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0.399209
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Mean effect on habitat-specific transition probability (± 95% credible intervals; log-odds scale) to each of seven landcover types for time-of-day covariates cos(Diel) and sin(Time). The variable cos(Diel) represents nocturnal and diurnal time periods, while sin(Time) represents the first half (12:00 a.m.–11:59 a.m.) and second half of the day (12:00 p.m.–11:59 p.m.).
PMC9902612
41598_2023_28937_Fig3_HTML.jpg
0.440904
1235720087974b2d882d89d5608f46b8
Mean effect on transition-specific probability (log-odds scale) of transitioning between all combinations of landcover types for the proportion of time spent performing each of three behaviors including foraging, stationary, and walking between each GPS location. Positive estimates reflect an increased probability of transitioning from a habitat to a habitat given an increase in the proportion of time spent in a specific behavior, and negative estimates reflect an increase in probability of transition given a decrease in the proportion of time spent in a specific behavior.
PMC9902612
41598_2023_28937_Fig4_HTML.jpg
0.434494
0611eceed31c46d29a8bbc178f1068ef
Mean effect on transition-specific probability (± 95% credible intervals; log-odds scale) of transitioning between all combinations of landcover types for ambient temperature (°C) derived from tracking devices. Negative estimates reflect transitions that were more probable at lower than average temperature, and positive estimates at higher than average temperature.
PMC9902612
41598_2023_28937_Fig5_HTML.jpg
0.446427
862af31baf794c07aebd8a3ce427b0dc
PMF plots for selected parameter values
PMC9902838
41060_2023_382_Fig1_HTML.jpg
0.523309
122c22206c8f49e4a77ea16c885e1ba6
The hrf visualization plots for NDRL distribution
PMC9902838
41060_2023_382_Fig2_HTML.jpg
0.424417
9aafe01b36b54fb8a40bc6b1f8e34b36
PP plots for the first dataset
PMC9902838
41060_2023_382_Fig3_HTML.jpg
0.448315
7a6883eb0d71429dada77d43d9efb81e
PP plots for the second dataset
PMC9902838
41060_2023_382_Fig4_HTML.jpg
0.395949
8d5bba21f1e24828b9197c702ca8731d
PP plots for the third dataset
PMC9902838
41060_2023_382_Fig5_HTML.jpg
0.4955
5693c85212074e9e8ade2eecfcff51d7
Flow model of grounded theory research.
PMC9902928
fpsyg-13-1023420-g001.jpg
0.48875
c8cdd710e0664eada969082e6c91e0f2
The framework of grounded theory research thinking.
PMC9902928
fpsyg-13-1023420-g002.jpg
0.481533
e897bb65c7714cb998c87eff60570ee8
Structural model of influencing factors of college students’ satisfaction. Due to the large number of tertiary nodes, only primary and secondary nodes are listed in the figure.
PMC9902928
fpsyg-13-1023420-g003.jpg
0.414132
859057f51d534e22a29ba083d8da1e34
Elevated numbers of exon‐12 skipped transcripts in the patient cells ART–PCR analysis of endogenous TAPT1 splicing products. To check exon 12 skipping, RT–PCR was performed using primers targeting exon 10 and exon 13 in one WT (WT1), one heterozygous carrier (IV.3 (F1)) and 3 patients (V.1 (F1), V.5 (F1), IV.1 (F2)). The data showed the presence of normal (234 bps) and exon 12‐skipped (157 bps) products in all tested samples. However, the truncated transcripts constitute the majority of products in the patient cells. Interestingly, the intensity of 2 bands is rather same in the heterozygous (IV.3 (F1)) sample. Sanger sequencing confirmed the accuracy of RT–PCR products. Source data are available online for this figure.
PMC9906387
EMMM-15-e16478-g001.jpg
0.472753
dea9e27f96e449bf889fd1377c2a56e9
TAPT1 c.1237‐52 G>A mutation triggers exon 12 skipping Schematic representation of TAPT1 and TAPT1‐AS1, indicating the causative intronic mutation (c.1237‐52 G>A). The transcription start sites and the direction of transcription are indicated by arrows. Scale bar represents 2 kb.Diagram showing the branchpoint scores for the target c.1237‐52 position and flanking nucleotides in TAPT1 intron 11 in both WT (+/+) and patient cells (−/−), as obtained from the RNABPS (Nazari et al, 2018), LaBranchoR (Paggi & Bejerano, 2018) and BPP (Zhang et al, 2017a) softwares. High branchpoint scores were predicted for the G>A transition in the patient cells using the RNABPS and LaBranchoR methods. The x‐axis represents the nucleotide distance to the 3′ splice site (3´SS).Schematic illustration of minigene constructs and RT–PCR analysis of splicing products. The pSPL3 vector contains SDv and SAv exons (gray boxes) and functional intron (black line) in its backbone. SDv: splice donor vector; SAv: splice acceptor vector. TAPT1 c.1237‐52 G>A mutant fragments containing 200 bps of intron 11, exon 12 and 500 bps of intron 12 (green) were cloned into the EcoRI and BamH1 cloning sites (pink) of the pSPL3 vector. Using site directed mutagenesis, the TAPT1 c.1237‐52 G>A mutant construct was rescued into c.1237‐52 A>G (Purple arrow: c.1237‐52 G>A; green arrow: rescued into c.1237‐52 A>G). Green and red lines show canonical and internal/aberrant splicing, respectively. Two TAPT1 minigene constructs and an empty pSPL3 vector were transfected into HEK293T cells for 24 h. Following RNA extraction and cDNA synthesis, RT–PCR was done using vector specific primers (F: SD6 forward; R: SA2 reverse). The 263 bp PCR product in the empty vector showed internal splicing between SDv and SA2 exons. In c.1237‐52 G>A mutant minigene construct, the majority of splicing products had a size of 263 bp due to the aberrant exon 12 skipping while in the rescued construct, most of the transcripts had the expected size of 340 bps. Direct Sanger sequencing confirmed the identity of the normal and exon‐12 skipped products. Source data are available online for this figure.
PMC9906387
EMMM-15-e16478-g002.jpg
0.466487
beb6befed069489a83c6717060dd6ea8
Homozygosity mapping followed by RNA‐seq uncovers a deep intronic recessive mutation in TAPT1 Schematic representation of the shared IBD region between both Jordanian families, located on Chromosome 4 (4p16.1–p15.31) with a size of ~ 12 cM. Although WES analysis did not reveal any mutations in the coding sequences located in the IBD region, RNA‐seq analysis helped us to identify the disease causative gene from this locus.Volcano plot showing differentially expressed genes between WT (WT1 and WT2) and patient (V.1 (F1), V.5 (F1)) primary dermal fibroblasts. The vertical axis (y‐axis) shows the −log10 P‐value, whereas the horizontal axis (x‐axis) displays the log2 fold change value. The red dots represent the upregulated transcripts; the blue dots represent the downregulated transcripts. A total of 172 genes were found significantly dysregulated. TAPT1, a gene located in the IBD region, appeared among the most significantly downregulated genes in the patients.Plot showing the alternative splicing analysis results from WT (WT1 and WT2) and patient (V.1 (F1), V.5 (F1)) primary dermal fibroblasts. The vertical axis (y‐axis) shows the −log10 FDR (False Discovery Rate), whereas the horizontal axis (x‐axis) represents the exon inclusion level (value ranging from −1 to 1). The red dots represent transcripts with exon inclusion events; the blue dots represent transcripts affected by exon skipping. A total of 63 aberrantly spliced genes were found in the patient cells, being TAPT1 the most significant exon skipping event.(Left) Schematic representation showing the complete loss of exon 12 from TAPT1 transcript in patient cells, as defined by our splicing analysis data. (Right) Chromatogram showing the novel intronic mutation (c.1237‐52 G>A) we found entirely segregating with the disease in all available family members. For display purposes, results from the targeted Sanger sequencing in WT, IV.3 (F1) and V.5 (F1) individuals are shown. The mutation is present in heterozygosis in IV.3 (F1) (unaffected mother) and in homozygosis in V.5 (F1) (affected patient).
