bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal features of non-accident critical events impact from tides around the Yangtze Estuary and adjacent coastal waters
Authors: Yao Chenyang , Gao Guoping , Chen Weijiong , Qin Tingrong , Li Zhuang
Published: January 2022

Applying non-accident critical events (NACEs) as an alternative measuring method to assess ship collision risk has become popular in recent years. NACEs has shown temporal features in different waters. This study uses the quaternion ship domain method to identify NACEs around the Yangtze Estuary and adjacent coastal waters from the Automatic Identification System (AIS) data in October 2019. The results indicate that NACEs show different temporal features in estuaries and coastal waters. The relationship between tides, channel types and ships is discussed. In addition, we established a statistical method for the occurrence time of NACEs and the state of tides according to the half-tide level and the nearest time. The outcomes of this study provide a direction for exploring the relationship between NACEs and environmental conditions, which is also instructive for the study of the causes of ship accidents.
Political Science at the NSF: The Politics of Knowledge Production
Authors: Moustafa Tamir
Published: January 2022

The National Science Foundation (NSF) recently replaced its long-standing Political Science Program with two new programs: the Security and Preparedness Program and the Accountable Institutions and Behavior Program. This article evaluates the likely impact of the reform by way of original survey data. The NSF Program Change Survey asked past recipients of the Political Science Program Standard Grant to evaluate their own previously funded proposals according to the new NSF program descriptions. Respondents were asked whether they would apply for the same research project under the new thematic programs and, if they would, whether they believed it would be necessary to change the framing or substance of their proposal. Data from the survey suggest that the new NSF program themes are likely to discourage some political scientists from applying, while encouraging many more applicants to shift the framing or substance of their research to accommodate the new call for proposals. In particular, the new Security and Preparedness Program carries significant consequences for new knowledge production.
Caspase-8 auto-cleavage regulates programmed cell death and collaborates with RIPK3/MLKL to prevent lymphopenia
Authors: Li Xiaoming , Li Fang , Zhang Xixi , Zhang Haiwei , Zhao Qun , Li Ming , Wu Xiaoxia , Wang Lingxia , Liu Jianling , Wu Xuanhui , Ou Yangjing , Xing Mingyan , Zhang Yue , Deng Jiangshan , Wang Xiuzhe , Luo Yan , Li Jinbao , Zhao Yuwu , Zhang Haibing
Published: January 2022

Caspase-8 is an initiator of death receptor-induced apoptosis and an inhibitor of RIPK3-MLKL-dependent necroptosis. In addition, caspase-8 has been implicated in diseases such as lymphoproliferation, immunodeficiency, and autoimmunity in humans. Although auto-cleavage is indispensable for caspase-8 activation, its physiological functions remain poorly understood. Here, we generated a caspase-8 mutant lacking E385 in auto-cleavage site knock-in mouse (Casp8ΔE385/ΔE385). Casp8ΔE385/ΔE385 cells were expectedly resistant to Fas-induced apoptosis, however, Casp8ΔE385/ΔE385 cells could switch TNF-α-induced apoptosis to necroptosis by attenuating RIPK1 cleavage. More importantly, CASP8(ΔE385) sensitized cells to RIPK3-MLKL-dependent necroptosis through promoting complex II formation and RIPK1-RIPK3 activation. Notably, Casp8ΔE385/ΔE385Ripk3−/− mice partially rescued the perinatal death of Ripk1−/− mice by blocking apoptosis and necroptosis. In contrast to the Casp8−/−Ripk3−/− and Casp8−/−Mlkl−/− mice appearing autoimmune lymphoproliferative syndrome (ALPS), both Casp8ΔE385/ΔE385Ripk3−/− and Casp8ΔE385/ΔE385Mlkl−/− mice developed transplantable lymphopenia that could be significantly reversed by RIPK1 heterozygosity, but not by RIPK1 kinase dead mutation. Collectively, these results demonstrate previously unappreciated roles for caspase-8 auto-cleavage in regulating necroptosis and maintaining lymphocytes homeostasis.
Monte Carlo optimum management of 241Am/Be disused sealed radioactive sources
Authors: Guembou Shouop Cebastien Joel , Mbida Mbembe Serge , Tayou Kamkumo Cedric , Beyala Ateba Jean Felix , Ndontchueng Moyo Maurice , Nguelem Mekongtso Eric Jilbert , Simo Augustin , Strivay David
Published: January 2022

The optimum encapsulation of 241Am/Be disused sealed radioactive sources (DSRS) based on PHITS Monte Carlo simulations for their long-term storage in Cameroon was performed. The country capacity for the management of disused neutron sources was also evaluated and showed that a Am1 P60 capsule is sufficient for the total available inventoried 241Am/Be DSRSs. The effective dose rate was computed in the enclosures of the DSRS container, which will be temporarily stored in the centralized radioactive waste facility. The obtained results were in agreement with the ALARA principle for the exposure rate optimization and the obtained exposure dose rates were found to be 1.830 μSv/h (horizontal calculation) and 0.137 μSv/h (vertical computation) which values are lower than the 2.5 μSv/h acceptable limit for the public area. The dose profile for 241Am/Be source obtained, the neutron flux, and gamma generated from neutron absorption showed agreement with the research hypothesis. The Monte Carlo assessment achieved in the present research will be useful for dismantling and preparing the waste package for long-term storage.
Label- and enzyme-free plasmon-enhanced single molecule fluorescence detection of HIV DNA fragments based on a catalytic hairpin assembly
Authors: Shi Ke , Na Na , Ouyang Jin
Published: January 2022

