id
int32
0
398k
text
stringlengths
204
42k
educational_score
float32
1
5
domain
class label
3 classes
document_type
class label
4 classes
396,018
We have found that pexiganan, a cationic antimicrobial peptide, can induce a stress response in S. aureus that results in a proteome-wide impact. Pexiganan treatment upregulates known virulence factors such as MprF, the capsule synthesis protein CapF, a wall teichoic acid TagG, the proteases ClpL and PepT and other proteins important for the interactions with the hosts. This could lead to a phenotypic cross-tolerance of other immune effectors of hosts and possibly complicate the bacterial infection in case of inefficient treatment where bacteria could be exposed to sub-lethal concentrations. This is a legitimate concern since AMP-resistant variants have been reported to have evolved which have shown some cross-resistance with immune system effectors (63, 64). This risk has been shown for pexiganan as well (12). Our data also provides input about possible induced physiological changes that would help S. aureus to adapt to the intra-host environment during its interaction with specific immune system effectors.
4
0biomedical
0Study
109,963
In an attempt to elucidate whether metformin induces DNA damage under glucose-depleted conditions, we measured the cytotoxic effects of metformin on a panel of DNA repair-deficient DT40 cells. The DNA repair-deficient mutants used in the present study covered homologous recombination repair (HR), non-homologous end joining (NHEJ), base excision repair (BER), nucleotide excision repair (NER), ICL repair (the FA pathway), the repair of DNA-topoisomerase (Topo) crosslinks, and translesion DNA synthesis (TLS) (Listed in S1 Table). These cells were incubated with metformin in glucose-free media for 24 h, and subsequently incubated in complete media to measure cell survival using a colony formation assay. The concentration of metformin that killed cells to the level of 50% of untreated cells (IC50) was assessed for each mutant (Fig 1B). fancc cells deficient in FANCC showed increased sensitivity to metformin under glucose-depleted conditions. FANCC is a component of the core FA complex that is required for the DNA damage-induced mono-ubiquitination of FAND2 and FANCI.
4
0biomedical
0Study
23,622
Globally and in most regions, age-standardised tuberculosis incidence, prevalence, and mortality rates showed a steady decline with rising SDI (figure 3). Many regions (eg, southeast Asia, south Asia, central Asia, eastern Europe, Andean Latin America, and sub-Saharan Africa) had higher than expected incidence, prevalence, and mortality rates, whereas a few others (eg, Oceania and north Africa and the Middle East) showed lower than expected levels over time (appendix). Of all regions in 2015, southern sub-Saharan Africa had the largest difference between observed and expected levels, although the observed mortality has begun to fall closer to expected levels since around 2007. The gaps between observed and expected incidence and mortality also gradually decreased over time in several other regions (eg, southeast Asia, south Asia, and Andean Latin America), but we observed little change in the gaps for central, eastern, and western sub-Saharan Africa. In east Asia, we observed little change in the gap between observed and expected levels of incidence and prevalence over time, although the observed mortality converged with expected levels during 2015. In eastern Europe, the observed incidence, prevalence, and mortality increased between 1990 and 2005 but has begun to fall closer to expected levels in the last decade.Figure 3Estimated observed and expected age-standardised rates of tuberculosis incidence (A), prevalence (B), and mortality (C) per 100 000 population among HIV-negative individuals based on SDI, 1990–2015Each point on a line represents 1 year, starting at 1990 and ending at 2015. In all regions, SDI has increased year on year, so progress in SDI is associated with later years for a given region. The black lines indicate trajectories for each geography expected based on SDI alone. SDI=Socio-demographic Index.
4
0biomedical
0Study
384,886
Myelin, the insulating axonal sheath that ensures correct transmission of nerve impulses, has a high lipid content (about 70% of its dry weight in humans and rats) . Galactosylceramides (GalCers) and glucosylceramides (GluCers), also called cerebrosides, are the most typical of these lipids, followed by ethanolamine-containing plasmalogens . In the present study, our LC-MS/MS method could not discriminate between GalCers and GluCers, and so we refer to the detected species as hexosylceramides (HexCer). HexCer species were measured using positive ion mode LC-MS and identified using their exact mass and the presence of an intense ion m/z 264.3, corresponding to the loss of the acyl group bound to the amine of the ceramide and to a double dehydration of the ceramide moiety, in the MS/MS mass spectrum. Plasmalogen-phosphoethanolamine (PE) and HexCer species were decreased in the cerebrum of one-month-old SD mice (Figure 4A). The targeted measurement of plasmalogen-PE (p36:1) in cerebrum and spinal cord confirmed that its concentration was decreased in SD mice compared to controls at one and two months (Figure 4B).
4
0biomedical
0Study
175,874
In 2004, University of California, Los Angeles (UCLA) researchers began clinical trials on psilocybin for the treatment of pain, anxiety and depression in patients with advanced-stage cancer. This may be considered the “third psychedelic renaissance”. A 2006 publication from the John Hopkins University heralded a new age for psychedelic research, reigniting worldwide interest . This led to the formation of the psychedelic research unit, and eventually, the Center for Psychedelic and Conscious Research (John Hopkins University) in 2006, which has since published over eighty peer-reviewed articles on psychedelic research . In September of 2020, the John Hopkins University built the Center for Psychedelic and Consciousness research, the first of its kind. To date, over 27,000 scientific articles have been published on psychedelic drugs, with over 1000 particularly on psilocybin . Currently, psilocybin is the most studied psychedelic .
4
0biomedical
1Other
293,648
In conclusion, we noted that the occurrence of AKI was independently associated with lower survival of patients treated with ICI, particularly in the first 120 days of its occurrence. However, among patients with AKI, those with AIN had higher survival than those without AIN indicating that this IrAE may be a marker of therapeutic response to ICI. Future studies could consider further phenotyping AKI cases using biomarkers and biopsy data to better understand the relationship of various etiologies of ICI-associated AKI with mortality.
4
0biomedical
0Study
101,361
\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$b_{ij}(t) \ge 0$$\end{document}bij(t)≥0 for all \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$i\not =j\in \{1,\ldots ,d\}$$\end{document}i≠j∈{1,…,d} and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$t\in I$$\end{document}t∈I,
1
0biomedical
1Other
182,067
Our results demonstrate that CSF1R-dependent macrophages are essential for early postnatal growth and organ development in the rat. The exclusive impact on postnatal growth distinguishes the Csf1rko from Igf1 and Igf2 mutations which impact the growth of the embryo . Interestingly, although Csf1r is highly-expressed in placenta, the lack of impact of the mutation on embryonic growth also indicates that placental function is CSF1R-independent. It is likely that any loss of macrophage-derived trophic factors in the embryo is mitigated to some extent by placental and maternal-derived growth factors. Severe postnatal growth retardation is not evident in human patients with bi-allelic CSF1R mutations . This may be indirect evidence that the mutant alleles in these individuals are hypomorphic, rather than complete loss-of-function. The only definitive human homozygous CSF1R null mutation described thus far was associated with severe osteopetrosis, brain developmental defects and infant mortality .
4
0biomedical
0Study
162,034
Staminate floral buds needed for all experiments were collected from androecious, monoecious and gynoecious plants from short-day variety USO31. Additionally, due to the marked dioecious character of the neutral-day variety Finola (which lacked monoecious specimens), only androecious and gynoecious individuals from this variety were used as donor plants. Seeds were germinated in pots (1 L) with fertilized commercial substrate composed of a mixture of black peat, granulated peat moss and perlite, with a pH value of 6 and a conductivity of 1 mS/cm. In order to induce the formation of male flowers in gynoecious individuals, 2 weeks after germination of the seeds, female plants were sprayed once a day (early in the morning), during five consecutive days, with an aqueous solution of silver thiosulphate anionic complex [(STS); 1 silver nitrate (AgNO3) and 8 sodium thiosulphate (Na2S2O3) w/w], as described by Ram and Sett (1982). After spraying, plants were kept in darkness for 1 h, and then returned to the growth chamber. Plants were grown under controlled environmental conditions at 25°C ± 1°C and 60% ± 1% relative humidity. During the whole cultivation process, photoperiod consisted of 12 h of light per day. Light was provided by Lumilight® Led Grow Monster LPW-220 (LUMILIGHT LED GROW Ltd., Valencia, Spain), equipped with Light Emitting Diodes (LEDs) of 220W and a color temperature of 2,470K, which supplied 16,700 lumens and 546 μmol m–2 s–1. Once a day, plants were watered (75% tap water + 25% osmotized water) through drip-irrigation. Following this protocol, staminate floral buds from all evaluated phenotypes were collected approximately 30 days after seed germination. Plants employed in this study were grown under license for the cultivation of C. sativa for research purposes, issued by the Spanish Ministry of Health via Spanish Agency of Medicines and Health Products (Agencia Española de Medicamentos y Productos Sanitarios or AEMPS) to Ploidy and Genomics Ltd.
4
0biomedical
0Study
351,806
An option to overcome that would be to combine acoustic information with linguistics systems based on transcripts generated from ASR systems. This idea would introduce automation, but also increase the complexity, and dependency on errors rate for ASR in a given language.
1
2other
1Other
64,875
The immunohistochemical data on protein expression (Table 2) provides an additional level of evidence related to the early response following implantation. In vivo expression of MMP-1, MMP-13 and Cat-K was found for both materials suggesting a similar pathway in the enzymatic breakdown of the components while the response to morselized autograft within the defect was less robust (Fig 7). Collagen degradation can be influence by many endopeptidases . While MMP-1 and 13 and Cat K expression was present for all materials in this study, differences in expression in other matrix metalloproteinases (MMP-2, 3, 9 and 10) as well as other cysteine and serine proteinases that may continue influence an inflammatory response through would be an interesting area of investigation in the future.
4
0biomedical
0Study
307,577
To analyze the effect of Larveel® on cells infected with Gram-negative and Gram-positive bacteria, fibroblast and keratinocyte co-cultures were infected with P. aeruginosa or S. aureus or both strains. Additionally, medium was supplemented with 0.5% antibiotics and different concentrations of Larveel®. Dermal cells inoculated with P. aeruginosa showed strong green fluorescence indicating massive bacterial growth in the medium (Figure 1, top). Furthermore, diffuse and destroyed fibroblast and keratinocyte cell nuclei (in blue) were observed in these wells. Addition of Larveel® in concentrations of 6 and 12 mg/mL diminished green P. aeruginosa fluorescence in a concentration-dependent manner. In contrast, S. aureus was observed as red fluorescent dots (Figure 1, middle), thus a vigorous bacterial proliferation was not observed with 0.5% antibiotics. No striking differences in S. aureus distribution and red fluorescence intensity after Larveel® application were seen in this experimental approach. P. aeruginosa and S. aureus co-culture with dermal cells exhibited an overgrowth of P. aeruginosa in the medium (Figure 1, bottom). Similar to the top line, the addition of Larveel® in concentrations of 6 and 12 mg/mL diminished the green P. aeruginosa fluorescence. Co-culture approaches with bacteria and with 0% antibiotics exhibited completely cloudy media due to severe bacterial growth and were discarded (not shown). Thus, we decided to use 0.5% antibiotics, on the one hand to allow the bacteria to grow, but on the other hand, to prevent uncontrolled expansion. A basal concentration of 0.5% antibiotics was constantly necessary in co-culture experiments to keep the eukaryotic cells alive and maintain the experimental conditions.
4
0biomedical
0Study
129,080
Among patients with acute myocardial infarction (AMI), left ventricular remodeling (LVR) is thought to occur as an adaptive phenomenon that later results in structural and functional changes such as left ventricular dilatation and reduction of ejection fraction (LVEF) in response to myocardial injury [1–3]. According to the historical definition of > 15% increase in left ventricular end-systolic volume (LVESV), LVR is observed in as many as 30% of anterior myocardial infarction (MI) cases and approximately 17% of non-anterior MI cases even with timely primary coronary intervention (PCI) and the use of cardiovascular-protective drugs such as angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, beta blockers, mineral corticoid receptor antagonists, and statins . Diabetes alone is known to cause LVR [5, 6], and in another concept of diabetes mellitus-related cardiomyopathy (DMCMP), LVR has no other cause besides DM .
