bluuebunny/crossref_metadata_2025_split huggingface dataset:
Volcano transition in a system of generalized Kuramoto oscillators with random frustrated interactions
Authors: Lee Seungjae , Jeong Yeonsu , Son Seung-Woo , Krischer Katharina 
Published: January 2024

Abstract
In a system of heterogeneous (Abelian) Kuramoto oscillators with random or ‘frustrated’ interactions, transitions from states of incoherence to partial synchronization were observed. These so-called volcano transitions are characterized by a change in the shape of a local field distribution and were discussed in connection with an oscillator glass. In this paper, we consider a different class of oscillators, namely a system of (non-Abelian) SU(2)-Lohe oscillators that can also be defined on the 3-sphere, i.e. an oscillator is generalized to be defined as a unit vector in four-dimensional Euclidean space. We demonstrate that such higher-dimensional Kuramoto models with reciprocal and nonreciprocal random interactions represented by a low-rank matrix exhibit a volcano transition as well. We determine the critical coupling strength at which a volcano-like transition occurs, employing an Ott–Antonsen ansatz. Numerical simulations provide additional validations of our analytical findings and reveal the differences in observable collective dynamics prior to and following the transition. Furthermore, we show that a system of unit 3-vector oscillators on the 2-sphere does not possess a volcano transition.
The criminal justice system in alcohol use treatment: a nationwide analysis of racial disparities in treatment referral and completion
Authors: Stenersen Madeline R , Peltier MacKenzie , McKee Sherry A 
Published: January 2024

Abstract

Background
Alcohol use and the criminal justice (CJ) system have long been integrally connected in the United States and have both disproportionally impacted Communities of Color. Despite this connection, scholarly literature has largely focused on substance use as a whole, and little literature has examined the influence of race on CJ referral to alcohol treatment and treatment outcomes.

Methods
A total of 749,349 cases from the treatment episodes dataset discharge were used in the current study. A series of ANOVA and logistic regression analyses were conducted to examine the impact of race on (i) likelihood of referral to alcohol treatment by the CJ system and (ii) the association between CJ referral and treatment completion.

Results
Results revealed significant disparities in both who is referred to alcohol treatment by the CJ system and the association of that referral to treatment completion. Notably, American Indian/Alaska Native people were significantly more likely than people of all other races to be referred by the CJ system. However, American Indian/Alaska Native people showed the smallest association between CJ referral and treatment completion.

Conclusions
Contrary to previous literature, findings showed that referral of and positive association between CJ referral and treatment completion are not equal across people of different races. Taken together, these results highlight continued racial inequities in the role of the CJ system in alcohol treatment and the unique potential for non-CJ-related treatment to best serve people combatting alcohol use disorder.
An expanded hydrogen-bonded organic framework formed by a tetrakis(terphenyl)ethene derivative
Authors: Yamaguchi Mao , Tomás Mario de la Hoz , Fujiwara Ayano , Oketani Ryusei , Okubo Kohei , Oka Kouki , Tohnai Norimitsu , Douhal Abderrazzak , Hisaki Ichiro 
Published: January 2024

Abstract
A low-density hydrogen-bonded organic framework (HOF) with channel aperture with dimensions of 33.8 Å × 55.2 Å was constructed from a tetrakis(terphenyl)ethene derivative. The structure was successfully characterized by single crystalline X-ray diffraction analysis. Although solvent molecules are included in the channel, the present framework is one of the HOFs with the largest aperture. The framework is based on H-bonded sql-networks that stack in an eclipse fashion. The interlayer interactions were thoroughly investigated on the basis of the crystal structure. Interestingly, thee analogues of tetraarylethene-based tetracarboxylic acids, including the title compounds, formed the same H-bonded sql-network as a lower-dimensional supramolecular motif. However, the motifs are assembled in completely different ways to give the corresponding three types of the framework, indicating the importance of precise design of the secondary interactions between the lower dimensional motifs. In solid state, the molecular unit of the constructed HOF shows a largely Stokes-shifted and strong emission due to a fast (&lt; 15 ps) ICT and a relatively slower (90 ps) intermolecular PT reaction, while in DMF it exhibits a strong H-bond with the solvent.
Common and distinct patterns underlying different linguistic tasks: multivariate disconnectome symptom mapping in poststroke patients
Authors: Jiang Yaya , Gong Gaolang 
Published: January 2024

