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Ferroquine is an ameliorated blood-schizonticidal 4-aminoquinoline developed by Sanofi-Aventis. Along with OZ439, it is a more effective parasite-killing compound against Plasmodium strains when compared to artesunate. Several preclinical studies have shown its benefits, particularly for treating patients infected with chloroquine-, amodiaquine-, and mefloquine-resistant malaria strains [46–48]. The greatest advantage of using ferroquine is its 30-h half-life, which is highly superior to that of other artemisinin derivatives. Two ferroquine Phase II trials were recently registered in the clinicaltrials.gov database (NCT02497612 and NCT00988507) focusing on P. falciparum and P. vivax malaria at the multicenter level. One study has been completed (NCT00988507) but no results are yet available. Most recently, a ferroquine-artesunate dose-ranging Phase II trial on P. falciparum-infected adults and children in eight African hospitals was conducted . The research findings were astonishing: 97 % polymerase chain reaction (PCR)-confirmed cure rates (95 % CI: 90–100) after treatment with 2 mg/kg ferroquine combined with 4 mg/kg artesunate. However, the cure rate was reduced (79 %; 95%CI: 68–88) when ferroquine monotherapy 4 mg/kg/day for 3-days regimen was used. Furthermore, exacerbated malaria symptoms were observed in 14 % of the individuals in the treatment cohort.
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346,587 |
By utilizing both the AVENIO ctDNA Surveillance Kit and the tumor tissue Surveillance kit, we were able to track tumor mutation changes over time. In the two patient examples forthwith with corresponding imaging data, detection of ctDNA preceded radiographic progression (per RECIST 1.1). In some subjects, the allele frequencies of mutations detected in ctDNA increased consecutively 3–5 months before clinical evidence of disease progression. For example, in one subject who had been treated with carboplatin plus pemetrexed, the allele frequency of mutations in TP53 (CDS mutation: c.712 T > G) increased from 3.0% at diagnosis to 8.5% at day 47 and to 10.6% at day 68 post-treatment. However, the CT scans did not show evidence of disease progression (75% increase in the diameters of target lesions plus new lesion development in the liver) until day 159—a difference of 91 days (Fig. 1a). Similar trends were uncovered in another subject in whom mutations in TP53 and SLITRK5 were detected. Molecular progression (defined as a consecutive increase in mutation allele frequencies) was apparent on day 33 post-diagnosis of metastatic disease, but clinical disease progression was not seen until day 174 (Fig. 1b). We also examined the relationship between total ctDNA level, which sum up all mutant molecules detected in plasma sample, and treatment response. For example, the analysis had shown that the ctDNA level from one study subject changed with therapy administration and clinical disease progression (specifically, development of a new non-target lesion) (Fig. 1c). Fig. 1Correlation between allele frequencies in ctDNA and clinical disease in a subject with a a single somatic mutation and b two somatic mutations. c Correlation between total ctDNA load and clinical disease. The duration of treatment with chemotherapy is represented by the green band, radiation by the beige band, and targeted therapy by the light purple band. The overlap in radiation and targeted therapy is represented by the dark purple band. ctDNA, circulating tumor DNA; mGE, mutated genome equivalent; PD, progressive disease
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272,226 |
Table 4 shows the bivariate analysis results between demographic variables and the WTP and WTIT questions. Significant higher WTIT in brushing minutes per day was found in parents with a higher level of education and having children aged two years or older. In the highest education category, 64% were willing to brush for more than 3 min a day compared to 42% in the low to medium educated category (χ2 (2) = 6.960, p = 0.03). When the child was over two years of age, 63% were willing to brush for at least 3 min compared to 40% for children under two (χ2 (2) = 6.982, p = 0.03).
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82,010 |
Of the 29 laboratories from 11 countries (Austria, Canada, Croatia, Denmark, France, Germany, Italy, The Netherlands, Spain, UK, USA) that took part in the FXI:C assignment, there were 8 clinical laboratories, 9 therapeutics producers, 6 diagnostics manufacturers, 5 regulatory laboratories, and 1 research laboratory. Eleven laboratories (2 clinical laboratories, 1 diagnostics manufacturer, 6 plasma therapeutics producers and 2 regulatory laboratories) from 8 countries (Austria, Canada, Denmark, France, Germany, Spain, UK, USA) carried out assays for FXI:Ag.
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95,750 |
The data also suggest that biomedical scientists in the UK are working long hours and over weekends for relatively little financial reward: 53% worked more than five days in the week before they took the survey, and only 16% reported receiving an annual salary of over £35,000. A recent online poll of readers conducted by the journal Nature revealed that almost 40% of the 12,000 respondents worked more than 60 hours a week on average ( Powell, 2016), a substantially higher number than that found in this survey (12% across all career stages). One explanation is that while the Nature poll asked readers (from all scientific disciplines) to report their average working week, the survey presented here instead asked respondents to report the number of hours worked in the week immediately preceding the survey, and to estimate an average only if this value was atypical. This approach was adopted to limit over-estimation and to provide a more accurate dataset. The same Nature poll also reported that almost two thirds of readers have considered leaving research altogether, and that 15% have actually left, again, far higher than numbers reported here ( Powell, 2016). While approximately 30% of UK-based biomedical scientists surveyed here reported their plans to leave research, it is possible that this figure is somewhat inflated. Firstly, as with any survey or poll, individuals who do not engage are just as illustrative as those who do. It is likely that there exists a population of biomedical researchers who are satisfied enough with their work/life balance that that they choose not to engage with articles addressing such issues, which would tend to dilute more positive views. Secondly, despite approximately 30% of respondents surveyed here stating their intention to leave research, it is probable that some fraction of these will decide to remain, and the number who actually do leave may well be lower. However, considering that the majority of respondents were PhD students, it is likely that many will indeed pursue a career outside of academia – a Royal Society report from 2010 estimates that 53% of science PhD students do not pursue an academic career – making a leaving rate of 30% seem more likely ( The Royal Society, 2010).
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77,107 |
Previously published non-autonomous gap gene circuits suggest a specific regulatory structure for the gap gene network in D. melanogaster (Fig 3A) . This structure is consistent with the network predicted by the static-Bcd model of Manu et al. , and with the extensive genetic and molecular evidence available in the published literature on gap gene regulation . Unfortunately, it is difficult to derive insights about dynamic regulatory mechanisms from a static network diagram. Computer simulations help us understand which network interactions are involved in positioning specific expression domain boundaries across space and time [24–26, 34]. Although powerful, this simulation-based approach has its limitations. It cannot tell us how expression dynamics are brought about: for instance, why some gap domain boundaries remain stationary while others shift position over time. To gain a deeper understanding of the underlying regulatory dynamics, we analyse the configuration space of a fully non-autonomous gene circuit through instantaneous phase portraits (S1B Fig) , analogous to the autonomous phase-space analysis presented by Manu and colleagues (Fig 2). This type of analysis requires diffusion-less gap gene circuits to keep the dimensionality of phase space at a manageable level.
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128,457 |
As shown in Figure 4, ethosome® formulation B was able to mask the toxic effect of free ethanol. The free ethanol induced a significant cell mortality (p < 0.001) already after 24 h of exposure, with a cell viability reduction of 80%, while the same amount of ethanol as a component of ethosomes® elicited a minor reduction in cell viability after 24 h. After 72 h, the viability of cells treated with formulation B was three times greater than cells treated with the equal amount of free ethanol.
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389,496 |
AP, angina pectoris; BMI, body mass index; CABG, coronary artery bypass graft; CHD, coronary heart disease; HDL, high-density lipoprotein; LDL, low-density lipoprotein; MI, myocardial infarction; PCI, percutaneous coronary intervention; sd, standard deviation
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394,123 |
All samples were processed in duplicate (2840 total runs) on the Yumizen H550 instrument, using the manufacturer recommended reagents, calibrator and controls. Analyzer performance was monitored daily using three levels of quality control material. Calibration was completed at the start of the study and confirmed at the conclusion of the study.
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278,399 |
The apoptosis detection kit with annexin V/PI from BD Biosciences (San Jose, CA) was used to detect apoptosis. Further, the ELISA kit for Cell Death Detection from Roche Diagnostics (Indianapolis, IN) was used to determine DNA fragments associated with histones as per the provided instructions. Western blotting was carried out to determine apoptosis and protein cleavage.
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217,448 |
Angiotensin receptors function by binding to the angiotensin II hormone and play crucial roles in the human body, including renal regulation, cell growth, and survival . Angiotensin receptor blockers (ARBs) are antagonists such as valsartan and losartan, which are clinically used to treat high blood pressure . Many ARBs, including valsartan and losartan, are based on a biphenyl tetrazolo structure . In addition to these, ARBs have also been shown to have CAF reprogramming effects and reduce α-SMA+ CAF levels . However, an important challenge is that ARBs can cause hypotension. Hence, novel delivery systems are being demanded to reduce their on-target side effects in cancer application. An ARB nanoconjugate with valsartan attached to polyacetal (1,1,1-Tris(hydroxymethyl)ethane, di(ethylene glycol) divinyl ether and polyethylene glycol) . These nanoconjugates were designed to overcome the hypotension side effect generated by ARBs. Thus, the ARBs were chemically linked with an acid-degradable polymer that is sensitive to the pH of the tumor. These ARB nanoconjugates were examined in murine models, where they accumulated in high concentrations, were active in tumors, and remained inactive in the circulation. This system improved the BCAF-targeting capacity of ARBs and reduced the side effect of lowering the blood pressure. The ARB nanoconjugate significantly decreased α-SMA+ cells (mostly BCAFs, as well as the minute population of other cell types such as pericytes), collagen I expression, and solid stress compared to the unconjugated ARB in the murine TNBC model (4T1). Moreover, the ARB nanoconjugate enhanced the activities of T lymphocytes and immune checkpoint blockers .
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145,137 |
This study had some limitations. Participants of this study may not be a reflection of the entire physician population in the country. It would be valuable to obtain perceptions of all other disciplines who are involved as a multi-disciplinary team to deal with CVDs and its consequences. There were challenges found during data collection due to the current global pandemic, COVID-19. Also face-to-face interview would have been more suitable and comprehensive in conducting in-depth interviews. The perceptions of physicians in a rural setting may have differed due to limited resources and patient, physician and health setting factors. With the recordings, it is also possible the participants would have given ideal answers and restricted their actual views and opinions.
| 2 | 0biomedical
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347,717 |
To observe the effect of brain-wave music on sleep, participants with a regular habit of staying up late were enrolled in the experiment. We recruited 36 right-handed subjects who had the sub-healthy sleep quality (PSQI scores should be between 4 and 8) from UESTC, and three of them gave up in midway through the experiment. The data of the remaining 33 participants (16 females; mean = 21.4 ± 5.6 years of age) were finally included in our experiment. All subjects gave informed consent for participation and received compensation.
