bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intestinal permeability is associated with aggravated inflammation and myofibroblast accumulation in Graves’ orbitopathy: the MicroGO study
Authors: Fenneman Aline C. , van der Spek Anne H. , Hartstra Annick , Havik Stefan , Salonen Anne , de Vos Willem M. , Soeters Maarten R. , Saeed Peeroz , Nieuwdorp Max , Rampanelli Elena 
Published: December 2023

BackgroundGraves’ disease (GD) and Graves’ orbitopathy (GO) result from ongoing stimulation of the TSH receptor due to autoantibodies acting as persistent agonists. Orbital pre-adipocytes and fibroblasts also express the TSH receptor, resulting in expanded retro-orbital tissue and causing exophthalmos and limited eye movement. Recent studies have shown that GD/GO patients have a disturbed gut microbiome composition, which has been associated with increased intestinal permeability. This study hypothesizes that enhanced intestinal permeability may aggravate orbital inflammation and, thus, increase myofibroblast differentiation and the degree of fibrosis.MethodsTwo distinct cohorts of GO patients were studied, one of which was a unique cohort consisting of blood, fecal, and retro-orbital tissue samples. Intestinal permeability was assessed by measuring serum lipopolysaccharide-binding protein (LBP), zonulin, TLR5, and TLR9 ligands. The influx of macrophages and accumulation of T-cells and myofibroblast were quantified in orbital connective tissue. The NanoString immune-oncology RNA targets panel was used to determine the transcriptional profile of active fibrotic areas within orbital sections.ResultsGO patients displayed significantly higher LBP serum concentrations than healthy controls. Within the MicroGO cohort, patients with high serum LBP levels also showed higher levels of zonulin and TLR5 and TLR9 ligands in their circulation. The increased intestinal permeability was accompanied by augmented expression of genes marking immune cell infiltration and encoding key proteins for immune cell adhesion, antigen presentation, and cytokine signaling in the orbital tissue. Macrophage influx was positively linked to the extent of T cell influx and fibroblast activation within GO-affected orbital tissues. Moreover, serum LBP levels significantly correlated with the abundance of specific Gram-negative gut bacteria, linking the gut to local orbital inflammation.ConclusionThese results indicate that GO patients have enhanced intestinal permeability. The subsequent translocation of bacterial compounds to the systemic circulation may aggravate inflammatory processes within the orbital tissue and, as a consequence, augment the proportion of activated myofibroblasts, which actively secrete extracellular matrix leading to retro-orbital tissue expansion. These findings warrant further exploration to assess the correlation between specific inflammatory pathways in the orbital tissue and the gut microbiota composition and may pave the way for new microbiota-targeting therapies.
Total bilirubin and bilirubin-to-triglycerides ratio predict changes in glycated hemoglobin in healthy children
Authors: Puerto-Carranza Elsa , Nuevo-Casals Silvia , Roca-Portella Berta , Mas-Parés Berta , Gómez-Vilarrubla Ariadna , Carreras-Badosa Gemma , Niubó Maria , Prats-Puig Anna , de Zegher Francis , Ibáñez Lourdes , Bassols Judit , López-Bermejo Abel 
Published: December 2023

ObjectiveBilirubin and triglycerides can regulate insulin secretion and glucose uptake. The aim of our study is to analyze associations between total bilirubin (TB) and the bilirubin-to-triglycerides ratio (BTR) with metabolic markers in healthy prepubertal children.MethodsSubjects were 246 healthy children (mean age 8), of whom 142 (58%) were reevaluated 4 years later (mean age 12). The subjects were stratified according to age into three groups (&lt;7.8 years; 7.8-9.6 years; and &gt;9.6 years; n=82 each) at baseline and into two groups (&lt;12.9 years and ≥12.9 years; n=71 each) at follow-up. Anthropometrics and laboratory parameters [TB and its fractions (direct and indirect bilirubin), triglycerides, HDL-cholesterol, glucose, insulin, HOMA-IR, HOMA-B and glycated hemoglobin (HbA1c)] were assessed at both baseline and follow-up.ResultsTB and BTR showed independent and negative association with baseline and follow-up HbA1c. These associations were stronger for BTR and in the highest age group. No independent associations were observed with HOMA-IR or HOMA-B.ConclusionTB and BTR are independently associated with HbA1c and predict its changes over time in healthy children. Our results indicate that TB and BTR may be useful parameters in studies of glucose tolerance in healthy children.
Dermatophagoides farinae microRNAs released to external environments via exosomes regulate inflammation-related gene expression in human bronchial epithelial cells
Authors: He Kaiyue , Yang Ting , Yu Jinyan , Zang Xiao , Jiang Shangde , Xu Shuyue , Liu Jiaxi , Xu Zuyu , Wang Wei , Hong Shanchao 
Published: December 2023

