bluuebunny/crossref_metadata_2025 huggingface dataset:
Tree growth as affected by stem and crown structure
Authors: Pretzsch Hans
Published: March 2021

Key message

Prediction of tree growth based on size or mass as proposed by the Metabolic Scaling Theory is an over-simplification and can be significantly improved by consideration of stem and crown morphology.

Tree growth and metabolic scaling theory, as well as corresponding growth equations, use tree volume or mass as predictors for growth. However, this may be an over-simplification, as the future growth of a tree may, in addition to volume or mass, also depend on its past development and aspects of the current inner structure and outer morphology. The objective of this evaluation was to analyse the effect of selected structural and morphological tree characteristics on the growth of common tree species in Europe. Here, we used eight long-term experiments with a total of 24 plots and extensive individual measurements of 1596 trees in monospecific stands of European beech (Fagus sylvatica L.), Norway spruce (Picea abies (L.) Karst.), Scots pine (Pinus sylvestris L.) and sessile oak (Quercus petraea (Matt.) Liebl.). Some of the experiments have been systematically surveyed since 1870. The selected plots represent a broad range of stand density, from fully to thinly stocked stands. We applied linear mixed models with random effects for analysing and modelling how tree growth and productivity are affected by stem and crown structure. We used the species-overarching relationship $$\mathrm{iv}={{a}_{0}\times v}$$

iv
=

a
0

×
v

between stem volume growth, $$\mathrm{iv}$$
iv
and stem volume, $$v,$$

v
,

as the baseline model. In this model $${a}_{0}$$

a
0

represents the allometric factor and α the allometric exponent. Then we included tree age, mean stem volume of the stand and structural and morphological tree variables in the model. This significantly reduced the AIC; RMSE was reduced by up to 43%. Interestingly, the full model estimating $$\mathrm{iv}$$
iv
as a function of $$v$$
v
and mean tree volume, crown projection area, crown ratio and mean tree ring width, revealed a $$\alpha \cong 3/4$$

α
≅
3
/
4

scaling for the relationship between $$\mathrm{iv}\propto {v}^{\alpha }$$

iv
∝

v

α

. This scaling corresponded with Kleiber’s rule and the West-Brown-Enquist model of the metabolic scaling theory. Simplified approaches based on stem diameter or tree mass as predictors may be useful for a rough estimation of stem growth in uniform stands and in cases where more detailed predictors are not available. However, they neglect other stem and crown characteristics that can have a strong additional effect on the growth behaviour. This becomes of considerable importance in the heterogeneous mixed-species stands that in many countries of the world are designed for forest restoration. Heterogeneous stand structures increase the structural variability of the individual trees and thereby cause a stronger variation of growth compared with monocultures. Stem and crown characteristics, which may improve the analysis and projection of tree and stand dynamics in the future forest, are becoming more easily accessible by Terrestrial laser scanning.
Tracing the SW border of the Svecofennian Domain in the Baltic Sea region: evidence from petrology and geochronology from a granodioritic migmatite
Authors: Salin Evgenia , Woodard Jeremy , Sundblad Krister
Published: March 2021

Geological investigations of a part of the crystalline basement in the Baltic Sea have been performed on a drill core collected from the depth of 1092–1093 m beneath the Phanerozoic sedimentary cover offshore the Latvian/Lithuanian border. The sample was analyzed for geochemistry and dated with the SIMS U–Pb zircon method. Inherited zircon cores from this migmatized granodioritic orthogneiss have an age of 1854 ± 15 Ma. Its chemical composition and age are correlated with the oldest generation of granitoids of the Transscandinavian Igneous Belt (TIB), which occur along the southwestern margin of the Svecofennian Domain in the Fennoscandian Shield and beneath the Phanerozoic sedimentary cover on southern Gotland and in northwestern Lithuania. It is suggested that the southwestern border of the Svecofennian Domain is located at a short distance to the SW of the investigated drill site. The majority of the zircon population shows that migmatization occurred at 1812 ± 5 Ma, with possible evidence of disturbance during the Sveconorwegian orogeny.
The density of rational lines on hypersurfaces: a bihomogeneous perspective
Authors: Brandes Julia
Published: March 2021

LetFbe a non-singular homogeneous polynomial of degreedinnvariables. We give an asymptotic formula of the pairs of integer points$$(\mathbf {x}, \mathbf {y})$$(x,y)with$$|\mathbf {x}| \leqslant X$$|x|⩽Xand$$|\mathbf {y}| \leqslant Y$$|y|⩽Ywhich generate a line lying in the hypersurface defined byF, provided that$$n > 2^{d-1}d^4(d+1)(d+2)$$n>2d-1d4(d+1)(d+2). In particular, by restricting to Zariski-open subsets we are able to avoid imposing any conditions on the relative sizes ofXandY.
Discrepancy of stratified samples from partitions of the unit cube
Authors: Kiderlen Markus , Pausinger Florian
Published: March 2021

