bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell RNA transcriptomics reveals differences in the immune status of alcoholic and hepatitis B virus-related liver cirrhosis
Authors: Zhang Pengpeng , Li Hao , Peng Bo , Zhang Yu , Liu Kai , Cheng Ke , Ming Yingzi 
Published: February 2023

BackgroundAlcoholic and hepatitis B virus (HBV)-related liver cirrhosis has placed a tremendous burden on the healthcare system with limited treatment options. This study explored the differences in the immune status of alcoholic and HBV-related liver cirrhosis.MethodsA total of 15 human liver samples from the Third Xiangya Hospital of Central South University, including five healthy controls (HC group), five alcoholic cirrhosis patients (ALC group), and five HBV-related cirrhosis patients (HBV group) were used. Of these, eight samples, including 3 HC group, 2 ALC group and 3 HBV group, were randomly collected to do single-cell RNA sequencing (scRNA-seq). The degree of steatosis was assessed by H&amp;E staining and the presence of intrahepatic immune cells was evaluated by immunochemistry (IHC).ResultsThe immune status of alcoholic and HBV-related liver cirrhosis differed significantly. ScRNA-seq analysis identified a higher ratio of intrahepatic monocyte/macrophages and an obvious decreased ratio of T cells and B cells in the ALC group than in the HBV group. IHC staining of intrahepatic monocyte/macrophages, T and B cell exhibited similar results with scRNA-seq analysis. CD5L+ Kupffer cells, a cell type involved in lipid metabolism, were the major monocyte/macrophage subset in ALC liver tissue. H&amp;E staining indicated that the level of steatosis was more severe in the ALC than in the HBV group. Ligand/receptor analysis showed that the T cell exhaustion observed in the ALC liver may be related to the expression of Galectin-9 on Kupffer cells. Fewer B cells were also found in the ALC group and most had higher lipid metabolism, reduced ribosomal activity, and a dysregulated mitochondrial oxidative phosphorylation system. Moreover, scRNA-seq showed a significantly lower ratio of plasma B cells, indicating that the humoral immune response in the ALC liver was similarly dysfunctional. Ligand/receptor analysis also discovered that Galectin-9 expressed on Kupffer cells may inhibit humoral immunity.ConclusionPatients with ALC have different immune characteristics than those with HBV-induced cirrhosis, including an increased ratio of intrahepatic monocyte/macrophages and a dysfunctional adaptive immune response in the liver. Galectin-9 could serve as a potential therapeutic target for ALC treatment.
Radar echo simulation of dynamically rotating wind turbine blades based on 3D scattering center
Authors: Tang Bo , Xie Huanghai , Liu Gang , Zhang Longbin , Shang Zhiyu 
Published: February 2023

Introduction: High-fidelity simulation of the radar echo from the wind turbine (WT) for accurate acquisition of Doppler features, is the key issue in addressing radiation interference from the wind farm on the nearby radar station. In view of the limitation of the conventional scattering center-based equivalent model to reflect the complex surface of blades, it is difficult to simulate the rotating blades’echo accurately with the existing algorithm. Therefore, we proposed a simulation method based on a 3D scattering center extraction to deal with it.Methods: Therefore, we proposed a simulation method based on a 3D scattering center extraction to deal with it. First, the method of scattering center equivalence to blade scattering is used in order to reduce the modelling as well as the solution of electromagnetic scattering from the multi-space attitude of the blade, which is different from the existing algorithm. Since the geometry affects the parameters of the scattering center, an orthogonal matching pursuit greedy algorithm is used to extract the parameter of the 3D scattering center model.Results: Therefore, the temporal correspondence between the scattering center and the blade motion characteristics is established, resulting in a reconstruction of the scattered field data of the rotating blades. Consequently, the real-time simulation and Doppler characteristic of blades echoes are achieved using the Short Time Fourier Transform (STFT).Discussion: A comparison of the results with the data obtained from the GTD scattering center model verififies the accuracy of the proposed method.
Identification of immune related gene signature for predicting prognosis of cholangiocarcinoma patients
Authors: Zhang Zi-jian , Huang Yun-peng , Liu Zhong-tao , Wang Yong-xiang , Zhou Hui , Hou Ke-xiong , Tang Ji-wang , Xiong Li , Wen Yu , Huang Sheng-fu 
Published: February 2023

