bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokines and chemokines skin gene expression in correlation with immune cells in blood and severity in equine insect bite hypersensitivity
Authors: Jebbawi Fadi , Chemnitzer Alex , Dietrich Macsmeila , Pantelyushin Stanislav , Lam Juwela , Rhiner Tanya , Keller Giulia , Waldern Nina , Canonica Fabia , Fettelschoss-Gabriel Antonia 
Published: July 2024

BackgroundInsect bite hypersensitivity (IBH) is the most frequent skin allergy of horses and is highly debilitating, especially in the chronic phase. IBH is caused by IgE-mediated hypersensitivity reactions to culicoides midge bites and an imbalanced immune response that reduces the welfare of affected horses.ObjectiveIn the present study, we investigated the pathological mechanisms of IBH, aiming to understand the immune cell modulation in acute allergic skin lesions of IBH horses with the goal of finding possible biomarkers for a diagnostic approach to monitor treatment success.MethodsBy qPCR, we quantified the gene expression of cytokines, chemokines, and immune receptors in skin punch biopsies of IBH with different severity levels and healthy horses simultaneously in tandem with the analysis of immune cell counts in the blood.ResultsOur data show an increase in blood eosinophils, monocytes, and basophils with a concomitant, significant increase in associated cytokine, chemokine, and immune cell receptor mRNA expression levels in the lesional skin of IBH horses. Moreover, IL-5Ra, CCR5, IFN-γ, and IL-31Ra were strongly associated with IBH severity, while IL-31 and IL-33 were rather associated with a milder form of IBH. In addition, our data show a strong correlation of basophil cell count in blood with IL-31Ra, IL-5, IL-5Ra, IFN-γ, HRH2, HRH4, CCR3, CCR5, IL-12b, IL-10, IL-1β, and CCL26 mRNA expression in skin punch biopsies of IBH horses.ConclusionIn summary, several cytokines and chemokines have been found to be associated with disease severity, hence contributing to IBH pathology. These molecules can be used as potential biomarkers to monitor the onset and progression of the disease or even to evaluate and monitor the efficacy of new therapeutic treatments for IBH skin allergy. To our knowledge, this is the first study that investigated immune cells together with a large set of genes related to their biological function, including correlation to disease severity, in a large cohort of healthy and IBH horses.
Dissecting the mediating role of cytokines in the interaction between immune traits and sepsis: insights from comprehensive mendelian randomization
Authors: Zheng Xiangtao , Wang Yihui , Wang Yuming , Wang Xiaofeng , Pei Lei , Zhao Shanzhi , Gong Fangchen , Li Ranran , Liu Huan , Liu Wenbin , Mao Enqiang , Yang Zhitao , Chen Erzhen , Chen Ying 
Published: July 2024

BackgroundSepsis is a life-threatening organ dysfunction resulting from a dysregulated host response to infection, yet the potential causal relationship between the immunophenotype and sepsis remains unclear.MethodsGenetic variants associated with the immunophenotype served as instrumental variables (IVs) in Mendelian randomization (MR) to elucidate the causal impact of the immunophenotype on three sepsis outcomes. Additionally, a two-step MR analysis was conducted to identify significant potential mediators between the immunophenotype and three sepsis outcomes.ResultsOur MR analysis demonstrated a significant association between the immunophenotype and sepsis outcome, with 36, 36, and 45 the immunophenotype associated with the susceptibility, severity, and mortality of sepsis, respectively. Specifically, our analysis highlighted the CD14+ CD16+ monocyte phenotype as a significant factor across all three sepsis outcomes, with odds ratios (ORs) and corresponding confidence intervals (CIs) indicating its impact on sepsis (OR = 1.047, CI: 1.001-1.096), sepsis in Critical Care Units (OR = 1.139, CI: 1.014-1.279), and sepsis-related 28-day mortality (OR = 1.218, CI: 1.104-1.334). Mediation analyses identified seven cytokines as significant mediators among 91 potential cytokines, including interleukin-5 (IL-5), S100A12, TNF-related apoptosis-inducing ligand (TRAIL), T-cell surface glycoprotein CD6 isoform, cystatin D, interleukin-18 (IL-18), and urokinase-type plasminogen activator (uPA). Furthermore, reverse MR analysis revealed no causal effect of sepsis outcomes on the immunophenotype.ConclusionOur MR study suggests that the immunophenotype is significantly associated with the susceptibility, severity, and mortality of patient with sepsis, providing, for the first time, robust evidence of significant associations between immune traits and their potential risks. This information is invaluable for clinicians and patients in making informed decisions and merits further attention.
Four-year real-world experience of secukinumab in a large Italian cohort of axial spondyloarthritis
Authors: Ramonda Roberta , Lorenzin Mariagrazia , Chimenti Maria Sole , D’Angelo Salvatore , Marchesoni Antonio , Selmi Carlo , Lubrano Ennio , Santo Leonardo , Luchetti Gentiloni Michele Maria , Atzeni Fabiola , Cauli Alberto , Manara Maria , Rossini Maurizio , Foti Roberta , Cozzi Giacomo , Scagnellato Laura , Ferraioli Mario , Carriero Antonio , Luciano Nicoletta , Ruzzon Francesca , Fatica Mauro , Fracassi Elena , Doria Andrea , Foti Rosario , Carletto Antonio 
Published: July 2024

