorbidityDiabetes0.669 Yes1 (3.6)5 (7.2) No27 (96.4)64 (92.8)Dyslipidemia1.000 Yes3 (10.7)9 (13.0) No25 (89.3)60 (87.0)Hypertension0.060 Yes1 (3.6)14 (20.3) No27 (96.4)55 (79.7)Osteoporosis0.725 Yes4 (14.3)7 (10.1) No24 (85.7)62 (89.9)Vitamin D deficiency0.272 Yes1 (3.6)9 (13.0) No27 (96.4)60 (87.0)Baseline DAS28 with its subcomponentsDAS285.8 ± 1.25.8 ± 1.10.696Tender joint count 289.6 ± 8.310.7 ± 74.30.782Swollen joint count 286.6 ± 7.17.5 ± 5.70.872Global health55.3 ± 18.562.4 ± 20.20.167ESR54.7 ± 29.549.5 ± 27.30.379CRP3.0 ± 4.42.1 ± 2.50.113BMI: body mass index; ACPA: anticyclic citrullinated peptide antibody; DAS28: disease activity score 28 joints; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein.
4
0biomedical
0Study
[ "Rheumatology" ]
303,408
The inference timings per case are 11 ± 7 min (±standard deviation) for a single machine with 16 cores; 13 ± 8 s for 50 such machines in a cloud environment; and 8 ± 5 s for a commercially-available accelerator, Google Cloud Tensor Processing Unit (v2). These timings range from being comparable to significantly faster than slide preparation and digitization, which can take a few minutes per slide (multiplied by about ten slides per case on average; See Table 1).
4
0biomedical
0Study
[ "Medical Imaging", "Computational Biology" ]
160,843
Scheme 1 shows the developed synthetic scheme for compounds 1–4 and their controls. Briefly, the symmetric (NND)3–TPA, 1, was synthesized in 60% yield by the Pd-catalyzed Sonogashira cross coupling of tris-(4-iodo-phenyl)-amine and 4-ethynyl-N,N-dimethylaniline in degassed THF : TEA (1 : 1) under an argon atmosphere, in the presence of Pd(PPh3)4 and CuI. Next, (NND–TCBD1–3)3–TPA, 2–4, were synthesized via a [2 + 2] cycloaddition–retroelectrocyclization reaction with the strong electron acceptor TCNE. The reaction of 1 with one equivalent of TCNE in DCM at room temperature for 4 h resulted in an exclusive mono-TCBD bearing (NND–TCBD1)3–TPA, 2, in 63% yield. Similarly, the reaction of 1 with two equivalents of TCNE in DCM solvent at 40 °C for 12 h resulted in (NND–TCBD2)3–TPA, 3, in 65% yield, whereas increasing the reaction temperature to 80 °C in DCE solvent for 24 h using four equivalents of TCNE with 1 resulted in symmetrical (NND–TCBD3)3–TPA, 4, in 70% yield. The control compound C1 was synthesized by the Pd-catalyzed Sonogashira cross-coupling reaction of 4-ethynyl-N,N-dimethylaniline and iodobenzene in 60% yield. The acetylene linked control compound C1 was further subjected to a [2 + 2] cycloaddition-retro-electrocyclization reaction with one equivalent of TCNE at room temperature for 8 h, which resulted in TCBD substituted control compound C2 in 82% yield. The newly synthesized compounds were purified by silica gel (100–200 mesh) column chromatography using hexane:DCM as solvent and fully characterized by 1H, 13C NMR and high-resolution mass spectroscopy (HRMS) techniques (see the ESI for spectral details, Fig. S1–S18†).
4
0biomedical
0Study
[ "Organic Chemistry" ]
340,252
The studies included applied heterogeneous methodologies to investigate the role of miRNAs in OSCC patients. In particular, the time of sampling (i.e., before and/or after surgery/radiotherapy) was not reported in all the studies. The research protocols included stimulated or unstimulated saliva for analysis of either whole saliva or salivary supernatant. In addition, salivary samples were taken at different clinical stages of OSCC and the studies differed regarding patients’ demographic characteristics (i.e., smoke, alcohol consumption, positivity to HPV, patients’ age and sex, etc.) and possible comorbidities possibly affecting the outcomes. Some of the studies included did not account for such patients’ characteristics nor for the site of OSCC (buccal mucosa, gingiva, tongue, etc.). For this reason, the realization of a metanalysis was contraindicated and it is difficult to draw comprehensive conclusions on the topic. These heterogeneities might also explain why the type of miRNAs identified and the dysregulations detected in the various studies were mostly not superimposable.
