bluuebunny/crossref_metadata_2025_split huggingface dataset:
The extracellular serine protease from Staphylococcus epidermidis elicits a type 2-biased immune response in atopic dermatitis patients
Authors: Abdurrahman Goran , Pospich Rebecca , Steil Leif , Gesell Salazar Manuela , Izquierdo González Juan José , Normann Nicole , Mrochen Daniel , Scharf Christian , Völker Uwe , Werfel Thomas , Bröker Barbara M. , Roesner Lennart M. , Gómez-Gascón Lidia 
Published: June 2024

BackgroundAtopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease with skin barrier defects and a misdirected type 2 immune response against harmless antigens. The skin microbiome in AD is characterized by a reduction in microbial diversity with a dominance of staphylococci, including Staphylococcus epidermidis (S. epidermidis).ObjectiveTo assess whether S. epidermidis antigens play a role in AD, we screened for candidate allergens and studied the T cell and humoral immune response against the extracellular serine protease (Esp).MethodsTo identify candidate allergens, we analyzed the binding of human serum IgG4, as a surrogate of IgE, to S. epidermidis extracellular proteins using 2-dimensional immunoblotting and mass spectrometry. We then measured serum IgE and IgG1 binding to recombinant Esp by ELISA in healthy and AD individuals. We also stimulated T cells from AD patients and control subjects with Esp and measured the secreted cytokines. Finally, we analyzed the proteolytic activity of Esp against IL-33 and determined the cleavage sites by mass spectrometry.ResultsWe identified Esp as the dominant candidate allergen of S. epidermidis. Esp-specific IgE was present in human serum; AD patients had higher concentrations than controls. T cells reacting to Esp were detectable in both AD patients and healthy controls. The T cell response in healthy adults was characterized by IL-17, IL-22, IFN-γ, and IL-10, whereas the AD patients’ T cells lacked IL-17 production and released only low amounts of IL-22, IFN-γ, and IL-10. In contrast, Th2 cytokine release was higher in T cells from AD patients than from healthy controls. Mature Esp cleaved and activated the alarmin IL-33.ConclusionThe extracellular serine protease Esp of S. epidermidis can activate IL-33. As an antigen, Esp elicits a type 2-biased antibody and T cell response in AD patients. This suggests that S. epidermidis can aggravate AD through the allergenic properties of Esp.
Exploring gut microbiota’s role in rheumatic valve disease: insights from a Mendelian randomization study and mediation analysis
Authors: Chen Xiwei , Hu Guangwen , Ning Dong , Wang Daxin 
Published: June 2024

BackgroundInvestigating the relationship between gut microbiota and Rheumatic Valve Disease (RVD) is crucial for understanding the disease’s etiology and developing effective interventions. Our study adopts a novel approach to examine the potential causal connections between these factors.MethodsUtilizing a two-sample Mendelian Randomization (MR) framework, we incorporated a multi-variable MR (MVMR) strategy to assess the mediatory mechanisms involved. This approach involved analyzing data from the MiBioGen consortium for gut microbiota and the FinnGen for RVD, among other sources. Instrumental variables (IVs) were carefully selected based on rigorous MR principles, and statistical analysis was conducted using bidirectional two-sample MR, such as inverse variance-weighted (IVW), weighted median, MR-Egger regression and MR Steiger Test methods. The MR-PRESSO strategy was employed for outlier detection, and MVMR was used to untangle the complex relationships between multiple microbiota and RVD.ResultsOur analysis highlighted several gut microbiota classes and families with potential protective effects against RVD, including Lentisphaerae, Alphaproteobacteria, and Streptococcaceae. In contrast, certain genera, such as Eubacterium eligens and Odoribacter, were identified as potential risk factors. The MVMR analysis revealed significant mediation effects of various immune cell traits and biomarkers, such as CD4-CD8- T cells, CD3 on Terminally Differentiated CD8+ T cell and Pentraxin-related protein PTX, elucidating the complex pathways linking gut microbiota to RVD.ConclusionThis study underscores the intricate and potentially causal relationship between gut microbiota and RVD, mediated through a range of immune and hormonal factors. The use of MVMR in our methodological approach provides a more comprehensive understanding of these interactions, highlighting the gut microbiota’s potential as therapeutic targets in RVD management. Our findings pave the way for further research to explore these complex relationships and develop targeted interventions for RVD.
Transcriptomic profiling of thymic dysregulation and viral tropism after neonatal roseolovirus infection
Authors: Belean Andrei , Xue Eden , Cisneros Benjamin , Roberson Elisha D. O. , Paley Michael A. , Bigley Tarin M. 
Published: June 2024

