bluuebunny/crossref_metadata_2025_split huggingface dataset:
P1123 Social isolation, loneliness, and incident inflammatory bowel disease: results from a large prospective cohorts and Mendelian randomization
Authors: Zhao J , Zhang M , Ye J , Li X 
Published: January 2024

Abstract

Background
Background Social isolation and loneliness pose significant public health challenges globally. The objective of this study is to investigate the association between social isolation, loneliness, and the risk of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD).

Methods
Methods 275,157 UK adults from the UK Biobank (UKB) was analyzed. The exposures of interest were social isolation and loneliness. Social isolation was measured by the frequency of meeting family/friends, leisure and social activity, and communal/solitary living. Loneliness was evaluated by the subjective feeling of loneliness and the willingness to confide in others. The primary endpoint was incident IBD, including UC and CD. The twosample Mendelian randomization (MR) analysis was based on the genome-wide association studies of UKB and the a nonoverlapping European ancestry GWAS study.

Results
Results The UKB cohort study documented 1,565 IBD (1063 UC and 492 CD) cases during a mean follow-up of 13.49 years. Social isolation and loneliness showed significant associations with an elevated risk of IBD in UKB (social isolation [moderate vs least]: aHR 1.13, 95% CI 1.02-1.26; social isolation [most vs least]: aHR 1.31, 95% CI 1.01-1.70; loneliness [yes vs no]: aHR 1.29, 95% CI 1.04-1.60). These associations were evident among moderate genetic susceptibility to IBD. Social isolation and loneliness jointly increase the risk of IBD onset, with an aHR of 1.60 (95% CI 1.21-2.12). Two-sample MR analyses determined that engaging in fewer leisure/social activities (OR 3.42, 95% CI 1.55-7.58; 3.32, 95% CI 1.29-8.55; 3.09, 95% CI 1.35-7.07) were associated with increased IBD, UC and CD risk, whereas more activities-sports club or gym (OR 0.37, 95% CI 0.15-0.88) was associated with reduced IBD risk.

Conclusion
Conclusion Social isolation and loneliness are each associated with an elevated risk of IBD especially for individuals with a moderate genetic risk for IBD, with MR analyses suggesting potential causal links. The findings highlight the importance of promoting initiatives to address social isolation and loneliness as part of IBD prevention strategies.
P1200 Study of correlation between polymorphisms of vitamin D metabolism genes and perianal disease in Crohn's disease
Authors: Ribaldone D G , Cafasso C , Antonucci M , Palermiti A , Caviglia G P , Vernero M , D'Avolio A , Cusato J 
Published: January 2024

Abstract

Background
Vitamin D (VD) is a fat-soluble vitamin essential for calcium homeostasis and that acts at the extraskeletal level. UVB skin exposure allows the synthesis of provitamin D. This undergoes a first hydroxylation in the leaver by the CYP2R1 enzyme and a second hydroxylation in the kidney by the CYP27B1 enzyme: active VD is obtained. VD is transported into the circulation by VDBP and exerts its activity in the target cells binding its VDR receptor. Finally, VD is inactivated by the renal enzyme CYP24A1.
Perianal disease (pCD) is a severe phenotypic manifestation of CD that may present as perianal fistula, abscess, recto-vaginal fistula, or stenosis. Among the mechanisms involved in its pathogenesis we recognise local inflammation and intestinal microbiota alteration. Vitamin D (VD) seems to act on these elements.
As there are currently no studies on this subject in the literature, the aim of this study is to evaluate the presence of an association between SNPs of genes coding for enzymes, transporters and receptors involved in the VD pathway and the occurrence of pCD in CD patients.

Methods
The study was carried out on the biological samples of 206 patients with CD, including 34 with pCD, who were followed up at the inflammatory bowel disease clinic in Turin, Italy. Through the use of Real-Time PCR, the genotype distribution of the following genes were assessed: VDR, CYP27B1, CYP24A1, and GC. For the association study, chi-square test was performed with calculation of p value and, when significant, logistic regression and calculation of OR with 95% CI was performed.

Results
Studying the association between SNPs and the presence of pCD, the following results were obtained: BsmI p=0.0470 and Apal p=0.0251. For BsmI heterozygous genotype there was an OR=2.5 (95% CI 1.2-5.3) of developing perianal disease and p value=0.02, while for ApaI heterozygous there was OR=2.91 (95% CI 1.3-6.6) of presenting pCD, with p value=0.01.

