bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simple, sensitive and specific quantification of diamine oxidase activity in complex matrices using newly discovered fluorophores derived from natural substrates
Authors: Boehm Thomas , Karer Matthias , Gludovacz Elisabeth , Petroczi Karin , Resch Marlene , Schuetzenberger Kornelia , Klavins Kristaps , Borth Nicole , Jilma Bernd 
Published: June 2020

Abstract
Objective
To measure diamine oxidase (DAO) activity with high sensitivity in complex matrices like plasma or tissue extracts radioactive putrescine or horseradish peroxidase (HRP)/hydrogen peroxide (H2O2) coupling must be used. The use of radioactive material should be avoided and HRP/H2O2 coupling is compromised by antioxidants.

Methods and results
Condensation of ortho-aminobenzaldehyde (oABA) with delta-1-pyrroline and delta-1-piperideine, the autocyclization products of the DAO-oxidized natural substrates putrescine and cadaverine, generates new quinazoline fluorophores with absorption and excitation maxima of 430 and 460 nm, respectively, and peak emission at 620 nm. Fluorescent-based detection limits are 20–40 times lower compared to absorption measurements. This assay can be used to measure DAO activity in human plasma after spiking recombinant human (rh)DAO, in rat plasma after intravenous rhDAO administration, in pregnancy plasma and in tissue extracts of DAO wild-type and knock-out mice. Using rat plasma the correlation between rhDAO activity and ELISA data is 99%. Human and rat plasma without DAO spiking and tissue extracts from DAO knock-out mice showed stable and low fluorescence in the presence of high substrate concentrations.

Conclusions
Incubation of DAO with the natural substrates putrescine and cadaverine and oABA generates novel fluorophores increasing the detection limit compared to absorption measurements at least tenfold. This simple, sensitive and specific assay allows the non-radioactive quantification of DAO activity in complex matrices like plasma and tissue extracts without interference by antioxidants.
Spectral Determinants and an Ambarzumian Type Theorem on Graphs
Authors: Kiss Márton 
Published: June 2020

AbstractWe consider an inverse problem for Schrödinger operators on connected equilateral graphs with standard matching conditions. We calculate the spectral determinant and prove that the asymptotic distribution of a subset of its zeros can be described by the roots of a polynomial. We verify that one of the roots is equal to the mean value of the potential and apply it to prove an Ambarzumian type result, i.e., if a specific part of the spectrum is the same as in the case of zero potential, then the potential has to be zero.
Impact of β-glycerophosphate on the bioenergetic profile of vascular smooth muscle cells
Authors: Alesutan Ioana , Moritz Franco , Haider Tatjana , Shouxuan Sun , Gollmann-Tepeköylü Can , Holfeld Johannes , Pieske Burkert , Lang Florian , Eckardt Kai-Uwe , Heinzmann Silke Sophie , Voelkl Jakob 
Published: June 2020

Abstract
In chronic kidney disease, hyperphosphatemia is a key pathological factor promoting medial vascular calcification, a common complication associated with cardiovascular events and mortality. This active pathophysiological process involves osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs) via complex intracellular mechanisms that are still incompletely understood. Little is known about the effects of phosphate on the bioenergetic profile of VSMCs during the onset of this process. Therefore, the present study explored the effects of the phosphate donor β-glycerophosphate on cellular bioenergetics of VSMCs. Mitochondrial and glycolytic functions were determined utilizing extracellular flux analysis in primary human aortic VSMCs following exposure to β-glycerophosphate. In VSMCs, β-glycerophosphate increased basal respiration, mitochondrial ATP production as well as proton leak and decreased spare respiratory capacity and coupling efficiency, but did not modify non-mitochondrial or maximal respiration. β-Glycerophosphate-treated VSMCs had higher ability to increase mitochondrial glutamine and long-chain fatty acid usage as oxidation substrates to meet their energy demand. β-Glycerophosphate did not modify glycolytic function or basal and glycolytic proton efflux rate. In contrast, β-glycerophosphate increased non-glycolytic acidification. β-Glycerophosphate-treated VSMCs had a more oxidative and less glycolytic phenotype, but a reduced ability to respond to stressed conditions via mitochondrial respiration. Moreover, compounds targeting components of mitochondrial respiration modulated β-glycerophosphate-induced oxidative stress, osteo-/chondrogenic signalling and mineralization of VSMCs. In conclusion, β-glycerophosphate modifies key parameters of mitochondrial function and cellular bioenergetics in VSMCs that may contribute to the onset of phenotypical transdifferentiation and calcification. These observations advance the understanding of the role of energy metabolism in VSMC physiology and pathophysiology of vascular calcification during hyperphosphatemia.

