bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of severe exercise‐induced bronchoconstriction in Nigerian children with asthma
Authors: Kuti Bankole Peter , Kuti Demilade Kehinde , Teague Williams G.
Published: January 2020

Background/Purpose

Asthmatics with severe exercise‐induced bronchoconstriction (EIB) are at high risk of exacerbations. The purpose of this study was to determine the prevalence, phenotypic, and laboratory determinants of severe EIB in Nigerian children with asthma.

Methods

Children with controlled asthma (n = 101) underwent characterization and free‐running exercise bronchoprovocation at a center in Nigeria. Lung function was measured before, then 5, 10, 15, and 30 minutes after 6 to 8 minutes exercise. Severe EIB was defined as ≥50% decrease in forced expired volume in 1 second (FEV1) from preexercise. Serum vitamin D and total antioxidant capacity were measured chromatographically. Factors predicting severe EIB were tested by logistic regression.

Result

The sample was enriched in children with corticosteroid‐naïve, mild intermittent asthma (71%). Thirteen percent had no EIB, 22% had severe and 65% nonsevere EIB. Children with severe EIB had higher preexercise FVC (105% vs 96%; P = .03) and FEV1 (98% vs 90%; P = .07), greater obesity (13.6% vs 1.3%; P = .02), more allergic rhinitis (AR) (63.6% vs 35.4%; P = .03), but less exposure to household pets (31.8% vs 72.2%; P = .003) compared to children with nonsevere EIB. Significant determinants (odds ratios/confidence intervals) for severe EIB were obesity = 12.3 (1.2‐125.1), AR = 3.18 (1.19‐8.52), blood eosinophilia = 1.005 (1.001‐1.009), and hypovitaminosis D = 0.87 (0.81‐0.93).

Conclusion

In Nigerian children with asthma, severe EIB is common and associated with remediable comorbidities including type 2 pattern inflammation and vitamin D deficiency.
Role of a noncanonical disulfide bond in the stability, affinity, and flexibility of a VHH specific for the Listeria virulence factor InlB
Authors: Mendoza Matthew N. , Jian Mike , King Moeko T. , Brooks Cory L.
Published: January 2020

A distinguishing feature of camel (Camelus dromedarius) VHH domains are noncanonical disulfide bonds between CDR1 and CDR3. The disulfide bond may provide an evolutionary advantage, as one of the cysteines in the bond is germline encoded. It has been hypothesized that this additional disulfide bond may play a role in binding affinity by reducing the entropic penalty associated with immobilization of a long CDR3 loop upon antigen binding. To examine the role of a noncanonical disulfide bond on antigen binding and the biophysical properties of a VHH domain, we have used the VHH R303, which binds the Listeria virulence factor InlB as a model. Using site directed mutagenesis, we produced a double mutant of R303 (C33A/C102A) to remove the extra disulfide bond of the VHH R303. Antigen binding was not affected by loss of the disulfide bond, however the mutant VHH displayed reduced thermal stability (Tm = 12°C lower than wild‐type), and a loss of the ability to fold reversibly due to heat induced aggregation. X‐ray structures of the mutant alone and in complex with InlB showed no major changes in the structure. B‐factor analysis of the structures suggested that the loss of the disulfide bond elicited no major change on the flexibility of the CDR loops, and revealed no evidence of loop immobilization upon antigen binding. These results suggest that the noncanonical disulfide bond found in camel VHH may have evolved to stabilize the biophysical properties of the domain, rather than playing a significant role in antigen binding.
de Sitter Conjectures in Supergravity
Authors: Ferrara Sergio , Tournoy Magnus , Van Proeyen Antoine
Published: January 2020

Supergravity theories at allow to formulate the Swampland de Sitter conjectures in the complex field space of scalar components of chiral multiplets. We formulate the refined de Sitter conjecture by using the Kähler invariant ‐function and explore a class of models in the Landscape/Swampland scenario which obey and/or violate such conjectures. Furthermore we give a new construction of exponential potentials in supergravity. These depend on a chiral superfield with a Kähler potential parametrizing an geometry. We show that the construction allows for modifications to supergravity theories causing them to obey the de Sitter conjectures.
The F1534C voltage‐sensitive sodium channel mutation confers 7‐ to 16‐fold resistance to pyrethroid insecticides in Aedes aegypti
Authors: Fan Yinjun , Scott Jeffrey G
Published: January 2020

BACKGROUND

Recent outbreaks of dengue and Zika have emphasized the importance to effectively control Aedes aegypti, which vectors the viruses causing these diseases. Pyrethroid insecticides are primarily used to control adult A. aegypti, especially during disease outbreaks. However, pyrethroid resistance in A. aegypti is an increasing problem. Mutations in the voltage‐sensitive sodium channel (Vssc) are a common mechanism of pyrethroid resistance. The F1534C mutation is common and distributed globally in A. aegypti populations, but previous studies disagree about the role of this mutation in conferring resistance to pyrethroid insecticides.

RESULTS

We isolated a congenic strain (1534C:ROCK) which was closely related to a susceptible strain Rockefeller (ROCK), but was homozygous for the 1534C Vssc allele. We determined resistance levels against eight insecticides that target the VSSC: six pyrethroids, DDT and DCJW (the bioactivated metabolite of indoxacarb). The resistance levels ranged from 7‐ to 16‐fold, and resistance was inherited as an incompletely recessive trait. We also found a novel 367I+1520I+1534C allele, in addition to the 1534C and 1520I+1534C alleles, in mosquitoes from Thailand. The T1520I mutation did not increase pyrethroid resistance beyond what was conferred by the F1534C mutation alone.

