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Main interactions between global hemodynamics (HR and MAP), EEG based-parameters, REG geometric features (CBF lin) and REG Poincaré plot (CBF PP) parameters during steady state anesthesia. The post hoc non-parametric U Mann-Whitney test and statistical significance level p-value < 0.005 were considered.

PMC10013012

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Causal interactions from (A) CePropo to: (A1) EEG based-parameters (δ, θ, α, ß) and global hemodynamics (HR, MAP), (A2) REG geometric features and (A3) REG Poincaré plot features. (B) Causal interactions between global hemodynamics, EEG based-parameters, REG geometric features (CBF lin) and REG Poincaré plot (CBF PP) parameters in propofol concentration. The post hoc non-parametric U Mann-Whitney test and statistical significance level p-value < 0.005 were considered.

PMC10013012

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Causal interactions from (A) CeRemi to: (A1) EEG based-parameters (δ, θ, α, ß) and global hemodynamics (HR, MAP), (A2) REG geometric features and (A3) REG Poincaré plot features. (B) Causal interactions between global hemodynamics, EEG based-parameters, REG geometric features (CBF lin) and REG Poincaré plot (CBF PP) parameters in remifentanil concentration. The post hoc non-parametric U Mann-Whitney test and statistical significance level p-value < 0.005 were considered.

PMC10013012

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Causal interactions between global hemodynamics, EEG based-parameters, REG geometric features (CBF lin) and REG Poincaré plot (CBF PP) parameters (A) in atropine infusion and (B) in ephedrine infusion. The post hoc non-parametric U Mann-Whitney test and statistical significance level p-value < 0.005 were considered.

PMC10013012

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Causal interactions between global hemodynamics, EEG based-parameters, REG geometric features (CBF lin) and REG Poincaré plot (CBF PP) parameters (A) during Trendelenburg positioning and (B) during passive leg raising. The post hoc non-parametric U Mann-Whitney test and statistical significance level p-value < 0.005 were considered.

PMC10013012

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Classes of p-value histograms.(A) Examples of p-value histogram classes. Red lines denote the algorithmic threshold separating p-value histograms into discrete classes. (B) Summary of p-value histograms identified from GEO supplementary files. One p-value set was randomly sampled from each GEO series where p-values were identified. N = 4,616; 95% CI are credible intervals. The model object related to panel B can be downloaded from https://gin.g-node.org/tpall/geo-htseq-paper/src/v0.1/models/Class_1.rds.

PMC10013925

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Association of the p-value histogram class with a differential expression analysis tool.(A) Time courses for proportions of different p-value histogram classes for the 5 most frequently used DE analysis platforms. Lines denote best fit of the model [class ~ year + (year | de_tool), categorical likelihood]. Shaded areas denote 95% credible regions. N = 4,616. The data file is in S1 Data (B) Association of p-value histogram type with DE analysis tool; data is restricted to 2018–2020 GEO submissions. Points denote best fit of the model [n | trials(total in de_tool) ~ class + de_tool + class:de_tool, binomial likelihood]. Thick and thin lines denote 66% and 95% credible intervals, respectively. N = 2,930. The model object related to panel A can be downloaded from https://gin.g-node.org/tpall/geo-htseq-paper/src/v0.1/models/Class_year__year_detool_year.rds. The model object related to panel B can be downloaded from https://gin.g-node.org/tpall/geo-htseq-paper/src/v0.2/models/n__trials%28total_in_de_tool%29__Class_de_tool_Class:de_tool_2018up.rds. The data file is in S2 Data. See S3 Fig for a full set of identified DE analysis tools.

PMC10013925

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Association of the proportion of true null effects (π0) with DE analysis tool.(A) Histogram of π0 values estimated from anti-conservative and uniform p-value sets. N = 1,188. The data file is in S3 Data. (B) Robust linear model [pi0 ~ de_tool, beta likelihood] indicates an association of π0 with the DE analysis tool. Points denote best estimates for the mean π0 and thick and thin lines denote 66% and 95% credible intervals, respectively. N = 1,188. The data file is in S4 Data. (C) Histogram of π0 values in GEO cancer studies compared to non-cancer studies. The data file is in S5 Data. (D) Histogram of π0 values in GEO transcription factor studies compared to non-TF studies. The data file is in S6 Data. The model object related to panel B can be downloaded from https://gin.g-node.org/tpall/geo-htseq-paper/src/v0.1/models/pi0_detool_sample.rds.

PMC10013925

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The sample sizes of HT-seq DE experiments indicate low power.(A) Histogram of 2,393 sample sizes. The data file is in S7 Data. (B) Statistical power simulations using different π0 settings (shown as shades of blue coloring) and 2 different biological variation settings (“Gilad” corresponds to human liver samples and “Bottomly” to inbred mice; [33]). The data file is in S8 Data.

PMC10013925

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Association of the sample size of the HT-seq DE experiment with p-value distributional class.(A) Increasing sample sizes are associated with an increased fraction of anti-conservative p-value distributions. Logistic model [anticons ~ N], Bernoulli likelihood, N = 2,392. The data file is in S9 Data. (B) Non-anti-conservative p-value distributional classes are more likely to have extremely low sample sizes of 1 or 2 and less likely to have sample sizes of 4 or more. The y-axis denotes the proportion of experiments with a given sample size calculated from the total number of experiments in a given p-value distributional class. Logistic model [n | trials(total_in_class) ~ Class + Nb + Class:Nb], binomial likelihood, N = 2,392. Points denote best estimates for the mean and thick and thin lines denote 66% and 95% credible intervals, respectively. The data file is in S10 Data. The model object related to panel A can be downloaded from https://gin.g-node.org/tpall/geo-htseq-paper/src/v0.1/models/anticons__N.rds. The model object related to panel B can be downloaded from https://gin.g-node.org/tpall/geo-htseq-paper/src/v0.1/models/n%20%7c%20trials%28nn%29__Class%20+%20Nb%20+%20Class:Nb.rds.

