bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractThe 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

ABSTRACTThe 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

AbstractResearch 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

Abstract
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

Abstract
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

Abstract
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

AbstractAlthough 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

AbstractThis 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

AbstractCompetency-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

Abstract

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