bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Metabolic Profiling of Inflammation Indicated Key Roles of Glycerophospholipid and Arginine Metabolism in Coronary Artery Disease
Authors: Zhu Qian , Wu Yonglin , Mai Jinxia , Guo Gongjie , Meng Jinxiu , Fang Xianhong , Chen Xiaoping , Liu Chen , Zhong Shilong 
Published: March 2022

BackgroundSystemic immune inflammation is a key mediator in the progression of coronary artery disease (CAD), concerning various metabolic and lipid changes. In this study, the relationship between the inflammatory index and metabolic profile in patients with CAD was investigated to provide deep insights into metabolic disturbances related to inflammation.MethodsWidely targeted plasma metabolomic and lipidomic profiling was performed in 1,234 patients with CAD. Laboratory circulating inflammatory markers were mainly used to define general systemic immune and low-grade inflammatory states. Multivariable-adjusted linear regression was adopted to assess the associations between 860 metabolites and 7 inflammatory markers. Least absolute shrinkage and selection operator (LASSO) logistic-based classifiers and multivariable logistic regression were applied to identify biomarkers of inflammatory states and develop models for discriminating an advanced inflammatory state.ResultsMultiple metabolites and lipid species were linearly associated with the seven inflammatory markers [false discovery rate (FDR) &lt;0.05]. LASSO and multivariable-adjusted logistic regression analysis identified significant associations between 45 metabolites and systemic immune-inflammation index, 46 metabolites and neutrophil–lymphocyte ratio states, 32 metabolites and low-grade inflammation score, and 26 metabolites and high-sensitivity C-reactive protein states (P &lt; 0.05). Glycerophospholipid metabolism and arginine and proline metabolism were determined as key altered metabolic pathways for systemic immune and low-grade inflammatory states. Predictive models based solely on metabolite combinations showed feasibility (area under the curve: 0.81 to 0.88) for discriminating the four parameters that represent inflammatory states and were successfully validated using a validation cohort. The inflammation-associated metabolite, namely, β-pseudouridine, was related to carotid and coronary arteriosclerosis indicators (P &lt; 0.05).ConclusionsThis study provides further information on the relationship between plasma metabolite profiles and inflammatory states represented by various inflammatory markers in CAD. These metabolic markers provide potential insights into pathological changes during CAD progression and may aid in the development of therapeutic targets.
Effect of Serum Phosphate on the Prognosis of Septic Patients: A Retrospective Study Based on MIMIC-IV Database
Authors: Li Zhaoyang , Shen Tingwen , Han Yi 
Published: March 2022

ObjectiveTo assess the effect of serum inorganic phosphate (Pi) on the prognosis of patients with sepsis.MethodsA retrospective analysis of patients with sepsis selected from the Medical Information Mart for Intensive Care (MIMIC)-IV database was performed. Sepsis was diagnosed according to the Third International Consensus Definition for sepsis and septic shock (Sepsis-3). The time-weighted values of the serum Pi measurements within the first 24 h of sepsis were analyzed. The association between serum Pi and in-hospital mortality was evaluated with a generalized linear model (log-binomial model).ResultsThe analysis of 11,658 patients from six intensive care units (ICUs) showed a nearly linear correlation between serum Pi and in-hospital mortality in all patients with sepsis, especially in those with acute kidney injury (AKI). The increase of serum Pi was related to a higher risk of AKI, higher norepinephrine doses, ICU mortality, and in-hospital mortality. The generalized linear model showed that serum Pi was an independent predictor for in-hospital mortality in all patients with sepsis even within the normal range. The adjusted risk ratios (RRs) were also significant in subgroup analyses according to kidney function, gender, respiratory infection, vasopressor use, and Sequential Organ Failure Assessment (SOFA) score.ConclusionHigher levels of serum Pi, even within the normal range, were significantly associated with a higher risk of in-hospital mortality in patients with sepsis regardless of kidney function, gender, respiratory infection, vasopressor use, and SOFA score.
Socioeconomic Inequalities in COVID-19 Incidence During Different Epidemic Phases in South Korea
Authors: Yoo Dae-sung , Hwang Minji , Chun Byung Chul , Kim Su Jin , Son Mia , Seo Nam-Kyu , Ki Myung 
Published: March 2022