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273,241 |
In addition to unravelling the plant pathogenic fungi associated with beech decline, we frequently detected bacterial genera (i.e., Acidovorax, Erwinia, Pseudomonas, Xanthomonas) (Figure 4, Table S2) known to be potential pathogens in discolored wood samples . In fact, 11 out of 20 most abundant bacterial ASVs detected in this study belonged to such potential plant pathogenic bacterial genera (average relative abundances = 44.6%, ranged from 16.3–76.9% in all five discolored samples) (Figure 4). Erwinia spp. and Pseudomonas spp. were detected in all discolored wood samples. Specifically, Pseudomonas ASV000004 and ASV000005 (closest hit (100%) with Pseudomonas syringae) co-dominated or highly dominated the bacterial communities in all discolored wood samples (relative abundances ranged 11.4–60.6%) (Figure 4). Erwinia ASV000006 and ASV000007 (closest hit (100%) with Erwinia rhapontici and Erwinia amylovora, respectively) were highly dominating in sample D2 (43.3% of total detected bacterial sequences) and substantially contributed in other 3 samples (D1, D3 and D5 with relative abundances ranged from 4.2–8.3%) (Figure 4). Pseudomonas spp., especially various pathovars of Pseudomonas syringae are identified as main disease agents of bacteria blight, canker and dieback for woody plants in agroforest ecosystems . Erwinia spp. are important plant pathogenic bacteria associated with fire blight disease in woody plants, especially rosaceous hosts . It has been shown that Erwinia amilovora (the most intensively studied species in this genus) can enter plant tissues via blossoms and stomata or wounds to above- or below-ground organs, and later it can spread systemically through the vascular system . Moreover, from below ground Erwinia amylovora can also form aggregates/biofilms on tree root surfaces, colonize and infect the internal tissues of the roots, and later it can enter the stem tissues by xylem penetration . Overall, our results suggest that plant pathogenic bacteria can potentially be an additional agent for beech decline, especially for weak beech trees suffering from drought, which may already have wounds from fungal infection or insect infestation. The bacterial agents for beech decline may have been overlooked as fungal agents are also present at the same infection areas.
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200,749 |
Experiment of the bi‐shell valve. Photographs of bi‐shell valve: A) initial state, B) state (i) before snapping, and C) state (ii) after snapping. The top of the imperfect shell is outlined with a red cap to emphasize the difference between states. D–F) Pressure‐volume responses of the input chamber, the spherical cap, and the imperfect shell. P C is the theoretical critical pressure of a perfect spherical shell and V 0 is the volume of a hemisphere. The cyan domains in (E) and (F) show the envelope of the experimental response of three tested samples.
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124,247 |
The prevailing treatment strategy for tremors involves medication and surgical intervention. Medications such as propranolol, antiseizure medications, antidepressants, and benzodiazepines offer partial benefits but also some adverse effects . For instance, although the treatment response to propranolol is remarkable in some patients , its adverse effects, including hypotension, bradycardia, depression, and fatigue, may be intolerable, especially for older patients; severe bradycardia with syncope has even been reported . Some antiseizure medications and benzodiazepines are effective for tremor treatment, but the main side effect, sedation, usually results in the discontinuation of medications . Surgical intervention may include deep brain stimulation (DBS) or magnetic resonance-guided, focused ultrasound (MRgFUS) thalamotomy. DBS has demonstrated robust therapeutic effects ; however, possible DBS-related complications, including intracranial and intracerebral hemorrhage, infection, and improper DBS location, have been noted . DBS in the ventral intermediate nucleus of the thalamus may be associated with stimulation-induced paraesthesia, dysarthria, and ataxia . Other minor side effects such as paresthesia, headache, dysarthria, and dyskinesia have also been reported . Moreover, the invasive nature of DBS affects patients’ willingness to undergo treatment. The MRgFUS thalamotomy is a novel, noninvasive alternative . However, the cost and potential disequilibrium side effects sensation limit this treatment’s utility .
| 4 | 0biomedical
| 2Review
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364,843 |
J.B. designed the HAMAP-SPARQL system, implemented the software to convert HAMAP rules to SPARQL, ran the analysis, and co-wrote the manuscript. E.d.C. implemented the original HAMAP pipeline and assisted with the translation of the rules to SPARQL. D.B. implemented software to extract sequence/signature matches in RDF format from an Oracle database. S.G. helped to optimize SPARQL queries and define the rule data model. B.A.C. helped to define the RDF format for sequence/signature matches. A.H.A., E.C., C.H., P.M., I.P., and C.R. curate Swiss-Prot entries and HAMAP rules used in this manuscript. I.X. participated in the planning of the project. N.R. tested and revised the tutorial and co-wrote the manuscript. A.B. co-wrote and edited the manuscript. All authors provided critical feedback on the project.
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324,144 |
Analysis of the top negative correlations with the MS and SOMAscan proteomics data sets revealed that seroconversion correlates strongly with decreased plasma levels of subunits of the various complement pathways (Supplementary files 2,3). In fact, 10 of the top 20 negative correlations in the MS data set are complement subunits or complement regulators, and the top negative correlation in the SOMAscan data set is the complement subunit C1QC (Figure 4a,b, Figure 1—figure supplement 1b,c, Supplementary files 2,3). This led us to complete a more thorough investigation of the interplay between seroconversion and the complement pathways (Supplementary file 8).
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261,585 |
Development of remotely delivered therapy for treatment of PTSD in young people lags behind that for other disorders. Jaycox and colleagues23 report encouraging preliminary outcomes for a self-help web-based tool to augment and enhance usual school support services for trauma-exposed youth (7th – 12th grade, mean age 15 years). Kassam-Adams and colleagues24 showed that a digital intervention for preventing PTSD symptoms in injured children (8–12 years old) was feasible and clinically promising. Ruggiero and colleagues25 found that use of a web-based psychoeducation intervention for disaster-affected adolescents (mean age 14.5 years) was associated with improvements in PTSD symptoms. However, to our knowledge, no studies have yet reported on the development or evaluation of internet-delivered TF-CBT for treatment of PTSD in children and young people. This is surprising because face-to-face TF-CBT is well established as an effective treatment for PTSD in youth, and work with adults shows that PTSD is a disorder which is treatable via the internet.26
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177,255 |
Additional file 6 : Figure S1. Alteration frequencies of collagens in ACRG and HK/Pfizer datasets. A. Alteration frequencies of sequenced collagens in other stomach cancer cohorts. B. Kaplan-Meier analysis of COl11A1, COL5, COL4, COL6 mutations in the ACRG targeted sequencing dataset compared to the same set of collagen genes in the TCGA cohort. Figure S2. Survival analysis of somatic mutations in each collagen gene. A. Kaplan Maier analysis of tumors with any type of mutation in each collagen gene across the whole STAD TCGA cohort. Tumors with the designated collagen mutation are in red. Wild-type tumors are in blue. P-values determined by log-rank test. B. Kaplan Maier analysis of tumors with truncation mutations in each collagen gene across the whole STAD TCGA cohort. C. Kaplan Maier analysis of tumors with any type of mutation in each collagen gene in MSIH cases. D. Kaplan Maier analysis of tumors with truncation mutation in each collagen gene in MSIH cases. Figure S3. Identification of combinations of collagens genes associated with overall survival relative to background. A. All mutations across the whole TCGA cohort. B. Representative examples of combinations of 2 collagens associated with overall survival. C. Combinations of all mutations in MSS tumors only. D. Combinations of all mutations in MSIH tumors only. E. Example of collagen genes with truncation mutations most frequently associated with overall survival when combined, classify MSIH tumors into high and low overall survival risk. Figure S4. Collagen mutations have MSIH and MSS context dependent differences in overall survival. Mutations in COL5A3 and COL14A1 have different associations in MSIH and MSS tumors even though the total number of mutations is similar. Figure S5. MSIH and MSS tumors have distinct microenvironments in TCGA. A. MSI status was associated with outcome in ACRG but not in TCGA. B. Comparison of MSIH and MSS stomach tumors by pre-ranked GSEA reveals differences in expression. Each heatmap plots the Normalized Enrichment Scores (NES) from the GSEA. NABA ECM gene sets were expressed higher in MSS tumors compared to MSIH tumors. Many immune cell expression signatures including cytotoxic cells were expressed higher in MSIH tumors compared to MSS tumors. B cells were expressed higher in MSS tumors. The majority of cancer hallmark expression signatures were expressed significantly higher in MSIH tumors compared to MSS tumors. Figure S6. Pre-ranked GSEA of collagen mutation combinations in Table S4 for the whole TCGA STAD cohort shows consistent impact for each mutation combination. A. Hallmarks for combinations with both missense and truncation mutations. B. The NABA and immune signature genes sets for combinations with both missense and truncation mutations. C. Hallmark, NABA, and immune signature gene sets for combinations with just truncation mutations. D. Clustering of hallmark gene sets for tumors with missense mutations only in the whole TCGA cohort showed significant difference for the EMT hallmark relative to overall survival. P-value calculated by Kolmogorov-Smirnov. Figure S7. In MSS cases, pre-ranked GSEA of tumors with either a missense or truncation mutation combination as listed in Table S4 show impact of collagen mutations on pathways some of which are correlated with overall survival. A. For all mutations in MSS cases, some hallmarks such as EMT were associated with overall survival as shown in the heat map and box plot. P-value calculated by Kolmogorov-Smirnov. B. NABA ECM and immune signature gene sets in MSS tumors. Basement membrane and macrophage signature gene sets were among the gene sets most associated with overall survival, showing consistent downregulation in tumors with mutant collagens and higher expression in wild-type tumors. P-value calculated by Kolmogorov-Smirnov. Figure S8. In MSIH cases, pre-ranked GSEA of tumors with either a missense or truncation mutation combination as listed in Table S4 show impact of collagen mutations on pathways some of which are correlated with overall survival. A. Clustering of hallmark gene sets partitions tumors with collagen combinations by overall survival. Box plot shows the significant difference in the EMT hallmark as defined by combinations associated with high or low risk of overall survival. B. NABA gene sets showing large differences in Basement Membrane and ECM Affiliated gene sets relative to overall survival. C. Immune cell signature gene sets showing large difference in Tregs and Macrophage expression signatures. P-value calculated by Kolmogorov-Smirnov. Figure S9. In MSIH cases, pre-ranked GSEA of tumors with only missense mutation combinations as listed in Table S4 show impact of collagen mutations on pathways some of which are correlated with overall survival. A. Hallmark gene sets. B. NABA ECM sets. C. Immune cell gene signatures. P-value calculated by Kolmogorov-Smirnov. Figure S10. In MSIH cases, pre-ranked GSEA of tumors with only truncation mutation combinations as listed in Table S4 show impact of collagen mutations on pathways some of which are correlated with overall survival. A. Hallmark gene sets. B. NABA ECM and immune cell signature gene sets. P-value calculated by Kolmogorov-Smirnov. Figure S11. COL7A1 is expressed in some tumor cells in STAD. Representative images of COL7A1 protein and RNA expression in stomach adenocarcinoma. A. Immunohistochemistry (A, C, E) and in situ hybridization (B, D, F) for COL7. Stromal localization in C, E, D, and F, and mixed stromal and carcinoma localization (at white arrows; A, B). B. Higher magnification of panels A and B from S7A showing expression by IHC in panel A and ISH in panel B of COL7A1 in epithelial regions. The arrow shows ISH signal in tumor cells. C. Representative images at higher power of COL7A1 protein expression by IHC in the epithelium and stroma. D. Representative image of COL7A1 protein expression in normal human skin. Note the line of expression in the ECM between the dermal and epidermal layers (red arrow). Cells expressing COL7A1 show cytoplasmic signal as they are overexpressing COL7A1 to be secreted to form the “anchorage” line. Figure S12. Comparison of pathological germline and somatic mutations in STAD in three collagens. Comparison of the distribution of mutations across each gene and a lollipop plot mapping the somatic mutations to the protein domains. A. COL1A1 and COL1A2. B. COL4A1 and COL4A2. C. COL5A1 and COL5A2.
