bluuebunny/crossref_metadata_2025 huggingface dataset:
Lattice-Boltzmann modeling of centrifugal buoyancy-induced flows in rotating compressor cavities
Authors: Werner P. , Boussuge J. F. , Scholtes C. , Sagaut P.
Published: January 2024

Turbofan compressor cooling circuits exhibit inherent unsteadiness within their cavities due to the interplay of forced and natural convection phenomena. This dynamic is fueled by axial cooling throughflow, centrifugal forces, and large temperature gradients. This paper introduces an extended compressible lattice-Boltzmann approach tailored for accurately modeling centrifugal buoyancy-driven flows in such cavities. The approach integrates a local rotating reference frame model into a hybrid thermal lattice Boltzmann method, facilitating the simulation of rotating flows of perfect gases. Moreover, a new mass-conserving boundary treatment, based on the reconstruction of distribution functions, enhances precision in predicting rotor disk heat transfer. Finally, an adapted direct-coupling mesh-refinement strategy, accounting for source terms at grid transitions, enables efficient high buoyancy flow simulations. The proposed approach effectively recovers flow and heat transfer mechanisms on sealed and open rotating compressor cavity rigs, spanning a large range of Rayleigh numbers (up to 109). Through an analysis of the compressibility effects, adjustments to the adiabatic exponent and Eckert number allow for a significant boost in computational speed without undermining the reliability of the flow and heat transfer dynamics, aligning well with established theoretical models and numerical studies. With computational efficiency that outperforms conventional compressible finite volume solvers, the proposed approach stands as a promising method for industrial-scale modeling of turbomachinery cooling circuits.
Giant broadband spin-selective asymmetric transmission and wavefront shaping in transition-metal-dichalcogenide-based chiral metasurfaces
Authors: Chen Xiaolin , Gao Weiqing , Lei Dangyuan
Published: January 2024

Multidimensional spin-selective manipulation of optical waves is crucial for various intriguing applications in modern nanophotonics, such as quantum-information processing and chiral sensing and imaging. In this work, we observed giant broadband asymmetric transmission of circularly polarized waves and spin-preserving reflection, together with near-unity transmission circular dichroism, in a planar chiral metasurface composed of high-index transition-metal-dichalcogenide nanoantennas with large material anisotropy. The perpendicular and parallel electric and magnetic dipole moments excited in the nanoantennas under circularly polarized waves are explored to account for the asymmetric transmission and optical chirality. Combined with the Pancharatnam–Berry phase, we achieved the wavefront manipulation for transmitted circularly polarized waves with an efficiency approaching 91.5% and spin-selective focusing of an incident light via a metasurface metalens. Our work will pave the way for studying the multidimensional manipulation of optical spins through engineering transition-metal-dichalcogenide-based metasurfaces.
The warming-up effects of quantum-dot light emitting diodes: A reversible stability issue related to shell traps
Authors: Li Menglin , Zhang Xin , Bao Hui , Yan Yiran , Wu Xian-gang , Wang Cheng , Cao Yongqi , Yang Min , Chen Cuili , Hu Xiangmin , Hou Wenjun , Cao Weiran , Zhong Haizheng
Published: January 2024

The aging phenomenon is commonly observed in quantum-dot light emitting diodes (QLEDs), involving complex chemical or physical processes. Resolving the underlying mechanism of these aging issues is crucial to deliver reliable electroluminescent devices in future display applications. Here, we report a reversible positive aging phenomenon that the device brightness and efficiency significantly improve after device operation, but recover to initial states after long-time storage or mild heat treatment, which can be termed as warming-up effects. Steady and transient equivalent circuit analysis suggest that the radiative recombination current dramatically increases but electron leakage from the quantum dots (QDs) to hole transport layer becomes more accessible during the warming-up process. Further analysis discloses that the notable enhancement of device efficiency can be ascribed to the filling of shell traps in gradient alloyed QDs. This work reveals a distinct positive aging phenomenon featured with reversibility, and further guidelines would be provided to achieve stable QLED devices in real display applications.
Brownian motion in a viscous fluid of particles with constant and time-dependent friction
Authors: Tóthová Jana , Lisý Vladimír
Published: January 2024

The Brownian motion (BM) of particles in a fluid under the influence of a moving harmonic potential is described analytically. It is assumed that the bath is viscous and particles constituting it experience Stokes' force with friction coefficients that can depend on time. The generalized Langevin equation (GLE) is derived from the equations of motion for the bath and Brownian particles. It has a familiar form, but its memory kernel generalizes the expressions known from the literature even in the case of constant friction. Analytical solutions of the found GLE are obtained for the mean and mean squared displacements of the Brownian particle, assuming the overdamped character of its motion and both the overdamped and underdamped dynamics of bath particles. In the case of constant friction, the model well describes the BM when the external potential does not move so that the system is in equilibrium. The results determined by the time-dependent friction of the bath particles must be specified for concrete fluids. An example of Lennard–Jones atomic liquid is considered with the recently proposed exponential time dependence of the friction coefficient.
Variable-fidelity surrogate model based on transfer learning and its application in multidisciplinary design optimization of aircraft
Authors: Leng Jun-Xue , Feng Yuan , Huang Wei , Shen Yang , Wang Zhen-Guo
Published: January 2024

