bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular dynamics study of Cr doping on the crystal structure and surficial/interfacial properties of 2H-MoS2
Authors: Xing Jiqi , Shi Hongyu , Li Yingdi , Liu Juan
Published: January 2022

Substitution-doping of Cr will adjust the surface properties of 2H-MoS2. Using MD simulations, solvents for peeling Cr–MoS2 can be predicted.
Oxygen control: the often overlooked but essential piece to create betterin vitrosystems
Authors: Palacio-Castañeda Valentina , Velthuijs Niels , Le Gac Séverine , Verdurmen Wouter P. R.
Published: January 2022

Variations in oxygen levels play key roles in numerous physiological and pathological processes, but are often not properly controlled inin vitromodels, introducing a significant bias in experimental outcomes.
Prix Nobel de physiologie ou médecine 2021
Authors: Coste Bertrand
Published: January 2022

David Julius, 65 ans, professeur à l’université de Californie à Los Angeles (UCLA), et Ardem Patapoutian, 54 ans, professeur à l’institut de recherche Scripps à la Jolla (Californie), ont reçu le prix Nobel de physiologie ou médecine 2021 pour « leurs découvertes des récepteurs de la température et du toucher ». Leurs travaux sur la somesthésie, un sens global qui nous renseigne sur les forces physiques s’exerçant au sein de notre organisme et sur notre peau, ont permis de répondre à une question fondamentale : comment les stimulations thermiques et mécaniques sont-elles converties en signaux électriques dans le système nerveux ? Ces travaux ont conduit à l’identification des canaux ioniques qui sont à l’interface entre notre corps et son environnement.
The Fate of Nonoperative Management in Patients with Lytic Spondylolisthesis
Authors: Sinha Siddharth , George K. Joshi
Published: January 2022

Background There is a lack of consensus within the current literature about the role of nonoperative management in lytic spondylolisthesis. Our objective was to assess the fate that nonoperative management plays in patients diagnosed with lytic spondylolisthesis.

Methods Data were collected between May 2015 and February 2020 from 41 patients who were initially referred specifically for instrumented lumbar fixation but were instead planned for nonoperative management as they opted to avoid surgery. Magnetic resonance imaging (MRI) scans were used to determine spondylolisthesis grade, type of deformity, and radiologic features. Patient notes were reviewed to establish management plans. Furthermore, patients were also contacted via telephone to assess their symptoms and disease progression.

Results Twenty-six of the 41 patients had lytic spondylolisthesis (63.4%). Of these patients, the male-to-female ratio was 10:16. The median age was 60 (range: 22–76) years. A total of 12 patients were managed nonoperatively for 5 years or longer, with 2 patients showing progression from grade I to II.

Conclusion Nonoperative management of lytic spondylolisthesis is a reasonable option in a selected cohort of patients. The longer in duration patients are managed conservatively, the less likely they are to require a surgical intervention. Even severe radiologic foraminal stenosis without radicular pain does not seem to push patients toward surgery. Management decisions must be made on an individual basis. These data can give some reassurance to patients who wish to consider nonoperative management and help guide clinicians.
Diastereoselective Synthesis of Spirocyclopentene-Indanediones from Isocyanides, Acetylenic Esters, and NH-Acidic Compounds
Authors: Yavari Issa , Ravaghi Parisa , Safaei Maryam
Published: January 2022

A diastereoselective synthesis of spirocyclopentene-1H-indene-1,3(2H)-diones through a three-component reaction of alkyl isocyanides, dialkyl acetylenedicarboxylates, and 2-(alkylamino)-2-(1,3-dioxo-1H-inden-2(3H)-ylidene)acetonitriles is described. This reaction forms two stereogenic centers with remarkable diastereoselectivity. The crystal structure of a typical product has been determined by X-ray diffraction.
Ag/C60 heterojunctions for thermoelectricity
Authors: Kozachenko V. , Shmid V. , Podolian A. , Nadtochiy A. , Korotchenkov O.
Published: January 2022

A new composite fullerene C60/nanostructured Ag film is fabricated having the potential to be used for efficient thermoelectrics. It is shown that embedding C60 molecules into silver nanoparticle chains enhances the Seebeck coefficient S continuously by about 1 μV/K through the temperature range from 30 to 295 K. It is unlikely that this is due solely to the enhanced phonon and electron scattering at the C60 inclusions. It is therefore suggested that the Ag/C60 heterojunction thermopower contributes to the observed enhancement in S. The hybrid Ag/C60 system of this type can be used to tailor the thermoelectric energy conversion via Seebeck coefficient grading in Ag/C60 structures.
Ideal Bose gas in steep one-dimensional traps
Authors: Rovenchak Andrij , Krynytskyi Yuri
Published: January 2022

We study thermodynamic properties of a one-dimensional ideal Bose gas trapped by a steep potential of an exponential type U(q)=U0[e(2q/a)b−1]. Fugacity, energy, and heat capacity of such a system are calculated for various combinations of the potential parameters as well for several values of the number of particles N. Both the thermodynamic limit and finite N are considered. Estimations for the single-particle spectrum asymptotics are obtained in the analytical form involving the Lambert W function. In the thermodynamic limit, the Bose–Einstein condensation is predicted for 0 < b < 2. We associate such behavior with an effective temperature-dependent space dimensionality arising due to the influence of the external potential of the analyzed type.
Transport spectroscopy in degenerate quantum dot
Authors: Ponezha E. A.
Published: January 2022

