bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum cytokine and chemokine profiles and disease prognosis in hepatitis B virus-related acute-on-chronic liver failure
Authors: Zhu Bingbing , Gao Fangyuan , Li Yuxin , Shi Ke , Hou Yixin , Chen Jialiang , Zhang Qun , Wang Xianbo 
Published: April 2023

BackgroundHepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) has significant morbidity and mortality and is associated with the induction of cytokines/chemokines, which might contribute to the pathogenesis of liver injury. This study aimed to explore the cytokine/chemokine profiles of patients with HBV-ACLF and develop a composite clinical prognostic model.MethodsWe prospectively collected blood samples and the clinical data of 107 patients with HBV-ACLF admitted to the Beijing Ditan Hospital. The concentrations of 40-plex cytokines/chemokines were measured in 86 survivors and 21 non-survivors using the Luminex assay. Discrimination between the cytokine/chemokine profiles in different prognosis groups was analyzed using the multivariate statistical techniques of principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). An immune-clinical prognostic model was obtained using multivariate logistic regression analysis.ResultsThe PCA and PLS-DA indicated that cytokine/chemokine profiling could clearly distinguish patients with different prognoses. A total of 14 cytokines, namely, IL-1β, IL-6, IL-8, IL-10, TNF-α, IFN-γ, CXCL1, CXCL2, CXCL9, CXCL13, CX3CL1, GM-SCF, CCL21, and CCL23, were significantly correlated with disease prognosis. Multivariate analysis identified CXCL2, IL-8, total bilirubin, and age as independent risk factors that constituted the immune-clinical prognostic model, which showed the strongest predictive value of 0.938 compared with those of the Chronic Liver Failure Consortium (CLIF-C) ACLF (0.785), Model for End-Stage Liver Disease (MELD) (0.669), and MELD-Na (0.723) scores (p &lt; 0.05 for all).ConclusionThe serum cytokine/chemokine profiles correlated with the 90-day prognosis of patients with HBV-ACLF. The proposed composite immune-clinical prognostic model resulted in more accurate prognostic estimates than those of the CLIF-C ACLF, MELD, and MELD-Na scores.
Prediction of liver cancer prognosis based on immune cell marker genes
Authors: Liu Jianfei , Qu Junjie , Xu Lingling , Qiao Chen , Shao Guiwen , Liu Xin , He Hui , Zhang Jian 
Published: April 2023

IntroductionMonitoring the response after treatment of liver cancer and timely adjusting the treatment strategy are crucial to improve the survival rate of liver cancer. At present, the clinical monitoring of liver cancer after treatment is mainly based on serum markers and imaging. Morphological evaluation has limitations, such as the inability to measure small tumors and the poor repeatability of measurement, which is not applicable to cancer evaluation after immunotherapy or targeted treatment. The determination of serum markers is greatly affected by the environment and cannot accurately evaluate the prognosis. With the development of single cell sequencing technology, a large number of immune cell-specific genes have been identified. Immune cells and microenvironment play an important role in the process of prognosis. We speculate that the expression changes of immune cell-specific genes can indicate the process of prognosis.MethodTherefore, this paper first screened out the immune cell-specific genes related to liver cancer, and then built a deep learning model based on the expression of these genes to predict metastasis and the survival time of liver cancer patients. We verified and compared the model on the data set of 372 patients with liver cancer.ResultThe experiments found that our model is significantly superior to other methods, and can accurately identify whether liver cancer patients have metastasis and predict the survival time of liver cancer patients according to the expression of immune cell-specific genes.DiscussionWe found these immune cell-specific genes participant multiple cancer-related pathways. We fully explored the function of these genes, which would support the development of immunotherapy for liver cancer.
Effects of obesity with reduced 25(OH)D levels on bone health in elderly Chinese people: a nationwide cross-sectional study
Authors: Yuan Chunchun , Wang Jing , Zhang Weiqiang , Yi Honggang , Shu Bing , Li Chenguang , Liang Qianqian , Liang De , Chen Bolai , Xie Xingwen , Lin Xinchao , Wei Xu , Wang Hui , Chen Peizhan , Huang Chen , Xu Hao , Sun Yueli , Zhao Yongjian , Shi Qi , Tang Dezhi , Wang Yongjun 
Published: April 2023