ObjectiveArea-level socioeconomic status (SES) is associated with coronavirus disease 2019 (COVID-19) incidence. However, the underlying mechanism of the association is context-specific, and the choice of measure is still important. We aimed to evaluate the socioeconomic gradient regarding COVID-19 incidence in Korea based on several area-level SES measures.MethodsCOVID-19 incidence and area-level SES measures across 229 Korean municipalities were derived from various administrative regional data collected between 2015 and 2020. The Bayesian negative binomial model with a spatial autocorrelation term was used to estimate the incidence rate ratio (IRR) and relative index of inequality (RII) of each SES factor, with adjustment for covariates. The magnitude of association was compared between two epidemic phases: a low phase (&lt;100 daily cases, from May 6 to August 14, 2020) and a rebound phase (&gt;100 daily cases, from August 15 to December 31, 2020).ResultsArea-level socioeconomic inequalities in COVID-19 incidence between the most disadvantaged region and the least disadvantaged region were observed for nonemployment rates [RII = 1.40, 95% credible interval (Crl) = 1.01–1.95] and basic livelihood security recipients (RII = 2.66, 95% Crl = 1.12–5.97), but were not observed for other measures in the low phase. However, the magnitude of the inequalities of these SES variables diminished in the rebound phase. A higher area-level mobility showed a higher risk of COVID-19 incidence in both the low (IRR = 1.67, 95% Crl = 1.26–2.17) and rebound phases (IRR = 1.28, 95% Crl = 1.14–1.44). When SES and mobility measures were simultaneously adjusted, the association of SES with COVID-19 incidence remained significant but only in the low phase, indicating they were mutually independent in the low phase.ConclusionThe level of basic livelihood benefit recipients and nonemployment rate showed social stratification of COVID-19 incidence in Korea. Explanation of area-level inequalities in COVID-19 incidence may not be derived only from mobility differences in Korea but, instead, from the country's own context.
Analysis of Conjunctival Sac Microbiome in Dry Eye Patients With and Without Sjögren's Syndrome
Authors: Song Hang , Xiao Kang , Chen Zhengyu , Long Qin 
Published: March 2022

PurposeTo analyze the conjunctival sac microbial communities in patients with Sjögren's syndrome-associated dry eyes (SSDE) and non-Sjögren's syndrome-associated dry eyes (NSSDE), compared with normal controls (NC).MethodsConjunctival sac swab samples from 23 eyes of SSDE, 36 eyes of NSSDE, and 39 eyes of NC were collected. The V3–V4 region of the 16S ribosomal RNA (rRNA) gene high-throughput sequencing was performed on an Illumina MiSeq platform and analyzed using Quantitative Insights Into Microbial Ecology (QIIME). Alpha diversity was employed to analyze microbiome diversity through Chao1 and Shannon indexes. Beta diversity was demonstrated by the principal coordinates analysis (PCoA) and Partial Least Squares Discrimination Analysis (PLS-DA). The relative abundance was bioinformatically analyzed at the phylum and genus levels.ResultsThe alpha diversity was lower in patients with dry eye disease (Shannon index: NC vs. SSDE: P = 0.020, NC vs. NSSDE: P = 0.029). The beta diversity showed divergent microbiome composition in different groups (NC vs. SSDE: P = 0.001, NC vs. NSSDE: P = 0.001, NSSDE vs. SSDE: P = 0.005). The top 5 abundant phyla were Firmicutes, Proteobacteria, Actinobacteriota, Bacteroidota, and Cyanobacteria in all three groups. The top five abundant genera included Acinetobacter, Staphylococcus, Bacillus, Corynebacterium, and Clostridium_sensu_stricto_1. The relative microbiome abundance was different between groups. The Firmicutes/Bacteroidetes (F/B) ratio was 6.42, 7.31, and 9.71 in the NC, NSSDE, and SSDE groups, respectively (NC vs. SSDE: P = 0.038, NC vs. NSSDE: P = 0.991, SSDE vs. NSSDE: P = 0.048).ConclusionThe diversity of conjunctival sac microbiome in patients with NSSDE and SSDE was diminished compared with NC. The main microbiome at the phylum and genus level were similar between groups, but the relative abundance had variations. The Firmicutes/Bacteroidetes ratio was higher in the SSDE group.
Deciphering Key Foreign Body Reaction-Related Transcription Factors and Genes Through Transcriptome Analysis
Authors: Liu Wei , Xiong Shaoheng , Du Jing , Song Yajuan , Wang Tong , Zhang Yu , Dong Chen , Huang ZhaoSong , He Qiang , Yu Zhou , Ma Xianjie 
Published: March 2022