4
0biomedical
0Study
95,805
A female patient was diagnosed with thrombocytopenia due to persistent gum bleeding and lower extremity congestion at the age of 40 years in a local hospital. Subsequently, she was detected to have hypertension. She took nifedipine for hypertension for three years, but her health conditions worsened. A renal function examination showed an elevated serum creatinine (Scr) level (342 μmol/l), and symptomatic treatment did not improve renal function before dialysis. After six months of dialysis, the patient underwent kidney transplant operation since a 56-day-old infant who died from a central nerve system (CNS) tumor (suspected astrocytoma without pathological evidence) came to the hospital as a kidney donor by his parents and was found to be suitable for kidney donation. There was no history of rhabdoid tumors in the donor family history.
3
0biomedical
3Clinical case
258,246
It is also possible to use the uncertainty described by the posterior distribution to calibrate a model. For instance, when the finite-element modelling for the I-beam is repeated using a series of values for the Young's modulus varying between 65 and 75 GPa, then the series of coloured triangles in figure 3 represent the predicted displacement fields. Because the values for the Young's modulus that yield shape descriptors within the distribution lie between 67 and 71 GPa, it can be concluded that this range would be acceptable when considering the displacements in this region of interest.
2
2other
0Study
330,340
The choice of update rule for k-means clustering is also a concern, as there are two main varieties tailored to handling different situations. The first update rule weights each incoming sample by the total number of samples received. This version allows for features that encompass a large dataset to be iteratively determined without the loss of any information. Unfortunately, such an approach places emphasis on the initial training sequences, and is poorly suited to a continuous operation (as required by an event-based system) as each subsequent event exerts less influence on the feature weights.
2
2other
1Other
132,927
Another potential source of bias was the overrepresentation of dairy farmers. We decided to include both farm types in the cluster analysis and not to analyse them separately, because a similar proportion of both production types was enroled in the paratuberculosis control programmes in both federal states. The aim of our cluster analysis was to identify clusters among the participants solely based on their attitudes towards paratuberculosis and its control, not on the production type of their herds. We are aware that paratuberculosis is generally regarded as a problem of the dairy industry more than of the beef industry. Nonetheless, beef herds are affected by paratuberculosis as well. Therefore, we combined data from beef and dairy herds in our analysis. Our study did not aim at identifying differences between beef and dairy farmers in their attitudes and opinions regarding paratuberculosis and its control. The question as to whether these attitudes depend on production type is left to further research.
2
0biomedical
0Study
167,761
Elevated NLR and PLR have been shown to be significantly associated with worse outcomes in malignancies . Specifically, similar findings have been reported in cancer patients who received ICI therapy (Table S5) . In line with the literature, our study also noted that elevated NLR, and to a much lesser extent PLR, were associated with shorter OS and PFS in cancer patients who received at least one dose of ICI. However, as only 2 patients received anti-CTLA-4, the presented data should apply only to anti-PD1/PD-L1-based ICI. Biologically, the NLR can potentially reflect the balance of the immune system in the context of a malignancy. Controversy surrounds neutrophil function in cancer because neutrophils have been shown to possess both pro- and anti-tumor properties . With tumor progression, dynamic changes in neutrophil composition result in a switch from an overall anti- to pro-tumor neutrophil contribution . An increasing number of studies have linked increased peripheral blood neutrophils or NLR to tumor-infiltrating neutrophils. Gentles et al. analyzed cancer gene expression and clinical outcome data for approximately 18,000 patients and 39 distinct malignancies . Of the tumor-associated leukocytes, neutrophil signature emerged as the most adverse cancer-wide prognostic population . Lymphocytes are effective suppressors of cancer progression and their presence, particularly in the tumor microenvironment, is thought to reflect host immunity . Another interesting finding in our analysis was the reduction in NLR, but not PLR, after ICI therapy was associated with significantly improved OS. Hence, NLR, unlike PLR, could also be a measure of PMN-MDSCs suppressing anti-tumor T lymphocyte responses in the tumor microenvironment. Of interest, anti-CTLA-4 treatment has been demonstrated to decrease PMN-MDSCs in patients with metastatic melanoma . Therefore, the ability of NLR to reflect PMN-MDSC activity in anti-CTLA-4-based therapy needs to be examined.
4
0biomedical
0Study
156,116
We also calculated the aggregated risk scores across selected decision criteria for all counties in Virginia. The risk map based on the aggregated scores is shown in Fig. 8. Aggregated risk scores showed spatial variability with an average value of 14.3 across all counties and minimum and maximum values of 4 and 30, respectively. The model typically predicted higher aggregated risk scores (15 or higher) in the southwestern localities while lower scores (15 or lower) in the northern and eastern localities of the state, primarily due to additional hospital resources (e.g., number of general and ICU beds) in those counties.Figure 8Aggregated risk scores for individual counties in Virginia.
2
0biomedical
0Study
352,908
This study found a compelling relationship between MNTI, PAT, and MB G3 based on their overlapping methylation profiles. Our results are in line with a recent report by Ebel et al., who described a 4-month-old boy with an MNTI arising from the skull and clustering in the class family of MB G3 by methylation studies . In our series, 5/7 MNTI clustered in the class family MB G3 with an optimal score (>0.9), supporting the findings reported by Ebel et al. , as well as our index case (PAT, score 0.99). The remaining two MNTI cases clustered in the class family PLEX, PED B, with suboptimal scores (>0.45). However, when analyzed with the “Medulloblastoma classifier group 3/4 v1.0”, all seven MNTIs classified as high-risk MB G3 tumors, subtype II, with a score >0.45. Furthermore, compared with methylation data from a cohort of 36 medulloblastoma patients , all MNTIs and PATs displayed a global methylation profile very close to those of MB G3.
4
0biomedical
0Study
132,476
Two RCT were conducted among office workers who were classified as high risk for future LTSA by a screening questionnaire called the ‘Balansmeter’ in Dutch. The current paper describes a follow-up study on indicators of labor participation with a focus on SA parameters and termination of the employment contract. Similarities can be found between the preventive interventions in RCT I and RCT II in the timing of the preventive intervention and the use of a screening instrument to classify employees as high risk for LTSA. However, the preventive interventions differ in the type and intensity of treatment.
2
0biomedical
0Study
273,475
The data generation described in Section 4 needs several trajectory samples to accurately represent the workspace of the spacecraft-manipulator. However, workspace can have infinite possible locations of the target theoretically and it is impossible to do data generation for all possible goal poses. The Gaussian distribution introduced above can solve this problem by using the conditional distribution property. A probabilistic trajectory distribution can be conditioned to follow not only the desired start and goal state but also the via-points Paraschos et al., 2018. For example, if our trajectory has to pass through a desired state x * t the new mean and variance of the conditioned trajectory will beμw[new]=μw+L(xt∗−ψtTμw)Σw[new]=Σw−LψtTΣw(18)where L isL=Σwψt(Σx∗+ψtTΣwψt)−1(19)and Σx* is the desired accuracy to which the state (xt*) is to be reached.
4
2other
0Study
168,353
A preliminary study of the structure of protein PS1 was performed by constructing a plot with the tool TMHMM available in the suite ExPASy (Sonnhammer and Krogh, 1998; Krogh et al., 2001; Möller et al., 2001), based on the primary sequence of the protein. We obtained a plot for the probability distribution through Hidden Markov Models. The position and score of the transmembrane fragments containing the structure inside–outside of cellular membrane were also determined (Artimo et al., 2012; Guex and Peitsch, 1997).
3
0biomedical
0Study
160,841
Tetracyanoethylene (TCNE) is a strong electron acceptor due to the presence of four cyano groups, and undergoes a [2 + 2] cycloaddition reaction with electron rich alkynes to form cyclobutene rings followed by a retroelectrocyclization reaction to give 1,1,4,4-tetracyanobutadiene (TCBD) derivatives.41 The donor–acceptor systems containing the TCBD acceptor are potential candidates for organic photovoltaics and non-linear optics due to strong intramolecular charge transfer (ICT) and lower HOMO–LUMO gaps.42–48 The photochemical behavior of a few donor-TCBD derived systems have been reported in the literature.49–56 Although with high quantum yields, due to close proximity between the donor and acceptor entities, ultrafast charge separation and recombination was observed in these systems. That is, no charge stabilization could be accomplished. In this regard, developing higher analogs of donor-TCBD bearing systems that would exhibit novel photochemical properties including charge stabilization has been scarce due to the associated synthetic challenges. A recent example involved C3-symmetric central truxene-derived phenothiazine–TCBD and its expanded molecular systems.54 Although elegant, the central truxene made exclusively of saturated carbons played no role in stabilizing the charge separated states.
5
0biomedical
0Study
371,273
Additional file 1: Figure S1. Minimal dual-incision and mini plate internal fixation. (A, B) Incision locations are marked before surgery. (C, D) A medial small incision revealed a comminuted calcaneus inner wall, and the neurovascular tendon in the front of the incision. Both require careful protection. (E) Small lateral incision revealed a collapsed articular surface. The tendon sheath and nerves of the fibula must be protected. (F, G) General appearance of the incisions after fixation. (H, I) Intraoperative fluoroscopic images.
2
0biomedical
1Other
114,682
mAb2 variants were produced by transient expression in CHO K1 suspension adapted cells. The seeds were grown in an optimized, chemically defined, animal-component free, and serum-free media. Cells were transfected with a proprietary transfection agent. After transfection, cells were grown in an optimized media with proprietary recipe at 37 °C and 5% CO2 for 8 days.
4
0biomedical
0Study
134,320
Segmented piecewise linear regression was utilized to identify potential break points (thresholds) where the relationship between average daily Tair, PET, or UTCI, and hospital admissions was altered. Intervals of 0.1 °C were used to divide the data into subsets and then regression lines were fitted on subsets, modeling the association between the independent variable and the hospital admissions. The selection of breakpoint points was based on whether there was a statistically significant difference in the regression coefficients, as well as using the Akaike information criterion (AIC) and Bayesian information criterion (BIC) for evaluating competing models for best model fit .
4
0biomedical
0Study
237,836
There was a significant decrease in GSH, SOD, and catalase activity in the lead- and ZnO NP–treated groups, which was attenuated by α-lipoic acid treatment (Figures 9A–C). A significant increase in lead- and ZnO NP–treated groups alone and in combination was attenuated by α-lipoic acid treatment (Figure 9D). There was also a significant increase in the TBARS level in lead and ZnO NP–exposed groups compared to the control (Figure 9E).
4
0biomedical
0Study
44,512
The structural modularity of the CFNs (i.e. functional modularity) reflects the patterns described above and reveals a clear difference between the diffusion treatments, which are predominantly high-performing, and the non-diffusion treatments, which are predominantly low-performing (Fig 3A). The identification of the CFNs and functional modules reveal two insights. The first is that diffusion-based neuromodulation can be a strong inducer of functional modularity (Fig 3A). Second, if the CFN of an ANN is highly modular, regardless of diffusion, it will exhibit less, or no, catastrophic forgetting (Fig 3B and 3C). In the upper right quadrant of the scatter plots in Fig 3(B) and 3(C), where high-performing, high functional modularity ANNs are placed, there are mostly diffusion networks, but there are also a few non-diffusion networks. Thus, diffusion-based neuromodulation is a strong inducer of functional modules, but it is the functional modules that are allowing catastrophic forgetting to be mitigated.
4
0biomedical
0Study
196,265
Given that by inhibiting TrxR1 activity and increasing intracellular ROS, BBSKE induces a lethal endoplasmic reticulum stress and mitochondrial dysfunction in human gastric cancer cells . Hence, we were interested in whether ROS was involved in the synergistic effect of BBSKE and oxaliplatin. The present study showed that BBSKE and oxaliplatin combined treatment resulted in significant increases in ROS levels, and pretreatment with NAC fully reversed the combined treatment-induced ROS generation and apoptosis, suggesting that ROS play a critical role in the synergistic effect of BBSKE and oxaliplatin. By inducing ROS generation and oxidative stress, the combined treatment concomitantly activated p38 and JNK signaling pathways, as indicated by phosphorylation of both p38 and JNK. In addition, we found that BMS-582,949 or SP600125 could partially attenuate the combined treatment-induced cell growth inhibition and apoptosis, suggesting that activation of the p38 and JNK signaling pathways is essential for the effect of the combined treatment. Furthermore, we found that pretreatment with NAC markedly reversed the combined treatment-induced phosphorylation of p38 and JNK in both SGC-7901 and MGC-803 cells, suggesting that the activation of p38 and JNK signaling pathways is due to accumulation of intracellular ROS.
