bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor markers and depression scores are predictive of non-suicidal self-injury behaviors among adolescents with depressive disorder: A retrospective study
Authors: Yi Peng-cheng , Qin Yan-hua , Zheng Chun-mei , Ren Ke-ming , Huang Lei , Chen Wei 
Published: August 2022

BackgroundNon-suicidal self-injury (NSSI) is an important risk factor for suicide in adolescents with depressive disorders; therefore, it is important to predict NSSI occurrence as early as possible. Disturbances in biological rhythms are characteristic manifestations of depressive disorders and can lead to immune dysfunction, leading to changes in tumor markers. This study aimed to produce an index that utilizes tumor markers to predict NSSI behaviors among adolescents with depressive disorders.MethodsA total of 120 hospitalized adolescent patients with depressive disorders aged 14–24 years were included in this study. Participants were divided into NSSI and non-NSSI groups based on self-reports using the Ottawa Self-Injury Inventory. Demographics, tumor marker concentrations, other peripheral blood indices, Hamilton Depression Rating Scale (HDRS) scores, and Hamilton Anxiety Rating Scale (HAMA) scores were compared between the two groups. Logistic regression analysis was conducted to develop a joint index, and a receiver operating characteristic (ROC) curve was created to predict NSSI behaviors among adolescents with depressive disorders.ResultsCompared with the non-NSSI group, the NSSI group had significantly higher insight, retardation, insomnia, hopelessness, psychiatric anxiety, total HDRS and HAMA scores, and significantly higher levels of cancer antigen 125 (CA-125), cancer antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA). In addition, a joint index was developed by combining CA-125, CA19-9, CEA, HDRS total score, HAMA total score and age using multiple logistic regression to predict NSSI behaviors. The area under the curve was 0.831, with a sensitivity and specificity of 0.734 and 0.891, respectively.ConclusionA combination of depression score, tumor marker levels, and age can identify NSSI behaviors among adolescents with depressive disorders.
How brain-computer interface technology may improve the diagnosis of the disorders of consciousness: A comparative study
Authors: Spataro Rossella , Xu Yiyan , Xu Ren , Mandalà Giorgio , Allison Brendan Z. , Ortner Rupert , Heilinger Alexander , La Bella Vincenzo , Guger Christoph 
Published: August 2022

ObjectiveClinical assessment of consciousness relies on behavioural assessments, which have several limitations. Hence, disorder of consciousness (DOC) patients are often misdiagnosed. In this work, we aimed to compare the repetitive assessment of consciousness performed with a clinical behavioural and a Brain-Computer Interface (BCI) approach.Materials and methodsFor 7 weeks, sixteen DOC patients participated in weekly evaluations using both the Coma Recovery Scale-Revised (CRS-R) and a vibrotactile P300 BCI paradigm. To use the BCI, patients had to perform an active mental task that required detecting specific stimuli while ignoring other stimuli. We analysed the reliability and the efficacy in the detection of command following resulting from the two methodologies.ResultsOver repetitive administrations, the BCI paradigm detected command following before the CRS-R in seven patients. Four clinically unresponsive patients consistently showed command following during the BCI assessments.ConclusionBrain-Computer Interface active paradigms might contribute to the evaluation of the level of consciousness, increasing the diagnostic precision of the clinical bedside approach.SignificanceThe integration of different diagnostic methods leads to a better knowledge and care for the DOC.
Gene expression signatures and cardiometabolic outcomes following 8-week mango consumption in individuals with overweight/obesity
Authors: Keathley Justine , de Toro-Martín Juan , Kearney Michèle , Garneau Véronique , Pilon Geneviève , Couture Patrick , Marette André , Vohl Marie-Claude , Couillard Charles 
Published: August 2022

