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As a next step, I have described the interrelation of lived and physical body as a circularity of experiential process and (neuro-)physiological structure underlying development and learning. Here, the circular causality of higher- and lower-level processes is considered as unfolding in the diachronic dimension, based on the plasticity of the brain. Subjective and intersubjective experience constitutes a process of sense-making that includes cerebral processes so as to form modified neuronal structures, which in turn enable altered future interactions. Only conscious experience contains the intentional and meaningful relations to the environment whose correlates are functionally and morphologically inscribed in the brain throughout the course of socialization. This results in a spiral-shaped development: lived body and organic body mutually influence and modify each other. This is not only an individual development, however; the social and cultural environment with its shared meanings, habits, and artifacts constitutes the crucial ontogenetic niche for the individual formation of the brain. Analogously, human culture has also provided the decisive scaffolding for the phylogenetic evolution of the organic (in particular, neural) structures of the human being.
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36,077
Our results thus suggest strongly the feasibility of developing EMD-based algorithms to systematically detect all the HFOs and population spikes. In this regard, we note an existing method of detection of HFOs, which employs short-time energy or line length of the acquired data for HFOs in some small frequency ranges . Our method is capable of detecting HFOs and can be used to distinguish various oscillation profiles. Based on the detected HFOs and population spikes, extensive statistical analyses for the five critical phases during epileptogenesis, namely, pre-stimulation state, pre-seizure state, status epilepticus phase, epilepsy latent period, spontaneous/recurrent seizure period, can be carried out to gain unprecedented insights into epileptogenesis.
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Expression pattern in nodules of bacterial and NCR genes. (A) Schematic drawing of a Medicago nodule organized in functional zones. The meristem is bacterium free and contains dividing cells, allowing the organ to grow. In the early infection zone, bacteria proliferate in infection threads (green lines) and are released by endocytosis inside cells derived from the meristem. In the late infection zone and the so-called interzone, the bacteria differentiate into bacteroids. The fixation zone contains the fully differentiated, nitrogen-fixing bacteroids. The pictures show bacteria inside the nodule cells and are presented at the same scale (bar = 1 μm), allowing one to appreciate the transformation of the bacteria. (B) Against the backdrop of a changing landscape of NCR peptides (rainbow colors schematically represent peptides appearing and disappearing at different stages of symbiotic cell differentiation), the bacterial functions described in this study are critical at distinct stages of the bacteroid differentiation process. It should be noted that the functions that are essential in early stages, such as LpsB and BacA, can also be important in later stages of the bacteroid differentiation. However, the phenotypic analysis of the corresponding mutants cannot reveal these putative late roles. (C, D) The relative expression profiles (percentages of the total) of the studied bacterial genes lpsB, lpxXL, rpoH1, yejF, yejE, yejB, yejA, and bacA (C) and of NCR280, NCR247, NCR183, and NCR169 (D) in the meristem, early infection zone, late infection zone, interzone, and fixation zone of M. truncatula nodules are displayed. The expression patterns of the S. meliloti nifH gene, encoding a nitrogenase subunit, and of the M. truncatula leghemoglobin genes (MtLb) are included in panels C and D, respectively, as a reference indicating the completion of bacteroid formation and the onset of nitrogen fixation. Data were extracted from Guefrachi et al. (BMC Genomics 15:712, https://doi.org/10.1186/1471-2164-15-712) and were obtained by transcriptome sequencing (RNA-seq) analysis of laser-microdissected nodule tissues (Roux et al., Plant J 77:817–837, https://doi.org/10.1111/tpj.12442). Download FIG S1, PDF file, 0.2 MB.
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The top 10 ontology groups for saddlebrown (a), orange (b), darkgrey (c), and mediumpurple3 (d) are displayed, along with an FDR-adjusted q value that is based on all ontology group one-sided Fisher’s exact test p values that were tested (see Supplementary Data 6 for full ontology analysis for these four modules, including all p values and FDR-adjusted q values).
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68,795
In terms of low iron status during pregnancy, most of the evidence has examined the relationship of Hb concentration or anemia and increased risk of maternal and fetal adverse outcomes without consideration of concomitant inflammation . Low Hb concentrations associate with increased risk of low birthweight (LBW), small for gestational age (SGA), and preterm births and maternal mortality , but closer examination of the synthesized evidence reveals that this association holds for LBW and preterm birth with low Hb concentrations in the first trimester, but not the second or third trimesters . Although variable cutpoints for anemia and low Hb concentrations were used across the studies, a meta-analysis in 2012 found that the increased risk of SGA associated only with moderate to severe anemia or Hb concentrations <9 g/dL for SGA and preterm births . However, many factors can cause anemia, but only a few studies have examined the relationship of IDA, low SF and high sTfR with adverse pregnancy outcomes and reported less consistent findings than those examining the relationship of low Hb concentrations. Only one of two studies in the first trimester and one of three studies in the second trimester found an association of low SF with SGA or preterm birth and LBW, respectively . Dewey also reported that the higher iron status (lower sTfR or higher SF within normal ranges) early in pregnancy generally associated with better birth outcomes in three cohorts in Ghana, Malawi and Bangladesh, whereas later in pregnancy it did not. Despite the limited evidence and lack of control for confounding by inflammation, the current evidence does suggest s increased risk of maternal and fetal adverse outcomes with anemia and low iron status as assessed by SF and sTfR, particularly early in pregnancy.
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0biomedical
2Review
68,105
Several sources of bias limit the strength of the evidence on risk factors underlying micro-epidemiological patterns in malaria risk across different settings. As there has been no consistent use of the term ‘micro-epidemiology’ or other terms to describe studies that analyse variation in malaria risk within or between sub-village clusters or villages, defining a search strategy was not straightforward, and some potentially relevant studies may have been missed. Future reviews on this topic could consider a broader use of keywords. The choice of malaria diagnostic (microscopy, RDT or PCR) may impact the observed variation in malaria risk, as risk factors for asymptomatic carriage may differ from those for clinical cases particularly in high-endemicity settings. Passive case detection, compared to active case detection or population screening, may introduce confounding by health seeking behavior and miss groups of individuals at higher risk but with less access to care.
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2Review
389,601
On one hand, the high conductivity at low pH can be explained by the increased degree of ionization of the zein amino group . Moreover, the use of external additives such as acids and bases for pH adjustments could lead to the accumulation of an excess number of free ions in the solution . Consequently, these ions may act as major charge carriers, reducing the electrophoretic mobility of the polymer molecules and deteriorating the quality of the deposited coating . Therefore, in order to achieve stable solutions with high zeta potential and low conductivity values, no further pH adjustments of the EPD solutions were performed in this work.
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In this study, the validation approach included in Commission Regulation (EU) No 519/2014 was followed . This new Regulation is specifically intended for validation of semi-quantitative screening bioanalytical methods such as ELISA, lateral flow devices and immunosensors for the analysis of mycotoxins. The result of the measurement by these methods should be a numerical value. For these methods, the concept of STC is used. STC is a concentration of interest for detection of the mycotoxin. The Regulation requires to determine 2 parameters: a cut-off and a false suspected rate. The cut-off is the concentration measured in a sample, above which the sample is classified as “suspect”, meaning it may contain mycotoxin at a level higher than STC. The cut-off is calculated from the results obtained for 20 samples spiked at STC by using equation given in the Regulation : Cut-off = RSTC − t-value0.05 × SDSTC where RSTC is the mean response of the positive control samples at STC; t-value0.05 is the one tailed t-value for a rate of false negative results of 5%; and SDSTC is the standard deviation at STC.
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The systematic approach used herein, with combinations of several high-quality data sets, formal testing of hypotheses, and informed experimental design, demonstrate that stimulated uncoupled respiration in BMP4-treated white fat-derived beige adipocytes is independent of UCP1.
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299,591
Compression moulding machine (NG-BU-P11) operated at a temperature of 180 °C and pressure of 0.2 kPa for 10 min on each sample was employed. 180 °C was adopted because temperature trials above 180 °C produced burnt samples and below produced less compacted samples. Dump bell shape mould 150 mm length and 3 mm thickness was used in the preparation of samples for the tensile test. Samples for flexural and impact were prepared using a mould of dimension 150 × 50 × 3 (mm3) and 63.5 × 12.7 × 2.5 (mm3) according to Adediran et al.34. Samples for compressive strength were produced in moulds 40 mm diameter and 80 mm length. Wax was robbed in the mould cavity while the top and base of the mould were covered with Teflon sheets before compression. Samples were left to cure for 24 h sequel to careful removal from moulds and cleaning.
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In our study the severity of DPN was inversely correlated with the cobalamine level and directly correlated with higher levels of both methylmalonic acid, and homocysteine. Similarly, Wile and Toth found that the clinically worsened DPN was associated with lower cobalamine level and higher levels of both methylmalonic acid, and homocysteine40. It has been shown that elevated levels of total homocysteine significantly correlated with DPN, independent of other risk factors43,44. The serum MMA positively correlated with the severity of neuropathic pain and this can be used as a useful marker in assessment of peripheral neuropathy45.
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The use of a homofermentative LAB inoculant is preferable in order to maximise lactic acid production for pathogen inhibition and to minimise the production of undesirable metabolites from heterofermentative LAB. Pediococcus pentosaceus, a homofermentative LAB was present in the starter culture used in the study by Olstorpe et al. but was only detected when the diet was inoculated daily, suggesting that conditions were not suitable for the strain to grow and produce lactic acid and that it was outcompeted by resident microbiota. This indicates that strains already adapted to LF conditions should be isolated and used as starter cultures .
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312,194
The Lyapunov exponent reflects the average rate of convergence or divergence of two paths that are, initially, points that are very close in the phase space. Positive values indicate the existence of chaotic dynamics. Here, the algorithm described by BenSaïda and Litimi was used. Negative significant Lyapunov exponents were obtained in all cases (Supplementary Materials C, Table SC2). Thus, the assumption of chaotic behavior was rejected in all cases.
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TRILOGY was a randomized, parallel-group, double-blind, active-controlled study aimed to compare the efficacy of the single inhaler triple therapy vs. inhaled corticosteroid plus long-acting β2-agonist therapy [beclometasone dipropionate, formoterol fumarate, and glycopyrronium bromide (BDP/FF/GB) with beclometasone dipropionate and formoterol fumarate (BDP/FF)] over 52 weeks of treatment. Patients were 40 years or older, with a diagnosis of COPD, a FEV1 < 50%, a FEV1/FVC < 0·7, and at least one moderate or severe COPD exacerbation in the previous 12 months. Previous treatment included an inhaled corticosteroid plus a long-acting β2 agonist, or an inhaled corticosteroid plus a long-acting muscarinic antagonist, or a long-acting β2 agonist plus a long-acting muscarinic antagonist, or long-acting muscarinic antagonist monotherapy for at least 2 months before screening. Patients receiving triple therapy of an inhaled corticosteroid plus a long-acting β2 agonist plus a long-acting muscarinic antagonist were not eligible. Additionally, all patients needed to be symptomatic for inclusion, classified as a COPD Assessment Test (CAT) total score of 10 or more and a Baseline Dyspnea Index (BDI) focal score of 10 or less at screening, with the BDI criterion also confirmed at the randomization visit. 1,367 patients with symptomatic COPD have been enrolled. Three primary endpoints were assessed: change from baseline in pre-dose (morning) FEV1, change from baseline in 2-h post-dose FEV1, and Transition Dyspnea Index (TDI) focal score assessed at week 26. Results showed that BDP/FF/GB improved the morning pre-dose trough FEV1, and 2-h post dose FEV1 vs. ICS/LABA, and reduced exacerbations by 23% when compared with BDP/FF (77).
