Active Phase Research Articles

Quantitative assessment of transmural remission in Crohn's disease using low dose computed tomography (CT) enterography perfusion imaging: a single-centre study based on intestinal microcirculation.

To assess transmural remission in patients with Crohn's disease using low-dose small bowel computed tomography (CT) perfusion scans. Forty six patients were divided into active and remission phases based on Crohn's Disease Activity Index (CDAI) and C-reactive protein (CRP). Dual-source CT enterography with low-dose perfusion scans was conducted to generate perfusion parameter maps, including blood flow (BF), blood volume (BV), time to peak (TTP), mean transit time (MTT), and permeability of surface (PS). We compared differences in perfusion parameter values of intestinal walls, mesenteric fat, and lymph nodes between two groups. Receiver operating characteristic (ROC) curves were plotted, and area under the curve (AUC), sensitivity, specificity, and cutoff values were calculated. The BF, BV, TTP, MTT, and PS values of the intestinal wall were significantly higher in the active phase (P0.05). Additionally, lymph node BF and TTP displayed significant differences (P<0.01). Dual-source CT enterography with low-dose perfusion scans enables quantitative assessment of Crohn's disease microcirculation in intestinal walls, mesenteric fat, and lymph nodes. These quantitative indicators provide strong diagnostic efficacy and offer insights into whether the disease is in transmural remission.

Daytime DNase-I Administration Protects Mice From Ischemic Stroke Without Inducing Bleeding or tPA-Induced Hemorrhagic Transformation, Even With Aspirin Pretreatment.

Acute ischemic stroke treatment typically involves tissue-type plasminogen activator (tPA) or tenecteplase, but about 50% of patients do not achieve successful reperfusion. The causes of tPA resistance, influenced by thrombus composition and timing, are not fully clear. Neutrophil extracellular traps (NETs), associated with poor outcomes and reperfusion resistance, contribute to thrombosis. DNase-I, which degrades neutrophil extracellular traps, could improve thrombolytic efficacy. However, more studies are needed to understand the impact of DNase-I in tPA-sensitive stroke models, the safety of coadministering DNase-I and tPA regarding hemorrhagic transformation (HT), optimal timing for use, and effects on aspirin-treated animals. We used in situ thromboembolic stroke, a tPA-sensitive model, where late tPA administration causes HT. Middle cerebral artery occlusion was induced at different zeitgeber times (ZT) to study the optimal timing for administration. DNase-I, tPA, and aspirin were administered at various times to evaluate their effects. DNase-I reduced infarct volume and improved functional outcomes 24 hours post-middle cerebral artery occlusion by decreasing plasma and cortical neutrophil extracellular trap levels. DNase-I caused no bleeding or impact on HT induced by late tPA. Its protective effect was only seen when given during the daytime (rodent inactive phase; ZT4-7), not overnight (active phase; ZT13-16). Chronic aspirin pretreatment increased tPA-induced HT but did not change the protective effects of DNase-I, with or without tPA. Our study demonstrates that daytime (inactive phase) DNase-I administration is a safe and effective treatment for experimental stroke. This is particularly important given the 2 ongoing clinical trials for stroke patients. URL: https://www.clinicaltrials.gov; Unique identifier: NCT05203224 and NCT05880524.

Ni-Fe supported on CaAl2O4 obtained from Eggs Shell for Chemical Looping Technology

The development of oxygen carriers with specific properties is one of the main bottlenecks for applicability of Chemical looping processes. Considering this, the article presents an investigation of the physicochemical, structural, morphological and reactive properties of four oxygen carriers based on Fe and/or Ni supported on calcium aluminate. Three different calcium aluminates were prepared: one by the conventional Pechini method, the following two using eggshell residue as calcium source, one with the shell in natura and last calcined at 500°C. The support obtained from the eggshell in natura presented greater surface area and pore volume, being selected for continuity of the research. The active phase was added by the method of incipient wetness impregnation. XRD, TPR results showed that iron interacted with the support forming calcium ferrite, while nickel showed inert to the support. The reactivity by thermogravimetry showed that the OC Ni/CA presented practically 100% reactivity in the cycles of reduction with methane and oxidation with air, and its structural and morphological properties remained unchanged after its regeneration.