Enzyme- and label-free fluorescence detection of HIV DNA based on a catalytic hairpin assembly and plasmon resonance enhanced fluorescence.
Atomically dispersed Fe–N–C catalyst displaying ultra-high stability and recyclability for efficient electroreduction of CO2 to CO
Authors: Dong Bao-Xia , Peng Meng-Ting , Zheng Qiu-Hui , Cao Si-Min , Teng Yun-Lei , Zhong Di-Chang , Li Zong-Wei
Published: January 2022

By employing N-rich porphyrin-based MOFs PCN-224 and PCN-222 as precursors and adopting a mixed-ligand strategy, uniform dispersions of Fe SA catalysts were obtained with excellent CO2 → CO activity, super-stability, and recyclability.
Fluorescent probes for targeting endoplasmic reticulum: design strategies and their applications
Authors: Singh Deepmala , Rajput Deeksha , Kanvah Sriram
Published: January 2022

Fluorescent molecules for monitoring endoplasmic reticulum and chemical probes for the detection of ER cellular processes and analytes.
Anisotropic expansion effect of Sr doping on the crystal structure of hydroxyapatite
Authors: Wang Ming , Wang Yunli , Tian Yue , Zhu Yingchun
Published: January 2022

The anisotropic expansion effect of Sr on the HA crystal structure is proposed where the relative expansion rate in the c-axis direction is about 2.22 times that in the a-axis direction.
Formation of protonated water–hydrogen clusters in an ion trap mass spectrometer at room temperature
Authors: Mi Dongbo , Xu Junqiang , Zhang Yunpeng , Zhu Tenggao , Ouyang Jiewen , Dong Xiaofeng , Chingin Konstantin
Published: January 2022

The formation of protonated water-hydrogen clusters, [H+(H2O)n·m(H2)], in an ion trap at room temperature is demonstrated through the association of protonated water clusters H+(H2O)n with H2 gas, without any cooling necessary.
L’actualité scientifique de ce début 2022 vue par les étudiants de l’AMPS
Authors: Arcay Hippolyte , Chamouni Alexandre
Published: January 2022

L’AMPS rassemble les étudiants en santé qui, en plus de suivre une formation clinique, se forment à la recherche scientifique dans le but de devenir soignant-chercheurs. Elle promeut les interactions multidisciplinaires entre la santé et les sciences, et permet une émulation scientifique entre les étudiants des différentes facultés, aux profils, compétences et idées variés.
Comparative study of Tl-1223 superconductors prepared by the sol-gel route and solid-state reaction
Authors: Metskhvarishvili I. R. , Lobzhanidze T. E. , Dgebuadze G. N. , Bendeliani B. G. , Metskhvarishvili M. R. , Rusia M. Sh. , Giorganashvili G. R. , Gabunia V. M.
Published: January 2022

This paper presents sol-gel (SG) and solid-state reaction (SSR) pathways to produce multiphase ceramic precursors of BCCO and then the superconducting phase of Tl-1223. The heat treatments showed that to obtain high-purity precursors prepared by SG and SSR methods are sufficient to heat treatments at 915 and 945 °C, respectively. Furthermore, the diamagnetic onset temperature of the superconducting transition for the Tl-1223 samples prepared by precursors SG at 915 °C and SSR at 945 °C is approximately 120 K, and complete screening of applied ac magnetic fields observed at T ≈ 102 and ≈ 94 K, respectively. In addition, the value of the transport critical current density Jc for SSR was 128 A/cm2, whereas for the SG sample it was precisely 174 A/cm2. Thus, we could conclude that using wet chemistry offers some advantages over classical solid-state ceramic processing, significantly better chemical homogeneity, and higher reactivity of the precursor powder.
The first-principle study of substitutional impurities’ effect on elastic properties of TlInS2 layered crystal
Authors: Babuka T. , Gomonnai O. O. , Glukhov K. E. , Kharkhalis L. Yu. , Gomonnai A. V. , Makowska-Janusik M.
Published: January 2022

The elastic and vibrational properties of the TIInS2 and TlIn(S0.75Se0.25)2 crystals were first calculated applying DFT/PBE method augmented by dispersion correction (DFT/PBE-D). The elastic constants Cij, bulk modulus B, Young's modulus E, shear modulus G, Poisson's ratio σ, and coefficient B/G were calculated for the studied crystals. The phonon energy dispersion curves and partial densities of the phonon states for the TIInS2 and TlIn(S0.75Se0.25)2 were also calculated. The obtained data are comparable with the experimental results. Anomalies occurring in the phonon energies observed for the TlIn(S0.75Se0.25)2 crystal were explained.
Visualizing atomic processes using real-time scanning tunneling microscopy
Authors: Thompson Avery
Published: January 2022

Software and hardware developments reduce the time to create an STM image by several orders of magnitude, allowing for real-time atomic imaging.
Highly tunable directional optical antennas with large local angular chiroptical effects
Authors: Wang Yilin , Chen Weijin , Li Shilei , Hou Zhi-Ling , Yu Li
Published: January 2022