PMC9906387
EMMM-15-e16478-g003.jpg
0.484378
49cef25709264878b4a0eafaf4d56acd
Integrated analysis of SI‐NET‐seq and RNA‐seq data revealed enrichment of collagen and ECM‐related pathways in TAPT1‐null cells Volcano plot showing differentially expressed genes as determined by RNA‐seq in patient primary dermal fibroblasts (V.1 (F1), V.5 (F1)) compared with WT (WT1 and WT2) cells. The y‐axis shows the −log10 P‐value, whereas the x‐axis displays the log2 fold change value. The red dots represent 75 significantly upregulated genes, and the blue dots represent 97 significantly downregulated genes.qPCR validation test for 3 top dysregulated genes (RARRES2, ZIC1, and ZIC4) detected by RNA‐seq. The analysis was performed on RNA samples independent from those sent for RNA‐seq for 2 WTs (WT1 and WT2) and 2 patients (V.5 (F1) and IV.1 (F2)). Fold change relative to WT1 is plotted as mean ± SD of three technical replicates. Asterisks indicate statistical significance (Student's t‐test; ***P‐value < 0.001, ****P‐value < 0.0001).Volcano plot showing genes with an altered occupancy of transcriptionally engaged Pol II in patients (V.1 (F1) and V.5 (F1)) compared with WT (WT1 and WT2) primary fibroblast cells using SI‐NET‐seq. The y‐axis shows the −Log10 P‐value, whereas the x‐axis indicates the log2 fold change value for the Pol II occupancy. The Pol II density is increased in 222 genes (red dots), and decreased in 95 genes (blue dots). The yellow dot represents TAPT1.Bubble plot showing enrichment of collagen and extracellular matrix (ECM) pathways from the integrated reactome pathway analysis (Jassal et al, 2020) of the SI‐NET‐seq (light blue circles) and RNA‐seq (dark blue circles) data. Enriched pathways are indicated on the y‐axis, and the corresponding P‐values are shown on the x‐axis. The size of the circles represents the number of altered genes from each pathway.
PMC9906387
EMMM-15-e16478-g005.jpg
0.455125
51b472dea3b94febaf45e2c0911ee482
TAPT1 c.1237‐52 G>A mutation and TAPT1‐AS1 show no observable regulatory activity on TAPT1 mRNA stability and gene expression, respectively AqPCR analysis of c‐MYC and TAPT1 expression in WT1 and V.1 (F1) primary fibroblasts treated with actinomycin D (ActD) in different time points. ActD was used to check mRNA stability by inhibiting transcription. c‐MYC was considered as positive control with a short half‐life. The results showed that c‐MYC mRNA level dramatically decreased after 1.5 h treatment (~ x2), whereas the TAPT1 transcript level is unchanged. qPCR assays involved three technical replicates per sample per time point. For each graph, fold change relative to non‐treated condition is plotted as mean ± SD. Asterisks indicate conventional statistical significance (Student's t‐test; n.s. P‐value > 0.05, ****P‐value < 0.0001).BKnockdown of TAPT1‐AS1 transcript using two different GapmeRs (1 and 2) in WT (WT1) and patient (IV.1 (F2)) primary dermal fibroblasts. A non‐targeted (NT) GapmeR was used as control. qPCR analysis of TAPT1‐AS1 (top) and TAPT1 (bottom) transcript levels in the GapmeR‐transfected cells. Results show the successful knockdown of TAPT1‐AS1 by both GapmeRs 1 and 2 compared with the control NT GapmeR. However, TAPT1 mRNA levels are unaltered in both WT and patient cells. Fold change relative to WT1‐Control NT GapmeR is plotted as mean ± SD of three technical replicates. Asterisks indicate conventional statistical significance (Student's t‐test; n.s. P‐value > 0.05, **P‐value < 0.01, ***P‐value < 0.001).CWestern blotting of protein extracts from the GapmeR‐transfected cells, probing for TAPT1 (Sigma, HPA042567 antibody). Data shows that TAPT1 protein levels are unaffected by the knockdown of TAPT1‐AS1. GAPDH was used as loading control.D, EImmunofluorescence staining using two different TAPT1 commercial antibodies (A: Sigma, HPA042567; B: Sigma, HPA048658) in WT1 and IV.1 (F2) primary dermal fibroblasts. Similar fluorescent signal was detected in WT and TAPT1‐null cells in both cases. TAPT1 commercial antibodies are unsuitable for immunofluorescence experiments. Scale bar represents 10 μm. Source data are available online for this figure.
PMC9906387
EMMM-15-e16478-g006.jpg
0.438809
ff4102f34b544ba1939fbbb4ea64e24b
TAPT1 cellular localization and functional data TAPT1 predicted topology: a membrane‐spanning protein consisting of 5 transmembrane helices (Uniprot database).Western blot analyses for TAPT1 (~ 60 kDa) using cytosolic, Mito/ER/Golgi and nuclear protein extracts from primary dermal fibroblasts of two WTs (WT1 and WT2) and two patients (V.5 (F1) and IV.1 (F2)). TAPT1 protein is highly enriched in the Mito/ER/Golgi fraction, and to a lower extent in the nuclear fraction. GAPDH, TGN46 and BiP served as a cytosolic, Golgi network and ER markers, respectively. Adenylate Kinase (AK2) was used as a mitochondrial marker. Laminin A/C was used as a nuclear marker.Immunofluorescence staining of mitochondria using anti‐TOM20 (green), ER using anti‐CANX (red) and Golgi using anti‐GLG1 (red) in primary dermal fibroblasts from WT1 and V.5 (F1). Similar staining patterns are observed with the three antibodies in both cell lines. Scale bar represents 10 μm.qPCR analysis of a panel of canonical ER stress markers shows no significant differences in 3 patients (−/−) (V.I (F1), V.5 (F1) and IV.1 (F2)) primary dermal fibroblasts compared with WTs (+/+) (WT1, WT2 and WT3) cells. Fold change relative to WT is plotted as mean ± SD. Statistical significance was tested by Student's t‐test (n.s. P‐value > 0.05).CMV cell infection assay on 2 patient (V.1 (F1) and V.5 (F1)) and 3 WT (WT1, WT4 and WT5) primary dermal fibroblast cell lines, using β‐galactosidase activity as a readout. MRC5 cell line was used as a positive control. All of the cells were infected by the HCMV strain RC256 at a MOI = 0.1. Data are shown as mean ± SD of three technical replicates. Statistical significance was tested by Student's t‐test (n.s. P‐value > 0.05). Source data are available online for this figure.
PMC9906387
EMMM-15-e16478-g007.jpg
0.44777
361f10b448204d5bb5df4026244f20ca
Clinical pictures of the affected V.12 (F1) individualThe patient presented with multiple abnormalities including bone and joint deformities, pectus excavatum, plagiocephaly microphthalmia and bilateral hypotropia. Moreover, she had apparent dysmorphic facial features such as a depressed nasal bridge and low set of ears.
PMC9906387
EMMM-15-e16478-g008.jpg
0.39053
1c163b57dee74fcea2605bbad01e0d3a
Overlap analysis from homozygosity mapping and RNA‐seq data revealed TAPT1 as the only candidate gene List of the 39 candidate genes located in the mapped Chr. 4 IBD locus.Lists of the top 10 significantly downregulated (left, blue) and upregulated (right, red) genes obtained from our RNA‐seq differential expression analysis.Expression changes (x‐axis, log2FC) for genes with at least one alternative splicing event (skipped exon (SE), retained exon (RE), mutually exclusive exon (MXE), alternative 3′ or 5′ splice site (A3SS and A5SS) and retained intron (RI)).(Top) Venn diagram displaying overlapping genes between the Chr. 4 IBD candidate locus, and the top 10 upregulated and downregulated genes from our RNA‐seq data analysis. (Bottom) Venn diagram showing the overlapping genes between the differentially expressed set and the alternative spliced set from our RNA‐seq data analysis. TAPT1 appears as the only overlapping gene in both diagrams.
