bluuebunny/crossref_metadata_2025_split huggingface dataset:
A quantitative methodology for measuring the social sustainability of pavement deterioration
Authors: Okte Egemen , Boakye Jessica , Behrend Mark 
Published: January 2024

AbstractThe social pillar of pavement sustainability is understudied compared to economic and environmental pillars, making it difficult to integrate into life-cycle methodologies. While methods such as social life cycle assessment (S-LCA) exist, they usually focus on social governance rather than quantifying the impact of pavement investment decisions on communities. This study introduces a methodology to quantify the impact of road condition on vulnerable communities, specifically Environmental Justice (EJ) communities. The methodology calculates the impact of road condition on residents and analyzes fuel consumption (as an example impact) for road users during recurrent home-work trips as a function of pavement condition for EJ and non-EJ communities. It was found that EJ communities in Massachusetts are twice as likely to live near poor condition roads and consume twice as much excessive fuel during recurrent home-work trips. The proposed method is designed to integrate into existing life-cycle methods and represents a significant step towards integrating equity into pavement management decisions.
Analysis of scooter engine piston damage
Authors: Pleshakov Eduard , Bohun Lidia , Mierzwiński Dariusz , Shved Mariia 
Published: January 2024

The causes of operational damage to the piston of a single-cylinder two-stroke internal combustion engine (ICE) of a scooter, made of a piston aluminum-silicon alloy by mold casting, were investigated. It was found that the AK21M2.5H2.5 type alloy has a dispersed eutectic structure (α+β-Si) with a small number of primary silicon crystals of a compact shape, the size of which does not exceed 10 μm. The porosity of the cast alloy of the piston is less than the lowest 1st porosity point, as well as the quality structure, could not be the cause of its damage.
The average value of the microhardness measured on the surface of the piston head (70 HV0.98) is slightly less than the standardized hardness (90 НВ ÷ 100 НВ) of ingots after mold casting and artificial aging without preliminary hardening, which indirectly indicates overheating of the piston during operation. The detected damage to the outer surface of the piston in the form of deep scratches and worn stripes is not caused by metallurgical or technological factors, but by violations of operating conditions: overheating and lack of lubricant in the contact zone of the piston and cylinder.
Mouna Ben Halima – La Badira Hotel
Authors: Sellami Aziza , Ward-Perkins David 
Published: January 2024

Summary
Mouna Ben Halima, owner and director of the Badira Hotel, was thrust into the business world at the young age of 24 on the death of her father, a leading Tunisian hotelier. Against the advice of many, including her investors, she opened a new style of luxury hotel, one that would cater to the emerging aspirations of both Tunisian and European tourists. In doing so, she was questioning decades of opinion concerning the nature of tourism in Tunisia. She did so as a female entrepreneur in a fast developing, but still quite traditional society.

Information
© The Authors 2024
Comparative study on tribological behavior of foil journal bearings with micro pocket
Authors: Mourya Vishal , Bhore Skylab P 
Published: January 2024

Abstract
This study explores the tribological performance of bump foil journal bearing (FJB) equipped with micro-pocket. The influence of micro-pocket on the load capacity (LC) and friction factor (FF) of FJBs is evaluated for various foil materials, including Inconel X750 (IN), Spring steel EN42J (SP), SS 316, Beryllium copper (BC), and Phosphor bronze (PB). The compressible Reynolds equation is solved numerically to assess the tribological behavior of bump FJB under various operating conditions. Initially, the impact of micro pocket on the tribological characteristics such as load capacity and friction factor of bump FJB is examined by comparing their performance with plain FJB. Subsequently, the effect variable parameters such as pocket depth (PD), bearing number (Λ), and eccentricity ratio (ε), on the tribological behavior is analysed by using response surface methodology (RSM). The multi-objective grey relational analysis (GRA) technique is employed to determine the optimal values of these variable parameters for each foils material. The findings reveal that micro-pocket enhance the dimensionless LC of bump FJB beyond a bearing number of 2.061. Moreover, micro-pocket reduce the friction factor of bump FJBs. Within the presence of micro pocket, SS 316 exhibits the most significant foil material for the better tribological characteristics of bump FJB, while phosphor bronze is the least signifcant. For SS 316, the optimal values of pocket depth (PD), bearing number (Λ), and eccentricity ratio (ε) are 3 μm, 2.061, and 0.5 respectively. Under these optimal conditions, the load capacity (LC) and friction factor (FF) of bump FJBs are 0.7740 and 13.645, respectively. Micro-pocket reduces the friction factor (FF) by 2 to 15%. The impact of pocket depth on the LC and FF of bump FJB is significant for the phosphor bronze. Additionally, increasing the pocket depth enhances the dimensionless LC of bump FJBs while decreasing the friction factor.
FGF2, LIF, and IGF-1 supplementation improves mouse oocyte in vitro maturation via increased glucose metabolism
Authors: Nahar Asrafun , Becker John , Pasquariello Rolando , Herrick Jason , Rogers Heather , Zhang Mingxiang , Schoolcraft William , Krisher Rebecca L , Yuan Ye 
Published: January 2024

