bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential activity and selectivity of N-terminal modified CXCL12 chemokines at the CXCR4 and ACKR3 receptors
Authors: Jaracz-Ros Agnieszka , Bernadat Guillaume , Cutolo Pasquale , Gallego Carmen , Gustavsson Martin , Cecon Erika , Baleux Françoise , Kufareva Irina , Handel Tracy M. , Bachelerie Françoise , Levoye Angélique
Published: May 2020

Chemokines play critical roles in numerous physiologic and pathologic processes through their action on seven-transmembrane (TM) receptors. The N-terminal domain of chemokines, which is a key determinant of signaling via its binding within a pocket formed by receptors’ TM helices, can be the target of proteolytic processing. An illustrative case of this regulatory mechanism is the natural processing of CXCL12 that generates chemokine variants lacking the first two N-terminal residues. Whereas such truncated variants behave as antagonists of CXCR4, the canonical G protein-coupled receptor of CXCL12, they are agonists of the atypical chemokine receptor 3 (ACKR3/CXCR7), suggesting the implication of different structural determinants in the complexes formed between CXCL12 and its two receptors. Recent analyses have suggested that the CXCL12 N-terminus first engages the TM helices of ACKR3 followed by the receptor N-terminus wrapping around the chemokine core. Here we investigated the first stage of ACKR3-CXCL12 interactions by comparing the activity of substituted or N-terminally truncated variants of CXCL12 toward CXCR4 and ACKR3. We showed that modification of the first two N-terminal residues of the chemokine (K1R or P2G) does not alter the ability of CXCL12 to activate ACKR3. Our results also identified the K1R variant as a G protein-biased agonist of CXCR4. Comparative molecular dynamics simulations of the complexes formed by ACKR3 either with CXCL12 or with the P2G variant identified interactions between the N-terminal 2–4 residues of CXCL12 and a pocket formed by receptor's TM helices 2, 6, and 7 as critical determinants for ACKR3 activation.
SARS‐CoV‐2: Structural diversity, phylogeny, and potential animal host identification of spike glycoprotein
Authors: Dabravolski Siarhei Alexander , Kavalionak Yury Kazimirovich
Published: May 2020

To investigate the evolutionary history of the current pandemic outbreak of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), a total of 137 genomes of coronavirus strains with release dates between January 2019 and 25 March 2020, were analyzed. To investigate the potential intermediate host of the SARS‐CoV‐2, we analyzed spike glycoprotein sequences from different animals, with particular emphasis on bats. We performed phylogenetic analysis and structural reconstruction of the spike glycoproteins with subsequent alignment and comparison. Our phylogenetic results revealed that SARS‐CoV‐2 was more similar to the bats' betacoronavirus isolates: HKU5‐related from Pipistrellus abramus and HKU4‐related from Tylonycteris pachypus. We also identified a yak betacoronavirus strain, YAK/HY24/CH/2017, as the closest match in the comparison of the structural models of spike glycoproteins. Interestingly, a set of unique features has been described for this particular strain of the yak betacoronavirus. Therefore, our results suggest that the human SARS‐CoV‐2, responsible for the current outbreak of COVID‐19, could also come from yak as an intermediate host.
Sex difference in the development of hepatocellular carcinoma after direct‐acting antiviral therapy in patients with HCV infection
Authors: Watanabe Takao , Tokumoto Yoshio , Joko Kouji , Michitaka Kojiro , Horiike Norio , Tanaka Yoshinori , Tada Fujimasa , Kisaka Yoshiyasu , Nakanishi Seiji , Yamauchi Kazuhiko , Yukimoto Atsushi , Nakamura Yoshiko , Hirooka Masashi , Abe Masanori , Hiasa Yoichi
Published: May 2020

Sex differences in the predictors for hepatocellular carcinoma (HCC) development after direct‐acting antiviral (DAA) therapy was investigated. DAA therapy was given to 1438 (663 male, 775 female) patients. Sex differences in the HCC development rate and the factors contributing to HCC development after DAA therapy were investigated. Male patients had a significantly higher cumulative HCC incidence (log‐rank test, P =  .007). On multivariate analysis, the fibrosis‐4 index (HR = 1.11; 95%CI, 1.042‐1.202, P =  .002) and posttreatment α‐fetoprotein (AFP) (HR = 1.11; 95%CI, 1.046‐1.197, P  =  .001) were found to be independent factors that contributed to HCC development following DAA therapy in female patients, whereas only posttreatment AFP (HR  =  1.090; 95%CI, 1.024‐1.160, P  = .007) was an independent factor in male patients. The optimal posttreatment AFP cut‐off values were set based on receiver operating characteristic curve analyses. The optimal posttreatment AFP cut‐off value was much higher in females (6.0 ng/mL) than in male (3.5 ng/mL) patients. In conclusion both in male and female patients, posttreatment AFP was an independent predictor of HCC development after DAA therapy. However, the cut‐off values differed between the sexes. In male patients, HCC could be seen in patients with relatively low posttreatment AFP levels; more careful observation might be needed in such patients.
Joint line elevation and tibial slope are associated with increased polyethylene wear in cruciate‐retaining total knee replacement
Authors: Pourzal Robin , Cip Johannes , Rad Elmira , Laurent Michel P. , Berger Richard A. , Jacobs Joshua J. , Wimmer Markus A.
Published: May 2020