Poisoning effect of chlorine anions in the catalytic activity of CuO/CeO2/UiO-66 for CO-PROX reaction and strategy for catalyst activation.

UiO-66 was synthesized using ZrOCl2·8H2O as metal precursor, and CuO/CeO2/UiO-66 catalysts were prepared and tested for preferential CO oxidation in H2-rich streams (CO-PROX reaction), a reaction of practical significance in hydrogen purification for fuel cells. The study highlights the detrimental effect of residual chlorine anions from UiO-66 synthesis and DMF washing on the catalytic performance of CuO/CeO2/UiO-66. An activation strategy involving rigorous water washing and thermal treatment at 160 ºC under CO-PROX conditions was developed. Both steps were deemed necessary, as employing only one proved insufficient to reduce chlorine levels to non-poisoning thresholds. This activation procedure does compromise UiO-66 crystallinity and porosity, but it is justified by achieving a fully functional catalyst. TEM images confirm the uniform dispersion of the CuO/CeO2 active phase on the UiO-66 matrix post-activation and after catalytic testing. A 16-hour CO-PROX test at 160 ºC with the CuO/CeO2/UiO-66 catalyst, once activated, demonstrated stable performance throughout the extended long-term experiment. This research provides valuable insights into optimizing CuO/CeO2/UiO-66 catalysts for CO-PROX application.

The selection of target areas for orbital imaging, application of diethylenetriaminepentaacetic acid orbital imaging, clinical factors, alkaline phosphatase, and thyrotropin receptor antibodies in the staging and grading of thyroid-associated ophthalmopathy.

This study aimed to investigate the active phase of thyroid-associated ophthalmopathy (TAO), its correlations with clinical factors, serological tests, and orbital imaging parameters, and evaluate the diagnostic value of different orbital imaging target areas. A total of 45 patients with thyroid-related eye disease underwent imaging, serological tests, and clinical data collection. Clinical Activity Score (CAS) assessment, diplopia scores, and NOSPECS grading were conducted. Radioactive counts of extraocular muscles and tear glands were measured. Computed tomography scans assessed exophthalmos and extraocular muscle thickening. Correlations and differences among study parameters and grades were evaluated using receiver operating characteristic curves. Active TAO correlated significantly with radioactive counts of muscles and tear glands, alkaline phosphatase (ALP), thyrotropin receptor antibody (TRAb), and age. Significant differences were found among NOSPECS grades for studied variables (except ALP and TRAb). Extraocular muscle thickening was confirmed as a reliable diagnostic criterion. High consistency was found between orbital imaging and CAS staging. Treatment showed varying degrees of improvement in active patients, while nonactive patients showed no progression during follow-up. Receiver operating characteristic curves demonstrated high diagnostic efficacy for tear gland radioactive counts. Tear glands and extraocular muscles have high diagnostic value in TAO, with tear glands showing a higher value. Orbital imaging provides an objective and comprehensive assessment compared with CAS scoring alone. ALP, TRAb, and age also play significant roles in staging.

Establishment and Maintenance of a Digital Therapeutic Alliance in People Living With Negative Symptoms of Schizophrenia: Two Exploratory Single-Arm Studies.