AbstractNumerous studies have been devoted to neural mechanisms of a variety of linguistic tasks (e.g. speech comprehension and production). To date, however, whether and how the neural patterns underlying different linguistic tasks are similar or differ remains elusive. In this study, we compared the neural patterns underlying 3 linguistic tasks mainly concerning speech comprehension and production. To address this, multivariate regression approaches with lesion/disconnection symptom mapping were applied to data from 216 stroke patients with damage to the left hemisphere. The results showed that lesion/disconnection patterns could predict both poststroke scores of speech comprehension and production tasks; these patterns exhibited shared regions on the temporal pole of the left hemisphere as well as unique regions contributing to the prediction for each domain. Lower scores in speech comprehension tasks were associated with lesions/abnormalities in the superior temporal gyrus and middle temporal gyrus, while lower scores in speech production tasks were associated with lesions/abnormalities in the left inferior parietal lobe and frontal lobe. These results suggested an important role of the ventral and dorsal stream pathways in speech comprehension and production (i.e. supporting the dual stream model) and highlighted the applicability of the novel multivariate disconnectome-based symptom mapping in cognitive neuroscience research.
OP05 Primary efficacy and safety of mirikizumab in moderate to severe Crohn’s Disease: results of the treat-through VIVID 1 study
Authors: Ferrante M , Danese S , Chen M , D'Haens G , Ghosh S , Hisamatsu T , Jairath V , Kierkus J , Peyrin-Biroulet L , Siegmund B , Bragg S M , Crandall W , Hunter Gibble T , Lin Z , Ugolini Lopes M , Morris N , Carlier H , Sands B 
Published: January 2024

Abstract

Background
Mirikizumab (miri) is a selective IL23p19 monoclonal antibody approved for the treatment of ulcerative colitis. The primary focus of the VIVID-1 trial (NCT03926130) was to demonstrate the efficacy and safety of mirikizumab (miri) compared to placebo (PBO) in patients (pts) with moderate-to-severe Crohn’s disease. Here we present primary efficacy and safety of miri compared to placebo (PBO) up to Week 52 (W52) from the Phase 3, randomised, double-blind, double-dummy, active- and PBO-controlled, treat-through VIVID-1 study.

Methods
Adult pts (N=1065) were randomized 6:3:2 to miri (N=579) 900mg intravenously (IV) at W0, W4, and W8, then 300mg subcutaneously (SC) every 4 weeks (Q4W) from W12 to W52, placebo (PBO) (N=199), or ustekinumab (N=287) ~6mg/kg IV at W0 and SC dose of 90mg Q8W from W8 to W48. At W12, PBO responders continued PBO to W52; PBO non-responders received the same blinded miri regimen (IV then SC) as described above. The co-primary endpoints assessing superiority of miri over PBO were composite endpoints: 1) PRO clinical response at W12 and endoscopic response at W52, and 2) PRO clinical response at W12 and clinical remission by Crohn’s Disease Activity Index (CDAI) at W52. The adjusted risk differences were calculated, and the comparison was performed by CMH test. Nonresponder imputation was used.

Results
Baseline characteristics were similar across treatment groups. 48.7% of pts in the PBO, and 48.5% in the miri, group previously failed at least one biologic. 15.6% and 18.3% of the PBO and miri groups respectively failed more than one biologic. Both co-primary endpoints (Figure 1A, 1C, all p&lt;.000001) and all key secondary endpoints (Figure 1E, all p&lt;.000001 except endoscopic remission at W12: p&lt;.001 and W12 clinical remission by CDAI: p=0.001) were achieved. Robust and consistent efficacy at W52 was also demonstrated with similar response rates and treatment effect in patients with and without prior biologic failure (Figure 1B, 1D, all p&lt;.0001). Overall safety was consistent with the known safety profile of miri (Table 1).

