bluuebunny/crossref_metadata_2025_split huggingface dataset:
Branched-chain amino acid metabolism is regulated by ERRα in primary human myotubes and is further impaired by glucose loading in type 2 diabetes
Authors: Sjögren Rasmus J. O. , Rizo-Roca David , Chibalin Alexander V. , Chorell Elin , Furrer Regula , Katayama Shintaro , Harada Jun , Karlsson Håkan K. R. , Handschin Christoph , Moritz Thomas , Krook Anna , Näslund Erik , Zierath Juleen R. 
Published: June 2021

Abstract
Aims/hypothesis
Increased levels of branched-chain amino acids (BCAAs) are associated with type 2 diabetes pathogenesis. However, most metabolomic studies are limited to an analysis of plasma metabolites under fasting conditions, rather than the dynamic shift in response to a metabolic challenge. Moreover, metabolomic profiles of peripheral tissues involved in glucose homeostasis are scarce and the transcriptomic regulation of genes involved in BCAA catabolism is partially unknown. This study aimed to identify differences in circulating and skeletal muscle BCAA levels in response to an OGTT in individuals with normal glucose tolerance (NGT) or type 2 diabetes. Additionally, transcription factors involved in the regulation of the BCAA gene set were identified.

Methods
Plasma and vastus lateralis muscle biopsies were obtained from individuals with NGT or type 2 diabetes before and after an OGTT. Plasma and quadriceps muscles were harvested from skeletal muscle-specific Ppargc1a knockout and transgenic mice. BCAA-related metabolites and genes were assessed by LC-MS/MS and quantitative RT-PCR, respectively. Small interfering RNA and adenovirus-mediated overexpression techniques were used in primary human skeletal muscle cells to study the role of PPARGC1A and ESRRA in the expression of the BCAA gene set. Radiolabelled leucine was used to analyse the impact of oestrogen-related receptor α (ERRα) knockdown on leucine oxidation.

Results
Impairments in BCAA catabolism in people with type 2 diabetes under fasting conditions were exacerbated after a glucose load. Branched-chain keto acids were reduced 37–56% after an OGTT in the NGT group, whereas no changes were detected in individuals with type 2 diabetes. These changes were concomitant with a stronger correlation with glucose homeostasis biomarkers and downregulated expression of branched-chain amino acid transaminase 2, branched-chain keto acid dehydrogenase complex subunits and 69% of downstream BCAA-related genes in skeletal muscle. In primary human myotubes overexpressing peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α, encoded by PPARGC1A), 61% of the analysed BCAA genes were upregulated, while 67% were downregulated in the quadriceps of skeletal muscle-specific Ppargc1a knockout mice. ESRRA (encoding ERRα) silencing completely abrogated the PGC-1α-induced upregulation of BCAA-related genes in primary human myotubes.

Conclusions/interpretation
Metabolic inflexibility in type 2 diabetes impacts BCAA homeostasis and attenuates the decrease in circulating and skeletal muscle BCAA-related metabolites after a glucose challenge. Transcriptional regulation of BCAA genes in primary human myotubes via PGC-1α is ERRα-dependent.

Graphical abstract
Natural microbial polysaccharides as effective factors for modification of the catalytic properties of fungal cellobiose dehydrogenase
Authors: Sulej Justyna , Jaszek Magdalena , Osińska-Jaroszuk Monika , Matuszewska Anna , Bancerz Renata , Janczarek Monika 
Published: June 2021

