bluuebunny/crossref_metadata_2025 huggingface dataset:
Crystal structure ofAspergillus fumigatusAroH, an aromatic amino acid aminotransferase
Authors: Spizzichino Sharon , Pampalone Gioena , Dindo Mirco , Bruno Agostino , Romani Luigina , Cutruzzolà Francesca , Zelante Teresa , Pieroni Marco , Cellini Barbara , Giardina Giorgio
Published: September 2021

Aspergillus fumigatusis a saprophytic ubiquitous fungus whose spores can trigger reactions such as allergic bronchopulmonary aspergillosis or the fatal invasive pulmonary aspergillosis. To survive in the lungs, the fungus must adapt to a hypoxic and nutritionally restrictive environment, exploiting the limited availability of aromatic amino acids (AAAs) in the best possible way, as mammals do not synthesize them. A key enzyme for AAAs catabolism inA. fumigatusis AroH, a pyridoxal 5′‐phosphate‐dependent aromatic aminotransferase. AroH was recently shown to display a broad substrate specificity, accepting L‐kynurenine and α‐aminoadipate as amino donors besides AAAs. Given its pivotal role in the adaptability of the fungus to nutrient conditions, AroH represents a potential target for the development of innovative therapies againstA. fumigatus‐related diseases. We have solved the crystal structure ofAf‐AroH at 2.4 Å resolution and gained new insight into the dynamics of the enzyme's active site, which appears to be crucial for the design of inhibitors. The conformational plasticity of the active site pocket is probably linked to the wide substrate specificity of AroH.
Free‐Standing ZnSe‐Based Microdisk Resonators: Influence of Edge Roughness on the Optical Quality and Reducing Degradation with Supported Geometry
Authors: Seemann Wilken , Kothe Alexander , Tessarek Christian , Schmidt Gesa , Qiao Siqi , von den Driesch Nils , Wiersig Jan , Pawlis Alexander , Callsen Gordon , Gutowski Jürgen
Published: September 2021

Microdisk resonators offer a small mode volume and are therefore commonly investigated for their suitability as platforms for low‐threshold lasing. In addition, the inherent strong confinement of light not only renders such structures promising candidates for efficient single‐photon sources, but even motivates a key role for integrated photonic circuitry. Herein, ZnSe‐based microdisks with ZnCdSe quantum well (QW) structures in ZnMgSe barriers are analyzed. In microphotoluminescence (μPL), stimulated emission into whispering gallery modes (WGMs) is demonstrated. Scanning electron microscopy (SEM) is used to determine the edge roughness of a multitude of resonators using a fitting routine, revealing a correlation between the edge roughness and overall optical quality of the resonators. These results are confirmed by calculations based on the boundary element method using the measured roughness as input parameter. To avoid the common problem of degradation under excitation in ZnSe‐based structures, an alternative fabrication technique is introduced, which is new to this material system. It yields supported disks in direct contact with an Al2O3 layer on the substrate, which enhances the mechanical and thermal stability of the resonator. The occurrence of WGMs in supported ZnSe:Cl resonators is demonstrated in μPL experiments and confirmed by theoretical calculations.
A two‐stage drop‐the‐losers design for time‐to‐event outcome using a historical control arm
Authors: Abbas Rachid , Wason James , Michiels Stefan , Le Teuff Gwénaël
Published: September 2021

Phase II immuno‐oncology clinical trials screen for efficacy an increasing number of treatments. In rare cancers, using historical control data is a pragmatic approach for speeding up clinical trials. The drop‐the‐losers design allows dropping off ineffective arms at interim analyses. We extended the original drop‐the‐losers design for a time‐to‐event outcome using a historical control through the one‐sample log‐rank statistic. Simulated trials featured three arms at the first stage, one at the second stage, nine scenarios, eight sample sizes with 5%‐ and 10%‐ nominal family‐wise error rate (FWER). A numerical algorithm is provided to solve power calculations at the design stage. Our design was compared with a group of three independent single‐arm trials (fixed design) with and without correction for multiplicity. Our design allowed strict control of the FWER at nominal levels while the misspecification of survival distribution and fixed design inflated the FWER up to three times the nominal level. The empirical power of our design increased with the sample size, the treatment effect and the number of effective treatments and dropped when more patients were recruited at the second stage. The fixed design with correction showed comparable power, while our design advantageously included more patients to the most promising arm. Recommendations for future applications are given. By taking advantage of the use of historical control data and a time‐to‐event outcome, the drop‐the‐losers design is a promising tool to meet the challenge of improving phase II clinical trials in immuno‐oncology.
The effect of garlic (Allium sativum) supplementation on the lipid parameters and blood pressure levels in women with polycystic ovary syndrome: A randomized controlled trial
Authors: Zadhoush Roya , Alavi‐Naeini Amirmansour , Feizi Awat , Naghshineh Elham , Ghazvini Mohammad Reza
Published: September 2021

