bluuebunny/crossref_metadata_2025_split huggingface dataset:
P668 Does biotin deficiency play a role in the pathogenesis of Inflammatory Bowel Disease? Preliminary results of a cross-sectional study
Authors: Erbach J , Arnold A , Bonn F , Stein J M , Schröder O , Aksan A 
Published: May 2021

Abstract

Background
Biotin, a water-soluble B-vitamin, has been shown to have anti-inflammatory properties. A biotin-deficient diet was recently shown to induce a colitis-like phenotype in mice, alleviated by biotin substitution. Mice with DSS colitis showed biotin deficiency and significantly reduced levels of SDMT, a protein involved in biotin absorption. Oral biotin substitution reversed DSS colitis and induced remission by inhibiting NF-κB, a transcription factor that hinders inflammatory cytokine expression and plays a role in intestinal barrier integrity and IBD. We investigated for the first time a possible clinical role of biotin status in IBD.

Methods
In a comparative, cross-sectional study, serum samples of IBD patients were compared with samples of 80 healthy blood donors (40f;18-65y). CBC, albumin and hsCRP were determined by standard tests and samples assessed for presence/absence of inflammation (serum hsCRP, cutoff &lt;5mg/L). Since its known that serum biotin levels does not accurately reflect biotin status, serum 3-hydroxyisovaleryl carnitine (3HIAc) levels were determined by LC-MS/MS.

Results
138 IBD patients (67f;72 CD/66 UC;42.5±14.3y) were enrolled. Of these, 83/138 had inflammation (39f;43CD/40UC;42.5±14.6y) and 55/138 no inflammation (28f;29CD/26UC;42.5±13.9y). In IBD patients, mean serum 3HIAc levels were significantly higher vs. controls but similar with vs. without inflammation (Table 1). The reference serum 3HIAc level was calculated as 11.0–27.3 nmol/L from controls; biotin deficiency was defined as &gt;27.3 nmol/L 3HIAc (90thPC), since no validated cut-off exists. Biotin deficiency in IBD patients was significantly greater than in controls (Table 1).

Conclusion
High serum 3HIAc levels were associated with IBD. In line with preclinical studies, biotin deficiency was more pronounced in IBD patients than controls. No relation was found with inflammatory activity or disease type. Our findings suggest that biotin may have a bigger role than thought in IBD; whether as a cause or effect in IBD pathogenesis warrants investigation. Routine assessment and correction of biotin status may ameliorate IBD and help maintain intestinal integrity.
Table 1: 3-hydroxyisovaleryl carnitine levels and biotin deficiency
Classification performance of clinical risk scoring in suspected acute coronary syndrome beyond a rule-out troponin profile
Authors: Khan Ehsan , Lambrakis Kristina , Blyth Andrew , Seshadri Anil , Edmonds Michael J R , Briffa Tom , Cullen Louise A , Quinn Stephen , Horsfall Matthew , Morton Erin , French John K , Papendick Cynthia , Nelson Adam J , Chew Derek P 
Published: May 2021

Abstract

Aims
High-sensitivity cardiac troponin strategies can provide risk stratification in patients with suspected acute coronary syndrome (ACS) in the emergency department (ED). This study evaluated whether clinical risk scoring improves the classification performance of a rule-out profile in suspected ACS.

Methods and results
Patients presenting to ED with suspected ACS as part of the RAPID-TnT trial randomized to the intervention arm were included. Results ≥5 ng/L were available for all participants in this analysis. We evaluated the Thrombolysis In Myocardial Infarction (TIMI) risk score, History ECG Age Risk factors Troponin (HEART) score, and Emergency Department Assessment of Chest pain Score (EDACS) in addition to a rule-out profile based on the 0/1-h high-sensitivity cardiac troponin T protocol (&lt;5 ng/L or ≤12 ng/L and a change of &lt;3 ng/L at 1-h) using test performance parameters focusing on low-risk groups to identify the primary endpoint (TIMI ≤ 1, HEART ≤ 3, EDACS &lt; 16). Primary endpoint was a composite of type 1/2 myocardial infarction (MI) at index presentation and all-cause mortality or type 1/2 MI at 30 days. A total of 3378 participants were enrolled between August 2015 and April 2019 of which 108 were ineligible/withdrew consent (intervention arm: n = 1638). Sensitivity, specificity, negative predictive value (NPV), and area under the curve (AUC) of the rule-out profile was 94.4%, 76.8%, 99.6%, and 0.86, respectively with 72.9% identified as ‘low-risk’. Adding the clinical risk scores did not improve the sensitivity, NPV, or AUC with significantly lower specificity and ‘low-risk’ classified participants.

