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关键词： Spatial crime analysis   Guerry   Quetelet   19th century france   Local analysis  

摘要： Modern spatial criminology has its roots in the social statistics of 19th century France. Investigating the variation in property and violent crimes across French departments, Guerry (1832, 1833) and Quetelet (1831, 1842) found unique patterns for each crime classification. They also found relationships between crime and a number of social, demographic, economic, and climatic conditions. In this paper we revisit the work of Guerry and Quetelet using modern spatial statistical techniques. We find that the relationships identified by Guerry and Quetelet are robust when employing modern spatial analysis. Additionally, we find the patterns of crime in 19th century France are remarkably similar to contemporary crime patterns in other nations. These findings suggest that the spatial findings of Guerry and Quetelet hold up when using modern advanced spatial methodologies.

关键词： genetics   population diversity   precision medicine   type 1 diabetes   type 2 diabetes  

摘要： Aims: We have reported that a 9SNPs type 1 diabetes (T1D) Genetic Risk Score (GRS) developed from European data had a lower power in Indians to distinguish T1D from type 2 diabetes (T2D). We explore the performance of an improved (67SNPs) T1DGRS and also the potential reasons for lower discriminative ability to classify types of diabetes in Indians. Methods: We studied the discriminative ability of a 67SNPs European T1DGRS in 611 clinically diagnosed T1D and 1153 T2D patients, and 321 non-diabetic controls, using receiver operating characteristic (ROC) area under the curve (AUC). We also compared the frequency and effect sizes of HLA risk haplotypes between Indians and Europeans. Results: The T1DGRS was discriminative of T1D from T2D and controls. However, the ability is lower in Indians than Europeans (AUC, Europeans 0.92, Indians all T1D 0.83, AA-positive 0.86). The T1DGRS was higher in AA-positive than in AA-negative persons [13.01 (12.79-13.23) vs. 12.09 (11.64-12.56)], p < 0.0001. The association of common HLA-DQA1 similar to HLA-DQB1 haplotypes was broadly similar;however, important differences were noted in the frequency, direction and magnitude of effect for some haplotypes between Indians and Europeans. Conclusions: We confirm broad applicability of European 67SNPs T1DGRS to Indian T1D persons. However, differences in HLA allele frequencies, magnitude and directional differences reduced the predictive value. Our results stress the need to generate ancestry-specific GRS, which we plan to do in the near future.

关键词： anti-cytokine autoantibodies   dried blood spot   interferon gamma  

摘要： Background:High titer, neutralizing anti-cytokine autoantibodies (ACAA) to interferon gamma (IFNγ) are an emerging cause of adult-onset immunodeficiency, and detection can direct clinical management. Currently, the detection of ACAAs is performed on blood or plasma, which is time-sensitive, relatively expensive to obtain, and must be shipped from remote locations in specialized containers. We have adapted an easier method of collecting blood or plasma onto a paper card as dried blood spots (DBS), which is simple, inexpensive, and does not require a medical facility or special mailing. Methods:Whole blood, either from venipuncture or finger stick, was blotted onto filter paper to yield DBS from which samples were eluted. Samples from 4 groups were analyzed: patients with anti-IFNγ autoantibodies, either with or without neutralizing activity, disease controls with other ACAAs, and healthy controls (n= 50 total). Eluates and paired plasma samples were then screened for antibodies using a particle-based approach. Neutralizing activity was determined by flow cytometry, which examined immediate downstream effects of cytokine stimulation in healthy control monocytes. Results:Autoantibodies were demonstrated in DBS eluate from 17 previously diagnosed patients with anti-IFNγ autoantibodies. The autoantibodies recovered from DBS eluate with neutralizing anti-IFNγ autoantibodies remained fully neutralizing using IFNγ-induced STAT-1 phosphorylation in healthy control monocytes as a readout. Anti-IFNγ autoantibodies preserved as DBS were stable for downstream functional testing when stored at either 4°C, room temperature, or 40°C for a week. Conclusions:Dried blood and plasma spots are simple, inexpensive, durable, and allow functional anti-IFNγ autoantibodies to be easily recovered.