Using the microscopic model proposed by us earlier, the tunnel current and differential conductivity through a degenerate quantum dot weakly coupled to the external electrodes, depending on the bias and gate voltages, were calculated. The behavior of this system is analyzed at two types of electron-electron interaction in the quantum dot: repulsive and attractive. It is shown that in the case of the attractive interaction, the dependence of electron levels occupation on voltage becomes nonlinear, and the transport properties of the system change dramatically. The method of transport spectroscopy made it possible to determine through which of the levels (both ground and excited) tunneling takes place depending on the applied voltages and to estimate the current through these levels, as well as the orientation of electron spins on them. The results can be used to understand and predict the properties of a quantum dot as a potential element for new generations of nanodevices and quantum computers.
Design of a helical resonator with improved figure of merit
Authors: Nandi J. , Sikdar A. K. , Das P. , Ray A.
Published: January 2022

A helical resonator serves as a key element for the detection of the trapped charged particles in a Penning trap. In order to compare the performance of the helical resonators, the concept of figure of merit (FOM) was introduced by Ulmer et al. [Nucl. Instrum. Methods Phys. Res., Sect. A 705, 55–60 (2013)]. In this work, we optimized the geometrical parameters of a resonator by numerical simulations keeping its outer dimensions and the diameter of the copper wire fixed and obtained the best possible value of FOM under these constraints. The corresponding 95 MHz helical resonator has been designed and fabricated, and its measured value of FOM is in good agreement with the simulated values. An empirical relationship between the total length of the wire to make the helical coil and the resonance frequency has been obtained. The simulations show that the FOM increases considerably with the increase in the conductivity of the building material, and this would be useful in detecting the feeble trap signal in cryogenic environment.
Carriers of Sargassum and mechanism for coastal inundation in the Caribbean Sea
Authors: Andrade-Canto F. , Beron-Vera F. J. , Goni G. J. , Karrasch D. , Olascoaga M. J. , Triñanes J.
Published: January 2022

We identify effective carriers of Sargassum in the Caribbean Sea and describe a mechanism for coastal choking. Revealed from satellite altimetry, the carriers of Sargassum are mesoscale eddies (vortices of 50-km radius or larger) with coherent material (i.e., fluid) boundaries. These are observer-independent—unlike eddy boundaries identified with instantaneously closed streamlines of the altimetric sea-surface height field—and furthermore harbor finite-time attractors for networks of elastically connected finite-size buoyant or “inertial” particles dragged by ocean currents and winds, a mathematical abstraction of Sargassum rafts. The mechanism of coastal inundation, identified using a minimal model of surface-intensified Caribbean Sea eddies, is thermal instability in the presence of bottom topography.
Foliations on closed three-dimensional Riemannian manifolds with small modulus of mean curvature of the leaves
Authors: Bolotov Dmitrii Valerevich
Published: January 2022

We prove that the modulus of mean curvature of the leaves of a transversely oriented
foliation of codimension one with a generalized Reeb component on an oriented smooth
closed three-dimensional Riemannian manifold cannot be everywhere smaller than a certain
positive constant depending on the volume, the maximum value of the sectional curvature,
and the injectivity radius of the manifold. This means that foliations with
small modulus of
mean curvature of the leaves are taut.
Modification of Poincaré's
construction and its application in $CR$-geometry of hypersurfaces in $\mathbf{C}^4$
Authors: Beloshapka Valerii Konstantinovich
Published: January 2022

The modified Poincaré construction (a generalization of Poincaré's homological operator)
was earlier used to estimate the dimension of the local automorphism group for an arbitrary germ
of a real-analytic hypersurface in $\mathbf{C}^3$. In the present paper we prove the following
alternative. For every hypersurface in $\mathbf{C}^4$, this dimension is either infinite or does
not exceed $24$. Moreover, $24$ occurs only for a non-degenerate hyperquadric
(one of the two). If the hypersurface is $2$-nondegenerate (resp. $3$-non-degenerate)
at a generic point, the bound can be improved to $17$ (resp. $20$).
On a convex polyhedron in a regular point system
Authors: Shtogrin Mikhail Ivanovich
Published: January 2022

Faceting with a ‘filling’. An ideal crystal structure consists of finitely many equal
and parallel translational point lattices. In $\mathbb R^3$ it extends unboundedly in
all directions. We distinguish in it a finite part situated in a closed convex polyhedron every face of which contains nodes of a translational point lattice involved in the structure not belonging to the same straight line. Such a polyhedron is called a possible faceting of the ideal crystal structure.
There are 32 well-known crystal classes, or 32 crystallographic point groups. Among them is the symmetry group of the possible faceting calculated taking account of the nodes of the ideal crystal structure belonging to it. A cyclic subgroup $C_n$ of the symmetry group of any possible faceting has order $n\le 4$ or $n=6$.
Faceting without ‘filling’. In this paper we construct two crystal structures in which there are crystal polyhedra whose symmetry groups, calculated without taking account of the nodes of the crystal structure belonging to it, have rotation axes of orders $n=8$ and $n=12$. In both cases, the crystal polyhedron is a right prism of finite height. Without taking account of the internal structure, a possible faceting of a crystal structure in three-dimensional Euclidean space cannot have an axes of rotation of order $n$ satisfying $6<n<\infty$.
The proposed constructions are accompanied by a detailed analysis of ideal crystal structures, as well as Delone sets $S$ of type $(r, R)$ in $\mathbb R^2$ and $\mathbb R^3$.
In particular, we produce an expanded proof of one of the theorems stated in 2010 at an international conference dedicated to the 120th anniversary of B. N. Delone.
The real Plücker-Klein map
Authors: Krasnov Vyacheslav Alekseevich
Published: January 2022