Abstract
Chemically defined oocyte maturation media supplemented with FGF2, LIF, and IGF-1 (FLI medium) enabled significantly improved oocyte quality in multiple farm animals, yet the molecular mechanisms behind such benefits were poorly defined. Here, we first demonstrated that FLI medium enhanced mouse oocyte quality assessed by blastocyst formation after in vitro fertilization and implantation and fetal development after embryo transfer. We then analyzed the glucose concentrations in the spent media; reactive oxygen species concentrations; mitochondrial membrane potential; spindle morphology in oocytes; and the abundance of transcripts of endothelial growth factor–like factors, cumulus expansion factors, and glucose metabolism–related genes in cumulus cells. We found that FLI medium enabled increased glucose metabolism through glycolysis, pentose phosphate pathway, and hexosamine biosynthetic pathway, as well as more active endothelial growth factor–like factor expressions in cumulus cells, resulting in improved cumulus cell expansion, decreased spindle abnormality, and overall improvement in oocyte quality. In addition, the activities of MAPK1/3, PI3K/AKT, JAK/STAT3, and mTOR signaling pathways in cumulus cells were assessed by the phosphorylation of MAPK1/3, AKT, STAT3, and mTOR downstream target RPS6KB1. We demonstrated that FLI medium promoted activations of all these signaling pathways at multiple different time points during in vitro maturation.
A fast crystallization of TUN zeolite via the interzeolite conversion method
Authors: Lu Yao , Qin Feiyu , Wang Yong , Simancas Raquel , Cai Yibing , Kondo Junko N , Gies Hermann , Yokoi Toshiyuki 
Published: January 2024

Abstract
A TUN-type aluminosilicate zeolite was rapidly synthesized via the interzeolite conversion method (IZC) using a MWW-type one as a starting material. It was found that the co-addition of the organic structure direct agent (OSDA) and the seed played a crucial role in accelerating the crystallization of the TUN phase. The TUN zeolite synthesized via the IZC method exhibited comparable physicochemical properties to those of the conventional one crystallized from amorphous silica and alumina materials.
OP09 Oral ritlecitinib and brepocitinib in patients with moderate to severe active Crohn’s Disease: Data from the PIZZICATO umbrella study
Authors: Vermeire S , Allegretti J R , Kim H J , Long M D , Leszczyszyn J , Schreiber S , Mross M R , Kierkus J , Peeva E , Vincent M S , Shojaee N , Banfield C , Banerjee A , Gale J D , Hung K E 
Published: January 2024

Abstract

Background
Oral ritlecitinib (RIT; JAK3/TEC family kinase inhibitor) and brepocitinib (BRE; TYK2/JAK1 inhibitor) are being assessed in a 64-week (wk) phase 2a randomised, double-blind, induction-maintenance, umbrella study (PIZZICATO; NCT02958865) in participants (pts) with moderate-to-severe active Crohn’s disease (CD) with inadequate, loss of response or intolerance of corticosteroids, immunosuppressants or biologics. We report the efficacy and safety results from the 12-wk induction period.

Methods
Pts 18-75 years old with endoscopic confirmation of active CD with Simple Endoscopic Score for CD (SES-CD) ≥7/≥4 for isolated ileal disease, and average daily liquid/soft stool frequency (SF) ≥2.5 or daily abdominal pain (AP) ≥2.0 were included. Pts were randomised to RIT 200 mg once daily (QD) for 8 wks then 50 mg QD for 4 wks and matching placebo (PBO) in a 2:1 ratio or BRE 60 mg QD for 12 wks and matching PBO in a 2:1 ratio. Pts continued in their respective arms with open-label RIT 50 mg or BRE 30 mg QD for 52 wks. PBO arms were combined for analysis. Pts achieving SES-CD 50 (≥50% reduction in SES-CD from baseline [BL]; primary endpoint Wk 12), Clinical Disease Activity Index (CDAI) remission (CDAI&lt;150) and CDAI-100 response for pts with BL CDAI≥220, clinical response (≥30% reduction from BL in AP or SF; neither worse than BL) and remission (SF≤1.5 and AP≤1; neither worse than BL) were assessed. Safety was also evaluated.

