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Exploring the Complex Relationship Between Childhood Trauma and Self-Harm

ABSTRACT Previous research has linked self-harm to adverse childhood experiences (i.e. abuse and neglect). Despite the extensive literature on self-harm, it remains of high importance to examine psychological predictors of repetitive self-harming behaviors in those who report childhood trauma. This study explored the role of maladaptive emotion regulation strategies, dissociation proneness, and borderline personality (BP) features. An international sample with n = 374 participants (N = 287, 77%, reporting intentional use of self-harm), was recruited online via relevant mental health platforms and research sites. Within an anonymous survey, participants completed the Self-harm Inventory, Childhood Trauma Questionnaire, Dissociative Experience Scale, Cognitive Emotion Regulation Questionnaire, and Personality Assessment Inventory-Borderline Personality Features Scale. Structural equation modeling (SEM) was used to explore direct and indirect effects. Self-harm was positively correlated to severity of childhood trauma, maladaptive emotion regulation strategies, dissociation, and BP features. In the path-analytical model, independent indirect effects of childhood trauma severity via self-blame, catastrophizing, dissociation, as well as BP features on self-harm were found. Maladaptive emotion regulation, dissociation proneness, and BP features all seem to be important intermediary agents in the close association between childhood trauma and self-harm.

The association between trouble sleeping and obesity among the U.S. elderly from NHANES 2011–2014: A moderated mediation model of depressive symptoms and cognitive function

BackgroundStudies have shown a close association between trouble sleeping and obesity in older adults. However, no studies have explored the underlying mechanism of this relationship. The present study was designed to evaluate the roles of depressive symptoms and cognitive function in the association between trouble sleeping and obesity in older American adults. MethodsA cross-sectional study with 2575 participants (≥60 years old) in the National Health and Nutrition Examination Survey (NHANES) 2011–2014 was used for analysis. Obesity, depressive symptoms, and cognitive function (including Established Consortium for Word Learning in Alzheimer's Disease (CERAD-WL) (immediate learning and recall and delayed recall), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST)) were objectively measured, and trouble sleeping was assessed using a self-reported questionnaire. The moderated mediation analysis was conducted by Hayes' PROCESS macro. ResultsTrouble sleeping was positively associated with obesity among older adults. Depressive symptoms partially and indirectly mediated this association, and DSST moderated the association between trouble sleeping and depressive symptoms. Trouble sleeping had a lower impact on depressive symptoms in older adults with higher cognitive function. LimitationsThe cross-sectional design prevents making causal inferences, and part of self-reported information was not objective enough. ConclusionCognitive function moderated the mediation of depressive symptoms on the indirect, positive association between trouble sleeping and obesity; hence, incorporating methods to strengthen cognitive function and alleviate depressive symptoms may help weak the link between trouble sleeping and obesity among older adults.

Human Disease due to Mycobacterium bovis Linked to Free-Ranging Deer in Michigan.

A unique enzootic focus of Mycobacterium bovis in free-ranging deer was identified in northern lower Michigan in 1994, with subsequent evidence of transmission to local cattle herds. Between 2002 and 2017, 3 Michigan deer hunters with M. bovis disease were previously reported. We present 4 additional human cases linked to the zoonotic focus in deer, utilizing genomic epidemiology to confirm close molecular associations among human, deer and cattle M. bovis isolates. Identification of human tuberculosis (TB) cases with cultures of M. bovis was provided from the Michigan Department of Health and Human Services (MDHHS) tuberculosis database. Clinical review and interviews focused on risk factors for contact with wildlife and cattle. Whole genome sequences of human isolates were compared with a veterinary library of M. bovis strains to identify those linked to the enzootic focus. Three confirmed and 1 probable human case with M. bovis disease were identified between 2019 and 2022, including cutaneous disease, 2 severe pulmonary disease cases, and human-to-human transmission. The 3 human isolates had 0-3 single-nucleotide polymorphisms (SNPs) with M. bovis strains circulating in wild deer and domestic cattle in Michigan. Spillover of enzootic M. bovis from deer to humans and cattle continues to occur in Michigan. Future studies should examine the routes of transmission and degree of risk to humans through expanded epidemiological surveys. A One Health approach linking human, veterinary and environmental health should address screening for TB infection, public education, and mitigation of transmission.

