bluuebunny/crossref_metadata_2025_split huggingface dataset:
EEG during dynamic facial emotion processing reveals neural activity patterns associated with autistic traits in children
Authors: Hill Aron T , Ford Talitha C , Bailey Neil W , Lum Jarrad A G , Bigelow Felicity J , Oberman Lindsay M , Enticott Peter G 
Published: January 2025

Abstract
Altered brain connectivity and atypical neural oscillations have been observed in autism, yet their relationship with autistic traits in nonclinical populations remains underexplored. Here, we employ electroencephalography to examine functional connectivity, oscillatory power, and broadband aperiodic activity during a dynamic facial emotion processing task in 101 typically developing children aged 4 to 12 years. We investigate associations between these electrophysiological measures of brain dynamics and autistic traits as assessed by the Social Responsiveness Scale, 2nd Edition (SRS-2). Our results revealed that increased facial emotion processing–related connectivity across theta (4 to 7 Hz) and beta (13 to 30 Hz) frequencies correlated positively with higher SRS-2 scores, predominantly in right-lateralized (theta) and bilateral (beta) cortical networks. Additionally, a steeper 1/f-like aperiodic slope (spectral exponent) across fronto-central electrodes was associated with higher SRS-2 scores. Greater aperiodic-adjusted theta and alpha oscillatory power further correlated with both higher SRS-2 scores and steeper aperiodic slopes. These findings underscore important links between facial emotion processing-related brain dynamics and autistic traits in typically developing children. Future work could extend these findings to assess these electroencephalography-derived markers as potential mechanisms underlying behavioral difficulties in autism.
How Epistemic Community Shapes Global Governance of AI in Military Domain?
Authors: Qi Haotian , Kamnerdrat Wanmingkhwan 
Published: January 2025

Abstract
The rapid development and applications of artificial intelligence (AI) technology in the military realm pose significant technical, ethical, and geopolitical risks. This article examines how members of the epistemic community, particularly Chinese academic and policy players, influence and shape the governance of AI’s military applications. Using social network analysis and comparative case studies, this research explores China’s interactions with its Western and non-Western counterparts, comparing their engagement in knowledge production as well as the construction of cooperative mechanisms. Our findings reveal that while Chinese stakeholders are quickly developing within the epistemic community, they lag behind their international counterparts in terms of knowledge production and their patterns of interaction within the global network. These Chinese members could strengthen their contribution by using a wider range of platforms to engage stakeholders and collaborate with international peers to produce knowledge about military AI. Our research is based on an original dataset of international academic and policy collaboration in AI’s military applications since 2013. This dataset will support and expand future research in this area.
Spatial and trophic ecology of the estuarine Little Tern Sternula albifrons
Authors: Cerveira Lara R , Pereira Jorge M , Veríssimo Sara N , Paiva Vítor H , Ramos Jaime A 
Published: January 2025

Abstract
Little Terns Sternula albifrons are estuarine birds extensively using increasingly urbanized coastal areas. Given the increased exposure of these ecosystems to anthropogenic activities, it is crucial to study the ecology of this species and interactions with human stressors to establish management measures. We collected regurgitates (n = 182) and blood samples (n = 48) to study Little Terns’ diet, health condition and isotopic niche, and individually tracked breeding adults (n = 9, during 2021 and 2022) at 2 sandy beaches 21 km apart and located within Ria Formosa Natural Park, Algarve, Portugal. Although both areas are adjacent to foraging coastal marine areas and an estuarine lagoon system with saltpans, they differ in human disturbance. We also compared breeding success and adult health measures between these 2 colonies. The main prey for both populations were Sand Smelts Atherina spp. and Gobies Pomatoschistus spp., and no differences in δ13C and δ15N stable isotopic values between colonies were found. Tracking data revealed that individuals foraged in the surroundings of their breeding colonies. Entrance Channels and Ocean were the most frequently used habitats for foraging by individuals from the less disturbed colony. Adults from the more disturbed colony foraged mostly in Entrance Channels. Overall, all individuals tended to forage during daytime. There were no differences in health measures of individuals between colonies, though breeding success at the most disturbed colony was comparably lower. It is important to protect both breeding areas and adjacent foraging habitats for Little Terns, particularly given the expected increasing pressure from human activities on coastal areas worldwide.
OP25 Young Researcher Award: Lymphocytic colitis can be transcriptionally divided into channelopathic and inflammatory lymphocytic colitis
Authors: Bhardwaj A , Münch A , Montague J , Koch S , Rosenstiel P , Escudero-Hernández C 
Published: January 2025