BackgroundDermatophagoides farinae (DFA) is an important species of house dust mites (HDMs) that causes allergic diseases. Previous studies have focused on allergens with protein components to explain the allergic effect of HDMs; however, there is little knowledge on the role of microRNAs (miRNAs) in the allergic effect of HDMs. This study aimed to unravel the new mechanism of dust mite sensitization from the perspective of cross-species transport of extracellular vesicles-encapsulated miRNAs from HDMs.MethodsSmall RNA (sRNA) sequencing was performed to detect miRNAs expression profiles from DFA, DFA-derived exosomes and DFA culture supernatants. A quantitative fluorescent real-time PCR (qPCR) assay was used to detect miRNAs expression in dust specimens. BEAS-2B cells endocytosed exosomes were modeled in vitro to detect miRNAs from DFA and the expression of related inflammatory factors. Representative dfa-miR-276-3p and dfa-novel-miR2 were transfected into BEAS-2B cells, and then differentially expressed genes (DEGs) were analyzed by RNA sequencing. Protein-protein interaction (PPI) network analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) terms enrichment analyses were performed on the first 300 nodes of DEGs.ResultssRNA sequencing identified 42 conserved miRNAs and 66 novel miRNAs in DFA, DFA-derived exosomes, and DFA culture supernatants. A homology analysis was performed on the top 18 conserved miRNAs with high expression levels. The presence of dust mites and miRNAs from HDMs in living environment were also validated. Following uptake of DFA-derived exosomes by BEAS-2B cells, exosomes transported miRNAs from DFA to target cells and produced pro-inflammatory effects in corresponding cells. RNA sequencing identified DEGs in dfa-miR-276-3p and dfa-novel-miR2 transfected BEAS-2B cells. GO and KEGG enrichment analyses revealed the role of exosomes with cross-species transporting of DFA miRNAs in inflammatory signaling pathways, such as JAK-STAT signaling pathway, PI3K/AKT signaling pathway and IL-6-mediated signaling pathway.ConclusionOur findings demonstrate the miRNAs expression profiles in DFA for the first time. The DFA miRNAs are delivered into living environments via exosomes, and engulfed by human bronchial epithelial cells, and cross-species regulation may contribute to inflammation-related processes.
Profiling the autoantibody repertoire reveals autoantibodies associated with mild cognitive impairment and dementia
Authors: Ehtewish Hanan , Mesleh Areej , Ponirakis Georgios , Lennard Katie , Al Hamad Hanadi , Chandran Mani , Parray Aijaz , Abdesselem Houari , Wijten Patrick , Decock Julie , Alajez Nehad M. , Ramadan Marwan , Khan Shafi , Ayadathil Raheem , Own Ahmed , Elsotouhy Ahmed , Albagha Omar , Arredouani Abdelilah , Blackburn Jonathan M. , Malik Rayaz A. , El-Agnaf Omar M. A. 
Published: December 2023