Polycystic ovary syndrome (PCOS) is the most prevalent female endocrine‐related disorder in reproductive ages. The aim of the study was to investigate the effect of garlic on the lipid parameters and blood pressure levels in women with PCOS. The present study was a randomized, double‐blinded control trial, conducted on 80 PCOS patients. Participants were taught to intake either a total 800 mg/day garlic supplement or an identical placebo (starch) after lunch for 8 weeks. Physical activity, diet intake, anthropometric measures, and blood pressure were evaluated at baseline and end of the study. The blood sample was also taken to assess the change in outcomes of interest at the pre‐ and post‐intervention. Garlic supplementation significantly reduced serum total cholesterol (change mean difference: −8.05, 95% CI: −15.47, −0.62) and LDL‐C (change mean difference: −7.67, 95%CI: −14.64, −0.70) levels in comparison to the control group. In addition, a trend to a significant decrease was found in serum triglyceride levels and Systolic blood pressure; however, no significant difference was observed between two groups in HDL‐C and diastolic blood pressure levels. The present study suggested that garlic supplementation might be effective on lipid markers improvement. Further studies are needed to confirm our findings.
Topological indices and QSPR modeling of some novel drugs used in the cancer treatment
Authors: Havare Özge Çolakoğlu
Published: September 2021

Cancer is a deadly disease. There is no drug yet for the treatment of some types of cancer. New drug trials are being conducted to treat this disease. One of them is HDAC‐based multi‐target drugs. Topological indices (TIs) are the numerical descriptors of a molecular structure obtained by the molecular graph. TIs can be used in the structure–property relationship (QSPR) and structure–activity relationship studies to provide information about the physicochemical properties and biological properties of molecules. In this paper, vorinostat, tucidinostat, triciferol, and CUDC‐101 and CUDC‐907, which are seen as an important light in cancer treatment, are studied. M‐polynomials based on degree and NM‐polynomials based on the sum of degrees of neighboring vertices for chemical graphs of these drugs are calculated. By using these polynomials, many TIs that depend on the degree and the sum of neighboring degrees are obtained. Moreover, The QSPR models are designed using these TIs to estimate some physicochemical properties of these drugs. The QSPR studies are obtained using the curvilinear regression method.
O‐Alkylation Redirected Condensation of 5‐Hydroxy‐1,2‐oxazine‐6‐ones with Primary Amines for Synthesis of 5‐Hydroxyiminopyridine‐2,6(1H,3H)‐diones
Authors: Nizovtsev Alexey V. , Sokolov Anatolii I. , Smirnov Alexander Yu. , Mikhaylov Andrey A. , Myasnyanko Ivan N. , Belozerova Olga A. , Baleeva Nadezhda S. , Usmanova Liliia , Baranov Mikhail S.
Published: September 2021

Herein we report a short and general protocol for synthesis of potentially biologically active pyridine‐2,6‐diones. The approach is based on the redirection of the condensation of the intermediates of Dornow reaction – 5‐hydroxy‐1,2‐oxazine‐6‐ones with primary amines by their prior O‐alkylation. Such manipulation blocks their transformation into isoxazoles and allows one to obtain a library of 30+ previously undescribed 5‐alkoxy‐3‐(hydroxyimino)‐4‐aryl‐pyridine‐2,6(1H,3H)‐dione derivatives in 37–89 % yields.
Boosting Hydrogen Evolution Reaction via Electronic Coupling of Cerium Phosphate with Molybdenum Phosphide Nanobelts
Authors: Zhang Luyao , Hu Minghao , Li Huan , Cao Bo , Jing Peng , Liu Baocang , Gao Rui , Zhang Jun , Liu Bin
Published: September 2021

Molybdenum phosphide (MoP) is regarded as one of the most promising alternatives to noble‐metal based electrocatalysts for efficient hydrogen evolution reaction (HER) due to its similar d‐band electronic structure to noble metals and tunable features associated with phase and composition. However, it still remains a great challenge to construct MoP electrocatalysts with abundant active sites that possess ideal H binding strength to promote catalytic performance. In this work, it is found that by anchoring a rare earth compound, cerium phosphate (CePO4) on MoP (CePO4/MoP), the stabilized Ce3+ in CePO4 can significantly boost the formation of oxygen vacancies in ceria (CeO2) in situ formed on CePO4 surface during HER, which effectively regulates the d‐band electronic density‐of‐states of MoP, increases the numbers of active sites, and promotes the vectorial electron transfer, therefore greatly enhancing the HER performance of MoP. The optimized CePO4/MoP/carbon cloth (CC) electrocatalyst exhibits a significantly improved HER performance with an overpotential of 48 mV at 10 mA cm−2 and a Tafel slope of 38 mV dec−1, about two times better than the HER performance of MoP catalyst without CePO4 (with an overpotential >80 mV dec−1 at 10 mA cm−2), very close to commercial Pt/C catalyst.
Simultaneously Engineering the Coordination Environment and Pore Architecture of Metal–Organic Framework‐Derived Single‐Atomic Iron Catalysts for Ultraefficient Oxygen Reduction
Authors: Liu Feng , Shi Lei , Song Shaofeng , Ge Kai , Zhang Xiaopeng , Guo Yingchun , Liu Dong
Published: September 2021

