bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on time-frequency domain characteristics and cross-media communication of laser acoustic signals based on optical breakdown mechanism
Authors: Zhang Tongchang , Cao Xiaolong , Du Yuchen , Yao Jianquan
Published: January 2025

Cross-media communication is a hot research issue at present. The use of sound waves generated by laser induced sound mechanism for cross-media communication is a new topic proposed in recent years. It is of great significance to study the characteristics of laser acoustic signal and the feasibility study for cross-media detection. The time-frequency characteristics and directivity of the laser induced sound signal are studied on the self-built experimental platform. The results show that the pulse duration of the laser acoustic signal is about 2 × 10−4 s, and the peak frequency is about 14.9 ± 0.75 kHz. And the signal strength perpendicular to the water surface is the weakest, so it has a good horizontal distance transmission ability. This paper verifies the detection system of trans-air-sea interface communication and trans-air-sea interface communication based on laser sound and conducts the communication experiment of laser acoustic signal. By modulating laser energy, the underwater acoustic signal is modulated in time domain, and the signal communication with 0-bit error rate of 8 bps within the meter is realized. The detection threshold of acoustic signal is calculated to be 44.9 dB re 1μpa after horizontal transmission of 1 km. The analysis and simulation of water surface micro-motion based on laser induced sound are carried out. The results show that the wave crest of water surface generated by laser acoustic signal through underwater reflection reaches the order of micron and can be detected by radar. The surface wave intensity is little affected by the depth of detection, so it could work in deep water. This study provides a certain experimental and theoretical basis for laser communication across the air and sea interface.
Ultra slow-roll with a black hole
Authors: Croney Lewis , Gregory Ruth , Patrick Sam
Published: January 2025

We investigate ultra slow-roll inflation with a seed black hole in a de Sitter background.
By numerically tracking transitions from slow-roll to ultra slow-roll inflation, we find that quasi-normal mode solutions of the scalar field are excited following the decay of the slow-roll attractor, depending on the mass of the black hole.
For small black holes, the picture is similar to standard inflation with the usual damping of the scalar field; with a large black hole, we find that the ringing modes dominate. It is believed that the transition to ultra slow-roll in the pure inflationary case enhances the peak of the primordial power spectrum, thereby increasing the likelihood of primordial black hole formation. We comment on how the novel ringing behaviour due to the seed black hole might impact on cosmological perturbations.
ANNZ+: an enhanced photometric redshift estimation algorithm with applications on the PAU survey
Authors: Pathi Imdad Mahmud , Soo John Y.H. , Wee Mao Jie , Zakaria Sazatul Nadhilah , Ismail Nur Azwin , Baugh Carlton M. , Manzoni Giorgio , Gaztanaga Enrique , Castander Francisco J. , Eriksen Martin , Carretero Jorge , Fernandez Enrique , Garcia-Bellido Juan , Miquel Ramon , Padilla Cristobal , Renard Pablo , Sanchez Eusebio , Sevilla-Noarbe Ignacio , Tallada-Crespí Pau
Published: January 2025

annz is a fast and simple algorithm which utilises artificial neural networks (ANNs), it was known as one of the pioneers of machine learning approaches to photometric redshift estimation decades ago. We enhanced the algorithm by introducing new activation functions like tanh, softplus, SiLU, Mish and ReLU variants; its new performance is then vigorously tested on legacy samples like the Luminous Red Galaxy (LRG) and Stripe-82 samples from SDSS, as well as modern galaxy samples like the Physics of the Accelerating Universe Survey (PAUS). This work focuses on testing the robustness of activation functions with respect to the choice of ANN architectures, particularly on its depth and width, in the context of galaxy photometric redshift estimation. Our upgraded algorithm, which we named annz+, shows that the tanh and Leaky ReLU activation functions provide more consistent and stable results across deeper and wider architectures with > 1 per cent improvement in root-mean-square error (σ
RMS) and 68th percentile error (σ
68) when tested on SDSS data sets. While assessing its capabilities in handling high dimensional inputs, we achieved an improvement of 11 per cent in σ
RMS and 6 per cent in σ
68 with the tanh activation function when tested on the 40-narrowband PAUS dataset; it even outperformed annz2, its supposed successor, by 44 per cent in σ
RMS. This justifies the effort to upgrade the 20-year-old annz, allowing it to remain viable and competitive within the photo-z community today. The updated algorithm annz+ is publicly available at https://github.com/imdadmpt/ANNzPlus.
Exploring the swimming performance and the physical mechanisms of Tomopteris locomotion
Authors: Battista Nicholas A
Published: January 2025

Tomopterids are mesmerizing holopelagic swimmers. They use two modes of locomotion simultaneously: drag-based metachronal paddling and bodily undulation. Tomopteris has two rows of flexible, leg-like parapodia positioned on opposite sides of its body. Each row metachronally paddles out of phase to the other. Both paddling behaviors occur in concert with a lateral bodily undulation. However, when looked at independently, each mode appears in tension with the other. The direction of the undulatory wave is opposite of what one may expect for forward (FWD) swimming and appears to actively work act against the direction of swimming initiated by metachronal paddling. To investigate how these two modes of locomotion synergize to generate effective swimming, we created a self-propelled, fluid-structure interaction model of an idealized Tomopteris. We holistically explored swimming performance over a 3D mechanospace comprising parapodia length, paddling amplitude, and undulatory amplitude using a machine learning framework based on polynomial chaos expansions. Although undulatory amplitude minimally affected FWD swimming speeds, it helped mitigate the larger costs of transport that arise from either using more mechanically expensive (larger) paddling amplitudes and/or having longer parapodia.
Evolution of long scalp hair in humans
Authors: Chang Lo-Yu , Plikus Maksim V , Jablonski Nina G , Lin Sung-Jan
Published: January 2025