We extend the notion of jittered sampling to arbitrary partitions and study the discrepancy of the related point sets. Let$${\varvec{\Omega }}=(\Omega _1,\ldots ,\Omega _N)$$Ω=(Ω1,…,ΩN)be a partition of$$[0,1]^d$$[0,1]dand let theith point in$${{\mathcal {P}}}$$Pbe chosen uniformly in theith set of the partition (and stochastically independent of the other points),$$i=1,\ldots ,N$$i=1,…,N. For the study of such sets we introduce the concept of a uniformly distributed triangular array and compare this notion to related notions in the literature. We prove that the expected$${{{\mathcal {L}}}_p}$$Lp-discrepancy,$${{\mathbb {E}}}{{{\mathcal {L}}}_p}({{\mathcal {P}}}_{\varvec{\Omega }})^p$$ELp(PΩ)p, of a point set$${{\mathcal {P}}}_{\varvec{\Omega }}$$PΩgenerated from any equivolume partition$${\varvec{\Omega }}$$Ωis always strictly smaller than the expected$${{{\mathcal {L}}}_p}$$Lp-discrepancy of a set ofNuniform random samples for$$p>1$$p>1. For fixedNwe consider classes of stratified samples based on equivolume partitions of the unit cube into convex sets or into sets with a uniform positive lower bound on their reach. It is shown that these classes contain at least one minimizer of the expected$${{{\mathcal {L}}}_p}$$Lp-discrepancy. We illustrate our results with explicit constructions for smallN. In addition, we present a family of partitions that seems to improve the expected discrepancy of Monte Carlo sampling by a factor of 2 for everyN.
Pandemic-related emergency psychiatric presentations for self-harm of children and adolescents in 10 countries (PREP-kids): a retrospective international cohort study
Authors: Ougrin Dennis , Wong Ben Hoi-ching , Vaezinejad Mehrak , Plener Paul L. , Mehdi Tauseef , Romaniuk Liana , Barrett Elizabeth , Hussain Haseena , Lloyd Alexandra , Tolmac Jovanka , Rao Manish , Chakrabarti Sulagna , Carucci Sara , Moghraby Omer S. , Elvins Rachel , Rozali Farah , Skouta Ereni , McNicholas Fiona , Kuruppuaracchi Natalie , Stevanovic Dejan , Nagy Peter , Davico Chiara , Mirza Hassan , Tufan Evren , Youssef Fatima , Meadowcroft Ben , Landau Sabine
Published: March 2021

To examine the differences in hospital emergency psychiatric presentations for self-harm of children and adolescents during the covid-19 lockdown in March and April 2020 compared with the same period in 2019. Retrospective cohort study. We used electronic patient records from 23 hospital emergency departments in ten countries grouped into 14 areas. We examined data on 2073 acute hospital presentations by 1795 unique children and adolescents through age 18. We examined the total number of emergency psychiatric hospital presentations and the proportion of children and adolescents presenting with severe self-harm as our two main outcome measures. In addition, we examined sociodemographic and clinical characteristics and clinical management variables for those presenting with self-harm. To compare the number of hospital presentations between 2020 and 2019 a negative binomial model was used. For other variables, individual participant data (IPD) meta-analyses were carried out. Emergency psychiatric hospital presentations decreased from 1239 in 2019 to 834 in 2020, incident rate ratio 0.67, 95% CI 0.62–0.73; p < 0.001. The proportion of children and adolescents presenting with self-harm increased from 50% in 2019 to 57% in 2020, odds ratio 1.33, 1.07–1.64; p = 0.009 but there was no difference in the proportion presenting with severe self-harm. Within the subpopulation presenting with self-harm the proportion of children and adolescents presenting with emotional disorders increased from 58 to 66%, odds ratio 1.58, 1.06–2.36; p = 0.025. The proportion of children and adolescents admitted to an observation ward also decreased from 13 to 9% in 2020, odds ratio 0.52, 0.28–0.96; p = 0.036. Service planners should consider that, during a lockdown, there are likely to be fewer emergency psychiatric presentations. Many children and adolescents with psychiatric emergencies might not receive any service. A focus on developing intensive community care services with outreach capabilities should be prioritised.
Personalized biomechanical tongue models based on diffusion-weighted MRI and validated using optical tracking of range of motion
Authors: Kappert K. D. R. , Voskuilen L. , Smeele L. E. , Balm A. J. M. , Jasperse B. , Nederveen A. J. , van der Heijden F.
Published: March 2021

For advanced tongue cancer, the choice between surgery and organ-sparing treatment is often dependent on the expected loss of tongue functionality after treatment. Biomechanical models might assist in this choice by simulating the post-treatment function loss. However, this function loss varies between patients and should, therefore, be predicted for each patient individually. In the present study, the goal was to better predict the postoperative range of motion (ROM) of the tongue by personalizing biomechanical models using diffusion-weighted MRI and constrained spherical deconvolution reconstructions of tongue muscle architecture. Diffusion-weighted MRI scans of ten healthy volunteers were obtained to reconstruct their tongue musculature, which were subsequently registered to a previously described population average or atlas. Using the displacement fields obtained from the registration, the segmented muscle fiber tracks from the atlas were morphed back to create personalized muscle fiber tracks. Finite element models were created from the fiber tracks of the atlas and those of the individual tongues. Via inverse simulation of a protruding, downward, left and right movement, the ROM of the tongue was predicted. This prediction was compared to the ROM measured with a 3D camera. It was demonstrated that biomechanical models with personalized muscles bundles are better in approaching the measured ROM than a generic model. However, to achieve this result a correction factor was needed to compensate for the small magnitude of motion of the model. Future versions of these models may have the potential to improve the estimation of function loss after treatment for advanced tongue cancer.
Assessing the Belt and Road Initiative as a narrative: Implications for institutional change and international firm strategy
Authors: Casas-Klett Tomas , Li Jiatao
Published: March 2021