Designing highly efficient and durable electrocatalysts that accelerate sluggish oxygen reduction reaction kinetics for fuel cells and metal–air batteries are highly desirable but challenging. Herein, a facile yet robust strategy is reported to rationally design single iron active centers synergized with local S atoms in metal–organic frameworks derived from hierarchically porous carbon nanorods (Fe/N,S‐HC). The cooperative trithiocyanuric acid‐based coating not only introduces S atoms that regulate the coordination environment of the active centers, but also facilitates the formation of a hierarchically porous structure. Benefiting from electronic modulation and architectural functionality, Fe/N,S‐HC catalyst shows markedly enhanced ORR performance with a half‐wave potential (E1/2) of 0.912 V and satisfactory long‐term durability in alkaline medium, outperforming those of commercial Pt/C. Impressively, Fe/N,S‐HC‐based Zn–air battery also presents outstanding battery performance and long‐term stability. Both electrochemical experimental and density functional theoretical (DFT) calculated results suggest that the FeN4 sites tailored with local S atoms are favorable for the adsorption/desorption of oxygen intermediate, resulting in lower activation energy barrier and ultraefficient oxygen reduction catalytic activity. This work provides an atomic‐level combined with porous morphological‐level insights into oxygen reduction catalytic property, promoting rational design and development of novel highly efficient single‐atom catalysts for the renewable energy applications.
The effects of unemployment insurance in late career: Evidence from Social Security offsets
Authors: Toohey Desmond
Published: September 2021

This paper studies the effects of unemployment insurance (UI) benefits for retirement‐age workers. It shows that UI benefits can raise reported search effort and labor force participation for this population. Estimated effects on subsequent employment are positive but small and statistically indistinguishable from zero. The results are contrasted with estimates showing negative effects of UI on reemployment for younger workers. The identifying variation is generated by the elimination of Social Security offsets: state‐level policies that reduce unemployment benefits for Social Security beneficiaries. The findings are consistent with a simple model of UI claiming with participation and work search requirements.
Shell Measurements and Mold Thermal Mapping Approach to Characterize Steel Shell Formation in Peritectic Grade Steels
Authors: Balogun Damilola , Roman Muhammad , Gerald Rex E. , Huang Jie , Bartlett Laura , O'Malley Ronald
Published: September 2021

Herein, the prospects of detecting peritectic behavior in carbon steels (Fe–C) using solidified shell thickness measurements and real‐time mold thermal maps are investigated. Irregular steel shell thickness and localized shell thinning are negative conditions associated with the peritectic transformation in many steel grades. Detailed three dimensional (3D) thickness maps are generated to directly contrast peritectic from nonperitectic solidification features using a laboratory dip test. Characterization of the steel shell also includes measurement of 3D shell surface deviations from a nominally flat surface. The unevenness parameter, which is calculated using the coefficient of variation in shell thickness as a function of the carbon content in the steel, clearly peaks around 0.14%C. A distributed fiber‐optic sensor, embedded 1 mm from the working face of a 100 × 55 × 12 mm3 thick copper chill block, has been used to obtain real‐time mold thermal maps of the solidification event during immersion of the block into molten steel. A programmable drive is used to control the motion of the chill block during immersion into a steel bath to minimize variability in immersion speed, position, and time. The thermal mapping measurements are well correlated with the shell profile measurements.
Leu27IGF‐II‐induced hypertrophy in H9c2 cardiomyoblasts is ameliorated by saffron by regulation of calcineurin/NFAT and CaMKIIδ signaling
Authors: Lin Chin‐Yi , Shibu Marthandam Asokan , Wen Renee , Day Cecilia Hsuan , Chen Ray‐Jade , Kuo Chia‐Hua , Ho Tsung‐Jung , Viswanadha Vijaya Padma , Kuo Wei‐Wen , Huang Chih‐Yang
Published: September 2021

The insulin‐like growth factor II receptor (IGF‐IIR) induces myocardial hypertrophy under various pathological conditions like diabetes and hypertension via G protein receptors like Gαq or Gαs. Increased expression of the ligand IGF II and IGF‐IIR induces pathological hypertrophy through downstream signaling mediators such as calcineurin, nuclear factor of activated T cells 3 and calcium‐calmodulin (CaM)‐dependent kinase II (CaMKII)‐histone deacetylase 4 (HDAC4). The dried stigma of Crocus sativus L. (saffron) has a long repute as a traditional medicine against various disorders. In the present study, we have investigated whether C. sativus extract (CSE) canameliorate Leu27IGF‐II triggered hypertrophy and have elucidated the underlying mechanism of protection. Additionally, the effects of oleic acid (OA), an activator of calcineurin and CaMKII was investigated thereof. The results demonstrate that CSE can ameliorate Leu27IGF‐II‐induced hypertrophy seemingly through regulation of calcineurin‐NFAT3 and CaMKII‐HDAC4 signaling cascade.
Prenatally diagnosed pseudoaneurysm of mitral–aortic intervalvular fibrous area
Authors: Hogan W. J. , Punn R. , Dean P. , Strainic J. , Rychik J. , Williams R. V. , Moon‐Grady A. J. , Silverman N. H.
Published: September 2021

The mitral–aortic intervalvular fibrosa (MAIVF) is an avascular, fibrous structure that provides continuity between the anterior leaflet of the mitral valve and the aortic valve. Pseudoaneurysm of the MAIVF is rare and has been most commonly described in adults and, more rarely, in children following cardiac surgery or endocarditis. Few reports have been published on cases with congenital pseudoaneurysm of the MAIVF. Here, we describe five cases of congenital pseudoaneurysm of the MAIVF identified prenatally and an additional six cases diagnosed postnatally. This is an unusual finding of varying clinical significance, which can be isolated or associated with complex congenital heart disease but, importantly, can be identified and monitored in the fetus. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
Investigating the Role of Educational Robotics in Formal Mathematics Education: The Case of Geometry for 15-Year-Old Students
Authors: Brender Jérôme , El-Hamamsy Laila , Bruno Barbara , Chessel-Lazzarotto Frédérique , Zufferey Jessica Dehler , Mondada Francesco
Published: September 2021

