bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transgressive and parental dominant gene expression and cytosine methylation during seed development in Brassica napus hybrids
Authors: Orantes-Bonilla Mauricio , Wang Hao , Lee Huey Tyng , Golicz Agnieszka A. , Hu Dandan , Li Wenwen , Zou Jun , Snowdon Rod J. 
Published: April 2023

Abstract
Key message
Transcriptomic and epigenomic profiling of gene expression and small RNAs during seed and seedling development reveals expression and methylation dominance levels with implications on early stage heterosis in oilseed rape.

Abstract
The enhanced performance of hybrids through heterosis remains a key aspect in plant breeding; however, the underlying mechanisms are still not fully elucidated. To investigate the potential role of transcriptomic and epigenomic patterns in early expression of hybrid vigor, we investigated gene expression, small RNA abundance and genome-wide methylation in hybrids from two distant Brassica napus ecotypes during seed and seedling developmental stages using next-generation sequencing. A total of 31117, 344, 36229 and 7399 differentially expressed genes, microRNAs, small interfering RNAs and differentially methylated regions were identified, respectively. Approximately 70% of the differentially expressed or methylated features displayed parental dominance levels where the hybrid followed the same patterns as the parents. Via gene ontology enrichment and microRNA-target association analyses during seed development, we found copies of reproductive, developmental and meiotic genes with transgressive and paternal dominance patterns. Interestingly, maternal dominance was more prominent in hypermethylated and downregulated features during seed formation, contrasting to the general maternal gamete demethylation reported during gametogenesis in angiosperms. Associations between methylation and gene expression allowed identification of putative epialleles with diverse pivotal biological functions during seed formation. Furthermore, most differentially methylated regions, differentially expressed siRNAs and transposable elements were in regions that flanked genes without differential expression. This suggests that differential expression and methylation of epigenomic features may help maintain expression of pivotal genes in a hybrid context. Differential expression and methylation patterns during seed formation in an F1 hybrid provide novel insights into genes and mechanisms with potential roles in early heterosis.
Symmetry Results for Compactly Supported Steady Solutions of the 2D Euler Equations
Authors: Ruiz David 
Published: April 2023

AbstractIn this paper we present symmetry results regarding compactly supported solutions of the 2D steady Euler equations. Assuming that $$\Omega = \{x \in {\mathbb {R}}^2:\ u(x) \ne 0\}$$

Ω
=
{
x
∈

R

2

:

u

(
x
)

≠
0
}

is an annular domain, we prove that the streamlines of the flow are circular. We are also able to remove the topological condition on $$\Omega $$
Ω
if we impose regularity and nondegeneracy assumptions on u at $$\partial \Omega $$

∂
Ω

. The proof uses the corresponding stream function solves an elliptic semilinear problem $$-\Delta \phi = f(\phi )$$

-
Δ
ϕ
=
f
(
ϕ
)

with $$\nabla \phi =0$$

∇
ϕ
=
0

at the boundary. One of the main difficulties in our study is that f is not Lipschitz continuous near the boundary values. However, $$f(\phi )$$

f
(
ϕ
)

vanishes at the boundary values and then we can apply a local symmetry result of F. Brock to conclude. In the case $$\partial _{\nu } u \ne 0$$

∂
ν

u
≠
0

at $$\partial \Omega $$

∂
Ω

this argument is not possible. In this case we are able to use the moving plane scheme to show symmetry, despite the possible lack of regularity of f. We think that such result is interesting in its own right and will be stated and proved also for higher dimensions. The proof requires the study of maximum principles, The Hopf lemma and The Serrin corner lemma for elliptic linear operators with singular coefficients.
Population plasma and urine pharmacokinetics and the probability of target attainment of fosfomycin in healthy male volunteers
Authors: Edwina Angela Elma , Koch Birgit C. P. , Muller Anouk E. , al Jalali Valentin , Matzneller Peter , Zeitlinger Markus , Sassen Sebastiaan D. T. 
Published: April 2023

Abstract
Purpose
A population pharmacokinetic model of fosfomycin was developed in healthy volunteers after intravenous administration, and different dosing regimens were evaluated in terms of the probability of target attainment for Escherichia coli using both plasma and urinary pharmacokinetic/pharmacodynamic targets.

