bluuebunny/crossref_metadata_2025_split huggingface dataset:
An advanced in vitro human mucosal immune model to predict food sensitizing allergenicity risk: A proof of concept using ovalbumin as model allergen
Authors: Zuurveld Marit , Díaz Cristina Bueno , Redegeld Frank , Folkerts Gert , Garssen Johan , van’t Land Belinda , Willemsen Linette E.M. 
Published: January 2023

BackgroundThe global demand of sustainable food sources leads to introduction of novel foods on the market, which may pose a risk of inducing allergic sensitization. Currently there are no validated in vitro assays mimicking the human mucosal immune system to study sensitizing allergenicity risk of novel food proteins. The aim of this study was to introduce a series of sequential human epithelial and immune cell cocultures mimicking key immune events after exposure to the common food allergen ovalbumin from intestinal epithelial cell (IEC) activation up to mast cell degranulation.MethodsThis in vitro human mucosal food sensitizing allergenicity model combines crosstalk between IEC and monocyte-derived dendritic cells (moDC), followed by coculture of the primed moDCs with allogenic naïve CD4+ T cells. During subsequent coculture of primed CD4+ T cells with naïve B cells, IgE isotype-switching was monitored and supernatants were added to primary human mast cells to investigate degranulation upon IgE crosslinking. Mediator secretion and surface marker expression of immune cells were determined.ResultsOvalbumin activates IEC and underlying moDCs, both resulting in downstream IgE isotype-switching. However, only direct exposure of moDCs to ovalbumin drives Th2 polarization and a humoral B cell response allowing for IgE mediated mast cell degranulation, IL13 and IL4 release in this sequential DC-T cell-B cell-mast cell model, indicating also an immunomodulatory role for IEC.ConclusionThis in vitro coculture model combines multiple key events involved in allergic sensitization from epithelial cell to mast cell, which can be applied to study the allergic mechanism and sensitizing capacity of proteins.
Immune escaping of the novel genotypes of human respiratory syncytial virus based on gene sequence variation
Authors: Zhou Xiaohe , Jiang Mingli , Wang Fengjie , Qian Yuan , Song Qinwei , Sun Yu , Zhu Runan , Wang Fang , Qu Dong , Cao Ling , Ma Lijuan , Xu Yanpeng , De Ri , Zhao Linqing 
Published: January 2023

PurposeImmune escaping from host herd immunity has been related to changes in viral genomic sequences. The study aimed to understand the diverse immune responses to different subtypes or genotypes of human respiratory syncytial virus (RSV) in pediatric patients.MethodsThe genomic sequences of different subtypes or RSV genotypes, isolated from Beijing patients, were sequenced and systematically analyzed. Specifically, the antiviral effects of Palivizumab and the cross-reactivity of human sera from RSV-positive patients to different subtypes or genotypes of RSV were determined. Then, the level of 38 cytokines and chemokines in respiratory and serum samples from RSV-positive patients was evaluated.ResultsThe highest nucleotide and amino acid variations and the secondary and tertiary structure diversities among different subtypes or genotypes of RSV were found in G, especially for genotype ON1 with a 72bp-insertion compared to NA1 in subtype A, while more mutations of F protein were found in the NH-2 terminal, including the antigenic site II, the target of Palivizumab, containing one change N276S. Palivizumab inhibited subtype A with higher efficiency than subtype B and had stronger inhibitory effects on the reference strains than on isolated strains. However, RSV-positive sera had stronger inhibitory effects on the strains in the same subtypes or genotypes of RSV. The level of IFN-α2, IL-1α, and IL-1β in respiratory specimens from patients with NA1 was lower than those with ON1, while there were higher TNFα, IFNγ, IL-1α, and IL-1β in the first serum samples from patients with ON1 compared to those with BA9 of subtype B.ConclusionsDiverse host immune responses were correlated with differential subtypes and genotypes of RSV in pediatric patients, demonstrating the impact of viral genetics on host immunity.
The role of FOXO4/NFAT2 signaling pathway in dysfunction of human coronary endothelial cells and inflammatory infiltration of vasculitis in Kawasaki disease
Authors: Huang Hongbiao , Dong Jinfeng , Jiang Jiaqi , Yang Fang , Zheng Yiming , Wang Shuhui , Wang Nana , Ma Jin , Hou Miao , Ding Yueyue , Meng Lijun , Zhuo Wenyu , Yang Daoping , Qian Weiguo , Chen Qiaobin , You Guoping , Qian Guanghui , Gu Lei , Lv Haitao 
Published: January 2023

