bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulatory B Cells Dysregulated T Cell Function in an IL-35-Dependent Way in Patients With Chronic Hepatitis B
Authors: Liu YaYun , Luo Ying , Zhu Tong , Jiang Meng , Tian ZhaoFeng , Tang GuSheng , Liang XueSong 
Published: April 2021

Interleukin (IL)-35-secreting B (IL-35+B) cells are critical regulators in autoimmune and infectious diseases and exert suppressive functions in parallel with IL-10-producing B (B10) cells. However, the role of IL-35+B cells in persistent hepatitis B virus (HBV) infection remains unclear. To elucidate the role of IL-35+B cells in the progress of chronic HBV infection, we determined the frequency of IL-35+B cells and their relationship with the classical human regulatory B cell (Breg) subsets, namely, CD19+CD24hiCD38hi and CD19+CD24hiCD27+. Then, the regulatory effect and mechanism of Bregs on effector T cells were investigated in vitro. Here, we found that compared with healthy controls, the frequency of IL-35+B cells was increased in patients with chronic HBV infection and was enriched in human classical Breg subset CD19+CD24hiCD38hi B cells. Moderate correlation was observed between the frequency of IL-35+B cells and alanine aminotransferase levels (Spearman r = 0.401), but only mild correlation was noted between the frequency of IL-35+B cells and HBV DNA level (Spearman r = 0.314). The frequency of IL-35+B cells was negatively correlated with interferon-γ (IFN-γ)-producing CD4+ and CD8+ cells but positively correlated with IL-4-producing T cells. Bregs dysregulated T cell function through an IL-35-dependent mechanism and depended on cell-to-cell contact. In conclusion, IL-35+ B cell was enriched in CD19+CD24hiCD38hi B cell subset during persistent HBV infection and Breg cells exerted dysregulation in T cell function through IL-35 dependent mechanism and depend on cell-to-cell contact.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT03734783.
Carbamazepine Induces Focused T Cell Responses in Resolved Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Cases But Does Not Perturb the Immunopeptidome for T Cell Recognition
Authors: Mifsud Nicole A. , Illing Patricia T. , Lai Jeffrey W. , Fettke Heidi , Hensen Luca , Huang Ziyi , Rossjohn Jamie , Vivian Julian P. , Kwan Patrick , Purcell Anthony W. 
Published: April 2021

Antiseizure medications (ASMs) are frequently implicated in T cell-mediated drug hypersensitivity reactions and cause skin tropic pathologies that range in severity from mild rashes to life-threatening systemic syndromes. During the acute stages of the more severe manifestations of these reactions, drug responsive proinflammatory CD8+T cells display classical features of Th1 cytokine production (e.g.IFNγ) and cytolysis (e.g.granzyme B, perforin). These T cells may be found locally at the site of pathology (e.g.blister cells/fluid), as well as systemically (e.g.blood, organs). What is less understood are the long-lived immunological effects of the memory T cell pool following T cell-mediated drug hypersensitivity reactions. In this study, we examine the ASM carbamazepine (CBZ) and the CBZ-reactive memory T cell pool in patients who have a history of either Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) from 3-to-20 years following their initial adverse reaction. We show thatin vitrodrug restimulation of CBZ-reactive CD8+T cells results in a proinflammatory profile and produces a mainly focused, yet private, T cell receptor (TCR) usage amongst human leukocyte antigen (HLA)-B*15:02-positive SJS or TEN patients. Additionally, we show that expression of these CBZ-reactive TCRs in a reporter cell line, lacking endogenous αβTCR, recapitulates the features of TCR activation reported for ASM-treated T cell lines/clones, providing a useful tool for further functional validations. Finally, we conduct a comprehensive evaluation of the HLA-B*15:02 immunopeptidome following ASM (or a metabolite) treatment of a HLA-B*15:02-positive B-lymphoblastoid cell line (C1R.B*15:02) and minor perturbation of the peptide repertoire. Collectively, this study shows that the CBZ-reactive T cells characterized require both the drug and HLA-B*15:02 for activation and that reactivation of memory T cells from blood results in a focusedprivateTCR profile in patients with resolved disease.
Case Report: Infantile-Onset Fulminant Type 1 Diabetes Mellitus Caused by Novel Compound Heterozygous LRBA Variants
Authors: Totsune Eriko , Nakano Tomohiro , Moriya Kunihiko , Sato Daichi , Suzuki Dai , Miura Akinobu , Katayama Saori , Niizuma Hidetaka , Kanno Junko , van Zelm Menno C. , Imai Kohsuke , Kanegane Hirokazu , Sasahara Yoji , Kure Shigeo 
Published: April 2021

Lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency is a subtype of common variable immune deficiency (CVID). Numerous case reports and cohort studies have described a broad spectrum of clinical manifestations and variable disease phenotypes, including immune dysregulation, enteropathy, and recurrent infections. Although LRBA deficiency is an autosomal recessive primary immunodeficiency resulting in a phenotype similar to CVID, it is a monogenic disease and separate from CVID. Recently, in a report of monogenic primary immunodeficiency disorder associated with CVID and autoimmunity, the most common mutated gene was LRBA. We report the case of a girl who presented with fulminant type 1 diabetes at age 7 months. She later experienced recurrent bacterial infections with neutropenia and idiopathic thrombocytopenic purpura. Clinical genome sequencing revealed compound heterozygosity of the LRBA gene, which bore two novel mutations. A genetic basis should be considered in the differential diagnosis for very young patients with fulminant autoimmunity, and the diagnostic work-up should include evaluation of markers of immunodeficiency.
Development of a Phase Field Tool Coupling With Thermodynamic Data for Microstructure Evolution Simulation of Alloys in Nuclear Reactors
Authors: Guo Yaolin , Li Yifan , Liu Zhen , Shi Diwei , Song Jiexi , Zhang Biao , Bu Moran , Du Shiyu 
Published: April 2021

We have developed a new phase field tool PHAFIS to automatically incorporate the thermodynamic data for both of WBM and KKS phase field simulations, which are widely used in the simulation of microstructure evolution of nuclear materials. Based on the generic C/C++ programming language, PHAFIS is capable of automatically parsing the standard TDB files, extracting the free energy and diffusion potential varying with the composition in an analytical way. Based on the two diffrerent TDB files of Fe-Cr binary system and the interpolated data, the phase morphologies during spinodal decomposition at 700 K and liquid-solid transition at high temperatures above 1800 K are reproduced and compared with each other by WBM and KKS model, respectively. Specifically, both of interface-controlled and diffusion-controlled phase transition mechanisms are successfully revealed for solidification through our KKS simulation, consistent with classic phase transition theories. It can be concluded that even slight differences in thermodynamic data will cause significant changes in the microstructure evolution. The integrity of our software tool will facilitate the coupling of phase field methods with thermodynamic data for other materials, paving a fundamental step for coupling more factors required in microstructure simulation.
Evaluation of Donor and Recipient Characteristics Involved in Descemet Stripping Automated Endothelial Keratoplasty Outcomes
Authors: Lanza Michele , Boccia Rosa , Ruggiero Adriano , Melillo Paolo , Bifani Sconocchia Mario , Simonelli Francesca , Sbordone Sandro 
Published: April 2021

Aims: To evaluate both donor and recipient features involved in visual acuity restoring and complication insurgence in eyes that have undergone Descemet stripping automated endothelial keratoplasty (DSAEK).Methods: In this retrospective study, charts of 111 eyes of 96 patients (mean age 70.25 ± 8.58 years) that underwent DSAEK were evaluated. Only Fuch's Distrophy (FD) or Bullous Keratopathy (BK) due to cataract surgery eyes were included. A complete ophthalmic check with endothelial cell density (ECD) and central corneal thickness (CCT) measurement was performed before surgery and at 1, 3, 6, and 12 months follow-up. Each DSAEK was performed by the same well-trained surgeon; only pre-cut lenticules, provided by same Eye Bank, were implanted.Results: A total of 48 (43%) complications have been observed (most of them were 22 partial graft detachments and 17 IOP spikes). At the last follow-up (mean: 8.58 ± 4.09 months), a significant increase (p &lt; 0.05) of best corrected visual acuity (BCVA) was detected. Overall mean BCVA of the eyes evaluated was 0.40 ± 0.43 LogMAR with BK eyes showing a significantly higher improvement (p &lt; 0.05) compared to FD eyes. The only factor showing a significant correlation (p &lt; 0.05) with visual acuity enhancement was the implant of a lenticule thinner than 100 μm. Recipient features significantly (p &lt; 0.05) associated with complications observed after surgery were glaucoma and diabetes mellitus.Conclusion: The use of a graft thinner than 100 μm can provide better visual acuity recovery while recipients affected by glaucoma or diabetes mellitus are more prone to develop complications after surgery.
Quantitative Analysis of Synthetic Magnetic Resonance Imaging in Alzheimer’s Disease
Authors: Lou Baohui , Jiang Yuwei , Li Chunmei , Wu Pu-Yeh , Li Shuhua , Qin Bin , Chen Haibo , Wang Rui , Wu Bing , Chen Min 
Published: April 2021