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351,815 |
Peptides have been investigated for a long time and it is currently known that, similar to hormones, they can regulate many important body functions. They are characterized by many properties, including antihypertensive, antioxidant, antimicrobial, anticoagulant, and chelating effects (Figure 2). They are also responsible for the taste of food or inhibition of enzymes involved in the development of diseases. However, peptides may also show toxic activity or allergenic effects, especially in people with celiac disease. The activity of peptides depends on their structure and amino acid composition. Until recently, it was thought that bioactive peptides are composed of 2–20 amino acids. It is now known that they may contain more amino acids in their structure (for instance, insulin with the peptide-C structure), which play a special role in carbohydrate metabolism; hence, analysis of their content is an important factor in diabetic diagnosis .
| 4 | 0biomedical
| 2Review
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117,616 |
In realistic models of biochemical systems/physiological processes with (1) saturable signaling kinetics and (2) saturable reaction kinetics, it is a challenge to have an intuitive understanding of how a controller motif is able to compensate for large variations in the perturbation. The comprehensional difficulty lies in the fact that the controller's maximum impact on the compensatory flux of A is limited to 1, and the maximum dependence on the substrate species concentration is also only 1 (through the Michaelis–Menten relationship). As we will show, the key to understand this puzzle is found in the ratios of signaling values and Michaelis–Menten expressions at high and low levels of E and A, respectively, and from this we identify a relaxing component in physiological control.
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51,528 |
Primers were designed using Primer 3 software (Applied Biosystems, Foster City, CA, USA). Total RNA was extracted from EFV-treated Huh-7 cells using TRIzol reagent, as described previously . For ALDH3A2 detection, MMAB shRNA transfected Huh-7 cells were cultured for 48 h, and total RNA was extracted. Subsequently, cDNA was synthesized via RT-PCR with the SuperscriptⅡkit (Life Technologies, Karlsruhe, Germany). Real-time Q-RT-PCR was performed on a 25 μl reaction mixture containing 700 nM forward and reverse primers, 80 nmol template and 1 × Sybr Green reaction mix (Applied Biosystems, Foster City, CA, USA). Sybr Green fluorescence was determined with the ABI PRISM 7500 detection system (Applied Biosystems, Foster City, CA, USA). The mRNA expressions of genes were normalized against that of the control gene (Glyceraldehyde 3-phosphate dehydrogenase (GAPDH)). The primers of four differentially expressed genes used in study are shown in Table 2.
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97,491 |
Bacteria belonging to the genus Enterobacter spp. are Gram-negative Proteobacteria of the family Enterobacteriaceae and currently comprise 22 species . They represent a diverse group which are widely distributed in nature and possess multiple mechanisms to allow survival in a variety of environmental niches . In humans, they may cause a wide variety of clinical infections and are a common cause of bacteraemia , especially within adult and neonatal intensive care units (ICUs) [4, 5].Fig. 1Inclusion flowchart for case–control study
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315,583 |
2) The authors provide some experiments showing that there is no signal when either the padlock cannot be ligated or the SplintR ligase is omitted. While these experiments demonstrate that a circle must be formed in order for signal to be produced, they do not substitute for control experiments showing that there is no significant off-target hybridization. The authors do perform a blocking oligonucleotide experiment for Secretoglobin 1a1 which has a nice result. However, when they actually quantify the specificity using surfactant C, this reveals a 7.4% false positive rate, which in my opinion is far too high to be acceptable for any staining technique. Supplemental Figure 4A-B encapsulate how poor the specificity of Scrinshot is, where most cells in a cluster that express the neuroendocrine marker Ascl1 (in panel A) co-express the Club cell marker Secretoglobin 1a1 (in panel B). Clearly, one of the markers is spuriously labeling the cells, since they should be complementary, rather than co-expressed. Another striking example is the type I marker AGER in Figure 6A for which puncta are shown in all epithelial cells, including most of the surfactant C positive cells which are putative type II cells. The authors seem to be aware of the extent of this specificity problem, because in their definitions of each cell type, they permit detection of one incompatible marker as long as there are two appropriate markers. This is highly contrived and betrays the high level of false positive signal produced by Scrinshot.
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218,286 |
Therefore, the aim of our study was the following:To analyze the immunohistochemical PD-L1 staining pattern in a large series of CC, stages I–IV.To elucidate the role of PD-L1 immunohistochemistry in the context of the “budding and TIL combination” as tumor-host antagonists.To identify PD-L1-positive “budding/TIL” subgroups which might qualify as potential additional candidates for future immunooncogenic treatment decisions.
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202,133 |
Short-chain quinones are known to be toxic, especially those containing 0–3 isoprene units, whereas CoQ4 displays only minimal toxicity (Takahashi et al., 2018). During mitochondrial respiration the VK2 might transfer electrons from complex I or complex II directly or indirectly to cytochrome c, according to the diffusion mode of shuttling electrons along the respiratory chain (Nesci and Lenaz, 2021). This VK2 role as electron transporter in the respiratory chain (Colpa-Boonstra and Slater, 1958) is still controversial. Accordingly, in spite of reports which rule out this possibility (Cerqua et al., 2019), in an in vitro model VK2 enhanced respiratory chain efficiency and contributed to building the electrochemical proton gradient (ΔμH+) by respiratory complexes that are exploited to generate ATP, similarly to CoQ10 (Vos et al., 2012). Our findings show that the effect on mitochondrial respiration could depend on VK2 concentration, namely the positive effect shown at 5 μM VK2 may become harmful at high concentrations. The VK2 structural properties are consistent with the stimulation of mitochondrial respiration without any effect on glycolysis. Consistently, low VK2 concentrations can favor an energy boost in IPEC-J2 cell activation, proliferation, and differentiation by increasing the OXPHOS capability to produce ATP.
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240,397 |
In Germany, males of Physetopodahalensis occur with two colour variants, including a completely black form and a form with the mesosoma partly red. The colour forms exhibit minor morphological differences but were treated as conspecific (Petersen 1988). In Germany, the red form is restricted in its distribution to eastern Germany. The black form occurs mainly in western parts of Germany, in the state of Baden-Württemberg, but overlaps with the red form in Central and Eastern Europe. Here both forms are regarded to represent valid species, but the taxonomy of this species needs further investigation.
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115,171 |
Antigen-specific T cell recognition is an essential component of the adaptive immune response fighting infectious diseases and cancer. The T cell receptor (TCR)-based recognition profile of a given T cell population can be determined through interaction with fluorescently labeled multimerized peptide major histocompatibility complexes (pMHC multimers) (1), enabling visualization of specific pMHC-responsive T cells by flow cytometry (2). This analysis has become state of the art for antigen-specific CD8+ T cell detection and is important for pathophysiological understanding, target discovery, and diagnosis of immune-mediated diseases. Detection of pMHC-responsive T cells is challenged by the low-avidity interaction between the TCR and the pMHC, often resulting in poor separation of fluorescent signals distinguishing the MHC multimer-binding from non-binding T cells (3). Additionally, a given antigen-specific T cell population is in most cases present at low frequencies in the total lymphocyte pool (4).
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230,642 |
This work was supported by a PhD studentship from East London NHS Foundation Trust. The ERA study is funded by the 10.13039/501100000272National Institute for Health Research (NIHR) Health Technology Assessment programme [grant number 17/29/01]. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.
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78,466 |
Error bars displayed are standard deviations from the mean of at least three replicates, unless otherwise indicated. Comparison of two groups was performed using two-tailed pairwise student's t-tests. Logrank significance tests were performed on Kaplan-Meier survival curves with p-values generated via the pairwise multiple comparisons Holm-Sidak method. RPPA data analysis was performed by MD Anderson (see method above). p-values ≤ 0.05 were considered significant.
| 3 | 0biomedical
| 0Study
|
54,580 |
Furthermore, less than 6% of Cypriot patients reported severe ‘pain or discomfort’ problems, while approximately 45% patients reported moderate problems (Figure 4). Regarding pain effects, a study from Tomaaso et al. (2011)26, which evaluated pain perception in HD patients, concluded that pain is not a common symptom in HD. This is confirmed with other studies, were bodily pain was negatively related to the illness perceptions of HD patients27 , 28. This symptom is in contrast to other neurodegenerative diseases, such as PD29.
| 4 | 0biomedical
| 0Study
|
96,405 |
The intestinal immune system is the first defense line for the contact with dietary antigens. Intestinal changes caused by intestinal infection, oral milk or gluten protein antigens, and varied intestinal flora has been confirmed involved in the pathogenesis of DM (Luck et al., 2015). Prior to the occurrence of diabetes, the intestinal morphology and gut immune system have changed, and intestinal permeability increases (Graham et al., 2004). On the other hand, mesenteric lymphocytes transplantation of non-obese diabetic mice could transfer diabetes to the recipient mice, which indicates DM-caused T cells exist in the gut immune tissue (Antvorskov et al., 2014). As is well known, T2DM is a chronic inflammatory disease; many factors are associated with the onset of T2DM including intestinal flora disturbance, immune tolerance deficiency, intestinal barrier damage, pattern recognition receptor (PPRs) expressions changes in intestinal epithelial and immune cells and gut hormone change (Winer et al., 2016). With intestinal barrier defect, LPS and other intestinal bacteria products filter into the circulation and result in local and systemic chronic inflammation, which makes islet beta cell dysfunction and insulin resistance (Burcelin, 2012). However, the role of gut immune cells and inflammation in the pathogenesis of DM are still not fully explored.
| 4 | 0biomedical
| 0Study
|
363,924 |
In a first step, in the emotion course, artworks characterized by strong emotional facial expressions had first to be reproduced by students who were asked to focus on drawing the crucial characteristics in the artwork that revealed the emotions expressed. Students received two portraits with clearly recognizable emotions, namely fear and anger, and were asked to trace these portraits in the first step (Figure 1, Tracing- Drawing-Task 1, 2). In a second step, the emotionality of two portraits had to be intensified by means of drawing. Here, the adolescents received an ambiguous facial expression (e.g., a Rembrandt portrait whose facial expression might show surprise or fear). The students were asked to envision and draw this portrait in a way that it displays a clearly recognizable emotional expression of fear (Figure 1, Intensifying-Drawing-Task 3, 4). Finally, there was another task (Figure 1, Transfer-Drawing-Task, 5) in which the students were given a neutral painting that they should envision and draw in a way that it displays different emotions (anger, fear and as a transfer assignment the emotion sadness).
| 3 | 2other
| 1Other
|
208,772 |
In summary, this retrospective cohort study demonstrated that low ISBP might be associated with TND risk following STA-MCA anastomosis in adult patients with MMD. In patients with poor perfusion status, low ISBP increased the risk of TND. Our findings suggest that strict ISBP control might be required to prevent TND in this patient group, in particular, in patients with a poor perfusion status. Given the limitation due to retrospective design, further studies are needed to clarify these findings.
| 4 | 0biomedical
| 0Study
|
13,683 |
Prevalence rates of index surgeries performed between 2003 and 2013 and subsequently revised for infection between 2003 and 2014 were derived by year and type of index surgery. This provides a ‘surgeon’ perspective of revision for PJI by describing the proportion of knee replacements which required revision surgery for the management of infection. The prevalence rates were plotted by time from index surgery to revision for infection (≤3 months, 3–6 months, 6 months to 1 year, 1–2 years, 2–3 years, 3–4 years and 5–6 years). For two-stage surgeries, the date of stage 1 of a two-stage revision was selected to indicate the date of revision for PJI. Log-linear regression, using the year of the index knee replacement as a continuous independent factor, was used to investigate overall linear trends between 2005 and 2013. This period was selected as over 85% (proportion of procedure records submitted to the NJR compared with the levy returns for the number of implants sold) of knee replacements performed in 2005 and over 99% of those performed from 2007 onwards had been recorded in the NJR; prior to 2005, the data capture of the NJR was <75%.21 When evidence of a time trend was identified (year of surgery, p≤0.05), the year of surgery was reconsidered as a categorical variable using 2005 as the reference period. Estimated relative risk and related 95% CI quantified the relative increase in prevalence rates between the period of interest and 2005.