Key messages

β-Glycerophosphate modifies key parameters of mitochondrial respiration in VSMCs.

β-Glycerophosphate induces changes in mitochondrial fuel choice in VSMCs.

β-Glycerophosphate promotes a more oxidative and less glycolytic phenotype of VSMCs.

β-Glycerophosphate triggers mitochondrial-dependent oxidative stress in VSMCs.

Bioenergetics impact β-glycerophosphate-induced VSMC calcification.
Adults with early-onset type 2 diabetes (aged 18–39 years) are severely underrepresented in diabetes clinical research trials
Authors: Sargeant Jack A. , Brady Emer M. , Zaccardi Francesco , Tippins Frances , Webb David R. , Aroda Vanita R. , Gregg Edward W. , Khunti Kamlesh , Davies Melanie J. 
Published: June 2020

Abstract
Aims/hypothesis
Early-onset adult type 2 diabetes (diagnosed between ages 18 and 39 years) is increasingly prevalent and associated with poor long-term outcomes. We hypothesised that individuals with early-onset adult type 2 diabetes were underrepresented in the prominent research trials that underpin type 2 diabetes management guidelines.

Methods
We reviewed the mean age of the study populations recruited to 90 prominent trials in type 2 diabetes, including 37 cardio-renal outcomes trials across a range of pharmacological, non-pharmacological and multifactorial interventions, 28 trials from the phase III programmes of three representative glucose-lowering therapies used routinely in clinical practice (empagliflozin, liraglutide and sitagliptin) and 25 prominent trials of diabetes self-management education and support or intensive lifestyle interventions (diet or supervised exercise training). We then estimated the number of individuals within these trials who were aged between 18 and 39 years.

Results
Across all 90 trials, the mean age of 268,978 participants was 63 years (range 51–69 years in individual trials). In 73 trials (81%), <5% of participants were estimated to be aged 18–39 years, despite this age group representing ~15–20% of the adult type 2 diabetes population. Twenty-nine of these trials (32%; total 164,953 participants) excluded individuals below 40 years of age altogether.

Conclusions/interpretation
Guidelines for early-onset adult type 2 diabetes are extrapolated predominantly from evidence in older individuals. Strategies to support the participation of individuals with early-onset adult type 2 diabetes in future research are imperative to ensure guidelines for these high-risk individuals are evidence-based.
Foundations of Fully Dynamic Group Signatures
Authors: Bootle Jonathan , Cerulli Andrea , Chaidos Pyrros , Ghadafi Essam , Groth Jens 
Published: June 2020

AbstractGroup signatures allow members of a group to anonymously sign on behalf of the group. Membership is administered by a designated group manager. The group manager can also reveal the identity of a signer if and when needed to enforce accountability and deter abuse. For group signatures to be applicable in practice, they need to support fully dynamic groups, i.e., users may join and leave at any time. Existing security definitions for fully dynamic group signatures are informal, have shortcomings, and are mutually incompatible. We fill the gap by providing a formal rigorous security model for fully dynamic group signatures. Our model is general and is not tailored toward a specific design paradigm and can therefore, as we show, be used to argue about the security of different existing constructions following different design paradigms. Our definitions are stringent and when possible incorporate protection against maliciously chosen keys. We consider both the case where the group management and tracing signatures are administered by the same authority, i.e., a single group manager, and also the case where those roles are administered by two separate authorities, i.e., a group manager and an opening authority. We also show that a specialization of our model captures existing models for static and partially dynamic schemes. In the process, we identify a subtle gap in the security achieved by group signatures using revocation lists. We show that in such schemes new members achieve a slightly weaker notion of traceability. The flexibility of our security model allows to capture such relaxation of traceability.
FT-IR versus EC-QCL spectroscopy for biopharmaceutical quality assessment with focus on insulin—total protein assay and secondary structure analysis using attenuated total reflection
Authors: Delbeck Sven , Heise H. Michael 
Published: June 2020