Objectives: The purpose of this study was to evaluate the feasibility and whether synthetic MRI can benefit diagnosis of Alzheimer’s disease (AD).Materials and Methods: Eighteen patients and eighteen age-matched normal controls (NCs) underwent MR examination. The mini-mental state examination (MMSE) scores were obtained from all patients. The whole brain volumetric characteristics, T1, T2, and proton density (PD) values of different cortical and subcortical regions were obtained. The volumetric characteristics and brain regional relaxation values between AD patients and NCs were compared using independent-samples t-test. The correlations between these quantitative parameters and MMSE score were assessed by the Pearson correlation in AD patients.Results: Although the larger volume of cerebrospinal fluid (CSF), lower brain parenchymal volume (BPV), and the ratio of brain parenchymal volume to intracranial volume (BPV/ICV) were found in AD patients compared with NCs, there were no significant differences (p &gt; 0.05). T1 values of right insula cortex and T2 values of left hippocampus and right insula cortex were significantly higher in AD patients than in NCs, but T1 values of left caudate showed a reverse trend (p &lt; 0.05). As the MMSE score decreased in AD patients, the BPV and BPV/ICV decreased, while the volume of CSF and T1 values of bilateral insula cortex and bilateral hippocampus as well as T2 values of bilateral hippocampus increased (p &lt; 0.05).Conclusion: Synthetic MRI not only provides more information to differentiate AD patients from normal controls, but also reflects the disease severity of AD.
Wearable Devices for Assessing Function in Alzheimer's Disease: A European Public Involvement Activity About the Features and Preferences of Patients and Caregivers
Authors: Stavropoulos Thanos G. , Lazarou Ioulietta , Diaz Ana , Gove Dianne , Georges Jean , Manyakov Nikolay V. , Pich Emilio Merlo , Hinds Chris , Tsolaki Magda , Nikolopoulos Spiros , Kompatsiaris Ioannis ,   The RADAR-AD Consortium
Published: April 2021

Background: Alzheimer's Disease (AD) impairs the ability to carry out daily activities, reduces independence and quality of life and increases caregiver burden. Our understanding of functional decline has traditionally relied on reports by family and caregivers, which are subjective and vulnerable to recall bias. The Internet of Things (IoT) and wearable sensor technologies promise to provide objective, affordable, and reliable means for monitoring and understanding function. However, human factors for its acceptance are relatively unexplored.Objective: The Public Involvement (PI) activity presented in this paper aims to capture the preferences, priorities and concerns of people with AD and their caregivers for using monitoring wearables. Their feedback will drive device selection for clinical research, starting with the study of the RADAR-AD project.Method: The PI activity involved the Patient Advisory Board (PAB) of the RADAR-AD project, comprised of people with dementia across Europe and their caregivers (11 and 10, respectively). A set of four devices that optimally represent various combinations of aspects and features from the variety of currently available wearables (e.g., weight, size, comfort, battery life, screen types, water-resistance, and metrics) was presented and experienced hands-on. Afterwards, sets of cards were used to rate and rank devices and features and freely discuss preferences.Results: Overall, the PAB was willing to accept and incorporate devices into their daily lives. For the presented devices, the aspects most important to them included comfort, convenience and affordability. For devices in general, the features they prioritized were appearance/style, battery life and water resistance, followed by price, having an emergency button and a screen with metrics. The metrics valuable to them included activity levels and heart rate, followed by respiration rate, sleep quality and distance. Some concerns were the potential complexity, forgetting to charge the device, the potential stigma and data privacy.Conclusions: The PI activity explored the preferences, priorities and concerns of the PAB, a group of people with dementia and caregivers across Europe, regarding devices for monitoring function and decline, after a hands-on experience and explanation. They highlighted some expected aspects, metrics and features (e.g., comfort and convenience), but also some less expected (e.g., screen with metrics).
Effects of Wireless Remote Microphone on Speech Recognition in Noise for Hearing Aid Users in China
Authors: Chen Jing , Wang Zhe , Dong Ruijuan , Fu Xinxing , Wang Yuan , Wang Shuo 
Published: April 2021