BackgroundDementia is a debilitating neurological disease affecting millions of people worldwide. The exact mechanisms underlying the initiation and progression of the disease remain to be fully defined. There is an increasing body of evidence for the role of immune dysregulation in the pathogenesis of dementia, where blood-borne autoimmune antibodies have been studied as potential markers associated with pathological mechanisms of dementia.MethodsThis study included plasma from 50 cognitively normal individuals, 55 subjects with MCI (mild cognitive impairment), and 22 subjects with dementia. Autoantibody profiling for more than 1,600 antigens was performed using a high throughput microarray platform to identify differentially expressed autoantibodies in MCI and dementia.ResultsThe differential expression analysis identified 33 significantly altered autoantibodies in the plasma of patients with dementia compared to cognitively normal subjects, and 38 significantly altered autoantibodies in the plasma of patients with dementia compared to subjects with MCI. And 20 proteins had significantly altered autoantibody responses in MCI compared to cognitively normal individuals. Five autoantibodies were commonly dysregulated in both dementia and MCI, including anti-CAMK2A, CKS1B, ETS2, MAP4, and NUDT2. Plasma levels of anti-ODF3, E6, S100P, and ARHGDIG correlated negatively with the cognitive performance scores (MoCA) (r2 –0.56 to −0.42, value of p &lt; 0.001). Additionally, several proteins targeted by autoantibodies dysregulated in dementia were significantly enriched in the neurotrophin signaling pathway, axon guidance, cholinergic synapse, long-term potentiation, apoptosis, glycolysis and gluconeogenesis.ConclusionWe have shown multiple dysregulated autoantibodies in the plasma of subjects with MCI and dementia. The corresponding proteins for these autoantibodies are involved in neurodegenerative pathways, suggesting a potential impact of autoimmunity on the etiology of dementia and the possible benefit for future therapeutic approaches. Further investigations are warranted to validate our findings.
Influence of treatment-related lymphopenia on the efficacy of immune checkpoint inhibitors in lung cancer: a meta-analysis
Authors: Zhang Ye , Huang Cheng , Li Shanqing 
Published: December 2023

BackgroundTreatment-related lymphopenia (TRL) is common in patients with lung cancer, particularly in those with radiotherapy. However, the influence of TRL on the efficacy of immune checkpoint inhibitors (ICIs) for patients with lung cancer remains poorly understood. We performed a systematic review and meta-analysis to investigate the influence of TRL on survival of lung cancer patients on ICIs.MethodsIn order to accomplish the aim of the meta-analysis, a comprehensive search was conducted on databases including PubMed, Embase, Cochrane Library, and the Web of Science to identify observational studies with longitudinal follow-up. The Cochrane Q test was employed to evaluate heterogeneity among the included studies, while the I2 statistic was estimated. Random-effects models were utilized to merge the results, considering the potential impact of heterogeneity.ResultsTen cohort studies with 1130 lung cancer patients who were treated with ICIs were included. Among them, 427 (37.8%) had TRL. Pooled results showed that compared to patients without TRL, patients with TRL were associated with poor progression-free survival (hazard ratio [HR]: 2.05, 95% confidence interval [CI]: 1.62 to 2.60, p &lt; 0.001; I2 = 22%) and overall survival (HR: 2.69, 95% CI: 2.10 to 3.43, p &lt; 0.001; I2 = 0%). Sensitivity analysis limited to patients with non-small cell lung cancer showed similar results (HR: 2.66 and 2.62, both p &lt; 0.05). Moreover, subgroup analyses according to the diagnostic criteria of TRL, regression analysis model (univariate or multivariate), and indications of ICIs (for locally advanced or advanced lung cancer) showed consistent results (p for subgroup difference all &gt; 0.05).ConclusionTRL was associated with poor survival of lung cancer patients who were treated with ICIs.
Examining the mediating effects of motivation between job insecurity and innovative behavior using a variable-centered and a person-centered approach
Authors: Ma Bing , Zhou Yarong , Lassleben Hermann , Ma Guimei , Yang Rong 
Published: December 2023

IntroductionThe fierce market competition environment makes employees feel insecure at work. While it is difficult for enterprises to provide employees with a sense of security, they have to rely on employees’ innovative behavior to seek competitive advantage. Therefore, this study focuses on how employees engage in innovative behavior when they face job insecurity.MethodsUsing a variable-centered approach, this study aims to examine the mediating effects of intrinsic and impression management motivation in the relationship between quantitative and qualitative job insecurity and innovative behavior, including proactive and reactive innovative behavior. In addition, a person-centered approach is used to investigate whether it is possible to distinguish different combinations of quantitative and qualitative job insecurity, and examine the effect of these job insecurity profiles on motivation and innovative behavior. We used 503 data sets collected via the Credamo platform in China into the data analysis.ResultsThe study found that quantitative job insecurity affects proactive and reactive innovative behavior through impression management motivation and that qualitative job insecurity affects proactive and reactive innovative behavior through intrinsic and impression management motivation. In addition, three job insecurity profiles were identified: balanced high job insecurity, balanced low job insecurity, and a profile dominated by high quantitative job insecurity, all of which have significantly different effects on motivation and innovative behavior.DiscussionThis study contributes to provide new insights into the relationship between job insecurity and innovative behavior and compensate for the limitation of the traditional variable-centered approach that cannot capture heterogeneity within the workforce.
The efficacy of mindfulness-based interventions on mental health among university students: a systematic review and meta-analysis
Authors: Zuo Xinyi , Tang Yong , Chen Yifang , Zhou Zhimiao 
Published: December 2023