| 4 | 0biomedical
| 0Study
|
22,009 |
Chen and Pan (2005a) demonstrated that lead did not cause significant damage of A. platensis cells over 7 days of incubation at metal concentration ranging up to 20 mg/l. In the current study, higher heavy metal concentration increased chances of “contacting” ions with active binding sites which resulted in enhanced sorption. The adsorption of metal ions by filter paper has not been considered in previous studies where the same procedure of separating biosorbent from test solution was applied (Gong et al. 2005b; Parvathi et al. 2007; Şeker et al. 2008; Solisio et al. 2008). Therefore, it would be needed to revise results and findings reported in cited papers to verify actual efficiencies of lead(II) removal by microbial biomass.
| 4 | 0biomedical
| 0Study
|
184,576 |
Interestingly, both in small companion animals and equine, there are no reports about the effect of plasma transfusion and the subsequent interaction with vaccination. This might be worth further investigation. Indeed, the presence of antibodies has been shown to interfere with vaccination, plasma contains antibodies and plasma transfusion is a common practice in neonatal equine medicine.
| 2 | 0biomedical
| 1Other
|
298,244 |
This research investigated the role of films in developing intercultural competence and increasing wellbeing. An experimental design was used with two parallel, relatively equivalent groups (one in Romania and the other in Brunei), with two measurement moments, pretest and posttest, within-subject, and between-subjects. The results are not spectacular, but they are significant. The effectiveness of the intervention program on intercultural competence, cultural intelligence, and level of wellbeing has been demonstrated. The viewing of the two films (EPL and HT) and the non-formal discussions after the viewing resulted in an increase in the level of positive emotions felt, a higher level of engagement and awareness of the ways in which cultural background affects interactions with individuals from cultures different from one’s own.
| 1 | 2other
| 0Study
|
14,638 |
PCa is a complex disease; and many etiological factors, including genetic profile, nutrition, environmental exposures, etc., are thought to play important roles in cancer development6. It is widely acknowledged that genetic polymorphisms may act as a predictors of some characteristics of PCa, including incidence rate789, pathology10, progression11, etc.
| 3 | 0biomedical
| 0Study
|
337,080 |
We consider Krylov approximations to the matrix exponential function for the purpose of the solution of a linear, homogeneous system of differential equations\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\begin{aligned} \psi '(t)=M\psi (t),\quad \psi (0)=\psi _0, \quad \psi (t) = \mathrm{e}^{tM} \psi _0. \end{aligned}$$\end{document}ψ′(t)=Mψ(t),ψ(0)=ψ0,ψ(t)=etMψ0.The complex-valued matrix M commonly results from the discretization of a partial differential equation. In this work we present new results for precise a posteriori error estimation, which also extend to the evaluation of so-called \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\varphi $$\end{document}φ-functions. The application of these estimates for the purpose of time propagation is also discussed and illustrated. Theoretical results are verified by numerical experiments, which are classified into Hermitian (dissipative), skew-Hermitian (Schrödinger-type) and general non-normal problems.
| 4 | 0biomedical
| 0Study
|
205,582 |
This bias was rated as “low” for four studies because no conflict of interest was suspected based on authors’ affiliations and funding sources. However, for two studies (Pettersson et al., 2020, Suadicani et al., 2012) it was rated as “probably low” because one was funded by an insurance company, which could have interest in the outcomes of the study, and the other one was funded by several foundations even though a statement of no conflict of interest was provided. Still, the authors were affiliated with public research institutions and health universities, which makes competing interests unlikely (Fig. 4).
| 4 | 0biomedical
| 0Study
|
283,874 |
ZPPs were synthesized via the mini-EP process by mixing OA-ZnO NPs (0.2 g) with St or MMA monomer (2 mL), AA (0.06 mL, 3% wt based on St), and HD (0.06 mL, 3% wt based on St) . After sonicating for 2 min, SDS (1.5% wt of total volume) in an aqueous solution was added, and the mixture was stirred for 1 h before being ultrasonicated for 4 min at 60% amplitude (Branson 450 digital sonifier, Marshallscientific, Hampton, NH, USA) in an ice bath. After raising the temperature to 72 °C, the KPS solution (0.5% wt based of St) was poured into the emulsion to allow for the polymerization for 8 h under an N2 atmosphere. The concentrations of SDS surfactant, KPS initiator, and DVB comonomer were varied, as shown in Table 1.
| 4 | 0biomedical
| 0Study
|
152,090 |
Most NPs are thought to penetrate cells through forming vesicles, and these membrane-bound vesicles transport NPs along MT to intracellular compartments. During this process, the NPs might have indirect interactions with cytoskeletal proteins and change their organizations. It is not clear how they interact with those proteins while they are encapsulated inside lysosomes and endosomes . However, there are some evidence showing that NPs could directly interact with the cytoskeletal proteins. It has been found that carbon nanomaterials enter cells by adhesive interaction, enabling them to freely swim in the cytoplasm and directly interact with the subcellular structures of cells. For example, Lundqvist et al. found the presence of MT in the protein corona formed around the SiO2 NPs, suggesting the direct NPs–proteins interactions. Direct or indirect interaction with NPs may negatively affect the biological functions . Tian et al. showed that single-wall carbon nanotubes could enter cells and alter cell morphology by disturbing the actin networks. They observed that these NPs cause an irregular actin network in comparison to untreated cells. Various NPs-related parameters such as the shape, size, surface chemistry, concentration, and incubation time are important in assessing the toxicity of nanomaterials in cytoskeleton. The shape of the NPs can induce different effects on the cytoskeletal structure of cells. It has been shown that unlike silica NPs with small aspect ratios, silica nanorods with large aspect ratios can largely change the organization of the actin filament, particularly in the vicinity of the cell membrane, resulting in serious damages to the cytoskeletal structures . Ibrahim et al. used different techniques such as SEM, TEM, and immunofluorescence analysis to study the cytoskeletal changes in osteoblast-like cells underexposure of titanium-based orthopedic and dental implants NPs (nano-Tio2). Smaller particles were found to be more disruptive to the actin and microtubule cytoskeletal network in comparison to larger particles. In another work, Holt et al. used fluorescence lifetime microscopy to study the interactions of single-wall carbon nanotubes with HeLa cells. They showed that nanotubes preferentially interact with F-actin compared to G-actin and dramatically change their distribution. NPs even could disrupt the MT and actin network at non-toxic concentrations. Liu et al. showed that bare gold NPs with the size of 20 nm alter the microfilament arrangement of endothelial cells more than NPs with the size of 5 nm. In this study, five types of gold NPs with different sizes and surface coatings were used to determine the viability and cytoskeletal change of endothelial cells. They found that gold NPs do not affect the viability of cells; however, the force balance between intracellular tension and paracellular forces is broken in 20 nm bare gold NPs-treated cells. In another study, the sub-lethal concentration of silver NPs was used to investigate cytoskeletal changes in neural cells . They found that the percentage of AgNP-treated cells containing inclusions is doubled compared to control cells, indicating a significant disruption of actin filaments.
| 4 | 0biomedical
| 0Study
|
65,230 |
In summary, the current study completes a series of investigations examining the role of PDZ proteins in regulating the expression, trafficking and signaling of CRFR1. We find that PDZ proteins play an overlapping but distinguishable role in regulating the post-translational modification, ER-Golgi trafficking, endocytosis and signaling of CRFR1 . Although each of these proteins had a similar effect on CRFR1 endocytosis, as they each, with the exception of PDZK1, function to antagonize CRFR1 internalization, they exhibit pleiotropic effects on the regulation of CRFR1-mediated ERK1/2 activity. These observations indicate that there is likely no redundancy of function for PDZ proteins in the regulation of GPCR activity in vivo, and suggest that in a cellular context these proteins may interchangeably interact with GPCRs to differentially regulate the recruitment of signaling complexes required for their activation of mitogenic signaling pathways.
| 4 | 0biomedical
| 0Study
|
45,263 |
Pulmonary artery hypertension (PAH) is a life-threatening medical condition of lungs characterized by continuous vasoconstriction, refractory elevation of pulmonary arterial pressure, as well as the pathogenic hallmark of vascular remodeling that primarily involves smooth muscle layer of the vessel wall [1, 2]. Abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs) with the extension of smooth muscle into small, normally nonmuscular pulmonary arteries leads to medial muscularization and hypertrophy, resulting in obliteration and ultimately the obstruction of precapillary pulmonary arteries, and sustained elevation of pulmonary arterial pressure .
| 4 | 0biomedical
| 0Study
|
177,184 |
If our argument is plausible, it has a number of consequences especially for understanding the therapeutic process, which hitherto has been understood mostly in terms of the time and activities inside (in-session) and outside (inter-session) therapist's office (Orlinsky et al., 2004; Orlinsky, 2009; Hartmann et al., 2011). What we suggest here is that the dichotomy can be mediated by the time in-between, which is neither simply outside, nor inside, the physical journey to a psychotherapy session is the time of passing between the two states. It is a process of change, and not only a process of traveling.
| 1 | 2other
| 1Other
|
97,091 |
It is acknowledged that the number of studies included in this review is likely to be small and thus many of the analyses outlined above will not at the moment be possible. However, these methods are reported as this protocol is intended to inform future updates to this review where newer evidence may allow for these analyses.
| 2 | 0biomedical
| 2Review
|
383,460 |
To show the significance of the concept of affective milieus, I bring to mind the topic of climate change. As an exemplary instance of this topic, I want to focus on the public debate about the sustainability of cars. This example will purposefully be exaggerated and I am well aware that there are more subtle undertones which I deliberately pass over. Yet, with this hyperbolic juxtaposition, I hope to pointedly contour the issues at stake, and to specifically highlight the unique understanding that comes with the notion of affective milieus. On the one side of the exemplary debate about the sustainability of cars, environmental activists demand that owning and driving cars ought to be more expensive to meet the actual costs of emitting an excessive amount of CO2 through individual transport. This should be achieved, for example, by introducing carbon taxes that would make gas more expensive. The contrary position – the car lobbyist – usually stresses the cultural and practical value of cars in addition to important social unrests that might result from higher gas prices (see e.g., the Yellow Vests movement). These two positions strongly oppose each other and whenever there is something to be done in either direction, reactions of the opposing side are harsh.
| 1 | 2other
| 1Other
|
237,481 |
As shown in Table 2, independent two-sample t- test showed that the mean of missing primary teeth in male students was significantly higher than female students (p= 0.036). The means of other components in the two genders showed no significant difference (p< 0.05). The average number of family members was 4.56±1.43 ranged 3 to 14 people. One-way ANOVA illustrated that the means of all components in students with different number of family members were statistically significant (p< 0.05), so that with increasing family size, the mean of d, m, dmft, D and DMFT index of first permanent molars increased significantly (p< 0.05), while the mean of component f significantly decreased (p< 0.001). In addition, one-way ANOVA showed that the means of d, f and dmft in students with different birth ranks were significantly different (p< 0.05), so that with birth rank increase the means of d and dmft increased, while the mean of component f decreases significantly. The means of other components were not statistically different (p> 0.05).
