bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptive and innate immune responses in multiple sclerosis with anti-CD20 therapy: Gene expression and protein profiles
Authors: Fong Chloe C. , Spencer Julian , Howlett-Prieto Quentin , Feng Xuan , Reder Anthony T. 
Published: April 2023

BackgroundAnti-CD20 is a highly effective therapy for multiple sclerosis (MS), a disease with multiple abnormalities in function of B and T cells and innate immune cells. Anti-CD20 therapy depletes B cells, which alters antibody production and has diverse effects on B cell immunity. These changes potentially affect immunity beyond B cells in MS.ObjectiveDetermine if anti-CD20 therapy effects non-B cell, as well as B cell, gene expression, and serum protein levels.MethodsSamples were collected from 10 healthy controls and from clinically stable relapsing–remitting MS – 10 untreated, 9 interferon-β-treated, and 15 ocrelizumab-treated patients were studied before, and 2  weeks and 6  months after, the first anti-CD20 infusion. Peripheral blood mononuclear cells (PBMC) were analyzed with sensitive, 135,000-transcript RNA expression microarrays, using stringent criteria. Gene expression was compared to 43 MS-relevant serum immune and neurotrophic proteins, using multiplex protein assays.ResultsAnti-CD20 therapy reduced expression of 413 total genes and 185 B-cell-regulated genes at 2  weeks vs. pre-therapy. Expression of 19 (15%) of these B cell genes returned toward baseline by 6  months, including genes for the B cell activation protein, CD79A, and for immunoglobulin A, D, and G heavy chains. Expression pathways for Th17 and CD4 regulatory T-cell (Treg) development, differentiation, and proliferation also quieted. In contrast, expression increased in Th1 and myeloid cell antiviral, pro-inflammatory, and toll-like receptor (TLR) gene pathways.ConclusionThese findings have clinical implications. B cell gene expression diminishes 2  weeks after anti-CD20 antibody infusion, but begins to rebound by 6  months. This suggests that the optimum time for vaccination is soon before reinfusion of anti-CD20 therapy. In addition, at 6  months, there is enhanced Th1 cell gene expression and induction of innate immune response genes and TLR expression, which can enhance anti-viral and anti-tumor immunity. This may compensate for diminished B cell gene expression after therapy. These data suggest that anti-CD20 therapy has dynamic effect on B cells and causes a compensatory rise in Th1 and myeloid immunity.
Malocclusion impairs cognitive behavior via AgRP signaling in adolescent mice
Authors: Kusumoto Junya , Ataka Koji , Iwai Haruki , Oga Yasuhiko , Yamagata Keita , Marutani Kanako , Ishikawa Takanori , Asakawa Akihiro , Miyawaki Shouichi 
Published: April 2023

IntroductionOcclusal disharmony induced by deteriorating oral health conditions, such as tooth loss and decreased masticatory muscle due to sarcopenia, is one of the causes of cognitive impairment. Chewing is an essential oral function for maintaining cognitive function not only in the elderly but also in young people. Malocclusion is an occlusal disharmony that commonly occurs in children. The connection between a decline in cognitive function and malocclusion in children has been shown with chronic mouth breathing, obstructive sleep apnea syndrome, and thumb/digit sucking habits. However, the mechanism of malocclusion-induced cognitive decline is not fully understood. We recently reported an association between feeding-related neuropeptides and cognitive decline in adolescent mice with activity-based anorexia. The aim of the present study was to assess the effects of malocclusion on cognitive behavior and clarify the connection between cognitive decline and hypothalamic feeding-related neuropeptides in adolescent mice with malocclusion.MethodsFour-week-old mice were randomly assigned to the sham-operated solid diet-fed (Sham/solid), sham-operated powder diet-fed (Sham/powder), or malocclusion-operated powder diet-fed (Malocclusion/powder) group. We applied composite resin to the mandibular anterior teeth to simulate malocclusion. We evaluated cognitive behavior using a novel object recognition (NOR) test, measured hypothalamic feeding-related neuropeptide mRNA expression levels, and enumerated c-Fos-positive cells in the hypothalamus 1 month after surgery. We also evaluated the effects of central antibody administration on cognitive behavior impairment in the NOR test.ResultsThe NOR indices were lower and the agouti-related peptide (AgRP) mRNA levels and number of c-Fos-positive cells were higher in the malocclusion/powder group than in the other groups. The c-Fos-positive cells were also AgRP-positive. We observed that the central administration of anti-AgRP antibody significantly increased the NOR indices.DiscussionThe present study suggests that elevated cerebral AgRP signaling contributes to malocclusion-induced cognitive decline in adolescents, and the suppression of AgRP signaling can be a new therapeutic target against cognitive decline in occlusal disharmony.
The efficacy and the safety of eltrombopag in pediatric patients with severe aplastic anemia: a systematic review
Authors: Marrapodi Maria Maddalena , Mascolo Annamaria , Roberti Domenico , Martino Martina Di , Rafaniello Concetta , Riccardi Consiglia , Rossi Francesca 
Published: April 2023