Bioinformatic analysis of related immune cell infiltration and key genes in the progression of osteonecrosis of the femoral head.

Osteonecrosis of the femoral head (ONFH) is a common orthopedic condition that will prompt joint dysfunction, significantly impacting patients' quality of life. However, the specific pathogenic mechanisms underlying this disease remain elusive. The objective of this study is to examine the differentially expressed messenger RNAs (DE mRNAs) and key genes linked to ONFH, concurrently investigating the immune cell infiltration features in ONFH patients through the application of the CIBERSORT algorithm. Microarray was applied to scrutinize mRNA expression profiles in both ONFH patients and healthy controls, with data integration sourced from the GEO database. DE mRNAs were screened using the Limma method. The biological functions of DE mRNAs were explored through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, Gene Ontology (GO) functional analysis, and Gene Set Enrichment Analysis (GSEA). Additionally, support vector machine-recursive feature elimination (SVM-RFE) and the least absolute shrinkage and selection operator (LASSO) were employed to discern diagnostic biomarkers associated with the disease. Receiver operating characteristic (ROC) analysis was utilized to assess the statistical performance of the feature genes. The validation of key genes was performed using qRT-PCR in bone tissues obtained from ONFH patients and healthy controls. Osteogenic differentiation of BMSC was then performed and detected by alkaline phosphatase staining (ALP) and qRT-PCR to verify the correlation between key genes and osteogenic differentiation. Finally, immune cell infiltration analysis was executed to evaluate immune cell dysregulation in ONFH, concurrently exploring the correlation between the infiltration of immune cells and key genes. After consolidating the datasets, the Limma method revealed 107 DEGs, comprising 76 downregulated and 31 upregulated genes. Enrichment analysis revealed close associations of these DE mRNAs with functions such as cell migration, osteoblast differentiation, cartilage development and extracellular region. Machine learning algorithms further identified APOD, FBXO43 and LRP12 as key genes. ROC curves demonstrated the high diagnostic efficacy of these genes. The results of qRT-PCR showed that the expression levels of key genes were consistent with those of microarray analysis. In addition, the results of in vitro experiments showed that APOD was closely related to osteogenic differentiation of BMSC. Immune infiltration analysis suggested a close correlation between ONFH and imbalances in levels of Neutrophils, Monocytes, Macrophages M2, Dendritic cells activated and Dendritic cells resting. APOD is closely related to osteogenic differentiation of BMSCs and can be used as a diagnostic marker of ONFH. Immune cell infiltration significantly differs between controls and ONFH patients.

Association between red blood cell distribution width-to-albumin ratio and the prognosis in patients with autoimmune encephalitis: a retrospective cohort study.

Red blood cell distribution width-to-albumin ratio (RAR) is a combined new indicator reflecting immunology and has been reported to predict the prognosis of inflammation-related diseases and brain diseases. However, the association and predictive value of RAR in the prognosis of patients with autoimmune encephalitis (AE) has not been reported. This was a retrospective cohort study, and data were collected from the Henan Provincial People's Hospital. RAR was categorized according to quartile. The prognosis was assessed using the modified Rankin Scale (mRS), and an mRS score of ≥3 was defined as a poor prognosis. The logistical regression model was used to explore the association between RAR and the prognosis, with results reported as odds ratio (OR) and 95% confidence interval (CI). The predictive value of RAR was evaluated by calculating the area under the receiving operating curve (AUC), sensitivity, specificity, and accuracy. A total of 175 eligible patients were included for analysis, and 51 patients were identified as having poor prognosis. After adjusting age, cancer, other diseases, histological subtype, antiepileptic therapy, anti-tumor treatment, ICU treatment, and length of stay, RAR in the highest quartile (Q4) was found to be significantly associated with the high odds of poor prognosis (OR = 5.63, 95%CI: 1.98-16.02) compared to RAR in the lowest quartile (Q1). In addition, RAR was identified as a predictor for the prognosis of AE patients (AUC = 0.660, 95%CI: 0.574-0.746). This study found the close association and predictive value of RAR for the prognosis of AE patients, indicating that RAR might help clinicians identify high-risk populations.

