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This study is the first to emphasize the association between maternal unhealthy behaviors such as lack of sleep, physical inactivity, and prolonged use of electronic devices during pregnancy and the risk of childhood allergies in a sex-specific manner. In particular, there appeared to have a clear dose-response relationship, the more unhealthy maternal behaviors, the greater risk of childhood respiratory allergies. However, this risk mainly affects males. Our findings should be of interventional significance in early-life since maternal lifestyle behaviors are modifiable.
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The histologic diagnosis of MNTI is relatively straightforward and rarely represents a diagnostic challenge, provided it arises from the usual anatomic sites and adequate tissue material is available for examination. In our series, most MNTI originated from the head and neck region except in case 7, which presented as a right paratesticular mass. These findings are consistent with other reported cases as most MNTI involve the head and neck , with a subset occurring in the paratesticular region and other unusual locations . Histologically, all MNTI had biphasic morphology characterized by small primitive neuroblast-like cells and larger peripheral epithelioid cells containing melanin granules confirmed by immunohistochemistry. Remarkably, the possibility of metastatic neuroblastoma was excluded in all cases by negative imaging studies and negative expression of Phox2b, which is considered a highly sensitive and specific immunohistochemical marker for tumors of neuroblastic origin, whereas it was reported negative in MNTI . This immunostain can be used as a diagnostic aid in patients presenting with increased urinary levels of VMA, particularly in cases with limited biopsy material containing a predominantly neuroblastic-like morphology and expression of neuronal markers (i.e., synaptophysin, chromogranin A, PGP9.5, CD56).
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Australia has one of the largest Indigenous populations in the world, with Indigenous individuals from culturally and ancestrally distinct communities and over 250 different language groups comprising approximately three percent of the total Australian population (Australian Bureau of Statistics, 2021). Pharmacogenomic studies of these diverse Indigenous Australian populations have been hampered by several issues, including ethical concerns and lack of transparency resulting in the introduction of moratoriums on Indigenous genetic research by academic institutions such as the Australian National University in the 1990s (Claw et al., 2018; Australian Human Rights Commission, 2021). To improve knowledge regarding the pharmacogenomic landscape of Indigenous Australian populations, an Australian Indigenous reference genome is being created. Such a reference will facilitate the detection of rare unmapped variants unique to this population that cannot be identified using standard non-Indigenous population-based reference genomes. Herein, we review efforts to conduct the pharmacogenomic profiling of chronic diseases among Australian Indigenous populations and survey the potential impact of a lack of drug safety-related information on ADR risk among these communities.
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2Review
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Characterization of the graphene Hall elements with Ti/Au 1D edge contacts. (a) Output Hall voltage as a function of perpendicular magnetic field strength at 293 K and 75 K. (b) Output Hall voltage as a function of time at different applied magnetic fields at 293 K and (c) 75 K. Measurements are shown at a bias current of 90 μA and the background voltage offset is subtracted from the data.
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SNPs have been subsetted to calculate the GRM and have been applied for the subsequent prediction procedure based on GWAS results (considering 20 PCs) based on two viewpoints: First, the extraction of previously reported SNPs in association studies for the desired traits; Second, the most significant SNPs were extracted, which were identified by GWAS's construction on our dataset for each trait.
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The first full-time registered dietitian (RD) was hired by an American university athletic department in 1994 . The Collegiate and Professional Sports Dietitians Association (CPSDA) was chartered in 2010 to provide continuing education for and advancement of sports RDs. Since the National Collegiate Athletic Association’s (NCAA) deregulation of feeding in 2014, the number of sports RDs in the collegiate setting has grown exponentially to meet the new demand . Over the past decade, studies have been conducted to assess nutrition needs and problems of collegiate athletes. These problems can be summarized in three categories: inadequate macronutrients, inadequate micronutrients, and excessive macronutrients.
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(A) Huh7.5 cells were single or co-stimulated with 500 U/ml IFNα and 10 ng/ml IL1β. Cells were lysed at indicated time points and analyzed using quantitative immunoblotting. Error bars represent SEM of three biological replicates. (B) Primary mouse hepatocytes from mKate2-Stat3 knock-in mice were growth factor depleted overnight and stimulated with 50 ng/ml IL6 or left untreated. Representative images of cells expressing a mCerulean-histone-2B nuclear marker are depicted. The dotted line indicates the outline of the nuclei and white arrows indicate nuclear STAT3. Scale bar = 25 μm. Line plots represent the dynamics of nuclear STAT3 for the indicated conditions. The median value of the nuclear mKate2-STAT3 intensity was quantified based on 5 positions per well for each replicate (four replicates derived from two mice). The mean value and SEM (N = 4) of these four median values is plotted for each time point. (C) Primary mouse hepatocytes from mKate2-Stat3 knock-in mice were growth factor depleted overnight and stimulated with 500 U/ml IFNα, 10 ng/ml IL1β, co-stimulated or left untreated. The median value of the nuclear mKate2-STAT3 intensity was quantified based on 5 positions per well for each replicate (four replicates derived from two mice). The mean value and SEM (N = 4) of these four median values is plotted for each time point. Significance was tested by two-way ANOVA, ***, p<0.001. (D) Huh7.5 cells were pre-treated for 30 minutes with 10 μM STAT3 inhibitor Stattic followed by 500 U/ml IFNα in combination with 10 ng/ml IL1β. mRNA was extracted at indicated time points and analyzed using qRT-PCR. Error bars represent SD of biological triplicates.
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Self-injurious thoughts and behaviors (SITBs) are major public health concerns1–3. Researchers have proposed that SITBs result in part from biological causes in brain systems, and many studies have linked SITBs to specific brain differences4. Multiple researchers have proposed that examining the “suicidal brain” will improve our understanding of SITBs, accelerate the discovery of useful biomarkers, improve the identification of high-risk individuals, and inform therapeutic and pharmacological targets for treatment5–8. However, the results of neuroimaging studies examining SITBs vary considerably, making it difficult to synthesize evidence on specific brain differences based on qualitative reviews. As such, this study aims to quantitatively summarize existing brain imaging research on SITBs.
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To visualise the lineage diversity in Switzerland, the Basel area, and neighbouring European countries (Austria, France, Germany, and Italy) during the first 27 days of the pandemic in Basel, we visualized relative abundances of lineages using all high-quality, on GISAID (downloaded June 22nd 2020) available consensus sequences for the time until March 23rd from Austria (N = 188), France (N = 230), Germany (N = 133), and Italy (N = 98). For Switzerland (N = 673), we combined our sequences (N = 468) with other sequence data from Switzerland published on GISAID as of June 22nd 2020. To visualize the diversity for the Basel area we included sequnces from Basel-City (including Bettingen and Riehen) and Basel-Country (N = 506). To infer diversity, we calculated Simpson diversity (inverse Simpson concentration) for Switzerland, Germany, Italy, Austria, and France from onset of the pandemic in each country until March 23rd 2020, as implemented in the SpadeR package v.0.0.1 [45–47], which controls for lineage abundance differences between the countries, which is dependent on available sequence data, and which ranges from 0 (no diversity) to indefinite (large diversity).
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3. Please amend your list of authors on the manuscript to ensure that each author is linked to an affiliation. Authors’ affiliations should reflect the institution where the work was done (if authors moved subsequently, you can also list the new affiliation stating “current affiliation:….” as necessary).
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The mechanisms of action of BAC and DBNPA were discussed in the present study. BAC was confirmed to be a lytic biocide, since it disrupts the cytoplasmatic membrane and releases the intracellular cell components. Also, DBNPA, as a moderate electrophilic biocide, did not interact with the membrane, but it interfered with key components of cell’s metabolism. The analysis of the results obtained by the different methods used (CFUs counting, ATP, resazurin, membrane integrity, and TEM) were in accordance to what has been previously proposed in the literature.
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Near infrared (NIR) variance image and quantification of tissue differences. A, Variance image of the nodular basal‐cell carcinoma. The blue and the orange number indicate the region, where the histograms shown in B were measured. B, Histograms of the variance values in the tumor and nontumor regions. Both shape and average variance differ in the two regions. The two distributions are statistically different (f test, P < .001)
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Liquid state NMR spectroscopy was performed using a Bruker Avance spectrometer (Bruker BioSpin GmbH, Germany) equipped with a 5 mm SEL probe (1 H/D XYZ-gradient probe) operating at a proton frequency of 400.13 MHz. All one-dimensional spectra were recorded at 298.2 K without spinning using a conventional water presaturation pulse sequence based on the first increment of a nuclear Overhauser effect spectroscopy sequence (32 k data points, spectral width = 13 ppm, number of scans = 128/sample, relaxation delay = 2 s, mixing time = 0.12 s, acquisition time = 3.15 s).
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Example 2: Performance comparison under various clutter rates for pD,k=0.95. In this example, the performance of the proposed filter was evaluated with various clutter rates. The clutter rate λ changed from 1 to 100, and the probability of detection was set to pD,k=0.95. Figure 7 shows the comparison results in terms of the average OSPA errors for 250 sample runs of the different algorithms under different clutter rates, and their computing times are shown in Figure 8.
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Some experiments of stress detection combined more than one stressor such as arithmetic task with either Stroop test or relaxing videos and mental workload with public speaking . Moreover, as discussed by studies in , employing normal four frequency bands showed accuracy levels of 83.33% and 84.30% using NB and RF classification methods, respectively. However, Ahn et al. derived two frequency fields (low and high bands) and reached 77.90% accuracy by SVM whereas the accuracy of Jun et al. was about 96% by three different bands (theta, alpha, and beta) with SVM classifier.
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Endemic transmission of the human parasite Plasmodium vivax occurs across most of the Indonesian archipelago.1 The number of clinical attacks cannot yet be estimated with precision, but probably at least several million Indonesians suffer acute vivax malaria each year. Mortality due to vivax malaria, despite the dogma of a benign character, has been documented repeatedly in Indonesian hospitals over the past decade.2 This parasite poses a very significant and especially difficult threat to the health of the 130 million Indonesians living at risk of this infection.1
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This can be thought of as a function of (l,m,n)T, which is a function of (l,m,n). Clearly, this function is a basic elementary function—it is continuous and differentiable in the domain of the definition, and the minimum value must exist. At the point where the minimum value is obtained, the partial derivative of (l,m,n) exists and it is 0, and the partial derivative is obtained separately. (22){yl′=∑i=1N(Gi1GiTI)=0ym′=∑i=1N(Gi2GiTI)=0yn′=∑i=1N(Gi3GiTI)=0 .