Research has shown that Educational Robotics (ER) enhances student performance, interest, engagement and collaboration. However, until now, the adoption of robotics in formal education has remained relatively scarce. Among other causes, this is due to the difficulty of determining the alignment of educational robotic learning activities with the learning outcomes envisioned by the curriculum, as well as their integration with traditional, non-robotics learning activities that are well established in teachers’ practices. This work investigates the integration of ER into formal mathematics education, through a quasi-experimental study employing the Thymio robot and Scratch programming to teach geometry to two classes of 15-year-old students, for a total of 26 participants. Three research questions were addressed: (1) Should an ER-based theoretical lecture precede, succeed or replace a traditional theoretical lecture? (2) What is the students’ perception of and engagement in the ER-based lecture and exercises? (3) Do the findings differ according to students’ prior appreciation of mathematics? The results suggest that ER activities are as valid as traditional ones in helping students grasp the relevant theoretical concepts. Robotics activities seem particularly beneficial during exercise sessions: students freely chose to do exercises that included the robot, rated them as significantly more interesting and useful than their traditional counterparts, and expressed their interest in introducing ER in other mathematics lectures. Finally, results were generally consistent between the students that like and did not like mathematics, suggesting the use of robotics as a means to broaden the number of students engaged in the discipline.
Quantum simulation of gauge theory via orbifold lattice
Authors: Buser Alexander J. , Gharibyan Hrant , Hanada Masanori , Honda Masazumi , Liu Junyu
Published: September 2021

Abstract

We propose a new framework for simulating U(k) Yang-Mills theory on a universal quantum computer. This construction uses the orbifold lattice formulation proposed by Kaplan, Katz, and Unsal, who originally applied it to supersymmetric gauge theories. Our proposed approach yields a novel perspective on quantum simulation of quantum field theories, carrying certain advantages over the usual Kogut-Susskind formulation. We discuss the application of our constructions to computing static properties and real-time dynamics of Yang-Mills theories, from glueball measurements to AdS/CFT, making use of a variety of quantum information techniques including qubitization, quantum signal processing, Jordan-Lee-Preskill bounds, and shadow tomography. The generalizations to certain supersymmetric Yang-Mills theories appear to be straightforward, providing a path towards the quantum simulation of quantum gravity via holographic duality.
Torsional deformation of nonrelativistic string theory
Authors: Yan Ziqi
Published: September 2021

Abstract

Nonrelativistic string theory is a self-contained corner of string theory, with its string spectrum enjoying a Galilean-invariant dispersion relation. This theory is unitary and ultraviolet complete, and can be studied from first principles. In these notes, we focus on the bosonic closed string sector. In curved spacetime, nonrelativistic string theory is defined by a renormalizable quantum nonlinear sigma model in background fields, following certain symmetry principles that disallow any deformation towards relativistic string theory. We review previous proposals of such symmetry principles and propose a modified version that might be useful for supersymmetrizations. The appropriate target-space geometry determined by these local spacetime symmetries is string Newton-Cartan geometry. This geometry is equipped with a two-dimensional foliation structure that is restricted by torsional constraints. Breaking the symmetries that give rise to such torsional constraints in the target space will in general generate quantum corrections to a marginal deformation in the worldsheet quantum field theory. Such a deformation induces a renormalization group flow towards sigma models that describe relativistic strings.
Majorana fermion dark matter in minimally extended left-right symmetric model
Authors: Neves M. J. , Okada Nobuchika , Okada Satomi
Published: September 2021

Abstract

We present a minimal extension of the left-right symmetric model based on the gauge group SU(3)c× SU(2)L× SU(2)R× U(1)B−L× U(1)X, in which a vector-like fermion pair (ζL and ζR) charged under the U(1)B−L× U(1)X symmetry is introduced. Associated with the symmetry breaking of the gauge group SU(2)R× U(1)B−L× U(1)X down to the Standard Model (SM) hypercharge U(1)Y, Majorana masses for ζL,R are generated and the lightest mass eigenstate plays a role of the dark matter (DM) in our universe by its communication with the SM particles through a new neutral gauge boson “X”. We consider various phenomenological constraints of this DM scenario, such as the observed DM relic density, the LHC Run-2 constraints from the search for a narrow resonance, and the perturbativity of the gauge couplings below the Planck scale. Combining all constraints, we identify the allowed parameter region which turns out to be very narrow. A significant portion of the currently allowed parameter region will be tested by the High-Luminosity LHC experiments.
Characterisation of Ppy-lineage cells clarifies the functional heterogeneity of pancreatic beta cells in mice
Authors: Fukaishi Takahiro , Nakagawa Yuko , Fukunaka Ayako , Sato Takashi , Hara Akemi , Nakao Keiko , Saito Michiko , Kohno Kenji , Miyatsuka Takeshi , Tamaki Motoyuki , Matsuhisa Munehide , Matsuoka Taka-aki , Yamada Tetsuya , Watada Hirotaka , Fujitani Yoshio
Published: September 2021

Aims/hypothesis

Pancreatic polypeptide (PP) cells, which secrete PP (encoded by the Ppy gene), are a minor population of pancreatic endocrine cells. Although it has been reported that the loss of beta cell identity might be associated with beta-to-PP cell-fate conversion, at present, little is known regarding the characteristics of Ppy-lineage cells.