Conclusions
Addition of clinical risk scores to rule-out profile did not demonstrate improved classification performance for identifying the composite of type 1/2 MI at index presentation and all-cause mortality or type 1/2 MI at 30 days.

Clinical trials registration
URL: https://www.anzctr.org.au. Reg. No. ACTRN12615001379505.
Prognostic impact of non-culprit chronic total occlusion over time in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention
Authors: Milasinovic Dejan , Mladenovic Djordje , Zaharijev Stefan , Mehmedbegovic Zlatko , Marinkovic Jelena , Jelic Dario , Zobenica Vladimir , Radomirovic Marija , Dedovic Vladimir , Pavlovic Andrija , Dobric Milan , Stojkovic Sinisa , Asanin Milika , Vukcevic Vladan , Stankovic Goran 
Published: May 2021

Abstract

Aims
Previous studies indicated that a chronic total occlusion (CTO) in a non-infarct-related artery is linked to higher mortality mainly in the acute setting in patients with ST-elevation myocardial infarction (STEMI). Our aim was to assess the temporal distribution of mortality risk associated with non-culprit CTO over years after STEMI.

Methods and results
The study included 8679 STEMI patients treated with primary percutaneous coronary intervention (PCI). Kaplan–Meier cumulative mortality curves for non-culprit CTO vs. no CTO were compared with log-rank test, with landmarks set at 30 days and 1 year. Adjusted Cox regression models were constructed to assess the impact of non-culprit CTO on mortality over different time intervals. Tests for interaction were pre-specified between non-culprit CTO and acute heart failure and left ventricular ejection fraction. The primary outcome variable was all-cause mortality, and the median follow-up was 5 years. Non-culprit CTO was present in 11.6% of patients (n = 1010). Presence of a CTO was associated with increased early [30-day adjusted hazard ratio (HR) 1.91, 95% confidence interval (CI) 1.54–2.36; P &lt; 0.001] and late mortality (5-year adjusted HR 1.66, 95% CI 1.42–1.95; P &lt; 0.001). Landmark analyses revealed an annual two-fold increase in mortality in patients with vs. without a CTO after the first year of follow-up. The observed pattern of mortality increase over time was independent of acute or chronic LV impairment.

Conclusions
Non-culprit CTO is independently associated with mortality over 5 years after primary PCI for STEMI, with a constant annual two-fold increase in the risk of death beyond the first year of follow-up.
Naive 𝔸1-Homotopies on Ruled Surfaces
Authors: Balwe Chetan , Sawant Anand 
Published: May 2021

Abstract
We explicitly describe the $\mathbb{A}^1$-chain homotopy classes of morphisms from a smooth henselian local scheme into a smooth projective surface, which is birationally ruled over a curve of genus $&gt; 0$. We consequently determine the sheaf of naive $\mathbb{A}^1$-connected components of such a surface and show that it does not agree with the sheaf of its genuine $\mathbb{A}^1$-connected components when the surface is not a minimal model. However, the sections of the sheaves of both naive and genuine $\mathbb{A}^1$-connected components over schemes of dimension $\leq 1$ agree. As a consequence, we show that the Morel–Voevodsky singular construction on a smooth projective surface, which is birationally ruled over a curve of genus $&gt; 0$, is not $\mathbb{A}^1$-local if the surface is not a minimal model.
Energy content of intact and heat-treated dry extruded-expelled soybean meal fed to growing pigs
Authors: Koo Bonjin , Adeshakin Olumide , Nyachoti Charles Martin 
Published: May 2021