This article explores the role of narratives as drivers that guide the institutional change associated with globalization and deglobalization. For China’s Belt and Road Initiative (BRI) to succeed as a driver of institutional change in favor of globalization, it must pass the narrative “virality” test and successfully contend with competing narratives. Rival narratives will be launched by firms and organizations worldwide that expect to win or lose from deglobalization or from new forms of globalization. This study develops a useful framework for establishing the extent to which China’s BRI is a genuine narrative or just a story. In this regard, four testable propositions are put forth to ascertain whether the BRI is values-based, extends an invitation to participate, is open-ended, and is associated with economic performance for both Chinese and non-Chinese participants. The analysis of the BRI-related institutional change that leads to globalization applies a theoretical lens centered on the narrative economics perspective and on the institution-based view and political economy perspective. Implications for BRI stakeholders, international business practitioners, and international business scholarship are outlined.
Full‐scale shake‐table tests on two unreinforced masonry cavity‐wall buildings: effect of an innovative timber retrofit
Authors: Miglietta Marco , Damiani Nicolò , Guerrini Gabriele , Graziotti Francesco
Published: March 2021

Two full-scale building specimens were tested on the shake-table at the EUCENTRE Foundation laboratories in Pavia (Italy), to assess the effectiveness of an innovative timber retrofit solution, within a comprehensive research campaign on the seismic vulnerability of existing Dutch unreinforced masonry structures. The buildings represented the end-unit of a two-storey terraced house typical of the North-Eastern Netherlands, a region affected by induced seismicity over the last few decades. This building typology is particularly vulnerable to earthquake excitation due to lack of seismic details and irregular distribution of large openings in masonry walls. Both specimens were built with the same geometry. Their structural system consisted of cavity walls, with interior load-bearing calcium-silicate leaf and exterior clay veneer, and included a first-floor reinforced concrete slab, a second-floor timber framing, and a roof timber structure supported by masonry gables. A timber retrofit was designed and installed inside the second specimen, providing an innovative sustainable, light-weight, reversible, and cost-effective technique, which could be extensively applied to actual buildings. Timber frames were connected to the interior surface of the masonry walls and completed by oriented strands boards nailed to them. The second-floor timber diaphragm was stiffened and strengthened by a layer of oriented-strand boards, nailed to the existing joists and to additional blocking elements through the existing planks. These interventions resulted also in improved wall-to-diaphragm connections with the inner leaf at both floors, while steel ties were added between the cavity-wall leaves. The application of the retrofit system favored a global response of the building with increased lateral capacities of the masonry walls. This paper describes in detail the bare and retrofitted specimens, compares the experimental results obtained through similar incremental dynamic shake-table test protocols up to near-collapse conditions, and identifies damage states and damage limits associated with displacements and deformations.
Sound absorption properties of wood-based pulp fibre foams
Authors: Cucharero Jose , Ceccherini Sara , Maloney Thad , Lokki Tapio , Hänninen Tuomas
Published: March 2021

In this study, sound absorbing materials were produced through foam forming technique using hardwood and softwood pulps with varying chemical composition, ultrastructural, and morphological properties as raw materials. The sound absorption properties of the produced foams were measured and related to the ultrastructure and the morphology of the pulp fibres. All the fibre foams provided sound absorption properties comparable to those of conventional porous materials used for acoustic purposes. In general, further processing, as well as smaller fibre dimensions contribute to improve the sound absorption properties of the pulp fibre foams. The results provide valuable insight on the optimization of wood-based sound absorbing materials.

Graphic abstract
Coexistence of the native mussel, Mytilus edulis, and the invasive Pacific oyster, Crassostrea (Magallana) gigas, does not affect their growth or mortality, but reduces condition of both species
Authors: Joyce Patrick W. S. , Smyth David M. , Dick Jaimie T. A. , Kregting Louise T.
Published: March 2021

Ecological impacts caused by invasive alien species can be severe but may vary depending upon environmental conditions. Many European populations of the native mussel, Mytilus edulis, have been invaded by the Pacific oyster, Crassostrea (Magallana) gigas. Although widespread invasions have occurred, interactions between M. edulis and C. gigas have largely been investigated with regards to competition for space and food as well as effects on species assemblages. Experimental investigation of competitive interactions on physiological responses of the two species requires further exploration. To this end, we used a 12-month field manipulation experiment to examine growth rates, mortality and condition indices of the two species occurring in monospecific and heterospecific groups. Growth rates and mortality of both species were similar in monospecific and heterospecific groups, whereas condition indices were significantly reduced for both species in heterospecific groups. Growth rates and condition indices also differed amongst experimental sites, potentially due to differing water motion. Shell weight-length relationships did not explain the observed differences in condition for either species. We show that coexistence between the two species may occur but could be detrimental for both species. We also provide a preliminary viewpoint that water motion can mediate competitive interactions between these species.
An integrated torque-vectoring control framework for electric vehicles featuring multiple handling and energy-efficiency modes selectable by the driver
Authors: Mangia Andrea , Lenzo Basilio , Sabbioni Edoardo
Published: March 2021