Background: Silicone implants are widely used in the field of plastic surgery for wound repair and cosmetic augmentation. However, molecular mechanisms and signaling pathways underlying the foreign body reaction (FBR) of a host tissue to the silicone require further elucidation. The purpose of this study was to identify key FBR-related transcription factors (TFs) and genes through transcriptome analysis.Methods: We used a rat model with a subcutaneous silicone implant in the scalp and performed high throughput sequencing to determine the transcriptional profiles involved in the FBR. The function was analyzed by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-enrichment analysis. A protein-protein interaction (PPI) network of differentially expressed mRNAs (DEmRNAs) was constructed to identify the hub genes and key modules and to determine the regulatory TF-mRNA relationships. In addition, the hub gene and transcript expression levels were determined by Quantitative Reverse Transcription polymerase Chain Reaction (qRT-PCR). Myofibroblasts differentiation and macrophage recruitment were identified by immunofluorescence. The protein expression of MMP9 was detected by immunohistochemistry and Western blot.Results: We identified ten hub genes (Fos, Spp1, Fn1, Ctgf, Tlr2, Itgb2, Itgax, Ccl2, Mmp9, and Serpine1) and 3 TFs (FOS, IRF4, and SPI1) that may be crucial (particularly FOS) for the FBR. Furthermore, we identified multiple differentially expressed genes involved in several important biological processes, including leukocyte migration, cytokine‒ cytokine receptor interaction, phagocytosis, extracellular matrix (ECM) organization, and angiogenesis. We also identified potentially significant signaling pathways, including cytokine‒cytokine receptor interaction, phagosome, ECM‒receptor interaction, complement and coagulation cascades, the IL-17 signaling pathway, and the PI3K‒Akt signaling pathway. In addition, qRT-PCR confirmed the expression patterns of the TFs and hub genes, Western blot and immunohistochemistry validated the expression patterns of MMP9.Conclusion: We generated a comprehensive overview of the gene networks underlying the FBR evoked by silicone implants. Moreover, we identified specific molecular and signaling pathways that may perform key functions in the silicone implant-induced FBR. Our results provide significant insights into the molecular mechanisms underlying silicone-induced FBR and determine novel therapeutic targets to reduce complications related to silicone implantation.
Higher Burden of Cerebral Small Vascular Disease Predicts Major Adverse Cardiac and Cerebrovascular Events and Is Related to Abnormal Blood Pressure Variability Pattern in Hypertension Patients
Authors: Xu Xiaomeng , Huang Shu , Zeng YuE , Feng Yulan , Yue Dongqi , Shen Fanxia , Gao Yang , Zhang Bei , Yang Yang , Gu Lin , Fu Yi 
Published: March 2022

Background and ObjectivesThe study aims to test the hypotheses that a higher burden of cerebral small vascular disease (CSVD) predicts major adverse cardiac and cerebrovascular events (MACCE) in patients with hypertension (HTN) and that abnormal blood pressure variability (BPV) pattern aggravates total CSVD burden.MethodsWe retrospectively reviewed patients with HTN prospectively selected between February 2015 and February 2019 from three participating centers. Patients were included if they had HTN for over 1 year and had at least one MRI feature of CSVD. Independent predictors were found using multivariate logistic regression.ResultsAmong the 908 patients who finally enrolled in the study, the number of CSVD markers (OR = 1.940; 95% CI = 1.393–2.703; P &lt; 0.001) independently predicted MACCE with acceptable predictive value (C-statistic = 0.730; 95% CI = 0.669–0.791; P &lt; 0.001). An abnormal BPV pattern was identified as an independent risk factor for increased CSVD burden. Among them, reverse-dipper subtype demonstrated the most significant relationship (OR = 1.725; 95% CI = 1.129–2.633; P = 0.012).ConclusionTotal CSVD burden predicts an increased risk of composite MACCE independently. An abnormal BPV pattern is associated with a higher burden of CSVD.
Impact of Voluntary Muscle Activation on Stretch Reflex Excitability in Individuals With Hemiparetic Stroke
Authors: Patterson Jacqueline R. , Dewald Julius P. A. , Drogos Justin M. , Gurari Netta 
Published: March 2022