Abstract
An experiment was performed to evaluate the energy content of extruded-expelled soybean meal (EESBM) and the effects of heat treatment on energy utilization in growing pigs. Eighteen growing barrows (18.03 ± 0.61 kg initial body weight) were individually housed in metabolism crates and randomly allotted to one of three dietary treatments (six replicates per treatment). The three experimental diets were the following: a corn-soybean meal-based basal diet and two test diets with simple substitution of a basal diet with intact EESBM or heat-treated EESBM (heat-EESBM) at a 7:3 ratio. Intact EESBM was autoclaved at 121 °C for 60 min to make heat-treated EESBM. Pigs were fed the experimental diets for 16 d, including 10 d for adaptation and 6 d for total collection of feces and urine. Pigs were then moved into indirect calorimetry chambers to determine 24-h heat production and 12-h fasting heat production. The energy content of EESBM was calculated using the difference method. Data were analyzed using the Mixed procedure of SAS with the individual pig as the experimental unit. Pigs fed heat-EESBM diets showed lower (P &lt; 0.05) apparent total tract digestibility of dry matter (DM), gross energy, and nitrogen than those fed intact EESBM. A trend (P ≤ 0.10) was observed for greater heat increments in pigs fed intact EESBM than those fed heat-EESBM. This resulted in intact EESBM having greater (P &lt; 0.05) digestible energy (DE) and metabolizable energy (ME) contents than heat-EESBM. However, no difference was observed in net energy (NE) contents between intact EESBM and heat-EESBM, showing a tendency (P ≤ 0.10) toward an increase in NE/ME efficiency in heat-EESBM, but comparable NE contents between intact and heat-EESBM. In conclusion, respective values of DE, ME, and NE are 4,591 kcal/kg, 4,099 kcal/kg, and 3,189 kcal/kg in intact EESBM on a DM basis. It is recommended to use NE values of feedstuffs that are exposed to heat for accurate diet formulation.
Assessment of Ovarian Function in Phase III (Neo)Adjuvant Breast Cancer Clinical Trials: A Systematic Evaluation
Authors: Cui Wanyuan , Francis Prudence A , Loi Sherene , Hickey Martha , Stern Catharyn , Na Lumine , Partridge Ann H , Loibl Sibylle , Anderson Richard A , Hutt Karla J , Keogh Louise A , Phillips Kelly-Anne 
Published: May 2021

AbstractBackgroundLoss of ovarian function is a recognized adverse effect of chemotherapy for breast cancer and of great importance to patients. Little is known about the ovarian toxicity of newer cancer treatments. This study examined whether breast cancer clinical trials include assessment of the impact of trial interventions on ovarian function.MethodsEligible trials were phase III (neo)adjuvant trials of pharmacologic treatments for breast cancer, recruiting between June 2008 and October 2019, which included premenopausal women. MEDLINE, EMBASE, Clinicaltrials.gov, and EudraCT were searched. Data were extracted from trial publications, protocols, databases, and a survey sent to all trial chairs. Tests of statistical significance were 2-sided.ResultsOf 2354 records identified, 141 trials were eligible. Investigational treatments included chemotherapy (36.9%), HER2 targeted (24.8%), endocrine (12.8%), immunotherapy (7.8%), cyclin-dependent kinase 4/6 inhibitors (5.0%), and poly-ADP-ribose polymerase inhibitors (2.8%). Ovarian function was a prespecified endpoint in 13 (9.2%) trials. Forty-five (31.9%) trials collected ovarian function data, but only 33 (23.4%) collected posttrial-intervention data. Common postintervention data collected included menstruation (15.6%), pregnancy (13.5%), estradiol (9.9%), and follicle-stimulating hormone levels (8.5%). Only 4 (2.8%) trials collected postintervention anti-müllerian hormone levels, and 3 (2.1%) trials collected antral follicle count. Of 22 trials investigating immunotherapy, cyclin-dependent kinase 4/6 inhibitors, or poly-ADP-ribose polymerase inhibitors, none specified ovarian function as an endpoint, but 4 (18.2%) collected postintervention ovarian function data.ConclusionsThe impact of pharmacologic interventions on ovarian function is infrequently assessed in phase III breast cancer (neo)adjuvant trials that include premenopausal women. Trialists should consider inclusion of ovarian function endpoints when designing clinical trials, given its importance for informed decision making.
Chemical post-processing of magneto-hydrodynamical simulations of star-forming regions: robustness and pitfalls
Authors: Ferrada-Chamorro Simón , Lupi Alessandro , Bovino Stefano 
Published: May 2021

ABSTRACT
A common approach to model complex chemistry in numerical simulations is via post-processing of existing magneto-hydrodynamic simulations, relying on computing the evolution of chemistry over the dynamic history of a subset of particles from within the raw simulation. Here, we validate such a technique, assessing its ability to recover the abundances of chemical species, using the chemistry package krome. We also assess, for the first time, the importance of the main free input parameters, by means of a direct comparison with a self-consistent state-of-the-art simulation in which chemistry was directly coupled to hydrodynamics. We have found that the post-processing is highly reliable, with an accuracy at the per cent level, even when the most relaxed input parameters are employed. In particular, our results show that the number of particles used does not affect significantly the average properties, although it suppresses the appearance of possibly important spatial features. On the other hand, the choice of the integration time-step plays a crucial role. Longer integration time-steps can produce large errors, as the post-processing solution will be forced towards chemical equilibrium, a condition that does not always necessarily apply. When the interpolation-based reconstruction of chemical properties is performed, the errors further increase up to a factor of ∼2. Concluding, our results suggest that this technique is extremely useful when exploring the relative quantitative effect of different chemical parameters and/or networks, without the need of re-running simulations multiple times, but some care should be taken in the choice of particles sub-sample and integration time-step.
About the modelling of the SED for the inner boundary of protoplanetary discs at the lower stellar mass regime
Authors: Morales-Gutiérrez Sebastián , Nagel Erick , Barragan Oscar 
Published: May 2021