Association between high-mobility group box 1 levels and preeclampsia: a systematic review and meta-analysis.

Previous studies had demonstrated that high-mobility group box 1 (HMGB1) levels were elevated in preeclampsia (PE). However, the conclusion remains controversial. This study aimed to investigate the association between blood and placenta HMGB1 levels and PE in pregnant women. After a systematic literature search, eligible literature was screened according to inclusion and exclusion criteria. Data extraction and quality assessment were performed independently by two reviewers. The extracted data were analyzed using Review Manager 5.4 and STATA 12.0 software. Subgroup analysis and meta-regression analysis were conducted to find potential sources of heterogeneity. Twelve studies were included, with a total of 1145 participants. Compared with normal pregnancies, pregnant women with PE had significantly higher blood HMGB1 levels (SMD = 1.34, 95% CI: 0.72-1.95, p < 0.0001). Similarly, the expression of placental HMGB1 in PE was higher than that in normal controls by using Western blot (MD = 0.37, 95% CI: 0.27-0.47, p < 0.00001) or immunohistochemistry (OR = 6.36, 95% CI: 1.48-27.25, p = 0.01). In addition, the blood HMGB1 levels were positively correlated with the severity of PE, with higher blood HMGB1 levels in severe PE than those in mild PE (SMD = 3.35, 95% CI: 0.63-6.06, p = 0.02). The subgroup analysis indicated a close association of blood HMGB1 with PE in the Asian group, but not in the European group. Both blood and placental HMGB1 levels in patients with PE were significantly elevated, and higher blood HMGB1 levels indicated a more serious disease condition, suggesting that higher levels of HMGB1 were associated with the risk of PE.

Magnetosheath jets at Jupiter and across the solar system

The study of jets in the Earth’s magnetosheath has been a subject of extensive investigation for over a decade due to their profound impact on the geomagnetic environment and their close connection with shock dynamics. While the variability of the solar wind and its interaction with Earth’s magnetosphere provide valuable insights into jets across a range of parameters, a broader parameter space can be explored by examining the magnetosheath of other planets. Here we report the existence of anti-sunward and sunward jets in the Jovian magnetosheath and show their close association with magnetic discontinuities. The anti-sunward jets are possibly generated by a shock–discontinuity interaction. Finally, through a comparative analysis of jets observed at Earth, Mars, and Jupiter, we show that the size of jets scales with the size of bow shock.

Novel Sustainable Alternatives for the Study of the Chemical Composition of Cork

Cork is a natural and renewable material extracted from the cork oak Quercus suber L. (1) Background: The cellular structure and chemical composition of the plant wall give cork its physical and mechanical properties. Chemically, the composition of cork is principally dominated by the presence of suberin as the main structural cell wall component and affected by its close association with other components. The usual chemical analysis of cork has been partially adapted from wood and other lignocellulosic analytical methods and it is a method with extensive procedures. This study aims to (i) find quicker and more sustainable methods for testing the cork chemical composition, (ii) conduct extraction tests using alternative techniques, (iii) optimize alternative methodologies, and (iv) validate the proposed sustainable methodologies. (2) Methods: Microwave-assisted extraction (MAE) and accelerated solvent extraction (ASE) are explored as alternative systems to the traditional method. The percentages of the extractives obtained via MAE are lower than the percentages obtained by means of the classical composition. (3) Results: However, the percentages of suberin are very similar in both methods: 46.39% in the case of the classical composition and 45.11% in the case of microwave-assisted extraction. No significant differences are observed between the content of the extractives in the dichloromethane, ethanol, and water obtained via ASE and the results obtained with the classical methodology. (4) Conclusions: MAE and ASE are faster methods; they use less solvents and provide more reproducible results than the classical chemical composition methodology. These data pave the way for novel sustainable alternatives relative to the studies of the chemical composition of cork.

