bluuebunny/crossref_metadata_2025 huggingface dataset:
Trichterbrust-Korrektur-OP unter Zuhilfenahme einer 3-D-Rekonstruktion des Thorax zur präoperativen Anpassung des Korrekturstabes
Authors: Scheuermann-Poley Catharina , Andreß Sebastian Martin , Willy Christian , Lieber André
Published: July 2021

Hintergrund Die Trichterbrust ist eine angeborene Deformität des Thoraxskeletts, bei der das Sternum und die angrenzenden Rippen trichterförmig in Richtung Wirbelsäule einsinken. Die
Pathogenese ist bisher nicht eindeutig geklärt. Es gibt verschiedene Therapieansätze, von konservativen Maßnahmen über minimalinvasive Eingriffe bis hin zur offenen Korrektur-OP. Die
betroffenen Patienten leiden unter der ästhetischen Beeinträchtigung sowie kardiopulmonalen Einschränkungen durch die Einengung des Mediastinalraumes. Die Indikationsstellung zur
Trichterbrust-Korrektur-OP unterliegt funktionellen und ästhetischen Gründen.

Patienten Wir berichten über einen 23-jährigen männlichen Patienten mit einer subjektiv beeinträchtigenden und objektiv mäßiggradigen Trichterbrust. Präoperativ wurde ein CT des
Thorax angefertigt. Der sternovertebrale Abstand betrug 8 cm, der Thoraxquerdurchmesser 28,9 cm (Haller-Index 3,6). Im präoperativen Lungenfunktionstest zeigte sich eine leichte Restriktion.
Anamnestisch beschrieb der sonst gesunde Patient Kurzatmigkeit bei stärkerer Anstrengung. Die Indikation zur Trichterbrust-Korrektur-OP wurde gestellt. Diese erfolgte in kombinierter
Operationstechnik: untere Sternotomie und Knorpelkeilresektion nach Brunner/Grob sowie Implantation eines Metallbügels ohne seitliche Antirotationsplatte. Ein zeitaufwendiger Schritt der OP
besteht in der intraoperativen Anpassung des Metallbügels. Daher fertigten wir im Vorfeld der OP anhand des Thorax-CTs eine 3-D-Rekonstruktion des knöchernen Thorax mittels 3-D-Drucker an.
Der Metallbügel wurde daran angepasst und im OP eingesetzt. Dies verkürzte die Operationsdauer um mindestens 15 min.

Ergebnisse In den postoperativen Nachuntersuchungen zeigten sich ein aufgerichteter Trichter und ein zufriedenstellendes ästhetisches Ergebnis. Sieben Monate nach Implantation
erfolgte die planmäßige Stabexplantation. Die postoperative CT-Kontrolle ergab nun einen Haller-Index von 3,25, der Lungenfunktionstest eine funktionelle Verbesserung. Subjektiv war der
Patient allzeit beschwerdefrei.

Schlussfolgerung Die Implantatanfertigung am 3-D-Modell hilft, OP-Zeit zu sparen. Die Praktikabilität ist noch nicht etabliert, da durch die Erstellung eines 3-D-Modells des
knöchernen Thorax ein anderweitig höherer Aufwand entsteht. Mit zunehmender Digitalisierung der medizinischen Welt ist es jedoch vorstellbar, dass zukünftig die Erstellung von digitalen und
realen 3-D-Modellen einfacher und kostengünstiger wird.
Neuropeptides, Inflammation, Biofilms, and diabetic Foot Ulcers
Authors: Yang Shaoling , Hu Liye , Han Rui , Yang Yiwen
Published: July 2021

A diabetic foot ulcer (DFU) is a serious complication in patients with diabetes mellitus (DM). A DFU is the most common cause of non-traumatic limb amputation, and patients with DFUs have increased mortality rates within 5 years after amputation. DFUs also increase the risk of cardiovascular and cerebrovascular diseases; therefore, with the increasing incidence and prevalence of diabetic foot wounds, DFUs are gradually becoming a major public health problem. The pathophysiology of DFUs is complicated and remains unclear. In recent years, many studies have demonstrated that the pathophysiology of DFUs is especially associated with neuropeptides, inflammation, and biofilms. Neuropeptides, especially substance P (SP) and calcitonin gene-related peptide (CGRP), play an important role in wound healing. SP and CGRP accelerate the healing of cutaneous wounds by promoting neovascularization, inhibiting the release of certain proinflammatory chemokines, regulating macrophage polarization, and so on. However, the expression of SP and CGRP was downregulated in DM and DFUs. DFUs are characterized by a sustained inflammatory phase. Immune cells such as neutrophils and macrophages are involved in the sustained inflammatory phase in DFUs by extracellular traps (NETs) and dysregulated macrophage polarization, which delays wound healing. Furthermore, DFUs are at increased risk of biofilm formation. Biofilms disturb wound healing by inducing a chronic inflammatory response, inhibiting macrophage phagocytosis and keratinocyte proliferation migration, and transferring antimicrobial resistance genes. To understand the relationships among neuropeptides, inflammation, biofilms, and DFUs, this review highlights the recent scientific advances that provide possible pathophysiological insights into the delayed healing of DFUs.
Poorly Understood Pelvic Venous Disorders Require a Multidisciplinary Approach
Authors: Doganci Suat
Published: July 2021