Methods
Eight healthy men received fosfomycin as both intermittent 8 g q8h and continuous infusion 1 g/h with a loading dose of 8 g in a crossover study design. Dense sampling was conducted during both regimens. Population pharmacokinetic modelling was performed using NONMEM. Monte Carlo simulations were conducted to evaluate the Probability of Target Attainment (PTA) of different dosing regimens using bactericidal (AUC24h/MIC of 83 and 75%T>MIC) and bacteriostatic (AUC24h/MIC of 25) plasma targets and bacteriostatic (AUC24h/MIC of 3994) urine target.

Results
A total of 176 plasma and 86 urine samples were available for PK analysis. A two-compartment model with a urine compartment best described the data. Glomerular filtration rate (GFR) showed a significant correlation with renal clearance and was implemented in the final model. Simulation results show that the dose of 4 g q8h reached 100% of PTA using bactericidal and bacteriostatic targets for MIC up to 16 mg/L.

Conclusion
For the clinical breakpoint of 32 mg/L, the standard dosing regimen (4 g q8h) might not be sufficient to reach the bactericidal target. Higher dosing of 8 g q8h as an intermittent infusion or 0.75 g/h as a continuous infusion might be required. Continuous infusion resulted in better attainment of the %T>MIC target than intermittent infusion.
Metabarcoding inventory of an arctic tundra soil ecosystem reveals highly heterogeneous communities at a small scale
Authors: Jorna Jesse , Vandenbrink Bryan , Hogg Ian D. , Wall Diana H. , Adams Byron J. 
Published: April 2023

AbstractBiodiversity surveys of Arctic soil ecosystems are limited. Here, we provide a sequence-based inventory of soil fauna from an Arctic tundra ecosystem near the Canadian High Arctic Research Station in Cambridge Bay, Nunavut. Invertebrate communities were extracted at a vegetated and non-vegetated site in three replicates and inventoried using 18S metabarcode sequencing. A total of 361 amplicon sequence variants (ASV) were identified and assigned to the closest matching taxonomic orders, most of which belonged to the Nematoda and Arthropoda. Vegetated soils showed no significantly higher ASV richness relative to non-vegetated soils although they contained a significantly higher diversity of arthropod taxa including insects, mites, and springtails. Most taxa were found only at a single location and even samples from the same site displayed distinct communities, suggesting that belowground species richness in Arctic tundra habitats is highly heterogeneous. Preserving soil biodiversity in a changing Arctic is essential for Inuit communities who rely on intact tundra ecosystems for their health and wellbeing.
Halved contrast medium dose in lower limb dual-energy computed tomography angiography—a randomized controlled trial
Authors: Kristiansen Cathrine Helgestad , Thomas Owen , Tran Thien Trung , Roy Sumit , Hykkerud Dan Levi , Sanderud Audun , Geitung Jonn Terje , Lauritzen Peter M. 
Published: April 2023

Abstract
Objectives
To compare vascular attenuation (VA) of an experimental half iodine-load dual-layer spectral detector CT (SDCT) lower limb computed tomography angiography (CTA) with control (standard iodine-load conventional 120-kilovolt peak (kVp) CTA).

Methods
Ethical approval and consent were obtained. In this parallel RCT, CTA examinations were randomized into experimental or control. Patients received 0.7 vs 1.4 mL/kg of iohexol 350 mgI/mL in the experimental- vs the control group. Two experimental virtual monoenergetic image (VMI) series at 40 and 50 kiloelectron volts (keV) were reconstructed. Primary outcome: VA. Secondary outcomes: image noise (noise), contrast- and signal-to-noise ratio (CNR and SNR), and subjective examination quality (SEQ).

Results
A total of 106 vs 109 were randomized and 103 vs 108 were analyzed in the experimental vs, control groups, respectively. VA was higher on experimental 40 keV VMI than on control (p < 0.0001), but lower on 50 keV VMI (p < 0.022). Noise was higher on experimental 40 keV VMI than on control (p = 0.00022), but lower on 50 keV VMI (p = 0.0033). CNR and SNR were higher than the control on experimental 40 keV VMI (both p < 0.0001) and 50 keV (p = 0.0058 and p = 0.0023, respectively). SEQ was better on both VMIs in the experimental group than in the control (both p < 0.0001).

Conclusions
Half iodine-load SDCT lower limb CTA at 40 keV achieved higher VA than the control. CNR, SNR, noise, and SEQ were higher at 40 keV, while 50 keV showed lower noise.

Clinical relevance statement
Spectral detector CT with low-energy virtual monoenergetic imaging performed halved iodine contrast medium (CM) lower limb CT-angiography with sustained objective and subjective quality. This facilitates CM reduction, improvement of low CM-dosage examinations, and examination of patients with more severe kidney impairment.

