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PD-L1 as an immune checkpoint is critical in immune tolerance and preventing autoimmune response. Tumor cells utilize increased PD-L1 expression to escape from immune surveillance37 and to gain resistance for therapeutic agents such as tyrosine kinase inhibitors38. The similarities between cancer and IPF are increasingly recognized, and certain treatment options for cancer have been considered for IPF including the anti-PD-1/PD-L1 therapy7,8. However, understanding of PD-L1’s role as a pathological factor or therapeutic target for IPF is still in its infancy. In this study, we observed significantly increased PD-L1 expression in the lung tissues of IPF patients compared to normal subjects (Fig. 1b), suggesting a role for PD-L1 in the pathogenesis of IPF. We also found that PD-L1 expression was upregulated in the bleomycin induced preclinical PF model (Fig. 2b) as well as in the TGF-β preclinical model (Fig. 2d), further supporting that PD-L1 is an integral part of the development of PF. We also noted that those cells with elevated PD-L1 expression were also positive for α-SMA in the lung tissues of mice challenged with bleomycin but not saline (Fig. 2c), suggesting that PD-L1 may affect the FMT during PF progression in vivo.
| 4 | 0biomedical
| 0Study
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139,588 |
Tobacco use is the leading preventable cause of illness and death in the world today . Over 36 million Americans smoke tobacco . Sixteen million live with a smoking-attributable disease and yet 30–40% of these individuals continue to smoke . Cigarette smoking is responsible for over 400,000 deaths (1 out of every 5) in the United States each year . Most smokers are aware of the health consequences and want to quit, but have difficulty doing so. Only 3–5% of smokers who quit on their own are successful in maintaining long-term abstinence . Approved pharmacotherapies when coupled with behavioral counseling can lead to long-term abstinence rates up to 20–25% compared to 9% receiving counseling alone . Given this modest long-term efficacy, a significant unmet medical need exists for more effective and complementary approaches to treat nicotine addiction.
| 4 | 0biomedical
| 2Review
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332,256 |
In addition to the remarkable modifications of the male front legs, the male genitalia are also extraordinary, with fin-like structures on both the median lobe and tegmen. Before the soft tissues were removed, the basal portion of the aedeagus was heavily surrounded by muscle tissue, somewhat similar to the condition found in the subfamilies Eumolpinae and Cryptocephalinae.
| 3 | 0biomedical
| 0Study
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232,310 |
Peptide separation was performed using a reversed-phase analytical C-18 column (75 μm × 50 cm; 100 Å, 2-μm-bead-packed Acclaim PepMap RSLC, Thermo Scientific) and using an Ultimate-3000 system (Dionex, Thermo Scientific, Bremen, Germany) coupled to an LTQ-Velos Orbitrap Elite mass spectrometer (Thermo Scientific, Waltham, MA, USA). Firstly, 6 μL of peptide mixture were loaded on a C-18 pre-column at a constant flow rate of 5 μL/min in phase A. Total elution time for all runs was 360 min for a gradient of 2–35% phase B (99.9% acetonitrile, 0.1% formic acid) at a constant flow rate of 300 nL/min.
| 4 | 0biomedical
| 0Study
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316,083 |
To determine the differential expression of genes in LV-GFP and LV-EED containing ARC-ME fragments we used the gene-level edgeR100 analysis package. We performed an initial trimming and adapter removal pass using Trimmomatic101. Reads that passed Trimmomatic processing were aligned to the rn6 build of the rat genome with Bowtie2/Tophat2102,103, and assigned to gene-level genomic features with the Rsubread featureCounts package based on the Ensembl 83 annotation set. Differential expression between LV-GFP and LV-EED injected groups was analyzed using the generalized linear modeling approaches implemented in edgeR37. Lists of differentially expressed genes/transcripts were identified based on significance of pairwise comparisons. A subset of genes found to be differentially expressed was selected for subsequent RT-qPCR confirmation.
| 4 | 0biomedical
| 0Study
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33,211 |
The genome of strain Pf12BT was sequenced using paired-end Illumina sequencing at Hokkaido System Science Co., Ltd. (Japan). From a library with 350 bp inserts, the 10,511,386 reads were generated. After trimming of the reads, a total of 9,393,309 high-quality filtered paired end reads with a hash length of 95 bp were obtained. Reads were assembled de novo using Velvet version 1.2.08 into 26 high quality scaffolds. Gap closing analysis in these scaffolds was performed using Platanus version 1.2.1.
| 4 | 0biomedical
| 0Study
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138,734 |
Wastewater (24 h composite samples) was collected from the inflow at 14 NYC wastewater treatment plants and RNA isolated according to our previously published protocol2. While samples have been obtained and processed on a weekly basis since June 2020, we report herein the outcome of sequencing runs performed approximately every 2 weeks between January and June 2021. The specific dates of sampling were January 31st, February 28th, March 14th, April 5th, April 19th, May 10th, May 26th, June 7th, June 14th, and June 28th.
| 3 | 0biomedical
| 0Study
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325,904 |
In addition to hypoxia, hypocapnia associated with hypoxic hyperventilation also appears to modulate thermoregulation, as evidenced in cats (Gautier et al. 1989). However, while end-tidal CO2 partial pressure was not assessed within the current study, no main effect was observed for hypoxia on either respiratory rate, minute ventilation, or exhaled CO2, such as hypoxia-induced hyperventilation, and thus, hypocapnia appears to be negligible. The interaction of hypocapnia with the current findings warrants further investigation.
| 4 | 0biomedical
| 0Study
|
386,053 |
As presented in Fig. 10, the ROS production after the treatment with rutoside and then MB-PDT increased in A375 melanoma cancer cells compared to the free MB and control groups. It can be suggested that, ROS production could act as one of the main factors in the death mechanism of cancer cells using rutoside as pre-treatment and then MB-PDT.Fig. 10Effects of rutoside (50 μg/mL) as pre-treatment and then MB-PDT on intracellular ROS generation in A375 cells. The cells were stained with DCFH-DA (2 mM), and analyzed by flow cytometry. R rutoside
| 4 | 0biomedical
| 0Study
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48,616 |
Firstly, eight genetic variants (selected using a linkage disequilibrium filter out of 20 genotyped variants) at the 17q21 locus were tested for association (one at a time) with methylation levels at 26 CpG sites (one at a time) in the same region. The model included the main effects of breastfeeding and genetic variants and an interaction term between these variables. 10 out of the 26 CpGs were influenced by interactions between breastfeeding and genetic variants. This suggests that breastfeeding may modulate the epigenetic effects of some methylation quantitative trait loci (ie, the epigenetic effects of those mQTLs vary according to breastfeeding status). However, it is also possible that some genetic profiles reduce the plasticity of the epigenome, thus mitigating the epigenetic effects of environmental factors. For example, a single nucleotide polymorphism may abrogate a CpG site, thus preventing it from being methylated regardless of the states of other determinants of methylation levels at this specific site. It was not possible to investigate the interaction mechanisms of these associations because neither regression coefficients nor stratified results were available.
| 4 | 0biomedical
| 0Study
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122,150 |
For plate assays, 5 µl of cells from exponential phase in LB broth (supplemented with 1 mM arabinose and antibiotics when required) were spotted on LB-agar plates with or without 2% (w/v) SDS (also supplemented with 1 mM arabinose and antibiotics where required), using five serial dilutions (from 10−2 to 10−6). Plates were incubated overnight at 37 °C before imaging on a Syngene GBox gel documentation system.
| 4 | 0biomedical
| 0Study
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237,324 |
A high-quality ChIP-seq experiment typically results in a high coverage of sequenced reads at discrete regions throughout the genome, again referred to as “peaks,” although in low-quality ChIP-seq datasets, peaks are hard to distinguish from background signal (Figure 2). The shape, location, magnitude, and sensitivity to identify peaks differ depending on the protein–DNA interaction being measured and the complexity and sequencing coverage of the sequencing library (Hower et al., 2011; Jung et al., 2014). For example, TF peaks are typically sharp and enriched near the transcriptional start site (TSS), upstream and downstream of genes, whereas histone modifications and histone variant peaks are generally broader. The patterns and distribution of histone modifications have been well characterized in certain plant genomes (Zhang et al., 2007; Bernatavichute et al., 2008; Zhang et al., 2009; Li et al., 2019; Lu et al., 2019; Ricci et al., 2019; Montgomery et al., 2020; Zhao et al., 2020). There is a high similarity in the patterns and distributions of histone modifications among plant genomes. For example, trimethylation of lysine 4 of histone 3 (H3K4me3) is highly enriched around the TSS in plant genomes, whereas H3K4me2 and H3K4me1 are found within gene bodies (Zhang et al., 2009). These expected patterns and distributions at genes or other genomic features can be used to evaluate the quality of the enrichment. A novel method referred to as Cleavage Under Targets and Release Using Nuclease or Cleavage Under Targets and Tagmentation was recently developed to measure protein–DNA interactions (Skene and Henikoff, 2017; Kaya-Okur et al., 2019). Although the method is unique, most of the same methods used for the evaluation of data quality are the same as ChIP-seq. Additionally, Tn5-based chromatin profiling methods are biased toward detecting accessible chromatin, which requires extra scrutiny in downstream analyses (Wang and Zhang, 2021).
| 5 | 0biomedical
| 0Study
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271,158 |
In , a novel DoS attack called H2DoS was proposed. This attack exploits the flow control mechanism of HTTP/2. The authors also suggested preventive changes in the web server configuration. The study in from 2019 presented a next-generation application DDoS called Multiplexed Asymmetric DDoS Attack, which causes the victim’s processor to overload by exploiting HTTP/2 multiplexing. HTTP/2 can also be exploited for a man-in-the-middle attack via DNS cache poisoning and a spoofed TLS (Transport Layer Security) certificate, as published in .