We consider the generalized Plücker-Klein map from the set of all real marked biquadrics
to the set of real Kummer varieties. We find a necessary and sufficient condition on a real marked
biquadric in order that the corresponding real Kimmer variety be isomorphic to the real Kummer
variety induced by the real Jacobian of a double covering of the pencil of quadrics through the
given biquadric. We also give a deformation classification of the real Plücker-Klein map.
Evidence for a semisolid phase state of aerosols and droplets relevant to the airborne and surface survival of pathogens
Authors: Huynh Erik , Olinger Anna , Woolley David , Kohli Ravleen Kaur , Choczynski Jack M. , Davies James F. , Lin Kaisen , Marr Linsey C. , Davis Ryan D.
Published: January 2022

Significance

Ambient humidity can influence the survival of pathogens in respiratory aerosols and droplets, although the mechanism and optimum humidity level for public health remain unclear. Here, we present evidence for a humidity-dependent, semisolid state of aerosols and droplets relevant to pathogen survival. These observations indicate that a semisolid state may protect pathogens from inactivation by hindering disinfection reactions at intermediate-to-low humidity levels. The formation of the semisolid state was dependent on the composition of the aerosols, which suggests that the humidity for optimum pathogen destruction will depend on the composition of respiratory particles released from an infected host. These observations can be used to help interpret laboratory studies and inform public health recommendations.
Narratives imagined in response to instrumental music reveal culture-bounded intersubjectivity
Authors: Margulis Elizabeth H. , Wong Patrick C. M. , Turnbull Cara , Kubit Benjamin M. , McAuley J. Devin
Published: January 2022

Significance

Are we all imagining the same thing when we listen to music, or are our experiences hopelessly subjective? This research analyzes the similarity of responses from 622 participants in three locations on a highly unconstrained task: free-response descriptions of the stories they imagined while listening to instrumental music. Strikingly, participants in two separate locations that share an overarching culture imagine highly similar narratives to individual excerpts. But these similarity patterns do not extend to narratives imagined by participants in a third location with a distinct culture. This work shows that music—often considered an “abstract stimulus”—can trigger shared stories in listeners’ minds but that this intersubjectivity depends on a shared underlying culture.
Impact of ADAR-induced editing of minor viral RNA populations on replication and transmission of SARS-CoV-2
Authors: Ringlander Johan , Fingal Joshua , Kann Hanna , Prakash Kasthuri , Rydell Gustaf , Andersson Maria , Martner Anna , Lindh Magnus , Horal Peter , Hellstrand Kristoffer , Kann Michael
Published: January 2022

Significance

Viral RNA may be edited by enzymes of the ADAR family that deaminate adenosine residues with ensuing A→G mutations. We found multiple A→G mutations in minor viral populations of the SARS-CoV-2 genome. A→G mutations accumulated in the receptor binding domain of the spike gene, which may cause structural changes by altering binding to the ACE2 receptor. Presence of A→G mutations in minor viral populations was associated with reduced viral load, implying that ADAR may limit viral replication. Analyses of >250,000 European samples from 2020 revealed that A→G mutations in SARS-CoV-2 RNA were inversely correlated with mortality as a reflection of incidence. ADAR may thus be important in providing new variants of SARS-CoV-2 with altered infectivity and transmissibility.
Translanguaging as a pedagogical practice in Chinese language and (inter)culture courses
Authors: Li Yu , Liu Jin
Published: January 2022

As Chinese-as-an-additional-language (CAL) practitioners actively seek to bridge the language-culture divide in class instruction and curriculum, various strategies have been adopted to integrate cultural components into traditionally defined “language courses” or vice versa. However, many such strategies follow a “monolingual approach” that views L1 primarily as a source of interference in second language acquisition (SLA). Recognizing the importance of L1 use in additional-language classrooms, this paper proposes to apply the theory of translanguaging as the underlying pedagogy of CAL courses that holistically integrate language, culture, and intercultural learning. This approach fully recognizes students as multilingual and multicultural learners by judiciously and strategically combining L1 and L2 in order to maximize the growth of students’ overall linguacultural proficiency. The paper presents two course examples to discuss the implementation and benefits of this approach: a course on Chinese calligraphy for students with intermediate proficiency in the Chinese language and a course on Sino-US intercultural communication for students with advanced proficiency. These courses demonstrate that the translanguaging approach facilitates in-depth intellectual inquiries and critical thinking and encourages Chinese language learning in an interdisciplinary, intercultural, and interactive context. The paper concludes by extending the vision of translanguaging to the overall CAL curriculum and discussing its implication for the field.
Eye movements and visual perception in dyslexic children
Authors: Salem Taima , Elsherif Mayada , Mourad Mona , Abdou Rania , Hamouda Nesrine
Published: January 2022

Background

Many research has demonstrated that reading problems, such as dyslexia, can coexist with visual abnormalities. While remediation for phonological impairments in dyslexics is widely acknowledged and practiced, the potential impact of visual deficits, particularly on eye movements and visual perception, is rarely explored.

Objective

This study looks at the performance of eye movements and visual perception abilities in dyslexic children.