AimsThe Ca+/NFAT (Nuclear factor of activated T cells) signaling pathway activation is implicated in the pathogenesis of Kawasaki disease (KD); however, we lack detailed information regarding the regulatory network involved in the human coronary endothelial cell dysfunction and cardiovascular lesion development. Herein, we aimed to use mouse and endothelial cell models of KD vasculitis in vivo and in vitro to characterize the regulatory network of NFAT pathway in KD.Methods and ResultsAmong the NFAT gene family, NFAT2 showed the strongest transcriptional activity in peripheral blood mononuclear cells (PBMCs) from patients with KD. Then, NFAT2 overexpression and knockdown experiments in Human coronary artery endothelial cells (HCAECs) indicated that NFAT2 overexpression disrupted endothelial cell homeostasis by regulation of adherens junctions, whereas its knockdown protected HCAECs from such dysfunction. Combined analysis using RNA-sequencing and transcription factor (TF) binding site analysis in the NFAT2 promoter region predicted regulation by Forkhead box O4 (FOXO4). Western blotting, chromatin immunoprecipitation, and luciferase assays validated that FOXO4 binds to the promoter and transcriptionally represses NFAT2. Moreover, Foxo4 knockout increased the extent of inflamed vascular tissues in a mouse model of KD vasculitis. Functional experiments showed that inhibition NFAT2 relieved Foxo4 knockout exaggerated vasculitis in vivo.ConclusionsOur findings revealed the FOXO4/NFAT2 axis as a vital pathway in the progression of KD that is associated with endothelial cell homeostasis and cardiovascular inflammation development.
Combining with lab-on-chip technology and multi-organ fusion strategy to estimate post-mortem interval of rat
Authors: Du Qiu-xiang , Zhang Shuai , Long Fei-hao , Lu Xiao-jun , Wang Liang , Cao Jie , Jin Qian-qian , Ren Kang , Zhang Ji , Huang Ping , Sun Jun-hong 
Published: January 2023

BackgroundThe estimation of post-mortem interval (PMI) is one of the most important problems in forensic pathology all the time. Although many classical methods can be used to estimate time since death, accurate and rapid estimation of PMI is still a difficult task in forensic practice, so the estimation of PMI requires a faster, more accurate, and more convenient method.Materials and methodsIn this study, an experimental method, lab-on-chip, is used to analyze the characterizations of polypeptide fragments of the lung, liver, kidney, and skeletal muscle of rats at defined time points after death (0, 1, 2, 3, 5, 7, 9, 12, 15, 18, 21, 24, 27, and 30 days). Then, machine learning algorithms (base model: LR, SVM, RF, GBDT, and MLPC; ensemble model: stacking, soft voting, and soft-weighted voting) are applied to predict PMI with single organ. Multi-organ fusion strategy is designed to predict PMI based on multiple organs. Then, the ensemble pruning algorithm determines the best combination of multi-organ.ResultsThe kidney is the best single organ for predicting the time of death, and its internal and external accuracy is 0.808 and 0.714, respectively. Multi-organ fusion strategy dramatically improves the performance of PMI estimation, and its internal and external accuracy is 0.962 and 0.893, respectively. Finally, the best organ combination determined by the ensemble pruning algorithm is all organs, such as lung, liver, kidney, and skeletal muscle.ConclusionLab-on-chip is feasible to detect polypeptide fragments and multi-organ fusion is more accurate than single organ for PMI estimation.
Antibacterial activity and mechanism of flavonoids from Chimonanthus salicifolius S. Y. Hu. and its transcriptome analysis against Staphylococcus aureus
Authors: Zhou Huan , Chen Lingli , Ouyang Kehui , Zhang Qingfeng , Wang Wenjun 
Published: January 2023

