bluuebunny/crossref_metadata_2025 huggingface dataset:
P1208 MH002, an optimized live biotherapeutic product, for the treatment of inflammatory bowel diseases, has mode-of-actions linked to restoration of intestinal dysbiosis, mucosal integrity, and immune homeostasis
Authors: Bolca S , Pinheiro I , Gottardi D , Van den Bossche L , Haazen L , Possemiers S
Published: January 2024

Background

MH002 is a live biotherapeutic product consisting of 6 well-characterized commensal strains, that is in clinical development for the treatment of Ulcerative Colitis (UC) and acute Pouchitis. Both are multifactorial disorders which occur through a combination of dysregulated host inflammatory mechanisms and interactions with gut microbiota.

Methods

Faecal slurries of 6 UC patients with active disease were prepared to inoculate a standardized in vitro gut model (SHIME®) which mimics the colon microbiome of patients. A total of 24 simulators were run for 8d, with a single dose administration of MH002 (human equivalent dose [HED] ~1) or vehicle on Day0. Butyrate production in the simulators was quantified daily and host response effects were assessed in in vitro cell-based assays using samples from Day1. Caco-2 cells were co-cultured with human peripheral blood mononuclear cells and treated for 48h with Day1 samples, followed by transepithelial electrical resistance (TEER) and cytokine measurements. Wound healing was assessed by imaging of monolayers of T84 cells, scratched and treated with Day1 samples.

Furthermore, the effects of MH002 (daily, 24d, HED ~30) on disease activity index (DAI; body weight [BW], stool consistency, occult blood), local inflammation, and mucosal damage were evaluated in acute dextran sulfate sodium (DSS) induced colitis, when administered to C57BL/6 mice (15/group) as from 14d prior to DSS intake, and compared to 5-aminosalicylate (5-ASA; daily, 24d, 150mg/kg) and vehicle. Animals were euthanized in the acute (Day7; 10/group) and recovery phase (Day11; 5/group).

Results

In vitro administration of MH002 to patient-derived colonic microbiomes restored within 1d butyrate production and increased efficiency to improve epithelial barrier integrity, modulate T-cell-mediated immune responses, and promote mucosal wound healing in in vitro cell cultures (Table 1).

DSS intake induced a significant decrease in relative BW and an increase in DAI. A significant recovery (BW, DAI, stool consistency) was observed at Day11 for MH002 and 5-ASA. Moreover, at Day11, macroscopic inflammation (colon weight/length ratio) and histologic scores were lower with MH002 and 5-ASA as compared to vehicle (Figure 1).

Conclusion

By restoring intestinal dysbiosis and epithelial integrity, and attenuating local inflammation, MH002 treatment should lead to lower disease activity and, ultimately, to clinical remission without immune suppression. Indeed, study MH002-UC-201 in mild-to-moderate UC was completed with favourable treatment effects (endoscopic improvement, faecal calprotectin normalization, improved stool consistency) and no safety concerns (Abstract Vermeire et al.; EudraCT 2020-004355-33).
P1211 A faecal microbial signature, in combination with faecal calprotectin, to optimise endoscopic activity monitoring in Crohn’s Disease
Authors: Taboada-López S , Malagón M , Amoedo J , Ramió-Pujol S , Busquets D , Bahi A , Gilabert P , Rodríguez-Alonso L , Mañosa M , Cañete F , Torres P F , Morales V J , Delgado-Guillena P G , Domenech E , Guardiola J , Serra-Pagès M , Garcia-Gil L J , Aldeguer X
Published: January 2024

Background

Monitoring Crohn's Disease (CD) endoscopic activity (EA) is crucial to identify disease progression and tailor treatment. Faecal calprotectin (FC) provides a non-invasive and cost-effective alternative to colonoscopy; however, it exhibits only a moderate correlation with EA in CD, highlighting the need for a non-invasive approach that either replaces or complements FC.

This study aimed to identify a faecal microbial signature that could offer more precise monitoring of EA in CD.

Methods

A cohort of 55 CD patients was recruited from four Spanish hospitals. All participants provided a faecal sample before undergoing colonoscopy for the analysis of FC levels and microbial markers abundances, including Eubacteria (EUB), Escherichia coli (ECO), Faecalibacterium prausnitzii (FPRA) and its phylogroups I and II (PHG-I, and PHG-II), Ruminococcus spp. (RUM), Akkermansia muciniphila (AKK), Methanobrevibacter smithii (MSM), Clostridium clusters I and XIV (CLO, and XIV), Enterococcus sp. (ENT), Roseburia sp. (ROS), and Gammaproteobacteria (GAM). The Simplified Endoscopic Score for Crohn’s Disease (SES-CD) was employed to assess EA, being remission and activity defined as SES-CD≤2 and SES-CD>2, respectively.

Results

FC levels showed a significant correlation with SES-CD (rs=0.778, p<0.001) and a cut-off of 250 μg/g discerned EA with 86.49% sensitivity (SS), 75.65% specificity (SP), 77.06% positive predictive value (PPV) and 84.53% negative predictive value (NPV). Significant differences were identified when comparing the relative abundances of ECO (p<0.005), GAM (p<0.005), and RUM (p=0.026) between activity and remission. The relative abundance of ECO (rs=-0.495, p<0.001), GAM (rs=-0.492, p<0.001), and RUM (rs=0.274, p=0.042) also showed a significant correlation with SES-CD. None of the microbial markers alone exceeded FC performance.