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Thank you for submitting your manuscript to PLOS ONE. Both reviewers felt that the revised manuscript is improved. However, reviewer 1 requested some clarifications that require further revision. Therefore, we invite you to submit a new version of the manuscript that addresses the points raised by the reviewer.
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The characteristics of the study patients and prescriptions are presented in Table 1. The most prevalent comorbidities were dyslipidemia, hypertension, and diabetes mellitus in 97.2%, 95.5%, and 69.2% of the patients, respectively. Ambulatory prescriptions of analgesics were issued mainly at primary care clinics (80.3%), followed by general hospitals (7.6%), and hospitals (7.4%) (Figure 2a).
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Certain cancer risk factors can be addressed through clinical preventive services. As of 2017, the U.S. Preventive Services Task Force has recommended that all adults be screened for tobacco use and excessive alcohol use and offered counseling and intervention as needed and recommended the use of low-dose aspirin to prevent colorectal cancer and cardiovascular disease among adults who are considered to be at high risk for cardiovascular disease based on specific criteria (https://www.uspreventiveservicestaskforce.org/Page/Name/recommendations). A higher percentage of residents in nonmetropolitan areas than in metropolitan areas was uninsured (11), potentially limiting access to preventive services covered by insurance. The Advisory Committee on Immunization Practices recommends vaccination against two cancer-causing viruses, HPV (https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/hpv.html) and hepatitis B virus (https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/hepb.html). Data from the 2014 National Immunization Survey among persons aged 13–17 years indicate that vaccination rates for hepatitis B were similar in nonmetropolitan and metropolitan counties but that the vaccination rates for HPV among both boys and girls were lower in nonmetropolitan counties than in metropolitan counties (11).
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Eight samples of matched malignant and normal adjacent to tumor prostate tissue from four patients with prostate cancer were obtained from the Erasmus MC tissue bank. Use of the samples for research purposes was approved by the Erasmus MC Medical Ethics Committee according to the Medical Research Involving Human Subject Act (MEC-2004-261; MEC-2010-176) and patients were notified via an informed consent and asked for permission. Patients were selected based on the availability of RNA Seq data, and evaluation of hCRISPR expression levels (RPM) in each sample. From each sample total RNA was isolated. cDNA synthesis was performed using MiRCURY LNA RT kit (QIAGEN, Venlo, Netherlands, Cat. No. / ID: 339340) and in each RT-reaction 200 ng total RNA was used. RNA spike in template was added to each of the RT mixes according to manufacturer instructions. Quantitative real-time reactions were performed with custom designed primer assays (QIAGEN, Venlo, Netherlands Ct. No: 339317). Template sequence and Assay IDs are chr19_106 (5’-CTGACTAATACAGATTTTGGCACCAG-3’) GeneGlobe Design ID YCP1372825 and chr9_209 (5’-AGAGATATTCTTAGAATCTTTCATTATGGTACTCATAT-3’) GeneGlobe Design ID YCP-1372891. Real-time PCR reactions were performed with SensiMix™ SYBR® Low-ROX kit (Meridian bioscience, Boxtel, Netherlands) on an ABI 7500 Fast Real time PCR system (ThermoFisher, Breda, Netherlands). Four microliters of 60 times diluted cDNA was used for triplicate real-time PCR reactions. Cycling conditions were: Enzyme activation for 10 min at 95 °C, followed by 45 cycles of 15 sec at 95 °C, 30 sec at 55 °C, 15 sec at 72 °C. For the generation of standard curves for absolute quantification, synthetic 5’-phosphorylated RNA oligos mimicking the detected hCRISPRs were purchased (IDT, Breda, Netherlands). The oligo templates were mixed in an equimolar ratio and 10-fold serial dilutions were prepared over five orders of magnitude from 10 pM (~10 mln. copies) to 10 fM (~1000 copies). Real-time PCR was performed in high sensitivity AmpliStar-II 96-well plates (Westburg, Leusden, Netherlands, Cat. No: 1900WS). To detect chr9_209 with the SHERLOCK technology we used the Cas13a protein (MCLAB, San Francisco, USA). First, the following reaction mixtures were prepared. To generate a working stock solution of the sgRNA (5’-GAUUUAGACUACCCCAAAAACGAAGGGGACUAAAACUAAUGAAAGAUUCUAAGAAU-3’) (Synthego, Redwood city, USA) to detect the chr9_209 transcript (5’-AGAGATATTCTTAGAATCTTTCATTATGGTACTCATAT-3’), we added to the 5 nmol stock 20 μl of nuclease-free 1× TE buffer (Tris-EDTA, pH8.0) to get a final concentration of 250 μM (250 pmol/μl). To make a 10 μM working stock, we add 5 μl of the 250 μM sgRNA oligo to 120 μl of nuclease-free water to get a total volume of 125 μl of a 10 μM sgRNA working stock solution. Then a 1× NEBuffer 2.1 solution was prepared by mixing 100 µl of 10× stock NEBuffer 2.1 with 900 µl of nuclease-free water, to this solution 20 mg PEG 6000 was added. The reporter was diluted to get a 100 µl 10 µM solution by mixing 10 µl of 100 µM oligo stock with 90 µl of nuclease-free 1× TE buffer (Tris-EDTA) buffer. Then a cleavage reaction mixture was prepared by combining 2 μl cleavage buffer (400 mM Tris pH 7.4), with 12.8 μl UltraPure water, 0.5 μl of Cas13a (1 mg/ml, MCLAB), 1 μl of the gRNA (10 μM), 1 μl MgCl2 solution (120 mM), and 0.7 μl, of the Cas13 reporter (10 μM) (Lateral-Flow-Reporter: 5’-/6-FAM/rUrUrUrUrUrUrUrUrUrUrUrUrUrU/Bio/-3’) (IDT, Breda, Netherlands)). Then 2 μl of the chr9_209 synthetic transcript (1 μM) was added to the cleavage mix and incubated at 37 °C for 35 .min Hereafter 80 μl of 1× NEBuffer 2.1 with 2% PEG was added to each 20 μl reaction mixture and mixed thoroughly. We then placed the diluted reaction in a tube rack at room temperature, in which a HybriDetect Dipstick was added. The lateral-flow strip was allowed to run for two minutes at room temperature, where after the result was rated and picture captured at three minutes.
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Bone marrow-derived neutrophils were isolated from C57BL/6J male mice (3- to 6- mo old; n = 3) using the autoMACS Pro Separator (Miltenyi Biotec) with anti-Ly6G microbeads (Miltenyi Biotech, Cat. No. 130-120-337), as previously described (5). Neutrophils (1.5 × 106 cells) were resuspended in 1 mL RPMI 1640 (Gibco, Cat. No. 21875034), with 1% penicillin-streptomycin (Thermo Fisher Scientific, Cat. No. 15140-122). The cells were stimulated with S100A8/A9 (RnD Systems, Cat. No. 8916-S8-050; 500 ng/mL) for 15 min at 37°C. Unstimulated neutrophils served as negative controls. At the end of stimulation, samples were centrifuged at 800 g for 8 min. The secretome (supernatant) and cell pellet were separated, individually snap frozen, and stored at −80°C until use. MMP-9 release into the secretome was measured by immunoblotting, as an indicator of degranulation status.
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Utilization of carbohydrate-binding domains by commensal bacteria enzymes represents an important strategy for providing the ability to process fibrous chitin and for localization closer to the energy source, both as advantages in internal microbiome competition . Chit62J4 is capable of CM-chitin degradation to chitobiose, both in its intact form rChit62J4 and as the sole catalytic domain rChit62J4cat. Chit62J4 is thus capable of adsorbing on the surface of chitin particles and processing the accessible ends of chitin fibers.
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ST and RR contributed equally to this work and were responsible for study concept and design, performed the experiments, interpreted the results, and wrote the initial draft of the manuscript. TR analyzed the data and revised the manusript. LL and AS contributed to interpretation of results and revised the manuscript. MD was responsible for the concept and design of the study, supervised the work, contributed to interpretation of the results and revised the manuscript.
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We assessed effects of irradiance in a similar way by comparing “Low temperature: High irradiance (Lt:Hi)” and “Low temperature: Low irradiance (Lt:Li)” under low temperature and “Ht:Hi” and “Ht:Li” under high temperature. A total of nine consensus TE sequences were affected by irradiance among individuals from NT and ZT regions. Six presented higher expression under low irradiance, including three LINEs, one LTR Copia (ALYCopia52 – ale clade) and the TIRs MuDR-10 and MuDR-15, whereas three showed higher expression under high irradiance, including two class I LINE and one LTR Copia (ALYCopia76 – ivana clade).
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3rd instar larvae where grouped into genotype-specific cohorts of 10 individuals. The weights of at least five cohorts per genotype were averaged to calculate the mean weight of one respective larva. P values marked in bold indicate statistically significant deviations from the respective controls.
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Figure 5 presents graphical representations of the stern conversion maneuver. On the left is a finite state machine (FSM) representation of the decision logic, while on the right we have behaviour tree (BT) representation of the same maneuver. In the FSM representation the maneuver is made up of a series of states which execute lower level maneuvers and events allowing the FSM to transition from one state to another. As can be seen, this representation is rather simplistic such that at any point in time the agent can only be in one of five states. In the behaviour tree implementation the execution of behaviours is determined by the state of the conditional nodes in the tree. While more complex and flexible than the FSM representation, this representation still lacks the flexibility of a continuous plan generation. By using an automated planner to generate the stern conversion maneuver we allow for a more flexible representation that makes possible the recognition of complete behaviour trajectories according to highly sensitive cost functions.
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In clinical laboratory practice, antimicrobial susceptibility testing is currently performed by using growth-based manual or automated methods, such as agar diffusion assays and broth microdilution systems . However, these phenotypic methods are limited by turnaround times which do not satisfy the demand for timely information about the antimicrobial susceptibility of patient’s isolate. In contrast, molecular genetic methods are timely but able to only provide information about the absence or presence of an ESBL gene, which not always correlates to the phenotype . Reasonably, matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS), that is used for successful microbe identification , also direct from positive blood cultures (BCs) , in many clinical laboratories, has been explored as a tool for rapid antimicrobial resistance detection . In one of these newly generated assays , enzymatic cleavage of the β-lactam ring (in the β-lactam antibiotic) leads to specific mass shifts that can be easily monitored by MALDI-TOF MS. In another assay , comparison of the growth rates derived from cultivations of the same organism in the presence or absence of an antibiotic (virtually from all classes) enables organism’s susceptibility/resistance status to be assessed.