IntroductionChimonanthus salicifolius S. Y. Hu. (FCS) possess many biological activities, but the antibacterial activity and underlying mechanisms of flavonoids from Chimonanthus salicifolius S. Y. Hu. (FCS) is still unknown.MethodMaximum diameter of inhibition zone (DIZ), maximum diameter of inhibition zone (DIZ), the lowest minimum inhibition concentration (MIC), and the lowest minimum bactericide concentration (MBC) were used to detect the antibacterial activity. Meanwhile, related enzyme activities, the transcriptome analysis and quantitative RT-PCR were used to investigate the antibacterial activity mechanisms.ResultsThe results showed that FCS (with a purity of 84.2 ± 2.0%) has potential effects on tested strains with the maximum diameter of inhibition zone (DIZ) was 15.93 ± 2.63 mm, the lowest minimum inhibition concentration (MIC) was 1.56 mg/ml and the lowest minimum bactericide concentration (MBC) was 6.25 mg/ml. In addition, the bacterial growth curve test, release of extracellular alkaline phosphatase (AKP), loss of intracellular components, DNA damage and transmission electron microscope (TEM) suggested that FCS could destroy the cell wall and membrane, cause the loss of intracellular substance, cause DNA damage and even lead to cell death. Moreover, the antibacterial mechanism of FCS against Staphylococcus aureus (S. aureus, Gram-positive bacteria) was further confirmed by the transcriptome analysis and quantitative RT-PCR at the molecular level for the first time. A total of 671 differentially expressed genes (DEGs) were identified after treated with FCS (1/2 MIC), with 338 and 333 genes showing up-regulation and down-regulation, respectively. The highlighted changes were those related to the biosynthesis of bacteria wall and membrane, DNA replication and repair, and energy metabolism.DiscussionOverall, our research provides theoretical guidance for the application of FCS, which is expected to be potentially used as a natural antimicrobial agent in food safety.
Survival prediction for patients with glioblastoma multiforme using a Cox proportional hazards denoising autoencoder network
Authors: Yan Ting , Yan Zhenpeng , Liu Lili , Zhang Xiaoyu , Chen Guohui , Xu Feng , Li Ying , Zhang Lijuan , Peng Meilan , Wang Lu , Li Dandan , Zhao Dong 
Published: January 2023

ObjectivesThis study aimed to establish and validate a prognostic model based on magnetic resonance imaging and clinical features to predict the survival time of patients with glioblastoma multiforme (GBM).MethodsIn this study, a convolutional denoising autoencoder (DAE) network combined with the loss function of the Cox proportional hazard regression model was used to extract features for survival prediction. In addition, the Kaplan–Meier curve, the Schoenfeld residual analysis, the time-dependent receiver operating characteristic curve, the nomogram, and the calibration curve were performed to assess the survival prediction ability.ResultsThe concordance index (C-index) of the survival prediction model, which combines the DAE and the Cox proportional hazard regression model, reached 0.78 in the training set, 0.75 in the validation set, and 0.74 in the test set. Patients were divided into high- and low-risk groups based on the median prognostic index (PI). Kaplan–Meier curve was used for survival analysis (p = &lt; 2e-16 in the training set, p = 3e-04 in the validation set, and p = 0.007 in the test set), which showed that the survival probability of different groups was significantly different, and the PI of the network played an influential role in the prediction of survival probability. In the residual verification of the PI, the fitting curve of the scatter plot was roughly parallel to the x-axis, and the p-value of the test was 0.11, proving that the PI and survival time were independent of each other and the survival prediction ability of the PI was less affected than survival time. The areas under the curve of the training set were 0.843, 0.871, 0.903, and 0.941; those of the validation set were 0.687, 0.895, 1.000, and 0.967; and those of the test set were 0.757, 0.852, 0.683, and 0.898.ConclusionThe survival prediction model, which combines the DAE and the Cox proportional hazard regression model, can effectively predict the prognosis of patients with GBM.
Technical notes on the placement of cerebral microdialysis: A single center experience
Authors: Falcone Joseph A. , Chen Jefferson W. 
Published: January 2023

BackgroundCerebral microdialysis enables monitoring of brain metabolism and can be an important part of multimodal monitoring strategies in a variety of brain injuries. Microdialysis catheters can be placed in brain parenchyma through a burr hole, a cranial bolt, or directly at the time of an open craniotomy or craniectomy. The location of catheters in relation to brain pathology is important to the interpretation of data and guidance of interventions.MethodsHere we retrospectively review the use of cerebral microdialysis at a US Regional Medical Center between March 2018 and February 2022 and provide detailed descriptions and technical nuances of the different methods to place microdialysis catheters.ResultsEighty two unique microdialysis catheters were utilized in 52 patients. 35 (42.68%) were placed via a quad-lumen bolt and 47 (57.32%) were placed through craniotomies. 27 catheters (32.93%) were placed in a perilesional location, 50 (60.98%) were located in healthy tissue, and 6 (7.32%) were mispositioned. No significant difference was seen between placement by bolt or craniotomy in regard to perilesional location, mispositioning, or complications.ConclusionWith careful planning and thoughtful execution, cerebral microdialysis catheters can be successfully placed though a variety of strategies to optimize and individualize brain monitoring in different clinical settings. This paper provides a detailed guide for the various methods of catheter placement to help providers begin or expand their use of cerebral microdialysis.
Application of drug-induced sleep endoscopy in predicting the outcomes of velopharyngeal surgery in adult patients with Friedman stage II and III obstructive sleep apnea syndrome
Authors: Cao Xin , Zhou Yingqian , Zhang Junbo , Yin Guoping , Ye Jingying 
Published: January 2023

