bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fatty Acid Metabolic Signaling Pathway Alternation Predict Prognosis of Immune Checkpoint Inhibitors in Glioblastoma
Authors: Liu Rongrong , Liang Weidong , Hua Qian , Wu Longqiu , Wang Xiangcai , Li Qiang , Zhong Fangjun , Li Bin , Qiu Zhengang 
Published: February 2022

IntroductionGlioblastoma(GBM) is a highly malignant primary brain tumor. Even after undergoing surgery and chemotherapy, patients with this affliction still have little to no chance of survival. Current research on immunotherapy treatment for GBM shows that immune-checkpoint inhibitors (ICIs) may be a promising new treatment method. However, at present, the relationship between the fatty acid metabolic process and the prognosis of GBM patients who are receiving immunotherapy is not clear.MethodsFirst, we downloaded a GBM cohort that had been treated with immunotherapy, which included the mutation and prognosis data, and the TCGA-GBM and Jonsson-GBM queues. CIBERSORT and single sample gene set enrichment analysis(ssGSEA) were used to evaluate immune cell scores. Gene set enrichment analysis (GSEA) was used to evaluate the patient’s accessment score. The pRRophetic algorithm was used to evaluate the drug sensitivity of each patient. Univariable and multivariate cox regression analyses, as well as the Kaplan-Meier (KM) method, were used to evaluate the relationship between the fatty acid metabolic process and the prognosis of GBM patients.ResultsThe univariate and multivariate cox regression models showed that the fatty acid metabolic process mutant-type (MT) can be used as an independent predictor of the efficacy of immunotherapy for GBM patients. In addition, fatty acid metabolic process MT is related with significantly longer overall survival (OS) time than the wild-type(WT) variant. However, the mutation status of the fatty acid metabolic process has nothing to do with the prognosis of GBM patients who are receiving conventional treatment. Our analysis showed that fatty acid metabolic process MT correlated with significantly increased natural killer T (NKT) cells and significantly decreased CD8+T cells. At the same time, GSEA analysis revealed that fatty acid metabolic process MT was associated with significantly increased immune activation pathways and an enriched fraction of cytokine secretion compared with WT.ConclusionsWe found that fatty acid metabolic process MT may be used as an independent predictor of the efficacy of ICI treatment in GBM patients. Use of the fatty acid metabolic process MT will result in higher immunogenicity rates, a significant increase in the proportion of activated immune cells, and improvement of the immune microenvironment.
Cooperation of RNA-Binding Proteins – a Focus on Roquin Function in T Cells
Authors: Behrens Gesine , Heissmeyer Vigo 
Published: February 2022

Post-transcriptional gene regulation by RNA-binding proteins (RBPs) is important in the prevention of inflammatory and autoimmune diseases. With respect to T cell activation and differentiation, the RBPs Roquin-1/2 and Regnase-1 play pivotal roles by inducing degradation and/or translational silencing of target mRNAs. These targets encode important proinflammatory mediators and thus Roquin and Regnase-1 functions dampen cellular programs that can lead to inflammation and autoimmune disease. Recent findings demonstrate direct physical interaction of both RBPs. Here, we propose that cooperativity of trans-acting factors may be more generally used to reinforce the regulatory impact on selected targets and promote specific cell fate decisions. We develop this concept for Roquin and Regnase-1 function in resting and activated T cells and discuss the involvement in autoimmunity as well as how the therapeutic potential can be used in anti-tumor therapies.
HDAC3-Regulated PGE2 Production by Microglia Induces Phobic Anxiety Susceptibility After Stroke and Pointedly Exploiting a Signal-Targeted Gamma Visual Stimulation New Therapy
Authors: Zhu Hongrui , Guo Yi , Huang Ailing , Shen Huidan , Chen Yang , Song Jingyi , Guan Ao , Wu Liang , Wang Huiting , Deng Bin 
Published: February 2022