4
0biomedical
0Study
111,807
Thus, the functional organization of the EC system appears to be more complex than the structure-function dissociation between MEC-spatial and LEC-non-spatial. The MEC is mainly involved in spatial processing but may be able in some conditions to process also non-spatial information. Similarly, the LEC is mainly involved in non-spatial processing but may be able to process spatial information. According to this hypothesis, we expect an important role of MEC/LEC functional interactions via local connections.
4
0biomedical
0Study
125,037
Among 190 patients, 157 cases of peripheral vasculopathy were detected by colour Doppler ultrasound, including 132 cases of plaque, accounting for 84.1%; 64 cases of intimal thickening, accounting for 40.8%; and 38 cases of arteriosclerosis, accounting for 24.2%. There were 32 cases of vascular stenosis, accounting for 20.4%, and 16 cases of vascular occlusion, accounting for 10.2%. 105 cases of the posterior tibial artery were involved, accounting for 66.9%; 90 cases of the dorsal artery, accounting for 57.3%; 65 cases of the femoral artery, accounting for 41.4%; 54 cases of the anterior tibial artery, accounting for 34.4%; and 40 cases of radial artery 6, accounting for 25.5% (Figures 5 and 6).
4
0biomedical
0Study
349,604
Myostatin (growth/differentiation factor 8 (GDF8); gene name MSTN, gene ID 2260) is a member of the transforming growth factor β (TGF-β)3 superfamily of signaling proteins that is primarily expressed in skeletal muscle, with low-level expression reported in adipose and cardiac tissues (1, 2). Myostatin functions as a negative regulator of skeletal muscle growth, and its overexpression results in a substantial decrease in skeletal muscle mass (3, 4). Conversely, genetic deficiencies in myostatin in humans and other species result in significant increases in muscle mass with few apparent detrimental effects (1, 5–7). Thus, inhibition of myostatin signaling provides a therapeutic opportunity to impact diseases of muscle wasting.
4
0biomedical
0Study
299,872
Translation can be divided into four phases: initiation, elongation, termination, and ribosome recycling (Rodnina, 2018). We next compared the abundances of translation-associated factors via whole-cell lysate proteome analysis. Ribosome recycling factor (RRF) and elongation factor-G (EF-G) are involved in ribosome recycling (Prabhakar et al., 2017). The expression of RRF and EF-G was downregulated in the suppressor strain (Figure 3B and Supplementary Data Set 1B), indicating that the ribosome recycling was reduced, which may be caused by decreasing translation in suppressor cells. Although the expression of release factors mediating translation termination was upregulated, the efficiency of translation termination at three stop codons was only slightly increased (Figures 3B,C). This data showed that the translation termination rate was unaffected in suppressor cells. We observed that the protein abundance of elongation factors in suppressor cells was inconsistent and changed little in comparison with that in wild-type cells (Figure 3B and Supplementary Data Set 1B). To examine the efficiency of translation elongation, we measured its fidelity and speed through GFP fluorescence intensity measurement and LacZα induction assay, respectively. In strain MY1901, we observed a marked increase in translational frameshifting readthrough relative to that in the wild-type strain (Figure 3D), suggesting that the fidelity of translation elongation was decreased. Additionally, a LacZ induction assay was used to measure the translation elongation speed (Zhu et al., 2016). We used a cytoplasmic protein FusA and an inner membrane protein MsbA to define the level of translation elongation rate (Supplementary Figure 3). When cells were grown at the same rich growth media (Glucose + cAA), the growth rates of wild-type and suppressor cells were approximately 1.0 h–1 (Zhao et al., 2021) and 0.6 h–1, respectively (Supplementary Figure 3A and Supplementary Table 3). As expected, the translation elongation rate of suppressor cells was markedly decreased compared with that of wild-type cells (Figure 3E and Supplementary Figures 3B–F). As translation elongation rate closely depends on growth rate (Dai et al., 2016), we further reduced the growth rate of wild-type cells to 0.6 h–1 that was similar to that of suppressor cells (Supplementary Figure 3A). The elongation rate of the MsbA in suppressor cell was reduced by approximate 2.0 aa s–1 (amino acids per second) compared with that in wild-type cells, but the elongation rate of the FusA was similar in both wild-type and suppressor cells (Figure 3E and Supplementary Figures 3B–F). We also observed that the elongation rate of MsbA was slower than that of FusA (Figure 3E and Supplementary Figures 3B–F), which is consistent with the observation that the translation elongation speed of inner membrane proteins is slowed down during targeting, but not that of cytoplasmic proteins (Fluman et al., 2014).
4
0biomedical
0Study
50,871
Some aspects of our experimental procedures may limit the generalization of the findings. Firstly, we used a convenience sample with limited variability in age and educational level. Future research should rely on more representative and specific samples (e.g., parents, health practitioners), as well as investigate possible moderating variables (e.g., age, education, socioeconomic status) to account for a broader range of individual differences in how people comprehend scientific information. Also, our participants were domiciled in Italy or Scotland, which raises the question of possible effects of between-country heterogeneity in vaccine attitudes, which might introduce uncontrolled variance into our data. To the best of our knowledge, comparative data on vaccine attitudes and uptake in the UK and Italy are still lacking. However, some studies report a general shift towards a more positive perception of vaccines in both countries [54, 55]. Because our participants were randomly allocated to conditions, there is no reason to expect our results to be systematically biased by between-country heterogeneity. Because of the small sample size of our study, we are not able to ascertain whether these differences actually exist and are reflected in our findings. Secondly, self-reported vaccine uptake should be supplemented with objective data from primary records to produce a more reliable measure of uptake. Moreover, as beliefs can change and evolve dynamically over time, prospective longitudinal data are also needed to assess the robustness of changes in individual beliefs.
4
0biomedical
0Study
61,001
3)For the chain model, chain breakage due to competing substrates induced either an arrest of elongation in the strict chain model (see Figure 5) or a delay in growth in the chain recovery model (see Figure 5—figure supplement 1 ) with a delay time given by (tb − ta), where:
4
0biomedical
0Study
358,335
To increase the impact of CRISPRi, a 2013 study fused dCas9 with a range of transcriptional repressor domains . These domains are typically eukaryotic protein domains which regulate transcription. The Krüppel Associated Box (KRAB) repressor is most commonly used. It interacts with the scaffold protein KAP1, which recruits histone modifying proteins, ultimately creating a tightly-wound, inactive heterochromatin histone state (Figure 1d). Gilbert et al. found that addition of KRAB significantly increased the repression of genes at most tested loci, with one site reducing the ubiquitous EGFP expression by 15-fold in a GFP+HEK293 cell line . Unlike when using dCas9 alone to block transcriptional elongation, dCas9-KRAB can be targeted to either strand of the DNA, dramatically increasing the potential target sites .
4
0biomedical
0Study
107,835
The soil dilution method was adopted for isolation of the Trichoderma by using a Modified Potato- dextrose agar (PDAm) . In detail, 1 g of sediment sample was serially diluted and one milliliter (104 dilution factor) of the serially diluted sample was pipetted out into sterile PDAm Petri-dishes (90 x 15 mm) and spread over the surface of the PDAm by an L-shaped glass rod and incubated at 25±2°C for 5 to 7 days. After the incubation, the Trichoderma colonies were enumerated and calculated the Trichoderma load in the given sample using the standard formula for Colony Forming Unit (CFU) per gram of the sample. All the determinations were carried out in triplicate.
4
0biomedical
0Study
326,881
Pigs are often sub-clinically infected with Campylobacter spp. and contamination of meat during meat processing remains an important food safety risk . Previous studies estimated the prevalence of contamination in pigs varying between 50% and 100%, with excretion levels ranging from 102 to 107 Colony Forming Units (CFU) of Campylobacter per gram of faeces . This study aimed at estimating the prevalence and levels of contamination of thermotolerant Campylobacter in faeces and carcasses of pigs during slaughtering. An evaluation of possible correlations between the genotypic and phenotypic expressions for resistance to antimicrobials in the isolated strains was performed. A comparison between the multi-locus sequence typing (MLST) profiles obtained from pig and human strains, isolated in the same time period, was also conducted.
4
0biomedical
0Study
16,007
The conversion efficiency of the GERSW-based PSR with different number of graphene layer. (a) The ERI of the fundamental TE mode for the GERSW as a function of w g with 0 (blue solid line), 1 (red solid line), 3 (green solid line), 5 (pink solid line), and 7 (black solid line) layers of graphene. In order to satisfy the phase-matching condition between the TM mode in the RSW and the TE mode in the GERSW, the widths of the GERSW for these five cases are set at w g0 = 290 nm, w g1 = 291 nm, w g3 = 294 nm, w g5 = 297 nm, w g7 = 299 nm, respectively. (b) Conversion efficiency as a function of the coupling length (L) with the optimum widths of the GERSW. The vertical dashed lines represent the optimum coupling length (L 0 = 10.3 μm, L 1 = 10.4 μm, L 3 = 10.5 μm, L 5 = 10.8 μm, and L 7 = 11.1 μm, respectively), where the maximum conversion efficiency is achievable for the five cases. (c) Field distribution of light, |E|2, propagating along the 7-layer-graphene embedded PSR for the TE mode (left panel) and the TM mode (right panel) input. (d) Wavelength dependence on the ERI of the fundamental TM mode for the GERSW with 0 (blue solid line), 1 (red solid line), 3 (green solid line), 5 (pink solid line), and 7 (black solid line) layers of graphene. For the cases of 1, 3, 5, and 7 layers of graphene, the silicon layers above the top graphene layer are 105, 85, 65, and 45 nm, respectively. (e) Wavelength dependence of the PSR with the TM mode input. Each sheet of graphene used for the GERSW has the same length as that of the directional coupler, and the width four times as large as the width of the GERSW. Such a gap separation between the GERSW and the metallic electrodes is sufficiently large to avoid the influence of the metallic electrodes on the modal characteristics of the GERSW itself. Here, the wavelength is λ = 1550 nm, w gap = 150 nm, and the height of the RSW and GERSW in these five cases are h 20 = 210 nm, h 21 = 210.3 nm, h 23 = 211 nm, h 25 = 211.7 nm, and h 27 = 212.4 nm, respectively. In (a) and (e), the mesh grids used for the graphene and silicon layers are the same as those in Fig. 1. In (b–d), the simulation of the propagation characteristic is conducted by finite difference time domain (FDTD) simulation with non-uniform mesh grids. The maximum mesh grids for the silicon are set to be 15, 4, and 5 nm along the x, y, and z-directions, respectively, while those for graphene layers are 15, 4, and 0.085 nm along the x, y, and z-directions, respectively. All the mesh grids used in the following modeling work are the same as those in (b–d).
4
0biomedical
0Study
236,490
The first step in the ICU monitoring pipeline included a pre-processing stage that allowed the patients suitable for the study to be identified and for each of them to be assigned to one of the four age groups. Although MIMIC-III includes data from 61,532 ICU stays, the number of actual patients is 46,476, as some of them were admitted to ICU several times. As stated in Section 1, one of the objectives sought in this work was to customize the monitoring system taking into account the patient age range. For this purpose, four patient groups were defined. Age limits, denoted as Xi, were based on those used by the Centers for Medicare and Medicaid Services of the US Government , i.e., XA:(18, 45]; XB:(45, 65]; XC:(65, 85]; XD:(85, ∞]. Since the goal was to improve the monitoring system for the adult ICU, patients under the age of 18 were not part of the study.