PMC9906387
EMMM-15-e16478-g009.jpg
0.439355
5109bd625c40486eb0eb9575a2dc06fc
Exon‐12 skipped transcripts undergo NMD to create a protein‐null allele Schematic representation showing that the complete loss of exon 12 in TAPT1 results in a premature stop codon, which targets the transcript for nonsense‐mediated mRNA decay.qPCR results using specific primers for TAPT1 and TAPT1‐AS1 in 3 WT (WT1, WT2, V.2 (F1)) and 3 affected (V.1 (F1), V.5 (F1), IV.1 (F2)) primary fibroblasts. TAPT1 mRNA is significantly reduced in all patients compared with WTs, whereas TAPT1‐AS1 transcript levels are unaffected. Fold change relative to V.2 (F1) is plotted as mean ± SD. Asterisks indicate conventional statistical significance (Student's t‐test; n.s. P‐value > 0.05, ****P‐value < 0.0001).Western blot analysis of endogenous TAPT1 protein (~ 60 kDa) using whole protein extracts from primary dermal fibroblasts from WT (WT1 and WT2), heterozygous (IV.3 (F1)) and homozygous (V.1 (F1), V.5 (F1) and IV.1 (F2)) individuals and two different commercial antibodies (top: Sigma, HPA042567; bottom: Sigma, HPA048658). Results show a complete absence of TAPT1 protein in patient samples. GAPDH was used as a loading control.qPCR analysis of TAPT1 expression in 3 WT (WT1, WT2, WT3) and 3 affected (V.1 (F1), V.5 (F1), IV.1 (F2)) primary fibroblasts treated with cycloheximide (CHX). CHX was used to block nonsense mediated decay (NMD). Our results showed a time dependent increase in the level of TAPT1 transcripts in all 3 patient cells while TAPT1 RNA level remained constant in the WT cells. For each graph, fold change relative to non‐treated condition is plotted as mean ± SD. Asterisks indicate conventional statistical significance (Student's t‐test; n.s. P‐value > 0.05, ****P‐value < 0.0001). Source data are available online for this figure.
PMC9906387
EMMM-15-e16478-g010.jpg
0.402918
ff6505feee8646ab82a4e858c2a58cd4
SI‐NET‐seq analysis data Lists of the top 10 genes with significantly decreased (left, blue) or increased (right, red) RNA Pol II occupancy from our SI‐NET‐seq analysis.High Pearson's correlation coefficients (r ≥ 0.96) between replicates of Pol II gene occupancy indicate the reproducibility of SI‐NET‐seq measurements. Asterisks indicate conventional statistical significance (Student's t‐test; ***P‐value < 0.001).Volcano plot showing genes with an altered occupancy of transcriptionally engaged Pol II in the heterozygous parent (IV.3 (F1)) compared with WT (WT1 and WT2) primary fibroblast cells. The y‐axis shows the −log10 P‐value, whereas the x‐axis indicates the log2 fold change value for the Pol II occupancy. The Pol II density is increased in 149 genes (red dots) and decreased in 21 genes (blue dots). The yellow dot represents TAPT1.Bubble plot showing enrichment of collagen and extracellular matrix (ECM) pathways from the integrated Reactome pathway analysis from patients (red circles) and heterozygous parent (green circles) SI‐NET‐seq data. Enriched pathways are indicated on the y‐axis, and the corresponding P‐values are shown on the x‐axis. The size of the circles represents the number of altered genes from each pathway.Pol II occupancy changes (log) of genes associated with enriched collagen and extracellular matrix (ECM) pathways measured from patients (−/−) and heterozygous parent (+/−) SI‐NET‐seq data. Significant changes are highlighted (orange). Bold and underlined genes are shared between patients and heterozygous parent. Source data are available online for this figure.
PMC9906387
EMMM-15-e16478-g011.jpg
0.451071
3a8628cc09664a6096be924633cea771
Patients from two distantly related families present with a recessively inherited syndrome characterized by osteogenesis imperfecta and neonatal progeria A, BPedigrees of two distantly related consanguineous families from Jordan, showing an autosomal recessive mode of inheritance of the disease. Black symbols and crossed symbols represent affected and deceased individuals, respectively.C–EPictures of investigated patients showing severe bone deformities and fractures, neonatal progeria, wrinkled skin, prominent forehead and pectus excavatum.FRadiographs of affected V.1 (F1) showing several deficits in the bones including deformity, dysplasia, spared joints and evidence of previous fractures. Severe calcification defects can also be noticed, involving premature atherosclerotic vascular calcification, periarticular soft tissue calcification and irregular calcification of carpal bones.
PMC9906387
EMMM-15-e16478-g013.jpg
0.421079
c826fc6231604f98bf45c657d74d366e
Research framework
PMC9907198
10668_2023_2991_Fig1_HTML.jpg
0.511573
80bfcd95399d4b53807ba13a5229eaef
Panel A. Trends in obesity among women 15-49 years of age in 13 sub-Saharan African countries. Panel B. Trends in overweight among children under five years of age in 13 sub-Saharan African countries. Panel C. Trends in stunting among children under five years of age in 13 sub-Saharan African countries.
PMC9907765
1806-9460-spmj-136-05-454-gf1.jpg
0.552615
b733c9b7492c46dfbcf96db177f37fbb
Panel A. Trends in wasting among children under five years of age in 13 sub-Saharan African countries. Panel B. Trends in underweight among children under five years of age in 13 sub-Saharan African countries. Panel C. Trends in low birth weight among children under five years of age in 13 sub-Saharan African countries.
PMC9907765
1806-9460-spmj-136-05-454-gf2.jpg
0.483424
6ec58b4671a4458480899a84e776c8a6
Workflow of LIR predictions using AlphaFold2-multimer.(a) The amino acid sequence of the candidate protein (here the human selective autophagy receptor p62/SQSTM1) and the ATG8 protein (here human LC3B) are entered into AlphaFold2-multimer, (b) which then provides the predicted structures of the two proteins in complex. They are docked together with the LIR motif positioned into the hydrophobic pockets HP1 and HP2 in the so-called LIR docking site of LC3B as shown in the zoomed inset in b, lower right. This allows both identification of the LIR motif of p62/SQSTM1 (see looking glass in a), which is the already verified LIR motif and a structural model of how the tryptophan (W) and leucine (L) residues of the core LIR motif fits into HP1 and HP2. (c) A sequence logo was generated by WebLogo from verified LIR motifs found in 24 autophagy proteins with acidic amino acids indicated in red, basic ones in blue, phosphorylatable serines (S) and threonines (T) in green, and hydrophobic amino acids in black.
PMC9907820
pbio.3002002.g001.jpg
0.488974
756e93bb673a419eaa25ac8f2cdac3ee
Abdominal computed tomography image showing swelling of the gallbladder and a previously placed covered metal stent.
PMC9908391
1349-7235-62-0237-g001.jpg
0.408628
17a83aa1fa4f46c99ccfaa49e4f2fbef
A cholecystogram obtained through the PTGBD route showing that the cystic duct was patent and merged with the metallic stent from the right and cranial sides. PTGBD: percutaneous transhepatic gallbladder drainage
PMC9908391
1349-7235-62-0237-g002.jpg
0.456444
61baaf6392554c62884405e7936de73d
Fluoroscopic image showing cystic duct dilation with a balloon catheter.
PMC9908391
1349-7235-62-0237-g003.jpg
0.436689
c9112b172fb54fec80e2e3a1e75a57b5
Transpapillary gallbladder stent and covered metal stent. (a) Fluoroscopic image. (b) Endoscopic image.