CONCLUSION

The F1534C Vssc mutation is common in A. aegypti populations and confers 7‐ to 16‐fold resistance to pyrethroids, DDT, and DCJW in Aedes aegypti. These resistance levels are considerably less than previously reported for the S989P+V1016G mutations. Our results provide useful information for resistance management, specifically the levels of resistance conferred by the most common Vssc mutation in A. aegypti. © 2020 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
The Role Played by Graphene Oxide in the Photodeposition and Surface‐Enhanced Raman Scattering Activity of Plasmonic Ag Nanoparticle Substrates
Authors: Costa Ítalo A. , Maciel Ayessa P. , Sales Maria J. A. , Moreira Sanclayton G. C. , Paterno Leonardo G.
Published: January 2020

Layer‐by‐layer photocatalyst films made of TiO2 nanoparticles (TiO2NP) assembled with both poly(sodium 4‐styrenesulfonate) (PSS) and graphene oxide (GO) are used for the photodeposition of plasmonic Ag nanoparticles (AgNPs) and subsequently used in surface‐enhanced Raman scattering (SERS). Both photocatalyst films, TiO2NP/PSS and TiO2NP/GO, are capable of driving the formation of AgNP when they are wetted with a drop of AgNO3 diluted solution and submitted to UV irradiation (254 nm). The photodeposition of AgNP, as monitored by UV–vis spectroscopy, follows a first‐order kinetics process in both films and is slightly faster in the TiO2NP/PSS. In addition, scanning electron microscopy reveals that in the TiO2NP/PSS film, the photodeposited AgNPs are larger and isolated, whereas in the TiO2NP/GO film, they are smaller and highly interconnected. The SERS activity of the substrates is evaluated with rhodamine B. When samples are excited in resonance with rhodamine B absorption (514 nm), GO‐based substrates provide the largest enhancement because GO is able to quench the rhodamine B fluorescence, something that PSS is unable to do. Out of this condition (633 nm), the plasmonic effect of AgNP alone prevails regardless of the presence of GO.
Validation of a Finite Element Modeling Process for Auxetic Structures under Impact
Authors: Shepherd Todd , Winwood Keith , Venkatraman Prabhuraj , Alderson Andrew , Allen Thomas
Published: January 2020

Auxetic materials behave unconventionally under deformation, which enhances material properties such as resistance to indentation and energy absorption. Auxetics, therefore, have the potential to enhance sporting protective equipment. Herein, finite element modeling, additive manufacturing and impact testing of three auxetic lattices, and a conventional equivalent, with a view to advance auxetic implementation within sports equipment, are explored. The lattices are modeled and impacts are simulated between 1 and 5 J, for flat and hemispherical drop hammers. Simulation outputs including peak impact force, impact duration, maximum axial strain, and Poisson's ratio are compared with experimental results from equivalent impact energies on additively manufactured lattices, using an instrumented drop tower and a high‐speed camera. The simulation and experimental results show broad agreement for all lattices and scenarios, demonstrated by comparative force versus time plots and maximum compression images. The benefits of developing and validating finite element models of three auxetic lattices (and the conventional honeycomb lattice) under various impact scenarios, as a process, are discussed, including material characterization of an exemplar thermoplastic polyurethane. Future work can use the models to further investigate auxetic lattices, selecting and tailoring candidates to further explore their potential application to specific personal protective equipment in sport.
The quest for socio‐economic rights: The rule of law and violent protest in South Africa
Authors: Klaasen Abraham
Published: January 2020

Socio‐economic protests in South Africa are increasingly violent with citizens demanding their constitutionally guaranteed rights whilst ignoring the rule of law. The weakening of the rule of law holds serious implications for democracy in South Africa. This paper explores the rule of law, socio‐economic rights and violent protest in South Africa. The realisation of socio‐economic rights, the reasons for violent protest and the weakening of the rule of law are investigated. Two conventional methodologies for strengthening the rule of law, the institutional approach and the neocultural interventionist approach, are explored. This paper argues that violent citizen protest highlights the urgent need for reform to strengthen the rule of law in South Africa. Such reform can be found in the acknowledgment that the realisation of socio‐economic rights form part of the substantive components of the rule of law. This acknowledgment allows for an integrated and problem‐solving approach to the rule of law; focusing on problems experienced by end users of the law system. A problem‐solving approach to strengthening the rule of law allows the courts, legal scholars and legal practitioners to provide opportunities for communities to realise socio‐economic rights and thereby fulfilling the substantive components of the rule of law.
Universal inelastic electron scattering cross‐section including extrinsic and intrinsic excitations in XPS
Authors: Gnacadja Eustache , Pauly Nicolas , Tougaard Sven
Published: January 2020

The high importance of X‐ray photoelectron spectroscopy (XPS) in surface analysis is well established. In XPS, the shape of the measured peaks is affected by two classes of energy loss: extrinsic losses because of the transport of photoelectrons in the matter and intrinsic losses because of the sudden creation of the static core hole. In order to perform a quantitative, comprehensive determination of the zero‐energy loss spectrum, a systematic and physically meaningful background subtraction method must be used. In this paper, we propose a universal analytical expression to model the energy loss cross section of the emitted photoelectrons for transition metals and their oxides. The proposed expression is a generalization of the well‐known Tougaard's universal inelastic scattering cross section to also account for the intrinsic losses. We demonstrate the use of this to determine the primary excitation spectra of several transition metals and their oxides, and we compare the results with a more accurate calculation based on the dielectric response model for XPS.
Weighted Kaplan‐Meier estimators motivating to estimate HIV‐1 RNA reduction censored by a limit of detection
Authors: Ahmed Ismaïl , Flandre Philippe
Published: January 2020