The highly localized field of the plasmonic nanostructures can amplify the chiroptical effects. While most efforts have been focused on spectral responses in real space for chiroptical effects of the plasmonic nanostructures, we present alternative extrinsic chiroptical effects with respect to angular emission patterns in momentum space based on the designed directional nanoantennas. First, the chiroptical effects with respect to spectral responses for the antenna are investigated and decomposed based on the multipolar expansion method. Through the traditional spectral responses, there seems to be no chirality. However, when we turn to the angular emission patterns in the momentum space for the nanoantenna, large local angular chiroptical effects are observed. The chiroptical effects assessed by the difference of azimuth angle emission lobes under left- and right-circularly polarized light illumination can reach 180°. The multipolar analysis combined with Green's function method in a stratified medium is constructed to explain the unidirectional emission and chiral phenomenon, which agrees well with the simulation results. Moreover, the local angular chiroptical effects are also highly tunable by changing the refractive index of the surrounding medium. Our study on local angular chiroptical effects provides a new perspective to understand the chirality, and the large extrinsic chirality for the nanoantenna sheds a new light for biosensing and chiral photon detection.
Evolution of plasmon-like excited states in silver nanowires and nanorods
Authors: Dillon Alva D. , Gieseking Rebecca L. M.
Published: January 2022

Silver nanowires and nanorods are useful prototypical systems to study the emergence of plasmons within a quantum mechanical context because their high aspect ratios enable plasmons to emerge in smaller systems than for roughly spherical nanoclusters. Here, we quantify the plasmon-like character of the excited states of silver nanorods and nanowires based on three nearly orthogonal criteria: (1) collectivity, (2) dipole additivity, and (3) superatomic character. Based on these three criteria, we classify the excited states as plasmon-like, collective, single-particle, interband, or as intermediate between these categories. We show that linear nanowires have a longitudinal absorption peak that has single-particle character and a transverse absorption peak that evolves from a single-particle to plasmon-like to a mix of plasmon-like and interband with increasing length. Increasing the width tends to increase the plasmon-like character of the longitudinal excited state. In contrast, increasing the nanorod width tends to decrease the length at which interband transitions start mixing significantly into the transverse plasmon-like excited states.
Realization of Fomenko-Zieschang invariants in closed symplectic manifolds with contact singularities
Authors: Zot’ev D. B. , Sidel’nikov V. I.
Published: January 2022

The topological bifurcations of Liouville foliations on invariant

-manifolds that are induced by attaching toric

-handles are investigated. It is shown that each marked molecule (Fomenko-Zieschang invariant) can be realized on an invariant submanifold of a closed symplectic manifold with contact singularities which is obtained by attaching toric

-handles sequentially to a set of symplectic manifolds, while these latter have the structures of locally trivial fibrations over

associated with atoms.

Bibliography: 10 titles.
Time minimization problem on the group of motions of a plane with admissible control in a half-disc
Authors: Mashtakov A. P.
Published: January 2022

The time minimization problem with admissible control in a half-disc is considered on the group of motions of a plane. The control system under study provides a model of a car on the plane that can move forwards or rotate in place. Optimal trajectories of such a system are used to detect salient curves in image analysis. In particular, in medical image analysis such trajectories are used for tracking vessels in retinal images. The problem is of independent interest in geometric control theory: it provides a model example when the set of values of the control parameters contains zero at the boundary. The problem of controllability and existence of optimal trajectories is studied. By analysing the Hamiltonian system of the Pontryagin maximum principle the explicit form of extremal controls and trajectories is found. Optimality of the extremals is partially investigated. The structure of the optimal synthesis is described.

Bibliography: 33 titles.
A social perspective on perceived distances reveals deep community structure
Authors: Berenhaut Kenneth S. , Moore Katherine E. , Melvin Ryan L.
Published: January 2022

Significance

Community structure arising through relationships and interactions is essential to our understanding of the world around us. Leveraging social concepts of conflict and support, we introduce a method to transform input dissimilarity comparisons into output pairwise relationship strengths (or
cohesion
) and resulting weighted networks. The introduced perspective may be particularly valuable for data with varying local density such as that arising from complex evolutionary processes. Mathematical results, together with applications in linguistics, genetics, and cultural psychology as well as to benchmark data, have been included. Together, these demonstrate how meaningful community structure can be identified without additional inputs (e.g., number of clusters or neighborhood size), optimization criteria, iterative procedures, or distributional assumptions.
Identification of alternative protein targets of glutamate-ureido-lysine associated with PSMA tracer uptake in prostate cancer cells
Authors: Bakht Martin K. , Hayward John J. , Shahbazi-Raz Farsheed , Skubal Magdalena , Tamura Ryo , Stringer Keith F. , Meister Daniel , Venkadakrishnan Varadha Balaji , Xue Hui , Pillon Adam , Stover Mathew , Tronchin Adam , Fifield Bre-Anne , Mader Lavleen , Ku Sheng-Yu , Cheon Gi Jeong , Kang Keon Wook , Wang Yuzhuo , Dong Xuesen , Beltran Himisha , Grimm Jan , Porter Lisa A. , Trant John F.
Published: January 2022

Significance

Glutamate-ureido-lysine (GUL) probes are specific for prostate-specific membrane antigen (PSMA), overexpressed by most prostate cancers. This antigen can be lost as the cancer progresses. Recent reports have indicated that GUL probes can still identify these PSMA-negative tumors, indicating that the expression of alternative PSMA-like proteins may change during disease progression. In this study we identified two such candidate protein targets, NAALADaseL and mGluR8, by using a combined computational chemistry, data mining, molecular biology, radiochemistry, and synthetic chemistry approach. This work consequently prepares the groundwork for developing specific probes that can identify this progression, indicates directions for neuroendocrine prostate cancer research, and highlights the utility of a multidisciplinary approach for the rapid identification of unidentified proteins interacting with diagnostic probes.
Synchronous inhibitory pathways create both efficiency and diversity in the retina
Authors: Manu Mihai , McIntosh Lane T. , Kastner David B. , Naecker Benjamin N. , Baccus Stephen A.
Published: January 2022