Methods

A sample of 20 dyslexic children compared to 20 non-dyslexic age-matched children (aged 7–11). Both groups of the study underwent a video-nystagmography test and visual perception test.

Results

Our study revealed a statistically significant difference between dyslexic and non-dyslexic children in saccade and pursuit tracking tests. There was a statistically significant difference between case and control regarding the visual perception test. Among subgroups of dyslexic children with abnormal eye movements, they displayed visual perception weakness mainly in visual sequencing and discrimination tasks in comparison to dyslexic children with normal eye movements.

Conclusion

The poor oculomotor function affected dyslexic children in their proper control and leads to sluggish visual attention and poor visual perception. According to the major findings of this study, a routine eye examination should be part of the examination of any child with a learning disability.
Relationship between auditory processing disorders and attentional difficulties
Authors: Lotti Laura , Mazzoni Laura , Grigaliute Egle , Monzani Daniele , Genovese Elisabetta
Published: January 2022

Objectives

Attention deficit often emerges in individuals with auditory processing disorder and the relationship between them has not yet been completely understood. The aim of the present review is to investigate whether auditory attention deficit occurs in comorbidity or represents an expression of the same disorder and to compare different diagnostic and management criteria in the existing literature.

Methods

A literature review was performed on the PubMed database that yielded 59 records, which were subsequently screened using PICO model. Out of 22 selected articles, four were excluded for non-adherence to the clinical question. Finally, 18 articles were included: one narrative review and 17 empirical research studies.

Results

Twenty-two articles were analysed and compared in order to answer to the clinical question along with the assessment instruments of auditory processing and auditory attention.

Conclusions

Our review pointed out a greater tendency to consider auditory processing disorder and deficit of attention as distinct entities often in comorbidity. Thus, it is important to evaluate the attentional performances in subjects with auditory processing disorder with particular regard to those who are suspected to suffer also from behavioural, language development or learning difficulties.
Systems-level conservation of the proximal TCR signaling network of mice and humans
Authors: Nicolas Philippe , Ollier Jocelyn , Mori Daiki , Voisinne Guillaume , Celis-Gutierrez Javier , Gregoire Claude , Perroteau Jeanne , Vivien Régine , Camus Mylène , Burlet-Schiltz Odile , Gonzalez de Peredo Anne , Clémenceau Béatrice , Roncagalli Romain , Vié Henri , Malissen Bernard
Published: January 2022

We exploited traceable gene tagging in primary human T cells to establish the composition and dynamics of seven canonical TCR-induced protein signaling complexes (signalosomes) using affinity purification coupled with mass spectrometry (AP-MS). It unveiled how the LAT adaptor assembles higher-order molecular condensates and revealed that the proximal TCR-signaling network has a high degree of qualitative and quantitative conservation between human CD4+ and CD8+ T cells. Such systems-level conservation also extended across human and mouse T cells and unexpectedly encompassed protein–protein interaction stoichiometry. Independently of evolutionary considerations, our study suggests that a drug targeting the proximal TCR signaling network should behave similarly when applied to human and mouse T cells. However, considering that signaling differences likely exist between the distal TCR-signaling pathway of human and mouse, our fast-track AP-MS approach should be favored to determine the mechanism of action of drugs targeting human T cell activation. An opportunity is illustrated here using an inhibitor of the LCK protein tyrosine kinase as a proof-of-concept.
Tunable effective length of fractional Josephson junctions
Authors: Frombach Daniel , Recher Patrik
Published: January 2022

Topological Josephson junctions (TJJs) have been a subject of widespread interest due to their hosting of Majorana zero modes. In long junctions, i.e. junctions where the junction length exceeds the superconducting coherence length, TJJs manifest themselves in specific features of the critical current (Beenakker 2013 Phys. Rev. Lett.
110 017003). Here we propose to couple the helical edge states mediating the TJJ to additional channels or quantum dots, by which the effective junction length can be increased by tunable parameters associated with these couplings, so that such measurements become possible even in short junctions. Besides effective low-energy models that we treat analytically, we investigate realizations by a Kane–Mele model with edge passivation and treat them numerically via tight binding models. In each case, we explicitly calculate the critical current using the Andreev bound state spectrum and show that it differs in effectively long junctions in the cases of strong and weak parity changing perturbations (quasiparticle poisoning).
Tunable annular plasma photonic crystals in dielectric barrier discharge
Authors: Liu Fucheng , Liu Yining , Liu Qian , Wu Zhicheng , Liu Yahui , Gao Kuangya , He Yafeng , Fan Weili , Dong Lifang
Published: January 2022

We demonstrate an effective method for realization of robust, tailorable annular plasma photonic crystals (PPC) in dielectric barrier discharge with two water electrodes. Fast reconfiguration between triangular lattice, annular lattice, core-annular lattice and concentric-annular lattice has been achieved. An active control on the structure of plasma elements is realized by solely changing the applied voltage. The changes of photonic band gaps with reconfiguration of different annular PPCs have been studied both experimentally and numerically. The band gaps between 28.0–30.0 GHz for the core-annular lattice and the concentric-annular lattice are experimentally verified. A phenomenological reaction–diffusion model with two nonlinear-coupled interacting layers is established to mimic the formation of various plasma structures. Experimental observations and numerical simulation are in good agreement. Our approach provides a unique strategy to create reversibly deformable annular PPCs, which may offer new capabilities and serve as a promising platform for various applications.
N2 vibrational excitation in atmospheric pressure ns pulse and RF plasma jets
Authors: Richards Caleb , Jans Elijah , Gulko Ilya , Orr Keegan , Adamovich Igor V
Published: January 2022