Abstract

Background
The pathobiology of the moderate/non-destructive inflammatory bowel disease (IBD) lymphocytic colitis (LC) is poorly understood. We aimed to define an LC-specific mucosal transcriptome to gain insight into LC pathology, identify unique genomic signatures, and uncover potentially druggable disease pathways.

Methods
We performed bulk RNA-sequencing of LC and collagenous colitis (CC) colonic mucosa from patients with active disease, and healthy controls (n=4-10 per cohort). Differential gene expression was analyzed by gene-set enrichment and deconvolution analyses to identify pathologically relevant pathways and cells, respectively, altered in LC. Key findings were validated using reverse transcription quantitative PCR and/or immunohistochemistry. Finally, we compared our data to a previous cohort of ulcerative colitis and Crohn’s disease patients (n=4 per group) to distinguish non-destructive from classic IBD.

Results
LC can be subdivided into channelopathic LC, which is governed by organic acid and ion transport dysregulation; and inflammatory LC, which is driven by microbial immune responses. Inflammatory LC displays an innate and adaptive immunity that is limited compared to CC and classic IBD. Conversely, we noted a distinct induction of regulatory non-coding RNA species in inflammatory LC samples. Moreover, compared to CC, water channel and cell adhesion molecule gene expression decreased in channelopathic LC, whereas it was accentuated in inflammatory LC and associated with reduced intestinal epithelial cell proliferation.

Conclusion
We conclude that LC can be subdivided into channelopathic LC and inflammatory LC that could be pathomechanistically distinct subtypes despite their shared clinical presentation. Inflammatory LC exhibits a dampened immune response compared to CC and classic IBDs. Our results point to regulatory micro-RNAs as a potential disease-specific feature that may be amenable to therapeutic intervention.

References
1.Miehlke S, Guagnozzi D, Zabana Y, et al. European guidelines on microscopic colitis: United European Gastroenterology and European Microscopic Colitis Group statements and recommendations. United Eur Gastroenterol J. 2021;9(1):13-37. doi:10.1177/2050640620951905
2.Bhardwaj A, Münch A, Montague J, Koch S, Rosenstiel P, Escudero-Hernández C. Lymphocytic colitis can be transcriptionally divided into channelopathic and inflammatory lymphocytic colitis. United Eur Gastroenterol J. 2024;12(6):737-748. doi:10.1002/ueg2.12531
OP27 Unlocking Inflammatory Bowel Disease subtypes: a deep dive into transcriptomics and Machine Learning
Authors: Saini N , Acharjee A 
Published: January 2025

Abstract

Background
Identifying molecular subtypes of IBD is essential to address inconsistencies in gene expression-based classifications, clinical variability, and treatment responses in Crohn's Disease (CD) and Ulcerative Colitis (UC). Building on prior efforts using different methods and datasets, this study aimed to derive and validate IBD subtypes using transcriptomics data and unsupervised machine learning.

Methods
This study analysed RNA-sequenced data from inflamed and non-inflamed intestinal biopsies of 2,490 adult IBD patients. K-means clustering, guided by Within Cluster Sum of Squares (WCSS) to determine the optimal ‘K’, identified subtypes within the dataset. Distinct clusters for UC and CD were derived from gene expression, with gene set enrichment and network analysis characterizing their features. Statistical tests (Chi-squared and ANOVA) linked these clusters to clinical data for UC and CD.