Significance

Complex connections in neural circuits make it difficult to quantitatively assign even the most basic neural computations to the actions of specific neurons. Retinal ganglion cells are most sensitive to changes in intensity across space and over time. This property, caused by a region known as the receptive field surround, improves information transmission about natural scenes. We dynamically manipulated individual interneurons to directly measure their effect on retinal receptive fields, finding that two inhibitory neuron types, horizontal cells and amacrine cells, synchronously create the same contribution to the receptive field surround at different spatial scales. By analyzing large populations of ganglion cells, we show that this arrangement increases diversity in retinal signaling while preserving maximal information transmission about natural scenes.
河南获嘉方言阳声韵所对应Z变韵形式的语音分析
Authors: Wei Mengyang
Published: January 2022

本文分析了河南获嘉方言阳声韵所对应Z变韵形式的语音生成过程，笔者认为获嘉方言阳声韵基本韵母的早期形式在“加缀合音”、“合音变韵”、“韵尾变[-ŋ]”、“韵腹滋生介音[i]”、“音长趋普”、“单元音化”以及“主元音鼻化”规则的按顺序作用下就可以推导出合格的表层Z变韵形式。同时，本文对[-n]尾阳声韵基本韵母在Z变韵过程中发生的韵尾、韵腹主元音及韵头的变化情况分别进行了讨论。笔者认为Z变韵过程中，韵尾[-n]变韵尾[-ŋ]是后缀[u]在合音过程中被前一音节的韵尾鼻化后变音所致；韵腹主元音音质的变化则与Z变韵后期，咸山摄阳声韵所对应的Z变韵母走上与咸山摄阳声韵基本韵母一致的演变道路有关；而韵腹滋生介音[i]是[an]组和[en]组阳声韵基本韵母在合音变韵过程中分别混入[ai]组和[ei]组阴声韵进行演化的结果。通过对咸山摄阳声韵所对应Z变韵母的语音形式进行分析，本文进一步提出“变韵不一定由合音引起”的观点。
Brahmi’s children
Authors: Gnanadesikan Amalia E.
Published: January 2022

A survey of modern descendants of Brahmi shows that the letter forms and various other features of the scripts vary, but the use of an inherent vowel and of dependent, satellite signs for other vowels is remarkably stable. Comparison is made to other scripts invented in the same geographic region, Thaana and Sorang Sompeng, and to the Arabic script as used in Arabic, Persian, Sorani Kurdish, Uyghur, and Kashmiri. Arabic scripts maintain uniform letter forms but vary considerably in their treatment of vowels. Cultural factors may explain the visual diversity of Brahmic scripts as compared to Arabic scripts. The stable combination of inherent vowel and satellite vowels derives from the decodability of simple aksharas into pronounceable syllabic units in the acquisition of reading. This akshara advantage is related to the psychological grain size theory of reading, with the additional claim that the syllable has special status because it is pronounceable.
Atg39 links and deforms the outer and inner nuclear membranes in selective autophagy of the nucleus
Authors: Mochida Keisuke , Otani Toshifumi , Katsumata Yuto , Kirisako Hiromi , Kakuta Chika , Kotani Tetsuya , Nakatogawa Hitoshi
Published: January 2022

In selective autophagy of the nucleus (hereafter nucleophagy), nucleus-derived double-membrane vesicles (NDVs) are formed, sequestered within autophagosomes, and delivered to lysosomes or vacuoles for degradation. In Saccharomyces cerevisiae, the nuclear envelope (NE) protein Atg39 acts as a nucleophagy receptor, which interacts with Atg8 to target NDVs to the forming autophagosomal membranes. In this study, we revealed that Atg39 is anchored to the outer nuclear membrane via its transmembrane domain and also associated with the inner nuclear membrane via membrane-binding amphipathic helices (APHs) in its perinuclear space region, thereby linking these membranes. We also revealed that autophagosome formation-coupled Atg39 crowding causes the NE to protrude toward the cytoplasm, and the tips of the protrusions are pinched off to generate NDVs. The APHs of Atg39 are crucial for Atg39 crowding in the NE and subsequent NE protrusion. These findings suggest that the nucleophagy receptor Atg39 plays pivotal roles in NE deformation during the generation of NDVs to be degraded by nucleophagy.
Ultrafast carrier dynamics in a monolayer MoS2 at carrier densities well above Mott density
Authors: Khatua Durga Prasad , Singh Asha , Gurung Sabina , Khan Salahuddin , Tanwar Manushree , Kumar Rajesh , Jayabalan J
Published: January 2022

Due to the growing interest in monolayer (ML) molybdenum disulfide (MoS2) in several optoelectronic applications like lasers, detectors, sensors, it is important to understand the ultrafast behavior of the excited carriers in this material. In this article, a comprehensive study of the charge carrier dynamics of a monolayer MoS2 flake has been studied using transient transmission technique near A-exciton under high excitation densities well above the Mott density. Fluence dependent studies has been carried out to understand the origin of the processes which modifies its optical response under excitation. The dissociation of excitons leads to an observed fast bandgap renormalization. At later times when large number of carriers relax the remaining carriers forms excitons leading to a bleaching effect.
Integrated spatial model based evaluation methodology for optimal invasive species management: common ragweed in the Republic of Korea
Authors: Chung Hye In , Choi Yuyoung , Yoo Youngjae , Engler Robin , Lee Kyungil , Jeon Seong Woo
Published: January 2022