AbstractFor the quality control of biopharmaceutical products, which contain proteins as the most important active ingredients, shelf life may be limited due to inappropriate storage conditions or mechanical stress. For insulins as representatives of life-saving pharmaceuticals, analytical methods are needed, which are providing additional information than obtained by assays for total protein quantification. Despite sophisticated formulations, the chemical stability may be challenged by temperatures deviating from recommended conditions or shear rate exposure under storage, leading to misfolding, nucleation, and subsequent fibril formation, accompanied by a decrease in bioactivity. A reliable method for insulin quantification and determination of secondary structure changes has been developed by attenuated total reflection (ATR) Fourier-transform infrared spectroscopy of insulin formulations by a silver halide fiber-coupled diamond probe with subsequent dry-film preparation. A special emphasis has been placed on the protein amide I band evaluation, for which spectral band analysis provides unique information on secondary structure fractions for intact and misfolded insulins. Quantitative measurements are possible down to concentrations of less than 0.5 mg/ml, whereas the dry-film preparation delivers high signal-to-noise ratios due to the prior water evaporation, thus allowing a reliable determination of secondary structure information.
Holmium laser enucleation of the prostate: efficacy, safety and preoperative management in patients presenting with anticoagulation therapy
Authors: Deuker Marina , Rührup Jessica , Karakiewicz Pierre I. , Welte Maria , Kluth Luis A. , Banek Severine , Roos Frederik C. , Mandel Philipp , Chun Felix K.-H. , Becker Andreas 
Published: June 2020

Abstract
Purpose
We evaluated efficacy and safety profile of patients with anticoagulation therapy (AT) undergoing holmium laser enucleation of the prostate (HoLEP).

Methods
Within our prospective institutional database (11/2017 to 11/2019), we analyzed functional outcomes and 30-day complication rates of HoLEP patients according to Clavien–Dindo classification (CLD), stratified according to specific AT vs. no AT. Further analyses consisted of uni- and multivariate logistic regression models (LRM) predicting complications.

Results
Of 268 patients undergoing HoLEP, 104 (38.8%) received AT: 25.7% were treated with platelet aggregation inhibitors (PAI), 8.2% with new oral anticoagulants (NOAC) and 4.9% with AT-combinations or coumarins bridged with low molecular weight heparins (LMWH/combination). Patients receiving AT were significantly more comorbid (p < 0.01). Pre- and postoperative maximal flow rates, residual void urine and IPSS at 3 months after surgery were invariably improved after HoLEP for patients with/ without AT. Overall complication rate was 19.5% in patients with no AT vs. 26.1% vs. 27.3 vs. 46.2%, respectively, in patients with PAI, NOAC and LMWH/combination (p < 0.01). Major complications (CLD ≥ 3b) occurred in 6.1% of no AT patients vs. 4.3% vs. 4.5 vs. 0% in patients with PAI, NOAC and LMWH/combination, respectively (p < 0.01). In multivariate LRM, AT was not significantly associated with higher complication rates, whereas high ASA status (OR 2.2, p = 0.04), age (OR 1.04, p = 0.02) and bioptical or incidental prostate cancer (OR 2.5, p = 0.01) represented independent risk factors.

Conclusion
Despite higher overall complication rates in AT patients, major complications were not more frequent in AT patients. HoLEP is safe and effective in anticoagulated patients.
The diagnostic benefit of 16S rDNA PCR examination of infective endocarditis heart valves: a cohort study of 146 surgical cases confirmed by histopathology
Authors: Armstrong Christina , Kuhn Tim Christian , Dufner Matthias , Ehlermann Philipp , Zimmermann Stefan , Lichtenstern Christoph , Soethoff Jasmin , Katus Hugo A. , Leuschner Florian , Heininger Alexandra 
Published: June 2020

Abstract
Aims
Upon suspicion of infective endocarditis, the causative microorganism must be identified to optimize treatment. Blood cultures and culturing of removed valves are the mainstay of this diagnosis and should be complemented by growth-independent methods. We assessed the diagnostic benefit of examining removed endocarditis valves by broad-range bacterial PCR to detect causative bacteria in cases where culturing was not available, negative, or inconclusive because a skin commensal was detected, in patients from our clinical routine practice.