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1Other
338,885
Let T be a minimum spanning tree of G. For every subset \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$S\subseteq V$$\end{document}S⊆V, there exists a minimum spanning tree of G[S] which contains E(T[S]).
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1Other
152,629
The hypothetical ahla gene (GenBank accession no. NZ_JRTT01000008.1), including its signal peptide coding sequence and the putative RBS sequence (GGAGG), was amplified by PCR using PfuDNA polymerase (Thermo, Waltham, MA, USA) and genomic DNA from A. utahensis NRRL 12052 as a template. PCR was performed in Mastercycler Personal equipment (Eppendorf, Hamburg, Germany), and amplification conditions were set according to the high G + C content of the actinomycetes genome . XbaI and EcoRI restriction sites were included in the primers (Table 1) in order to subclone the PCR product in pENV19 vector. PCR products were purified by the commercial kit illustra GFX PCR DNA and Gel Band Purification (GE Healthcare, Chicago, IL, USA). Recombinant plasmid pENV19ahla was used to transform electrocompetent Rhodococcus sp. T104 cells .
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“Nevertheless, a single factor (i.e., attention and awareness of the present) can be used as the basis to assess mindfulness before expanding the concept of mindfulness to pose various dimensionalities, considering that a single-factor structure is easier to be studied and understood than a multi-factor structure.”
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1Other
153,533
This retrospective study was conducted at Sultan Qaboos University hospital, Muscat, Oman. A computerised search of medical records of the patient database was made from the hospital information system and Radiology information system (IntelliSpace PACS Enterprise, Philips Healthcare Informatics Inc., USA). A total of 183 patients who underwent post-RAI (ablation/therapy) whole body scintigraphy were recorded from January 2014 to August 2017.
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53,132
Schematic illustration of the proposed role of DEK in carcinogenesis of OSCC. OSCC progresses through a multistep process from normal mucosa to normal‐appearing mucosa (exposed to carcinogens, tobacco, or alcohol), hyperplasia, dysplasia, CIS, and invasive SCC. When DEK is upregulated and overexpressed by HPV, inflammation, or other insults, field cancerization and cancer development are promoted. Aberrant activation of the cell cycle, DNA replication, and RNA transcriptional elongation is involved in this oncogenic mechanism caused by DEK overexpression in OSCC. Upregulation of cell cycle progression‐, DNA replication‐, and RNA transcriptional elongation‐related genes (red) may contribute to the genomic, epigenetic, and chromosomal instabilities involved in carcinogenesis.
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At baseline, the IPSS and Incontinence Severity Index (ISI) questionnaires were completed by trial participants. Uroflowmetry, PVR measurements, and standard laboratory blood assessment were also undertaken. These questionnaires and measurements were repeated at scheduled follow-up visits at 1, 3, 6, 12, and 24 mo. Prostate-specific antigen (PSA) was assessed at baseline and 6 mo and then annually. Other questionnaires not repeated up to 24 mo were not included in this analysis. Adverse events occurring up to 12 mo after the initial treatment were adjudicated for severity by a clinical events committee. Events were assigned a Clavien-Dindo grade.
4
1clinical
1Other
69,530
This study examined multiple typologies of tobacco-related risk in adult smokers based on non-cigarette tobacco use, menthol cigarette smoking, and alcohol and drug use. Our results found three distinct classes of individuals who differed with respect to race, gender, poly-tobacco use, drug use, menthol cigarette use, and desire to quit smoking. A Menthol/Cigarillo group was identified that was four times more likely to smoke menthol cigarettes compared to the Primary Cigarette Smokers, and significantly more likely to be male and Black compared to this group. Older smokers in the Primary Cigarette Smokers class showed fewer substance use and tobacco-related comorbidities, were also most likely to want to quit smoking in the near future, but seemed to have some mental health vulnerability as indicated by their reports of being currently prescribed psychotropic medication. Lastly, younger smokers were identified in a Poly-Substance Users class. These individuals were highly educated, non-heavy smokers who used a wide array of tobacco products, but were also the least likely to want to quit smoking. While prior research shows that greater educational attainment is associated with interest in quitting and quit attempts, this work has been explored primarily among older adult samples . Poly-substance users in the current analysis were young adult users. This is a group that has been shown to be less likely to be motivated to quit using tobacco or to engage in tobacco cessation compared to older age groups . Poly-Substance Users and Primary Cigarette Smokers were equally likely to report menthol smoking. Ultimately, menthol use did not seem to be distinctive among two of the three classes, rather classes were distinguished by non-cigarette tobacco use and illicit drug use. These findings could be due to the high rates of menthol use in the sample overall. Lastly, sensitivity analyses showed that including menthol, alcohol, and drug use in addition to non-cigarette tobacco use were important indicators in determining typologies across menthol and non-menthol smokers.
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The substrate specificity of Tmm7211 was also analyzed. Tmm7211 can oxidize DMS, TMA, DMA, and methimazole, with TMA showing the highest affinity (Table 1). In general, the apparent KM values of Tmm7211 to different substrates are slightly higher than those of RnTmm, and the kcat values of Tmm7211 are lower (Table 1; Li et al., 2017), indicating that the enzymatic activity of Tmm7211 is lower than that of RnTmm in vitro.
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It has been reported that PGPB have a promoting effect on plant growth and heavy metal accumulation [11, 12, 23, 42]. For example, inoculation with the Pseudomonas aeruginosa strain CPSB1 promoted wheat growth under Cd stress . Inoculation with Sphingomonas SaMR12 promoted cadmium accumulation in S. alfredii . In this study, SaMR12 inoculation led to an increase in plant biomass and Cd accumulation (Figs. 2 and 3), which suggested that SaMR12 could be used to promote growth and Cd accumulation in other non-host plants, such as oilseed rape. Therefore, it is a promising way to establish a plant-microbe interaction remediation system for the promotion of phytoremediation efficiency.
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AMPK modulates metabolism for cellular energy demand by responding to changes in the AMP/ATP ratio [52–54]. AMPK suppresses protein synthesis in rat skeletal muscle through the down-regulation of mTOR signalling . AMPK activation can phosphorylate both TSC2 and Raptor, resulting in the depression of mTORC1 signalling . AMPK appears to provide an overriding switch that links p70s6k regulation to cellular energy metabolism . In the present study, the increased phosphorylation level of AMPK by DEX treatment indicated that the stimulated AMPK pathway by DEX. Leucine supplementation, however, down-regulated the phosphorylation of AMPK. The result suggests that AMPK synergizes mTOR underlying in the regulation of GCs and leucine on muscle protein synthesis. These novel observations of the synergy effect of AMPK and mTOR pathways are consistent with the results of Lang et al. and Du et al. , who reported that leucine stimulates mTOR, at least partially, through the inactivation of AMPK.
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170,535
In addition, the current study also contributes to understanding the patterns of work-related stress symptoms. In particular, we found that forensic healthcare workers who experience their work as more emotionally demanding are also more likely to be confronted with matters that affect them personally. Likewise, workers who have more contact with difficult patients are more likely to end up in harrowing situations at the workplace. The results further showed that workers who are confronted in their work with matters that affect them personally are also more often approached by others for personal matters. Finally, those who have contact with difficult patients may also experience that their work requires more persuasion. In short, this study reveals which work-related stress symptoms tend to occur together. This knowledge could be useful for developing stress management interventions at the workplace.