Invasive species have become a global problem owing to their wide-ranging adverse effects. With intensifying climate change and artificial impacts (human-mediated disturbances), which exacerbate the adverse effects of invasive species, there is an urgent need to implement strategies for the management of these species. Various removal policies have been implemented globally to manage the common ragweed (Ambrosia artemisiifolia var. elatior (L.,) Decs) owing to its high tendency to ‘spread’. Several studies on the control method, application of spatial perspective, and optimization have been conducted to establish and evaluate management strategies using different spatial models. Although each of these methods is essential for improving control efficiency, an integrated form of study is needed to determine the practicality of various policies. In this study, we developed an integrated spatial model using the species distribution model BIOMOD2, land change model LCM, dispersal model MigClim, and optimization model prioritizr, to construct an evaluation methodology. For modelling an optimal invasive species removal policy under climate change and human-mediated disturbances (2011–2079), we created two strategies from a spatial perspective, outside-in and inside-out, with the former entailing removal from the low-density outliers to the high-density centre of the colonized area and the latter processing in the opposite direction. The optimal removal sites for each strategy were set for each removal rate. Subsequently, a novel index, ‘removal effect index’, was proposed for the evaluation, in time series. The results indicate that the removal effect of the outside-in strategy was more effective, and the newly dispersed sites were efficiently removed. Furthermore, it was verified that with the implementation of the outside-in strategy having a removal rate of 65% by the 2070s, the species would be completely eradicated. Thus, this study is expected to help improve the efficiency of policy implementation for invasive species.
Reduced theory for hard magnetic rods with dipole–dipole interactions
Authors: Sano Tomohiko G
Published: January 2022

Hard magnetic elastomers are composites of soft elastic foundations and magnetic particles with high coercivity. We formulate a theoretical framework to predict the large deformation of a hard magnetic elastomeric rod. In the previous work, the magnetic Kirchhoff rod equations, which constitute a framework for analyzing instabilities for hard magnetic rods, have been developed and validated experimentally for negligible dipole–dipole interactions. Building on previous studies, we derive the magnetic Kirchhoff rod equations with dipole–dipole interactions. The derived equations are integro-differential equations, representing the force and moment balance along the rod centerline that include long-ranged dipole-magnetic force and torque. On the basis of its discrete numerical simulation, we systematically study the effect of the the dipole–dipole interactions strength on the large deformation of hard magnetic rods. In addition, we find that our theory can predict previous experimental results without any adjustable parameters.
Increase efficiency and process optimization for an existing gas compressor station unit in Oil and Gas industry
Authors: Brezean Octavian Andrei
Published: January 2022

As most gas compression facilities in Romania are from the 60’s-80, there is an increased demand to increase their efficiency. The paper explains researches on energy, economic and functional efficiency of equipment and processes during the modernization of a compressor station in oil and gas industry. It is meant to serve as a general guide for methods and procedures usually used in the industry in Romania, to improve the efficiency of an existing compressor station.
Spray cryotherapy versus continued radiofrequency ablation in persistent Barrett’s esophagus
Authors: Genere Juan Reyes , Visrodia Kavel , Zakko Liam , Hoefnagel Sanne J M , Wang Kenneth K
Published: January 2022

Radiofrequency ablation (RFA) is the first-line treatment for flat Barrett’s esophagus (BE) with dysplasia, however its role for persistent Barrett’s esophagus (PBE) is unclear. PBE requires additional RFA sessions or application of cryotherapy to improve therapeutic response. We performed a retrospective cohort study evaluating cases of PBE treated by endoscopic eradication programs, with and without spray cryotherapy, and evaluated their safety and efficacy. We retrospectively identified patients with PBE, defined as ≤50% BE reduction or unchanged dysplasia after at least two RFA sessions. PBE was treated either by continued RFA (RFA Group) or converting to spray cryotherapy (CRYO Group), both followed by surveillance period. The rate of adverse events (AE), complete response of intestinal metaplasia (CRIM) and complete response of dysplasia (CRD) were recorded. A total of 46 patients, 23 per group, underwent 622 endoscopic therapies. Circumferential BE length was longer in the CRYO Group, but other baseline characteristics were similar, including maximal BE length. Esophageal strictures accounted for 14/16 total AE, 71% of which were RFA related, compared with 14% related to spray cryotherapy (P = 0.02). Overall CRIM/CRD rates in CRYO (83%) and RFA (96%) groups were not statistically different (P = 0.16), however cases in the CRYO Group required more treatment encounters (Median 19 vs. 12, P ≤ 0.01). Multimodal endotherapy is effective for eradicating PBE. Treatment programs incorporating spray cryotherapy are associated with less esophageal strictures but may require more treatment sessions to achieve eradication.
OP13 Modified 2-stage vs. 3-stage ileal pouch-anal anastomosis result in equivalent long-term functional outcomes and pouch survival: A matched-pair analysis
Authors: Holubar MD- MS S , Prien C , Jia X , Liska D , Kessler H , Valente M , Lightner A , Gorgun E , Hull T , Steele S
Published: January 2022

Background

Long-term outcomes data after modified 2-stage ileal pouch anal anastomosis (IPAA), defined as completion proctectomy (CP) and IPAA without loop ileostomy, is lacking. We aimed to describe long-term functional results, patient satisfaction, and pouch survival in a cohort of patients from a high-volume center. We hypothesized selective m2-stage can result in comparable long-term pouch survival relative to a 3-stage approach.