ObjectiveThis study aimed to evaluate the predictive value of drug-induced sleep endoscopy (DISE) for the outcomes of velopharyngeal surgery in adult patients with Friedman stage II and III obstructive sleep apnea syndrome (OSAS).MethodsA total of 39 male OSAS patients with Friedman stage II and III were retrospectively analyzed. Subjects with an apnea-hypopnea index (AHI) &gt; 5 events/h indicated by polysomnography (PSG) and typical symptoms, such as snoring, sleep apnea, and daytime sleepiness, were included in this study. All these patients underwent pre-operative DISE examinations and were treated by velopharyngeal surgery and evaluated by velum, oropharynx, tongue base, and epiglottis (VOTE) scoring system. Clinical, polysomnographic parameters (e.g., hypopnea, apnea, AHI, lowest oxygen saturation, etc.), cephalometric variables, and DISE findings were evaluated. The treatment outcomes were assessed by polysomnography at least 6 months after surgery.ResultsAll 39 patients showed complete velopharyngeal airway collapses during pre-operative DISE examinations. After surgery, the AHI was significantly improved from 50.2 ± 21.6 to 19.8 ± 19 events/h (P &lt; 0.05). There were 23 responders (59.0%) and 16 non-responders (41.0%). The glossopharyngeal airway collapse degree (GA-CD) was significantly different between responders and non-responders (P &lt; 0.05). The velopharyngeal airway collapse pattern (VA-CP) and GA-CD were independently predictive of treatment outcomes (both P &lt; 0.05). Patients with non-lateral VA-CP and grade II GA-CD (collapse degree &gt; 50%) had a significantly lower surgical success rate than those without (P &lt; 0.05).ConclusionThe VA-CP and GA-CD in DISE examination are valuable for predicting the treatment outcomes of velopharyngeal surgery in patients with Friedman stage II and III OSAS. Patients with lateral VA-CP and grade I GA-CD are appropriate candidates for velopharyngeal surgery.
EMG biofeedback combined with rehabilitation training may be the best physical therapy for improving upper limb motor function and relieving pain in patients with the post-stroke shoulder-hand syndrome: A Bayesian network meta-analysis
Authors: Feng Sisi , Tang Mingzhi , Huang Gan , Wang JuMei , He Sijin , Liu Duo , Gu LiHua 
Published: January 2023

BackgroundPost-stroke shoulder-hand syndrome (SHS), although not a life-threatening condition, may be the most distressing and disabling problem for stroke survivors. Thus, it is essential to identify effective treatment strategies. Physical therapy is used as a first-line option for treating SHS; however, it is unclear which treatment option is preferred, which creates confusion in guiding clinical practice. Our study aims to guide clinical treatment by identifying the most effective physical therapy interventions for improving clinical symptoms in patients with post-stroke SHS using Bayesian network meta-analysis.MethodsWe conducted a systematic and comprehensive search of data from randomized controlled trials using physical therapy in patients with SHS from database inception to 1 July 2022. Fugl-Meyer Upper Extremity Motor Function Scale (FMA-UE) and pain visual analog score (VAS) were used as primary and secondary outcome indicators. R (version 4.1.3) and STATA (version 16.0) software were used to analyze the data.ResultsA total of 45 RCTs with 3,379 subjects were included, and the intervention efficacy of 7 physical factor therapies (PFT) combined with rehabilitation training (RT) was explored. Compared with the control group, all the PFT + RT included were of statistical benefit in improving limb motor function and pain relief. Also, our study indicated that EMG biofeedback combined with RT (BFT + RT) [the surface under the cumulative ranking curve (SUCRA) = 96.8%] might be the best choice for patients with post-stroke SHS.ConclusionEMG biofeedback combined with rehabilitation training may be the best physical therapy for improving upper limb motor function and relieving pain in patients with post-stroke SHS according to our Bayesian network meta-analysis results. However, the above conclusions need further analysis and validation by more high-quality RCTs.Systematic review registrationwww.crd.york.ac.uk/prospero/, identifier: CRD42022348743.
Cerebral venous sinus thrombosis in traumatic brain injury: A systematic review of its complications, effect on mortality, diagnostic and therapeutic management, and follow-up
Authors: Netteland Dag Ferner , Sandset Else Charlotte , Mejlænder-Evjensvold Magnus , Aarhus Mads , Jeppesen Elisabeth , Aguiar de Sousa Diana , Helseth Eirik , Brommeland Tor 
Published: January 2023