IntroductionHerpesviruses, including the roseoloviruses, have been linked to autoimmune disease. The ubiquitous and chronic nature of these infections have made it difficult to establish a causal relationship between acute infection and subsequent development of autoimmunity. We have shown that murine roseolovirus (MRV), which is highly related to human roseoloviruses, induces thymic atrophy and disruption of central tolerance after neonatal infection. Moreover, neonatal MRV infection results in development of autoimmunity in adult mice, long after resolution of acute infection. This suggests that MRV induces durable immune dysregulation.MethodsIn the current studies, we utilized single-cell RNA sequencing (scRNAseq) to study the tropism of MRV in the thymus and determine cellular processes in the thymus that were disrupted by neonatal MRV infection. We then utilized tropism data to establish a cell culture system.ResultsHerein, we describe how MRV alters the thymic transcriptome during acute neonatal infection. We found that MRV infection resulted in major shifts in inflammatory, differentiation and cell cycle pathways in the infected thymus. We also observed shifts in the relative number of specific cell populations. Moreover, utilizing expression of late viral transcripts as a proxy of viral replication, we identified the cellular tropism of MRV in the thymus. This approach demonstrated that double negative, double positive, and CD4 single positive thymocytes, as well as medullary thymic epithelial cells were infected by MRV in vivo. Finally, by applying pseudotime analysis to viral transcripts, which we refer to as “pseudokinetics,” we identified viral gene transcription patterns associated with specific cell types and infection status. We utilized this information to establish the first cell culture systems susceptible to MRV infection in vitro.ConclusionOur research provides the first complete picture of roseolovirus tropism in the thymus after neonatal infection. Additionally, we identified major transcriptomic alterations in cell populations in the thymus during acute neonatal MRV infection. These studies offer important insight into the early events that occur after neonatal MRV infection that disrupt central tolerance and promote autoimmune disease.
Circadian rhythm disruption-mediated downregulation of Bmal1 exacerbates DSS-induced colitis by impairing intestinal barrier
Authors: Zhang Zhongchao , Li Wanneng , Han Xu , Tian Dean , Yan Wei , Liu Mei , Cao Li 
Published: June 2024

BackgroundCircadian rhythm disruption (CRD) is thought to increase the risk of inflammatory bowel disease. The deletion of Bmal1, a core transcription factor, leads to a complete loss of the circadian rhythm and exacerbates the severity of dextran sodium sulfate (DSS)-induced colitis in mice. However, the underlying mechanisms by which CRD and Bmal1 mediate IBD are still unclear.MethodsWe used a CRD mouse model, a mouse colitis model, and an in vitro model of colonic epithelial cell monolayers. We also knocked down and overexpressed Bmal1 in Caco-2 cells by transfecting lentivirus in vitro. The collected colon tissue and treated cells were assessed and analyzed using immunohistochemistry, immunofluorescence staining, quantitative reverse transcription-polymerase chain reaction, western blot, flow cytometry, transmission electron microscopy, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling staining.ResultsWe found that CRD mice with downregulated Bmal1 expression were more sensitive to DSS-induced colitis and had more severely impaired intestinal barrier function than wild-type mice. Bmal1-/- mice exhibited more severe colitis, accompanied by decreased tight junction protein levels and increased apoptosis of intestinal epithelial cells compared with wild-type mice, which were alleviated by using the autophagy agonist rapamycin. Bmal1 overexpression attenuated Lipopolysaccharide-induced apoptosis of intestinal epithelial cells and impaired intestinal epithelial cells barrier function in vitro, while inhibition of autophagy reversed this protective effect.ConclusionThis study suggests that CRD leads to the downregulation of Bmal1 expression in the colon, which may exacerbate DSS-induced colitis in mice, and that Bmal1 may serve as a novel target for treating inflammatory bowel disease.
Distinct metabolomic and lipidomic profiles in serum samples of patients with primary sclerosing cholangitis
Authors: Fererberger Tanja , Buechler Christa , Kandulski Arne , Elger Tanja , Loibl Johanna , Schmid Stephan , Sommersberger Stefanie , Gunawan Stefan , Zundler Sebastian , Huss Muriel , Bettenworth Dominik , Kempa Sally , Weidlich Simon , Föh Bandik , Huang Xinyu , Grzegorzek Marcin , Derer-Petersen Stefanie , Günther Ulrich L. , Marquardt Jens U. , Kunst Claudia , Gülow Karsten , Müller Martina , Sina Christian , Schmelter Franziska , Tews Hauke C. 
Published: June 2024