PMC10013925

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π0-s calculated from anti-conservative p-value sets do not behave in accordance to statistical theory.(A) Calculated π0-s (on the y-axis) from simulated data vs. given “true” proportions of DE-features (on the x-axes). Sample sizes are indicated in color code. The dotted line shows the perfect correspondence between the given π0-s and the estimated π0. The data file is in S11 Data. (B) Dependence of mean π0 from the binned sample sizes with 95% CI. Robust linear model [pi0 ~ N], Student’s likelihood. Points denote best estimates for the mean and thick and thin lines denote 66% and 95% credible intervals, respectively. The data file is in S12 Data. Model object related to panel B can be downloaded from https://gin.g-node.org/tpall/geo-htseq-paper/src/v0.1/models/pi0%20~%20N.rds.

PMC10013925

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Removal of low-count features results in an increasing proportion of anti-conservative p-value histograms.(A-F) Sankey charts of transformation of p-value histogram shape. Ribbon size is linearly proportional to the number of p-value sets that change their distributional class. Only the 3,426 experiments that could be subjected to this treatment are depicted. (A) Complete data, N = 3,426. (B) The subset where the p-values were calculated with cuffdiff, N = 1,116. (C) The subset where the p-values were calculated with DESeq, N = 252. (D) The subset where the p-values were calculated with DESeq2, N = 1,114. (E) The subset where the p-values were calculated with edgeR, N = 515. (F) The subset where the p-values were calculated with limma, N = 73. (G) Posterior summaries of anti-conservative p-value histogram proportions in raw and filtered p-value sets. Filtered p-value data is from a Bernoulli model [anticons ~ de_tool], N = 3,426. The data files are in S13 Data and in S14 Data (for raw data). (H) Effect sizes in percentage points of low-count feature filtering to the proportion of anti-conservative p-value histograms. The data files are in S13 Data and in S14 Data (for raw data). (I) Posterior summaries of π0 values of p-value histograms in raw and filtered p-value sets. Filtered p-value data is the p-value from the beta model [pi0 ~ de_tool], N = 2,042. The data files are in S15 Data and in S16 Data (for raw data). (J) Effect sizes in π0 units (percentage points) of low-count feature filtering to π0. The data files are in S15 Data and in S16 Data (for raw data). The model object related to filtered p-value sets in panel G can be downloaded from https://gin.g-node.org/tpall/geo-htseq-paper/src/v0.1/models/anticons_detool_filtered.rds. The model object related to filtered p-value sets in the panel I can be downloaded from https://gin.g-node.org/tpall/geo-htseq-paper/src/v0.1/models/pi0_detool_full_data_filtered.rds. See S16 Fig for all platforms.

PMC10013925

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bcfed2270b77450eb4441c7e943d5a92

Pedigree chart with age of the patient and family members in years. Maternal uncle was diagnosed with anaplastic thyroid cancer at the age of 44 years and died from metastatic disease at the age of 45 years. Patient was diagnosed with papillary thyroid carcinoma and B-ALL at the age of 12 years.

PMC10014590

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(A) Thyroidectomy reveals thyroid tissue with focal chronic inflammation and a papillary carcinoma (H&E stain, 100×). (B) Representative bone marrow biopsy reveals hypocellular marrow with trilineage hematopoiesis and no overt dysplasia (H&E stain, 400×). (C) Representative bone marrow aspirate reveals few erythroid and granulocytic cells with no overt dysplasia (Giemsa stain, 400×). (D) Karyotyping showing deletion of 7q. (E) Karyotyping showing absence of deletion 7q in most recent bone marrow specimen. (F Next generation sequencing (NGS) showing detection of leukemic clones at relapse and remission (0 residual clonal cells) at 1, 2 and 3 years after receiving tisagenlecleucel.

PMC10014590

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Timeline of clinical events.

PMC10014590

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The pipeline of the human EMMI system.a An MRI scan is performed while the subject is wearing up to 24 MRI patches containing up to 192 markers. b An optical 3D scan of the body surface is performed while the subject is wearing electrode patches in the corresponding positions as the MRI patches. c Body surface electromyograms are simultaneously recorded from up to 192 pin-type unipolar electrodes assembled as patches. EMMI generates d, a body-uterus geometry from MR images with electrode locations on the body surface and, e a body surface potential map by rendering the electromyograms at each electrode at an instant in time on the body surface. EMMI combines the two data sets to reconstruct f uterine surface potential maps (electrical activity across the uterus at a single time point). With the potential maps, we can generate the electrograms g electrical waveforms over time at each uterine site, and then derive h, the uterine region, and chronological sequence of electrical activation visualized as isochrone maps in 3D. 3D three-dimensional, MRI magnetic resonance imaging, EMMI electromyometrial imaging.

PMC10015052

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Quantification of contractions with 3D uterine surface potential maps.a A representative body surface EMG was measured at the location labeled as star (*) in Subject #2 experiencing a uterine contraction in the latent phase of labor. One segment from ~18th second to 41st second was magnified. b–e Sequential potential maps on the body surface and uterine surface in anterior view at the indicated times. Each row corresponds to the time window labeled as b–e in a, respectively. EMG electromyogram. Source data are provided as a Source Data file.