ObjectivesThis study aims to evaluate in a real-life Italian multicenter cohort of axial spondyloarthritis (axSpA) (1) the 4-year effectiveness and safety of secukinumab, (2) the drug retention rate (DRR), and (3) the impact of the line of bDMARDs treatment, subtype of axSpA, and sex on achieving low disease activity (LDA) and very low disease activity (VLDA).MethodsConsecutive axSpA patients receiving secukinumab between 2016 and 2023 were prospectively evaluated. Data on disease characteristics, previous/ongoing treatments, comorbidities, and follow-up duration were collected. Treatment response was evaluated at 6 and 12 months after initiation and yearly up to 48 months (T48). DRR and effectiveness outcomes were evaluated according to bDMARDs treatment, axSpA subtype, and sex. Infections and adverse events (AEs) were recorded.ResultsWe enrolled 272 patients (48.2% male; median age, 51; 39.7% HLA-B27+; 40.4% nr-axSpA), of whom 30.9% were naïve to secukinumab. Overall, secukinumab yielded improvement in effectiveness outcomes; the naïve patients maintained lower disease activity vs. the non-naïve ones. At T48, the LDA and VLDA rates were higher in naïve patients and in male individuals. Treatment was discontinued in 104 patients due to primary/secondary loss of effectiveness and in 34 patients due to AEs. The DRR at T48 was 67.4% in the whole population, regardless of treatment line, axSpA subtype, and sex.ConclusionsSecukinumab was safe and effective in all axSpA patients irrespective of treatment line, disease subtype, and sex. The patients achieved sustained 4-year remission and DRR.
Carnitine O-octanoyltransferase (CROT) deficiency in mice leads to an increase of omega-3 fatty acids
Authors: Okui Takehito , Kuraoka Shiori , Iwashita Masaya , Itagawa Rei , Kasai Taku , Aikawa Masanori , Singh Sasha A. , Aikawa Elena 
Published: July 2024

Introduction: Carnitine O-octanoyltransferase (CROT) is a well-established peroxisomal enzyme involved in liver fatty acid oxidation, but less is known about its recently discovered role in promoting vascular calcification, and whether CROT-dependent liver metabolism contributes to the latter. To date, CROT function in the context of calcification potential has been conducted in the dyslipidemic low-density lipoprotein receptor-deficient (Ldlr−/−) mice.Objectives: To differentiate peroxisome and CROT-dependent lipid biology from that of lipoprotein-mediated lipid biology, we therefore conducted a metabolomic analysis of the liver and plasma of normolipidemic CROT-deficient (Crot−/−) mice.Methods: We performed LC-MS-based metabolomics on liver and plasma derived from Crot−/− and Crot +/− mice and sibling Crot+/+ mice, using a dual-phase metabolite extraction protocol, and multiple LC-MS acquisition strategies.Results: We identified between 79 to 453 annotated metabolites from annotated metabolites from liver samples, and 117 to 424 annotated metabolites from plasma samples. Through differential abundance analysis, we determined that omega-3 fatty acids such as EPA, DPA, and DHA were higher in the liver of Crot−/− and Crot +/− mice than Crot+/+ mice. EPA were higher in plasma of Crot−/− mice than Crot+/+ mice. We also determined that the anti-inflammatory dicarboxylic acids, tetradecanedioic acid and azelaic acid, were higher in the plasma of CROT-deficient mice.Conclusion: Our study associated genetic CROT deletion with increased levels of anti-inflammatory molecules in mouse liver and plasma. These results suggest a potential mechanism for anti-calcification effects of CROT suppression and the potential use of omega-3 fatty acids as biomarkers for future CROT inhibition therapies.
The role of Immune cells in Alzheimer's disease: a bidirectional Mendelian randomization study
Authors: Zhang Erdong , Chen Tingting , Chen Yanqin , Long Chenxiang , Tao Ling , Shen Xiangchun , Dai Fengqiu 
Published: July 2024