AbstractPolysaccharides are biopolymers composed of simple sugars like glucose, galactose, mannose, fructose, etc. The major natural sources for the production of polysaccharides include plants and microorganisms. In the present work, four bacterial and two fungal polysaccharides (PS or EPS) were used for the modification and preservation of Pycnoporus sanguineus cellobiose dehydrogenase (CDH) activity. It was found that the presence of polysaccharide preparations clearly enhanced the stability of cellobiose dehydrogenase compared to the control value (4 °C). The highest stabilization effect was observed for CDH modified with Rh110EPS. Changes in the optimum pH in the samples of CDH incubated with the chosen polysaccharide modifiers were evidenced as well. The most significant effect was observed for Rh24EPS and Cu139PS (pH 3.5). Cyclic voltammetry used for the analysis of electrochemical parameters of modified CDH showed the highest peak values after 30 days of incubation with polysaccharides at 4 °C. In summary, natural polysaccharides seem to be an effective biotechnological tool for the modification of CDH activity to increase the possibilities of its practical applications in many fields of industry.
Prospective assessment of diagnostic efficacy and safety of SonazoidTM and SonoVue® ultrasound contrast agents in patients with focal liver lesions
Authors: Lv Ke , Zhai Hongyan , Jiang Yuxin , Liang Ping , Xu Hui-Xiong , Du Lianfang , Chou Yi-Hong , Xie Xiaoyan , Luo YuKun , Lee Young Joon , Lee Jae Young , Hu Bing , Luo Baoming , Wang Yi , Luan Ying , Kalli Christina , Chen Kun , Wang Wenping , Liang Ja-Der 
Published: June 2021

Abstract
Objectives
To assess the respective diagnostic value of Sonazoid™ and SonoVue® for characterizing FLLs as benign or malignant and the corresponding safety.

Methods
This prospective Phase 3 study was conducted at 17 centres in China and Korea (May 2014 to April 2015); 424 patients (20 to 80 years) with at least 1 untreated focal liver lesion (FLL) (< 10 cm in diameter) underwent a contrast-enhanced ultrasound (CEUS) examination (218 received Sonazoid of 0.12 μL microbubbles/kg; 206 received SonoVue of 2.4 mL). Three independent blinded readers evaluated pre- and post-contrast images characterising the FLLs as benign or malignant.

Results
Sonazoid-enhanced and SonoVue-enhanced ultrasound provided a statistically significant improvement in specificity for all 3 readers comparing to unenhanced ultrasound (for Sonazoid: p = 0.0093, < 0.0001, 0.0011; for SonoVue: p = 0.002, 0.03, 0.12, respectively). Difference in accuracy improvement between the 2 groups was within the pre-specified non-inferiority margin of 20% for all 3 readers (6.1%, 95% CI: − 5.0 to 17.2; − 7.5%, 95% CI: − 18.4 to 3.5; − 0.3%, 95% CI: − 11.3 to 10.7).
The diagnostic confidence level for all 3 readers increased with post-contrast images relative to pre-contrast images. Both contrast agents were well tolerated.

Conclusion
Results showed a similar efficacy for Sonazoid™ and SonoVue® in diagnosing FLLs as benign or malignant, and underlined the benefit of CEUS imaging over unenhanced ultrasound imaging in reaching a confident diagnosis without having to refer patients for additional imaging exams.
DEtection of ProxImal Coronary stenosis in the work-up for Transcatheter aortic valve implantation using CTA (from the DEPICT CTA collaboration)
Authors: van den Boogert Thomas P. W. , Claessen Bimmer E. P. M. , Opolski Maksymilian P. , Kim Won-Keun , Hamdan Ashraf , Andreini Daniele , Pugliese Francesca , Möllmann Helge , Delewi Ronak , Baan Jan , Vis M. Marije , van Randen Adrienne , van Schuppen Joost , Stoker Jaap , Henriques José P. , Planken R. Nils 
Published: June 2021

Abstract
Objectives
Computed tomography angiography (CTA) is performed routinely in the work-up for transcatheter aortic valve implantation (TAVI), and could potentially replace invasive coronary angiography (ICA) to rule out left main (LM) and proximal coronary stenosis. The objectives were to assess the diagnostic yield and accuracy of pre-TAVI CTA to detect LM and proximal coronary stenosis of ≥ 50% and ≥ 70% diameter stenosis (DS).