Conclusion
In this phase 3 CD study, miri demonstrated statistically significant and clinically meaningful improvements vs PBO in both co-primary composite endpoints and all key secondary endpoints, with an acceptable safety profile.
OP06 Risankizumab Maintenance Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: Efficacy and Safety in the Randomised Phase 3 COMMAND Study
Authors: Louis E , Panaccione R , Parkes G , Peyrin-Biroulet L , Ferrante M , Hisamatsu T , Siegmund B , Kalabic J , Levine P , Neimark E , Wallace K , Chen S , Cheng L , Duan W R , Armuzzi A , Biederman L , Loftus E , Melmed G , Schreiber S 
Published: January 2024

Abstract

Background
Risankizumab (RZB), a monoclonal antibody targeting interleukin-23 p19, was evaluated for maintenance therapy in patients with moderately to severely active ulcerative colitis (UC) and clinical response to RZB intravenous (IV) induction treatment in a phase 3 double-blind, placebo (PBO)-controlled withdrawal (WD) maintenance study, COMMAND (NCT03398135).

Methods
Patients with moderately to severely active UC who achieved a clinical response per Adapted Mayo score after 12 or 24 weeks (wks) of RZB IV treatment in the phase 2b and phase 3 INSPIRE induction studies (NCT03398148)1 were randomized 1:1:1 in COMMAND to RZB 180 mg (RZB180), 360 mg (RZB360), or PBO (RZB withdrawal) subcutaneous (SC) treatment every 8 wks for 52 wks. The efficacy analysis included responders to 12 wk of RZB IV, while the safety analysis included responders to 12 or 24 wk of RZB IV. The primary endpoint was clinical remission per Adapted Mayo score at wk 52. Key secondary endpoints included endoscopic improvement, HEMI, endoscopic remission, steroid-free clinical remission, maintenance of clinical remission, no bowel urgency, and no abdominal pain at wk 52.

Results
At baseline of induction, demographics and disease characteristics were similar between treatment groups; 75% of 548 patients had history of inadequate response or intolerance to ≥ 1 advanced therapy (AT). Patients receiving RZB180 (40.2%) and RZB360 (37.6%) achieved significantly higher rates of clinical remission vs WD (25.1%) (adjusted treatment difference vs WD: 16.3% and 14.2%, respectively; P ≤ .01) (Fig. 1A). Greater proportions of patients achieved endoscopic improvement, HEMI, endoscopic remission, steroid-free clinical remission, maintenance of clinical remission, no bowel urgency, and no abdominal pain with RZB180 and RZB360 vs WD (Fig. 1B). The overall rates of adverse events (AEs), and serious infections were similar among treatment groups (Table 1). Serious (presented as events/100 patient-years [E/100 PY]) (RZB180: 5.9; RZB360: 6.3; WD: 11.4) and severe AEs (RZB180: 1.6; RZB360: 4.0; WD: 8.0) were lower in the RZB arms vs WD. No active tuberculosis, adjudicated anaphylaxis, serious hypersensitivity, or adjudicated major adverse cardiovascular events were reported in any treatment group.

Conclusion
In patients with moderately to severely active UC responding to 12-week RZB induction therapy, RZB maintenance dosing with 180 mg and 360 mg SC was superior to placebo in achieving clinical remission as well as other key clinical, endoscopic, and histological-endoscopic endpoints. RZB was well-tolerated, with no new safety concerns observed.
OP17 IBD ulcers are characterized by bioactive interleukin-1 and transcriptomic hallmarks of stromal cell state reprogramming
Authors: Mitsialis V , Losa M , Field M , Collen L , Barends J , Ringel A , Bresnahan M , Yang J , Tumminkatti R , Sveen M , Bearup R , Kotlarz D , Klein C , Argmann C , Schadt E , Muise A , Thiagarajah J , Eran A , Horwitz B , Snapper S 
Published: January 2024

Abstract

Background
The programs that perpetuate the inflammation and prevent epithelial repair in Inflammatory Bowel Disease (IBD) remain unclear. Interleukin (IL)-1 plays a role in the maintenance of mucosal homeostasis but also in IBD. Expansion of IL-1 expressing myeloid cells is a hallmark of IBD tissue, including severe and anti-TNF unresponsive disease, and IL-1 expression is highly localized to ulcer beds. However, little is known about the presence of bioactive IL-1 proteins in the cell-free mucosal environment of IBD, nor whether IL-1-driven programs affect epithelial regeneration in IBD ulcers.