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The incidence and prevalence of nontuberculous mycobacteria pulmonary diseases (NTM-PD) have been increasing worldwide . In the United States, the annual incidence and prevalence of NTM-PD were estimated to increase by 5.2% and 7.5% from 2008 to 2015, respectively . Clinical, radiological, and microbiological criteria are equally critical for the diagnosis of NTM-PD . The most common species that induced disease is Mycobacterium avium complex (MAC), followed by Mycobacterium abscessus complex. The characteristic computed tomography (CT) findings of NTM-PD are bilateral bronchiectasis, multifocal bronchiolitis, lobular consolidation, and cavitation .
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Between March 2012 and October 2018, a total of 104 NSCLC patients received palliative surgery for spinal metastasis at the authors’ institution. Among these patients, 19 were excluded from the analysis for the following reasons: (1) ten due to missing data on EGFR mutation analysis results, (2) five with an unidentified survival period or death, and (3) four who died within two weeks after surgery due to immediate postoperative complications (two pneumonia, one cardiac arrest, and one disseminated intravascular coagulation due to massive bleeding; Figure 1). As a result, 85 patients (58 males and 27 females) with a mean age of 60.9 (range, 32–81) years were analyzed in the current study. The characteristics of the study population are described in Table 2.
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A higher rate of AF in patients with non-TTS MINOCAs is remarkable, even when considering they are younger and with less hypertension than patients with TTS. The association of AF with MINOCAs could be explained as emboli being the underlying physiopathological mechanism for the event (1, 4, 5).
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In 20 of the 49 follow-up documents, concerns regarding genetic variation are mentioned, and in 15 of these documents, conservation goals for genetic diversity are expressed (Table 1). Such goals are strongly stated in the EU Biodiversity Strategy to 2020 and the EU Guidelines for establishing Natura 2000 network in the marine environment, which concerns EU implementation of, e.g., the Habitats and Birds Directives, as well as in the CBD Strategic Plan 2011-2020 including Aichi Target 13 directly focusing on genetic biodiversity (COP10 Decision X/2, 2010; www.cbd.int/sp/targets/; Table 1).
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Two independent reviewers (LJ Zeng and CL Xiang) performed data extraction (first author, year of publication, sample size, age, FIGO stage, pathology, histological grade, intervention, and outcome data) and evaluated the quality of included studies according to Cochrane Collaboration’s risk of bias tool in Cochrane Handbook for Systematic Reviews of Interventions 5.1.0. Consensus was used to resolve discrepancies. The end points of interest were: overall survival (OS), progression-free survival (PFS), no residual disease, residual disease ≤1 cm, and optimal cytoreduction rate. The definition of optimal cytoreductive surgery is residual tumor diameter ≤1 cm or no residual disease after debulking surgery.
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In this cross-sectional population-based study, a comprehensive statistical method (i.e., latent factor regression model for grouped outcomes with confirmatory latent predictors) was introduced to evaluate the association of stressful life events with psychological problems. In the present study, psychological distress, anxiety, and depression were considered as grouped outcomes and two domains of stressful life events (personal and social) as confirmatory latent predictors. Overall, according to the findings of the current study, it was observed that stressful life events directly associated with components of psychological problems and their profile scores, with greater associations in females than in males.
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We previously reported that educational lectures are effective in reducing the use of oral third-generation cephalosporins . Educational intervention commenced in 2018, and the monthly mean DOTs per 1000 patient-days of oral quinolone for outpatients significantly decreased by 49% in 2020 compared to 2013. However, before the educational intervention, oral quinolone use had significantly decreased by 11% in 2014 and remained at a low level thereafter. Since 2014, several global and national guidelines were published to tackle the spread of antimicrobial resistance . These guidelines may have affected changes in the prescriptions of oral quinolones. The Manuals of Antimicrobial Stewardship state that patients with acute respiratory tract infections and acute diarrhea should not be prescribed antibiotics . In this study, to investigate the number of prescriptions for oral quinolones, representative data were collected during December 2013, December 2019, and December 2020. We found a significant reduction in unnecessary antibiotic prescriptions for outpatients. However, no prescriptions for these conditions were detected in hospitalized patients. This was because patients prescribed unnecessary antibiotics are usually mild and are treated in outpatient settings; therefore, they are not commonly treated as inpatient in hospitals. According to Asian guidelines for the prevention of surgical site infections, quinolones should be used as alternative agents for patients with a penicillin allergy . We previously reported a reduction in the use of oral quinolones for outpatients in the Department of Oral and Maxillofacial Surgery between 2013 and 2018 after adopting the National Action Plan . Consistent with these reports, we found that prescriptions of oral quinolones were significantly reduced for perioperative prophylaxis in inpatients and dental infections in outpatients. The guidelines for acute cholangitis and cholecystitis recommend that quinolones should be prescribed to patients with a beta-lactam allergy or if the isolate is susceptible to quinolones . Bacteroides fragilis is one of the commonly isolated commensals in patients with intra-abdominal infections, and antibiotics used against anaerobic infections are often selected as empiric therapy . Most oral quinolones used in Japan have no activity against anaerobes , and thus, oral quinolone use is considered to be inappropriate for these infections. In the present study, there was a significant reduction in the number of prescriptions for inpatients with intra-abdominal infections. These findings suggest that global and national guidelines, as well as educational interventions, may contribute to a significant downtrend in the use of oral quinolones. Although we found a considerable reduction in the use of oral quinolone for outpatients, no significant changes were detected in the number of patients who received intravenous therapy after oral quinolone prescriptions. This indicates that the reduction in quinolone prescription did not negatively influence the outcomes for these patients.
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ISI. (A) There was no clear difference in the mean number of episodes completed in the 0.5, 2, and 8 s ISI conditions. (B) Parameter fits show a similar outcome of no effect over the three ISIs. (C) The mean number of actions visited per state is also not significantly different for the three ISIs. Error bars denote ±1 SEM for 11 participants. (D) Model comparison for the ISI experiment. Here, the Dyna-Q and “exploration vs. exploitation” models provide the best account of the data. *p < 0.05 for the indicated comparisons.
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Figure 1a,b show the average durations of PA with light and moderate to vigorous intensities for the GPAQ 50+, MW8, and MM+ in hours per day. Figure 1c illustrates the duration of sedentariness that was assessed with the MW8 and the MM+. Two extreme values in the duration of PA with light activity assessed with GPAQ 50+ and the MM+ were identified and excluded from data analysis. Significant differences (p ≤ 0.01) in the durations of all PA intensities were found between all of the assessment methods, except for PA with moderate to vigorous intensity between the MM+ and the GPAQ 50+ (p = 0.412).
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29,448
In Sect. 6, we define SPR and TBR operations on networks. These operations generalize the NNI operation, as well as the well-known subtree prune and regraft (SPR) and tree bisection and reconnection (TBR) operations on trees (cf. Allen and Steel 2001). The SPR and TBR operations allow parts of a network to be chopped off and reconnected somewhere onto the resulting network, in contrast to the NNI and triangle operations which are local in nature. In Sect. 7, we derive bounds for the diameter of the SPR and TBR metrics on the set on \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\mathcal {N}}}_i(X)$$\end{document}Ni(X). We conclude in Sect. 8 with a discussion of some possible future directions.
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“And sometimes I even go along with their conversation for fun and then I think ‘yes, that is what you want to hear right? That is not what I think...’ Yes, but what else should I do, it is all a game, unfortunately. It sounds very manipulative what I'm saying now, but that's how it works. [...] So if they [colleagues from ethnic majority] make racist remarks, ‘yes, there are those street youths around these days, surely many of them are Moroccans’. Yes, that’s just what it is, I agree with them.” (S1, female)
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The patients in the control group were given laparoscopic radical surgery with the following specific steps. The modified bladder lithotomy position was taken and a cushion was put under the buttocks of the patient, an incision was made at 4 cm away from the upper edge of the nabhi chakra, the casing needle was inserted to establish the pneumoperitoneum, the intraabdominal pressure was maintained between 12 and 15 mmHg, the laparoscopy was inserted to observe the abdominal cavity and the pelvic cavity, and the hysterectomy was performed according to the image displayed by the laparoscopy; after surgery, the wound was rinsed, sutured, disinfected, and bound up [16–18].
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This was a cross-sectional study conducted in Brazil on users of the HealthRise program—a program targeting the reduction of premature death from chronic non-communicable diseases, such as diabetes and hypertension—in Vitória da Conquista, aimed at improving users’ access to primary health services, qualifying care, implementing medical records, and offering special tests to patients with chronic diseases (hypertension and diabetes) .
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337,145
In our test setting we use \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$U=5$$\end{document}U=5 and parameter-dependent values for electron hopping \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$v_{ij}=v_{ij}(\omega )\in {\mathbb {C}}$$\end{document}vij=vij(ω)∈C with \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\omega \in (0,2\pi ]$$\end{document}ω∈(0,2π]:\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\begin{aligned}&v_{11}=v_{88}=-1.75,\quad v_{jj}=-2\quad \text {for}\quad j=2,\ldots ,7,\\&v_{j,j+1}={\bar{v}}_{j+1,j}=-\cos \omega +\mathrm{i}\,\sin \omega \quad \text {for}\quad j=1,\ldots ,7\quad \text {and}\quad v_{ij}=0\quad \text {otherwise}. \end{aligned}$$\end{document}v11=v88=-1.75,vjj=-2forj=2,…,7,vj,j+1=v¯j+1,j=-cosω+isinωforj=1,…,7andvij=0otherwise.For this choice of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$v_{ij}(\omega )$$\end{document}vij(ω) we obtain a Hermitian matrix \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$H_\omega \in {\mathbb {C}}^{n\times n}$$\end{document}Hω∈Cn×n with 43,980 nonzero entries (for a general choice of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\omega $$\end{document}ω) and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {spec}(H_\omega )\subseteq (-19.1,8.3)$$\end{document}spec(Hω)⊆(-19.1,8.3). The spectrum of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$H_\omega $$\end{document}Hω is independent of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\omega $$\end{document}ω.
4
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101,567
That pain hypersensitivity in female mice is independent of microglia, which are innate immune cells, led to considering the possibility that cells of the adaptive immune system may be necessary in females . It has been previously reported that male mice lacking adaptive immune cells develop less hypersensitivity after nerve injury [69, 70]. In contrast, it was found that nerve-injured adaptive immune cell knockout mice (B6.129S7-Rag1 tm1Mom/J and NU/J) display equivalent hypersensitivity to their wildtype counterparts, regardless of sex. However, interrogation of pain signalling mechanisms in these mice revealed that females lacking adaptive immune cells employ a microglia-dependent pathway in the mediation of pain hypersensitivity. Immune system reconstitution of female Rag1 knockouts with spleenocytes causes a ‘switch’ to a microglia-independent pathway. Therefore, it is hypothesized that the presence of adaptive immune cells, likely T cells, is necessary to drive the non-microglia pathway (Fig. 1). T cells migrate into the spinal cord after nerve injury and have been implicated as key regulators of hypersensitivity [69–71].