Methods

We used Ppy-Cre driver mice and a PP-specific monoclonal antibody to investigate the association between Ppy-lineage cells and beta cells. The molecular profiles of endocrine cells were investigated by single-cell transcriptome analysis and the glucose responsiveness of beta cells was assessed by Ca2+ imaging. Diabetic conditions were experimentally induced in mice by either streptozotocin or diphtheria toxin.

Results

Ppy-lineage cells were found to contribute to the four major types of endocrine cells, including beta cells. Ppy-lineage beta cells are a minor subpopulation, accounting for 12–15% of total beta cells, and are mostly (81.2%) localised at the islet periphery. Unbiased single-cell analysis with a Ppy-lineage tracer demonstrated that beta cells are composed of seven clusters, which are categorised into two groups (i.e. Ppy-lineage and non-Ppy-lineage beta cells). These subpopulations of beta cells demonstrated distinct characteristics regarding their functionality and gene expression profiles. Ppy-lineage beta cells had a reduced glucose-stimulated Ca2+ signalling response and were increased in number in experimental diabetes models.

Conclusions/interpretation

Our results indicate that an unexpected degree of beta cell heterogeneity is defined by Ppy gene activation, providing valuable insight into the homeostatic regulation of pancreatic islets and future therapeutic strategies against diabetes.

Data availability

The single-cell RNA sequence (scRNA-seq) analysis datasets generated in this study have been deposited in the Gene Expression Omnibus (GEO) under the accession number GSE166164 (www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE166164).

Graphical abstract
Rivaroxaban compared with low-dose aspirin in individuals with type 2 diabetes and high cardiovascular risk: a randomised trial to assess effects on endothelial function, platelet activation and vascular biomarkers
Authors: Pistrosch Frank , Matschke Jan B. , Schipp Dorothea , Schipp Bernhard , Henkel Elena , Weigmann Ingo , Sradnick Jan , Bornstein Stefan R. , Birkenfeld Andreas L. , Hanefeld Markolf
Published: September 2021

Aims/hypothesis

Individuals with type 2 diabetes mellitus and subclinical inflammation have stimulated coagulation, activated platelets and endothelial dysfunction. Recent studies with the direct factor Xa inhibitor rivaroxaban in combination with low-dose aspirin demonstrated a significant reduction of major cardiovascular events, especially in individuals with type 2 diabetes and proven cardiovascular disease. Therefore, we asked the question of whether treatment with rivaroxaban could influence endothelial function, arterial stiffness and platelet activation.

Methods

We conducted a multi-centre, prospective, randomised, open-label trial in 179 participants with type 2 diabetes (duration 2–20 years), subclinical inflammation (high-sensitivity C-reactive protein 2–10 mg/l) and at least two traits of the metabolic syndrome to compare the effects of the direct factor Xa inhibitor rivaroxaban (5 mg twice daily) vs aspirin (100 mg every day) on endothelial function (assessed by forearm occlusion plethysmography), skin blood flow (assessed by laser-Doppler fluxmetry), arterial stiffness (assessed by pulse wave velocity) and serum biomarkers of endothelial function and inflammation. Furthermore, we investigated phosphorylation of vasodilator-stimulated phosphoprotein (VASP) in platelets, the concentration of platelet-derived microparticles (PMPs) and the effects of isolated PMPs on HUVEC proliferation in vitro.

Results

Rivaroxaban treatment for 20 weeks (n = 89) resulted in a significant improvement of post-ischaemic forearm blood flow (3.6 ± 4.7 vs 1.0 ± 5.2 ml/100 ml, p = 0.004), a numerically increased skin blood flow and reduced soluble P-Selectin plasma level vs aspirin. We did not find significant differences of arterial stiffness or further biomarkers. Neither rivaroxaban nor aspirin influenced VASP phosphorylation of platelets. The number of PMPs increased significantly with both rivaroxaban (365.2 ± 372.1 vs 237.4 ± 157.1 μl−1, p = 0.005) and aspirin (266.0 ± 212.7 vs 201.7 ± 162.7 μl−1, p = 0.021). PMPs of rivaroxaban-treated participants stimulated HUVEC proliferation in vitro compared with aspirin. Rivaroxaban was associated with a higher number of bleeding events.

Conclusions/interpretation

Our findings indicate that the direct factor Xa inhibitor rivaroxaban improved endothelial function in participants with type 2 diabetes and subclinical inflammation but also increased the risk of bleeding.

Trial registration:

ClinicalTrials.gov NCT02164578.

Funding

The study was supported by a research grant from Bayer Vital AG, Germany.

Graphical abstract
Anatomical Comparative Study of the External Nasal Nerve in Caucasian and Asian: Application for Minimizing Nerve Damage in Rhinoplasty
Authors: Chen Yue , Carr Catherine B.
Published: September 2021

Background

The numbness of the nasal tip is the main symptom of the external nasal nerve injury, especially after rhinoplasty. This postoperative syndrome can reduce the patient’s satisfaction with the operation. Having a better understanding of the anatomical structure and intraoperative protection can effectively avoid nerve injury. At present, the anatomical research on this nerve is all from Asia. This study aims to fill the gap in the anatomical study of this nerve in Caucasians and provides comparative results with Asians.