PMC9908391
1349-7235-62-0237-g004.jpg
0.431885
7640020a605d4c29a506da01f301004c
Transpapillary gallbladder stent and covered metal stent after removal of the PTGBD tube. PTGBD: percutaneous transhepatic gallbladder drainage
PMC9908391
1349-7235-62-0237-g005.jpg
0.445323
2b32253021b2463abb77adcd347930ea
a Total number of monkeypox infections in the USA was plotted as a function of time from 3rd June, 2022 to 27th September 2022. b Log–Log plot of number of infections of the USA as a function of time, the two vertical lines indicate the spectrum of scale-free behavior. The data points are overlaid with a linear regression’s best fit
PMC9908498
13360_2023_3709_Fig1_HTML.jpg
0.479435
0a62d23857fb43c1ac8a93d6f7f847d6
a Total number of infections for the smallpox outbreak of Tokyo, Japan, in 1907 was plotted as a function of time from 18th December 1907 to 25th July 1908. b Log–Log plot of number of infections as a function of time, the two vertical lines indicate the spectrum of scale-free behavior. The data points are overlaid with a linear regression best fit
PMC9908498
13360_2023_3709_Fig2_HTML.jpg
0.427051
047b3f1d9e0d441c85e00a09ab6e2eef
Schematic depiction of architecture of Echo state model
PMC9908498
13360_2023_3709_Fig3_HTML.jpg
0.477039
f4b8fffafd9148bcb6fd3e235b24e976
Prediction of monkeypox cumulative infection per day for nine most infected countries listed in the Table 1. Red solid line indicates the realtime cumulative infection data, and open blue circles represent the prediction of the test set by the ESN model and forecasting done by the ESN model is represented by green triangles extended from the predicted set
PMC9908498
13360_2023_3709_Fig4_HTML.jpg
0.398466
45667c69dfa240039e4c9bd6ebb51542
Total number of monkeypox infections in all the countries that were taken for analysis is plotted as a function of time from initial infection to 4th November 2022
PMC9908498
13360_2023_3709_Fig5_HTML.jpg
0.482144
f787f08b13b243a4830d73c651685566
Study Flow-chart.Of the 30 planned patients, only 12 patients were ultimately enrolled (n = 4 per center) (2013 – 2016). One reason for the lower-than-expected inclusion rate was the strict inclusion and exclusion criteria, which followed those used in previous studies and were approved by the applicable ethics committees. For the primary outcome “time to first alcohol use”, data was available for all n = 12 participants from baseline until the end of the blinded study period at month 6 (100%). For the secondary outcomes, data was available at baseline for all participants and for 9 participants at months 6 and 18. After 18 months, 75% of included participants (n = 9) had completed the study.
PMC9908935
41398_2023_2337_Fig1_HTML.jpg
0.414977
4df43c4f6c454483a8f3e631d9124840
Overview of electrode localization in standard space.All electrodes, colored by center, were reconstructed from preoperative magnetic resonance imaging and postoperative computer tomography, following the default pipeline of the LEAD-DBS software [75]. In the left image, the target area, i.e. the nucleus accumbens, is depicted as white mesh. The right image displays the projection on 2D slices for each contact level. All images are superimposed on slices of a 7 Tesla brain scan in MNI space [76].
PMC9908935
41398_2023_2337_Fig2_HTML.jpg
0.390913
b0641f94b22e4198af67cc44ad7065f5
Effect of NAc DBS on time to first alcohol use.Kaplan–Meier curves illustrating the time until first alcohol use after randomization (primary outcome) in the active stimulation group (DBS EARLY-ON) and sham stimulation group (DBS LATE-ON), which did not differ significantly between both groups (95%CI = 95% Confidence Interval).
PMC9908935
41398_2023_2337_Fig3_HTML.jpg
0.400376
178c6c1557954192b780a16bc1ca18a9
Effect of NAc DBS on alcohol use, abstinent days and heavy drinking days.Depiction of median values and of significant longitudinal changes and group differences in A mean alcohol use (mean over last 30 days), B proportion of abstinent days, and C the proportion of heavy drinking days, at baseline, at the 6-month visit (i.e., end of blinded phase), and at 18 months (after all patients had been actively stimulated for at least 12 months). *Significant differences between time points or study groups, as indicated, at p < 0.05, determined using Wilcoxon tests and Mann–Whitney U tests.
PMC9908935
41398_2023_2337_Fig4_HTML.jpg
0.382091
552d527d5a7f4794a283952fb365d553
Effects of NAc DBS on anhedonia, alcohol craving and quality of life.Depiction of median values and of significant longitudinal changes and group differences in A anhedonia (SHAPS), B, C alcohol craving (OCDS and AUQ), and D quality of life (WHOQOL-BREF) at baseline, at the 6-month visit (i.e., end of blinded phase), and at 18 months (after all patients had been actively stimulated for at least 12 months). *Significant differences between time points or study groups, as indicated, at p < 0.05, determined using Wilcoxon tests and Mann–Whitney U tests.
PMC9908935
41398_2023_2337_Fig5_HTML.jpg
0.408057
7b0ff588cd014dd6be09e2074afcce7a
Inhibitory rate (%) of fermentation supernatant of C1, M8, L6, M1, and M4 at 300 mg/mL against spore germination of Penicillium roqueforti at different time points after inoculation (2, 3, 4, 5, and 6d). The more green the color, the lower the inhibitory effect, and the more red the color, the higher the inhibitory effect. Values are mean (n = 3) ± standard error.
PMC9909597
fmicb-13-1076511-g001.jpg
0.440497
dae9070dcc4a42b1a85782b7eaffcec1
SEM micrographs of hyphae and microconidia of P. roqueforti treated by fermentation supernatant of C1, M8, L6, M1, and M4 at 300 mg/mL. Images obtained at 20.0 k × magnification. Red ellipses showed the bending, shrinkage, twisted, broken, or wrinkled hyphae and microconidia.
PMC9909597
fmicb-13-1076511-g002.jpg
0.470601
36db9eb1e4234872a899153cd2ae3886
Total DNA content of P. roqueforti in the control group and probiotic fermentation supernatant (C1, M8, L6, M1, and M4) treatment group were analyzed by DRAQ5 staining.
PMC9909597
fmicb-13-1076511-g003.jpg
0.390729
9c2a2ca9a20a4ef6b01008d260fed085
Toxins accumulation in P. roqueforti treated with antimycotics at 300 mg/mL. Data are the mean ± SE. The different letters indicate significant (p < 0.05) differences according to Duncan’s multiple range test.
PMC9909597
fmicb-13-1076511-g004.jpg
0.463641
0b51a4612ac94eb4a779d39dc19e68b8
Expression level of genes involved in toxin synthesis in P. roqueforti treated with fermentation supernatant of C1, L6, M8, and M4 at 300 mg/mL. Data are the mean ± SE. The different letters indicate significant (p < 0.05) differences according to Duncan’s multiple range test.
PMC9909597
fmicb-13-1076511-g005.jpg
0.493305
5b61657ac7a04749a05c8f2b61b2a9f9
Heatmap reflects the relative abundance of compounds with significant changes in probiotics fermented-MRS compared with the control group.
PMC9909597
fmicb-13-1076511-g006.jpg
0.407385
be5b03499cc24916bd732ef5409a7eb6
Protocatechuic acid was most responsible for the antimycotic properties of the five probiotics by sPLS-DA.
PMC9909597
fmicb-13-1076511-g007.jpg
0.41811
575cef50ad3f4bcaac62a63adb5609a6
Flow diagram of data and patient outcomes.
PMC9910028
gr1.jpg
0.470686
56b97cb27b6d4269b26d48195b15b2ca
a) Proportion of deaths during different periods of management. b) Proportion of mortality by age group. c) Proportion of deaths among patients with and without comorbidity.
PMC9910028
gr2.jpg
0.404968
edb71b146381416996310bba8badc6fd
a) Disease severity as risk factor for mortality. HR = hazard ratio. b) Age as risk factor for mortality. HR = hazard ratio.
PMC9910028
gr3.jpg
0.475062
f9a2b590f2a94d73a46e2378d4c41b0c
Comorbidities as risk factors for mortality. Kaplan-Meier curve of mortality related to a) hypertension b) diabetes mellitus (DM), c) coronary heart disease (CHD) and d) chronic kidney disease (CKD). HR = hazard ratio.
PMC9910028
gr4.jpg
0.470317
363c4aeb07a64dadbecbd65672aaec74
Relationship between treatment provided and patient survival. Kaplan-Meier curve shows the survival difference of the mild/moderate patients receiving a) steroid, c) favipiravir, e) remdesivir and g) antibiotics. Similar comparison shows the survival difference of the severe patients receiving b) steroid, d) favipiravir, f) remdesivir and h) antibiotics and i) ventilator. HR = hazard ratio.