4
0biomedical
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191,979
Two previous reviews have suggested that it may be more beneficial to perform resistance training before endurance training than vice versa for lower-body strength adaptations [61, 62]. This could therefore be a confounding factor in the present analysis if the sequential order was considerably different among our categories. However, this was not the case, as the sequential order of endurance and resistance training was relatively similarly distributed in the three categories. Interestingly, a recent study did not detect any difference in maximal strength development, although some negative effects were noted for power, between concurrent training modalities performed in different orders when the two training sessions were separated by 3 h of rest . Thus, it could be that the sequential order is only important if insufficient recovery is presented between the resistance and endurance training sessions. However, more research is needed to confirm this.
4
0biomedical
2Review
19,080
The limitations of this study can be the inability to validate the in vivo conditions in the absence of a biological self-healing environment. The second limitation is the computer, which makes it harder to apply more than 106 cycles during the damage simulation of the bone.
2
0biomedical
0Study
94,169
To examine the affect of TPMT on cellular responses to cisplatin, wild type and variant TPMT were transfected into two murine inner ear cells lines and a dose-response of cisplatin concentration and cell viability was established. Relative to TPMT*3A-expressing HEI-OC1 cells, viability was increased in TPMT*1-expressing cells at all cisplatin concentrations tested and this was reflected in a significantly higher cisplatin IC50 value in these cells as determined by MTT assay (Fig 2 and S2 Table). A moderately enhanced cell viability effect was observed when endogenous Tpmt was reduced by knockdown in UB/OC-1 cells that have a 3-fold lower basal expression of Tpmt as quantified by qPCR (Fig 2 and S2 Table). TPMT*1 particularly influenced cell viability at sub-IC50 cisplatin concentration where statistically significant differences were noted at 10 μM cisplatin in HEI-OC1 cells and 3.16 and 10 μM cisplatin in UB/OC-1 cells (S3 Fig). Similar observations were made in a colony survival assay performed with HEI-OC1 cells, where expression of TPMT*1 led to increased colony numbers and improved cellular morphology in this assay compared to expression of TPMT*3A (S3 Fig). These data suggest that overexpression of the functional TPMT allele (TPMT*1) reduces the susceptibility of murine inner ear cells to cisplatin-mediated cell death.
4
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332,530
a Integrated plot depicting the relationship between CRISPR-derived gene dependence scores and, from top to bottom, gene copy number variations; the DNA methylation profiles; the mRNA transcription levels; and gene dependence scores. b Bar graph showing the statistically significant Pearson’s correlation scores between the mRNA expression levels of oncogenes encoding MAPK pathway proteins and their corresponding gene dependence scores. c Pearson’s correlation between MYC proto-oncogene mRNA expression levels and the CRISPR-derived MYC gene dependence score. d Comparison of mRNA transcript levels. e From left to right: correlation between the KRAS transcript levels and the KRAS gene dependence scores, and the mean difference in the KRAS dependence between pancreatic cancer cell lines (pancreatic cancers have the highest frequencies of KRAS mutations) and all other cancer cell lines; the mean difference in KRAS dependence score between KRAS mutant cell lines and cell lines that do not harbour KRAS mutations. f Correlation between the MAPK1 transcript levels and the MAPK1 dependence scores, and the mean difference in MAPK1 dependence score between skin cancer cell line and all other cancer cell lines. g (Left) correlation between BRAF transcript levels and BRAF dependence scores, and the mean difference in the BRAF dependence score between skin cancer cell lines (cancer type with most BRAF mutations) and all other cancer cell lines. (Right) The mean difference in the BRAF dependence score between BRAF mutant cell lines and cell lines that do not harbour BRAF mutations.
4
0biomedical
0Study
341,528
Does our parameter u capture behavioral flexibility, as we hoped? We argue that it does, up to a point, with negative u corresponding to higher behavioral flexibility than positive u. In all situations we have tested, negative u leads to faster learning; and when we set operant level against preparedness, in simulating the experiments of Chow et al. (2016), a negative u value enabled what was learned to be controlled by operant level (which would be a commonsense expectation in any situation) rather than being captured by preparedness. In both these senses, therefore, negative u is associated with freedom from instinctual constraints – and as we saw in the first part of the present paper, that was the original meaning of behavioral flexibility, and still perhaps represents its core meaning. Of course, operant levels might themselves result from the animal’s instinctual repertoire, but they need not: so far as our model is concerned, they are simply the outcome of the response strengths with which the animal approaches the situation, and these will be the result of all its previous experience as well as any innate tendencies.
4
0biomedical
0Study
7,507
The viral load of 8 different tissues (cerebrum, heart, kidney, liver, lung, small intestine, skin, and skeletal muscle) was determined post mortem for all birds 2–4 DPI (Table 1). BCRV was detected in all tissue types analyzed at 2 DPI and viral loads differed among tissues (F7,21 = 61.28, p<0.0001). Viral load in the cerebrum was significantly higher than all other tissues at 2 DPI and load in the lungs was significantly higher than all tissues except the cerebrum (Tukey’s p<0.001 for all significant pairwise comparisons). Viral load decreased from 2 DPI to 4 DPI in the cerebral tissues (F2,9 = 5.01, p = 0.035, Tukey p = 0.049 comparing 2 DPI and 4 DPI) and the lung tissues (F2,9 = 5.35, p = 0.030, Tukey p = 0.024 comparing 2 DPI and 4 DPI).
4
0biomedical
0Study
127,252
To explore how LINK-A regulates aggressiveness and inflammation of RA FLSs, we sought to identify intracellular targeting proteins of LINK-A using RNA-Seq. Figure 4A shows the LINK-A silencing-induced top 10 mRNA KEGG pathway enrichment results, including HIF-1 signaling pathway. Consistent with our data, a recent study shows that lncRNA LINK-A activates normoxic HIF-1α signaling in breast cancer tumorigenesis (14); therefore, we speculated that LINK-A might regulate HIF-1α pathway in RA FLSs. As we expected, we demonstrated that LINK-A knockdown with siRNA significantly decreased the mRNA and protein levels of HIF-1α (Figure 4, B and C), while LINK-A overexpression promoted HIF-1α expression (Figure 4, D and E). For exploring the role of LINK-A in regulating HIF-1α activation, we evaluated the effect of LINK-A knockdown or overexpression on nuclear HIF-1α expression. We demonstrated that LINK-A knockdown or overexpression reduced or increased nuclear HIF-1α expression in RA FLSs (Figure 4, C and E). On the other hand, we determined that HIF-1α knockdown did not influence LINK-A expression (Figure 4F). These data suggest that HIF-1α is a downstream targeting protein of LINK-A.
5
0biomedical
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55,646
Safranin O/ Fast Green staining was used to visualize cartilaginous callus formation in paraffin wax sections (8 μm) of femurs at 10, 14 and 21 days following osteotomy. Tissue sections were dewaxed, rehydrated and stained in 0.05% Fast Green for 5 min. Slides were directly transferred to 0.1% Safranin O for 5 min and following dehydration in graded alcohols, mounted in DPX. Images were captured using a Leica M205C stereo microscope (Leica Microsystems, Heerbrugg, Switzerland) fitted with a digital camera (Canon EF-S18-55IS2). The ratio of Safranin O positive area to callus area was determined using NIH ImageJ software, where at least three serial tissue sections of the central callus region between the inner screws from 7 to 10 mice per group were analysed.
4
0biomedical
0Study
170,530
Furthermore, in support of the argument that resilience can serve as a “buffer” against workplace stress (23), we also found that forensic healthcare workers with higher levels of resilience perceive fewer personal attacks or threats at the workplace from patients. This is in line with our hypothesis that resilience would be negatively associated with work-related stress symptoms. Resilient workers may appraise potentially stressful situations as less threatening and reduce distress because of their ability to think flexible and apply adaptive coping strategies (18–22). Last but not least, the current study showed that workers who have contact with difficult clients or patients, are less likely to actively avoid sneezing people. In order to successfully deal with challenging clients or patients, one might need to adopt a more flexible approach when interacting with them. As a result, the worker might become more proficient in social interactions and perhaps less fearful of interacting with others during the Covid-19 pandemic, even with those who sneeze.
2
0biomedical
0Study
151,186
Substantial efforts have been made in molecular image technology. Mass spectrometry imaging (MSI) has developed rapidly in recent years and can be used to identify multiple metabolites on a spatial level with high sensitivity and resolution, and without the need for labeling (Unsihuay et al., 2021; Zullig and Kofeler, 2021). For example, matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI–MSI) has been used for the in situ analysis of metabolites in DKD research, although this method usually requires a high-vacuum environment and matrix assistance for ionization (Tanaka et al., 2018). Desorption electrospray ionization mass spectrometry imaging (DESI–MSI) is a powerful tool that has been used for lipid detection in the renal cortex of a type-1 diabetes mellitus (T1DM) mouse model, whereas reveals relatively low spatial resolution (Zhang et al., 2020a). Similar to DESI–MSI, tissue identified by airflow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI–MSI) exhibits great specificity, high sensitivity, and a wide coverage for spatial metabolomics since it can map a large number of metabolites located in diverse metabolic pathways (He et al., 2018; Sun et al., 2019; Wang et al., 2020b). However, the high-throughput discovery of type 2 DKD metabolic alterations has not been previously reported.
5
0biomedical
0Study
342,491
In order to better understand the results, we investigated the number of samples in the smallest group (NSSG) obtained doing a cluster analysis resulting in two groups. This number should be close to 50 for the balanced data set and close to 25 for the skewed data sets. Moreover, if this number is very small it indicates that the clustering is governed by just a few samples (outliers). Interestingly, the ARI-differences and NSSG-differences were correlated, so that methods with relatively high ARI also had a relatively high NSSG, see Table 3 and Supplementary Table 5. In particular SD had considerably lower NSSG than the other methods, especially for the balanced data, see Supplementary Table 5.