The combination of FC levels with the abundances of the microbial markers ECO, RUM, GAM, PHG-II, and XIV in a unique signature outperformed FC alone in discerning EA, with 97.57% SS, 93.59% SP, 91.65% PPV, and 97.57% NPV. The false positive (FP) and negative (FN) rates were reduced by 60.00% and 75.00%, respectively, compared to FC alone. Notably, all the FN presented mild endoscopic activity, indicating accurate monitoring of patients with moderate or severe EA.

Conclusion

A new faecal microbial signature combined with FC has been defined to monitor EA in CD with higher performance than FC alone. This tool may improve clinical decision support systems in CD management, refining endoscopic allocation, and providing a more patient-friendly and cost-effective approach. Further studies are needed to validate these results.
P1213 The effects of Escherichia coli Nissle 1917 on the gut microbiota composition in ulcerative colitis patients
Authors: Puca P , Del Chierico F , Graziani C , Masi L , Coppola G , Di Vincenz F , Capobianco I , Lopetuso L R , Barbaro M R , Masucci L , Putignani L , Petito V , Marasco G , Sanguinetti M , Barbara G , Gasbarrini A , Scaldaferri F
Published: January 2024

Background

Escherichia coli Nissle (EcN) 1917 is a Gram-negative bacterium currently used as probiotic in the management of infectious gastroenteritis and ulcerative colitis (UC).

We evaluated the effect of administration of EcN on the composition of the gut microbiota and on intestinal permeability in patients affected by UC.

Methods

Five patients with stable UC were treated with EcN one pill daily for ten days followed by two pills per day for further twenty days. Fecal samples were collected before the treatment (T0), after ten days (T1) and after one month of treatment (T2). Alpha diversity, microbiota composition and taxonomy were analyzed.

Results

Alpha diversity increased through treatment: Good’s coverage index revealed an increase in the number of operational taxonomic units (OTUs) at T2. At phylum taxonomic level, Firmicutes relative abundance decreased at T1 compared to T0. At family level, Clostridiacae relative abundance at T1 was higher than T0 and T2. The T test on gut microbiota variations at species level reveals the variability at the two timepoints (T0 and T2), with significant increase for Actinomyces, Anaerostipes, Bacteroides, Bulleidia, Corynebacterium, Dialister, Enterobacteriaceae, Erysipelotrichaceae, Finegoldia, Granulicatella, Lactobacillaceae, Peptoniphilus, Phascolarctobacterium, Roseburia, Serratia, Veillonellaceae, Veillonella dispar.

Furthermore, the administration of EcN improved intestinal permeability, assessed on a CaCO2 monolayer.

Conclusion

Treatment with EcN leads to an improvement in the qualitative composition of the gut microbiota in patients affected by UC, in terms of both diversity and taxonomy. These effects are stronger at the end of treatment.
P1223 Lactobacillus rhamnosus GG/p40 encapsuled cationic host defense peptide play protective roles on immune-related colitis by inducing differentiation and immune suppression of regulatory T cells
Authors: Zhou Q , Liu X , Tang H , Zeng Y , Shi Q , Lu B , Qian J , Chen M , Xu Y , Wang M , Tan B
Published: January 2024

Background

The immune-related colitis (IRC) is the most prominent in immune-related adverse events (irAE). The association between gut microbiota and IRC development has been revealed. Our study aimed to explore the protective effect and mechanism of the probiotic Lactobacillus rhamnosus GG (LGG) and its secretory protein p40 on IRC. The self-assembled cationic host defense peptide (CHDP) hydrogel was applied to protect oral p40 protein from digestive damage and target enriched the site of colitis.

Methods

The IRC model mice were intervened with LGG by gavage (i.g.), p40 by enema (en.), or p40 encapsuled by CHDP (i.g.). The T cell phenotype of colonic lamina propria mononuclear cells (LPMC) was measured by flow cytometry. The indocyanine green (ICG) encapsuled by CHDP was gavage in IRC model mice, the distribution of CHDP was monitored by fluorescence signals imaging via IVIS, to assess the adhesive effect of CHDP in mice colitis. In vitro, the proportion of regulatory T cells (Treg) differentiated was measured by LGG supernatant co-cultured with CD4+ naïve T cells, and the division index of CD4+T cells was measured by LGG supernatant co-cultured with CD4+T cells and Treg (CD4+T cells: Treg=1:1) by carboxyfluorescein succinimidyl ester (CFSE) staining test.

Results

Compared with DSS+anti-PD-1+anti-CTLA-4 IRC model group, LGG (i.g.) group had lower weight loss, DAI score, histopathological score, relative IL-6 and TNF-α mRNA level, IL-6 and TNF-α concentration and higher colon length (P<0.05) (Fig.1A-L). P40 (en.) group had lower weight loss, DAI score, histopathological score and higher colon length (P<0.05) (Fig.1M-T). CHDP+p40 (i.g.) group had lower weight loss, DAI score, histopathological score, relative IL-6 and TNF-α mRNA level, IL-6 concentration and higher colon length (P<0.05) (Fig.1M-W). The percentages of CD25+FoxP3+Treg/CD4+T cells of colonic LPMC in LGG, p40 (en.), and CHDP+p40 (i.g.) group were significantly higher than IRC model group (P<0.05) (Fig.1X-Z, α). The average 28hr-residual rate of fluorescence imaging radiance in IRC-CHDP+ICG group was higher than both NC-CHDP+ICG and IRC-ICG group (Fig.2β-δ), and the average radiance of colon in IRC-CHDP+ICG group was also the highest (P<0.05) (Fig.2ε-ζ). In vitro, LGG 107 CFU/mL, 108 CFU/mL and 5 × 108 CFU/mL (P<0.05) could significantly promote Treg differentiation with concentration dependent manner (Fig.2η-ι), and the suppression of Treg on CD4+T cells with lower division index compared with control group (Fig.2κ).