The ability to grow long scalp hair is a distinct human characteristic. It probably originally evolved to aid in cooling the sun-exposed head, although the genetic determinants of long hair are largely unknown. Despite ancestral variations in hair growth, long scalp hair is common to all extant human populations, which suggests its emergence before or concurrently with the emergence of anatomically modern humans (AMHs), approximately 300 000 years ago. Long scalp hair in AMHs was also a trait that was selected because it conveyed essential signals related to an individual’s age, sexual maturity, health and social status. Biologically, hair length is primarily determined by the amount of time that a hair follicle spends in the active growth phase (anagen). While anagen duration is typically tightly regulated in most mammals, the inherent ability of a hair follicle to continuously recruit new dividing progenitors to its base, where hair fibre is generated, theoretically removes limits on maximal anagen duration. We propose a model wherein hair cycle progression into and out of anagen is regulated by evolutionary malleable molecular checkpoints. Several animal species and domesticated animal breeds display long body hair, which suggests that extremely long scalp hair in humans emerged via attenuation of an existing out-of-anagen checkpoint mechanism rather than via a newly evolved molecular programme. Studying congenital and somatic mosaicism conditions featuring altered hair length could potentially unveil the currently unknown molecular basis underlying this human trait.
Computational simulation study of flow dynamics in plga microsphere generation using lab-on-a-chip for prostatic embolisation
Authors: Gómez Blanco J C , Sánchez Peralta L F , Patrocinio Caballero D , Sun F , Lucas Cava V , Pagador Carrasco J B , Sánchez Margallo F M
Published: January 2025

Introduction

Transarterial chemoembolisation is a therapeutic approach for vascularised tumours, such as prostate tumours, involving the administration of drug-eluting microspheres. Its efficacy arises from the combined effects of anti-tumour drugs and blood flow occlusion. Microspheres are now commonly generated using lab-on-a-chip systems. This study presents a computational simulation model to evaluate the input flow conditions required to produce PLGA microspheres of specific sizes.

Methods

The simulations were conducted using COMSOL Multiphysics 5.5, with rheological data for PLGA and the continuous phase derived from prior studies. The chip design was based on standard commercial double-T models, featuring 300 µm inlet and 500 µm outlet channels. Eight simulations were performed, varying the input velocity ratio (Rv = Vc/Vd) while maintaining a constant Vd of 8 mm/s. The evaluated ratios included: 1.500, 1.750, 1.875, 2.000, 2.125, 2.250, 2.375, and 2.500.

Results

The findings indicate that no microspheres are generated at Rv values below 1.875 or above 2.375. For intermediate ratios, microsphere sizes ranged from 240 to 275 µm, with droplet generation rates of 32 to 37 spheres per second for Rv values between 1.750 and 2.250, respectively.

Conclusion

This computational simulation system provides a rapid method for evaluating flow conditions. For the proposed chip geometry, it is possible to generate an average of 35 microspheres per second with a diameter of 250 µm in PLGA.
Hepatopancreatoduodenectomy: a complex operation
Authors: Perra T , Porcu A
Published: January 2025

Introduction

The only potentially curative treatment for cholangiocarcinoma is surgical resection (R0). In select cases, this involves complex interventions such as hepatopancreatoduodenectomy.

Clinical case

A 67-year-old male was admitted with obstructive jaundice due to extrahepatic cholangiocarcinoma, classified as Type IV according to the Bismuth-Corlette system. Preoperative percutaneous biliary drainage was performed. Following a multidisciplinary discussion, a super-extended right hepatectomy (segments 1-4-5-6-7-8) was planned. Three weeks before surgery, selective embolization of the right branch of the portal vein was carried out. Residual liver volume, measured using 3D liver reconstruction software, was 27%. The patient had chronic liver disease, and an indocyanine green test was conducted, yielding an R15 of 9.5%. The patient underwent super-extended right hepatectomy, complete excision of the extrahepatic bile duct, and simultaneous pancreaticoduodenectomy due to tumor involvement of the distal common bile duct, as confirmed by intraoperative frozen section. Consequently, the surgery performed was classified as a hepatopancreatoduodenectomy. Histopathological examination of the surgical specimen revealed moderately differentiated cholangiocarcinoma, 15 negative nodes, and micronodular cirrhosis. The postoperative course was complicated by transient liver failure, which was managed with medical therapy, and delayed gastric emptying. The patient was discharged on postoperative day 58 without chemotherapy. After 34 months, the patient remains in stable health.

Discussion

Hepatopancreatoduodenectomy is a complex operation that requires meticulous surgical planning, rapid identification, and careful management of potential complications, particularly in patients with chronic liver disease.
Bioinformatic analysis of the therapeutic potential of the secretome released by menstrual blood-derived stromal cells (menscs) as an adjuvant in the treatment of ovarian cancer
Authors: De Pedro M Á , Pulido M , Álvarez V , Marchena A M , Sánchez-Margallo F M , López E
Published: January 2025

Introduction

Treatment of ovarian cancer (OC) usually consists of a combination of surgery and chemotherapy, with carboplatin, often in combination with paclitaxel, being the most employed drug regimen. While effective, this approach has significant side effects and is associated with long-term chemoresistance, highlighting the need for alternative therapeutic strategies. This study aims to evaluate, through in silico methods, the therapeutic potential of the secretome from menstrual blood-derived stromal cells (MenSCs) as a potential adjuvant to conventional OC therapy.

Methods

MenSCs (n=5) were cultured in DMEM with 1% ITS for 48 hours. The resulting conditioned medium was ultrafiltered (3 kDa) to obtain the secretome (S-MenSCs), which was then analysed using transcriptomics and proteomics. Bioinformatics tools were employed to identify OC-associated genes using DisGeNET, drug target genes via DGIdb, and to predict protein and miRNA interactions with these drug target genes using FunRich and miRTargetLink2.0, respectively. NcDR was used to establish miRNAs related to drug resistance. Subsequently, the proteins and miRNAs from S-MenSCs were compared with those previously identified, and various interaction networks were constructed using Cytoscape.