Results
K-means clustering revealed three distinct clusters in UC and CD, whose significant association with IBD severity (UC: p = 0.000263; CD: p = 0.007006) and IBD region (p &lt; 0.000001) was determined by Chi Squared test. ANOVA showed age significantly influenced UC clusters (p = 0.0000345) but not CD clusters (p = 0.285). In UC, Cluster 1 focused on RNA processing, DNA repair, and rapid cell turnover, with upregulation of EXOSC genes and other related genes. Cluster 2 highlighted autophagy, stress response, and signaling processes, with upregulated expression of ATG13, VPS37C, and DVL2. Cluster 3 emphasized cytoskeletal stability over metabolic activity, marked by the upregulation of SRF, SRC, and ABL1. Notably, all UC clusters demonstrated upregulation of COX1, TMSB10, and ACTB. In CD, Cluster 1 was defined by cytoskeletal dynamics and reduced protein synthesis, with upregulated expression of CFL1, F11R, and RAD23A. Cluster 2 exhibited increased protein synthesis and stress response pathways, associated with aggressive disease phenotypes, with upregulation of MTREX, SART3, and GTF3C3. Cluster 3 prioritised cytoskeletal organisation over metabolism, featuring upregulation of TESK1, ABL1, and DVL2, along with other genes. Across all CD clusters, COX1, CDH1, and SF3B1 were consistently up-regulated.

Conclusion
Despite certain limitations, this study categorizes UC and CD into three transcriptomics-based subtypes, identifying meaningful IBD-associated patterns, key subtyping genes, and insights into the disease's complex pathogenesis. These findings may advance new therapeutic strategies and personalized medicine for patients with distinct IBD subtypes.
OP37 Delineating molecular and microbial signatures across disease severity in Inflammatory Bowel Disease in adult treatment naive patients through single-cell transcriptomic and microbiome profiling.
Authors: Leipner M , Rimmer P , Paun A , Cheesbrough J , Danilin S , Klein A , Scepanovic P , Sharma N , Trenkle P , Regan-Komito D , Iqbal A , Iqbal T 
Published: January 2025

Abstract

Background
Inflammatory Bowel Disease (IBD), including Crohn's disease (CD) and Ulcerative Colitis (UC), is a chronic inflammatory condition with complex etiology involving genetic, immune, microbiome, and environmental factors. This study aims to elucidate the cellular and microbial landscape of adult treatment-naive IBD patients with varying disease severity to identify potential disease mechanisms and therapeutic targets, presenting one of the largest single-clinic, IBD single-cell datasets to date.

Methods
Tissue biopsies were collected from inflamed and non-inflamed regions of the colon in UC patients and colon + ileum in CD patients. Using 10x Genomics single-cell RNA sequencing (scRNA-seq), we analyzed 1.4 million cells from 68 treatment-naive IBD patients (38 CD, 30 UC) and 70 symptomatic healthy controls. Shotgun metagenomic sequencing was performed on 36 IBD patients with matched scRNA-seq data to explore host-microbe interactions, and a further 49 patients with paired clinical data. At presentation, standard clinical metadata, Patient Reported Outcomes, post-biopsy treatment, and 6/12-month treatment response were collected for stratification across disease severity and response.

Results
Our analysis revealed distinct cellular populations and gene expression profiles between IBD patients and healthy controls along the disease severity axis. Specific immune cell subsets were significantly expanded in IBD patients, with inflammatory monocytes particularly prominent in those with higher disease severity, exhibiting upregulated expression of pro-inflammatory cytokines and chemokines. Additionally, a shift from IgA to IgG antibody-producing cells was observed along the disease severity axis, indicating a dysregulated immune response associated with disease progression. Fecal microbial community typing based on pathway abundance revealed two clusters defined by low or high abundance of Bacteroidetes phylum taxa. Integration with clinical metadata and transcriptional profiles showed that Bacteroidetes-high UC patients displayed lower levels of inflammation and up-regulation of interferon signaling in B cells and myeloid cells.

Conclusion
This comprehensive profiling of adult treatment-naive IBD patients provides valuable insights into the cellular and microbial factors contributing to IBD prior to treatment perturbation. Our findings offer a deeper understanding of the underlying disease pathology of IBD patients at the time of presentation along the axis of disease severity, expanding the dynamic range of IBD patient profiling and informing future therapeutic strategies that may more quickly put patients on the right treatment and better address the causes of IBD in addition to the inflammatory response alone.
DOP004 Proactive fecal calprotectin testing in ulcerative colitis: Initial results of the PROMOTE UC study
Authors: Rosenfeld G , Narula N , Leung Y , Afif W , Williams A J , Huang V , Singh H , McCurdy J , Jairath V , Lam M , Loomes D , Zezos P , Stewart M , Ma C , Ropeleski M , Ancheta-Schmit M , Tavakoli P , Khanna R , Lewis J , Colombel J F , Bressler B ,   Canadian Inflammatory Bowel Disease Research Consortium (CIRC)
Published: January 2025