| 1 | 2other
| 1Other
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138,822 |
SIS49D applied to adult male and female C57BL/6J mice decreased the number of hippocampal Ki67-positive neurons in males and females, without hippocampal DCX-positive cells were only decreased in females when tested five weeks following SIS (Yohn et al., 2019). Nineteen-day SIS applied to young-adult male SJL mice induced complex changes in subunits of big potassium (BK) channels, which are involved in BK channel excitability, in the adrenal medulla and pituitary gland (Chatterjee et al., 2009).
| 4 | 0biomedical
| 0Study
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343,621 |
Sand flies were collected from three sites (Galgamuwa, Maho, and Polpithigama) in Kurunegala District, using three standard entomological techniques, namely cattle-baited net trap (CBNT), light trap (LT), and outdoor hand catch (HC), using a battery operated aspirator. The collected sand flies were housed in insect cages until the transportation to the insectary facility at the Department of Parasitology, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka.
| 3 | 0biomedical
| 0Study
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316,541 |
Therefore, the curcumin cytotoxicity in breast cancer might be related to the chemotherapeutic effect of this compound in drug-resistant breast cancer cells. Previous studies indicated that curcumin growth inhibitory effect in cancer cells might be attributed to its inhibitory effect on NF-KB related pathway which leads to cellular apoptotic response and the modulation of arachidonic acid metabolism .
| 4 | 0biomedical
| 0Study
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311,337 |
To get first hints on properties of the novel Rgs proteins, we analyzed their protein sequences with the Phobius transmembrane topology prediction tool (19). In RgsA and RgsS, a large N-terminal cytoplasmic domain and a C-terminal periplasmic domain separated by a transmembrane helix were predicted. RgsE was predicted to be primarily located in the cytoplasm, anchored in the inner membrane via two transmembrane helices (Fig. 2B; Data Set S2). Periplasmic location and signal peptides were predicted for RgsB, RgsD, RgsG, RgsH, and RgsF, whereas RgsC was suggested to be an extracytoplasmic protein without a signal peptide (Fig. 2B; Data Set S2).
| 4 | 0biomedical
| 0Study
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16,069 |
In agreement with Walters & Walters our data confirm that lapwings reoccupied their territories even before the floodwaters completely receded (S1A Fig, Fig 1A and 1B; Fig 3: vcA, S1 and S2 Audios). Moreover, the low nocturnal activity of V. chilensis during moonlight nights in late April suggests that the lapwings roosted in one of the distant terra firma areas rather than on their inundated territories.
| 1 | 2other
| 0Study
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104,691 |
T-cells are broadly classified as naïve or antigen experienced based on their encounter with antigen and differentiation status. Antigen specific T-cells are further classified based on their differentiation status into central memory (TCM), effector memory (TEM), and terminally differentiated effector cells (TE) . Recent emerging data describes a population of T-cells with stem cell like properties (TSCM) that would have the potential for prolonged persistence and further replication in-vivo [28–30]. In earlier clinical trials, adoptively transferred anti-tumor T-cells clones, even when infused in large numbers, demonstrated only limited clinical efficacy, which was primarily attributed to the lack of persistence of the T-cells infused . Subsequent studies evaluated the potential of different T-cell subsets with respect to in-vivo activity and persistence. In both animal models and humans, recent studies have shown that adoptively transferred TCM phenotype T-cells, with high expression of L-selectin (CD62L), CCR7 and CD44 provide durable immunity against infections such as CMV [31–33]. Berger et al. demonstrated that TCM derived T-cells when adoptively transferred into macaques persisted for prolonged periods in-vivo and re-acquired the phenotypic markers of TCM cells, and subsequently Wang et. al. showed prolonged engraftment of TCM derived cells in an immunodeficient mouse model. In TCR transgenic mouse models, Restifo et al. have demonstrated that antigen specific naïve and TCM cells are more effective than TE cells in eradicating large established tumors, and paradoxically, differentiated T-cells displaying high functional activity in-vitro were less effective in eradicating tumors in-vivo . In recent clinical trials, persistence of adoptively transferred T-cells has been correlated with regression of disease . Therefore, such TCM cells are a desirable T- cell population for adoptive immunotherapy because they have the potential to provide durable protection against disease by virtue of their lymphoid homing properties in-vivo , lending to their prolonged survival after infusion.
| 4 | 0biomedical
| 0Study
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390,151 |
Treatment still relies on surgical resection. Tumor recurrence is infrequent. With the wider use of immunohistochemistry, these lesions can be more clearly differentiated. However, in settings where access to this resource is unavailable, misdiagnoses may occur. Retroperitoneal malignancies such as liposarcomas can remain undiagnosed, drastically worsening patient prognosis.
| 2 | 0biomedical
| 1Other
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108,076 |
On the contrary, for the complete model, the Weber number is higher or very close to 12.3 for a wide range of velocities. Hence, the possibility of entrapping powder can be easily predicted. Considering the values in Table 1, it can be assessed that since 480 s the risk of defect formation is extremely high.
| 2 | 2other
| 0Study
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81,210 |
Her treatment began with oral nystatin drops four times daily; miconazole gel, local application four times daily; IV Penetrex (enoxacin), a broad-spectrum fluoroquinolone antibacterial agent, 4.5 g three times daily; paracetamol, 500 mg two tablets if needed; cetirizine, 10 mg orally at night; calamine lotion local application three times daily; Fucidin®, a topical antibiotic ointment, local application three times daily; IV tramadol, 25 mg diluted in 20 cc normal saline twice daily; Vitamin D3 injection once weekly; IV hydrocortisone sodium succinate, 100 mg three times daily; prednisolone, 5 mg orally three times daily; linezolid, 400 mg orally twice daily; omeprazole, 40 mg orally twice daily; and diclofenac sodium, 50 mg twice daily.
| 2 | 1clinical
| 3Clinical case
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183,264 |
Coronavirus disease 2019 (COVID-19) and measles are a huge burden on the health systems of Africa. Measles is caused by the Rubeola virus causing immunosuppression (i.e., fever, seizures, cough, flu, blindness, rash, diarrhea, pneumonia, and brain inflammation) that lead to fatality mainly among children below 14 years. It is the most transmittable virus ever known. The estimated mortality due to measles according to reports from the weekly epidemiology reports has increased from 89,780 in 2016 to 207,500 in 2019 . Likewise, COVID-19 is caused by novel coronavirus inflicting respiratory illness outbreak with 1.81 million deaths in the 1st year . Since its emergence in China, it has been declared a global health threat.
| 2 | 0biomedical
| 1Other
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4,862 |
The response to preoperative chemotherapy was evaluated in 10 of 19 patients with ovarian and extra-ovarian metastases. Nearly all patients with ovarian metastases were unresponsive to preoperative chemotherapy, but those with extra-ovarian metastases had good responses (Figure 3A and Supplementary Table 2). Of the 10 patients who received preoperative chemotherapy, 9 had measurable metastases to extra-ovarian sites and to the ovaries; 5 of these 9 patients (56%) achieved partial response (PR) or complete response (CR) at the extra-ovarian sites. On the other hand, only 1 of the 9 patients (11%) achieved stable disease (SD) at ovarian sites, whereas 8 of the 9 patients (89%) exhibited progressive disease (PD).
| 4 | 0biomedical
| 0Study
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136,747 |
Then, using the measured rate of incomplete division based on live imaging and adjusting just four fit parameters (the effective rates of syncytial fragmentation and cell loss, the period over which cell loss occurs for the GFRα1+ compartment, and the effective proliferation rate of GFRα1– cells), we found that the model could quantitatively capture the wide range of clone behaviors for GFRα1- and Ngn3-induced donor cells from TP2 through to TP30. These include the clone survival rate (i.e., the probability that a clone maintained one or more GFRα1+ cells; Figure 4B; Figure S3A), the average and distribution of clone size (as scored by the constituent number of GFRα1+ cells; Figures 4C and 4E; Figures S3B and S3D), the length composition of syncytial units in the GFRα1+ compartment (Figure 4F; Figure S3E), and production of GFRα1– cells (Figure 4D; Figure S3C), which were all predicted by the model with high accuracy (Figure S3F–S3H; STAR Methods). Such a high predictive capacity of the model, despite its simplicity, lead to the conclusion that the divergent clonal fates of donor cells following transplantation may simply be a consequence of stochastic fate selection of equipotent SSCs rather than due to innate heterogeneity in the potency of SSCs or local niche regulation.
| 5 | 0biomedical
| 0Study
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225,140 |
A total of 14 regions were identified by the Δ(SNP-index) value or the G-value (Table 2 and Figures 2, 3). These loci were located on chromosomes 1, 3–7, and 9, and the interval size ranged from 0.43 to 3.54 Mb (Table 2). Four unique QTL for ML—qML1.1 (Pop5, 6.57–8.12 Mb), qML1.2 (Pop4, 14.21–17.32 Mb), qML1.3 (Pop2, Pop3, Pop6, and Pop8, 18.59–21.12 Mb), and qML1.4 (Pop4 and Pop 12, 36.59–39.67 Mb)—were identified on chromosome 1. Three adjacent QTL were isolated on chromosome 3. Of these, qML3.1 was detected in Pop3 and located at the interval of 25.12–27.50 Mb, whereas qML3.2 was discovered in Pop8 and Pop12 and fixed at 27.21–32.30 Mb. qML3.3, unearthed in Pop9, was set at the interval of 35.72–36.15 Mb. Two loci were found to exist on chromosome 4. Of these, qML4.1 was recognized at Pop10 and situated at the interval of 19.59–21.92 Mb, whereas qML4.2, fixed at 25.50–27.13 Mb, was discovered at Pop8. On chromosome 5, only qML5.1 was identified from Pop8 and located at the 8.99- to 11.03-Mb region. Another genomic region (2.59–5.12 Mb) identified on chromosome 6 with Δ(SNP-index) plots greater than the statistical confidence intervals (P < 0.05) was named as qML6.1. Two adjacent QTL (qML7.1 and qML1.2) were identified on chromosome 7. Besides, qML7.1 (4.35–8.65 Mb) was identified in Pop4, Pop6, and Pop9, whereas qML7.2 (13.69–18.49 Mb) was identified in Pop4, Pop6, Pop8, Pop9, Pop11, and Pop12. In addition, only one locus, qML9.1 (11.53–15.28 Mb), was identified on chromosome 9 in Pop5 and Pop12.