BackgroundAlzheimer's disease (AD) is a leading cause of dementia, characterized by the accumulation of amyloid-beta (Aβ) and hyperphosphorylated tau proteins, leading to neuroinflammation and neuronal damage. The role of the immune system in AD pathogenesis is increasingly recognized, prompting an exploration of the causal relationship between immune cells and AD by using Mendelian randomization (MR) approaches.MethodsUtilizing genome-wide association study (GWAS) data from European cohorts, we conducted an MR study to investigate the causal links between immune cell phenotypes and AD. We selected single nucleotide polymorphisms (SNPs) associated with immune cell traits at a genome-wide significance threshold and applied various MR methods, including MR Egger, Weighted median, and inverse variance weighted analysis, to assess the causality between 731 immune phenotypes and AD.ResultsOur MR analysis identified 15 immune cell types with significant causal relationships to AD pathogenesis. Notably, the absolute count of CD28−CD4−CD8− T cells and the expression of HLA DR on B cells were linked to a protective effect against AD, while 13 other immune phenotypes were identified as contributing to the risk factors for the disease. The causal effects of AD on immunophenotypic traits are predominantly negative, implying that AD may impair the functionality of immune cells. Validation through independent datasets, such as FinnGen and GCST90027158, confirmed the causal association between six specific immune cells and AD.ConclusionThis comprehensive MR study elucidates the intricate network of causal relationships between diverse immunophenotypic traits and AD, providing novel insights into the immunopathogenesis of AD. The findings suggest potential immunological targets that could be leveraged for early diagnosis, disease monitoring, and therapeutic intervention.
Assessment of corneal nerve regeneration after axotomy in a compartmentalized microfluidic chip model with automated 3D high resolution live-imaging
Authors: Bonneau Noémie , Potey Anaïs , Blond Frédéric , Guerin Camille , Baudouin Christophe , Peyrin Jean-Michel , Brignole-Baudouin Françoise , Réaux-Le Goazigo Annabelle 
Published: July 2024

IntroductionDamage to the corneal nerves can result in discomfort and chronic pain, profoundly impacting the quality of life of patients. Development of novel in vitro method is crucial to better understand corneal nerve regeneration and to find new treatments for the patients. Existing in vitro models often overlook the physiology of primary sensory neurons, for which the soma is separated from the nerve endings.MethodsTo overcome this limitation, our novel model combines a compartmentalized microfluidic culture of trigeminal ganglion neurons from adult mice with live–imaging and automated 3D image analysis offering robust way to assess axonal regrowth after axotomy.ResultsPhysical axotomy performed by a two-second aspiration led to a reproducible 70% axonal loss and altered the phenotype of the neurons, increasing the number of substance P-positive neurons 72 h post-axotomy. To validate our new model, we investigated axonal regeneration after exposure to pharmacological compounds. We selected various targets known to enhance or inhibit axonal regrowth and analyzed their basal expression in trigeminal ganglion cells by scRNAseq. NGF/GDNF, insulin, and Dooku-1 (Piezo1 antagonist) enhanced regrowth by 81, 74 and 157%, respectively, while Yoda-1 (Piezo1 agonist) had no effect. Furthermore, SARM1-IN-2 (Sarm1 inhibitor) inhibited axonal regrowth, leading to only 6% regrowth after 72 h of exposure (versus 34% regrowth without any compound).DiscussionCombining compartmentalized trigeminal neuronal culture with advanced imaging and analysis allowed a thorough evaluation of the extent of the axotomy and subsequent axonal regrowth. This innovative approach holds great promise for advancing our understanding of corneal nerve injuries and regeneration and ultimately improving the quality of life for patients suffering from sensory abnormalities, and related conditions.
Effects of nusinersen on motor function in children with spinal muscular atrophy: a retrospective study
Authors: Chen Yuyi , Yang Dongling , Huang Xuelin , Feng Juntan , Zhao Qingqing , Huang Huixian , Liang Lushi , Zhang Xinxin , Ruan Yiyan 
Published: July 2024