A key feature achievable by electric vehicles with multiple motors is torque-vectoring. Many control techniques have been developed to harness torque-vectoring in order to improve vehicle safety and energy efficiency. The majority of the existing contributions only deal with specific aspects of torque-vectoring. This paper presents an integrated approach allowing a smooth coordination among the main blocks that constitute a torque-vectoring control framework: (1) a reference generator, that defines target yaw rate and sideslip angle; (2) a high level controller, that works out the required total torque and yaw moment at the vehicle level; (3) a low level controller, that maps the required force and yaw moment into individual wheel torque demands. In this framework, the driver can select one among a number of driving modes that allow to change the vehicle cornering response and, as a second priority, maximise energy efficiency. For the first time, the selectable driving modes include an “Energy efficiency” mode that uses torque-vectoring to prioritise the maximisation of the vehicle energy efficiency, thus further increasing the vehicle driving range. Simulation results show the effectiveness of the proposed framework on an experimentally validated 14 degrees of freedom vehicle model.
Astrocytes as Perspective Targets of Exercise- and Caloric Restriction‐Mimetics
Authors: Lalo Ulyana , Pankratov Yuriy
Published: March 2021

Enhanced mental and physical activity can have positive effects on the function of aging brain, both in the experimental animals and human patients, although cellular mechanisms underlying these effects are currently unclear. There is a growing evidence that pre-clinical stage of many neurodegenerative diseases involves changes in interactions between astrocytes and neurons. Conversely, astrocytes are strategically positioned to mediate the positive influence of physical activity and diet on neuronal function. Thus, development of therapeutic agents which could improve the astroglia-neuron communications in ageing brain is of crucial importance. Recent advances in studies of cellular mechanisms of brain longevity suggest that astrocyte-neuron communications have a vital role in the beneficial effects of caloric restriction, physical exercise and their pharmacological mimetics on synaptic homeostasis and cognitive function. In particular, our recent data indicate that noradrenaline uptake inhibitor atomoxetine can enhance astrocytic Ca2+-signaling and astroglia-driven modulation of synaptic plasticity. Similar effects were exhibited by caloric restriction-mimetics metformin and resveratrol. The emerged data also suggest that astrocytes could be involved in the modulatory action of caloric restriction and its mimetics on neuronal autophagy. Still, the efficiency of astrocyte-targeting compounds in preventing age-related cognitive decline is yet to be fully explored, in particular in the animal models of neurodegenerative diseases and autophagy impairment.
Agreement between rhinomanometry and computed tomography-based computational fluid dynamics
Authors: Berger Manuel , Giotakis Aris I. , Pillei Martin , Mehrle Andreas , Kraxner Michael , Kral Florian , Recheis Wolfgang , Riechelmann Herbert , Freysinger Wolfgang
Published: March 2021

Purpose

Active anterior rhinomanometry (AAR) and computed tomography (CT) are standardized methods for the evaluation of nasal obstruction. Recent attempts to correlate AAR with CT-based computational fluid dynamics (CFD) have been controversial. We aimed to investigate this correlation and agreement based on an in-house developed procedure.

Methods

In a pilot study, we retrospectively examined five subjects scheduled for septoplasty, along with preoperative digital volume tomography and AAR. The simulation was performed with Sailfish CFD, a lattice Boltzmann code. We examined the correlation and agreement of pressure derived from AAR (RhinoPress) and simulation (SimPress) and these of resistance during inspiration by 150 Pa pressure drop derived from AAR (RhinoRes150) and simulation (SimRes150). For investigation of correlation between pressures and between resistances, a univariate analysis of variance and a Pearson’s correlation were performed, respectively. For investigation of agreement, the Bland–Altman method was used.

Results

The correlation coefficient between RhinoPress and SimPress was r = 0.93 (p < 0.001). RhinoPress was similar to SimPress in the less obstructed nasal side and two times greater than SimPress in the more obstructed nasal side. A moderate correlation was found between RhinoRes150 and SimRes150 (r = 0.65; p = 0.041).

Conclusion

The simulation of rhinomanometry pressure by CT-based CFD seems more feasible with the lattice Boltzmann code in the less obstructed nasal side. In the more obstructed nasal side, error rates of up to 100% were encountered. Our results imply that the pressure and resistance derived from CT-based CFD and AAR were similar, yet not same.
Empirical and theoretical perspectives in sales and operations planning
Authors: Kreuter Tobias , Scavarda Luiz Felipe , Thomé Antonio Márcio Tavares , Hellingrath Bernd , Seeling Marcelo Xavier
Published: March 2021

