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Abstract Background With existing researches identifying an increased rate of long-term conditions (LTCs) among Inflammatory Bowel Disease (IBD) patients, yet there is a lack of exploration into the patterns of comorbidity and prognostic rates for IBD patients with multiple morbidities. Methods The study included 8,305 participants who self-reported having IBD, comprising ulcerative colitis (UC) and Crohn’s disease (CD). Latent class analysis (LCA) was utilized to create optimal categories of LTC combinations for UC and CD patients with additional long-term conditions. Using Cox proportional hazards models, we compared the all-cause mortality rates over a 16-year follow-up among UC and CD patients within different LTC categories, both without LTCs and with the addition of one LTC, the probability of major adverse cardiovascular events (MACE), and the rates of IBD-related surgeries. Results A total of 5,617 participants reported having two or more LTCs, with the LCA method identifying three prevalence categories among CD patients, and four prevalence categories among UC patients. The highest mortality rate among CD patients was found in category 3: (HR 1.789, 95% CI (1.439–2.224)), and the highest rates of MACE were also in category 3: (HR 11.432, 95% CI (9.332–14.005)), with hypertension being the distinguishing characteristic of this category, and the highest rates of IBD-related surgeries being associated with pain in category 1: (HR 1.217, 95% CI (0.983–1.506)). Among UC patients, the highest mortality rate was in category 3: (HR 2.221, 95% CI (1.837–2.684)), with the highest MACE rates found in category 3: (HR 6.422, 95% CI (5.659–7.288)), and the highest rates of IBD-related surgeries being associated with pain, also in category 3: (HR 1.218, 95% CI (1.041–1.425)). Conclusion The rates of adverse health outcomes in IBD patients is closely associated with multimorbidity patterns, underscoring the need to fully consider multimorbidity patterns in the assessment, management, and treatment strategies for IBD.

IntroductionInflammatory bowel disease (IBD) is a multi-organ autoimmune disease that commonly affects the gastrointestinal tract, but can also affect other organs throughout the body. Less is known, however, about kidney involvement in IBD. Although IBD has been associated with chronic kidney disease (CKD) and end-stage renal disease (ESRD), these results have been inconsistent. The present study analyzed the prevalence of concurrent CKD and ESRD in patients with IBD.MethodsPubMed, Cochrane, Web of Science, and Embase were searched for studies published through October 2023 on IBD patients with concurrent CKD or ESRD. Outcomes included the incidence rates and odds ratios (OR) of concurrent CKD and ESRD in IBD patients. The quality of included studies was assessed using the Newcastle-Ottawa Scale, and sequential sensitivity was analyzed. Publication bias was evaluated using Egger’s test.ResultsNine studies were included in this meta-analysis. The combined results of eight studies, which included 239,042 IBD patients, showed that the prevalence of CKD in IBD patients was 5% (95% confidence interval [CI]: 1–9%). The combined results of two studies, which included 40,341 IBD patients, showed that the prevalence of ESRD in IBD patients was 0.2% (95% CI: −0.08–0.12%). The combined results of six case–control studies reported that the risk of CKD was significantly higher in patients with than without IBD (OR 1.36, 95% CI: 1.08–1.70, p = 0.008).ConclusionAlthough studies have shown an increased risk of CKD in IBD, due to the small number of included studies and high heterogeneity across studies, it is not enough to definitively conclude that CKD is more common in patients with IBD. But patients with IBD should be regularly monitored for CKD.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/.

Background and aimsInflammatory bowel disease (IBD) is a common chronic inflammatory bowel disease characterized by diarrhea and abdominal pain. Recently human metabolites have been found to help explain the underlying biological mechanisms of diseases of the intestinal system, so we aimed to assess the causal relationship between human blood metabolites and susceptibility to IBD subtypes.MethodsWe selected a genome-wide association study (GWAS) of 275 metabolites as the exposure factor, and the GWAS dataset of 10 IBD subtypes as the outcome, followed by univariate and multivariate analyses using a two-sample Mendelian randomization study (MR) to study the causal relationship between exposure and outcome, respectively. A series of sensitivity analyses were also performed to ensure the robustness of the results.ResultsA total of 107 metabolites were found to be causally associated on univariate analysis after correcting for false discovery rate (FDR), and a total of 9 metabolites were found to be significantly causally associated on subsequent multivariate and sensitivity analyses. In addition we found causal associations between 7 metabolite pathways and 6 IBD subtypes.ConclusionOur study confirms that blood metabolites and certain metabolic pathways are causally associated with the development of IBD subtypes and their parenteral manifestations. The exploration of the mechanisms of novel blood metabolites on IBD may provide new therapeutic ideas for IBD patients.