BackgroundLittle is known about the impact of mango consumption on metabolic pathways assessed by changes in gene expression.MethodsIn this single-arm clinical trial, cardiometabolic outcomes and gene expression levels in whole blood samples from 26 men and women were examined at baseline and after 8 weeks of mango consumption and differential gene expression changes were determined. Based on changes in gene expression profiles, partial least squares discriminant analysis followed by hierarchical clustering were used to classify participants into subgroups of response and differences in gene expression changes and in cardiometabolic clinical outcomes following the intervention were tested.ResultsTwo subgroups of participants were separated based on the resemblance of gene expression profiles in response to the intervention and as responders (n = 8) and non-responders (n = 18). A total of 280 transcripts were significantly up-regulated and 603 transcripts down-regulated following the intervention in responders, as compared to non-responders. Several metabolic pathways, mainly related to oxygen and carbon dioxide transport as well as oxidative stress, were found to be significantly enriched with differentially expressed genes. In addition, significantly beneficial changes in hip and waist circumference, c-reactive protein, HOMA-IR and QUICKI indices were observed in responders vs. non-responders, following the intervention.ConclusionThe impact of mango consumption on cardiometabolic health appears to largely rely on interindividual variability. The novel transcriptomic-based clustering analysis used herein can provide insights for future research focused on unveiling the origins of heterogeneous responses to dietary interventions.Clinical Trial Registration[clinicaltrials.gov], identifier [NCT03825276].
Alleviating effects of pea peptide on oxidative stress injury induced by lead in PC12 cells via Keap1/Nrf2/TXNIP signaling pathway
Authors: Li Ning , Wen Liuding , Wang Fangyu , Li Tiange , Zheng Haodan , Wang Tianlin , Qiao Mingwu , Huang Xianqing , Song Lianjun , Bukyei Erkigul , Li Mingming 
Published: August 2022

BackgroundLead poisoning causes an oxidative stress response – a key “bridge” connecting various pathways – in the human body. Oxidative stress usually implies an imbalance between pro-oxidants and antioxidants. Moreover, Nrf2, Keap1, and TXNIP proteins play an essential role in oxidative stress. Some studies showed that pea peptides could alleviate the oxidative stress response. However, the effect and mechanism of pea peptide on oxidative stress response induced by lead in PC12 cells has not been reported.AimInvestigating the effect and mechanism of pea peptides in alleviating oxidative damage in PC12 cells induced by lead.MethodsIn this study, cell viability was measured by CCK8 (Cell Counting Kit-8). Superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), reactive oxygen species (ROS), and lipid peroxidation (MDA) were measured using the corresponding Biochemical kits. The Keap1, Nrf2, and TXNIP protein expressions were tested using Western blot.ResultsPea peptides PP3, PP4, and PP6 could reverse the decrease of cell viability caused by lead exposure (P &lt; 0.05), the elevation of ROS and MDA caused by lead exposure, and the decrease of CAT, SOD, GR, GPx, and GSH/GSSG caused by lead exposure (P &lt; 0.05). Moreover, PP3, PP4, and PP6 could reduce the elevated expression of Keap1 and TXNIP caused by lead exposure; and increase the expression of Nrf2 (P &lt; 0.05).ConclusionPP3, PP4, and PP6 can alleviate lead-induced oxidative stress damage in PC12 cells, and the Nrf2/Keap1/TXNIP signaling pathway may play an essential role in this process.
Investigational cyclin-dependent kinase 4/6 inhibitor GLR2007 demonstrates activity against isocitrate dehydrogenase wild-type glioblastoma and other solid tumors in mice xenograft models
Authors: Yin Lei , Yao Zhenglin , Wang Yue , Mazuranic Michelle 
Published: August 2022

Cyclin-dependent kinases, CDK4 and CDK6, are essential in regulating the cell cycle, which is disrupted in cancers like isocitrate dehydrogenase wild-type glioblastoma (GBM). Currently marketed CDK4/6 inhibitors, including abemaciclib, have shown preclinical efficacy in solid tumors, but factors such as poor blood–brain barrier (BBB) penetration limit their efficacy in GBM. GLR2007 is an investigational CDK4/6 inhibitor with the potential for improved BBB penetration. In vitro assays were used to assess the potency and inhibition of CDK4/6 enzymatic activity of GLR2007. Using in vivo assays, the distribution of radiolabeled GLR2007 in rats was determined through quantitative whole-body autoradiography. The antitumor efficacy of GLR2007 was evaluated in human GBM and breast cancer orthotopic mice xenograft models, and human lung, colorectal, and liver cancer in a subcutaneous xenograft model. In tumor cell line proliferation assays, GLR2007 inhibited proliferation at lower concentration values than abemaciclib in 19 of 20 GBM, five of seven breast, 20 of 21 lung, and 24 of 24 liver cancer cell lines. Total levels of radiolabeled GLR2007 in the brains of rats exceeded those in plasma by 2.3–4.5-fold from 2–6 hours after dosing. A xenograft model showed that, compared with vehicle control, 50 mg/kg GLR2007 induced 95.9% tumor growth inhibition (TGI) (P&lt;0.001) in GBM orthotopic xenografts, 81.4% TGI (P=0.037) in breast cancer orthotopic xenografts, and 91.5% TGI (P&lt;0.001) in colorectal cancer subcutaneous xenografts. These studies show possible BBB penetration of GLR2007 and demonstrate its potential as a CDK4/6 inhibitor for the treatment of solid tumors, including GBM.
Viral infections in hospitalized children in Germany during the COVID-19 pandemic: Association with non-pharmaceutical interventions
Authors: Terliesner Nicolas , Unterwalder Nadine , Edelmann Anke , Corman Victor , Knaust Andreas , Rosenfeld Leonard , Gratopp Alexander , Ringe Hannelore , Martin Luise , von Bernuth Horst , Mall Marcus A. , Kallinich Tilmann 
Published: August 2022