Time-resolved N2 vibrational temperature and translational–rotational temperature in quasi-two-dimensional atmospheric pressure plasma jets sustained by ns pulse and RF discharges in nitrogen/noble gas mixtures are measured by the broadband vibrational Coherent Anti-Stokes Raman Scattering (CARS) . The results indicate a much stronger vibrational excitation in the RF plasma jet, due to the lower reduced electric field and higher discharge power. In a ns pulse discharge in N2/He, N2 vibrational temperature is significantly lower compared to that in N2/Ar, due to the more rapid vibration–translation (V–T) relaxation of nitrogen by helium atoms. In the RF plasma jets in N2/Ne and N2/Ar, the vibrational excitation increases considerably as the nitrogen fraction in the mixture is reduced. The experimental data in the RF plasma jet in N2/Ar jet are compared with the kinetic modeling predictions. The results indicate that nitrogen vibrational excitation in N2/Ar plasma jets with a small N2 fraction in the mixture (several percent) is controlled primarily by electron impact, anharmonic vibration–vibration (V–V) pumping, and V–T relaxation by N atoms. In comparison, V–V energy transfer from the vibrationally excited molecules in the first excited electronic state, N2(A3Σu
+, v), which are generated primarily by the energy transfer from the metastable Ar atoms, has a minor effect on the vibrational populations of the ground electronic state, N2(X1Σg
+, v). Although the discharge energy fraction going to electronic excitation is significant, the predicted quasi-steady-state N2(A3Σu
+) number density, controlled by the energy pooling and quenching by N atoms, remains relatively low. Because of this, the net rate of N2(X1Σg
+) vibrational excitation by the V–V energy transfer from N2(A3Σu
+) is much lower compared to that by the direct electron impact. The results show that atmospheric pressure RF plasma jets can be used as sources of highly vibrationally excited N2 molecules and N atoms.
Polymer crystallization under external flow
Authors: Sheng Junfang , Chen Wei , Cui Kunpeng , Li Liangbin
Published: January 2022

The general aspects of polymer crystallization under external flow, i.e., flow-induced crystallization (FIC) from fundamental theoretical background to multi-scale characterization and modeling results are presented. FIC is crucial for modern polymer processing, such as blowing, casting, and injection modeling, as two-third of daily-used polymers is crystalline, and nearly all of them need to be processed before final applications. For academics, the FIC is intrinsically far from equilibrium, where the polymer crystallization behavior is different from that in quiescent conditions. The continuous investigation of crystallization contributes to a better understanding on the general non-equilibrium ordering in condensed physics. In the current review, the general theories related to polymer nucleation under flow (FIN) were summarized first as a preliminary knowledge. Various theories and models, i.e., coil–stretch transition and entropy reduction model, are briefly presented together with the modified versions. Subsequently, the multi-step ordering process of FIC is discussed in detail, including chain extension, conformational ordering, density fluctuation, and final perfection of the polymer crystalline. These achievements for a thorough understanding of the fundamental basis of FIC benefit from the development of various hyphenated rheometer, i.e., rheo-optical spectroscopy, rheo-IR, and rheo-x-ray scattering. The selected experimental results are introduced to present efforts on elucidating the multi-step and hierarchical structure transition during FIC. Then, the multi-scale modeling methods are summarized, including micro/meso scale simulation and macroscopic continuum modeling. At last, we briefly describe our personal opinions related to the future directions of this field, aiming to ultimately establish the unified theory of FIC and promote building of the more applicable models in the polymer processing.
Storage requirements in a 100% renewable electricity system: extreme events and inter-annual variability
Authors: Ruhnau Oliver , Qvist Staffan
Published: January 2022

In the context of 100% renewable electricity systems, prolonged periods with persistently scarce supply from wind and solar resources have received increasing academic and political attention. This article explores how such scarcity periods relate to energy storage requirements. To this end, we contrast results from a time series analysis with those from a system cost optimization model, based on a German 100% renewable case study using 35 years of hourly time series data. While our time series analysis supports previous findings that periods with persistently scarce supply last no longer than two weeks, we find that the maximum energy deficit occurs over a much longer period of nine weeks. This is because multiple scarce periods can closely follow each other. When considering storage losses and charging limitations, the period defining storage requirements extends over as much as 12 weeks. For this longer period, the cost-optimal storage needs to be large enough to supply 36 TWh of electricity, which is about three times larger than the energy deficit of the scarcest two weeks. Most of this storage is provided via hydrogen storage in salt caverns, of which the capacity is even larger due to electricity reconversion losses (55 TWh). Adding other sources of flexibility, for example with bioenergy, the duration of the period that defines storage requirements lengthens to more than one year. When optimizing system costs based on a single year rather than a multi-year time series, we find substantial inter-annual variation in the overall storage requirements, with the average year needing less than half as much storage as calculated for all 35 years together. We conclude that focusing on short-duration extreme events or single years can lead to an underestimation of storage requirements and costs of a 100% renewable system.
OP32 Pyroptosis Inhibition Prevents the Cytotoxicity Induced by IL-17 Without Impairing Its Beneficial Effects
Authors: Hong S N , Joo Hye S , Dong Kyung C , Young-Ho K , Ji Eun K , Ye Ji S
Published: January 2022

Background

Th17 cells and their main secreting cytokine interleukin-17A (IL-17) are considered as the main pathogenic factors in inflammatory bowel diseases (IBDs). However, anti-IL-17 neutralizing antibodies, a theoretically curative medication for IBDs, paradoxically aggravated intestinal inflammation. The mechanisms by which it mediates the protective and pathologic effects of IL-17 remain unclear in the intestinal epithelium.