BackgroundPhobic anxiety present after stroke (called poststroke anxiety, PSA) can hamper the rehabilitation of patients and disrupt their usual activities. Besides, the symptoms and mechanisms of PSA are different from those in nonstroke populations that have generalized anxiety disorder. What’s more, the treatment approaches for phobic anxiety are confined to unitary or general methods with poor efficiency.MethodsBehavioural test screen combined bioinformatics analysis explored molecular changes between generalized anxiety disorder in nonstroke mice (restraint stress, RS) and photothrombotic stroke mice exposed to environmental stress (PTS + RS, mimicking PSA). Multiple molecular biological and neurobiological methods were employed to explain mechanisms in vitro and in vivo. And exploiting gamma flicker stimulation device for therapy.ResultsMicroglial (MG) overactivation is a prominent characteristic of PTS + RS. HDAC3 was mainly upregulated in activated-microglia from damaged cortex and that local prostaglandin E2 (PGE2) production increased in MG via HDAC3-mediated activation of NF-κB signalling by p65 deacetylation. A high content of PGE2 in damaged ischaemic cortex could diffuse freely to amygdala, eliciting anxiety susceptibility of PSA via EP2. Importantly, gamma flicker stimulation relieved anxious behaviour of PTS + RS by modulating the HDAC3/Cox1/EP2 network at some extent.ConclusionsHDAC3-regulated PGE2 production by microglia constitutes phobic anxiety susceptibility after stroke and a protective approach of gamma visual stimulation can be a candidate new therapy.
Prediction Model of Immunosuppressive Medication Non-adherence for Renal Transplant Patients Based on Machine Learning Technology
Authors: Zhu Xiao , Peng Bo , Yi QiFeng , Liu Jia , Yan Jin 
Published: February 2022

ObjectivesPredicting adherence to immunosuppressive medication (IM) is important to improve and design future prospective, personalized interventions in Chinese renal transplant patients (RTPs).MethodsA retrospective, multicenter, cross-sectional study was performed in 1,191 RTPs from October 2020 to February 2021 in China. The BAASIS was used as the standard to determine the adherence of the patients. Variables of the combined theory, including the general data, the HBM, the TPB, the BMQ, the PSSS and the GSES, were used to build the models. The machine learning (ML) models included LR, RF, MLP, SVM, and XG Boost. The SHAP method was used to evaluate the contribution of predictors to predicting the risk of IM non-adherence in RTPs.ResultsThe IM non-adherence rate in the derivation cohort was 38.5%. Ten predictors were screened to build the model based on the database. The SVM model performed better among the five models, with sensitivity of 0.59, specificity of 0.73, and average AUC of 0.75. The SHAP analysis showed that age, marital status, HBM-perceived barriers, use pill box after transplantation, and PSSS-family support were the most important predictors in the prediction model. All of the models had good performance validated by external data.ConclusionsThe IM non-adherence rate of RTPs was high, and it is important to improve IM adherence. The model developed by ML technology could identify high-risk patients and provide a basis for the development of relevant improvement measures.
Colorful Treasure From Agro-Industrial Wastes: A Sustainable Chassis for Microbial Pigment Production
Authors: Grewal Jasneet , Woła̧cewicz Mikołaj , Pyter Weronika , Joshi Namrata , Drewniak Lukasz , Pranaw Kumar 
Published: February 2022

Graphical AbstractAn illustration exhibiting perusal of natural pigment production as a safe alternative to synthetic ones.
ROBOCOP (ROBOtic Care of Poststroke Pain): Study Protocol for a Randomized Trial to Assess Robot-Assisted Functional and Motor Recovery and Impact on Poststroke Pain Development
Authors: Pignolo Loris , Tonin Paolo , Nicotera Pierluigi , Bagetta Giacinto , Scuteri Damiana 
Published: February 2022

BackgroundStroke is one of the most frequent causes of death and disability worldwide. It is accompanied by the impaired motor function of the upper extremities in over 69% of patients up to hemiplegia in the following 5 years in 56% of cases. This condition often is characterized by chronic poststroke pain, difficult to manage, further worsening quality of life. Poststroke pain occurs within 3–6 months. Robot-assisted neurorehabilitation using the Automatic Recovery Arm Motility Integrated System (ARAMIS) has proven efficacy in motor function recovery exploiting the movements and the strength of the unaffected arm. The rationale of the ROBOCOP (ROBOtic Care of Poststroke pain) randomized trial is the assessment of the impact of robot-assisted functional and motor recovery on the prevention of poststroke pain.MethodsA total of 118 patients with hemiplegic arms due to stroke will be enrolled and randomly allocated with a 1:1 ratio to ARAMIS or conventional neurorehabilitation group. After a baseline screening at hospital discharge, ARAMIS or conventional rehabilitation will be performed for 8 weeks. The primary endpoint is the prevention of the development of poststroke pain and the secondary endpoints are prevention of spasticity and efficacy in clinical motor rehabilitation. The primary outcome measures consist in the visual analog scale and the doleur neuropatique 4 and the secondary outcome measures include: the Modified Ashworth Scale, the Resistance to Passive movement Scale; the Upper Extremity Subscale of the Fugl–Meyer Motor Assessment; the Action Research Arm Test; the Barthel Index for activities of daily living; and the magnetic resonance imaging (MRI) recovery-related parameters. After baseline, both primary and secondary outcome measures will be performed in the following time points: 1 month after stroke (t1, half of the rehabilitation); 2 months after stroke (t2, after rehabilitation); and 3 months (t3) and 6 months (t4) after stroke, critical for poststroke pain development.DiscussionThis is the first clinical trial investigating the efficacy of robot-assisted neurorehabilitation using ARAMIS on poststroke pain prevention. This study could remarkably improve the quality of life of stroke survivors.
Efficacy of Transcranial Direct Current Stimulation Over Dorsolateral Prefrontal Cortex in Patients With Minimally Conscious State
Authors: Peng Yuan , Zhao Jingpu , Lu Xiao , Dong Juntao , Zhang Shunxi , Zhang Jin , Liu Huihua , Zheng Xiuyuan , Wang Xin , Lan Yue , Yan Tiebin 
Published: February 2022