Conclusion

LGG/p40 played protective role by promoting the differentiation and immune suppression of Treg cells in IRC. CHDP hydrogel could protect p40 protein from the digestive damage, and target enriched the inflamed lesion to improve the efficacy.
P1228 The EISER Study: Identifying Microbial Factors Associated with Subclinical Gut Inflammation in Psoriatic Arthritis Patients Who Develop Inflammatory Bowel Disease
Authors: Marín Jimenez I , Boix-Amorós A , Blank R B , Cantor A , Sanz Sanz J , Gutiérrez-Casbas A , Gratacós J , Rodríguez-Lago I , Trujillo E , Plaza Z , Domínguez-Álvaro M , Díaz-González F , Cañete J D , Scher J U , Clemente J C
Published: January 2024

Background

Nearly 8% of patients with spondyloarthritis (SpA) manifest symptoms that are compatible with active inflammatory bowel disease (IBD). It is well established that microbial dysbiosis is associated with different immune-mediated diseases. We therefore hypothesized that the gut microbiome could be a modulator of intestinal inflammation and factor in the pathogenesis of IBD in SpA patients.

Methods

As part of the EISER study, we selected a subset of 193 subjects diagnosed with psoriatic arthritis (PsA), a form of SpA, who had no prior diagnosis of IBD. The presence of subclinical symptoms compatible with IBD was evaluated at time of enrollment. For patients with fCAL levels of 80 µg/g or higher, colonoscopy was performed and histological analysis of biopsies collected during the procedure were used to diagnose IBD. Capsule endoscopy was performed on those patients with a negative colonoscopy result. Stool samples were collected from all participants, and microbial DNA was extracted for shotgun metagenomic sequencing using the Illumina HiSeq platform. Sequenced data was processed using MetaPhlAn 4 to estimate taxonomic composition, MMEDS for overall microbiome analysis, and R for additional statistical analyses.

Results

Twenty-five out of 193 subjects in our cohort (12.95%) had symptoms that were compatible with subclinical IBD (sIBD) and five patients (2.6% of total) were confirmed to have clinical IBD (cIBD). The use of nonsteroidal anti-inflammatory drugs (NSAIDs) resulted in significant differences in overall alpha (Shannon entropy, p=0.03) and beta microbial diversity (PERMANOVA, p=0.043), while the use of proton-pump inhibitors (PPI) resulted in significant differences in beta diversity (PERMANOVA, p= 0.036). Patients with cIBD had significantly higher abundance of taxa including Prevotella copri and Prevotella stercorea. P. copri, P. stercorea and fCAL were all significantly elevated in cIBD patients (Wilcoxon’s p=0.0278, 0.0007, 0.0161), although with a larger effect size in P. copri and P. stercorea (Cohen’s D: P. copri = 1.074; P. stercorea = 1.269; fCAL= 0.629). fCAL was also significantly elevated in patients who used PPIs (p= 4.456e-11), while P. copri and P. stercorea abundances were not impacted (Wilcoxon’s p: P. copri = 0.2394; P. stercorea = 0.0643).

Conclusion

Microbiome composition was impacted by the use of NSAIDs and PPI. We identified taxa differentially enriched in cIBD patients, including Prevotella copri and P. stercorea. Importantly, while fCAL was significantly higher in cIBD patients, its discriminatory power was not as strong as that of P. copri and P. stercorea, suggesting that these taxa could be potentially used as biomarkers of co-morbid IBD in patients with PsA.
N12 The Experience of Post-traumatic Growth Process in Newly Diagnosed Chinese Patients with Crohn’s Disease: A Longitudinal Qualitative Study
Authors: Chen L , Zhou Y , Liu J
Published: January 2024

Background

The impact of Crohn’s disease (CD) is not purely negative, it may become an opportunity for patients to undergo positive psychological adjustments and achieve personal growth. To date there has been limited in-depth research to understand the patients’ experiences of post-traumatic growth (PTG) process following an CD diagnosis using a qualitative study with a longitudinal perspective.

Methods

A longitudinal qualitative design was adopted. Sixteen newly diagnosed Chinese patients with CD were recruited through purposive sampling. Semi-structured interviews were conducted on three occasions: 3, 6 and 12 months post-diagnosis. Data were collected between November 2021 and December 2022. Data analysis of each time point was based on conventional content analysis. Afterwards, all data were combined for a comprehensive re-analysis to capture change.

Results

Four themes and fifteen sub-themes were formed through analysis (table 1). The process of PTG was shown in Figure 1. Within the first year post-diagnosis, patients with CD experienced considerable physical discomforts and psychological distress. Their personal development was also limited. With increased disease knowledge, and driven by a strong sense of responsibility and external support, the patients’ disease acceptance transformed from "difficult to accept" to "have to accept" to "should accept" then to "be able to accept". Living with CD, they actively engaged in monitoring disease condition, cooperating with treatment, exploring patterns of flare-ups, relieving stress and focusing on problem solving to eliminate negative emotions, and regaining hope and positively planning for future. Over time, the impact of CD on the patients’ lives became smaller, they integrated their disease as a part of themselves, and achieved personal growth. This growth was manifested by "developing closer relationships with others", "increasing personal strength", "changing in life philosophy" and "emerging new possibilities". Overall, as disease duration increased, the disease related sufferings diminished, and CD patients’ disease acceptance improved. In addition, as time goes by, the patients’ ability to self-manage disease enhanced, and their experience of personal growth increased.