BackgroundNon-pharmaceutical interventions (NPI) during the COVID-19 pandemic aimed at prevention of SARS-CoV-2 transmission also influenced transmission of viruses other than SARS-CoV-2. The aim of this study was to describe and compare the burden of common viral respiratory and gastrointestinal infections in children admitted to Berlin University Children's Hospital (BCH) before and during the COVID-19 pandemic at different levels of public NPI measures.MethodsIn this retrospective study, we analyzed the frequency of detection of common human respiratory and gastrointestinal viruses from January 2016 through January 2022 in all patients admitted to BCH. We compared virus detection before and during the COVID-19 pandemic at different levels of public NPI measures.ResultsThe frequency of detection of seasonal enveloped and non-enveloped viruses [Boca-, Corona-, Influenza-, Metapneumo-, Parainfluenza-, Rota-, and Respiratory Syncytial Viruses (RSV)] was diminished during the COVID-19 pandemic, whereas detection rates of non-seasonal viruses (Rhino-/Entero-, and Adenoviruses) were stable during the pandemic. After withdrawal of major NPI measures, we observed an out of season surge of the detection rates of Boca-, Corona-, Parainfluenzaviruses, and RSV. In contrast, no increased detection frequency was observed for Influenza-, Metapneumo-, and Rotaviruses as of January 2022.ConclusionCorona-, Boca-, Parainfluenzaviruses, and RSV returned as frequently detected pathogens after withdrawal of major NPI measures. The out of season rise might be attributed to an “immune-debt” due to missing contact to viral antigens resulting in waning of population immunity during the COVID-19 pandemic.
Disruptions to routine childhood vaccinations in low- and middle-income countries during the COVID-19 pandemic: A systematic review
Authors: Cardoso Pinto Alexandra M. , Ranasinghe Lasith , Dodd Peter J. , Budhathoki Shyam Sundar , Seddon James A. , Whittaker Elizabeth 
Published: August 2022

BackgroundThe COVID-19 pandemic has disrupted routine childhood vaccinations worldwide with low- and middle-income countries (LMICs) most affected. This study aims to quantify levels of disruption to routine vaccinations in LMICs.MethodsA systematic review (PROSPERO CRD42021286386) was conducted of MEDLINE, Embase, Global Health, CINAHL, Scopus and MedRxiv, on the 11th of February 2022. Primary research studies published from January 2020 onwards were included if they reported levels of routine pediatrics vaccinations before and after March 2020. Study appraisal was performed using NHLBI tool for cross-sectional studies. Levels of disruption were summarized using medians and interquartile ranges.ResultsA total of 39 cross-sectional studies were identified. These showed an overall relative median decline of −10.8% [interquartile range (IQR) −27.6%, −1.4%] across all vaccines. Upper-middle-income countries (upper-MICs) (−14.3%; IQR −24.3%, −2.4%) and lower-MICs (−18.0%; IQR −48.6%, −4.1%) showed greater declines than low-income countries (−3.1%; IQR −12.8%, 2.9%), as did vaccines administered at birth (−11.8%; IQR −27.7%, −3.5%) compared to those given after birth (−8.0%; IQR −28.6%, −0.4%). Declines during the first 3 months of the pandemic (−8.1%; IQR −35.1%, −1.4%) were greater than during the remainder of 2020 (−3.9%; IQR −13.0%, 11.4%) compared to baseline.ConclusionThere has been a decline in routine pediatric vaccination, greatest in MICs and for vaccines administered at birth. Nations must prioritize catch-up programs alongside public health messaging to encourage vaccine uptake.Systematic review registrationIdentifier: CRD42021286386.
Development and validation of a UPLC-MS/MS method with volumetric absorptive microsampling to quantitate cyclophosphamide and 4-hydroxycyclophosphamide
Authors: Harahap Yahdiana , Steven Steven , Suryadi Herman 
Published: August 2022