Objective:This study was aimed at evaluating improvements in speech-in-noise recognition ability as measured by signal-to-noise ratio (SNR) with the use of wireless remote microphone technology. These microphones transmit digital signals via radio frequency directly to hearing aids and may be a valuable assistive listening device for the hearing-impaired population of Mandarin speakers in China.Methods:Twenty-three adults (aged 19–80 years old) and fourteen children (aged 8–17 years old) with bilateral sensorineural hearing loss were recruited. The Mandarin Hearing in Noise Test was used to test speech recognition ability in adult subjects, and the Mandarin Hearing in Noise Test for Children was used for children. The subjects’ perceived SNR was measured using sentence recognition ability at three different listening distances of 1.5, 3, and 6 m. At each distance, SNR was obtained under three device settings: hearing aid microphone alone, wireless remote microphone alone, and hearing aid microphone and wireless remote microphone simultaneously.Results:At each test distance, for both adult and pediatric groups, speech-in-noise recognition thresholds were significantly lower with the use of the wireless remote microphone in comparison with the hearing aid microphones alone (P&lt; 0.05), indicating better SNR performance with the wireless remote microphone. Moreover, when the wireless remote microphone was used, test distance had no effect on speech-in-noise recognition for either adults or children.Conclusion:Wireless remote microphone technology can significantly improve speech recognition performance in challenging listening environments for Mandarin speaking hearing aid users in China.
Identification of Hub Genes Associated With Melanoma Development by Comprehensive Bioinformatics Analysis
Authors: Jiang Jie , Liu Chong , Xu Guoyong , Liang Tuo , Yu Chaojie , Liao Shian , Zhang Zide , Lu Zhaojun , Wang Zequn , Chen Jiarui , Chen Tianyou , Li Hao , Zhan Xinli 
Published: April 2021

IntroductionThis study aimed to identify important genes associated with melanoma to further develop new target gene therapies and analyze their significance concerning prognosis.Materials and methodsGene expression data for melanoma and normal tissue were downloaded from three databases. Differentially co-expressed genes were identified by WGCNA and DEGs analysis. These genes were subjected to GO, and KEGG enrichment analysis and construction of the PPI visualized with Cytoscape and screened for the top 10 Hub genes using CytoHubba. We validated the Hub gene’s protein levels with an immunohistochemical assay to confirm the accuracy of our analysis.ResultsA total of 435 differentially co-expressed genes were obtained. Survival curves showed that high expression of FOXM1,\ EXO1, KIF20A, TPX2, and CDC20 in melanoma patients with 5 of the top 10 hub genes was associated with reduced overall survival (OS). Immunohistochemistry showed that all five genes were expressed at higher protein levels in melanoma than in paracancerous tissues.ConclusionFOXM1, EXO1, KIF20A, TPX2, and CDC20 are prognosis-associated core genes of melanoma, and their high expression correlates with the low prognosis of melanoma patients and can be used as biomarkers for melanoma diagnosis, treatment, and prognosis prediction.
Intravoxel Incoherent Motion Model in Differentiating the Pathological Grades of Esophageal Carcinoma: Comparison of Mono-Exponential and Bi-Exponential Fit Model
Authors: Liu Nian , Yang Xiongxiong , Lei Lixing , Pan Ke , Liu Qianqian , Huang Xiaohua 
Published: April 2021