Results

S-MenSCs contained approximately one third of the proteins and miRNAs that interact with the target genes of both chemotherapeutics. Of these, 14 miRNAs were identified as chemosensitizers for paclitaxel.

Conclusion

S-MenSCs hold promise as an adjuvant agent, potentially allowing for the reduction of chemotherapeutic doses, thus decreasing adverse effects and overcoming chemoresistance, as determined in silico.
OP28 Anti-integrin αvβ6 autoantibodies are detected in preclinical, incident and established colonic Crohn’s disease
Authors: Livanos A , Ganjian D Y , Acharya A A , Chiramel M J , Dunn A , Bloemen H , Ostroff J , Bourgonje A R , Chen X , Dunkin D , Ungaro R C , Shapiro J M , Shah S A , Sands B E , Laird R M , Porter C K , Suarez-Farinas M , Argmann C , Torres J , Dervieux T , Vermeire S , Verstockt B , Colombel J F , Mehandru S
Published: January 2025

Background

Anti-integrin αvβ6 autoantibodies (anti-αvβ6) are present in up to 90% of ulcerative colitis (UC) patients and predate disease development, but there is a paucity of data regarding anti-αvβ6 in Crohn’s disease (CD). We hypothesized that anti-αvβ6 would be present in colonic CD given the shared biological characteristics with UC.

Methods

We measured anti-αvβ6 IgG in peripheral blood samples from seven distinct cohorts representing diverse ethnic backgrounds, geographical locations and stages of disease including preclinical, incident and established IBD as well as non-IBD controls (HC). Seropositivity was defined as greater than the log10 transformed mean + 2 standard deviations of HC. We determined associations with CD disease location (L1: Ileal, L2: colonic, L3: ileocolonic), disease activity, fecal calprotectin and pANCA.

Results

We assessed for anti-αvβ6 in adult and pediatric subjects from Mount Sinai Hospital (MSH), NY (MSCCR-adult, n=599 and pediatric, n=75). Anti-αvβ6 levels as well as seropositivity were significantly higher in adult CD (16%) compared to HC (2%) (P=0.0330, P<0.0001), but lower than in UC (64%) (Fig. 1A-B). In the Pediatric cohort, we observed similar results with CD seropositivity (22%) greater than HC (0%) (P=0.0073), but lower than UC (79%) (Fig. 1C-D). Next, we examined anti-αvβ6 by CD location. Patients with L2 disease had higher levels than L1 across all cohorts including 2 incident cohorts (MSCCR P<0.0001; Pediatric P=0.0531; COMPASS n=81, P<0.0001; OSCCAR n=167, P=0.0099), while patients with L3 disease had intermediate levels (Fig. E-H). These findings were validated in an independent cohort (Prometheus n=730) using a commercially available ELISA kit (MBL) (Fig. 1I). A significant positive correlation between anti-αvβ6 and pANCA was observed in L2 CD and L3 CD (Spearman r=0.52, P<0.0001; r=0.46, P=0.0012) but not L1 CD (Fig. 1J). In the Leuven cohort (n=163), anti-αvβ6 levels were significantly higher in those with moderate-severe disease activity (SES-CD≥7) and in those with elevated fecal calprotectin (≥150μg/g) (P=0.0024, P=0.0057) (Fig. 1K-L). Finally, in the PREDICTs cohort, anti-αvβ6 were significantly higher in CD subjects compared to HC at all 4 timepoints (n=824) including up to 10 years before diagnosis (Fig. 2A-B) and when stratifying by location, this was primarily driven by patients who develop L2 disease (Fig. 2C).

Conclusion

In patients with CD, anti-αvβ6 differentiate colonic from ileal disease and predate clinical disease by up to 10 years, potentially serving as a novel biomarker for clinical and preclinical colonic CD.
OP33 Efficacy and safety of subcutaneous guselkumab induction therapy in patients with moderately to severely active Crohn’s disease: Results through Week 48 from the phase 3 GRAVITI study
Authors: Hart A , Panaccione R , Steinwurz F , Danese S , Hisamatsu T , Cao Q , Olurinde M , Vetter M L , Yang Z , Wang Y , Johanns J , Terry N A , Sands B E , D’Haens G
Published: January 2025

Background

Guselkumab (GUS) is a dual-acting IL-23p19 subunit inhibitor that was efficacious in phase 3 trials (GALAXI 2/3) of pts with CD using IV induction and SC maintenance. We evaluated the efficacy and safety of GUS SC induction/maintenance in GRAVITI, a phase 3 treat-through trial in pts with moderately to severely active CD.

Methods

Eligible pts had a history of inadequate response or intolerance to oral corticosteroids, AZA, 6-MP, MTX, or biologics (BIO-IR). Randomization was stratified by baseline (BL) CDAI, SES-CD, and BIO-IR status, with 347 pts allocated 1:1:1 to GUS 400mg SC q4w (x3)→GUS 200mg SC q4w (N=115), GUS 400mg SC q4w (x3)→GUS 100mg SC q8w (N=115), or PBO (N=117). Pts were rescued at Wk16: PBO pts switched to GUS, and GUS pts stayed on GUS per treat-through design (sham rescue). The co-primary endpoints were clinical remission at Wk12 and endoscopic response at Wk12. Other multiplicity-controlled endpoints were clinical remission at Wk24, PRO-2 remission at Wk12, clinical response at Wk12, clinical remission at Wk48, and endoscopic response at Wk48. All endpoints assessed through Wk12 compared the combined GUS 400mg SC treatment arm to PBO; assessments after Wk12 compared each GUS SC maintenance regimen to PBO. All pts who met rescue criteria were considered not to have met efficacy endpoints after Wk16. Safety was assessed through Wk48.