Methods

The intestinal epithelial responses induced by IL-17 was evaluated using the human small intestinal organoid (enteroid) model.

Results

Organoid-forming efficiency, cell viability and proliferation of enteroids were decreased in proportion to the concentration of IL-17, which did not differ between the enteroids derived from controls and patients with Crohn’s disease. Bulk RNA-sequencing revealed the enrichment of secretion signaling in IL17-treated enteroids. Among its components, PIGR was up-regulated significantly as the concentration of IL-17 increased, resulting in IgA transcytosis and protective role against pathogens. The IL-17-induced cytotoxicity was predominantly mediated by pyroptosis with activation of CASP1 and cleavage of GSDMD. Single-cell RNA- sequencing identified pyroptosis occurred actively in intestinal stem cells (ISCs) and enterocytes. Anti-IL-17 antibody, izekizumab, completely restored IL-17-induced cytotoxicity, but suppressed mucin secretion and IgA transcytosis. CASP1 inhibitor, Ac-YVAD-cmk, restores cytotoxicity induced by IL-17, without impairing its beneficial effects.

Conclusion

IL-17 induces pyroptosis of ISCs and enterocytes, as well as mucin secretion and PIGR-induced IgA transcytosis. Paradoxical gastrointestinal effects of IL-17 neutralizing antibodies may be associated with inhibition of mucin secretion and IgA transcytosis. The inhibition of pyroptosis using the CASP1 inhibitor prevents the cytotoxicity induced by IL-17 without compromising its beneficial effects.
OP38 Tofacitinib for the treatment of Ulcerative Colitis: An integrated summary of safety data from the global OCTAVE and RIVETING clinical trials
Authors: Sandborn W J , D’Haens G R , Sands B E , Panaccione R , Ng S C , Lawendy N , Kulisek N , Guo X , Mundayat R , Su C , Panés J
Published: January 2022

Background

Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Efficacy and safety of tofacitinib were evaluated in randomised, placebo-controlled Phase (P)2 (NCT00787202) and P3 (NCT01465763; NCT01458951; NCT01458574) studies, an open-label, long-term extension (OLE) study (NCT01470612) and an ongoing P3b/4 study (NCT03281304). We report updated tofacitinib safety analyses from the tofacitinib UC clinical programme, with inclusion of a 6-month interim analysis of data from the P3b/4 study, up to 7.8 years of tofacitinib exposure.

Methods

This analysis included 1157 patients (pts) receiving tofacitinib 5 or 10 mg BID from completed P2/P3/OLE studies, and the ongoing P3b/4 study (as of 20 Feb 2020; Overall+P3b/4 Cohort). Proportions and incidence rates (IRs; unique pts with events/100 pt-years [PY] of exposure) were evaluated for deaths and adverse events (AEs) of special interest. Opportunistic infections (OIs), malignancies, major adverse cardiovascular events (MACE) and gastrointestinal perforations were adjudicated.

Results

Table 1 shows demographics and clinical characteristics. In the Overall+P3b/4 Cohort, 1157 pts received ≥1 dose of tofacitinib 5 or 10 mg BID; 955 (83%) received a predominant dose of 10 mg BID; 397/1157 (34.3%) pts had received tofacitinib for >4.1 years. Median treatment duration was 623 (range, 1–2850) days (2999.7 PY of exposure). Table 2 shows safety data for AEs of special interest in the Overall+P3b/4 Cohort. IRs (95% confidence intervals) for all tofacitinib doses: deaths, 0.23 (0.09, 0.46); serious infections, 1.69 (1.26, 2.21); herpes zoster (non-serious and serious), 3.30 (2.67, 4.04); OIs, 1.03 (0.70, 1.46); malignancies (excluding non-melanoma skin cancer [NMSC]), 0.84 (0.55, 1.24); NMSC, 0.73 (0.45, 1.10); MACE, 0.29 (0.13, 0.55); deep vein thrombosis, 0.03 (0.00, 0.18); pulmonary embolism, 0.19 (0.07, 0.42); and gastrointestinal perforations, 0.10 (0.02, 0.28). IRs for AEs of special interest were similar to prior Overall Cohort analyses.1

Conclusion

The safety profile of tofacitinib in pts with UC from the tofacitinib UC clinical programme was generally consistent with that of other UC therapies, including biologics, with the exception of herpes zoster.2 IRs for AEs of special interest have remained stable over an extended period of time (up to 7.8 years) with inclusion of final data from the OLE study and an interim analysis of data from the P3b/4 study.1,3

References

1. Sandborn WJ et al. United European Gastroenterol J 2021; 9 (Suppl 8): Abstract OP152.

2. Curtis JR et al. Inflamm Bowel Dis 2021; 27: 1394–1408.

3. Sandborn WJ et al. United European Gastroenterol J 2020; 8 (Suppl 8): Abstract OP494.
DOP09 Phenotypic and genetic determinants of medication response in patients in the UK IBD BioResource
Authors: Zhang Q , Fachal L , Shawky R , Lamb C , Parkes M , Anderson C , Raine T
Published: January 2022

Background

Inflammatory bowel disease (IBD) exhibits heterogeneity at genetic, phenotypic, and therapeutic levels [1]. Although several studies have investigated genetic effects on IBD subtypes and drug adverse events [2,3], few have comprehensively explored the phenotypic and genetic determinants of IBD drug efficacy in a sufficiently powered cohort.