摘要： We read with great the article by Elhani et al. recently published in the European Journal of Internal Medicine [ 1]. This study attempts to establish the relationship between interleukin-18 (IL-18) and autoinflammatory diseases (AIDs) using serum...

关键词： Deoxynivalenol   Pyroptosis   Gasdermin D   IL-1 beta secretion  

摘要： Deoxynivalenol (DON), a trichothecene mycotoxin, exerts pro-inflammatory and immunomodulatory activity. Interleukin (IL)-1 beta serves a crucial part as a gate keeper of inflammation in DON-induced macrophages, but an overview of how DON exposure elicits IL-1 beta secretion from RAW264.7 cells has not been fully illustrated. Here we found that the cellular phenomenon, involved with a type of programmed cell death known as pyroptosis, contains: 1) increase of pro-IL-1 beta expression, 2) motivation of caspase-1, 3) caspase-1-dependent maturement of IL-1 beta, 4) caspase-1 fragmentation of gasdermin D (GSDMD), and 5) IL-1 beta secretion through GSDMD pore. Mechanistically, the present study certified that DON both as first and second signals engaged in IL-1 beta release is mediated by purinergic P2X7 receptor (P2X7R)-Src signaling. During this process, P2X7R signal is required for GSDMD pore forming course in ASC-independent manner. Moreover, blocking of K+ efflux, ROS formation, as well as cathepsin B activity decreases IL-1 beta export. Our data show that exposure to DON does cause pyroptosis and IL-1 beta secretion via P2X7R signal in RAW264.7 macrophages. Overall, these results provide new mechanistic clue for DON as a pro-inflammatory factor in innate immune signaling events.

关键词： pediatric   Crohn's disease   anti-TNF  

摘要： Background The 2021 ECCO-ESPGHAN guideline on the medical management of pediatric Crohn's disease promotes early risk stratification and top-down anti-TNF for patients deemed high risk of severe disease *** We aimed to objectively assess the risk-benefit profile of the guideline's risk stratification policy and guidance on top-down anti-TNF in a nationwide population-based cohort *** Using a prospectively identified nationwide cohort of all new pediatric patients (<17 years) diagnosed with Crohn's disease in Scotland between January 1, 2016 and December 31, 2020 and retrospectively applying the current management algorithm, we explored the guideline's ability to accurately risk stratify patients. Phenotypic and treatment data were retrospectively collected from electronic medical records with a maximum follow-up of 18 months *** Four hundred and eighteen children (258/418 [62%] male;median [interquartile range {IQR}] age at diagnosis: 13.2 [11.2-14.8] years) were included. High-risk phenotype was present in 224/418 (54%) with 53/224 (24%) of high-risk patients not requiring anti-TNF therapy within 18 months of diagnosis. Conversely, 78/194 (40%) of the low-risk group received anti-TNF within 18 months. High-risk patients were more likely to require anti-TNF (171/224 [76%] vs 78/194 [40%], P < .001) and had shorter median (IQR) time to anti-TNF start (5.0 [1.0-8.0] months vs 6.5 [3.3-13.0] months, P = .01).Conclusions Our data support the guideline's ability to identify patients more likely to require early treatment escalation. However, this approach would have led to potential over- and under-treatment in a substantial proportion of patients. This underscores the importance of frequent and comprehensive monitoring, along with flexible treatment strategies that adapt to changes in disease status. In a historic nationwide cohort of patients with pediatric Crohn's disease categorized as high or low risk using the 2021 ECCO-ESPGHAN