| 4 | 0biomedical
| 0Study
|
330,443 |
For the experiments with primary BMDMs, cells were incubated in serum‐free DMEM and treated with EC144 (1 µM) or DMSO (0·1% v/v) for 15 min prior to the addition of LPS (100 ng ml−1 or 1 µg ml−1) for 4 h. Supernatants were collected, and cells were lysed (150 mM NaCl, 50 mM Tris–HCl, 1% v/v Triton‐X‐100, pH 7·3, supplemented with a protease inhibitor cocktail). IL‐6 release was determined in the supernatant by ELISA (DY406, R&D Systems) according to the manufacturer's instructions. NLRP3, IL‐1β and HSP70 levels were assayed by Western blotting of the cell lysates. Proteins were separated by Tris–glycine SDS–PAGE and transferred onto nitrocellulose membranes. Membranes were blocked (1 h, RT) in 5% w/v milk in PBS with 0·1% v/v Tween‐20 (PBS‐T) before incubation (overnight, 4°) with antibodies targeting either NLRP3 (Cryo2, Adipogen, Liestal, Germany), IL‐1β (AF‐401, R&D) or HSP70 (4872, Cell Signaling Technology, Waltham, MA). Membranes were washed three times for 5 min in PBS‐T before incubation with appropriate HRP‐conjugated secondary antibodies. Membranes were washed a further three times before visualization using Amersham ECL Prime detection agent and captured using G:Box Chemi XX6 (Syngene, Cambridge, UK). Membranes were reprobed for β‐actin (AC‐15, HRP‐conjugated, Sigma, Poole, UK) to ensure equal protein loading.
| 5 | 0biomedical
| 0Study
|
8,209 |
The data were analyzed with version 21.0 of the SPSS statistical software package (IBM Corp., Armonk, NY). Separate linear models were constructed for each neuropsychological outcome at the intervention session as dependent variables. The groups (modafinil and placebo) were fixed factors, and neuropsychological test scores at the baseline were used as covariates to account for within-group variance in preexisting cognitive performance. In the intervention session, test versions with higher difficulty levels were used to minimize learning effects. The statistical approach allowed us to account for the cognitive level at baseline on performance after the intervention without potential confounding effects related to differential task difficulty. Additional covariates (National Adult Reading Test, age, etc.) were selected if they accounted for a significant proportion of the variance in linear models. Sidak correction was applied for adjustment of multiple comparisons. All p values reported are corrected for multiple comparisons. Estimates of effect sizes are reported as partial eta squared (ηp2) values. Qualitative interpretations of effect sizes as small, medium, and large correspond to ηp2 values of .001, .059, and .138, respectively (25).
| 4 | 0biomedical
| 0Study
|
8,771 |
It appears that the similar protective effect of nanomolar and micromolar α-T cannot be explained by the fact that nanomolar α-T may accumulate in neurons in the course of long preincubation. Thus, according to the data obtained by Saito and co-authors the presence of 100 nM α-T in the incubation medium does not lead to any increase in the α-T content of brain cortical neurons after 24 h of incubation with this antioxidant, but the presence of 1 µM α-T in the incubation medium for 24 h leads to accumulation of approximately 250 pmol of α-T per mg of protein in brain cortical neurons. That is in contrast to α-tocotrienol which penetrates better to the cortical neurons and accumulates in them even if it is present in the incubation medium in nanomolar concentrations (100–250 nM) .
| 4 | 0biomedical
| 0Study
|
223,711 |
The SRB method was used to assess cell viability. Firstly, HepG2 cells were cultured in a 96-well plate at density of 1 × 105 cells per mL. To determine the toxicity, HepG2 cells were exposed to different concentrations of OA (0–2 mM) for 24 and 48 h, or kaempferol (0–100 μM) or kaempferide (0–100 μM) for 48 h. To determine the lipid accumulation inhibiting effect of kaempferol and kaempferide, HepG2 cells were incubated with kaempferol (5, 10 and 20 μM) or kaempferide (5, 10 and 20 μM) in the presence of 0.5 mM OA for 48 h. After incubation, the medium was then replaced with 25 μL of 50% cold trichloroacetic acid and incubated at 4 °C for 1 h. The plates were washed with distilled water for five times, and air-dried at room temperature for 1 h. After that, the cells were stained with 70 μL of 0.4% SRB for 30 min in the dark. Dyed cells were washed four times with 1% acetic acid and the protein-bound dye was dissolved by adding 100 μL of 10 mM Tris base buffer and shaking on an orbital shaker for 20 min. Finally, absorbance at 540 nm was measured with microplate reader (Molecular Devices, CA, USA).
| 4 | 0biomedical
| 0Study
|
328,994 |
In addition to the failure of generating in vivo phenotypes, reproducing those that could be obtained appears less than certain (Table 1). Perhaps the most striking example of this concerns one of the most studied lncRNAs, Hotair, whose biological significance recently became a subject of debate [26, 50, 144, 145]. In 2013, Howard Chang’s lab reported that a targeted homozygous deletion of Hotair in the mouse genome led to homeotic transformation, derepression of genes including HoxDs, and skeletal malformations . However, in 2016, Denis Duboule’s lab obtained the Hotair deletion strain of mice from the Chang’s team and crossed it with animals of a different background . They found no detectable change in the HoxD gene expression and no significant morphological alterations in the progeny harboring the homozygous deletion of the lncRNA . Overall, of the 3 anatomical phenotypes associated with the Hotair knockout reported by the Chang’s group, 2 could not be found by the Duboule’s team at all and one was found in a very subtle form and attributed to DNA-dependent events . Furthermore, the Duboule’s team could not reproduce any of the previously reported effects of the Hotair knockout on gene expression . In another example, the Gomafu lncRNA was associated with an anxiety-like behavior in mice where this transcript was knocked down in the medial prefrontal cortex using ASOs . However, a later study in knockout mice lacking Gomafu in the entire brain showed no difference in the same behavioral tests .
| 4 | 0biomedical
| 0Study
|
185,693 |
In this study, we investigated the impact of two carbohydrate-based natural products (named P1 and P2) which were selected from a previous screen consisting of an in-house natural extract library, on their abilities to stimulate in vitro Solanum lycopersicum (tomato) pollen germination and pollen tube growth under thermic stress (4, 8, 13, 22, and 28°C). No pollen germination was observed at 4°C in any condition; however, both P1 and P2 were able to stimulate in vitro pollen germination and pollen tube growth at low temperatures (8 and 13°C) compared to untreated pollen. Therefore, to understand the stimulatory effects of these two carbohydrate-based activators, we investigated molecular markers of pollen tube growth such as gene expression of several CalS and Rboh genes, callose plug number, and PME activity.
| 4 | 0biomedical
| 0Study
|
1,851 |
Hemiarthroplasty is useful for minor bone loss situations such as primary malignant tumors limited to the humeral head and metastatic lesions not amenable to intramedullary nailing. Because shoulder function with hemiarthroplasty is dependent on the integrity of the rotator cuff and greater tuberosity which is often compromised by tumor involvement it is not surprising that functional scores are limited. Although the mechanical complication rate was relatively high in this systematic review, it can be partially attributed to the frequency of subluxation requiring soft tissue reconstruction [3, 4]. Glenoid wear can be expected in young patients with hemiarthroplasty , but most oncological patients requiring hemiarthroplasty are >50 years old. Conversion of a painful hemiarthroplasty to total shoulder arthroplasty lead to a high rate of unsatisfactory results .
| 4 | 0biomedical
| 2Review
|
306,214 |
The absence of differences between the relaxation and mindfulness training strategies on the main outcomes of interest (particularly state mindfulness) highlights a general challenge in experimental studies of behavioural interventions that seek to selectively and potently activate a specific therapeutic process of interest (e.g. mindful attention). The challenge particularly arises in the design of suitable control conditions, namely conditions that resemble the active intervention and are equivalently credible, but are relatively inert (e.g. do not activate the neurophysiological/neurocognitive processes underlying mindful attentional states). In the current study, we designed the mindfulness and relaxation strategy instructions to be closely-matched in terms of duration, complexity, credibility and expectancy. Although we were successful in these respects, similar increases in state mindfulness in the two strategy conditions suggest that the relaxation instructions may have been insufficiently distinct from the mindfulness instructions, resulting in both strategies equivalently activating mindfulness-like subjective states. For example, both sets of strategy instructions indicated that participants should return to employing the strategy if their attention drifted. Thus, the relaxation instructions may have unintentionally activated a form of meta-cognitive awareness that is more typical of mindfulness exercises than relaxation. In addition, expert raters evaluated the strategy instructions to be ‘moderately’ (rather than highly) distinct in terms of the subjective and physiological states they were likely to engage (see Supplemental material). These considerations suggest that future research in this area should aim to employ more distinctive control strategies, which are nonetheless designed to be equivalent to active mindfulness conditions on credibility, expectancy, etc. (e.g. affective/cognitive suppression or reappraisal; Beadman et al., 2015).
| 4 | 0biomedical
| 0Study
|
232,387 |
MCF-7 cells were simultaneously transfected with si-NC and si-ADAMTS9-AS1, and treated with JAK STAT signaling pathway inhibitor INCB018424 (HY-50856, MedchemExpress; Punwani et al., 2012). qRT-PCR result indicated that the expression of ADAMTS9-AS1 in si-ADAMTS9-AS1 + DMSO group was markedly lower than that in si-NC + DMSO group (p < 0.05). While there was no significant difference in ADAMTS9-AS1 expression between the si-ADAMTS9-AS1 + DMSO group and the si-ADAMTS9-AS1 + INCB018424 group (Figure 6A). The expression of JAK STAT signaling pathway-related proteins was detected by western blot. The result suggested that compared with si-NC + DMSO group, the protein expression levels of p-JAK1, p-JAK2, p-STAT1 and p-STAT3 in si-ADAMTS9-AS1 + DMSO group were remarkably increased. Compared with si-ADAMTS9-AS1 + DMSO group, the protein expression levels in si-ADAMTS9-AS1 + INCB018424 group were notably decreased (p < 0.05) (Figure 6B). In vitro colony formation (Figure 6C), EdU (Figure 6D), and Transwell (Figure 6E) assays indicated that compared with the si-NC + DMSO group, the proliferative ability and invasive ability of breast cancer cells in the si-ADAMTS9-AS1 + DMSO group were prominently increased. Compared with the si-ADAMTS9-AS1 + DMSO group, the proliferative and invasive abilities of breast cancer cells in si-ADAMTS9-AS1 + INCB018424 group were markedly decreased (p < 0.05). Western blot result exhibited that compared with si-NC + DMSO group, the expression levels of Ki67, PCNA, MMP-2 and MMP-9 in si-ADAMTS9-AS1 + DMSO group were markedly boosted, indicating increased tumor proliferative activity. Compared with si-ADAMTS9-AS1 + DMSO group, the expression levels of Ki67, PCNA, MMP-2 and MMP-9 in si-ADAMTS9-AS1 + INCB018424 group were prominently constrained, indicating decreased tumor proliferative activity (p < 0.05) (Figure 6F). In general, ADAMTS9-AS1 could suppress the proliferation and invasion of breast cancer cells by regulating the JAK STAT signaling pathway. Besides, JAK inhibitor did not impact TGFBR2 levels according to detection results (Supplementary Figure 3).
| 4 | 0biomedical
| 0Study
|
3,273 |
We assessed the linear morphometric variation in our sample through external and cranial data. The external measurements were classified into two categories: standard and carapace. Standard measurements include the traditional measures recorded from freshly dead individuals and were taken from specimen labels. They include six variables: total length (T), head-body length (HB), tail length (TA), hind foot length (HF), ear length (E), and weight (W). When only total length was provided, we subtracted the recorded tail length from it to obtain the values of the head and body length.
| 4 | 0biomedical
| 0Study
|
266,001 |
In vitro, hepatic macrophages are skewed towards M1, similar to that of macrophages exposed to lipopolysaccharide (LPS), IL-12, IFN-γ, TNF-α, or GM-CSF. Activated M1-like macrophages produce a set of pro-inflammatory mediators (e.g., IL-1β, IL-12, TNF-α, CCL2, and CCL5) and increased reactive oxygen species (ROS) and nitric oxide (NO) intermediates, displaying an IL-12hiIL-23hiIL-10lo phenotype, and exert pro-inflammatory, anti-tumor, and anti-bacterial effects. In contrast, M2-like macrophages, which are primed by IL-4, IL-13, IL-33, or IL-14, release IL-10, IL-4, IL-13, and TGF-β cytokines, displaying an IL-12loIL-23loIL-10hi phenotype, triggering an anti-inflammatory response and tissue repair.