IntoductionIdentification of specific metabolome and lipidome profile of patients with primary sclerosing cholangitis (PSC) is crucial for diagnosis, targeted personalized therapy, and more accurate risk stratification.MethodsNuclear magnetic resonance (NMR) spectroscopy revealed an altered metabolome and lipidome of 33 patients with PSC [24 patients with inflammatory bowel disease (IBD) and 9 patients without IBD] compared with 40 age-, sex-, and body mass index (BMI)-matched healthy controls (HC) as well as 64 patients with IBD and other extraintestinal manifestations (EIM) but without PSC.ResultsIn particular, higher concentrations of pyruvic acid and several lipoprotein subfractions were measured in PSC in comparison to HC. Of clinical relevance, a specific amino acid and lipid profile was determined in PSC compared with IBD and other EIM.DiscussionThese results have the potential to improve diagnosis by differentiating PSC patients from HC and those with IBD and EIM.
Lipid safety of tenofovir alafenamide during 96-week treatment in treatment-naive chronic hepatitis B patients
Authors: Zhao Wenjuan , Liu Yi , Zhang Mengdi , Cui Zixin , Qu Zhan , Li Yiyang , Wan Meijuan , Wang Wen , Chen Yunru , Shi Lei , Li Jianzhou , Ye Feng 
Published: June 2024

BackgroundThis study was aimed at investigating the dynamics of lipids and the effect of TAF on the lipid profile of patients including fatty liver disease in CHB patients.MethodsThe data of TC, LDL-c, HDL-c, TG, and TC/HDL ratio were collected at baseline, 24 weeks, 48 weeks, 72 weeks, and 96 weeks. CHB patients with fatty liver at baseline were further analyzed in a subgroup.ResultsA total of 137 CHB patients treated with TAF were enrolled in this study. During 96 weeks of TAF treatment, there was no significant change in TC, LDL-c, HDL-c, and TG level (P &gt; 0.05). The TC/HDL-c ratio was increased with no significant change (+0.24, P &gt; 0.05). In CHB patients with fatty liver (n = 48), TC, LDL-c, and TC/HDL-c ratio increased gradually during TAF treatment, TG levels increased to 146.63 mg/dL at 48 weeks (P = 0.057) and then decreased, but there was still no significant change compared with the baseline level by 96 weeks (P &gt; 0.05).ConclusionTAF treatment had a low effect on the lipid profile of CHB patients over the course of 96 weeks, and it was safe even in patients with fatty liver.Clinical trial registration[https://www.chictr.org.cn/showproj.html?proj=65123], identifier [ChiCTR2000041005].
The impact of pre-rehydration guided by carotid corrected flow time on hypotension prevention following general anesthesia induction in patients undergoing gastrointestinal surgery: a prospective randomized controlled trial
Authors: Li Min , Li Feng , Yu Jiali , Tang Xixi , Zhou Chengfu , Chen Qi , Liu Hongliang 
Published: June 2024