Results
A total of 244 pts were randomised and received treatment in the induction period with BL mean age of 34.6-36.5 years, median SES-CD 11-14, and prior biologics experience 69-76% across groups. The proportion of pts achieving SES-CD 50 was significantly higher at Wk 12 with RIT 200/50 mg QD and BRE 60 mg vs PBO (change from PBO: RIT 14.3% [90% CI, 4.0, 24.5], BRE 21.4% [10.0, 32.9]; Table). Statistical significance vs PBO was observed for RIT at Wks 8 and 12 and BRE at Wk 12 for CDAI remission, CDAI-100, clinical response and remission by SF or AP. Most treatment emergent adverse events (TEAEs) in both groups were mild or moderate. Herpes infections occurred in 1 pt in each group and serious infections in 1 pt in RIT and 2 in BRE. No deaths or malignancies occurred. No events of thromboembolism or MACE occurred for RIT. One pt on BRE had a TEAE of pulmonary embolism. There were no clinically significant observations for labs.

Conclusion
Both RIT and BRE met the primary endpoint in the induction period with significant clinical improvement vs PBO in pts with active CD. Other meaningful efficacy endpoints had similar results to the primary endpoint for both therapies. RIT and BRE had an acceptable safety and tolerability profile that was consistent with previous studies.
OP13 Anti-integrin αvβ6 autoantibodies are increased in PSC-IBD and correlate with liver disease severity
Authors: Bloemen H , Livanos A , Martins A , Tankelevich M , Herb J , Cho J , Santos A , Bravo A C , Petralia F , Colombel J F , Schiano T , Torres J , Levy C , Mehandru S 
Published: January 2024

Abstract

Background
Anti-integrin αvβ6 autoantibodies (anti-αvβ6) are a novel biomarker of ulcerative colitis (UC) that precede disease diagnosis by up to 10 years. Given that integrin αvβ6 is also expressed on the biliary epithelium and that primary sclerosing cholangitis (PSC) co-occurs with inflammatory bowel disease (IBD) in up to 90% of patients, we aimed to determine the prevalence of anti-αvβ6 in patients with PSC and to understand the impact of anti-αvβ6 on PSC disease course.

Methods
Three cohorts of pre-liver transplant patients with PSC and controls (IBD and non-IBD) were recruited from New York, Lisbon and Miami. Anti-αvβ6 levels were measured using ELISA and normalized for serum IgG concentration. Statistical analyses across groups and clinical parameters were performed using the Kruskal-Wallis and Spearman correlation test. Multivariable linear regression was conducted to assess the association between anti-αvβ6 and liver disease severity, correcting for covariates. A mixed-effects model was applied to assess change in anti-αvβ6 over time.

Results
In total, 94 patients with PSC (53 (56.4%) PSC-UC, 20 (21.3%) PSC-Crohn’s disease (CD) and 21 (22.3%) PSC alone) and 129 controls (74 (57.4%) IBD and 55 (42.6%) non-IBD) were enrolled; table 1 shows the baseline characteristics of the patients with PSC. Follow-up samples (n=22) were collected from 1 up to 3 years after initial baseline sampling from 17 PSC patients. Median (IQR) age was similar in PSC patients (43, 33-56 years) and controls (47, 32-62 years; p=0.59). Median (IQR) anti-αvβ6 levels were significantly higher in PSC-UC (1.07, 0.48-2.65) and UC (1.83, 1.12-3.03) compared to PSC alone (0.40, 0.23-0.63; p=0.0004 and p&lt;0.0001 respectively) and non-IBD controls (0.39, 0.17-0.65; p&lt;0.0001 and p&lt;0.0001 respectively). Anti-αvβ6 levels were comparable between PSC alone and non-IBD controls (p&gt;0.999) (figure 1A). Anti-αvβ6 levels did not increase over time (p=0.23). A positive correlation between anti-αvβ6 levels and the Mayo PSC risk score (r=0.28, p=0.008) as well as alkaline phosphatase (r=0.29, p=0.007) was observed (figure 1B). These associations remain significant after correcting for covariates including age at diagnosis of PSC, gender, race/ethnicity and IBD type in a multivariable linear regression.