PMC9910028
gr5af.jpg
0.44486
178e9aa0f61841739bcedb4f4eee42cc
Radiological diagnosis. Computed tomography pulmonary angiography in a 71-year-old woman with progressive shortness of breath, a positive ventilation/perfusion study (not shown) and a mean pulmonary arterial pressure of 38 mmHg. a) Lung windows demonstrate striking mosaic lung attenuation with alternating areas of normal density perihilar lung and hypodense peripheral lung (asterisks). b) Despite this, there is no chronic pulmonary embolism evident in the proximal vasculature. c) Thin sections are critical to identify subtle pulmonary artery filling defects as seen here in the inferior lingula (arrow) and d) sagittal multiplanar reformats are key in revealing subtle eccentric wall thickening in the right lower lobe (arrowhead).
PMC9910339
ERR-0132-2022.01.jpg
0.48293
698afb47d49a49488549191c31a6e010
Multimodal chronic thromboembolic pulmonary hypertension (CTEPH) treatment. PA: pulmonary artery; PEA: pulmonary endarterectomy; BPA: balloon pulmonary angioplasty.
PMC9910339
ERR-0132-2022.02.jpg
0.484661
fb1bcbef316d4f1bbf55964e540fe1ea
Evolution of the rate of lung injury (% per session) over time.
PMC9910339
ERR-0132-2022.03.jpg
0.409389
3187518515fd4971b93cd13938a29fdc
Knockout of Sp1/Sp3 in ECs decreases angiogenesis in vivo.A, B Representative immunofluorescence staining of Sp1 and Sp3 in gastrocnemius muscle biopsies of patients with critical limb ischemia (CLI) compared to healthy subjects. CD31 is an endothelial cell marker. Scale bar: 20 μm. C Quantification of immunofluorescence staining of Sp1 and Sp3 in A and B. n = 5. D Retinal whole-mount staining of isolectin-B4 in P5 VE-CAD-CreERT2-/Sp1fl/fl/Sp3fl/fl (CTR) and VE-CAD-CreERT2+/Sp1fl/fl/Sp3fl/fl (dKO) mice. Red arrowheads show tip cell sprouting and filopodia. Right, quantification of vascular/total retinal area, vasculature length, branch points per field, tip cell number per field, tip sprout number per field, and filopodia number per sprout. Scale bars: 500 (row 1), 100 (row 2), 50 (row 3), and 10 μm (row 4). n = 6. E Representative laser Doppler images of the legs acquired on days –1 (before surgery), 0 (immediately after surgery), 7, 14, 21, and 28 after surgery. Right, quantification of blood flow recovery after hindlimb ischemia as determined by the ratio of foot perfusion between ischemic (left) and non-ischemic (right) legs in CTR and dKO mice. n = 6. F Immunohistochemistry (IHC) analysis of CD31+ staining (capillary density) in the ischemic gastrocnemius muscle. Bottom, quantification of CD31+ vessels per mm2 in CTR and dKO mice. n = 6. Scale bar: 50 μm. G Excisional cutaneous wounds were created using a 5 mm biopsy punch on the dorsal skin of CTR and dKO mice. n = 6. Bottom right, quantification of the wound area at days 0, 3, 5, and 7. Two-tailed Student’s unpaired t-test was used for analysis in C, D and F. Two-way ANOVA followed by Bonferroni multiple-comparison analysis was used for E and G. Data are presented as mean ± SEM. Source data are provided as a Source Data file.
PMC9911748
41467_2023_36409_Fig1_HTML.jpg
0.398507
1df1e2afee994621a160a39c774418e4
ACEI promotes angiogenesis via Sp1/Sp3.A Retinal whole-mount staining of isolectin-B4 in P5 CTR and dKO mice treated with the vehicle or angiotensin-converting enzyme inhibitor (ACEI). n = 6. Red arrowheads show tip cell sprouting and filopodia. Right, quantification of vascular/total retinal area, vasculature length, branch points per field, tip cell number per field, tip sprout number per field, and filopodia number per sprout. Scale bars: 500 (row 1), 100 (row 2), 50 (row 3), and 10 μm (row 4). n = 6. B Aortic ring assays showing the number of aortic sprouts from CTR and dKO mice treated with vehicle or ACEI embedded in Matrigel stimulated with vascular endothelial growth factor (VEGF, 20 ng/mL) for 6 days. Bottom, quantification of sprout number. n = 6. C Capillary network formation in mouse lung endothelial cells (MLECs) isolated from CTR and dKO mice treated with or without ACEI on Matrigel (VEGF stimulation for 4 h). Bottom, quantification of junction number and relative tube length. n = 6. Scale bar: 50 μm. Two-way ANOVA followed by Bonferroni multiple comparison analysis was performed for A–C. Data are presented as mean ± SEM. Source data are provided as a Source Data file.
PMC9911748
41467_2023_36409_Fig2_HTML.jpg
0.394647
e0c69551e4354b6f8a94c45f5171565b
ACEI promotes pathological angiogenesis via Sp1/Sp3.A Representative laser Doppler images of the legs on day –1 (before surgery), 0 (immediately after surgery), 7, 14, 21, and 28. Right, quantification of blood flow recovery after hindlimb ischemia as determined by the ratio of foot perfusion of the ischemic (left) and non-ischemic (right) legs in CTR and dKO mice treated with or without ACEI. n = 6. B Assessment of capillary density by IHC analysis using CD31+ staining in the ischemic gastrocnemius muscle. Bottom, quantification of CD31+ vessels per mm2 in CTR and dKO mice treated with or without ACEI. n = 6. Scale bar: 50 μm. C Images of the Matrigel plugs retrieved from CTR or dKO mice treated with or without ACEI and immunofluorescence staining of CD31+ vessels in the Matrigel plugs. Right, quantification of vessel density and mRNA expression levels of CD31 and VE-cadherin assessed using qPCR analysis. n = 6. Scale bars: 1 cm (row 1) and 20 μm (row 2). Two-way ANOVA followed by Bonferroni multiple comparison analysis was performed for A–C. Data are presented as mean ± SEM. Source data are provided as a Source Data file.
PMC9911748
41467_2023_36409_Fig3_HTML.jpg
0.400545
dee371cb8e8f49dfbd971e81991a1062
ACEI promotes angiogenesis via USP7.A Western blot analysis of Sp1 and Sp3 in human umbilical vascular endothelial cells (HUVECs) transfected with CTR siRNA or USP7 siRNA and treated with cycloheximide (CHX) for 0, 1, 2, 4, or 6 h. Bottom, quantification of western blot. n = 6. B Retinal whole-mount staining of isolectin-B4 in P5 pups treated with vehicle, vehicle + ACEI, P22077 + ACEI, or P5091 + ACEI. n = 6. Red arrowheads show tip cell sprouting and filopodia. Bottom, quantification of vascular/total retinal area, vasculature length, branch points per field, tip cell number per field, tip sprout number per field, and filopodia number per sprout. Scale bars: 500 (row 1), 100 (row 2), 50 (row 3), and 10 μm (row 4). C Capillary network formation of HUVECs with different treatments on Matrigel (VEGF stimulation for 4 h). Bottom, quantification of junction number and relative tube length. n = 6. Scale bar: 50 μm. D Images of the Matrigel plugs retrieved from mice treated with vehicle, vehicle + ACEI, P22077 + ACEI, or P5091 + ACEI, and immunofluorescent staining of CD31+ capillaries in the Matrigel plugs. Right, quantification of vessel density. n = 6. Scale bars: 1 cm (row 1) and 20 μm (row 2). Two-way ANOVA followed by Bonferroni multiple-comparison analysis for A. One-way ANOVA followed by Bonferroni multiple-comparison analysis was used for B–D. Data are presented as mean ± SEM. Source data are provided as a Source Data file.
