bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative localization of parathyroid glands in secondary hyperparathyroidism: correlations between 99mTc-MIBI-SPECT/CT, ultrasound, and pathological characteristics
Authors: Li Binghan , Zhao Xiaoli , Luo Sha , Zhong Qi , Zhao Hanxue , Du Chengxiang , Zhang Guojuan 
Published: February 2025

Abstract

Objective
To investigate the association between imaging findings and histopathological characteristics of parathyroid glands in patients with secondary hyperparathyroidism (SHPT).

Design and Methods
74 glands from 21 patients with SHPT who underwent parathyroidectomy were evaluated for their pathological characteristics. The detection rates of parathyroid glands using ultrasound (US) and 99Tc-MIBI-SPECT/CT (MIBI) were compared. Glands were classified as either US-positive or US-negative, and MIBI-positive or MIBI-negative. Morphological and pathological differences between the positive and negative groups were systematically analyzed.

Results
The detection rates for parathyroid glands were 71% with US, 65% with MIBI, and 82% when combining both methods. US and MIBI showed similar localization accuracy in SHPT (P = 0.38). MIBI-positive glands had significantly larger oxyphil nodules compared to MIBI-negative glands (area: 10.92 mm² vs 3.09 mm², P &lt; 0.01; area proportion: 61% vs 30%, P = 0.002), while no significant differences were found in chief nodules. US-positive group had fewer and smaller chief nodules (number: 2 vs 9, P = 0.005; area: 1.53 mm² vs 11.08 mm², P = 0.033) and a higher percentage of oxyphil nodules (74% vs 33%, P = 0.003) compared to US-negative group. 13 glands undetected by both US and MIBI had smaller oxyphil nodule areas (3.59 mm² vs 13.24 mm²) and lower oxyphil nodule area percentages (25% vs 68%). These pathological features, including adipose infiltration, intra-gland hemorrhage, cyst formation, and calcification, showed no correlation with the gland's imaging results.

Conclusion
Ultrasound and 99Tc-MIBI-SPECT/CT had similar value in preoperative localization of SHPT. Parathyroid glands with more and larger oxyphil nodules were more likely to be detected by both 99Tc-MIBI-SPECT/CT and ultrasound.
Comparison between the effect of mid-late-life high-intensity interval training and continuous moderate-intensity training in old mouse hearts
Authors: Li Qiaowei , Liu Qin , Lin Zhong , Lin Wenwen , Lin Zhonghua , Huang Feng , Zhu Pengli 
Published: February 2025

Abstract
The impact of mid-late-life exercise on the aging heart remains unclear, particularly the effects of high-intensity interval training (HIIT) and continuous moderate-intensity training (CMIT). This study was the first to examine cardiac function, tissue characteristics, electrical remodeling, mitochondrial morphology and homeostasis in old mice subjected to CMIT or HIIT, compared to untrained controls. Our results showed that 8-week HIIT significantly improved the survival rate of old mice. HIIT presented advantages on cardiac function, deposition of collagen fibers, neovascularization, aging biomarkers and mitochondrial homeostasis. Only CMIT alleviated age-related cardiac hypertrophy. However, CMIT potentially exacerbated adverse cardiac electrical remodeling. Those findings suggested HIIT as a particularly appealing option for clinical application for aging populations.
A8 GREATER DISEASE BURDEN AMONG CANADIANS WITH CELIAC DISEASE MOST ECONOMICALLY DEPRIVED: FINDINGS FROM THE NATIONWIDE STATE OF CELIAC SURVEY
Authors: King J A , McAuley C , Secord M , pinto-sanchez M , Turner J , Gidrewicz D , Case S , Duerksen D 
Published: February 2025

Abstract

Background
Individuals with celiac disease (CeD) most economically deprived may face challenges adhering to the gluten-free diet (GFD). However, it is less clear how income may be associated with symptoms or comorbidity.

Aims
To determine symptom and comorbidity status across the economic spectrum among Canadians living with CeD.

Methods
At the end of 2022, the State of Celiac Disease in Canada Survey was administered to individuals living with CeD in Canada. Questions on GFD adherence, symptoms, and comorbidities were recorded by respondents. Participants who did not provide information on their household income (before tax) were excluded from analysis. The total number of symptoms and comorbidities were calculated per respondent, with symptoms further stratified into gastrointestinal (n=10), non-gastrointestinal (n=15), and neuropsychiatric (n=5). Tests of proportions and Kruskal-Wallis tests were used to assess for differences in outcomes across income levels. The Benjamini-Hochberg correction was used to account for multiple testing.