ObjectiveCerebral venous sinus thrombosis (CVST) is increasingly being recognized in the setting of traumatic brain injury (TBI), but its effect on TBI patients and its management remains uncertain. Here, we systematically review the currently available evidence on the complications, effect on mortality and the diagnostic and therapeutic management and follow-up of CVST in the setting of TBI.MethodsKey clinical questions were posed and used to define the scope of the review within the following topics of complications; effect on mortality; diagnostics; therapeutics; recanalization and follow-up of CVST in TBI. We searched relevant databases using a structured search strategy. We screened identified records according to eligibility criteria and for information regarding the posed key clinical questions within the defined topics of the review.ResultsFrom 679 identified records, 21 studies met the eligibility criteria and were included, all of which were observational in nature. Data was deemed insufficiently homogenous to perform meta-analysis and was narratively synthesized. Reported rates of venous infarctions ranged between 7 and 38%. One large registry study reported increased in-hospital mortality in CVSP and TBI compared to a control group with TBI alone in adjusted analyses. Another two studies found midline CVST to be associated with increased risk of mortality in adjusted analyses. Direct data to inform the optimum diagnostic and therapeutic management of the condition was limited, but some data on the safety, and effect of anticoagulation treatment of CVST in TBI was identified. Systematic data on recanalization rates to guide follow-up was also limited, and reported complete recanalization rates ranged between 41 and 86%. In the context of the identified data, we discuss the diagnostic and therapeutic management and follow-up of the condition.ConclusionCurrently, the available evidence is insufficient for evidence-based treatment of CVST in the setting of TBI. However, there are clear indications in the presently available literature that CVST in TBI is associated with complications and increased mortality, and this indicates that management options for the condition must be considered. Further studies are needed to confirm the effects of CVST on TBI patients and to provide evidence to support management decisions.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier: PROSPERO [CRD42021247833].
Effects of chin tuck against resistance exercise on post-stroke dysphagia rehabilitation: A systematic review and meta-analysis
Authors: Liu Jing , Wang Qiuyi , Tian Jing , Zhou Wanqiong , Gao Yitian , Chen Xuemei , Zhang Wei , Gao Yajing , Zhou Lanshu 
Published: January 2023

BackgroundChin tuck against resistance (CTAR) exercise was introduced to substitute for the commonly used Shaker exercise for dysphagia rehabilitation. The effects of CTAR exercise in stroke survivors needs to be validated.ObjectiveTo investigate the effects of Chin tuck against resistance (CTAR) exercise on the swallowing function and psychological condition in stroke survivors compared to no exercise intervention and the Shaker exercise.Materials and methodsThe Cochrane Library, PubMed, Web of Science, EMBASE, CINAHL and four Chinese databases were searched for randomized controlled trails (RCTs) and quasi-RCTs from inception to February 2022.ResultsAfter screened and assessed the methodological quality of the studies, nine studies with 548 stroke survivors were included in the systematic review. 8 studies were included in the meta-analysis using RevMan 5.4 software. The mean difference (MD) or standardized mean difference (SMD) with 95% confidence intervals (CIs) were calculated. The results revealed that CTAR exercise is effective in improving swallowing safety (MD, −1.43; 95% CI, −1.81 to −1.06; P &lt; 0.0001) and oral intake ability (SMD, −1.82; 95% CI, −3.28 to −0.35; P = 0.01) compared with no exercise intervention, CTAR exercise is superior to Shaker exercise in improving swallowing safety (MD, −0.49; 95% CI, −0.83 to −0.16; P = 0.004). The psychological condition in CTAR group is significant better than the control group (MD, −5.72; 95% CI, −7.39 to −4.05; P &lt; 0.00001) and Shaker group (MD, −2.20; 95% CI, −3.77 to −0.64; P = 0.006).ConclusionsOur findings support CTAR exercise as a superior therapeutic exercise for post-stroke dysphagia rehabilitation than Shaker exercise. More high-qualities RCTs from larger multicenter are needed to analysis the effects of CTAR exercise in patients with different type and phase of stroke and explore the optimal training dose.