Methods
The DEPICT CTA database consists of individual patient data from four studies with a retrospective design that analyzed the diagnostic accuracy of pre-TAVI CTA to detect coronary stenosis, as compared with ICA. Pooled data were used to assess diagnostic accuracy to detect coronary stenosis in the left main and the three proximal coronary segments on a per-patient and a per-segment level. We included 1060 patients (mean age: 81.5 years, 42.7% male).

Results
On ICA, the prevalence of proximal stenosis was 29.0% (≥ 50% DS) and 15.7% (≥ 70% DS). Pre-TAVI CTA ruled out ≥ 50% DS in 51.6% of patients with a sensitivity of 96.4%, specificity of 71.2%, PPV of 57.7%, and NPV of 98.0%. For ≥ 70% DS, pre-TAVI CTA ruled out stenosis in 70.0% of patients with a sensitivity of 96.7%, specificity of 87.5%, PPV of 66.9%, and NPV of 99.0%.

Conclusion
CTA provides high diagnostic accuracy to rule out LM and proximal coronary stenosis in patients undergoing work-up for TAVI. Clinical application of CTA as a gatekeeper for ICA would reduce the need for ICA in 52% or 70% of patients, using a threshold of ≥ 50% or ≥ 70% DS, respectively.

Key Points
• Clinical application of CTA as a gatekeeper for ICA would reduce the need for ICA in 52% or 70% of TAVI patients, using a threshold of ≥ 50% or ≥ 70% diameter stenosis.
• The diagnostic accuracy of CTA to exclude proximal coronary stenosis in these patients is high, with a sensitivity of 96.4% and NPV of 98.0% for a threshold of ≥ 50%, and a sensitivity of 96.7% and NPV of 99.0% for a threshold of ≥ 70% diameter stenosis.
• Atrial fibrillation and heart rate did not significantly affect sensitivity and NPV. However, a heart rate of < 70 b/min during CTA was associated with a significantly improved specificity and PPV.
Hamiltonian Aspects of Three-Layer Stratified Fluids
Authors: Camassa R. , Falqui G. , Ortenzi G. , Pedroni M. , Ho T. T. Vu 
Published: June 2021

AbstractThe theory of three-layer density-stratified ideal fluids is examined with a view toward its generalization to then-layer case. The focus is on structural properties, especially for the case of a rigid upper lid constraint. We show that the long-wave dispersionless limit is a system of quasi-linear equations that do not admit Riemann invariants. We equip the layer-averaged one-dimensional model with a natural Hamiltonian structure, obtained with a suitable reduction process from the continuous density stratification structure of the full two-dimensional equations proposed by Benjamin. For a laterally unbounded fluid between horizontal rigid boundaries, the paradox about the non-conservation of horizontal total momentum is revisited, and it is shown that the pressure imbalances causing it can be intensified by three-layer setups with respect to their two-layer counterparts. The generator of thex-translational symmetry in then-layer setup is also identified by the appropriate Hamiltonian formalism. The Boussinesq limit and a family of special solutions recently introduced by de Melo Viríssimo and Milewski are also discussed.
The effect of exercise and nutrition interventions on physical functioning in patients undergoing haematopoietic stem cell transplantation: a systematic review and meta-analysis
Authors: Prins Marianne C. , van Hinte Gerben , Koenders Niek , Rondel Anne Lieke , Blijlevens Nicole M. A. , van den Berg Manon G. A. 
Published: June 2021