Results
A total of 3,950 respondents were included. Significant differences in gastrointestinal symptoms before and after diagnosis were detected across income groups (e.g., p&lt;0.05 for those under $30,000 compared to all other income groups). Similar findings were present for non-gastrointestinal symptoms (e.g., p&lt;0.01 for those under $30,000 compared to all other income groups except $30,000–49,999 before diagnosis) and neuropsychiatric symptoms (e.g., p&lt;0.01 for those under $30,000 compared to all other income groups). The number of comorbidities also differed significantly across certain income levels (e.g., p&lt;0.01 for those under $30,000 compared to all other income groups). There were no differences in accidental gluten consumption across income categories, although a borderline significant difference (p=0.06) was observed for intentional gluten consumption between those with income under $30,000 compared to those with income greater than $150,000.

Conclusions
There are notable differences in CeD across an economic gradient, with those in lower income brackets living with a greater number of symptoms and comorbidities. Further attention is warranted to minimize additional burden from CeD among individuals with limited income.
Comorbidity status and gluten consumption across income levels

Symptoms experienced before and after diagnosis across income level

Funding Agencies
Celiac Canada
A11 FERMENTABLE DIETARY FIBER INTAKE IS ASSOCIATED WITH A DECREASED RISK OF DEVELOPING CROHN’S DISEASE IN HEALTHY FIRST-DEGREE RELATIVES
Authors: McShane C , Xue M , Kim J , Leibovitzh H , Shao J , LI Q , Khorasaniha R , Madsen K , Griffiths A , Moayyedi P , Lee S , Armstrong H , Croitoru K , Turpin W 
Published: February 2025

Abstract

Background
The cause of Crohn’s Disease (CD) remains unclear; however evidence suggests that diet plays a key role. With a rising incidence and no definitive cure, identification of modifiable risk factors is critical in preventing CD development.

Aims
To study the association between fermentable dietary fiber intake and the future development of CD in an at risk population.

Methods
Participants were recruited in the CCC-GEM study, a prospective cohort study of healthy first-degree relatives of patients with CD. At enrolment, a validated food frequency questionnaire was administered. Pectin, β-glucan, inulin, fructooligosaccharides (FOS), and arabinoxylan intake were quantified, and values energy-adjusted. Survival analysis was used to test the association between intake of fiber subtypes and risk of CD development. Generalized estimating equation was used to test the association between fiber intake and baseline impaired intestinal permeability (fractional urinary excretion of lactulose to mannitol ratio (LMR)&gt;0.025); gut sub-clinical inflammation (fecal calprotectin (FCP)&gt;100 μg/g); and fecal microbiome composition via 16s rRNA sequencing.

Results
Of the 2,659 participants 76 developed CD with a median follow-up of 8.9 years (IQR=5.7-12.3). Median age at recruitment was 17 years (IQR=12-25). 47% were male. Higher intake of inulin (HR = 0.78; 95% CI=0.61–0.99; p=0.04) and β-glucan (HR = 0.78; 95% CI=0.61–0.99; p=0.04) were associated with a reduced risk of CD development. No fiber subtype was associated with a higher risk of CD development. Lower intake of pectin, inulin, FOS and β-glucan was associated with impaired intestinal permeability. Lower inulin intake was associated with high FCP levels. Higher pectin intake was associated with increased alpha diversity. Higher inulin, FOS and pectin intake was associated with a shift in microbial taxa previously shown to be protective against CD onset in the GEM cohort; a reduction in Ruminococcus torques and an increase in NK4A214 group (phylum Firmicutes) presence (3.25×10−10&lt;q&lt;0.04).

Conclusions
This study demonstrates that fermentable fiber subtypes are associated with a reduced risk of CD development as well as with pleiotropic changes in CD risk biomarkers including microbiome, intestinal permeability, and subclinical inflammation. This suggests that the potential benefit of fermentable fibers on CD risk may involve changes in barrier function, and microbiome composition and function. Targeted interventions based on these findings could prove effective in preventing the onset of CD.
Submitted on behalf of the Crohn’s and Colitis Canada GEM Project Research Consortium, www.gemproject.ca.
Funding Agencies:
A17 ROLE OF SEX-SPECIFIC GUT EPITHELIAL α2,6-SIALYLATED GALACTOSE IN COLONIC MUCUS FUNCTION, MICROBIAL ECOLOGY, AND PROTECTION FROM COLITIS.
Authors: Bergstrom K , Melvin M , Jafaripour S , Fancy N , Irungu J , Daneshgar P , Inaba R , Hans G , ma c , Liang Q , vallance B , Zandberg W 
Published: February 2025