Pelvic venous diseases encompasses all chronic pathologies of pelvic veins caused by venous hypertension and retrograde flow in pelvic veins. It is commonly unexplained and often underdiagnosed cause of chronic pelvic pain in women of productive age. Pelvic venous pathologies are a part of multidisciplinary problem that should be considered in a holistic approach. Newly offered SVP classification may help correctly classifying patients and using the same nomenclature. Endovascular treatment options are highly effective with good long-term results. Patients with inconclusive gynecologists examinations should be referred to a specialist for the investigation of pelvic venous disorders.
Advances in the Semi-Synthesis of Triterpenoids
Authors: Liao Jin-Xi , Sun Jian-Song , Hu Zhen-Ni , Liu Hui
Published: July 2021

Recent achievements in triterpenoid semi-synthesis are discussed in this short review, which is divided into three parts according to the type of synthetic strategy being employed. These strategies include functionalization, modification of the carbon skeleton, and glycosylation. In the section on functionalization strategies, both functional group interconversions and new functional group installations on triterpenoid starting materials are described. The section on modification of the carbon skeleton is divided into three parts according to the tactic being applied, and incorporates rearrangement of the carbon skeleton, ring scission, and introduction of an additional heterocyclic ring. Meanwhile, in the section on glycosylation, notable achievements in the semi-synthesis of both natural and artificial triterpene saponins are discussed. Overall, the pivotal transformations that have brought about striking chemical structure variations of triterpenoid starting materials are highlighted herein, and it is hoped that this short review will provide inspiration to both established and new investigators engaged in this field of research.

1 Introduction

2 Semi-Synthesis of Triterpenoids via Functionalization Strategies

2.1 Functionalization of Rings with Functional Groups

2.2 Functionalization of a Side Chain

2.3 Functionalization of Rings without Existing Functional Groups

2.4 Functionalization of Angular Methyl Groups

2.5 Functionalization of Angular Methyl Groups and Functional-Group-Free Rings

2.6 Multisite Modifications

3 Semi-Synthesis of Triterpenoids via C-Skeleton Modification Strategies

3.1 Rearrangement Tactics

3.2 Ring-Opening Tactics

3.3 Additional Ring Introduction Tactics

4 emi-Synthesis of Triterpenoids via a Glycosylation Strategy

5 Conclusions and Outlook
Factor momentum, option-implied volatility scaling, and investor sentiment
Authors: Grobys Klaus , Kolari James W. , Rutanen Jere
Published: July 2021

Factor momentum produces robust average returns that exhibit a similar economic magnitude as stock price momentum. To the extent that the post-earnings announcement drift (PEAD) factor captures mispricing, winner factors earn profits from being long on underpriced stocks and short on overpriced stocks. Conversely, loser-factors’ negative exposure to the PEAD factor suggests that loser factors capture mispricing by being long on overpriced stocks and short on underpriced stocks. Option-implied volatility scaling increases both the economic magnitude and statistical significance of factor momentum. Factor momentum is not exposed to the same crashes as stock price momentum and therefore could provide a hedge for stock price momentum crash risks. Also, factor momentum mispricing is more pronounced when investor sentiment is high.
An Investigation of Five Component [3+2] Self-Assembled Cage Formation Using Amidinium···Carboxylate Hydrogen Bonds
Authors: Thomas Chriso M. , Foyle Émer M. , Walker Samuel E. , White Nicholas G.
Published: July 2021

The assembly of hydrogen bonded cages using amidinium···carboxylate hydrogen bonding interactions was investigated. A new tris-amidinium hydrogen bond donor tecton based on a tetraphenylmethane scaffold was prepared and its self-assembly with the terephthalate anion studied, and a new tricarboxylate hydrogen bond acceptor tecton was synthesised and its assembly with the 1,3-benzenebis(amidinium) hydrogen bond donor explored. In both cases, molecular modelling indicated that the formation of the cages was geometrically feasible and 1H NMR spectroscopic evidence was consistent with interactions between the components in competitive d6-DMSO solvent mixtures. DOSY NMR spectroscopy of both systems indicated that both components diffuse at the same rate as each other, and diffusion coefficients were consistent with cage formation, and with the formation of assemblies significantly larger than the individual components. An X-ray crystal structure showed that one of the assemblies did not have the desired cage structure in the solid state.
A system of circumstantial evidence for fact-finding in criminal trial
Authors: Ri Yong-Sok , Kwon Yong-Min , Pang Wi-Song
Published: July 2021

One of the most intractable, but significant problems in the theory of legal evidence concerns circumstantial
evidence. The diversity and complexity of criminal cases cause some bottlenecks and difficulties in developing reasonable methods
to prove the criminal issue by means of circumstantial evidence. The main purpose of this paper is to present more effective
methods of fact-finding just by means of a system of circumstantial evidence (SCE). On the basis of analysis of the nature of
circumstantial evidence, we find it necessary for the prosecution to construct a SCE in order to make a judge or jury accept the
prosecution’s conclusion as the best explanation. We also present a reasonable logical structure of such a system and address some
legal and logical problems in introducing it.
Lingue, dialetti e religione nelle aree occitane e francoprovenzali
Authors: Rivoira Matteo
Published: July 2021