| 4 | 0biomedical
| 0Study
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291,698 |
From this model, the replacement rate for an infected breeding is defined as:(16)αpath=μr+m−μris=α+m−μris where is is the proportion of symptomatic infected goats in a given time. Thus, according to the relation between the disease-related mortality and the reproduction rate for the Symptomatic infected compartment, the article define how much larger the replacement rate should be in the presence of CAE infection.
| 4 | 0biomedical
| 0Study
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154,664 |
Two researchers (C.Y.C, M.L.G) searched the databases, identified duplicate articles, and excluded articles in which the participants were not women in labor for delivery. These two researchers screened the full-text articles to independently confirm the included articles, and the third researcher (C.J.H) made the final decision in the case of disagreement between the other two. Fig 1 shows the preferred reporting items for systematic reviews and meta-analyses (PRISMA) for searching and identifying the included studies. The results from the two independent reviewers regarding the suitability of articles were compared. If the meaning of the study title was unclear, the article was investigated further. Among the studies, 20 were related to labor pain articles. After removing 12 non-RCT or non-CCT papers, eight were selected in the final list for analysis, as shown in Fig 1.
| 4 | 0biomedical
| 0Study
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17,718 |
Polyphyllin G (purity > 98%) was purchased from Santa Cruz Biotechnology (Santa Cruz, CA) and was dissolved in dimethyl sulfoxide (DMSO) and diluted in cell culture medium to the final concentration before use. The final concentration of DMSO for all treatments was consistently less than 0.1%. All cell culture-related reagents were purchased from Invitrogen (Carlsbad, CA). DAPI dye, propidium iodide (PI), RNase A, protease inhibitor cocktail, phosphatase inhibitor cocktail, and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) were purchased from Sigma-Aldrich (St Louis, MO). Antibody against cleaved caspase-3, -8, and -9, cleaved poly (ADP-ribose) polymerase (PARP), Bcl-2, Bcl-xL, Bax, LC3B, Beclin1, p62, p-AKT, AKT, p-ERK1/2, ERK1/2, p-JNK1/2, JNK1/2, p-p38, p38, PI3K, mTOR (ser2448), mTOR, Raptor, Rictor, GβL and β-actin were purchased from Cell Signaling Technology (Danvers, MA). Specific inhibitors for AKT inhibitor (LY294002), ERK1/2 (U0126), p38 MAPK (SB203580), JNK (SP600125), z-VAD-FMK, Wortmannin and Bafilomycin A1 (Baf A1) were purchased from Santa Cruz Biotechnology (Santa Cruz, CA).
| 2 | 0biomedical
| 1Other
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135,377 |
The effective reproduction number, or Rt, is defined as “the expected number of new infections caused by an infectious individual in a population where some individuals may no longer be susceptible” . Calculation of Rt can provide information on dynamics of COVID-19 transmission during specific time-steps . To eliminate virus transmission, Rt will need to be reduced to 0. However, to bring the pandemic under control, the Rt must be less than 1 . Therefore, estimates of situation- and time-specific values of Rt can help us to understand the extent of pathogen transmissibility at a given point in time. Among the different methods that have been developed to estimate Rt, we selected the instantaneous reproductive number method developed by Cori et al. which is as follows:(2)Rt=It∑s=1tIt−sws
| 4 | 0biomedical
| 0Study
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356,643 |
The results of this research are expected to enable a situation diagnosis in such a way that will make it possible to adapt the recommended interventions to optimize the use of cesarean section. Our findings will contribute to the design of strategies for a more context-sensible implementation. The possibility of having information from the point of view of health professionals and women will increase the chances of acceptance and sustainability of those interventions. More specifically, the results of this research will contribute to the preliminary qualitative work in which the design and implementation of the QUALI-DEC (Adequate use of cesarean section by means of quality decision making by women and health professionals “QUALI-DEC”) study intervention will be based . QUALI-DEC is a strategy with four active ingredients: (1) opinion leaders to improve physicians' compliance with evidence-based practices; (2) auditing of the cesarean section indications to help providers identify potentially unnecessary cesarean sections; (3) tool to help women make an informed decision as regards the type of delivery; and (4) Companion chosen by the woman during delivery to support women during vaginal delivery. This research will be implemented in four countries, including Argentina.
| 4 | 0biomedical
| 0Study
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128,272 |
Most of the family research on similarity or accuracy focuses on parent–child dyads or on romantic dyads. The similarity is, for example, investigated in studies on value similarity (Hoellger et al., 2020), personality similarity (Wang et al., 2018), or similarity in the perception of relationship conflict in parent–adolescent child dyads (Mastrotheodoros et al., 2020). Accuracy is investigated especially regarding bias in perception of characteristics of the partner (Pusch et al., 2021). Fewer studies investigate similarity and accuracy on the same construct in the same study. One exception is Decuyper et al. (2012) who studied personality similarity and accuracy in dating and married dyads.
| 2 | 2other
| 2Review
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148,976 |
We opt to restrict the survey to publications from 2009 onwards for several reasons: First, the publication of the Surviving Sepsis Campaign in 2008 (48) was a sentinel event for sepsis care and resulted in wide uptake. Second, the epidemiology of sepsis changed substantially in most geographical regions with a shift from meningococcal sepsis to other pathogens (11). Third, fundamental critical care treatment approaches developed substantially during 1990–2008 with the establishment of interventions such as early goal directed therapy or low tidal volume ventilation, and optimal glucose management, and the time from 2009 onwards is more likely comparable to current practice.
| 4 | 0biomedical
| 0Study
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109,355 |
To verify the effectiveness of the proposed new TSPSO MPP scheme under PSCs, the conventional P&O method and PSO algorithm are also applied to the cascaded five-level PV-converter system and the results are compared. The step voltage of the conventional P&O method used in the paper is set 0.1 V. Table 3 shows the basic parameters used in the PSO algorithm and the proposed algorithm, including the inertia weight ω, acceleration factors c 1 and c 2, number of particles S, number of groups M, and maximum iterative number J.Table 3The basic parameters of two algorithms.Method c 1 c 2 w S M J PSO0.60.80.512—3TSPSO0.60.8self-adaption (ω max = 0.9, ω min = 0.4)1233
| 2 | 2other
| 0Study
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279,781 |
We dissolved 3 g (0.091 mol) n-dodecylbenzenesulfonic acid (HDBSA: Tokyo Kasei Kogyo Co., Tokyo, Japan) in 50 mL of de-ionized water. The mixture was slowly stirred until a homogeneous solution was obtained, followed by the addition of 9 g (0.0968 mol) of aniline (Tokyo Kasei Kogyo Co., Tokyo, Japan); the solution was stirred until clear. Eventually, Fe3O4 or Fe3O4(OA) obtained from the previous experiment was added, and the mixture was stirred again until homogeneous so to obtain a water phase. The concentration of DBSA was about 1.82 M, well above the critical concentration (CMC) to create micelles.
| 4 | 0biomedical
| 0Study
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340,551 |
The adjacency and non-adjacency of KERs was considered by Hassan et al. (2017), Doering et al. (2018) and Foran et al. (2019). Hassan et al. (2017) developed the non-adjacent KER using literature data to model the gaps. Doering et al. (2018) used non-adjacent KERs to check and verify the linkage between KEs and the AO. Foran et al. (2019) proposed a modular approach as a feasible solution to the AOPs lacking empirical dose- and time-response data. Zgheib et al. (2019) used a mathematical inversion technique to derive chemical-independent KERs from a series of dose–time–response relationships. Four qAOPs incorporated kinetics: Battistoni et al. (2019), Hassan et al. (2017), Margiotta-Casaluci et al. (2016) and Muller et al. (2015). Furthermore, Battistoni et al. (2019) included a modulating factor, i.e. identifying that ethanol can also inhibit retinoic acid synthesis, and a negative feedback loop, i.e. regulation of retinoic acid resulting from increased synthesis of CYP26A1. Doering et al. (2018, 2019) developed a qAOP that is applicable across species. The uncertainty of the model was considered by Hassan et al. (2017), Doering et al. (2018), Battistoni et al. (2019) and Foran et al. (2019). Sensitivity analysis was performed by Margiotta-Casaluci et al. (2016) and Zgheib et al. (2019). The mathematical equations and/or the code of the qAOP models of Hassan et al. (2017), Doering et al. (2018), Zgheib et al. (2019) and Muller et al. (2015) are accessible.
| 4 | 0biomedical
| 2Review
|
345,706 |
Two months after neonate release in both 2018 and 2019 trials, the soil was gently removed from the rootstock roots. They were carefully examined for any signs left by larvae while boring (gum secretion and erosion) and, then, peeled to detect live or dead larvae. The infestation and gumming rates were calculated as percentage of plants with boring or gumming signs, respectively, out of the total number of plants assayed for each treatment. In the 2018 trial, the plant-colonization rate by C. tenebrionis larvae was expressed as percentage of plants infested by at least one live larva per treatment out of total number of plants assayed for each treatment. The results were binomial and, due to low number of replicates, statistical analysis was not done. In the 2019 trial, the larval colonization rate of the plants was expressed as percentage of number of larvae found in the infested rootstock out of the total number of neonates released per pot. At the end of the 2019 trial, the mycosis rate was calculated as a percentage of larvae with mycosis out of the total number of larvae released to each plant. The length of the galleries excavated by the larvae was also measured.