Measuring the magnitude of reduction in HIV‐1 RNA levels accurately is difficult because many patients have a censored reduction due to the limit of detection (LOD) of the virologic assay being employed. The use of censored methods has improved the analysis of such reductions compared with crude methods but implies independent censoring. For HIV‐1 RNA reduction data, the value at which a patient's HIV‐1 RNA reduction becomes censored is mainly determined by the patient's baseline HIV‐1 RNA level. We suggest two possibilities based on modification of the redistribution to the right algorithm to handle the situation of dependence either from a single continuous marker, that is, the baseline HIV‐1 RNA level, or from multiple markers. Two series of simulation, one in the HIV‐1 RNA setting and one in the classical censoring setting, compared performance of the previous methods with our suggestions. Our proposed estimators show good performances when the dependent censoring is due to LOD. Overall, in the classical censoring setting, our suggestions perform as well as other methods including the Inverse Probability of Censoring Weighted and the Kaplan‐Meier imputation with Bootstrap. We applied those estimators to estimate the HIV‐1 RNA reduction at week 8 of 502 patients who received a raltegravir‐containing regimen and to data from the Mayo Clinic trial in primary biliary cirrhosis.
Recent Progress on Exploring Stable Metal–Organic Frameworks for Photocatalytic Solar Fuel Production
Authors: Wang Xu‐Sheng , Li Lan , Li Dan , Ye Jinhua
Published: January 2020

Solar energy, a clean and sustainable energy source, can be harvested and converted to solar fuel to meet the ever‐increasing energy demand. Integrating the photosensitizers and active catalytic sites into a single solid, metal–organic framework (MOF) with high void architectures and tunable chemical structures, is proposed as a promising platform for photocatalysis. However, compared with the traditional inorganic photocatalysts, the photocatalytic applications of MOFs are greatly hindered by its instability, especially the chemical instability. In this review, the background related to solar fuel production and MOFs are first discussed. Then, several strategies for designing stable MOFs are presented. Third, newly developed approaches for synthesizing highly efficient solar fuel production MOFs are summarized. Finally, the challenges and future perspectives using MOFs for solar fuel production are discussed. This review is expected to provide a deeper understanding of highly stable MOF design and new insights for the application of stable MOFs for solar fuel production.
Three‐Dimensional GeSe Microstructured Air Brick Photocathode for Advanced Solar Water Splitting
Authors: Wang Kang , Huang Dingwang , Li Lintao , Feng Kuang , Harada Takashi , Ikeda Shigeru , Li Jingbo , Jiang Feng
Published: January 2020

Air brick‐structured GeSe is first synthesized by a rapid box thermal deposition method, and the GeSe thin film with such air brick novel structure demonstrates advanced photoelectrochemical (PEC) performance. It is found that the electrode position of a few CdS nanoparticles (NPs) on a GeSe microair brick (MAB) prior to the chemical bath deposition (CBD) of CdS buffer affects the coverage/passivation efficiency of CdS onto GeSe MAB. In this case, the electrodeposited CdS particles were likely to be the seed for CdS growth/adsorption of Cd2+ during the subsequent CBD process and also could serve as active sites between the adsorbed layer and buffer layer for collecting electrons and facilitating their transfer, ultimately reducing the recombination loss. The PEC performance, especially the current density, is obviously improved (8 mA cm−2 at 0 VRHE) compared with that of a device without CdS NPs (3.6 mA cm−2 at 0 VRHE). Moreover, surface modification with an 80 nm atomic layer deposition TiO2 protective layer not only slows the photocorrosion of the CdS layer to 5 h but also promotes the half‐cell solar‐to‐hydrogen efficiency to 1.47%. More than 180 μmol H2 and 90 μmol O2 are evolved during 3 h of sustained solar light illumination with the final Pt–TiO2/CdS/CdS‐NP/GeSe MAB device.
Experimental investigation of asymmetrical reinforced concrete spatial frame substructures against progressive collapse under different column removal scenarios
Authors: Du Ke , Bai Jiulin , Teng Nan , Yan Deng , Sun Jingjiang
Published: January 2020

The progressive collapse resistance design approach is generally applied in the context of a “column‐removal” scenario to assess the structural vulnerability to progressive collapse. To obtain a better understanding of the complex progressive collapse resistance of 3D asymmetrical column‐beam‐slab systems, five one‐third scale 2 × 2 bay asymmetrical reinforced concrete (RC) spatial frame substructure specimens were tested to analyze their collapse mechanisms under five different column removal scenarios, namely, an interior column removal scenario (INT), an exterior column removal scenario in the asymmetrical direction (EXT‐X), an exterior column removal scenario in the symmetrical direction (EXT‐Y), a corner column removal scenario at the long bay (COR‐L), and a corner column removal scenario at the short bay (COR‐S), which are among the most critical scenarios for analyzing structural resistance against progressive collapse. The test results showed that INT had the highest progressive collapse resistance capacity among the scenario substructures and exhibited two progressive collapse‐resisting mechanism stages: a primary mechanism stage (beam and compressive membrane mechanism) under small deformations and a secondary mechanism stage (catenary and tensile membrane mechanism) under large deformations in both the X‐direction and the Y‐direction. In EXT‐X and EXT‐Y, the collapse resistance was mainly provided by the double‐span beam at both the primary mechanism stage and the secondary mechanism stage. In COR‐L and COR‐S, the tensile membrane mechanism could not be mobilized, as the single‐span beams in both the X‐direction and the Y‐direction behaved like cantilevers. Additionally, the asymmetrical span design reduced the resistance of the structure against progressive collapse.
Late‐onset laryngeal paralysis: Owner perception of quality of life and cause of death
Authors: Sample Susannah J. , Stilin Allison , Binversie Emily E. , Baker Lauren A. , Hardie Robert J.
Published: January 2020