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Six articles and two abstracts that were published in English and five journal articles that were published in Vietnamese met our criteria and were included in the review. We included a further seven articles that focused specifically on risk factors for breast cancer in order to provide contextual and demographic information including articles on NCDs, global surgery and general cancer control in Vietnam. A search and review of grey literature produced eight documents comprising reports from government, public agencies and non-governmental organisations (see Flowchart 1 and Table 1).Flowchart 1.A flow-chart showing the process of article selection for this review. Table 1.Breast cancer in Vietnam: articles identified within the scoping review (not inclusive of grey literature, e.g. government reports/decrees/NGO reports).AuthorDateTitleFindingsLanguageMeeting inclusion criteria (keywords: ‘Breast Cancer’ & ‘Vietnam’ (English) and ‘Breast Cancer’ (Vietnamese) in the title)Trieu, P. D. et al.2017Risk factors of female breast cancer in Vietnam: a case-control study● Significant association between breast density, menopause status, number of pregnancies, number of babies born, hormone use and levels of physical activity with breast cancer in Vietnamese womenEnglishNguyen, J. et al.2016A matched case-control study of risk factors for breast cancer risk in Vietnam● Body mass index, lower parity, and later first childbirth all associated with breast cancerEnglish ● Four or more births significantly reduced the chance of breast cancer ● No significant difference between breast cancer and age at menarche, age at first parity, total months breastfeeding, oral contraceptive use, and menopause Trieu, P. D. Y. et al.2015Female breast cancer in Vietnam: a comparison across Asian specific regions● Breast cancer is the most common cancer for women in Vietnam. In the 1990s, the most common site-cancer was cervical/uterusEnglish ● Breast cancer is commonly diagnosed at later stages (Stage II = 61.2%) and in women between the ages of 45 and 55 ● Geographical variations. Hanoi has almost double the incidence of Ho Chi Minh City Le Thanh Duc et al2015The role, efficacy, feasibility of neoadjuvant AP regimen in inoperable stage III breast cancer (PhD thesis)● By using AP regimen as neoadjuvant chemotherapy, the survival of the patients with inoperable stage III breast cancer was improvedVietnameseNguyen, T.T.C. et al.2014Cost–utility analysis of Trastuzumab in treatment of metastatic HER2-positive breast cancer in Vietnam● The treatment of metastatic HER2-positive breast cancer with Trastuzumab is considered cost-effective in VietnamEnglishDieu, B.2013Trends of breast cancer in Vietnam● From 2004 to 2008, the prevalence of breast cancer increased rapidly from the age of 30 to 34 and peaked at 55–59 at the rate of 135.0/100,000 peopleVietnameseLan, N. H. et al.2013Survival probability and prognostic factors for breast cancer patients in Vietnam● Survival rates for breast cancer in Vietnam is lower than other countries of similar socio-economic level and that have similar stages of diagnosisEnglish ● Married women with breast cancer have a significantly lower survival rate than unmarried women, and women diagnosed at later stages had worse survival rates Lan, N. H. et al.2013Cost of treatment for breast cancer in central Vietnam● Direct medical costs for the treatment of breast cancer in Vietnam were estimated at $975 per patient (range: $11.7–3955)English ● Patients without health insurance had significantly lower levels of service utilisation ● Costs do not differ for patients diagnosed early or late, but survival times differ significantly Lan, N. H. et al.2013Cost-effectiveness analysis of a screening program for breast cancer in Vietnam● Implementation of a CBE programme for women aged 40–55 would increase life years gainedEnglish ● CBE screening in Vietnam, by WHO criteria, is considered a cost-effective screening intervention Thuan Tran Van et al2013Breast cancer and risk factors related to family history in Vietnamese women● Approximately 10% of breast cancers are inherited ● The rate of breast cancer is higher in those who smoke, drink alcohol, live in rural areas and have higher BMI, but the difference was not significantVietnameseDinh Nguyen, T.2011Breast cancer in surgery in Vietnam● Breast cancer is often diagnosed late in VietnamEnglish ● Most women undergo mastectomy ● Demonstrated effectiveness in curative treatments, with low recurrence and high five-year survival Tu Nguyen Thi Nhu et al2010Factors related to breast cancer knowledge of women in Binh Dinh province in 2010● General knowledge and awareness of symptoms and signs of breast cancer was lowVietnameseDuc Nguyen Ba et al2003Breast cancer● Women who have mothers, sisters and daughters with breast cancer were at higher risk than those who have no family history of breast cancerVietnameseAdditional published articles included within analysis (keywords not in title)Thuan, T. V. et al.2016Cancer control in Vietnam. Where are we?● 49.5% of women diagnosed at Stages III & IVEnglish ● Screening campaigns are costly, and emphasis should be put on increasing levels of awareness of symptoms and treatment options ● High costs for patients and partial insurance coverage leads to high levels of treatment non-completion Tiep Do Quoc2015Knowledge of cancer prevention in Quang Binh province● Knowledge about the risk of breast cancer was limitedVietnamese ● Knowledge about signs or symptoms of breast cancer was also low Thuan Tran Van2013Cancer prevention● Increased risk of breast cancer in women with menstruation after 18 years of age; the first births over 20 years old are statistically significantVietnameseDieu, B. et al.2012Cancer challenges and national cancer control programs to 2020 (Vietnam)● The breast cancer incidence in Vietnam has increased steadily over the last decade from a crude rate of 13.8 per 100,000 women in 2000 to 29.9 per 100,000 women in 2010, with an estimated 12,533 breast cancer cases in the country. The estimated number of breast cancer cases in 2020 is 38.1 per 100,000VietnameseDuc Nguyen Ba et al.2010Results of national cancer program 2008–2010● 9 of 63 provincial hospitals had no functioning pathology departments and 10 cannot admit patients with cancer. Cancer patients are referred to other hospitals with oncology departmentsVietnameseVach Trinh Huu2010Assessment of the need for cancer prevention for the community in Hanoi, Hue and Ho Chi Minh City● Only 16% are aware of the risk factor of non-breastfeeding. Other factors such as not having children or late first childbirth, unhealthy diet, smoking, using hormone therapies over a prolonged long time (including birth control pills) were very lowVietnameseGrey Literature (Government Reports, NGO reports etc)Vietnam Women’s Union2017 (accessed)Awareness raising for breast cancer in women in Vietnam (2013–2015)● After 3 years of implementation, the project, ‘Awareness Raising for Breast Cancer in Women in Vietnam’ has been implemented in 180 communesVietnameseWe Care for Her Campaign2017 (accessed)We Care for Her campaign website● Between 2013 and 2014, the campaign, ‘Breast Cancer at the age of 40’ conducted free breast screening for 4000 women in five provinces: Hanoi, Ho Chi Minh City, Da Nang, Thua Thien Hue and Can ThoVietnamese ● In 2016, free screening was provided to 12,000 women over 40 years of age from October to November in Hanoi, Ho Chi Minh, Da Nang Ministry of Health, Vietnam2015Joint Annual Health Review 2014: Strengthening prevention and control of non-communicable disease● Breast cancers diagnosed at early stages are less expensive to treat cancer diagnosed at later stages ● The main obstacles preventing scale up of screening include a shortage of trained personnel, lack of appropriate diagnostic equipment and the lack of health insurance reimbursement for screening servicesEnglish ● With available capacity, the existing network of cancer prevention and control can only meet approximately 30–40% of the need for oncology services among the population Ministry of Health, Vietnam2013Decisions and guidelines for cancer diagnosis and treatment● Surgical interventions should take place at national and provincial levels; Benign tumours can be surgically removed at district level.VietnameseWHO2011Recommendations for strengthening NCD prevention and control in Vietnam● Vietnam’s NCD services are vertically organised and disease-specific ● Among others, recommendations for improving NCD service provision include strengthening primary care services; developing effective monitoring and surveillance systems; and investing significantly in human resources to tackle NCDsEnglishHarper, C. (WHO)2011Vietnam Noncommunicable Disease Prevention and Control Programme 2002–2010. Implementation review● Details the establishment of the national target programme for NCD prevention and control ● ‘A key challenge is the organization of the health system in Vietnam’ in particular through hospital outpatient departmentsEnglish ● Integrated, intersectoral approach is required to control and manage NCDs ● Establish a population-based model for breast cancer screening ● ‘Establish registries to follow up women who have been screened for breast cancer, to ensure treatment is provided’ Vietnam Health Insurance Agency2009Decree 62/2009/ND-CP. Detailed regulations and implementation guidelines of articles related to the Vietnam Law on Health Insurance● Cancer patients are reimbursed 80% of examination and treatment costs. 20% of costs are paid out-of-pocket. For certain drugs, only 50% of costs are reimbursed. These drugs include Trastuzumab and other specialist drugs for the treatment of cancers and breast cancerVietnameseVietnam Health Insurance Agency2009Intersectoral Circular No. 09/2009 on guidance on implementation of health insurance● Provides an overview of demographic and economic categories related to the provision of health insuranceVietnamese
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After applying Bowtie2 to align clean reads to the reference gene sequence, and then using RSEM to calculate the gene expression level of each sample, we obtained differentially expressed genes (DEGs) between diverse groups via DESeq2 analysis (Q value <= 0.05) (Tables S1–S3). Based on this screening criterion, LP BM-MSCs compared with EP, 9,557 genes were found to be differentially expressed between these two groups (Fig. 2A). Among them, 4,632 DEGs were up-regulated in LP BM-MSCs and 4,925 DEGs were down-regulated. Further, we compared EP BM-MSCs before and after aspirin exposure, including 1,245 DEGs, of which 569 genes were up-regulated and 676 DEGs were down-regulated after aspirin exposure (Fig. 2C). Compared with LP BM-MSCs with or without aspirin treatment, including 458 DEGs, of which 228 DEGs were up-regulated and 230 DEGs were down-regulated (Fig. 2E). Additionally, clustered heatmaps of the top 20 up-regulated and down-regulated DEGs expression were shown in Figs. 2B, 2D, 2F based on z-scores normalization, respectively.
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Signals of SFs were subjected to a sequence of processes from raw images: (1) Get rid of irrelevant background noise using reduced Gaussian filter54. (2) Adjust the variance and magnitude of the signal using generic Gaussian and Laplacian filters. (3) Enhance crossing bright line using a linear Gaussian sensor55. (4) Conduct local binarization via a combination of Gaussian weighted adaptive means and global thresholding55. (5) Segment SFs mask to get a skeleton of binary SFs mask. (6) Identify branch points in a skeleton structure by MATLAB built-in function bwmorph. (7) Identify different branches of fibers as the residual images by subtracting branch points from the skeleton. (8) Trace and reconnect these segmented fiber-branches to enable reconstructed SFs (three basic criteria for connection procedure: the orientation of two compared fibers are less than 18°; the Euclidean maximum distance between two fiber branches endings are less than 8 pixels; and the mean intensity values and the width of fibers are to consistency, which is within 1.2 folds of difference) (Supplementary Fig. 3A).
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All statistical analysis was performed using GraphPad Prism 8.0 software. Differentiation of ADSCs to beige adipocytes and immunostaining (Fig. 1d, e) is representative of independent experiments performed >10 times. The SEM/TEM (Fig. 1b/1c) was independently repeated twice with similar results. All transplant, histological, and immuno-analysis (Fig. 5g–j) were representative of transplants found in several host recipients. All images in supplementary figures (Supplementary Figs. 3B, 4, 5A, 5C, 7A–C, 8A, 8C, 15C) are representative of multiple fields of view and from at least two independent experiments.
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Lastly, we quantified the distance of the six vectors connecting all four buildings in a trial pair. This resulted in a ‘neighborhood distance', which was low when both start and both target buildings were in the same area of Donderstown. These distances were larger for pairs in the 0° modulo 60° condition (T23 = 54.20, p<0.001). We attempted to control for effects of imagining directions in specific parts of Donderstown with this analysis (Figure 3—figure supplement 7, bar III).
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0Study
74,177
There may be a dilution of primary care skills and approaches over time for a GP fully integrated in A&E and their effectiveness will decrease over time as they become subsumed into the secondary care culture. However, if secondary care seek to recruit less experienced GPs to fill these roles, this may be more of a problem, as they may not have sufficient primary care experience as an independent practitioner to maintain their professional skills and identity in a secondary care environment. A GP in A&E requires an accommodation of a culture which is used to handling uncertainty with a culture which seeks to reduce uncertainty in diagnosis and treatment of patients.
4
0biomedical
1Other
219,742
Metyrosine, a tyrosine hydroxylase inhibitor that blocks the rate-limiting step in catecholamine synthesis, is usually used in patients at high risk for catecholamine release during the procedure despite alpha blockade, or those intolerant to alpha-blockers . Special situations when metyrosine could be used include anticipated difficult resection or patients undergoing thermal ablation with anticipated significant catecholamine release from the treated metastasis . In these cases, the protocol used at Mayo in 122 cases with PPGL is described in Table 1. Other studies reported using doses from 600 to 4000 mg per day, with mean doses of 1000–2000 mg for less-complicated situations . However, this is an expensive agent, as 30 capsules cost more than USD 11,000, and it is not available in all countries.