PurposeTo compare the diagnostic efficiency of the mono-exponential model and bi-exponential model deriving from intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in differentiating the pathological grade of esophageal squamous cell carcinoma (ESCC).MethodsFifty-four patients with ESCC were divided into three groups of poorly-differentiated (PD), moderately-differentiated (MD), and well-differentiated (WD), and underwent the IVIM-DWI scan. Mono-exponential (Dmono, D*mono, and fmono) and bi-exponential fit parameters (Dbi, D*bi, and fbi) were calculated using the IVIM data for the tumors. Mean parameter values of three groups were compared using a one-way ANOVA followed by post hoc tests. The receiver operating characteristic curve was drawn for differentiating pathological grade of ESCC. Correlations between pathological grades and IVIM parameters were analyzed.ResultsThere were significant differences in fmono and fbi among the PD, MD and WD ESCC groups (all p&lt;0.05). The fmono were 0.32 ± 0.07, 0.23 ± 0.08, and 0.16 ± 0.05, respectively, and the fbi were 0.35 ± 0.08, 0.26 ± 0.10, and 0.18 ± 0.07, respectively. There was a significant difference in the Dmono between the WD and the PD group (1.48 ± 0.51* 10-3 mm2/s versus 1.05 ± 0.44*10-3 mm2/s, p&lt;0.05), but there was no significant difference between the WD and MD groups, MD and PD groups (all p&gt;0.05). The D*mono, Dbi, and D*bi showed no significant difference among the three groups (all p&gt;0.05). The area under the curve (AUC) of Dmono, fmono and fbi in differentiating WD from PD ESCC were 0.764, 0.961 and 0.932, and the sensitivity and specificity were 92.9% and 60%, 92.9% and 90%, 85.7% and 100%, respectively. The AUC of fmono and fbi in differentiating MD from PD ESCC were 0.839 and 0.757, and the sensitivity and specificity were 78.6% and 80%, 85.7% and 70%, respectively. The AUC of fmono and fbi in differentiating MD from WD ESCC were 0.746 and 0.740, and the sensitivity and specificity were 65% and 85%, 80% and 60%, respectively. The pathologically differentiated grade was correlated with all IVIM parameters (all p&lt;0.05).ConclusionsThe mono-exponential IVIM model is superior to the bi-exponential IVIM model in differentiating pathological grades of ESCC, which may be a promising imaging method to predict pathological grades of ESCC.
Adjuvant EGFR-TKIs for Patients With Resected EGFR-Mutant Non-Small Cell Lung Cancer: A Meta-Analysis of 1,283 Patients
Authors: Chen Rui-Lian , Sun Ling-Ling , Cao Yang , Chen Han-Rui , Zhou Jing-Xu , Gu Chu-Ying , Zhang Ying , Wang Si-Yu , Hou Wei , Lin Li-Zhu 
Published: April 2021

BackgroundCisplatin-based chemotherapy was previously considered as the standard adjuvant therapy for improved overall survival (OS) in patients with non-small cell lung cancer (NSCLC) after surgery. However, the benefit was limited due to high risks of recurrence and adverse events. In the present study, the efficacy of adjuvant epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for EGFR-mutant patients after surgery was investigated using the latest updated data.MethodsThis meta-analysis included a comprehensive range of relevant studies identified from database searches. Disease-free survival (DFS) and OS with hazard ratios (HRs) were calculated using random-effect or fixed-effect models. Subgroup analysis was also performed.ResultsA total of seven randomized clinical trials were included in the meta-analysis and involved 1,283 NSCLC patients harboring EGFR mutations. In resected EGFR-mutant NSCLC patients, adjuvant EGFR-TKIs were significantly better than chemotherapy in terms of DFS (HR: 0.41; 95%CI: 0.24–0.70, P = 0.001), without showing any benefit in OS (HR: 0.72; 95%CI: 0.37–1.41, P = 0.336). No significant difference in DFS was observed between patients with EGFR exon 19 deletion and those with L858R mutation. Resected EGFR-mutant NSCLC patients treated with osimertinib experienced improved DFS and a lower risk of brain recurrence than those treated with gefitinib or erlotinib. Adjuvant EGFR-TKIs reduced the risk of bone and lung relapse, without decreasing the risk of local recurrence and liver relapse.ConclusionThis meta-analysis shows that adjuvant EGFR-TKI therapy could significantly prolong DFS in patients with resected EGFR-mutant NSCLC. Treatment with osimertinib showed improved DFS with a lower risk of brain recurrence than treatment with gefitinib or erlotinib for resected disease.