BackgroundThe treatment of patients in a minimally conscious state (MCS) remains challenging. Transcranial direct current stimulation (tDCS) is a non-invasive therapeutic method in treating neurologic diseases by regulating the cortical excitability. The aim is to investigate the effect of tDCS in patients with MCS in this study.MethodsEleven patients in MCS were enrolled in the study. All the patients received 5 daily sessions of 20-min sham tDCS, followed by 10 sessions of 20-min real tDCS. The anodal electrode and cathodal electrodes were placed over the left dorsolateral prefrontal cortex (DLPFC) and the right eyebrow, respectively. Assessment of Coma Recovery Scale-Revised (CRS-R) scores and resting-state functional MRI (rs-fMRI) scans was conducted three times in each patient: before tDCS (baseline, T0), post-sham tDCS at week 1 (T1), and post-real tDCS at week 2 (T2). The whole-brain functional connectivity (FC) was obtained by bilaterally computing FC from six seed regions: precuneus, middle frontal gyrus, supplemental motor area, angular gyrus, superior temporal gyrus, and occipital lobe. One-way repeated measure ANOVA was used to compare the differences of CRS-R scores and FC at T0, T1, and T2. The false discovery rate correction of p &lt; 0.001 was adopted for controlling multiple comparisons in FC analysis.ResultsFive patients with MCS showed obvious clinical improvement represented by increased CRS-R scores post- 2-week real tDCS. The CRS-R scores did not change post- 1-week sham treatment. No side effects were reported during the study. The FC of the bilateral supplementary motor area, right angular gyrus, and right superior temporal gyrus were significantly enhanced after 2-week real tDCS compared with that after 1-week sham-tDCS. In addition, FC of bilateral occipital lobe and right precuneus were significantly enhanced post- 2-week real tDCS compared with the baseline.ConclusionOur findings indicated that tDCS over DLPFC could serve as a potentially effective therapy for improving the consciousness state in patients with MCS. The FC in rs-fMRI can be modulated by tDCS at both the stimulation site (left DLPFC) and the distant regions.
A Dynamic Nomogram to Predict the Risk of Stroke in Emergency Department Patients With Acute Dizziness
Authors: Bi Ying , Cao Fei 
Published: February 2022

ObjectiveTo develop a risk prediction tool for acute ischemic stroke (AIS) for patients presenting to the emergency department (ED) with acute dizziness/vertigo or imbalance.MethodA prospective, multicenter cohort study was designed, and adult patients presenting with dizziness/vertigo or imbalance within 14 days were consecutively enrolled from the EDs of 4 tertiary hospitals between August 10, 2020, and June 10, 2021. Stroke was diagnosed by CT or MRI performed within 14 days of symptom onset. Participants were followed-up for 30 days. The least absolute shrinkage and selection operator (LASSO) logistic regression analysis was conducted to extract predictive factors that best identified patients at high risk of stroke to establish a prediction model. Model discrimination and calibration were assessed and its prediction performance was compared with the age, blood pressure, clinical features, duration, and diabetes (ABCD2) score, nystagmus scheme, and finger to nose test.ResultsIn this study, 790 out of 2,360 patients were enrolled {median age, 60.0 years [interquartile range (IQR), 51–68 years]; 354 (44.8%) men}, with complete follow-up data available. AIS was identified in 80 patients. An online web service tool (https://neuroby.shinyapps.io/dynnomapp/) was developed for stroke risk prediction, including the variables of sex, trigger, isolated symptom, nausea, history of brief dizziness, high blood pressure, finger to nose test, and tandem gait test. The model exhibited excellent discrimination with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.889 (95% CI: 0.855–0.923), compared with the ABCD2 score, nystagmus scheme, and finger to nose test [0.712 (95% CI, 0.652–0.771), 0.602 (95% CI, 0.556–0.648), and 61.7 (95% CI, 0.568–0.666) respectively].ConclusionOur new prediction model exhibited good performance and could be useful for stroke identification in patients presenting with dizziness, vertigo, or imbalance. Further externally validation study is needed to increase the strength of our findings.
Electronic Cigarette Vaping Did Not Enhance the Neural Process of Working Memory for Regular Cigarette Smokers
Authors: Kim Dong-Youl , Jang Yujin , Heo Da-Woon , Jo Sungman , Kim Hyun-Chul , Lee Jong-Hwan 
Published: February 2022