4
0biomedical
0Study
131,823
Sugars in honey account for 95% to 99% of its dry weight, mainly fructose and glucose . The fluctuation between the fructose and glucose content in 4–7 days honey was likely related to various enzyme activities and the addition of new honey. The content of monosaccharides (fructose and glucose) in all honey samples was not less than 60%. There were no obvious differences (p > 0.05) in the monosaccharide during the honey ripening process. The sucrose content of all honey samples was in good consistency with the specification of less than 5% .
4
0biomedical
0Study
192,280
Despite continuous progress in techniques and methods to minimize periprocedural complications including paravalvular leak or bleeds , several studies have suggested that primary hemostasis disorders secondary to persistent loss of high-molecular-weight (HMW) multimers of the von Willebrand factor (vWF) may still contribute to late bleeding complications . vWF is a multimeric protein secreted by endothelial cells and platelets. This HMW glycoprotein mediates the adhesion of platelets to sites of vascular damage through glycoprotein Ib-vWF interactions .
4
0biomedical
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166,153
For swelling study purposes, microparticles ranging in size from 11 to 44 µm were produced using microfluidic techniques. Figure 3 demonstrates the morphology and monodispersity of generated particles. Polydispersity index (PDI) was used to measure the consistency of microparticle size within each sample population. The PDI (σ) was calculated by Eq. (1):1\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sigma = \frac{\delta }{{D_{A} }} \times 100\% ,$$\end{document}σ=δDA×100%,Figure 3Magnification of 29 µm microparticles demonstrating the monodispersity (PDI = 1.6%) and morphology. ×4 magnification (a) and ×40 magnification (b) on an inverted microscope. Scale bar is 29 µm.
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0Study
9,729
Psoriasis is also associated with multiple comorbidities including psoriatic arthritis (PsA) , obesity , hypertension [2, 15], malignancies , metabolic syndrome [3, 5, 26], and cardiovascular diseases [2, 19, 28, 34]. Patients with psoriasis have an increased risk of depression/anxiety [7, 9, 23, 32] and suicidality [16, 25]. Although psoriasis is physically and psychologically devastating on its own, the presence of comorbidities increases the burden of the disease [4, 21, 22, 24, 30, 39]. Moreover, the burden of comorbidities increases with increasing psoriasis severity [20, 39]. Psoriasis patients with comorbidities are more likely to require urgent care, have greater hospitalization rates and more frequent outpatient visits, and incur greater costs than psoriasis patients without comorbidities . Comorbidities result in higher overall pharmacy, and medical costs (adjusted annual cost differences per patient $17,696, and $5077, respectively) . In addition, in a recent study conducted in the US in psoriasis and PsA patients, 92% of unemployed participants reported that they could not work solely due to psoriasis or PsA, revealing considerable work productivity burden of these diseases .
4
0biomedical
2Review
209,348
Effect of voluntary exercise on hypothalamic (A) and plasma (B) levels of leptin in the control group (C), type 2 diabetic group (D), voluntary exercise group (Ex), and type 2 diabetic-voluntary exercise group (D-Ex) (all groups, n=8). **; P<0.01 and ***; P<0.001 show the statistical difference between C and different groups. ###; P<0.001 shows the statistical difference between D and the D-Ex groups
3
0biomedical
0Study
15,252
Seventeen years ago, Bohle and Stasko communicated two compounds of type [{PtL}3(μ3-ctc)], where H6ctc is cyclotricatechylene (Scheme 1) and L is a diphosphine.27 Both compounds show three low-potential oxidations by cyclic voltammetry, indicating that the [ctc]6– catecholate rings are oxidised sequentially from the cat to sq levels. No characterisation of those unusual radical species was undertaken, however. More recently cage complexes28 and supramolecular assemblies29 based on [ctc]6– have been crystallographically characterised, although their redox properties also remain to be explored.
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88,513
The patients' immunity-cicatricial condition is essential for the success of the repair. The tumor necrosis factor-α (TNFα) is a cytokine involved in the systemic inflammation and has an important role in the development of the acute phase reaction. However, this response must be closely balanced because overproduction of TNFα can also lead directly to apoptotic injury. Furthermore, excessive activation of NF-κB can also have pathological effects, instead of protecting against apoptosis. For example, the exaggerated NF-κB activation that occurs in sepsis syndromes may explain some of the pathophysiological changes, including the intravascular coagulopathy . Studies demonstrate that TNFα induces matrix metalloproteinases (MMPs) that may disrupt skin integrity. The TNFα increases collagenolytic activity of MMP-1, which is probable via upregulation of MMP-3 leading to gradual loss of type I collagen in the human skin .
4
0biomedical
0Study
168,249
Evidently, the role of MSCs in tumor development is not straightforward, and there is still no clear answer to what makes MSCs pro-tumorigenic or anti-tumorigenic. Deeper understanding of factors leading to the promotion of tumor growth or its suppression by MSCs is imperative for their safe and successful application as cell-based therapeutics or for potential manipulation of MSCs with the aim of targeting tumor cells and modulating TME to be unfavorable for tumor development. One of the factors that influences the behavior of MSCs to a great degree is senescence, and in the next sections we will go deeper into the role of this phenomenon in carcinogenesis and tumor progression.
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2Review
10,206
Basal cell carcinoma (BCC), a cancer of epidermal basal keratinocytes, is the most common cancer in the United States. BCCs are locally invasive epithelial tumors that are caused by activating mutations in the HH pathway, typically through the loss of the receptor PTCH1 or by activating SMO. BCCs represent an ideal model system to study mechanisms of cancer development in HH-driven tumors due to their exceptionally high mutational load from exposure to environmental mutagens and their ease of accessibility . Genomic analysis has revealed that BCCs are typically diploid and carry a high frequency of non-silent single nucleotide variants compared to other tumor types[6–8]. Indeed, BCCs bear the highest rate of recurrent mutations in all cancers at 65 mutations per megabase. PTCH1 and SMO mutations have been described in BCC development, but missense mutations in other HH proteins like SUFU are also frequently found and are of unknown significance. Recent studies reveal that up to 8% of BCCs possess SUFU variants , our previous analysis indicates that up to 50% of BCC variants are functionally silent and requiring functional validation (6). How clinically observed SUFU variants alter SUFU function remains poorly described.
5
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386,766
Our present findings suggest that acute sleep loss—as often experienced in shift work, for example—results in an evening to morning increase in plasma levels of t-tau, without concomitant changes in plasma levels of other biomarkers of AD, such as Aβ species. Whether the changes in t-tau in plasma in response to sleep loss reflect increased neuronal activity during sustained wakefulness, or alternatively, disrupted central or peripheral clearance, is unclear.
4
0biomedical
0Study
80,486
TcsL-induced Rac/Cdc42 glucosylation were next analyzed upon pharmacological inhibition of p38alpha/beta. SB203580 treatment of either p38alpha−/− MSCV p38alpha and p38alpha−/− MSCV empty vector MEFs resulted in an almost complete loss of pT222-MAPKAPK2, confirming effective p38 inhibition (Figure 5 and Figure 6). TcsL-catalyzed Rac/Cdc42 glucosylation and PAK1/2 deactivation were responsive to SB203580 treatment in both p38alpha−/− MSCV p38alpha and p38alpha−/− MSCV empty vector MEFs, both in time- (Figure 5) and concentration-dependent (Figure 6) experiments. The observation that cell rounding and Rac/Cdc42 glucosylation in p38alpha−/− MSCV empty vector MEFs are responsive to SB203580 suggests that the protective effects of SB203580 involve inhibition of both p38alpha and p38beta. Taken together, p38alpha/beta inhibition-mediated protection of fibroblasts from TcsL-induced actin reorganization coincides with protection from TcsL-catalyzed Rac/Cdc42 glucosylation.
4
0biomedical
0Study
54,498
The last step from diacylglycerol (DAG) to triacylglycerol (TAG) is catalyzed by diacylglycerol O-acyltransferase (DGAT, EC:2.3.1.20). This enzyme is down regulated in N. oleoabundans under all tested conditions compared to the fresh water replete conditions. DGAT has been extensively studied since it is regarded as one of the most important rate limiting steps in TAG biosynthesis. Over expression of this gene or several subunits have resulted in very different outputs. In Phaeodactylum tricornutum there have been very promising results, resulting in higher levels of TAG synthesis, but in the green alga C. reinhardtii there have not been consistent increases in TAG content in combination with DGAT over expression [82–85]. The fact that DGAT does not seem to be over expressed under nitrogen-deplete conditions is surprising, since TAG accumulation is occurring in N. oleoabundans under these circumstances. In this study only one DGAT gene could be identified and it is known from other species that there are several genes that encode for DGAT enzymes and that they have very different expression profiles as a response to nitrogen deprivation . More research needs to be done to understand and identify the different DGAT enzymes in N. oleoabundans.
4
0biomedical
0Study
80,869
Laurdan-labeled HIV GUVs treated for at least 15 minutes with MβCD exhibited lower Laurdan GP values than untreated controls, indicating a decrease in lipid packing induced by this compound (Fig. 4a, right), which was consistent with the effect observed in Laurdan-stained virus particles12. At the end time-points of incubation, homogeneous phase GUVs with a low GP value co-existed with vesicles displaying lateral separation of more fluid and less fluid domains (see Supplementary Fig. S5 for an example of the latter). These findings give further support to the intrinsic capacity of the complex HIV membrane to access a variety of lipid packing states, which evolve modulated by the Chol content as in the surrogate mixtures (see previous Fig. 2a). Emphasizing the functional relevance of this capacity, Chol extraction by MβCD blocks virus-cell entry343538 (Fig. 4a, left).
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0biomedical
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119,702
As a control, we identified a set of 156 “cell-dedifferentiation markers” that were consistently RA-repressed (Additional file 2: Figure S1A). These 156 “cell-dedifferentiation markers” significantly over-represented the 775 MYC/MAX targets identified by ChIP-on-ChIP (21 overlap, p = 3.1e-7, odds ratio = 4.1, Additional file 2: Figure S1B). Interestingly, no recurrent somatic mutation was reported for these cell-dedifferentiation markers. We conclude that a high rate of the mutated differentiation markers over the mutated dedifferentiation markers may be associated with aggressiveness in HR-NB.