BackgroundAcquired aplastic anemia (AAA) in pediatric patients is a rare disorder characterized by hypocellular bone marrow and pancytopenia. Eltrombopag, an oral thrombopoietin receptor agonist, provides a hematologic improvement in adults with severe aplastic anemia (SAA) refractory to immunosuppressive therapy (IST). The association of ELT and IST was approved by the US Food and Drug Administration (FDA) for adults and children ≥2 years of age as a first-line treatment for SAA. However, the effects of ELT on pediatric patients with SAA remain controversial and limited.Methods and findingsWe conducted a systematic review of the most recent literature from Pubmed, Web of Science, and Embase, published up to 20th December 2022, in order to evaluate the available evidence on the efficacy and safety of ELT added to IST for the treatment of SAA in the pediatric population.ConclusionEltrombopag added to the IST has shown a good safety profile, without manifestations of excessive toxic effects, although not all the results obtained from our studies support the addition of ELT to the IST in the first-line treatment of children with SAA.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD42022325859.
Association between vitamin D level and pediatric inflammatory bowel disease: A systematic review and meta-analysis
Authors: Sun Yan-hong , Tian Dan-dan , Zhou Jian-ming , Ye Qing 
Published: April 2023

BackgroundPrevious studies have reported that the incidence of pediatric inflammatory bowel disease (IBD) is related to vitamin D, but it is still unclear. This study intends to calculate the relationship between pediatric IBD and vitamin D.MethodsA comprehensive literature search from inception to January 2023 was performed in the PubMed, EMBASE, Medline, Web of Science, and Google Scholar databases. Relevant data were extracted as required and used for subsequent calculations.ResultsSixteen papers were included, and there was no significant difference between the average vitamin D level in IBD patients and healthy controls. In addition, the overall pooled results showed that C-reactive protein (CRP) was 2.65 higher before vitamin D supplementation than after supplementation [SMD = 2.65, 95% CI = (2.26, 3.04)]. Moreover, patients with IBD in remission were 0.72 higher before vitamin D supplementation than after supplementation [OR = 0.72, 95% CI = (0.52, 1.00)].ConclusionThis study suggested that there was no obvious relationship between pediatric IBD and vitamin D, while vitamin D supplementation can improve disease activity. Therefore, follow-up still needs many prospective studies to confirm the relationship between pediatric IBD and vitamin D.
Therapeutic hypothermia can cause non-infective C-reactive protein elevating
Authors: Wang Xiaohong , Shi Liping , Wang Chenhong , Ma Xiaolu 
Published: April 2023

ObjectiveTo analyze the relationship between therapeutic hypothermia (TH) and whole blood high-sensitivity C-reactive protein (hs-CRP) in neonates with hypoxic-ischemic encephalopathy (HIE).MethodRetrospective analysis was made on the clinical data of hospitalized infants diagnosed with asphyxia in our neonatal intensive care unit from January 2014 to June 2021. According to whether TH was performed, they were divided into two groups, the control group (missed the time in other hospitals and did not receive TH) and the treatment group (TH group). In their first ten days, analysis was made on the hs-CRP, white blood cell (WBC) count, neutrophil percentage, platelet count (PLT), and brain MRI. The correlation analysis was carried out based on the severity of brain injury displayed by the brain MRI and the time of hs-CRP elevation to summarize the relationship between TH and the time of hs-CRP elevation and the severity of HIE.Results83 infants were included, 28 in the control group and 55 in the TH group. After birth, 33 infants (60.0%) in the TH group and 2 patients (7.1%) in the control group had elevated hs-CRP, which was statistically significant (P &lt; 0.05). The time window for CRP elevation after TH was 72–96 h after the end of treatment; The results of the brain MRI showed 23 in the TH group and 11in the control group with moderate and severe HIE. 21 infants (all in the TH group) had elevated hs-CRP. MRI showed that the number of infants with mild injury or regular infants whose hs-CRP raised in the TH group was 12, and the rate of hs-CRP elevation was 37.5%; in the control group, the rate was 11.8%. The difference was significant. TH can decrease PLT and WBC, but no significance in the two groups. Blood and sputum cultures were negative in all infants, and there were no signs of infection.ConclusionsTH can increase the blood hs-CRP of HIE neonates, and the probability of its occurrence is related to the severity of HIE. The heavier the HIE, the higher the risk of hs-CRP elevation after TH; The hs-CRP elevation has little to do with infection, and it doesn't recommend using antibiotics actively.
Survivin inhibition with YM155 ameliorates experimental pulmonary arterial hypertension
Authors: Blanco Isabel , Marquina Maribel , Tura-Ceide Olga , Ferrer Elisabet , Ramírez Ana M. , Lopez-Meseguer Manuel , Callejo Maria , Perez-Vizcaino Francisco , Peinado Victor Ivo , Barberà Joan Albert 
Published: April 2023