Methods

We used data from 32,199 patients in the UK IBD BioResource to investigate the effects of clinical phenotypes and demographics on drug efficacy and combined this with genome-wide genetic data for a subset of 11,536 individuals (Table 1). Drug efficacy was defined using a combination of clinician reported efficacy and persistence on drug without treatment escalation. Anti-TNF, thiopurine, steroids, and mesalazine were explored. We estimated phenotypic effects on drug efficacy using multivariable logistic regression and the genetic effects by genome-wide logistic regression. To explore whether drug efficacy and IBD disease susceptibility share a genetic basis, we estimated the proportion of variance in drug efficacy explained by known IBD risk variants [4]. Associations with Bonferroni corrected P-values < 0.05 were defined as statistically significant in phenotypic analyses and a genome-wide significance threshold of P=5x10-8 was adopted for genetic analyses.

Results

Drug efficacy was generally lower in patients with Crohn’s disease (CD) compared to those with other subtypes (OR ranges from 0.40 to 0.79), but anti-TNF showed a higher efficacy rate (OR = 1.21) in CD patients. Increasing age at diagnosis was associated with evidence of increased efficacy of thiopurine and mesalazine (Table 2). We found evidence of a genetic contribution to variation in drug efficacy for most drugs studied. However, known IBD risk variants showed little contribution (Figure 1). Using genome-wide association testing, we identified three loci showing a significant association with drug efficacy; two were related to steroid response and one to thiopurines (Table 3). None of these was an IBD disease susceptibility locus (P > 0.05).

Conclusion

Using a large, well-characterised cohort we found both genetic and phenotypic determinants of drug efficacy. Three loci were reported to be associated with drug efficacy in the first phase of the genetic analysis; at least 4,200 extra genotyped samples will be included before the ECCO meeting, thus increasing the power to detect additional loci. Our results suggest the genetic causes of drug efficacy and disease susceptibility are largely independent. These findings may provide opportunities for exploring the biology of drug efficacy and improving medication prioritization in IBD patients.

References

1. PMID: 16819502

2. PMID: 26490195

3. PMID: 30806694

4. PMID: 28067908
DOP13 The Arborisation index: An MRI-based measure of mesenteric hyperaemia in Crohn’s Disease
Authors: Naim I , Darie A M , Hoad C , Gowland P , Moran G W
Published: January 2022

Background

Robust and sensitive therapeutic targets are key in effective management of Inflammatory Bowel Disease1. Mesenteric hyperaemia is a recognized sign of active disease and in cross-sectional image is described as the comb sign. Although it is subjectively described, no automated quantitative MRI-based measures have been developed.

We aim to develop an automated methodology using contrast-less time of flight (TOF) Magnetic resonance angiography (MRA).

Methods

A MATLAB algorithm was developed to track the vessels on a 3D maximum intensity projection of a TOF MRA data set and calculate an arborization Index which is the number of branching points in the intrabdominal vessels (figure 1). 2D TOF scans were acquired in the transverse plane between the top of the hip joint and L4 vertebra using a 3T Ingenia Wide bore scanner (Philips, The Netherlands). The primary outcome was a comparison of the arborization index between Crohn’s disease (CD) and healthy volunteers (HV) groups. A planned sub-analysis was undertaken across CD and HV matched for BMI to investigate the effect of visceral fat on the arborization index. Repeated measures were undertaken to evaluate the variability of the quantification method. No contrast agents were used for the TOF MRA scans. Biological variations within each group and test-retest repeatability were assessed using the coefficient of variation (CV). Statistical analysis with unpaired, two-tailed t-tests were conducted and differences were considered significant when the p-value ≤0.05. All absolute values are presented as mean ±standard deviation (SD).

Results

In this prospective pilot study, 7 CD patients (C-Reactive Protein=5.2±6.1 mg/L, Faecal Calprotectin 611±981μg/g, BMI=23±3 kg/m2) and 15 HVs (BMI=29±7 kg/m2) were recruited. Patients showed a significantly higher arborization index when compared to HVs (mean arborization in HV=94±21 and CD=139±26; p-value=0.002). The difference in arborization index persisted in a sub-analysis of 7 HVs (BMI=24±2 kg/m2) and 7 CD patients (mean arborization in matched HVs=101±22 vs mean index in CD=139±26; p=0.01) (Figure 2). The CV was 23% for HVs and 18% for CD indicating biological variation. Test-retest variability calculated from multiple TOF scans of the same subjects gave a mean CV of 6±5% for both groups combined.

Conclusion

Our preliminary data suggest that the arborization index may be a useful measure of hypervascularity and hence intestinal inflammation in Inflammatory Bowel Disease. Further validation to standard disease activity measures is needed across larger cohorts to better investigate the utility of this potential biomarker as a non-invasive measure of disease activity and its reversibility to IBD therapies.