4
0biomedical
2Review
[ "Oncology", "Molecular Biology" ]
54,739
(A) Molecular Structure of BiP (Protein Data Bank ID: 5E84). (B) Domain architecture of BiP. Nucleotide binding domain (NBD) is shown in blue color, whereas the SBD-α and SBD-β are shown in green and purple colors, respectively. Hydrophobic linker connecting the NBD and SBD is shown in red color.
4
0biomedical
1Other
[ "Biochemistry", "Molecular Biology" ]
228,548
To confirm T. whipplei positive samples, PCR products were sequenced using the Sanger sequencing method. Finally, The nucleotide sequences were blasted in GenBank (https://blast.ncbi.nlm.nih.gov/Blast.cgi) and compared with the deposited wips genes of T. whipplei in the GenBank.
4
0biomedical
0Study
[ "Microbiology" ]
152,519
Another strategy to fight Ebola virus is to prevent infection by vaccine usage. Recently ionizable dendrimer-based nanomaterial, a lipid-anchored PEG and self-replicating RNA were used together as a vaccine nanoparticles—MDNPs. The platform created was used to carry and successfully deliver RNA, which results in antibody production and antigen-specific CD8+ T-cell responses towards the encoded protein antigen. The platform can be also used as a vaccine against Toxoplasma gondii and H1N1 influenza . For Ebola vaccine creation, PAMAM G4 dendrimers were also used. The dendrimers delivered artificial polyepitope T-cell immunogens in the form of a DNA. Due to relatively low immunogenicity, this approach needs more research .
4
0biomedical
0Study
[ "Virology", "Immunology" ]
129,359
Cells were lysed in NP40 lysis buffer (50 mM Tris pH 7.4, 250 mM NaCl, 5 mM EDTA, 50 mM NaF, 1 mM Na2VO4, 1% Nonidet P40, 0.02% NaN3, with freshly added PMSF [1 mM], aprotinin, leupeptin) for 30 min, 4°C, vortexing every 10 min. Lysates were clarified by spinning at 13,200 g for 10 min at 4°C, and protein contents in clarified lysates were quantified by Bradford assay before gel loading. Gel and western conditions are listed in Supplementary file 1. Twenty to 35 µg lysate per sample was prepared with SDS loading buffer, resolved by SDS–PAGE, and following wet transfer for 2 hr at 40 V, membranes were blocked with 5% milk in Tris-buffered saline (TBS) for at least 30 min, 23°C, and were incubated with primary antibodies in 5% milk in TBS-T (0.1% Tween 20/TBS) overnight at 4°C. Membranes were washed in TBS-T and incubated with the corresponding secondary antibodies conjugated with HRP (Thermofisher) or near-infrared fluorescent dyes (Abcam, Cambridge, UK) in TBS-T for 1 hr, 23°C, and washed again. Blots were detected with Western Lightning PLUS ECL (PerkinElmer, Waltham, MA) on Hyblot CL film (Thomas Scientific, Swedesboro, NJ). Proteins with infrared fluorescent dyes were detected using a Li-Cor Odyssey Infrared scanner and Image Studio version 5.2 software.
4
0biomedical
0Study
[ "Biochemistry", "Molecular Biology" ]
41,329
This is the first report of a P. donghuensis isolate obtained from a bulk soil sample, and from the Southern hemisphere. Similarly to what has been recently described for the Polish tomato-rhizospheric isolate P. donghuensis P482, SVBP6 showed a strong antagonistic activity against a variety of fungal pathogens, but, in contrast to isolate P482, it appears that the antagonistic mechanism is not based on the production of VOCs. Besides, SVBP6 displayed antibacterial activity against a Gram-positive representative (B. subtilis) and an Enterobacterial representative (E. coli), a feature that could be attributed to the expression of identified bacteriocin or toxoflavin production genes. The availability of the genome sequence of this isolate, as well as the successful generation of a random Tn5 mutagenic clone library, will provide the basis for the elucidation of the genetic basis responsible for the broad antifungal activity of P. donghuensis SVBP6 isolate.
4
0biomedical
0Study
[ "Microbiology" ]
383,086
Identification of differentially expressed genes (DEGs) among the TCGA and GSE6631 datasets of HNSCC with the cut-off criteria of |logFC| ≥ 1.0 and adj. P < 0.05. (A) Volcano plot of DEGs in the TCGA dataset. (B) Volcano plot of DEGs in the GSE6631 dataset. (C) The Venn diagram of genes among DEG lists and co-expression module. In total, 29 overlapping genes in the intersection of DEG lists and two co-expression modules.