PMC10015052

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Quantification of contractions with electrograms on the uterine surfaces.a For a contraction in Subject #2 that the clinical TOCO monitor confirmed, b the electrical activations are defined as the initiation of UEB in the multichannel electrograms at about 320 uterine sites covering the entire uterine surface. In the 5 representative uterine electrograms from the indicated sites marked A through E in d, red step lines denote the UEB, green arrows denote the electrical activations, and the dashed black lines denote the earliest and latest electrical activations. c The entire activation process is visualized by the generation process of the uterine activation isochrone map and the activation curve. The former shows the activation location and time across the 3D uterine surface; the latter shows how the activation ratio increases over time. It occurs during the first part of the TOCO signal of contraction. d The complete isochrone map reflects the electrical activity of the myometrium in time and space during the contraction, where warm colors denote uterine regions that are activated early, cool colors denote the regions that are activated late, and gray denotes the regions that are never inactivated. e In the early activation map, inactive regions are in gray, and activated regions are divided into two parts: early activation (red) the 33% of areas that are activated first in time, and late activation (blue) the remaining 67%. The fundal boundary is labeled as a dashed white curve. f The activation curve reflects the temporal progression of the electrical activation during the contraction. EMMI indices (MAR, ACS, and FAR) quantify the electrical properties of the myometrium. TOCO tocodynamometry, UEB uterine electrogram burst, AR activation ratio, EMMI electromyometrial imaging, MAR maximal activation ratio, ACS activation curve slope, FAR fundal early activation ratio. Source data are provided as a Source Data file.

PMC10015052

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EMMI activation patterns of uterine contractions during active labor in nulliparous women.a In Subject #1, the cervical dilation changed from 3.5 cm to 4 cm during the electrical recording and the cervix fully dilated to 10 cm 7.01 h after the recording was completed. The cervical dilation rate was calculated at 0.86 cm per h. 3D EMMI isochrone maps for three representative contractions were shown in four views. The uterine regions in warm colors were activated earlier, cool colors regions activated later, and gray regions were inactivated. The color bar on the left denotes the activation time. The activation curve and associated EMMI indices were derived from each contraction. The early activation map highlighted the early activations (earliest 33% percent of activation, red), and the fundal area was labeled by a white dashed line. b–e Results for Subjects #2, #3, #4, and #5. Same format with Subject #1. 3D three-dimensional, EMMI electromyometrial imaging, CD cervical dilation, MAR maximal activation ratio, ACS activation curve slope, FAR fundal early activation ratio. Source data are provided as a Source Data file.

PMC10015052

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EMMI activation patterns of uterine contractions during active labor in multiparous women.a In Subject #6, the cervical dilation remained at 4 cm and reached 10 cm in 6.95 h after the EMMI recording was completed. b–e Results for Subjects #7, #8, #9, and #10. Same format with Subject #6. 3D three-dimensional, EMMI electromyometrial imaging, CD cervical dilation, MAR maximal activation ratio, ACS activation curve slope, FAR fundal early activation ratio. Source data are provided as a Source Data file.

PMC10015052

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Chest X-ray showing cardiomegaly with prominent bronchovascular markings

PMC10015394

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Axial section of contrast-enhanced computed tomography of the chest showing pericardial effusion with prominent bronchovascular markings

PMC10015394

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(a and b) T2-weighted image axial section showing pericardial effusion and hyperintensities along with thickening along peribronchovascular regions, interlobular septa, and lymphatics (blue arrow), suggestive of lymphangiectasia

PMC10015394

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Reports of Markovnikov-selective epoxide hydrogenation.

PMC10015984

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MEPs for the RuPNP- and RuPNN-catalyzed hydrogenation of propylene oxide. Throughout this work, atoms in bold and blue represent the atoms principally involved in bond-breaking and bond-forming events in transition states. Energies given represent free energies in kcal/mol at 356.15 K (83 °C), corrected to 1.0 M concentrations in solution, relative to RuH and the small-molecule reactants.

PMC10015984

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Comparison of the branched (left) and linear (right) pathways for epoxide ring-opening. For both the RuPNP and RuPNN systems, the branched pathway is preferred by approximately 4 kcal/mol.

PMC10015984

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Comparison of SN2 (left) and Noyori-like (right) transition states for epoxide ring-opening. For both RuPNP and RuPNN systems, the SN2 pathway is preferred by approximately 23 kcal/mol.

PMC10015984

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Kinetic data for 1-tetradecene oxide hydrogenolysis catalyzed by RuMACHO-BH. The top plots (points) show the time course of epoxide concentration using different initial concentrations of the Ru complex, hydrogen pressures, and initial concentrations of the epoxide. The solid lines represent linear fits to the natural logarithm of [epoxide] over time. The bottom plots show the kobs values determined from the slopes of the linear fits (black points). The solid gray lines show the predicted kobs values from a global fit of all seven experiments, according to the rate law shown in eq 1.

PMC10015984

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Kinetic data for tetradecene oxide hydrogenolysis catalyzed by RuPNNimine. The top plots (points) show the time course of epoxide conversion using different initial concentrations of the Ru complex, hydrogen pressures, and initial concentrations of the epoxide. The solid lines represent linear fits to the logarithm of [epoxide] over time. The bottom plots show the kobs values determined from the slopes of the linear fits (black points). The solid gray lines show the predicted kobs values from a global fit of all nine experiments, according to the rate law shown in eq 2.

PMC10015984

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Mechanistic Overview of Noyori-Type Catalytic Hydrogenation

PMC10015984

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Simplified Scheme Determining the Kinetics for Epoxide Hydrogenolysis for the RuPNN System

PMC10015984

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Standard Conditions for Kinetic Experiments

PMC10015984

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Soundscape recording stations in the Northern Adriatic Sea; vessel traffic (a) and bathymetry (b) are highlighted. Vessel traffic is represented as total number of vessel passages in 2020, obtained from EMODnet Human Activities, Vessel Density Map. (revision date 2022-03-21).

PMC10016184

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Workflow of the acquisition and processing of underwater noise data to obtain SPL20,60 dataset.

PMC10016184

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Sketch of the SOUNDSCAPE standard rig deployed on the seafloor, with hydrophone set at ~3 m above the seafloor (range from 2 to 6 m).

PMC10016184

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Examples of SPL20,60 data post processing outputs generated applying the Python post processing script to the released dataset.

PMC10016184

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(A) Traumatic ear defect preserving the concha, ear lobe, and root of helix. (B) Posterior auricular view of ear defect.