Abstract

Background
Fecal calprotectin (FC) is a biomarker of mucosal inflammation widely used in the management of inflammatory bowel disease (IBD). Given the convenience of home-based FC testing, we hypothesized that intensive, proactive FC monitoring would prevent symptomatic ulcerative colitis (UC) flares by detecting elevated FC levels prior to symptom onset and allowing clinicians to optimize therapy.

Methods
This prospective, multicenter, randomized, observational clinical trial evaluated intensive home-based, FC testing (IBDoc, Bühlmann Laboratories) versus usual care in adults with UC in clinical remission, defined as a modified partial Mayo score (mpMayo) ≤2 with no rectal bleeding. Patients in the intervention arm used the home testing kit every 2 months for 18 months or until symptomatic flare. The decision to modify therapy based on an elevated FC result was left to the discretion of the attending physician. Patients in the control group were followed according to usual care for 18 months or until symptomatic flare. Clinical data were collected at baseline and every 6 months. The primary endpoint was the time to symptomatic flare, defined as an increase in mpMayo ≥2 points from baseline or a rectal bleeding score ≥1.

Results
A total of 584 patients were followed at 14 sites in Canada and Australia until symptomatic flare or end of study. Demographics were similar between the control (n=293) and intervention arms (n=291), including mean age (41.9 vs 41.9 years), sex (46.8% vs 49.1% male), disease duration (1.61 vs 1.44 years), and mean mpMayo (0.39 vs 0.40) (Table). At study end, the flare rate of 30.9% in the intervention arm with proactive monitoring was slightly lower than the flare rate of 32.8% in the control arm (median follow-up 549 and 562 days, respectively). Overall, HR for flare in the intervention vs control arm was 1.01 (95% CI: 0.76, 1.34; p=0.96) (Figure). Risk for flare was also similar when analyzed by disease extent (proctitis: 1.13 [0.60, 2.14, p=0.71]; left-sided disease: 0.99 [0.61, 1.58, p=0.95]; pancolitis: 0.96 [0.60, 1.53, p=0.86]) or biologic use (biologics: 1.29 [0.86, 1.95, p=0.22], non-biologics: 0.78 [0.52, 1.18, p=0.24]) at baseline.

Conclusion
In this large, prospective clinical trial, approximately one-third of patients with UC in clinical remission developed a symptomatic flare within 18 months. Longitudinal proactive FC monitoring was not associated with a reduction in clinical flares. Further study is needed to determine the utility of home-based FC testing in guiding the management of UC.
DOP049 Vedolizumab is more effective at inducing histo-endoscopic healing in early Crohn’s Disease compared to late CD, with comparable healing rates regardless of disease location: data from the LOVE-CD trial
Authors: Lenfant M , De Hertogh G , Baert F , Bossuyt P , Löwenberg M , Clasquin E , Hoentjen F , Molnár T , D'Haens G , Vermeire S 
Published: January 2025

Abstract

Background
Achieving deep remission, encompassing clinical, endoscopic, and biological remission, is a long-term goal in Crohn's disease [CD] according to the STRIDE-2 guidelines. The role of histological remission in CD remains unclear. We evaluated the efficacy of vedolizumab [VDZ] for inducing histo-endoscopic remission in early versus late CD in the prospective, open-label LOVE-CD trial conducted in Belgium, the Netherlands and Hungary.