Astratta

Gli stretti e complessi rapporti tra religione e lingua sono ormai uno degli ambiti di studio della sociologia del linguaggio. L’adozione in ambito religioso di determinati codici discende in genere dalla disponibilità di varietà elaborate nel repertorio linguistico comunitario, ma al contempo essa può determinare ristrutturazioni del repertorio stesso,in primissullo status delle lingue implicate. Lingua e religione, inoltre, possono essere individuate come forti simboli di appartenenza a una storia e a un’identità culturale. Nel presente lavoro saranno tratteggiati gli aspetti storici e macro-sociolinguistici che caratterizzano l’area galloromanza italiana (Valle d’Aosta e Piemonte occidentale). Ne verranno in particolare presentate le strutture repertoriali e discusso il ruolo del francese e delle altre varietà locali nel contesto religioso, caratterizzato dalla presenza storica di due diverse confessioni cristiane (cattolica e evangelica valdese). Infine saranno discusse le scelte linguistiche e religiose operate nei diversi contesti, in una prospettiva tesa ad evidenziare le implicazioni identitarie.
La romaní in Italia tra rappresentazione e legittimazione
Authors: Scala Andrea
Published: July 2021

Astratta

L’articolo esamina le dinamiche connesse con la (auto-)rappresentazione e la legittimazione della romaní in Italia. Comunità di lingua romaní sono presenti in Italia fin dalla prima età moderna e tutti i parlanti di romaní di antico insediamento nella penisola sono cittadini italiani, tuttavia la legge 482/1999 della Repubblica Italiana "Norme in materia di tutela delle minoranze linguistiche storiche" non include la romaní tra le lingue di minoranza da tutelare. L’esclusione della romaní dalla legge trova la sua radice prima in un’errata rappresentazione dei suoi locutori, generalmente percepiti come nomadi, mentre non lo sono più da tempo. La legge 482/1999 di fatto tutela le minoranze linguistiche legate a un territorio e la falsa, ma diffusa, percezione dei parlanti romaní come nomadi ha offerto un comodo pretesto a chi voleva escludere dalla tutela la lingua dei rom e dei sinti italiani. Il panorama linguistico della romaní in Italia risulta assai complesso e l’articolo si sforza di descriverlo e spiegarlo in diversi aspetti. I gruppi rom e sinti stanziati in Italia parlano dialetti piuttosto diversi, hanno repertori linguistici differenti, non percepiscono di essere accomunati da un’unica origine etnico-linguistica e non hanno gli stessi atteggiamenti nei confronti dell’uso pubblico della romaní. Questi fattori, insieme alla rappresentazione distorta delle comunità rom e sinte presso la cultura maggioritaria, rendono assai complessa la progettazione di un percorso di tutela. Tuttavia il riconoscimento della romaní come lingua di minoranza in Italia rimane un obbiettivo di alto valore civile, che si potrà forse perseguire con leggi regionali mirate.
Taking an authorial stance in English and Arabic research article discussions
Authors: Alotaibi Hmoud S.
Published: July 2021

Taking an authorial stance is essential in academic writing but remains a challenge for novice researchers,
especially EFL/ESL writers. This study explores how authors of English and Arabic research article discussions employ evaluative
language resources while commenting on their results. To this end, the study investigated the employment of Engagement resources
within Appraisal Theory (Martin & White 2005). The findings exhibited a great
divergence between the two language groups as Arabic discussions relied more on Contracting strategies, which indicate the
tendency to close down the space for dialogic alternatives, while their English counterparts preferred Expanding resources, which
open up the dialogic space for alternative voices. The study, therefore, bears some pedagogical implications for L2 learners.
Hedged Turkish complaints and requests in the Problem-Solution text pattern
Authors: Karatepe Çiğdem
Published: July 2021

This study investigates to what extent Turkish formal complaint letters followed the ‘Problem-Solution Pattern’ (Hoey 1983), and on how the writers expressed their wishes when they explained their problem and asked the authorities to amend a mistake. The study is based on a corpus of 134 Turkish complaint letters. It draws upon Flowerdew’s (2008,2012) approach to the problem-solution pattern and the role of clause relations in this text pattern.

Results showed that age-old Turkish rhetorical norms led writers’ choice of lexico-grammatical patterns in reflecting politeness in order to maintain their own and the recipients’ faces. The speech acts (complaint and request) in the ‘Problem and Solution’ parts below were hedged and impersonalized. The Turkish traditional rhetorical formula that was used in the request does not explicitly ask the reader to do something; in this way, the writers attempt to protect both their own face and that of the reader.
Austenite/ferrite interface movement during intercritical annealing of a medium Mn steel
Authors: Bai M. K. , Yang D. P. , Wang G. D. , Ryu J. H. , Lee K. Y. , Misra R. D. K. , Yi H. L.
Published: July 2021

The austenite/ferrite interface movement during intercritical annealing of 0.15C–8.0Mn–2.1Al (wt-%) steel was simulated by DICTRA software under local equilibrium and then confirmed experimentally. The simulation results show that the austenite volume fraction exceeds the thermodynamic equilibrium amount during isothermal annealing and then decreases because the interface returns from ferrite to austenite. The reverse interface movement is verified in simulated batch annealing experiment for the first time by ex-situ determining the austenite volume fraction using characterisation of XRD as well as by in-situ measuring the bulk volume change led by phase transformation using dilatometric curves.
Lorentz covariance of optical Dirac equation and spinorial photon field
Authors: You Xiao-Lu , Li Chun-Fang
Published: July 2021

In a recent paper (2014 New J. Phys.
16 093008) Barnett discussed the so-called optical Dirac equation and referred to the involved wave function as a spinor. But as he claimed explicitly, he did not really associate that wave function with a true spinor. Here we show that if the optical Dirac equation is interpreted as the dynamical equation for the photon in conventional quantum mechanics, the wave function, called the photon field, does transform under the Lorentz transformation as a spinor. For the optical Dirac equation to be Lorentz covariant, however, a constraint on the photon field is required, which can be cast into the form of Maxwell’s divergence equations. It is found that the spinorial photon field not only satisfies the principle of locality but also has the right dimensionality as is required by conventional quantum mechanics.
Why is living alone in older age related to increased mortality risk? A longitudinal cohort study
Authors: Abell Jessica G , Steptoe Andrew
Published: July 2021

Background

Living alone has been associated with increased mortality risk, but it is unclear whether this is a result of a selection effect or the impact of stressful life changes such as widowhood or divorce leading to changes in living arrangements. We therefore examined the association between living alone, transitions in living arrangements and all-cause mortality.