This paper’s purpose is to evaluate empirical and theoretical perspectives in Sales and Operations Planning (S&OP). The methodology consists of a systematic literature review, analysing 292 publications from academics and practitioners. The results reveal that the empirical evidence has been initially obtained by practitioners and subsequently acquired by academics with a growing interest in recent years. Three main research streams are identified: S&OP and performance, implementation of S&OP, and contextualisation of S&OP designs. The investigation of theoretical foundations reveals an upward trend in external general theory usage and first signs of internal theory development in S&OP. The research findings call for more exploratory research to enhance the knowledge in the identified research streams and their interrelation. Herein, applying the design science approach is recommended to integrate practitioners into academic research. Further implications embrace a call for more theory-informed empirical S&OP research in a two-prone agenda: applying general theories from other fields and developing internal theories through middle-range theorising. A limitation of this paper is its focus on empirical studies, not embracing conceptual papers. Applications of this paper’s findings can help academics and practitioners to advance their understanding of the S&OP phenomenon. The awareness of study findings in the three main research streams, combined with empirical and theoretical research implications, can support the development of solutions to improve the S&OP effectiveness and evidence-based decisions in real-life settings. This work’s originality lies in the analysis of the S&OP literature with the focus on the evolution of empirical evidence and the theoretical foundations.
A solution for factorial validity testing of three-item scales: An example of tau-equivalent strict measurement invariance of three-item loneliness scale
Authors: Czerwiński Stanisław K. , Atroszko Paweł Andrzej
Published: March 2021

Ultra-short scales are increasingly popular in surveys. Congeneric model fit of a three-item scale cannot be tested with Confirmatory Factor Analysis (CFA) without additional assumptions because the number of degrees of freedom is equal to zero. A more rigorous tau-equivalent model, assuming equality of factor loadings can be tested instead. The objective of this study was to demonstrate this approach with an example of the psychometric study of the Polish version of the Three-Item Loneliness Scale (TILS), and to discuss the arising problems and possible solutions. There seems to be a high need for such analysis because currently, some properties of CFA make it an approach still predominant over Item Response Theory (IRT) models in the quality of life research. A sample of 3510 students completed TILS together with the questionnaires measuring a variety of indicators of well-being. The results provided evidence for a good fit of a tau-equivalent model. Furthermore, multi-group CFAs provided support for strict measurement invariance of this model. To the Authors’ knowledge, it is the first practical application of a tau-equivalent model to testing the factorial validity of an ultra-short scale and probably the first empirical case of tau-equivalent measurement invariance in psychological literature in general. TILS showed good criterion validity and satisfactory reliability. Unidimensionality of three-item scales can be examined with a tau-equivalent model that has some favorable psychometric properties. However, it might be exceedingly restrictive in certain practical cases. When developing a new short scale, it is recommended to maintain at least four items.
Non-native speaker perception of Intelligent Virtual Agents in two languages: the impact of amount and type of grammatical mistakes
Authors: Obremski David , Lugrin Jean-Luc , Schaper Philipp , Lugrin Birgit
Published: March 2021

Having a mixed-cultural membership becomes increasingly common in our modern society. It is thus beneficial in several ways to create Intelligent Virtual Agents (IVAs) that reflect a mixed-cultural background as well, e.g., for educational settings. For research with such IVAs, it is essential that they are classified as non-native by members of a target culture. In this paper, we focus on variations of IVAs’ speech to create the impression of non-native speakers that are identified as such by speakers of two different mother tongues. In particular, we investigate grammatical mistakes and identify thresholds beyond which the agents is clearly categorised as a non-native speaker. Therefore, we conducted two experiments: one for native speakers of German, and one for native speakers of English. Results of the German study indicate that beyond 10% of word order mistakes and 25% of infinitive mistakes German-speaking IVAs are perceived as non-native speakers. Results of the English study indicate that beyond 50% of omission mistakes and 50% of infinitive mistakes English-speaking IVAs are perceived as non-native speakers. We believe these thresholds constitute helpful guidelines for computational approaches of non-native speaker generation, simplifying research with IVAs in mixed-cultural settings.
Assessing the costs and environmental benefits of IMO regulations of ship-originated SOx and NOx emissions in the Baltic Sea
Authors: Repka Sari , Erkkilä-Välimäki Anne , Jonson Jan Eiof , Posch Maximilian , Törrönen Janne , Jalkanen Jukka Pekka
Published: March 2021

To assess the value of the environmental benefits of the Sulphur Emission regulation (SECA) that came into force in 2015, changes in depositions of SOx and NOx from ship exhaust gas emissions were modelled and monetized for the Baltic Sea region for the years 2014 and 2016. During this period, the total deposition of SOx in the study area decreased by 7.3%. The decrease in ship-originated SOx deposition from 38 kt to 3.4 kt (by over 88%) was translated into a monetary value for the ecosystem impacts of nearly 130 million USD, according to the EcoValue08 model. This is less than the modelled health benefits, but it is not insignificant. For NOx, there was no decreasing trend. The exceedance of the critical loads of SOx and NOx was also estimated. The effect of Baltic shipping on the exceedance of critical loads of acidification after SECA is very small, but Baltic shipping still has a considerable effect on the exceedance of critical loads for eutrophication.
Mapping Viscoelastic Properties Using Helical Magnetic Nanopropellers
Authors: Ghosh Arijit , Ghosh Ambarish
Published: March 2021