Causal role of immune cells in generalized anxiety disorder: Mendelian randomization study.

Generalized anxiety disorder (GAD) is a prevalent emotional disorder that has received relatively little attention regarding its immunological basis. Recent years have seen the widespread use of high-density genetic markers such as SNPs or CNVs for genotyping, as well as the advancement of genome-wide association studies (GWAS) technologies, which have facilitated the understanding of immunological mechanisms underlying several major psychiatric disorders. Despite these advancements, the immunological basis of GAD remains poorly understood. In light of this, we aimed to explore the causal relationship between immune cells and the disease through a Mendelian randomization study. The summary information for GAD (Ncase=4,666, Ncontrol=337,577) was obtained from the FinnGen dataset. Summary statistics for the characterization of 731 immune cells, including morphological parameters (MP=32), median fluorescence intensity (MFI=389), absolute cells (AC=118), and relative cells (RC=192), were derived from the GWAS catalog. The study involved both forward MR analysis, with immune cell traits as the exposure and GAD as the outcome, and reverse MR analysis, with GAD as the exposure and immune cell traits as the outcome. We performed extensive sensitivity analyses to confirm the robustness, heterogeneity, and potential multi-biological effects of the study results. Also, to control for false positive results during multiple hypothesis testing, we adopted a false discovery rate (FDR) to control for statistical bias due to multiple comparisons. After FDR correction, GAD had no statistically significant effect on immunophenotypes. Several phenotypes with unadjusted low P-values are worth mentioning, including decreased PB/PC levels on B cells(β=-0.289, 95%CI=0.044~0.194, P=0.002), reduced PB/PC AC in GAD patients (β=-0.270, 95% CI=0.77~0.92, P=0.000), and diminished PB/PC on lymphocytes (β=-0.315, 95% CI=0.77~0.93, P=0.001). GAD also exerted a causal effect on CD27 on IgD-CD38br (β=-0.155,95%CI=0.78~0.94,P=0.002), CD20-%B cell (β= -0.105,95% CI=0.77~0.94, P=0.002), IgD-CD38br%lymphocyte(β=-0.305, 95%CI=0.79~0.95, P=0.002), FSC-A level on granulocytes (β=0.200, 95%CI=0.75~0.91, P=8.35×10-5), and CD4RA on TD CD4+(β=-0.150, 95% CI=0.82~1.02, P=0.099). Furthermore, Two lymphocyte subsets were identified to be significantly associated with GAD risk: CD24+ CD27+ B cell (OR=1.066,95%CI=1.04~1.10,P=1.237×10-5),CD28+CD4+T cell (OR=0.927, 95%CI=0.89~0.96, P=8.085×10-5). The study has shown the close association between immune cells and GAD through genetic methods, thereby offering direction for future clinical research.

Multidimensional Transcriptomics Unveils RNF34 as a Prognostic Biomarker and Potential Indicator of Chemotherapy Sensitivity in Wilms' Tumour.

Nephroblastoma, colloquially known as Wilms' tumour (WT), is the predominant malignant renal neoplasm arising in the paediatric population. Modern therapeutic approaches for WT incorporate a synergistic combination of surgical intervention, radiotherapy, and chemotherapy, which substantially ameliorate the overall patient survival rate. Despite this, the optimal sequence of chemotherapy and surgical intervention remains a matter of contention, with each strategy presenting its own strengths and weaknesses that could influence clinical decision-making. To make some headway on this clinical dilemma, we deployed a multidimensional transcriptomics integration approach by analysing bulk RNA sequencing data with 136 samples, as well as single-nucleus RNA sequencing (snRNA-seq) and paired spatial transcriptome sequencing (stRNA) data from 32 WT specimens. Our findings identified a distinct elevation of RNF34 expression within WT samples, which correlated with unfavourable prognostic outcomes. Leveraging the Genomics of Drug Sensitivity in Cancer (GDSC), we simultaneously revealed that patients with high expression of RNF34 have higher sensitivity to commonly used chemotherapy drugs for WT. Furthermore, our analysis of snRNA and stRNA data unveiled a reduced proportion of RNF34 expression in neoplastic cells after chemotherapy. Moreover, stRNA data delineated a significant association between a higher proportion of RNF34 expression in cancer cells and adverse features such as anaplastic histology and tumour recurrence. Intriguingly, we also observed a close association between elevated RNF34 expression and a characteristic exhausted tumour immune microenvironment. Collectively, our findings underscore the pivotal role of RNF34 in the prognostic prediction potential and treatment sensitivity of WT. This comprehensive analysis can potentially inform and refine clinical decision-making for WT patients and guide future studies towards the development of optimized, rational therapeutic strategies.