Background

Late‐onset laryngeal paralysis (LoLP) is an idiopathic disease of older dogs, and is common in the Labrador Retriever. Owner perspective of how LoLP affects their pet's quality of life (QOL), the degree to which LoLP is perceived to be a life‐limiting disease, and how a glottic opening procedure affects these perceptions is not known.

Objectives

(a) To determine owner's perception of late‐onset laryngeal paralysis (LoLP) with respect to their dog's QOL; (b) To determine whether LoLP is considered by owners to be a life‐limiting disease; (c) To evaluate whether a glottic opening procedure altered QOL and perceived cause of death in affected dogs.

Methods

Owners of Labrador Retrievers with LoLP completed a questionnaire. Questions were asked pertaining to a dog's LoLP, including clinical progression and perception of cause of death, and whether a glottic opening procedure was undertaken. Owners also completed a pet‐owner administered QOL survey.

Results

Seventy‐six owners participated. Overall, 94% of owners felt their dog's LoLP affected QOL, and 47% of owners felt LoLP was a large contributing factor in their dog's death. Dogs that underwent a glottic opening procedure were reported to have a better QOL, and the contribution of LoLP towards their death was less than dogs that did not have surgery.

Conclusion

Owners of Labrador Retrievers with LoLP perceive LoLP to be a life‐limiting disease that negatively impacts their dog's QOL. Arytenoid lateralization surgery had a positive impact on QOL in affected dogs.
Following the messenger: Recent innovations in live cell single molecule fluorescence imaging
Authors: Schmidt Andreas , Gao Guoming , Little Saffron R. , Jalihal Ameya P. , Walter Nils G.
Published: January 2020

Messenger RNAs (mRNAs) convey genetic information from the DNA genome to proteins and thus lie at the heart of gene expression and regulation of all cellular activities. Live cell single molecule tracking tools enable the investigation of mRNA trafficking, translation and degradation within the complex environment of the cell and in real time. Over the last 5 years, nearly all tools within the mRNA tracking toolbox have been improved to achieve high‐quality multi‐color tracking in live cells. For example, the bacteriophage‐derived MS2‐MCP system has been improved to facilitate cloning and achieve better signal‐to‐noise ratio, while the newer PP7‐PCP system now allows for orthogonal tracking of a second mRNA or mRNA region. The coming of age of epitope‐tagging technologies, such as the SunTag, MoonTag and Frankenbody, enables monitoring the translation of single mRNA molecules. Furthermore, the portfolio of fluorogenic RNA aptamers has been expanded to improve cellular stability and achieve a higher fluorescence “turn‐on” signal upon fluorogen binding. Finally, microinjection‐based tools have been shown to be able to track multiple RNAs with only small fluorescent appendages and to track mRNAs together with their interacting partners. We systematically review and compare the advantages, disadvantages and demonstrated applications in discovering new RNA biology of this refined, expanding toolbox. Finally, we discuss developments expected in the near future based on the limitations of the current methods.

This article is categorized under:

RNA Export and Localization > RNA Localization

RNA Structure and Dynamics > RNA Structure, Dynamics, and Chemistry

RNA Interactions with Proteins and Other Molecules > RNA–Protein Complexes
The investigation of semi‐strip's stress state with a longitudinal crack
Authors: Vaysfeld N. , Zhuravlova Z.
Published: January 2020

The article is dedicated to the investigation of the stress state of a semi‐strip weakened by a longitudinal crack. Two statements of the problem are considered. The integral Fourier transform is applied directly to the initial problem. The discontinuous boundary problem which is formulated in vector form is solved with the help of the matrix differential calculation and the Green's matrix‐function's discontinuous properties. The solving of the problem is reduced to the solving of the system of three singular integral equations (SSIE). This system is solved by two methods regarding to the conditions at the semi‐strip's short edge. The orthogonal polynomials method is used when the semi‐strip is loaded at the center of its short edge, and the special generalized scheme, which allows consideration of fixed singularities, this is applied when the whole semi‐strip's short edge is loaded. The stress intensity factors (SIF) are investigated for the two cases.
Meromorphic continuation of Selberg zeta functions with twists having non-expanding cusp monodromy
Authors: Fedosova Ksenia , Pohl Anke
Published: January 2020

We initiate the study of Selberg zeta functions $$Z_{\Gamma ,\chi }$$ZΓ,χ for geometrically finite Fuchsian groups $$\Gamma $$Γ and finite-dimensional representations $$\chi $$χ with non-expanding cusp monodromy. We show that for all choices of $$(\Gamma ,\chi )$$(Γ,χ), the Selberg zeta function $$Z_{\Gamma ,\chi }$$ZΓ,χ converges on some half-plane in $$\mathbb {C}$$C. In addition, under the assumption that $$\Gamma $$Γ admits a strict transfer operator approach, we show that $$Z_{\Gamma ,\chi }$$ZΓ,χ extends meromorphically to all of $$\mathbb {C}$$C.
Random strict partitions and random shifted tableaux
Authors: Matsumoto Sho , Śniady Piotr
Published: January 2020