PMC10016212

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Anterior view of the amputated ear segment.

PMC10016212

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Preserved de-skinned amputated cartilage.

PMC10016212

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(A) Pre-pocket burial approximation of the reconstruction plan. (B) Superior and (C) anterior view of pre-pocket burial native cartilage approximation. (D) Posterior view of pre-pocket burial approximation, revealing the future defect that will require full-thickness skin grafting.

PMC10016212

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Postoperative result of stage 1: de-skinned amputated ear cartilage buried in posterior auricular pocket with native ear wound closure and bacitracin dressing.

PMC10016212

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Anterior view of healed pocket burial.

PMC10016212

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Anterior view of the helical rim showing suture wrapped around the edge of the helix.

PMC10016212

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(A) Ear reconstruction at 2 weeks postoperatively. (B) Ear reconstruction at 3 months postoperatively.

PMC10016212

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PRISMA flowchart.

PMC10017178

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Forest plot of overall and stratified pooled prevalence estimates by individual professions.

PMC10017178

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Forest plot of subgroup analysis by study level characteristics.

PMC10017178

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Risk of bias summary.

PMC10017178

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Forest plot of subgroup analysis by JBI risk of bias criteria.

PMC10017178

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Forest plot of odds ratio comparing the prevalence of probable mental health disorders in Hospital HCWs working in high risk and low risk units.

PMC10017178

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Forest plot of prevalence odds ratio comparing the prevalence of probable mental health disorders in Hospital HCWs providing direct care and no direct care.

PMC10017178

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Forest plot of prevalence odds ratio comparing the prevalence of probable mental health disorders in women and men.

PMC10017178

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FlowchartCRT, conformal radiotherapy; ITT, intention-to-treat; TACE, transcatheter arterial chemoembolisation.

PMC10017427

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Kaplan–Meier curves showing (A) liver PFS and (B) liver TTP in the ITT population evaluated without and after PS.CRT, conformal radiotherapy; ITT, intention-to-treat; PFS, progression-free survival; PS, propensity score; TACE, transcatheter arterial chemoembolisation; TTP, time to tumour progression.

PMC10017427

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Kaplan–Meier curves showing treated liver PFS and TTP in the per-protocol population without and after PS.CRT, conformal radiotherapy; ITT, intention-to-treat; PFS, progression-free survival; PS, propensity score; TACE, transcatheter arterial chemoembolisation; TTP, time to tumour progression.

PMC10017427

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Kaplan–Meier curves showing probability of portal hypertension-related grade III–IV adverse event in the ITT population without and after PS.CRT, conformal radiotherapy; ITT, intention-to-treat; PS, propensity score; TACE, transcatheter arterial chemoembolisation.

PMC10017427

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OS in the ITT population without and after PS.CRT, conformal radiotherapy; ITT, intention-to-treat; OS, overall survival; PS, propensity score; TACE, transcatheter arterial chemoembolisation.

PMC10017427

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Csf1r-expressing fetal definitive progenitors give rise to adult testicular macrophages.a Strategy for 4-hydroxytamoxifen-induced (4-OHT) lineage-tracing and harvesting of testes from Csf1r-creER; Rosa-Tomato embryos and juvenile/adult mice. The embryo image was created with BioRender.com software (BioRender.com). b–n Representative images (n = 3) of testes at various stages from Csf1r-creER; Rosa-Tomato mice exposed to 4-OHT at E8.5 (b–d), E10.5 (e–g, k, l), or E12.5 (h–j, m, n). In all figures throughout this study, prime figures (e.g., a’ relative to a) are higher-magnification images of the boxed regions in the image to their left. Dashed lines indicate the gonad–mesonephros boundary. Arrowheads denote Tomato-expressing F4/80+ macrophages and arrows denote Tomato-expressing F4/80-negative cells. Thin scale bar, 100 μm; thick scale bar, 25 μm. o–r Graphs showing quantification (n = 3 independent gonads) of percent Tomato-expressing F4/80+ macrophages at E14.5, E16.5, or E18.5 (o), number of Tomato-expressing F4/80− cells per unit area at E14.5, E16.5, or E18.5 (p), and percent Tomato-expressing interstitial (CD206+) and peritubular (MHCII+) macrophages at P30 (q) or P90 (r) in Csf1r-creER; Rosa-Tomato testes induced with 4-OHT at various embryonic stages. Data are shown as mean +/− SD. *P < 0.05; **P < 0.01 (two-tailed Student’s t test). Exact P values are provided in the Source Data file.

PMC10017703

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392866076ada418dad8602aee718be95

Contribution of AGM-derived HSCs to adult testicular macrophages occurs within a specific recruitment window during fetal development.a Strategy for 4-OHT-induced lineage-tracing and harvesting of testes from KitcreER; Rosa-Tomato embryos and juvenile/adult mice. Embryo image was created with BioRender.com software (BioRender.com). b–m Representative images (n = 3 independent gonads) of testes at various stages from KitcreER; Rosa-Tomato mice exposed to 4-OHT at E8.5 (b, f, g), E10.5 (c–e, h, i), E12.5 (j, k), or E14.5 (l, m). Dashed lines indicate gonad–mesonephros boundary. Black arrowheads denote Tomato-expressing PECAM1+ endothelial cells, white arrowheads denote Tomato-expressing F4/80+ macrophages, black arrows denote Tomato-expressing CYP17A1+ Leydig cells, and white arrows denote Tomato-expressing F4/80-negative cells. Thin scale bar, 100 μm; thick scale bar, 25 μm. n–q Graphs showing quantification (n = 3 independent gonads) of percent Tomato-expressing F4/80+ macrophages at E14.5, E16.5, or E18.5 (n), number of Tomato-expressing F4/80− cells per unit area at E14.5, E16.5, or E18.5 (o), and percent Tomato-expressing interstitial (CD206+) and peritubular (MHCII+) macrophages at P30 (p) and P90 (q) in KitcreER; Rosa-Tomato testes induced with 4-OHT at various embryonic stages. Data are shown as mean +/− SD. *P < 0.05; **P < 0.01; ***P < 0.001 (two-tailed Student’s t test). Exact P values are provided in the Source Data file.