Material and Methods

A total of 20 Caucasian cadavers were embalmed using the Thiel method. On dissection, after complete exposure of the external nasal nerves, the distance between the exit point of the external nasal nerve and the nasal midline was measured, and the morphology of the nerves was compared with the Asian data. The nerves were classified into types based on their branching pattern.

Results

The nerve plane was the same as the Asian record. The distance ranged from 5.08 to 11.94 mm (mean, 8.31 ± 1.85 mm). This distance has statistical significant difference compared with the Asian population (P < 0.01). The average distance is larger, and the distribution range of the exit point is wider. On classification, 35 of 40 cases had the same type results as those previously reported, with the primary types I, II and III. Five new varieties were found which are classified as subtypes of the primary types and a new type IV. Furthermore, the bifurcation position in two-thirds of the type II cases and variations is proximal to that seen in the Asian population.

Conclusions

The anatomical structure of the external nasal nerve in Caucasians and Asians has obvious differences. This nerve in Caucasians is more likely to be damaged during rhinoplasty than Asians. Except the primary types, the classification of the external nasal nerve also includes subtypes and type IV.

Level of Evidence III

This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
Best practices for analyzing imputed genotypes from low-pass sequencing in dogs
Authors: Buckley Reuben M. , Harris Alex C. , Wang Guo-Dong , Whitaker D. Thad , Zhang Ya-Ping , Ostrander Elaine A.
Published: September 2021

Although DNA array-based approaches for genome-wide association studies (GWAS) permit the collection of thousands of low-cost genotypes, it is often at the expense of resolution and completeness, as SNP chip technologies are ultimately limited by SNPs chosen during array development. An alternative low-cost approach is low-pass whole genome sequencing (WGS) followed by imputation. Rather than relying on high levels of genotype confidence at a set of select loci, low-pass WGS and imputation rely on the combined information from millions of randomly sampled low-confidence genotypes. To investigate low-pass WGS and imputation in the dog, we assessed accuracy and performance by downsampling 97 high-coverage (> 15×) WGS datasets from 51 different breeds to approximately 1× coverage, simulating low-pass WGS. Using a reference panel of 676 dogs from 91 breeds, genotypes were imputed from the downsampled data and compared to a truth set of genotypes generated from high-coverage WGS. Using our truth set, we optimized a variant quality filtering strategy that retained approximately 80% of 14 M imputed sites and lowered the imputation error rate from 3.0% to 1.5%. Seven million sites remained with a MAF > 5% and an average imputation quality score of 0.95. Finally, we simulated the impact of imputation errors on outcomes for case–control GWAS, where small effect sizes were most impacted and medium-to-large effect sizes were minorly impacted. These analyses provide best practice guidelines for study design and data post-processing of low-pass WGS-imputed genotypes in dogs.
Mutational landscape of marginal zone B-cell lymphomas of various origin: organotypic alterations and diagnostic potential for assignment of organ origin
Authors: Vela Visar , Juskevicius Darius , Dirnhofer Stefan , Menter Thomas , Tzankov Alexandar
Published: September 2021

This meta-analysis aims to concisely summarize the genetic landscape of splenic, nodal and extranodal marginal zone lymphomas (MZL) in the dura mater, salivary glands, thyroid, ocular adnexa, lung, stomach and skin with respect to somatic variants. A systematic PubMed search for sequencing studies of MZL was executed. All somatic mutations of the organs mentioned above were combined, uniformly annotated, and a dataset containing 25 publications comprising 6016 variants from 1663 patients was created. In splenic MZL, KLF2 (18%, 103/567) and NOTCH2 (16%, 118/725) were the most frequently mutated genes. Pulmonary and nodal MZL displayed recurrent mutations in chromatin-modifier-encoding genes, especially KMT2D (25%, 13/51, and 20%, 20/98, respectively). In contrast, ocular adnexal, gastric, and dura mater MZL had mutations in genes encoding for NF-κB pathway compounds, in particular TNFAIP3, with 39% (113/293), 15% (8/55), and 45% (5/11), respectively. Cutaneous MZL frequently had FAS mutations (63%, 24/38), while MZL of the thyroid had a higher prevalence for TET2 variants (61%, 11/18). Finally, TBL1XR1 (24%, 14/58) was the most commonly mutated gene in MZL of the salivary glands. Mutations of distinct genes show origin-preferential distribution among nodal and splenic MZL as well as extranodal MZL at/from different anatomic locations. Recognition of such mutational distribution patterns may help assigning MZL origin in difficult cases and possibly pave the way for novel more tailored treatment concepts.
Development of an integrated competency framework for postgraduate paediatric training: a Delphi study
Authors: Robbrecht Marieke , Norga Koen , Van Winckel Myriam , Valcke Martin , Embo Mieke
Published: September 2021

Competency-based education (CBE) has transformed medical training during the last decades. In Flanders (Belgium), multiple competency frameworks are being used concurrently guiding paediatric postgraduate CBE. This study aimed to merge these frameworks into an integrated competency framework for postgraduate paediatric training. In a first phase, these frameworks were scrutinized and merged into one using the Canadian Medical Education Directives for Specialists (CanMEDS) framework as a comprehensive basis. Thereafter, the resulting unified competency framework was validated using a Delphi study with three consecutive rounds. All competencies (n = 95) were scored as relevant in the first round, and twelve competencies were adjusted in the second round. After the third round, all competencies were validated for inclusion. Nevertheless, differences in the setting in which a paediatrician may work make it difficult to apply a general framework, as not all competencies are equally relevant, applicable, or suitable for evaluation in every clinical setting. These challenges call for a clear description of the competencies to guide curriculum planning, and to provide a fitting workplace context and learning opportunities.