Conclusion
In the literature, there are several studies examining the association between the heterozygous Aa genotypes of ApaI and Bb genotypes of BsmI and increased inflammatory markers. In addition, some studies suggest that these two genotypes represent a risk factor for some diseases, including multiple myeloma, systemic lupus erythematosus, and mild cognitive disorder. This study demonstrates for the first time an impact of polymorphisms of genes associated with the VD pathway in predicting the onset of pCD. Specifically, the presence of the heterozygous genotype of BsmI and ApaI significantly increases the risk. Future studies need to be performed in different and larger cohorts of patients in order to confirm these data.
Evaluation of bone-related mechanical properties in female patients with long-term remission of Cushing's syndrome using quantitative computed tomography–based finite element analysis
Authors: Giuliodori Agustina , Soudah Eduardo , Malouf Jorge , Martel-Duguech Luciana , Amodru Vincent , Gil Joan , Hernández Joaquín A , Domingo Manuel Puig , Webb Susan M , Valassi Elena 
Published: January 2024

Abstract

Background
Hypercortisolism in Cushing's syndrome (CS) is associated with bone loss, skeletal fragility, and altered bone quality. No studies evaluated bone geometric and strain–stress values in CS patients after remission thus far.

Patients and methods
Thirty-two women with CS in remission (mean age [±SD] 51 ± 11; body mass index [BMI], 27 ± 4 kg/m2; mean time of remission, 120 ± 90 months) and 32 age-, BMI-, and gonadal status–matched female controls. Quantitative computed tomography (QCT) was used to assess volumetric bone mineral density (vBMD) and buckling ratio, cross-sectional area, and average cortical thickness at the level of the proximal femur. Finite element (FE) models were generated from QCT to calculate strain and stress values (maximum principal strain [MPE], maximum strain energy density [SED], maximum Von Mises [VM], and maximum principal stress [MPS]). Areal BMD (aBMD) and trabecular bone score (TBS) were assessed by dual-energy X-ray absorptiometry (2D DXA).

Results
Trabecular vBMD at total hip and trochanter were lower in CS as compared with controls (P &lt; .05). Average cortical thickness was lower, and buckling ratio was greater in CS vs controls (P &lt; .01). All strain and stress values were higher in CS patients vs controls (P &lt; .05). 2D DXA–derived measures were similar between patients and controls (P &gt; .05). Prior hypercortisolism predicted both VM (β .30, P = .014) and MPS (β .30, P = .015), after adjusting for age, BMI, menopause, delay to diagnosis, and duration of remission.

Conclusions
Women with prior hypercortisolism have reduced trabecular vBMD and impaired bone geometrical and mechanical properties, which may contribute to an elevated fracture risk despite long-term remission.
Could care giving have altered the evolution of human immune strategies?
Authors: Gilbert Bethany L P , Kessler Sharon E 
Published: January 2024

Abstract
Life history theory indicates that individuals/species with a slow pace of life invest more in acquired than innate immunity. Factors that decrease the pace of life and predict greater investment in acquired immunity include increased nutritional resources, increased pathogen exposure and decreased risk of extrinsic mortality. Common care behaviors given to sick individuals produce exactly these effects: provisioning increases nutritional resources; hygiene assistance increases disease exposure of carers; and protection can reduce the risk of extrinsic mortality to sick individuals. This study, therefore, investigated under what conditions care giving behaviors might impact immune strategy and pace of life. The study employed an agent-based model approach that simulated populations with varying levels of care giving, disease mortality, disease transmissibility, and extrinsic mortality, enabling measurements of how the immune strategy and age structure of the populations changed over evolutionary time. We used multiple regressions to examine the effects of these variables on immune strategy and the age structure of the population. The findings supported our predictions that care was selected for an acquired immunity. However, the pace of life did not slow as expected. Instead, the population shifted to a faster, but also more cost-intensive reproductive strategy in which care improved child survival by subsidizing the development of acquired immune responses.
Description of self-care behaviours in patients with non-valvular atrial fibrillation on oral anticoagulant therapy: a scoping review
Authors: Magon Arianna , Hendriks Jeroen M , Conte Gianluca , Caruso Rosario 
Published: January 2024

Abstract

Aims
The primary aim of this scoping review was to explore and categorize the medication-related self-care behaviours exhibited by patients with non-valvular atrial fibrillation (NVAF) who are on oral anticoagulant (OAC) therapy.