Abstract

Background
The heavily glycosylated Mucin-2 (MUC2) comprises gut mucus, which protects the colon from microbially-induced inflammation. Over 100 unique oligosaccharides (glycans) are found on MUC2, contributing to its barrier and microbiota-modulating functions. A major sugar on MUC2 glycans is sialic acid (Sia), which can occur via different stereoisomeric linkages, including an α2,6 linkage to galactose (Siaα2,6Gal). Siaα2,6Gal is a capping structure on mucus glycans that interacts with the microbiota. Synthesis of Siaα2,6Gal epitopes is mediated by beta-galactoside alpha-2,6-sialyltransferase 1 (ST6Gal1), and is implicated in sex-specific pathologies. However, its impact on gut mucus, microbiota, and colitis, along with the degree to which this is sex-specific, is unknown.

Aims
The aim of this study was to determine if the loss of gut epithelial Siaα2,6Gal has a sex-specific impact on gut mucus, microbiota and susceptiblity to colitis.

Methods
To address our aim, we generated mice conditionally deficient in ST6Gal1 in intestinal epithelial cells (IEC) using CreLox technology (IEC St6gal1-/- mice). We compared “floxed” male and female St6gal1f/f (wild-type, WT) and IEC St6gal1-/- littermates, focusing on mucus structure in situ, mucin glycomics via High-Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS), and microbiota composition through 16S rRNA profiling and metabolomic analysis. Clinical disease activity and histologic scores of colitis were assessed at baseline and following exposure to chemical (2.5% Dextran Sodium Sulfate, DSS) and microbial (Citrobacter rodentium) agents.

Results
Lectin staining confirmed a complete loss of Siaα2,6Gal in the colon crypts of IEC St6gal1-/- mice, validating the functionality of our model. At baseline, no major clinical symptoms or differences in mucus barrier integrity were observed between WT and IEC St6gal1-/- mice of either sex. However, sialomic and glycomic analyses revealed sex- and genotype-specific differences, with a notable impact on the relative mucin sulfation status in female IEC St6gal1-/- mice. Microbiota profiling highlighted an increased abundance of Bifidobacterium spp. in WT mice, a higher proportion of certain Firmicutes members in male IEC St6gal1-/- mice, and sex-specific differences in short-chain fatty acid production. DSS-induced colitis showed mildly worsened disease outcomes in male IEC St6gal1-/- mice, while acute bacterial-induced colitis caused by C. rodentium led to more severe large-intestinal inflammation in female IEC St6gal1-/- mice.

Conclusions
This work expands the current knowledge of the role of Siaα2,6Gal in vivo and its sex-specific impact on overall glycosylation, microbial ecology, and colitis susceptiblity.

Funding Agencies
CCC
A24 INCREASE IN OXIDATIVE STRESS AS MEASURED BY SERUM CYSTEINE-BASED REDOX SENSING, IS ASSOCIATED WITH FUTURE RISK OF CROHN’S DISEASE.
Authors: Mu K , Dang C , Xue M , Shao J , Lee S , LI Q , Griffiths A , Steinhart A , Dieleman L , Aumais G , Panaccione R , Turpin W , Croitoru K 
Published: February 2025

Abstract

Background
Crohn’s disease (CD) is a gastrointestinal disorder characterized by chronic inflammation. While increased oxidative stress is observed in established CD patients, it remains unknown whether a shift in redox status is present before the diagnosis of CD and whether it is correlated with changes in immune response and microbial composition. Our hypothesis is that oxidative stress plays a role in the development of CD, and it could be detected before the diagnosis of CD.

Aims
We aimed to assess the association between the serum redox state-related indicators, specifically cysteine (reduced form) and cysteine sulfinic acid (oxidized form), quantified by mass spectrometry, with future risk of CD and if this is further correlated with markers of systemic inflammation and alterations in gut microbiota composition.

Methods
In the Genetic Environment Microbial Project, a cohort of first-degree relatives (FDRs) of CD patients was prospectively followed. Among them, we identified subjects who later developed CD, defined as pre-CD (n=69), and matched them at a 1:4 ratio with FDRs who remained disease-free (n=276). Conditional logistic regression assessed the association with future CD. Partial Spearman regression evaluated correlation with systemic inflammation, as indicated by c-reactive protein (CRP), and with changes in gut microbiota composition (determined by fecal 16S rRNA sequencing).