The purpose of this retrieval study was to determine the effect of implant positioning on wear, taking patient‐related factors into account. Therefore, the volumetric material loss of 59 retrieved tibial liners was quantitatively determined using a coordinate measuring‐machine. All retrievals were made of the same polyethylene and design by a single manufacturer. Using time in‐situ and linear regression, a wear rate for each liner was determined and corrected for bedding‐in. Backside damage was qualitatively scored. The following implant positioning parameters were obtained from radiographs: anatomical lateral‐distal femoral angle, anatomical medial‐proximal tibial angle, femoral tilt angle, and posterior tibial slope. The patella position was assessed by the Blackburne‐Peel index and the Insall‐Salvati ratio. Unlike the Insall‐Salvati ratio, the Blackburne‐Peel index is known to detect surgical joint line elevation. Using general linear modeling the most impactful factors on wear rate and backside damage was determined, thereby taking patient demographic factors into account. The mean volumetric wear rate was 11.6 mm3/y. Wear decreased with older age (P = .021) and female sex (P = .001). The wear rate increased with joint line elevation as indicated from a decreased Blackburne‐Peel index (P = .019), and increased with increased posterior tibial slope (P = .026). The backside damage score also increased with joint line elevation (P = .036). A Blackburne‐Peel index decrease of 0.1, signifying joint line elevation, was found to increase the wear rate by 1.8 mm3/y and increase back‐sided wear. A high tibial slope (>7°) led to a 9.3 mm3/y increase in wear rate compared with a low tibial slope (<3°). The results of this study demonstrate that tibial liner positioning has a significant impact on polyethylene wear with potential implications on osteolysis over time.
Effect of stress‐shielding‐induced bone resorption on glenoid loosening in reverse total shoulder arthroplasty
Authors: Zhang Min , Gregory Thomas , Hansen Ulrich , Cheng Cheng‐Kung
Published: May 2020

Aseptic loosening of the glenoid component is one of the main reasons for the high revision rates of reverse total shoulder arthroplasty (RTSA). It has been reported that the bulky implant designs may lead to stress shielding. However, it is uncertain whether the shielding effect is severe enough to lead to bone resorption and glenoid loosening. The purpose of this study was to evaluate the level of stress‐shielding and assess whether bone resorption plays a role in aseptic glenoid loosening following RTSA. A cadaveric in vitro test model was used to validate a finite element model (FEM) of the scapula. The FEM of the scapula, incorporating adaptive bone remodeling algorithms, was used to predict changes in postoperative bone density after RTSA. Changes in bone strength after implantation were also analyzed. The strain values predicted from the FEM of the scapula were in agreement with the in vitro measurements. Analysis of postoperative bone adaptation revealed that strain‐induced bone resorption began at the peg of the implant and around the resected bone surface and then gradually expended to the peripheral regions. The bone strength also reduced postoperatively and appeared particularly around the implant peg. Strain‐induced bone resorption is a likely source of the bone loss commonly observed in RTSA. The finite element glenoid bone remodeling simulation may be used as a tool to evaluate glenoid implant design.
Sedimentary and foraminiferal records of Late Quaternary environmental change west of Ireland and implications for the last British–Irish Ice Sheet
Authors: Peters Jared L. , Benetti Sara , Dunlop Paul , Wheeler Andrew J.
Published: May 2020

Palaeoenvironmental change following deglaciation of the last British–Irish Ice Sheet on the continental shelf west of Ireland was investigated using multiproxy analyses of sediment and foraminifera data from nine sediment cores. Lithofacies associations record various depositional regimes across the shelf, which evolve from subglacial to postglacial conditions. Census data provide the first characterisation of benthic foraminifera populations across the continental shelf and multivariate analyses reveal three distinct biotopes. Biomineralization within these biotopes is restricted to ≤21 200 cal a bp by four radiocarbon ages. The transition from glacial to postglacial benthic foraminifera populations near the shelf break marks the establishment of productive, nutrient‐rich, ice‐distal conditions at ~20 900 cal a bp; these conditions may also mark the start of favourable conditions for postglacial cold‐water coral growth. Postglacial conditions on the inner shelf were not established until <14 500 cal a bp, suggesting glacial conditions west of Ireland may have persisted into the Bølling–Allerød Interstadial.
Enzyme‐catalyzed acylation improves gel properties of rapeseed protein isolate
Authors: Chen Chong , Zhang Cheng , Zhang Ruixue , Ju Xingrong , He Rong , Wang Zhigao
Published: May 2020

BACKGROUND

Although rapeseed protein isolate (RPI) possessed some good functional properties, the use of RPI as an ingredient in the food industry is restricted mainly due to its inferior gelation. The purpose of this study was to improve the heat‐induced gel properties of RPI using double processes of acylation and additional transglutaminase catalysis.

RESULTS

Scanning electron microscopy showed that the gel formed by native RPI exhibited randomly aggregated particulate network structures whereas transglutaminase (TG)‐assisted RPI gels significantly improved gelation properties. More importantly, the combined modifications of RPI using TG‐assisted acylation can form a gel with unique percolating and small porous structure. Furthermore, TG‐catalyzed 5% acylated RPI gel (100 U g‐1, protein basis) exhibited excellent gel properties in terms of gel strength, thermal stability, surface roughness and apparent viscosity compared to non‐treated or single modification of RPI gel as determined by texture analyzer, atomic force microscopy and rheometer. Mechanistically, Fourier‐transform infrared spectra and gel dissociation test revealed that TG‐catalyzed acylation extensively unfolded the hydrophobic and sulfhydryl residues of RPI, in turn, reinforced re‐assembly of protein molecules via hydrophobic interactions and disulfide bonds during gel formation.