Background: Imbalance between cell proliferation and apoptosis underlies the development of pulmonary arterial hypertension (PAH). Current vasodilator treatment of PAH does not target the uncontrolled proliferative process in pulmonary arteries. Proteins involved in the apoptosis pathway may play a role in PAH and their inhibition might represent a potential therapeutic target. Survivin is a member of the apoptosis inhibitor protein family involved in cell proliferation.Objectives: This study aimed to explore the potential role of survivin in the pathogenesis of PAH and the effects of its inhibition.Methods: In SU5416/hypoxia-induced PAH mice we assessed the expression of survivin by immunohistochemistry, western-blot analysis, and RT-PCR; the expression of proliferation-related genes (Bcl2 and Mki67); and the effects of the survivin inhibitor YM155. In explanted lungs from patients with PAH we assessed the expression of survivin, BCL2 and MKI67.Results: SU5416/hypoxia mice showed increased expression of survivin in pulmonary arteries and lung tissue extract, and upregulation of survivin, Bcl2 and Mki67 genes. Treatment with YM155 reduced right ventricle (RV) systolic pressure, RV thickness, pulmonary vascular remodeling, and the expression of survivin, Bcl2, and Mki67 to values similar to those in control animals. Lungs of patients with PAH also showed increased expression of survivin in pulmonary arteries and lung extract, and also that of BCL2 and MKI67 genes, compared with control lungs.Conclusion: We conclude that survivin might be involved in the pathogenesis of PAH and that its inhibition with YM155 might represent a novel therapeutic approach that warrants further evaluation.
Therapeutic effects and mechanism of Atractylodis rhizoma in acute lung injury: Investigation based on an Integrated approach
Authors: Shi Kun , Wang Yan , Xiao Yangxin , Tu Jiyuan , Zhou Zhongshi , Cao Guosheng , Liu Yanju 
Published: April 2023

Acute lung injury (ALI) is characterized by an excessive inflammatory response. Atractylodes lancea (Thunb.) DC. is a traditional chinese medicine with good anti-inflammatory activity that is commonly used clinically for the treatment of lung diseases in China; however, its mechanism of against ALI is unclear. We clarified the therapeutic effects of ethanol extract of Atractylodis rhizoma (EEAR) on lipopolysaccharide (LPS)-induced ALI by evaluation of hematoxylin-eosin (HE) stained sections, the lung wet/dry (W/D) ratio, and levels of inflammatory factors as indicators. We then characterized the chemical composition of EEAR by ultra-performance liquid chromatography and mass spectrometry (UPLC-MS) and screened the components and targets by network pharmacology to clarify the signaling pathways involved in the therapeutic effects of EEAR on ALI, and the results were validated by molecular docking simulation and Western blot (WB) analysis. Finally, we examined the metabolites in rat lung tissues by gas chromatography and mass spectrometry (GC-MS). The results showed that EEAR significantly reduced the W/D ratio, and tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6) levels in the lungs of ALI model rats. Nineteen components of EEAR were identified and shown to act synergetically by regulating shared pathways such as the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling pathways. Ferulic acid, 4-methylumbelliferone, acetylatractylodinol, atractylenolide I, and atractylenolide III were predicted to bind well to PI3K, AKT and MAPK1, respectively, with binding energies &lt; -5 kcal/mol, although only atractylenolide II bound with high affinity to MAPK1. EEAR significantly inhibited the phosphorylation of PI3K, AKT, p38, and ERK1/2, thus reducing protein expression. EEAR significantly modulated the expression of metabolites such as D-Galactose, D-Glucose, serine and D-Mannose. These metabolites were mainly concentrated in the galactose and amino acid metabolism pathways. In conclusion, EEAR alleviates ALI by inhibiting activation of the PI3K-AKT and MAPK signaling pathways and regulating galactose metabolism, providing a new direction for the development of drugs to treat ALI.
High-efficiency 100-W Kerr-lens mode-locked Yb:YAG thin-disk oscillator
Authors: Chen Hongshan , Yan Lisong , Liu Heyan , Hao Jingjie , Yang Tingting , Liu Hongyu , Zhang Jin , Li Quanming , Wang Hailin , Zhu Guangzhi , Zhu Xiao , Xuan Hongwen , Wang Qing , Zhang Jinwei 
Published: April 2023