Trial registration
Retrospectively registered 5 August 2022 at clinicaltrials.gov NCT05488899.

Key Points
• Contrast medium dosage may be halved in lower limb dual-energy CT angiography with virtual monoenergetic images at 40 keV, which may reduce contrast medium consumption in the face of a global shortage.
• Experimental half-iodine-load dual-energy CT angiography at 40 keV showed higher vascular attenuation, contrast-to-noise ratio, signal-to-noise ratio, and subjective examination quality than standard iodine-load conventional.
• Half-iodine dual-energy CT angiography protocols may allow us to reduce the risk of PC-AKI, examine patients with more severe kidney impairment, and provide higher quality examinations or salvage poor examinations when impaired kidney function limits the CM dose.
Quo vadis Radiomics? Bibliometric analysis of 10-year Radiomics journey
Authors: Volpe Stefania , Mastroleo Federico , Krengli Marco , Jereczek-Fossa Barbara Alicja 
Published: April 2023

Abstract
Objectives
Radiomics is the high-throughput extraction of mineable and—possibly—reproducible quantitative imaging features from medical imaging. The aim of this work is to perform an unbiased bibliometric analysis on Radiomics 10 years after the first work became available, to highlight its status, pitfalls, and growing interest.

Methods
Scopus database was used to investigate all the available English manuscripts about Radiomics. R Bibliometrix package was used for data analysis: a cumulative analysis of document categories, authors affiliations, country scientific collaborations, institution collaboration networks, keyword analysis, comprehensive of co-occurrence network, thematic map analysis, and 2021 sub-analysis of trend topics was performed.

Results
A total of 5623 articles and 16,833 authors from 908 different sources have been identified. The first available document was published in March 2012, while the most recent included was released on the 31st of December 2021. China and USA were the most productive countries. Co-occurrence network analysis identified five words clusters based on top 50 authors’ keywords: Radiomics, computed tomography, radiogenomics, deep learning, tomography. Trend topics analysis for 2021 showed an increased interest in artificial intelligence (n = 286), nomogram (n = 166), hepatocellular carcinoma (n = 125), COVID-19 (n = 63), and X-ray computed (n = 60).

Conclusions
Our work demonstrates the importance of bibliometrics in aggregating information that otherwise would not be available in a granular analysis, detecting unknown patterns in Radiomics publications, while highlighting potential developments to ensure knowledge dissemination in the field and its future real-life applications in the clinical practice.

Clinical relevance statement
This work aims to shed light on the state of the art in radiomics, which offers numerous tangible and intangible benefits, and to encourage its integration in the contemporary clinical practice for more precise imaging analysis.

Key Points
• ML-based bibliometric analysis is fundamental to detect unknown pattern of data in Radiomics publications.
• A raising interest in the field, the most relevant collaborations, keywords co-occurrence network, and trending topics have been investigated.
• Some pitfalls still exist, including the scarce standardization and the relative lack of homogeneity across studies.
The estimated causal effect on the variance based on the front-door criterion in Gaussian linear structural equation models: an unbiased estimator with the exact variance
Authors: Kuroki Manabu , Tezuka Taiki 
Published: April 2023

AbstractIn this paper, we assume that cause–effect relationships between random variables can be represented by a Gaussian linear structural equation model and the corresponding directed acyclic graph. Then, we consider a situation where a set of random variables that satisfies the front-door criterion is observed to estimate a total effect. In this situation, when the ordinary least squares method is utilized to estimate the total effect, we formulate the unbiased estimator of the causal effect on the variance of the outcome variable. In addition, we provide the exact variance formula of the proposed unbiased estimator.
Effects of hyperventilation on oxygenation, apnea breaking points, diving response, and spleen contraction during serial static apneas
Authors: Pernett Frank , Bergenhed Pontus , Holmström Pontus , Mulder Eric , Schagatay Erika 
Published: April 2023

Abstract
Purpose
Hyperventilation is considered a major risk factor for hypoxic blackout during breath-hold diving, as it delays the apnea breaking point. However, little is known about how it affects oxygenation, the diving response, and spleen contraction during serial breath-holding.