Conclusion

The process of PTG in patients with CD within the first year of diagnosis primarily consists of four stages: "enduring hardships", "accepting illness", "living with illness", and "achieving personal growth". This growth was not linear, but rather cyclical. Nurses could provide targeted guidance to patients based on the trajectory identified in this study, helping them unearth inner resources and create conditions for PTG.
N23 Incorporating a patient facing application and home calprotectin based patient initiated follow up and monitoring in IBD Home® digital care
Authors: Schranz J , Whitehead E , Peaks H , Turnbull J , Robertson H , Fitzgerald A , Sebastian S
Published: January 2024

Background

The need for directed self-are is fundamental to the safe management of relapsing and remitting course in IBD and access to timely assessment and modification of treatment is essential during IBD flares to avoid the need for hospitalisation. Similarly, scheduled care models may cause significant disruption to activities of daily living for patients

IBD Home is a whole system model is comprehensive, integrated, and holistic approach to value-based care to provide `multidisciplinary ring` of supported care around the needs of patients in their own homes. Electronic- and virtual-based platforms have been developed to routinely monitor IBD patients and guide appropriate interventions. We incorporated a patient-facing app called MyIBD Care® and CalproSmart™ self-calprotectin test in two cohorts of patients participating in IBD Home in our IBD unit

Methods

Eligible IBD patients were invited to participate in the project. We piloted two cohorts of patients in this phase – cohort 1: patients in long-term remission on no therapies /and or mezalazine . Cohort 2: Patients on self-administered biologics or immunomodulatory agents. Following consent to digital data sharing and training, home FC results and patient reported measures entered by patient in portal of My IBD Care App. The interval of PROMS and frequency of home calprotectin tests were personalised to the cohort. IBD care navigator reviewed the information and those with raised calprotectin was reviewed virtually by IBD nurse in the clinician portal with a bidirectional record of the contact.

Results

1382 patients were eligible and invited to participate the two cohorts (29.5% of the entire Hull IBD cohort). 594 patients (43%) joined cohort (284 in cohort 1 and 310 in cohort 2). 550 patients (total number of PROMS 2309, mean 4.25) completed PROM. PROM engagement is depicted in figure 1. One hundred and forty seven patients had an intermediate or high calprotectin results among whom 94 had symptoms suggestive of flare on PROMs. In patients with elevated home calprotectin test 42 needed in person appointment and 24 others had change in therapy. One hundred and eleven patients in cohort 1 did not require an annual clinic review because of PROM result and low calprotectin levels. At 12 months, 41 patients (6.9%) were withdrawn from the cohorts.

Conclusion

Patient initiated follow up using My IBD care app along with self-monitoring of calprotectin is feasible in IBD patients in long-term remission and may reduce in person appointment. In those who join, the engagement to the PROM completion and continuation in pathway remains high at 12 months .Identification of suitability and studying patient preferences is important to increase uptake rates in digital pathways.
N25 "I Felt So Alone” Exploration of experience of being newly diagnosed with inflammatory bowel disease: a phenomenological study
Authors: Chaudhary A , Norton C , Watson N , Czuber-Dochan W
Published: January 2024

Background

Individuals recently diagnosed with Inflammatory bowel Disease (IBD) often have unmet informational and psychological needs, leading to distress and anxiety. This lack of support negatively affects their quality of life, mental health, social functioning, and physical outcomes. Additionally, the absence of counselling and peer support isolates many people and places an emotional burden on them. Delayed diagnosis or misdiagnoses due to symptoms being dismissed by health professionals exacerbate the problem. Acknowledging these unmet needs and adverse outcomes, this study aims to shed light on patients' experiences to inform improvements in clinical practice, support services, and workplace policies, particularly during the immediate diagnosis phase.

Aim

The aim of this study is to explore the experience of people newly diagnosed with IBD and their need for support.

Methods

The study employed interpretive phenomenology semi-structured interviews following a topic guide and analysed the data using Braun & Clark's (2023) thematic analysis method and Nvivo software. Crohn's and Colitis UK (CCUK) charity acted as the gatekeeper for access to participants. Participants were purposively selected on specific criteria: IBD diagnosis ≤1 year, aged 16 or older, English language proficiency and diversity of demographic and clinical variables.

Results

Of 49 volunteers who responded to the research advertisement, 15 were selected based on eligibility criteria. Participant characteristics are shown in Table 1. Four themes emerged (Fig 1), with 12 subthemes. Participants expressed extreme dissatisfaction, either due to misdiagnosis or diagnostic delays, indicating the need for timely streamlined diagnosis. Additionally, IBD diagnosis itself triggered distress and anxiety. Participants reported the need for continuous psychological counselling and peer support. Due to symptoms like blood loss and diarrhoea, IBD profoundly affects physical health, emotional wellbeing, social interactions, and work-life balance, hence challenging patients' sense of normalcy. However, patients demonstrated resilience via lifestyle adjustments, social support networks, and coping strategies.

Conclusion

This qualitative study sheds light on the profound impact of an IBD diagnosis. It reveals emotional struggles and the need for streamlined diagnosis and psychological support. Lifestyle disruptions affect physical and mental health, but participants adapt through support and coping. These insights have practical implications for improving care, mental health services, workplace adjustments, social support, and coping resources for the newly diagnosed IBD population. Future research should expand to larger, diverse patient samples.

Table 1:
N30 Development and implementation of a microlearning programme for patients with Inflammatory Bowel Disease. The ADEII project
Authors: Sanromán L , De Castro Parga M L , Figueira M , Hernández V , Martinez.Cadilla J , Rodriguez-Prada I
Published: January 2024

Background

Information and communication technologies (ICTs) represent a novel approach to chronic disease management. However, their use in Inflammatory Bowel Disease (IBD) is lacking, as no specific tools are available. Microlearning is a pedagogical concept that facilitates learning by breaking down concepts into micro-contents, which can be easily integrated into everyday activities. We aimed to develop a microlearning programme for IBD patients and implement it in clinical practice.