ObjectiveTo identify the gene subtypes related to immune cells of cholangiocarcinoma and construct an immune score model to predict the immunotherapy efficacy and prognosis for cholangiocarcinoma.MethodsBased on principal component analysis (PCA) algorithm, The Cancer Genome Atlas (TCGA)-cholangiocarcinoma, GSE107943 and E-MTAB-6389 datasets were combined as Joint data. Immune genes were downloaded from ImmPort. Univariate Cox survival analysis filtered prognostically associated immune genes, which would identify immune-related subtypes of cholangiocarcinoma. Least absolute shrinkage and selection operator (LASSO) further screened immune genes with prognosis values, and tumor immune score was calculated for patients with cholangiocarcinoma after the combination of the three datasets. Kaplan-Meier curve analysis determined the optimal cut-off value, which was applied for dividing cholangiocarcinoma patients into low and high immune score group. To explore the differences in tumor microenvironment and immunotherapy between immune cell-related subtypes and immune score groups of cholangiocarcinoma.Results34 prognostic immune genes and three immunocell-related subtypes with statistically significant prognosis (IC1, IC2 and IC3) were identified. Among them, IC1 and IC3 showed higher immune cell infiltration, and IC3 may be more suitable for immunotherapy and chemotherapy. 10 immune genes with prognostic significance were screened by LASSO regression analysis, and a tumor immune score model was constructed. Kaplan-Meier (KM) and receiver operating characteristic (ROC) analysis showed that RiskScore had excellent prognostic prediction ability. Immunohistochemical analysis showed that 6 gene (NLRX1, AKT1, CSRP1, LEP, MUC4 and SEMA4B) of 10 genes were abnormal expressions between cancer and paracancer tissue. Immune cells infiltration in high immune score group was generally increased, and it was more suitable for chemotherapy. In GSE112366-Crohn’s disease dataset, 6 of 10 immune genes had expression differences between Crohn’s disease and healthy control. The area under ROC obtained 0.671 based on 10-immune gene signature. Moreover, the model had a sound performance in Crohn’s disease.ConclusionThe prediction of tumor immune score model in predicting immune microenvironment, immunotherapy and chemotherapy in patients with cholangiocarcinoma has shown its potential for indicating the effect of immunotherapy on patients with cholangiocarcinoma.
Persistence of spike-specific immune responses in BNT162b2-vaccinated donors and generation of rapid ex-vivo T cells expansion protocol for adoptive immunotherapy: A pilot study
Authors: Mestiri Sarra , Merhi Maysaloun , Inchakalody Varghese P. , Taib Nassiba , Smatti Maria K. , Ahmad Fareed , Raza Afsheen , Ali Fatma H. , Hydrose Shereena , Fernandes Queenie , Ansari Abdul W. , Sahir Fairooz , Al-Zaidan Lobna , Jalis Munir , Ghoul Mokhtar , Allahverdi Niloofar , Al Homsi Mohammed U. , Uddin Shahab , Jeremijenko Andrew Martin , Nimir Mai , Abu-Raddad Laith J. , Abid Fatma Ben , Zaqout Ahmed , Alfheid Sameer R. , Saqr Hassan Mohamed Hassan , Omrani Ali S. , Hssain Ali Ait , Al Maslamani Muna , Yassine Hadi M. , Dermime Said 
Published: February 2023

IntroductionThe BNT162b2 mRNA-based vaccine has shown high efficacy in preventing COVID-19 infection but there are limited data on the types and persistence of the humoral and T cell responses to such a vaccine.MethodsHere, we dissect the vaccine-induced humoral and cellular responses in a cohort of six healthy recipients of two doses of this vaccine.Results and discussionOverall, there was heterogeneity in the spike-specific humoral and cellular responses among vaccinated individuals. Interestingly, we demonstrated that anti-spike antibody levels detected by a novel simple automated assay (Jess) were strongly correlated (r=0.863, P&lt;0.0001) with neutralizing activity; thus, providing a potential surrogate for neutralizing cell-based assays. The spike-specific T cell response was measured with a newly modified T-spot assay in which the high-homology peptide-sequences cross-reactive with other coronaviruses were removed. This response was induced in 4/6 participants after the first dose, and all six participants after the second dose, and remained detectable in 4/6 participants five months post-vaccination. We have also shown for the first time, that BNT162b2 vaccine enhanced T cell responses also against known human common viruses. In addition, we demonstrated the efficacy of a rapid ex-vivo T cell expansion protocol for spike-specific T cell expansion to be potentially used for adoptive-cell therapy in severe COVID-19, immunocompromised individuals, and other high-risk groups. There was a 9 to 13.7-fold increase in the number of expanded T cells with a significant increase of anti-spike specific response showing higher frequencies of both activation and cytotoxic markers. Interestingly, effector memory T cells were dominant in all four participants’ CD8+ expanded memory T cells; CD4+ T cells were dominated by effector memory in 2/4 participants and by central memory in the remaining two participants. Moreover, we found that high frequencies of CD4+ terminally differentiated memory T cells were associated with a greater reduction of spike-specific activated CD4+ T cells. Finally, we showed that participants who had a CD4+ central memory T cell dominance expressed a high CD69 activation marker in the CD4+ activated T cells.
Intralymphatic glutamic acid decarboxylase administration in type 1 diabetes patients induced a distinctive early immune response in patients with DR3DQ2 haplotype
Authors: Puente-Marin Sara , Dietrich Fabrícia , Achenbach Peter , Barcenilla Hugo , Ludvigsson Johnny , Casas Rosaura 
Published: February 2023