Results
Elevated cysteine was negatively associated with the likelihood of developing CD (Est = -1.18; p = 0.02) and negatively correlated with CRP levels (coeff = -1.04; p = 0.028). In contrast, cysteine sulfinic acid was positively associated with CD (Est = 1.15; p = 0.0004) and positively correlated with CRP levels (coeff = 1.11; p = 0.001). Specifically, their association with CD is independent of CRP levels. Three microbial risk taxa, which we previously reported to be associated with the future development of CD, were significantly correlated with cysteine sulfinic acid (p = 0.05).

Conclusions
This study is the first to report that when redox status shifts towards oxidative stress, as indicated by the level of cysteine and cysteine sulfinic acid, the likelihood of CD increases. Furthermore, these markers also correlate with early pre-clinical inflammation, as indicated by CRP levels as well as gut microbiota composition, indicating a change of gut microbiota composition when the redox status shifts towards oxidative stress.
Funding Agencies:
A25 INVESTIGATING THE ROLE OF TOLL-INTERACTING PROTEIN DURING CITROBACTER RODENTIUM INFECTION
Authors: Forneris P , Hannawayya R , Cirone K , Cobo E 
Published: February 2025

Abstract

Background
Diarrheal diseases are a threat to human health, being the second leading cause of death in children. Diarrheic enterocolitis can be caused by attaching/effacing (A/E) pathogens like enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC). Citrobacter rodentium (CR), a mouse A/E pathogen, mimics EPEC and EHEC infections, causing goblet cell depletion, crypt hyperplasia, and leukocyte infiltration. Autophagy, a critical immune pathway linked to goblet cell mucus secretion, is involved in the defence against CR. Toll-interacting protein (Tollip) is an intracellular mediator of autophagy and immunity, but its role in A/E infections remains elusive. This study aims to test the hypothesis that Tollip plays a protective role in CR infection.

Aims
- Assess CR infection kinetics in WT and Tollip-/- mice.
- Assess colitis in CR-infected WT and Tollip-/- mice.

Methods
Bacterial load was assessed by fecal colony forming unit (CFU) count in CR-infected WT and Tollip-/- mice. Histological damage was evaluated by scoring epithelial damage, leukocyte infiltration and crypt hyperplasia in H&E-stained distal colon sections. Apoptotic cells were identified by TUNEL. Acid and neutral mucin production was evaluated by Alcian-PAS staining. Glycosylation patterns were determined by immunofluorescence with lectins specific to sialic acid- and fucose-bound mucins.

Results
Tollip -/- and WT mice showed similar infection kinetics during the establishment and expansion phases (2-6 days post-infection (dpi)) and steady-state (7-14 dpi), with a peak of bacterial counts at 10 dpi. WT mice cleared CR by day 15, but Tollip-/- still shed bacteria by 17 dpi. The colitis grade was similar between WT and Tollip-/- mice, with marked epithelial damage at 8 dpi and increased leukocyte infiltration at 17 dpi. Scarce apoptotic cells (&lt;4 per field) were detected in WT and Tollip-/- mice during infection. Tollip-/- showed a thinner colonic mucin barrier and less mucin-filled goblet cells at 17 dpi compared to WT mice. CR-infected Tollip-/- mice showed altered mucin glycosylation patterns, with lower fucosylated mucins in the upper crypt and lumen and increased sialic acid-bound mucins in the luminal barrier and lower crypt. The mucin barrier, goblet cells, and mucin glycosylation were similar in uninfected Tollip-/- and WT mice.

Conclusions
This study demonstrates a new protective role for Tollip, particularly during the resolution phase, as a lack of Tollip delayed the clearance of CR. This phenotype could be explained by deficiencies in the mucin layer observed in Tollip-/- mice, evidenced by lower mucin production and anomalies in mucin glycosylation. By enhancing our understanding of host-pathogen interactions during enteric infections, this research serves as a step in the development of new treatments and prevention strategies.

Funding Agencies
None
A27 THE IMPACT OF MICROBIAL-DERIVED METABOLITES ON TYPE III INTERFERON SIGNALING IN INTESTINAL EPITHELIAL CELLS
Authors: Olumade T , Lantin C , Fedorova Y , Nelson R , Ogungbola O , Fedorova O , Bording-Jorgensen M , Armstrong H , Santer D 
Published: February 2025

Abstract

Background
Interferons (IFNs) are key cytokines that protect mucosal barriers. There are three types – types I, II and III. Unlike types I and II, which are pro-inflammatory, type III interferons (IFN-λs) are highly expressed in the gut and exert beneficial effects such as mucosal healing and dampening inflammation in mouse colitis models. Gut microbes can directly induce IFN-λ expression and prior studies have shown that microbial-derived metabolites can upregulate IFN-λ activity in the lungs. However, much less is known about the role of gut microbial-derived metabolites in the regulation of IFN-λ activity in the gut.