| 4 | 0biomedical
| 0Study
|
78,704 |
In the synthesis of CNRs through the copyrolysis of C6H6 and C5H6 over cocatalysis of Fe and Mg, Zou et al. observed no activity below 400 °C. At 500 °C, short CNRs were produced. In the 600–700 °C range, longer CNRs were obtained in large quantity (ca. 90% yield). At 800 °C, carbon particles were formed. Over Ni nanoparticles derived from sol-gel synthesis followed by hydrogen reduction, we synthesized CNRs (0.386 g) composed of carbon nanoflakes through the catalytic decomposition of benzene at temperature as low as 350 °C . The yield of CNRs was ca. 1,537%. There were nanorods of several microns in length and 200–400 nm in diameter (Figure 16). In Figure 16b, one can observe that the CNRs are composed of nanoflakes. It is known that interaction between graphitic layers is weak, and rupture of this kind of CNRs should be easy. We found “clear-cut” ends of CNRs different from those of CNTs, CNCs, and CNFs, and attributed the phenomenon to the fracture of flake-composed CNRs. Based on the FE-SEM images, we estimated a CNR selectivity of ca. 90%; the rest are coiled nanowires and nanotubes of irregular morphology. When the decomposition temperature was 460 °C, ca. 1.103 g of CNRs was collected, corresponding to ca. 4,579% yield of CNRs, much higher than that of CNRs obtained at 350 °C. With a change of decomposition temperature from 350 to 460 °C, there was an increase of CNR yield and a change in CNR morphology: the nanorods of CNRs obtained at 460 °C became curly in shape and bigger in diameter (ca. 500 nm). A closer TEM investigation revealed that the curly nanorods were also composed of carbon nanoflakes. However, at 550 °C, the majority of carbon species were MWNTs with inner diameter ca. 5 nm and outer diameter ranging from 15 to 40 nm; the selectivity to CNTs was high, up to ca. 88%. All the results demonstrated that the reaction temperature is an important factor in CNR formation.
| 4 | 0biomedical
| 0Study
|
349,481 |
Anti-acanthamoebic drug therapy is the cornerstone of medical management for Acanthamoeba infection, which often involves the use of combination strategies to provide synergistic effects and improved treatment outcomes. The treatment regimen normally involves using 0.02% biguanides and 0.1% diamidines . Biguanides (Polyhexamethylene (PHMB) or chlorhexidine gluconate (CHX)) represent the first-line therapeutic option and have proven efficacy in curing patients with AK . Biguanides target the plasma membrane of the amoeba leading to membrane damage, lysis, and death. The antiseptic diamidines (propamidine isethionate and hexamidine) are active against the trophozoites and cysts and exert their effects by disrupting the biosynthesis of protein and nucleic acids . An earlier study discouraged the use of propamidine, owing to potential neurotoxicity and resistance of the cysts to the drug . Therefore, combination treatment regimens involving antiseptic agents have been advocated, however, the evidence for the superiority of the combination treatment over monotherapy remains inconclusive . In fact, treatment of AK using 0.02% PHMB had similar efficacy to combined biguanide and diamidine therapy . Effective treatment of AK requires early diagnosis and timely implementation of a strict treatment regimen in order to achieve sufficient eradication of the susceptible trophozoites before they form cysts, which are very difficult to eliminate. The treatment regimen starts with hourly administration of eye drops during the first two days, followed by hourly eye drops per daytime only for the following five days . Given the challenges associated with the management of Acanthamoeba infection, significant efforts have been made to develop and test several drugs against Acanthamoeba, such as antiseptics, antibiotics and antifungal drugs affecting various targets/functions in Acanthamoeba (Figure 2).
| 5 | 0biomedical
| 2Review
|
6,063 |
High choline intake during gestation and the early postnatal period has been shown to enhance cognitive performance in childhood, adulthood and into old age in multiple animal models and in some human studies. Moreover, choline is neuroprotective in a variety of experimental models of neuronal damage. Choline intake in adulthood may also be critical for normal cognitive function in people. The maternal choline supply during pregnancy modifies fetal DNA and histone methylation , implicating an epigenomic mechanism in these long-term effects. While these epigenomic mechanisms may also operate in the adult, the effects of dietary choline both during development and in the adult brain may also be mediated, at least in part, by an influence on the peripheral and central metabolism of polyunsaturated species of PC. Taken together, the available evidence strongly supports the notion that adequate choline intake during pregnancy, and throughout life, is an important determinant of brain development, cognitive performance in the adult, and resistance to cognitive decline associated with aging and neurodegenerative disease.
| 5 | 0biomedical
| 2Review
|
347,650 |
All reagents used in this work were at least of analytical reagent grade and used as received. SFE experiments were performed using CO2 and ethanol as modifier. Solvents were purchased from Air Product and Chemicals (Allentown, PA, USA) and VWR chemicals (Radnor, PA, USA). Ottawa sand was provided by Fisher Scientific (Leicestershire, UK). Glass wool was acquired from Sigma-Aldrich (Steinhemin, Germany). LC-MS-grade acetonitrile was purchased from Fisher chemicals (Waltham, MA, USA) and double-deionized water (conductivity of <18.0 MΩ) was obtained using a Milli-Q system acquired from Millipore (Bedford, MA, USA). Formic acid was purchased from Sigma-Aldrich (Steinheim, Germany). Apigenin, loganic acid, kaempferol 3-glucoside, quercetin, and verbascoside were purchased either from Fluka, Sigma-Aldrich (Steinheim, Germany) or Extrasynthese (Genay Cedex, France).
| 2 | 0biomedical
| 0Study
|
271,248 |
Quality of life was assessed using the “Medical Outcomes Study 36 (SF36)” questionnaire . The Medical Outcomes Study 36 (SF36) has been translated and validated into Portuguese by Ciconelli et al. for the Brazilian population. A multidimensional questionnaire comprises 13 items, divided into eight dimensions: physical functioning, physical role, pain, general health, vitality, social function, emotional role, and emotional well-being. The results of each scale vary from 0 to 100 (worse to best possible status).
| 4 | 0biomedical
| 0Study
|
25,160 |
where ΔEA−M, ΔEB−M, ΔEC−M, ΔED−M, ΔEE−M, ΔEF−M are the interaction energies of M with A, B, C, D, E, F fragments and ΔEab−M, ΔEbc−M, ΔEad−M, ΔEde−M, ΔEbe−M, ΔEef−M, ΔEcf−M are interaction energies of M with ab, bc, ad, de, be, ef, cf conjugated caps and ΔEg−M, ΔEh−M are the interaction energies of M with the overlapped area of surface g and h (colored yellow).
| 5 | 0biomedical
| 0Study
|
343,056 |
Many studies reported that MRI‐fusion biopsy shows a higher detection rate of clinically significant prostate cancer (csPC) than TRUS‐guided biopsy. 5 , 7 Due to the widespread use of active surveillance in low‐risk PC patients, 8 the importance of CSPC detection has increased like never before. Therefore, targeted biopsies based on imaging studies such as MRI fusion biopsy are becoming more common, especially for men with negative results on previous biopsy. 9
| 4 | 0biomedical
| 0Study
|
377,688 |
In 2008, the INTERDEM group recommended 22 outcome measures for use across 9 domains.15 We found 11 of these 22 measures (50%) were used by the studies included in this review, one of the recommended domains (staff carer morale) was not applicable to the studies included in this review. All measures recommended for measuring patient mood, and patient quality of life were charted in this review. Only one of the recommended measures for the activities of daily living, caregiver mood, caregiver burden and caregiver quality of life domains were charted and no measures under the global measures domain were charted in this review. This indicates that there is some consistency between which measures are recommended and which measures are used, this is largely for patient measures and there is less consistency for caregiver measures.
| 4 | 0biomedical
| 2Review
|
155,170 |
As the fuzzy logic provides a significant contribution to research using unclear data, often expressed in linguistic terms, and quite close to human perception, its possibilities for use are extensive. For example, fuzzy modeling can be useful for social sciences and applied social sciences to analyze issues such as poverty, social capital and upgrading (economic, social or environmental). As well, as studies involving more specific analysis such as governance, performance, risk (credit, production or management) and decision-making processes.
| 1 | 2other
| 1Other
|
256,455 |
Toxicities during the treatment are shown in Table 2. Myelosuppression, gastrointestinal reaction, and infection were the main adverse events during the treatment. The most severe adverse reaction was infection, which resulted in 3 deaths. Other common reactions included 9 cases of constipation and 8 cases of fatigue. There were 16 cases of leukopenia, anemia, and thrombocytopenia, including 11 cases of grade 1 and 2 and 5 cases of grade 3 and 4. After drug withdrawal or symptomatic treatment, the myelosuppression could be removed from the sixteen cases mentioned above. Nausea and vomiting were the common gastrointestinal reactions, including 7 patients of grade 1–2 and 2 patients of grade 3–4. In addition, 5-hydroxytryptamine-3 antagonist can relieve nausea and vomiting.
| 4 | 0biomedical
| 0Study
|
379,397 |
It is obvious that fast and reliable diagnosis of shedding animals is fundamental to any control program of C. burnetii. The aim of this study was to evaluate recombinant Com1 as ELISA antigen for use in Q fever diagnosis of ruminants. In the future, these data will allow the production of a pen side serodiagnostic test or other assay formats for pathogen detection.
| 3 | 0biomedical
| 0Study
|
237,493 |
In this study, children who used dental floss had significantly lower dmft and DMFT index of first permanent molars than children who did not use dental floss. This indicates the importance of flossing in reducing dental caries, especially in posterior teeth. This result is consistent with the study of Ramezani et al. [ 20]. In the study of Yousofi et al. [ 19], there was no significant difference between dmft in terms of dental floss usage. Since the positive effect of dental flossing is obtained when the dental floss is applied correctly, this difference may be due to differences in the use of dental floss in the two studies.
| 4 | 0biomedical
| 0Study
|
344,689 |
An electrocompetent strain C. pasteurianum R525 and a PDO lacking mutant strain, referred to as C. pasteurianum dhaB mutant strain in this work, were used in this study. The generation of both strains from C. pasteurianum DSM 525 was described in detail by Schmitz et al. . Two media were used: Reinforced Clostridial Medium (RCM) and a modified medium from Biebl with pure glycerol (99.5% purity). The medium composition, preparation, and strain maintenance were the same as described by Sabra et al. . Initial glycerol concentration for the fed‐batch cultivations was 25 g L–1. The feeding solution consisted of Biebl medium with 500 g L–1 pure glycerol. The fermentation medium additionally contained 1 g L–1 of d‐xylose as an internal standard for calculation of the cell‐specific concentration of intracellular compounds. No metabolization of d‐xylose was observed.