Evidence-based digital therapeutics represent a new treatment modality in mental health, potentially providing cost-efficient, accessible means of augmenting existing treatments for chronic mental illnesses. CT-155/BI 3972080 is a prescription digital therapeutic under development as an adjunct to standard of care treatments for patients 18 years of age and older with experiential negative symptoms (ENS) of schizophrenia. Individual components of CT-155/BI 3972080 are designed based on the underlying principles of face-to-face treatment. A positive therapeutic alliance between patients and health care providers is linked with improved clinical outcomes in mental health. Likewise, establishing a similar therapeutic alliance with a digital therapeutic (ie, digital working alliance [DWA]) may be important for engagement and treatment effectiveness of this modality. This study aimed to investigate the establishment and maintenance of a DWA between a beta version of CT-155/BI 3972080 (CT-155 beta) and adults with ENS of schizophrenia. Two multicenter, exploratory, single-arm studies (study 1: CT-155-C-001 and study 2: CT-155-C-002) enrolled adults with schizophrenia and ENS receiving stable antipsychotic medication (≥12 weeks). Participants had access to CT-155 beta and were presented with daily in-app activities during a 3-week orientation phase that included lessons designed to facilitate building of a DWA. In study 2, the 3-week orientation phase was followed by an abbreviated active 4-week phase. Digital literacy at baseline was evaluated using the Mobile Device Proficiency Questionnaire (MDPQ). The mobile Agnew Relationship Measure (mARM) was used to assess DWA establishment after 3 weeks in both studies, and after 7 weeks in study 2 to assess DWA maintenance. Participant safety, digital literacy, and correlations between negative symptom severity and DWA were assessed in both studies. Of the enrolled participants, 94% (46/49) and 86% (43/50) completed studies 1 and 2, respectively. Most were male (study 1: 71%, 35/49; study 2: 80%, 40/50). The baseline digital literacy assessed through MDPQ score was comparable in both studies (study 1: mean 30.56, SD 8.06; study 2: mean 28.69, SD 8.31) indicating proficiency in mobile device use. After 3 weeks, mARM scores (study 1: mean 5.16, SD 0.8; study 2: mean 5.36, SD 1.06) indicated that a positive DWA was established in both studies. In study 2, the positive DWA established at week 3 was maintained at week 7 (mARM: mean 5.48, SD 0.97). There were no adverse events (AEs) in study 1, and 3 nonserious and nontreatment-related AEs in study 2. A positive DWA was established between participants and CT-155 beta within 3 weeks. The second 7-week study showed maintenance of the DWA to the end of the study. Results support the establishment and maintenance of a DWA between adults with ENS of schizophrenia and a beta version of CT-155/BI 3972080, a prescription digital therapeutic under development to target these symptoms. Clinicaltrials.gov NCT05486312; https://clinicaltrials.gov/study/NCT05486312.

Surface Template Realizing Oriented Perovskites for Highly Efficient Solar Cells.

Formamidinium lead iodide (FAPbI3) perovskite films, ensuring optically active phase purity with uniform crystal orientation, are ideal for photovoltaic applications. However, the optically active α-FAPbI3 phase is easy to degrade into δ-phase due to numerous defects within randomly oriented films. Here, a "quasi-2D" perovskite template is pre-deposited on the film surface within the crystallization process based on the two-step preparation technology, which directly induced pure and highly orientated crystallization of α-FAPbI3 across the downward growth process. Furthermore, the enlarged interaction between 2D components with colloidal properties and lead iodide delayed the crystallization process effectively, yielding high crystallinity with low trap state density. The resulting perovskite photovoltaic devices exhibited a champion efficiency as high as 25.79% with comprehensively improved device stability. This work provides new insights into the utilization of 2D components and the formation mechanism behind 2D perovskites.

ANXA2 promotes chondrocyte differentiation and fracture healing by regulating the phosphorylation of STAT3 and PI3K/AKT signaling pathways.

Fractures are common and serious skeletal injuries, and accelerating their healing while alleviating patient suffering remains a clinical challenge. Annexin A2 (ANXA2) is a widely distributed, calcium-dependent, phospholipid-binding protein involved in bone remodeling. However, its role in chondrocyte differentiation and endochondral ossification remains unclear. In this study, we found that ANXA2 is expressed in chondrocytes during growth plate development and fracture healing, as well as during chondrocyte differentiation and maturation in vitro, with its highest expression occurring in the most active differentiation phase. Moreover, ANXA2 knockdown inhibited chondrocyte differentiation, while its overexpression significantly promoted it. We also demonstrated that ANXA2 regulates the chondrogenic and hypertrophic differentiation by mediating the phosphorylation and nuclear translocation of STAT3, as well as activating the PI3K/AKT pathway. Finally, recombinant ANXA2 protein was injected into the tibial fracture sites of mice, verifying its role in promoting endochondral ossification during fracture healing. In conclusion, our study shows that ANXA2 promotes chondrocyte differentiation, partially through the STAT3 and PI3K/AKT pathways. These findings provide insights that could aid in developing new therapies to enhance fracture healing.