BackgroundSpinal muscular atrophy (SMA) is a genetic progressive neuromuscular disease. Nusinersen is the first disease modifying drug approved to treat patients with SMA. Our study aimed to evaluate the efficacy of nusinersen treatment on motor function in children with SMA.MethodsA retrospective analysis was conducted on the data of 52 genetically confirmed SMA patients from November 2020 to September 2023. Motor function was assessed based on standardized scales from baseline to 14 months of follow-up.ResultsOf patients in this study, the majority had SMA type 2 (40/52, 76.9%), 5 (9.6%) and 7 (13.5%) patients had SMA types 1 and 3, respectively. The median disease duration was 11 months (range 0–52), and the median age at initiation of treatment was 44.5 months (range 5–192). Motor function of all the patients with SMA improved from baseline to 14 months of follow-up. Mean increases of 4.6-point (p = 0.173), 4.7-point (p = 0.021) and 2.7-point (p = 0.013) were observed from baseline to 14 months of follow-up for the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores, the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM), respectively. Increased disease duration and age of treatment initiation were negatively correlated with the changes in HFMSE scores (r = −0.567, p = 0.043; r = −0.771 and p = 0.002, respectively). Similar results were observed for the RULM scores (r = −0.714, p = 0.014; r = −0.638 and p = 0.035, respectively).ConclusionOur study suggested that 14 months of treatment with nusinersen was effective and improved the motor function of children with SMA types 1, 2, or 3. In addition, disease duration and age at treatment initiation were negatively correlated with treatment outcome in the patients.
Chronic oral LPS administration does not increase inflammation or induce metabolic dysregulation in mice fed a western-style diet
Authors: Harvei Silje , Skogen Vemund , Egelandsdal Bjørg , Birkeland Signe , Paulsen Jan Erik , Carlsen Harald 
Published: July 2024

IntroductionLipopolysaccharides (LPS) present in the intestine are suggested to enter the bloodstream after consumption of high-fat diets and cause systemic inflammation and metabolic dysregulation through a process named “metabolic endotoxemia.” This study aimed to determine the role of orally administered LPS to mice in the early stage of chronic low-grade inflammation induced by diet.MethodsWe supplemented the drinking water with E. coli derived LPS to mice fed either high-fat Western-style diet (WSD) or standard chow (SC) for 7 weeks (n = 16–17). Body weight was recorded weekly. Systemic inflammatory status was assessed by in vivo imaging of NF-κB activity at different time points, and glucose dysregulation was assessed by insulin sensitivity test and glucose tolerance test near the end of the study. Systemic LPS exposure was estimated indirectly via quantification of LPS-binding protein (LBP) and antibodies against LPS in plasma, and directly using an LPS-sensitive cell reporter assay.Results and discussionOur results demonstrate that weight development and glucose regulation are not affected by LPS. We observed a transient LPS dependent upregulation of NF-κB activity in the liver region in both diet groups, a response that disappeared within the first week of LPS administration and remained low during the rest of the study. However, WSD fed mice had overall a higher NF-κB activity compared to SC fed mice at all time points independent of LPS administration. Our findings indicate that orally administered LPS has limited to no impact on systemic inflammation and metabolic dysregulation in mice fed a high-fat western diet and we question the capability of intestinally derived LPS to initiate systemic inflammation through a healthy and uncompromised intestine, even when exposed to a high-fat diet.
Increasing the frequency of plant-based food intake in daily diets reduces the risk of cardiovascular disease among elderly Chinese: a cohort study
Authors: Hou Xin-Zheng , Wu Qian , Lv Qian-Yu , Yang Ying-Tian , Li Lan-Lan , Ye Xue-Jiao , Yang Chen-Yan , Lv Yan-Fei , Wang Shi-Han 
Published: July 2024