Cyclophosphamide (CP) is an anti-cancer alkylating prodrug, metabolized by CYP450 into its active metabolite 4-hydroxycyclophosphamide (4-OHCP). Its therapeutic effectiveness is determined by the 4-OHCP concentration. Several analytical methods in plasma and dried blood spots have been developed to analyze cyclophosphamide and 4-OHCP; however, there are many disadvantages. The objective of this study was to develop and validate the ultraperformance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method by volumetric absorptive microsampling (VAMS) and 4-hydroxycyclophosphamide-d4 (4-OHCP-d4) as an internal standard. VAMS requires small sample volumes, and it is not affected by the hematocrit values; therefore, it is an efficient sampling method. The samples were derivatized with 5 μL semicarbazide hydrochloride (SCZ) and 25 μL of the resulting 4-OHCP-SCZ; 4-OHCP-d4-SCZ derivatives were absorbed by VAMS and extracted by protein precipitation. The optimum conditions were obtained using the Waters Acquity® UPLC BEH C18 (2.1 × 100 mm; 1.7 μm) column; flow rate 0.15 ml/min; mobile phase 0.01% formic acid and methanol; gradient elution mode for 6 min by positive electrospray ionization; and multiple reaction monitoring of m/z 260.7 &gt; 140.0 for CP, 333.7 &gt; 221.0 for 4-OHCP-SCZ, and 337.7 &gt; 225.1 for 4-OHCP-d4-SCZ. The method met the validation requirements set by the FDA. The cyclophosphamide LLOQ value was 5 ng/mL, and the calibration curve range was 5—60,000 ng/ml. Furthermore, the 4-OHCP LLOQ value was 2.5 ng/ml, and the calibration curve range was 2.5—1,000 ng/ml.
Antioxidant and Anti-Inflammatory Properties of Hydroxyl Safflower Yellow a in Diabetic Nephropathy: A Meta-Analysis of Randomized Controlled Trials
Authors: Fu Shunlian , Zhou Qian , Gao Yang , Yang Yunjiao , Chen Huizhen , Yuan Lijun , Li Zinan , Chen Qiu 
Published: August 2022

Background: Diabetic kidney disease (DKD) is a chronic progressive disorder which is a leading cause of chronic kidney disease (CKD). As an important pathogenesis of DKD, the overproduction of reactive oxygen species (ROS) and the inflammatory response have been considered central mediators in the progression of DKD. Herbal products are increasingly being applied as antioxidants and anti-inflammatory agents. Of those, the effect of hydroxyl safflower yellow A (HSYA) on oxidative stress and inflammatory reactions has gradually been investigated for DKD treatment, which may provide therapies for DKD with new insights and promote its application in clinical practice.Methods: We searched CNKI, the Chinese Biomedical Literature Database, the Wanfang Database, PubMed, and Embase from the establishment date of the database to 22 April 2022. The included literature in our study was randomized controlled trials (RCTs) using HSYA to treat DKD. We performed a meta-analysis by calculating the standard mean difference (SMD) with a 95% confidence interval (CI). The inverse-variance method with a random effect was used in our meta-analysis using Stata software and RevMan software.Results: A total of 31 articles with 31 groups containing a total of 2487 participants were included in this meta-analysis. The pooled results showed a statistical improvement in the following measurements: fasting blood glucose (FBG), postprandial blood glucose (PBG), blood urea nitrogen (BUN), urinary albumin excretion rates (UAER), serum creatinine (SCR), hypersensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), fasting insulin (FINS), total cholesterol (TC), triglycerides (TGs), hemoglobin A1c (HbA1C), homeostasis model assessment insulin resistance (HOMA-IR), and malondialdehyde (MDA).Conclusion: HSYA can effectively treat DKD by inhibiting inflammatory reactions and oxidative stress, decreasing blood glucose and blood lipids, and improving renal function indices. However, more RCTs are still needed in the future to further demonstrate the effect of HSYA on biomarkers of oxidative stress and inflammatory reactions in patients with DKD due to the low quality and small sample size of the literature included in this study.Systematic Review Registration: PROSPERO: CRD 42021235689
Inhibiting vascular smooth muscle cell proliferation mediated by osteopontin via regulating gut microbial lipopolysaccharide: A novel mechanism for paeonol in atherosclerosis treatment
Authors: Shi Xiaoyan , Wu Hongfei , Liu Yarong , Huang Hanwen , Liu Ling , Yang Yulong , Jiang Tingting , Zhou Min , Dai Min 
Published: August 2022