PMC10017703

41467_2023_37199_Fig2_HTML.jpg

3a2a1622b957482daa2300ebe3519c75

Flt3-expressing fetal HSC-derived multipotent progenitors give rise to adult testicular macrophages.a–h Representative images (n = 3 independent gonads) of Flt3-cre; Rosa-Tomato testes at E14.5 (a), E16.5 (b), E18.5 (c), P7 (d), P30 (e, f), and P90 (g, h). Arrowheads denote Tomato-expressing F4/80+ macrophages and arrows denote Tomato-expressing F4/80-negative cells. Thin scale bar, 100 μm; thick scale bar, 25 μm. i–k Graphs showing quantification of percent Tomato-expressing F4/80+ macrophages (i), number of Tomato-expressing F4/80-negative cells per unit area at E14.5 (n = 3 independent gonads), E16.5 (n = 3), E18.5 (n = 5) or P7 (n = 3) (j), and percent Tomato-expressing interstitial (CSF1R+) and peritubular (MHCII+) macrophages at P30 (n = 3) and P90 (n = 4) (k) in Flt3-cre; Rosa-Tomato testes. Data are shown as mean +/− SD. *P < 0.05; **P < 0.01; ***P < 0.001 (two-tailed Student’s t-test). Exact P values are provided in the Source Data file.

PMC10017703

41467_2023_37199_Fig3_HTML.jpg

8d8c7f67704b43bcb6908b37a996feeb

Fetal testis monocytes gradually differentiate into testicular macrophages after birth.a Strategy for 4-OHT-induced lineage-tracing and harvesting of testes from Cx3cr1creER; Rosa-Tomato embryos and juvenile/adult mice. The embryo image was created with BioRender.com software (BioRender.com). b–j Representative images (n = 3 independent gonads) of testes at various stages from Cx3cr1creER; Rosa-Tomato mice exposed to 4-OHT at E12.5 (b–d), E18.5 (e, f), or to TAM at P4 and P5 (g–j). Arrowheads denote Tomato-expressing IBA1+ or F4/80+ macrophages and arrows denote Tomato-negative CD45+ cells. Thin scale bar, 100 μm; thick scale bar, 25 μm. k–n Graphs showing quantification (n = 3 independent gonads) of percent Tomato-expressing F4/80+ macrophages at E18.5 or P7 (k), percent Tomato-expressing CD45+ cells at E18.5 or P7 (l), and percent Tomato-expressing interstitial (CD206+) and peritubular (MHCII+) macrophages at P30 (m) or P90 (n) in Cx3cr1creER; Rosa-Tomato testes induced with 4-OHT or TAM at various embryonic or postnatal stages. Data are shown as mean +/– SD. **P < 0.01; ***P < 0.001 (two-tailed Student’s t test). Exact P values are provided in the Source Data file.

PMC10017703

41467_2023_37199_Fig4_HTML.jpg

acb126ee843e494f8e3dbebafca3d0ef

Sertoli cells regulate testicular immune cell recruitment.a–l Representative images (n = 3 independent gonads) of control (a, c, e, g, i, k) and Amh-cre; Rosa-DTA (b, d, f, h, j, l) testes at various fetal stages. Thin scale bar, 100 μm; thick scale bar, 25 μm. m, n Graphs showing number (n = 3 independent gonads) of F4/80+ cells (m) or number of CD45+ IBA1-negative cells (n) per unit area of gonadal interstitium at E14.5, E16.5, or E18.5 in control versus Amh-cre; Rosa-DTA fetal testes, as determined by stereology-based cell counts. o Representative flow cytometry analyses of E18.5 control (left) and Amh-cre; Rosa-DTA (right) fetal testes for CD45+ cells (top) and for F4/80-hi CD11b-hi (macrophages; red gate) versus F4/80-lo CD11b-hi cells (monocytes and other myeloid cells; blue gate) (bottom). p–s Graph showing flow-cytometric-based quantification of percent CD45+ cells among live total gonadal cells (p), number of CD45+ cells per 1 × 105 live total gonadal cells (q), percent F4/80-hi CD11b-hi and F4/80-lo CD11b-hi cells among CD45+ cells (r), and number of F4/80-hi CD11b-hi and F4/80-lo CD11b-hi cells per 1 × 105 live total gonadal cells (s) for E18.5 control (n = 3) versus Amh-cre; Rosa-DTA (n = 4) fetal testes. Data are shown as mean +/– SD. *P < 0.05 (two-tailed Student’s t-test). Exact P values are provided in the Source Data file.