Results

BL characteristics were similar across groups (overall mean age, 37.5yrs; mean CD disease duration, 8.0yrs; mean CDAI, 296.9; mean SES-CD, 12.0; BIO-IR, 46.4%).

The co-primary and all multiplicity-controlled endpoints were met. GUS 400mg SC induction demonstrated superiority to PBO at Wk12. Both SC maintenance dose regimens were also superior to PBO at Wks 24 and 48 (Figure). In prespecified analyses of subpopulations defined by prior biologic history, greater proportions of GUS-treated pts achieved the endpoints than PBO.

Key safety event rates per 100 pt years through Wk48 were similar among groups (Table). Proportions of GUS-treated pts experiencing ≥1 serious AE or AE leading to discontinuation of study agent were not greater than PBO. The numbers of GUS-treated pts with serious infections or AEs of special interest were low.

Conclusion

GRAVITI established the efficacy of GUS SC induction followed by SC maintenance in CD. These results build on the GALAXI 2/3 data and demonstrate that both IV and SC induction are efficacious. Safety findings were consistent with the known safety profile of GUS in approved indications.
DOP003 Cromoendoscopy versus second generation Narrow band Imaging for dysplasia detection in IBD. A prospective randomized controlled trial
Authors: Martin Arranz E , Suarez Ferrer C , García Ramirez L , Sanchez Azofra M , Rueda Garcia J L , Poza Cordon J , Martín-Arranz M D
Published: January 2025

Background

Neoplastic risk is increased in long-standing colitis. Dye chromoendoscopy (CE) and virtual chromoendoscopy are surveillance methods. The aim of this trial is to compare methylene blue chromoendoscopy (CE) with second generation narrow band imaging (NBI) virtual chromoendoscopy in the detection of IBD-associated colonic neoplasia.

Methods

Prospective randomized controlled trial (NBICromo NCT04403997) including patients with clinical indication for surveillance (>8 years of disease, left-sided or extensive colitis, colonic Crohn´s disease with >2 colonic segments affected or associated primary sclerosing cholangitis). Patients were randomized on 1:1 ratio to CE with methylene blue 0,1% or NBI. All procedures were performed with Olympus HQ190 endoscopes by endoscopists with experience in IBD and chromoendoscopy. All visible lesions were resected or biopsied depending on the optical diagnosis. The primary endpoint is the difference in total number of neoplastic lesions detected in each group. Neoplastic lesions include dysplasia and serrated lesions. Secondary endopoints include withdrawal time, total number of lesions, adverse events. The study has been approved by the Hospital Ethics Committee and patients signed informed consents.

Results

200 patients were included, 26 were excluded due to presence of inflammation or poor bowel preparation and finally 174 were randomized, 81 to CE arm and 93 to NBI Basal characteristics are shown in Figure 1.

118 (67,8%) patients had at least one lesion. 59 (72,8%) in the CE group and 59 (63,4%) in the NBI group p=0.22. 51 patients (29,5%) had neoplastic lesions, 24 patients in CE group (29,6%) and 25 patients with NBI (26,8%)

299 lesions were detected. 173 with CE and 126 with NBI. Of these 75 (25,1%) were neoplastic. 37 neoplastic lesions were found in NBI group and 38 in CE group p ns. 10 lesions were serrated, 6 in the NBI group and 4 in CE group p ns. No invasive cancer was detected.

Lesion characteristics are shown in figure 2

Total withdrawal time (including staining and/or therapeutics) was significantly shorter in the NBI group (median 15 min (Interquartile range 11-21 vs 24 (IQ range 18-32 p<0.001).AE were 1 post moderate resection bleeding and 1 mild fever, both in the CE group.

Conclusion

In patients with IBD undergoing colitis associated neoplasia screening we found no difference between virtual chromoendoscopy with NBI and methylene blue chromoendoscopy in neoplasia detection. NBI reduces procedure time significantly.
DOP005 Long-term efficacy and safety of mirikizumab treatment for Crohn’s Disease: Results from the VIVID-2 open-label extension study
Authors: Vermeire S , Sands B E , D’Haens G , Hisamatsu T , Kelly C R , Lu N , Morris N , Moses R , Durand F , Protic M , Hozak R R , Lopes M U , Regueiro M , Laharie D
Published: January 2025

Background

VIVID-2 (NCT04232553) is an ongoing open-label long-term extension study of efficacy and safety of mirikizumab (MIRI), a selective interleukin-23p19 inhibitor, in patients with moderately to severely active Crohn’s disease (CD). We present efficacy and safety results from patients randomised to MIRI in the phase 3 VIVID-1 study (NCT03926130) who received MIRI for a second year in VIVID-2, with or without reinduction.

Methods

In VIVID-1, the MIRI group received induction with 900 mg intravenously (IV) at weeks (W) 0, 4, and 8, then 300 mg subcutaneously (SC) every 4W. Week 52 endoscopic responders (≥50% reduction from baseline in Simple Endoscopic Score for CD [SES-CD]) continued the same MIRI SC dosing in VIVID-2. Endoscopic non-responders received reinduction with MIRI IV at the start of VIVID-2 followed by SC dosing (IV-SC) as described. Outcomes at W104 of MIRI treatment included endoscopic response and endoscopic remission (SES-CD ≤4 and ≥2-point reduction from baseline with no subscore >1 for any individual variable). The cutoff date was 02 August 2024; VIVID-2 patients entered after 01 August 2023 were excluded from this interim analysis. Safety was assessed from the first dose in VIVID-2 through the cutoff date. Discontinuations or missing data were handled using modified nonresponder imputation (mNRI) and observed cases (OCs).