Methods and results
A scoping review was performed, and the systematic search of the literature yielded an initial 887 records. After deduplication and screening, 61 studies were included in the analysis, ranging from 2003 to 2023. The studies represented a wide geographical distribution and diverse methodologies. The results identified 16 self-care behaviours: a higher focus of the included literature on self-care monitoring (60.65% of studies), followed by self-care management and self-care maintenance (each 16.39%). These behaviours ranged from regular blood testing to consulting healthcare providers and lifestyle changes. The results also highlighted the relationship between treatment satisfaction, self-efficacy, and adherence. Several studies emphasized the critical role of healthcare providers in influencing medication adherence. Furthermore, patient knowledge, quality of life, and psychological factors were identified as key elements affecting self-care behaviours.

Conclusion
The review provides a comprehensive landscape of medication-related self-care behaviours among NVAF patients on OAC therapy. It underscores the predominance of self-care monitoring behaviours and the critical roles of healthcare providers, psychological factors, and patient knowledge in influencing these behaviours. The findings also highlight the necessity for an integrated, patient-centred approach to improving self-care and self-management in OAC treatment. Future research should focus on addressing the identified gaps, including the relative lack of studies on lifestyle modification, emotional well-being, and technology-assisted interventions.

Registration
This review is part of a broader project and is documented at ClinicalTrials.gov: NCT05820854.
The evolution of sexual dimorphism in gene expression in response to a manipulation of mate competition
Authors: Mishra Prashastha , Rundle Howard D , Agrawal Aneil F 
Published: January 2024

Abstract
Many genes are differentially expressed between males and females and patterns of sex-biased gene expression (SBGE) vary among species. Some of this variation is thought to have evolved in response to differences in mate competition among species that cause varying patterns of sex-specific selection. We used experimental evolution to test this by quantifying SBGE and sex-specific splicing in 15 Drosophila melanogaster populations that evolved for 104 generations in mating treatments that removed mate competition via enforced monogamy, or allowed mate competition in either small, simple, or larger, structurally more complex mating environments. Consistent with sex-specific selection affecting SBGE, initially sex-biased genes diverged in expression more among treatments than unbiased genes, and there was greater expression divergence for male- than female-biased genes. It has been suggested the transcriptome should be “feminized” under monogamy because of the removal of sexual selection on males; we did not observe this, likely because selection differs in additional ways between monogamy vs. polygamy. Significant divergence in average expression dimorphism between treatments was observed and, in some treatment comparisons, the direction of the divergence differed across different sex-bias categories. There was not a generalized reduction in expression dimorphism under enforced monogamy.
Mutations of ribosomal protein genes induce overexpression of catalase in Saccharomyces cerevisiae
Authors: Hsu Ching-Hsiang , Liu Ching-Yu , Lo Kai-Yin 
Published: January 2024

Abstract
Ribosome assembly defects result in ribosomopathies, primarily caused by inadequate protein synthesis and induced oxidative stress. This study aimed to investigate the link between deleting one ribosomal protein gene (RPG) paralog and oxidative stress response. Our results indicated that RPG mutants exhibited higher oxidant sensitivity than the wild type (WT). The concentrations of H2O2 were increased in the RPG mutants. Catalase and superoxide dismutase (SOD) activities were generally higher at the stationary phase, with catalase showing particularly elevated activity in the RPG mutants. While both catalase genes, CTT1 and CTA1, consistently exhibited higher transcription in RPG mutants, Ctt1 primarily contributed to the increased catalase activity. Stress-response transcription factors Msn2, Msn4, and Hog1 played a role in regulating these processes. Previous studies have demonstrated that H2O2 can cleave 25S rRNA via the Fenton reaction, enhancing ribosomes’ ability to translate mRNAs associated with oxidative stress-related genes. The cleavage of 25S rRNA was consistently more pronounced, and the translation efficiency of CTT1 and CTA1 mRNAs was altered in RPG mutants. Our results provide evidence that the mutations in RPGs increase H2O2 levels in vivo and elevate catalase expression through both transcriptional and translational controls.
Epigenetic and Genetic Differentiation Between Coregonus Species Pairs
Authors: Venney Clare J , Mérot Claire , Normandeau Eric , Rougeux Clément , Laporte Martin , Bernatchez Louis 
Published: January 2024