IntroductionWe aimed to estimate the effect of mindfulness therapy on mental health.MethodsTwo researchers searched 12 databases to identify relevant trials that were published from 1 January 2018 to 1 May 2023. We performed a meta-analysis to determine the effect of mindfulness therapy on depression, which was measured by the Beck Depression Inventory (BDI), Patient Health Questionnaire-9 (PHQ-9), Quick Inventory of Depressive Symptomatology (QIDS), Hamilton Depression Rating Scale (HDRS), Patient-Reported Outcomes Measurement Information System (PROMIS), Hospital Anxiety and Depression Scale (HADS), and Depression Anxiety Stress Scales (DASS); anxiety, which was measured by the Beck Anxiety Inventory (BAI), PROMIS, and DASS, Generalized Anxiety Disorder-7 (GAD-7); stress, which was measured by the Perceived Stress Scale (PSS), DASS, and GAD-7; mindfulness, which was measured by the GAD-7, Five Facet Mindfulness Questionnaire (FFMQ), Mindful Attention Awareness Scale (MAAS), Short Form-12 Mental Component Score (SF-12 MCS) and Short Form-12 Physical Component Score (SF-12 PCS); and sleep quality, which was measured by the Pittsburgh Sleep Quality Index (PSQI). After screening studies based on the inclusion and exclusion criteria, 11 randomized controlled trials (RCTs) involving 1,824 participants were ultimately included.ResultsAll these studies demonstrated positive effects of mindfulness therapy on depression (SMD = −0.33, 95% CI: [−0.44, −0.22], p &lt; 0.00001, I2 = 29%), anxiety (SMD = −0.35, 95% CI: [−0.46, −0.25], p &lt; 0.00001, I2 = 40%), stress (SMD = −0.39, 95% CI: [−0.48, −0.29], p &lt; 0.00001, I2 = 69%) and sleep quality scores (SMD = −0.81, 95% CI: [−1.54, −0.09], p = 0.03, I2 = 0%). However, there was no significant difference in mindfulness (SMD = −0.12, 95% CI: [−0.36, −0.12], p = 0.34, I2 = 34%) between the mindfulness therapy group and the control group.DiscussionIn future studies, it is necessary to consider the investigation on whether the strategies of improving the mindfulness therapy in adherence and fidelity can work on the improvement of the outcomes in mental health.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, https://www.crd.york.ac.uk/PROSPERO/, identifier [CRD42023469301].
Modern glucose-lowering drugs in liver transplant recipients: improvement in weight, glycemic control, and potentially allograft steatosis
Authors: Atthota Srilakshmi , Joyal Kayla , Cote Mariesa , Scalzo Riley , Singh Ruby , Consul Nikita , Kilcoyne Aoife , Bethea Emily D. , Dageforde Leigh Anne 
Published: December 2023

IntroductionRecurrent allograft steatosis occurs in one-third of transplanted livers. Antidiabetic agents like glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium-glucose cotransporter type-2 (SGLT2) inhibitors are effective in the management of obesity and hepatic steatosis in the general population; however, there is limited evidence supporting their use in allograft steatosis. We aimed to evaluate their effects on steatosis, body weight, and glycemic control in liver transplant recipients at our institution.MethodsIn this single-center retrospective cohort study of liver transplant recipients currently on a GLP1RA or SGLT2 inhibitor (transplanted 2015–2022), we compared clinical and radiological data before medication use and at follow-up. Differences were compared using Wilcoxon signed-rank test.ResultsThirty-seven liver transplant recipients were taking the agents. Diabetes was the most common indication (n = 33) followed by obesity (n = 4). Median follow up was 427 days (301,798). Among those with documented steatosis (n = 21), steatosis improved in 5, worsened in 4, remained unchanged in 1, and change could not be evaluated in 11 due to lack of comparable pre and post imaging. Average weight loss was 3.2 kg (p &lt; 0.001) and BMI decreased by 1.2 kg/m2 (p &lt; 0.001). Hemoglobin A1c decreased by 0.6 mmol/mol (p = 0.0014), insulin requirement reduced by 7 units/day (p = 0.02), and there was no change in additional antidiabetic medications.DiscussionGLP1RA and SGLT-2 inhibitors are tolerated in transplant patients and result in weight loss and better glycemic control. They are promising agents to treat recurrent or de-novo liver allograft steatosis, but further research is needed to evaluate long-term outcomes in liver transplant recipients.
Environmental chemical exposures and mental health outcomes in children: a narrative review of recent literature
Authors: James Ashley A. , OShaughnessy Katherine L. 
Published: December 2023