Methods

Prospective cohort study in patients with IBD (18 to 70 years old) who underwent a microlearning programme over a 2-month period, Four-minute videos recorded by IBD unit´s own staff, and organised in individualised pathways.were sent via mobile phone. The interaction with the user was maintained through a Telegram bot that uses methods from the Django REST API for content sequencing. The basic sequencing consists of a video followed by 4 quiz questions. Depending on the answers, the user receives more questions, additional content on the same topic or moves on to the next video. We conducted a final survey about the information shown in the videos.

All the contents can be found on the website: https://adeii.webs.uvigo.es/ This QR links to the promotional video of the ADEII project (Figure 1).

Results

We recorded 24 videos about IBD and treatment and another 2 about patients´personal experiences. Between 1 June and 31 October 2022, 1226 videos were sent to 200 IBD patients: 103 females (51.5%), mean age 46.1 (13) years, 105 ulcerative colitis (52.5%), and time from IBD diagnosis 13 (10) years. (Table 1). All patients received by their smart-phone the 4-video main pack, consisting of 2 videos with information about their disease (ulcerative colitis or Crohn's disease), 1 video on adherence and another one on corticosteroids.

To these we added as many videos as the number of drugs that each patient used to control IBD. Mean number of videos per patient was 6 (1), range (5-9) and their distribution is shown in Figure 1. Seven patients declined to participate in this course because of fear of information and one left the study. Altogether 156 patients (78%) attended this microlearning programme, 117 fully (58,5%). A telephone contact, planned to solve technical incidents or doubts, rose the attendants to 170 (90%), 152 (76%) fully. After the course, 72,5% of the participants (145) answered correctly more than 83% of the questions based on the IBD information included in this programme.

Conclusion

A microlearning ICT-based course was widely accepted by IBD patients, and can increase the knowledge about their disease. However there are acceptance and technological barriers that must be taken into account when approaching it.
ECCO Fellowship Effect of diet on disease development and faecal microbiota transplantation efficacy in humanized SAMP/Yit and DSS mice models
Authors: Deleu Sara , Scaldaferri Franco
Published: January 2024

Background and Aims

The gut microbiome and diet have been shown to be associated with IBD pathogenesis, and to be implicated as triggers in disease development. Increasing evidence shows that dysbiosis and Western diets may drive and sustain intestinal inflammation. Therefore, faecal microbiota transplantation (FMT) has been hypothesized to restore a balanced microbiome, leading to reduced inflammation and improved intestinal function.

The mechanisms by which FMT exerts its therapeutic effects in IBD are not fully understood. Yet, FMT has shown promising effects in controlling disease in randomized controlled studies in UC. In contrast, data on FMT in CD are scarce and worsening of disease has even been described (Vermeire et al., 2016). Unfortunately, up to day, this different effect of FMT in UC versus CD remains unexplained.

Therefore, the aim of this project is to evaluate the effect of FMT in a preclinical model of CD, and compare it to a UC-model and study the effect of ultra-processed Western diets.

Methods

The mice models which will be used include the acute DSS-induced colitis model for UC and the spontaneous terminal ileitis (SAMP/Yit) model for CD. Upon humanization of the mice with UC or CD patient’s stool, mice will be randomized to dietary interventions being a Western diet, a regular diet, or a Mediterranean diet. Subsequently, the mice will be randomized to receive either autologous (patient) FMT or one out of four healthy donor FMTs possessing different enterotypes.

Anticipated Impact

By evaluating, clinical endpoints, as well as microbiota and transcriptomic endpoints, this project will provide insights in the differences between FMT success in UC and CD, as well as in the importance of donor selection (enterotype matching) and additional effect of dietary interventions on inflammation. Herewith predicting that this project will aid to bring microbiota-targeted treatment strategies to the IBD clinic.
D-ECCO Grant Dietary patterns during early life and risk of inflammatory bowel disease
Authors: Brusco De Freitas M , Anneberg O M , Jess T
Published: January 2024

Background and Aims

Diet plays a key role in modulating the intestinal microbiota, thereby impacting the regulation of intestinal inflammation. The Western diet has been linked to non-communicable diseases such as obesity, cardiovascular disease, diabetes, and metabolic syndrome, and its role in inflammatory disorders is subject to increasing attention. It is of interest to understand, how maternal nutrition directly impacts fetal development and, together with the child’s own nutrition, influences the later susceptibility to immune mediated diseases. This ambitious project will assess how maternal exposures and dietary patterns during pregnancy combined with early life exposures at birth influence the risk of inflammatory bowel disease (IBD) in offspring.

Methods

We will use the Danish National Birth Cohort (about 100,000 women and 91,383 children were included in the cohort) in which 72,821 completed the food frequency questionnaire (FFQ) in early pregnancy and nationwide health data to 1) characterize the dietary patterns of mothers in mid-pregnancy, and 2) use this information to assess the association of maternal dietary pattern with risk of IBD in offspring. Furthermore, we will examine 3) the impact of diets rich in ultra-processed foods, and 4) mothers' fish consumption in mid-pregnancy and the association with risk of IBD in offspring.