BackgroundPatients undergoing gastrointestinal surgery often experience hypotension following general anesthesia induction due to insufficient volume. This study aimed to assess whether pre-rehydration guided by carotid corrected flow time (FTc) could mitigate post-induction hypotension induced by general anesthesia.MethodsPatients undergoing resection of gastrointestinal tumors were assigned to either the conventional treatment group (Group C) or the fluid treatment group based on FTc (Group F). Within Group F, patients were further divided into Group A (carotid FTc &lt;340.7 ms) and Group B (carotid FTc ≥340.7 ms) based on pre-rehydration carotid FTc values. Group A patients received pre-rehydration with 250 mL of colloids (hydroxyethyl starch—HES) administered within 15 min until carotid FTc reached ≥340.7 ms to counteract hypovolemia prior to induction. Patients in Group B and Group C received a continuous HES infusion at a rate of 6 mL/kg/h 30 min before induction to compensate for physiological fluid loss. All patients received a perioperative background infusion of 3 mL/kg/h compound sodium chloride, with infusion rates optimized based on mean arterial pressure (MAP) and heart rate (HR). The incidence of post-induction hypotension was compared between Group C and Group F, as well as between Group A and Group B.ResultsThe incidence of hypotension after induction was significantly lower in Group F compared to Group C (26.4% vs. 46.7%, respectively; p &lt; 0.001). Patients in Group A received significantly more pre-rehydration, leading to a greater increase in carotid FTc values compared to Group B (336.5 ± 64.5 vs. 174.3 ± 34.1 ms, p = 0.002). However, no significant difference in carotid FTc values after pre-rehydration was observed between the groups. There was no significant difference in the incidence of hypotension after general anesthesia induction between Group A and Group B (22.9% vs. 28.8%, p = 0.535).ConclusionPre-rehydration based on FTc can effectively reduce the occurrence of post-induction hypotension in patients undergoing gastrointestinal surgery who present with insufficient volume.Clinical trial registrationhttps://www.chictr.org.cn/showprojEN.html?proj=201481.
Bioinformatics analysis of the potential receptor and therapeutic drugs for Alzheimer’s disease with comorbid Parkinson’s disease
Authors: Zhou Xuerong , Liu Zhifan , Bai Guiqin , Dazhang Bai , Zhao Peilin , Wang Xiaoming , Jiang Guohui 
Published: June 2024

BackgroundNow, there are no sensitive biomarkers for improving Alzheimer’s disease (AD) and comorbid Parkinson’s disease (PD). The aim of the present study was to analyze differentially expressed genes (DEGs) in brain tissue from AD and PD patients via bioinformatics analysis, as well as to explore precise diagnostic and therapeutic targets for AD and comorbid PD.MethodsGFE122063 and GSE7621 data sets from GEO in NCBI, were used to screen differentially expressed genes (DEGs) for AD and PD, and identify the intersected genes, respectively. Intersected genes were analyzed by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then, STRING site and Cytoscape were used to construct a protein–protein interaction (PPI) network, CytoNCA algorithm to analyze and evaluate centrality, Mcode plug-in to analyze module, and Cytohubba to screen key genes. Combined GO-KEGG enrichment analysis with Cytoscape algorithm to screen the key gene in AD complicated with PD. Then, the DEGs for AD and PD were imported into the Association Map (CMap) online platform to screen out the top 10 small molecule drugs, and using molecular docking techniques to evaluate the interactions between small molecule drugs and key genes receptors.ResultsIn total, 231 upregulated genes and 300 downregulated genes were identified. GO analysis revealed that the DEGs were highly enriched in signal transduction, and KEGG analysis revealed that the DEGs were associated with the MAPK and PI3K-Akt signaling pathways. Epidermal growth factor receptor (EGFR) was identified as a potential receptor gene in AD and comorbid PD. EGFR was upregulated in both AD and PD, and the proteins that interact with EGFR were enriched in the Ras/Raf/MAPK and PI3K/Akt signaling pathways. Semagacestat was identified as a drug with therapeutic potential for treating AD complicated with PD. There was a high binding affinity between semagacestat and EGFRNTD, with seven hydrogen bonds and one hydrophobic bond.DiscussionSemagacestat may improve the health of patients with AD complicated with PD through the regulation of the Ras/Raf/MAPK and PI3K/Akt signaling pathways by EGFR, providing evidence supporting the structural modification of semagacestat to develop a more effective drug for treating AD complicated with PD.
How movies move us – movie preferences are linked to differences in neuronal emotion processing of fear and anger: an fMRI study
Authors: Zwiky Esther , König Philine , Herrmann Rebekka Maria , Küttner Antonia , Selle Janine , Ptasczynski Lena Esther , Schöniger Konrad , Rutenkröger Mareike , Enneking Verena , Borgers Tiana , Klug Melissa , Dohm Katharina , Leehr Elisabeth J , Bauer Jochen , Dannlowski Udo , Redlich Ronny 
Published: June 2024