Results

Among MIRI endoscopic responders (N=251) who continued MIRI SC, 81.8% (mNRI)/87.6% (OC) maintained endoscopic response at W104 (Fig. 1A). At W104, endoscopic remission was maintained by 72.5% (mNRI)/78.6% (OC) of the 137 patients also in endoscopic remission at W52 and gained by a further 33.3% (mNRI)/35.4% (OC) of the 112 patients not in endoscopic remission at W52 (Fig. 1A). Among MIRI endoscopic nonresponders (N=179) who received reinduction with MIRI IV at the start of VIVID-2 followed by MIRI SC, 30.9% (mNRI)/36.1% (OC) gained endoscopic response; 12.1% (mNRI)/13.7% (OC) of the 174 patients not in endoscopic remission at W52 gained endoscopic remission at W104 (Fig. 1B). Treatment-emergent adverse events (AEs) were reported in 64.3% (MIRI SC) and 65.3% (MIRI IV-SC) of patients, and serious AEs were reported in 6.8% (MIRI SC) and 9.0% (MIRI IV-SC) of patients (Table 1).

Conclusion

In VIVID-2, high maintenance rates of endoscopic response and endoscopic remission were observed in patients with moderately to severely active CD who were endoscopic responders at 1 year, with additional patients gaining endoscopic remission in year 2 of MIRI treatment. Over 30% of endoscopic nonresponders at 1 year gained endoscopic response with MIRI reinduction. Overall, safety was consistent with the known MIRI safety profile.
DOP006 Long term maintenance treatment with vedolizumab in pediatric IBD: a three-year follow-up of the prospective multicenter VEDOKIDS study
Authors: Atia O , Shavit-Brunschwig Z , Orlanski-Meyer E , Stein R , Efrat B , Hyams J , Granot M , Rosh J , Hussey S , Markowitz J , Russell R K , Turner D
Published: January 2025

Background

Long-term data on the use of vedolizumab in children with Crohn’s disease (CD) and ulcerative colitis (UC) are lacking and the drug is not yet approved in pediatrics. The VEDOKIDS prospective multicenter cohort study aimed to assess the effectiveness and safety of vedolizumab as maintenance therapy in children with CD and UC; this study reports the 3-year final visit outcomes (ClinicalTrials.gov, NCT02862132).

Methods

Children commenced on vedolizumab at any disease duration and with any degree of disease activity were enrolled in 17 pediatric centers in Europe, the USA and the Middle East and followed prospectively through 3 years. The primary outcome was complete remission at 3 years (i.e. steroid-free clinical remission and normal ESR/CRP with sustained vedolizumab treatment and without a surgery). Secondary outcome was loss of response (PUCAI ≥ 10 or wPCDAI ≥ 12.5 for children with UC and CD, respectively) in those achieving clinical remission at week 6.

Results

Altogether, 137 children were enrolled, of whom 53 (39%) continued vedolizumab treatment through three years. Sustainability rate was higher in UC (35/73 [48%]) than in CD (18/64 [28%]; OR 2.4 [95%CI 1.2-4.8]). Complete remission at three years was achieved in 19/73 (26%) children with UC vs. 9/64 (14%) with CD (OR 2.2 [95%CI 0.9-5.2]) using ITT analysis.

The best predictor of complete remission at 3 years was clinical remission at week 6 measured in CD by wPCDAI ≤12.5 (AUROC 0.78 [95%CI 0.64-0.963]), and in UC by PUCAI<10 (AUROC 0.74 [0.63-0.85]). Similarly, in adjusted multivariable logistic regression, complete remission at 3 years was more likely in week-6 remitters or responders compared to non-responders (HR 2.6 [95%CI 1.1-7.2]). Of the 51 (37%) children who achieved clinical remission at week 6 (32 UC and 19 CD), the likelihood of achieving complete remission at 3 years was 41% for UC and 26% for CD (OR 1.9 [95%CI 0.6-6.6]). Of those achieving clinical remission at week 6, 22%, 28%, 31% and 38% lost response by 30, 54, 108 and 162 weeks, respectively, for UC, while for the fewer children with CD who achieved remission at week 6, 5%, 5%, 11% and 16%, respectively, lost response (Figure).

Forty adverse events were recorded in 23 children (17%) as possibly related to vedolizumab, none were serious, with the most common being headache, myalgia and fever.

Conclusion

Vedolizumab was safe and effective for maintaining long-term remission in children with UC and CD. Remission rates were higher in UC compared to CD at the end of induction, but UC patients experienced a higher rate of loss of response over time. Achieving clinical remission by week 6 after initiation of the drug was the best predictor of long-term effectiveness in both UC and CD.
P0209 Unraveling the microbial dynamics in Crohn’s Disease-associated Fibrosis: insights from RNA-seq and Spatial Transcriptomics
Authors: Nicolo’ S , Massimino L , Parigi T L , Errico C , Salvatore S , Bozzetti V , Facoetti A , Cagliani S , Riva M , Danese S , Ungaro F
Published: January 2025

Background

In Crohn’s disease (CD), over 50% of cases develop fibrosis, often resulting in strictures. Despite advances in anti-inflammatory therapies, these complications persist due to chronic inflammation, which causes tissue injury and disrupts mucosal functions. Recent studies highlight microbiota dysbiosis as a potential inflammation-independent driver of fibrosis in CD 1,2, but specific microbial signatures across fibrosis stages remain underexplored.

Methods

We performed a meta-analysis of RNA-seq data from fibrotic CD-associated and healthy tissues. Cells, including immune, fibroblast, endothelial, and epithelial populations, were isolated via flow cytometry (FACS) and analyzed at the transcriptomic level. Co-culture experiments were conducted to explore cellular-bacterial interactions in fibrosis progression, and fibrosis markers (alpha-SMA, vimentin, and FAP) in fibroblasts were evaluated through immunofluorescence (IF).

Results

Gene ontology analysis revealed activation of antimicrobial immune processes, indicating a targeted response to microbiota during fibrosis progression. Microbiota analysis showed an increased abundance of Roseomonas mucosa in CD patients compared to controls across multiple cell types (endothelial, epithelial, fibroblast, and immune cells). Moreover, fibroblast co-cultures with Roseomonas mucosa (50 MOI/cell) displayed elevated fibrosis markers in IF compared to unstimulated controls.