Variable-fidelity surrogate models leverage low-fidelity data with low cost to assist in constructing high-precision models, thereby improving modeling efficiency. However, traditional machine learning methods require high correlation between low-precision and high-precision data. To address this issue, a variable-fidelity deep neural network surrogate model based on transfer learning (VDNN-TL) is proposed. VDNN-TL selects and retains information encapsulated in different fidelity data through transfer neural network layers, reducing the model's demand for data correlation and enhancing modeling robustness. Two case studies are used to simulate scenarios with poor data correlation, and the predictive accuracy of VDNN-TL is compared with that of traditional surrogate models (e.g., Kriging and Co-Kriging). The obtained results demonstrate that, under the same modeling cost, VDNN-TL achieves higher predictive accuracy. Furthermore, in waverider shape multidisciplinary design optimization practice, the application of VDNN-TL improves optimization efficiency by 98.9%. After optimization, the lift-to-drag ratio of the waverider increases by 7.86%, and the volume ratio increases by 26.2%. Moreover, the performance evaluation error of the model for both the initial and optimized configurations is less than 2%, further validating the accuracy and effectiveness of VDNN-TL.
Two-temperature principle for evaluating electrothermal performance of GaN HEMTs
Authors: Shen Yang , Cao Bingyang
Published: January 2024

Self-heating effects in Gallium nitride (GaN) high-electron-mobility transistors (HEMTs) can adversely impact both device reliability and electrical performance. Despite this, a holistic understanding of the relationship among heat transport mechanisms, device reliability, and degradation of electrical performance has yet to be established. This Letter presents an in-depth analysis of self-heating effects in GaN HEMTs using technology computer-aided design and phonon Monte Carlo simulations. We examine the differential behaviors of the maximum channel temperature (Tmax) and the equivalent channel temperature (Teq) in response to non-Fourier heat spreading processes, highlighting their respective dependencies on bias conditions and phonon ballistic effects. Our study reveals that Tmax, a crucial metric for device reliability, is highly sensitive to both heat source-related and cross-plane ballistic effects, especially in the saturation regime. In contrast, Teq, which correlates with drain current degradation, shows minimal bias dependence and is predominantly influenced by the cross-plane ballistic effect. These findings emphasize the importance of optimizing device designs to mitigate both Tmax and Teq, with a particular focus on thermal designs influenced by the heat source size. This work contributes to a deeper understanding of self-heating phenomena in GaN HEMTs and provides valuable insights for enhancing device performance and reliability.
Astrocytic TIMP-1 regulates production of Anastellin, an inhibitor of oligodendrocyte differentiation and FTY720 responses
Authors: Sutter Pearl A. , Willis Cory M. , Menoret Antoine , Nicaise Alexandra M. , Sacino Anthony , Sikkema Arend. H. , Jellison Evan R. , Win Kyaw K. , Han David K. , Church William , Baron Wia , Vella Anthony T. , Crocker Stephen J.
Published: January 2024

Astrocyte activation is associated with neuropathology and the production of tissue inhibitor of metalloproteinase-1 (TIMP1). TIMP1 is a pleiotropic extracellular protein that functions both as a protease inhibitor and as a growth factor. Astrocytes that lack expression of
Timp1
do not support rat oligodendrocyte progenitor cell (rOPC) differentiation, and adult global
Timp1
knockout (
Timp1
KO
) mice do not efficiently remyelinate following a demyelinating injury. Here, we performed an unbiased proteomic analysis and identified a fibronectin-derived peptide called Anastellin (Ana) that was unique to the
Timp1
KO
astrocyte secretome. Ana was found to block rOPC differentiation in vitro and enhanced the inhibitory influence of fibronectin on rOPC differentiation. Ana is known to act upon the sphingosine-1-phosphate receptor 1, and we determined that Ana also blocked the pro-myelinating effect of FTY720 (or fingolimod) on rOPC differentiation
in vitro.
Administration of FTY720 to wild-type C57BL/6 mice during MOG
35-55
-experimental autoimmune encephalomyelitis ameliorated clinical disability while FTY720 administered to mice lacking expression of
Timp1
(
Timp1
KO
) had no effect. Analysis of
Timp1
and fibronectin (
FN1
) transcripts from primary human astrocytes from healthy and multiple sclerosis (MS) donors revealed lower
TIMP1
expression was coincident with elevated
FN1
in MS astrocytes. Last, analyses of proteomic databases of MS samples identified Ana peptides to be more abundant in the cerebrospinal fluid (CSF) of human MS patients with high disease activity. A role for Ana in MS as a consequence of a lack of astrocytic TIMP-1 production could influence both the efficacy of fingolimod responses and innate remyelination potential in the MS brain.
Manifold fitting with CycleGAN
Authors: Yao Zhigang , Su Jiaji , Yau Shing-Tung
Published: January 2024