Abstract
Phenotypic diversification is classically associated with genetic differentiation and gene expression variation. However, increasing evidence suggests that DNA methylation is involved in evolutionary processes due to its phenotypic and transcriptional effects. Methylation can increase mutagenesis and could lead to increased genetic divergence between populations experiencing different environmental conditions for many generations, though there has been minimal empirical research on epigenetically induced mutagenesis in diversification and speciation. Whitefish, freshwater members of the salmonid family, are excellent systems to study phenotypic diversification and speciation due to the repeated divergence of benthic–limnetic species pairs serving as natural replicates. Here we investigate whole genome genetic and epigenetic differentiation between sympatric benthic–limnetic species pairs in lake and European whitefish (Coregonus clupeaformis and Coregonus lavaretus) from four lakes (N = 64). We found considerable, albeit variable, genetic and epigenetic differences between species pairs. All SNP types were enriched at CpG sites supporting the mutagenic nature of DNA methylation, though C&gt;T SNPs were most common. We also found an enrichment of overlaps between outlier SNPs with the 5% highest FST between species and differentially methylated loci. This could possibly represent differentially methylated sites that have caused divergent genetic mutations between species, or divergent selection leading to both genetic and epigenetic variation at these sites. Our results support the hypothesis that DNA methylation contributes to phenotypic divergence and mutagenesis during whitefish speciation.
On the retrieval of body waves from ambient noise based on regional seismic arrays
Authors: Xie Jinyun , Luo Yinhe , Bao Xueyang , Dai Andy , Xie Yanan , Yang Yingjie 
Published: January 2024

SUMMARY
Ambient noise technology can efficiently extract surface wave signals from seismic background noise and has been extensively utilized in imaging lithospheric structures. However, retrieving crustal body wave signals, such as PmP or SmS phases, still poses a challenge. Only a limited number of reports have successfully extracted these regional-scale body wave signals from ambient noise in only a few limited study areas. It remains unclear why these signals are difficult to retrieve from ambient noise data. To investigate the mechanism of recovering body wave signals in noise cross-correlations, we calculate cross-correlation functions at four regions and observe the similarity of the recovered body waves. Through a series of synthetic simulations, we demonstrate that the appearance of body wave signals in noise cross-correlations is closely related to the distribution of noise sources. Among these signals, the post-critical SmS wave proves to be the most readily recoverable from ambient noise data, primarily stemming from distant sources. In contrast, the recovery of P-wave requires the array to be in proximity to the sources. Our experiments also reveal that the main origin of PL waves is the multiple reflections of S-waves propagating in the crust.
SPINT2 mutations in the Kunitz domain 2 found in SCSD patients inactivate HAI-2 as prostasin inhibitor via abnormal protein folding and N-glycosylation
Authors: Huang Nanxi , Wang Qiaochu , Bernard Robert B , Chen Chao-Yang , Hu Je-Ming , Wang Jehng-Kang , Chan Khee-Siang , Johnson Michael D , Lin Chen-Yong 
Published: January 2024

Abstract
Mutations in the Kunitz-type serine protease inhibitor HAI-2, encoded by SPINT2, are responsible for the pathogenesis of syndromic congenital sodium diarrhea (SCSD), an intractable secretory diarrhea of infancy. Some of the mutations cause defects in the functionally required Kunitz domain 1 and/or subcellular targeting signals. Almost all SCSD patients, however, harbor SPINT2 missense mutations that affect the functionally less important Kunitz domain 2. How theses single amino acid substitutions inactivate HAI-2 was, here, investigated by the doxycycline-inducible expression of three of these mutants in HAI-2-knockout Caco-2 human colorectal adenocarcinoma cells. Examining protein expressed from these HAI-2 mutants reveals that roughly 50% of the protein is synthesized as disulfide-linked oligomers that lose protease inhibitory activity due to the distortion of the Kunitz domains by disarrayed disulfide bonding. Although the remaining protein is synthesized as monomers, its glycosylation status suggests that the HAI-2 monomer remains in the immature, lightly glycosylated form, and is not converted to the heavily glycosylated mature form. Heavily glycosylated HAI-2 possesses full anti-protease activity and appropriate subcellular targeting signals, including the one embedded in the complex-type N-glycan. As predicted, these HAI-2 mutants cannot suppress the excessive prostasin proteolysis caused by HAI-2 deletion. The oligomerization and glycosylation defects have also been observed in a colorectal adenocarcinoma line that harbors one of these SPINT2 missense mutations. Our study reveals that the abnormal protein folding and N-glycosylation can cause widespread HAI-2 inactivation in SCSD patents.
CYTOKINE MULTI-OMICS AND MACHINE LEARNING IDENTIFY MIP1ALPHA AS A NOVEL MEDIATOR IN INFLAMMATORY BOWEL DISEASE
Authors: O'Brien Eileen , Potdar Chinmay , Mulder Daniel 
Published: January 2024

Abstract

BACKGROUND
Macrophage inflammatory protein 1 alpha (MIP1a) is a proinflammatory cytokine previously related to murine models of inflammatory bowel disease (IBD), but not definitively in the human disease. MIP1a acts as a chemoattractant of immune cells from the blood to the gut mucosa. We aimed to delineate the alterations to MIP1a and macrophages in relation to a range of IBD severity.