4
0biomedical
1Other
293,880
To analyze whether TMZ differentially transcriptionally regulates important factors involved in resistance, qPCR analyses were performed (Suppl. Fig. S7d). The data revealed a significant repression of Survivin in SurvNES and RAD51sh cells and a missing transcriptional induction of c-IAP2 in RAD51sh and RAD51sh-Surv cells. Since c-IAP2 is a target of NF-κB, which plays an important role in the maintenance of TMZ-induced senescence , this might be a hint for missing senescence induction in these cells. This was further supported by marginal (RAD51sh) or absent (RAD51sh-Surv) senescence-associated secretory phenotype (SASP) activity, as shown by low or no induction of IL6 and IL8, which was in complete contrast to LN-SurvNES cells showing huge IL6/IL8 induction and a significant induction of c-IAP2. The missing senescence induction was further proven by ß-Gal staining (Suppl. Fig. S5d). Interestingly, whereas RAD51 expression was reduced in LN229, LN-SurvNES and RAD51sh cells, TMZ did not alter RAD51 expression in RAD51sh-Surv cells. A significant induction of RAD51 in LN229-Surv cells was accompanied by protein stabilization, and a transient p21 induction led to reduction in p21 protein expression (see Fig. 3d).
4
0biomedical
0Study
65,378
In summary, mice with reduced SynDIG1 exhibit deficits in the structure and function of excitatory synapses. Mature synapses are still present, albeit at a significantly reduced number, suggesting that synapses can reach maturity without SynDIG1. However, the overall reduction in the number of mature synapses by multiple criteria suggests that SynDIG1 is important for normal development. The increase in overall synapse number may be due to compensation for this loss of mature synapses or because SynDIG1-deficient synapses fail to be eliminated. Indeed, the increased response to glutamate uncaging demonstrates fundamentally altered excitatory synapse function in SynDIG1 mutant mice. Nevertheless, no candidate glutamate receptor subunits or MAGUKs appear to be altered in the composition of mutant postsynaptic densities, and AMPA/NMDA ratios are unaltered. Therefore, SynDIG1 appears to play an important role in the ability of excitatory synapses to reach or sustain maturity in vivo without gross changes to normal synapse composition.
4
0biomedical
0Study
41,292
Pairwise Two-way ANI score was computed among all closely related genomes of SVBP6 using the ani.rb script developed by Luis M. Rodriguez-R and available at enveomics.blogspot.com. ANI score is a result from a whole genome comparison. ANI index is used to delineate species from genomes sequence data . Therefore, if two genomes display an ANI value of 95% or higher, both strains are believed to belong to the same species. Phylogenetic analysis was used to support ANI results.
4
0biomedical
0Study
364,366
Public bulk transcriptomics datasets used in this study are as follows: GEO: GSE47189 (Human macrophage stimulations) (Xue et al., 2014); GEO: GSE93624 (mucosal biopsies from ileal Crohn’s disease) (Marigorta et al., 2017); GEO: GSE59071 (mucosal biopsies from ulcerative colitis) (Vanhove et al., 2015); ArrayExpress: E-MTAB-792 (BMDMs treated with GM-CSF for 24 h) (Lacey et al., 2012); GEO: GSE109040 (colonic murine macrophages from control or DSS-treated mice) (Castro-Dopico et al., 2019); GEO: GSE37448 (Immgen Consortium Phase 2).
4
0biomedical
0Study
319,315
Given the data gaps identified for storage stability data on dithianon residues in grape wine, and for the magnitude of the metabolites Reg. No. 4107273, Reg. No. 31062, Reg. No. 4005234 (phthalic acid) and Reg. No. 4110933 in apple and grapes processed commodities, the consumer exposure assessment could not be concluded on and this was identified as a critical area of concern. An acute intake concern has already been identified for table grapes (149% ARfD) in the previous EFSA conclusion.
2
0biomedical
0Study
308,036
On the one hand, the microenvironment in bone provides the “soil” for the colonized tumor cells (seeds). On the other hand, tumor cells can create an immune microenvironment suitable for proliferation at the metastatic site. Tumor cells release cytokines, which break the balance between osteoblasts and osteoclasts, to cause bone destruction and create an immunosuppressive microenvironment, thus promoting tumor progression and forming a “vicious cycle” [44–46]. As previously mentioned, increased osteoclast activity in patients with bone metastases is directly related to T cell involvement [29, 30]. In fact, enhanced osteoclast activity can be seen even in osteogenic metastases . This interaction among tumor proliferation, bone destruction, and the immune response could be a basis for the treatment of bone metastases.
4
0biomedical
0Study
323,603
N1,N1-Dimethyl-N4-(2,4-dimethylbenzenesulfonamide)-biguanidine (6). Compound 6 was prepared from 2,4-dimethylbenzenesulfonyl chloride to yield off-white solid, 0.24 g, (42%). 1H NMR ((CD3)2SO): δ ppm 8.11 (bs, 2H), 7.73 (, J = 8.0 Hz, 1H), 7.13 (s, 1H), 7.10 (d, J = 8.0 Hz, 1H), 6.87 (bs, 1H), 6.56 (bs, 1H), 2.91 (s, 6H), 2.52 (s, 3H), 2.30 (s, 3H); 13C NMR ((CD3)2SO): δ ppm 159.62, 158.34, 141.26, 139.23, 135.76, 132.61, 127.31, 125.95, 36.45 (2C), 20.64, 19.63. MS (ESI+) for C12H20N5O2S (M+H)+: Calcd 298.39, Found 298.10. Anal. Calcd for (C12H19N5O2O2S *0.2 (CH3)2CO): C, 48.98; H, 6.46; N, 22.66 Found: C, 49.00; H, 6.38; N, 22.35.
4
0biomedical
0Study
100,831
The association effect of rs738409 on BMI was also tested, and no significant association was found in the enrolled subjects (β’ = -0.045, P = 0.113) or in any of the behavioral subgroups (P > 0.05). We found a marginal association of rs738409 with BMI in non-NAFLD children (β’ = -0.072, P = 0.0175), and the association was not significant in children with NAFLD (β’ = 0.083, P = 0.244). The results were shown in the Additional file 1: Table S1.
4
0biomedical
0Study
22,409
“We had a teacher here and he would ask you a question, but before you could even respond he would intimidate you. He would shout saying ‘I'm going to beat you!’ so by the time he asks you a question you are already scared … you cannot give him the right answer because you are just panicking” (Male student, urban intervention school).
1
2other
1Other
284,421
The analyses of high throughput screening of the 1018 compounds of essential NCL against the 87 receptors of the dataset was performed and data analysis is presented hereafter. Table 1 shows the top ten results of the protein-ligand complex ranking. The free energies of binding and the population associated with these clusters indicate the high affinity of these ligands towards the considered targets. Further bioassays will be performed to investigate the in vitro activity of these compounds on Toxoplasma gondii. Nevertheless, the comparison of top ligand 393 and co-crystallized ligand 9DG on protein 1FSG (Figure 5) shows that they are co-localized in the binding site. Due to structure analogy, similar hydrogen bonds are highlighted as well as π-stacking interactions.
4
0biomedical
0Study
19,879
Unclustered missing transverse momentum: The uncertainty arising from the component of the missing transverse momentum that is not due to particles reconstructed as leptons and photons or clustered in jets (“unclustered \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p_{\mathrm {T}} ^\text {miss}$$\end{document}pTmiss ”) is determined by varying it by ±10%.
1
2other
1Other
238,306
Staff were split between COVID-19 and non–COVID-19 cohorts in proportion to the number of residents in each. Staff who became infected were sent home and replaced by temporary workers while they recovered. Staff had a constant daily risk of infection from the community, which was set to reflect different levels of community prevalence (eTable 1 in the Supplement). We examined a range of values for the probability of infection. For our primary analysis, we used our highest value to understand intervention effectiveness in settings with intense community transmission, such as winter 2020 to 2021 in many parts of the US.7,11
4
0biomedical
0Study
23,782
Transcriptional modules associated with protection in (A) malaria and (B) typhoid postvaccination challenge studies. Rows correspond to pathways or gene modules. Columns correspond to one of the following time points: time of first vaccination, between first and second vaccinations, time of second vaccination, between second and third vaccinations, time of third vaccination, between third vaccination and challenge, time of challenge, and postchallenge. Green squares represent a positive correlation with time to diagnosis and pink squares a negative correlation.
4
0biomedical
0Study
332,280
Since the national launch of TB/HIV collaborative activities in Ghana in 2007 and operation in 2009, not many studies have focused on the operational effectiveness of the integrative process, especially in the Volta Region. This study, therefore, assessed the TB/HIV collaborative activities in a district hospital in the Volta Region of Ghana.
2
0biomedical
0Study
169,861
The muskrat (Ondatra zibethicus) is seen as a fixture of wetlands across North America, being one of the most common and widely distributed furbearer species on the continent. They are found primarily in marshes, but also in ponds, sloughs, lakes, ditches, rivers, and streams from the east coast to the west and from the Mackenzie Delta in Canada's north to northern Mexico in the south (Boutin & Birkenholz, 1987). The muskrat also ranks as the top harvested wild furbearer in North America of the 20th century (Obbard et al., 1987) and has contributed more than any other animal to the combined income of North America's fur trappers over the past 150 yrs (OFMF, 2019). In the early 1900s, millions of muskrats were trapped and sold across North America, and though harvest numbers are lower today, muskrats remain a major source of income for fur trappers and are still among the most prevalent species trapped for fur (Fur Institute of Canada, 2019).
2
2other
1Other
24,539
Finally, we asked if rod- and cone-specific ATAC-seq peaks were enriched for distinct sequence features. To define rod- and cone-specific regions, we used DESeq256 to test for differences in accessibility between rods and cones (Methods). This analysis yielded 48,143 shared peaks, 6,324 cone-specific peaks and 693 rod-specific peaks (Supplementary Table S5). To focus on elements likely to contain cell type-specific enhancers, we removed peaks overlapping promoters, peaks shared with non-photoreceptor cell types, and peaks with >70% overlap with repeat sequences. Filtering reduced the totals to 17,485 photoreceptor-specific peaks, 3,606 cone-specific peaks, and 394 rod-specific peaks (Fig. 7A). Thus, we found that the vast majority of photoreceptor-specific peaks were shared between rods and cones, and that there were approximately 10-fold more cone-specific peaks than rod-specific peaks.
4
0biomedical
0Study
262,399
Particulate matter (PM) was monitored as a measure of smoke emission (Figure 1b), and as expected, PM fluctuated with changes in wind speed and direction. Similar concentration profiles were observed for the different PM sizes, with PM10 > PM2.5 > PM1.0, in agreement with particle size distributions previously reported for smoke from domestic wood fires . PM was detected immediately after the combustion of barley straw commenced, with lower levels observed when wind speeds were highest and smoke dispersed more quickly (i.e., between 70 and 100 min). With the exception of one time point (i.e., 297 min), PM levels remained below 50 µg/m3 after 270 min, which was attributed to the corresponding drop in wind (Figure 1a). Nevertheless, PM data demonstrate the presence and density of smoke throughout the trial.