Conclusion
Anti-αvβ6 autoantibodies are a new biomarker of PSC-IBD and are associated with liver disease severity.
OP14 Effect of mirikizumab on clinical and endoscopic outcomes after 1 anti-TNF failure in patients with moderately to severely active Ulcerative Colitis
Authors: Hart A , Martín-Arranz M D , Laharie D , Matsuoka K , Dhesi E , Redondo I , Baygani S , Zaremba-Pechmann L , Samaan K , Navabi S 
Published: January 2024

Abstract

Background
Mirikizumab (miri), an anti-IL-23p19 antibody, has demonstrated efficacy and safety in moderately to severely active ulcerative colitis (UC) Phase 3 trials (LUCENT-1 and -2; NCT03518086, NCT03524092) among patients who had an inadequate response, loss of response, or intolerance to conventional or advanced therapy. At the LUCENT-1 induction baseline, 41% of the population had experienced a biologic/tofacitinib failure, and 36.3% experienced at least one anti-TNF failure. Among patients with one prior anti-TNF failure only, this analysis evaluated the clinical efficacy of miri compared to placebo (PBO) in induction and maintenance therapy and the efficacy of miri in extended induction.

Methods
In LUCENT-1, UC patients were randomized to receive 3 intravenous (IV) doses of 300mg miri or PBO every four weeks (Q4W) at W0, W4, and W8 (induction population). In LUCENT 2, responders to miri induction at W12 were re-randomized to subcutaneous (SC) 200mg miri or PBO Q4W through W52 of continuous therapy (maintenance population). Patients not achieving clinical response with miri 300mg IV at W12 received extended induction treatment with open-label 300mg miri IV at W12, W16, and W20 (extended induction population). Patients responding to extended induction at W24 entered open-label maintenance and received 200mg miri Q4W SC until W52 (extended induction responders). Endpoints evaluated were clinical response, clinical remission, symptomatic remission, endoscopic remission, corticosteroid (CS)-free remission, and histologic-endoscopic mucosal remission (HEMR). Efficacy in the subgroup of patients with failure of one anti-TNF only was assessed using Cochran-Mantel-Haenszel tests at W12 (induction population) and W52 (maintenance population).

Results
At LUCENT-1 baseline, of patients who experienced anti-TNF failure, 45% of patients (n=190) had one prior anti-TNF failure only (Table 1). In the induction and maintenance populations, a significantly greater proportion of miri-treated patients achieved the following efficacy endpoints compared with PBO [miri vs. PBO, p-value]: clinical response (W12: [64.4% vs. 34.1%, p=0.001]; W52: [67.2% vs. 44.8%, p=0.03]); clinical remission (W52: [44.3% vs. 17.2%, p=0.017]); symptomatic remission (W52: [63.9% vs. 34.5%, p=0.005]) (Table 2). Among the extended induction population, 45.7% achieved clinical response at W24; 75% achieved clinical response, 30% achieved clinical remission and CS-free remission at W52 (Table 2).

Conclusion
Mirikizumab is efficacious for induction and maintenance therapy in patients with moderately to severely active UC who have failed one prior anti-TNF.
OP22 Topical Sphingosine-1-Phosphate (S1P) Receptor 1 Modulation Regulates Gut Angiogenesis in Inflammatory Bowel Diseases
Authors: Wang J , West G , Lin S , Mukherjee P , Maddux R , Wu C , Hu S , Nguyen Q T , Czarnecki D , Le H N , Mao R , Chandra J , Hu S , Gordon I , Petersen A , Harris S , Rieder F 
Published: January 2024

Abstract

Background
S1P receptor (S1PR)1/5 modulators have been tested successfully in clinical development programs in ulcerative colitis (UC), leading to their FDA approval. They are believed to act through lymphocyte redistribution in peripheral lymphoid tissue and reduced numbers of circulating lymphocytes, but evidence from other organs suggests potential additional mechanisms of action.

Methods
A post-hoc analysis of the phase 3 trial of the S1PR1/5 modulator Ozanimod in patients with moderately to severely active UC was performed assessing an association of absolute lymphocyte count (ALC) with efficacy. Expression levels of S1PRs were analyzed in human intestinal tissues and primary cells using qPCR and/or immunohistochemistry (IHC). Effects of S1P, S1PR1/5 modulators and S1P1 knockdown on migration, proliferation, cytokine production, downstream signaling (immunoblot), tube formation of human intestinal microvascular endothelial cells (HIMEC) was evaluated. S1P and S1PR1/5 modulators were examined in a murine matrix plug angiogenesis model and with topical and systemic S1PR1/5 modulator therapy in dextrane sodium sulfate (DSS) colitis in vivo.