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0biomedical
0Study
43,891
The concept of regulatory focus has been verified by Lee and Aaker in their health-related study involving a grape juice advertisement with various message frames and regulatory focuses. The results confirmed that when the advertisement manipulated the participants into a promotion focus orientation by emphasizing the high vitamin C and iron content of the grape juice, gain framing (i.e., to improving nutrition) for the advertising slogan was more effective than loss framing (i.e., not missing the opportunity to improving nutrition). Conversely, loss framing (i.e., not missing the opportunity to prevent cardiovascular disease) for the advertising slogan was more effective than gain framing (i.e., to prevent cardiovascular disease) for the slogan when the advertisement induced a prevention focus orientation by emphasizing the antioxidant content in the juice and its effect on cardiovascular disease prevention. The findings indicated that the advertisement induced fluent thinking and generated positive feelings when the message was oriented toward a regulatory fit; therefore, a more persuasive effect was generated. In addition, rather than exploiting the viewers’ regulatory focus orientations, the persuasiveness of the advertisement can be enhanced by steering viewers toward a temporary regulatory focus orientation and then delivering a framed message that fits their perceptions. Zhao and Pechmann reported similar results in their study on antismoking advertisements targeting adolescents. The study suggested that social marketers could manipulate regulatory focus by their choice of the message context because we might not know anyone’s psychological orientation. Thus, a gain-framed message could be aired during a show that primes a promotion orientation and a loss-framed message could be aired during a show that primes a prevention orientation. The aforementioned studies show that persuasiveness can be enhanced when the presented message fits the regulatory focus of the intended audience . Therefore, this study proposed the following hypotheses and research framework (Figure 1).
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0Study
36,071
Contour representation of massive data from rat EEG. Contour plot of log10⁡σs for Rat001. (a) The whole σs range. Different types of data are classified according to the value of log10⁡σs. In (b), the contour is for values of 102≤σs≤103 (good data), and the remaining values of σs are set to 50 so that the dark blue area marks all abnormal data.
3
0biomedical
0Study
185,623
Considering the aforementioned factors, this study aims to implement the RESHAPE framework into three Australian coal mining sites. It is hypothesised that the RESHAPE framework will lead to greater wellness outcomes for the individual (weight loss) compared to standard, once off wellness initiatives which are current practice in this industry. This paper presents baseline findings from a pilot study that implements RESHAPE and investigates the issue of overweight and obesity in the coal mining industry. Knowledge gaps remain alongside concerns regarding the success of diet and physical activity programs within blue-collar workers, particularly miners. This paper looks to bolster this shortcoming of the literature base and provides discourse concerning wellness in blue-collar male dominated industries.
3
0biomedical
0Study
282,636
“My friend circle motivated me a lot by giving examples like, look nothing happened to us. As they were taking the weed, nitrogen tablets, brown sugar for a long time, and life is a matter of enjoyment, and ultimately I got involved.” [Male participant 23 years, Chhetri, FGD].
1
2other
0Study
1,783
Homoplasy values in the stepwise demographic expansion model for different values of the expansion time parameter τ. The points in each plot are the average values for each statistic across 100 simulations for plots (a-c), those average values were used to calculate the mean values of the homoplasy index (P), mean size homoplasy (MSH) and distance homoplasy (DH) that are plotted as points in (d). The dashed lines are the approximated expected values estimated from our derivations. a π ISM and π SMM; b \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ {F}_{ISM}^i $$\end{document}FISMi and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ {F}_{SMM}^i $$\end{document}FSMMi; c F ISM and F SMM d P, MSH and DH
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0biomedical
0Study
33,043
3D echocardiographic examination showed that LV volumes and EF were similar in both groups (Table 3). Similarly to the 2D echocardiography, LV mass was significantly higher in patients. Moreover, the 3D LV mass values were higher than the 2D-derived ones, which is consistent with the results of previous studies comparing 2D and 3D echocardiographic parameters . All parameters of 3D LV deformation tended to be lower in CoA group, however, only GAS differed significantly in the CoA group. No differences in LV deformation data were found between patients with bicuspid aortic valves compared with tricuspid ones. Nor did the method of CoA correction influenced the LV deformation values. Similarly, there were no differences in 3D deformation values between patients with hypertensive treatment and patients with no medications, although higher LV mass and lower diastolic RR in individuals on antihypertensive medications were observed (Table 4). Both subgroups of patients differ significantly from the control group in terms of GAS values (p < 0.05).Table 3Real-time three-dimensional echocardiographic assessmentCoarctation patientsHealthy controls p valueLV EDV (mL)107.8 ± 33.6113.5 ± 23.3NSLV ESV (mL)41.3 ± 17.644.2 ± 12.0NSSV (mL)65.8 ± 17.469.4 ± 13.6NSCO (L/min)4.13 ± 1.44.68 ± 1.3NSLV EF (%)61.8 ± 6.961.4 ± 4.8NSSphericity index0.45 ± 0.090.44 ± 0.09NSLVM (g)137.6 ± 22.4124.3 ± 16.50.02LVM index75.423 ± 11.967.944 ± 8.60.01GLS (%)−16.6 ± 3.8−18.4 ± 2.5NSGCS (%)−16.7 ± 2.8−17.5 ± 2.4NSGAS (%)−28.8 ± 4.1−31.7 ± 2.70.007GRS (%)47.1 ± 10.151.3 ± 6.5NS EDV end-diastolic volume, ESV end-systolic volume, SV stroke volume, CO cardiac output, LVM left ventricular mass, GLS global longitudinal strain, GCS global circumferential strain, GAS global area strain, GRS global radial strain Table 4Selected clinical parameters and echocardiographic indices in coarctation patients with no hypertension and in coarctation patients on antihypertensive medicationsCoA pts with no hypertension (n = 11)CoA pts on antihypertensive medications (n = 15) p valueMean age (year)25.5 ± 6.423.5 ± 7.0NSSystolic blood pressure (mmHg)129.7 ± 11.4128.3. ± 12.3NSDiastolic blood pressure (mmHg)84.8 ± 7.576.3 ± 10.10.01LVM index87.5 ± 14.5106.4 ± 43.80.01GLS (%)−16.0 ± 4.4−17.0 ± 3.4NSGCS (%)−16.0 ± 1.6−17.2 ± 3.4NSGAS (%)−27.9 ± 4.0−29.4 ± 4.1NSGRS (%)44.9 ± 8.848.7 ± 11.0NS CoA aortic coarctation, LVM left ventricular mass, GLS global longitudinal strain, GCS global circumferential strain, GAS global area strain, GRS global radial strain
4
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131,864
Keloids are benign lesions with invasive growth beyond the original wound borders, in which the hyperproliferation of fibroblasts and excessive accumulation of extracellular matrix can be observed . The claw-like extension of keloids not only causes cosmetic disfigurement, but also brings about uncomfortable feelings such as itch and pain, as well as local dysfunction, resulting in impaired emotional wellbeing and reduced quality of life. However, the exact mechanism of keloid scarring remains unknown. Any disorder during wound healing, including an enhanced inflammatory response, overexpression of growth-related factors, and excessive activation of fibroblasts, is conducive to abnormal collagen deposition in keloids . Transforming growth factor-β (TGF-β), connective tissue growth factor (CTGF), vascular endothelial growth factor (VEGF) and the renin–angiotensin system were reported to be potential targets in keloid management considering their participation in wound healing and keloid formation [3, 4]. In addition, miRNA modulation may be a novel therapeutic solution . However, neither first-line therapies nor developing treatments could guarantee satisfying curative effects, which calls for more research on effective targets. Currently, the contribution of epithelial-mesenchymal transition (EMT) to keloid overgrowth is appealing as a potential treatment target. High expression of mesenchymal markers, such as vimentin and fibronectin, and decreased expression of the epithelial marker E‐cadherin confirmed EMT phenomenon in keloids . EMT refers to the biological process associated with the loss of polarity of epithelial cells and their transformation into mesenchymal cells with migratory and invasive characteristics . It has been reported that inflammatory stimuli and a hypoxic microenvironment may induce the transition from keratinocytes to fibroblasts, facilitating the invasive growth of keloids .
5
0biomedical
2Review
392,605
In conclusion, 5DCNS+ is an efficient and valuable method to readily provide detailed additional information on the integrity of the fetal CNS. Its clinical applicability has been clearly demonstrated; this workflow-based volumetric approach supports the evaluation of the brain in a standardized manner (1), and it might aid early and systematic assessments of fetal cortical development (2) and potentially allows for the detection of subtle anatomic changes of the CNS (3). Our data illustrate the potential of this technique in helping extract essential information from CNS anatomy and providing a link to postnatal imaging and (re) assessment of the spatial arrangement and severity of fetal anomalies.
4
0biomedical
0Study
196,357
Fresh tissue (an aorta) was placed in the device and subjected to the following steps: fixation, permeabilization, blocking, staining and washing. The valve was kept actuated at ~34 kPa during the experiment. There was neither leakage nor diffusion of dyes (verified with Dextran-R and Hoechst, respectively) outside the assay microchannels after 10 min of perfusion (Fig. 8a-1), even though the tissue was fixed and permeabilized on-chip. To confirm that multiple staining steps can indeed be performed in the same location, we washed all the microchannels with PBS, and the valve was deactivated for 2 min (Fig. 8a-2). Next, the valve was actuated, and Sytox Green was flowed through all the channels (Fig. 8a-3). Notably, the fluorescence signals from all the channels colocalized to the fluorescence signal measured in the previous step, confirming that the tissue remains in the same position and thus allowing for multiple staining steps in the same channel (Fig. 8b). Finally, the tissue section can be recovered for downstream high-resolution imaging or molecular analysis by easily peeling off the top and bottom PDMS layers (Fig. 8a-4).Fig. 8Parallel fluorescence immunohistochemical (IHC) staining inside our microfluidic platform.A fresh aortic tissue en face was fixed and permeabilized on the chip. a (1) Dextran-R and Hoechst were perfused through the 8 microchannels (step 1). (2) After washing away Dextran-R and Hoechst, the valve was depressurized, allowing for the detection of Hoechst-stained cells. (3) After valve repressurization, Dextran-R and Sytox Green overlapped with the Hoechst signal. (4) Tissue sections can be recovered from the microfluidic device for further analysis. Scale bar: 500 µm. b The nuclei of elongated smooth muscle stained with Hoechst (blue) are observably different from the rounded endothelial nuclei stained with Sytox (green). Right scale bar: 100 µm, left scale bar: 10 µm. c IHC for Von Willebrand factor on a fixed aorta en face. Cell nuclei were stained with Sytox Green; scale bar: 500 µm. d Magnification of the blue square in panel (b), highlighting some of the combinations tested. e Magnification of the indirect IHC staining of cell nuclei (Sytox Green) and Von Willebrand Factor IHC (Alexa Fluor 594, orange). Note that some cells are out of focus because of the surface irregularities of the tissue. Right scale bar: 100 µm, left scale bar: 10 µm
4
0biomedical
0Study
334,399
In our “escalation of non-classicality”, we “scratch the current borderline” between non-classical observables allowing a faithful orthogonal (and thus quantum mechanical) representation with a very “meager” set of two-valued states: this is “as bad as it might get” before the complete absence of all two-valued states interpretable as classical truth assignments (subject to admissibility rules) Indeed, these states are so scarce that they do not acquire the vale “1” in at least one (but usually many) of its atomic propositions: every classical representation requires these observables not to occur at all times; regardless of the preparation state. These sets of states are called unital .