4
0biomedical
0Study
136,801
RNA was extracted from the isolated microglia with a Qiagen’s RNeasy Micro kit (Hilden, Germany) with on-column DNase digestion following the manufacturer’s instructions. Then, 50 ng of RNA for each sample was processed using the nCounter Mouse Neuroinflammation Panel (Seattle, WA, USA), gene expression analysis was performed on the nCounter system (NanoString Technologies), and analyzed using nSolver analysis software (NanoString Technologies) according to the manufacturer’s instructions. Further details are specified in the Supplementary Information.
4
0biomedical
0Study
4,791
After processing of the reads, we obtained between 25 and 28x106 paired-end reads for the different samples (Additional file 1). These were then assembled de novo and sorted into “plant-“(80.4%) and “fungal”-derived (15.2%) via BLAST analyses against the C. purpurea genome, a rye cDNA database and NCBI databases. Transcripts mapping to both, plant and fungal sequences, were excluded (4.5%). A principal component analyses (PCA) of these data sets shows that the four plant transcriptomes were all significantly different, indicating that the infection process of the strains induces specific responses within the host (Fig. 2a). The sizes of the fungal data sets differ considerably with 9.81% (Cp20.1), 1.62% (Δcptf1) and 0.03% (Δcpcdc42) of reads mapping to the C. purpurea reference (Additional file 1) and obviously reflect the colonization levels of the strains. The PCA also reveals significantly different transcriptomes for the three fungal data sets (Fig. 2b). However, due to the low quantity of fungal transcripts in the ∆cpcdc42 infected material, this data set was not included in further quantitative evaluations. The reads of the other data sets were mapped against the C. purpurea and the rye genome to analyze the transcriptomic changes during infection in more detail [21, 22].Fig. 2Principal component analysis of de novo assembled transcripts: a plant sequences and b fungal sequences. Compared were the FPKM values of the reads matching the transcripts of all four samples (mock, Cp20.1 infected, ∆cptf1 infected, ∆cpcdc42 infected) plus a reference data set for plant and fungal sequences (ref; all data points set to zero)
4
0biomedical
0Study
21,464
We examined the effect of temporal frequency in narrowband maskers (1 octave full-width at half-height; see also Fig. 2b) on CFS suppression duration. Temporal frequencies were centred at rates of 0, 0.375, 0.75, 1.5, 3, 6.25, 12.5 and 25 Hz. Data were analysed in a one-way (masker temporal frequency) repeated-measures ANOVA. The effect of masker frequency was highly significant, with F(6, 72) = 17.5, p < 0.0001, ηp2 = 0.59, and results are plotted in Fig. 3a as normalized suppression duration in a semilog plot. Consistent with the frequency spectrum of the Mondrian, suppression was much stronger at low than at high frequencies, yet the pattern follows a bandpass tuning that was well described by a Gaussian normal function. The Gaussian was fitted using a maximum likelihood routine with three free parameters: mean, standard deviation and vertical offset. Amplitude was not a free parameter and was defined as the maximum normalised suppression duration minus the baseline. The best-fitting Gaussians had the following parameters: mean = 0.97 Hz (SD = 0.48), standard deviation = 1.42 octaves (SD = 0.63), baseline = 0.44 (SD = 0.20) and amplitude = 1.52 (SD = 0.59).
4
0biomedical
0Study
304,139
Transcriptome profiling of Azucena and IR64 root zones under control and water stress conditions and the intersections of DEGs across 6 interaction of genotypes, zones and conditions. (A) The number of genes not expressed in any sample (the silent group) (FPKM < 1 in none of the doublet sets of replicates), expressed in less than 20% of samples (Low frequency), expressed in 20–80% of samples (Intermediate frequency), and expressed in more than 80% of samples (Constitutive). (B) The number of genes expressed in only one genotype (All replicates of three zones; Genotype specific), one condition (All replicates of the condition; Condition specific), and one zone (All replicates of the zone; Zone specific). (C) Principal component analysis (PCA) visualization of all 24 samples in a 2D space. PCA were used on Log2 transformed FPKM values of a set of 24742 genes (about 65% of all identified annotated genes) expressed in at least one set of doublet replicates (FPKM > 1) in this analysis. The color indicates genotype and condition (IRn, IR64 under normal condition; AZn, Azucena under normal condition; IRs, IR64 under stress condition; AZs, Azucena under stress condition) and the shapes indicates root zones. (D) Horizontal bar graph represents the number of up- (Red boxes) and down- (Blue boxes) regulated DEGs (FDR adjusted p-value cut-off of ≤ 0.05) based on their fold changes. (E) The intersections of DEGs across the six gene lists in the vertical bar graph (40 out of 62 intersections presented and the information on the others can be found in Supplementary Table S6). Sections colored in red/blue depict genes up/down regulated synchronously, while the gray sections are the ones upregulated in one and downregulated in the other and vice versa. The circles below each bar with black color indicate which sets are in the intersection. (F) The significantly enriched BPs are shown as barplots in the bottom panel based on their –log10 adjusted p-values. The proportion of gene numbers included in each BP in annotated gene numbers of the cluster (white text) along with the proportion of total gene numbers included in each BP in annotated gene numbers of the background (yellow text) were mentioned in the bars. IRsnZ1, expression changes in zone1 of IR64 (Stress vs. Control); IRsnZ2, expression changes in zone2 of IR64 (Stress vs. Control); IRsnZ3, expression changes in zone3 of IR64 (Stress vs. Control); AZsnZ1, expression changes in zone1 of Azucena (Stress vs. Control); AZsnZ2, expression changes in zone2 of Azucena (Stress vs. Control); AZsnZ3, expression changes in zone3 of Azucena (Stress vs. Control).
4
0biomedical
0Study
377,668
The studies included in this review are described in table 1, including diagnosis of included participants, number of intervention groups, details on the interventions and comparisons tested and the number of outcomes measures used. The included studies were published between 2002 and 2019.
4
0biomedical
2Review
106,013
We sought to address the limitations of lipid monolayer coated affinity grids by employing a GO derivative that minimizes background signal due to the single atom thickness and improved conductivity as a way to combat sample charging and instability during image capture16. Here we demonstrate the utility of affinity grids using Langmuir-Schaefer (L-S) transfer of GO monolayer sheets that have been functionalized with covalently linked Nα, Nα-dicarboxymethyllysine (GO-NTA). Using these affinity grids, we were able to selectively capture both His6-T7 bacteriophage and His6-GroEL. When the prepared grids were further modified with bovine serum albumin (BSA), a common antifouling agent that limits non-specific adsorption of non-targeted cellular debris, we were able to selectively capture these proteins directly from bacterial lysate while avoiding deposition of non-target proteins (Fig. 1).
4
0biomedical
0Study
106,561
Several techniques101112 have been developed for the recovery of a rough shape of the original time series solely from the information of its recurrence plot. However, we have chosen to focus on the RPR method we previously proposed in 200811 because (i) it works, even if the original time series is multivariate, and (ii) we have proven a theorem13 that the metric space recovered using our prior method11 is equivalent to the original Euclidean metric under mild conditions. In addition, the RPR method is known to be rather robust, even if we change the definition of the closeness14. Therefore, we used the method to reconstruct the 3D chromosome structure from Hi-C data.
4
0biomedical
0Study
372,753
The in situ XRD dataset is also refined using the Rietveld method with crystal structure parameters (atomic positions, thermal parameters) fixed, and the Rwp of the refinements ranged from 6.1 to 9.0. Figure 5a,b display the lattice parameter variations vs. the Li content during cycle B. The differences between the b and c values of the three phases were small, whereas the differences between the a values of the CFP and the other two phases were large. Table 2 lists the lattice parameters of the pristine LCFP phase, the average values of L0.6CFP and CFP, and differences between them. The lattice parameters of L0.6CFP and CFP remained nearly constant during the charge and discharge, owing to their approximately constant compositions, whereas the lattice parameters of LCFP changed continuously during cycling because of its solid solution nature. It is clear that the lattice parameter changes are anisotropic, and so are the stresses induced. The differences in volume were mainly caused by the changes in the a-axis. The volumes contracted by 2.57% from LCFP to L0.6CFP, and by 4.39% from L0.6CFP to CFP, a total of ~6.85% from LCFP to CFP (similar to the volume change from LFP to FP (6.81%)) . This relatively large volume contraction/expansion is likely to crack the cathode material during cycling, especially in the all solid-state battery, thus deteriorating the material and leading to its eventual failure.
4
0biomedical
0Study
240,632
Nitrogenase expression in the yejE and yejF mutant bacteroids in Medicago truncatula nodules. (A) Confocal microscopy of sections of nodules infected with S. meliloti Sm1021.pHC60-pnifH::GFP (WT), Sm1021.ΔbacA.pHC60-pnifH::GFP (bacA), Sm1021.ΔyejE.pHC60-pnifH::GFP (yejE), or Sm1021.ΔyejF.pHC60-pnifH::GFP (yejF) and stained with propidium iodide (red stain). Green-stained bacteroids are functional, while red-stained bacteroids are nonfunctional. (B) Flow cytometry determination of GFP levels in nodule bacteria (upper panels) and heat-killed nodule bacteria (lower panels). The green square shows the position of the GFP-positive bacteroids. FSC, forward scatter.
4
0biomedical
0Study
386,437
Our experiment investigated the underlying structure of three-dimensional spatial behaviour and foraging patterns in rats. We first focused on characterising their movement through space and the existence of possible home bases in two 2D environments: a high-walled arena (“Walled arena”) and a platform with low walls (“Platform arena”) vs two 3D environments: a lattice aligned to the orientation of the room and gravity (“Aligned lattice”) and the same lattice tilted with respect to gravity (“Tilted lattice”). The apparatus and procedure are presented in Fig. 1.
4
0biomedical
0Study
388,564
Statistical analyses compromised student’s unpaired t-test, Mann–Whitney U, analysis of variance (ANOVA), Kruskal–Wallis (K-W), paired sample t-test, Pearson’s Chi-square (χ2) test, Fisher’s exact test and binary logistic regression analyses, as appropriate. The cardiovascular-related confounders (age, gender, smoking status, HbA1c, systolic blood pressure (SBP), LDL, CRP as well as eGFR and UACR) were included as covariates in multivariable models. Adjusted odds ratios (adjOR) were determined by multivariable analyses and presented per one SD increase (95% confidence interval (CI)). Confounding was identified by a change in OR greater than 10.0%, according to Rothman . Constructing a receiver operating characteristic (ROC) curve, the area under the curve (AUC) was computed. All statistical assessments were evaluated two-sided at a significance level of < 0.05; a two-tailed probability level of < 0.01 was considered highly significant.
4
0biomedical
0Study
385,925
Figure 16 shows the examples of quantization when {E, V} = {50, 19}, which presents the highest value of R2. In shape 8, points at sharp convexities are allotted between s19 and s17, while points at sharp concavities are allotted to s1. In shape 5, the points at gradual convexities are allotted between s15 and s12, while points at gradual concavities are allotted to s9. In shape 6, the points at plane surfaces are allotted to s10. This suggests that the convexities and concavities of sample shapes B are allotted to different states based on their sharpness by setting parameters at {E, V} = {50, 19}. Note that the reason why V becomes an odd number is to prevent overestimating minute unevenness, the same as sample shapes A.
2
2other
0Study
103,227
We observed increased Col IV vessel density in AD specimens compared to control subjects, with a similar increase in Tg APP brain. Previous works have reported increased thickening of basement membranes in AD (Mancardi et al., 1980; Kalaria, 2002; Miao et al., 2005), in particular Col IV (Miao et al., 2005; Tong et al., 2005), associated or not with differences in density. In Tg APP mice similar changes were observed (Tong et al., 2005). Although the exact cause of increased basement membrane is unknown, several factors could be involved such as soluble Aβ and its progressive deposition in vessels, inflammatory mediators derived from activated glial cells around vessels and chronic changes in levels of vasoactive mediators (Grammas, 2011). Cannabinoid agonists, in particular CB2 selective agonists, impinge on several of these factors by decreasing glial activation, inflammation and Aβ levels (Ramírez et al., 2005; Martín-Moreno et al., 2012; Wu et al., 2013; Chiurchiù et al., 2015), explaining the normalization in vessel density following prolonged oral treatment with the drugs. At the ultrastructural level, aortic endothelial cells appeared normal in Tg APP aortae, in agreement with their preservation found in other works (Iadecola et al., 1999; Miao et al., 2005), which contrasts with the endothelial disruption in Aβ treated vessels (Thomas et al., 1996). Therefore, altered vessel function is not a consequence of endothelial disruption or death. Interestingly the major change observed in Tg APP aortae compared to wt mice was the increase in Col IV in the basement membrane, paralleling the changes in AD brain microvasculature, which may be involved in altered vessel contractility.