Results
Baseline ALC and relative or absolute ALC reductions were neither correlated with nor predictive of clinical or endoscopic outcomes. In murine DSS colitis topical therapy with a S1PR1/5 modulator ameliorated colitis but did not alter peripheral lymphocyte numbers. S1PR1 gene and protein expression was increased in UC and Crohn’s disease (CD) patients and predominantly expressed on HIMEC. S1P promoted HIMEC migration, proliferation, tube formation, IL-8 secretion, indicative of pro-angiogenic responses in vitro. Modulation of S1PR1/5 and knockdown of S1PR1 markedly inhibited these pro-angiogenic functions in the presence of high concentrations of S1P, but enhanced angiogenesis when low S1P concentrations were present. S1PR5 had no effect on angiogenesis. In the murine plug assay, S1PR1 induced angiogenesis. In acute DSS colitis, treatment of S1PR modulator by enema reduced blood vessels, but left lymphatics unaffected.

Conclusion
We present a novel mechanism of action of S1PR1 modulators in IBD intestinal tissue, potentially explaining a disconnect between ALC and efficacy observed in a post-hoc analysis of the phase 3 Ozanimod UC trial. The data presented suggest that S1P induced angiogenesis is attenuated by S1PR1 modulation in HIMEC from IBD patients when S1P levels comparable to blood were present. In the presence of S1P at concentrations consistent with lymph fluid angiogenesis was increased. Together with reduced numbers of circulating lymphocytes, this may contribute to efficacy of S1PR1 modulators in IBD patients.
OP31 Single-cell analyses identify immune and stromal signatures of perianal fistulizing Crohn's Disease
Authors: Cao S , Nguyen K , Colonna M , Deepak P 
Published: January 2024

Abstract

Background
Perianal fistulas occur in ~30-40% of Crohn’s disease (CD) patients associated with high morbidity and an impaired quality of life. The management of perianal fistulizing CD is a major clinical challenge, where its underlying etiology remains poorly understood.

Methods
We recruited patients with 1) CD with perianal fistulas (PCD; n = 12); 2) CD without perianal involvement (NPCD; n = 10); 3) idiopathic perianal fistulas (IPF; n = 21). Biopsies were taken from the fistula tracts, external opening of the fistulas, and rectal mucosa during examination under anesthesia or colonoscopy. Mucosal immune cells were analyzed using mass cytometry (or CyTOF), while all cells from PCD and IPF fistula tracts (n = 5 or 6) were characterized using single-cell RNA-sequencing.

Results
CyTOF revealed a skewed mucosal immune landscape in PCD. E.g., PCD fistula tracts harbored elevated CD45RO+ T cells including Tregs with increased expression of TIGIT and CD226 compared to IPF. PCD also expanded Th17 cells in the fistula tracts and IL-17-producing CD8 T cells (Tc17) in the rectum. Altered exhaustion markers CD39 and CD127 were present in both CD4 and CD8 T cells from PCD fistula tracts, external fistula openings, and rectum compared to IPF and NPCD. Regulatory B cells (Bregs), with immunomodulatory function in the gut, were dramatically diminished in PCD compared to IPF. In addition, PCD fistula tracts, fistula opening, and rectum all exhibited substantially higher CD172+TREM1+ macrophages, which were previously found to promote luminal CD (Figure 1; only fistula tract data are shown). Using scRNA-seq, we unraveled immune and stromal cell compartments in PCD and IPF fistula tracts (Figure 2). We also identified a small mast cell population, which was diminished in PCD. Mast cells are involved in tissue repair and remodeling in other diseases, although their presence in perianal fistulas was previously unknown. Three fibroblast populations (cluster 4, 6, 7 in figure 2D), with elevated activities in interferon signaling, IL-6-JAK-STAT3 pathway, TNF signaling, as well as TGF-B and epithelial-mesenchymal transition, were dramatically increased in PCD compared to IPF. Ongoing studies are focusing on spatial transcriptomics and functional analysis of fistula-associated immune cells and fibroblasts.

Conclusion
Using single cell analysis of the fistula tracts and nearby tissues from an extensive patient population, we revealed previously unknown immune and stromal cell landscapes of PCD. Our findings highlight the pathogenic roles of IL-17 signaling, T cell exhaustion, pathogenic macrophages, and pro-inflammatory/remodeling fibroblasts in the pathogenesis of PCD. This study may open new avenues for disease-specific therapies for this challenging condition.