Methods

Our institutional ileal pouch database was retrospectively reviewed to identify patients who underwent index IPAA surgery from 1983–2019. Adults >18 years of age who underwent CP with IPAA were included. At our specialized institution, m2-stage is performed selectively based on surgeon judgement. Patients were stratified into 2 groups (3-stage vs m2-stage) and matched on a 1:1 basis based on age ±5, year of operation ±3, gender, preoperative diagnosis, double-stapled vs handsewn, and laparoscopy. Primary outcome was pouch survival, with pouch failure defined as permanent diversion, pouch excision, or conversion to a Kock pouch.

Results

In total, 2,433 patients were included, of whom 2,198 (90.3%) underwent 3-stage IPAA and 235 (9.7%) m2-stage IPAA. Matching resulted in 223 matched pairs, and long-term pouch survival (95.5% vs 93.2%, p=0.32) did not significantly differ (Figure 1). Short-term outcomes in the matched pairs revealed a shorter postoperative length of stay in the 3-stage patients (5 vs 8 days, p<0.001), but no significant difference in postoperative complications (12.1% vs 17%, p=0.09) was seen between the matched 3-stage and m2-stage patients, respectively. Functionally, there was no difference in the number of stools/24 hours (7 vs 7, p=0.33) or in proportion of patients requiring seepage protection at night (29.7% vs 24.6%, p=0.31). However, 3-stage patients required significantly more seepage protection during the day (25.1% vs 15.0%, p=0.02). Regarding pouchitis, there was no difference in the proportion of patients reporting recent symptoms (33.4% vs 33.3%, p=1.0), episodes in the last year (0 vs 0, p=0.51), or pouchitis requiring continuous medication (16.7% vs 10.1%, p=0.10). Patient satisfaction was similar as no difference in the proportion of those who would have surgery again (90.4% vs 93.7%, p=0.34), those who would recommend surgery (94% vs 95.5%, p=0.68), or overall patient satisfaction with surgery on a scale of 1 – 10 (highest) (3 vs 7, p=0.07) was reported.

Figure 1: Kaplan-Meier curve for pouch survival (matched pairs)

Conclusion

Long-term outcomes were similar in patients who underwent modified 2-stage and 3-stage IPAA. Modified 2-stage IPAA is an alternative for selected patients with limited options if performed at high-volume centers in experienced hands.
DOP08 Transcriptional signatures of blood derived immune cells associated with disease location-based heterogeneity in IBD
Authors: Sudhakar P , Verstockt B , Cremer J , Verstockt S , Sabino J , Ferrante M , Vermeire S
Published: January 2022

Background

Disease location is a prominent axis of heterogeneity in Inflammatory Bowel Disease (IBD) with many implications. Using genome-wide profiling of the transcriptome of monocytes and CD4+ T cells isolated and purified from whole blood, we aimed to identify molecular signatures and mechanisms associated with different locations among IBD patients.

Methods

Blood was collected from 125 IBD patients (87 CD, 38 UC) with endoscopy-proven active disease (presence of ulcerations). Cell separation and fluorescence activated cell sorting were performed to separate the monocyte and CD4+ T cell fractions, from which RNA was subsequently isolated and sequenced (Illumina HiSeq 4000NGS). We used different supervised and unsupervised approaches (differential expression, pathway based data integration, latent factor based models, regularized generalized canonical correlation analysis and co-expression networks) to interpret the differences in the gene expression datasets of monocytes and CD4+ T cells from patients with different disease locations (Montreal classification). Functional enrichment analysis was performed using the ReactomePA package. Regulatory relationships and therapeutic relevance information were retrieved from the ChEA3 and the OpenTargets resources respectively. Comparison with single-cell and bulk-derived gene expression signatures from other auto-immune diseases were performed using the ADEX resource.

Results

Highly variant disease-location (DL)-associated genes (FDR <= 0.1) in monocytes and CD4+ T cells were identified using latent factor based unsupervised models. These genes were known to be involved in IBD pathogenesis and/or intestinal inflammation. Additional supervised analysis revealed significant differences in CD4+ T cells between ileal CD patients and UC patients. RAF-independent MAPK-activation pathway and FOXO-mediated transcriptional pathway (downregulated in UC patients) were over-represented (FDR <= 0.05) among the features distinguishing ileal CD and UC patients based on signature sets derived from the above-mentioned multiple approaches. Of note was the finding that 12.5% of the DL associated co-expression modules were also annotated as IBD drug targets. Based on gene expression signature from bulk and single-cell sources, the DL associated genes were found to be active in many other auto-immune diseases such as rheumatoid arthritis, systemic sclerosis, Sjögren’s syndrome, type 1 diabetes and Systemic lupus erythematosus, suggesting their role in mediating immune malfunctions.

Conclusion

We identified signaling pathways and transcription factors which could drive the expression differences observed in the circulating immune cells between ileal CD and UC patients.
DOP20 Functional viral neutralisation responses after SARS-CoV-2 infection in Inflammatory Bowel Disease patients receiving infusion therapies: Report from the ICARUS-IBD Consortium
Authors: Wellens J , Edmans M , Obolski U , Marlow L , Brann S , Dunachie S , Eyre D , Helmus D , Barnes E , Colombel J F , Wong S Y , Klenerman P , Lindsay J O , Thompson C P , Satsangi J
Published: January 2022

Background

Recent data have highlighted adverse clinical outcomes in IBD patients treated with infliximab/thiopurines (IFX/THIO) upon infection with SARS-CoV-2, as well as attenuated serological responses after infection and vaccination in patients treated with IFX. To provide mechanistic insight, we explored the serological and functional anti-viral response after infection in IBD patients treated with VDZ, IFX or IFX/THIO compared to healthy controls to guide clinical decision-making regarding treatment and vaccination strategies.