Manifold fitting, which offers substantial potential for efficient and accurate modeling, poses a critical challenge in nonlinear data analysis. This study presents an approach that employs neural networks to fit the latent manifold. Leveraging the generative adversarial framework, this method learns smooth mappings between low-dimensional latent space and high-dimensional ambient space, echoing the Riemannian exponential and logarithmic maps. The well-trained neural networks provide estimations for the latent manifold, facilitate data projection onto the manifold, and even generate data points that reside directly within the manifold. Through an extensive series of simulation studies and real data experiments, we demonstrate the effectiveness and accuracy of our approach in capturing the inherent structure of the underlying manifold within the ambient space data. Notably, our method exceeds the computational efficiency limitations of previous approaches and offers control over the dimensionality and smoothness of the resulting manifold. This advancement holds significant potential in the fields of statistics and computer science. The seamless integration of powerful neural network architectures with generative adversarial techniques unlocks possibilities for manifold fitting, thereby enhancing data analysis. The implications of our findings span diverse applications, from dimensionality reduction and data visualization to generating authentic data. Collectively, our research paves the way for future advancements in nonlinear data analysis and offers a beacon for subsequent scholarly pursuits.
Hybrid magnon-photon system for sensing weak phase
Authors: Han Jia-Yun , Tian Zhao-Peng , Cheng Yu-Di , Huang Hai-Bo , Zhou Xue-Liang , Wu Wen-Huan , Zhou Yuan , Wang Qing-Lan
Published: January 2024

It belongs to a hot topic to sense or detect the weak and even ultra-weak physical quantities by utilizing quantum platforms and methods. We here propose a hybrid magnon-photon system of the yttrium iron garnet (YIG) magnon mode coupled to a microwave cavity, which also includes another degree of freedom with respect to the thermal vibration of this YIG microsphere. In this quasi-tripartite coupling system, we generalize the condition for satisfying energy degeneracy and anti-crossing behaviors. Especially around the zero-energy area, we can get the joint quantum effects of anti-crossing behavior and degeneracy of systemic energy, and then reach a significantly enhanced sensitivity to this phase disturbance. Therefore our proposal can characterize this weak vibration through a phase disturbance and indicate a group of clearly resolvable output spectra. This investigation may be considered as an encouraging attempt on sensing weak quantity by engineering the systemic energy into the critical area for further enlarging its sensitivity to the weak disturbance.
Arc root dynamics in the context of lightning strikes to aircraft
Authors: Andraud V , Martins R Sousa , Zaepffel C , Landfried R , Testé P , Lalande P
Published: January 2024

During lightning strikes to aircraft, there is a displacement of the impacted area on the aircraft’s surface and the dynamic of the arc root is a key to understanding and predicting the damage produced on the aircraft skin. This work aims at studying experimentally this dynamic with a new method of producing sweeping arcs based on a stationary arc and an electromagnetic launcher propelling aeronautical test samples. The experiments are also achieved with a wind tunnel that blows the arc on the test sample for comparison. After a description of the previous experiments of arc root displacement and a distinction between the cathodic and anodic emission processes, this paper characterizes the arc root physical properties with direct visualization through high-speed cameras and electric measurements for different initial conditions. The results are separated by the arc root polarity and discussed to give an insight into the influence of the experimental conditions on the interaction between the electric arc root and the test sample during swept-stroke. It is shown that for a cathodic arc root, the nature of the displacement—continuous or jumping—highly depends on the current level and the speed of the relative motion between the electric arc and the test sample. For an anodic arc roots, the variations of these parameters provoke jumping modes of displacement with different characteristics.
A building electrical system fault diagnosis method based on random forest optimized by improved sparrow search algorithm
Authors: Li Zhangling , Wang Qi , Xiong Jianbin , Cen Jian , Dai Qingyun , Liang Qiong , Lu Tiantian
Published: January 2024

Addressing the problems of manual dependence and low accuracy of traditional building electrical system fault diagnosis, this paper proposes a novel method, which is based on random forest (RF) optimized by improved sparrow search algorithm (ISSA-RF). Firstly, the method utilizes a fault collection platform to acquire raw signals of various faults. Secondly, the features of these signals are extracted by time-domain and frequency-domain analysis. Furthermore, principal component analysis is employed to reduce the dimensionality of the extracted features. Finally, the reduced features are input into ISSA-RF for classification. In ISSA-RF, the ISSA is used to optimize the parameters of the RF. The parameters for ISSA optimization are n_estimators and min_samples_leaf. In this case, the accuracy of the proposed method can reach 98.61% through validation experiment. In addition, the proposed method also exhibits superior performance compared with traditional fault classification algorithms and the latest building electrical fault diagnosis algorithms.
Optimized absorption of light in perovskite nanowire solar cells
Authors: Salimian Sina , Anttu Nicklas
Published: January 2024

Metal halide perovskite nanowires (PrvNWs) have recently emerged as an interesting path for nanostructured solar cells. Here, we model the absorption of light in PrvNW arrays for varying diameter and length of the PrvNWs and period for the array by solving the Maxwell equations. For long enough bare PrvNW arrays, we find that the optimum diameter is fixed to that which places the absorption peak from the HE11 waveguide mode in the PrvNWs to the vicinity of the bandgap wavelength. In contrast, when we include a transparent conductive oxide (TCO) top contact layer, the optimum diameter shifts to a larger value by 100 nm. The origin of this shift is traced to a reduced reflection at the interface between the TCO layer and the PrvNW array when the PrvNW’s diameter is larger. Overall, we find that 1500 nm long PrvNWs can reach 90% of the broadband absorption potential, making this system of high interest for photovoltaics.
Optimisation of the processing parameters for the fabrication of high-quality joints between Y–Ba–Cu–O single grain, bulk superconductors
Authors: Congreve J V J , Shi Y , Druiff H , Dennis A R , Taylor R W , Bumby C W , Cardwell D A , Durrell J H
Published: January 2024