Methods
We established a highly sensitive assay (~500-fold greater than ELISA) to assess bioactive extracellular IL-1 from previously cryopreserved IBD biopsies. We assessed a cohort of Crohn’s Disease (CD, n=23), Ulcerative Colitis (UC, n=18) and non-IBD (n=17) patients, with biopsies from paired inflamed/uninflamed regions (primarily colon but also ileal). We assessed IL-1 bioactivity, including IL-1α vs IL-1β contributions, and performed RNA-seq of samples’ matched cellular compartments. An ulcer-associated gene signature was interrogated in a single-cell (sc)RNA-seq cohort (n=42) of very early onset (VEO)IBD including monogenic disorders, as well as publicly available IBD bulk RNA-seq datasets and scRNA-seq of mouse models of colitis.

Results
IL-1α and IL-1β bioactivity corresponded with disease and ulcer severity in CD and UC. The most extreme signals were seen in select CD patients with deep ulceration. IL-1α was the predominant contributor to total IL-1 bioactivity in most patients although several with ulcers displayed IL-1β predominance. IL-1 bioactivity correlated with IL-1 transcripts in matched RNA-seq, and weighted gene co-expression network analysis revealed a compelling ulcer-specific module. This module contained transcription factors and genes related to cell state, validated in publicly available datasets (e.g. RISK cohort of ileal CD and scRNA-seq of murine DSS colitis), that when interrogated in a scRNA-seq dataset of VEOIBD (including patients with IL-10RA mutations characterized by deep ulcers), suggests an orchestrated IL-1-driven myeloid/stromal response to epithelial ulceration involving cell state reprogramming and loss of key myofibroblast populations.

Conclusion
Mucosal ulceration in IBD is associated with bioactive IL-1α and IL-1β proteins, and transcriptomic evaluation of the same correlates with bioactive signal. An ulcer-associated gene module, validated in other datasets, sheds light on IL-1 biology in intestinal epithelial repair. Results strongly suggest the IL-1 signaling pathway being an attractive and precision-based therapeutic target in subsets of IBD patients.
OP39 Vedolizumab response in ulcerative colitis associates with reduced IgG+ plasma cells and FcγR signaling
Authors: Canales-Herrerias P , Uzzan M , Al-taie Z , Seki A , Verstockt B , Livanos A , Tankelevich M , Ganjian D , Cossarini F , Jha D , Taylor M D , Rosenstein A , Cerutti A , Petralia F , Argmann C , Suarez-Farinas M , Polydorides A D , Colombel J F , Mehandru S 
Published: January 2024

Abstract

Background
Vedolizumab (VDZ) targets the gut-homing receptor α4β7. Despite its widespread use as a frontline therapy for ulcerative colitis (UC), its mode of action (MOA) remains unclear. Previously, we documented that response to VDZ is associated with size loss of gut-associated lymphoid tissues (GALT). To further understand drug MOA, here we aimed at defining the relationship between GALT attrition and resolution of inflammation.

Methods
Tissue immunofluorescence (IF) was performed on two independent UC cohorts (n=60, n=21) studied longitudinally pre- and post-VDZ. Peripheral blood mononuclear cells from UC patients (n=56) were examined at week 0 (pre-VDZ) and 14 (post-VDZ) by flow cytometry, while intestinal biopsies were analyzed in a subset of patients. Transcriptomic analyses were performed in a third cohort of 401 UC patients and 243 controls where bulk RNA-sequencing was performed on intestinal biopsies. Finally, data from a fourth validation cohort (n=31) was examined pre- and post-VDZ.