Conclusion: A competency framework for paediatric post-graduate training was developed by combining three existing frameworks, and was validated through a Delphi study. This competency framework can be used in setting the goals for workplace learning during paediatric training.

What is Known:•Benefits of competency-based education and its underlying competency frameworks have been described in the literature.•A single and comprehensive competency framework can facilitate training, assessment, and certification.

What is New:•Three existing frameworks were merged into one integrated framework for paediatric postgraduate education, which was then adjusted and approved by an expert panel.•Differences in the working environment might explain how relevant a competency is perceived.
Exploration of motivation to participate in a study of cancer-related cognitive impairment among patients with newly diagnosed aggressive lymphoma: a qualitative sub-study
Authors: Gates Priscilla , Dhillon Haryana , Gough Karla , Wilson Carlene , Hawkes Eliza , Scudder Lindsay , Cushion Tania , Krishnasamy Meinir
Published: September 2021

Purpose

Cancer-related cognitive impairment (CRCI) is a recognised adverse consequence of cancer and its treatment. This qualitative sub-study was undertaken as part of a larger prospective longitudinal study in which recruitment and retention were very high. The aim was to gain an understanding of participants reasons for ongoing participation, at a time of heightened stress related to a new diagnosis of aggressive lymphoma and the rapid commencement of treatment.

Methods

This qualitative descriptive sub-study included semi-structured interviews with twenty-seven participants. Interviews were recorded and transcribed, and a thematic descriptive approach was used to analyse the data.

Results

Twenty-seven interviews were completed. Four themes described participants’ motivation to consent and continue with the study. These included ease of participation, personal values, self-help and valued additional support. Participants understood the requirements of the study, and data collection occurring during hospital visits was perceived to be convenient. Interviewees confirmed that the study fulfilled desire to “help others”. Although testing was intense and challenging, it provided feedback on current functioning and was described by some as a “welcome distraction” and enjoyable. Finally, interaction with the study nurse was perceived as an additional beneficial oversight and support.

Conclusion

Achieving sustained participation in a prospective study with patients undergoing treatment is facilitated where the logistical demands of data collection are minimised; a clinician from the service is included; the tasks are seen as inherently interesting; and care is taken to provide empathic support throughout.

Trial registration

Australian New Zealand Clinical Trials Registry ACTRN12619001649101
Energy Absorption Performance of Bio-inspired Honeycombs: Numerical and Theoretical Analysis
Authors: Sherman John , Zhang Wen , Xu Jun
Published: September 2021

Energy absorption performance has been a long-pursued research topic in designing desired materials and structures subject to external dynamic loading. Inspired by natural bio-structures, herein, we develop both numerical and theoretical models to analyze the energy absorption behaviors of Weaire, Floret, and Kagome-shaped thin-walled structures. We demonstrate that these bio-inspired structures possess superior energy absorption capabilities compared to the traditional thin-walled structures, with the specific energy absorption about 44% higher than the traditional honeycomb. The developed mechanical model captures the fundamental characteristics of the bio-inspired honeycomb, and the mean crushing force in all three structures is accurately predicted. Results indicate that although the basic energy absorption and deformation mode remain the same, varied geometry design and the corresponding material distribution can further boost the energy absorption of the structure, providing a much broader design space for the next-generation impact energy absorption structures and systems.
Unravelling the interplay between water and food systems in arid and semi-arid environments: the case of Egypt
Authors: Terwisscha van Scheltinga Catharien , de Miguel Garcia Angel , Wilbers Gert-Jan , Heesmans Hanneke , Dankers Rutger , Smaling Eric
Published: September 2021

Food system analysis in arid and semi-arid countries inevitably meets water availability as a major constraining food system driver. Many such countries are net food importers using food subsidy systems, as water resources do not allow national food self-sufficiency. As this leaves countries in a position of dependency on international markets, prices and export bans, it is imperative that every domestic drop of water is used efficiently. In addition, policies can be geared towards ‘water footprints’, where water use efficiency is not just evaluated at the field level but also at the level of trade and import/export. In this paper, Egyptian food systems are described based on production, distribution and consumption statistics, key drivers and food system outcomes, i.e., health, sustainable land and water use, and inclusiveness. This is done for three coarsely defined Egyptian food systems: traditional, transitional and modern. A water footprint analysis then shows that for four MENA countries, differences occur between national green and blue water volumes, and the volumes imported through imported foods. Egypt has by far the largest blue water volume, but on a per capita basis, other countries are even more water limited. Then for Egypt, the approach is applied to the wheat and poultry sectors. They show opportunities but also limitations when it comes to projected increased water and food needs in the future. An intervention strategy is proposed that looks into strategies to get more out of the food system components production, distribution and consumption. On top of that food subsidy policies as well as smart water footprint application may lead to a set of combined policies that may lead to synergies between the three food system outcomes, paving the way to desirable food system transformation pathways.
Experimental approach for assessing filter-cake removability derived from reservoir drill-in fluids
Authors: Elmgerbi Asad , Thonhauser Gerhard , Fine Alexander , Hincapie Rafael E. , Borovina Ante
Published: September 2021