High-strength permanent magnets are essential for a wide range of technologies, including levitation devices, motors, generators and magnetic separators. Replacing permanent magnets with single grain, bulk superconductors will enable a step-change in the performance of these technologies by providing an order-of-magnitude increase in magnetic field. However, there remain many key challenges to the practical implementation of bulk superconductors, of which size and geometry are the most fundamental. The current limits to the size and geometry of (RE)-Ba–Cu–O single grain, bulk superconductors would be overcome substantially by the ability to fabricate high-quality joints between these technologically important materials. In this work we present new insights into the creation of superconducting joints between single grain bulk YBCO superconductors using a YBCO-Ag intermediate composition. We have investigated the effect of the joint fabrication temperature on the quality of the joint in order to begin to optimise the joint fabrication route for YBCO. We report on 35 joints produced at different joining temperatures as part of this study. The trapped field properties of the resulting joined samples were measured and the microstructure at each joint was examined. We show that this simple and rapid joining technique is robust to small changes in joint fabrication temperature and suggest routes to further optimise this potentially transformative technique.
Influence of thickness and domain structure on the vortex instability of superconducting/ferromagnetic bilayers
Authors: Blatter G , Sirena M , Lee Yeonkyu , Yun Jinyoung , Kim Jeehoon , Biasi E De , Haberkorn N
Published: January 2024

We report on the vortex instability in superconducting/ferromagnetic (FM) bilayers. Samples consisting of a 23 nm thick Mo2N superconducting layer with a capping layer of Co, Fe20Ni80, or FePt ferromagnets were grown by sputtering at room temperature on silicon (100). Our study reveals that the critical vortex velocity in these superconducting bilayers is significantly influenced by the thickness of the FM layers rather than the specific magnetic domain structure. When comparing samples with FM layers of 10 nm and 50 nm thickness, we observe a notable increase in vortex velocities at low magnetic fields, with speeds rising from approximately 3.5 km s−1 to around 6 km s−1 as the thickness increases. This trend extends to moderate and high magnetic fields. Furthermore, we establish a direct correlation between vortex velocities and the thermal conductance of the FM layers. These findings provide valuable insights for the interplay of magnetic and thermal properties within these hybrid systems, with potential implications for the design of future devices and applications.
Wavefront reconstruction based on ASH-Net with less lenslets SHWFS
Authors: Wang Hongyan , Zhang Qi , Hu Ming , Xu Xingyu , Wu Jingjing , Hu Lifa
Published: January 2024

Generally, the number of lenslets in Shack–Hartman wavefront sensor (SHWFS) determines its spatial sampling frequency. However, increasing the number of lenslets is limited by the data processing delay time and low sensitivity in the adaptive optics system. In this paper, a wavefront reconstruction method based on ASH-Net for SHWFS is presented to recover the distorted wavefront from the light spots array with high accuracy with a spatial sampling frequency than traditionally required. The results show that the maximum number of Zernike modes recovered by the method is 36, 54, and 70 for 4 × 4, 6 × 6, and 8 × 8 lenslets arrays, respectively. Residual wavefront root mean square values are as low as about 0.02 μm, corresponding to a Strehl Ratio of 0.99. This method breaks the limitation that the number of reconstructed Zernike modes in the traditional wavefront reconstruction algorithm must be less than the number of effective lenslets. Experiments in lab are used to validate the method. Additionally, fewer lenslets is valuable to improve the detection capability of SHWFS for faint targets. This is important for applications of adaptive optics in areas such as astronomy and retinal imaging.
High sensitive optical thermometry based on redshift of charge transfer band in Ba2CaWO6:Eu3+ phosphors
Authors: Xie Jialiang , Zhong Lei , Jiang Sha , Wang Yutong , Li Yanru , Huang Binyao , Li Li , Wang Yongjie , Xiang Guotao , Zhou Xianju
Published: January 2024

Optical thermometry has emerged as a promising technology to overcome the limitations of traditional thermometry techniques. Herein, we report an Eu3+-activated tungstate Ba2CaWO6 phosphors for luminescent thermometry with a maximum relative sensitivity of 4.84% based on a single-band ratiometric technique. By monitoring the 5D0 → 7F1 (595 nm) emission of Eu3+, excitation spectrum of the as-prepared sample was measured, showing a dominant broad band ranging from 240 to 345 nm corresponding to the O2−-W6+ charge transfer band (CTB). The intensity of CTB gradually decreases and the CTB edge shows an appreciable red shift when the temperature increases due to thermal population of the [WO6]6− moiety at higher vibrational levels. The opposite temperature dependences of the two specific excitations, one at the peak of CTB and the other from the edge of CTB, were employed to design a luminescence intensity ratio thermometry scheme in the tungstate. When compared to other related schemes, our scheme showed a higher relative sensitivity.
Flexible pressure sensor constructed by polyurethane composite conductive sponge
Authors: Dong Liang , Li Chen , Zhou Youjun , Zhao Mengxi , Song Longgang , Han Peiying , Zhang Heng
Published: January 2024