BackgroundElectronic cigarettes (e-cigs) as substitute devices for regular tobacco cigarettes (r-cigs) have been increasing in recent times. We investigated neuronal substrates of vaping e-cigs and smoking r-cigs from r-cig smokers.MethodsTwenty-two r-cig smokers made two visits following overnight smoking cessation. Functional magnetic resonance imaging (fMRI) data were acquired while participants watched smoking images. Participants were then allowed to smoke either an e-cig or r-cig until satiated and fMRI data were acquired. Their craving levels and performance on the Montreal Imaging Stress Task and a 3-back alphabet/digit recognition task were obtained and analyzed using two-way repeated-measures analysis of variance. Regions-of-interest (ROIs) were identified by comparing the abstained and satiated conditions. Neuronal activation within ROIs was regressed on the craving and behavioral data separately.ResultsCraving was more substantially reduced by smoking r-cigs than by vaping e-cigs. The response time (RT) for the 3-back task was significantly shorter following smoking r-cigs than following vaping e-cigs (interaction: F (1, 17) = 5.3, p = 0.035). Neuronal activations of the right vermis (r = 0.43, p = 0.037, CI = [-0.05, 0.74]), right caudate (r = 0.51, p = 0.015, CI = [0.05, 0.79]), and right superior frontal gyrus (r = −0.70, p = 0.001, CI = [−0.88, −0.34]) were significantly correlated with the RT for the 3-back task only for smoking r-cigs.ConclusionOur findings suggest that insufficient satiety from vaping e-cigs for r-cigs smokers may be insignificant effect on working memory function.
Psoas Muscle Index Can Be Used to Predict Long-Term Mortality in Young Male Patients With Acute-on-Chronic Liver Failure
Authors: Xu Manman , Li Tongzeng , Kong Ming , Geng Nan , Song Wenyan , Guo Guanya , Duan Zhongping , Han Ying , Chen Yu 
Published: February 2022

ObjectiveThe use of psoas muscle index (PMI) in acute-on-chronic liver failure (ACLF) has not been reported, and the aim of this study was to evaluate the predictive value of PMI for the prognosis of patients with ACLF.MethodsIn this study, male ACLF patients who underwent abdominal CT between 2015 and 2019 in our center were included to analyze the association between PMI and 1-year mortality in male ACLF patients, and subgroup analyses were performed according to age stratification (≤ 40 and &gt;40 years).ResultsWe included 116 male patients with confirmed ACLF, with a mean PMI of 5.98 ± 1.68 cm2/m2 and a 1-year mortality of 51.7% (60). Univariate COX regression analysis showed that PMI was a protective factor [hazard ratio (HR), 0.851, 95%CI: 0.734–0.987] for 1-year mortality in male patients with ACLF. Nevertheless, multivariate analysis did not find an independent relationship between PMI and 1-year mortality. Subgroup analysis by age found that adjusted for MELD score, PMI was independently associated with 1-year mortality in young (age ≤ 40 years) male patients with ACLF (HR 0.689, 95% CI: 0.496–0.958). While no effect of PMI on 1-year mortality in non-young (age &gt; 40 years) male ACLF patients was found. Correlation analysis found that there was no significant correlation between PMI and age in young (age ≤ 40 years) male ACLF patients, but, PMI decreased with age (r = −0.246, P &lt; 0.05) in non-young (age &gt; 40 years) male ACLF patients.ConclusionPMI was found to be associated with 1-year mortality in male ACLF patients, especially in patients younger than 40 years, PMI predict 1-year mortality independent of MELD score.
A Composite Biomarker of Derived Neutrophil–Lymphocyte Ratio and Platelet–Lymphocyte Ratio Correlates With Outcomes in Advanced Gastric Cancer Patients Treated With Anti-PD-1 Antibodies
Authors: Pan Yuting , Si Haiyan , Deng Guochao , Chen Shiyun , Zhang Nan , Zhou Qian , Wang ZhiKuan , Dai Guanghai 
Published: February 2022