4
0biomedical
0Study
[ "Genomics", "Oncology" ]
92,319
Two types of sound characteristics were modulated in Dialogs Games. The first type was related to “performance”. Individuals increased the duration, rhythm and loudness of whistles when competing and produced numerous whistles to persuade their partner and win the contest. Interestingly, contestants used a second type of sound characteristics, the accentuation of the first whistle of utterances, which can be related to “prosody”. Whistlers used this subtle sound variation to affirm their dominance or motivation to win the contest. When they took the turn, winners produced a longer initial whistle than losers. In contrast, lengthening whistles within an utterance did not affect the winning success. Listeners hearing two contestants differing only in this accentuation evaluated that the winner was the one lengthening the first whistle. Competition for resources can hence be solved through a prosodic feature only, recognised as a dominant cue by listeners.
4
0biomedical
0Study
[ "Ethology" ]
107,700
The control group was not exposed to the Nutriathlon challenge objectives (i.e. no team) or Nutriathlon website access. They were only exposed to the usual school curriculum which did not include a specific nutrition program. Throughout the study, participants had access to a plain website in order to record their consumption of V/F and M/A at specific periods. It should be noted that the data collection on the web-based platform for the control group in no way referred to Team Nutriathlon. In addition, to reduce the emphasis on V/F, M/A, eating behaviours and body weight, the research objective that was presented to the participants was “to explore the effects of different lifestyle interventions on health and well-being”.
2
0biomedical
0Study
[ "Nutrition" ]
378,914
Referred to the diagnostic criteria of BBS, clinical diagnosis is made by the presence of either four major features or three major features and two minor features . Family A met four major features (rod-cone dystrophy, polydactyly, obesity, and genital anomalies); however, family B only met two major features (rod-cone dystrophy and polydactyly). Nonetheless, the proband of family B presented with the gastrointestinal and endocrine/metabolic abnormalities, which were considered as minor features of BBS . Forsyth and Gunay-Aygan pointed out the limitation of the clinical criteria that many of these clinical features emerge throughout infancy, childhood, and young adulthood, and for the individuals who are considered, the diagnosis of BBS, periodically review is needed . Phenotypic spectrum of disease due to genetic variation should be taken into account, rather than just the clinical diagnosis itself.
4
0biomedical
0Study
[ "Genetics" ]
389,938
While we model cells and microbeads as discrete entities, we assume that the concentration of oxygen ω(x, t) is continuous and can be described via a reaction-diffusion equation, with oxygen consumption by live tumour cells modelled by placing point sinks at the centres of viable cells. Written in dimensional form, the equation governing the spatio-temporal evolution of the oxygen concentration is thus ∂ω∂t=Dω∇2ω-κω∑iδ(x-xi)(1) for x ∈ Ω, where xi is the location of viable cell i, the parameter Dω is the assumed constant diffusion coefficient of oxygen, κ is the oxygen consumption rate and Ω is the simulation domain, which we take to be a square domain large enough to fully enclose the spheroid. δ(x) is the delta function (δ(x) = 1 when x = 0; δ(x) = 0 otherwise).
4
0biomedical
0Study
[ "Mathematical Biology" ]
190,555
For the first time, the biological activities and phytochemical profiles of the aerial parts of N. baytopii, endemic from Turkey, were evaluated. Extraction of the aerial parts was performed using solvents of different polarity. Furthermore, the essential oil of the plant was prepared by hydro-distillation. The water/methanol and water extracts possessed appreciable amounts of phenolic compounds and showed the highest antioxidant capacities in vitro. Phytochemical profiling revealed the presence of flavones, such as luteolin and apigenin and their derivatives in both the water and methanol extracts. The ethyl acetate extract showed pronounced inhibitory properties against butyrylcholinesterase, highlighting the possibility for a new, efficient Alzheimer’s disease therapeutic agent. The high cytotoxicity of N. baytopii aerial parts methanol extract against HepG2 suggests further future investigations in this area. The data presented here showed that the endemic N. baytopii possessed many interesting biological activities and is certainly encouraging for a future application in the pharmaceutical and nutraceutical fields, although further tests are necessary.