As the main core component of wearable devices, flexible strain sensors have broad application prospects in health monitoring, motion monitoring, human-machine interface, rehabilitation, entertainment technology and other fields. In this paper, a rectangular sandwich resistive pressure sensor is constructed with porous conductive sponge, and its working mechanism is analyzed. The linearity of the sensor is improved and the stress range is increased by gel modification. Through experimental tests, it can withstand more than 80% compressive strain, and shows a sensitivity of 0.398 kPa−1 in the range of 6 ∼ 11 kPa; the maximum range is close to 40 kPa, and the minimum detection limit is 20 Pa; under constant loading/releasing speed, the response/recovery time is about 133/150 ms; it also shows good linearity and stability. With the help of a single sensor entity, Morse code can be sent, and some human activity signals can be measured, such as speech recognition, weighing measurement, limb movement; and 8 sensors create an interesting smart insole for gait recognition. The results show that piezoresistive sensors with porous composite materials have broad application prospects in motion monitoring and human-computer interaction.
OP08 Multi-ancestry genome-wide association study of inflammatory bowel disease identifies 125 novel loci and directly implicates new genes in disease susceptibility
Authors: Fachal L
Published: January 2024

Background

Genome-wide association studies (GWASs) have identified 320 loci associated with inflammatory bowel disease (IBD). About 15% of these loci include genes that lie in pathways targeted by drugs currently approved to treat IBD. Thus, identifying new loci can not only provide further insights into causal biology but also reveal novel therapeutic targets.

Methods

We performed a multi-ancestry GWAS meta-analysis of 67 cohorts, from European, East Asian and South Asian populations. The final dataset included 125,992 IBD patients (59,734 with CD; 57,565 with UC) and more than 1.2 million population controls (Fig 1).

Genotype imputation was undertaken using the TOPMed diverse population panel and association tests were performed using REGENIE. The results were meta-analysed using a fixed effects meta-analysis via Metal.

To prioritise effector genes and generate therapeutic hypotheses, we integrated our results with bulk and single cell transcriptome data from relevant tissues and cell types. Through colocalization analyses we identified those signals driving the expression of nearby genes (cis-eQTL), suggesting that aberrant expression of these genes underpins the association.

Results

We identified 290 new independent disease susceptibility association signals. Out of these, 125 new signals are located >1Mb from any previously reported loci. Six new loci contain genes implicated in monogenic syndromes that include colitis GUCY2C, G6PC3, NFKBIA, PIK3CD, PIK3R1, ZBTB24.

Up to 40% of all disease susceptibility association signals colocalize with a cis-eQTL. For instance, a new variant associated with increased risk of UC (P=8x10-14) decreases the expression of the transmembrane mitochondrial protein TSPO in T cells, B cells, macrophages, and transverse colon. Pro-inflammatory macrophages show consistent TSPO downregulation. Loss of TSPO in mice causes exacerbated DSS-induced colitis. Ongoing clinical trials are evaluating whether targeting this gene could ameliorate the immune response in multiple sclerosis patients. We also identified a new CD susceptibility variant (P=3x10-16) associated with increased expression of WNK1 in monocytes and macrophages. Whereas loss of WNK1 in mice show increased expression of IL-1B in response to NLRP3 inflammasome activation; it also stimulates autophagy through the upregulation of the PI3KC3 complex. Impaired autophagy has shown to be key in promoting CD susceptibility.

Conclusion

Integrating molecular data from multiple cell types and conditions not only expands our ability to determine novel candidate causal genes, it also provides additional evidence of the utility of genetics as an instrument to guide the development of new therapeutic drugs or the repurposing of existing molecules.
DOP20 Changes in systemic antibody epitope repertoires from preclinical to established Inflammatory Bowel Disease
Authors: Bourgonje A R , Andreu-Sánchez S , Gacesa R , Klompus S , Kalka I N , Leviatan S , Weinberger A , Segal E , Fu J , Zhernakova A , Vogl T , Weersma R K
Published: January 2024

Background

Inflammatory bowel diseases (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), exhibit unique immunological changes early in development. Although >300 IBD-specific antibody responses have been identified1, systemic antibody epitope repertoires of preclinical IBD remain elusive. This study aimed to profile systemic antibody responses at unprecedented depth in individuals before and after the onset of IBD, aiming to identify preclinical disease biomarkers.

Methods

This study included individuals participating in the Lifelines Cohort Study, a large prospective population-based cohort study in the Netherlands including 167,000 individuals with longitudinal follow-up. Participants without IBD at baseline were screened for any reported IBD diagnosis during follow-up (2006-2021). Individuals who reported IBD during follow-up and with available serum samples were included. Samples at baseline (pre-diagnosis) and during follow-up (post-diagnosis) were used to profile antibody repertoires against 344,000 rationally selected microbial-, food-, and immune antigens using phage-display immunoprecipitation sequencing (PhIP-Seq).