| 4 | 0biomedical
| 0Study
|
54,309 |
As per cross-over design, all participants received the intervention (TN), either during the first 12 months or the last 12 months of the study. When in the TN group, participants attended a first face-to-face medical and nursing consultation at the start of TN (T0 for group 1; T12 for group 2). This visit allowed the TN nurse to introduce herself, explain how the telephone consultation would be carried out and get to know the child’s clinical, social and family situation. For the following 12 months, the participants received a monthly telephone call. In addition, the participating parent or child was given a telephone number to contact, when needed, the TN nurse on duty during normal office hours on week days.
| 4 | 0biomedical
| 0Study
|
27,860 |
In order to observe the role of the CNT-immobilization in influencing the entire structure of the receptor, root-mean-square deviations (RMSDs) of backbone atoms for all the OR systems under study were calculated and the result is shown in Fig. 1. The results show that the RMSD values of the four systems approach to convergence during the last several hundred nanoseconds. The adsorption induces significant variations on the structure of the receptor, as evidenced by larger RMSD values of the immobilized receptor than that of the free one. Compared to the free receptors, the immobilized ones present smaller RMSD fluctuations, implying enhanced rigidity upon CNT-immobilization and supporting the experimental observations that the immobilization could improve the stability of proteins to some extent25,26. In addition, the RMSD values of the hOR2AG1 homology model are significantly larger than those of the opsins both for the CNT-immobilized type and the free one, which should be attributed to instability of the homology model.Figure 1RMSD values of backbone atoms for the two OR models during the 1000 ns simulation time. The RMSD values are deviations from the crystal structure for the opsin model and from the initial homology structure for the hOR2AG1 model.
| 4 | 0biomedical
| 0Study
|
34,797 |
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) with human leukocyte antigen (HLA)-identical sibling or unrelated donor is the main way for treatment for high-risk hematological malignancies. For patients without a suitable donor, especially those in urgent need of transplantation, haploidentical allo-HSCT (HID-SCT) is an option . HID-SCT was unsuccessful for many years because of graft rejection and high incidence of acute graft-versus-host disease (GVHD), but the progress in GVHD prophylaxis and conditioning regimen has made HID-SCT possible . A multicenter phase-2 study from the Chinese Bone Marrow Transplant Cooperative Group (CBMTCG) showed that the combination of cyclosporine A, methotrexate, mycophenolate mofetil (CsA + MTX + MMF) for GVHD prophylaxis significantly decreased the incidence of acute GVHD without an increase in relapse or any adverse impact on survival in standard-risk patients compared with historical controls in ISD-SCT . Similarly, ATG deletes T lymphocytes chronically in vivo, and prevents GVHD without increasing the risks of relapse . Some institutions demonstrated HID-SCT using conditioning regimen including ATG yielded similar outcomes to ISD-SCT for hematological malignancies . Some studies also indicated similar outcomes after HID-SCT compared to HLA-identical allo-HSCT . At present, HID-SCT has been accepted by many transplantation centers. Over the past decades, much progress has been made to improve the outcomes of transplantation, including in the conditioning regimen; prophylaxis; lower cumulative incidence rates of GVHD, transplantation-related mortality/ no-relapse mortality (TRM/NRM) and relapse; higher rates of OS and DFS/LFS/PFS. However, there haven’t been well-controlled studies to compare the efficacy of HID-SCT and ISD-SCT. Therefore, our meta-analysis aims to investigate whether HID-SCT has similar outcomes compared with ISD-SCT.
| 5 | 0biomedical
| 0Study
|
278,978 |
In our study, we saw a malposition and need for correction in only 1.9% of pedicle approaches (3/154). 98.1% of accurate pedicle approaches is an excellent result of our series compared to the previous studies with rates ranging from 78 to 100% in open and MIS surgical procedures [14, 24–27, 29–31]. The fact that an additional haptic control of intrapedicular course of the implant is not possible in MIS surgery did not have any effect on accuracy in our series. The accuracy of the MIS cohort did not show a statistical significant worse value, there was even a tendency towards higher accuracy in the MIS-group. This shows the proof of feasibility for the prescribed technique that has potential to further improve patient safety.
| 4 | 0biomedical
| 0Study
|
153,189 |
Neuro-oncological ventral antigens 1 and 2 (NOVA1 and NOVA2) are two members of the NOVA family, regulating neuron-specific alternative splicing. They belong to splicing factors and mainly enriched in brain tissue and are responsible for neuronal viability and maturity. NOVA1 is distributed in the cerebellum and spine, whereas NOVA2 is located in the cortex. NOVAs regulates various receptors and voltage-gated channels which are critical for the signal transduction of neuromuscular junctions. As an alternative splicing method for a key regulator of glycine α2 exon 3A (GlyRα2E3A) pre-mRNA splicing, NOVA1 recognizes an adjacent intronic splice site, alternatively inducing exon 3A inclusion. NOVA1, together with TDP-43, participates in RNA recognition and induces various neurodegenerative diseases such as schizophrenia and amyotrophic lateral sclerosis . NOVA1 participates in the splicing of RNA-binding protein RBM8A and regulates RNA metabolism, causing neurological damage-like symptoms of AD.
| 4 | 0biomedical
| 0Study
|
38,453 |
We measured cell proliferation in PDAC after miR-145 mimic or selinexor treatment. We found that the miR-145 mimic or selinexor treatment inhibited proliferation rate of PDAC cells (Figure 3A-3D). These results suggest that inhibition of cellular proliferation by selinexor is at least partially controlled through induction of miR-145 expression.
| 4 | 0biomedical
| 0Study
|
169,520 |
Importantly, the accumulation of RAD-51 foci and embryonic lethality of app-1(tm1715) mutants is rescued by a single-copy transgene that expresses wild type APP-1 using the regulatory elements of the app-1 gene (S1D Fig). These findings confirm that APP-1 is required for normal viability and to prevent the accumulation of SPO-11-independent DNA damage in the germ line.
| 4 | 0biomedical
| 0Study
|
188,785 |
Fragment-based drug discovery (FBDD) is a lead generation strategy based on the screening of small polar compounds that typically exhibit low affinity towards protein targets. Previous binding thermodynamics studies revealed that fragments bind to protein hotspots by choice1–3. Their polar character prevents apolar desolvation compensation for rigid body entropy loss4 and generates productive fragment binding. Indeed, fragments have been shown to bind to protein hotspots by a limited number of optimal geometry H-bonds5,6. Good overlap with the structure-based pharmacophores at the primary hotspot (binding site region with the largest contribution to the ligand binding free energy) leads to robust binding3. Therefore the nature and quality of binding interactions is fundamental to the choice of fragment starting points for drug discovery programs7. Recent studies have shown that there is still significant controversy on the applicability of the fragment-based approach to drug discovery3,8. When reviewing fragment starting points, target specificity was often identified as an issue. An analysis of the active fragments from 35 campaigns on 20 targets at Novartis indicated that 63% of the screened fragments had never been observed as hits9. Instead, the team promoted privileged fragments as high-value library members active on more than one target. Another analysis found that 20% of fragments in crystallized complexes in the Protein Data Bank (PDB) have multiple protein targets10. Since there is often an opportunity to build selectivity while evolving fragments11, features encoded in frequent hitter fragments can productively be considered part of a representative set of binding pharmacophores. The evolutionarily conserved nature of binding hotspots12 and the conservation of pharmacophores found in certain target classes13, suggests that the number of distinct structure-based pharmacophores should be limited. Our idea was to identify the set of fragment pharmacophores that covers the diversity of known hotspots and use them to design a small, efficient fragment library to recognize this diversity.
| 5 | 0biomedical
| 0Study
|
122,847 |
Pre-operative and 6-month post-operative EEGs were performed in all four patients. Pre-operative EEGs were recorded during resting-state for 5 min, while post-operative EEGs were recorded for 5 min under the following two conditions: (1) CI switch-on with a music stimulus (classical music from a radio channel) to the CI ear presented directly to the external audio processor via an audio cable at the most comfortable loudness level for each patient (CI-on); and (2) CI switch-off with no sound stimulus (CI-off).
| 4 | 0biomedical
| 0Study
|
112,213 |
Here we have taken advantage of long and short read technologies to produce an annotated and highly contiguous assembly of the haddock genome, with comparable gene content and assembly statistics to the recently released Atlantic cod genome assembly (Table 1). The genic completeness of the assembly is high, as seen by the BUSCO score, where > 90% of the 4584 genes are found complete (Table 1). PacBio reads span more repeated regions than Illumina reads, and the contig N50 is therefore longer for the haddock assembly than other fishes sequenced with only Illumina reads, for instance the Asian arowana and the seahorse . With the increased affordability, availability and usage of such long-read sequencing technologies as PacBio and Oxford Nanopore reads, more complete assemblies for diverse species are likely to arrive in near future.
| 4 | 0biomedical
| 0Study
|
181,831 |
Malnutrition is still one of the leading causes of morbidity and mortality among children worldwide. It has been directly or indirectly responsible for 60 percent of the 10.9 million deaths among children under the age of five each year, with two-thirds of these deaths frequently associated with inappropriate feeding practices [1, 2]. Children are particularly vulnerable to malnutrition in developing countries due to inadequate dietary intakes, a lack of appropriate care, and inequitable food distribution within households [3, 4].
| 4 | 0biomedical
| 2Review
|
149,743 |
A total of 9,974 MM-InDels with random DNA sequences of insertion or deletion were filtered, and the occurrence of MM-InDels with random sequences was further characterized. In fact, there should be much more MM-InDels with random DNA sequences that can be observed when lowering the filtering threshold of allele frequency. For the generation of MM-InDels with random sequences, the more frequent presence of adjacent InDels was observed within 20 bp (Figure 2A), while most InDels within multi-InDel markers were also under 20 bp (95.16%). In fact, the enrichment of neighboring polymorphisms has been reported in the human genome (Hodgkinson and Eyre-Walker, 2010), which is in line with our observation. A correlation of the separate mutational events forming MM-InDels might be assumed in a closer distance with shorter mutational sequence lengths.