Methods
In the LOVE-CD trial, patients with moderate-to-severe disease (Crohn’s Disease Activity Index 220-450 and presence of ulcers at baseline endoscopy) received intravenous vedolizumab over a 52-week period. Early CD was defined as a diagnosis &lt;24 months (treatment-naive or history of corticosteroid and/or immunomodulator use), and late CD as a diagnosis &gt;24 months with prior anti-TNF exposure. Ileocolonoscopies were performed at three timepoints (baseline, week 26, week 52) during which biopsies were systematically collected in the terminal ileum and colon. Both the endoscopies and biopsies were centrally scored by experienced readers for the simple endoscopic score for Crohn's disease [SES-CD], Robarts’ histopathology index [RHI], and Geboes score [GS]. Endoscopic remission, histo-endoscopic mucosal improvement [HEMI], and histo-endoscopic mucosal remission [HEMR] were defined as SES-CD &lt;4, GS ≤3B.1, and GS &lt;2B.1 respectively. The association between histologic and endoscopic scores was studied with Spearman’s correlation coefficient. Intention-to-treat analysis with non-responder imputation was used to handle missing data.

Results
Of the 260 patients included in LOVE-CD (Table), 440 biopsies (336 colon, 114 ileum) from 179 patients at week 26, and 435 biopsies (323 colon, 112 ileum) from 177 patients at week 52 were analysed. There was a strong correlation between the endoscopic and histological assessment (colon r 0.69, ileum r 0.64, total r 0.64, p&lt;0.001). Patients with early CD were more likely to achieve histological remission than patients with late CD at week 52 (38.4 % vs. 14.9%, p=0.00004). Endoscopic and histological healing rates at week 26 (endoscopic remission 36.9%, HEMI 30.4%, HEMR 24.2%) and week 52 (endoscopic remission 35%, HEMI 30%, HEMR 22.7%) were comparable. When looking at disease location, histological remission rates in the colon and ileum did not significantly differ (35.2% vs. 27.8%, p=0.15).

Conclusion
Vedolizumab was more efficient at inducing histo-endoscopic remission in early CD as compared to late CD, with most of the histo-endoscopic healing occurring during the first 26 weeks. Histo-endoscopic healing rates under vedolizumab were comparable in colonic and ileal disease. Histological scores (RHI, GS) are also applicable for the evaluation of ileal and colonic CD.
DOP055 Upadacitinib for induction of remission in pediatric Crohn’s disease: An international multicenter study
Authors: Yerushalmy-Feler A , Spencer E A , Dolinger M T , Suskind D L , Mitrova K , Hradsky O , Conrad M A , Kelsen J R , Uhlig H H , Tzivinikos C , Henderson P , Wlazlo M , Hackl L , Shouval D S , Bramuzzo M , Urlep D , Olbjørn C , D'Arcangelo G , Pujol-Muncunill G , Yogev D , Kang B , Gasparetto M , Rungoe C , Kolho K L , Hojsak I , Norsa L , Rinawi F , Sansotta N , Magen Rimon R , Granot M , Scarallo L , Trindade E , Velasco Rodríguez-Belvís M , Turner D , Cohen S 
Published: January 2025

Abstract

Background
Data on upadacitinib therapy in children with Crohn’s disease (CD) are scarce. We aimed to evaluate the effectiveness and safety of upadacitinib as an induction therapy in pediatric CD.

Methods
A multicenter retrospective study of children treated with upadacitinib for the induction of remission of active CD from 30 centers worldwide affiliated with the IBD Interest and Porto group of the ESPGHAN between 2022 and 2024. Demographic, clinical, laboratory, and imaging data as well as adverse events (AEs) were recorded at week 8 post induction. The analysis of the primary outcome was based upon the intention-to-treat (ITT) principle.

Results
One-hundred children (median age 15.8 [interquartile range 14.3–17.2] years) were included. All children were previously treated with biologic therapies and 89 with ≥2 biologics. At the end of the 8-week induction period, clinical response, clinical remission and corticosteroid- and exclusive enteral nutrition-free clinical remission (CFR) were observed in 75%, 56% and 52% of the children, respectively. Normal C-reactive protein was achieved in 68% of the children and fecal calprotectin (FC) &lt;150 mcg/g in 58%. Combined CFR and FC remission was observed in 13/31 (42%) children with available data at 8 weeks [13% of the ITT population]. AEs were recorded in 24 children, the most frequent was acne (n=12). Two AEs (severe acne and hypertriglyceridemia) led to discontinuation of therapy.

Conclusion
Upadacitinib is an effective induction therapy for refractory pediatric CD. Efficacy should be weighed against the potential risks of AEs.