Results

A total of 178 individuals with new-onset IBD were identified (Fig. 1). Median follow-up time until diagnosis was 3.9 (IQR: 3.4-4.3) years. Most individuals reported newly developed UC (n=123, 69.1%), followed by CD (n=44, 24.7%), and undetermined IBD (IBD-U, n=11, 6.2%). A total of 5,174 antibody responses were observed in 5-95% of participants. Fifty-nine antibodies were differentially abundant (FDR<0.05) pre-diagnosis vs. post-diagnosis (Fig. 2), 14 of which (24%) were previously reported as IBD-specific1. Thirteen were more (22%) and 46 less (78%) frequently observed post-diagnosis. Those developing UC exhibited 33 differentially abundant antibody responses, while those with CD exhibiting only four (FDR<0.05). Individuals developing IBD exhibited lower frequencies of antibody responses against EBV-associated peptides post-diagnosis, e.g. Epstein-Barr nuclear antigen-1 (EBNA-1) and capsid protein V26, and varicella-zoster virus, alongside higher antibody responses against bacterial flagellins. Individuals developing UC showed elevated antibody responses mainly against viruses (e.g. human adenovirus C, enteroviruses B/C) and particular pathogenic bacterial species (e.g. pneumococcal histidine triad proteins) post-diagnosis compared to pre-diagnosis.

Conclusion

Distinct antibody responses appear years before IBD diagnosis, indicating potential involvement in pre-clinical disease development. Furthermore, post-diagnosis, lower frequencies of antibody responses against EBV may suggest reduced immunogenicity against this virus in early disease pathogenesis.

1. Bourgonje et al. Immunity. 2023.
DOP21 Histo-endoscopic remission (HEMR) Predicts Future Relapse in Patients with Ulcerative Colitis and is Associated with Lower Colectomy Risk
Authors: Lenfant M , De Hertogh G , Sabino J , Verstockt B , Ferrante M , Vermeire S
Published: January 2024

Background

Treating beyond clinical and endoscopic remission, aiming for histological remission, is an aspiring target in ulcerative colitis [UC]. Hence, combined histo-endoscopic endpoints are increasingly being embraced. We assessed different degrees of histologic remission in patients with UC and their association with long-term outcomes.

Methods

UC patients achieving endoscopic improvement (Mayo endoscopic score [MES] ≤1) were recruited at colonoscopy. Clinical data were retrospectively collected from medical records. Endoscopies were video-recorded and biopsies from the most affected segment were collected for histological assessment and RNAseq (in case of MES 0 rectosigmoid biopsies were collected according to previous disease extent). Geboes Score [GS] and Robarts Histopathology Index [RHI] were determined for each biopsy by two pathologists blinded to the endoscopic scores. Non-histo-endoscopic remission [NHR], histo-endoscopic mucosal remission [HEMR] and histo-endoscopic mucosal normalization [HEMN] were defined as GS ≥2B.1, GS <2B.1 and GS ≤0.1. Clinical relapse was defined as the need for dose optimization, switching therapy or initiation of corticosteroids during follow-up. Long-term outcomes were analysed using log-rank test and Cox regression.

Results

Between 2016 and 2022, a total of 172 UC patients were included (Table). Endoscopic remission (MES 0) was achieved in 104 (60.4%) patients. NHR, HEMR and HEMN were observed in 15 (14.4%), 69 (85.6%), 51 (49.0%) of MES 0 patients and 32 (47.1%), 36 (52.9%), 18 (26.5%) of MES 1 patients. During a median [IQR] follow-up of 2.8 (1.9-3.9) years, 51 (29.7%) patients relapsed, and 7 (4.0%) patients needed colectomy. Relapse- and colectomy-free survival (Figure) were significantly higher when comparing HEMR to NHR (p<0.001 for both). This difference was not observed for endoscopic score (MES 0 vs. 1) or different degrees of histologic remission (HEMN vs. HEMR). The univariate Cox regression showed that histo-endoscopic activity, clinical activity (i.e., patient reported outcomes (PRO-2) for stool frequency or rectal bleeding > 0) and prior advanced therapy failure were associated with an increased risk of relapse. The multivariate Cox regression identified histo-endoscopic activity as the only risk factor for relapse (adjusted hazard ratio [HR]) = 3.01, 95% confidence interval [1.69-5.34], p<0.001).

Conclusion

In this cohort of UC patients with endoscopic improvement, 14.4% of MES 0 and 47.1% of MES 1 patients still showed signs of histologic activity (i.e., presence of neutrophils in the lamina propria or epithelium. Histologic remission was a superior predictor of future outcome (relapse, colectomy) when compared to endoscopic remission and showed to be the sole predictor of relapse.
DOP52 Guselkumab improves symptoms of fatigue in patients with moderately to severely active Ulcerative Colitis: Phase 3 QUASAR induction study results at Week 12
Authors: Dignass A , Panés J , Rubin D T , Huang K H G , Germinaro M , Pandya D , Han C , Miao Y , Zhang H , Gu F , Rowbotham D , Mihaly E , Bressler B , Lichtenstein G R , Allegretti J R
Published: January 2024

Background

Fatigue is a common symptom in patients with ulcerative colitis (UC) that impairs health-related quality of life. The Phase 3 QUASAR Induction Study (NCT04033445) was a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of guselkumab (GUS), an interleukin-23 p19 subunit antagonist, in patients with moderately to severely active UC. The impact of GUS IV induction on patient-reported symptoms of fatigue is reported here.