4
0biomedical
0Study
[ "Pharmacognosy", "Phytochemistry" ]
66,555
The 25 participants agreed that the reporting assignment was useful, that it was consistent with their daily work and duties and that it made them more aware of medication and patient safety. Only nine participants (36.0%) thought that the reporting assignment cost a lot of time. Twenty-one participants (84.0%) agreed that the reporting assignment changed how they dealt with ADRs. The results of the participant evaluation are displayed in Fig. 2.Fig. 2Results of evaluation (on a 5-point Likert scale) of a pharmacovigilance reporting assignment, part of a prescribing qualification course for specialist oncology nurses, and discussion of reported adverse drug reactions (ADRs)
2
0biomedical
0Study
[ "Pharmacology" ]
124,571
Transient transfection of plasmids for overexpression purposes was performed using X-tremeGENE™ HP (Roche Diagnostics) according to manufacturer’s instructions. The cells were harvested 24–48 h after transfection. mRNA was measured 24 h after transfection and protein was measured 48 h after transfection.
4
0biomedical
0Study
[ "Molecular Biology" ]
9,260
Table 3 also shows the E:S ratio obtained at the end of each treatment. All treatments have values higher than 0.31 (control E:S ratio from seeds stored during 12 weeks at 4°C) although not significant differences were found for some of the treatments against control (Table 3). This results point out the important role of some of the conditions used during dormancy–breaking and incubation procedures on embryo development and justifies the modeling in order to understand which and how they affect germination.
3
0biomedical
0Study
[ "Plant biology" ]
326,792
Our study received approval by NMDGF and the United States Fish and Wildlife Service prior to conducting the work. The authors confirm that all methods and experiments were performed in accordance with the relevant guidelines and regulations of these agencies.
1
2other
1Other
[ "Research ethics", "administration" ]
63,554
A benefit of the use of multiple genetic variants is the possibility to differentiate between pleiotropy and mediation, two mechanisms by which a genetic variant may be associated with a measured covariate (Figure 3). If a genetic variant is associated with a covariate independently of the risk factor (pleiotropy, or “horizontal pleiotropy”), then the instrumental variable assumptions are likely to be violated and the genetic variant should be excluded from an instrumental variable analysis, as the association with the covariate is likely to open a causal pathway from the variant to the outcome not via the risk factor. However, if the genetic variant is associated with a covariate due to its association with the risk factor of interest (mediation or “vertical pleiotropy”), and there is no alternative causal pathway from the variant to the outcome except for that via the risk factor, then the genetic variant is a valid instrumental variable.23
4
0biomedical
0Study
[ "Genetics", "Epidemiology" ]
117,251
Many reports have suggested that disturbances in Wnt/β-catenin signaling are linked to AD [17, 18]. Aβ-induced activation of apoptosis and synaptotoxicity are reported to be antagonized by certain Wnt agonists such as Wnt-3a, implying that Aβ disrupts Wnt signaling, possibly through interaction with frizzled receptors [41–45]. Since the Wnt signaling pathway negatively regulates GSK3β , it is plausible that treatment with Aβ oligomers inhibits Wnt/β-catenin signaling and induces activation of GSK3β. In the canonical Wnt signaling pathway, phosphorylation of β-catenin by GSK3β facilitates β-catenin degradation [17, 18]. However, our finding that p-β-catenin levels were reduced by Aβ-O exposure suggests that the decrease in β-catenin in our experimental system was independent of β-catenin phosphorylation.
4
0biomedical
0Study
[ "Neurobiology" ]
51,944
Quite a few studies have attempted to describe the mechanism of gain modulation. It has been shown that tonic inhibition creates a divisive operation during physiological excitation in which the cell is under continuous bombardment of synaptic activity [26–30]. In other studies [22, 29, 31–33], it was shown that depolarizing the membrane potential in the presence of synaptic noise increases the response gain. In both mechanisms (i.e. increase in tonic inhibition and depolarization of the membrane potential), the change has an additive effect on the input-output function, and in both, the amplitude of the baseline noise determines the shift from additive to multiplicative operations [26, 31]. Indeed, theoretical studies [31, 32] have shown that in the presence of noise, the firing frequency becomes a power-law function of the membrane potential but only for a limited range of values, and that this is primarily visible at low firing frequencies. Due to this limitation, these mechanisms cannot be considered a robust driver of gain modulation at supra-threshold conditions .
5
0biomedical
0Study
[ "Neuroscience" ]
191,807
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1
2other
1Other
[ "N", "A" ]