Global Registry of Adverse Clinical Events (GRACE©): A Prospective, Multicenter, Observational Cohort Evaluating Complications Associated with Aesthetic Injectables.

A review of Health Canada's post-market surveillance database has revealed that the reporting of adverse events (AEs) following aesthetic injectable treatments is significantly underreported. To increase reporting, investigators have recently developed a novel Electronic Data Capture system: The Global Registry of Adverse Clinical Events (GRACE©). To identify the incidence of AEs associated with aesthetic injectable treatments. Aesthetic clinicians from 10 Canadian sites were recruited. Demographic and clinical data were recorded within the database, which included over 45 patient variables. Throughout the active phase of the trial (duration: 27 months), 123,124 injectable treatments were conducted. One hundred and eleven patients, experiencing a total of 235 AEs, were entered into the portal. This equated to an AE incidence rate of 0.19%, per treatment. Thirty unique products were associated with AEs. In total, there were 112/235 (47.66%) mild, 88/235 (37.45%) moderate, and 35/235 (14.90%) severe AEs. The most common complication (n = 48/235; 20.43%) was swelling, with a prevalence of 0.04%. Of the documented AEs, only 5 were reported to other sources, including 1 case being reported to Health Canada and 4 cases to the respective product manufacturer. The initial feasibility of a registry assessing safety outcomes following injectable treatment has been demonstrated. Findings support that the implementation of the GRACE Portal is an effective outreach strategy for increasing AE reporting by health care professionals. The data represent a more accurate depiction of the safety profile of approved aesthetic injectables in Canada.

P0186 The Significance of BACH2 Expression in Mesenteric Lymph Nodes of Crohn’s Disease

Abstract Background In Crohn’s disease (CD), the active phase is characterized by lymphatic edema, mesenteric thickening, and enlarged mesenteric lymph nodes (MLNs). Numerous lymphoid follicle-like structures are observed in inflamed areas, suggesting that lymphoid follicles and germinal centers play critical roles in CD pathogenesis. Surgical resection including thickened mesentery may reduce recurrence; however, the role of MLNs remains unclear. BACH2, a key regulator of germinal center B-cell function, was analyzed to clarify its significance in MLNs from CD patients. Methods MLNs were collected from 28 CD patients undergoing bowel resection with lymph node dissection. Control MLNs were obtained from macroscopically and microscopically normal ileocecal regions in patients with colorectal cancer. BACH2 expression was evaluated via immunohistochemistry. MLNs with expression levels comparable to or exceeding those of normal MLNs were categorized as strong positive (SP), while those with lower expression were classified as weak positive (WP). Lymphoid structures (LS) were defined as clusters of ≥100 mononuclear cells; primary follicles lacked germinal centers, while secondary follicles contained germinal centers. Data are presented as medians. Results The median MLN diameter in CD patients was 5.6 mm, significantly larger than in controls (2.9 mm, P&amp;lt;0.0001). BACH2 expression was classified as SP in 64.3% and WP in 35.7% of cases. The number of dissected lymph nodes did not differ between SP and WP groups. No significant differences were observed in the total LS count or the area of primary and secondary follicles per MLN between the groups. However, SP patients were younger at the time of surgery (33.9 vs. 51.9 years, P=0.0153) and diagnosis (22.9 vs. 40.0 years, P=0.0055). Preoperative CRP levels were lower in SP patients (0.51 vs. 2.63 mg/dL, P=0.0307), and serum albumin levels were higher (3.9 vs. 3.1 g/dL, P=0.0087). Although no significant differences were observed in postoperative endoscopic recurrence rates, recurrence was more frequent in the WP group (22.2%) compared to the SP group (6.25%). Conclusion Reduced BACH2 expression in MLNs was observed in 35.7% of CD patients. These patients exhibited later disease onset, higher preoperative inflammation, and poorer nutritional status, with a potential trend toward higher postoperative recurrence rates. These findings suggest that reduced BACH2 expression in MLNs may reflect impaired immune regulatory in CD.