AbstractPurposeHaematopoietic stem cell transplantation (HSCT) is potentially lifesaving. However, it comes with negative consequences such as impaired physical functioning, fatigue and poor quality of life. The aim of this systematic review and meta-analysis is to determine the effect of exercise and nutrition interventions to counteract negative consequences of treatment and improve physical functioning in patients receiving HSCT.MethodsThis systematic review and meta-analysis included randomised controlled trials from three electronic databases between 2009 and 2020. The trials included adult patients receiving HSCT and an exercise or nutrition intervention. Study selection, bias assessment and data extraction were independently performed by two reviewers. Physical functioning outcomes were meta-analysed with a random-effects model.ResultsThirteen studies were included using exercise interventions (n = 11) and nutrition interventions (n = 2); no study used a combined intervention. Meta-analysis of the trials using exercise intervention showed statistically significant effects on 6-min walking distance (standardised mean difference (SMD) 0.41, 95% CI: 0.14–0.68), lower extremity strength (SMD 0.37, 95% CI 0.12–0.62) and global quality of life (SMD 0.27, 95% CI: 0.08–0.46).ConclusionOur physical functioning outcomes indicate positive effects of exercise interventions for patients receiving HSCT. Heterogeneity of the exercise interventions and absence of high-quality nutrition studies call for new studies comparing different types of exercise studies and high quality studies on nutrition in patients with HSCT.
Reducing pain in children with cancer at home: a feasibility study of the KLIK pain monitor app
Authors: Simon Julia D. H. P. , Schepers Sasja A. , Grootenhuis Martha A. , Mensink Maarten , Huitema Angelique D. , Tissing Wim J. E. , Michiels Erna M. C. 
Published: June 2021

Abstract
Purpose
This study assessed adherence to, feasibility of, and barriers and facilitators of implementation of an app developed to monitor and follow-up with pain in children with cancer at home.

Methods
Children (8–18 years) receiving cancer treatment (all diagnoses) or their parents (of children aged 0–7 years) used the KLIK Pain Monitor app for 3 weeks. Pain was assessed twice daily using an 11-point numeric rating scale (NRS-11) (ranging from 0 to 10). Healthcare professionals (HCP’s) from the hospital’s Pediatric Pain Service were instructed to follow-up with clinically significant pain scores (≥ 4) within 120 min (scores 4–6) or 30 min (scores 7–10). Adherence, feasibility, and implementation outcomes were assessed using questionnaires, app log data, and interviews.

Results
Twenty-seven children (M age = 7.3 years, 51.8% male) and six HCP’s participated. Sixty-three percent (N = 17) of families used the app on a daily basis during three weeks, and 18.5% (N = 5) reported pain scores twice daily during that time (family adherence). Twelve out of 27 children (44.4%) reported a clinically significant pain score at least once. In 70% (14/20) of clinically significant pain scores, HCP’s followed-up with families within the set timeframe (HCP adherence). Outcomes reveal feasibility for the majority of app functions (i.e., positive evaluation by ≥ 70% families/HCP’s), and non-feasible aspects could be resolved. Identified barriers and facilitators were used to improve future implementation efforts.

Conclusion
Use of the KLIK Pain Monitor app seems feasible. Future research will determine its effectiveness in reducing pain in children with cancer at home.
Alternative Magnetflussführung in Elektromotoren
Authors: Schauerte Benedikt , Gilch Ines , Neuwirth Tobias , Sebold Simon , Leuning Nora , Schulz Michael , Volk Wolfram , Hameyer Kay 
Published: June 2021