Methods
18 volunteers with little or no experience in freediving performed two series of 5 apneas with cold facial immersion to maximal duration at 2-min intervals. In one series, apnea was preceded by normal breathing and in the other by 15 s of hyperventilation. End-tidal oxygen and end-tidal carbon dioxide were measured before and after every apnea, and peripheral oxygen saturation, heart rate, breathing movements, and skin blood flow were measured continuously. Spleen dimensions were measured every 15 s.

Results
Apnea duration was longer after hyperventilation (133 vs 111 s). Hyperventilation reduced pre-apnea end-tidal CO2 (17.4 vs 29.0 mmHg) and post-apnea end-tidal CO2 (38.5 vs 40.3 mmHg), and delayed onset of involuntary breathing movements (112 vs 89 s). End-tidal O2 after apnea was lower in the hyperventilation trial (83.4 vs 89.4 mmHg) and so was the peripheral oxygen saturation nadir after apnea (90.6 vs 93.6%). During hyperventilation, the nadir peripheral oxygen saturation was lower in the last apnea than in the first (94.0% vs 86.7%). There were no differences in diving response or spleen volume reduction between conditions or across series.

Conclusions
Serial apneas revealed a previously undescribed aspect of hyperventilation; a progressively increased desaturation across the series, not observed after normal breathing and could heighten the risk of a blackout.
The HDAC inhibitor domatinostat induces type I interferon α in Merkel cell carcinoma by HES1 repression
Authors: Srinivas Nalini , Song Lina , Lei Kuan Cheok , Gravemeyer Jan , Furtmann Frauke , Gambichler Thilo , Becker Jürgen C. , Sriram Ashwin 
Published: April 2023

Abstract
Background
Class I selective histone deacetylase inhibitors (HDACi) have been previously demonstrated to not only increase major histocompatibility complex class I surface expression in Merkel cell carcinoma (MCC) cells by restoring the antigen processing and presentation machinery, but also exert anti-tumoral effect by inducing apoptosis. Both phenomena could be due to induction of type I interferons (IFN), as has been described for HDACi. However, the mechanism of IFN induction under HDACi is not fully understood because the expression of IFNs is regulated by both activating and inhibitory signaling pathways. Our own preliminary observations suggest that this may be caused by suppression of HES1.

Methods
The effect of the class I selective HDACi domatinostat and IFNα on cell viability and the apoptosis of MCPyV-positive (WaGa, MKL-1) and -negative (UM-MCC 34) MCC cell lines, as well as, primary fibroblasts were assessed by colorimetric methods or measuring mitochondrial membrane potential and intracellular caspase-3/7, respectively. Next, the impact of domatinostat on IFNA and HES1 mRNA expression was measured by RT-qPCR; intracellular IFNα production was detected by flow cytometry. To confirm that the expression of IFNα induced by HDACi was due to the suppression of HES1, it was silenced by RNA interference and then mRNA expression of IFNA and IFN-stimulated genes was assessed.

Results
Our studies show that the previously reported reduction in viability of MCC cell lines after inhibition of HDAC by domatinostat is accompanied by an increase in IFNα expression, both of mRNA and at the protein level. We confirmed that treatment of MCC cells with external IFNα inhibited their proliferation and induced apoptosis. Re-analysis of existing single-cell RNA sequencing data indicated that induction of IFNα by domatinostat occurs through repression of HES1, a transcriptional inhibitor of IFNA; this was confirmed by RT-qPCR. Finally, siRNA-mediated silencing of HES1 in the MCC cell line WaGa not only increased mRNA expression of IFNA and IFN-stimulated genes but also decreased cell viability.

Conclusion
Our results demonstrate that the direct anti-tumor effect of HDACi domatinostat on MCC cells is at least in part mediated via decreased HES1 expression allowing the induction of IFNα, which in turn causes apoptosis.
Practice variation and outcomes of minimally invasive minor liver resections in patients with colorectal liver metastases: a population-based study
Authors: de Graaff Michelle R. , Klaase Joost M. , de Kleine Ruben , Elfrink Arthur K. E. , Swijnenburg Rutger-Jan , M. Zonderhuis Babs , D. Mieog J. Sven , Derksen Wouter J. M. , Hagendoorn Jeroen , van den Boezem Peter B. , Rijken Arjen M. , Gobardhan Paul D. , Marsman Hendrik A. , Liem Mike S. L. , Leclercq Wouter K. G. , van Heek Tjarda N. T. , Pantijn Gijs A. , Bosscha Koop , Belt Eric J. T. , Vermaas Maarten , Torrenga Hans , Manusama Eric R. , van den Tol Petrousjka , Oosterling Steven J. , den Dulk Marcel , Grünhagen Dirk J. , Kok Niels F. M. ,   For Dutch Hepato Biliary Audit Group, Collaborators
Published: April 2023

Abstract
Introduction
In 2017, the Southampton guideline stated that minimally invasive liver resections (MILR) should considered standard practice for minor liver resections. This study aimed to assess recent implementation rates of minor MILR, factors associated with performing MILR, hospital variation, and outcomes in patients with colorectal liver metastases (CRLM).