CONCLUSION

Combined processes of acylation and additional TG catalysis improved the thermal gelation properties by altering inter‐ and intra‐protein structures. Such sequential processes will provide a promising approach to improve the protein gelation that could be potentially applied in the food industry. © 2020 Society of Chemical Industry
Ellagic acid induces esophageal squamous cell carcinoma cell apoptosis by modulating SHP‐1/STAT3 signaling
Authors: Xu Ying‐Ying , Wang Wan‐Wei , Huang Jing , Zhu Wei‐Guo
Published: May 2020

Ellagic acid (EA) has been reported to have antiproliferative and antioxidant properties, but its function in esophageal squamous cell carcinoma (ESCC) has not been investigated yet. In the current study, EA was found have a significant anti‐tumor activity in ESCC. In specific, EA inhibited ESCC cell survival in both of a concentration‐ and time‐dependent manner. And our results showed that EA promoted ESCC cell apoptosis, including inducing the cleavages of PARP, and inhibiting the expression of anti‐apoptotic proteins. In mechanistic, EA markedly suppressed STAT3‐driven luciferase activity, and inhibited both of the endogenous and cytokines‐induced STAT3 activation in ESCC cells. Further investigations indicated that EA could significantly upregulate SHP‐1 expression, a negative modulator of STAT3 signaling. In contrast, knockdown of SHP‐1 could attenuate the effects of EA on inhibiting ESCC cell survival. Moreover, we found that EA could inhibit RNF6 expression, an E3 of SHP‐1, and overexpressing RNF6 could also significantly attenuate the effects of EA on inhibiting ESCC cell survival, which further revealed that EA could inhibit STAT3 signaling by modulating RNF6/SHP‐1 axis. Our present study indicated that EA could be as a novel STAT3 inhibitor for the treatment of ESCC.
Friction and wear properties of phenolic composites with dual inorganic oxide‐modified titanate whiskers
Authors: Chen Yinjie , Song Renfeng , Guo Ke , Wang Tao , Zhao Yunhui , Zhu Kongying , Yuan Xiaoyan
Published: May 2020

Inorganic oxides, alumina and silica, were successively modified on titanate whiskers surface. Enrolled into phenolic resin, the phenolic/whisker composites were prepared by melting molding, with intentions for wearing property. The alumina‐coated whisker surface fulfilled wear resistance, while the outer silica layer was less stiff for compatible with polymer matrix. The dual surface modifications improved the whiskers dispersion in the matrix, enhanced interfacial adhesion, and significantly triggered wear resistance of the composites. With 7.5 wt% multiply modified whiskers involved, the phenolic composite showed specific wear rate of 0.49 × 10−5 mm3/Nm, remarkably lower than that of phenolic resin (4.79 × 10−5 mm3/Nm). The worn surface of the composites detected by a scanning electron microscope showed abrasive wear with slight fatigue wear. Optical microscope images indicated that the whisker‐filled composite had a shallow scratch on the worn surface, which positively favored wear resistance.
Trajectories of Big Five Personality Traits: A Coordinated Analysis of 16 Longitudinal Samples
Authors: Graham Eileen K. , Weston Sara J. , Gerstorf Denis , Yoneda Tomiko B. , Booth Tom , Beam Christopher R. , Petkus Andrew J. , Drewelies Johanna , Hall Andrew N. , Bastarache Emily D. , Estabrook Ryne , Katz Mindy J. , Turiano Nicholas A. , Lindenberger Ulman , Smith Jacqui , Wagner Gert G. , Pedersen Nancy L. , Allemand Mathias , Spiro Avron , Deeg Dorly J.H. , Johansson Boo , Piccinin Andrea M. , Lipton Richard B. , Schaie K. Warner , Willis Sherry , Reynolds Chandra A. , Deary Ian J. , Hofer Scott M. , Mroczek Daniel K.
Published: May 2020

This study assessed change in self–reported Big Five personality traits. We conducted a coordinated integrative data analysis using data from 16 longitudinal samples, comprising a total sample of over 60 000 participants. We coordinated models across multiple datasets and fit identical multi–level growth models to assess and compare the extent of trait change over time. Quadratic change was assessed in a subset of samples with four or more measurement occasions. Across studies, the linear trajectory models revealed declines in conscientiousness, extraversion, and openness. Non–linear models suggested late–life increases in neuroticism. Meta–analytic summaries indicated that the fixed effects of personality change are somewhat heterogeneous and that the variability in trait change is partially explained by sample age, country of origin, and personality measurement method. We also found mixed evidence for predictors of change, specifically for sex and baseline age. This study demonstrates the importance of coordinated conceptual replications for accelerating the accumulation of robust and reliable findings in the lifespan developmental psychological sciences. © 2020 European Association of Personality Psychology
Decline in internal migration levels in Australia: Compositional or behavioural effect?
Authors: Kalemba Sunganani Violet , Bernard Aude , Charles‐Edwards Elin , Corcoran Jonathan
Published: May 2020