We study asymptotics of randomshiftedYoung diagrams which correspond to a given sequence of reducibleprojectiverepresentations of the symmetric groups. We show limit results (Law of Large Numbers and Central Limit Theorem) for their shapes, provided that the representation character ratios and their cumulants converge to zero at some prescribed speed. Our class of examples includes uniformly random shifted standard tableaux with prescribed shape as well as shifted tableaux generated by some natural combinatorial algorithms (such as shifted Robinson–Schensted–Knuth correspondence) applied to a random input.
Diagnostic approach for myocardial contusion: a retrospective evaluation of patient data and review of the literature
Authors: Van Lieshout Esther M. M. , Verhofstad Michael H. J. , Van Silfhout Dirk Jan T. , Dubois Eric A.
Published: January 2020

Purpose

Myocardial contusion can be a life-threatening condition in patients who sustained blunt thoracic trauma. The diagnostic approach remains a subject of debate. The aim of this study was to determine the sensitivity and specificity of echocardiography, electrocardiography, troponins T and I (TnT and TnI), and creatine kinase muscle/brain (CK-MB) for identifying patients with a myocardial contusion following blunt thoracic trauma.

Methods

Sensitivity and specificity were first determined in a 10-year retrospective cohort study and second by a systematic literature review with meta-analysis.

Results

Of the 117 patients in the retrospective study, 44 (38%) were considered positive for myocardial contusion. Chest X-ray, chest CT scan, electrocardiograph, and echocardiography had poor sensitivity (< 15%) but good specificity (≥ 90%). Sensitivity to cardiac biomarkers measured at presentation ranged from 59% for TnT to 77% for hs-TnT, specificity ranged from 63% for CK-MB to 100% for TnT. The systematic literature review yielded 28 studies, with 14.5% out of 7242 patients reported as positive for myocardial contusion. The pooled sensitivity of electrocardiography, troponin I, and CK-MB was between 62 and 71%, versus only 45% for echocardiography and 38% for troponin T. The pooled specificity ranged from 63% for CK-MB to 85% for troponin T and 88% for echocardiography.

Conclusion

The best diagnostic approach for myocardial contusion is a combination of electrocardiography and measurement of cardiac biomarkers. If abnormalities are found, telemonitoring is necessary for the early detection of life-threatening arrhythmias. Chest X-ray and CT scan may show other thoracic injuries but provide no information on myocardial contusion.
Nonlinear impact of financial deepening on income inequality
Authors: Benczúr Péter , Kvedaras Virmantas
Published: January 2020

This paper looks at the influence of financial deepening (private bank credit) on income inequality in developed economies. Building on a model of financially open economies (Kunieda et al. (Macroecon Dyn 18:1091–1128, 2014)), defining its endogenous economic growth rate, and extending its implications also for top income shares, it is shown that the impact of bank credit on inequality depends on the gap between the real interest rate and the GDP growth rate (‘$$r-g$$

r
-
g

’). This finding is robustly confirmed by the empirical analysis on a few samples of OECD and EU countries, both for the Gini index and for top income shares. Both the econometric evidence and simple evidence show that the presence of this type of non-linearity (an interaction between financial deepening and $$r-g$$

r
-
g

) is likely to be one of the reasons for the mixed results that may be found in the empirical literature on the relationship between the financial deepening and income inequality.
Erstellung und Etablierung einer wissensbasierten Fallsammlung für forensische Bildgebung – WiFas
Authors:   Arbeitsgemeinschaft Forensische Bildgebung (AGFB) der Deutschen Gesellschaft für Rechtsmedizin (DGRM), Heinze S. , Grunert S. , Grabherr S. , Labudde D.
Published: January 2020

Einleitung

Mit der Weiterentwicklung und Verbreitung radiologischer Techniken wie Computertomographie und Magnetresonanztomographie hat in den letzten 2 Jahrzehnten die forensische Bildgebung einen immer größeren Stellenwert eingenommen. Um die damit verbundenen Ergebnisse und daraus gewonnenen Erkenntnisse sowie die in diesem Zusammenhang stehenden radiologischen Daten, welche diese neuen Techniken hervorbringen, allen Mitgliedern der Deutschen Gesellschaft für Rechtsmedizin zugänglich zu machen, wurde die Wissensbasierte Fallsammlung (WiFas) entwickelt.

Material und Methoden

Die Datenbank wurde als Webapplikation entwickelt. Es können externe Dokumente, Bilder und Dateiarchive zu Einzelgutachten in die Datenbank geladen und verwaltet werden. Ein systeminternes Nutzer-Rollen-Konzept verhindert den unautorisierten Systemzugriff durch unbefugte Personen.

Ergebnisse

Es ist eine Datenbank entstanden, die jedem Nutzer einen individuellen Zugang zu zahlreichen rechtsmedizinischen Fällen erlaubt. In der WiFas ist es möglich, sowohl eine Übersicht an Fällen zu erhalten, als auch gezielt nach einzelnen Fallarten zu suchen und Befunde in verschiedenen Dokumenten und Bildmaterial zu vergleichen.