Methods and results
Patients from Heidelberg University Hospital with suspicion of endocarditis, followed by valve replacement and analysis by 16S rDNA PCR, between 2015 and 2018, were evaluated. 146 patients with definite infective endocarditis, confirmed by the valve macroscopics and/or histology, were included. Valve PCRs were compared to corresponding blood and valve culture results. Overall, valve PCR yielded an additional diagnostic benefit in 34 of 146 cases (23%) and was found to be more sensitive than valve culture. In 19 of 38 patients with both negative blood and valve cultures, valve PCR was the only method rendering a pathogen. In 23 patients with positive blood cultures detecting skin commensals, 4 patients showed discordant valve PCR results, detecting a more plausible pathogen, and in 11 of 23 cases, valve PCR confirmed commensals in blood culture as true pathogens. Only the remaining 8 patients had negative valve PCRs.

Conclusion
Valve PCR was found to be a valuable diagnostic tool in surgical endocarditis cases with negative blood cultures or positive blood cultures of unknown significance.

Trial registration
S-440/2017 on 28.08.2017 retrospectively registered.

Graphic abstract
Subdividing of all infective endocarditis patients in this study, showing that valve PCR yields valuable information for patients with skin commensals in blood cultures, which were either confirmed by the same detection in valve PCR or refuted by the detection of a different and typical pathogen in valve PCR. Additionally, benefit was determined in patients with negative or not available blood cultures and only positive detection in valve PCR. +: Positive; −: negative; n/a: not available results
Inhibition of NaV1.8 prevents atrial arrhythmogenesis in human and mice
Authors: Pabel Steffen , Ahmad Shakil , Tirilomis Petros , Stehle Thea , Mustroph Julian , Knierim Maria , Dybkova Nataliya , Bengel Philipp , Holzamer Andreas , Hilker Michael , Streckfuss-Bömeke Katrin , Hasenfuss Gerd , Maier Lars S. , Sossalla Samuel 
Published: June 2020

AbstractPharmacologic approaches for the treatment of atrial arrhythmias are limited due to side effects and low efficacy. Thus, the identification of new antiarrhythmic targets is of clinical interest. Recent genome studies suggested an involvement of SCN10A sodium channels (NaV1.8) in atrial electrophysiology. This study investigated the role and involvement of NaV1.8 (SCN10A) in arrhythmia generation in the human atria and in mice lacking NaV1.8. NaV1.8 mRNA and protein were detected in human atrial myocardium at a significant higher level compared to ventricular myocardium. Expression of NaV1.8 and NaV1.5 did not differ between myocardium from patients with atrial fibrillation and sinus rhythm. To determine the electrophysiological role of NaV1.8, we investigated isolated human atrial cardiomyocytes from patients with sinus rhythm stimulated with isoproterenol. Inhibition of NaV1.8 by A-803467 or PF-01247324 showed no effects on the human atrial action potential. However, we found that NaV1.8 significantly contributes to late Na+ current and consequently to an increased proarrhythmogenic diastolic sarcoplasmic reticulum Ca2+ leak in human atrial cardiomyocytes. Selective pharmacological inhibition of NaV1.8 potently reduced late Na+ current, proarrhythmic diastolic Ca2+ release, delayed afterdepolarizations as well as spontaneous action potentials. These findings could be confirmed in murine atrial cardiomyocytes from wild-type mice and also compared to SCN10A−/− mice (genetic ablation of NaV1.8). Pharmacological NaV1.8 inhibition showed no effects in SCN10A−/− mice. Importantly, in vivo experiments in SCN10A−/− mice showed that genetic ablation of NaV1.8 protects against atrial fibrillation induction. This study demonstrates that NaV1.8 is expressed in the murine and human atria and contributes to late Na+ current generation and cellular arrhythmogenesis. Blocking NaV1.8 selectively counteracts this pathomechanism and protects against atrial arrhythmias. Thus, our translational study reveals a new selective therapeutic target for treating atrial arrhythmias.
Structural control in micelles of alkyl acrylate-acrylate copolymers via alkyl chain length and block length
Authors: Azeri Özge , Schönfeld Dennis , Noirez Laurence , Gradzielski Michael 
Published: June 2020

AbstractAmphiphilic copolymers with poly (alkyl acrylate) as hydrophobic and poly (acrylic acid) (AA) as hydrophilic block have been synthesised. The alkyl chain was varied from butyl to dodecyl, thereby varying systematically the polarity of the hydrophobic block whose length was between 35 and 70, while the PAA block had ~ 100 units. Such relatively short amphiphiles should equilibrate quickly in aqueous solution, and their corresponding self-assembly properties were characterised by means of critical micelle concentration (cmc) determination. Detailed information regarding the aggregate structures was obtained by static light scattering (SLS) and small angle neutron scattering (SANS). This could be correlated with the molecular architecture of the copolymers and the degree of ionisation of the PAA block. Generally, it is found that the aggregation numbers become smaller upon fully charging the PAA head group and only for dodecyl acrylate really well-defined micellar aggregates are formed. This means that the extent of hydrophobicity of the alkyl acrylate block and its length determine in a clear fashion the propensity for micelle formation and the mass and aggregation number of the formed micelles.
Etiologies of olfactory dysfunction in a pediatric population: based on a retrospective analysis of data from an outpatient clinic
Authors: Schriever Valentin Alexander , Hummel Thomas 
Published: June 2020