ZusammenfassungNicht-kornorientiertes Elektroblech ist eine Kernkomponente im Aufbau rotierender elektrischer Maschinen. Es dient der gezielten Führung und Verstärkung des magnetischen Flusses. Eine möglichst starke magnetische Kopplung zwischen Rotor- und Statorfluss ist hierbei entscheidend für die Effizienz und Leistungsdichte des elektrischen Antriebs.Zu diesem Zweck werden in permanentmagneterregten Synchron-Maschinen und Synchron-Reluktanzmaschinen Flussbarrieren eingebracht, um Streuflüsse zu unterdrücken und eine gezielte Führung des magnetischen Flusses zu gewährleisten. Die Flussbarrieren werden typischerweise durch Aussparungen im Rotorquerschnitt realisiert. Die resultierenden filigranen Strukturen des Elektroblechs führen zu einer mechanischen Schwächung des Rotors und somit zu geringeren erreichbaren Drehzahlen und Leistungsdichten.In dieser Arbeit wird ein alternativer Ansatz zur Führung des magnetischen Flusses auf Basis des Villari-Effekts vorgestellt. Lokal veränderte magnetische Werkstoffeigenschaften werden durch erhöhte Eigenspannungen in geprägten Werkstoffbereichen erzielt. Der Zusammenhang zwischen umformtechnisch eingebrachten Eigenspannungen und der reduzierten magnetischen Leitfähigkeit des Elektroblechs wird anhand homogen geprägter Proben untersucht. Höhere Umformkräfte, die mit gesteigerten mechanischen Spannungen einhergehen, führen zu einer stärkeren Reduktion der magnetischen Permeabilität. Die Funktionsweise dieser alternativen magnetischen Flusssperren wird anhand kreisförmiger Prägemuster gezeigt. Neben der Darstellung des Einflusses variierender Prägeparameter auf die magnetischen Eigenschaften des Elektroblechs wird vor allem die Reproduzierbarkeit der veränderten magnetischen Eigenschaften durch umformtechnisch hervorgerufene Eigenspannungen nachgewiesen.
Differential expression of miRNAs and functional role of mir-200a in high and low productivity CHO cells expressing an Fc fusion protein
Authors: Bryan Laura , Henry Michael , Barron Niall , Gallagher Clair , Kelly Ronan M. , Frye Christopher C. , Osborne Matthew D. , Clynes Martin , Meleady Paula 
Published: June 2021

Abstract
Objectives
We used miRNA and proteomic profiling to understand intracellular pathways that contribute to high and low specific productivity (Qp) phenotypes in CHO clonally derived cell lines (CDCLs) from the same cell line generation project.

Results
Differentially expressed (DE) miRNAs were identified which are predicted to target several proteins associated with protein folding. MiR-200a was found to have a number of predicted targets associated with the unfolded protein response (UPR) which were shown to have decreased expression in high Qp CDCLs and have no detected change at the mRNA level. MiR-200a overexpression in a CHO CDCL was found to increase recombinant protein titer by 1.2 fold and Qp by 1.8 fold.

Conclusion
These results may suggest a role for miR-200a in post-transcriptional regulation of the UPR, presenting miR-200a as a potential target for engineering industrially attractive CHO cell phenotypes.
Ethnic differences in COVID-19 mortality during the first two waves of the Coronavirus Pandemic: a nationwide cohort study of 29 million adults in England
Authors: Nafilyan Vahé , Islam Nazrul , Mathur Rohini , Ayoubkhani Daniel , Banerjee Amitava , Glickman Myer , Humberstone Ben , Diamond Ian , Khunti Kamlesh 
Published: June 2021

AbstractEthnic minorities have experienced disproportionate COVID-19 mortality rates in the UK and many other countries. We compared the differences in the risk of COVID-19 related death between ethnic groups in the first and second waves the of COVID-19 pandemic in England. We also investigated whether the factors explaining differences in COVID-19 death between ethnic groups changed between the two waves. Using data from the Office for National Statistics Public Health Data Asset, a linked dataset combining the 2011 Census with primary care and hospital records and death registrations, we conducted an observational cohort study to examine differences in the risk of death involving COVID-19 between ethnic groups in the first wave (from 24th January 2020 until 31st August 2020) and ﻿the first part of the second wave (from 1st September to 28th December 2020). We estimated age-standardised mortality rates (ASMR) in the two waves stratified by ethnic groups and sex. We also estimated hazard ratios (HRs) for ethnic-minority groups compared with the White British population, adjusted for geographical factors, socio-demographic characteristics, and pre-pandemic health conditions. The study population included over 28.9 million individuals aged 30–100 years living in private households. In the first wave, all ethnic minority groups had a higher risk of COVID-19 related death compared to the White British population. In the second wave, the risk of COVID-19 death remained elevated for people from Pakistani (ASMR: 339.9 [95% CI: 303.7–376.2] and 166.8 [141.7–191.9] deaths per 100,000 population in men and women) and Bangladeshi (318.7 [247.4–390.1] and 127.1 [91.1–171.3] in men and women) background but not for people from Black ethnic groups. Adjustment for geographical factors explained a large proportion of the differences in COVID-19 mortality in the first wave but not in the second wave. Despite an attenuation of the elevated risk of COVID-19 mortality after adjusting for sociodemographic characteristics and health status, the risk was substantially higher in people from Bangladeshi and Pakistani background in both the first and the second waves. Between the first and second waves of the pandemic, the reduction in the difference in COVID-19 mortality between people from Black ethnic background and people from the White British group shows that ethnic inequalities in COVID-19 mortality can be addressed. The continued higher rate of mortality in people from Bangladeshi and Pakistani background is alarming and requires focused public health campaign and policy changes.
Resolution à la Kronheimer of $$\mathbb {C}^3/\Gamma $$ singularities and the Monge–Ampère equation for Ricci-flat Kähler metrics in view of D3-brane solutions of supergravity
Authors: Bianchi Massimo , Bruzzo Ugo , Fré Pietro , Martelli Dario 
Published: June 2021