Artificial micro/nanomachines have been envisioned and demonstrated as potential candidates for targeted drug or gene delivery, cell manipulation, environmental and biological sensing and in lab on chip applications. Here, we have used helical nanomachines to measure the local rheological properties of a viscoelastic media. The position of the helical nanomachine/nanopropeller was controlled precisely using magnetic fields with simultaneous measurements of the mechanical properties of a complex and heterogeneous fluidic environment. We demonstrated that the motion of the helical nanopropeller is extremely sensitive to fluid elasticity and the speed of propulsion of the nanopropeller can be used as a measure of the local elastic relaxation time. Taken together, we report a promising new technique of mapping the rheological properties by helical nanopropellers with very high spatial and temporal resolutions, with performance superior to existing techniques of passive or active microrheology.
MACMIC Reveals a Dual Role of CTCF in Epigenetic Regulation of Cell Identity Genes
Authors: Wang Guangyu , Xia Bo , Zhou Man , Lv Jie , Zhao Dongyu , Li Yanqiang , Bu Yiwen , Wang Xin , Cooke John P. , Cao Qi , Lee Min Gyu , Zhang Lili , Chen Kaifu
Published: March 2021

Numerous studies of relationship between epigenomic features have focused on their strong correlation across the genome, likely because such relationship can be easily identified by many established methods for correlation analysis. However, two features with little correlation may still colocalize at many genomic sites to implement important functions. There is no bioinformatic tool for researchers to specifically identify such feature pairs. Here, we develop a method to identify feature pairs in which two features have maximal colocalization minimal correlation (MACMIC) across the genome. By MACMIC analysis of 3306 feature pairs in 16 human cell types, we reveal a dual role of CCCTC-binding factor (CTCF) in epigenetic regulation of cell identity genes. Although super-enhancers are associated with activation of target genes, only a subset of super-enhancers colocalized with CTCF regulate cell identity genes. At super-enhancers colocalized with CTCF, CTCF is required for the active marker H3K27ac in cell types requiring the activation, and also required for the repressive marker H3K27me3 in other cell types requiring repression. Our work demonstrates the biological utility of the MACMIC analysis and reveals a key role for CTCF in epigenetic regulation of cell identity. The code for MACMIC is available at https://github.com/bxia888/MACMIC.
Gigantic Genomes Provide Empirical Tests of Transposable Element Dynamics Models
Authors: Wang Jie , Itgen Michael W. , Wang Huiju , Gong Yuzhou , Jiang Jianping , Li Jiatang , Sun Cheng , Sessions Stanley K. , Mueller Rachel Lockridge
Published: March 2021

Transposable elements (TEs) are a major determinant of eukaryotic genome size. The collective properties of a genomic TE community reveal the history of TE/host evolutionary dynamics and impact present-day host structure and function, from genome to organism levels. In rare cases, TE community/genome size has greatly expanded in animals, associated with increased cell size and changes to anatomy and physiology. Here, we characterize the TE landscape of the genome and transcriptome in an amphibian with a giant genome — the caecilianIchthyophis bannanicus, which we show has a genome size of 12.2 Gb. Amphibians are an important model system because the clade includes independent cases of genomic gigantism. The I. bannanicus genome differs compositionally from other giant amphibian genomes, but shares a low rate of ectopic recombination-mediated deletion. We examine TE activity using expression and divergence plots; TEs account for 15% of somatic transcription, and most superfamilies appear active. We quantify TE diversity in the caecilian, as well as other vertebrates with a range of genome sizes, using diversity indices commonly applied in community ecology. We synthesize previous models that integrate TE abundance, diversity, and activity, and test whether the caecilian meets model predictions for genomes with high TE abundance. We propose thorough, consistent characterization of TEs to strengthen future comparative analyses. Such analyses will ultimately be required to reveal whether the divergent TE assemblages found across convergent gigantic genomes reflect fundamental shared features of TE/host genome evolutionary dynamics.
Pediatric high risk neuroblastoma with autologous stem cell transplant – 20 years of experience
Authors: Khan Saadiya , AlSayyad Khulood , Siddiqui Khawar , AlAnazi Awatif , AlSeraihy Amal , AlAhmari Ali , ElSolh Hassan , Ghemlas Ibrahim , AlSaedi Hawazen , AlJefri Abdullah , Ali Afshan , AlFawaz Ibrahim , AlKofide Amani , Ayas Mouhab
Published: March 2021

Background and Objective:

Neuroblastoma is the most common extracranial solid tumor found in pediatric patients. High-risk neuroblastoma (HR-NBL) can be characterized by metastasis, age, and other tumor characteristics that result in an adverse outlook for this patient cohort. The standard of care includes induction chemotherapy, surgery, followed by stem cell autologous transplant (ASCT), and later, antidisialoganglioside (anti-GD2) antibodies. In this study, we provide the survival and toxicity data of our HR-NBL patients treated with a single ASCT.

Methods:

We retrospectively analyzed pediatric HR-NBL patients treated with single ASCT after a carboplatin, etoposide, and melphalan (CEM) regimen in our institution between January 1993 and December 2014.

Results:

There were 99 evaluable patients with male predominance. The median age at diagnosis was 3 years. Most of our HR-NBL patients were stage 4 (88%). All patients received ASCT. Peripheral blood was the graft source in 58% of the patients. Time for hematological count recovery with bone marrow as a graft source was prolonged but not statistically significant when compared with PBSCs. Of all the patients, 58% received radiation therapy to residual disease. Overt secondary leukemia was not seen in any of these patients. Three-year overall survival (OS) was 68.5% ± 5.2% and the 3-year event-free survival (EFS) was (48.3% ± 5.2%).