Lithological mapping of Nidar ophiolite complex, Ladakh using high-resolution data

Ophiolites represents a distinctive variety of igneous rock that comprises fragments of oceanic crust with the underlying mantle portion. Their mineral assemblages and distribution relation, both spatial and temporal are in close association with the complex mantle dynamics of the Earth. Nidar ophiolite complex located towards SE of Ladakh is one of such ophiolite assemblages exposed well in the Indus Suture Zone of Himalayas. It represents parts of Neo-Tethys ocean that existed during Mesozoic-Cenozoic period between continental plates of India and Eurasia. The earlier studies for Indian ophiolites are mostly field and analytical based with a limited work carried out using remote sensing techniques and that adds scope to apply this approach for further exploration of ophiolites. Advanced tools and techniques especially, hyperspectral remote sensing and machine learning based approach can be effective operational tools for exploration of ophiolites that provide assessable terrains for characterization of Earth’s mantle, serve analogs for planetary crustal rocks and also have economic significance. This study has utilized high-resolution multispectral (Landsat OLI and ASTER) and hyperspectral data from various missions including the recent PRISMA mission which has provided the first hyperspectral datasets for lithological mapping of Nidar ophiolite section. The multiple high-resolution datasets were used for identification and mapping of the various lithounits of the Nidar ophiolites together with the underlying and overlying associated rocks based on band ratioing, derived spectral compositional indices and spectral characterization. The differentiated lithounits of the Nidar ophiolites are interpreted based on spectral response of lithological units in different bands. In addition, classification based on machine learning techniques have been applied to the PRISMA data to generate a detailed classification map of the study area where the various lithological units of the ophiolites and associated rock exposures belonging to various geological formations are clearly discernible. The results have been validated from geological field visit to the study area and spectral analysis of the field samples.

Comprehensive analysis of senescence-associated genes in sepsis based on bulk and single-cell sequencing data.

Background: Sepsis is a pathological state resulting from dysregulated immune response in host during severe infection, leading to persistent organ dysfunction and ultimately death. Senescence-associated genes (SAGs) have manifested their potential in controlling the proliferation and dissemination of a variety of diseases. Nevertheless, the correlation between sepsis and SAGs remains obscure and requires further investigation. Methods: Two RNA expression datasets (GSE28750 and GSE57065) specifically related to sepsis were employed to filter hub SAGs, based on which a diagnostic model predictive of the incidence of sepsis was developed. The association between the expression of the SAGs identified and immune-related modules was analyzed employing Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) and Microenvironment Cell Populations-counter (MCP-counter) analysis. The identified genes in each cohort were clustered by unsupervised agreement clustering analysis and weighted gene correlation network analysis (WGCNA). Results: A diagnostic model for sepsis established based on hub genes (IGFBP7, GMFG, IL10, IL18, ETS2, HGF, CD55, and MMP9) exhibited a strong clinical reliability (AUC = 0.989). Sepsis patients were randomly assigned and classified by WGCNA into two clusters with distinct immune statuses. Analysis on the single-cell RNA sequencing (scRNA-seq) data revealed high scores of SAGs in the natural killer (NK) cells of the sepsis cohort than the healthy cohort. Conclusion: These findings suggested a close association between SAGs and sepsis alterations. The identified hub genes had potential to serve as a viable diagnostic marker for sepsis.