Maternal, Paternal, and Dual-Parental Alcohol Exposures Result in Both Overlapping and Distinct Impacts on Behavior in Adolescent Offspring.

Emerging research reveals that alcohol use by fathers before conception can affect the growth and development of their offspring. Here, we used a C57BL/6J mouse model to study the effects of alcohol exposure on the behavior of the first-generation (F1) offspring, comparing the impacts of alcohol exposure by mothers, fathers, and both parents. Our goal was to determine how alcohol exposure by each parent or both parents influences the behavior of the offspring. We found that adolescent male offspring of alcohol-exposed fathers showed reduced anxiety-like behaviors as they spent more time in the center of the testing arena during the open field test. Both maternal and paternal alcohol exposure caused sex-specific increases in the nestlet shredding test while decreasing the number of buried marbles in the marble burying test. Interestingly, dual-parental alcohol exposure did not produce any significant changes in these same tests. However, during novel object recognition testing, we found that dual-parental male and female offspring exhibit an increased preference for novel objects, suggesting an increased risk preference. Finally, at sixteen weeks, male offspring of dual-exposed parents exhibited decreased voluntary physical activity on running wheels during the active phase, suggesting alterations in their circadian rhythms. Although differences in parental exposure histories between treatment groups make interpretation challenging, our findings suggest that exposure to alcohol by both parents may have unique effects on behavior and that studying both maternal and paternal alcohol use is essential for understanding the full range of factors influencing the penetrance and severity of alcohol-related phenotypes.

Evolution of long scalp hair in humans.

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.

Confining Surface Oxygen Redox in Double Perovskites for Enhanced Oxygen Evolution Reaction Activity and Stability

AbstractNickel‐based double perovskites AA′BB′O6 are an underexplored class of oxygen evolution reaction (OER) catalysts, in which B‐site substitution is used to tune electronic and structural properties. BaSrNiWO6, with a B‐site comprised of alternating Ni and W, exhibits high oxygen evolution activity, attributed to the evolution of a highly OER active surface phase. The redox transformation of Ni2+(3d8) to Ni3+(3d7) combined with partial W dissolution into the electrolyte from the linear Ni(3d)‐O(2p)‐W(5d) chains drives an in situ reconstruction of the surface to an amorphized, NiO‐like layer, promoting oxygen redox in the OER mechanism. However, the high valence W6+(5d0) acts as a stabilizing electronic influence in the bulk, preventing the mobilization of lattice oxygen which is bound in highly covalent W─O bonds. It is proposed that the surface generated during the OER can support a lattice oxygen evolution mechanism (LOEM) in which oxygen vacancies are created and preferentially refilled by electrolytic OH−, while bulk O species remain stable. This surface LOEM (sLOEM) allows BaSrNiWO6 to retain structural integrity during OER catalysis. With a Tafel slope of 45 mV dec−1 in 0.1 m KOH, BaSrNiWO6 illustrates the potential of Ni‐based double perovskites to offer both OER efficiency and bulk stability in alkaline electrolysis.