ObjectiveThere is limited research on the relationship between the frequency of plant-based food intake and the risk of cardiovascular disease (CVD) among elderly Chinese. This study aims to evaluate the association between plant-based dietary index (PDI) and CVD risks, providing evidence for elderly Chinese to reduce CVD risks by increasing the frequency of plant-based food consumption.MethodsThis study analyzed data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) 2011–2018, employing a multivariate modified Poisson regression model, trend tests, and restricted cubic spline (RCS) analysis to assess the linear and non-linear relationship between the PDI and CVD risks. Subgroup analyses and interaction tests were conducted to evaluate the robustness and population-specificity of the results.ResultsThis study included a total of 1,414 elderly Chinese, and at the end of follow-up, 487 participants had developed CVD. The multivariate modified Poisson regression model revealed a negative association between PDI and CVD risks [RR = 0.983, 95%CI = (0.970, 0.997)]. Similarly, the multivariate trend test (p = 0.031) and RCS analysis (P for nonlinear = 0.600) indicated a linear relationship between PDI and CVD risks. Subgroup analyses showed that the relationship between PDI and CVD risk was not influenced by gender, BMI, smoking, alcohol use, or exercise.ConclusionThe PDI was negatively correlated with CVD risks, indicating that increasing the frequency of plant-based food intake in the diet may reduce CVD risks among elderly Chinese.
A new method for assessing tibial torsion using computerized tomography in a pediatric population
Authors: Gavira Nathaly , Cochard Blaise , Guanziroli Nastassia , Di Laura Frattura Giorgio , Dayer Romain , Ceroni Dimitri 
Published: July 2024

PurposeTibial torsion disorders may lead to abnormal gait, frequently leading to a consultation with a pediatric orthopedic surgeon. The present study evaluated an alternative method for assessing tibial torsion on computerized tomography (CT) images that considers the tibial distal axis to be equivalent to the geometric axis of the tibiotalar joint.MethodsOne hundred CT scans were reviewed retrospectively, and four measurements were taken: proximal transtibial angle (PTTA), posterior margin tibial plateau angle (PMTPA), intermalleolar angle (IMA), and talar angle (TA). The tibial torsion angle was then calculated using these different angles.ResultsThe patient cohort comprised 38 girls and 62 boys, with a mean age of 12 ± 4.4 years. Median PTTA and PMTPA were −8.4° ± 14.7° and −8.8° ± 14.2°, respectively, with no statistically significant difference. Mean IMA and TA were 23° ± 16.2° and 17.2° ± 16.9°, respectively, with a statistically significant difference. Mean total measurement time per patient was 6'44", with means of 2'24" for PTTA, 36" for PMTPA, 2'14" for IMA, and 1'12" for TA.ConclusionTibial torsion values may differ significantly depending on the axis chosen to define tibial orientation. At the level of the proximal tibia, the choice of PTTA or PMTPA had little influence on the calculation of the tibial torsion angle. There was a significant difference of 5.8° when measuring the distal tibia. Measuring the PMTPA and TA is probably more suited for use in clinical practice because their tracing is simple and faster.
Preemptive oral analgesia with steroidal and nonsteroidal anti-inflammatory drugs in periodontal surgery: a systematic review
Authors: Lages Lívio Portela de Deus , Bergamaschi Cristiane de Cássia , Lopes Luciane Cruz , da Frota Eduardo Gomes , Silva Marcus Tolentino , Monte Thiago Lima , Motta Rogério Heládio Lopes 
Published: July 2024

Introduction: Periodontal procedures can promote prolonged intense pain, particularly in clinical situations requiring surgical procedures. In this context, preemptive analgesia has also been assessed for its utility in controlling post-operative pain and discomfort in patients undergoing periodontal invasive procedures. This study assessed the efficacy and safety of preemptive oral analgesia with steroidal and non-steroidal anti-inflammatory drugs in periodontal surgeries.Methods: This systematic review performed a search in the following electronic sources: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via PubMed), EMBASE (via Ovid), Web of Science, Virtual Health Library and in clinical trials electronic databases for relevant randomized clinical trials (RCTs); published up to July 2023. Primary outcomes assessed were post-operative pain, edema and trismus. A narrative synthesis of the findings was carried out.Results: Six RCTs, involving a total of 250 participants, were included. The studies reviewed had a high risk of bias, particularly due to allocation concealment and blinding of participants and personnel. The RCTs reported only the outcome pain. The preemptive use of dexamethasone 8 mg, etoricoxib 90 mg or 120 mg and ketorolac 20 mg seems to be more effective for controlling post-operative pain than placebo.Discussion: The anti-inflammatory drugs evaluated proved to be effective for controlling post-operative pain. However, given the limitations regarding lack of studies, methodological biases, disparities in drugs and doses, report restricted the pain outcome; further RCTs confirming the effectiveness and safety of these drugs in periodontal surgical procedures are warranted.