Levels of internal migration have declined since the 1980s in many advanced economies. Australian studies remain largely descriptive, making it difficult to ascertain the extent to which the decline in aggregate levels of migration is due to shifts in the socio‐demographic composition of the Australian population or driven by deeper behavioural changes. This paper aims to address this gap by applying an Oaxaca‐Blinder decomposition method to individual‐level data from the 2001 and 2016 censuses. Our results confirm the strong impact of population ageing on the decline in migration although its effect has been fully counteracted by other compositional changes such as education and immigration. We find behavioural effects to be the principal factor explaining this downward trend. This finding points to a secular shift in migration behaviour and represents a starting point in developing a more comprehensive understanding of the factors underpinning the long‐term decline in internal migration in Australia.
Using G‐Rich Sequence to Enhance the Peroxidase‐Mimicking Activity of DNA‐Cu/Ag Nanoclusters for Rapid Colorimetric Detection of Hydrogen Peroxide and Glucose
Authors: Du Zhiwei , Wei Chunying
Published: May 2020

Four kinds of DNA‐based Ag and Cu/Ag nanoclusters (NCs) were synthesized and their fluorescence properties were investigated at pH 7.0 and 5.5. Among them the Cu/Ag NCs templated by DNA containing both C‐rich and G‐rich sequences (the c‐myc TBA−Cu/Ag NCs) give the strongest and the most stable fluorescence emission at ∼555 nm under neutral and acidic conditions. Unexpectedly, the c‐myc TBA−Cu/Ag NCs can catalyze efficiently and rapidly the reaction of hydrogen peroxide (H2O2) with 3,3′,5,5′‐tetramethylbenzidine (TMB) to produce blue TMB oxide (TMBox) under acidic conditions, indicating the high peroxidase‐mimicking activity. Based on this nanozyme the detection for H2O2 and glucose was performed using colorimetric method. The results indicate that the linear range of detection for H2O2 is from 0.1 to 1 mM with the detection limit (LOD) of 7.42 μM, while the linear range is from 0.1 to 0.7 mM and LOD was calculated to be 9.38 μM for glucose. Additionally, glucose can be successfully detected in diluted serum samples and has an acceptable recovery rate, indicating that this nanozyme has a potential application prospect.
DNA‐Driven Two‐Layer Core–Satellite Gold Nanostructures for Ultrasensitive MicroRNA Detection in Living Cells
Authors: Meng Dan , Ma Wei , Wu Xiaoling , Xu Chuanlai , Kuang Hua
Published: May 2020

It is a significant challenge to achieve controllable self‐assembly of superstructures for biological applications in living cells. Here, a two‐layer core–satellite assembly is driven by a Y‐DNA, which is designed with three nucleotide chains that hybridized through complementary sequences. The two‐layer core–satellite nanostructure (C30S5S10 NS) is constructed using 30 nm gold nanoparticles (Au NPs) as the core, 5 nm Au NPs as the first satellite layer, and 10 nm Au NPs as the second satellite layer, resulting in a very strong circular dichroism (CD) and surface‐enhanced Raman scattering. After optimization, the yield is up to 85%, and produces a g‐factor of 0.16 × 10−2. The hybridization of the target microRNA (miRNA) with the molecular probe causes a significant drop in the CD and Raman signals, and this phenomenon is used to detect the miRNA in living cells. The CD signal has a good linear range of 0.011–20.94 amol ngRNA−1 and a limit of detection (LOD) of 0.0051 amol ngRNA−1, while Raman signal with the range of 0.052–34.98 amol ngRNA−1 and an LOD of 2.81 × 10−2 amol ngRNA−1. This innovative dual‐signal method can be used to quantify biomolecules in living cells, opening the way for ultrasensitive, highly accurate, and reliable diagnoses of clinical diseases.
Electroweak phase transition in non-minimal Higgs sectors
Authors: Basler Philipp , Mühlleitner Margarete , Müller Jonas
Published: May 2020

Abstract

Higgs sector extensions beyond the Standard Model (BSM) provide additional sources of CP violation and further scalar states that help to trigger a strong first order electroweak phase transition (SFOEWPT) required to generate the observed baryon asymmetry of the Universe through electroweak baryogenesis. We investigate the CP-violating 2-Higgs-Doublet Model (C2HDM) and the Next-to-Minimal 2-Higgs-Doublet Model (N2HDM) with respect to their potential to generate an SFOEWPT while being compatible with all relevant and recent theoretical and experimental constraints. The implications of an SFOEWPT on the collider phenomenology of the two models are analysed in detail in particular with respect to Higgs pair production. We provide benchmark points for parameter points that are compatible with an SFOEWPT and provide distinct di-Higgs signatures.
The minimal seesaw model with a modular S4 symmetry
Authors: Wang Xin , Zhou Shun
Published: May 2020

Abstract

In this paper, we incorporate the modular S4 flavor symmetry into the supersymmetric version of the minimal type-I seesaw model, in which only two right-handed neutrino singlets are introduced to account for tiny Majorana neutrino masses, and explore its implications for the lepton mass spectra, flavor mixing and CP violation. The basic idea is to assign two right-handed neutrino singlets into the unique two-dimensional irreducible representation of the modular S4 symmetry group. Moreover, we show that the matter-antimatter asymmetry in our Universe can be successfully explained via the resonant leptogenesis mechanism working at a relatively-low seesaw scale ΛSS≈ 107 GeV, with which the potential problem of the gravitino overproduction can be avoided. In this connection, we emphasize that the observed matter-antimatter asymmetry may lead to a stringent constraint on the parameter space and testable predictions for low-energy observables.
Perturbative 4D conformal field theories and representation theory of diagram algebras
Authors: de Mello Koch Robert , Ramgoolam Sanjaye
Published: May 2020