| 4 | 0biomedical
| 0Study
|
55,218 |
Each record in the data collection corresponds to one participant. The first step of the preliminary statistical analysis was to distribute the obtained data into three categories. The first category Basic data contains the following information about each participant:1.the group the participant belongs to (0 – the member of the Mensa Czech Republic, 1 – the person visiting the Days of Science and Technology 2016),2.gender (0 male, 1 – female),3.age.
| 2 | 0biomedical
| 0Study
|
63,180 |
Percent missing: BMI (0.1), education level (0.3), household income (15.3), medical insurance (0.4), smoking status (0.7), physical activity (0.06), alcohol consumption (2.6), occupation (0.06), hypertension (0.06), diabetes (1.1), hyperlipidemia (1.4), LVMI (0.1), LV hypertrophy (0.1), LV systolic diameter (0.1)
| 2 | 0biomedical
| 0Study
|
337,786 |
Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.
| 1 | 2other
| 1Other
|
282,481 |
Genetic studies of P. p. phocoena show that a geographic stratification exists, resulting in the formation of two or three subpopulations depending on the source (Wiemann et al., 2010): apart from the mentioned Baltic Sea subpopulation (Baltic Proper), other subpopulations have been identified in the North Sea (including Skattegat) and the Belt Sea (Wiemann et al., 2011). These subpopulations demonstrate a minor dispersal level, amounting to about 1%, as the exchange of specimens between them is low in relation to the total population size (Wiemann et al., 2011). However, these subpopulations are characterized by substantial asymmetry in size, with only several hundred specimens recorded within the Baltic Proper against tens of thousands in the remaining regions (Hammond et al., 2002). Indeed, the harbor porpoises of the Baltic Proper subpopulation differ from other subpopulations of this subspecies in terms of morphology and genetics, and as such, they should be subject to a special level of conservation (Wiemann et al., 2010).
| 4 | 0biomedical
| 0Study
|
33,712 |
To show that the initial cluster centroids obtained by density-based algorithm can quicken the convergence of clustering algorithm, the traditional FCM is adopted for verification. The number of clusters is assigned as the true value, with the convergence threshold being 10−5. Because the random selection of initial cluster centroids has a large influence on FCM, the experiment of each dataset is done repeatedly for 50 times, and the round numbers of the mean of algorithmic iterations are compared. The specific experimental result is shown in Table 3.
| 2 | 2other
| 0Study
|
73,817 |
STAs are one of NICE's decision‐making processes in which evidence about a selected technology (often medicines) is evaluated in three distinct phases (scoping, assessment and appraisal). In the last phase of this process, an independent appraisal committee evaluates evidence in a meeting (or multiple meetings), partly held in public but with the latter half taking place in a “closed” session. During the meeting(s), the committee considers evidence based on clinical and cost‐effectiveness, as well as statements expressed by patients, commissioning experts and clinical specialists.5 The Institute encourages patient experts attending the meeting to provide both written and oral commentary about their personal view in the current management of the condition and the expected role and use of the technology—in particular how it might provide benefit to patients.
| 3 | 0biomedical
| 1Other
|
187,435 |
IMPC and IDC-NOS tissue samples were collected for primary cell culture. The samples were washed twice in normal saline and cut into small pieces (< 1 mm). Then 1.5 mL cell dispersing enzyme EZ solution was added, and samples were digested at 37 °C for 2 h on an oscillator. After the digestion was completed (i.e., many cells were observed to be separated from the tissue under a microscope), the cells were filtered with a 308 µM nylon net. The cell precipitates were re-suspended in 3 mL modified medium, then transferred to a 6 cm dish. The primary IMPC and IDC-NOS tumor cells were cultured in DMEM/F12 medium, which was supplemented with 5% horse serum, 10 µg/mL insulin, 20 ng/mL Maxime EGF, 0.5 µg/mL hydrocortisone, 100 ng/mL cholera toxin, 10 µM RhoA kinase inhibitor (Y - 27632), 4 mM L-glutamine, 1 mM pyruvate, 0.05% bovine pituitary extract, and 1% penicillin-streptomycin. Then the cells were cultured in an incubator at 37 °C, with 5% CO2.
| 4 | 0biomedical
| 0Study
|
274,005 |
The children's data consisted of 25 children from the general population (8 male) with a mean age of 9.5 (0.9) years within a range from 8 to 11 years. These data were collected as part of the first wave in a large longitudinal study on brain development in Utrecht, the Netherlands: The YOUth cohort study (Onland‐Moret et al., 2020). The subset included in this study is labeled as pilot data. The children's parents or guardians gave written consent. Included MR images were of good quality after exclusion of scans with poor contrast or major motion artifacts such as ringing.
| 3 | 0biomedical
| 0Study
|
390,052 |
We collected multiple samples of P. acinosa from different regions of Hunan to determine their potassium accumulation characteristics. The results indicated that stems and leaves were the main tissues for high potassium accumulation in P. acinosa. We cultured seedlings of P. acinosa in solutions of varying K+ concentrations, analyzed the potassium contents in different tissues, and found that P. acinosa showed a strong ability for K+ absorption in roots and a large capability of potassium accumulation in shoots. P. acinosa demonstrated good growth and could complete its lifecycle even in severe potassium deficiency soil, showing adaptability under a wide range of external potassium levels. To reveal the mechanism of K+ uptake and transport in the high K+ plant P. acinosa, we compared the expression of K+ uptake/transport-related genes at the level of the global transcriptome between K+ starved plants and normal cultured plants. Eighteen members of HAK/KT/KUP, 10 members of AKT, and 1 HKT were identified in P. acinosa with global transcriptome analysis. These transporters might coordinatively mediate K+ uptake and transport in P. acinosa and result in high potassium accumulation in plant tissues. The model of K+ uptake/transport mediated by high-affinity K+ transporters was hypothesized in different tissues of P. acinosa. In addition, we found that expression of nearly 30 members of ABC transporters, belonging to subfamilies of ABCB, ABCC, ABCF, and ABCG, was strongly induced by K+ starvation treatment. This indicated that ABC transporters may be important for K+ uptake and transport of P. acinosa under conditions of K+ deficiency.
| 4 | 0biomedical
| 0Study
|
43,053 |
In each patient, Patlak’s graphical analysis was implemented from Eq. 1, setting kb = 0. Eleven cancer tissue TAC data points and the corresponding 11 data points of the experimental 18F-FDG IF, ranging 7.5–57.5 min post-injection, were used. The lower limit of 7.5 min for this range was chosen in order to limit the analysis to data collected for the period t > t* after injection, as required by Eq. 1 validity [7, 8]. Ki was determined as the slope of the linear fitting of the Patlak’s plot showing AT(t)/Ap(t) versus the ratio of time integral of the right hand side of Eq. 1 to Ap(t), i.e., the so-called stretched time.
| 4 | 0biomedical
| 0Study
|
341,973 |
The TGF-β family, in particular, has a crucial role in idiopathic and secondary ERM formation. It is involved in normal tissue repair and development of fibrosis. TGF-β members upregulate ECM production, inhibit protease synthesis and mediate both inflammatory response and myofibroblast differentiation, while retinal Müller cells and hyalocytes produce and activate TGF-β . TGF-β members, in turn, regulate how Müller cells proliferate, migrate and transdifferentiate [18, 94]. However, involvement of transdifferentiated Müller cells in the synthesis of collagen in idiopathic ERM is not clarified. Specific profibrotic cytokines can induce retinal Müller cells to transdifferentiate into a myofibroblast-like phenotype, to produce a-SMA and trigger tissue contraction .
| 4 | 0biomedical
| 0Study
|
157,720 |
The sequence comparison between AR and ERs shows a similar sequence for the palmitoylation, a post-translational modification, present in both types of sex steroid receptors. The palmitoylation of a conserved motif in the ligand-binding domain is critical for the membrane localization of both ERs and AR . The localization at the level of the plasma membrane of the AR and its interaction with caveolin-1 (Cav-1), a major component of the caveolae membrane structure, is due to palmitoylation . Cav-1 enhances AR-transcriptional activity after the androgen binds to the AR as it may increase nuclear translocation and phosphorylation of the AR itself. On the other hand, a down-regulation of Cav-1 decreases AR membrane localization . Overall, the effects elicited by androgens are obtained by different signal transduction pathways (e.g., nuclear and extra-nuclear), whose activation depends on the cellular context of the target cell, the AR intracellular localization (e.g., membrane-bound, cytosolic, nuclear), and the ligand itself (e.g., T vs. DHT).
| 5 | 0biomedical
| 0Study
|
34,853 |
The alkaloid-rich acid solution was diluted (1:10) with the mobile phase (potassium phosphate, 5% KH2PO4, pH 2.5), filtered with a 0.45 μm pore membrane, and analyzed by HPLC (LaChron Elite®, L-2000 system; Merck–Hitachi, Tokyo, Japan). The column was a Merck/Lichrospher® 60 RP, select B, 5 μm, 250 × 4mm, with a flow rate of 1 mL/min and an injection volume of 20 μL. The oven was set to 50°C and a UV detector was used at 216 nm. External standards were used to identify and quantify the alkaloids . All solvents used in HPLC analysis were from Merck KGaA (Darmstadt, Germany).
| 4 | 0biomedical
| 0Study
|
309,886 |
The effects of different variables on the breast cancer were examined using Bayesian logistic regression. In Model I, all variables are included in a unique model. The result of this Model is not statistically valid due to the strong collinearity of BPA concentrations in urine and tissue (r = 0.898, P value < 0.001), which leads to the non-significance effect of the two variables. Model II refers to the univariate analysis of different variables on the cases in which the effects of both BPA concentrations in urine and tissue were statistically significant when the effects of age and BMI were not adjusted. Finally, in Model III and IV, the effects of BPA concentration in tissue and urine were separately evaluated when the effects of age and BMI were adjusted.