Method

We analysed data from 4,888 individuals who participated in both wave 2 (2004–2005) and wave 4 (2008–2009) of the English Longitudinal Study of Ageing. Transitions in living arrangements over this period were identified. Mortality status was ascertained from linked national mortality registers. Cox proportional hazards analysis was used to examine the association between living alone and mortality over an average 8.5 year follow-up period.

Results

An association was found between living alone at wave 4 and mortality (hazard ratio (HR): 1.20, 95% CI 1.04–1.38) in a model adjusted for multiple factors including socioeconomic status, physical health, health behaviours and loneliness. We also found that participants who moved to living alone after divorce or bereavement had a higher risk of mortality compared with those who lived with others at both time points (HR: 1.34, 95% CI 1.01–1.79), while those who moved to living alone for other reasons did not show an increased mortality risk.

Conclusions

The relationship between living alone and mortality is complicated by the reasons underlying not living with others. A greater understanding of these dynamics will help to identify the individuals who are at particular health risk because of their living arrangements.
Community development as a key element in social work education and practice in Spain
Authors: Anleu-Hernández Claudia María , García-Moreno Cristina
Published: July 2021

Social work has always recognized the importance of community development as a key element in intervention and social change. Even so, the neoliberal context currently affecting the reality of most of the countries in the Global North is directly influencing the weakening of community actions and is reinforcing more individualistic positions. The main objective of this paper is to analyze the extent to which neoliberal policies are impacting on the teaching of community development content on social work programs in Spain and to study the impact of this reality on the implementation of community plans and projects in Catalonia. The methodology used was qualitative and was based on a systematic review of institutional documentation, community programs and specialized literature. Likewise, the study plans of the 32 universities currently teaching the social work degree in Spain were carefully reviewed to identify and analyze the subjects that focus their primary content on community development. We highlight the purpose of public and private institutions to maintain and promote community development plans and programs and the need to broaden and promote the community development approach in social work study plans. Finally, we present recommendations on how to promote social intervention and community development as key elements in both the training and practice of the social work profession.
Sleep Deprivation Impairs Learning-Induced Increase in Hippocampal Sharp Wave Ripples and Associated Spike Dynamics during Recovery Sleep
Authors: Li Rong-Rong , Yan Jie , Chen Hao , Zhang Wei-Wei , Hu Yu-Bo , Zhang Jie , Hu Zhi-An , Xiong Yan , Yao Zhong-Xiang , Hu Bo
Published: July 2021

Sleep deprivation (SD) causes deficits in off-line memory consolidation, but the underlying network oscillation mechanisms remain unclear. Hippocampal sharp wave ripple (SWR) oscillations play a critical role in off-line memory consolidation. Therefore, we trained mice to learn a hippocampus-dependent trace eyeblink conditioning (tEBC) task and explored the influence of 1.5-h postlearning SD on hippocampal SWRs and related spike dynamics during recovery sleep. We found an increase in hippocampal SWRs during postlearning sleep, which predicted the consolidation of tEBC in conditioned mice. In contrast, sleep-deprived mice showed a loss of tEBC learning-induced increase in hippocampal SWRs during recovery sleep. Moreover, the sleep-deprived mice exhibited weaker reactivation of tEBC learning-associated pyramidal cells in hippocampal SWRs during recovery sleep. In line with these findings, tEBC consolidation was impaired in sleep-deprived mice. Furthermore, sleep-deprived mice showed augmented fast excitation from pyramidal cells to interneurons and enhanced participation of interneurons in hippocampal SWRs during recovery sleep. Among various interneurons, parvalbumin-expressing interneurons specifically exhibited overexcitation during hippocampal SWRs. Our findings suggest that altered hippocampal SWRs and associated spike dynamics during recovery sleep may be candidate network oscillation mechanisms underlying SD-induced memory deficits.
An international audit of the management of dyslipidaemia and hypertension in patients with rheumatoid arthritis: results from 19 countries
Authors: Rollefstad Silvia , Ikdahl Eirik , Wibetoe Grunde , Sexton Joe , Crowson Cynthia S , van Riel Piet , Kitas George D , Graham Ian , Dahlqvist Solbritt Rantapää , Karpouzas George , Myasoedova Elena , Gonzalez-Gay Miguel A , Sfikakis Petros P , Tektonidou Maria G , Lazarini Argyro , Vassilopoulos Dimitrios , Kuriya Bindee , Hitchon Carol A , Stoenoiu Maria Simona , Durez Patrick , Pascual-Ramos Virginia , Galarza-Delgado Dionicio Angel , Faggiano Pompilio , Misra Durga Prasanna , Borg Andrew , Mu Rong , Mirrakhimov Erkin M , Gheta Diane , Myasoedova Svetlana , Krougly Lev , Popkova Tatiana , Tuchyňová Alena , Tomcik Michal , Vrablik Michal , Lastuvka Jiri , Horák Pavel , Medková Helena , Semb Anne Grete
Published: July 2021

Aims

To assess differences in estimated cardiovascular disease (CVD) risk among rheumatoid arthritis (RA) patients from different world regions and to evaluate the management and goal attainment of lipids and blood pressure (BP).