Abstract

The correlators of free four dimensional conformal field theories (CFT4) have been shown to be given by amplitudes in two-dimensional so(4, 2) equivariant topological field theories (TFT2), by using a vertex operator formalism for the correlators. We show that this can be extended to perturbative interacting conformal field theories, using two representation theoretic constructions. A co-product deformation for the conformal algebra accommodates the equivariant construction of composite operators in the presence of non-additive anomalous dimensions. Explicit expressions for the co-product deformation are given within a sector of $$ \mathcal{N} $$
N
= 4 SYM and for the Wilson-Fischer fixed point near four dimensions. The extension of conformal equivariance beyond integer dimensions (relevant for the Wilson-Fischer fixed point) leads to the definition of an associative diagram algebra U★, abstracted from Uso(d) in the limit of large integer d, which admits extension of Uso(d) representation theory to general real (or complex) d. The algebra is related, via oscillator realisations, to so(d) equivariant maps and Brauer category diagrams. Tensor representations are constructed where the diagram algebra acts on tensor products of a fundamental diagram representation. A similar diagrammatic algebra U★, 2, related to a general d extension for Uso(d, 2) is defined, and some of its lowest weight representations relevant to the Wilson-Fischer fixed point are described.
Duality and transport for supersymmetric graphene from the hemisphere partition function
Authors: Gupta Rajesh Kumar , Herzog Christopher P. , Jeon Imtak
Published: May 2020

Abstract

We use localization to compute the partition function of a four dimensional, supersymmetric, abelian gauge theory on a hemisphere coupled to charged matter on the boundary. Our theory has eight real supercharges in the bulk of which four are broken by the presence of the boundary. The main result is that the partition function is identical to that of $$ \mathcal{N} $$
N
= 2 abelian Chern-Simons theory on a three-sphere coupled to chiral multiplets, but where the quantized Chern-Simons level is replaced by an arbitrary complexified gauge coupling τ. The localization reduces the path integral to a single ordinary integral over a real variable. This integral in turn allows us to calculate the scaling dimensions of certain protected operators and two-point functions of abelian symmetry currents at arbitrary values of τ. Because the underlying theory has conformal symmetry, the current two-point functions tell us the zero temperature conductivity of the Lorentzian versions of these theories at any value of the coupling. We comment on S-dualities which relate different theories of supersymmetric graphene. We identify a couple of self-dual theories for which the complexified conductivity associated to the U(1) gauge symmetry is τ/2.
Traumatic brain injury and alcohol intoxication: effects on injury patterns and short-term outcome
Authors: Leijdesdorff Henry Alexander , Legué Juno , Krijnen Pieta , Rhemrev Steven , Kleinveld Sanne , Schipper Inger Birgitta
Published: May 2020

Purpose

A significant number of patients with traumatic brain injuries (TBI) are diagnosed with elevated blood alcohol concentration (BAC). Recent literature suggests a neuroprotective effect of alcohol on TBI, possibly associated with less morbidity and mortality. Our goal is to analyze the association of different levels of BAC with TBI characteristics and outcome.

Methods

Adult patients with moderate to severe TBI (AIS ≥ 2) and measured BAC admitted to the Trauma Centre West (TCW), during the period 2010–2015, were retrospectively analyzed. Data included injury severity (AIS), length of hospitalization, admittance to the Intensive Care Unit (ICU) and in-hospital mortality. The association of BAC with ICU admittance and in-hospital mortality was analyzed using multivariable logistic regression analysis with correction for potentially confounding variables.

Results

BACs were available in 2,686 patients of whom 42% had high, 26% moderate, 6% low and 26% had normal levels. Patients with high BAC’s were predominantly male, were younger, had lower ISS scores, lower AIS-head scores and less concomitant injuries compared to patients in the other BAC subgroups. High BACs were associated with a lower risk for in-hospital mortality (AOR 0.36, 95% CI 0.14–0.97). Also, patients with moderate and high BACs were less often admitted to the ICU (respectively, AOR 0.36, 95% CI 0.25–0.52 and AOR 0.40, 95% CI 0.29–0.57).

Conclusion

The current study suggests that in patients with moderate to severe TBI, increasing BACs are associated with less severe TBI, less ICU admissions and a higher survival. Further research into the pathophysiological mechanism is necessary to help explain these findings.
Adrenal insufficiency is a contraindication for omalizumab therapy in mast cell activation disease: risk for serum sickness
Authors: Molderings G. J. , Dumoulin F. L. , Homann J. , Sido B. , Textor J. , Mücke M. , Qagish G. J. , Barion R. , Raithel M. , Klingmüller D. , Schäfer V. S. , Hertfelder H. J. , Berdel D. , Tridente G. , Weinstock L. B. , Afrin L. B.
Published: May 2020