P0436 The rare case of Littoral Cell Angioma concomitant with Crohn’s Disease: our centre’s experience

Abstract Background Littoral Cell Angioma (LCA) is a rare splenic vascular tumor, first described in 1991. Although it is usually benign and clinically non-specific, the outcome is not predictable, and some cases with malignant behavior have been described.The pathogenesis of this lesion remains unknown, although a correlation with important immune disorders such as Crohn’s disease (CD) is established. The aim of the report is to present the experience of our center. We report the 5th described case of LCA in a patient affected by CD. Methods We describe the case of a 32-year-old patient diagnosed with CD stenosing dijuno-ileal and colic associated with splenomegaly (Dec 2011). He was treated with Adalimumab (Feb-Sep 2012, discontinued due to ineffectiveness), Infliximab (Oct 2012-Dec 2014, discontinued due to healing mucosa) and AZA since Dec 2013. For subsequent finding of splenic parenchymal lesions of difficult clinical-instrumental definition, in Jan 2023 splenectomy, digiunal resection (20cm) and digiuno-digiunal. Michelassi strictureplasty (30cm) were performed. Results Histological examination showed CD in a severe phase of activity with reactive lymphadenitis. In the splenic parenchyma there were circumscribed and demarcated areas consisting of blood exudates and an exudative/productive inflammatory infiltrate with histiocytic elements. Immunohistochemistry: CAM5.2-, CK7-, CDX-2-, CD68-PMG1+, CD1a-, CD207-. In light of the clinical- instrumental picture, histological preparations and immunohistochemical investigations, the morphological and immunophenotypical findings were compatible with splenic LCA. Conclusion LCA is often associated with immune diseases. Its diagnosis should be evoked in case of splenomegaly contextual toCD. The tumor may be related to the natural history of CD, and splenomegaly may be present at the time of diagnosis. The entero-RM to establish the degree of CD activity could represent an opportunity in the study of the prevalence and natural history of thisrare splenic neoplasia.

Unraveling the Role of Alkali on Cobalt Catalyst Performance in Ethanol Steam Reforming by Operando DRIFT Studies and DFT Modeling.

Hydrogen, a sustainable and environmentally friendly fuel, can be obtained through the ethanol steam reforming (ESR) process. The most promising catalysts for this process are those based on non-noble metals such as cobalt. The activity, selectivity, and stability of these catalysts strongly depend on the presence of alkali dopants. In this work, we have taken on the challenge of understanding the role of alkali. We synthesized a series of cobalt-containing catalysts supported on α-alumina and doped with Na, K, Rb, and Cs, which were thoroughly characterized using spectroscopic and microscopic techniques. We elucidated the significant difference in the efficiency of undoped and alkali-doped catalysts, based on diffuse reflectance infrared Fourier transform (DRIFT) operando spectroscopy studies under ESR conditions. The catalytic test results indicated a strong effect of alkali promoters on the interaction between the acetaldehyde byproduct and the Co/α-Al2O3 catalyst surface. Experimental data were confronted with the results of periodic DFT-GGA+U molecular modeling. It has been shown that electron transfer from alkali atoms to the cobalt active phase strongly influences the ethanol reforming pathway by increasing the adsorption energy of the aldehyde intermediate and facilitating the key C-C bond-breaking step.

P1318 Temporal Changes of Gut Microbiota and Micro-RNAs according to Disease Activity in Chronic Colitis