Results
Using IF, we examined follicular naïve B (FB) cells (IgD+), germinal center (GC) B cells (BCL6+CD3-) and total T cells (CD3+), and identified three GALT types: organized aggregates (demarcated B/T cell zones) with GC, organized aggregates without GC, and poorly organized aggregates (Fig1A). When comparing pre- and post-VDZ, Responders (R) had a significant reduction in GALT organization, while no change was seen in Non-Responders (NR). The number of FB cells was significantly reduced post-VDZ in R but not in NR (Fig1B), with no change in T cells (Fig1C). The reduction in FB was validated using transcriptomic data (Fig1D). To explore potential consequences of GALT attrition, we analyzed circulating β7+ (GALT-generated) and β7- plasmablasts (PB). The frequencies of β7+IgG+ and β7+IgA+ PB were significantly reduced post-VDZ in R, but not in NR (Fig1E). No change was observed in β7- PB post-VDZ (Fig1F). Among β7+ PB, there was a greater reduction in IgG+ compared to IgA+ (Fig1G). Furthermore, colonic IgG+ plasma cells (PC) were significantly reduced post-VDZ in R but not in NR (Fig1H). To evaluate IgG-mediated proinflammatory function, we studied the expression of FcγR-pathway genes in colonic biopsies. Importantly, the FcγR-pathway was enhanced in inflamed tissues of UC patients (Fig1I-J) and was significantly reduced in R (but not in NR) post-VDZ (Fig1K).

Conclusion
Our work demonstrates a novel effect of anti-α4β7 blockade that results in intestinal lymphoid aggregate attrition through impaired recruitment of naïve B cells, leading to the suppression of IgG-driven immune responses and proinflammatory FcγR signaling. These data highlight the targeting of GALT as a novel therapeutic paradigm in IBD.
DOP40 Inflammatory Bowel Disease single cell atlas construction to enable cell type-specific target identification
Authors: De Baets G , D'Rozario J , Gehrman U , Mattsson J , Castiblanco D , Kaymak I , Moldoveanu A L , Giorgio C , Prandi F , Jawale C , Honsa P , Ruppova K , Valny M , Macuchova E , Freinkman E , Sponarova J , Platt A , Ort T , Corridoni D 
Published: January 2024

Abstract

Background
Advances in single-cell technologies enable the unbiased study of cellular heterogeneity. Recently, single-cell RNA sequencing (scRNA-seq) has been utilised on intestinal and blood samples from patients with inflammatory bowel disease (IBD) and healthy individuals, often in conjunction with cell surface proteome and TCR repertoire analyses. These individual studies revealed novel cell subpopulations of immune, mesenchymal, and epithelial cells in UC and CD, but are not sufficiently powered to consistently identify granular cell subsets or establish their association with disease status and response to treatment. Integration of these studies into a unified IBD single-cell atlas would provide a more robust data foundation for therapeutic target discovery. Here, we constructed a comprehensive, multi-modal single-cell atlas of human IBD tissue, combining a large breadth of meta-analysis with the depth of single-cell resolution.

Methods
Raw data from 20 public datasets were curated and reprocessed to generate a harmonised data foundation to support downstream discovery efforts. Low-quality cells and doublets were removed using thresholds for gene number, gene count, and percentage of counts originating from mitochondrial genes, and the resulting data were normalised and adjusted for batch effects. Published clinical metadata from each study were re-annotated with controlled vocabularies. Associations between clinical metadata and cellular/molecular features were discovered using computational and ML approaches.

Results
We generated a large-scale integrated single-cell atlas for IBD comprising &gt;500 tissue samples from &gt;200 IBD patients and relevant controls, with harmonised clinical metadata including treatment history and response. This tissue atlas comprises &gt;990k high-quality cells with granular annotations of 129 cell types/states. IBD inflammation and non-response to anti-TNF treatment were associated with unique transcriptional signatures in specific mononuclear phagocyte, CD4 T cell, and fibroblast subpopulations. Further prioritisation and validation of genes comprising these signatures may yield future therapeutic targets for IBD.

Conclusion
This atlas integrates single-cell data across the largest available collection of IBD patient-derived tissue samples. Leveraging high-resolution cell type annotations and harmonised clinical metadata, meta-analyses of this data foundation will broaden the understanding of IBD biology to identify novel targets and pathways for drug discovery.