Conclusion

Our findings suggest that Roseomonas mucosa, or its products, may modulate the transcriptional state of mucosal cells, including fibroblasts, contributing to intestinal fibrosis. To further elucidate the role of bacterial proteins in the progression from healthy to fibrotic tissue, we are performing spatial transcriptomics analysis on ileo-cecal resection tissues, followed by RNA-scope with bacteria-specific probes. This integrative approach aims to map the temporal progression of fibrosis in relation to microbiota, offering deeper insights into its development.

References

1.Massimino, L. et al. The Inflammatory Bowel Disease Transcriptome and Metatranscriptome Meta-Analysis (IBD TaMMA) framework. Nat. Comput. Sci. 1, 511–515 (2021).

2.Watanabe, D. & Kamada, N. Contribution of the gut microbiota to intestinal fibrosis in crohn’s disease. Front Med (Lausanne) 9, 826240 (2022).
P0213 Salivary Veillonella parvula from Crohn’s Disease Patients Exacerbates Intestinal Inflammation
Authors: Xiang B , Hu J , Zhi M , Xu Z , Zhang M , Peng X
Published: January 2025

Background

The gut microbiota plays a significant role in the development of inflammatory bowel disease (IBD). There is a close interaction between the oral and gut microbiota. However, the role of the "oral-gut" microbial axis in the development of IBD is not yet clear.

Methods

1. Analyzed oral-gut microbiota patterns in 97 IBD patients using 16S rDNA sequencing and bioinformatics methods.

2. A mouse colitis model with DSS was used. It was gavaged with oral microbiota from CD patients to assess the impacts on colitis and gut microbiota.

3. Isolated specific differential bacteria, Veillonella, from CD patient saliva and evaluated their effects on DSS-induced colitis in mice.

Results

1. IBD patients had a reduced core gut microbiota, lower diversity (P < 0.05), and increased abundance of potential pathogens such as Escherichia-Shigella.

2. CD patients showed more correlations between saliva and fecal microbiota, with the most significant correlation between Veillonella in saliva and Escherichia-Shigella in fecal (P=0.00018) .

3. The mice which were gavaged with saliva from CD patients showed significant weight loss (P < 0.0001), reduced colon length (P=0.03), increased histopathological scores (P=0.01), decreased expression of colonic mucosal barrier proteins ZO-1 and E-cadherin, and exacerbated gut microbiota dysbiosis .

4. The mice which were gavaged with Veillonella parvula from CD patients showed significant weight loss (P < 0.0001), reduced colon length (P=0.02), increased histopathological scores (P=0.02), decreased expression of colonic mucosal barrier proteins ZO-1 and E-cadherin, and exacerbated gut microbiota dysbiosis.

Conclusion

The interplay between the oral and gut microbiota potentially influences the progression of IBD, with oral bacteria such as Veillonella possibly intensifying intestinal inflammation in IBD patients by disrupting the gut microbiota balance. Targeted modulation of the gut microbiota and interference with oral-gut microbial interactions may offer a promising therapeutic strategy for managing IBD.
P0217 Colonic stromal cells are a source of sphingosine-1-phosphate and may be defining responsiveness to sphingosine-1-phosphate receptor modulators in Ulcerative Colitis
Authors: Drygiannakis I , Damianaki A , Filidou E , Theodoraki E , Coucoutsi C , Foteinogiannopoulou K , Spathakis M , Kandilogiannakis L , Dovrolis N , Kolios G , Valatas V , Koutroubakis I
Published: January 2025

Background

Sphingosine-1-phosphate (S1P) receptor (S1PR) modulators (S1PRMs) block chemotaxis of cells of immunity to the locus of inflammation. S1PRM effectiveness depends on the extent of the pathway activation. We explored the contribution of colonic stromal cells (CSC) to S1P production in patients with ulcerative colitis (UC) and healthy controls (HC).

Methods

We looked into the two S1P-producing kinases (SPHK1, SPHK2), the transporter exocytosing S1P (SPNS2) and the lyase degrading it (SGPL1). Basal mRNA transcription in primary CSC in culture from UC patients and from HC was assayed with quantitative reverse-transcription PCR. The effect of each one of the principal T helper (Th) 1 (ΤNF-α, IFN-γ), Th2 (IL-4, IL-13) or regulatory T (Treg; TGF-β, IL-10) cytokines was also tested. Medians of ΔΔCT and statistical significance between groups of unpaired, paired or between scale variables with Mann-Whitney, Wilcoxon or Spearman’s rho test, respectively, are reported.

Results

Eleven patients with UC (mean age: 49 years; 9 males; 7 with left-sided and 4 with extensive disease; mean UC duration: 180 months) and 9 HC were included. CSC from both UC and HC had a basal expression of SPHK1, slightly lower in UC (0.56x10-3 vs 2.18x10-3, p<0.04), and of SPHK2 (8.04x10-4, 1.05x10-3, respectively). However, CSC from UC patients with an endoscopic Mayo component of 3 vs 2 and from UC patients with higher erythrocyte sedimentation rate expressed more SPHK1 (3.69x10-3 vs 0.45x10-3, p<0.05; r 0.762, p<0.04). Similarly, both UC and HC CSC expressed SPNS2 (5.96x10-5, 3.46x10-4, respectively) and SGPL1, with the latter overexpressed in UC (5.41x10-2 versus 2.68x10-3, p<0.001).

CSC from UC, in sharp contrast with those from HC, were responsive to proinflammatory cytokines. In detail, SPHK1 was upregulated by TNF-α (x5 times, p<0.034; Figure 1A). SPHK2 was downregulated by TGF-β (/3 times, p<0.042). SPNS2 was downregulated by IFN-γ (/18 times, p<0.001; Figure 2B) and by TGF-β (/8 times, p<0.02; Figure 2B). SGPL1 was downregulated by IFN-γ (/16 times, p<0.001; Figure 2C) and by IL-10 (/7 times, p<0.04; Figure 2C).