4
0biomedical
0Study
229,946
Commensal gut microflora like Lactobacilli and bifidobacteria produce large amounts of acetic acid and lactic acid, maintaining a low pH level in the gut, inhibiting the growth of pathogenic bacteria and yeasts. While the yeast dies easily in such conditions, pathogenic bacteria survive due to an active proton pump and the commensal flora is resistant to these acids. The pathogenic survival is, however, short-lived and they are gradually eradicated, as they cannot keep up with the ATP supply required for the energy of their proton pumps.
4
0biomedical
1Other
285,075
Three possible mechanisms have been proposed to explain the effect of paternal alcohol consumption on the offspring: (a) An alteration of the sperm chemical composition, leading to behavioral, biochemical, and hormonal disturbances in the offspring; (b) A failure of the elimination of EtOH-damaged sperm; and (c) An induction of genetic mutations in sperm DNA that can be transmitted to the offspring . Although chemical alterations in sperm and/or seminal plasma may compromise embryonic development, this remains to be confirmed. The second hypothesis refers to the mechanisms of natural selection that may fail to remove spermatozoa damaged by EtOH during spermatogenesis, in favor of genetically intact spermatozoa. The third hypothesis emphasizes a heritable genetic change in EtOH consumers, and seems to be the most accepted . However, a study published in 2017 was not able to identify any association between the phenotypes observed in mice exposed to EtOH (fetal growth restriction and altered developmental programming) and the paternal DNA methylation profiles, questioning the transgenerational effect of EtOH exposure . EtOH-related epigenetic effects on the paternal germline might provide an explanation for the transgenerational influence of the father’s lifestyle habits on the development of the offspring, and it surely deserves more investigation .
4
0biomedical
0Study
120,685
The scratch-wounded HUVECs monolayer was incubated with or without DTX (Fig. 5). In Fig. 5A, the black line was the front of cell migration at injury site. The images were imported into Image J and converted to stacks for determine degree of migration. After the presence of DTX at 0.05, 0.5 and 5 nM for 6–36 h, the distances of HUVECs migration were 60.00–415.00, 60.67–369.00 and 53–262.33 µm, respectively, while in the absence of drug, the distances of HUVECs migration were 86.67–644.67 µm (Fig. 5B). The degrees of wound repair in the presence of DTX at 0.05, 0.5 and 5 nM for 6–36 h were 9.30–63.67, 8.83–55.00 and 7.87–38.67%, respectively, while those of the control group were 13.77–96.67% (Fig. 5C). The findings indicated that the migration and wound repair of HUVECs were inhibited by DTX in a time- and concentration-dependent manner.
4
0biomedical
0Study
331,207
The human allogenic use of ASCs appears to be safe and effective in the studies analyzed. No severe adverse effects were found. In each case, while autologous ASCs therapy has shown great clinical application in many fields, it appears to be necessary to perform additionally higher-quality studies before considering it as a standard cellular therapy the allogenic use of ASCs.
4
0biomedical
2Review
158,764
Table 4 shows the findings and the quality of evidence for associations between the intake of micronutrients and the incidence of hip fracture. The quality of evidence was very low for all micronutrient exposures. Near-significant inverse associations were observed between dietary intake of carotenoids or lycopene and hip fracture (higher vs lower intakes; carotenoids OR: 0.72 (0.51, 1.01); lycopene OR: 0.84 (0.69, 1.01)) . Significant positive associations were observed between dietary vitamin A and retinol intake and hip fracture in meta-analyses of higher vs lower comparisons, respectively (vitamin A RR: 1.29 (1.06, 1.57); retinol RR: 1.40 (1.02, 1.91)) . In dose-response meta-analyses (per 300 mg increase per day), no clear association was observed between hip fracture and dietary calcium intake . In meta-analyses comparing higher vs lower intakes, no clear association was observed between hip fracture and dietary intake of vitamin C , a-carotene , b-carotene , b-cryptoxanthin , lutein/zeaxanthin , ALA , EPA with DHA , or antioxidant vitamins .
4
0biomedical
0Study
295,910
We first normalized this data using TPM. Then, a matrix was generated using log2(TPM+1). The transcript levels of immune checkpoints, the genes with the most relevant for C. albicans infection were identified in bulk RNA-seq using ggstatsplot (version 0.5.0) package.
4
0biomedical
0Study
348,927
A total of 33 healthy Holstein dairy cows in their second lactation period were selected from the Yangzhou University experimental farm. The 33 animals with similar body weights were fed with total mixed ration (TMR) . Milk samples of the 33 dairy cows were collected from the left anterior mammary region on early lactation (30 days after calving (30 d)), peak lactation (90 days after calving (90 d)), mid lactation (180 days after calving (180 d)), and late lactation (270 days after calving (270 d)), and transported on ice to the lab within 2 h for the determination of milk composition. Three Holstein dairy cow (A, B, C) mammary glands were collected using surgical methods at six lactation stages (−7 d, 30 d, 90 d, 180 d, 270 d, 315 d) . In detail, the biopsy site was shaved and disinfected with 75% ethanol, and 1 mL procaine was injected subcutaneously. Then, the disinfected biopsy site was incised along the midpoint to collect the parenchymal mammary glands. Lastly, the parenchymal mammary glands were transferred to sterile tubes and frozen in liquid nitrogen until RNA isolation.
4
0biomedical
0Study
146,210
Firstly, a review of existing research on social attachment is conducted to understand the concept and structure of social attachment. Secondly, the literature analysis software CiteSpace is used to search the relevant domestic and international literature and to analyze the existing methods of developing scales for attachment multidimensional variables. Drawing on the scale measurement paradigm of attachment theory within the scope of existing research hotspot areas, reference is made to the rationale for the development of multidimensional scales for brand attachment, local attachment, parent–child attachment and adult attachment. Again, in-depth interviews and focus groups were used to further capture the perceptions of social attachment based on the perspectives of local Chinese social media users. The interview outline focuses on the following three levels: general information on the use behavior of local social media users, including the behavioral habits, content used, and inner experience of using local social media; past experiences of using local social media; and the emotional relationship between users and the app in the process of using local social media. The general context is broader, with past experiences focusing on the act of using local social media itself, and emotional relationships aiming to draw out the theme of attachment relationships further. On this basis, this study conducted follow-up interviews with users of the above three social media software from March to December 2018, and as of December 10, 2018, a total of 27 users of the three social media were selected for data collection, and after categorizing and processing the interview transcripts of 27 users, the data were cleaned to form a word file, which became the source of developing the social attachment initial questionnaire imported as a source of material. The demographic characteristics of the in-depth interview sample are shown in Table 1.
3
2other
0Study
377,033
Crosslinked polyethylene (XLPE) has long been favored as an insulating material for extruded high-voltage (HV) alternating-current (AC) power cable systems due to its benefits of outstanding electrical, mechanical and thermal properties , but in the case of direct-current (DC), with power cable systems trending towards higher voltages and a larger capacity, one of the urgently desired characteristics for polyethylene insulating materials is a high DC breakdown strength with good temperature stability . In the past decades, various methods have been developed to enhance the DC breakdown strength of polyethylene, and nanocomposites have arisen much attention in this context. Nanofillers like MgO, Al2O3, SiO2, TiO2 and so on can improve the DC breakdown strength of polyethylene . Based on lots of positive results acquired, nanocomposite addition is considered as one of the most promising techniques to realize the target of improving DC breakdown strength as well as related good temperature stability. However, it has been reported that the effect of adding nanofillers into polyethylene or XLPE on DC breakdown strength is inconsistent, and decreased DC breakdown strength of nanocomposites is even observed, which may come from the diversity of sample process or moisture absorption by the nanofillers . Moreover, it is also of concern that internal stresses due to the mismatch of thermal expansion coefficients might lead to the insulation failure when a high electric field is applied .
4
2other
0Study
135,071
AMR is classified by the intensity or degree of microbial resistance to one or more antibiotics. For example, bacteria may exhibit multidrug resistance (MDR), extensive drug resistance (XDR), or even pan drug resistance (PDR) phenotypes. MDR typically refers to bacteria that are resistant to at least one antibiotic in three or more antibiotic classes. XDR means bacteria are susceptible to only one or two antibiotic classes, whereas PDR indicates that bacteria are not susceptible to any known antibiotic class (Magiorakos et al., 2012). The WHO established a list of AMR “priority pathogens” which includes bacteria that pose the greatest danger to human health. The list has been divided into three key priorities: “Critical, High, and Medium,” based on the urgency and need for new antibiotics or novel therapeutics. The highest priority “Critical” group includes bacteria that are extremely resistant to current antibiotics, including last resort treatments. These bacteria pose serious threats to hospitals, particularly patients whose care involves use of medical devices or surgical procedures. The opportunistic bacterium, Pseudomonas aeruginosa (Pa) is one of three highest priority “Critical” bacterial species on the WHO list.
4
0biomedical
2Review
243,479
It is known that the Drucker–Prager failure criterion may overestimate the failure stress in the parametric area of tensile volumetric stresses. Thus, this criterion is often supplemented by the Rankine condition:(8b)σ1=σt, where σ1 is maximum principal stress. Rankine criterion limits the main tensile stress to the tensile cut-off.
2
2other
1Other
230,034
We recently demonstrated the possibility that innervation status by motor neurons is a major regulatory factor to maintain AQP4 expression in the skeletal muscles in vivo (Ishido & Nakamura, 2017, 2018). Therefore, in the present study, AQP4 expression levels were expected to be maintained during cast immobilization even if skeletal muscle atrophy was induced. However, a significant decrease in AQP4 expression was observed in the immobilized skeletal muscles.
4
0biomedical
0Study
374,716
To the best of our knowledge, a handful of studies have specifically described the characteristics of AVN after PFNF. In 1962, Ratliff et al. first described three patterns of AVN after PFNF according to a review of 29 cases: the highest incidence was of AVN occupying the total head (type I, 15 cases), followed by partial necrosis of the epiphysis (type II, 7 cases) and necrosis between the epiphyseal plate and the fracture line (type III, 7 cases). Numerous subsequent studies adapted this criterion (Table 1); however, the limited sample size of enrolled patients was insufficient for demonstrating the prognostic value of Ratliff’s classification. In addition, few studies have confirmed the relationship between the prognosis of AVN after PFNF and other recognized prognostic factors for most types of AVN, including hip symptoms, the presence of collapse at diagnosis, and the location of the lesion [25, 26]. Table 1The outcomes of AVN after PFNF in the published literature as described by the Ratliff classification system and assessmentAuthorsYearPatientsMean age, years (range)AVNRatliff classification*Ratliff assessment**IIIIIISatisfiedUnsatisfiedStone et al. 20152211.0 (4.5–17.4)852135Panigrahi et al. 20152810.5 (4–15)4022NANABukva et al. 20152810.7 (4–14)11632NANAHadju et al. 2011811.6 (3–15)1010NANABali et al. 20113610.0 (3–16)761007Nayeemuddin et al. 20091410.0 (6–14)110001Inan et al. 20093911.1 (4–16)11812110Varshney et al. 20092111.8 (5–15)3120NANADhammi et al. 20052610.8 (3–17)4NANANA04Togrul et al. 20056110.2 (2–14)9810NANAFlynn et al. 2002188.0 (2–13)1010NANABagatur et al. 20021711.0 (7–14)942309Mirdad et al. 2002149.1 (4–16)7430NANAMorsy et al. 20015310.2 (3–16)21NANANA021Ng et al. 1996329.5 (NA)9711NANAForlin et al. 19921611.7 (4.6–16)14554212Canale et al. 1977609.7 (0.5–17)262114125Chong et al. 197520NA (5–19)1055028Zolczer et al. 197227NA (13–19)725052Lam et al. 197175NA (≦ 17)11623NANARatliff 196271NA (< 17)291577326Total686203104452917130Percentage29.6%58.4%25.3%16.3%11.6%88.4%AVN avascular necrosis, NA missing value/not clear*Classification of avascular necrosis as proposed by Ratliff**Classification of final result according to Ratliff
4
0biomedical
0Study
317,397
Propensity score matching was used to reduce selection bias in this study. The matching process was conducted with a minimum-distance scoring method and a 1-to-1 match between the ACEI/ARB(-) group and the ACEI/ARB(+) group. In this study, propensity scores were calculated through a binary logistic regression model, including covariates of age, sex, body mass index (BMI), fasting blood glucose (FBG), hemoglobin (HGB), eGFR, low-density lipoprotein cholesterol (LDL-C), history of smoking and dyslipidemia, previous medication history including antiplatelet agent, beta-blocker, and statins. Ultimately, 1050 ACEI/ARB(+) patients were individually 1:1 matched to 1050 ACEI/ARB(-) controls using nearest available score matching. The statistical analysis software SPSS version 24.0 was used for the matching.