4
0biomedical
0Study
386,500
Caveolin-1 protein levels were also analysed in six control and six OA chondrocytes after being exposed to exogenous oxidative stress and left to recover for different lengths of time, as described in the Materials and Methods. It was observed that in the control cells, caveolin-1 protein levels were upregulated to statistically significant higher values at 1 and 3 h post-treatment compared to the non-treated (NT) condition and decreased back to basal levels after 24 h in recovery. In contrast, in OA chondrocytes, the levels of caveolin-1 did not show any differences between the NT condition and any time point post-treatment (Figure 2A,C).
4
0biomedical
0Study
107,190
The key lignocellulose processing step in terms of energy and chemical demand is pretreatment, opening up the structure of the cell wall matrix, facilitating enzymes to access their substrates and improving hydrolysis of biomass polysaccharides (Galbe and Zacchi, 2012). Pretreatments modify the composition and architecture of the cell wall and can result in the production of fermentation inhibitors such as formic acid, acetic acid, or furfural, which often require removal prior to fermentation (Jönsson et al., 2013; Phitsuwan et al., 2013). While a wide range of pretreatments have been assessed, few have been implemented in commercial operations. These include the advanced steam explosion pretreatment technology by ANDRITZ Inc. and Proesa® for Project LIBERTY and GranBio or Beta Renewables, respectively, the dilute acid pretreatment technology by Iogen for the Raizen project, and the more exploratory ones such as ionic liquids or the mild alkali pretreatment technology developed by the National Renewable Energy Laboratory for DuPont.
4
0biomedical
0Study
394,877
Qualitative and quantitative variables were compared using the chi-square test or Fisher’s test and using a nonparametric (Wilcoxon) test, respectively. Data were presented with 95% confidence intervals calculated using standard methods based on a binomial distribution. Survival analyses were performed with Kaplan–Meier method. A log-rank test and a Cox proportional hazard model were used to compare patients according to UGT1A1 status (WT vs. SH type). Both efficacy and safety analyses included all patients who received at least one dose of irinotecan. All analyses were performed using SPSS ver. 25 (IBM, Armonk, NY, USA). All tests were two-sided, and a p value of < 0.05 was considered statistically significant.
4
0biomedical
0Study
20,034
This cross-sectional study was conducted at the only public reference service in neuroendocrinology in the state of Maranhão at the Presidente Dutra University Hospital (Hospital Universitário Unidade Presidente Dutra (HUUPD)) and the Clinical Research Center (Centro de PesquisaClínica (CEPEC)) of the same hospital. This is part of a doctorate thesis carried out in the Post-graduation Program in Public Health at the Federal University of Maranhão . The data were collected between April 2015 and July 2015. All 75 patients with a diagnosis of acromegaly and follow-up at the hospital in April 2015 were evaluated. The routine of the service was to evaluate patients every three months with recording of clinical and laboratory data (IGF-I and GH levels). The inclusion criteria were individuals older than 18 years who were in clinical follow-up for at least six months. The exclusion criteria were the presence of active neoplasia, severe cardiovascular disease (unstable coronary artery disease or heart failure type NYHA III-IV), pregnancy or breastfeeding, and severe depression.
4
0biomedical
0Study
89,136
Uncoupling the ETS with CCCP allows insights into the theoretical maximum respiratory capacity of the mycelium. Comparing the maximum respiratory capacity of glucose-limited mycelium and phosphate-limited mycelium to their respective steady state respiration (expressed as 100% value) revealed the following (Figures 5, 7): In glucose-limited mycelium the maximum respiratory capacity was approximately 29% higher than the steady state respiration, indicating that there is still surplus respiratory capacity to meet metabolic demands. This is in line with a previous study with P. ochrochloron, where we found oxygen consumption of glucose-limited mycelium increased after a glucose pulse (Vrabl et al., 2008). In contrast, in phosphate-limited mycelium the maximum respiratory capacity was merely 7% higher than the corresponding steady state respiration. This means that under these conditions phosphate-limited grown mycelia approached the maximum respiratory capacity far more to meet metabolic demands.
4
0biomedical
0Study
353,467
Second, the GPIPP is an opportunity sample of online volunteers and, thus, not nationally representative (Gosling et al., 2004). Yet we have no theoretical reason to suspect that this nonrepresentativeness spuriously caused our results. Further ameliorating representativeness concerns, the person-culture match effect in the domain of religiosity replicates across the GPIPP (Gebauer et al., 2017) and the world-representative Gallup World Poll (Diener et al., 2011). Moreover, the robustness and generalizability of our main results are reassuring because they suggest that the results do not hinge on specifics of our main sample (i.e., self-reports as reporting method, countries as cultural units, religiosity as match domain, and self-esteem as well-being indicator). Nonetheless, replication attempts with nation-representative data would be particularly valuable.
2
2other
0Study
66,664
Since its initial identification, EV-D68 has been rarely identified, but more recently, it has become increasingly recognized in the context of enhanced surveillance for poliolike diseases (3). The extent of EV-D68 circulation is underestimated because of the scarcity of laboratories equipped to detect it and poor awareness among physicians. However, in the past decade, EV-D68 has emerged as a major respiratory pathogen, especially in children (1,4). Moreover, concurrent with the unprecedented respiratory outbreak of EV-D68 in North America in 2014, an apparent increased incidence of acute flaccid myelitis (AFM), consistent with poliolike illness, has been reported in several US states (5). These neurologic cases have been temporally associated with EV-D68 infection, although virus sequences were detected almost exclusively in respiratory specimens. Concurrently, EV-D68 was circulating in Europe, where the disease burden was more moderate than in the United States (4). Indeed, EV-D68 has been only rarely detected in the cerebrospinal fluid (CSF) of children with neurologic involvement (6,7).
5
0biomedical
0Study
367,409
It is known that civil, aerospace, marine, pipeline, and mechanical infrastructures deteriorate after being built due to ageing induced cracks, man-made hazards such as vehicle collisions and blasts, and natural disasters such as earthquakes or hurricanes . These can have deleterious effects on the integrity of the engineering structures during their service life, leading to catastrophic operational failures. It is important to establish procedures to assess the deterioration of the structures which are strategically important to human life and safety over their serviceable life to facilitate the maintenance and/or rehabilitation planning processes in this modern society that encourages sustainable development. Hence, structural health monitoring (SHM) which can help detect, locate, and diagnose damages and predict their prognosis is of paramount importance. Some of the recent studies conducted by industries show that early detection of damages can save great expenses and increase the lifespan of a structure, thereby providing value to the industry and society in general . Therefore, a technologically and economically feasible SHM method to identify and assess defects/cracks in structures at an early stage of formation to the micro/nano scale is essential to safeguard the structural integrity and operation throughout the service life.
1
2other
1Other
349,122
Additional file 1: Figure S1. Gene expression associated with promoter and enhancer changes. (A-B) Distribution of significant gene expression changes (RNA log2FC) associated with promoter H3K4me3 peaks either significantly decreased or increased in LM2 vs Par (A) or BrM2 vs Par (B). (C-D) Distribution of significantly gene expression changes (RNA log2FC) linked with either significantly increased or decreased enhancer H3K27ac peaks in LM2 vs Par (C, left) or BrM2 vs Par (D, left). Linkages determined using HiChIP. Shuffle indicates the same plot after randomly shuffling the linkages. P values were calculated using Wilcox U-test. Figure S2. Common promoter and enhancer activation in metastatic cells. (A) Genome track view of the promoter region of PLCB1 demonstrating shared H3K4me3 changes in metastatic sub-populations. (B) Genome track view of APOBEC3G demonstrating shared enhancer H3K27ac changes in metastatic sub-populations. Promoter-enhancer linkage was determined by HiChIP. Figure S3. metATAC workflow and ontology. (A) Schematic of how the TCGA cohort data and cell line ATAC data were integrated and analyzed. MDA-MB-231 lines were processed using the same method as indicated in Corces et al. , and top differentially accessible chromatin regions were used to generate the metATAC signature. Each patient in the TCGA cohort (n = 69) was then assigned a score based on their open chromatin similarity to Par or metastatic sub-populations (common metATAC score). Significantly different regions defined by p < 5e-5, as determined by DESeq2 and BH correction. (B) GREAT gene ontology results associated with increased (up) and decreased (down) peaks in the signature. (C) Distribution of metATAC score between ER positive and negative patients as determined by IHC. P-value determined using Wilcoxon rank sum test. (D) Kaplan-Meier plots of patients separated into ER positive (left) and negative (right) as determined by IHC. metATAC quantile was assigned before splitting the patient into the two groups. Figure S4. Scheme for regulatory motif prediction. Scheme for identification of TFs associated with differentially expressed genes between each metastatic sub-population and Par. Reproducible linkages between ATAC peaks were first determined using HiChIP data and subsequently annotated to be either distal or proximal (promoter) to the TSS of each gene. Gene expression is then used to determine significantly up- or down-regulated genes. ATAC peaks that are linked to these gene modules (both distal and proximal) and also follow the same direction of signal change are elected as regulatory regions. Hypergeometric tests are then performed on regulatory regions using all regions as background to determine enriched TF motif clusters (based on RSAT). Motif clusters are finally re-assigned to transcription factors that fall within each respective cluster. Figure S5. Regulatory motifs and associated transcription factors. (A) TFs associated with motif clusters enriched in regions of increased accessibility (gained) in either LM2 compared to Par, BrM2 compared to Par, or both. TFs names are color-coded to indicate membership in the respective motif cluster. (B) Same as (A) but with motif clusters enriched in regions of decreased accessibility (lost) in the indicated comparison. Figure S6. Subtype specificity of metATAC score and transcription factor expression. (A-B) Distribution of LM2- (A) or BrM2-specific (B) metATAC score across PAM50 subtypes. (C-D) Expression of the indicated transcription factors across subtypes. (E) Kaplan-Meier curve of SMAD1 expression and brain metastasis-free survival. (F) Expression of SMAD1 across subtypes. (G) Kaplan-Meier curve of NRBF2 expression and brain metastasis-free survival. (H) Expression of NRBF2 across subtypes. NS non-significant. Figure S7. Subtype specificity of metATAC score and transcription factor expression. (A) Kaplan-Meier curve of RUNX2 and lung metastasis-free survival within basal-like patients. (B) Kaplan-Meier curve of JUN and brain metastasis-free survival within basal-like patients. N = 38.
5
0biomedical
0Study
71,548
The concentration of cadmium and lead in the marl-cement mixture with 20% EAFD was 0.58 and 0.12 mg/l, respectively, and the corresponding values for the 30%-EAFD mixture were 0.67 and 0.17 mg/l, respectively. These values are well below the corresponding allowable values of 1 and 5 mg/l22. Therefore, the examined EAFD-stabilized marl mixtures fulfilled the leachability requirements.