ObjectiveTo characterize how, following a stretch-induced attenuation, volitional muscle activation impacts stretch reflex activity in individuals with stroke.MethodsA robotic device rotated the paretic elbow of individuals with hemiparetic stroke from 70° to 150°, and then back to 70° elbow flexion at an angular speed of 120°/s. This stretching sequence was repeated 20 times. Subsequently, participants volitionally activated their elbow musculature or rested. Finally, the stretching sequence was repeated another 20 times. The flexors' stretch reflex activity was quantified as the net torque measured at 135°.ResultsData from 15 participants indicated that the stretching sequence attenuated the flexion torque (p &lt; 0.001) and resting sustained the attenuation (p = 1.000). Contrastingly, based on data from 14 participants, voluntary muscle activation increased the flexion torque (p &lt; 0.001) to an initial pre-stretch torque magnitude (p = 1.000).ConclusionsStretch reflex attenuation induced by repeated fast stretches may be nullified when individuals post-stroke volitionally activate their muscles. In contrast, resting may enable a sustained reflex attenuation if the individual remains relaxed.SignificanceStretching is commonly implemented to reduce hyperactive stretch reflexes following a stroke. These findings suggest that stretch reflex accommodation arising from repeated fast stretching may be reversed once an individual volitionally moves their paretic arm.
The Impact of Mean Arterial Pressure and Volume Contraction in With Acute Ischemic Stroke
Authors: Bahouth Mona N. , Saylor Deanna , Hillis Argye E. , Gottesman Rebecca F. 
Published: March 2022

Background and PurposeHydration at the time of stroke may impact functional outcomes. We sought to investigate the relationship between blood pressure, hydration status, and stroke severity in patients with acute ischemic stroke (AIS).MethodsWe evaluated hydration status, determined by blood urea nitrogen (BUN)/creatinine ratio, in consecutive patients with AIS from a single comprehensive stroke center. Baseline mean arterial pressure (MAP) was analyzed using a linear spline with a knot at 90 mmHg. Baseline stroke severity was defined based on admission NIH Stroke Scale scores (NIHSSS) and MRI diffusion-weighted imaging.ResultsAmong 108 eligible subjects, 55 (51%) presented in a volume contracted state. In adjusted models, in the total sample, for every 10 mmHg higher MAP up to 90 mmHg, NIHSSS was 2.8 points lower (p = 0.053), without further statistically significant association between MAP above 90 and NIHSSS. This relationship was entirely driven by the individuals in a volume contracted state: MAP was not associated with NIHSSS in individuals who were euvolemic. For individuals in a volume contracted state, each 10 mmHg higher MAP, up to 90 mmHg, was associated with 6.9 points lower NIHSSS (95% CI −11.1, −2.6). MAP values above 90 mmHg were not related to NIHSSS in either dehydrated or euvolemic patients.ConclusionsLower MAP contributes to more severe stroke in patients who are volume contracted, but not those who are euvolemic, suggesting that hydration status and blood pressure may jointly contribute to the outcome. Hydration status should be considered when setting blood pressure goals for patients with AIS.
A Radiomics Approach to Assess High Risk Carotid Plaques: A Non-invasive Imaging Biomarker, Retrospective Study
Authors: Chen Sihan , Liu Changsheng , Chen Xixiang , Liu Weiyin Vivian , Ma Ling , Zha Yunfei 
Published: March 2022

ObjectiveThis study aimed to construct a radiomics-based MRI sequence from high-resolution magnetic resonance imaging (HRMRI), combined with clinical high-risk factors for non-invasive differentiation of the plaque of symptomatic patients from asyptomatic patients.MethodsA total of 115 patients were retrospectively recruited. HRMRI was performed, and patients were diagnosed with symptomatic plaques (SPs) and asymptomatic plaques (ASPs). Patients were randomly divided into training and test groups in the ratio of 7:3. T2WI was used for segmentation and extraction of the texture features. Max-Relevance and Min-Redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) were employed for the optimized model. Radscore was applied to construct a diagnostic model considering the T2WI texture features and patient demography to assess the power in differentiating SPs and ASPs.ResultsSPs and ASPs were seen in 75 and 40 patients, respectively. Thirty texture features were selected by mRMR, and LASSO identified a radscore of 16 radiomics features as being related to plaque vulnerability. The radscore, consisting of eight texture features, showed a better diagnostic performance than clinical information, both in the training (area under the curve [AUC], 0.923 vs. 0.713) and test groups (AUC, 0.989 vs. 0.735). The combination model of texture and clinical information had the best performance in assessing lesion vulnerability in both the training (AUC, 0.926) and test groups (AUC, 0.898).ConclusionThis study demonstrated that HRMRI texture features provide incremental value for carotid atherosclerotic risk assessment.
Effects of Early-Stage Blood Pressure Variability on the Functional Outcome in Acute Ischemic Stroke Patients With Symptomatic Intracranial Artery Stenosis or Occlusion Receiving Intravenous Thrombolysis
Authors: Yao Mian-Xuan , Qiu Dong-Hai , Zheng Wei-Cheng , Zhao Jiang-Hao , Yin Han-Peng , Liu Yong-Lin , Chen Yang-Kun 
Published: March 2022