Background: Mental health is an important factor for children’s overall wellbeing. National health statistics show that millions of children are diagnosed with mental health disorders every year, and evidence from studies on chemical pollutants like lead and bisphenols indicate that environmental exposures are linked to mental health illnesses in youth. However, the relationship between children’s mental health and the environment is not well understood. This paper aims to review recent literature on prenatal and/or childhood environmental chemical exposures and mental health problems related to mood, anxiety, and behavior. This work also identifies areas of insufficient data and proposes suggestions to fill the data gaps.Methods: A narrative review was performed by searching Google Scholar and PubMed for literature published in the last 6 years (2017–2022), using search terms related to children, mental health, and environmental chemical exposure. Additional relevant studies were identified by screening the references in these papers.Results: A total of 29 studies are included in this review and results are summarized by chemical category: heavy metals, endocrine-disrupting chemicals, and pesticides. The majority of studies reported positive and significant associations between chemical exposures and child mental health outcomes including internalizing and externalizing behaviors.Conclusion: This review demonstrates that there is a growing body of literature that suggests developmental exposure to some environmental chemicals increases a child’s risk of mood, anxiety, and behavior problems. Future research should expand on these findings to understand cumulative impacts, chemical mixtures, neurotoxic mechanisms, sex differences, and windows of vulnerability.
Lipid Profile in Olympic Athletes: Proposal for a “Lipid Athlete Score” as a Clinical Tool to Identify High-Risk Athletes
Authors: Di Gioia Giuseppe , Buzzelli Lorenzo , Maestrini Viviana , Nenna Antonio , Monosilio Sara , Squeo Maria Rosaria , Lemme Erika , Pelliccia Antonio 
Published: December 2023

Dyslipidemia is a major risk factor for atherosclerosis. Identification of dyslipidemia in athletes has raised interest in establishing preventive strategies and reducing cardiovascular (CV) events. Nowadays, targets or “scores” for athletes are undefined. The aim of our study was to create a “Lipid Athlete Score” based on lipid parameters and derive score indexes to identify high-risk athletes. We retrospectively enrolled 957 Olympic athletes practicing different sporting disciplines (power, skills, endurance, and mixed), analyzing their CV profiles and anthropometrics; 55.4% were male, the mean age was 27.1 ± 5 years, and the mean body mass index (BMI) was 23.1 ± 3.2 kg/m2. Three hundred and forty-three athletes (35.8%) were dyslipidemic (LDL ≥ 115 mg/dL or LDL/HDL ≥ 1.90). Multivariate analysis revealed the following: male p = 0.001, OR 1.88 [0.41–2.51], familiarity for dyslipidemia p = 0.001, OR 2.82 [1.72–4.59], BMI ≥ 30 kg/m2 p = 0.001, OR 2.53 [1.46–4.38], and fat mass p = 0.001, OR 2.29 [1.38–3.80] were significant. Endurance athletes presented the lowest CV risk. We proposed a lipid athlete score including major (LDL ≥ 115 mg/dL and LDL/HDL ≥ 1.90) and minor criteria (male, BMI > 30 kg/m2 or fat mass >22% for males and 32% for females, familiarity for dyslipidemia, and conventional CV risk factors). Twelve athletes (1.2%) were at high risk, 150 athletes (15.7%) at medium risk, 171 athletes (17.9%) at low risk, and 624 (65.2%) were at no risk. Dyslipidemia is very common in elite athletes. We have defined a specific lipid athlete score based on lipid parameters and derived score indexes for the stratification of risk. In accordance with this tool, a substantial proportion of athletes (16.9%) were at medium-to-high risk and need early preventive strategies to improve their lipid profiles and reduce the future development of atherosclerotic CV diseases.