2
2other
0Study
372,017
The present work demonstrates for the first time, a regulatory crosstalk between HO-1 and p53 in ES cells. Another remarkable conclusion that emerges from these data is that HO-1 expression increases during differentiation suggesting an important role of this protein in stem cells biology. Additionally, the lack of p53 correlates with increased HO-1 protein levels presumably as a cellular mechanism to maintain redox homeostasis. This study also highlights that p53 modulates HO-1 expression at the post-transcriptional level, emphasizing the connection between these proteins.
4
0biomedical
0Study
123,729
The main objective of this data curation task is to explore literature-based consistency assessment. To address the questions raised in the previous section, we have built a data curation test set, based on the scatter plot of Figure 3a. We divided the data into three interesting zones to explore, as illustrated in Figure 4a. Zone A covers the centroid region, Zone B covers the south outlier region, and Zone C covers the east outlier region. Figure 4b shows the records effectively selected to be included in the test dataset for the curation task. The zones B and C contain 100 records each. In region A, which is very dense, we have randomly selected 100 records. Additionally, we have randomly selected 100 records from the whole dataset to be included in the test set for comparison. This gave us a total of 400 records to be curated in order to answer the questions previously posed. Figure 4. Curation task. (a) Zones curated. (b) Records curated. (c) Results of the curation task.
3
0biomedical
0Study
142,564
Prior to the introduction of residents, employed internal medicine hospitalist physicians would care for an average of 18 patients per day (range 15 to 21 patients). All patients were admitted by either a nocturnist or admitting internist. There were 8-12 non-teaching hospitalist rounding teams, depending on hospital census. On July 1, 2019, a new inpatient teaching service structure was created for the internal medicine residents, consisting of four inpatient teams. Each team consisted of a teaching hospitalist with two interns. The teaching hospitalist teams average 15 patients (range 12 to 18 patients). All of the teaching hospitalists were a part of the employed hospitalist group. The teaching and non-teaching hospitalists were all admitting patients for the entire period studied.
3
1clinical
1Other
9,782
for all n = 1, …, N, where 0 < θ < 1 is the threshold chosen by the user for the sake of stabilizing the influence of the low quefrency component in the nonlinear mask design. C~f∈ℂN×αM is the upsampled version of Cf in the quefreqncy axis by α ∈ ℕ times that is defined by
2
0biomedical
1Other
264,791
Figure 4 shows the extent that a dog-bite injury can have. A substance defect in the upper and lower lip was the result. Plastic reconstruction of the upper and lower lip was performed in an extensive operation under general anesthesia. Figure 5 shows the postoperative result for the patient about half a year after the accident.
2
1clinical
3Clinical case
300,111
Univariate Cox regression models analysis of DEGs was conducted using survival package to screen out prognosis-related m6A phenotype modifying genes with P-value <0.05. The samples were clustered according to the expression of prognosis-related m6A phenotype modifying genes using the ConsensusClusterPlus package, so as to identify gene clusters for the next step of analysis(the same as step-m6A cluster).
4
0biomedical
0Study
215,938
Wolfgang Mastank 23 thinks that DMN can be considered a form of inner intelligence, highly sensitive to music. For this reason it should be developed through an adequate musical education. This theory is shared by Bashwiner et al. (2016), who considers that “musically creative people have greater cortical surface area or volume in 1) regions associated with domain-specific higher-cognitive motor activity and sound processing 2) domain-general creative-ideation regions associated with the default mode network and 3) emotion-related regions These findings suggest that domain-specific musical expertise, default mode cognitive processing style, and intensity of emotional experience might all coordinate to motivate and facilitate the drive to create music” 24 .
2
0biomedical
1Other
278,427
Shiqi Kong: Data curation (equal); Investigation (equal); Methodology (equal). Xinbo Ge: Data curation (equal). Xin Li: Data curation (equal). Zhenbo Liu: Conceptualization (equal); Formal analysis (equal). Rui Zhang: Data curation (equal). Ming Yang: Formal analysis (equal). Zhenhai Wang: Formal analysis (equal). Zhenzhong Li: Project administration (equal).
1
2other
1Other
232,583
There was no significant difference in the levels of electrolytes (serum chloride, calcium, and sodium) and blood pH with respect to the control, model, and ZZAE groups. However, urea, creatinine, and potassium levels increased in the model group compared to the control group. Interestingly, ZZAE significantly (P < 0.05) decreased elevated urea and creatinine levels compared to the model group (Figure 6).
4
0biomedical
0Study
100,779
In the supervised learning context the classifier threshold is a parameter that is found during the learning stage. Training the classifier maximizing the area under ROC curve is an strategy for the classifier learn the training set. Consequently, the proposed strategy could be considered as a "learning rule". However, the performance over new examples is not guaranteed. Other point which can improve the manuscript would be to consider the ability of generalization of the proposed strategy. Could the author add a discussion in this sense?
2
0biomedical
1Other
51,888
Water deprived rats were trained in an odor discrimination maze that consisted of 4 arms, where at each trial one randomly chosen arm contained water at its far end. Rats in the trained group had to choose the water containing arm based on a positive odor cue which signified the presence of water in the containing arm and negative odor cue which signified no water in the containing arm. The task was difficult to learn, as it took the rats 7–8 days to reach the learning criterion of the first odor pair (negative and positive odors). The training was terminated once the rats demonstrated enhanced learning capabilities using a different odor pair, which in average lasted 1–2 days only. Rats designated to the pseudo-trained group were rewarded with water when choosing any odor in a random manner and their exposure time to the odor maze was artificially matched with the rats of the trained group. Rats in the naive group were left in their home-cages and were water deprived only. 4–5 days after training termination, in which rats stayed in their home cage, whole-cell recordings were made from identified pyramidal cells in slices taken from the piriform cortex. In these recordings spontaneously evoked miniature synaptic events could be identified. Each cell exhibited only excitatory miniature postsynaptic synaptic currents (mEPSCs) or inhibitory synaptic currents (mIPSCs), due to a different pharmacology, holding potential and pipette solution (Materials and Methods).
4
0biomedical
0Study
217,625
Herein, we propose a 3D-printed structure (characterized by a low value of thermal conductivity) evaluation scheme using active thermography with halogen lamp excitation in a long pulse regime, and dedicated data processing algorithms. The aim of the work was to conduct a procedure enabling an assessment of the possibility of effective extraction of information about even small defects while maintaining short inspection times. Therefore, two areas of using the obtained data should be distinguished in the presented work.
4
0biomedical
0Study
143,843
Due to its efficient timesaving protocols and effectiveness, HIE has been the subject of more and more attention in recent years among athletes, bodybuilders, and individuals with chronic diseases. However, along with the increasing interest in HIE, there are questions that need consideration. One such question relates to the relationship between HIE and oxidative stress. This question may directly affect the arrangement of athletic training loads, the choice of fitness methods, and the safety of exercise for patients with chronic diseases.
2
0biomedical
1Other
120,989
Sample sizes varied from 24 to 797 parents. Participants were predominantly mothers, although only two studies exclusively recruited mothers (Landy and Menna 2006; Sheeber and Johnson 1994). Three studies recruited couples (Gross et al. 1995; Pisterman et al. 1992; Wolfson et al. 1992), while the remaining studies included mixed samples consisting of the mother, father or another primary caregiver. None focused on fathers exclusively.
3
0biomedical
0Study
373,754
Compound binding was verified by in silico modeling, where S13 binds to the KRAS-GAP interface between Switch-I of KRAS and the turn between α19- and α20-helices of GAP, while reaching into a small pocket of GAP between α17-helix and a turn motif consisting of residues 785–789 (Fig. 6). To experimentally verify structural interaction between the new molecules and the KRAS-GAP complex, crystallization trials are in progress. The efficacy of such small molecules are demonstrated in human cancer cell cultures, where this compound inhibits the proliferation of cells containing the KRAS G12D allele with some preference .Fig. 6A compound promoting interaction between mutant KRAS and GAP. Model of S13 (cf Table 1) bound to GAP-KRAS-G12D complex is shown as sticks with atomic coloring (carbon: salmon; oxygen: red; nitrogen: blue; sulfur: yellow; phosphorus: orange). GDP is shown as sticks with atomic coloring (carbon: black, other elements as above). GAP is shown as cyan cartoon; KRAS is represented as white cartoon. Surface of residues interacting with S13 is shown. Dashed black line represents hydrogen bonding. Figure was made by using PyMOL Molecular Graphics System
5
0biomedical
0Study
303,782
The effects of FSs on the glutamatergic system are currently less investigated. Early life frequently repetitive FSs resulted in selective deficits in GluN2A subunit tyrosine phosphorylation after NMDA treatment in the hippocampal CA1 areas of adult rats . Chen et al. showed that GluN2B Tyr1472 phosphorylation gradually increased and maintained a high level for 7 days after prolonged FSs, without any apparent change in the total GluN2B expression level .
4
0biomedical
0Study
313,777
In human immunodeficiency virus (HIV) life cycle, HIV RNA genome post-viral entry is reverse-transcribed into a double-stranded DNA, followed by transportation into the nucleus. Such a viral DNA/integrase complex preferentially integrates into the transcriptionally active sites of host chromosomes . Notably, HIV DNA integration is an essential hallmark of viral production as integrated proviral DNA serves as a dominant template in the process of HIV replication, compared with unintegrated viral DNA forms . By contrast, nonintegrated linear viral DNAs are unstable and accompanied by limited transcription to transiently express early viral elements , while nonintegrated long terminal repeat (LTR) circles, representing extrachromosomal bystander products that failed upon viral integration , basically lose the capacity of viral replication and are ultimately diluted due to cell proliferation . However, the sporadic emergence of linear viral DNA and 2-LTR circles observed under ART is perhaps indicative of ongoing viral replication at low levels . In the context of HIV replication from provirus transcription to virion assembling, unspliced RNA (~9-Kb) and more than 100 differentially spliced transcripts (predominant two-class sizes of early ~2-Kb and late ~4-Kb RNA) are generated : the unspliced transcript is a template for gag/pol translation and viral RNA genome packaging; 4Kb incompletely spliced transcripts encode viral proteins env, vif, vpr, and vpu following export into the cytoplasm; and multiply spliced viral RNAs (~2 Kb) express regulatory tat, rev, and nef for transactivation and nuclear export of the viral RNAs (Figure 1). Therefore, various cell-associated HIV RNA/DNA forms may reflect the different viral replication status and clinical significance . For example, HIV gag RNA transcripts represent bona fide genomic HIV RNA or gag and gag-pol polyproteins in viral replication ; spliced HIV tat/rev RNAs are functional for viral replication and production ; and integrated proviral DNA is a marker to estimate the proviral reservoirs . A small number of HIV-infected cells harboring proviral DNA may replenish proviral reservoirs through clonal expansion or cell division, maintaining viral persistence .