IntroductionAs a source of audio-visual stimulation, movies expose people to various emotions. Interestingly, several genres are characterized by negative emotional content. Albeit theoretical approaches exist, little is known about preferences for specific movie genres and the neuronal processing of negative emotions.MethodsWe investigated associations between movie genre preference and limbic and reward-related brain reactivity to close this gap by employing an fMRI paradigm with negative emotional faces in 257 healthy participants. We compared the functional activity of the amygdala and the nucleus accumbens (NAcc) between individuals with a preference for a particular movie genre and those without such preference.Results and discussionAmygdala activation was relatively higher in individuals with action movie preference (pTFCE-FWE = 0.013). Comedy genre preference was associated with increased amygdala (pTFCE-FWE = 0.038) and NAcc activity (pTFCE-FWE = 0.011). In contrast, crime/thriller preference (amygdala: pTFCE-FWE ≤ 0.010, NAcc: pTFCE-FWE = 0.036), as well as documentary preference, was linked to the decreased amygdala (pTFCE-FWE = 0.012) and NAcc activity (pTFCE-FWE = 0.015). The study revealed associations between participants’ genre preferences and brain reactivity to negative affective stimuli. Interestingly, preferences for genres with similar emotion profiles (action, crime/thriller) were associated with oppositely directed neural activity. Potential links between brain reactivity and susceptibility to different movie-related gratifications are discussed.
Associations between renal function, hippocampal volume, and cognitive impairment in 544 outpatients
Authors: Wu Lei-Yun , Lu Yuan-Yuan , Zheng Shuang-Shuang , Cui Ya-Dong , Lu Jie , Zhang Ai-Hua 
Published: June 2024

BackgroundCognitive impairment and brain atrophy are common in chronic kidney disease patients. It remains unclear whether differences in renal function, even within normal levels, influence hippocampal volume (HCV) and cognition. We aimed to investigate the association between estimated glomerular filtration rate (eGFR), HCV and cognition in outpatients.MethodsThis single-center retrospective study enrolled 544 nonrenal outpatients from our hospital. All participants underwent renal function assessment and 3.0 T magnetic resonance imaging (MRI) in the same year. HCV was also measured, and cognitive assessments were obtained. The correlations between eGFR, HCV, and cognitive function were analyzed. Logistic regression analysis was performed to identify the risk factors for hippocampal atrophy and cognitive impairment. Receiver-operator curves (ROCs) were performed to find the cut-off value of HCV that predicts cognitive impairment.ResultsThe mean age of all participants was 66.5 ± 10.9 years. The mean eGFR of all participants was 88.5 ± 15.1 mL/min/1.73 m2. eGFR was positively correlated with HCV and with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. Univariate and multivariate logistic regression analysis showed Age ≥ 65 years, eGFR &lt; 75 mL/min/1.73 m2, Glucose ≥6.1 mmol/L and combined cerebral microvascular diseases were independent risk factors for hippocampal atrophy and Age ≥ 65 years, left hippocampal volume (LHCV) &lt;2,654 mm3 were independent risk factors for cognitive impairment in outpatients. Although initial unadjusted logistic regression analysis indicated that a lower eGFR (eGFR &lt; 75 mL/min/1.73 m2) was associated with poorer cognitive function, this association was lost after adjusting for confounding variables. ROC curve analysis demonstrated that LHCV &lt;2,654 mm3 had the highest AUROC [(0.842, 95% CI: 0.808–0.871)], indicating that LHCV had a credible prognostic value with a high sensitivity and specificity for predicting cognitive impairment compared with age in outpatients.ConclusionHigher eGFR was associated with higher HCV and better cognitive function. eGFR &lt; 75 mL/min/1.73 m2 was an independent risk factor for hippocampal atrophy after adjusting for age. It is suggested that even eGFR &lt; 75 mL/min/1.73 m2, lower eGFR may still be associated with hippocampal atrophy, which is further associated with cognitive impairment. LHCV was a favorable prognostic marker for predicting cognitive impairment rather than age.