Methods

Patients were randomized 3:2 to receive GUS 200 mg IV or placebo IV at Weeks 0, 4, and 8. At baseline and Week 12, patients completed the Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue Short Form 7a (SF7a) which includes 7 items to evaluate symptoms of fatigue (ie, tiredness, exhaustion, mental tiredness, and lack of energy) and associated impacts on daily activities (ie, activity limitations related to work, self-care, and exercise). PROMIS-Fatigue-SF7a raw scores were converted to a standard T-score based on a general US population of mean=50 and SD=10. Higher scores indicate more severe fatigue symptoms. PROMIS-Fatigue SF7a outcomes were evaluated at Week 12 based on the improvements of ≥3, ≥5 and ≥7 points from baseline in PROMIS-Fatigue SF7a T-score. A ≥7-point improvement was defined as fatigue response (multiplicity-controlled secondary endpoint). A cumulative distribution function (CDF) curve and a probability density function (PDF) plot were used to demonstrate consistency of fatigue response.

Results

Seven hundred one patients were randomized and treated in the primary analysis population (mean UC duration, 7.5yrs, Mayo endoscopy subscore=3 [severe disease], 67.9%, and mean modified Mayo score, 6.9, at baseline). The mean (SD) PROMIS-Fatigue SF7a T-scores at baseline were similar between the treatment groups: 56.0 (8.77) for GUS 200 mg IV and 56.4 (8.90) for placebo IV. At Week 12, the mean change from baseline in PROMIS-Fatigue SF7a T-score was -5.7 for GUS and -2.1 for placebo (nominal p<0.001). Compared with placebo at Week 12, a higher proportion of GUS-treated patients achieved fatigue response (Table 1) and clinically meaningful ≥3-point and ≥5-point improvements in PROMIS-Fatigue SF7a T-scores (56.8% and 49.4% vs 34.6% and 26.4%, respectively, both nominal p<0.001). Both the CDF curve and PDF plot demonstrated consistency of greater treatment effect of GUS on fatigue vs placebo (Figure 1).

Conclusion

Moderately to severely active UC patients who received GUS induction treatment showed greater improvement in patient-reported symptoms of fatigue at Week 12 compared with placebo-treated patients.
P022 Development of a novel experimental model for studying creeping fat in Crohn's Disease
Authors: Clua L , Suau R , Guasch M , Monfort-Ferré D , Vañó I , Serena C , Domènech E , Bartolí R , Manyé J
Published: January 2024

Background

A characteristic feature of Crohn's disease (CD) is the transformation of mesenteric adipose tissue into creeping fat (CrF), which becomes inflamed and surrounds the transmural lesion. The occurrence of this condition has been associated with the severity of inflammation and post-surgical recurrence. In this study, we present a promising model of CD induced by 2,4,6-trinitro-benzene sulfonic acid (TNBS) that exhibits experimental CrF. This model provides an innovative tool for the development of surgical techniques as well as the implementation of new therapeutic strategies, as it more accurately depicts the nature of the pathology.

Methods

Acute colitis was induced by intrarectal instillation of TNBS under conventional conditions. Five days after the administration, acute colitis developed (Fig. A). The variation in the percentage of weight compared to the initial weight was analyzed. Clinical activity was assessed through colonoscopy on the third and fifth days based on parameters such as hyperemia, the extension of ulcers, and presence of stenosis. Further, the weight-to-length ratio of the colon, as well as the area of the lesions, was also collected. All obtained data were analyzed in order to identify any possible differences between the sexes or between the groups that presented CrF or not.

Results

The frequency of CrF occurrence was approximately 50% in both sexes. Even though, females had smaller volume of CrF and a greater presence of fistulas. As compared to controls, the weight of the animals with CrF decreased (Fig. B) and their clinical activity index increased (Fig. C). Moreover, the area of the lesion was significantly increased in the group with CrF as compared with the group without CrF (Fig. D). The CrF group also demonstrated a significant increase in the weight-to-length ratio of the colon. There were no significant differences between the sexes in the aspects mentioned above.

Conclusion

The group presenting CrF showed a significant increase in all parameters of disease severity analyzed. We would like to emphasize that animals exhibiting severe symptoms by the fifth day were precisely those that manifested the development of CrF. Importantly, it is noteworthy that monitoring the disease through colonoscopy avoids the necessity for the sacrifice of animals, thereby facilitating a reduction in sample size.
P036 Microbiota Metabolite Butyrate Attenuates Intestinal Inflammation Through Autophagy Activation
Authors: Mao Q , Zhang W , Zhang Y , Lin B , Cao Q , Xu M
Published: January 2024

Background

Alteration of the microbiota metabolite short chain fatty acids (SCFAs) may contribute to the development of inflammatory bowel disease (IBD). Butyrate, one of the SCFAs produced by bacteria, is known to be beneficial in attenuating intestinal inflammation. However, the mechanisms underlying anti-inflammatory effects of butyrate have not yet been entirely investigated.

Methods

In vivo, wild-type C57BL/6J mice were given a gavage of sodium butyrate (SB) (0.12g/ml) for 5 days. The mice were then administered 2% dextran sodium sulfate to induce experimental colitis models. Fecal microbiota was analysed by 16S rDNA sequencing. In vitro, HCT116 cell line was used to investigate the protective roles of SB on lipopolysaccharide (LPS)-induced inflammatory response. The levels of inflammatory cytokines, intestinal tight junction and autophagy were detected by western blotting and quantitative polymerase chain reaction.