BackgroundStudies exploring the relationship between blood pressure (BP) fluctuations and outcome in acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT) are limited. We aimed to investigate the influence of blood pressure variability (BPV) during the first 24 h after IVT on early neurological deterioration (END) and 3-month outcome after IVT in terms of different stroke subtypes.MethodsClinical data from consecutive AIS patients who received IVT were retrospectively analyzed. The hourly systolic BP of all patients were recorded during the first 24 h following IVT. We calculated three systolic BPV parameters, including coefficient of variability (CV), standard deviation of mean BP (SD) and successive variation (SV), within the first 6, 12, and 24 h after IVT. END was defined as neurological deterioration with an increase in the National Institutes of Health Stroke Scale (NIHSS) score ≥ 4 points within the first 72 h after admission. Follow-up was performed at 90 days after onset, and favorable and poor outcomes were defined as a modified Rankin Scale scores (mRS) of ≤1 or ≥2, respectively.ResultsA total of 339 patients, which were divided into those with (intracranial artery stenosis or occlusion group, SIASO group) and without (non-SIASO group) SIASO, were included. Among them, 110 patients (32.4%) were with SIASO. Patients in SIASO group had higher NIHSS on admission and difference in term of mRS at 90 days compared with non-SIASO group (P &lt; 0.001). In SIASO group, patients in favorable outcome group were younger and had lower NIHSS on admission, lower SV-24 h (14.5 ± 4.3 vs. 11.8 ± 3.2, respectively) and lower SD-24 h (12.7 ± 3.8 vs. 10.9 ± 3.3, respectively), compared with patients with poor outcome (all P &lt; 0.05). In the multivariable logistic regression analysis, compared with the lowest SV (SV &lt; 25% quartile), SV50−75% [odds ratio (OR) = 4.449, 95% confidence interval (CI) = 1.231–16.075, P = 0.023] and SV&gt;75% (OR = 8.676, 95% CI = 1.892–39.775, P = 0.005) were significantly associated with poor outcome at 3 months in patients with SIASO, adjusted for age, NIHSS on admission and atrial fibrillation. No BPV parameters were associated with END in SIASO group. In non-SIASO group, there were no significant association between BPV patterns and END or 90-day outcome.ConclusionsSV-24 h had a negative relationship with 3-month outcome in AIS patients with SIASO treated with IVT, indicating that BPV may affect the outcome of AIS.
Significant Structural Alterations and Functional Connectivity Alterations of Cerebellar Gray Matter in Patients With Somatic Symptom Disorder
Authors: Liang Huai-Bin , Dong Liao , Cui Yangyang , Wu Jing , Tang Wei , Du Xiaoxia , Liu Jian-Ren 
Published: March 2022

ObjectiveRecent studies have revealed a strong association between the cerebellum and psychiatric disorders. However, the structural changes in the cerebellar regions and functional connectivity (FC) patterns in patients with somatic symptom disorder (SSD) have not been elucidated.MethodsThirty-seven patients with SSD (29 drug-naive and 8 medicated patients) and 37 sex- and age-matched healthy controls (HCs) were recruited and underwent resting-state functional magnetic resonance imaging scans. The spatially unbiased infratentorial (SUIT) cerebellar atlas-based voxel-based morphometry was used to investigate the changes in cerebellar regional gray matter (GM). Seed-based FC was further computed to explore the pattern of abnormal FC across the whole brain. Correlations were calculated to investigate the relationship between cerebellar structural (and FC) changes and clinical characteristics.ResultsAfter controlling for age, sex, total intracranial volume, medication, and mean FD covariates, all patients with SSD had increased mean GM volume (GMV) in the posterior lobules of the cerebellum bilaterally when compared with HCs, specifically, in the bilateral cerebellar crura I and II. Patients with SSD showed significantly stronger FC between the right crura I and II and bilateral precuneus inferior parietal region, and postcentral gyrus, extending to the superior parietal lobe, cingulate gyrus, and the white matter subgyral. In addition to the two clusters, right lingual gyrus was also a surviving cluster with significantly higher FC. Partial correlation analysis revealed that the degree of regional GMV increases in the two significant clusters and the Hamilton Depression Scale (HAMD) score was negatively correlated. Moreover, the FC of right crura I and II with the left parietal lobe and right lingual gyrus were also negatively associated with the HAMD score.ConclusionsSSD exhibited significant microstructural changes and changes in FC pattern in the posterior cerebellar lobe. These results shed new light on the psychological and neural substrates of SSD and may serve as a potential treatment target for SSD based on the cerebellar area.