GAD-alum given into lymph nodes to Type 1 diabetes (T1D) patients participating in a multicenter, randomized, placebo-controlled double-blind study seemed to have a positive effect for patients with DR3DQ2 haplotype, who showed better preservation of C-peptide than the placebo group. Here we compared the immunomodulatory effect of GAD-alum administered into lymph nodes of patients with T1D versus placebo with focus on patients with DR3DQ2 haplotype.MethodsGAD autoantibodies, GADA subclasses, GAD65-induced cytokine secretion (Luminex panel) and proliferation of peripheral mononuclear cells were analyzed in T1D patients (n=109) who received either three intra-lymphatic injections (one month apart) with 4 µg GAD-alum and oral vitamin D supplementation (2000 IE daily for 120 days), or placebo.ResultsHigher GADA, GADA subclasses, GAD65-induced proliferation and cytokine secretion was observed in actively treated patients after the second injection of GAD-alum compared to the placebo group. Following the second injection of GAD-alum, actively treated subjects with DR3DQ2 haplotype had higher GAD65-induced secretion of several cytokine (IL4, IL5, IL7, IL10, IL13, IFNγ, GM-CSF and MIP1β) and proliferation compared to treated individuals without DR3DQ2. Stratification of samples from GAD-alum treated patients according to C-peptide preservation at 15 months revealed that “good responder” individuals with better preservation of C-peptide secretion, independently of the HLA haplotype, had increased GAD65-induced proliferation and IL13 secretion at 3 months, and a 2,5-fold increase of IL5 and IL10 as compared to “poor responders”. The second dose of GAD-alum also induced a more pronounced cytokine secretion in “good responders” with DR3DQ2, compared to few “good responders” without DR3DQ2 haplotype.ConclusionPatients with DR3DQ2 haplotype had a distinct early cellular immune response to GAD-alum injections into the lymph node, and predominant GAD65-induced IL13 secretion and proliferation that seems to be associated with a better clinical outcome. If confirmed in the ongoing larger randomized double-blind placebo-controlled clinical trial (DIAGNODE-3), including only patients carrying DR3DQ2 haplotype, these results might be used as early surrogate markers for clinical efficacy.
IFN regulatory factor 3 of golden pompano and its NLS domain are involved in antibacterial innate immunity and regulate the expression of type I interferon (IFNa3)
Authors: Sun Yun , Cao Zhenjie , Zhang Panpan , Wei Caoying , Li Jianlong , Wu Ying , Zhou Yongcan 
Published: February 2023