Conclusion:

Our HR-NBL patients tolerated high-dose chemotherapy well followed by single autologous stem cell transplant. Tandem transplant is a feasible option in our patient cohort. Apart from secondary solid tumors, there were no long-term complications seen.
Cost-Effectiveness Analysis: Lymph Node Transfer vs Lymphovenous Bypass for Breast Cancer-Related Lymphedema
Authors: Sekigami Yurie , Char Sydney , Mullen Cate , Huber Kathryn , Cao Yu , Buchsbaum Rachel , Graham Roger , Nardello Salvatore , Singhal Dhruv , Chatterjee Abhishek
Published: March 2021

BACKGROUND:

Lymph node transfer (LNT) and lymphovenous bypass (LVB) have been described as 2 major surgical options for patients with breast cancer-related lymphedema (BCRL) who have failed conservative therapy. The objective of our study was to perform a cost-effectiveness analysis comparing LNT and LVB for the treatment of BCRL.

STUDY DESIGN:

Rates of infection, lymph leak, and failure of LNT and LVB were obtained from a previously published meta-analysis. Failure of surgery was defined as the inability to cease compression therapy postoperatively. Procedural costs were calculated from Medicare reimbursement rates. Cost of conservative management of postoperative surgical site infection, lymph leak, and continued decongestive physiotherapy after failed surgery were obtained from literature review. Average utility scores for each health state were calculated using a visual analog scale survey, then converted to quality-adjusted life years (QALYs). A decision tree was constructed, and incremental cost-effectiveness ratio was assessed at $50,000/QALY. Deterministic and probabilistic sensitivity analyses were performed to evaluate the robustness of our findings.

RESULTS:

LNT was less costly ($22,492 vs $31,927) and more effective (31.82 QALY vs 29.24 QALY) than LVB. One-way (deterministic) sensitivity analysis demonstrated that LNT became cost-ineffective when its failure rate was more than 43.8%. LVB became more cost-effective than LNT when its failure rate was less than 21.4%. Probabilistic sensitivity analysis using Monte-Carlo simulation indicated that even with uncertainty present in the variables analyzed, the majority of simulations (97%) favored LNT as the more cost-effective strategy.

Conclusions: LNT is a dominant, cost-effective strategy compared to LVB for the treatment of BCRL.
Somatic Genetic Mosaicism in the Apolipoprotein E-null Mouse Aorta
Authors: Valencia-Morales María del Pilar , Sanchez-Flores Alejandro , Colín-Castelán Dannia , Alvarado-Caudillo Yolanda , Fragoso-Bargas Nicolás , López-González Gladys , Peña-López Tania , Ramírez-Nava Magda , de la Rocha Carmen , Rodríguez-Ríos Dalia , Lund Gertrud , Zaina Silvio
Published: March 2021

In addition to genetic and epigenetic inheritance, somatic variation may contribute to cardiovascular disease (CVD) risk. CVD-associated somatic mutations have been reported in human clonal hematopoiesis, but evidence in the atheroma is lacking. To probe for somatic variation in atherosclerosis, we sought single-nucleotide private variants (PVs) in whole-exome sequencing (WES) data of aorta, liver, and skeletal muscle of two C57BL/6J coisogenic male ApoE null/wild-type (WT) sibling pairs, and RNA-seq data of one of the two pairs. Relative to the C57BL/6 reference genome, we identified 9 and 11 ApoE null aorta- and liver-specific PVs that were shared by all WES and RNA-seq datasets. Corresponding PVs in WT sibling aorta and liver were 1 and 0, respectively, and not overlapping with ApoE null PVs. Pyrosequencing analysis of 4 representative PVs in 17 ApoE null aortas and livers confirmed tissue-specific shifts toward the alternative allele, in addition to significant deviations from mendelian allele ratios. Notably, all aorta and liver PVs were present in the dbSNP database and were predominantly transition mutations within atherosclerosis-related genes. The majority of PVs were in discrete clusters approximately 3 Mb and 65 to 73 Mb away from hypermutable immunoglobin loci in chromosome 6. These features were largely shared with previously reported CVD-associated somatic mutations in human clonal hematopoiesis. The observation that SNPs exhibit tissue-specific somatic DNA mosaicism in ApoE null mice is potentially relevant for genetic association study design. The proximity of PVs to hypermutable loci suggests testable mechanistic hypotheses.
Pre-Hospital Antiplatelet Therapy for STEMI Patients Undergoing Primary Percutaneous Coronary Intervention: What We Know and What Lies Ahead
Authors: Fabris Enrico , Korjian Serge , Coller Barry S. , Ten Berg Jurrien M. , Granger Christopher B. , Gibson C. Michael , van 't Hof Arnoud W. J.
Published: March 2021