Results

We observed that SB treatment significantly attenuated colitis in rodent models with reduced tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) and interleukin-1β expression, and tended to restore intestinal barrier dysfunction. Mechanically, we identified that the inclusion of SB enhanced protein level of Atg16l1, which indicated enhanced autophagy function. In vitro cell experiments also proved that mRNA levels of IL-6 and TNF-α were decreased, while autophagy-related Beclin was enhanced. Furthermore, our results revealed a distinct alteration mediated by butyrate in the gut microbiota by restored ratio of Firmicutes/Bacteroides, increasing Erysipelotrichaceae and reduced Desulfovibrio abundance.

Conclusion

This study provides the first data demonstrating that butyrate supplementation attenuates intestinal inflammation probably via promoting autophagy and regulating intestinal microbiota. Our findings provide new insights into butyrate-mediated remission of IBD and butyrate as a potential modulator for autophagy to prevent and treat IBD.
P044 Evaluation of the CO2 Footprint of Laparoscopic Ileocecal Resection for Terminal Ileitis in Crohn's Disease
Authors: Munster L , van der Zwet B M , de Groof E J , Mundt M W , D'Haens G R A M , Bemelman W A , Buskens C J , Stobernack T , van der Bilt J D W
Published: January 2024

Background

Each year, huge amounts of carbon dioxide (CO2/equivalents) are generated and healthcare systems play a major role in the production of those so called greenhouse gases (GHG). The aim of this study is to assess the environmental impact, in particular the CO2 footprint, of laparoscopic ileocecal resection (ICR) for terminal ileitis in Crohn’s disease (CD) patients.

Methods

This is a prospective, multicentre evaluation of the carbon dioxide (CO2) emission caused by the care of CD patients undergoing laparoscopic ICR for terminal ileitis. All processes and products used during laparoscopic ICR for terminal ileitis in adult CD patients (≥16 years) between March and May 2023 were collected by one monitor. A Life Cycle Assessment (LCA) was conducted, including midpoint and endpoint analysis, to evaluate and compare the environmental impact, mainly focussing on CO2 (-equivalents), of all products and processes.

Results

The total CO2 footprint of a laparoscopic ICR for terminal ileitis in one CD patient (including transport of staff and patients) was 139 kg CO2eq, which equals a one way trip by car from Amsterdam to Berlin. Major contributors to CO2 emissions (“hotspots”) were transport of employees, transport of patients, medication, laparoscopic tools, electricity in theatre and a combination of standard surgery items. In addition to the carbon footprint, a significant impact on ozone formation, human carcinogenic and ecotoxicity, water consumption and mineral resource scarcity was found. The amount of disability-adjusted life years (DALY’s) as a result of the environmental impact of one laparoscopic ICR are equal to approximately 2.5 hours of health damage per laparoscopic ICR.

Conclusion

The “5 R principle” (refuse, reduce, reuse, repurpose, recycle) is an import aspect in reduction of the CO2 footprint and in current medical guidelines, which should be taken into account by all employees (e.g. consider traveling by train/carpooling). The total CO2 footprint of a laparoscopic ICR for terminal ileitis in one CD patient is 139 kg CO2eq. In addition to quality of life (QoL) and overall costs, the carbon footprint and overall the environmental impact of all medical procedures, should be taken into consideration and should be optimized if possible in the multimodal treatment of patients with CD terminal ileitis. Therefore, further research into the environmental impact of (medical/surgical) treatment of CD patients is warranted and more process data should become available.
P046 Real-world data on the treatment with Mirikizumab in a mostly biological-experienced Ulcerative colitis cohort
Authors: Lande R , Kubesch A , Farrag K , Dienethal A , Sprinzl K , Zeuzem S , Blumenstein I
Published: January 2024

Background

Mirikizumab was approved for treating Ulcerative colitis (UC) in May 2023. However, real-world data, especially in biological-experienced patients, is scarce. We aimed to determine the treatment efficacy and persistence of Mirikizumab in mostly treatment-experienced UC patients.

Methods

All patients treated for UC in the Inflammatory Bowel Disease (IBD) outpatient clinic of the University Hospital Frankfurt from 07/23-11/23 were analyzed retrospectively. Data on clinical (Simple Clinical Colitis Activity Index (SCCAI)) and biochemical disease activity (fecal calprotectin (FC)), as well as patient history, were collected. Patients were followed up for at least 12 weeks.

Results

Seventeen patients with UC were included. Sixteen patients had already received at least one biological agent before starting Mirikizumab. Twelve patients were exposed to ≥ 2 biological agents, and four patients to ≥ 4 biological agents before starting Mirikizumab. One patient received Mirikizumab as a first-line treatment. 4 patients were treated with Ustekinumab before the therapy with Mirikizumab. Nine patients received oral steroids as a concomitant treatment. The median SCCAI at the time of the first infusion/start of induction was 7. We report a reduction in clinical disease activity from 7 to 5 based on the preliminary data of the SCCAI. Biochemical disease activity was assessed with FC levels. The median FC level at the start of the induction was 557.5. At week 8, the median FC level was 513 based on 7 out of 17 patients reached week eight until November 2023. Intravenous induction therapy was extended in 2 of 17 patients.

There was no report of adverse events.

Conclusion

We report preliminary real-world data on the evidence and efficacy of Mirikizumab. In our interim analysis, Mirikizumab is an effective and safe treatment in biological-experienced UC patients.