Methods and results

The survey of CVD risk factors in patients with RA was conducted in 14 503 patients from 19 countries during 2014–19. The treatment goal for BP was <140/90 mmHg. CVD risk prediction and lipid goals were according to the 2016 European guidelines. Overall, 21% had a very high estimated risk of CVD, ranging from 5% in Mexico, 15% in Asia, 19% in Northern Europe, to 31% in Central and Eastern Europe and 30% in North America. Of the 52% with indication for lipid-lowering treatment (LLT), 44% were using LLT. The lipid goal attainment was 45% and 18% in the high and very high risk groups, respectively. Use of statins in monotherapy was 24%, while 1% used statins in combination with other LLT. Sixty-two per cent had hypertension and approximately half of these patients were at BP goal. The majority of the patients used antihypertensive treatment in monotherapy (24%), while 10% and 5% as a two- or three-drug combination.

Conclusion

We revealed considerable geographical differences in estimated CVD risk and preventive treatment. Low goal attainment for LLT was observed, and only half the patients obtained BP goal. Despite a high focus on the increased CVD risk in RA patients over the last decade, there is still substantial potential for improvement in CVD preventive measures.
Effects of topography and basins on seismic wave amplification: the Northern Chile coastal cliff and intramountainous basins
Authors: García-Pérez Tiaren , Ferreira Ana M G , Yáñez Gonzalo , Iturrieta Pablo , Cembrano José
Published: July 2021

During earthquakes, structural damage is often related to soil conditions. Following the 2014 April 1 Mw 8.1 Iquique earthquake in Northern Chile, damage to infrastructure was reported in the cities of Iquique and Alto Hospicio. In this study, we investigate the causes of site amplification in the region by numerically analysing the effects of topography and basins on observed waveforms in the frequency range 0.1–3.5 Hz using the spectral element method. We show that topography produces changes in the amplitude of the seismic waves (amplification factors up to 2.2 in the frequency range 0.1–3.5 Hz) recorded by stations located in steep areas such as the ca. 1-km-high coastal scarp, a remarkable geomorphological feature that runs north–south, that is parallel to the coast and the trench. The modelling also shows that secondary waves—probably related to reflections from the coastal scarp—propagate inland and offshore, augmenting the duration of the ground motion and the energy of the waveforms by up to a factor of three. Additionally, we find that, as expected, basins have a considerable effect on ground motion amplification at stations located within basins and in the surrounding areas. This can be attributed to the generation of multiple reflected waves in the basins, which increase both the amplitude and the duration of the ground motion, with an amplification factor of up to 3.9 for frequencies between 1.0 and 2.0 Hz. Comparisons between real and synthetic seismic waveforms accounting for the effects of topography and of basins show a good agreement in the frequency range between 0.1 and 0.5 Hz. However, for higher frequencies, the fit progressively deteriorates, especially for stations located in or near to areas of steep topography, basin areas, or sites with superficial soft sediments. The poor data misfit at high frequencies is most likely due to the effects of shallow, small-scale 3-D velocity heterogeneity, which is not yet resolved in seismic images of our study region.
Mitigating the ill-posedness of first-arrival traveltime tomography using slopes: application to the eastern Nankai Trough (Japan) OBS data set
Authors: Sambolian S , Gorszczyk A , Operto S , Ribodetti A , Tavakoli F. B
Published: July 2021

First-arrival traveltime tomography is one of the most used velocity model building techniques especially in sparse wide-angle acquisitions for deep crustal seismic imaging cases. Relying on the inversion of a picked attribute, the absolute traveltimes, the approach is ill-posed in terms of non-uniqueness of the solution. The latter is remedied by proper regularization or the introduction of prior information. Indeed, since traveltime kernels are vulnerable to the velocity–depth ambiguity, the inversion is stabilized by the introduction of complementary data like reflections and explicit reflectors in the velocity models. Here, we propose to supplement first-arrival traveltimes by their slopes, in other words the horizontal component of the slowness vectors at the sources and/or receivers. Slopes are a crucial attribute in state of the art scattering-based or reflection-based tomographic methods like slope tomography or wavefront tomography where the differential information is needed in order to locate the scattering events position or to parametrize the wavefront. The optional but valuable injection of slopes as an objective measure in first-arrival traveltime tomography stabilizes the problem by constraining the emergence angle or in turn implicitly the turning point depth of the rays. We explain why slopes have a tremendous added value in such a tomographic problem and highlight its remedial effect in cases where the medium is unevenly illuminated. We also show that the contribution of slopes become even more significant when the acquisition is sparse as it is generally the case with ocean-bottom seismometer surveys. The inferred models from such an extended time-attributes tomography will be used as initial guesses in a full-waveform inversion workflow context. The proposed strategy is benchmarked in 2-D media against a dip section of the SEG/EAGE overthrust model and then followed by a revisit of ocean bottom seismometers data from the eastern-Nankai subduction margin as a real deep crustal case study.
C4-monomethylsterol β-glucoside and its synthase in Aurantiochytrium limacinum mh0186
Authors: Endo Ikumi , Watanabe Takashi , Miyamoto Tomofumi , Monjusho-Goda Hatsumi , Ohara Junichiro , Hayashi Masahiro , Hama Yoichiro , Ishibashi Yohei , Okino Nozomu , Ito Makoto
Published: July 2021