1
2other
1Other
313,626
The iACTwithPain intervention will be developed by the psychologist members of this research team taking into consideration the psychological flexibility model applied to CP (e.g., Vowles et al., 2009; Dahl and Lundgren, 2016), with the addition of compassion-based elements (Gilbert, 2009; Neff and Germer, 2018) specifically adapted to CP. The research team’s experience on CP’s psychosocial impact and related psychological processes (Carvalho et al., 2018a,b, 2019, 2020), and in developing and delivering ACT and compassion-based interventions to chronically ill populations such as CP, cancer (Trindade et al., 2020), inflammatory bowel disease (ClinicalTrial.gov NCT03840707, undergoing), as well as psychiatric populations (Pinto-Gouveia et al., 2017; ClinicalTrial.gov NCT04101032, undergoing) will be integrated to assure the development of an adequate and rigorous intervention.
4
0biomedical
0Study
9,527
This paper presents a complete localization framework of the ground-based stereo guidance system. This system could be used to pilot the UAV for landing autonomously and safely in the GNSS-denied scenario. Compared with the onboard solutions and other state-of-the-art ground-based approaches, this ground-based system profited enormously from the computation capacity and flexible configuration with the baseline and sensors. The separate deployed configurations did not improve the detection distance, which was discussed in our previous works ; however, they enhance the maximum range for depth estimation. Although the system has some pitfalls, such as the low accuracy at a long distance in the depth axis and not supporting the attitude measurement, this low-cost system could be arranged quickly for any proposed environment. Additional future work will focus on estimate errors over time and investigate methods to improve inevitable error propagation through the inclusion of additional sensors, such as GNSS and on-board sensors.
1
2other
0Study
301,148
The mean transcripts per millions (TPMs) for each BnaFLS candidate gene per organ is listed. Single-end RNA-Seq data generated in this study derived from leaves (35 DAF) and seeds (23 and 35 DAF) of Express 617 are marked with an asterisk. The remaining organs are based on publicly available paired-end B. napus RNA-Seq data sets. The number of analyzed data sets per organ is stated via (n = X). The color gradient from white via light blue to dark blue indicates the expression strength with dark blue symbolizing high expression. DAF, days after flowering; DAP, days after pollination; SAM, shoot apical meristem.
4
0biomedical
0Study
221,480
To maintain a balanced design for the experiment, an observation period between 6 and 31 days of incubation whereby most of the voltage slopes were 0 +/- 0.5 mV was used. Starting from the first day, the voltage values were grouped in time periods of 3, 4, 5, and 6 consecutive measurements which corresponded to 1.5, 2, 2.5, and 3 days, respectively. For each time period, the slope between points was calculated for each replicate and for each treatment, which was used to determine the point of stability. Output of the slopes by point grouping are in S1 File.
4
0biomedical
0Study
132,580
In children with severe haemophilia, average AJBR were low across haemophilia types. One in three children did however experience a joint bleed during the 12-month data collection period. The majority of those included would have typically been provided prophylaxis from an early age and continue to adhere to a prophylaxis regime, but 30% of children still experienced haemarthrosis during the 12 month data collection period. HJHS itemised by joint were very low in children (table 3) suggesting either minimal joint disease or that the HJHS might not be sensitive to early joint changes following haemarthrosis. Reliability of the HJHS has been explored in children and young adults and is reported to be sensitive to early joint changes,24 25 although individual joint HJHS of less than three at the knee and ankle are less able to identify pathological joint change when compared with magnetic resonance and ultrasound imaging.18 Similarly in children, correlations between the HJHS and the Haemophilia Early Arthropathy Detection with UltraSound (HEAD-US) have shown good correlations in the identification of joint pathology at the elbows and knees, however, at the ankles significant difference are reported between HJHS and HEAD-US scores with under-reporting of ankle joint pathology in both instances.26 Therefore, a combined approach to joint health assessment may identify pathology especially at the ankle joint prior to the progression to haemarthropathy. Canine, mouse and human in vitro models have demonstrated chondrocyte apoptosis and reduced proteoglycan synthesis affecting cartilage matrix turnover within 48–96 hours of an induced joint bleed, suggesting a single joint bleed may have detrimental effects on joint cartilage.27–29 Formally reported bleed rates in the NHD are relatively low, however, microbleeding (subclinical bleeding not clinically detectable, or experienced by the patient) is an emerging theme in haemophilia. Episodes of subclinical bleeding may contribute to the deterioration of joint health despite no clinically detectable signs of a joint bleed, therefore, point-of-care ultrasound tools such as the HEAD-US may provide early evidence of joint disease.3
5
0biomedical
0Study
233,814
The candidate features of the multivariate logistic regression analysis included age, gender, CT-reported LN status, radiomics signature, and deep learning signature. The Akaike information criterion (26) was used as the stop criterion to determine the best features using a stepwise backward method. Additionally, the prediction model developed using logistic regression for the training cohort was also suitable for the internal as well as the external validation cohorts. Then, we developed a nomogram based on the developed prediction model.
4
0biomedical
0Study
300,692
Model 1, no adjustments for other variables; Model 2, adjustments for sex and age; and Model 3, adjustments for sex, age, and other environmental factors, such as obesity, sleep duration, smoking, alcohol consumption, education level, household income, occupation, physical activity, and comorbidities.
3
0biomedical
0Study
10,868
Most positive results in both US and FOI in patients with non-inflammatory diseases were found in the wrists. Interestingly, these results are compatible with observations in a healthy control group whose wrists were examined by MRI, where a high prevalence of increased volumes of joint fluid, signal changes similar to bone marrow edema, and bony depressions resembling erosions were found . Both MRI and FOI findings might reflect mechanical stress through the high use of this part of the hand during daily activity.
3
0biomedical
0Study
239,842
** Data for all violent deaths were collected in 36 states (Alabama, Alaska, Arizona, California, Colorado, Connecticut, Delaware, Georgia, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Minnesota, Missouri, Nebraska, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, Utah, Vermont, Virginia, Washington, West Virginia, and Wisconsin), and the District of Columbia. Three states (California, Illinois, and Pennsylvania) collected data from a subset of counties in their state. Data for violent deaths that occurred in Illinois include 28 counties that represent 86% of the state’s population (Adams, Boone, Champaign, Cook, DuPage, Effingham, Fulton, Kane, Kankakee, Kendall, Lake, Lasalle, Livingston, Logan, McDonough, McHenry, McLean, Macoupin, Madison, Peoria, Perry, Rock Island, St. Clair, Sangamon, Tazewell, Vermillion, Will, and Winnebago). Data for violent deaths that occurred in Pennsylvania include 39 counties that represent 82.2% of the state’s population (Adams, Allegheny, Armstrong, Beaver, Berks, Blair, Bradford, Bucks, Cambria, Carbon, Centre, Chester, Clarion, Clearfield, Clinton, Columbia, Crawford, Dauphin, Delaware, Fayette, Forest, Greene, Indiana, Jefferson, Lackawanna, Lancaster, Lehigh, Luzerne, Monroe, Montgomery, Montour, Northampton, Philadelphia, Schuylkill, Union, Wayne, Westmoreland, Wyoming, and York). Data for violent deaths that occurred in California include 21 counties that represent 54% of the state’s population (Amador, Butte, Fresno, Humboldt, Imperial, Kern, Kings, Lake, Los Angeles, Marin, Mono, Placer, Sacramento, San Benito, San Diego, San Francisco, San Mateo, Shasta, Siskiyou, Ventura, and Yolo). Denominators for the rates for these three states (California, Illinois, and Pennsylvania) represent only the populations of the counties from which the data were collected.
1
2other
0Study
263,146
Despite the theoretical fragility of RMD patients related to immunosuppressive therapies, our results showed that treatment with any kind of DMARD is not associated with an increased risk of SARS-CoV-2 infection. However, our serological analysis confirms the increased dose-dependent infectious risk associated with the chronic use of GCs (20), which is already known from several studies conducted on other types of infection and also emerged in a recent epidemiological analysis conducted by our group (21). Beyond the anti-rheumatic treatment, in our cohort the risk factors for SARS-CoV-2 infection were confirmed as those already known in the general population, namely the presence of comorbidities such as hypertension and obesity (22). The comparative analysis and the search for factors associated with SARS-CoV-2 seropositivity was conducted only on anti-RBD IgG which has been shown to provide the best specificity for SARS-CoV-2 and appear to decrease more slowly over time than levels of other classes of antibody (23, 24). IgM and IgA antibodies have been included to define the seropositivity rate but no comparative analysis has been performed on these antibody classes. However, we found that patients who tested positive to IgM or IgA and negative to IgG had higher rate of asymptomatic infections than IgG positive patients. Since both IgM and IgA have been shown to appear in the first 3 to 4 days of SARS-CoV-2 infection (25), our hypothesis is that we identified patients in the very early phase of COVID-19, before they developed symptoms or even seroconverted to IgG.