Anticipated Impact

The applicant has assembled a unique team of collaborators, which, together with access to exclusive Danish resources, will guarantee the success of the project, with the primary objective is to understand how diet influences the development and worsening of IBD, improve quality of life, and to pave the way for improved dietary guidance for a growing global group of young people with chronic diseases.
Novel breast cancer susceptibility loci under linkage peaks identified in African ancestry consortia
Authors: Ochs-Balcom Heather M , Preus Leah , Du Zhaohui , Elston Robert C , Teerlink Craig C , Jia Guochong , Guo Xingyi , Cai Qiuyin , Long Jirong , Ping Jie , Li Bingshan , Stram Daniel O , Shu Xiao-Ou , Sanderson Maureen , Gao Guimin , Ahearn Thomas , Lunetta Kathryn L , Zirpoli Gary , Troester Melissa A , Ruiz-Narváez Edward A , Haddad Stephen A , Figueroa Jonine , John Esther M , Bernstein Leslie , Hu Jennifer J , Ziegler Regina G , Nyante Sarah , Bandera Elisa V , Ingles Sue A , Mancuso Nicholas , Press Michael F , Deming Sandra L , Rodriguez-Gil Jorge L , Yao Song , Ogundiran Temidayo O , Ojengbede Oladosu , Bolla Manjeet K , Dennis Joe , Dunning Alison M , Easton Douglas F , Michailidou Kyriaki , Pharoah Paul D P , Sandler Dale P , Taylor Jack A , Wang Qin , O’Brien Katie M , Weinberg Clarice R , Kitahara Cari M , Blot William , Nathanson Katherine L , Hennis Anselm , Nemesure Barbara , Ambs Stefan , Sucheston-Campbell Lara E , Bensen Jeannette T , Chanock Stephen J , Olshan Andrew F , Ambrosone Christine B , Olopade Olufunmilayo I , the Ghana Breast Health Study Team  , Conti David V , Palmer Julie , García-Closas Montserrat , Huo Dezheng , Zheng Wei , Haiman Christopher
Published: January 2024

Background

Expansion of genome-wide association studies across population groups is needed to improve our understanding of shared and unique genetic contributions to breast cancer. We performed association and replication studies guided by a priori linkage findings from African ancestry (AA) relative pairs.

Methods

We performed fixed-effect inverse-variance weighted meta-analysis under three significant AA breast cancer linkage peaks (3q26-27, 12q22-23, and 16q21-22) in 9241 AA cases and 10 193 AA controls. We examined associations with overall breast cancer as well as estrogen receptor (ER)-positive and negative subtypes (193,132 SNPs). We replicated associations in the African-ancestry Breast Cancer Genetic Consortium (AABCG).

Results

In AA women, we identified two associations on chr12q for overall breast cancer (rs1420647, OR = 1.15, p = 2.50×10−6; rs12322371, OR = 1.14, p = 3.15×10−6), and one for ER-negative breast cancer (rs77006600, OR = 1.67, p = 3.51×10−6). On chr3, we identified two associations with ER-negative disease (rs184090918, OR = 3.70, p = 1.23×10−5; rs76959804, OR = 3.57, p = 1.77×10−5) and on chr16q we identified an association with ER-negative disease (rs34147411, OR = 1.62, p = 8.82×10−6). In the replication study, the chr3 associations were significant and effect sizes were larger (rs184090918, OR: 6.66, 95% CI: 1.43, 31.01; rs76959804, OR: 5.24, 95% CI: 1.70, 16.16).

Conclusion

The two chr3 SNPs are upstream to open chromatin ENSR00000710716, a regulatory feature that is actively regulated in mammary tissues, providing evidence that variants in this chr3 region may have a regulatory role in our target organ. Our study provides support for breast cancer variant discovery using prioritization based on linkage evidence.
Restoration of injured motoneurons reduces microglial proliferation in the adult rat facial nucleus
Authors: Ishijima Takashi , Nakajima Kazuyuki
Published: January 2024

In the axotomized facial nucleus (axotFN), the levels of choline acetyltransferase, vesicular acetylcholine transporter, and gamma amino butyric acid A receptor α1 are decreased, after which the microglia begin to proliferate around injured motoneuron cell bodies. We conjectured that an injury signal released from the injured motoneurons triggers the microglial proliferation in the axotFN. However, it is unclear whether the level of microglial proliferation is dependent on the degree of motoneuronal insult. In this study, we investigated the relationship between the extents of motoneuronal injury and microglial proliferation in a rat axotFN model. Administration of glial cell line-derived neurotrophic factor, N-acetyl L-cysteine, or salubrinal at the transection site ameliorated the increase in c-Jun and the reductions in levels of phosphorylated cAMP response element binding protein (p-CREB) and functional molecules in the injured motoneurons. Concurrently, the levels of the microglial marker ionized calcium-binding adapter molecule 1 and of macrophage colony-stimulating factor (cFms), proliferating cell nuclear antigen, and p-p38/p38 were significantly downregulated in microglia. These results demonstrate that the recovery of motoneuron function resulted in the reduction in microglial proliferation. We conclude that the degree of neuronal injury regulates the levels of microglial proliferation in the axotFN.
Cone-beam computed tomography-guided online adaptive radiotherapy for pharyngeal cancer with whole neck irradiation: dose-volume histogram analysis between adapted and scheduled plans
Authors: Uehara Takuya , Nishimura Yasumasa , Ishikawa Kazuki , Inada Masahiro , Matsumoto Kenji , Doi Hiroshi , Monzen Hajime , Matsuo Yukinori
Published: January 2024