Thraustochytrids, unicellular marine protists, synthesize polyunsaturated fatty acids (PUFAs) and PUFA-containing phospholipids; however, little is known about their glycolipids and their associated metabolism. Here, we report two glycolipids (GL-A, B) and their synthases in Aurantiochytrium limacinum mh0186. Two glycolipids were purified from A. limacinum mh0186, and they were determined by gas chromatography, mass spectrometry and 2D nuclear magnetic resonance to be 3-O-β-D-glucopyranosyl-stigmasta-5,7,22-triene (GL-A) and 3-O-β-D-glucopyranosyl-4α-methyl-stigmasta-7,22-diene (GL-B), both of which are sterol β-glucosides (β-SGs); the structure of GL-B has not been reported thus far. Seven candidate genes responsible for the synthesis of these β-SGs were extracted from the draft genome database of A. limacinum using the yeast sterol β-glucosyltransferase (SGT; EC 2.4.1.173) sequence as a query. Expression analysis using Saccharomyces cerevisiae revealed that two gene products (AlSGT-1 and 2) catalyze the transfer of glucose from uridine diphosphate (UDP)-glucose to sterols, generating sterylglucosides (SGs). Compared to AlSGT-1, AlSGT-2 exhibited wide specificity for sterols and used C4-monomethylsterol to synthesize GL-B. The disruption of alsgt-2 but not alsgt-1 in strain mh0186 resulted in a decrease in the total SG and an almost complete loss of GL-B, indicating that AlSGT-2 is responsible for the synthesis of β-SGs in A. limacinum mh0186, especially GL-B, which possesses a unique sterol structure.
How the Gulf States are using their air space to assert their sovereignty
Authors: Gaub Florence , Boswinkel Lotje
Published: July 2021

All Arab states, including the Gulf states, are regularly considered an anomaly in International Relations: allegedly artificially created, lacking clear identity, borders and sovereignty. We challenge this assertion by looking at one dimension of sovereignty often overlooked: the air space. We measure this assertion along the classical lines of sovereignty: do the states have the institutions, regulations and capacity to manage their air space, do they use it for economic and diplomatic purposes, do they have the means to conduct war in it, and does it feature in their national identity? We find that particularly since 1990, the Gulf States have affirmed their sovereignty markedly in all these areas. These findings show two things: that sovereignty can be a feature of a state regardless of the nature of its creation, and that it can be affirmed in a space previously overlooked, the air.
Who stays and who leaves? Immigration and the selection of natives across locations
Authors: Ortega Javier , Verdugo Gregory
Published: July 2021

We study the impact of local immigration inflows on natives’ wages using a large French administrative panel from 1976 to 2007. We show that local immigration inflows are followed by reallocations of blue-collar natives across commuting zones. Because these reallocations vary with the initial occupation, and blue-collar location movers have wages below the blue-collar average, controlling for changes in local composition is crucial to assess how wages adjust to immigration. Immigration temporarily lowers the wages of blue-collar workers, with unskilled workers experiencing larger losses. Location movers lose more than stayers in terms of daily wages but move to locations with cheaper housing.
Metabolic surgery in China: present and future
Authors: Tu Yinfang , Bao Yuqian , Zhang Pin
Published: July 2021

Obesity and its related complications comprise a serious public health problem worldwide, and obesity is increasing in China. Metabolic surgery is a new type of treatment with unique advantages in weight loss and obesity-related metabolic complications. The pathogenesis of obesity is complex and not yet fully understood. Here, we review the current efficacy and safety of metabolic surgery, as well as recent progress in mechanistic studies and surgical procedures in China. The exciting and rapid advances in this field provide new opportunities for patients with obesity and strike a balance between long-term effectiveness and safety.
Improving a Parent Coaching Model of Music Interventions for Young Autistic Children
Authors: Hernandez Ruiz Eugenia , Braden Blair B
Published: July 2021

Parenting a child on the autism spectrum can be rewarding and enriching, but it may also increase risk of parental fatigue, stress, anxiety, and depression. Parent-mediated interventions contribute to increase family satisfaction and child social communication while helping to decrease parental stress and fatigue. Parent coaching, the education of parents in evidence-based strategies, has become common in the autism field. However, parent coaching in music therapy has only recently emerged and has limited research with families with an autistic member. In this study, we attempted to improve a previously published model of parent coaching, adapting only one aspect of the Early Start Denver Model (ESDM), the sensory social routine (SSR) to create a music intervention. Four parents participated in this 6-session parent coaching study. We compared the SSR-based intervention with and without music, in an alternating treatment design. Measures included parental responsiveness, child receptive and initiation joint attention, parent–child similar affect and synchronized gaze, and the Parent Coaching-ESDM (PC-ESDM) parent fidelity rating system. Results from these observational measures were mixed, with better parental responses in the no-music condition, but improved child responses and parent–child synchrony in the music condition for 3 out of the 4 participants. Parent learning increased for all participants, and 3 out of the 4 reached fidelity (a score of at least 80%), according to the PC-ESDM. Although mixed results were observed across participants, implications for practice are possible. Better outcome measures of this complex intervention are needed.
Tonkinensine B induces apoptosis through mitochondrial dysfunction and inactivation of the PI3K/AKT pathway in triple-negative breast cancer cells
Authors: Sun Xuanrong , Zhang Tianwei , Cai Yue , Yang Ke , Peng Tingting , Liu Renhao , Li Xing-Nuo
Published: July 2021

Objectives

Tonkinensine B, a novel compound with cytisine–pterocarpan skeleton isolated from the root of Sophora tonkinensis Gagnep, was reported to have a significant antitumor effect. The effect and intrinsic mechanism of tonkinensine B on tumour need to be further investigated.