BackgroundLimited studies have investigated the relationship between systemic oxidative stress and inflammatory bowel disease (IBD). The purpose of this study was to explore the relationship between oxidative balance score (OBS) and IBD.MethodsWe included 175,808 participants from the UK Biobank database from 2006 to 2010. OBS scores were calculated based on 22 lifestyle and dietary factors. Multiple variable Cox proportional regression models, as well as gender stratification and subgroup analysis, were utilized to investigate the relationship between OBS and IBD.ResultsThere is a significant negative correlation between OBS and the occurrence of IBD, ulcerative colitis (UC), and Crohn’s disease (CD). Additionally, OBS is significantly negatively correlated with intestinal obstruction in CD patients. Gender stratified analysis suggest a significant correlation between OBS and CD in female patients, particularly pronounced in those under 60 years old. Sensitivity analysis indicates a significant negative correlation between lifestyle-related OBS and diet-related OBS with the occurrence of CD in females, diet-related OBS is negatively correlated with CD in males.ConclusionOBS showed a significant negative correlation with IBD, especially in female CD patients. This study underscores the importance of antioxidant diet and lifestyle, which may provide a greater advantage for female CD patients.

BackgroundThe Oxidative Balance Score (OBS) is commonly used to assess oxidative stress and provides a comprehensive evaluation of dietary and lifestyle-related exposures. However, there is limited research on the association between OBS and colorectal cancer (CRC), its subsites, and complications. The objective of this study was to assess the relationship between OBS and the risk of CRC, its subsites, and common complications in a large prospective cohort study.MethodsWe included data from 175,808 participants in the UK Biobank data sample repository from 2006 to 2010. We evaluated OBS using a scoring system based on 22 dietary and lifestyle factors. Multiple adjustments, including multivariate Cox proportional hazard regression, gender stratification, subgroup analysis, and sensitivity analysis, were performed to fully explore the relationship between OBS and CRC, its subsites, and complications. The mediation analysis was conducted to investigate whether serum albumin, uric acid, and neutrophil levels mediate the relationship between OBS and CRC.ResultsAfter adjusting for potential confounding factors, a significant negative correlation was found between OBS and the risk of CRC and its subsites (proximal colon cancer, distal colon cancer, and rectal cancer). This correlation was particularly pronounced in male CRC patients. Serum albumin, uric acid, and neutrophil count, which are biomarkers, were found to have a significant mediating effect between OBS and CRC.ConclusionOur study suggests that higher exposure to antioxidants assessed through OBS (diet and lifestyle rich in antioxidants) may decrease the occurrence of CRC and its subsites.

ObjectiveSignificant differences have been discovered between subtypes of Crohn’s disease (CD) and ulcerative colitis (UC). The role of gut microbiota in promoting the onset of UC and CD is established, but conclusions regarding subtype-specific analyses remain limited.MethodsThis study aims to explore the influence of gut microbiota on subtypes of UC and CD, offering novel insights into the pathogenesis and treatment of UC and CD.Two-sample Mendelian randomization (MR) analysis was employed to examine the causal relationship between subtypes of UC and CD and gut microbiota composition. Gut microbiota data were sourced from the International Consortium MiBioGen, while UC and CD data were obtained from FINNGEN. Eligible single nucleotide polymorphisms (SNPs) were selected as instrumental variables. Multiple analytical approaches such as inverse variance-weighted (IVW), MR-Egger regression, weighted median, weighted mode, and MR-RAPS were utilized. Sensitivity analyses including MR-Egger intercept test, Cochran’s Q test, and leave-one-out analysis were conducted for quality control. Subsequently, we employed multivariable IVW, MR-Egger, weighted median, and LASSO regression methods to identify independently significant genera or families and conducted sensitivity analyses.ResultsWe have determined that Hungatella, Acidaminococcaceae, and 15 other microbial taxa act as protective factors for various CD and UC subtypes, while Terrisporobacter, Anaerostipes, and 23 other microbial taxa are associated with increased risk for different CD and UC subtypes. Furthermore, through multivariable MR analysis, we have identified significant genera or families with independent effects.ConclusionOur study confirms a causal relationship between dysbiosis of gut microbiota and the occurrence of CD and UC subtypes. Furthermore, it validates etiological distinctions among different subtypes of CD and UC. A novel approach to adjunctive therapy involving distinct UC or CD subtypes may involve the use of probiotics and represents a potential avenue for future treatments.