AbstractIn this paper, we analyze the relevance of the generalized Kronheimer construction for the gauge/gravity correspondence. We begin with the general structure of D3-brane solutions of type IIB supergravity on smooth manifolds $$Y^\Gamma $$

Y
Γ

that are supposed to be the crepant resolution of quotient singularities $$\mathbb {C}^3/\Gamma $$

C

3

/
Γ

with $$\Gamma $$
Γ
a finite subgroup of SU(3). We emphasize that nontrivial 3-form fluxes require the existence of imaginary self-dual harmonic forms $$\omega ^{2,1}$$

ω

2
,
1

. Although excluded in the classical Kronheimer construction, they may be reintroduced by means of mass deformations. Next we concentrate on the other essential item for the D3-brane construction, namely, the existence of a Ricci-flat metric on $$Y^\Gamma $$

Y
Γ

. We study the issue of Ricci-flat Kähler metrics on such resolutions $$Y^\Gamma $$

Y
Γ

, with particular attention to the case $$\Gamma =\mathbb {Z}_4$$

Γ
=

Z
4

. We advance the conjecture that on the exceptional divisor of $$Y^\Gamma $$

Y
Γ

the Kronheimer Kähler metric and the Ricci-flat one, that is locally flat at infinity, coincide. The conjecture is shown to be true in the case of the Ricci-flat metric on $$\mathrm{tot} K_{{\mathbb {W}P}[112]}$$

tot

K

W
P

[
112
]

that we construct, i.e., the total space of the canonical bundle of the weighted projective space $${\mathbb {W}P}[112]$$

W
P

[
112
]

, which is a partial resolution of $$\mathbb {C}^3/\mathbb {Z}_4$$

C

3

/

Z
4

. For the full resolution, we have $$Y^{\mathbb {Z}_4}={\text {tot}} K_{\mathbb {F}_{2}}$$

Y

Z
4

=
tot

K

F
2

, where $$\mathbb {F}_2$$

F
2

is the second Hirzebruch surface. We try to extend the proof of the conjecture to this case using the one-parameter Kähler metric on $$\mathbb {F}_2$$

F
2

produced by the Kronheimer construction as initial datum in a Monge–Ampère (MA) equation. We exhibit three formulations of this MA equation, one in terms of the Kähler potential, the other two in terms of the symplectic potential but with two different choices of the variables. In both cases, one can establish a series solution in powers of the variable along the fibers of the canonical bundle. The main property of the MA equation is that it does not impose any condition on the initial geometry of the exceptional divisor, rather it uniquely determines all the subsequent terms as local functionals of this initial datum. Although a formal proof is still missing, numerical and analytical results support the conjecture. As a by-product of our investigation, we have identified some new properties of this type of MA equations that we believe to be so far unknown.