PMC9911748
41467_2023_36409_Fig4_HTML.jpg
0.532596
62be8508aafe49b2a7bf3121635f4c57
ACEI stabilizes Sp1/Sp3 protein via USP7-mediated deubiquitination.A Representative western blot of HA-ubiquitin after anti-Flag immunoprecipitation of HEK293T cells ectopically expressing Flag-Sp1 (left) or Flag-Sp3 (right) either alone or in combination with Myc-USP7-WT or Myc-USP7-CS (C233S). B Representative western blot of HA-ubiquitin after anti-Flag immunoprecipitation of HEK293T cells ectopically expressing Flag-Sp1 (left) or Flag-Sp3 (right) either alone or in combination with Myc-USP7-WT treated with USP7 inhibitors P22077 or P5091. C Representative western blot of HA-ubiquitin after anti-Flag immunoprecipitation of HEK293T cells ectopically expressing Flag-Sp1 (left) or Flag-Sp3 (right), either alone or in combination with HA-ubiquitin-WT or mutant (K48R or K63R). D HEK293T cells ectopically expressing Flag-Sp1 (left) or Flag-Sp3 (right) were co-transfected with Myc-USP7 deletion mutants, as indicated. The interactions were analyzed using the Co- immunoprecipitation assay. E Chromatin immunoprecipitation (ChIP) assay showing binding of Sp1 or Sp3 to the NOTCH1 promoter in HUVECs treated with ACEI either alone or in combination with P22077 or P5091. n = 6. F Representative western blot analysis for USP7 after anti-Sp1 (left) or anti-Sp3 (right) immunoprecipitation of HUVECs treated with ACEI either alone or in combination with the HDAC1 inhibitor SAHA or TSA. G Representative western blot analysis of USP7 after anti-Sp1 (left) or anti-Sp3 (right) immunoprecipitation of HUVECs transfected with CTR siRNA or HDAC1 siRNA, in combination with or without ACEI. H Representative western blot analysis of USP7 after anti-Flag immunoprecipitation of HUVECs ectopically expressing Flag-Sp1-WT (left, Flag-Sp3-WT) or Flag-Sp1-K703A (right, Flag-Sp3-K551R) treated with or without ACEI. I ChIP assay showing the binding of Sp1 or Sp3 to the NOTCH1 promoter in HUVECs transfected with CTR siRNA or HDAC1 siRNA, in combination with or without ACEI. n = 6. Two-way ANOVA followed by Bonferroni multiple-comparison analysis was employed for E and I. Data are presented as mean ± SEM. Source data are provided as a Source Data file.
PMC9911748
41467_2023_36409_Fig5_HTML.jpg
0.466162
bba2cdb20bd74a7da5bc691e4566261e
ACEI increases nuclear localization of USP7.A Representative western blot analysis of USP7 and ubiquitin after anti-Sp1 (top) or anti-Sp3 (bottom) immunoprecipitation of HUVECs treated with ACEI for different time, as indicated in combination with CTR siRNA or histone deacetylase 1 (HDAC1) siRNA. The protein levels of USP7 were measured by western blot analysis in nuclear, cytoplasmic, and whole-cell lysates. B Representative confocal microscopy images of immunofluorescence staining for USP7 and DAPI in HUVECs treated with ACEI for 0, 30, 60 and 90 min, in combination with CTR siRNA or HDAC1 siRNA as indicated. Scale bar: 20 μm. Bottom, quantification of the ratio of USP7 in the nuclear to cytoplasmic fractions. n = 6. C Capillary network formation in HUVECs on Matrigel treated with ACEI in combination with different genetic perturbations as indicated. Bottom, quantification of junction number and relative tube length. n = 6. Scale bar: 50 μm. One-way ANOVA followed by Bonferroni multiple-comparison analysis was employed for B and C. Data are presented as mean ± SEM. Source data are provided as a Source Data file.
PMC9911748
41467_2023_36409_Fig6_HTML.jpg
0.444459
d573603ea6e94543b2f75d6978b043a7
Endothelial Sp1/Sp3 negatively regulates Notch signaling to govern angiogenesis.A Western blot analysis of Notch1, Notch intracellular domain (NICD), DLL4, Sp1, and Sp3 protein levels in isolated retinal endothelial cells from CTR and dKO mice. B qPCR analysis of NOTCH1, HES1, HEY1, and DLL4 mRNA levels in isolated retinal endothelial cells from CTR and dKO mice. n = 6. C Representative microscopy images and quantification of immunofluorescence staining for Notch1 in isolectin-B4+ vessels of retinas from CTR and dKO mice. Scale bar: 30 μm. n = 5. D Representative microscopy images and quantification of immunofluorescence staining for phospho-VEGFR2 (Y1175) in isolectin-B4+ vessels of retinas from CTR and dKO mice. Scale bar: 30 μm. n = 5. E Retinal whole-mount staining of isolectin-B4 in P5 CTR and dKO mice, with or without the DAPT (γ-secretase inhibitor). Red arrowheads show tip cell sprouting and filopodia. Bottom, quantification of vascular/total retinal area, vasculature length, branch points per field, tip cell number per field, tip sprout number per field, and filopodia number per sprout. Scale bars: 500 (row 1), 100 (row 2), 50 (row 3), and 10 μm (row 4). n = 6. F Representative laser Doppler images of legs on days –1 (before surgery), 0 (immediately after surgery), 7, 14, 21, and 28. Bottom, quantification of blood flow recovery after hindlimb ischemia as determined by the ratio of foot perfusion between ischemic (left) and non-ischemic (right) legs in CTR and dKO mice with or without DAPT. n = 6. G IHC analysis of CD31+ staining (capillary density) in the ischemic gastrocnemius muscle. Right, quantification of CD31+ vessels per mm2 in CTR and dKO mice, with or without DAPT. Scale bar: 50 μm. n = 6. H Western blot analysis of phosphorylated VEGFR2 (Y1175, Y1059), VEGFR2, PLCγ (Y783), PLCγ, ERK1/2 (Thr202/Tyr204) and ERK1/2 in mithramycin or Ad-NICD treated HUVECs. Two-tailed Student’s unpaired t-test was used for B–D. One-way ANOVA followed by Bonferroni multiple-comparison analysis was employed for E and G. Two-way ANOVA followed by Bonferroni multiple-comparison analysis was performed for F. Data are presented as mean ± SEM. Source data are provided as a Source Data file.
PMC9911748
41467_2023_36409_Fig7_HTML.jpg
0.408751
76ebb35efe094da4a9ff23f445b5cd90
Sp3 enhances Sp1-mediated transcriptional repression activity of NOTCH1 in ECs.A Western blot analysis of Notch1, NICD, DLL4, Sp1, and Sp3 protein levels in HUVECs transfected with CTR, Sp1, Sp3, or Sp1 + Sp3 siRNA. n = 6. B qPCR analysis of NOTCH1, HES1, HEY1, and DLL4 mRNA levels in HUVECs transfected with siRNAs for CTR, Sp1, Sp3, or Sp1 + Sp3. n = 6. C Chromatin immunoprecipitation (ChIP) assay showing the binding of Sp1 or Sp3 to the NOTCH1 promoter in HUVECs. D Relative luciferase activity was shown by the indicated serial promoter deletions of NOTCH1 in HEK293T cells infected with Ad-GFP, Ad-Sp1, or Ad-Sp3. n = 6. E Relative luciferase activity of wild-type (NOTCH1-WT) and mutant constructs (NOTCH1-mutant) of the NOTCH1 promoter in HEK293T cells infected with Ad-GFP, Ad-Sp1, Ad-Sp3, or Ad-Sp1+Ad-Sp3. n = 6. F Relative luciferase activity of VEGFR2 promoter in HUVECs with different treatments. n = 5. G Retinal whole-mount staining of isolectin-B4 in P5 CTR, Sp1ECKO, Sp3ECKO, and dKO mice. n = 6. Red arrowheads show tip cell sprouting and filopodia. Right, quantification of vascular/total retinal area, vasculature length, branch points per field, tip cell number per field, tip sprout number per field, and filopodia number per sprout. Scale bars: 500 (row 1), 100 (row 2), 50 (row 3), and 10 μm (row 4). One-way ANOVA followed by Bonferroni multiple-comparison analysis was used for A–G. Data are presented as mean ± SEM. Source data are provided as a Source Data file.