We demonstrate a Kerr-lens mode-locked femtosecond Yb:YAG thin-disk oscillator and investigate the approach to increase the optical-to-optical efficiency based on the scheme of direct multiple passes of the laser beam through the thin-disk medium. With twelve passes through the thin disk, 266-fs pulses were delivered from the oscillator with an average power of 105.6 W at a repetition rate of 20 MHz. The corresponding optical-to-optical efficiency is 31.1%, which is, to the best of our knowledge, the highest efficiency of any mode-locked thin-disk oscillator with pulse duration below 300 fs. This demonstration paves the way to even more efficient mode-locked femtosecond thin-disk oscillators, and provides an excellent laser source for the applications such as non-linear frequency conversion and high-precision industrial processing.
Response of wheat aphid to insecticides is influenced by the interaction between temperature amplitudes and insecticide characteristics
Authors: Xing Kun , Zhang Shu-Ming , Jia Mei-Qi , Zhao Fei 
Published: April 2023

Introduction: Climate change not only directly affects the phenotype of organisms but also indirectly impacts their physiology, for example, by altering their susceptibility to insecticides. Changed diurnal temperature fluctuations are an important aspect of climate change; ignoring the impact of these fluctuations on the biological effects of various chemical insecticides can lead to inaccurate assessments of insecticide risk under the current and future climate change scenarios.Methods: In this study, we studied effects of different temperature amplitudes (± 0, ± 6, ± 12°C) at the same mean temperature (22°C) on the life history traits of a globally distributed pest (Sitobion avenae, wheat aphid), in response to low doses of two insecticides. The first, imidacloprid shows a positive temperature coefficient; the second, beta-cypermethrin has a negative temperature coefficient.Results: Compared with the results seen with the constant temperature (22°C), a wide temperature amplitude (± 12°C) amplified the negative effects of imidacloprid on the survival, longevity, and fecundity of S. avenae, but significantly increased the early fecundity of the wheat aphid. Beta-cypermethrin positively impacted the wheat aphid at all temperature amplitudes studied. Specifically, beta-cypermethrin significantly increased the survival, longevity, and fecundity of S. avenae under medium temperature amplitude (± 6°C). There were no significant differences in the survival, longevity, and the early fecundity of S. avenae when it was treated with beta-cypermethrin at the wide temperature amplitude (± 12°C). However, the negative effect of beta-cypermethrin on the intrinsic rate of increase of S. avenae decreased gradually with the increase in temperature amplitude.Discussion: In conclusion, the response of S. avenae to positive temperature coefficient insecticides was markedly affected by temperature amplitude, while negative temperature coefficient insecticides increased the environmental adaptability of S. avenae to various temperature amplitudes. Our results highlight the importance of the integrated consideration of diurnal temperature fluctuations and different temperature coefficient insecticide interactions in climate-change-linked insecticide risk assessment; these results emphasize the need for a more fine-scale approach within the context of climate change and poison sensitivity.
Features of gut microbiota and short-chain fatty acids in patients with first-episode depression and their relationship with the clinical symptoms
Authors: Yu Shuhan , Wang Lan , Jing Xinyang , Wang Yujing , An Cuixia 
Published: April 2023