Conclusion

In health and UC, CSC express the machinery synthetizing, exocytosing and catabolizing S1P. In UC the transcription of these genes is controlled by cytokines. Hence, activity of the pathway in CSC should be further investigated as a parameter to the direction of personalised treatment with S1PRMs in UC.
P0325 Is the augmentation index a good marker of cardiovascular risk in Crohn’s disease?
Authors: Fissah M , Rechach A , Charifi M , Menzou F , Djouhri M , Chibane A
Published: January 2025

Background

The axiom which defines that the high prevalence of cardiovascular risk factors is by definition correlated with the risk of cardiovascular events does not seem to apply to subjects with IBD, according to several studies which have reported that the prevalence of classic cardiovascular risk factors is lower in subjects with IBD than in the general population. This leads us to look for other markers to identify this risk at an early stage. The Augmentation index (Aix) is one such marker, based on the reflection of the pulse wave in the blood, and is a recognised measure of arterial stiffness and a risk factor for cardiovascular disease

Methods

This was a prospective cross-sectional study of 107 patients with Crohn’s disease (CD) diagnosed on the basis of clinical, endoscopic, morphological and histological criteria. Classical cardiovascular risk factors were analysed, as well as data concerning CD: duration, location, phenotype, clinical relapse, extradigestive manifestations, ano-perineal lesions (APL) and C-reactive protein (CRP). The augmentation index (Aix) was assessed using the SphygmoCor-XCEL Sydney. The Chi2 test was used for qualitative variables and the Kruskal Wallis test for quantitative variables. The informed consent of all patients was obtained.

Results

57.9% were men, mean age was 36.9 ± 11.7 years, 5.6% of patients had coronary heredity, 11.2% hypertensive, mean systolic blood pressure: 120.1 ± 12.7 mm/hg, mean diastolic blood pressure: 74.4 ± 8.1 mm/hg, pulse pressure: 45.7 ±9.3 mm/hg, AIx was positive in 31.8% of patients, 7.5% of women were postmenopausal, mean BMI was 22 ± 5.91 Kg/m2, 9.3% were obese, 11.2% were sedentary, 20.6% were active smokers, only two patients were diabetic. 57.9% had dyslipidaemia, and 13.1% had a low cardiovascular risk according to the Framingham score. 74% had an ileal location, 6.8% colonic and 19.2% ileocolic, 19.8% had an inflammatory form, 43,4% stenosing and 36,8% penetrating, 25.5% with ano-perineal lesions, 31.4% had an extradigestive manifestation, 59.4% of patients were in clinical relapse, 47.2% of whom had a CRP > 6mg/l, 38% of subjects had had at least one relapse in the year prior to recruitment, and the mean duration of the disease was 57.3 ± 57 months. Statistical analysis showed a significant association between AIx and clinical relapse (p=0.03), disease duration (p=0.008), and no significant association with phenotype, location, APL, extradigestive manifestations and CRP (p>0.05).

Conclusion

Our results suggest that the augmentation index could be a good tool for detecting subclinical cardiovascular damage in Crohn’s disease. Clinical relapse and the duration of the disease would be two predominant factors in the increase in this index
P0536 Clinical profile and treatment outcomes in patients receiving advanced therapies for ulcerative colitis – the READ-UC real-world study
Authors: Fernandes S R , Tavares de Sousa H , Portela F , Ministro P , Lago P , Branquinho D , Freitas I , Martins Machado N , Magro F
Published: January 2025

Background

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that requires effective treatment with the main goal of inducing and maintaining remission. This study aimed to characterize UC patients receiving advanced therapies (AT), by describing their demographic and clinical characteristics and remission outcomes.

Methods

Cross-sectional and retrospective study in 5 IBD referral centres. Eligible subjects (≥18 years-old with UC diagnosis and receiving AT for ≥16 weeks) were consecutively enrolled at a standard of care appointment (study appointment). The primary endpoints were the proportion of patients achieving remission, defined as both symptomatic [Mayo subscores stool frequency of 0 or 1 and rectal bleeding of 0] and faecal biomarker remission [faecal calprotectin <150 µg/g]. Data on patients’ demographic and clinical characteristics, including extraintestinal manifestations (EIMs), comorbidities and treatment patterns, and on healthcare resource utilization were also collected.

Results

The study included 219 patients (50.9% female, median [P25;P75] age 46 [36;58] years) presenting a median disease duration of 9 [5;14] years. History or current evidence of EIMs and comorbidities were reported in 13.7% and 43.8% of patients, respectively. At diagnosis, 17.0% of patients had ulcerative proctitis, 38.1% had left-sided UC, and 44.8% had extensive UC. Over half (58.4%) were diagnosed with moderate or severe UC. Most patients (57.1%) were on their first AT, mostly on infliximab (47.5%) and vedolizumab (37.4%), while a minority received ustekinumab (5.9%), adalimumab (5.5%), tofacitinib (2.3%), and golimumab (1.4%). After treatment (26 [14; 47] months), symptomatic and faecal biomarker remission was achieved in 35.2% of patients, while 83.9% presented symptomatic remission and 46.1% of patients attained faecal biomarker remission (). There were no significant differences between patients who achieved symptomatic and faecal biomarker remission and those who did not (Table 1). Patients were prescribed concomitant specific therapies [5-ASA derivatives (78.0%), immunosuppressants (34.7%), and steroids (6.4%)]. Steroid-free remission was achieved in 34.9% of patients (Figure 1), who were off this medication for a median of 26 [15;45] months. Since AT initiation, 20.6% of patients relapsed, 11.9% were hospitalized, and 27.4% visited an emergency department.