PMC10017703

41467_2023_37199_Fig5_HTML.jpg

420ac3d31baa470e9e6c15d0ec4cf5b3

EMPs and HSC-derived macrophages have distinct functions during fetal testis development.a–d Images of E13.5 fetal testes from C57BL/6 J embryos exposed at E6.5 to either control rat IgG2a antibody (a, c) or anti-CSF1R blocking antibody to deplete YS-derived macrophages (b, d). Shown in (a, b) and (c, d) are representative images from n = 4 and n = 5 independent gonads, respectively. Dashed lines indicate gonad–mesonephros boundary. Asterisks denote fused or branched testis cords. Insets in c and d are higher-magnification images of the boxed regions highlighting CD11b+ cells (likely monocytes) in the gonad–mesonephros border region. Thin scale bar, 100 μm; thick scale bar in c and d insets, 25 μm. e qRT-PCR analyses of whole E13.5 fetal testes showing fold change of gene expression in YS-macrophage-depleted samples (n = 6 independent gonads) versus controls (n = 6 independent gonads). f–h Graphs showing quantification of testis cord height (f), testis cord width (g), and percent abnormal (fused and/or branched) testis cords (h) in E13.5 YS-macrophage-depleted samples (n = 11 independent gonads) versus controls (n = 9 independent gonads). i–l Representative images (n = 3 independent gonads) of E18.5 fetal testes from C57BL/6 J embryos exposed at E6.5 to either control rat IgG2a antibody (i, k) or anti-CSF1R blocking antibody to deplete YS-derived macrophages (j, l). Arrowheads denote cells exhibiting co-expression of F4/80 and CYP11A1; white arrows denote CD11b+ monocytes; black arrow denotes the higher background for CD11b in endothelial cells in control samples due to rat IgG2a antibody injection. Thin scale bar, 100 μm; thick scale bar, 25 μm. m qRT-PCR analyses of whole E18.5 fetal testes showing fold change of expression in YS-macrophage-depleted samples (n = 6 independent gonads) versus controls (n = 6 independent gonads). n Graph showing E18.5 testis cord number per unit area in YS-macrophage-depleted samples (n = 6 independent gonads) versus controls (n = 4 independent gonads). All graph data are shown as mean +/– SD. *P < 0.05; **P < 0.01; ***P < 0.001 (two-tailed Student’s t test). Exact P values are provided in the Source Data file.

PMC10017703

41467_2023_37199_Fig6_HTML.jpg

d61efe4f6ebb42048545aafc35649990

Adult interstitial macrophages promote Leydig cell proliferation and steroidogenesis.a–h Representative images (n = 3 independent experiments) of primary cell culture after 3 days (a–d) and 6 days (e–h) from adult (3-month-old) C57BL/6 J testes for pre-separation (a, e), CD45-depleted (b, f), CD45-enriched (c, g), and F4/80-enriched (d, h) populations. i–l Graphs showing quantification (n = 3 independent experiments from 6 testes) of percent EdU+ Leydig cells (i), percent EdU+ macrophages (j), and testosterone concentration (n = 4 independent experiments from 8 testes) in culture media after 0–3 days of culture (k) and 3–6 days of culture (l) in the 4 different cell populations. m Representative images of Ccr2GFP/+ testes and graph showing quantification (n = 3 independent testes) of percent GFP-expressing interstitial (CD206+) and peritubular (MHCII+) macrophages at P60. Arrowheads denote GFP-expressing MHCII+ peritubular macrophages. n FACS isolation and culture of testicular macrophages from adult Ccr2GFP/+ testes. Flow cytometry plot (left) shows peritubular macrophages (Peri Mφ: GFP+CD206–), interstitial macrophages (Int Mφ: GFP–CD206+) and Leydig cells (GFP–CD206–) gated on total live cells as indicated; graph (right) shows testosterone concentrations (n = 5 independent experiments from 10 testes) in culture media after 3 days of culture of Leydig cells alone and Leydig cells co-cultured with Int Mφ or Peri Mφ. Thin scale bar, 100 μm; thick scale bar, 25 μm. All graph data are shown as mean +/– SD. *P < 0.05; **P < 0.01; ***P < 0.001 (two-tailed Student’s t test). Exact P values are provided in the Source Data file.

PMC10017703

41467_2023_37199_Fig7_HTML.jpg

02b4d29736c643038fde338debd8feca

Go/No-go task procedure.

PMC10018214

fpsyg-14-983361-g001.jpg

bdd2ed939fc845e88e54438d20367538

N2 and P3 ERP components linked to the target processing in the Go/No-go task. Average ERPs of a set of electrodes around FCz and Pz are shown for N2 and P3 components, respectively.

PMC10018214

fpsyg-14-983361-g002.jpg

f7ba731282bb4ef794e0f85a4fcf5efe

Correlation plots for the Go/No-go behavioral measures and the difference in peak amplitude (Go minus No-go condition) of the N2 ERP component.

PMC10018214

fpsyg-14-983361-g003.jpg

bb9d9d8fc93747a5a63cbe56e328d7c1

Structural equations model to predict IC at 5  years of age from EA in infancy and IC in toddlerhood.

PMC10018214

fpsyg-14-983361-g004.jpg

6fbd9c40543c4a468aa9db7b7b2b2543

Magnetic resonance imaging of the proband's (A) brain, (B) cervical spine, (C) thoracic spine and (D) lumbar spine did not reveal any obvious pathognomonic alterations.

PMC10018243

mmr-27-04-12966-g00.jpg

6677dc511c9a4c1fbfc25a00b7d5c581

SPG4 family pedigree of 17 members. I-1, grandfather, deceased, exhibited difficulty walking. I-2, grandmother, deceased, who did not exhibit muscle weakness. II-1, oldest aunt who has no muscle weakness. II-2, second aunt who has no muscle weakness. II-3, oldest uncle, 66 years old, who has SPG4. II-4, father, 61 years old, who has SPG4. II-5, youngest uncle, deceased, who had SPG4. II-6, third aunt who has no muscle weakness. III-1 and III-2, children of older aunt who have no muscle weakness. III-3 and III-4, children of second aunt who have no muscle weakness. III-5, older brother, 33 years old, who has SPG4. III-6, proband (arrow), 30 years old, who has SPG4. III-7, sister who has no muscle weakness. III-8 and III-9, third aunt's children who have no muscle weakness. /, deceased family member; SPG4, spastic paraplegia type 4.

PMC10018243

mmr-27-04-12966-g01.jpg

dc95ac58d95f4aab838e8353cf5d1e72

Sanger sequencing results. The (A) oldest uncle (II-3), (B) father (II-4), (C) brother (III-5) and (D) proband (III-6) all carried the c.1785C>A missense mutations in the SPAST gene. The (E) third aunt (II-6) and (F) and sister (III-7) carried a wild-type SPAST. SPAST, spastin.