| 4 | 0biomedical
| 0Study
|
290,942 |
The risk factors of PE and eclampsia are to some extent the risk factors of PRLS, arising from physiological changes during pregnancy.7 The results of this study found that, in the control group, the changes in systolic blood pressure and mean arterial pressure were more obvious (P<0.05). It suggested that, elevated blood pressure was an important factor in the formation of PRLS. Mueller-Mang et al. (2009) proposed that, the degree of blood pressure elevation is closely related to the PRLS patient’s basal blood pressure. If the basal blood pressure rises significantly, even if the blood pressure is normal, it will develop into PRLS.8 Additionally, the serum uric acid level in the control group was significantly lower than that in the research group (P<0.05). Studies have pointed out than 9 and the level of 24h serum uric acid in women with severe PE was significantly higher than the group without RPLS (P=0.012).10
| 4 | 0biomedical
| 0Study
|
256,042 |
Legionella is a Gram-negative bacterium belonging to the Legionellaceae family associated with respiratory pathologies . The family Legionellaceae consists of a single genus Legionella with more than 60 known species currently . Legionella is widespread in natural aqueous environments and in man-made water systems such as potable water systems, cooling towers, air-conditioning units, and various water plumbing fixtures . From these different sources, Legionella can be transmitted to humans through the inhalation of contaminated water aerosols. This results in the colonization of human lung alveolar macrophages, where the microorganisms replicate. Legionella infection is called legionellosis . The term legionellosis commonly indicates both a mild flu-like illness, i.e., Pontiac fever, and a potentially fatal form of pneumonia, i.e., Legionnaires’ disease (LD) . The risk of legionellosis is related to various factors, such as smoking, old age, and underlying diseases .
| 4 | 0biomedical
| 0Study
|
277,341 |
The anthropometric measurements were taken after overnight fasting for a minimum of 12 h (body weight and height analyses with accuracy to 0.1 kg (certified weigh) and to 0.1 cm (stadiometer) in light underwear, with no shoes). Waist circumference was measured at the midway between the costal arch and the upper iliac crest and hip circumference at the level of the greater trochanters. Obtained data were further used to calculate a body mass index (BMI), calculated as weight divided by height squared (kg/m2), WHR (Waist–Hip Ratio) calculated as waist measurement divided by hip measurement, and ABSI (A Body Shape Index) calculated by dividing waist circumference by its estimate obtained from allometric regression of weight and height. In addition, body composition measurements were assessed using bioelectrical impedance analysis, carried out with a TANITA BC-418 device (Tanita Corp., Tokyo, Japan). It was used to estimate total body adipose tissue, lean body mass, and water content.
| 4 | 0biomedical
| 0Study
|
307,825 |
Drosophila APPL has been implicated in neural development (Cassar and Kretzschmar, 2016; Nicolas and Hassan, 2014) and is required for learning and memory (Preat and Goguel, 2016). Drosophila APPL is a homologue of human APP and has been used as a model for understanding the physiological function of the APP family (Soldano and Hassan, 2014; van der Kant and Goldstein, 2015). We previously reported that appl genetically interacts with components of the Wnt-PCP pathway (Soldano et al., 2013) during mushroom body (MB) axon growth. The MBs are a bilateral neuronal structure in the fly brain required for learning and memory (Heisenberg, 2003). To understand the role of APPL in axonal PCP signaling, we first explored the specific nature of the genetic interaction between appl and the gene encoding the PCP protein Van Gough (Vang). In contrast to control MBs, 17% of male appl null mutant flies (appld/Y, henceforth Appl-/-) displayed a loss of the MBb-lobe (Figure 1A,A’). The PCP receptor Vang is also required for β-lobe growth (Shimizu et al., 2011); we observed that flies homozygous for the null allele vangstbm-6 exhibited 50% β-lobe loss. Whereas vangstbm-6 heterozygotes show no MB defects, the loss of one copy of vang in Appl-/- flies is comparable (43% β-lobe loss) to the complete loss of vang (Figure 1B). Therefore, in the absence of appl, vang is haploinsufficient. Next, we performed rescue experiments of Appl-/- mutant flies. Re-expression of APPL in the mutant MBs significantly rescued β-lobe loss. In contrast, the overexpression of Vang in Appl-/- null flies failed to do so. These loss and gain of function data suggest that Wnt-PCP signaling requires APPL to regulate axonal growth (Figure 1B).
| 4 | 0biomedical
| 0Study
|
132,258 |
To investigate the effect of rock properties on the recovery process, two outcrop rock types were selected. Berea and Keuper outcrops mimic to a certain extent the potential fields. The main properties are summarized in Table 6. Berea is a yellowish grey sandstone consisting of very homogeneous, well-sorted sand with on average 90% quartz, 4% feldspar, and approximately 6% clays (mainly kaolinite with small amounts of illite and chlorite). Calcite, siderite, and pyrite can be present with quantities <1%. Keuper sandstone is a well-sorted arenite, which main minerals are quartz (97%), clays (~3%), and plagioclase and calcite (both <1%). Accessory minerals are ilmenite, rutile, and goethite. The iron oxides cover the mineral grains and cause the reddish color of the rock. Further information on the outcrops used in this work can be seen in our previous work .
| 1 | 2other
| 0Study
|
38,814 |
B. miyamotoi DNA or RNA were detected in blood samples up to day 30 of disease (Figure 2, panel A). However, despite such a wide range, 90% of all observations were in the first 8 days of the disease. We showed in a previous study (20) that 7 (9.1%) positive samples, which were obtained from patients given a diagnosis of B. miyamotoi disease during the second week of disease (or later), were assumed to be caused by a relapse of fever. However, this assumption could not be confirmed because of lack of availability of clinical materials. Pathogen DNA or RNA were detected in blood samples from patients with Lyme borreliosis obtained up to day 24 of disease (Figure 2, panel B).
| 4 | 0biomedical
| 0Study
|
126,255 |
Using the search terms and strategy provided in S1 Appendix, our initial search identified 314 studies. One trainee author (SB) screened results for duplicates, removing 38 studies, leaving 276 articles which we subjected to a three‐stage process for study selection: title, abstract, and full‐text review. At each stage, two independent reviewers (SB, SM) assessed the citations against inclusion criteria. Differences in assessment were resolved by consensus. We also hand-searched the reference lists of articles and sought input from subject expert for additional studies that might meet our inclusion criteria. We used the Critical Appraisal Skills Programme (CASP) Qualitative Research Checklist to assess the quality of included studies in the following domains: research aims, design, methodology, recruitment, data collection, data analysis, ethical issues, participant-researcher relationship, findings, and research value. High quality studies met criteria of 8 or more items on the CASP Qualitative Research Checklist, medium quality studies met that of 5–7 items, and low-quality studies met that of less than 5 items. Two authors (AW, SM) independently evaluated the quality of each included publication and resolved disagreements through discussion until consensus was reached.
| 4 | 0biomedical
| 0Study
|
207,957 |
Electrodermal activity data were cleaned using AcqKnowledge software (Biopac Systems Inc., Goleta, California). The data were converted to microSiemens (μS) and square root transformed to correct for positive skew. A semi-automated process was used to correct periods of excessive noise and signal drop that were removed and linearly interpolated as in previous analyses (Johannsen and Zak, 2020). To remove high-frequency noise, a 10-Hz low-pass filter was applied (Norris et al., 2007). All data were visually inspected to ensure that the automatic process accurately identified and corrected artifacts. Following artifact correction, skin conductance levels (SCL, a tonic measure of electrical conductivity) was derived from EDA. The SCL data during the 2-min communication period was used to predict subsequent behavior and was baseline-corrected for each participant.
| 4 | 0biomedical
| 0Study
|
7,142 |
The claim that a psychiatric diagnoses provide information about the causal structures by which sets of symptoms are maintained sits well with the fact that specific therapies for some psychiatric disorders often achieve reductions in some symptoms by optimally intervening on others (Borsboom & Cramer, 2013, p. 98). For example, cognitive-behavioural therapy for MDD employs the notion that thoughts, actions, emotions, and bodily symptoms can all influence one another. The idea is that intervening on the patient's negative thoughts and level of activity through cognitive restructuring and behavioural activation might then lead to improvements in his or her mood and interest level. Therefore, under the symptom network approach, the causal information conveyed by a psychiatric diagnosis can provide a rational basis for therapeutic intervention.
| 4 | 0biomedical
| 1Other
|
205,679 |
The participants’ educational levels were significantly associated with their consumption behavior before and during pregnancy. For example, participants with a low or medium educational level (10.7%) were more likely to be dual users before pregnancy compared to those participants with a high educational level (4.8%) (p = 0.047) (Table 2). Participants with a low educational level (28.6%) were more likely to consume tobacco cigarettes during early pregnancy compared to individuals with a medium (17.6%) or high educational level (4.0%) (p < 0.001), while not having a partner (p = 0.017) was associated with tobacco cigarette use during late pregnancy (Table 1). Pregnant women with a partner who used tobacco cigarettes exclusively were more likely to exclusively consume tobacco cigarettes before pregnancy (p < 0.001) and during early (p < 0.001), and late pregnancy (p < 0.001).Table 2Consumption patterns of the pregnant women by sociodemographic characteristics and consumption behavior of the partnersConsumption patterns before pregnancyConsumption patterns during early pregnancyConsumption patterns during late pregnancySociodemographic characteristicsExclusive tobacco cigarette useExclusive e-cigarette useDual useExclusive tobacco cigarette useExclusive e-cigarette useExclusive tobacco cigarette usen (%)p (χ2)n (%)1n (%)p (χ2)n (%)p (χ2)n (%)1n(%)p (χ2)Total540 (%)108 (20.0)7 (1.3)35 (6.5)47 (8.7)2 (0.4)15 (2.8)Age group (in years).013/.218.286/.1443 18 to 29156 (29.1)43 (27.6)4 (2.6)14 (9.0)17 (10.9)1 (0.6)7 (4.5) 30 to 34204 (38.0)39 (19.1)2 (1.0)9 (4.4)13 (6.4)0 (0.0)2 (1.0) > 34177 (33.0)26 (14.7)1 (0.6)12 (6.8)17 (9.6)1 (0.6)6 (3.4)Immigrant background.271/.695.385/.0313 No398 (73.8)75 (18.8)3 (0.8)25 (6.3)32 (8.0)1 (0.3)7 (1.8) Yes141 (26.2)33 (23.4)4 (2.8)10 (7.1)15 (10.6)1 (0.7)8 (5.7)Educational level < .001/.047 < .001/ < .0013 Low28 (5.5)13 (46.4)3 (10.7)3 (10.7)8 (28.6)1 (3.6)7 (25.0) Medium131 (25.6)37 (28.2)1 (0.8)14 (10.7)23 (17.6)0 (0.0)5 (3.8) High353 (68.9)53 (15.0)2 (0.6)17 (4.8)14 (4.0)1 (0.3)3 (0.8)Having a partner.5893/.1503.1013/.0173 Yes517 (96.1)103 (19.9)6 (1.2)32 (6.2)43 (8.3)2 (0.4)12 (2.3) No21 (3.9)5 (23.8)1 (4.8)3 (14.3)4 (19.0)0 (0.0)3 (14.3)Exclusive tobacco cigarette use of the partners2 < .001/.509 < .001/.0013 No404 (79.1)60 (14.9)5 (1.2)24 (5.9)23 (5.7)0 (0.0)4 (1.0) Yes107 (20.9)43 (40.2)1 (0.9)8 (7.5)20 (18.7)2 (1.9)8 (7.5)Exclusive e-cigarette use of the partners21.0003/.60031.0003/1.0003 No497 (97.3)100 (20.1)6 (1.2)31 (6.2)42 (8.5)2 (0.4)12 (2.4) Yes14 (2.7)3 (21.4)0 (0.0)1 (7.1)1 (7.1)0 (0.0)0 (0.0)Dual use of the partners2.0433/.0513.0233/1.0003 No497 (97.3)97 (19.5)5 (1.0)29 (5.8)39 (7.8)2 (0.4)12 (2.4) Yes14 (2.7)6 (42.9)1 (7.1)3 (21.4)4 (28.6)0 (0.0)0 (0.0)Percentages are based on valid cases1Due to the small number of cases we did not calculate a Pearson Chi-square test/Fisher’s exact test2Participants without a partner were excluded (n = 517)3 ≥ 25% of expected frequencies less than 5
| 4 | 0biomedical
| 0Study
|
187,882 |
If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.