PMC9911748
41467_2023_36409_Fig8_HTML.jpg
0.450662
5556a18a4951484ab5adc63cd2d279c4
Schematic diagram depicting the production process and characterization of postbiotic components using representative postbiotics from culture medium, food, and gut, respectively. The bioactivities and mechanism of actions are briefly illustrated
PMC9913028
12602_2023_10045_Fig1_HTML.jpg
0.485191
7c7d4059debc4cb39e3543f7128b5bd9
Wide applications of postbiotics
PMC9913028
12602_2023_10045_Fig2_HTML.jpg
0.429118
23b6ce577a404d06a6fbe9a828e6ad0d
Genetic landscape of hepatocellular carcinoma. We figured the main somatic genetic drivers observed in hepatocellular carcinoma, their frequencies across BCLC stages and the main signaling pathways dysregulated. Activating mutations are reported in red, whereas inactivating mutations are in blue. LGDN: low-grade dysplastic nodule; HGDN: high-grade dysplastic nodule; HCC: hepatocellular carcinoma.
PMC9913369
cancers-15-00817-g001.jpg
0.405768
67f3d8a704ba441fb68b433cbc9b1eba
Possible applications of circulating tumor DNA in the management of HCC. Circulating tumor DNA (ctDNA) reflects tumor burden and has been tested for early cancer detection and minimal residual disease (MRD) monitoring in the early stage of HCC. In addition, ctDNA should be evaluated for the identification of targetable mutations and biomarkers and, therefore, be used for therapy selection. The non-invasiveness and the ability to reflect the patient’s oncological picture in real time makes ctDNA an ideal tool for longitudinal monitoring and early detection of acquired resistance, leading to a switch to second- or third-line therapy.
PMC9913369
cancers-15-00817-g002.jpg
0.525806
48704cc1c8e54896a6a64c514d6c07ef
Immunotherapy treatments currently recommended for advanced NSCLC.
PMC9913378
cancers-15-00689-g001.jpg
0.380789
78413e70d22c45a9aa871ee038eda490
(A) Angulated coronal CT image in the portovenous phase showing a diffuse enlarged pancreas with peripheral calcifications. (B) CT Maximum Intensity Projection (MIP) reconstruction of a shunt (arrow) between the left portal vein and middle hepatic vein. (C) T1-weighted fat-suppressed MRI subtraction image in the arterial phase in transverse direction. Diffuse enhancement of the extremely enlarged pancreas is visible with multiple low intensity foci corresponding to calcifications. (D) Fused image of the Gallium-68 DOTATATE scan in transverse direction, showing diffuse increased uptake of the enlarged pancreas.
PMC9914007
diagnostics-13-00572-g001.jpg
0.400057
f07f5a43c05a4db5b91decd190609235
Relationship of the relative humidity (RH) of the room air to the temperature of the discharge air from the evaporation coils (from [8], with permission).
PMC9914392
foods-12-00466-g001.jpg
0.392869
ef08e929efd54df0a2af5497bba9c236
The amount of condensed water (litres per week) from a room with plastic bins and a room with wooden bins (150 tons of pears per room) (from [8,54], with permission).
PMC9914392
foods-12-00466-g002.jpg
0.442124
e2a0ed4735d046c59ea2a275196429b8
(a) Manual collection of water outside a CA room from the evaporation coils inside the room. There is a drain trap on the water pipe inside the CA room, to maintain airtight conditions. The volume collected in the green container is measured to determine moisture loss from the fruit, since 1 L collected equals 1 kg of weight loss from the fruit in the room. (b) Device for computerised electronic collection of water outside a CA room, from the evaporation coils inside the room (https://storage.isolcell.com/en/sentinel/). This system can redirect drainage water either back into the storeroom (onto the floor) or outside, according to the humidity requirements.
PMC9914392
foods-12-00466-g003.jpg
0.450515
f08b75880cd34920a11b01c18cf65116
Selection process of the study.
PMC9915195
ijerph-20-02406-g001.jpg
0.392648
47df3642a2884d5eb481e38fef7d7910
Sample game card used in playing Dealodontics© Teams only see the image. The reverse side with questions of increasing difficulty is seen by the dealer.
PMC9915391
ijerph-20-02039-g001.jpg
0.444522
1ddd054637ad423181df1affd09400c3
There are four types of team cards.
PMC9915391
ijerph-20-02039-g002.jpg
0.454802
56915e8943854d0eaef4dd8925dc6849
Sample word clouds. Word clouds demonstrate words used by students based on frequency describing the gameplaying experience (without prompts). AY 2019–2020 Word Cloud: 239 D2 students responded (RR = 66%). Most reported words were: 64% “fun”, 17% “educational”, 15% “engaging”, and 13% “challenging”. AY 2021–2022 Word Cloud: 115 D2 students responded (RR = 47%). Most reported words were: 54% “fun”, 25% “challenging”, 13% “engaging”, and 10% “educational”. “Fun” was the most commonly occurring word in all years surveyed.
PMC9915391
ijerph-20-02039-g003.jpg
0.448202
f21d8854d3d44c6eacde9f51573be73f
Logarithmic comparison of EIS resistance between CAD and control group within the range from 1 kHz to 1 MHz.
PMC9915397
ijerph-20-02745-g001.jpg
0.435427
df114bc5a18b4b0984025413989756fb
Logarithmic comparison of EIS capacitance between CAD and control group within the range from 1 kHz to 1 MHz.
PMC9915397
ijerph-20-02745-g002.jpg
0.451794
ae5163c991d94ec5bb7cc111a33923bc
Frequency dependence of the relative permittivity (●—CAD; ◊—control). Solid and dashed lines indicate slope m for CAD and controls.
PMC9915397
ijerph-20-02745-g003.jpg
0.454214
dcfef0b455a74d7e84b1c6ce26442e69
Frequency dependence of the electrical conductivity (●—CAD; ◊—control).
PMC9915397
ijerph-20-02745-g004.jpg
0.494414
51f7e9194e844a54806304e4a64b3e0f
Cole–Cole plots of the experimental data (●—CAD; ◊—control).
PMC9915397
ijerph-20-02745-g005.jpg
0.396064
2afbd7de1c8e48eaa782aafe5f665a03
The results for the three monocyte subpopulations’ frequency based on the CD14, CD16 and SLAN expression. The comparison between glioma patients and the control group showed less numerous representations of classical and non-classical glioma patients’ monocytes. Unpaired t-student was used for graph A. In other cases U Mann-Whitney was used.
PMC9915868
ijms-24-01879-g001.jpg
0.514473
c73099cc42f14870b2087ba67f88fa84
The results for immune checkpoint molecules expression on glioma patients’ monocytes vs. healthy individuals. Percentage of classical (A), intermediate (B) and non-classical (C) monocytes with PD-1 expression. As a consequence of the expression exceeding 95% for the PD-L1 (D–F) and SIRPalpha (G–I), the MFI was evaluated. Percentage of classical (J), intermediate (K) and non-classical (L) monocytes with TIM-3 expression. In all presented analyses, the U Mann-Whitney test was used. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001. PD-1, programmed cell death 1 protein; PD-L1, programmed cell death 1 ligand; MFI, mean fluorescence intensity; SIRPalpha, signal-regulatory protein alpha.
PMC9915868
ijms-24-01879-g002.jpg
0.445123
e43f7537a15645e59f4bd854872a5767
The identification of the differences in the immune checkpoint molecules: PD-1 (A) PD-L1 (B), TIM-3 (C) and SIRPalpha (D,E) expression between classical, intermediate and non-classical monocytes. Due to the expression exceeding 95% (D), for SIRPalpha the MFI assessment was used (E). * p < 0.05, ** p < 0.01, **** p < 0.0001 PD-1, programmed cell death 1 protein; PD-L1, programmed cell death 1 ligand; MFI, mean fluorescence intensity; SIRPalpha, signal-regulatory protein alpha.