5
0biomedical
0Study
94,270
The associations between the median plasma CCL27 concentrations and clinical variables for the 104 NPC patients are presented in Table 1.Table 1Associations between plasma CCL27 levels and clinical characteristics of the patients with NPCCharacteristicsNo.Median(range)P value Age0.8556≤4552405.35(107.33-1296.94)>4552383.76(84.03-872.33) Sex0.5555Female25375.12(107.33-917.17)Male79403.27(84.03-1296.94) pT stage0.8991PT1-pT225403.27(217.84-1067.05)pT347403.96(84.03-1296.94)pT432395.68(108.98-872.26) pN stage0.1946pN 0/153373.05(84.03-1067.05)pN 2/351420.32(109.05-1296.94) Stage0.9685I + II13376.25(227.77-1067.05)III50397.70(84.03-1296.94)IV41403.27(108.98-872.26)
4
0biomedical
0Study
390,688
METTL3 promotes TFAP2C expression and cellular viability of TCam‐2/CDDP cells under CDDP treatment condition through regulation of TFAP2C mRNA stability. TCam‐2/CDDP cells were transfected with empty vector control, METTL3 overexpression plasmid and METTL3 siRNA, respectively, and incubated for 72 h. The expression of TFAP2C was measured by qPCR (A) and immunoblotting (B), and GAPDH was used as internal control. Another batch of transfected cells (METTL3 overexpression and interference, 72 h) was treated with actinomycin D to investigate the effect of METTL3 on decay rate of TFAP2C mRNA at different time‐points (0, 2, 4, 6, 8, 12 h). qPCR was performed to examine the relative TFAP2C mRNA level, and 18S rRNA was used as internal control (C). Dotted line represents mRNA half‐lives. To investigate the effect of METTL3 on cellular viability of TCam‐2/CDDP cells in response to CDDP treatment, the cells with METTL3 overexpression or inhibition were treated with CDDP (at the concentration of IC25) for 72 h. CCK8 cell viability assay was conducted for the determination of cell viability in cell proliferation (D). Apoptotic rate was analysed by FCM assays (E), and DNA damage rate was detected by gamma‐H2AX immunofluorescence assay (F). CCK8, Cell Counting Kit 8; DAPI, 4',6‐diamidino‐2‐phenylindole; FCM, flow cytometry; H2AX, H2A histone family member X; IC25, inhibition concentration 25%; rRNA, ribosomal RNA. The data were presented as the mean ± SD of triplicate tests. **P < 0.01, ***P < 0.001, ns, not significant
4
0biomedical
0Study
3,946
This article presents an overview of the content development and performance of the first national interdisciplinary training program for the treatment of transgender veterans. In the first three cohorts of learners, 111 interdisciplinary VHA providers were trained. All didactic sessions performed well, with learners from a variety of disciplines reporting that they were satisfied. Overall, learners rated the didactics as effective and reported acquiring new knowledge and skills. Veteran-specific case consultation was offered both in session and in the veteran's electronic medical record for 39 treatment questions.
2
2other
1Other
95,801
The MRC Biobank has been collaborating with an increasing number of pharmaceutical companies involving biomarker studies. Biobank samples have been provided to industrial partners such as Pfizer , and Bristol-Myers-Squibb for identification of serum and urine biomarkers (manuscript submitted). Due to high number of requests, the biobank has improved its access procedures and recently introduced a ‘cost recovery plan’. Cost recovery involves the sharing of costs incurred for sample collection and management. When third parties apply to use the stored samples, they may be asked to provide money to the biobank to help cover the sample collection and management costs. These charges are applied to reduce some of the storage costs and support the availability of funds for ongoing sample collection and preservation; however, no profit is generated from the use or storage of biobank samples. The charges are under regular review to ensure that it is being used appropriately and fairly.
2
0biomedical
1Other
227,259
Unsurprisingly, the present study detected a significant heterogeneity among the four clusters in genomic variation. A total of 16 significantly mutated genes were identified as drivers involved in the tumorigenesis and evolution of gliomas. Of these, PTEN mutation, co-occurring with EGFR but repelling with IDH1 mutation, was more specific to C1; FLG mutation, repulsive to IDH mutation, occurred more frequently in C2; ATRX and TP53 mutations were significantly enriched in C3; and IDH1 mutation was more specific to C4. PTEN, EGFR, ATRX, TP53 and IDH mutations were all oncogenic drivers, predominantly related to molecular diagnosis and different prognosis in glioma (Louis et al., 2016; Diplas et al., 2018). FLG mutation, associated with ichthyosis vulgaris and atopic eczema (Akiyama, 2010), was first identified as a biomarker linked to a poor prognosis in glioma. For copy number variation, the clusters also exhibited distinct characteristics, as summarized in Supplementary Table S10. The most frequent alterations were located on chromosomes 1p, 7, 10, and 19q, in line with the focus of earlier studies (Louis et al., 2016; Stichel et al., 2018). Copy number variation can lead to oncogene activation or tumor suppressor gene (TSG) inactivation in cancer. In the present study, it was detected that 7q21.2 (CDK6) and 7q31.2 (MET), more specific to C1, were appreciably amplified; 10q23.31 (PTEN), occurred more frequently in C1, and 1p32.3 (CDKN2C), 1p36.23 (ERRFI1), 1p36.32 (AJAP1 and HES3), and 19q13.41 (PPP2R1A), more specific to C4, were appreciably deleted. These oncogene-relevant amplifications and TSG-relevant deletions may contribute to the tumorigenesis and progression of glioma. In addition, the present study also revealed that 12q14.1 amplification, and 6q22.31, 6q26, 13q14.2, 13q22.1, 15q14, 22q13.32, and 4q34.3 deletions were significantly related to prognosis in glioma, implying that these alterations may be able to serve as novel prognostic biomarkers.
5
0biomedical
0Study
344,330
DKD is characterized as glomerulosclerosis and tubulo-interstitial fibrosis. Glomerular hyperfiltration, inflammation, oxidative stress and altered lipid metabolism have been implicated in the pathogenesis of DKD . In addition, the release of cytokines and chemokines and infiltration of immune cells contribute to the onset and progression of DKD . Inflammatory signaling pathways promote the mesangial expression of transforming growth factor (TGF)-β and production of extracellular matrix (ECM) via nuclear factor (NF)-κB activation , leading to the development of thickening of the glomerular basement membrane (GBM) and glomerulosclerosis . These inflammatory and fibrotic responses also cause tubulo-interstitial fibrosis. Podocyte injury is also a key feature in the early stage of DKD. Podocytes participate in the formation of the filtration barrier and regulate glomerular filtration, along with the GBM and endothelium . Therefore, podocyte loss under diabetic conditions results in the damage and hyperpermeability of glomerular endothelial cells, leading to the development of albuminuria .
5
0biomedical
0Study
96,976
537 teeth (4.2%) had undergone root canal treatment, with a ratio of one tooth being treated endodontically per patient. This rate is lower than that found by Matijević et al. (8.5%) , Ilić et al. (12.5%) , and Boucher et al. (19%) , almost similar to that declared by Peters et al. (4.8%) , and higher than that found by Jiménez-Pinzón et al. (2.4%) .
4
0biomedical
0Study
35,183
A model was established consisting of the following components: A realistic model of the auditory periphery activated by click sounds. Click sounds were chosen because these are known to be effective at activating octopus cells and they have a broadband profile.A modified leaky integrate-and-fire (LIF) model of the octopus cell used to recreate the firing behavior of octopus cells. This is simpler than a Hodgkin-Huxley model, but adequate to capture the relevant dynamics.A conventional STDP model of synaptic weight adjustments used to adjust the weights of the connections between the periphery model, and the octopus cell model.
4
0biomedical
0Study
204,185
Management of HT is considered a cornerstone for neonatal resuscitation as it reduces rates of neonatal mortality and morbidity [2, 21, 22]. According to the United Nations Children’s Fund (UNICEF), these interventions can reduce the outcomes of HT by 18–42% . These interventions that have been proposed to prevent HT in newborn infants include using a plastic cap, polyethylene bag wrapping, thermal mattress, controlling the room temperature, and active warming during cesarean delivery [9, 17, 23, 24]. A quality improvement project on the implementation of thermoregulatory interventions showed a significant reduction of neonatal HT, which in turn improved neonatal outcomes .
4
0biomedical
0Study
135,719
Biometric devices based on PMMA, including hard tissue implants, are used to restore tissue functionality. Unfortunately, their major disadvantages are the lack of integration into the host tissue, monomer toxicity, potential bone necrosis due to exothermic reaction, and inflammatory response. These undesirable properties have forced scientists to find another resorbable alternative to PMMA, which is, for example, injectable calcium cement with calcium phosphate. This material undergoes endothermic curing at a temperature of 37 °C. Another advantage is its resorbability and osteo-induction. However, this material has a significant disadvantage: its degradation rate does not correspond to the level of new bone formation. Materials that are actively involved in the healing process are still being sought, while at the same time they should exhibit mechanical properties comparable to that of the host bone. Due to their good biocompatibility, bioactivity, and ability to degrade in vivo by dissolution and osteoclastic resorption, calcium phosphates have been thoroughly tested as synthetic materials for bone implants. Polymer-ceramic composites have been considered as implants that can integrate with native bone and can carry considerable weight. Nonporous composites have been obtained through reactive compression moulding of mineralised allograft bone particles (MBP), with two-component biodegradable PU networks as the polymer binder, which is obtained from a polyester polyol and a lysine-derived isocyanate. PU can be used for injectable applications, i.e., bone cements. This is due to its two-component reactive liquid formulation. In addition, the polyurethane covalently binds to the filler of allogeneic bone by reacting isocyanate groups with collagen that occurs in the bone. Thanks to bone dimineralisation, the surface area that can react is increased. The mechanical properties increase due to the strong polymer bonding and filler phases. Due to the presence of the collagen layer, the adhesion of osteoblast-like cells is increased .