Mineralogy and element geochemistry of the Bayan Obo (China) carbonatite dykes: Implications for REE mineralization

The Bayan Obo deposit in China is the world's largest rare earth element (REE) deposit. However, its genesis remains highly debated. It is considered to have a close genetic association with carbonatites because of the presence of nearby carbonatite dykes and the geochemical similarities between these dykes and the orebody. However, the evolution of these dykes and associated REE mineralization remain poorly understood, hindering the origin interpretation of the deposit. This study provides new insights into the petrography, mineralogy, and major- and trace-element geochemistry of these carbonatite dykes and rock-forming minerals to reconstruct the magmatic evolution and REE enrichment of the deposit. The dykes evolved from dolomite- to calcite-dominated (i.e., calcite and fenitized calcite) carbonatites, and their REE content remarkably increased, with the latter developing strong REE mineralization. The dolomites and minor calcites within the dolomite carbonatites exhibit a steep negative slope with high light REE (LREE) enrichment and heavy REE (HREE) depletion, similar to the whole rock. In contrast, the calcites from the calcite-dominated carbonatites exhibit flat REE patterns with HREE enrichment. Combined with previous isotopic data and our petrology, mineralogy, and geochemistry study, we propose that these rocks are derived directly from the low-degree melting of the underlying mantle source. REE mineralization may be related to the progressive crystallization of rock-forming calcites of calcite-dominated carbonatites. Monazite, bastnäsite, parisite, and huanghoite are the dominant REE minerals and exhibit intimate associations with barite and alkaline silicate minerals such as aegirine, biotite, K-feldspar, and albite. This assemblage indicates that the REE were primarily transported via REE–sulfate and REE–alkali complexes, with the latter favoring HREE, and the precipitation of alkaline silicate minerals destabilized these REE complexes, facilitating REE mineralization.

Breviscapine protects against pathological cardiac hypertrophy by targeting FOXO3a-mitofusin-1 mediated mitochondrial fusion

Forkhead box O3a (FOXO3a)-mediated mitochondrial dysfunction plays a pivotal effect on cardiac hypertrophy and heart failure (HF). However, the role and underlying mechanisms of FOXO3a, regulated by breviscapine (BRE), on mitochondrial function in HF therapy remain unclear. This study reveals that BRE-induced nuclear translocation of FOXO3a facilitates mitofusin-1 (MFN-1)-dependent mitochondrial fusion in cardiac hypertrophy and HF. BRE effectively promotes cardiac function and ameliorates cardiac remodeling in pressure overload-induced mice. In addition, BRE mitigates phenylephrine (PE)-induced cardiac hypertrophy in cardiomyocytes and fibrosis remodeling in fibroblasts by inhibiting ROS production and promoting mitochondrial fusion, respectively. Transcriptomics analysis underscores the close association between the FOXO pathway and the protective effect of BRE against HF, with FOXO3a emerging as a potential target of BRE. BRE potentiates the nuclear translocation of FOXO3a by attenuating its phosphorylation, other than its acetylation in cardiac hypertrophy. Mechanistically, over-expression of FOXO3a significantly inhibits cardiac hypertrophy and mitochondrial injury by promoting MFN-1-mediated mitochondrial fusion. Furthermore, BRE demonstrates its ability to substantially curb cardiac hypertrophy, reduce mitochondrial ROS production, and enhance MFN-1-mediated mitochondrial fusion through a FOXO3a-dependent mechanism. In conclusion, nuclear FOXO3a translocation induced by BRE presents a successful therapeutic avenue for addressing cardiac hypertrophy and HF through promoting MFN-1-dependent mitochondrial fusion.

Finger motor representation supports the autonomy in arithmetic: neuroimaging evidence from abacus training.