HYPOTHESIS
To characterize the changes to MIP1a production and localization in response to disease activity in IBD.

APPROACH
Both IBD (n=63) and control patients (n=118) were enrolled in this study (HSREB 6033229). Cytokine profiles were investigated using a 17-plex multi-fluorescent bead-based immunoassay (FirePlex, Abcam, Cambridge, UK) on serum from a subset of patients. Disease activity and macrophage levels were extracted from the clinical record. Activity was quantified using the Physician Global Assessment Score. Machine learning (ML) was performed with custom R scripts utilizing the tidymodels package (version 1.1) to determine the optimal model. Immunohistochemistry (IHC) was used to localize MIP1a in patient biopsies and quantified using QuPath software (v0.4).

RESULTS
An extreme gradient boost ML model was found to have optimal sensitivity and specificity for predicting disease activity based on serum cytokine levels. Within this model lower levels of serum MIP1a were associated with higher severity of IBD activity. However, in GI mucosal biopsies, the percentage of MIP1a positive cells in colon tissue increased with the severity of IBD. Macrophage concentrations in the peripheral blood were higher in patients on prednisone, and relatively similar across all other medications used in our cohort.

CONCLUSIONS
With the data collected, we identify MIP1a as a possible prognostic tool for quantifying IBD activity.
TRENDS OF INFLAMMATORY BOWEL DISEASE BURDEN IN THE UNITED STATES (1990-2019), PROJECTIONS OF DEATHS TO 2040: INSIGHTS FROM THE 2019 GLOBAL BURDEN OF DISEASE STUDY
Authors: Patel Rahul , Roy Vivek , Kunhipurayil Suraj , Patel Krina Manojbhai , Elassar Samar , Sojitra Vani , Desai Hardik Dineshbhai 
Published: January 2024

Abstract

BACKGROUND
Inflammatory Bowel Disease (IBD) ranks as the 9th primary cause of deaths and 7th for disabilities among all digestive diseases, affecting over 3 million Americans with a continuous upsurge.

METHOD
Utilizing the Global Burden of Disease methodology, we evaluated the prevalence, incidence, mortality, and Disability Adjusted Life Years (DALYs) of IBD from 1990 to 2019 in the U.S. based on age, sex, and year via a standardized statistical model. Furthermore, we forecasted deaths and Years of Life Lost (YLLs) up to 2040 through a regression framework.

RESULTS
IBD prevalence showed a decline from 982,981 (95%UI: 846,832-1,129,782) in 1990 to 762,889 (712,356-813,653) in 2019. From 1990-2019, the total annual incidence reduced by 12% (4-18), while deaths surged by 172% (81-199), and DALYs increased by 16% (2-34) (Figure 1). The Age-Standardized Rate (ASR) for mortality rose from 0.62 (0.60-0.82) per 100,000 cases in 1990 to 1.02 (0.8-1.11) in 2019. In raw counts, Nevada saw the most significant rise in incidence (87%), deaths (486%), and DALYs (174%) from 1990-2019. Based on ASR, West Virginia and Kentucky led in mortality increases with 87% and 83% respectively (Figure 2). In 2019, the age group 80-84 reported the highest deaths (848), while ages 25-29 saw the most significant incidence (8429), and ages 60-64 the highest DALYs (20933). Comparing genders, females had a steeper increase in DALYs (17% vs. 13% for males), whereas males saw a higher rise in deaths (181% vs. 167% for females) between 1990-2019. By 2040, IBD-related age-standardized mortality rates are predicted to climb by 0.9 per 100,000.

CONCLUSION
In 2019, IBD was responsible for 4.56% of all digestive disease deaths. Highlighting a comprehensive challenge for the U.S. healthcare, IBD's impact is not just clinical or economic but also profoundly psychosocial. Emphasizing early detection, cutting-edge treatments, and comprehensive patient support is crucial to lessen the severe implications of IBD in the U.S.