| 4 | 0biomedical
| 0Study
|
45,723 |
Numerical solutions of Eq (1) with the logistic growth term (2) and resection are shown for a one dimensional system in Fig 1. Surprisingly, we find that the resection does not lead to any detectable delay of the propagation of the front: The post-resection front initiated by the truncated, low cell density tail of the cancer cell distribution coincides with the unperturbed original front (see also S1 Movie). This behaviour appears to be independent of model parameters including the resection threshold δ.
| 5 | 0biomedical
| 0Study
|
37,628 |
Folic acid has been reported to increase fecal Zn excretion, which might indicate an inhibitory effect on Zn absorption (Ghishan et al. 1986; Simmer et al. 1987; Krebs 2000). Intriguingly, pregnant women are encouraged to supplement folic acid in their diet, as a lack of folic acid has been associated with birth defects such as spina bifida. However, recent studies suggest that excessive amounts of folate might increase the risk for the occurrence of ASD (Raghavan et al. 2016). One might speculate that the underlying patho-mechanism could be a prenatal Zn deficiency that has been shown to induce autism-like behavior in mice (Grabrucker et al. 2014, 2016; Grabrucker 2014).
| 4 | 0biomedical
| 0Study
|
97,327 |
The contact angle of a water droplet in the surface of the as prepared solid was measured from images taken with the CCD camera of a digital microscope. The water was dispensed using a micro-syringe and the contact angle evaluated by fitting the drop profile according to the Young-Laplace method using the software Image J for image processing . Mineral oil, Pfeiffer D-35614 Asslar Oil P3 (Pfeiffer, Asslar, Germany), was used to observe the fiber structure interaction with a non-polar substance.
| 4 | 0biomedical
| 0Study
|
199,697 |
Curve fitting methods are a valuable tool to understand epidemic data that are not sufficiently used in practice and thus worth popularising. The aim of this paper is to present a simple method based on curve fitting to the reported data on confirmed cases of infection and to study and compare the infection dynamics between countries (or regions). This method, based on Johnson cumulative density function (CDF) fitting to the cumulative epidemic curves, was tested using data from 80 countries from 6 continents (Africa, Asia, Europe, Oceania, and North and South America). Additionally, Johnson CDFs were used to calculate basic parameters of the infection wave dynamics, such as the percentage of the population infected during the infection wave, the days of the start, peak and end of the infection wave, the duration of the infection wave, and the duration of the wave’s increase and decrease. These parameters are simple to interpret and can be used in further statistical analyses of epidemic dynamics. This is exemplified by the indirect influences of gross domestic product (GDP) per capita and population density on the percentage of infections and the first day and duration of the first infection wave in the countries concerned. The method presented and the techniques employed are both straightforward and well known; they illustrate how simple techniques can be used to solve otherwise complex problems, such as describing an epidemic wave.
| 4 | 0biomedical
| 0Study
|
245,713 |
Evidence for using platelet biomarkers as a prognostic and stratifying tool in DVT is still scarce. Interestingly, a recent study described platelet-related parameters in patients with confirmed VTE compared to patients with suspected but unconfirmed VTE, independent of the underlying cardiovascular profile (183). Herein VTE patients were characterized with elevated expression of platelet activation markers in combination with lower platelet-dependent thrombin generation in vitro. These findings clearly underscore the role of platelets in VTE. A current overview of platelet released activation biomarkers in arterial and venous cardiovascular diseases determined by ELISA-based tests is presented in Figure 2.
| 4 | 0biomedical
| 0Study
|
387,155 |
(A) Transcript abundance of Cxcl2, IL-1β, and IL-6 in labiar tissue extracted 1 day after 10 daily challenges on the labia relative to vehicle challenged controls. The black dotted line denotes y = 1. Results normalized to housekeeping gene β2m mRNA levels; n = 9/treatment group, representative of 3 separate experiments. (B) Relative transcript abundance of Cxcl2, IL-1β, and IL-6 21 days after 10 daily MI challenges. Black dotted line denotes y = 1. Results normalized to housekeeping gene β2m mRNA levels and vehicle challenged controls; n = 6/treatment group, representative of 2 independent experiments. (C-E) Protein concentration of Cxcl2 (C), IL-1β (D) and IL-6 (E) 1 and 21 days after 10 MI labiar challenges, determined via ELISA and normalized to total protein concentration from DC assay; n = 3-8/treatment group. Significance with respect to control group ** p<0.01, *** p<0.001. (F) Tissue eosinophil peroxidase levels measured by optical density/g wet labiar tissue 1 day and 21 days after 10th MI challenge; n = 2-7/treatment group, representative of 2 separate experiments. Significance with respect to control group ** p<0.01. (G) Tissue myeloperoxidase levels measured as optical density/g wet labiar tissue at 1 day after 10 MI challenges; n = 5-7/treatment group, representative of 2 separate experiments. Significance with respect to control group * p<0.05.
| 4 | 0biomedical
| 0Study
|
186,777 |
Table 3 shows the percentage of titratable acidity in tomato paste treated with ohmic heating (between 0.32% and 0.46%). The highest measured titratable acidity (0.46%) was at 2.73 V/cm of the electric field, 90 °C, and 0.5 bar of pressure. This result was similar to those of who estimated the titratable acidity range between 0.31% and 0.43% in tomato paste treated by ohmic heating and concluded that ohmic heating reduced acidity loss. The regression models for titratable acidity were significant with no significant lack of fit, indicating that the model was adequate for predicting both values.
| 4 | 0biomedical
| 0Study
|
44,760 |
Only three sub‐themes had a significance value of 0.05 or less: (1) “This purpose can be achieved by… having courage and commitment” (p = .044); (2) “The factors that inhibit or enable the achievement of this purpose include… resources” (p = .015); and (3) “I do not feel valued as a person when… I'm being undermined and lied to” (p = .006). This indicates that there was a relationship between care experience and the inclusion of those sub‐themes in the students’ responses. When the phi coefficients for these sub‐themes were calculated (Table 3), two were very low (−0.198 and −0.264), indicating that the effect for these themes was very small. The effect was large for the theme “The factors that inhibit or enable the achievement of this purpose include… resources” (phi = 0.23).
| 3 | 0biomedical
| 0Study
|
74,338 |
There were four major changes to the original intervention in the prototype intervention. First, behaviour change goals for both participants and HCPs were specified, as these were not explicitly specified in the original intervention. Second, theoretical methods (general techniques for influencing change in determinants of behaviour ) were identified to provide a theoretical foundation for the intervention’s activities. These included tailoring (matching the intervention to participant characteristics ), persuasive communication (using arguments to guide an individual towards adoption of an action ), and facilitation (creating an environment that reduces barriers to action ). Third, an extensive nutrition programme with a dietician replaced the protein supplementation in the original intervention. In order to fit better with the participants’ regular dietary pattern, protein intake was to be increased using a range of protein-rich products, instead of just one drink. Guidance by a dietician was perceived necessary to enable the participants to perform this nutrition intervention. Finally, a training programme for implementing professionals was designed to ensure quality implementation. As the original intervention had not been implemented in practice, the training programme for HCPs was an element of the adapted intervention.
| 4 | 0biomedical
| 0Study
|
288,369 |
\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ {x}_j^l $$\end{document}xjl is the jth feature of the layer l.\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ {\beta}_1^l $$\end{document}β1l is the Subsampling coefficient.\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ {b}_j^l $$\end{document}bjl is the bias parameter, down(•) is a sub-sampling function, f(•) is the activation function.
| 4 | 0biomedical
| 0Study
|
296,492 |
A key tool being promoted for determining disability in children to measure the disability inclusiveness of education programs in low- and middle-income countries is the UNICEF/Washington Group Child Functioning Module (CFM) . This includes 24 questions regarding difficulties across 13 activity and participation domains of the International Classification of Functioning, Disability, and Health (ICF) . The CFM was considered a strong candidate tool for disability disaggregation of Fiji’s EMIS (FEMIS) due to several factors. It is relatively short and simple to administer without medical expertise, it identifies children with different functional difficulties, and would enable comparison of school data to national data collections administered by the National Statistics Office (for which the CFM was designed). In addition, the use of data on functioning to identify children with disabilities is a positive shift from the diagnostic or impairment data used previously in Fiji and commonly in other low- and middle-income country EMISs .
| 4 | 0biomedical
| 1Other
|
209,986 |
Quantification of images from IHC, IF and migration assays was performed by using 10 non-overlapping fields from stained tissue sections and the data were analyzed by ImageJ. Statistical analysis for comparison of two groups was done by t test. Comparisons of three or more groups were performed by one-way ANOVA and Tukey’s multiple comparison tests using GraphPad Prism 7.
| 4 | 0biomedical
| 0Study
|
47,720 |
The numbered steps prior to and after the radiotherapy (RT) taken by the patients were normalized to the average number of daily steps taken by the patients prior to the RT. Comparison of the daily activity level of the patient prior to (pre-RT) vs. after RT (seven days post-RT) were made using the Wilcoxon signed-rank test. Error bars represent standard error of the means.
| 4 | 0biomedical
| 0Study
|
68,812 |
Despite the potential dominance of hegemonic forms of masculinity, it is said to exist amongst non-hegemonic (subjugated) forms of masculinity . This raises the potential for more flexible interpretations of masculinity as documented in several recent studies. [26–28]. With illnesses such as PCa, coronary heart disease, and depression, some men re-negotiate masculinity in an attempt to cope with the medical and psychological consequences of physical health problems . This research compliments work undertaken in the areas of psychological flexibility, positive masculinity, and coping flexibility, and the benefits such attributes confer on well-being [30–32].
| 2 | 2other
| 1Other
|
229,727 |
The staff became aware of the patients’ physical, social, and psychological needs, and the patients naturally benefited from these changes in the medical care and pain control programs introduced into the home. The authors believe that further studies are needed to implement this method of home procedural analgesia for pain control, as provided by Italian Law 38/2010.