Diskussion

Sowohl die klinische forensische Bildgebung als auch die postmortale Bildgebung sind nicht mit der klinischen Radiologie gleichzusetzen. Oftmals werden seitens der Ermittlungsbehörden rekonstruktive Fragen gestellt, deren Beantwortung nicht nur radiologisches Wissen, sondern auch rechtsmedizinisches Fachwissen fordert. Außerdem sind häufig spezifische Darstellungen der Bilddaten (z. B. dreidimensionale Darstellungen von Befunden) erforderlich. Im gesamten Gebiet der forensischen Bildgebung ist dementsprechend interdisziplinäres radiologisches und rechtsmedizinisches Wissen notwendig. Mit der WiFas wird erstmals eine Plattform angeboten, auf deren Grundlage verschiedenste Informationen aus den Bereichen der Rechtsmedizin und der Radiologie zusammenfließen können.
Hormonal and gene dynamics in de novo shoot meristem formation during adventitious caulogenesis in cotyledons of Pinus pinea
Authors: Alvarez José M. , Bueno Natalia , Cuesta Candela , Feito Isabel , Ordás Ricardo J.
Published: January 2020

Key message

Several members of WOX and KNOX gene families and several plant growth regulators, basically cytokinins and auxins, play a key role during adventitious caulogenesis in the conifer Pinus pinea.

Similar to Arabidopsis thaliana, Pinus pinea shoot organogenesis is a multistep process. However, there are key differences between both species, which may alter the underlying physiological and genetic programs. It is unknown if the genic expression models during angiosperm development may be applicable to conifers. In this work, an analysis of the endogenous content of different plant growth regulators and the expression of genes putatively involved in adventitious caulogenesis in P. pinea cotyledons was conducted. A multivariate analysis of both datasets was also realized through partial least squares regression and principal component analysis to obtain an integral vision of the mechanisms involved in caulogenesis in P. pinea. Analyses show that cotyledons cultured in the presence of benzyladenine during long times (2–6 days) cluster separately from the rest of the samples, suggesting that the benzyladenine increase observed during the first hours of culture is sufficient to trigger the caulogenic response through the activation of specific developmental programs. In particular, the most relevant factors involved in this process are the cytokinins trans-zeatin, dihydrozeatin, trans-zeatin riboside and isopentenyl adenosine; the auxin indoleacetic acid; and the genes PpWUS, PpWOX5, PpKN2, PpKN3 and PipiRR1. WUS is functional in pines and has an important role in caulogenesis. Interestingly, WOX5 also seems to participate in the process, although its specific role has not been determined.
Tikhonov–Fenichel Reduction for Parameterized Critical Manifolds with Applications to Chemical Reaction Networks
Authors: Feliu Elisenda , Kruff Niclas , Walcher Sebastian
Published: January 2020

We derive a reduction formula for singularly perturbed ordinary differential equations (in the sense of Tikhonov and Fenichel) with a known parameterization of the critical manifold. No a priori assumptions concerning separation of slow and fast variables are made, or necessary. We apply the theoretical results to chemical reaction networks with mass action kinetics admitting slow and fast reactions. For some relevant classes of such systems, there exist canonical parameterizations of the variety of stationary points; hence, the theory is applicable in a natural manner. In particular, we obtain a closed form expression for the reduced system when the fast subsystem admits complex-balanced steady states.
The Phylogeny and Functional Characterization of Peanut Acyl-ACP Thioesterases
Authors: Peng Zhenying , Zhang Hui , Tian Haiying , Shan Lei , Zhang Zhimeng , Ding Hong , Gao Wenwei , Li Xinguo
Published: January 2020

Fatty acyl-acyl thioesterases (FATs), which hydrolyze the thioester bond linking acyl chains to an acyl carrier protein, thereby terminating their elongation, contribute significantly to the fatty acid (FA) content and composition of seed storage lipids. The peanut (Arachis hypogaea L.) genome was found to harbor 21 FAT (AhFAT) genes, distributed over 12 of the 20 chromosomes. The length of their predicted translation products varied from 74 to 415 residues, and all but one included the 1–2 Acyl-ACP_TE conserved domains. All of the coding sequences were interrupted by at least one intron, with the exon number ranging from two to 12, and five of the genes were liable to alternative splicing. When the RNA-Seq platform was used to assess the transcriptional behavior of the 21 AhFAT genes, transcription of only 13 was detectable in samples of root, leaves, and developing seed; among these, six were transcribed throughout the plant, three were root-specific and one was leaf-specific. A detailed analysis of a pair of homologous AhFATs showed that the coding region of each was split into six exons and that both were transcribed in all of the plant organs surveyed (although the intensity of their transcription was not the same in immature seed). The product of both genes was deposited in the chloroplast outer membrane. The constitutive expression of these genes in either yeast or Arabidopsis thaliana increased the FA content, especially that of saturated FAs. In peanut genome, 21 AhFAT genes were found and two of them were transformed into yeast and Arabidopsis for function identification. Results showed that overexpression of these two genes could increase the FA content, especially the saturated FAs content.
Surgical rescue for persistent head and neck cancer after first-line treatment
Authors: Steinbichler Teresa Bernadette , Golm L. , Dejaco D. , Riedl D. , Kofler B. , Url C. , Wolfram D. , Riechelmann H.
Published: January 2020

Purpose

Surgical rescue is a treatment option for persistent disease after first-line treatment treatment of head and neck cancer (HNC).

Methods

Patients with persistent HNC treated with rescue surgery between 2008 and 2016 were included. Patients who received a rescue neck dissection (ND only) and who received primary site surgery ± ND were analysed separately (primary site surgery ± ND).