Aims
We hypothesized that specific gut microbial-derived metabolites upregulate IFN-λ activity in human gut epithelial cells.

Methods
Caco-2 cells were pre-treated for 2 hours with anaerobic whole microbe secretions (1-10% v/v) and microbial-derived metabolites, including short-chain fatty acids (SCFAs; acetate, butyrate, and propionate), a metabolic intermediate (succinate), and a tryptophan metabolite (kynurenine). Next, cells were treated with or without IFN-λ3 (20-50ng/ml) for 22 hours (n=3 biological repeats). IFN-stimulated genes (ISGs; MX1 and IFIT1) were quantified by RT-qPCR. IFN-λR1 levels were quantified by flow cytometry.

Results
Out of microbe secretions added from four gut microbes thus far, secretions from one pathobiont inhibited IFN-λ activity. All SCFAs tested had a concentration-dependent inhibitory effect on IFN-λ3 induction of ISGs (MX1 and IFIT1; p&lt;0.05). Succinate and kynurenine did not affect ISG induction by IFN-λ3 at any concentration tested. Only specific metabolites affected surface IFN-λR1 levels on Caco-2 cells.

Conclusions
Our findings demonstrate that specific microbial-derived metabolites can regulate intestinal IFN-λ immune responses. Contrary to our hypothesis, some metabolites can downregulate IFN-λ activity. Knowledge from this study provides fundamental knowledge about IFN-λ regulation in the human gut with implications for how to promote optimal IFN-λ activity to promote gut health, such as in inflammatory bowel diseases.

Funding Agencies
Children’s Hospital Research Institute of Manitoba, University of Manitoba
A31 IS AN ORAL SODIUM SULFATE SOLUTION MORE EFFECTIVE FOR PATIENTS WITH PRIOR CHALLENGING COLONOSCOPY PREPARATION? - A PROSPECTIVE CASE SERIES
Authors: Khan A , Rai M , McKay J , Mohanna R , Hookey L 
Published: February 2025

Abstract

Background
A considerable proportion of patients encounter difficulties with existing bowel cleansing regimens for colonoscopy resulting in suboptimal bowel visualization. This impacts patients, endoscopists, those on the waiting list, and the endoscopy unit overall.

Aims
Oral Sulfate Solution (OSS) has been proven to be efficacious in many situations and therefore this study aims to explore its benefit in patients who had challenging preparations during their previous colonoscopy.

Methods
This prospective case series was conducted at Kingston Health Sciences Centre. Patients scheduled for outpatient colonoscopy were considered for enrolment if previous colonoscopy reports indicated criteria of suboptimal preparation. Participants were allowed a light breakfast the day before the colonoscopy and consumed the first dose of OSS in a split dose fashion. The primary outcome was adequacy of bowel preparation using the Boston Bowel Preparation Scale (BBPS), defined as an overall score greater than 6, with each segment scoring at least 2. Secondary outcome measures included time to cecum, volume suctioned, and tolerability rating.

Results
A total of 120 patients with colonoscopies that were deemed as challenging to prepare were included in this study. Inclusion criteria for 109 of these patients was documentation of extensive washing and suctioning for adequate view of the colon, 5 had poor or fair preparation with images revealing obvious debris and 6 either vomited or consumed 80% or less of the preparation. Participants mean age was 67 years (SD=7.151), 66 (55%) were male and 24 (20%) had diabetes. The average BBPS score was 7 (SD=1.757) and 88% of the patients had adequate preparation. Participants’ prior colonoscopy preparations were primarily polyethylene glycol (52.5%) and a picosulfate based agent with bisacodyl (40.8%). Mean time to cecum was 7 minutes and 29 seconds (SD= 4 minutes and 29 seconds). The mean total volume suctioned was 1048.78mls (SD= 708.621). Tolerability data demonstrated 107 (89.2%) participants cumulatively rated OSS overall as tolerable, easy or very easy to use. Nausea was reported by 46 participants (38.3%), while vomiting occurred in 10 (8.3%). Abdominal distension or bloating was noted by 34 participants (28.3%), and 51(42.5%) experienced abdominal cramping, discomfort, or pain.

Conclusions
OSS showed a reduction to 12% inadequate bowel preparation. This is very encouraging given this group of patients had challenging preparation in the past. Its combination of effect, ease of use, and tolerability could deem it superior to traditional choice in these patients and can be used as a standard low volume preparation.

Funding Agencies
Pendopharm