| 2 | 0biomedical
| 1Other
|
126,956 |
The results of a phase I CheckMate 012 study evaluated combination therapy with nivolumab and ipilimumab in patients with advanced NSCLC (NCT01454102). In NSCLC, first-line nivolumab plus ipilimumab had a tolerable safety profile and showed encouraging clinical activity, characterized by a high response rate and durable response. These results brought about the CheckMate 227 study and CheckMate 9LA study. CheckMate 227 clinical trial compared this regimen to standard first-line chemotherapy, nivolumab monotherapy or combination therapy with chemotherapy and nivolumab for patients with advanced NSCLC. This study showed that first-line treatment with nivolumab plus ipilimumab resulted in a longer duration of overall survival than chemotherapy in NSCLC patients independent of the PD-L1 expression . CheckMate 9LA indicated that nivolumab plus ipilimumab with two cycles of chemotherapy provided a significant improvement in overall survival versus chemotherapy alone, and had a favorable risk-benefit profile . Thanks to the beneficial results of the above study, investigators propose an idea to addition of ipilimumab to nivolumab, after primary resistance to anti-PD-1 therapy, which could cause radiographic tumor regression. The study NCT03262779 included NSCLC patients who had progression after anti-PD-1 therapy without initial response to such therapy (primary resistance). Moreover, a smaller cohort of patients with acquired resistance to anti-PD-1 therapy (progression after initial response) was also enrolled to this study.
| 4 | 0biomedical
| 0Study
|
166,321 |
Optical signals, which can be infrared or visible light, typically employ LEDs as transmitters and imaging sensors or photodetectors as receivers. For instance, when using coding techniques with LED emissions and Quadrature Angular Diversity Aperture (QADA) receivers, positioning results with precision in the range of a few decimeters can be obtained . This performance is similar to the one achieved with acoustic systems , on which this work focuses. Both acoustic and optical systems are constrained by the physical limits of the indoor spaces (walls, furniture, etc.).
| 2 | 2other
| 0Study
|
210,560 |
The THD is computed point by point using a pure sine as the input signal for 200 points. The simulated THD is compared to the THD measured by the manufacturer in Figure 10. The pressure signal is low pass filtered at 16 kHz before the THD estimation, as it is described in the data sheet of the loudspeaker. There is a good agreement between the absolute level of the THD between 40 and 200 Hz, where the difference between the two curves is below 20%. Above 500 Hz, the difference between the simulated and measured frequency responses is the cause of the difference between the THD curves and around the distortion peak at about 6.4 kHz, the difference is maximum and above 100%. Qualitatively, the shape of the curve around the resonance of the loudspeaker has a similar shape, capturing the effect of the resonance of the loudspeaker and the one of the coupler on the THD.
| 2 | 2other
| 0Study
|
251,711 |
Our findings showed significant association between SNPs of DNA repair genes and risk of severe subcutaneous fibrosis in patients of OPC treated with radiotherapy. These are encouraging results and suggest that genetic variations contribute to the severity of normal tissue toxicities after radiotherapy. More importantly, we also performed a haplotype association analysis of two polymorphisms for predicting the combined risk of severe subcutaneous fibrosis. Haplotype-based analysis may offer better genetic information and help improve the detection of causal genetic variants when compared with single SNP-based analysis (44).
| 4 | 0biomedical
| 0Study
|
80,074 |
Cell culture and transfection was performed as described in (Hallier et al., 2016). For heterologous expression in H5 cells, full-length Prc was cloned into the pFastBacDual vector (Life Technologies). The endogenous stop codon of Prc was removed and a C-terminal FLAG tag was inserted by appropriate primer design. Truncated versions of Pericardin were established using the respective FLAG tagged construct as a template.
| 4 | 0biomedical
| 0Study
|
164,188 |
Shapiro–Wilk test results indicated that PU (p = .136) and SN (p = .11) satisfied the assumptions of normality, but the other five factors did not (p < .05). For PU and SN, a paired samples t-test was conducted to determine whether each of the two factors significantly changed after teachers’ experience with OEP. The results (see Table 1) suggested no significant changes on teachers’ PU [t(53) = 0.25, p = .81], and SN [t(53) = 1.61, p = .11]. For the other five factors, a Wilcoxon signed-rank test was conducted. The results indicated that teachers’ PE and SE towards OER significantly improved after the OEP experience. According to Cohen (1992), the effect size is small if r is below 0.1. The effect sizes represent medium and large if their r values are respectively above 0.3 and 0.5. Both effect sizes in our study range between small and medium. Specifically, post-test scores for PE (Mdn = 12.00) were significantly higher than that of pre-tests (Mdn = 11.00), Z = 2.68, p = .01, r = 0.26. For SE, post-test scores (Mdn = 8.00) also significantly improved from pre-tests (Mdn = 8.00), Z = 2.54, p = .01, r = 0.25. Additionally, though participants’ IN was not significantly improved, the median of this factor increased after the OEP experience.Table 1Quantitative results of factors influencing teachers’ acceptance of OERFactorsResults of paired samples t-testPre-tests (N = 54)Post-tests (N = 54)MSDMSDtdfpCohen’s dPU11.802.2111.892.690.25530.810.03SN10.282.1010.722.121.61530.110.22Results of Wilcoxon signed-rank testMdnSDMdnSDZdfprPE11.002.3512.002.472.68530.01*0.26AT12.002.4812.002.630.44530.660.04JF15.003.3716.003.260.61530.540.06SE8.002.248.001.842.54530.01*0.25IN10.002.3611.002.880.00531.000.00*p < 0.05 indicates the result is significant
| 1 | 2other
| 0Study
|
156,944 |
As described in the introduction, wireless environmental monitoring techniques show promise in dealing with the usual characteristics of historic buildings, which are often large and thick walled. In order to explore the potential of these technologies in the field of cultural heritage conservation, a wireless monitoring system was developed to assess indoor air conditions at the baroque church of Saint Thomas and Saint Philip Neri in Valencia .
| 1 | 2other
| 1Other
|
52,873 |
Matrigel (Corning, Kennebunk, ME, USA) was added into a 96-well plate (50 μl per well) and allowed to polymerize for 30 min at 37 °C. ECs were seeded at 1 × 104 per well and grown in M131 supplemented with 5% MVGS for 24 h in a incubator at 37 °C with 5% CO2. The images were acquired 6 h after incubation. Branching points in three randomly selected fields (x4 magnified) were counted and data are presented as the average number of branching points per field.
| 4 | 0biomedical
| 0Study
|
328,823 |
2. The individual microbiota graphs need to be provided in the main text vs. as supplementary files. Furthermore, it appears that for most statistical endpoints reported in the group averages, only 1 or 2 individuals in each group drove those changes represented in the averages. For example Proteobacteria at the Phylum level are so varied, even amongst the controls, that it appears that the averages presented in Figures 3 and 4 are not necessarily representative of the whole group.
| 4 | 0biomedical
| 0Study
|
21,516 |
Six REBOA procedures resulted in complications. Five of them were related to local thrombus formation in the iliac or femoral artery, and all five occurred when using 11 cm introducers. Two of these patients had a surgical thrombectomy and three patients were treated with low-molecular heparin. All five patients recovered successfully. One patient, as previously reported , had an aortic tear that was treated surgically and recovered without any permanent sequelae. There were no complications regarding the insertion of the J-curved guide wire or the balloon catheter. The shorter introducer length (11 cm) was strongly associated with arterial thrombus formation (ρ = 0.50, P = 0.002). In addition, there was a strong negative correlation between uterine artery embolization and hysterectomy (ρ = -0.50, P = 0.002).
| 4 | 0biomedical
| 0Study
|
367,806 |
It is established that the duration of the lag phase depends on the rates of multiple parallel microscopic processes, such as the formation of primary nuclei and their amplification through elongation and secondary nucleation processes . Because variations of the former process do not affect the growth phase, while changes in elongation and secondary nucleation modify both the lag phase and the growth phase, it seems possible that di-ubiquitination of tau protein could interfere with the growth and proliferation of primary nuclei rather than with their formation. This was more evident for di-ubiquitinated, rather than mono-ubiquitinated, tau protein. Since the inhibitory effect was dependent on the length of the ubiquitin chain, the impact on tau protein aggregation is likely be a result of a combination of structural motif at the tau-ubiquitin conjugating point and of the presence of the distal ubiquitin moiety which adds steric hindrance. Yet, we do not exclude the possibility that a further elongation of the polyubiquitin chain could elicit different results, particularly if considering that longer ubiquitin chains have lower thermodynamic stability and can form fibrils themselves under specific conditions .
| 4 | 0biomedical
| 0Study
|
30,520 |
In the STRUCTURE analysis, SSR datasets from the two locations were analysed jointly. The highest ΔK value was obtained with K = 2 for the putative parents and hybrids (Table S4; Fig. S1), indicating the presence of two genetic clusters. For L. duciformis, all individuals (15) from Mt. Maoniu and most individuals (18/20) from Heihai Lake were assigned to one purebred cluster (qi > 0.90; Fig. 4A). For L. paradoxa, all individuals (18) from Mt. Maoniu and most individuals (17/18) from Heihai Lake were assigned to the other purebred cluster (qi > 0.90). However, a few individuals that were morphologically identified as L. duciformis or L. paradoxa were assigned to the mixed cluster with high probability (qi (HD18) = 0.828, qi (HD20) = 0.885, qi (HP15) = 0.880). For L. ×maoniushanensis, eight individuals from Mt. Maoniu and nine from Heihai Lake were inferred to have a genetic composition deriving from both L. duciformis and L. paradoxa, and were unassigned to either cluster (0.10 < qi < 0.90). The remaining two individuals of L. ×maoniushanensis were assigned to the L. paradoxa cluster (qi > 0.90).