To explore the key odorants and their concentration changes in high-salt liquid-state fermentation soy sauce (HLFSS) during storage, solvent extraction coupled with solvent-assisted flavor evaporation was applied to isolate the volatiles in HLFSS, and the volatiles were analyzed by gas chromatograph-mass spectrometry-olfactory and gas chromatograph-flame ionization detector-olfactometry combined with the aroma extract dilution assay. A total of 37 odor-active compounds with flavor dilution (FD) factors ranging from 1 to 1024 were identified, and 23 aroma components with odor activity values ≥1 were considered as key odorants. Methional, 3-methylbutanoic acid, phenethyl alcohol, sotolon, 4-hydroxy-2-methyl-5-ethyl-3(2H)-furanone (HEMF), and 4-hydroxy-2,5-dimethylfuran-3(2H)-one (HDMF) had the highest FD factors of 1024. The results of quantitative analysis through the internal standard curve showed that the concentrations of HEMF, HDMF, acetic acid, 1-hydroxy-2-butanone, acetol, and furfuryl alcohol varied greatly during storage, so these compounds might be used as the indicators to determine the shelf life of HLFSS. The recombination experiment also confirmed the important contribution of these compounds. This result will provide valuable information for understanding the flavor changes of HLFSS.

ABSTRACT The Cre/lox system is a fundamental tool for functional genomic studies, and a number of Cre lines have been generated to target genes of interest spatially and temporally in defined cells or tissues; this approach has greatly expanded our knowledge of gene functions. However, the limitations of this system have recently been recognized, and we must address the challenge of so‐called nonspecific/off‐target effects when a Cre line is utilized to investigate a gene of interest. For example, cathepsin K (Ctsk) has been used as a specific osteoclast marker, and Cre driven by its promoter is widely utilized for osteoclast investigations. However, Ctsk‐Cre expression has recently been identified in other cell types, such as osteocytes, periosteal stem cells, and tenocytes. To better understand Ctsk‐Cre expression and ensure appropriate use of this Cre line, we performed a comprehensive analysis of Ctsk‐Cre expression at the single‐cell level in major organs and tissues using two green fluorescent protein (GFP) reporters (ROSA nT‐nG and ROSA tdT) and a tissue clearing technique in young and aging mice. The expression profile was further verified by immunofluorescence staining and droplet digital RT‐PCR. The results demonstrate that Ctsk‐Cre is expressed not only in osteoclasts but also at various levels in osteoblast lineage cells and other major organs/tissues, particularly in the brain, kidney, pancreas, and blood vessels. Furthermore, Ctsk‐Cre expression increases markedly in the bone marrow, skeletal muscle, and intervertebral discs in aging mice. These data will be valuable for accurately interpreting data obtained from in vivo studies using Ctsk‐Cre mice to avoid potentially misleading conclusions. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

A language-independent automatic speech recognizer (ASR) is one that can be used for phonetic transcription in languages other than the languages in which it was trained. Language-independent ASR is difficult to train, because different languages implement phones differently: even when phonemes in two different languages are written using the same symbols in the international phonetic alphabet, they are differentiated by different distributions of language-dependent redundant articulatory features. This article demonstrates that the goal of language-independence may be approximated in different ways, depending on the size of the training set, the presence vs. absence of familial relationships between the training and test languages, and the method used to implement phone recognition or classification. When the training set contains many languages, and when every language in the test set is related (shares the same language family with) a language in the training set, then language-independent ASR may be trained using an empirical risk minimization strategy (e.g., using connectionist temporal classification without extra regularizers). When the training set is limited to a small number of languages from one language family, however, and the test languages are not from the same language family, then the best performance is achieved by using domain-invariant representation learning strategies. Two different representation learning strategies are tested in this article: invariant risk minimization, and regret minimization. We find that invariant risk minimization is better at the task of phone token classification (given known segment boundary times), while regret minimization is better at the task of phone token recognition.