Omalizumab is an effective therapeutic humanized murine IgE antibody in many cases of primary systemic mast cell activation disease (MCAD). The present study should enable the clinician to recognize when treatment of MCAD with omalizumab is contraindicated because of the potential risk of severe serum sickness and to report our successful therapeutic strategy for such adverse event (AE). Our clinical observations, a review of the literature including the event reports in the FDA AE Reporting System, the European Medicines Agency Eudra-Vigilance databases (preferred search terms: omalizumab, Xolair®, and serum sickness) and information from the manufacturer’s Novartis database were used. Omalizumab therapy may be more likely to cause serum sickness than previously thought. In patients with regular adrenal function, serum sickness can occur after 3 to 10 days which resolves after the antigen and circulating immune complexes are cleared. If the symptoms do not resolve within a week, injection of 20 to 40 mg of prednisolone on two consecutive days could be given. However, in MCAD patients whose adrenal cortical function is completely suppressed by exogenous glucocorticoid therapy, there is a high risk that serum sickness will be masked by the MCAD and evolve in a severe form with pronounced damage of organs and tissues, potentially leading to death. Therefore, before the application of the first omalizumab dose, it is important to ensure that the function of the adrenal cortex is not significantly limited so that any occurring type III allergy can be self-limiting.
Shifts of finite type as fundamental objects in the theory of shadowing
Authors: Good Chris , Meddaugh Jonathan
Published: May 2020

Shifts of finite type and the notion of shadowing, or pseudo-orbit tracing, are powerful tools in the study of dynamical systems. In this paper we prove that there is a deep and fundamental relationship between these two concepts. Let X be a compact totally disconnected space and $$f:X\rightarrow X$$f:X→X a continuous map. We demonstrate that f has shadowing if and only if the system $$(f,X)$$(f,X) is (conjugate to) the inverse limit of a directed system satisfying the Mittag-Leffler condition and consisting of shifts of finite type. In particular, this implies that, in the case that X is the Cantor set, f has shadowing if and only if (f, X) is the inverse limit of a sequence satisfying the Mittag-Leffler condition and consisting of shifts of finite type. Moreover, in the general compact metric case, where X is not necessarily totally disconnected, we prove that f has shadowing if $$(f,X)$$(f,X) is a factor of the inverse limit of a sequence satisfying the Mittag-Leffler condition and consisting of shifts of finite type by a quotient that almost lifts pseudo-orbits.
Tightly shut: flexible valve margins and microstructural asymmetry in pterioid bivalves
Authors: Harper Elizabeth M. , Checa Antonio G.
Published: May 2020

An organic-rich columnar prismatic outer shell layer, which extends far beyond the underlying nacre, has allowed pterioid bivalves (the pearl oysters and their allies) to develop flexible valve margins, allowing a tight hermetic seal when shut. In some taxa, the microstructural arrangement is known to be asymmetrically developed between the two valves. The asymmetry was surveyed across 29 taxa of pterioids (including representatives of known genera) confirming that it is typically the right valve which has a greater expanse of prism-only shell (and less nacre) and showing that this portion of the right valve has more organic content (more than twice the value in some instances) than the equivalent in the left. A more detailed investigation of prismatic material in Pteria penguin comparing the right and left valves revealed that the right valve flange has a higher density of smaller prisms, each with its organic envelope, and not a greater thickness of the organic envelopes themselves. The flange is also thinner on the right valve and shown here to be very flexible when wet. This allows it to bend against the rigid left valve when the shell is closed. Comparison of this structural asymmetry in the pterioids with five outgroup taxa in the Ostreidae and Pinnidae suggests that clades with the asymmetry have been freed from the constraints of a flattened valve morphology and to develop inequivalved forms.
A linear-time branching-time perspective on interface automata
Authors: Vogler Walter , Lüttgen Gerald
Published: May 2020

Over the past two decades, de Alfaro and Henzinger’s interface automata (IA) have become a popular formal framework for the component-based specification of concurrent systems. IA’s parallel composition assumes that a component may wait on inputs but never on outputs, implying that an output must be consumed immediately or a communication error occurs. By now, the literature contains a number of semantics for IA: linear-time semantics based on traces observing communication errors, quiescence and/or divergence, as well as branching-time semantics based on alternating simulation. This article surveys these semantics from Rob van Glabbeek’s linear-time branching-time perspective, which does not consider settings with communication errors. We shed light onto the subtleties implied by IA’s pruning of all behaviour that might lead a component to autonomously enter an error state, and investigate when exactly de Alfaro and Henzinger’s restriction of input-determinism is needed. In addition, we introduce several new semantics for IA, in particular the linear-time ready semantics and the branching-time ready simulation.
Characteristic invariants in Hennessy–Milner logic
Authors: Jasper Marc , Schlüter Maximilian , Steffen Bernhard
Published: May 2020

In this paper, we prove that Hennessy–Milner Logic (HML), despite its structural limitations, is sufficiently expressive to specify an initial property $$\varphi _0$$φ0 and a characteristic invariant $$\upchi _{_I}$$χI for an arbitrary finite-state process P such that $$\varphi _0 \wedge \mathbf{AG }(\upchi _{_I})$$φ0∧AG(χI) is a characteristic formula for P. This means that a process Q, even if infinite state, is bisimulation equivalent to P iff $$Q \models \varphi _0 \wedge \mathbf{AG }(\upchi _{_I})$$Q⊧φ0∧AG(χI). It follows, in particular, that it is sufficient to check an HML formula for each state of a finite-state process to verify that it is bisimulation equivalent to P. In addition, more complex systems such as context-free processes can be checked for bisimulation equivalence with P using corresponding model checking algorithms. Our characteristic invariant is based on so called class-distinguishing formulas that identify bisimulation equivalence classes in P and which are expressed in HML. We extend Kanellakis and Smolka’s partition refinement algorithm for bisimulation checking in order to generate concise class-distinguishing formulas for finite-state processes.
Implementation of eHealth and AI integrated diagnostics with multidisciplinary digitized data: are we ready from an international perspective?
Authors: Bukowski Mark , Farkas Robert , Beyan Oya , Moll Lorna , Hahn Horst , Kiessling Fabian , Schmitz-Rode Thomas
Published: May 2020