BackgroundObesity is often accompanied by lower 25(OH)D levels, whereas these two parameters exhibit opposite effects on bone health. It is uncertain what are the effects of lower 25(OH)D levels in obesity on bone health in elderly Chinese people.MethodsA nationally representative cross-sectional analysis of China Community-based Cohort of Osteoporosis (CCCO) was performed from 2016 to 2021, which consisted of 22,081 participants. Demographic data, disease history, Body mass index (BMI), bone mineral density (BMD), the levels of the biomarkers of vitamin D status and those of bone metabolism markers were measured for all participants (N = 22,081). The genes (rs12785878, rs10741657, rs4588, rs7041, rs2282679 and rs6013897) related to 25(OH)D transportation and metabolism were performed in a selected subgroup (N = 6008).ResultsObese subjects exhibited lower 25(OH)D levels (p &lt; 0.05) and higher BMD (p &lt; 0.001) compared with those of normal subjects following adjustment. The genotypes and allele frequency of rs12785878, rs10741657, rs6013897, rs2282679, rs4588 and rs7041 indicated no significant differences among three BMI groups following correction by the Bonferroni’s method (p &gt; 0.05). The levels of total 25(OH)D (ToVD) were significantly different among the GC1F, GC1S and GC2 haplotype groups (p &lt; 0.05). Correlation analysis indicated that ToVD levels were significantly correlated with parathyroid hormone levels, BMD, risk of osteoporosis (OP) and the concentration levels of other bone metabolism markers (p &lt; 0.05). Generalized varying coefficient models demonstrated that the increasing BMI, ToVD levels and their interactions were positively associated with BMD outcomes (p &lt; 0.001), whereas the reduced levels of ToVD and BMI increased the risk of OP, which was noted notably for the subjects with reduced ToVD levels (less than 20.69 ng/ml) combined with decreased BMI (less than 24.05 kg/m2).ConclusionThere was a non-linear interaction of BMI and 25(OH)D. And higher BMI accompanied by decreased 25(OH)D levels is associated with increased BMD and decreased incidence of OP, optimal ranges exist for BMI and 25(OH)D levels. The cutoff value of BMI at approximately 24.05 kg/m2 combined with an approximate value of 25(OH)D at 20.69 ng/ml are beneficial for Chinese elderly subjects.
Integrative single-cell RNA sequencing and metabolomics decipher the imbalanced lipid-metabolism in maladaptive immune responses during sepsis
Authors: She Han , Tan Lei , Wang Yi , Du Yuanlin , Zhou Yuanqun , Zhang Jun , Du Yunxia , Guo Ningke , Wu Zhengbin , Li Qinghui , Bao Daiqin , Mao Qingxiang , Hu Yi , Liu Liangming , Li Tao 
Published: April 2023

BackgroundTo identify differentially expressed lipid metabolism-related genes (DE-LMRGs) responsible for immune dysfunction in sepsis.MethodsThe lipid metabolism-related hub genes were screened using machine learning algorithms, and the immune cell infiltration of these hub genes were assessed by CIBERSORT and Single-sample GSEA. Next, the immune function of these hub genes at the single-cell level were validated by comparing multiregional immune landscapes between septic patients (SP) and healthy control (HC). Then, the support vector machine-recursive feature elimination (SVM-RFE) algorithm was conducted to compare the significantly altered metabolites critical to hub genes between SP and HC. Furthermore, the role of the key hub gene was verified in sepsis rats and LPS-induced cardiomyocytes, respectively.ResultsA total of 508 DE-LMRGs were identified between SP and HC, and 5 hub genes relevant to lipid metabolism (MAPK14, EPHX2, BMX, FCER1A, and PAFAH2) were screened. Then, we found an immunosuppressive microenvironment in sepsis. The role of hub genes in immune cells was further confirmed by the single-cell RNA landscape. Moreover, significantly altered metabolites were mainly enriched in lipid metabolism-related signaling pathways and were associated with MAPK14. Finally, inhibiting MAPK14 decreased the levels of inflammatory cytokines and improved the survival and myocardial injury of sepsis.ConclusionThe lipid metabolism-related hub genes may have great potential in prognosis prediction and precise treatment for sepsis patients.
A risk prediction model for type 2 diabetes mellitus complicated with retinopathy based on machine learning and its application in health management
Authors: Pan Hong , Sun Jijia , Luo Xin , Ai Heling , Zeng Jing , Shi Rong , Zhang An 
Published: April 2023