ABSTRACT
In order to improve the physical interpretation about innermost dusty regions in protoplanetary discs around brown dwarf (BD), and even very low mass star (VLMS), we present a grid of models taking into account two different sets: (i) The set called standard model, that simulates an axisymmetric dusty disc with an inner curved wall. (ii) The perturbed one called non-standard where the axisymmetry of the inner edge has been broken. We have achieved a fitting for the disc structure able to explain the spectral energy distribution (SED). As the main condition, we assume that the changes of the inner wall geometry in the tongue-like shape depend on the Rayleigh–Taylor instability (R-TIns) generated in the inner disc edge. For each object, we parametrize the shape of the inner wall to find a time-dependent model that enables us to explain the photometric near-Infrared variability and connect the changes on the inner disc structure with the amplitude of such variability. We re-analysed photometric measurements from near to mid-infrared wavelengths of a sample of 6 BDs and one VLMS in different cloud associations which were previously studied by other authors. We also show that the flux change calculated between the non-standard and the standard configurations models the observed variability in LRLL 1679. The magnitude changes due to these fluctuations slightly depend on the wavelength and they can present differences of up to 0.9 mag. We suggest that if the R-TIns persist enough time, the features in the protoplanetary inner disc, e.g. inner holes or gaps evolve.
Magnetic dynamos in white dwarfs – I. Explaining the dearth of bright intermediate polars in globular clusters
Authors: Belloni Diogo , Schreiber Matthias R , Salaris Maurizio , Maccarone Thomas J , Zorotovic Monica 
Published: May 2021

ABSTRACT
Recently, Bahramian et al. investigated a large sample of globular clusters (GCs) and found that bright intermediate polars (IPs) are a factor of 10 less frequent in GCs than in the Galactic field. We theoretically investigate here this discrepancy based on GC numerical simulations. We found that, due to disruptive dynamical interaction, there is on average a reduction of only half of bright IP progenitors, which is clearly not enough to explain the observed deficiency. However, if the rotation- and crystallization-driven dynamo scenario recently proposed by Schreiber et al. is incorporated in the simulations, the observed rareness of bright IPs in GCs can be reproduced. This is because bright cataclysmic variables (CVs) in GCs are typically very old systems (≳10 Gyr), with white dwarfs that almost fully crystallized before mass transfer started, which does not allow strong magnetic fields to be generated. The observed mass density of bright IPs in GCs can be recovered if around one-third of the bright CVs dynamically formed through mergers have magnetic field strengths similar to those of IPs. We conclude that the observed paucity of bright IPs in GCs is a natural consequence of the newly proposed rotation- and crystallization-driven dynamo scenario.
The hen’s egg test for micronucleus induction (HET-MN): validation data set
Authors: Reisinger Kerstin , Fieblinger Dagmar , Heppenheimer Andreas , Kreutz Jürgen , Liebsch Manfred , Luch Andreas , Maul Katrin , Poth Albrecht , Strauch Pamela , Dony Eva , Schulz Markus , Wolf Thorsten , Pirow Ralph 
Published: May 2021