PMC10018243

mmr-27-04-12966-g02.jpg

408d63b656854ddaae6ad6d24b4232dd

mRNA and protein structural predictions of the Spastin mutation. Structural predictions of (A) wild-type and (B) c.1785C>A missense mutant mRNA. Polarity predictions of (C) wild-type and (D) p.Ser595Arg Spastin amino acids. Secondary protein structure predictions of (E) wild-type and (F) p.Ser595Arg proteins. Tertiary protein structure predictions of (G) wild-type and (H) p.Ser595Arg proteins. (I) Evolutionary conservation of Ser595 among species (red box).

PMC10018243

mmr-27-04-12966-g03.jpg

2349b33401cc486483ec171b0829a8fc

Synthesis scheme of poly(MM-EM-BM).

PMC10018717

ao2c07516_0001.jpg

ed71210067f641b09cb3f27104fd4f0e

Infrared spectrum of poly(MM-EM-BM).

PMC10018717

ao2c07516_0002.jpg

a023a28fff6a42dba6570f8b9feb5b52

Particle size distribution of oil-based nanosealer poly(MM-EM-BM).

PMC10018717

ao2c07516_0003.jpg

6a54b68aa3684e0987b0950ad1fd7d79

TG analysis of poly(MM-EM-BM).

PMC10018717

ao2c07516_0004.jpg

ef9dccb31b7447d88c8de5c9818861f6

Apparent viscosity curve for the addition of poly(MM-EM-BM) with different mass concentrations of drilling fluids.

PMC10018717

ao2c07516_0005.jpg

2038c87e4112475c9efed3dc9ead6e8c

Plastic viscosity curve for the addition of poly(MM-EM-BM) with different mass concentrations of drilling fluids.

PMC10018717

ao2c07516_0006.jpg

04a4721b15614b66abea6a0da1b059c7

Yield value curve for the addition of poly(MM-EM-BM) with different mass concentrations of drilling fluids.

PMC10018717

ao2c07516_0007.jpg

8d4d6022fb3f492aa42dd87bb3c5b78e

Yield value/plastic viscosity curve for the addition of poly(MM-EM-BM) with different mass concentrations of drilling fluids.

PMC10018717

ao2c07516_0008.jpg

b182b1110c2046b7ac65714863288b0d

Demulsification voltage curve for the addition of poly(MM-EM-BM) with different mass concentrations of drilling fluids.

PMC10018717

ao2c07516_0009.jpg

31868bd30743481e8355986f22868247

HTHP variation curve for the addition of poly(MM-EM-BM) with different mass concentrations of drilling fluids.

PMC10018717

ao2c07516_0010.jpg

f3de1206901b4d679e93051c89f1d273

Evaluation of the HTHP mud cake after adding poly(MM-EM-BM) in OBDFs.

PMC10018717

ao2c07516_0011.jpg

dc6f36f6048b4c7aad9571ab142aa979

Effect of adding poly(MM-EM-BM) with different mass concentration on the rates of permeability and sealing.

PMC10018717

ao2c07516_0012.jpg

39f8d918dd7f4194be6fcf8b338bfddc

Sealing mechanism of poly(MM-EM-BM) used in OBDFs.

PMC10018717

ao2c07516_0013.jpg

3f54cdbf98ec4911bb5f44a98e1b9974

The hypothetical diagram of the mechanism of organ-specific autoimmunity and viral infection affecting Treg and Th17 mediation. Organ-specific autoimmunity: target autoantigens are concentrated in the area around blood vessels and cause perivascular inflammation. Viral infection causes dendritic cells to recognize and accept antigens. Dendritic cells stimulate T and B cells to produce inflammatory mediators such as IL-6, and even excessive production of IgG. In this context, viral infection causes immunogenic inflammation and leads to CLIPPERS. Th17 is formed by the differentiation of THO cells stimulated by IL-23. Th17 has an independent regulatory mechanism of differentiation and development. NF-κB can promote the secretion of IL-17 by Th17. Th17 cells can secrete and produce IL-17a, IL-17f, IL-6, and TNF-α to mobilize, recruit and activate neutrophils. At the same time, IL-17 is mainly an inflammatory cytokine, which can promote the activation of T cells and stimulate epithelial cells, endothelial cells, and fibroblasts to produce a variety of cytokines such as IL-6, IL-8, and other pro-inflammatory factors. It leads to the incidence of CLIPPERS from the above 3 aspects. CLIPPERS = chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. IL = interleukin, NF-κB = nuclear factor-κB, Th17 = helper T lymphocyte 17, TNF = tumor necrosis factor.

PMC10019105

medi-102-e33211-g001.jpg

8ebf47f57ebd4b38a03e418c4f43cdf1

Overview of the mitochondrial respiratory chain of E. multilocularis. Fumarate respiration (NADH:fumarate reductase system) involves complex I, rhodoquinone (RQ), and complex II (quinol:fumarate reductase, QFR). In this system, electrons from NADH are transferred to RQ through complex I, and then transferred to fumarate by the QFR activity of complex II. An electrochemical gradient is maintained by the activity of complex I, and ATP is generated by oxidative phosphorylation (complex V) even under hypoxic conditions. Oxygen respiration is performed by complexes I, II, III, and IV, with ubiquinone (UQ) acting as an electron carrier between complexes I/II and III, and cytochrome c (Cyt c) between complexes III and IV. Complex II transfers electrons from succinate to UQ, acting as a succinate:quinone reductase (SQR). At the end of oxygen respiration, the electrons from NADH and succinate are used to reduce oxygen molecules to form water. Flutolanil and atovaquone are quinone binding site inhibitors of complexes II and III, respectively.

PMC10019194

aac.01428-22-f001.jpg

1c1874f0c3d741ad8956ef5380c19b3b

Model structure of E. multilocularis complex II using AlphaFold2. Fp (SDHA), Ip (SDHB), CybL (SDHC), and CybS (SDHD) subunits are colored green, cyan, purple, and yellow, respectively. Four prosthetic groups, FAD, [2Fe–2S], [4Fe–4S], and [3Fe–4S], were also modeled based on the reported crystal structures of A. suum and porcine complex II.