ObjectiveThis study aimed to establish a risk prediction model for diabetic retinopathy (DR) in the Chinese type 2 diabetes mellitus (T2DM) population using few inspection indicators and to propose suggestions for chronic disease management.MethodsThis multi-centered retrospective cross-sectional study was conducted among 2,385 patients with T2DM. The predictors of the training set were, respectively, screened by extreme gradient boosting (XGBoost), a random forest recursive feature elimination (RF-RFE) algorithm, a backpropagation neural network (BPNN), and a least absolute shrinkage selection operator (LASSO) model. Model I, a prediction model, was established through multivariable logistic regression analysis based on the predictors repeated ≥3 times in the four screening methods. Logistic regression Model II built on the predictive factors in the previously released DR risk study was introduced into our current study to evaluate the model’s effectiveness. Nine evaluation indicators were used to compare the performance of the two prediction models, including the area under the receiver operating characteristic curve (AUROC), accuracy, precision, recall, F1 score, balanced accuracy, calibration curve, Hosmer-Lemeshow test, and Net Reclassification Index (NRI).ResultsWhen including predictors, such as glycosylated hemoglobin A1c, disease course, postprandial blood glucose, age, systolic blood pressure, and albumin/urine creatinine ratio, multivariable logistic regression Model I demonstrated a better prediction ability than Model II. Model I revealed the highest AUROC (0.703), accuracy (0.796), precision (0.571), recall (0.035), F1 score (0.066), Hosmer-Lemeshow test (0.887), NRI (0.004), and balanced accuracy (0.514).ConclusionWe have built an accurate DR risk prediction model with fewer indicators for patients with T2DM. It can be used to predict the individualized risk of DR in China effectively. In addition, the model can provide powerful auxiliary technical support for the clinical and health management of patients with diabetes comorbidities.
Analysis of the current status of rehabilitation motivation and its influencing factors in older adults with stroke: a cross-sectional study
Authors: Tan Mingyang , Li Hongyu , Wang Xiuli 
Published: April 2023

ObjectiveAmong stroke patients, exercise adherence is an important factor in reducing the rate of physical disability and mortality. Rehabilitation exercise after stroke is a safe and effective measure to restore normal body functions, but the analysis of factors influencing patients’ motivation for rehabilitation is not well established. Therefore, this study will explore the influencing factors of rehabilitation motivation in older adults with stroke so as to reduce the disability rate of stroke.MethodA convenience sampling method was used to study 350 patients in a stroke ward of a tertiary care hospital in Jinzhou, Liaoning Province. Patients’ general demographic data, Multidimensional Scale of Perceived Social Support (PSSS), Questionnaire of Exercise Adherence (EAQ), Tampa scale of kinesiophobia (TSK-11), and Motivation in stroke patients for rehabilitation scale (MORE) were assessed. ANOVA or t-test analysis, correlation analysis, and linear regression analysis were used to explore the factors influencing the motivation for rehabilitation in older adults with stroke.ResultsThe results showed that stroke patients’ motivation for rehabilitation was at a moderate level. Perceived social support, exercise adherence, and stroke motivation were positively correlated (r = 0.619, p &lt; 0.01; r = 0.569, p &lt; 0.01), and kinesiophobia was negatively correlated with stroke motivation (r = −0.677, p &lt; 0.01). Time of stroke, location of the lesion, perceived social support, exercise adherence, and kinesiophobia are influential factors affecting patients’ motivation to recover.ConclusionIn the rehabilitation program for older adult patients with stroke, healthcare providers should specify targeted rehabilitation measures according to the different degrees of the patient’s condition, so as to improve the effectiveness of rehabilitation medical implementation.
Anterior basolateral amygdala neurons comprise a remote fear memory engram
Authors: Hammack Robert J. , Fischer Victoria E. , Andrade Mary Ann , Toney Glenn M. 
Published: April 2023