Results

During the observation period, 35 patients received ND only and 17 primary site surgery ± ND. No perioperative mortality was observed. In nine patients with ND only and 12 patients with primary site surgery ± ND at least one complication was encountered. 41/52 (79%) patients had a complete response. Median overall survival of patients receiving rescue surgery was 56 months (95% CI 44–69 months). Median overall survival was best for patients with initial laryngeal and oropharyngeal cancer and worst for patients with hypopharyngeal cancer (p = 0.02). Functional deficits following rescue surgery were mainly observed in the domains speech, nutrition, and shoulder/arm mobility. The risk of functional impairment was higher for patients with rescue surgery at the primary tumor site (OR 2.5 ± 2;p = 0.07).

Conclusion

Rescue surgery offers patients with resectable, persistent disease a realistic chance to achieve long-term survival. Especially patients with laryngeal and oropharyngeal cancer profited from rescue surgery. Rescue neck dissection is an effective and safe procedure. Patients with rescue surgery at the primary tumor site ± ND should expect complications and permanent functional impairment.
Mid-term evaluation of perioperative i.v. corticosteroid treatment efficacy on overall and audiological outcome following CO2 laser stapedotomy: a retrospective study of 84 cases
Authors: Székely L. , Gáborján A. , Dános K. , Szalóki T. , Fent Z. , Tamás L. , Polony G.
Published: January 2020

Purpose

Our aim was to determine whether perioperatively administered corticosteroid treatment has any beneficial effect on the outcome of stapes surgery, with special regard to the audiological results and early postoperative morbidity.

Methods

84 CO2 laser stapedotomies performed in our institute between 2013 and 2018 were included in our investigation. All cases underwent preoperative and mid-term postoperative pure-tone audiometric evaluation. Vestibular complications were also evaluated. The cases were subdivided into two groups, 23 patients received perioperative i.v. methylprednisolone treatment (“S”) while the other 61 patients (“nS”) did not receive any adjuvant pharmacological therapy. The data were analyzed retrospectively using IBM SPSS Statistics.

Results

CO2 laser stapedotomy proved to be a successful intervention with a significant improvement in ABG and AC thresholds as well. Long-term BC levels were significantly better compared to preoperative ones in the S group; however, in the nS group, no difference could be shown. Hearing and ABG gain were significantly superior in group S [28.1 dB (SD11.2) vs. 18.1 dB (SD 10.9) and 23.9 dB(SD 9.8) vs. 17.2 dB (SD 9.5), respectively].

Conclusion

No significant inner ear damage was detectable in the results of our CO2 laser stapedotomy method; however, the positive effect of corticosteroid treatment could be demonstrated through the postoperative hearing levels. We found no statistical difference in early postoperative morbidity. According to our data, the routine administration of corticosteroids during stapes surgery could be an issue worthy of consideration. The effects of perioperative treatment vs that on the first day after surgery, and topical vs. systemic treatment could be the subject of further investigation in a prospective manner.
PD-1/PD-L1 expression and tumor-infiltrating lymphocytes are prognostically favorable in advanced high-grade serous ovarian carcinoma
Authors: Martin de la Fuente Laura , Westbom-Fremer Sofia , Arildsen Nicolai Skovbjerg , Hartman Linda , Malander Susanne , Kannisto Päivi , Måsbäck Anna , Hedenfalk Ingrid
Published: January 2020

The response rate to checkpoint inhibitors for women with high-grade serous carcinoma of the ovary, fallopian tube, and peritoneum (HGSC) is modest, and development of predictive biomarkers is needed. The main focus has been on tumor cell PD-L1 expression, but its assessment alone is insufficient for patient selection in most malignancies. We mapped the presence of macrophages (CD68 and CD163) and lymphocytes (CD3) located within the tumor epithelium, the cell type–specific expression of PD-L1 and PD-1, and their impact on 5-year overall survival (OS) in a consecutive cohort of 130 women diagnosed with advanced HGSC between 2011 and 2015. PD-L1 was expressed mainly by macrophages (not by tumor cells) and PD-1 by lymphocytes. Women with higher CD3, PD-L1, and PD-1 expression had improved OS (P = 0.03,P = 0.007, andP = 0.02, respectively). In the external data set (203 women), high expression ofCD274(encoding PD-L1) was associated with improved OS (P = 0.03), in accordance with our results. Furthermore, higher CD163 expression was associated with better outcome in women with no residual tumor after primary surgery (P = 0.02). Thus, women with greater lymphocyte tumor infiltration had better outcome and PD-L1/PD-1 expression, regardless of PD-1/PD-L1 being markers for immune suppressive pathways, conferred a survival benefit in our cohort. Our results highlight that tumor immunity may be harnessed in subsets of HGSC.
Exclusive neuronal detection of KGDHC-specific subunits in the adult human brain cortex despite pancellular protein lysine succinylation
Authors: Dobolyi Arpad , Bago Attila , Palkovits Miklos , Nemeria Natalia S. , Jordan Frank , Doczi Judit , Ambrus Attila , Adam-Vizi Vera , Chinopoulos Christos
Published: January 2020