The present study aimed to evaluate whether an adapted plan with Ethos™ could be used for pharyngeal cancer. Ten patients with pharyngeal cancer who underwent chemoradiotherapy with available daily cone-beam computed tomography (CBCT) data were included. Simulated treatments were generated on the Ethos™ treatment emulator using CBCTs every four to five fractions for two plans: adapted and scheduled. The simulated treatments were divided into three groups: early (first–second week), middle (third–fourth week), and late (fifth–seventh week) periods. Dose-volume histogram parameters were compared for each period between the adapted and scheduled plans in terms of the planning target volume (PTV) (D98%, D95%, D50% and D2%), spinal cord (Dmax and D1cc), brainstem (Dmax) and ipsilateral and contralateral parotid glands (Dmedian and Dmean). The PTV D98%, D95% and D2% of the adapted plan were significantly higher than those of the scheduled plans in all periods, except for D98% in the late period. The adapted plan significantly reduced the spinal cord Dmax and D1cc compared with the scheduled plan in all periods. Ipsilateral and contralateral parotid glands Dmean of the adapted plan were lower than those of scheduled plan in the late period. In conclusion, the present study revealed that the adapted plans could maintain PTV coverage while reducing the doses to organs at risk in each period compared with scheduled plans.
Differential expression and evolutionary diversification of RNA helicases in Boechera sexual and apomictic reproduction
Authors: Binmöller Laura , Volkert Christopher , Kiefer Christiane , Zühl Luise , Slawinska Magdalena W , Loreth Anna , Nauerth Berit H , Ibberson David , Martinez Rafael , Mandakova Terezie M , Zipper Reinhard , Schmidt Anja
Published: January 2024

In higher plants, sexual reproduction is characterized by meiosis of the first cells of the germlines, and double fertilization of the egg and central cell after gametogenesis. In contrast, in apomicts of the genus Boechera, meiosis is omitted or altered and only the central cell requires fertilization, while the embryo forms parthenogenetically from the egg cell. To deepen the understanding of the transcriptional basis underlying these differences, we applied RNA-seq to compare expression in reproductive tissues of different Boechera accessions. This confirmed previous evidence of an enrichment of RNA helicases in plant germlines. Furthermore, few RNA helicases were differentially expressed in female reproductive ovule tissues harboring mature gametophytes from apomictic and sexual accessions. For some of these genes, we further found evidence for a complex recent evolutionary history. This included a homolog of Arabidopsis thaliana FASCIATED STEM4 (FAS4). In contrast to AtFAS4, which is a single-copy gene, FAS4 is represented by three homologs in Boechera, suggesting a potential for subfunctionalization to modulate reproductive development. To gain first insights into functional roles of FAS4, we studied Arabidopsis lines carrying mutant alleles. This identified the crucial importance of AtFAS4 for reproduction, as we observed developmental defects and arrest during male and female gametogenesis.
Cross-Species Comparative DNA Methylation Reveals Novel Insights into Complex Trait Genetics among Cattle, Sheep, and Goats
Authors: Chen Siqian , Liu Shuli , Shi Shaolei , Yin Hongwei , Tang Yongjie , Zhang Jinning , Li Wenlong , Liu Gang , Qu Kaixing , Ding Xiangdong , Wang Yachun , Liu Jianfeng , Zhang Shengli , Fang Lingzhao , Yu Ying
Published: January 2024

The cross-species characterization of evolutionary changes in the functional genome can facilitate the translation of genetic findings across species and the interpretation of the evolutionary basis underlying complex phenotypes. Yet, this has not been fully explored between cattle, sheep, goats, and other mammals. Here, we systematically characterized the evolutionary dynamics of DNA methylation and gene expression in 3 somatic tissues (i.e. brain, liver, and skeletal muscle) and sperm across 7 mammalian species, including 3 ruminant livestock species (cattle, sheep, and goats), humans, pigs, mice, and dogs, by generating and integrating 160 DNA methylation and transcriptomic data sets. We demonstrate dynamic changes of DNA hypomethylated regions and hypermethylated regions in tissue-type manner across cattle, sheep, and goats. Specifically, based on the phylo-epigenetic model of DNA methylome, we identified a total of 25,074 hypomethylated region extension events specific to cattle, which participated in rewiring tissue-specific regulatory network. Furthermore, by integrating genome-wide association studies of 50 cattle traits, we provided novel insights into the genetic and evolutionary basis of complex phenotypes in cattle. Overall, our study provides a valuable resource for exploring the evolutionary dynamics of the functional genome and highlights the importance of cross-species characterization of multiomics data sets for the evolutionary interpretation of complex phenotypes in cattle livestock.
Incidence, risk factors and outcome of postoperative acute kidney injury in China
Authors: Cheng Yichun , Nie Sheng , Zhao Xingyang , Xu Xin , Xu Hong , Liu Bicheng , Weng Jianping , Chunbo Chen , Liu Huafeng , Yang Qiongqiong , Li Hua , Kong Yaozhong , Li Guisen , Wan Qijun , Zha Yan , Hu Ying , Shi Yongjun , Zhou Yilun , Su Guobin , Tang Ying , Gong Mengchun , Hou Fan Fan , Ge Shuwang , Xu Gang
Published: January 2024

Background

Postoperative acute kidney injury (AKI) is a common condition after surgery, however, the available data about nationwide epidemiology of postoperative AKI in China from large and high-quality studies are limited. This study aimed to determine the incidence, risk factors and outcomes of postoperative AKI among patients undergoing surgery in China.

Methods

This was a large, multicentre, retrospective study performed in 16 tertiary medical centres in China. Adult patients (≥18 years of age) who underwent surgical procedures from 1 January 2013 to 31 December 2019 were included. Postoperative AKI was defined by the Kidney Disease: Improving Global Outcomes creatinine criteria. The associations of AKI and in-hospital outcomes were investigated using logistic regression models adjusted for potential confounders.