Researches have reported the close association between fingers and arithmetic. However, it remains unclear whether and how finger training can benefit arithmetic. To address this issue, we used the abacus-based mental calculation (AMC), which combines finger training and mental arithmetic learning, to explore the neural correlates underlying finger-related arithmetic training. A total of 147 Chinese children (75 M/72 F, mean age, 6.89 ± 0.46) were recruited and randomly assigned into AMC and control groups at primary school entry. The AMC group received 5years of AMC training, and arithmetic abilities and resting-state functional magnetic resonance images data were collected from both groups at year 1/3/5. The connectome-based predictive modeling was used to find the arithmetic-related networks of each group. Compared to controls, the AMC's positively arithmetic-related network was less located in the control module, and the inter-module connections between somatomotor-default and somatomotor-control modules shifted to somatomotor-visual and somatomotor-dorsal attention modules. Furthermore, the positive network of the AMC group exhibited a segregated connectivity pattern, with more intra-module connections than the control group. Overall, our results suggested that finger motor representation with motor module involvement facilitated arithmetic-related network segregation, reflecting increased autonomy of AMC, thus reducing the dependency of arithmetic on higher-order cognitive functions.

Shameless Dogs: Cynics and Nonhuman Animal Ethics

Abstract Various philosophical systems have been applied to questions of nonhuman animal ethics, but the ancient Cynics have been ignored despite their close association with dogs and their commitment to philosophy as a way of life. After explaining the neglect and clearing away some obstacles to treating Cynic ethics seriously, this article looks closely at Cynic shamelessness and its connection with conventions that may fail to withstand critical scrutiny. It then goes on to discuss Diogenes’ relationship with food conventions and explores what ancient Cynicism has to offer when it comes to thinking through virtuous relationships between humans and other animals.

Association between gut microbiota and glioblastoma: a Mendelian randomization study.

Background: Glioblastoma (GBM) is the most prevalent malignant brain tumor, significantly impacting the physical and mental wellbeing of patients. Several studies have demonstrated a close association between gut microbiota and the development of GBM. In this investigation, Mendelian randomization (MR) was employed to rigorously evaluate the potential causal relationship between gut microbiota and GBM. Methods: We utilized summary statistics derived from genome-wide association studies (GWAS) encompassing 211 gut microbiota and GBM. The causal association between gut microbiota and GBM was scrutinized using Inverse Variance Weighted (IVW), MR-Egger, and Weighted Median (WM) methods. Cochrane's Q statistic was employed to conduct a heterogeneity test. MR-Pleiotropic Residuals and Outliers (MR-PRESSO) were applied to identify and eliminate SNPs with horizontal pleiotropic outliers. Additionally, Reverse MR was employed to assess the causal relationship between GBM and pertinent gut microbiota. Results: The MR study estimates suggest that the nine gut microbiota remain stable, considering heterogeneity and sensitivity methods. Among these, the family.Peptostreptococcaceae and genus.Eubacterium brachy group were associated with an increased risk of GBM, whereas family.Ruminococcaceae, genus.Anaerostipes, genus.Faecalibacterium, genus.LachnospiraceaeUCG004, genus.Phascolarctobacterium, genus.Prevotella7, and genus.Streptococcus were associated with a reduced risk of GBM. Following Benjamini and Hochberg (BH) correction, family.Ruminococcaceae (OR = 0.04, 95% CI: 0.01-0.19, FDR = 0.003) was identified as playing a protective role against GBM. Conclusion: This groundbreaking study is the first to demonstrate that family.Ruminococcaceae is significantly associated with a reduced risk of GBM. The modulation of family_Ruminococcaceae for the treatment of GBM holds considerable potential clinical significance.

Alterations in leukocyte DNA methylome are associated to immunosuppression in severe clinical phenotypes of septic patients.