Reference

1.Turner,D.,et al.Gastro.2021;160(5):1570–1583.
DOP25 Clinical outcomes of COVID-19 and Impact on Disease Course in Patients with Inflammatory Bowel Disease
Authors: Wetwittayakhlang P , Albader F , Golovics P , Drügg Hahn G , Bessissow T , Bitton A , Afif W , Wild G , Lakatos PhD P L
Published: January 2022

Background

The impact of COVID-19 has been of great concern in patients with inflammatory bowel disease (IBD) worldwide, including an increased risk of severe outcomes and/or possible flare of IBD. This study aims to evaluate prevalence, outcomes, the impact of COVID-19 in patients with IBD, and risk factors associated with severe COVID-19 or flare of IBD activity.

Methods

A consecutive cohort of IBD patients followed at the McGill University Health Care Centre diagnosed with COVID-19 infection was obtained between March 1, 2020, and April 30, 2021. Demographics, comorbidities, IBD (type, treatments, pre-and post-COVID clinical activity, biomarkers, and endoscopic activity), and COVID-related outcomes (pneumonia, hospitalization, death, and flare of IBD disease) were analyzed.

Results

A total of 3,516 IBD cohort patients were included. 82 patients (2.3%) were diagnosed with COVID-19 infection (median age 39.0 (IQR 27.8–48.0), 77% with Crohn’s disease, 50% were female). The prevalence of COVID infection in IBD was significantly lower compared to the general population in Canada and Quebec (3.5% vs. 4.3%, p<0.001). Severe COVID occurred in 6 patients (7.3%); 2 patients (2.4%) died. A flare of IBD post-COVID infection was reported in 8 patients (9.8%) within 3 months. Biologic therapy was held during active COVID infection in 37% of patients. Age ≥55 years (odds ratio (OR):11.1, 95%CI:1.8–68.0), systemic corticosteroid use (OR:4.6, 95%CI:0.7–30.1), active IBD (OR:3.8, 95%CI:0.7–20.8) and comorbidity (OR:4.9, 95%CI:0.8–28.6) were factors associated with severe COVID. After initial infection, 61% of IBD patients received COVID-19 vaccinations.

Conclusion

The prevalence of COVID-19 infection among patients with IBD was lower than that in the general population in Canada. Severe COVID, mortality, and flare of IBD were relatively rare, while a large proportion of patients received COVID vaccination. Older age, comorbidities, active IBD disease, and systemic corticosteroid, but not immunosuppressive or biological therapy were associated with severe COVID infection.
DOP34 Comparison of the risk of clinical recurrence after ileocolonic resection for Crohn’s Disease for modified Rutgeerts’ score i2a and i2b categories: Individual patient data meta-analysis
Authors: Riviere P , Pekow J , Hammoudi N , Wils P , De Cruz P , Wang C , Mañosa M , Ollech J , Allez M , Nachury M , Kamm M , Maya A , Ferrante M , Buisson A , Singh S , Laharie D , Momar D , Fumery M
Published: January 2022

Background

The modified Rutgeerts’ score (mRS) differentiates i2a – lesions confined to the anastomosis – and i2b – neoterminal ileum lesions – categories. Its relevance for therapeutic management of Crohn’s disease (CD) patients after ileocolonic resection is still debated. Our objective was to compare the postoperative recurrence (POR) risk in patients with a mRS i2a or i2b score using an individual patient data meta-analysis.

Methods

We conducted a systematic literature search of Medline, Embase and abstracts from international conferences (until July 2020) to identify all relevant studies reporting the risk of clinical and/or surgical POR and the i2a/i2b status in the year following ileocolonic resection. Initial datasets were obtained from the corresponding authors. Time from endoscopy to clinical and surgical POR was estimated using Kaplan-Meier method. The association between time to event and mRS was evaluated using a mixed Cox with centre as the random effect.

Results

From the 17 studies identified, 7 published between 2008 and 2019 (cohort studies, n=4; clinical trials, n=2) corresponding to a total of 400 patients (median (InterQuartileRange) age at surgery 34 (26,47) years; 52% female) were included. In the year following ileocolonic resection, 189 (47%) patients displayed an i2a mRS and 211 (53%) an i2b. In the i2b group, we observed more male patients (56% versus 41%, p=0.01), more patients with previous ileocolonic resection (31% versus 21%, p=0.03) and temporary ileostomy (14% versus 6%, p=0.03) and an immunosuppressant or antiTNF therapy was more frequently initiated after endoscopy (42% versus 26%, p<0.01 and 36% versus 54%, p<0.01, respectively). The risk of clinical POR at 1, 3 and 5 years was 11% [6%-15%], 25% [18%-32%] and 36% [27%-43%] in the i2a group and 9% [5%-13%], 33% [26%-41%] and 47% [39%-56%] in the i2b group (p=0.63, p=0.12, et p=0.05 respectively). No significant difference was observed in terms of time to clinical POR (Hazard Ratio (HR)=1.27; Confidence Interval 95% [0.91,1.76]; p=0.16) (Figure 1) or surgical POR (HR=0.94; CI95% [0.44,2.00]; p=0.87). After exclusion of patients having initiated an immunosuppressant or a biologic in the 3 months after endoscopy (remaining cohort, n=361), no difference was observed in terms of clinical POR (HR=1.29 [0.92,1.80]; p=0.13) or surgical POR (HR=0.85 [0.39,1.84]; p=0.68).

Conclusion

In this individual patient data meta-analysis, no difference is observed between i2a and i2b mRS subcategories in terms of clinical, surgical or endoscopic POR. Limits of the mRS may explain this lack of predictive value.