4
0biomedical
0Study
324,645
Methicillin-resistance Staphylococcus aureus (MRSA) is multidrug resistant pathogenic bacteria that has become a major healthcare burden (Highlander et al., 2007). To determine the virulence and resistance mechanism, we analyzed the translatomic response of the S. aureus USA300-HOU-MR strain under antibiotic treatment using the STATR pipeline. One of the oxazolidinone linezolid was treated with a sub-lethal dosage to reproduce the antibiotic treatment carried out in clinics. In the Ribo-Seq dataset, the 3’ end of the reads showed a clearer three-nucleotide periodicity than the 5’ end (Figure 6A). Interestingly, the ribosome density of the linezolid-treated S. aureus on close vicinity of the start codon was significantly higher than the control sample (Figure 6B). Linezolid is a translation initiation inhibitor that binds to the A site of the ribosome, preventing cognate-charged tRNA entering as a result (Renslo, 2010; Zhanel et al., 2015). Considering that the A site of the ribosome lies ~14 nt upstream of the 3’ end of the RPF (Mohammad et al., 2019), the increased RPF profile indicates ribosome stalling at the start codon (Figure 6B). As this example shows, Ribo-Seq analysis with STATR provides a nucleotide-resolution mechanistic understanding of translation in vivo. Next, we analyzed the differential translation of genes involved in the response toward linezolid treatment. Before analysis, the reproducibility between biological replicates and between the different treatment groups was examined. The two biological replicates were clustered well and the different experimental groups were separated distinctly (Figure 6C and 6D). By analyzing the normalized expression levels, we discovered 342 differentially expressed (translated) genes (DEGs) in which the expression level was significantly changed (adjusted p-value lower than 0.05) when treated with linezolid (Figure 6E). It has been reported that the transcription of the accessory gene regulator (Agr) is induced upon exposure to linezolid (Choe et al., 2018). Agr proteins are the major regulators of the virulence and pathogenesis of S. aureus (Queck et al., 2008), whose translation in response to linezolid has never been reported. DEG analysis revealed that the translational levels of Agr regulators are activated similar to the transcriptional levels (Figure 6E). Overall, STATR provides a simple and robust analysis pipeline for translational studies, including high-resolution ribosome footprinting, allowing for a molecule-level study of translation, as well as a genome-wide understanding of translation.
4
0biomedical
0Study
345,213
GFAP is an indicator of astrocytic plasticity; retraction of astrocytic processes or GFAP filaments from the surrounding of neurons is pivotal for the development of ischemic brain injury (Wang and Parpura, 2016, 2018). If blocking abnormal astrocytic plasticity in the SON can reduce vasopressin secretion, it should also block GFAP reduction in Zone D of the cortex. To test this hypothesis, we compared bilateral GFAP expressions in the cortex of MCAO rats without and with microinjection of TGN-020 in the SON. As shown in Figure 4Aa, there was no significant difference between bilateral cortex in sham rats (85.4 ± 10.2%, n = 6 in Zone A vs. 82.0 ± 10.3%, n = 6 in Zone D, p = .694 by paired t test; Figure 4Ab). In MCAO rats, GFAP expression in the MCAO side was significantly lower than the non-MCAO side (55.6 ± 13.2%, n = 6 in Zone D vs. 80.9 ± 35.0%, n = 6 in Zone A, p = .047 by paired t test; Figure 4Ab).
4
0biomedical
0Study
159,873
To determine the strength of aptamer and spike trimer antigen interaction, we have determined the dissociation constant of selected aptamer (S1 and S14) candidates using BLI. It is a label-free technology to measure biomolecular interactions in real-time. The 5′ biotinylated aptamer was immobilized on a streptavidin (SA) sensor, and spike trimer protein at various concentrations (7.4–600 nM) was used as an analyte. The aptamer evinced a very tight binding with the spike protein, which is characterized by a KD in low nanomolar range using an appropriate (1:1) ligand binding model (Figure 3B). The aptamer S14 evinced ∼3-fold higher affinity (KD = 21.8 nM) then S1 (KD = 68.9 nM). Considering the higher affinity of aptamer S14, it was selected for further evaluation.
4
0biomedical
0Study
373,710
This model is an improved version for the classification of DR stages in this study. Algorithm 2 presents the details of the proposed model. Let ℋ = {DenseNet-121, ResNet50, Inception-V3} be pretrained models. The models are fine-tuned with three fundus images datasets (X,Y), under the same conditions as Model 1 (Section 3.2). The proposed bagging ensemble for Model 2 is illustrated in Figure 4.
2
0biomedical
0Study
352,147
This work aimed to convert the transient synNotch receptor activation to an event of much longer duration than temporary reporter fluorophore expression. We considered the induction of genetic marks by CRISPR/Cas9 technology as the most versatile approach to storing molecular information in a cell’s DNA for later readout (Figure 9). This assessment is supported by a previous study in which an inactive dCas9-derivative fused to a VP64 transactivator was used to specifically induce reporter gene expression (mCherry) after receptor activation.
4
0biomedical
0Study
57,288
Several physical and immunological factors influence Candida skin infections, which display a preference for occluded regions of skin where humidity and CO2 accumulate and the skin is constantly experiencing friction . For example, such conditions can be found while infants are in diapers, where the combination of elevated pH and the presence of lipases and proteases from feces commonly leads to secondary Candida infections, mainly caused by C. albicans from the gastrointestinal tract, resulting in diaper dermatitis, as reviewed in . Recurrent Candida infections of the skin and mucosal surfaces are referred to as chronic mucocutaneous candidiasis (CMC), which occurs mainly in individuals with primary or acquired immunodeficiencies , upon antibiotic treatment or injury with varying individual risk factors dependent on the epithelial surfaces . Increased Candida colonization has also been associated with other skin disorders, including atopic dermatitis and psoriasis . In addition to colonization, the risk for superficial Candida infections is increased for individuals suffering from psoriasis. In part, this may also be favored by the treatment of psoriasis with corticosteroids or novel immunosuppressive agents such as tumor necrosis factor alpha (TNFα) or interleukin-17 (IL-17) inhibitors, as these pharmacological interventions specifically affect antifungal immune responses . Interestingly, psoriasin, which is produced in psoriatic plaques, has been shown to have broad antifungal activity by inducing apoptosis in several filamentous fungi, but it is not active against C. albicans .
5
0biomedical
2Review
122,003
Palv– loops reflect the effects of factors operating during spontaneous tidal breathing at rest, while several variables reported in Table 4 to which loop derived parameters have been related, were recorded during vital capacity maneuvers. For example, the amount of gas trapping as estimated by RV/TLC% or by a decrease of VC% does not ensure that gas trapping were present during spontaneous breathing.
3
0biomedical
0Study
188,172
Sixteen percent of the sample met diagnostic criteria for GAD. A larger treatment effect on the LSAS total score was seen in subjects with comorbid GAD (−35.0 ± 7.26 for JNJ-42165279 and −18.4 ± 6.96 for PBO, LS mean difference −16.6 ± 10.09, p = 0.059, Cohen’s D = 0.70) (Table 4S SOM). A significant treatment effect was seen on the GAD-7 (LS mean difference −1.9 ± 0.82, p = 0.01, Table 5S SOM). There was a modest reduction in anxiety symptoms on the HAM-A which met the statistical threshold for effect (p = 0.19) but was not clinically meaningful. Ten percent of the sample had comorbid MDD, and depression severity on the Hamilton depression scale was low at baseline. Little change in symptom severity occurred over the trial and there was no significant treatment effect although there was not much room to demonstrate a change (Table 3S, SOM).
4
0biomedical
0Study
1,945
For some medical applications, the rigidity and brittleness of the PLA are undesirable and the addition of elastomers is the easiest solution to overcome this drawback. TPU are among the most used polymers in 3D printing. They are also attractive for some biomedical applications due to their biocompatibility, high elongation at break and good abrasion resistance. As shown before, the use of different fillers impart to PLA exceptional mechanical strength, electrical conductivity, and enhanced thermal stability. Among them, composites with carbon fibers and graphene oxide (GO) proved to be also suitable for 3D-printing process. The addition of GO and TPU may have a cumulative effect of increased flexibility and mechanical strength. Chen et al. studied both the influence of the GO concentration and printing orientation on the mechanical properties of a TPU/PLA (7/3) blend . Compression modulus tests have shown an increasing trend with the increase of GO content from 0.5 to 5 wt.% for both printing orientations, but the highest values were found for the specimens having the same printing orientation and height direction. The addition of only 0.5 wt.% GO determined an increase of the tensile modulus by 75% as compared with TPU/PLA sample, further addition of nanofiller determining a reduction of properties. This was explained by the percolation effect, which appeared below 2 wt.% GO content. All TPU/PLA/GO scaffolds supported fibroblast cells growth and proliferation, with the optimum effect at 0.5 wt.%.
4
0biomedical
0Study
380,370
That said, it is not obvious that segregation will exacerbate the association between district socioeconomic status and achievement. If the average achievement in a school district is simply a function of that district’s characteristics and composition, then there is no reason to expect segregation to have any independent effect on district achievement or the gradient. Segregation certainly shapes the socioeconomic composition of a community and leads to greater variability in district average socioeconomic status, but that alone does not imply that the relationship between achievement and socioeconomic status would be stronger when segregation is higher. Thus, it is an open question whether segregation exacerbates the between-district socioeconomic achievement gradient.
1
2other
1Other
184,406
Total RNA was isolated using the RNeasy Micro Kit (Qiagen), as previously described37. Isolated RNA was reverse transcribed into cDNA using oligo deoxy-thymidine (oligo (dT)) primer and SuperScript III First-Strand Synthesis System (Invitrogen). Real-time qPCR was then performed using Taqman Universal PCR Mastermix and Taqman primers for glyceraldehyde-phosphate dehydrogenase (Gapdh; Mm99999915_g1), Acta2 (α-sma; Mm01546133_m1), and IL-1β (Mm004324228_m1) (Life Technologies). The results were analyzed by comparative threshold cycle method and normalized to GAPDH as an internal control.
4
0biomedical
0Study
72,008
More recently, Munyangango et al. developed a method for scoring active disease in OcMMP, by dividing each eye into four quadrants and measuring erythema from 1 to 4 (+) for each quadrant . This conjunctival inflammation scoring tool was later adopted into a systemic MMP scoring tool by consensus of an international panel of bullous diseases experts at a MMP conference .
4
0biomedical
0Study
6,047
In this review, we summarize the results of studies in animal models and humans on the effects of perinatal choline nutrition on brain development, on cognitive function in the adult, and on the progression of several neurodegenerative diseases. We also discuss emerging evidence for neuroprotective effects of dietary choline consumption during adulthood. While we focus on choline, it is important to recognize that other nutrients such as folate, vitamin B12 and vitamin B6, influence the metabolism of choline, and their availability may modify the requirements for choline.