Conclusion

The READ-UC study provides a detailed real-world characterization of UC patients on AT. The high proportion of patients not achieving symptomatic and faecal biomarker remission or steroid-free remission, highlights the urgent need for implementing strategies that improve UC management and outcomes of these patients.
P0552 Incisional and parastomal hernia after surgical management of inflammatory colitis: a common complication presenting a real therapeutical challenge in a tertiary expert center
Authors: Lelièvre O , Abdalla S , Meyer A , Amiot A , Carbonnel F , Penna C , Benoist S , Brouquet A
Published: January 2025

Background

Surgical management of inflammatory colitis often requires a staged approach involving multiple interventions with or without stoma creation. Data on the incidence, risk factors, impact and management of incisional and parastomal hernias (IH and PSH) in UC patients are limited. This study aims to assess the incidence of IH and PSH after surgical completion in colitis patients and to identify associated risk factors.

Methods

All patients undergoing surgical management for inflammatory colitis between March 2010 and May 2024 were eligible. The primary endpoint was the incidence of IH and/or PSH and/or and/or stoma prolapse. Risk factors of hernia (IH and/or PSH) were analysed using univariate and multivariate analyses.

Results

A hundred and nine patients had surgical management for inflammatory colitis and were included in the analysis (87 UC [80%], 6 Crohn’s disease [5.5%], 14 indeterminate [13%], 2 drug-induced [1.8%]). Mean age was 46 ± 17 years. Indications included refractory colitis (n=32, 29%), severe acute colitis (n=58, 54%), and dysplasia (n=19, 17%). Procedures performed were ileal pouch anal anastomosis (IPAA) in 73(67%) patients, ileorectal anastomosis (IRA) in 23(21%), and non-restorative proctocolectomy with end ileostomy in 13(12%). Patients underwent a mean of 2.7±0.96 procedures with 99 patients requiring 2 or more procedures. Temporary stomas were created in 84(77%), and 19(17%) had permanent stomas. Median follow-up time was 44[21-91] months. 25(23%) patients had parietal complications after a median delay of 25[11-35] months following the last procedure: 22(20%) IH, 4(3.6%) PSH, and 3(2.8%) stomas prolapse*. None of the 4 patients with prophylactic biological mesh placement during stoma closure developed complications. Among 25 patients with parietal complications, 20 underwent abdominal wall repair. Of these, 6(30%) had recurrence requiring redo abdominal wall surgery in 3(15%). Adjusted risk factors for parietal complications included BMI≥25 (OR=3.13;95%CI=1.11-8.82;p=0.031) and permanent stoma (OR=5.86;95%CI=1.83-18.80; p=0.003). The type and number of procedures, and surgical indications were not associated with parietal complications.

* Several patients had several complications

Conclusion

Parietal complications represent a major clinical challenge in the surgical management of inflammatory colitis. Nearly one-quarter of patients develop abdominal incisional or parastomal hernias, and one-third of patient experience recurrence following abdominal wall repair. Prophylactic mesh placement at the stoma closure site should be studied as an option to reduce this risk.

References

None
P0563 Prevalence and clinical impact of abnormal hepatobiliary biochemistry in newly diagnosed inflammatory bowel disease – a prospective population-based inception cohort study
Authors: Attauabi M , Madsen G R , Bendtsen F , Seidelin J B , Burisch J
Published: January 2025

Background

Abnormal hepatobiliary biochemistry is frequently observed in patients with inflammatory bowel diseases (IBD), encompassing ulcerative colitis (UC) and Crohn’s disease (CD). However, its prevalence and clinical implications in IBD remain unclear. We aimed to determine the occurrence and clinical impact of abnormal hepatobiliary biochemistry in patients with newly diagnosed IBD.

Methods

Between May 1, 2021, and April 30, 2023, all adult and pediatric patients with incident IBD within a catchment area covering 20% of Denmark were enrolled in the prospective, population-based Copenhagen IBD Inception Cohort.1 Herein, all adult patients underwent hepatobiliary blood tests (alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, and INR) at IBD diagnosis. Multivariate Cox proportional hazard analyses adjusting for age, sex, smoking, and disease phenotype were performed (adjusted HR, aHR, 95% confidence interval).

Results

A total of 527 patients (UC: 326; CD: 201) were included in the cohort, with 290 (89.0%) and 189 (94.0%) undergoing blood tests, respectively, within a median of two days (interquartile range: -14 - 6) before IBD diagnosis. No demographic or clinical phenotypical differences were observed between patients who underwent blood test and those untested.

Abnormal hepatobiliary biochemistry was found in 49 (16.7%) and 46 (24.3%, p<0.01) patients with UC and CD, respectively, primarily driven by higher median ALP levels in CD (80 U/L [IQR 69-97]) versus UC (74 U/L [IQR 61-90], p<0.01). No associations were observed between abnormal hepatobiliary biochemistry and sex, age, initial extent or location of IBD, or disease activity (Table 1). However, stricturing or penetrating CD was significantly associated with abnormal hepatobiliary biochemistry (adjusted OR = 4.62 [1.70; 12.54]).

During a follow-up of 2.1 years (IQR 1.6-2.6), abnormal hepatobiliary biochemistry was not associated with the initial course of UC; however, an increased risk of requiring resective surgery for CD was observed (aHR= 3.27 [1.04-10.24], Table 2).

Conclusion

In this prospective, population-based cohort, abnormal hepatobiliary biochemistry was present in approximately one in six patients with UC and one in four patients with CD at diagnosis, with no association with IBD disease activity. Although it did not correlate with the initial course of UC, these findings underscore the need for increased attention to hepatobiliary biochemistry in patients with CD.

References

1.Attauabi M, Madsen GR, Bendtsen F, et al. Influence of Genetics, Immunity and the Microbiome on the Prognosis of Inflammatory Bowel Disease (IBD Prognosis Study): the protocol for a Copenhagen IBD Inception Cohort Study. BMJ Open. 2022;12(6):e055779. doi:10.1136/bmjopen-2021-055779