| 1 | 2other
| 1Other
|
8,811 |
Intercropping involves the aboveground and belowground interaction of crops. In previous studies, the aboveground interaction in intercropping systems altered the canopy micro-ecology, resulting in improved solar light use efficiency and soil water storage capacity, and a reduction in the evaporation of soil moisture . In recent years, more studies have been focused on soil nutrients and root exudates . In legume/cereal intercropping systems in alkaline calcareous soils with low phosphorus, legume root exudates including malic acid and citric acid have been shown to acidify the rhizosphere and mobilize insoluble P while improving legume nodulation and nitrogen fixation . Meanwhile, increased rhizosphere phosphorus availability was also observed in durum wheat and chickpea intercropping in neutral soil, but rhizosphere acidification was not observed; in fact, the pH value increased . Moreover, in acidic soil, He et al. suggested that the increase in plant P uptake was due to the changes in the microbial community composition in maize/chickpea and maize/soybean intercropping systems. Therefore, belowground interspecific interactions are complex, and further research is needed.
| 4 | 0biomedical
| 0Study
|
103,870 |
Laboratory reference ranges currently used in clinical and research settings in Zimbabwe such as the University of Zimbabwe-University of California San Francisco (UZ-UCSF) collaborative research program are derived from several sources, including textbooks and local studies of varying rigor, many of which are over a decade old [5, 6, 7, 8, 9, 10]. Textbook reference ranges are often based on Western populations and significant differences have been observed from those of African origin [1, 3]. The Clinical Laboratory and Standards Institute (CLSI) guidelines recommend that reference ranges be descriptive of a specific population and ideally are to be verified every 5 years .
| 4 | 0biomedical
| 0Study
|
114,590 |
Bone morphogenetic protein 4 (BMP4), retinoic acid, and epidermal growth factor improve early corneal/limbal differentiation process. Quantitative real‐time polymerase chain reaction analysis of BRACHYURY, RAX, BMP4, CK8, ECADHERIN, and ΔNp63 genes for groups G2–G8 compared with control group (G1) presented as z scores (A–F). z score was calculated using the following formula: z score = D/SEM where D is the difference between the two means and SEM is the standard error of mean (computed from the data). Dotted lines represent 90% confidence level. Abbreviation: BMP4, bone morphogenetic protein 4.
| 4 | 0biomedical
| 0Study
|
330,969 |
After the transfection of RL95-2 and Ishikawa cells, cells were treated with non-serum medium and starved for 24 h. Then, the cell culture medium was collected to detect the lactate production using a Lactate Assay Kit (KeyGen, Nanjing, China). Lactate production was normalized on the basis of the total protein concentration.
| 4 | 0biomedical
| 0Study
|
123,067 |
The frequency and severity of traveler’s diarrhea due to Campylobacter, coupled with its high rate of fluoroquinolone resistance, are important considerations for clinicians providing advice regarding antibacterial prophylaxis and treatment for civilian and military travelers. The low level of azithromycin resistance observed in this study supports its empiric use for treatment of diarrhea cases among travelers from the US to Thailand.
| 4 | 0biomedical
| 0Study
|
70,671 |
To assess tolerance of elevated perchlorate concentrations cells were grown to stationary phase, centrifuged, and washed as described above. Resuspended cells were aliquoted into 160-ml serum bottles to which either 0.01, 0.1, or 1 M perchlorate was added; each perchlorate treatment was incubated with aerobic (21% oxygen) or anoxic (flushed with nitrogen) headspaces. Experimental treatments without perchlorate included oxic, no electron acceptor, and an autoclaved kill control. All treatments were performed in triplicate.
| 4 | 0biomedical
| 0Study
|
315,281 |
(a–d) Data from 34 trees paired for size and species, where one tree had weaver ants and the other did not. The gray line shows a slope of 1.0, that is, points on this line indicate pairs that do not differ. (a) Number of arthropods (excluding ants and suborder Homoptera). (b) Number of arthropods belonging to the orders Lepidoptera and Coleoptera. (c) Percent leaf damage estimated on 10 leaves distributed around the tree. (d) Percent leaf damage estimated on a clipped branch
| 2 | 2other
| 0Study
|
126,160 |
This review has identified a line of evidence in the scientific literature that supports the positioning of specific plant-derived terpenes, pinene, and linalool (both in isolation and as major components of botanical extracts) as key candidates for further research as novel medicines for an array of brain illnesses. This includes therapeutic potential in stroke and cerebral ischemia, inflammatory and neuropathic pain (including migraine), cognitive impairment (including models of Alzheimer's disease and ageing-related cognition), insomnia (and associated cognitive impairment and anxiety), anxiety (including social anxiety), and depression. There is some evidence that these terpenes provide therapeutic efficacy similar to existing commercial medications for several indications, including analgesics, anti-inflammatories, anti-anxiety and anti-depressant drugs, with fewer adverse effects e.g., sedation and motor impairment. The mechanisms by which pinene and linalool exert their effects are largely unknown; however, evidence shows that these molecules enter the circulation and/or brain (via multiple routes of administration: inhalation, oral, i.p.) and alter neurochemical and neurotrophic signalling in discrete regions of the brain implicated in cognition, anxiety and depression, including the hippocampus, frontal cortex, striatum, and midbrain. However, this should be interpreted with caution as a therapeutic concentration of pinene or linalool in the brain or circulation for any indication is unknown. Pinene and linalool influence GABA, glutamate, serotonin, dopamine, acetylcholine, as well as inflammatory, oxidative stress, and neurotrophic (BNDF) pathways in the brain. Although limited, the evidence showing that these terpenes alter brain function and change cognitive and affective behaviours demonstrates that pinene and linalool are, by definition, psychoactive compounds.
| 4 | 0biomedical
| 2Review
|
368,134 |
Additionally SALSA was developed so as to incapsulate all the characteristics of the experimental model in configuration files separate from the simulator code. This choice minimizes the programming knowledge required to use it, thus making SALSA accessible to a larger user base than other available simulators (Chaste33, PhysiCell34, BioFVM35).
| 3 | 0biomedical
| 1Other
|
207,387 |
Why were EVs taken up to different amounts in the examined organs, depending on the cell line of origin? Several factors might influence the specific uptake of EVs by recipient cells, which might play a more or less important role in the individual physiological or pathological condition looked at. One explanation is the different distribution of surface molecules on the membrane of extracellular vesicles, which are involved in receptor-mediated uptake. Here, for example, integrins could be shown to be involved , as were cytokines , CD47 , and surface glycans . Apart from that, the size of the EVs, the vascularization and microenvironment of the target organ, and the order in which the single organs are passed by the injected EVs are other possible factors influencing their uptake . However, in our study, we saw no huge differences in particle size, except from the cell line BPH1, whose EVs were only half as large as the ones from the other five cell lines.
| 4 | 0biomedical
| 0Study
|
247,407 |
Earlier work using the yeast two-hybrid method showed the interaction of a truncated TRF1 protein (14-285aa) with NM23-H2; the interaction of TRF1 with NM23-H1, however, was not significant. Further, the authors used recombinant GST-tagged NM23-H1 and H2 and translated full-length TRF1 with S35 labelled methionine in vitro to confirm a strong and direct association of NM23-H2 with TRF1. The interaction of NM23-H1 with TRF1 was again found to be insignificant .
| 4 | 0biomedical
| 0Study
|
311,813 |
The arbitrary material points in undeformed (reference) and deformed (current) configurations of the shell body can be described by position vectors X and x, respectively, as shown in Figure 2. The position vector X can be defined by the linear function of thickness coordinate θ3 as:(2)X(θ1,θ2,θ3)=F(θ1,θ2)+θ3 A3(θ1,θ2) where F represents a position vector to a material point on the mid-surface in reference configuration and A3 denotes a unit-magnitude vector field (the director vector) that is perpendicular to the tangent plane of any point belongs to mid-surface in reference configuration (Figure 2). As given in Equation (2), both F and A3 are only functions of the in-plane coordinates θα. Taking partial derivative of F with respect to θα provides the covariant base vectors Aα of the mid-surface in reference configuration as:(3)Aα=F,α where, hereafter, (·),α≡∂(·)∂θα represents a partial derivative with respect to in-plane coordinate θα. The director vector, A3, can be defined by normalized cross product of these covariant base vectors Aα as:(4)A3=A1×A2A1×A2
| 3 | 0biomedical
| 0Study
|
237,014 |
The immune response prevented complete spread of infection throughout the spatial domain in all 100 simulation replicas of 0.01, 0.05, and 0.1 initial infection fraction, and decreasingly so with increasing initial infection fraction (Fig. 6). After 2 days of simulation time, infected and virus-releasing cells were more prominently distributed throughout the spatial domain compared to local immune cells. However, a strong immune response recruited sufficient immune cells to nearly cover the entire epithelial sheet by days 7, 6, and 5 for initial infection fractions 0.01, 0.05, and 0.1, respectively, resulting in significant killing of virus-releasing cells and prevention of further infection. By 2 weeks of simulation time for all initial conditions and simulation replicas, virus and cytokine levels were near zero, most immune cells had left the spatial domain and the epithelial sheet consisted of susceptible cells with significant distributions of dead cells. Initial infection fractions of 0.01, 0.05, and 0.1 resulted in final fractions of dead cells of around 0.5, 0.625, and 0.75, respectively. Fig. 6Spatial model results of viral infection and immune response in a quasi-two-dimensional, epithelial sheet. Results shown for 1% (top), 5% (middle), and 10% (bottom) initially infected cells at 0, 2, 3, 4, 7, and 14 days in simulation time. Epithelial cells shown as in Fig. 1. Immune cells shown as dark red. Lower-right color bar shows levels in the virus and cytokine fields, from blue (0) to red (0.05)
| 4 | 0biomedical
| 0Study
|
321,924 |
We included individuals from the Swedish BioFINDER studies (BioFINDER-1, clinical trial NCT01208675; BioFINDER-2, clinical trial NCT03174938). BioFINDER-1 included 53 CU and 48 CI participants (14 mild cognitive impairment [MCI] and 34 AD dementia). CU individuals were aged ≥60 years and did not have MCI or dementia.2–4 Exclusion criteria included presence of objective cognitive impairment, severe somatic disease, and current alcohol or substance abuse. Patients with MCI fulfilled the DSM-5 criteria for minor cognitive impairment.5 Patients with AD dementia fulfilled the DSM-5 criteria for major cognitive impairment due to AD.5 Patients with MCI and patients with AD had low CSF Aβ42/Aβ40 levels (<0.10). Exclusion criteria were cognitive impairment that could better be accounted for by another non-neurodegenerative condition, severe somatic disease, and current alcohol or substance abuse. Longitudinal cognitive data were available in all individuals from BioFINDER-1. To validate cross-sectional results, we also included 389 participants from the Swedish BioFINDER-2 study (245 CU and 144 CI participants) (table e-1, doi.org/10.5061/dryad.p5hqbzkkx).
| 4 | 0biomedical
| 0Study
|
336,957 |
According to the objective fluorescein corneal staining findings, then enrolled subjects were classified into either the group with PPCS (PPCS group) or the group with SPK and without PPCS (non-PPCS group). PPCS was defined as the fluorescein staining that was densely distributed in a mottled pattern unlike ordinary SPK. Subjects were classified as a PPCS group when at least one PPCS was observed, even if the appearance of other staining corresponded to ordinary SPK (Figure 2A). SPK without PPCS was diagnosed only when all staining corresponded to ordinary SPK (Figure 2B). In all cases, the density or range of SPK was not considered in the classification. Under the agreement of 3 ophthalmologists (S.K., N.Y., H.K.), all cases were evaluated from the photographs obtained after fluorescein staining using a slit-lamp microscope.
| 4 | 0biomedical
| 0Study
|
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