IntroductionThreatening environmental cues often generate enduring fear memories, but how these are formed and stored remains actively investigated. Recall of a recent fear memory is thought to reflect reactivation of neurons, in multiple brain regions, activated during memory formation, indicating that anatomically distributed and interconnected neuronal ensembles comprise fear memory engrams. The extent to which anatomically specific activation-reactivation engrams persist during long-term fear memory recall, however, remains largely unexplored. We hypothesized that principal neurons in the anterior basolateral amygdala (aBLA), which encode negative valence, acutely reactivate during remote fear memory recall to drive fear behavior.MethodsUsing adult offspring of TRAP2 and Ai14 mice, persistent tdTomato expression was used to “TRAP” aBLA neurons that underwent Fos-activation during contextual fear conditioning (electric shocks) or context only conditioning (no shocks) (n = 5/group). Three weeks later, mice were re-exposed to the same context cues for remote memory recall, then sacrificed for Fos immunohistochemistry.ResultsTRAPed (tdTomato +), Fos +, and reactivated (double-labeled) neuronal ensembles were larger in fear- than context-conditioned mice, with the middle sub-region and middle/caudal dorsomedial quadrants of aBLA displaying the greatest densities of all three ensemble populations. Whereas tdTomato + ensembles were dominantly glutamatergic in context and fear groups, freezing behavior during remote memory recall was not correlated with ensemble sizes in either group.DiscussionWe conclude that although an aBLA-inclusive fear memory engram forms and persists at a remote time point, plasticity impacting electrophysiological responses of engram neurons, not their population size, encodes fear memory and drives behavioral manifestations of long-term fear memory recall.
Safety and efficacy of endovascular recanalization for symptomatic non-acute atherosclerotic intracranial large artery occlusion
Authors: Chu Xi , Meng Yao , Zhang Jun , Sun Lili , Yin Hao , Dong Kaiyue , Chen Yingkun , Song Yun , Zheng Meimei , Wang Wei , Zhao Wei , Han Ju 
Published: April 2023

Background and objectiveThe optimal treatment for patients with symptomatic non-acute atherosclerotic intracranial large artery occlusion (ILAO) despite medical treatment is not well established. We aimed to assess the safety, efficacy, and feasibility of angioplasty and stenting for these patients.MethodsA total of 251 consecutive patients with symptomatic non-acute atherosclerotic ILAO treated with interventional recanalization were retrospectively collected in our center from March 2015 to August 2021. The rate of successful recanalization, perioperative complications, and follow-up outcomes were evaluated.ResultsSuccessful recanalization was achieved in 88.4% (222/251) of the patients. A total of 24 (24/251, 9.6%) symptomatic complications occurred among 251 procedures. In the 193 patients with clinical follow-up during 19.0 ± 14.7 months, 11 (11/193, 5.7%) patients developed ischemic stroke and four (4/193, 2.1%) patients developed transient ischemic attack (TIA). In the 106 patients with vascular imaging follow-up during 6.8 ± 6.6 months, seven (7/106, 6.6%) patients had restenosis and 10 (10/106, 9.4%) patients had reocclusion.ConclusionThis study suggests that interventional recanalization may be a feasible, basically safe, and an effective alternative in carefully selected patients with symptomatic non-acute atherosclerotic ILAO who have failed medical management.
A method for capturing dynamic spectral coupling in resting fMRI reveals domain-specific patterns in schizophrenia
Authors: Alaçam Deniz , Miller Robyn , Agcaoglu Oktay , Preda Adrian , Ford Judith , Calhoun Vince 
Published: April 2023