Abstract Background Both gut microbiota and micro-RNAs (miRNAs) have been implicated in the pathogenesis of inflammatory bowel disease. We aimed to investigate the temporal changes and their interactions between gut microbiota and miRNAs according to the disease activity using multi-omics analysis in a murine chronic colitis model. Methods Chronic colitis was induced in the C57BL/6 mice by three rounds of 2.5% DSS exposure. Mice were divided into three groups (n= 8 per group): control group, active group (sacrified at 3 days after the third DSS), and recovery group (sacrificed at 80 days after the third DSS). Clinical activities including weight change and histologic findings of colonic segments were examined. DNA was extracted from mouse feces, and 16S rRNA gene sequencing was performed to evaluate changes in gut microbiota. miRNA expression levels were measured by microarray analysis from mouse colonic tissues. Correlation and network analyses were performed to evaluate the interactions between gut microbiota and miRNAs. Results Alpha diversity indices were increased in the active group compared to control and recovery group. PCoA of metagenomic sequencing showed that the gut microbial profile of the active group was distinctly different from the control group, while the gut microbial profile of the recovery group was similar to the control group. On the other hand, PCoA of miRNA microarray showed that the active group had a significantly different miRNA expression pattern compared to the control group, while the recovery group had a similar miRNA expression pattern to the active group. In taxonomic and miRNA analyses, 147 differential abundant bacterial ASVs and 30 differential expressed miRNAs were identified in the active group compared to the recovery group. Spearman correlation and network analysis between gut microbiota and miRNAs, which showed significant differences between the active and the recovery groups, revealed significant associations between the genera Akkermansia and Phocaeicola and miR-34c-3p, miR-483-5p, miR-200b-3P, and miR-378a-3p. Conclusion In the active phase of chronic colitis, the gut microbial composition and miRNA expression were significantly altered, while in the recovery phase of chronic colitis, the gut microbial profile was similar to that of control, but a significantly different miRNA expression pattern was observed. Specific miRNAs were associated with specific bacterial ASVs, suggesting the interactions between miRNAs and gut microbiota in the development of chronic colitis. Our data suggested significant correlations between the genera Akkermansia and Phocaeicola and miR-34c-3p, miR-483-5p, miR-200b-3P, and miR-378a-3p in the active phase of chronic colitis.

P0031 The role of LAT1 in colitis and colitis-associated tumourigenesis

Abstract Background Inflammatory bowel disease (IBD) remains a public health challenge, with its incidence and prevalence increasing globally [1]. IBD is known to have an increasing risk of developing colitis-associated cancer (CAC) [2], and it is important to elucidate the pathophysiology of CAC to invent a counteraction to prevent it. L-type amino acid transporter 1 (LAT1) has been reported to be upregulated during the active phase of ulcerative colitis [3] and colorectal cancer (CRC) [4]. However, its role and mechanisms in the progression of colitis and CRC development from a chronic inflammatory background remain unclear. Methods To investigate the role of LAT1 in tumour development with a colitis background, mice with intestinal epithelium-specific deletions of LAT1 (LAT1fl/fl; vil-cre) were subjected to azoxymethane/ dextran sulfate sodium (AOM/DSS) CAC model. Organoids derived from these mice were also analysed. Results LAT1 was detected at the base of colonic crypts and upregulated in DSS-induced colitis. Deletion of LAT1 in intestinal epithelium led to more severe inflammatory injury and delayed tissue repair following DSS treatment. Crypts derived from LAT1fl/fl; vil-cre mice formed fewer colonic organoids than LAT1fl/fl crypts. Furthermore, LAT1 was also upregulated in AOM/DSS-induced tumour tissues. The expression of inflammatory cytokine genes was significantly increased in LAT1-deleted tumours; however, no overall difference in colon tumour number or size was observed between the two groups. Accordingly, cell proliferation and apoptotic cell number were similar between LAT1-deleted tumours and those with sufficient LAT1. Conclusion The results of this study showed that LAT1 deficiency exacerbated intestinal inflammatory injury and delayed tissue repair by impairing the maturity of colonic crypt cells. Contrary to the expectation, however, LAT1 deficiency did not phenotypically affect overall colonic tumour development in the AOM/DSS-induced model. It may be partly because of the severe chronic colitis and increased inflammatory status within the tumours due to LAT1 deficiency in LAT1fl/fl; vil-cre mice, which might have compensated for tumour growth advantage of sufficient amino acid supplementation in LAT1 expressing control mice. Our results offer insights into how nutrient intake, such as daily diet, may influence the progression of colitis, and provide insights into the potential of LAT1-targeted therapies for clinical CRC treatment.