Early recanalization of the infarct-related artery to achieve myocardial reperfusion is the primary therapeutic goal in patients with ST-elevation myocardial infarction (STEMI). To decrease the duration of ischaemia, continuous efforts have been made to improve pre-hospital treatment and to target the early period after symptom onset. In this period the platelet content of the fresh coronary thrombus is maximal and the thrombi are dynamic, and thus more susceptible to powerful antiplatelet agents. There have been substantial advances in antiplatelet therapy in the last three decades with several classes of oral and intravenous antiplatelet agents with different therapeutic targets, pharmacokinetics, and pharmacodynamic properties. New parenteral drugs achieve immediate inhibition of platelet aggregation, and fast and easy methods of administration may create the opportunity to bridge the initial gap in platelet inhibition observed with oral P2Y12 inhibitors. Moreover, potential future management of STEMI could directly involve patients in the process of care with self-administered antiplatelet agents designed to achieve rapid reperfusion. However, the potential anti-ischaemic benefits of potent antiplatelet agents will need to be balanced against their risk of increased bleeding. This study presents a comprehensive and updated review of pre-hospital antiplatelet therapy among STEMI patients undergoing primary percutaneous intervention and explores new therapies under development.
Sulodexide in the Treatment of Patients with Early Stages of COVID-19: A Randomized Controlled Trial
Authors: Gonzalez-Ochoa Alejandro J. , Raffetto Joseph D. , Hernández Ana G. , Zavala Nestor , Gutiérrez Obed , Vargas Arturo , Loustaunau Jorge
Published: March 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may induce several vascular endothelial-dependent systemic complications, and sulodexide has pleiotropic actions on the vascular endothelium, which may prove beneficial. We aimed to assess the effect of sulodexide when used within 3 days of coronavirus disease 2019 (COVID-19) clinical onset. We conducted a randomized placebo-controlled outpatient trial. To be included, patients must have been at high risk for severe clinical progression. Participants received sulodexide (oral 1,000 LRU/d) or placebo for 21 days. The primary endpoint was the need for hospital care. Also assessed were patients' need for supplemental oxygen as well as D-dimer and C-reactive protein (CRP) levels, thromboembolic events, major bleeding, and mortality. A total of 243 patients were included in the per-protocol analysis from June 5 to August 30, 2020. Of these, 124 received sulodexide and 119 received a placebo. Only 17.7% of the patients in the sulodexide group required hospitalization, compared with 29.4% in the placebo group (p = 0.03). This benefit persisted in the intention-to-treat analysis (15% in sulodexide group vs. 24% with placebo [p = 0.04]). With sulodexide, fewer patients required supplemental oxygen (30 vs. 42% [p = 0.05]). After 2 weeks, fewer patients had D-dimer levels >500 ng/dL (22 vs. 47% [p < 0.01]), and patients also had lower mean CRP levels (12.5 vs. 17.8 mg/dL [p < 0.01]). There were no between-group differences in thromboembolic events, major bleeding, or mortality. Treatment of COVID-19 patients with sulodexide, when provided within 3 days of clinical onset, improved their clinical outcomes. Although the results should be confirmed, sulodexide could be valuable in an outpatient setting.
Congenital Heart Defects in Patients with Classic Bladder Exstrophy: A Hitherto Neglected Association?
Authors: Promm Martin , Gerling Stephan , Schepp Carsten P. , Rösch Wolfgang H.
Published: March 2021

Introduction Classic bladder exstrophy (BE) is regarded as an isolated malformation without any further anomalies, but some studies have indicated a higher incidence of cardiac anomalies. This cross-sectional study is planned to evaluate the prevalence of congenital heart defects (CHDs) and the clinical relevance for patients with BE admitted for primary closure.

Materials and Methods Patients were prospectively recruited between March 2012 and January 2019. Patients' profiles including demographic data, results of transthoracic echocardiography (TTE), as well as essential peri- and postoperative data were assessed.

Results Thirty-nine (25 boys and 14 girls) patients with BE (median age 61 days) underwent delayed primary bladder closure. Thirty-seven (24 boys and 13 girls) patients had received TTE 1 day before surgery. CHD was detected in 7 (18.9%) out of the 39 patients, but no clinical differences between patients with and without CHD were observed peri- or postoperatively.

Discussion and Conclusion This prospective systematic evaluation shows an even higher rate of CHD in patients with BE than assumed previously. Although peri- and postoperative outcome did not differ between patients with and without CHD, we consider TTE an important additional method for ensuring a safe peri- and postoperative courses and a short- and long-term care for patients with CHD.
Conformers, Properties of the Anticancer Drug Plocabulin, and its Binding Mechanism with p-Glycoprotein: DFT and MD Studies
Authors: Lü Xudong , Ma Yufei , Tao Yulian , Yan Fei , Song Ce , Wang Cuihong , Zhang Meiling
Published: March 2021

Plocabulin (PM060184) is a promising new anticancer drug as a microtubule inhibitor. The conformational structure and properties of plocabulin have been studied theoretically. The initial structure was screened by the B3LYP/3-21G* method, and then 32 unique conformations were further optimised with the B3LYP/6-311G* method. The single-point energies were determined at the M06-L/6-311G(2df,p) level. The UV excitation of the most stable plocabulin conformation in methanol was studied by the TD-CAM-B3LYP/6-311G(2df,p) method. High-quality human p-glycoprotein model was obtained through homology modelling. The binding interaction between p-glycoprotein and plocabulin was studied by docking and MD simulation. LEU65, TYR310, ILE340, THR945, PHE983, MET986, and GLN990 were found to be important amino acid residues in the interaction. From a certain perspective, the ‘reverse exclusion’ mechanism of plocabulin with p-glycoprotein was illustrated, and this mechanism provides theoretical guidance for the structural modification of plocabulin and for design of drug’s to avoid p-glycoprotein-mediated drug resistance.