IntroductionResting-state functional magnetic resonance imaging (rs-fMRI) is a powerful tool for assessing functional brain connectivity. Recent studies have focused on shorter-term connectivity and dynamics in the resting state. However, most of the prior work evaluates changes in time-series correlations. In this study, we propose a framework that focuses on time-resolved spectral coupling (assessed via the correlation between power spectra of the windowed time courses) among different brain circuits determined via independent component analysis (ICA).MethodsMotivated by earlier work suggesting significant spectral differences in people with schizophrenia, we developed an approach to evaluate time-resolved spectral coupling (trSC). To do this, we first calculated the correlation between the power spectra of windowed time-courses pairs of brain components. Then, we subgrouped each correlation map into four subgroups based on the connectivity strength utilizing quartiles and clustering techniques. Lastly, we examined clinical group differences by regression analysis for each averaged count and average cluster size matrices in each quartile. We evaluated the method by applying it to resting-state data collected from 151 (114 males, 37 females) people with schizophrenia (SZ) and 163 (117 males, 46 females) healthy controls (HC).ResultsOur proposed approach enables us to observe the change of connectivity strength within each quartile for different subgroups. People with schizophrenia showed highly modularized and significant differences in multiple network domains, whereas males and females showed less modular differences. Both cell count and average cluster size analysis for subgroups indicate a higher connectivity rate in the fourth quartile for the visual network in the control group. This indicates increased trSC in visual networks in the controls. In other words, this shows that the visual networks in people with schizophrenia have less mutually consistent spectra. It is also the case that the visual networks are less spectrally correlated on short timescales with networks of all other functional domains.ConclusionsThe results of this study reveal significant differences in the degree to which spectral power profiles are coupled over time. Importantly, there are significant but distinct differences both between males and females and between people with schizophrenia and controls. We observed a more significant coupling rate in the visual network for the healthy controls and males in the upper quartile. Fluctuations over time are complex, and focusing on only time-resolved coupling among time-courses is likely to miss important information. Also, people with schizophrenia are known to have impairments in visual processing but the underlying reasons for the impairment are still unknown. Therefore, the trSC approach can be a useful tool to explore the reasons for the impairments.
Functional regionalization of the differentiating cerebellar Purkinje cell population occurs in an activity-dependent manner
Authors: Dorigo Alessandro , Valishetti Komali , Hetsch Florian , Matsui Hideaki , Meier Jochen C. , Namikawa Kazuhiko , Köster Reinhard W. 
Published: April 2023

IntroductionThe cerebellum is organized into functional regions each dedicated to process different motor or sensory inputs for controlling different locomotor behaviors. This functional regionalization is prominent in the evolutionary conserved single-cell layered Purkinje cell (PC) population. Fragmented gene expression domains suggest a genetic organization of PC layer regionalization during cerebellum development. However, the establishment of such functionally specific domains during PC differentiation remained elusive.Methods and resultsWe show the progressive emergence of functional regionalization of PCs from broad responses to spatially restricted regions in zebrafish by means of in vivo Ca2+-imaging during stereotypic locomotive behavior. Moreover, we reveal that formation of new dendritic spines during cerebellar development using in vivo imaging parallels the time course of functional domain development. Pharmacological as well as cell-type specific optogenetic inhibition of PC neuronal activity results in reduced PC dendritic spine density and an altered stagnant pattern of functional domain formation in the PC layer.DiscussionHence, our study suggests that functional regionalization of the PC layer is driven by physiological activity of maturing PCs themselves.
18F-labeled FGFR1 peptide: a new PET probe for subtype FGFR1 receptor imaging
Authors: Chen Yang , Han Jingya , Zhao Yan , Zhao Xinming , Zhao Mengmeng , Zhang Jingmian , Wang Jianfang 
Published: April 2023

IntroductionThe fibroblast growth factor receptor (FGFR) family is highly expressed in a variety of tumor types and represents a new target for cancer therapy. Different FGFR subtype aberrations have been found to exhibit highly variable sensitivity and efficacy to FGFR inhibitors.MethodsThe present study is the first to suggest an imaging method for assessing FGFR1 expression. The FGFR1-targeting peptide NOTA-PEG2-KAEWKSLGEEAWHSK was synthesized by manual solid-phase peptide synthesis and high-pressure liquid chromatography (HPLC) purification and then labeled with fluorine-18 using NOTA as a chelator. In vitro and in vivo experiments were conducted to evaluate the stability, affinity and specificity of the probe. Tumor targeting efficacy and biodistribution were evaluated by micro-PET/CT imaging in RT-112, A549, SNU-16 and Calu-3 xenografts.ResultsThe radiochemical purity of [18F]F-FGFR1 was 98.66% ± 0.30% (n = 3) with excellent stability. The cellular uptake rate of [18F]F-FGFR1 in the RT-112 cell line (FGFR1 overexpression) was higher than that in the other cell lines and could be blocked by the presence of excess unlabeled FGFR1 peptide. Micro-PET/CT imaging revealed a significant concentration of [18F]F-FGFR1 in RT-112 xenografts with no or very low uptake in nontargeted organs and tissues, which demonstrated that [18F]F-FGFR1 was selectively taken up by FGFR1-positive tumors.Conclusion[18F]F-FGFR1 showed high stability, affinity, specificity and good imaging capacity for FGFR1-overexpressing tumors in vivo, which provides new application potential in the visualization of FGFR1 expression in solid tumors.