Impact of early versus late artificial rupture of membranes during oxytocin induction of labour on the incidence of chorioamnionitis: a randomised controlled trial (ARM trial)

BackgroundThe approach to induction of labour differs internationally, with timing of amniotomy being controversial. Some institutions favour performing artificial rupture of membranes prior to commencement of oxytocin infusion, with the belief that the labour will progress more efficiently. In other institutions, the approach recommended is for oxytocin infusion with intact amniotic membranes until the person has reached the active phase of labour, citing risk of infection with early amniotomy. Current evidence is inconclusive. We are performing a randomised controlled trial assessing whether delaying amniotomy until the active phase of labour can decrease the rate of chorioamnionitis.MethodsThis is a randomised controlled trial at a single centre in New Zealand. Pregnant people undergoing induction of labour at ≥ 37 weeks gestational age with intact membranes and a singleton gestation are eligible for the trial. Participants are randomised to ‘Early’ amniotomy, at the commencement of oxytocin infusion, or to ‘Late’ amniotomy, when they have reached a cervical dilation of 6 or more centimetres or when they have been receiving oxytocin infusion for 12 h. The primary outcome of the trial is chorioamnionitis. To detect a decrease in chorioamnionitis from 9 to 3% with a power of 80% and a 95% CI, we will require 488 participants in total, randomised in a 1:1 ratio.DiscussionIf delaying amniotomy reduces the rate of chorioamnionitis, this is important to inform future practice. Chorioamnionitis entails risk to both the pregnant person and the fetus and is an important contributor to neonatal sepsis, neonatal intensive care unit admission, maternal sepsis, caesarean, wound infection and postoperative infective complications. Conversely, if the rate of chorioamnionitis is not affected by timing of amniotomy, this will allow for safe individualization of care.Trial registrationThe trial is registered on the Australian and New Zealand Clinical Trials Registry, anzctr.org.au. Full registry title is ‘Impact of early versus late artificial rupture of membranes during oxytocin induction of labour on the incidence of chorioamnionitis: A randomised controlled trial’. Trial ID: ACTRN12621000405819. Date registered 14 April 2021.

Facilitators and barriers to implementing mental health apps among interdisciplinary staff in the Veterans Health Administration.

The U.S. Department of Veterans Affairs (VA) developed evidence-informed mental health mobile applications (MH apps) to supplement treatment and serve as self-care resources for veterans. However, lack of awareness and understanding of how to integrate MH apps into care pose barriers to uptake. The VA Mobile Mental Health Apps Project was conducted from 2019 to 2021 to train and support VA health care staff in integrating VA MH apps into practice using implementation facilitation. Interdisciplinary staff (N = 1,110) from 19 VA sites, led by local site champions, and supported by project Facilitators, participated. The training phase successfully equipped staff with key knowledge and skills for MH app integration (McGee-Vincent et al., 2023), but training is not sufficient for practice change (Schueller & Torous, 2020). The current article summarizes results from a mixed methods evaluation of the preimplementation planning and active implementation phases of the project. Survey data from 3-month posttraining (n = 362) and qualitative interview data (n = 27) assessed within the Consolidated Framework for Implementation Research (Damschroder et al., 2022b) were analyzed to highlight facilitators and barriers to implementation. Results showed positive perceptions, meaningful adoption, and expanded reach of MH apps for veterans by staff across VA. Given that the project was well-received and perceived to be sustainable, the adaptability of the innovation and implementation model, and the relatively limited number of perceived barriers, this project may serve as a model for other practice changes. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Insights into the High Activity of Hydrotreating Catalysts for Heavy Gas Oil

The objective of this work was to develop a highly active hydrotreating catalyst for processing heavy gas oil to provide qualified feedstock for hydroisomerization or a hydrocracking unit. The NiMo/γ-Al2O3 catalysts doped with phosphate were prepared by introducing two kinds of additives, and the influencing factors for highly active hydrodenitrogenation (HDN) were revealed. TEM analysis results showed that the catalyst with a small MoS2 stack length tended to have high activity due to more active sites being exposed. Laser Raman spectroscopy demonstrated that the catalysts contained PMo12O403− metal active phases. For industrial heavy VGO feedstock, the nitrogen content can be reduced to 2 ppm with a hydrotreating process. The VI of the hydrotreated product can be improved from 132 to 145 after hydrotreatment, which is necessary to produce group III base oil as the most valuable base oil type. This work provides an insight into the high activity of hydrotreating catalysts for industrial lubricant hydroprocessing.