4
0biomedical
0Study
267,068
The MIC of GaN in RPMI-HS-CAA was identical or only twice that of GaM for all the susceptible species, implying that the inhibitory activity of these compounds is nearly equivalent in vitro. In ASM, GaM was effective on both P. aeruginosa and M. abscessus, whereas only P. aeruginosa was susceptible to GaN. While the inhibitory activity of both GaM and GaN were previously documented for both P. aeruginosa and M. abscessus,32−34 unexpected results were obtained with bacteria belonging to the Bcc. Indeed, previous work argued against an antibacterial effect of GaN on Bcc, since high concentrations of GaN (from 4 to 18 mg/L, corresponding to 30–260 μM) were required to inhibit the growth of Bcc in a chemically defined (minimal salt) medium.35 However, in the present work, lower concentrations of GaM and GaN (1–4 μM) prevented Bcc growth in RPMI-HS-CAA (Table 1). This apparent discrepancy highlights the need to establish appropriate methods to assess the antibacterial activity of Ga(III) compounds, depending on the test species. The anti-Bcc activity of Ga(III) in the presence of HS is of particular relevance considering that septicemia often occurs when Bcc pulmonary infections evolve into a potentially fatal condition known as “cepacia syndrome”.36 This raises the possibility that intravenous administration of GaN, which is already approved by the FDA, could help in treatment of systemic Bcc infection. Similar to Bcc, the previously established MIC of GaN for S. maltophilia (MIC = 512 μg/mL corresponding to 2000 μM)37 was higher than that determined in this study using RPMI-HS-CAA (MIC = 0.25–8 μM), and also for this species it should be taken into account that the previous MIC assays were performed in CAMHB,37 where the elevated iron content would mask Ga(III) activity (Table 1; Table S2). Interestingly, also A. xylosoxidans CF-3 and CF-4 were susceptible to GaN and GaM in RPMI-HS-CAA, providing the first evidence of Ga(III) activity against this CF pathogen. H. influenzae, S. aureus, and S. pneumoniae were completely resistant to both GaN and GaM in all media used in the present study. In addition to medium composition and iron levels, species- and strain-specific factors could affect Ga(III) activity against CF pathogens. For instance, in P. aeruginosa the pyoverdine siderophore and exoproteases increase Ga(III) tolerance in media supplemented with iron chelating proteins,38 whereas the pyochelin siderophore decreases Ga(III) tolerance by contributing to its internalization.39 It can therefore be speculated that siderophores, exoproteases, and possibly other species- and strain-specific factors could explain the variable response to Ga(III) compounds in other CF pathogens.
4
0biomedical
0Study
67,278
SEPP1 rs3877899 effect on SOD1 activity in the individuals supplemented with selenium. A significant SNP effect was observed in the interaction with time. Data adjusted for age, sex, BMI, and baseline selenium. p values for the MANCOVA indicated in the figure. According to the particular time point analysis, a significant difference in GPx3 activity as compared to baseline was shown for AlaAla homozygotes during washout (p = 0.04)
4
0biomedical
0Study
227,298
The samples placed in cold oxygenated Krebs solution were transferred to the laboratory (Inserm research unit U1235, TENS, University of Nantes, Nantes, France). Segments of distal and proximal colon were placed in the longitudinal direction in an organ chamber (Radnoti, California, USA) with 15 mL of Krebs solution at 37°C, continuously bubbled with 95% O2 and 5% CO2. The contractile response of colonic segments was continuously recorded using isometric force transducers (No. TRI202PAD, Panlab, Cornellã, Spain) coupled to a computer equipped with the PowerLab 8/30 System and Labchart data analysis software (AD Instruments, Spechbach, Germany). Segments were stretched with a pre-load of 1 gram, which was maintained during an equilibration period of 60 min.
4
0biomedical
0Study
258,196
The modified version of the Copenhagen Psychosocial Questionnaire with modifications was used to assess the stress and sleep pattern of the respondents before COVID-19 and during COVID-19 among respondents . Concerning stress and irritability, respondents were asked to provide the frequency of experiencing emotional irritability, exhaustion, tension, and physical exhaustion. The same questions were asked pre-COVID-19 and during COVID-19. Regarding sleep, respondents were asked if they experienced sleep disturbances such as restlessly and sleeping badly; having difficulty to go to sleep; waking up several times and found it difficult to get back to sleep; waking up too early and not being able to get back to sleep; or none of the options. The questionnaire also comprised the following questions: “rating sleep quality”, “number of sleeping hours per night”, and “describing energy level during the day”. The repose options for describing energy level were energized; neutral; lazy. The repose options for rating sleep quality were very good; good; poor.
2
0biomedical
0Study
266,961
This study focused on free‐roaming domestic dogs, which is the primary means of dog management in the study area, indeed in much of sub‐Saharan Africa. The primary reasons cited for allowing dogs to roam freely included to reduce the dogs’ aggressive behavior and because the dogs dislike being chained (Mutwiri, unpublished data). The field data obtained in this study indicate that the dogs moved considerably during the observation period, with some dogs traveling up to 24km daily, though heterogeneity between individual dogs was noted. The median core HR of 0.4ha reported in this study was similar to that described in other studies that also used the biased random bridge method (Dürr et al., 2017; Hudson et al., 2017; Molloy et al., 2017), while the median extended HR of 9.3 ha was slightly higher. However, as also described elsewhere (Dürr et al., 2017; Dürr & Ward, 2014; Hudson et al., 2017; Molloy et al., 2017), in our study we observed a wide range in both the core and extended HR of dogs, suggesting that heterogeneity in dog movement patterns is also present in western Kenya. Indeed, differences in the size and shape of the HRs were observed both between, and within, study sites. One putative reason for these differences may be the topography of the area, with major roads in the urban centers curtailing some of the dog's movements, compared to those dogs that lived further away from the urban centers. Another explanation could be related to management practices, such as frequency of feeding and dog purpose. Unfortunately, we were unable to explore the effect of these explanatory variables in our study due to lack of variation. Lastly, we think that “human geography” may also play a role, whereby the dog's behavior is highly connected with the way people move and behave in different places, consequently influencing the shape and size of their HRs.
4
0biomedical
0Study
135,360
Calculating accurate values for Rt remains a challenging task. Two main methodologies have been used to calculate Rt, including: (1) the case reproductive number and (2) the instantaneous reproductive number . The first method calculates transmission within a specific cohort of people, while the second method calculates transmission at a specific point in time. Gostic et al. reported that the instantaneous reproductive number is a more accurate method for estimating Rt. Therefore, we used this method to calculate Rt in this study.
4
0biomedical
0Study
323,491
A total of 84,140 individuals were enumerated of whom 45,058 (54%) were eligible individuals invited to participate in the survey. Of them, 43,779 (97%) were enrolled. Of them 43,121 (99.9%) completed the symptom screening interview and 43,069 (99.8%) underwent chest x-ray screening. The overall participation rate was 95.7% [Fig 1].
3
0biomedical
0Study
97,707
First, a CTAB solution was prepared. Mixing of a CTAB solution is difficult at room temperature, therefore, the solution was heated to 45 °C under constant magnetic stirring until a clear solution was obtained. This solution was cooled down to room temperature before further processing. To the CTAB solution, various volumes of 0.1 M HAuCl4 stock solution were added to obtain different concentrations of HAuCl4 in different solutions. The solutions were mixed a few times by inversion. To these solutions, various amounts of 1 M HCl were added. This was followed by addition of various volumes of 0.1 M AgNO3. Subsequently, different volumes of 0.1 M AA solution were added. In each solution, the HAuCl4-to-AgNO3 molar ratio of 5 and the AA-to-HAuCl4 molar ratio of 1.4 was maintained. For example, the lowest HAuCl4 concentration of 0.5 mM in growth solution was obtained by adding 50 μl of 0.1 M HAuCl4 solution in 10 ml of CTAB solution. To this solution, 10 μl of 0.1 M AgNO3 and 70 μl of 0.1 M AA were added making the final concentration of AgNO3 and AA to be 0.1 and 0.7 mM, respectively.
4
0biomedical
0Study
120,025
It has been well-established that hyperglycemia and Ang II increase cellular oxidative stress (reactive oxygen species, ROS) and play key roles in the pathogenesis of DN3,36,37. Our data showed that Ang II and H2O2 directly and dose-dependently promote Hhip expression and the TGFβ1-Smad2/3 cascades and that catalase attenuates the stimulatory effect of high glucose on Hhip protein expression. Hhip is known to play a critical role in cell apoptosis, angiogenesis and tumorigenesis11,19,38. While several mechanisms involving cross-talk among oxidative stress, hedgehog signaling, and TGFβ1 signaling have been associated with certain pathologic conditions such as diabetic retinopathy39, brain ischemia40, renal fibrosis34,35, pulmonary fibrosis41 and cancer-related epithelial to mesenchymal transition and metastasis42. Together, these observations led us to hypothesize that Hhip could interact with ROS and/or TGFβ1-signaling to result in EndoMT associated with DN-fibrosis/apoptosis.
4
0biomedical
0Study
147,096
Double emulsion/solvent evaporation method: Briefly, cholesterol and egg lecithin were dissolved in 5 mL chloroform and 20 mg of the drug was prepared in 1ml water at 60°C. Then aqueous phase was transferred in to the organic medium under sonication (Digitec, Hamburg, Germany) forming the primary emulsion. This emulsion was transferred into 19 mL of phosphate buffer in order to form the double emulsion water-in-oil-in-water (W1/O/W2). The organic solvent was totally evaporated (170 mm Hg) by rotary evaporator.10 Then the sample was taken to ultrasonic processor as described earlier. All steps were done at 60°C. Finally, it was filtered and kept at +4°C (Figure 1C).
4
0biomedical
0Study
318,414
Several neuromediators in crustacean reproduction, including serotonin (27) and RPCH (103), and in addition the juvenoid substance MF (29) are reported to indirectly exert their stimulatory effects by inducing the release of putative VSH from the thoracic ganglion. In M. rosenbergii, serotonin-primed thoracic ganglion medium stimulated oocyte growth and ovarian maturation (46). Furthermore, in vitro and in vivo studies have demonstrated that the release of putative gonad-stimulating factors from the brain and thoracic ganglia could be hampered by the presence of copper and cadmium (157), while stimulated by the application of calcium ionophore (A23187) (104). However, whether the proposed VSH functions directly or indirectly is yet to be conclusively confirmed. Although there are many studies where VIH has been extracted and chemically characterized based on the extensive collection of sinus glands, such as that has been accomplished by Tsutsui et al. in L. vannamei (158), the equivalent type of experimentation remains difficult with respect to isolating and characterizing crustacean VSH. This is because the concept of a putative VSH is tied to the existence of different stage-specific factors that stimulate vitellogenesis; or alternatively, a situation where an actual substance does not actually exist, but rather is based on a negative feedback mechanism to which the XO/SG complex is central (159). Thus, identifying and characterizing VSH in crustaceans remains a challenging research topic, the outcome of which could be of immense use in controlling the maturation of shrimp and other commercially-useful crustacean species in captivity, thus having important implications for the further development of the aquaculture industry.
4
0biomedical
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274,197
The patient also had notably elevated inflammatory markers on admission with C-reactive protein (CRP) of 183.5 mg/dL and ferritin of 17,899 μg/L. Other abnormal labs included elevated aspartate transaminase (AST) of 681 U/L, alanine aminotransferase (ALT) of >700 U/L, D-dimer of 2,573 ng/mL, and procalcitonin (PCT) of 5.32 ng/mL on day one. Blood cultures, HIV, and hepatitis screening were negative.
4
0biomedical
3Clinical case