Sepsis patients experience a complex interplay of host pro- and anti-inflammatory processes which compromise the clinical outcome. Despite considering the latest clinical and scientific research, our comprehension of the immunosuppressive events in septic episodes remains incomplete. Additionally, a lack of data exists regarding the role of epigenetics in modulating immunosuppression, subsequently impacting patient survival. To advance the current understanding of the mechanisms underlying immunosuppression, in this study we explored the dynamics of DNA methylation using the Infinium Methylation EPIC v1.0 BeadChip Kit in leukocytes from patients suffering from sepsis, septic shock, and critically ill patients as controls, within the first 24 h after admission in the Intensive Care Unit of a tertiary hospital. Employing two distinct analysis approaches (DMRcate and mCSEA) in comparing septic shock and critically ill patients, we identified 1,256 differentially methylated regions (DMRs) intricately linked to critical immune system pathways. The examination of the top 100 differentially methylated positions (DMPs) between septic shock and critically ill patients facilitated a clear demarcation among the three patient groups. Notably, the top 6,657 DMPs exhibited associations with organ dysfunction and lactate levels. Among the individual genes displaying significant differential methylation, IL10, TREM1, IL1B, and TNFAIP8 emerged with the most pronounced methylation alterations across the diverse patient groups when subjected to DNA bisulfite pyrosequencing analysis. These findings underscore the dynamic nature of DNA methylation profiles, highlighting the most pronounced alterations in patients with septic shock, and revealing their close association with the disease.

Association between Perceived Activity Restriction Due to People's Perception of Aging and Unmet Medical Needs among Middle-Aged and Elderly People: A Population-Based Study.

Background and Objectives: The older members of a population might experience unmet medical needs, despite desiring medical care due to activity limitations driven by their perception of aging. This study conducted a cross-sectional analysis of the association between perceived activity restriction (PAR) due to people's own perception of aging and unmet medical needs (UMN) in late middle-aged and older Koreans based on the Korean National Health and Nutrition Examination Survey (KNHANES). Materials and Methods: The 2016-2020 KNHANES was used to analyze a total of 2008 participants among groups aged 45 years or older by applying individual weights imposed from the raw data. The independent variable of PAR was assessed using self-reported questionnaires based on the global activity limitation indicator. Also, the dependent variable of UMN, referring to the state in which a patient's medical care or service was insufficient, inadequate, or lacking, was assessed using a single question. After excluding missing values, the data on 2008 individuals were analyzed using a chi-square test, weighted logistic regression, and a stratified analysis of gender, age, and the presence of chronic illnesses. Results: The group that experienced PAR had an OR 2.13 higher (odds ratio [OR]: 2.13; 95% confidence interval [CI]: 1.27-3.56) to present UMN than the group that did not experience PAR. Furthermore, the results of the stratified analysis indicated that, in the group of female participants with chronic illness and in the group of elderly people, experiencing PAR was associated with a higher experience of UMN. Conclusions: There was a close association between PAR and UMN. In particular, when PAR occurred in the group of female participants with chronic illness and in the group of elderly people, the incidence rate of UMN was also found to be high. This finding highlights the need for policies and institutional measures to reduce UMN within vulnerable groups with an increased risk of medical inaccessibility due to activity restriction.

Shigella virulence protein VirG is a broadly protective antigen and vaccine candidate

Diarrhea caused by Shigella has been associated with high morbidity and mortality in young children worldwide. There are no licensed vaccines, and those clinically advanced have restricted coverage as they elicit serotype-specific immunity while disease is caused by multiple circulating serotypes. Our group had previously reported a close association between serum antibodies to the Shigella virulence factor VirG (or IcsA) and clinical protection in infected individuals. VirG is highly conserved among Shigella strains and appealing as a broad-spectrum vaccine candidate. In this study, we investigated the immunogenicity and protective capacity of VirG as a subunit vaccine in mice. The surface-exposed alpha (α) domain of VirG (VirGα) was produced as a recombinant protein. This region has almost identical immune reactivity to full-length VirG. Administered intramuscularly with alum, VirGα elicited robust immune responses and high protective efficacy against S. flexneri 2a and S. sonnei. Almost complete protection was afforded by VirGα given intranasally with the E. coli double mutant heat-labile toxin (dmLT). VirGα-specific antibodies recognized VirG expressed on live Shigella, and blocked Shigella adhesion and invasion to human colonic cells. These results show for the first time that VirGα is a promising cross-protective vaccine candidate to prevent Shigella infection.