BackgroundThe highly heterogeneous characteristics of GC may limit the accuracy of a single biomarker for screening populations benefiting from immunotherapy. However, the combination of multiple indicators can provide more directed information for the detection of potential immune benefit subgroups. At present, there are no recognized complex indexes to identify advanced GC (AGC) in patients who likely benefited from immunotherapy. The objective of this research is to explore whether the composite biomarker of derived neutrophil–lymphocyte ratio (dNLR) and platelet–lymphocyte ratio (PLR) can be used as a reliable prognostic factor for the survival of AGC patients receiving immunotherapy.MethodsFrom December 2014 to May 2021, a total 238 AGC patients at a single Center were included in this retrospective cohort research study. The cutoff value of dNLR was obtained by the ROC curves to predict the disease progression rate at the 8th month and the cutoff value of PLR was estimated by the median value. The cutoff values of dNLR and PLR were 1.95 and 163.63, respectively. The high levels of dNLR (≥1.95) and PLR (≥163.63) were considered to be risk factors. Based on these two risk factors, patients were categorized into 3 groups: the risk factor number for the “good” group was 0, that for the “intermediate” group was 1, and that for the “poor” group was 2. The subjects were divided into two groups: dNLR/PLR-good and dNLR/PLR-intermediate/poor.ResultsOf the 238 patients, the median overall survival (mOS) and progression-free survival (mPFS) were 12.5 and 4.7 months, respectively. Multivariate analysis revealed that the good dNLR/PLR group was independently associated with better prognosis. The intermediate/poor dNLR/PLR group was independently correlated with an over 1.4 times greater risk of disease progression (4.1 months vs. 5.5 months; p = 0.016) and an over 1.54 times greater risk of death (11.1 months vs. 26.3 months; p = 0.033) than the good dNLR/PLR group. However, no clear differences in the disease control rate (DCR) and overall response rate (ORR) were observed between the intermediate/poor dNLR/PLR group and the good dNLR/PLR group (51.5% vs. 56.3%, 26.3% vs. 29.6%; p = 0.494, p = 0.609).ConclusionOur study firstly verifies that the composite biomarker of dNLR and PLR is an independent prognostic factor affecting survival of advanced AGC patients receiving immunotherapy. It may be difficult for patients with the intermediate/poor dNLR/PLR group to benefit from immunotherapy.
Treatment Modality for Stage IB Peripheral Non-Small Cell Lung Cancer With Visceral Pleural Invasion and ≤3 cm in Size
Authors: Huang Weijia , Deng Han-Yu , Lin Ming-Ying , Xu Kai , Zhang Yu-Xiao , Yuan Chi , Zhou Qinghua 
Published: February 2022

PurposeTo compare the survival difference among lobectomy, segmentectomy, and wedge resection and investigate the role of adjuvant chemotherapy for early-stage small-sized non-small cell lung cancer (NSCLC) with visceral pleural invasion (VPI).MethodsPatients diagnosed with stage IB peripheral NSCLC with VPI and ≤3 cm in size in the Surveillance, Epidemiology, and End Results database between 2004 and 2015 were included, and the pleural layer (PL) invasion status was identified to recognize the tumors with VPI, including PL1 and PL2. We conducted Cox proportional hazards model in multivariable analysis and subgroup analysis via propensity score matching (PSM) method and Cox regression method to figure out the optimal therapy for these patients.ResultsA total of 1,993 patients were included, all of whom received surgery, and the median follow-up was 33 months (range, 1–83 months). In multivariable analysis, age, gender, histology, pathological grade, lymph node examination, surgical approaches, and radiotherapy were independent prognostic factors for overall survival (OS). Lobectomy was superior to sublobar resection [hazard ratio (HR) = 1.41; 95% CI, 1.08–1.83], and wedge resection was associated with impaired survival compared to lobectomy (HR = 1.64; 95% CI, 1.22–2.20) in PSM analyses. In subgroup analysis, lobectomy was superior to sublobar resection among those aged &lt;70 years (HR = 1.81; 95% CI, 1.13–2.90), female (HR = 1.75; 95% CI, 1.21–2.53), and 1–20 mm in size (HR = 1.61; 95% CI, 1.11–2.33). No survival benefit was observed for adjuvant chemotherapy.ConclusionsLobectomy was superior to wedge resection and comparable with segmentectomy for stage IB NSCLC (≤3 cm) with VPI, and adjuvant chemotherapy could not benefit these patients, even in those with sublobar resection. The preferred surgical procedure remains to be studied in prospective controlled trials.