Results

Among 520 707 patients included in our study, 25 830 (5.0%) patients developed postoperative AKI. The incidence of postoperative AKI varied by surgery type, which was highest in cardiac (34.6%), urologic (8.7%) and general (4.2%) surgeries. A total of 89.2% of postoperative AKI cases were detected in the first 2 postoperative days. However, only 584 (2.3%) patients with postoperative AKI were diagnosed with AKI on discharge. Risk factors for postoperative AKI included older age, male sex, lower baseline kidney function, pre-surgery hospital stay ≤3 days or >7 days, hypertension, diabetes mellitus and use of proton pump inhibitors or diuretics. The risk of in-hospital death increased with the stage of AKI. In addition, patients with postoperative AKI had longer lengths of hospital stay (12 versus 19 days) and were more likely to require intensive care unit care (13.1% versus 45.0%) and renal replacement therapy (0.4% versus 7.7%).

Conclusions

Postoperative AKI was common across surgery type in China, particularly for patients undergoing cardiac surgery. Implementation and evaluation of an alarm system is important for the battle against postoperative AKI.
Circulating Hsa-miR499a-5p as markers in dysmobility syndrome patients: a new index for diagnosing dysmobility syndrome based on osteoporosis and predicting fracture risk
Authors: Geng Zixiang , Wang Peige , Yang Guangyue , Li Yifei , Zhao Yongfang
Published: January 2024

Background

Dysmobility syndrome based on osteoporosis (ODS) is a disease characterized by low bone mass and low muscle mass. Its features are high fracture and high fall risk. Falls and fractures are the most important factors affecting the quality of life and lifespan of ODS. However, there is no serum marker for the evaluation of ODS patients.

Our previous studies have shown that the expression of circulating miRNA is stable and is a good marker for disease diagnosis. Therefore, this study aims to explore potential serum markers of ODS.

Methods

A total of 78 subjects were included in this study. The data including appendicular skeletal muscle mass index, bone mineral density, bone metabolism markers, and other relevant information were collected for analysis. Real-time quantitative polymerase chain reaction was used to detect 19 miRNAs associated with muscle mass reduction. The correlation of quantitative data was analyzed by Pearson. The receiver operating characteristic curve was used to evaluate the performance of miRNA as a biomarker.

Results

In this study, we found that the muscle mass and strength of patients with ODS are significantly reduced and are negatively correlated with the risk of fracture. The hsa-miR-499a-5p is specifically downregulated in ODS, and is positively correlated with muscle mass and strength, and negatively correlated with the risk of fracture. Compared with muscle mass and strength, hsa-miR-499a-5p has better sensitivity and specificity as a diagnostic marker.

Conclusion

hsa-miR-499a-5p is a potential serum biomarker for assessing muscle function and predicting fall or fracture risk in the ODS population.
Incorporating Trauma-informed Approaches to Care in Vascularized Composite Allotransplantation
Authors: Thys Erika , Laspro Matteo , Chaya Bachar F. , Rodriguez Eduardo D. , Kimberly Laura L.
Published: January 2024

Since 1998, vascularized composite allotransplantation (VCA) has been a growing area of research in the field of reconstructive surgery. Although conditions treated with VCA often result from a traumatic injury, there has been limited emphasis on incorporating trauma-informed care (TIC) models in VCA. Considering the importance of psychosocial well-being in VCA candidates and recipients, applying best practices in TIC to the face, upper extremity, and penile transplantation may be critical in minimizing retraumatization throughout the perioperative process. There are six main principles of TIC: safety; trustworthiness and transparency; peer support; collaboration and mutuality; empowerment and choice; and cultural, historical, and gender issues, which may be further incorporated in care for VCA patients. Evaluating for PTSD and incorporating TIC may have substantial benefit to postoperative outcomes.
Visceral Fat Predicts New-Onset Diabetes After Necrotizing Pancreatitis
Authors: Trikudanathan Guru , Abdallah Mohamed , Munigala Satish , Vantanasiri Kornpong , Jonason David , Faizi Nauroze , Schat Robben , Chauhan Anil , Freeman Martin L. , Bellin Melena D.
Published: January 2024

Objectives

We aimed to estimate the incidence of new-onset diabetes (NOD) and identify risk factors for NOD in patients with necrotizing pancreatitis (NP).

Methods

Necrotizing pancreatitis patients were reviewed for NOD, diagnosed >90 days after acute pancreatitis. Baseline demographics, comorbidities, clinical outcomes, computed tomography (CT) characteristics of necrotic collections, and CT-derived abdominal fat measurements were analyzed to identify predictors for NOD.

Results

Among 390 eligible NP patients (66% men; median age, 51 years; interquartile range [IQR], 36–64) with a median follow-up of 400 days (IQR, 105–1074 days), NOD developed in 101 patients (26%) after a median of 216 days (IQR, 92–749 days) from NP. Of the NOD patients, 84% required insulin and 69% developed exocrine pancreatic insufficiency (EPI). Age (odds ratio [OR], 0.98), male sex (OR, 2.7), obesity (OR, 2.1), presence of EPI (OR, 2.7), and diffuse pancreatic necrosis (OR, 2.4) were independent predictors. In a separate multivariable model assessing abdominal fat on CT, visceral fat area (highest quartile) was an independent predictor for NOD (OR, 3.01).

Conclusions

New-onset diabetes was observed in 1 of 4 patients with NP, most within the first year and requiring insulin. Male sex, obesity, diffuse pancreatic necrosis, development of EPI, and high visceral adiposity identified those at highest risk.