4
0biomedical
0Study
359,377
West blot results of samples. a showed the results of western blot about Occludin and Claudin-1. After treated for 24 h, various concentrations of betaine (0-2 mmol/L) improve the expression Occludin and Claudin-1 in IPEC-J2 cells. c confirms that LPS down-regulate the protein levels of Occludin and Claudin-1, while betaine totally attenuated the down-regulation and recovered to a normal level. b and d were the statistical graphs of the density ratios of different proteins to β-actin calculated by Image J and analyzed by Graphpad Prism6. All the results were repeated four times (n = 4, *P < 0.05, **P < 0.01 compared with control)
4
0biomedical
0Study
53,691
The list of genes that are silenced by DNA methylation in OPSCC is growing rapidly and includes genes involved in several pathways, including apoptosis, cell cycle, DNA repair, and WNT signaling. A selection of the most frequently hypermethylated genes in OPSCC is given in Table 1. Notably, differences in DNA methylation profiles between HPV-positive and HPV-negative OPSCC have been frequently observed in several studies. Overall, while HPV-negative cancers are mainly characterized by genome-wide hypomethylation, the HPV-positive counterpart displays higher levels of promoter methylation (Table 1).Table 1Genes hypermethylated in OPSCCPathwayGeneNameHypermethylated inRegion analyzedReferenceApoptosisDAPKDeath-associated protein kinase 1HPV-negative/positivePromoter regionRASSF1Ras association domain-containing protein 1HPV-negative− 244 from TSSa Promoter region[45, 51]STAT5Signal transducer and activator of transcription 5HPV-negative+ 42 from TSSCell cycleCCNA1Cyclin A1HPV-positivePromoter region+ 7 from TSSCDKN2ACyclin-dependent kinase inhibitor-2AHPV-negativePromoter region[43–45, 51]HPV-positiveThree loci within the CpG island of CDKN2A geneCHFRb Checkpoint with forkhead and ring finger domainsHPV-negativePromoter regionTP73Tumor protein p73HPV-negative/positivePromoter regionCell fate determinationAPCAdenomatous polyposis coliHPV-negative/positivePromoter regionDNA repairMGMTO6-methylguanine-DNA methyltransferasesHPV-negative− 272 from TSS[50, 51]Protein glycosylationTUSC3Tumor suppressor candidate 3HPV-positive+ 29 from TSSInflammationJAK3Janus kinase 3HPV-positive+ 64 from TSSInvasion and metastasisCADM1Cell Adhesion Molecule 1HPV-positivePromoter regionCDH11Cadherin 11HPV-positive− 354 from TSSCDH13a Cadherin 13HPV-negative/positivePromoter regionIGSF4Immunoglobulin superfamily member 4HPV-positivePromoter regionSPDEFSAM pointed domain-containing Ets transcription factorHPV-negative+ 116 from TSSTIMP3TIMP metallopeptidase inhibitor 3HPV-positivePromoter region[39, 51]SYBL1Synaptobrevin-like 1HPV-positive− 349 from TSSSignalingESR1Estrogen receptor 2HPV-negative/positivePromoter regionESR2Estrogen receptor 2HPV-negative+ 66 from TSSGALR1Galanin receptor type 1/2HPV-positiveTwo loci within the CpG island of the GALR1 geneGRB7Growth factor receptor-bound protein 7HPV-positive− 160 from TSSRARβa Retinoic acid receptor βHPV-negative/positivePromoter regionTranscriptionRUNX1T1RUNX1 translocation partner 1HPV-positive+ 145 from TSSTCF21Transcription factor 21HPV-positivePromoter regionWNT signalingSFRP1Soluble frizzled receptor protein 1DrinkersPromoter regionSFRP4Soluble frizzled receptor protein 4HPV-positivePromoter regionWIF1WNT inhibitory factor 1NAPromoter region NA not applicable a TSS transcription start site bHypermethylation of these genes is associated with development of radioresistance in other tumor types
4
0biomedical
0Study
142,530
To recapitulate the pathogen invasion-induced apoptosis, we also infected Raw264.7 cells with adenovirus to induce apoptosis (Supplementary Fig. S21a, b). Adenovirus is a DNA virus that is recognized by Pol III and activates IFN-β expression by RIG-I-dependent pathway50. Again, IFN-β induction by adenovirus was markedly reduced in PARP1-deficient cells or non-cleavable PARP1 (D214N)-expressing cells (Supplementary Fig. S21c, d), suggesting that PARP1 cleavage promotes IFN-β expression and apoptosis during pathogen infection.
4
0biomedical
0Study
217,886
Even with molecular diagnosis, Pap smear is still the screening method used in low-income countries: its replacement by more expensive methods is a distant reality3. Even in high-income countries, well-structured implementation of programs using the Pap smear has reduced cervical cancer incidence and mortality rates by up to 65% in the last 40 years8.
3
0biomedical
1Other
327,619
We used epitope-tagging to localize a few of the HCMPs which were up-regulated during interaction with IECs (e.g., ORFs 7715, 91707, and 115066). These HCMPs were plasma membrane-associated but they were also partially localized around the peripheral vesicles, ER and nuclear membrane. The localization HCMP91707 varied with generation numbers in culture, which suggests that certain HCMPs can display a dynamic localization between internal and external membranes. Some HCMPs are also released into the surrounding environment during host cell interactions (Ma’ayeh et al., 2017). The presence of epidermal growth factor (EGF)-like domains within many of the HCMPs might relate to possible functions associated with this dynamic localization inside and outside the giardial cell. EGF-like domains are usually present in secreted proteins but they can function intracellularly upon ligand binding to mediate the release of transcriptional factors or modulate transcription within the nucleus (e.g., NOTCH signaling) (Kiyota and Kinoshita, 2004; Lai, 2004). This domain is also associated with diverse functions including calcium binding (Handford et al., 1991), adhesion (Stenflo, 1991), protein–protein interactions and intracellular and extracellular signaling (Wouters et al., 2005). It will be interesting to identify which exact role HCMPs and EGF-like domain have in Giardia.
4
0biomedical
0Study
176,935
For mining regulators potentially responsible for CAPG dysregulation, we found that CAPG in OC is associated with a network of proteins including DHX9, HIPK2, and Myc family. Puca et al. demonstrated that overexpression of HIPK2 circumvents the blockade of apoptosis in chemoresistant ovarian cancer . Patel et al. found that loss function of DHX9 protected BRCA1-mutant mice against tumorigenesis . Various studies indicate that the Myc family network can be viewed as a functional module which acts to convert environmental signals into specific gene regulatory programs . Yang et al. reported that N-Myc and STAT Interactor (NMI) and CAPG were upregulated in glioblastoma, functioning as an inflammatory response . Sheng et al. showed that cisplatin-mediated miR-145 downregulation increased PD-L1 expression via targeting the c-Myc transcription factor, thereby inducing T cell apoptosis in OC . Jimenez-Sanchez et al. investigated associated immune cell exclusion with the amplification of Myc target genes in treatment-naive OC . Our results, partly in line with the findings in the above studies, showed that CAPG participated in cancer progression and immune regulation with genes like Myc. However, the mechanisms behind these interactions require further investigation.
4
0biomedical
0Study
270,741
Lumbar spine areal BMD was measured from L1–L4 using a Discovery Wi DXA system (Hologic Inc., Marlborough, MA, USA) and TBS was retrospectively calculated from L1–L4 from the same DXA scans using TBS iNsight® software (version 3.0.2.0; Medimaps Group, Geneva, Switzerland). For the BMD T-score calculation, the manufacturer’s age-specific reference curve for Japanese women was used.
4
0biomedical
0Study
193,155
The bottom-up approach is data-driven without semantic information but grounded in the connotation of primitive features such as color, intensity, shape, and texture that are simple to implement . The bottom-up methods compute uniqueness in primitive features of image pixels and surrounding regions. These saliency detection methods have extensively used different visual rarities to separate foreground and background regions in images. The visual rarities include color prior , contrast prior , brightness prior , background prior , boundary prior , center prior , shape prior , context prior , object position prior , and connectivity prior . However, despite the development of several methods for salient object detection, there are still intrinsic challenges with different categories of images. The presence of cluttered and non-homogeneous background regions, inter-object dissimilarity, heterogeneous objects with varying sizes, counts, and positions have led to ambiguous and diverse challenges. Examples of image categories are salient objects with erratic sizes, positions, and counts, cluttered backgrounds, and low dissimilarity among regions of heterogeneous foreground or heterogeneous background. The task of completely highlighting salient objects in different image categories is still not adequately resolved in most of the existing saliency methods . The other major challenge is the mitigation of computational complexity because salient object detection is an essential preprocessing stage in computer vision.
4
0biomedical
0Study
10,111
The equation used to calculate the prognostic score in the development cohort was (Stage Group*0.397) - (Treatment*1.094) + (Age*0.024) - (log(Histogram Energy)*1.320) + (log(TLG)*1.748) + (Histogram Kurtosis*0.198). This calculation was derived using published methods . The median score of quartile 1 was −0.73 (n = 76, range −1.66 to −0.45), quartile 2 was −0.14 (n = 76, −0.45 to 0.29), quartile 3 was 0.76 (n = 75, 0.31 to 1.06) and quartile 4 was 1.38 (n = 75, 1.08 to 2.15). There was a significant difference in OS between quartiles (X2 143.14, df 3, p < 0.001) (Fig. 2). Median OS of quartiles 1 to 4 was 36.0 months (95% CI 31.1-40.9), 21.0 months (16.1-25.9), 14.0 months (11.7-16.3) and 8.0 months (5.9-10.1), respectively. The interaction test revealed no statistical difference in performance of the prognostic score between curative and palliative treatments (X2 1.344, df 1, p = 0.246).Fig. 2Kaplan-Meier plot demonstrating overall survival curves of prognostic score quartiles in the development group (X2 143.14, df 3, p < 0.001). Q1 quartile; Q2 quartile 2; Q3 quartile 3; Q4 quartile 4. Median OS of Q1 to Q4 was 36.0 months (95% CI 31.1-40.9), 21.0 months (16.1-25.9), 14.0 months (11.7-16.3) and 8.0 months (5.9-10.1), respectively
4
0biomedical
0Study
176,763
In leaves under salt stress, 30 genes were encoding ERF, 17 encoding MYB, 16 encoding bHLH, and 11 encoding NAC prominently expressed in R7 (Figure 7D), whereas there were 8 encoding ERF, 6 encoding NAC, 6 encoding SBP, and 6 encoding bHLH prominently expressed in S4 (Figure 7E). In root tissues, bHLH, ERF, WRKY, and MYB TF families were prominently induced by salt stress in both R7 and S4 (Figures 7H,I). There were 29 genes encoding bHLH, 25 encoding ERF, and 19 encoding WRKY preferentially induced in R7 (Figure 7J), whereas 27 genes were encoding ERF, 19 encoding NAC, and 18 encoding MYB preferentially induced in S4 (Figure 7K).
4
0biomedical
0Study
29,542
The number of SPR operations from any given network N in tier \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$i\ge 2$$\end{document}i≥2 can be given an upper bound as follows.
1
2other
1Other
73,845
Because, you know, they're the people who are actually suffering and they're telling you what a huge difference it can make to their lives or the… the length of time they have left so that's sometimes quite a struggle…So it's hard… it's hard to keep… to stay neutral, I think, at times”
1
2other
1Other
351,374
To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols
2
0biomedical
1Other
371,348
AK045171 is involved in the regulation of MG53/GSK3/β-catenin and MG53/NFκB pathways. Western blotting was used to evaluate the expression levels of proteins in the MG53/GSK3/β-catenin (A, B) and MG53/NFκB (C, D) pathways. (E) Immunofluorescence staining of p65 was performed to observe nuclear transfer of p65. * p<0.05 vs Ad-vector group; # p<0.05 vs Ad-AK054171+si-nc group.
4
0biomedical
0Study