Methods

With the help of cell cytotoxicity, the effect of tonkinensine B on MDA-MB-231 cells was investigated. By observing mitochondrial function changes, the intrinsic mechanism was further studied. The levels of key apoptosis-associated proteins Bcl-2, Bax, caspase-9, caspase-3 and AKT in MDA-MB-231 cells were analysed to determine whether tonkinensine B caused apoptosis via the mitochondrial pathway.

Key findings

After treated with tonkinensine B, MDA-MB-231 cells multiplication was repressed, and the decreased mitochondrial membrane potential, loss of ATP synthesis and elevated ROS generation were detected. Furthermore, the proportions of Bax/Bcl-2, cleaved caspase-3 and caspase-9 proteins production were up-regulated, indicating that tonkinensine B acted on intrinsic mitochondrial-mediated apoptosis pathway. In addition, tonkinensine B also reduced phosphorylation levels of AKT, and thus the activation of apoptosis might likewise be correlated with the inhibition of the PI3K/AKT pathway.

Conclusions

Tonkinensine B may be a hopeful candidate for human triple-negative breast cancer, and further structural optimization is expected to improve its anti-tumour activity.
Ionospheric effects in VLBI measured with space-ground interferometer RadioAstron
Authors: Popov M V , Bartel N , Burgin M S , Smirnova T V , Soglasnov V A
Published: July 2021

We report on slow phase variations of the response of the space-ground radio interferometer RadioAstron during observations of pulsar B0329+54. The phase variations are due to the ionosphere and clearly distinguishable from effects of interstellar scintillation. Observations were made in a frequency range of 316–332 MHz with the 110-m Green Bank Telescope and the 10-m RadioAstron telescope in 1-h sessions on 2012 November 26, 27, 28, and 29 with progressively increasing baseline projections of about 60, 90, 180, and 240 thousand kilometres. Quasi-periodic phase variations of interferometric scintles were detected in two observing sessions with characteristic time-scales of 12 and 10 min and amplitudes of up to 6.9 radians. We attribute the variations to the influence of medium-scale Travelling Ionospheric Disturbances. The measured amplitude corresponds to variations in vertical total electron content in ionosphere of about $0.1\times 10^{16}\, \text{m}^{-2}$. Such variations would noticeably constrain the coherent integration time in VLBI studies of compact radio sources at low frequencies.
MOMC-1. Employing the Zika Virus to kill paediatric nervous system tumour cells
Authors: Sherwood Matthew , Ewing Robert , Kaid Carolini , Mitsugi Thiago Giove , Okamoto Keith
Published: July 2021

Malignant paediatric nervous system tumours, such as Medulloblastoma, Neuroblastoma and ATRT commonly harbour tumour cells with stem-like features which are highly tumorigenic and resistant to conventional cancer therapies. These tumours can exhibit high lethality and may result in severe sequelae, including cognitive and motor deficits that significantly affect patients’ quality of life. Oncolytic virotherapy is a novel therapy class that exploits viruses that preferentially infect and destroy tumour cells. These viruses present a unique advantage in targeting highly heterogeneous cancers, such as nervous system tumours, as they possess a secondary mechanism of action through which they induce a tumour-specific immune response. Clinical studies employing oncolytic virotherapy have in general reported low toxicity and minimal adverse effects, deeming oncolytic virotherapy as a potentially attractive and safer intervention against paediatric tumours.

The Zika virus (ZIKV) is capable of infecting and destroying neural stem-like cancer cells from human embryonal Central Nervous System (CNS) tumours in vitro and in vivo. Infection of CNS tumour cells with ZIKV effectively inhibits tumour metastasis in mice and, in some cases, induces complete tumour remission. Neuroblastoma arises from immature nerve cells and multiple Neuroblastoma cell lines are susceptible to ZIKV infection and oncolysis. These initial findings have demonstrated the potential for a ZIKV-based virotherapy against paediatric nervous system tumours and warrants examination into the molecular mechanisms through which ZIKV executes its oncolytic ability. My research goal is to elucidate the mechanisms which are of paramount importance for ZIKV-induced oncolysis of brain tumour and Neuroblastoma cells. Utilising global expression omics profiling of ZIKV infection and mapping of viral protein-host protein interactions will identify these mechanisms both at the cellular pathway and molecular levels. These collectively will inform our understanding of how we can employ a future ZIKV-based virotherapy against paediatric nervous system tumours.
NGMA-5. An in vivo functional genomics screen to identify novel drivers of lung-to-brain metastasis
Authors: Aghaei Nikoo , Lam Fred C , Kasper Ekkhard , Venugopal Chitra , Singh Sheila
Published: July 2021

Introduction

Brain metastases, the most common tumors of the central nervous system, occur in approximately 20% of primary adult cancers. In particular, 40% of patients with non-small cell lung cancer develop brain metastasis. As systemic therapies for the treatment of non-small cell lung cancer become increasingly effective at controlling primary disease, patients are ironically succumbing to their brain metastases. This highlights a large unmet need to develop novel targeted therapies for the treatment of lung-to-brain metastases (LBM). We hypothesize that an in vivo functional genomic screen can identify novel genes that drive LBM.