IntroductionThe transcription factor interferon regulatory factor 3 (IRF3) plays an important role in host defence against viral infections. However, its role during bacterial infection in teleosts remains unclear. In the present study, we evaluated the antibacterial effects of Trachinotus ovatus IRF3 (TroIRF3) and how it regulates type I interferon (IFN).MethodsSubcellular localisation experiments, overexpression, and quantitative real-time PCR (qRT-PCR) were performed to examine the nuclear localisation signal (NLS) of TroIRF3 and its role in the antibacterial regulatory function of TroIRF3. We assessed the binding activity of TroIRF3 to the IFNa3 promoter by luciferase reporter assay.Results and DiscussionThe results showed that TroIRF3 was constitutively expressed at high levels in the gill and liver. TroIRF3 was significantly upregulated and transferred from the cytoplasm to the nucleus after Vibrio harveyi infection. By overexpressing TroIRF3, the fish were able to inhibit the replication of V. harveyi, whereas knocking it down increased bacterial replication. Moreover, the overexpression of TroIRF3 increased type I interferon (IFNa3) production and the IFN signalling molecules. The NLS, which is from the 64–127 amino acids of TroIRF3, contains the basic amino acids KR74/75 and RK82/84. The results proved that NLS is required for the efficient nuclear import of TroIRF3 and that the NLS domain of TroIRF3 consists of the key amino acids KR74/75 and RK82/84. The findings also showed that NLS plays a key role in the antibacterial immunity and upregulation of TroIFNa3 induced by TroIRF3. Moreover, TroIRF3 induces TroIFNa3 promoter activity, whereas these effects are inhibited when the NLS domain is deficient. Overall, our results suggested that TroIRF3 is involved in the antibacterial immunity and regulation of type I IFN in T. ovatus and that the NLS of TroIRF3 is vital for IRF3-mediated antibacterial responses, which will aid in understanding the immune role of fish IRF3.
Agonistic and antagonistic targeting of immune checkpoint molecules differentially regulate osteoclastogenesis
Authors: Brom Victoria C. , Strauss Andreas C. , Sieberath Alexander , Salber Jochen , Burger Christof , Wirtz Dieter C. , Schildberg Frank A. 
Published: February 2023

IntroductionImmune checkpoint inhibitors are used in the treatment of various cancers and have been extensively researched with regard to inflammatory and autoimmune diseases. However, this revolutionary therapeutic strategy often provokes critical auto-inflammatory adverse events, such as inflammatory reactions affecting the cardiovascular, gastrointestinal, nervous, and skeletal systems. Because the function of these immunomodulatory co-receptors is highly cell-type specific and the role of macrophages as osteoclast precursors is widely published, we aimed to analyze the effect of immune checkpoint inhibitors on these bone-resorbing cells.MethodsWe established an in vitro model of osteoclastogenesis using human peripheral blood mononuclear cells, to which various immune checkpoints and corresponding antagonistic antibodies were administered. Formation of osteoclasts was quantified and cell morphology was analyzed via immunofluorescence staining, cell size measurements, and calculation of cell numbers in a multitude of samples.ResultsThese methodical approaches for osteoclast research achieved objective, comparable, and reproducible results despite the great heterogeneity in the form, size, and number of osteoclasts. In addition to the standardization of experimental analyses involving osteoclasts, our study has revealed the substantial effects of agonistic and antagonistic checkpoint modulation on osteoclastogenesis, confirming the importance of immune checkpoints in bone homeostasis.DiscussionOur work will enable more robust and reproducible investigations into the use of immune checkpoint inhibitors in conditions with diminished bone density such as osteoporosis, aseptic loosening of endoprostheses, cancer, as well as the side effects of cancer therapy, and might even pave the way for novel individualized diagnostic and therapeutic strategies.
Assessing differences in acoustic characteristics from impact and vibratory pile installation and their potential effects on the large yellow croaker (Pseudosciaena crocea)
Authors: Niu Fuqiang , Xie Jiarui , Zhang Xuexin , Xue Ruichao , Chen Benqing , Liu Zhenwen , Yang Yanming 
Published: February 2023

Underwater noise from anthropogenic activities can have negative behavioral and physical effects on marine life, including physical changes, injuries, and death. Impact pile driving and vibratory pile driving are generally used for the construction of ocean-based foundations. Based on the field data under the same marine engineering and marine environment, this paper addresses the characteristics of underwater noise from impact and vibratory pile driving, their differences, and the effects of noise on populations of the large yellow croaker (Pseudosciaena crocea). The impact pile driving pulse had a median peak-to-peak sound pressure source level (SPLpp) of 244.7 dB re 1 μPa at 1 m and a median sound exposure source level (SELss) of 208.1 dB re 1 μPa2s at 1 m by linear regression. The waveform of vibratory pile driving appears to be continuous with a low SPLpp, but the cumulative SEL (SELcum) in 1 min is very high, reaching 207.5 dB re 1 μPa2s at 1 m. The range of behavioral response for adult large yellow croaker (20–23 cm) is predicted to be 4,798 m for impact pile driving and 1,779 m for vibratory pile driving. The study provides evidence of the comparative potential effects of vibratory and impact pile driving on the large yellow croaker and reference for the conservation of croaker.
Neuroanatomical and neurocognitive changes associated with subjective cognitive decline
Authors: Rivas-Fernández Miguel Ángel , Lindín Mónica , Zurrón Montserrat , Díaz Fernando , Lojo-Seoane Cristina , Pereiro Arturo X. , Galdo-Álvarez Santiago 
Published: February 2023