关键词： Interleukin   IL-17D   Immune regulation   Chub mackerel  

摘要： Interleukin-17D (IL-17D) is a pro-inflammatory cytokine implicated in T helper 17 cell-mediated immune responses. Although its role in mammalian immunity is well established, its function in fish remains relatively unexplored. This study delves into the functional characteristics of IL-17D in chub mackerel (Scomber japonicus). We identified and characterized a chub mackerel IL-17D homolog (SjIL-17D) and investigated its spatial and temporal expression patterns, as well as the impact it has on downstream gene expression, apoptosis, cell proliferation, and nitric oxide (NO) production. SjIL-17D exhibited a wide tissue distribution, showing the highest expression in the blood, followed by the brain and skin. Upon immune challenges with polyinosinic:polycytidylic acid, lipopolysaccharide (LPS), Vibrio harveyi, and Streptococcus iniae, SjIL-17D expression was significantly upregulated in the blood. Functional analysis revealed that recombinant SjIL-17D (rSjIL-17D) stimulated the expression of pro-inflammatory cytokines, transcription factors, mitogen-activated protein kinases, and antiviral response genes in fish cell lines. Furthermore, rSjIL-17D attenuated LPS-induced apoptosis, promoted M1 macrophage polarization, and enhanced wound healing. Additionally, rSjIL-17D was found to stimulate NO production in macrophages and exhibit antiviral activity against viral hemorrhagic septicemia virus. These findings collectively demonstrate the crucial role that IL-17D plays in regulating immune responses in chub mackerel, providing valuable insights into the innate immune mechanisms of this economically important fish species.

摘要： The human leukocyte antigen (HLA) region is highly diverse and plays a crucial role in immune regulation and antigen presentation. Accurate HLA typing is essential for understanding disease susceptibility, transplantation compatibility, and pharmacogenetics. However, its application in African descent populations is challenging due to complex linkage disequilibrium patterns and the lack of ancestry-matched populations in HLA reference panels. Here, we leveraged the latest whole-genome sequencing (WGS) data from UK Biobank African individuals to perform better HLA genotyping, and further utilized allelic and haplotypic data to explore population genetics patterns of this region. With WGS-inferred HLA alleles, we identified specific admixture patterns (predominant West and East African and minor European ancestries) within British African population, revealing their complex evolutionary history. Not only did we reveal the genetic diversity within this population, but also highlighted its differences from African Americans, ancestral Africans, and other global populations. We further identified regional ancestry differences in the HLA genomic region, highlighting discordance between global and local admixture estimates. British Africans also presented unique HLA frequency distributions for both typical and disease-associated alleles or haplotypes. These findings emphasize the need for expanding African-specific HLA reference panel and prove better HLA typing can be achieved by coupling sequencing technologies with computational approaches. The HLA genetic characteristics observed in British Africans provide valuable insights into population-specific immune responses and susceptibility. Overall, this study advances our understanding of HLA diversity and genetic admixture in British African population, with important implications for both disease mechanism and clinical utility.

关键词： Oral squamous cell carcinoma   Interleukin-1 receptor antagonist   Type I interferon response   Interferon alpha   Interferon beta  

摘要： Interleukin-1 receptor antagonist (IL1RA) is an anti-inflammatory and anti-tumor protein, and a member of the Interleukin-1 (IL-1) family. Our previous finding showed that IL1RA is a tumor marker for oral squamous cell carcinoma (OSCC), but the exact mechanism is unknown. The present study aims to investigate the biological role of IL1RA in the progression of OSCC in vitro and in vivo and the underlying molecular mechanism. IL1RA was lowly expressed in OSCC specimens and cells, and its overexpression significantly inhibited the proliferation and migration of OSCC cell lines CAL27 and HN6. In nude mice bearing OSCC xenografts, in vivo overexpression of IL1RA significantly reduced tumor growth without influencing epithelial-mesenchymal transition (EMT). Differentially expressed genes (DEGs) in OSCC cells overexpressing IL1RA were identified by RNA sequencing (RNA-seq), and they were significantly enriched in cancer-associated signaling pathways like type I interferon response. IL1RA upregulated interferon alpha (IFNA) and interferon beta (IFNB), known for their anti-cancer properties, in OSCC cells and specimens. In conclusion, IL1RA inhibits the malignant progression of OSCC by mediating the type I interferon response.