PMC10019194

aac.01428-22-f002.jpg

9df03def0446410a8c3ebcc88bd65df4

Predicted interaction between AF derivatives and complex II. (A) The position of D5 and a flutolanil derivative (NN23) were merged to predict the interaction between D5 and amino acid residues of E. multilocularis complex II based on the cocrystal structure of A. suum complex II with NN23. (B) The 4-OH in D5 may contribute to forming hydrogen bonds with both Tyr107D and Trp197B. Hydrogen bonds are represented as red dotted lines. The red double arrow shows the electrostatic interactions between the guanidino group of Arg76C and the benzene ring of D5. The benzene group of Phe73C, which is not conserved in A. suum and porcine complex II, might stabilize the binding of D5 by forming hydrophobic interactions with the linker shown as an orange double arrow and red rings.

PMC10019194

aac.01428-22-f003.jpg

ac1100cc9e63442b95cf0352c993fa0e

Binding sites of D5 to A. suum and E. multilocularis complex II and respective IC50 values are denoted. D5 inhibits E. multilocularis complex II (IC50 = 0.047 μM) more strongly than that of A. suum (IC50 = 11 μM). Ip, CybL, and CybS are colored cyan, purple, and yellow, respectively. The Phe73 in CybL and corresponding amino acid residue from A. suum are colored red. The dimensions of the entrance to the quinone binding site from A. suum and E. multilocularis complex II are 11 × 11 Å (top left panel) and 6 × 11 Å (top right panel), respectively. In the model structure of E. multilocularis complex II, D5 fits neatly into the pocket without steric hindrance with Phe73C (bottom right panel), while a large gap between the benzene group of D5 and pocket inner-surface of A. suum complex II can be seen (bottom left panel). The bottom of the figure shows a comparison of the amino acid sequences of CybL from A. suum and E. multilocularis. The arrow indicates that Gly73C from A. suum is replaced with Phe73C in E. multilocularis.

PMC10019194

aac.01428-22-f004.jpg

f7b6085a84934dd195a67e37dbc3f965

Viability of E. multilocularis protoscoleces in ex vivo culture assay. The E. multilocularis protoscoleces were treated with ascofuranone (AF) and its derivatives in culture under aerobic and anaerobic conditions (O2 <0.3%). Each compound was added to the culture medium at a final concentration of 50 μM. The control group was supplemented with 0.5% (vol/vol) dimethyl sulfoxide (DMSO). Atovaquone (ATV) was used as positive control and to ensure anaerobic conditions in the culture. The viability of protoscoleces was evaluated by their ability to exclude trypan blue. The data are presented as the mean ± standard deviation (n = 3).

PMC10019194

aac.01428-22-f005.jpg

6aff868c958a4cf0a4040f5d9e21dd3f

Different modes of radical generation in photoinduced ATRP. (a) Conventional photo-ATRP. (b) Organocatalyzed ATRP. (c) ATRP with photoredox/copper dual catalysis.

PMC10019465

ma2c02537_0002.jpg

74be5b99754447ec9684c83346da86fb

(a) Proposed mechanism of EY/Cu-catalyzed ATRP. (b) Deprotonation of EYH2 in PBS solution. (c) Formation of new polymer chains.

PMC10019465

ma2c02537_0003.jpg

dfd4df1158c24eb18f1bf04e843f3135

Kinetics of the optimized EY/Cu-catalyzed ATRP of OEOA480. (a) First-order kinetic plot. (b) Evolution of molecular weight and molecular weight distribution with conversion, (c) and molecular weight distribution evolution with time. Reaction conditions: [OEOA480]/[HO-EBiB]/[EYH2]/[CuBr2]/[Me6TREN] = 200/1/0.01/0.2/0.3 in PBS with DMSO (10% v/v), irradiated under green LEDs (520 nm, 25.0 mW/cm2) in an open vial with stirring at 500 rpm.

PMC10019465

ma2c02537_0004.jpg

f1a66fabda6e40aeab6e5710d3d7a1fa

(a) Temporal control in EY/Cu-catalyzed ATRP of OEOA480. (b) SEC analysis of the resulting polymer after 110 min (four cycles of light on/off periods). (c) SEC analysis of poly(OEOA480) with varying targeted DP.

PMC10019465

ma2c02537_0005.jpg

93c70665938449fe97b26257d70a4418

(a) In situ chain extension of poly(OEOA480). (b) Small-volume ATRP. (c) Synthesis of an acrylate-based protein-polymer hybrid.

PMC10019465

ma2c02537_0006.jpg

a3fd96724d6840d8b630995e37c76a95

Example of a choice task (English translation).Compared to the ban (reference policy) both tax alternatives result in lower reduction in farmers’ use of glyphosate (respectively of 75% for option 2 and 85% for option 3, to be compared with the 100% reduction of the ban) but have a lower cost for consumers (respectively +€2 per week for option 2 and +€3 per week for option 3, to be compared with the +€4 per week for the ban). The two tax alternatives also differ in the way the government spends the revenue from the tax (respectively for environmental programs for option 2 and for an additional support to farmers’ transition for option 3). The attribute levels are different in the other choice tasks. A full description of the 12 choice tasks is provided in S1 Table in the S1 File.

PMC10019652

pone.0283131.g001.jpg

ab88a37ee5d64de4a48371406dd83c1e

Inclusion and exclusion criteria of the study participants.

PMC10019954

gr1.jpg

d86a22dd86d7468a9cfbf79a33a86037

Somer’s D coefficient, concordance between BMI-for-age Z-score and BMI-for-age centiles.

PMC10019954

gr2.jpg

7742d5246b144b47a90cb97100b717f4

Schematic illustration for biomedical applications of phototherapy based on 2D materials.

PMC10020212

FBIOE_fbioe-2023-1141631_wc_sch1.jpg