Methods

To do this, we developed a patient-derived xenograft (PDX) mouse model of LBM using patient lung cancer cell lines. This PDX model of LBM enables the use of fluorescent and bioluminescent in vivo imaging to track the progression of lung tumor and brain metastases.

Results

We have performed an in vivo genome-wide CRISPR activation screening to identify novel drivers of LBM. We will derive candidate genes through mouse brain and lung tissue sequencing after mice reach endpoint.

Expected Area of findings

This platform will lead to potential therapeutic targets to prevent the formation of LBM and prolong the survival of patients with non-small cell lung cancer.

Conclusion

To the best of our knowledge, this is the first genome-wide in vivo CRISPR activation screen searching for drivers of LBM using a PDX animal model. This study can provide a framework to gain a deeper understanding of the regulators of BM formation which will hopefully lead to targeted drug discovery.
OPTC-5. Molecular signatures of podoplanin expressing glioblastoma cell subsets with putative role in cancer associated thrombosis and microthrombosis
Authors: Tawil Nadim , Bassawon Rayhaan , Meehan Brian , Montermini Laura , Choi Dongsic , Nehme Ali , Najafabadi Hamed , Riazalhosseini Yasser , De Jay Nicolas , Kleinman Claudia , Gayden Tenzin , Spinelli Cristiana , Adnani Lata , Couturier Charles , Petrecca Kevin , Jabado Nada , Rak Janusz
Published: July 2021

Vascular anomalies, including thrombosis, are a hallmark of glioblastoma (GBM) and an aftermath of dysregulated cancer cell genome and epigenome. Upregulation of podoplanin (PDPN) by cancer cells has recently been linked to an increased risk of venous thromboembolism in glioblastoma patients. Thus, regulation of this platelet activating transmembrane protein by transforming events and release from cancer cells into the circulation are of considerable interest. We took advantage of single-cell and bulk GBM transcriptome dataset mining and investigated the pattern of PDPN expression across several databases. Our analysis indicated that PDPN is expressed by distinct (mesenchymal) glioblastoma cell subpopulations and is downregulated by oncogenic mutations of EGFR and IDH1 genes, via changes in chromatin modifications (EZH2) and DNA methylation, respectively. Additionally, we utilized isogenic and stem GBM cell lines, xenograft models in mice, ELISA assays for PDPN, tissue factor (TF), platelet factor 4 (PF4) and clotting activation markers (D-dimer), and multicolor nano-flow cytometry to show that GBM cells exteriorize PDPN and/or TF as cargo of exosome-like coagulant extracellular vesicles EVs. We also documented an increase of platelet activation (PF4) or coagulation markers (D-dimer) in mice harboring the corresponding PDPN- or TF-expressing glioma xenografts, respectively. While PDPN was a dominant regulator of systemic platelet activation, co-expression of PDPN and TF impacted local microthrombosis. Our work suggests that distinct cellular subsets drive multiple facets of GBM-associated thrombosis and may represent targets for diagnosis and intervention.
OMRT-2. Liquid biopsy for patient stratification and monitoring of dacomitinib clinical trial in patients with EGFR amplified recurrent glioblastoma
Authors: Yekula Anudeep , Kitchen Robert , Chakrabortty Sudipto , Carter Bob , Breakefield Xandra , Skog Johan , Balaj Leonora
Published: July 2021

Introduction

Liquid biopsy for the detection and monitoring of brain tumors is of significant clinical interest. The ability to non-invasively profile tumors can avoid a risky biopsy and opens avenues for testing novel therapies by accurately stratifying patients to receive the right therapy. Here, we provide evidence of EV RNA-based diagnosis, patient stratification, and assessment of response to therapy in the setting of a clinical trial evaluating the efficacy of dacomitinib, an EGFR tyrosine kinase inhibitor in patients with recurrent, EGFR amplified GBM(NCT01112527).

Methods

We performed RNASeq on long RNA extracted from the serum samples, pre-treatment and 1-month post-treatment.

Results

Firstly, longRNASeq allowed the detection of thousands of mRNA, lincRNAs and antisense RNAs enabling the study of a wider repertoire of potential RNA based biomarkers.

Secondly, we observed a differential expression profile in serum EV RNA of GBM patients and healthy controls. Combining our findings with TCGA data and literature screening, we generated a 25 gene signature representative of critical pathways in several hallmarks of cancer.

Thirdly, we observed a differential expression profile in serum EV RNA of responders to dacomitinib compared to non-responders in pre-treatment serum. Specifically, the EV mRNAs ZNF35 and LAMTOR2 distinguish responders from non-responders (p-adjusted = 2.6E-8 and 2.4E-6, respectively) allowing potential patient stratification.

Finally, we observed a differential expression profile in serum EV RNA of responders to dacomitinib compared to non-responders in post-treatment serum. EV mRNA DNMT3A is significantly enriched (p-adjusted = 1.8E-4) in post-treatment serum of responders compared to non-responders to dacomitinib allowing potential monitoring of response to therapy.

Conclusion

This study represents the first longitudinal profiling of the EV transcriptome in a cohort of genomically selected GBM patients. These findings are a tantalizing step toward liquid biopsy-based biomarkers for the detection of GBM, as well as patient stratification and monitoring.