Digitization of medicine requires systematic handling of the increasing amount of health data to improve medical diagnosis. In this context, the integration of the versatile diagnostic information, e.g., from anamnesis, imaging, histopathology, and clinical chemistry, and its comprehensive analysis by artificial intelligence (AI)–based tools is expected to improve diagnostic precision and the therapeutic conduct. However, the complex medical environment poses a major obstacle to the translation of integrated diagnostics into clinical research and routine. There is a high need to address aspects like data privacy, data integration, interoperability standards, appropriate IT infrastructure, and education of staff. Besides this, a plethora of technical, political, and ethical challenges exists. This is complicated by the high diversity of approaches across Europe. Thus, we here provide insights into current international activities on the way to digital comprehensive diagnostics. This includes a technical view on challenges and solutions for comprehensive diagnostics in terms of data integration and analysis. Current data communications standards and common IT solutions that are in place in hospitals are reported. Furthermore, the international hospital digitalization scoring and the European funding situation were analyzed. In addition, the regional activities in radiomics and the related publication trends are discussed. Our findings show that prerequisites for comprehensive diagnostics have not yet been sufficiently established throughout Europe. The manifold activities are characterized by a heterogeneous digitization progress and they are driven by national efforts. This emphasizes the importance of clear governance, concerted investments, and cooperation at various levels in the health systems.

Key Points

•Europe is characterized by heterogeneity in its digitization progress with predominantly national efforts. Infrastructural prerequisites for comprehensive diagnostics are not given and not sufficiently funded throughout Europe, which is particularly true for data integration.

•The clinical establishment of comprehensive diagnostics demands for a clear governance, significant investments, and cooperation at various levels in the healthcare systems.

•While comprehensive diagnostics is on its way, concerted efforts should be taken in Europe to get consensus concerning interoperability and standards, security, and privacy as well as ethical and legal concerns.
Storyline description of Southern Hemisphere midlatitude circulation and precipitation response to greenhouse gas forcing
Authors: Mindlin Julia , Shepherd Theodore G. , Vera Carolina S. , Osman Marisol , Zappa Giuseppe , Lee Robert W. , Hodges Kevin I.
Published: May 2020

As evidence of climate change strengthens, knowledge of its regional implications becomes an urgent need for decision making. Current understanding of regional precipitation changes is substantially limited by our understanding of the atmospheric circulation response to climate change, which to a high degree remains uncertain. This uncertainty is reflected in the wide spread in atmospheric circulation changes projected in multimodel ensembles, which cannot be directly interpreted in a probabilistic sense. The uncertainty can instead be represented by studying a discrete set of physically plausible storylines of atmospheric circulation changes. By mining CMIP5 model output, here we take this broader perspective and develop storylines for Southern Hemisphere (SH) midlatitude circulation changes, conditioned on the degree of global-mean warming, based on the climate responses of two remote drivers: the enhanced warming of the tropical upper troposphere and the strengthening of the stratospheric polar vortex. For the three continental domains in the SH, we analyse the precipitation changes under each storyline. To allow comparison with previous studies, we also link both circulation and precipitation changes with those of the Southern Annular Mode. Our results show that the response to tropical warming leads to a strengthening of the midlatitude westerly winds, whilst the response to a delayed breakdown (for DJF) or strengthening (for JJA) of the stratospheric vortex leads to a poleward shift of the westerly winds and the storm tracks. However, the circulation response is not zonally symmetric and the regional precipitation storylines for South America, South Africa, South of Australia and New Zealand exhibit quite specific dependencies on the two remote drivers, which are not well represented by changes in the Southern Annular Mode.
Probabilistic neural network-based 2D travel-time tomography
Authors: Earp Stephanie , Curtis Andrew
Published: May 2020

Travel-time tomography for the velocity structure of a medium is a highly nonlinear and nonunique inverse problem. Monte Carlo methods are becoming increasingly common choices to provide probabilistic solutions to tomographic problems but those methods are computationally expensive. Neural networks can often be used to solve highly nonlinear problems at a much lower computational cost when multiple inversions are needed from similar data types. We present the first method to perform fully nonlinear, rapid and probabilistic Bayesian inversion of travel-time data for 2D velocity maps using a mixture density network. We compare multiple methods to estimate probability density functions that represent the tomographic solution, using different sets of prior information and different training methodologies. We demonstrate the importance of prior information in such high-dimensional inverse problems due to the curse of dimensionality: unrealistically informative prior probability distributions may result in better estimates of the mean velocity structure; however, the uncertainties represented in the posterior probability density functions then contain less information than is obtained when using a less informative prior. This is illustrated by the emergence of uncertainty loops in posterior standard deviation maps when inverting travel-time data using a less informative prior, which are not observed when using networks trained on prior information that includes (unrealistic) a priori smoothness constraints in the velocity models. We show that after an expensive program of network training, repeated high-dimensional, probabilistic tomography is possible on timescales of the order of a second on a standard desktop computer.
Anticipatory experience in everyday autonomous driving
Authors: Lindgren Thomas , Fors Vaike , Pink Sarah , Osz Katalin
Published: May 2020