IntroductionSubjective Cognitive Decline (SCD) can progress to mild cognitive impairment (MCI) and Alzheimer’s disease (AD) dementia and thus may represent a preclinical stage of the AD continuum. However, evidence about structural changes observed in the brain during SCD remains inconsistent.Materials and methodsThis cross-sectional study aimed to evaluate, in subjects recruited from the CompAS project, neurocognitive and neurostructural differences between a group of forty-nine control subjects and forty-nine individuals who met the diagnostic criteria for SCD and exhibited high levels of subjective cognitive complaints (SCCs). Structural magnetic resonance imaging was used to compare neuroanatomical differences in brain volume and cortical thickness between both groups.ResultsRelative to the control group, the SCD group displayed structural changes involving frontal, parietal, and medial temporal lobe regions of critical importance in AD etiology and functionally related to several cognitive domains, including executive control, attention, memory, and language.ConclusionDespite the absence of clinical deficits, SCD may constitute a preclinical entity with a similar (although subtle) pattern of neuroanatomical changes to that observed in individuals with amnestic MCI or AD dementia.
Validation of depression determinants in caregivers of dementia patients with machine learning algorithms and statistical model
Authors: Cho Kangrim , Choi Junggu , Han Sanghoon 
Published: February 2023

IntroductionDue to its increasing prevalence, dementia is currently one of the most extensively studied health issues. Although it represents a comparatively less-addressed issue, the caregiving burden for dementia patients is likewise receiving attention.MethodsTo identify determinants of depression in dementia caregivers, using Community Health Survey (CHS) data collected by the Korea Disease Control and Prevention Agency (KDCA). By setting “dementia caregiver's status of residence with patient” as a standard variable, we selected corresponding CHS data from 2011 to 2019. After refining the data, we split dementia caregiver and general population groups among the dataset (n = 15,708; common variables = 34). We then applied three machine learning algorithms: Extreme Gradient Boosting (XGBoost), Logistic Regression (LR), and Support Vector Classifier (SVC). Subsequently, we selected XGBoost, as it exhibited superior performance to the other algorithms. On the feature importance of XGBoost, we performed a multivariate hierarchical regression analysis to validate the depression causes experienced in each group. We validated the results of the statistical model analysis by performing Welch's t-test on the main determinants exhibited within each group.ResultsBy verifying the results from machine learning via statistical model analysis, we found “sex” to highly impact depression in dementia caregivers, whereas “status of economic activities” is significantly associated with depression in the general population.DiscussionThe evident difference in causes of depression between the two groups may serve as a basis for policy development to improve the mental health of dementia caregivers.
Analyzing breast cancer invasive disease event classification through explainable artificial intelligence
Authors: Massafra Raffaella , Fanizzi Annarita , Amoroso Nicola , Bove Samantha , Comes Maria Colomba , Pomarico Domenico , Didonna Vittorio , Diotaiuti Sergio , Galati Luisa , Giotta Francesco , La Forgia Daniele , Latorre Agnese , Lombardi Angela , Nardone Annalisa , Pastena Maria Irene , Ressa Cosmo Maurizio , Rinaldi Lucia , Tamborra Pasquale , Zito Alfredo , Paradiso Angelo Virgilio , Bellotti Roberto , Lorusso Vito 
Published: February 2023

IntroductionRecently, accurate machine learning and deep learning approaches have been dedicated to the investigation of breast cancer invasive disease events (IDEs), such as recurrence, contralateral and second cancers. However, such approaches are poorly interpretable.MethodsThus, we designed an Explainable Artificial Intelligence (XAI) framework to investigate IDEs within a cohort of 486 breast cancer patients enrolled at IRCCS Istituto Tumori “Giovanni Paolo II” in Bari, Italy. Using Shapley values, we determined the IDE driving features according to two periods, often adopted in clinical practice, of 5 and 10 years from the first tumor diagnosis.ResultsAge, tumor diameter, surgery type, and multiplicity are predominant within the 5-year frame, while therapy-related features, including hormone, chemotherapy schemes and lymphovascular invasion, dominate the 10-year IDE prediction. Estrogen Receptor (ER), proliferation marker Ki67 and metastatic lymph nodes affect both frames.DiscussionThus, our framework aims at shortening the distance between AI and clinical practice