Predicting formation damage in cased-hole and open-hole completion wells is of high importance. This is especially relevant when the damage is caused by reservoir drill-in fluids hence being well-bore induced. Cake filter removal has proven to be a good approach to estimate induced damage and to evaluate drill-in fluids’ performance. We present an experimental methodology to evaluate filter cake removal, which could be achieved during the well's initial production. An improved experimental setup, to the ones presented in literature, has been developed to enhance data quality. A twofold approach was used for setup design, and first, it can be integrated with devices used to evaluate the static/dynamic filter-cake. Second, it can be used to simulate more realistic cases (field related) by adjusting the experiment parameters. Hence, to replicate the expected drawdown pressure as well as the corresponding flow rate of the studied reservoir. Three key indicators directly related to filter-cake removal were used as evaluators in this work. Lift-off pressure, internal and external filter cakes removal efficiency. Three reservoir fluid systems were studied, two polymer-based and one potassium carbonate. Results show that pressure required to initiate the collapsing process of the filter cake is not significant. Polymer-based drilling fluids showed better performance in terms of external and internal filter cake cleaning efficiency comparing to potassium carbonate. Moreover, we observed that filtrate volume has no clear relation with the degree of residual damage.
Ecological, Commercial and Economic Significance of the Tree Lucerne: A Review
Authors: Habtemariam Akale Assamere
Published: September 2021

Currently, the Lucerne tree is becoming well-established and adapted in many parts of the world. It can be grow in and around apple trees, near Rahminus prinoides, and within the vegetables. According to African Rising Stations project on Tree Lucerne, line planting, cutting, periodic pruning, and reduce the height by 1.5 m is that the simplest caring mechanism. It has also been shown that this care can result in a 20% increase in DM production on grazing alone. It store about 6 tonnes CO2 equivalent per hectare per year and highest N-fixer among legume, it fixes about 590 kg of N2 per year per hectare. It is mainly used for animal husbandry, treat degraded ecosystems and to have good nutrients. Beyond the nutrients, it is an alternative food guarantee as it can withstand drought and stay green during the summer, especially when there is a shortage of food. Lucerne tree is used as a raw material for pulp and paper work as a group of eucalyptus, holocellulose, lingin, xylan and acetyl groups. However, in addition to fodder, there are significant limitations on energy, paper, tissue and chemical use. The leftovers should be converted into useful products. Therefore, these plants should be used for good quality of wood trim for grain and paperwork.
Every positive integer is the order of an ordinary abelian variety over $${{\mathbb {F}}}_2$$
Authors: Howe Everett W. , Kedlaya Kiran S.
Published: September 2021

We show that for every integer$$m > 0$$m>0, there is an ordinary abelian variety over $${{\mathbb {F}}}_2$$F2that has exactlymrational points.
After global governance
Authors: Neyer Jürgen
Published: September 2021

Technology is of crucial importance for understanding the recent crisis of global governance and concomitant practices of re-territorializing sovereignty. It is far more than an instrument for putting ideas and interests into practice; it is embedded in relationships of power, gives expression to normative decisions and shapes the conditions under which politics is conducted. Technology empowers some actors and disempowers others. It makes new forms of political action possible and others more costly. This crucial role of technology has been emphasized in many dispersed parts of the IR discourse since long. What has often been overlooked, however, is that technological innovation can have a disruptive effect on international institutions. This paper traces this disruptive effect in the administration of the internet by underlining the close nexus between technology, sovereignty and global governance. It finally discusses promising avenues for future research.
Influence of beliefs about romantic love on the justification of abusive behaviors among early adolescents
Authors: Ruiz‐Palomino Estefanía , Ballester‐Arnal Rafael , Giménez‐García Cristina , Gil‐Llario María Dolores
Published: September 2021

Introduction

Romantic experiences during adolescence have an important influence on functioning later in life. Romantic love has been associated with the acceptance of abusive behaviors. This study examined the relationship between myths of romantic love and the perceived severity of different types of abusive behaviors, as well as the influence of gender.

Methods

The sample comprised 448 Spanish adolescents (M = 12.92 years old; SD = 0.85), of which 50.3% were male and 49.7% were female. Participants were evaluated in the school setting. The Perception of Abuse Scale and the Myths, Fallacies, and Misconceptions about Romantic Love Scale were administered.

Results

Statistically significant negative associations between the myths of romantic love and the perceived severity of abusive behaviors were found. Myths regarding possession, dedication, and exclusivity were associated with a lower perceived severity of abusive behaviors in adolescent males. Myths regarding the omnipotence of love were associated with a lower perceived severity of abusive behaviors in adolescent females. Believing in jealousy as a demonstration of love (myth of jealousy) and in the need to establish a steady union when you love someone (marriage myth) explained a lower perceived severity of abusive behaviors in regression models. However, being female and having these beliefs explained a higher perceived severity of abusive behaviors.

Conclusions

The myths of romantic love are already present during early adolescence. These beliefs are implicated in the construction of gender inequality and difficulties in the identification of dating abuse behavior severity. A gendered perspective is necessary to understand this issue. Early intervention strategies should address the cognitive and emotional components of intimate relationships.