PMC9915868
ijms-24-01879-g003.jpg
0.508655
b0d55b12447144129c84442307ccd91f
The comparison of the cytokine expression between classical, intermediate and non-classical monocytes. The pro-inflammatory molecules are noted in panels (A,B) (TNF and IL-12, respectively), whereas anti-inflammatory cytokines are distinguished in (C,D) graphs (TGF-beta and IL-10, respectively). * p < 0.05, ** p < 0.01, **** p < 0.0001. TNF, tumor necrosis factor; IL-12, interleukin 12; TGF-beta, transforming growth factor beta; IL-10, interleukin 10.
PMC9915868
ijms-24-01879-g004.jpg
0.462416
4f046d2c10604f479b9a4498faf42668
The results of cytokine molecules’ expression for three monocyte subpopulations compared to the healthy volunteers’ group. Both, pro-inflammatory TNF, IL-12 (A–C; D–F, correspondingly) and anti-inflammatory TGF-beta, IL-10 (G–I; J–L, respectively) were evaluated. Unpaired t-student was used for the statistical test, the results of which are presented in graph (B,K). In other cases U Mann-Whitney was used. *** p < 0.001, **** p < 0.0001. TNF, tumor necrosis factor; IL-12, interleukin 12; TGF-beta, transforming growth factor beta; IL-10, interleukin 10.
PMC9915868
ijms-24-01879-g005.jpg
0.391072
80d9d9d13da34f0dba8f701f78a7930e
The figure shows differences between monocyte subpopulations’ cytokine expression in the context of MGMT gene promoter methylation status. Graphs (A–F) focus on pro-inflammatory molecules (TNF, IL-12), though graphs (G–L) visually present data on anti-inflammatory cytokines (TGF-beta, IL-10). ‘MGMT-‘ stands for MGMT-unmethylated tumor status, ‘MGMT+’ stands for MGMT-methylated tumor status; * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.
PMC9915868
ijms-24-01879-g006.jpg
0.426954
e6f81443c5794e2f8c6d77fda3c178bc
RNA transcript expression of CD274, PDCD1LG2, HAVCR2, PDCD1, SIRPA genes in GBM and LGG tissues and healthy control. Panel (A) summarizes differences in expression of analysed genes, it presents median Z-score. The lower TPM of each of the analysed genes is connected with more favorable overall survival when comparing gliomas (including LGG and GBM) vs. healthy tissue (C,E,G). The greatest benefit of low transcription is illustrated by Kaplan-Meier curve for CD274 (C). Z-score of PDCD1 gene in comparison between GBM and control showed significant difference (D). Additionaly, TIM-3 coding gene is characterised by a higher number of transcripts in both LGG and GBM (F). No significant differences were noted for CD274, PDCD1 and SIRPA (B,H,I). The data described above were downloaded from The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx). The asterisk symbol (*) in the figure indicates a statistically significant difference between two compared groups. * p < 0.05 HAVCR2- Hepatitis A virus cellular receptor 2, TIM-3 gene; CD274- PD-L1 coding gene; PDCD1LG2-PD-L2 coding gene; PDCD1-PD-1 coding gene; SIRPA- SIRPalpha coding gene; TPM- transcript per million; LGG-low grade glioma (WHO grading I and II); GBM-glioblastoma (WHO grading IV).
PMC9915868
ijms-24-01879-g007.jpg
0.517883
371ecbca2ebd4c2693768a4a1e51c6b6
The gating strategy for monocyte subpopulations is demonstrated in (A–D) dot plots. Doublets elimination and setting up gate covering on singles population is presented in panel (A). Therefore, FSC-A vs. SSC-A gating was used for monocyte selection (B). For a more accurate determination of the monocyte population, assessment of CD14 V450 vs. CD16 FITC was used (C). The gating from the panel (D) CD16 FITC vs. SLAN APC was used to identify classical (CD14+ CD16− SLAN−), intermediate (CD14dim CD16+ SLAN−) and non-classical (CD14low/− CD16+ SLAN+) monocytes. The assessment of immune checkpoint molecules based on fluorescence-minus-one (FMO) control for classical monocytes (CD14+ CD16− SLAN−) is shown in dot plots (E–H).
PMC9915868
ijms-24-01879-g008.jpg
0.466761
10a7f7bab5be42e089fc1ce7723ccd8a
Map of urban public spaces used for recreation in the city of Ljubljana.
PMC9916178
ijerph-20-02159-g001.jpg
0.459617
afbb18129dc54a4d823f2446fce93356
Recreation hot spots in urban public spaces selected for surveying.
PMC9916178
ijerph-20-02159-g002.jpg
0.443212
e659ca1782a4486689340ede56c93aad
Semi-optical snapshots of calcium-crosslinked GG microspheres (A,B) and SEM images at ×100 magnification (C) and ×200 magnification (D).
PMC9916199
ijms-24-01949-g001.jpg
0.536354
a765317af17449a7993a455793e6c3ba
FTIR spectra (absorbance vs. wavenumber) of calcium-crosslinked GG microspheres (A) and GG powder (B).
PMC9916199
ijms-24-01949-g002.jpg
0.457404
b4559ba07d554a48b6884db8a4c22760
SDS-PAGE and Western blot of the recovered supernatants from the initial batch for both calcium- and nickel-crosslinked microspheres (35 mL GG microspheres for both ions represented). MW—molecular weight; I—sample that did not bind to GG microspheres at 10 mM MES pH 6.2; II—washing step with 10 mM Tris pH 8; III—elution step with 10 mM Tris pH 9.2; IV—elution step with 10 mM Tris pH 11; arrows indicate STEAP1 complexes.
PMC9916199
ijms-24-01949-g003.jpg
0.439336
5822ea79e0f948ba9801f9901c9698ee
Western blot of the detergent screening for solubilization of STEAP1 (control represents insolubilized lysate samples) (A) and recovered supernatants from the initial batch lysate dilution screening following a simple three step sequence per dilution: binding—10 mM MES pH 6.2; washing—10 mM Tris pH 8; elution—10 mM Tris pH 11 (B).
PMC9916199
ijms-24-01949-g004.jpg
0.448809
1e9462fbc63a4c99aa7451da9713a87b
SDS-PAGE and Western blot of the recovered supernatants from the optimized batch for calcium-crosslinked GG microspheres (35 mL GG microspheres); I—sample that did not bind to GG microspheres at 10 mM MES pH 6.2; II—washing step with 10 mM Tris pH 8; III—elution step with 10 mM Tris pH 9.2; IV—elution step with 10 mM Tris pH 11.
PMC9916199
ijms-24-01949-g005.jpg
0.506821
8fa7ee384e684698b183dc70cd02b1d5
SDS-PAGE and Western blot of the recovered supernatants from affinity batch with nickel-crosslinked GG microspheres; I—sample that did not bind to GG microspheres at 10 mM Tris pH 9.2 with 150 mM NaCl and 5 mM imidazole; II—washing step with 10 mM Tris pH 9.2 with 150 mM NaCl and 50 mM imidazole; III—elution step with 10 mM Tris pH 9.2 with 150 mM NaCl and 500 mM imidazole.
PMC9916199
ijms-24-01949-g006.jpg
0.416266
c9c215393b5049899301da34f38fe817
SDS-PAGE and Western blot of the recovered supernatants from the ionic exchange batch for calcium-crosslinked GG microspheres for both a four-step batch (A) and condensed batch (B) (35 mL GG microspheres); I—sample that did not bind to GG microspheres at 10 mM MES pH 6.2; II—wash step with 10 mM Tris pH 8 and 100 mM NaCl; III—elution step with 10 mM Tris pH 8 and 200 mM NaCl; IV—elution step with 10 mM Tris pH 11 and 500 mM NaCl.
PMC9916199
ijms-24-01949-g007.jpg
0.442471
a94b7e28820444edbab66a6f8b61b30f
SDS-PAGE and Western blot of the entire purification workflow: the initial total protein content in K.pastoris lysate, the clarified sample from calcium-crosslinked GG batch and the purified co-immunoprecipitated STEAP1.
PMC9916199
ijms-24-01949-g008.jpg