Methods
This population-based study included all patients who underwent minor liver resection for CRLM in the Netherlands between 2014 and 2021. Factors associated with MILR and nationwide hospital variation were assessed using multilevel multivariable logistic regression. Propensity-score matching (PSM) was applied to compare outcomes between minor MILR and minor open liver resections. Overall survival (OS) was assessed with Kaplan–Meier analysis on patients operated until 2018.

Results
Of 4,488 patients included, 1,695 (37.8%) underwent MILR. PSM resulted in 1,338 patients in each group. Implementation of MILR increased to 51.2% in 2021. Factors associated with not performing MILR included treatment with preoperative chemotherapy (aOR 0.61 CI:0.50–0.75, p < 0.001), treatment in a tertiary referral hospital (aOR 0.57 CI:0.50–0.67, p < 0.001), and larger diameter and number of CRLM. Significant hospital variation was observed in use of MILR (7.5% to 93.0%). After case-mix correction, six hospitals performed fewer, and six hospitals performed more MILRs than expected. In the PSM cohort, MILR was associated with a decrease in blood loss (aOR 0.99 CI:0.99–0.99, p < 0.01), cardiac complications (aOR 0.29, CI:0.10–0.70, p = 0.009), IC admissions (aOR 0.66, CI:0.50–0.89, p = 0.005), and shorter hospital stay (aOR CI:0.94–0.99, p < 0.01). Five-year OS rates for MILR and OLR were 53.7% versus 48.6%, p = 0.21.

Conclusion
Although uptake of MILR is increasing in the Netherlands, significant hospital variation remains. MILR benefits short-term outcomes, while overall survival is comparable to open liver surgery.

Graphical abstract
Robotic-assisted versus laparoscopic bowel anastomoses: randomized crossover in vivo experimental study
Authors: Haney Caelán Max , Kowalewski Karl-Friedrich , Schmidt Mona Wanda , Lang Franziska , Bintintan Vasile , Fan Carolyn , Wehrtmann Fabian , Studier-Fischer Alexander , Felinska Eleni Amelia , Müller-Stich Beat Peter , Nickel Felix 
Published: April 2023

Abstract
Background
Initial learning curves are potentially shorter in robotic-assisted surgery (RAS) than in conventional laparoscopic surgery (LS). There is little evidence to support this claim. Furthermore, there is limited evidence how skills from LS transfer to RAS.

Methods
A randomized controlled, assessor blinded crossover study to compare how RAS naïve surgeons (n = 40) performed linear-stapled side-to-side bowel anastomoses in an in vivo porcine model with LS and RAS. Technique was rated using the validated anastomosis objective structured assessment of skills (A-OSATS) score and the conventional OSATS score. Skill transfer from LS to RAS was measured by comparing the RAS performance of LS novices and LS experienced surgeons. Mental and physical workload was measured with the NASA-task load index (NASA-Tlx) and the Borg-scale.

Outcomes
In the overall cohort, there were no differences between RAS and LS for surgical performance (A-OSATS, time, OSATS). Surgeons that were naïve in both LS and RAS had significantly higher A-OSATS scores in RAS (Mean (Standard deviation (SD)): LS: 48.0 ± 12.1; RAS: 52.0 ± 7.5); p = 0.044) mainly deriving from better bowel positioning (LS: 8.7 ± 1.4; RAS: 9.3 ± 1.0; p = 0.045) and closure of enterotomy (LS: 12.8 ± 5.5; RAS: 15.6 ± 4.7; p = 0.010). There was no statistically significant difference in how LS novices and LS experienced surgeons performed in RAS [Mean (SD): novices: 48.9 ± 9.0; experienced surgeons: 55.9 ± 11.0; p = 0.540]. Mental and physical demand was significantly higher after LS.

Conclusion
The initial performance was improved for RAS versus LS for linear stapled bowel anastomosis, whereas workload was higher for LS. There was limited transfer of skills from LS to RAS.