4
0biomedical
2Review
98,379
To verify our findings in the H/R RTEC model, an in vivo renal I/R injury model was created using KM/NIH mice. Samples of kidney tissue from the treated mice were collected for RNA extraction. Next, qRT-PCR was performed to measure the mRNA levels of several cytokines. Mice injected with MSCs or htMSCs had increased levels of cell protective cytokines (HGF, IGF-1, TGF-β, and VEGF). The levels of those cytokines in mice injected with miR-223 knockdown MSCs were significantly lower than those in both the I/R + MSC and I/R + htMSC groups (P < 0.05). However, even though the miR-223 levels in MSCs had been reduced, the miR-233 levels in the I/R + MSC group were still higher than those in the I/R group (Fig. 8a). These results confirmed our findings from the in vitro assays, which showed that induction with I/R could initiate the innate production of miR-223. In accord with the results from in vitro assays, the expression levels of antiapoptosis molecules Bcl-2 and Bcl-XL were enhanced, while those of several proapoptosis molecules (caspase-1, caspase-3, and NLRP3) were suppressed in the groups treated with functional MSCs (Fig. 8b and c). Details of the histological changes seen in the mouse models are shown in Fig. 9. H&E staining revealed that administration of MSCs with active miR-223 restored cellular structures that had been damaged due to I/R induction (Fig. 9a). The degrees of kidney fibrosis were also reduced by administration of functional MSCs (Fig. 9b). Additionally, we also used an immunohistochemical assay to detect Notch1 expression in the RTECs obtained from our mouse model. Interestingly, both the expression and distribution of Notch1 in the mouse kidneys were increased (Notch1-positive cells were stained brown) (Fig. 9c), which might signify initiation of a self-protection response in I/R-injured kidney tissues. Our TUNEL staining results showed that the numbers of apoptotic RTECs were decreased after treatment with MSCs when compared with those numbers in the I/R group. This reduced level of apoptosis in the I/R + MSC group was absent when miR-223 was inhibited. When compared with the levels of apoptosis in the I/R and I/R + MSC groups, a significant inhibition of apoptosis was found after treatment with htMSCs (P < 0.05) (Fig. 9d). In a similar manner, results of BUN assays also indicated that treatment with MSCs or htMSCs significantly decreased the levels of BUN, whereas suppression of miR-223 impeded the reduction in BUN induced by MSCs or htMSCs (P < 0.05) (Fig. 9e). We also examined the creatinine clearance rates in mice which received the different treatments, and found that the creatinine clearance rates were significantly increased in the I/R + MSC group and were even upregulated in the I/R + htMSC group (Fig. 9f). Interestingly, downregulation of miR-223 significantly reduced creatinine clearance rates in the I/R + MSC group, indicating that miR-223 plays a role in the ability of MSCs to treat I/R-induced kidney injuries.Fig. 8Knockdown of miR-223 blocked the protective effect of mesenchymal stem cells (MSCs) on renal tubular epithelial cells (RTECs). After the kidney ischemia/reperfusion (IR) KM/NIH mouse models were established, the mice were abdominally intravenously injected with MSCs, miR-223 inhibitor (miR-223 in) transfected MSCs or hypoxia-pretreated MSCs (htMSCs). Kidney tissues were harvested at 24 h after injection. a The concentrations of hepatocyte growth factor (HGF), insulin-like growth factor-1 (IGF-1), transforming growth factor beta (TGF-β), and vascular endothelial growth factor (VEGF) in blood samples were measured with ELISA. b Expression of B-cell lymphoma-2 (Bcl-2), B-cell lymphoma-XL (Bcl-XL), cysteine protease protein-1 (caspase-1) and cysteine protease protein-3 (caspase-3) in kidney tissue was detected by qRT-PCR. c Representative images from Western blot assays for apoptosis-related indicators. a P < 0.05, versus the IR model group; b P < 0.05, versus the I/R + MSC group. GAPDH glyceraldehyde-3-phosphate dehydrogenase, NLRP3 NLR family-pyrin domain containing 3 Fig. 9Perfusion of mesenchymal stem cells (MSCs) attenuated ischemia/reperfusion (IR)-induced damage to kidney tissue, and initiated Notch signaling in the mouse kidney. a Representative images of hematoxylin and eosin (H&E) stained tissue sections (×200). Administration of MSCs containing active miR-223 restored the integrity of cellular structures that had been damaged as a result of IR induction. b Representative images from periodic acid-silver methenamine (PASM) staining studies (×100 magnification). The collagen fibers are stained dark and the amount of kidney fibrosis was attenuated by perfusion with functional MSCs. c Representative images from immunochemical assays (×100 magnification); Notch1-positive cells are stained brown. Notch1 expression in the kidney cells of model mice was initiated by perfusion of MSCs transfected with a NC inhibitor or MSCs pretreated with hypoxia (htMSCs). d Representative images from TUNEL staining studies (×200 magnification). Apoptotic cells are stained brown, and their numbers were decreased after treatment with MSCs transfected with a negative control inhibitor or MSCs pretreated with hypoxia. Six fields were analyzed in the assay. e Blood urea nitrogen (BUN) assays showed that treatment with MSCs or htMSCs significantly decreased the levels of BUN compared to those in the IR group; however, a decrease in miR-223 expression reversed the reductions in BUN caused by MSCs or htMSCs. f The creatinine clearance rates were elevated in both the IR + MSC and IR + htMSC groups. The loss of miR-233 alleviated the increase in creatinine clearance caused by MSCs or htMSCs. a P < 0.05, versus the IR model group; b P < 0.05, versus the IR + MSC group. miR-233 in miR-233 inhibitor
4
0biomedical
0Study
188,318
Two isolates were evaluated in a neutropenic mouse lung infection model, which showed different MIC profiles for some antibiotics which were active against S. maltophilia (Table 1). S. maltophilia strain SR202006 showed relatively high MIC values to trimethoprim-sulfamethoxazole, minocycline, levofloxacin, and ciprofloxacin within the MIC range of each antibiotic. In contrast, S. maltophilia strain SR201934 showed MIC values for each of these antibiotics corresponding to concentrations around the MIC50 values.
4
0biomedical
0Study
60,482
Some participants who were allocated to their treatment preference, but claimed that they would have accepted the alternative fully comprehended the process of and rationale for randomisation (Table 5). However, one participant (participant 13) also expressed complete trust in her healthcare team and a certain belief in the ‘equivalence’ of the treatment options (as if there were evidence that the options were equally good rather than that there was currently no evidence of differences in HRQL), which could have indicated a misunderstanding about clinical equipoise and hence a therapeutic misconception associated with the trial.Table 5Hypothetical altruists with trial understanding [Preference] Was to have as much surgery done in one go really to be honest […] because from being diagnosed, the whole treatment pathway it’s really lengthy, everyone can appreciate that. In my mind delaying the reconstruction would have just lengthened that even more […] From what I remember, I could’ve pulled out at any time from the trial anyway. I wouldn’t have wanted to and I don’t think I would have done, but I was fully aware that I could pull out at any time which was fair and I did appreciate that. [On randomisation] …people can be put into a system and you were randomly picked [for different surgical options] from what I believe…. It makes it a little bit more fair doesn’t it? Hopefully you get a completely different cross-section of ladies taking part, following each process really, but you’re not getting say for example, all the ladies my age doing it one way and then all the ladies of an older age doing it the other way, then of course it’s not a fair representation is it of everybody involved. Trial acceptor, full understanding of randomisation (participant 15) Participant: I was told from very early on if you have a strong view and it comes back with what you don’t want you can opt out of the trial at any time […] I didn’t want an implant because I looked further into possible post-op complications and things and when it came back it was a non-implant so that was fine. I actually in the couple of days, because I went, I think it was the Thursday, and they put me in for the trial and then the randomisation came back on the Monday, so over the weekend I was thinking please don’t let it be an implant, please don’t let it be an implant. Anyway it came back and it wasn’t an implant so that was fine. Interviewer: What do you think you would have done if it had come back with the other option? Participant: I probably would have gone with it anyway because I absolutely trust the team that are looking after me. I think that was the most important thing that you trust the team that are caring for you and my surgeon was absolutely adamant that both outcomes would be as good. [On randomisation] In order to be able to be on the trial I had to be suitable for either a reconstruction with an implant or without an implant … and the randomisation happened in that no one person decided, a computer spit it out or somebody spit it out and it meant that it wasn’t down to my choice […] Nobody chose, it was a computer or a person picking a name out of a hat that chose rather than the surgeon and stuff so that meant that my experience wasn’t influenced by anybody. Trial acceptor, full understanding of randomisation (participant 13)
4
0biomedical
0Study
94,123
The A. “prasinus”complex.—As currently treated (e.g., Table 1, Dickinson & Remsen Jr, 2013; Del Hoyo & Collar, 2014), A. “prasinus” either is a widely distributed and highly variable biological species or it comprises multiple species (Fig. 1). So far as is known, Aulacorhynchus toucanets are nonmigratory (AOU, 1998), but as O’Neill & Gardner (1974) and Navarro et al. (2001) noted, members of the genus can wander widely during the nonbreeding season. Short & Horne (2001) considered Central American forms from Mexico to Panama to be partially migratory, with downslope movements to lowlands also occurring during the nonbreeding season (but less commonly) throughout the A. “prasinus” range. The sexes are alike by plumage (sexually monochromatic), but sexual size dimorphism is apparent in all taxa examined.
1
2other
0Study
56,826
According to the manoeuver capacity of an UAV, the velocity of UAV from 50m/s to 150m/s is divided into 10 sets, and in one speed set, the horizontal overload capacity −2g to 2g is divided into 41 sets. Therefore there are 10×41 tentacles totally, we consider this division ensure an occupancy grid can be divided averagely.
1
2other
1Other
59,152
In our study, the correlations of CSF cytokine/chemokines with severity at admission and disability at follow up were not statistically significant unlike previous studies [21, 59, 60]. However a subset of cytokines showed positive correlations on cluster analysis heat maps in patients with severe encephalopathy at admission, and disability at follow up, and these molecules (CXCL13 and CXCL10) were also identified as markers of inflammation in all encephalitis groups irrespective of the cause. The observed correlations suggest that these molecules may be considered as potential targets of immune therapy. Tacrolimus (FK506) and monoclonal antibodies against CXCL10 have been shown to reduce clinical symptoms and specifically reduce high levels of intrathecal CXCL10, thereby reducing T cell access to the CNS with interruption of the feedback loop in CNS inflammation [61, 62]. Similarly anti-CXCL13 antibody demonstrated efficacy in mouse models of autoimmunity including multiple sclerosis by reducing B cell infiltration and subsequent interactions with T cells [63–65].
4
0biomedical
0Study
132,615
The plant material was collected from the premises of Quaid-i-Azam University, Islamabad, Pakistan. These plants were identified by Prof. Dr. Rizwana Aleem Qureshi (Taxonomist), Department of Plant Sciences, Quaid-i-Azam University, Islamabad. A voucher specimen number (HPM-460) was deposited in the herbarium of Quaid-i-Azam University. Fresh green plants were surface sterilized, and tissue cultured on Murashige and Skoog (MS) medium. Transgenic hairy roots were generated through rolABC containing A. rhizogenes mediated transformation. Intact plants were regenerated from hairy roots by following the previously optimized method in our lab . Polymerase chain reaction (PCR) was performed for the confirmation of transformation and stable integration of rol genes in transformed roots and regenerants . Untransformed tissue cultured plants and transgenic regenerants of A. bracteosa plants were used in this study.
4
0biomedical
0Study
208,096
Ground-based simulations of µg have been conducted to explore the effects of pro-oxidative environments. Overall, oxidative stress is implicated in the pathophysiology of CVD. An imbalance between ROS and antioxidants increases the risk of oxidative damage and inflammation. An abundance of ROS can damage cellular components such as lipids, proteins, and DNA . Lee et al. demonstrated elevated levels of oxidative stress and inflammatory biomarkers during spaceflight. These levels returned quickly to preflight levels upon return to Earth . Oxidative stress is important in the pathogenesis of AS. Impaired arterial function and thickening of the carotid arteries are two sub-clinical indicators of the development of AS. AS is associated with the build-up of an atheromatous plaque. This mainly consists of oxidised low-density lipoprotein (LDL) and macrophages inside the artery walls . Total cholesterol and LDL are elevated during spaceflight but return to preflight levels shortly after spaceflight. In the progression of AS, the differentiation of stem cells to VSMCs contributes to the increased IMT. However, these mechanisms are currently unknown and speculative .