Abstract
The classical in vitro genotoxicity test battery is known to be sensitive for indicating genotoxicity. However, a high rate of ‘misleading positives’ was reported when three assays were combined as required by several legislations. Despite the recent optimisations of the standard in vitro tests, two gaps could hardly be addressed with assays based on 2D monolayer cell cultures: the route of exposure and a relevant intrinsic metabolic capacity to transform pro-mutagens into reactive metabolites. Following these considerations, fertilised chicken eggs have been introduced into genotoxicity testing and were combined with a classical read-out parameter, the micronucleus frequency in circulating erythrocytes, to develop the hen’s egg test for micronucleus induction (HET-MN). As a major advantage, the test mirrors the systemic availability of compounds after oral exposure by reflecting certain steps of Absorption, Distribution, Metabolism, Excretion (ADME) without being considered as an animal experiment. The assay is supposed to add to a toolbox of assays to follow up on positive findings from initial testing with classical in vitro assays. We here report on a validation exercise, in which &gt;30 chemicals were tested double-blinded in three laboratories. The specificity and sensitivity of the HET-MN were calculated to be 98 and 84%, respectively, corresponding to an overall accuracy of 91%. A detailed protocol, which includes a picture atlas detailing the cell and micronuclei analysis, is published in parallel (Maul et al. Validation of the hen’s egg test for micronucleus induction (HET-MN): detailed protocol including scoring atlas, historical control data and statistical analysis).
Prolonged Trachyte Storage and Unusual Remobilization at Piton de la Fournaise, La Réunion Island, Indian Ocean: Li, O, Sr, Nd, Pb and Th Isotope Study
Authors: Vlastelic I , Bachèlery P , Sigmarsson O , Koga K T , Rose-Koga E R , Bindeman I , Gannoun A , Devidal J -L , Falco G , Staudacher T 
Published: May 2021

Abstract
La Réunion Island includes two major volcanic systems. About 0·5 Myr ago, Piton des Neiges volcano declined, while Piton de la Fournaise volcano grew on its flank. Since then the Piton de la Fournaise shield volcano has produced homogeneous lavas with chemical compositions transitional between alkali and tholeiitic basalts. In April 2007, the volcano emitted a very small volume of trachytic pumice during its largest historical eruption. We conducted a comprehensive petrological and geochemical study of the pumice to understand the occurrence of such silicic melt in the feeding system of this highly active basaltic volcano. Isotopes of Sr, Nd, Pb and O, together with trace elements, indicate that the trachyte is genetically related to the La Réunion mantle plume and derives from crystallization of a typical basalt. The trachyte chemistry records a long and complex history of differentiation and outgassing. The extensive depletion of moderately volatile elements (F, Cl, B, Cs, Cu, Li) and less volatile uranium is consistent with exsolution of dense fluids at depths of several kilometres. Lithium isotopes point to closed-system degassing during the very late stages of crystallization. U-series isotopes and radiogenic 208Pb*/206Pb* constrain the age of U loss to between 0·4 and 2·1 Ma. This age is as old as or older than the Piton de la Fournaise shield edifice. The 2007 trachyte could thus be a liquid remnant of an extinct volcano, such as Piton des Neiges or Les Alizés (Piton de la Fournaise proto-volcano). It could also result from partial melting of an old syenite intrusion or remobilization of interstitial melts not fully solidified. Thermal modelling indicates that the sustained heat flux from hot basaltic magmas rising from the mantle can maintain temperatures above 800 °C in the central feeding system, and prevent total solidification of magmas trapped in this hot core.
Phytophthora sojae apoplastic effector AEP1 mediates sugar uptake by mutarotation of extracellular aldose and is recognized as a MAMP
Authors: Xu Yuanpeng , Zhang Yunhuan , Zhu Jinyin , Sun Yujing , Guo Baodian , Liu Fan , Huang Jie , Wang Haonan , Dong Suomeng , Wang Yan , Wang Yuanchao 
Published: May 2021

Abstract
Diseases caused by Phytophthora pathogens devastate many crops worldwide. During infection, Phytophthora pathogens secrete effectors, which are central molecules for understanding the complex plant–Phytophthora interactions. In this study, we profiled the effector repertoire secreted by Phytophthora sojae into the soybean (Glycine max) apoplast during infection using liquid chromatography–mass spectrometry. A secreted aldose 1-epimerase (AEP1) was shown to induce cell death in Nicotiana benthamiana, as did the other two AEP1s from different Phytophthora species. AEP1 could also trigger immune responses in N. benthamiana, other Solanaceae plants, and Arabidopsis (Arabidopsis thaliana). A glucose dehydrogenase assay revealed AEP1 encodes an active AEP1. The enzyme activity of AEP1 is dispensable for AEP1-triggered cell death and immune responses, while AEP-triggered immune signaling in N. benthamiana requires the central immune regulator BRASSINOSTEROID INSENSITIVE 1-associated receptor kinase 1. In addition, AEP1 acts as a virulence factor that mediates P. sojae extracellular sugar uptake by mutarotation of extracellular aldose from the α-anomer to the β-anomer. Taken together, these results revealed the function of a microbial apoplastic effector, highlighting the importance of extracellular sugar uptake for Phytophthora infection. To counteract, the key effector for sugar conversion can be recognized by the plant membrane receptor complex to activate plant immunity.