Methods

Serum from 640 IBD patients attending routine infusions in Oxford and London in May to December 2020 was screened for anti-SARS-CoV-2 antibody responses by the Abbott assay. Serum from seropositive patients was compared to seropositive health care workers (Table 1). Antibody reactivity to the SARS-CoV-2 wild type strain receptor-binding domain (RBD), full-length spike, and nucleocapsid was assayed by IgG/IgA ELISA over time as well as by IgG high-throughput MSD V-PLEX ELISA at the time of seropositivity. A pseudotyped SARS-CoV-2 virus microneutralization assay was used to detect neutralising antibodies to the wild type, and an ELISA-based inhibition assay to compare differential inhibition of the wild type vs. delta variant SARS-CoV-2 RBD-ACE2 interaction.

Results

All IBD patients showed significantly reduced IgG antibody responses compared to healthy controls for all SARS-CoV-2 antigens, using MSD V-PLEX ELISA (Figure 1). The greatest reduction in IgG response by ELISA was observed in individuals treated with IFX/THIO (p=0.00019), whereas IgG response over time declined significantly faster in the IFX treated group (p=0.019). IgA responses were significantly reduced in the IFX/THIO group compared to healthy controls (p=0.009), but not in the IFX or VDZ monotherapy group. The rate of decline in these monotherapy groups was also not significantly different to healthy controls. Functional SARS-CoV-2 neutralisation was significantly lower in all IBD patients compared to healthy controls, with the greatest reduction in patients receiving IFX/THIO (Figure 2A; p=0.00000091). The delta variant inhibition capacity was significantly reduced in 68.1% of IBD patients (30/44, Figure 2B; p=0.0005).

Conclusion

IFX/THIO is associated with significantly lower IgA and IgG responses, and with impaired functional SARS-CoV-2 neutralising antibody capacity, compared to healthy individuals. Whilst IgG and neutralisation responses are reduced in each group of IBD patients, these findings were most pronounced in the combination treatment group. As neutralising antibody responses are associated with protection, this observation may impact on decision-making regarding treatment and vaccination/antiviral strategies.
DOP23 Long-term health consequences of COVID-19 in patients with Inflammatory Bowel Diseases – A Danish prospective population-based cohort study
Authors: Attauabi M , Dahlerup J F , Poulsen A , Hansen M R , Vester-Andersen M K , Eraslan S , Prahm A P , Pedersen N , Larsen L , Jess T , Neumann A , Haderslev K V , Molazahi A , Lødrup A B , Glerup H , Oppfeldt A M , Jensen M D , Theede K , Kiszka-Kanowitz M , Seidelin J B , Burisch J
Published: January 2022

Background

The vast majority of patients with ulcerative colitis (UC) and Crohn’s disease (CD) who acquire coronavirus disease 2019 (COVID-19) survive the infection. Still, the long-term health consequences of COVID-19 are not well described in patients with underlying inflammatory bowel disease (IBD).

Methods

We conducted a population-based study investigating the outcomes of COVID-19 among patients with UC and CD in Denmark. The Danish COVID-19 IBD Database is an extensive population-based database which prospectively monitors the disease course of laboratory-confirmed COVID-19 among patients with UC and CD. Severe COVID-19 was defined as COVID-19 necessitating intensive care unit admission, ventilator use, or death, while adverse COVID-19 was defined as requirement of COVID-19 related hospitalization. Sequelae following COVID-19 were defined as symptoms that developed during or after an infection consistent with COVID-19, were present for more than 12 weeks, and were not attributable to alternative diagnoses.

Results

The study included 319 patients with UC and 197 patients with CD from January 28th, 2020, to April 1st, 2021. Of these, a total of 137 (42.9%) and 85 (43.1%), respectively, participated in a subsequent investigation of post-COVID-19 sequelae after a median of 5.1 months (IQR 4.5–7.9) after infection (Table 1). An equal proportion of patients with UC (58 (42.3%)) and CD (39 (45.9%), p=0.60) reported persisting symptoms of COVID-19 for at least 12 weeks, consistent with the development of post-COVID-19 syndrome. The most common persisting patient-reported symptoms included fatigue (UC: 49 (35.8%), CD: 31 (36.5%), p=0.92), anosmia (UC: 37 (27.0%), CD: 25 (29.4%), p=0.70), ageusia (UC: 26 (19.0%), CD: 24 (28.2%), p=0.11), headache (UC: 19 (13.9%), CD: 16 (18.8%), p=0.32), dyspnea (UC: 19 (13.9%), CD: 16 (18.8%), p=0.32), and arthralgia (UC: 17 (12.4%), CD: 14 (16.5%), p=0.40) (Figure 1). Only discontinuation of immunosuppressive therapies for UC during COVID-19 (OR=1.50 (95% CI 1.07–10.22), p=0.01) and the severity of COVID-19 among patients with CD were independently associated with the long-term effects of COVID-19 (OR=2.76 (95% CI 1.05–3.90), p=0.04) (Tables 2–3).

Conclusion

This Danish population-based study found a high occurrence of patient-reported persisting symptoms following the acute phase of COVID-19 infection, which were associated with the discontinuation of immunosuppressive therapies for UC during COVID-19 and the severity of COVID-19 among patients with CD. These findings might have implications for planning the healthcare of patients with inflammatory bowel diseases in the post-COVID-19 era.
DOP33 Role of adherent and invasive E. coli in Crohn’s Disease: Lessons from the postoperative recurrence model
Authors: Buisson A , Sokol H , Hammoudi N , Nancey S , Treton X , Nachury M , Fumery M , Hébuterne X , Rodrigues M , Hugot J P , Boschetti G , Stefanescu C , Wils P , Seksik P , Le Bourhis L , Bezault M , Sauvanet P , Pereira B , Allez M , Barnich N
Published: January 2022

Background

We used the postoperative recurrence model to better understand the role of AIEC bacteria in Crohn’s disease (CD), taking advantage of a well-characterized postoperative cohort.