The ketoglutarate dehydrogenase complex (KGDHC) consists of three different subunits encoded by OGDH (or OGDHL), DLST, and DLD, combined in different stoichiometries. DLD subunit is shared between KGDHC and pyruvate dehydrogenase complex, branched-chain alpha-keto acid dehydrogenase complex, and the glycine cleavage system. Despite KGDHC’s implication in neurodegenerative diseases, cell-specific localization of its subunits in the adult human brain has never been investigated. Here, we show that immunoreactivity of all known isoforms of OGDHL, OGDH, and DLST was detected exclusively in neurons of surgical human cortical tissue samples identified by their morphology and visualized by double labeling with fluorescent Nissl, while being absent from glia expressing GFAP, Aldhl1, myelin basic protein, Olig2, or IBA1. In contrast, DLD immunoreactivity was evident in both neurons and glia. Specificity of anti-KGDHC subunits antisera was verified by a decrease in staining of siRNA-treated human cancer cell lines directed against the respective coding gene products; furthermore, immunoreactivity of KGDHC subunits in human fibroblasts co-localized > 99% with mitotracker orange, while western blotting of 63 post-mortem brain samples and purified recombinant proteins afforded further assurance regarding antisera monospecificity. KGDHC subunit immunoreactivity correlated with data from the Human Protein Atlas as well as RNA-Seq data from the Allen Brain Atlas corresponding to genes coding for KGDHC components. Protein lysine succinylation, however, was immunohistochemically evident in all cortical cells; this was unexpected, because this posttranslational modification requires succinyl-CoA, the product of KGDHC. In view of the fact that glia of the human brain cortex lack succinate-CoA ligase, an enzyme producing succinyl-CoA when operating in reverse, protein lysine succinylation in these cells must exclusively rely on propionate and/or ketone body metabolism or some other yet to be discovered pathway encompassing succinyl-CoA.
Proportional assist ventilation (PAV) versus neurally adjusted ventilator assist (NAVA): effect on oxygenation in infants with evolving or established bronchopulmonary dysplasia
Authors: Hunt Katie A. , Dassios Theodore , Greenough Anne
Published: January 2020

Both proportional assist ventilation (PAV) and neurally adjusted ventilatory assist (NAVA) provide pressure support synchronised throughout the respiratory cycle proportional to the patient’s respiratory demand. Our aim was to compare the effect of these two modes on oxygenation in infants with evolving or established bronchopulmonary dysplasia. Two-hour periods of PAV and NAVA were delivered in random order to 18 infants born less than 32 weeks of gestation. Quasi oxygenation indices (“OI”) and alveolar-arterial (“A-a”) oxygen gradients at the end of each period on PAV, NAVA and baseline ventilation were calculated using capillary blood samples. The mean “OI” was not significantly different on PAV compared to NAVA (7.8 (standard deviation (SD) 3.2) versus 8.1 (SD 3.4), respectively, p = 0.70, but lower on both than on baseline ventilation (mean baseline “OI” 11.0 (SD 5.0)), p = 0.002, 0.004, respectively). The “A-a” oxygen gradient was higher on PAV and baseline ventilation than on NAVA (20.8 (SD 12.3) and 22.9 (SD 11.8) versus 18.5 (SD 10.8) kPa, p = 0.015, < 0.001, respectively).

Conclusion: Both NAVA and PAV improved oxygenation compared to conventional ventilation. There was no significant difference in the mean “OI” between the two modes, but the mean “A-a” gradient was better on NAVA.What is Known:• Proportional assist ventilation (PAV) and neurally adjusted ventilatory assist (NAVA) can improve the oxygenation index (OI) in prematurely born infants.• Both PAV and NAVA can provide support proportional to respiratory drive or demand throughout the respiratory cycle.What is New:• In infants with evolving or established BPD, using capillary blood samples, both PAV and NAVA compared to baseline ventilation resulted in improvement in the “OI”, but there was no significant difference in the “OI” on PAV compared to NAVA.• The “alveolar-arterial” oxygen gradient was better on NAVA compared to PAV.
Assessing key clinical parameters before and after intraventricular hemorrhage in very preterm infants
Authors: Lampe Renée , Rieger-Fackeldey Esther , Sidorenko Irina , Turova Varvara , Botkin Nikolai , Eckardt Laura , Alves-Pinto Ana , Kovtanyuk Andrey , Schündeln Michael , Felderhoff-Müser Ursula
Published: January 2020

Intraventricular cerebral hemorrhage (IVH) is one of the most severe complications of premature birth, potentially leading to lifelong disability. The purpose of this paper is the assessment of the evolution of three of the most relevant parameters, before and after IVH: mean arterial pressure (MAP), arterial carbon dioxide pressure (pCO2), and cerebral blood flow (CBF). Clinical records of 254 preterm infants with a gestational age of 23–30 weeks, with and without a diagnosis of IVH, were reviewed for MAP and arterial pCO2in the period up to 7 days before and 3 days after IVH or during the first 10 days of life in cases without IVH.

Conclusion: A statistically significant increase in pCO2and decrease in MAP in patients with IVH compared with those without were detected. Both the mean values and the mean absolute deviations of CBF were computed in this study, and the latter was significantly higher than in control group. High deviations of CBF, as well as hypercapnia and hypotension, are likely to contribute to the rupture of cerebral blood vessels in preterm infants, and consequently, to the development of IVH.What is Known:•The origin of IVH is multifactorial, but mean arterial pressure, carbon dioxide partial pressure, and cerebral blood flow are recognized as the most important parameters.• In premature infants, the autoregulation mechanisms are still underdeveloped and cannot compensate for cerebral blood flow fluctuations.What is New:•The numerical simulation of CBF is shown to be a promising approach that may be useful in the care of preterm infants.• The mean values of CBF before and after IVH in the affected group were similar to those in the control group, but the mean absolute deviations of CBF in the affected group before and after IVH were significantly higher than that in the control group.