In this paper, we discuss how people’s user experience (UX) of autonomous driving (AD) cars can be understood as a shifting anticipatory experience, as people experience degrees of AD through evolving advanced driver assistance systems (ADAS) in their everyday context. We draw on our ethnographic studies of five families, who had access to AD research cars with evolving ADAS features in their everyday lives for a duration of 1½ years. Our analysis shows that people gradually adopt AD cars, through a process that involves anticipating if they can trust them, what the ADAS features will do and what the longer-term technological possibilities will be. It also showed that this anticipatory UX occurs within specific socio-technical and environmental circumstances, which could not be captured easily in experimental settings. The implication is that studying anticipation offers us new insights into how people adopt AD in their everyday commute driving.
Nonlinear optical microscopy is a novel tool for the analysis of cutaneous alterations in pseudoxanthoma elasticum
Authors: Kiss Norbert , Fésűs Luca , Bozsányi Szabolcs , Szeri Flóra , Van Gils Matthias , Szabó Viktória , Nagy Anikó Ilona , Hidvégi Bernadett , Szipőcs Róbert , Martin Ludovic , Vanakker Olivier , Arányi Tamás , Merkely Béla , Wikonkál Norbert M. , Medvecz Márta
Published: May 2020

Pseudoxanthoma elasticum (PXE, OMIM 264800) is a rare autosomal recessive disorder with ectopic mineralization and fragmentation of elastin fibers. It is caused by mutations of the ABCC6 gene that leads to decreased serum levels of inorganic pyrophosphate (PPi) anti-mineralization factor. The occurrence of severe complications among PXE patients highlights the importance of early diagnosis so that prompt multidisciplinary care can be provided to patients. We aimed to examine dermal connective tissue with nonlinear optical (NLO) techniques, as collagen emits second-harmonic generation (SHG) signal, while elastin can be excited by two-photon excitation fluorescence (TPF). We performed molecular genetic analysis, ophthalmological and cardiovascular assessment, plasma PPi measurement, conventional histopathological examination, and ex vivo SHG and TPF imaging in five patients with PXE and five age- and gender-matched healthy controls. Pathological mutations including one new variant were found in the ABCC6 gene in all PXE patients and their plasma PPi level was significantly lower compared with controls. Degradation and mineralization of elastin fibers and extensive calcium deposition in the mid-dermis was visualized and quantified together with the alterations of the collagen structure in PXE. Our data suggests that NLO provides high-resolution imaging of the specific histopathological features of PXE-affected skin. In vivo NLO may be a promising tool in the assessment of PXE, promoting early diagnosis and follow-up.
A two-layer elasto-visco-plastic rheological model for the material parameter identification of bone tissue
Authors: Reisinger Andreas G. , Frank Martin , Thurner Philipp J. , Pahr Dieter H.
Published: May 2020

The ability to measure bone tissue material properties plays a major role in diagnosis of diseases and material modeling. Bone’s response to loading is complex and shows a viscous contribution to stiffness, yield and failure. It is also ductile and damaging and exhibits plastic hardening until failure. When performing mechanical tests on bone tissue, these constitutive effects are difficult to quantify, as only their combination is visible in resulting stress–strain data. In this study, a methodology for the identification of stiffness, damping, yield stress and hardening coefficients of bone from a single cyclic tensile test is proposed. The method is based on a two-layer elasto-visco-plastic rheological model that is capable of reproducing the specimens’ pre- and postyield response. The model’s structure enables for capturing the viscously induced increase in stiffness, yield, and ultimate stress and for a direct computation of the loss tangent. Material parameters are obtained in an inverse approach by optimizing the model response to fit the experimental data. The proposed approach is demonstrated by identifying material properties of individual bone trabeculae that were tested under wet conditions. The mechanical tests were conducted according to an already published methodology for tensile experiments on single trabeculae. As a result, long-term and instantaneous Young’s moduli were obtained, which were on average 3.64 GPa and 5.61 GPa, respectively. The found yield stress of 16.89 MPa was lower than previous studies suggest, while the loss tangent of 0.04 is in good agreement. In general, the two-layer model was able to reproduce the cyclic mechanical test data of single trabeculae with an root-mean-square error of 2.91 ± 1.77 MPa. The results show that inverse rheological modeling can be of great advantage when multiple constitutive contributions shall be quantified based on a single mechanical measurement.
Multi-grounded action research
Authors: Goldkuhl Göran , Cronholm Stefan , Lind Mikael
Published: May 2020

The research approach of multi-grounded action research (MGAR) is presented and analyzed. This is based on a review of issues and concerns in information systems action research. MGAR builds on the epistemological principles of multi-grounding. This combines empirical, theoretical and internal grounding. The multi-grounded approach builds on elements from grounded theory; i.e. building theory inductively from data through coding procedures, but it also comprises an abductive use of extant theory. MGAR is described through six knowledge contributions: (1) the MGAR process model, (2) the MGAR knowledge model, (3) the MGAR theory model, (4) the principle of the multi-grounded change outcome, (5) the principle of the multi-grounded theory outcome and (6) the principle of mutuality of purposes. MGAR has been applied in an IT service management (ITSM) case, which serves an illustration and a validation of MGAR. In this MGAR case, the improvement of ITSM has been conducted and studied through a multi-organizational setting. In the case, there was a special focus on the service quality of IT services and the relations between service providers and customers.