Methods

From the REMIND prospective, multicenter cohort of operated CD patients (ileocolonic resection), AIEC identification was performed within the surgical specimen (M0) (N=181 patients) and the neo-terminal ileum (n=119 patients/181) during colonoscopy performed 6 months after surgery (M6). Endoscopic postoperative recurrence was graded using Rutgeerts’ index, which was interpreted, either from a clinical point of view (postoperative endoscopic recurrence ≥ i2b or severe ≥ i3), or from a pathophysiological point of view (reappearance of the first ileal lesions = i1 and more advanced postoperative ileal recurrence = i2b + i3). The mucosa-associated microbiota was analyzed by 16S sequencing at M0 and M6. Relative risks (RR) or odds ratios (OR) were adjusted on potential confounders ((gender, smoking, CD duration, CD phenotype, prior bowel resection, indication for surgery, granuloma, preventive treatment, antibiotics).

Results

Among the 228 patients included at the time of the analyzes, the search for AIEC was carried out in 181 patients at M0, and 119 patients at M6. Among these 181 patients included in our study, 46.3% did not receive any preventive treatment for endoscopic postoperative endoscopic recurrence while 24.3% have been treated with anti-TNF to prevent postoperative recurrence.

AIEC prevalence was two-fold higher within the neo-terminal ileum at M6 (30.3%) than within the surgical specimen (14.9%) (p<0.001). AIEC within the neo-terminal ileum at M6 was associated with higher rate of early ileal lesions (i1) (41.6% vs 17.1%; aRR=3.49[1.01–12.04], p=0.048) or ileal lesions (i2b + i3) (38.2% vs 17.1%; aRR=3.45[1.06–11.30], p=0.040) compared to no lesion (i0). AIEC within the surgical specimen was predictive of higher risk of i2b-endoscopic POR (aOR=2.54[1.01–6.44], p=0.049) and severe endoscopic POR (aOR=3.36 [1.25–9.06], p=0.017). While only 5.0% (6/119) of the patients were AIEC-positive at both M0 and M6, 43.7% (52/119), patients with history of AIEC infection (M0 or M6) had higher risk of ileal endoscopic POR (aOR=2.32 [1.01–5.39], p=0.048]), i2b-endoscopic postoperative recurrence (aOR = 2.41[1.01–5.74]; p=0.048) and severe endoscopic postoperative (aOR = 3.84[1.32–11.18], p=0.013). AIEC colonization was associated with a specific microbiota signature including increased abundance of Ruminococcus gnavus.

Conclusion

Based on the postoperative recurrence model, our data support the role of AIEC in the early steps of ileal CD.
DOP40 Impact of corticosteroid usage on efficacy and safety outcomes in patients receiving upadacitinib for Ulcerative Colitis
Authors: Raine T , Ishiguro Y , Rubin D , Finney-Hayward T , Dapo I , Phillips C , Cheng E , Targownik L , Loftus E V
Published: January 2022

Background

The oral, selective Janus kinase inhibitor upadacitinib (UPA) has demonstrated efficacy as induction and maintenance therapy in patients with moderately to severely active Ulcerative Colitis (UC) in a Phase 3 clinical programme comprising two identical induction trials (U-ACHIEVE Induction [NCT02819635] and U-ACCOMPLISH [NCT03653026]) and a maintenance study (U-ACHIEVE Maintenance). This analysis assessed the impact of baseline corticosteroid (CS) use on the efficacy and safety of UPA in patients in these trials.

Methods

Patients were randomised 2:1 to UPA 45 mg once daily (QD) or placebo (PBO) for 8 weeks. Patients who achieved a clinical response at Week 8 were re-randomised 1:1:1 to UPA 15 mg QD, UPA 30 mg QD or PBO for 52 weeks. Here, we report induction and maintenance endpoints and safety data stratified by baseline CS use.

Results

Baseline demographics and disease characteristics were generally well balanced across treatment groups, regardless of baseline CS use. Clinical remission rates among patients receiving UPA 45 mg induction therapy did not differ by baseline CS use (Figure 1A). In the induction period, rates of treatment-emergent adverse events of special interest (AESI), including serious and opportunistic infections, were increased in the UPA 45 mg plus baseline CS group compared with the PBO and UPA without baseline CS groups (Table 1). In the maintenance study, CS tapering was mandated. CS-free remission at Week 52 (defined as clinical remission, per Adapted Mayo Score, and CS free for ≥90 days immediately prior to Week 52) was significantly increased with UPA 30 and 15 mg compared with PBO (both p<0.001; Figure 1B). Among patients receiving UPA maintenance, rates of treatment-emergent AESIs in the baseline CS versus no baseline CS groups were 33% versus 39% and 27% versus 35% in the UPA 30 mg and UPA 15 mg groups, respectively. Malignancy, major adverse cardiovascular events, venous thromboembolic events, and serious and opportunistic infections were reported infrequently in patients receiving UPA (Table 1).

Conclusion

This post hoc analysis suggests that, in patients with moderately to severely active UC, UPA is superior to PBO in conferring CS-free remission. Baseline CS use was not associated with any apparent efficacy benefit and carried a potential increased safety risk. These results suggest that achieving early disease control with UPA and without CS use is an optimal treatment strategy for this population.