Abstract
Purpose
Although the prevalence of olfactory dysfunction in children is thought to be lower compared to adults, little is known about the actual frequency of etiologies of smell dysfunction in children. Aim of the study was (i) to describe the epidemiology of olfactory dysfunction in a pediatric population and (ii) to compare the distribution of etiologies to adults.

Material and methods
Data of patients consulting a smell and taste clinic between 2000 and 2017 were retrospectively analyzed. Frequency of major causes of olfactory dysfunction was examined with a focus on the pediatric population.

Results
A total of 7153 patients (164 children) were included in the analysis. Most children presented with congenital olfactory dysfunction (67%), or head-trauma (12%). In contrast, the cumulative frequency of olfactory loss associated with sinonasal disorders or acute infections of the upper airways was 6%. The frequency of etiologies of olfactory dysfunction changed with age: While the frequency of patients with congenital anosmia decreased, the frequency of causes related to infections of the upper respiratory tract and idiopathic causes increased.

Conclusion
About 2/3 of olfactory dysfunction in children are congenital while 1/3 is acquired. The frequency of etiologies causing olfactory dysfunction change significantly from children to an adult population.
Diagnostic accuracy of a smartphone bedside
test to assess the fixation suppression of the vestibulo-ocular reflex: when nothing else
matters
Authors: Gandor Florin , Tesch Manfred , Neuhauser Hannelore , Gruber Doreen , Heinze Hans-Jochen , Ebersbach Georg , Lempert Thomas 
Published: June 2020

Abstract
Objective
Validation of a bedside test to objectify the fixation suppression of
the vestibulo-ocular reflex (FS-VOR) in patients with a cerebellar syndrome and
healthy controls.

Methods
The vestibulo-ocular reflex and its fixation suppression were assessed
by video-nystagmography (VNG) in 20 healthy subjects (mean age 56 ± 15) and 19
patients with a cerebellar syndrome (mean age 70 ± 11). The statistical cutoff
delineating normal from pathological FS-VOR was determined at the 2.5th percentile of
the normal distribution of the healthy cohort. VNG was then compared to a bedside
test, where eye movements were recorded with a smartphone while patients were rotated
on a swivel chair at a defined speed and amplitude. These videos were rated as normal
or pathological FS-VOR by six blinded raters, and results compared to VNG.

Results
VNG in healthy controls showed FS-VOR with a reduction of nystagmus
beats by 95.0% ± 7.2 (mean ± SD). The statistical cutoff was set at 80.6%. Cerebellar
patients reduced nystagmus beats by only 26.3% ± 25.1. Inter-rater agreement of the
smartphone video ratings was 85%. The sensitivity of the video ratings to detect an
impaired FS-VOR was 99%, its specificity 92%. Inter-test agreement was 91%.

Conclusion
The smartphone bedside test is an easily performed, reliable, sensitive,
specific, and inexpensive alternative for assessing FS-VOR.
An intergrid transfer operator using radial basis functions with application to cardiac electromechanics
Authors: Salvador Matteo , Dede’ Luca , Quarteroni Alfio 
Published: June 2020

AbstractIn the framework of efficient partitioned numerical schemes for simulating multiphysics PDE problems, we propose using intergrid transfer operators based on radial basis functions to accurately exchange information among different PDEs defined in the same computational domain. Different (potentially non-nested) meshes can be used for the space discretization of the PDEs. The projection of the (primary) variables that are shared by the different PDEs (through the coupling terms) is carried out with Rescaled Localized Radial Basis Functions. We validate our approach by a numerical test for which we also show the scalability of the intergrid transfer operator in the framework of high performance computing. Then, we apply it to the electromechanical model for the human heart function, and simulate a heartbeat of an idealized left ventricle. We show that our approach enables the solution of large-scale multiphysics problems, especially when the individual models exhibit very different spatial scales.