| 4 | 0biomedical
| 0Study
|
178,063 |
Ochrobactrum species are gram-negative, non-lactose fermenting, aerobic bacilli closely related to the Brucella genus. The Ochrobactrum genus was first identified in 1988. It was previously categorized as the Centers for Disease Control and Prevention (CDC) group Vd 1-2 . Ochrobactrum species can be found in the environment such as water, soil, animals, and plants, as well as in polluted environments . It is also thought to be part of the normal flora of our large intestines . The Ochrobactrum genus includes nine different species: O. anthropi, O. intermedium, O. lupini, O. tritici, O. grignonense, O. gallinifaecis, O. oryzae, O. pseudintermedium, and O. cytisi. Out of these, only O. anthropi, O. intermedium, and O. pseudintermedium have been reported to cause clinical manifestations .
| 4 | 0biomedical
| 0Study
|
271,554 |
Astragalus floccosus Boiss. rich fraction of flavonoid has a high affinity to bind to estrogen receptors alpha and beta which are present in the skin tissue and play role in wound therapy. This study showed that RFF has a wound healing activity in in vitro and in vivo conditions with low toxicity. This extract can be considered as an adjuvant therapy for skin wounds due to the presence of compounds (especially isoflavonoids) and can be used for further clinical and commercial evaluations. Due to the limitation of our study to isolate isoflavone glycoside from the extract, it is better to evaluate each one of the LC/MS result compounds for wound healing analysis in future studies.
| 4 | 0biomedical
| 0Study
|
120,488 |
SRM validation of the differences in AACT found using LC-MS/MS. a Chromatograms of secretome samples showing the transitions of the 2 proteotypic peptides: ITLLSALVETR (A.1) and LYGSEAFATDFQDSAAAK (A.2). As it is shown in the figure, the m/z values selected in the first quadrupole were 608.37 and 946.44, respectively. On the right, quantification of the three transitions (area under the curve) that were monitored for each peptide. The different m/z values selected in the third quadrupole are indicated in the figure. b Chromatograms of plasma samples showing the transitions of the proteotypic peptide AVLDVFEEGTEASAATAVK (m/z 954.48) and quantification of each transition (area under the curve) in plasma samples. The different m/z values selected in the third quadrupole are indicated in the figure
| 4 | 0biomedical
| 0Study
|
199,549 |
Since Dusp9 has been suggested to be responsible for the reduction of global CpG methylation levels typically observed in female mESCs (20–30% compared to 60–80% in male mESCs) [13, 25, 31], we analyzed how over-expression of Dusp9 and Klhl13 affected global DNA methylation through the pyrosequencing-based luminometric DNA methylation assay (LUMA; Fig. 3g). Upon Dusp9 over-expression, global DNA methylation levels were reduced from ~ 60% in NTC-transduced control cells to 53% and 42%, but were unaffected by Klhl13 over-expression. Our results confirm a previously described effect of Dusp9 on global DNA methylation .
| 4 | 0biomedical
| 0Study
|
277,257 |
Overall grassland quality, as measured by the Normalized Difference Vegetation Index (NDVI), slightly improved after GECP implementation, but there was significant variation across regions. On average, NDVI increased by 1.2% in GECP regions from the pre-program period (2006–2010) to the program period (2011–2015) (Supplementary Table 1). Figure 1 shows the change in grassland quality by displaying NDVI measures before GECP implementation (Fig. 1a), NDVI measures after implementation (Fig. 1b), and the difference in NDVI between the two periods (Fig. 1c). Figure 1 also indicates that NDVI increased in some areas and decreased in other areas.Fig. 1Temporal and spatial trends of NDVI.a Average before Grassland Ecological Compensation Program (GECP) implementation (2006−2010); b average NDVI after GECP implementation (2011-2015); c difference in NDVI before and after GECP implementation. NDVI stands for the Normalized Difference Vegetation Index, which is a measure for grassland quality. It was constructed based on infrared and near-infrared channel remote sensing images and has been widely used as an indicator of vegetation coverage.
| 1 | 2other
| 0Study
|
325,272 |
Opening the apparatus in all three tests was defined by the same criteria—contact between the apparatus and any part of the dog other than the tail which resulted in the restrainer door moving away from the apparatus. In addition to the binary outcome of whether the dog opened the apparatus, the latency (in seconds) to open the apparatus was also recorded. A latency of 120 seconds (the maximum length of the test) was assigned to tests in which the dog did not open the apparatus. Latencies were natural log-transformed to reduce skew and kurtosis.
| 4 | 0biomedical
| 0Study
|
145,287 |
SARS-CoV-2-specific T lymphocytes were detected by Interferon-gamma (IFN-γ) Enzyme-linked Immunospot (EliSpot) assay. In short, after PBMC isolation from whole blood samples using discontinuous density gradient centrifugation and resuspension in culture medium, which was comprised of RPMI1640 (Lonza, Vervies, Belgium, #BE12-702F) with 10% of human AB serum (C.C.pro, Oberdorla, Germany, #S-41-M), at a concentration of 1 x 107 cells/ml, the cells were plated in 24-well plates for overnight resting. On the next day, the rested PBMCs were transferred to anti-IFN-γ pre-coated EliSpot plates (Lophius Biosciences, Regensburg, Germany, #12100010) in co-culture with specific antigens of interest for 16–18 h at a density of 2.5 x 105 cells/well. Overlapping peptide pools against the following peptides were used for stimulation at a final concentration of 1 μg of each peptide/ml peptide pool: SARS-CoV-2 membrane protein (M, #130-126-703), nucleocapsid protein (N, #130-126-699), and CMV phosphoprotein 65 (pp65, #130-093-435) (all Miltenyi Biotec, Bergisch Gladbach, Germany) as well as SARS-CoV-2 proteins S1 and S2 (PM-WCPV-S), huCoV epitopes (strains 229E, #PM-229E-S-1 and OC43, #PM-OC43-S-1; S1 and S2), and antigens derived from human RSV (nucleoprotein, NP, #PM-HRSVB-NCPN) and IAV (matrix protein 1, MP1, PM-INFA-MP1-H1N1) (all JPT, Berlin, Germany). A positive control (PC) consisted of cells stimulated with staphylococcal enterotoxin B (1 μg/ml, SEB, Merck, Taufkirchen, Germany, #S4881) while PBMCs in culture medium alone served as a negative control (NC). The detection of IFN-γ was achieved using streptavidin-alkaline phosphatase (Mabtech Stockholm, Sweden, #12360002-S) and 5-13 bromo-4-chloro-3-indolyl phosphate/nitroblue tetrazolium (BCIP/NBT Liquid Substrate, SERVA, Heidelberg, Germany, #15246.01). Emerging IFN-γ spots were counted on an AID iSpot spectrum reader system using the AID EliSpot 8.0 Software (both from AID, Strassberg, Germany). For duplicate wells, means were calculated and for each specific antigen, the result was expressed as the number of spots per well (spw). For determining non-responders to this assay, a threshold was set at ≥3 spw or >2xNC. Additionally, spots/10,000 CD3+ T cells were calculated based on staining of PBMCs with anti-CD3 FITC (BD Biosciences, #345764), anti-CD4 PerCP (BD Biosciences, #345770), anti-CD8 APC (BD Biosciences, 345775), and anti-CD45 APC-H7 (BD BioSciences, #641417) followed by flow cytometric analysis.
| 4 | 0biomedical
| 0Study
|
256,108 |
As an important antimicrobial peptide in mammals, β-defensin can not only play a bacteriostatic role on anti-pathogenic microbes but can also participate in the protection of reproductive system tissues from bacterial infection . Reproductive and urinary tract infections remain an important global public health problem. Male genital tract infections affect reproductive capability and reduce semen quality. Several β-defensins have been identified in the urogenital tract, including human , rat and dog . These β-defensins have been found to have antibacterial activity and play a role in protecting the reproductive tract from microbial infection . In addition, it has been found that porcine β-defensins 1 (PBD1) and 2 (PBD2) at 3 μM, as an antimicrobial in liquid-stored boar semen, have no detrimental effect on sperm viability and motility and are able to control microbial growth effectively .
| 4 | 0biomedical
| 0Study
|
135,608 |
Celastrol is another major bioactive terpenoid in the root of Tripterygium wilfordii, in addition to the diterpenoid triptolide. Celastrol exerted neuroprotection in ischemic stroke mainly via its anti-inflammatory activity. It is reported that celastrol promoted the polarization of microglia/macrophages from the proinflammatory M1 phase to the anti-inflammatory M2 phase by decreasing proinflammatory cytokine IL-33 and its corresponding receptor ST2 (growth stimulation expressed gene 2) in pMCAO rats . Besides, celastrol also inhibited the JNK/NF-κB pathway to suppress the inflammatory cascade in the ischemic brain . The neuroprotective efficacy of celastrol was relatively high, improving cerebral infarction and neurological deficits with low effective doses (1-3 mg/kg, i.p.). Yet, similar to triptolide, celastrol also had high toxicity and poor solubility problems, which limited its pharmacological applications .
| 4 | 0biomedical
| 0Study
|
191,642 |
The scientific names of the plant species tested, their botanic families, parts of the plants fractionated, the ethnomedicinal uses and the countries where the studies were performed are shown in Table 2. Among the 72 articles, 54 of them evaluated the antimalarial activities of one plant species each while 18 of them evaluated two or three plant species each, giving rise to a total of 90 plant species, some of which were studied by more than one author. The three most studied families were Fabaceae, Apiaceae and Lamiaceae. The plant species evaluated for antimalarial activities corresponded to 44 botanical families; the parts of the plants tested were aerial parts, leaves, leaf latex, rhizomes, roots, root bark, stem bark, whole stem, branches, twigs, petiole, cortex, flower, fruits, fruit pulp, unripe fruits, and whole plant (Table 2).
| 4 | 0biomedical
| 0Study
|
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