ObjectiveTo compare the differences in gut microbiota and short-chain fatty acids (SCFAs; metabolites of gut microbiota) in the serum of patients with first-episode depression and the healthy population and to analyze the relationship between gut microbiota and metabolite SCFAs and the clinical symptoms of major depressive disorder (MDD).MethodsA total of 45 patients with first-episode depression and 22 healthy volunteers were chosen to complete relevant scale evaluations, and feces samples and venous blood samples were collected. The 16S RNA method was used to analyze the intestinal microflora and the characteristics of serum SCFAs detection by ELISA kit, as well as the intestinal flora, SCFAs content and their correlation with MDD clinical indicators.ResultsThe abundance of Akkermansia, Megamonas, Prevotellaceae NK3B31 group, and butyrate-producing bacteria, Lachnospira, Subdoligranulum, Blautia, and Dialister, and acetate-producing bacteria, Streptococcus, in the gut microbiota of the MDD group was lower than that in the control (C) group. The abundance of Parasutterella in the MDD group was higher than that in the C group. Dialister negatively correlated with all measured clinical symptoms (r &lt; 0, P &lt; 0.05). The serum SCFA content in the MDD group was higher than that in the C group, and the content positively correlated with the Hamilton anxiety scale scores (r = 0.584, P &lt; 0.05).ConclusionThe results demonstrated that the MDD group differed from the C group in terms of gut microbiota and SCFAs in the serum and that the change in certain intestinal bacteria might participate in the pathogenic mechanism of MDD.
Chinese version of Dominic Interactive – A self-report video game for assessing mental health in young children
Authors: Kovess-Masfety Viviane , Yan Guoli , Yin Huifang , Sun Ling , Hou Xiaofei , Li Minghui , Li Peiyao , Su Xuyang , Phillips Michael R. , Xu Guangming 
Published: April 2023

ObjectivesAssess the validity of the Chinese version of theDominic Interactive(DI), a 91-item, video-based diagnostic screening instrument for children that assesses four internalized disorders (phobias, separation anxiety disorder, generalized anxiety disorder, and major depressive disorder) and three externalized disorders (attention-deficit/hyperactivity disorder, conduct disorder, oppositional defiant disorder).Methods(1) Compare DI-generated “probable” or “possible” diagnoses to diagnoses based on the Development and Well-Being Assessment (DAWBA) instrument in 113 psychiatric outpatients and 20 community controls. (2) Administer DI to 1,479 children from elementary schools in Tianjin.ResultsIn the validation sample, DI with DAWBA concordance was much greater for internalized disorders (mean Kappa = 0.56) than for externalized disorders (mean kappa = 0.11). The positive predictive value of DI diagnoses ranged from 0.96 (generalized anxiety disorder) to 25% (oppositional defiant disorder) and negative from 0.81 to 0.96. Using “probable” cuts provides better results. In the survey, prevalence of probable DI disorders ranged from 1.0% (conduct disorder) to 13.1% (phobias). Internal consistency of all DI items was excellent (Cronbach alpha = 0.93) and that of the seven subscales ranged from 0.64 (phobias) to 0.87 (major depressive disorder). In multilevel SEM analyses, SRMR (Standardized root mean square residual) or each of the seven diagnoses was below 0.08 and each coefficient of determination was below 0.60.ConclusionThe Chinese DI is a convenient method of screening common mental disorders in Chinese children mainly for internalized disorders, which are the most prevalent diagnoses in that population. However its high negative predictive values for externalized could be used for screening.
Impairments in recognition of emotional facial expressions, affective prosody, and multisensory facilitation of response time in high-functioning autism
Authors: Hoffmann Jonatan , Travers-Podmaniczky Gabrielle , Pelzl Michael Alexander , Brück Carolin , Jacob Heike , Hölz Lea , Martinelli Anne , Wildgruber Dirk 
Published: April 2023

IntroductionDeficits in emotional perception are common in autistic people, but it remains unclear to which extent these perceptual impairments are linked to specific sensory modalities, specific emotions or multisensory facilitation.MethodsThis study aimed to investigate uni- and bimodal perception of emotional cues as well as multisensory facilitation in autistic (n = 18, mean age: 36.72 years, SD: 11.36) compared to non-autistic (n = 18, mean age: 36.41 years, SD: 12.18) people using auditory, visual and audiovisual stimuli.ResultsLower identification accuracy and longer response time were revealed in high-functioning autistic people. These differences were independent of modality and emotion and showed large effect sizes (Cohen’s d 0.8–1.2). Furthermore, multisensory facilitation of response time was observed in non-autistic people that was absent in autistic people, whereas no differences were found in multisensory facilitation of accuracy between the two groups.DiscussionThese findings suggest that processing of auditory and visual components of audiovisual stimuli is carried out more separately in autistic individuals (with equivalent temporal demands required for processing of the respective unimodal cues), but still with similar relative improvement in accuracy, whereas earlier integrative multimodal merging of stimulus properties seems to occur in non-autistic individuals.