4
0biomedical
0Study
354,560
Real time connectivity: Tests are connected and/or a reader or mobile phone is used to power the reaction and/or read test results to provide required data to clinicians and users.Ease of specimen collection: Tests should be designed for use with non-invasive specimens.Affordable: Tests are affordable to end-users and the health system.Sensitive: Avoid false negatives.Specific: Avoid false positives.User-friendly: Procedure of testing is simple — can be performed in a few steps, requiring minimum training.Rapid and Robust: Results are available to ensure treatment of patient at first visit (typically, this means results within 15 min to 2 h) and the tests can survive the supply chain without requiring additional transport and storage conditions such as refrigeration.Equipment free and environmentally friendly: Ideally the test does not require any special equipment or can be operated in very simple devices that use solar or battery power. Completed tests are easy to dispose and manufactured from recyclable materials.Deliverable to end-users: Accessible to those who need the tests the most.
4
0biomedical
1Other
293,676
We also calculated the GFLOPs of the CNN model (U-Net) to introduce the computational costs behind the proposed framework. We called the THOP library function to estimate the number of FLOPs and parameters. The GFLOPs of the model was 10.112532480. The number of parameters was 4,320,609.
2
2other
1Other
325,864
In the retrospective cohort study, all participants underwent a phone call session to answer trial questions (“What is your pain level for your nasal symptoms?”) using the 11-point NRS, where 0 is not painful and 10 is the most worse painful (Kazi et al., 2019).
2
0biomedical
0Study
216,585
The efficiency of studied markers in the early diagnosis of secondary tumors and metastasis during the PPTT treatment course was evaluated. Within a month before the clinical appearance of secondary tumors, there was an increase in C-MYC values (Pre-predictive value n = 10, Mean ± SE = 0.86 ± 0.05 & predictive value n = 12 Mean ± SE = 0.90 ± 0.06). However, this increase was not statistically significant (F1,8 = 1.11, p = 0.3225). Also, the increases in “predictive” values of studied markers did not appear to be statistically significant (Table 5).Table 5Comparison between AAbs values measured just before the appearance of secondary tumors and metastasis (predictive), and last values measured before the predictive values (pre-predictive).EventMarkerSampling timeOverallPPTTSurgery + PPTT (n = 2)NMean ± SEFdf, pnMean ± SEt(df) , pMean ± SEt(df) , pSecondary tumorPCNAPre-predictive101.16 ± 0.13F1,11 = 1.01p = 0.333881.18 ± 0.11t(12) = 0.33p = 0.98641.08 ± 0.60t(11) = 1.28p = 0.5927Predictive121.16 ± 0.13101.13 ± 0.101.29 ± 0.73P53Pre-predictive101.26 ± 0.13F1,11 = 0.11p = 0.742081.38 ± 0.12t(12) = 0.14p = 0.99900.78 ± 0.09t(11) = 0.31p = 0.9894Predictive121.24 ± 0.12101.34 ± 0.120.73 ± 0.11MUC-1Pre-predictive101.52 ± 0.12F1,11 = 0.07p = 0.790381.53 ± 0.07t(12) = 0.01p = 0.99081.52 ± 0.72t(11) = 0.31p = 0.9892Predictive121.48 ± 0.12101.48 ± 0.111.46 ± 0.61C-MYCPre-predictive100.86 ± 0.05F1,8 = 1.11p = 0.322580.85 ± 0.06t(8) = 0.87p = 0.81960.91 ± 0.05t(7) = 0.74p = 0.8775Predictive120.90 ± 0.06100.89 ± 0.070.98 ± 0.05MetastasisPCNAPre-predictive51.20 ± 0.24F1,6 = 0.04p = 0.854031.29 ± 0.23t(6) = 0.09p = 0.99971.08 ± 0.60t(6) = 0.32p = 0.9873Predictive51.26 ± 0.2831.24 ± 0.301.29 ± 0.73P53Pre-predictive51.12 ± 0.18F1,6 = 0.21p = 0.662831.34 ± 0.20t(6) = 0.89p = 0.81110.78 ± 0.09t(6) = 0.13p = 0.9990Predictive51.26 ± 0.2731.61 ± 0.290.73 ± 0.11MUC-1Pre-predictive51.60 ± 0.31F1,6 = 0.01p = 0.991331.66 ± 0.37t(6) = 0.07p = 0.99981.52 ± 0.72t(6) = 0.07p = 0.9998Predictive51.61 ± 0.3231.71 ± 0.441.46 ± 0.61C-MYCPre-predictive50.87 ± 0.06F1,6 = 3.12p = 0.127830.84 ± 0.11t(6) = 2.08p = 0.25960.91 ± 0.05t(6) = 0.58p = 0.9340Predictive51.02 ± 0.0431.05 ± 0.050.98 ± 0.05The overall values were calculated regardless of treatments. Significant results at p < 0.05 if (bold).
4
0biomedical
0Study
327,370
These bacteria cause an inflammatory infection called an overwhelming post-splenectomy infection (OPSI), which is associated with high mortality . Infections result in splenectomy with two patterns, which include primary infections and delayed infections; the first one is mainly linked to surgery and its associated infections, and the second one is related to an impairment of the immune system due to the absence of the spleen. Post-splenectomy infections are the most common cause of morbidity during surgery and mainly include infections of the lower respiratory tract, intra-abdominal infections, wound infections, and non-specific infections requiring antibiotics . Preventing infections in patients with splenectomy will require the following three strategies:
4
0biomedical
1Other
342,207
The interview schedule (see Supplementary Material 1) was developed by several researchers in the CODES team to ensure clinical relevance and methodological rigor. The schedule was also discussed with a Service User (i.e., a patient representative) involved in the wider CODES project. The topics of relevance to the current paper were a) the experience of taking part in the CODES trial, b) their views on the treatment to which they were assigned, and c) their perception of treatment outcome. The remaining topics that were explored (participants' experience of receiving the diagnosis and the impact of DS on their life) will be reported elsewhere. A mid-way review of the interview schedule resulted in the addition of a further question that asked whether any reduction in DS had been accompanied by increased anxiety or depression. This addition arose because two participants interviewed by that point had said that this had been their experience. Positive as well as negative reflections were encouraged.
2
0biomedical
0Study
307,608
Male (vs female) sex is associated with higher rates of hospitalization and admission to intensive care units from COVID-19 infection.4 It has been hypothesized that the observed sex differences may be mediated through androgen regulation of cellular processes.2 Androgens and the androgen-regulated transmembrane protease, serine 2 (TMPRSS2) play an important role in prostate cancer cell invasion, tumor growth, and metastasis.3,5 The TMPRSS2:ERG gene fusion is the most frequent genomic alteration in prostate cancer, leading to an androgen-regulated fusion oncogene.6,7 The TMPRSS2 protein also plays a central role in SARS-CoV-2 pathogenicity; the viral spike glycoprotein is cleaved by TMPRSS2, activating SARS-CoV-2 for virus-cell fusion.6 Of substantial therapeutic interest is the potential for androgen deprivation therapy (ADT) to downregulate TMPRSS2 transcription in pulmonary tissue and, in turn, reduce host susceptibility to or severity of SARS-CoV-2 infection.4,8 Other types of therapy, such as the use of androgen receptor inhibitors (ARIs), may also exert an effect through mechanisms associated with the androgen axis or pathway.9
4
0biomedical
0Study
375,058
Participants with chronic clinical conditions (T2DM, cardiovascular diseases (CVD), cancer, gastrointestinal disease, osteopenia/osteoporosis, thyroid, liver and renal dysfunction), on any medication or vitamin D supplementation and whose baseline 25(OH)D levels were above 50 nmol/L were excluded from the study. A total of 84 participants were excluded because of the presence of the mentioned conditions for exclusion in their data file and another 27 participants were excluded for having baseline 25(OH)D levels above 50 nmol/L. All excluded participants(N = 111) were from the intervention group. Hence, 230 participants [intervention group, N = 146 (53 males and 93 females); control group, N = 57 (25 males and 32 females)] qualified for this interventional study (Figure 1).
4
0biomedical
0Study
120,792
This prevalence survey, along with many others from all across Indonesia, indicates an important epidemiological principle with malaria—risk across demographic groups is practically invariable between the two dominant species of Plasmodium. This is clearly seen in Figure 3. This relative homogeneity points to equal risk of exposure by the biting anophelines carrying each species, that is, it appears to be the same mosquitoes and any resident at risk of infection by one species is essentially at equal risk of infection by the other. This has important implications regarding policy for attacking vivax malaria because a diagnosis of P. falciparum in such settings also carries a very high probability of carriage of P. vivax hypnozoites. Douglas and others12 in Thailand decisively demonstrated this phenomenon: 51% of patients having a primary diagnosis of P. falciparum experienced a relapse of P. vivax within just 2 months. A diagnosis of any species of plasmodia anywhere in endemic Indonesia should rationally and reasonably prompt therapy against P. vivax hypnozoites.13 Treatment policy in Indonesia does not currently recommend presumptive primaquine therapy against hypnozoites with a diagnosis of P. falciparum malaria, principally due to the risk of harm caused by primaquine.
4
0biomedical
0Study
27,747
We sought to replicate these findings in the HCP sample, in which subjects are healthy and have a similar age range as the GSP sample. We selected 590 non-Hispanic/Latino Europeans aged between 22 and 35 years, comprising 72 MZ twin pairs, 69 DZ twin pairs, 253 full siblings of twins and 55 singletons (single birth individuals without siblings). We estimated the shape heritability for brain structures that had significantly heritable shapes in the GSP sample using an ACE model (A: additive genetics; C: common environment; E: unique or subject-specific environment), where the additive genetic similarity was derived from pedigree information and the common environment term reflected household sharing between subjects. We also obtained the s.e. of the shape heritability estimates using a block bootstrapping procedure (see Methods). All the shapes we analysed were significantly heritable in the HCP sample: accumbens area 0.309±0.081; caudate 0.583±0.062; cerebellum 0.653±0.060; corpus callosum 0.558±0.068; hippocampus 0.363±0.095; third ventricle 0.536±0.067; and putamen 0.483±0.106. We also observe that the HCP shape heritability estimates were consistently larger than the GSP estimates, which is theoretically expected because the SNP heritability estimated from unrelated GSP subjects only captured the genetic variation tagged by common SNPs in the data set, and is thus a lower bound for the classical narrow-sense heritability estimated from familial data such as the HCP sample.
4
0biomedical
0Study
385,953
It is well known that inflammatory reaction is a common pathological phenomenon and widely exists in a variety of diseases. Not only cancers are strongly linked to inflammatory reaction, but their staging and prognosis are inversely associated with the expression of genes related to inflammation (Kim et al., 2012; Ma et al., 2013). It was found that PC-II, a polysaccharide from Poria cocos, inhibited the IFN-γ-induced production of inflammation marker IP-10 dose-dependently, demonstrating that PC-II might be a promising lead compound in the development of novel anti-inflammatory agents (Lu et al., 2010). Notably, PC-II exhibited no toxicity to human vascular endothelial cells (ECs), indicating its safety. It was demonstrated that the expression of IP-10 was regulated by PC-II at the translational level rather than the transcriptional level, so it may participate in regulating inflammatory-related diseases (Lu et al., 2010). Lee et al. revealed that treatment with PCP obviously promoted NO production and iNOS transcription in mouse RAW 264.7 cells by activating NF-kB/Rel, indicating that PCP could induce macrophages to produce NO by inducing the iNOS gene expression (Lee and Jeon, 2003). The effects of CMP33 from Poria cocos on inflammatory bowel disease (IBD) were studied with colitis induced by TNBS in mice. It was observed that CMP33 obviously ameliorated the colitis in mice by decreasing the levels of pro-inflammatory cytokines and increasing the levels of anti-inflammatory cytokines in the serum and colon tissue of colitic mice, demonstrating that CMP33 could protect IBD in mice through the potential TPG (targeting protein group) and PMP (key protein-metabolite pathways) (Liu et al., 2018).
4
0biomedical
0Study