Background: Although the gut microbiota is involved in metabolic disease such as atherosclerosis, the underlying mechanism remains elusive. Paeonol (Pae) is a natural phenolic compound isolated from Cortex Moutan, which exhibits anti-atherosclerotic effects. Our previous research demonstrated gut microbiota as a site of Pae action. However, the mechanism by which Pae exerts its anti-atherosclerotic effect by the regulation of gut microbiota remains unclear.Objective: To investigate a potential mechanistic link between the gut microbial lipopolysaccharide (LPS) and vascular smooth muscle cell (VSMC) proliferation in atherosclerosis progression and explore the possible role of Pae.Methods: Experimental atherosclerosis was established in ApoE−/− mice, and the atherosclerosis mice were treated with Pae for 4 weeks before being sacrificed for analyses while conducting fecal microbiota transplantation (FMT). The plaque area, levels of serum LPS, expressions of inflammatory factors in serum or aorta, and intestinal barrier permeability were determined. VSMCs were co-cultured with THP-1 cells. CCK-8 assay and EdU staining were performed to assess the proliferative capacity of VSMCs. Immunofluorescence staining was performed to observe the nuclear transfer of p65. Western blotting was used to detect the candidate protein expression level, and quantitative real-time PCR (qRT-PCR) was used to detect the mRNA expression level in tissues or cells of each group.Results: During atherosclerosis progression, gut dysbiosis leads to the peripheral accumulation of gut microbial LPS, which acts as a trigger to stimulate osteopontin (OPN) production from circulating monocytes, inducing cell-to-cell crosstalk to promote VSMC proliferation in the aorta. Importantly, the elevation of LPS and OPN concentrations in the blood was also observed in patients with atherosclerosis. Pae could significantly improve atherosclerosis, suppress gut microbial LPS accumulation, and inhibit monocyte/macrophage activation and VSMC proliferation.Conclusions: The present study provides a mechanistic scenario for how long-term stimulation of gut microbial LPS in circulating blood generates a pathological secondary response that leads to abnormal proliferation of VSMCs using high OPN expression in circulating monocytes and suggests a novel strategy for atherosclerosis therapy by remodeling the gut microbiota.
Significant metabolic alterations in non-small cell lung cancer patients by epidermal growth factor receptor-targeted therapy and PD-1/PD-L1 immunotherapy
Authors: Yan Chen , Wu Dan , Gan Lingling , Wang Jun , Yang Wenyu , Xu Bei 
Published: August 2022

Background: Cancer-related deaths are primarily attributable to lung cancer, of which non-small cell lung cancer (NSCLC) is the most common type. Molecular targeting therapy and antitumor immunotherapy have both made great strides in the treatment of NSCLC, but their underlying mechanisms remain unclear, especially from a metabolic perspective.Methods: Herein, we used a nontargeted metabolomics approach based on liquid chromatography-mass spectrometry to analyze the metabolic response of NSCLC patients to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) or PD-1/PD-L1 inhibitors. Multiple analyses, including principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA) and pathway analysis, were used for metabolic data analysis. Additionally, differential metabolites were analysed and identified by publically available and integrated databases.Results: After treatment with EGFR-TKIs or PD-1/PD-L1 inhibitors, glutamate/glutamine, phenylalanine, n-acetyl-l-leucine, n-acetyl-d-tryptophan, D-n-valine, arachidonic acid, and linoleic acid levels were significantly increased in patients with NSCLC, whereas carnitine, stearyl carnitine, palmitoyl carnitine, linoleic carnitine, and palmitic acid levels were markedly decreased. Compared with newly diagnosed, untreated patients, there were three shared metabolic pathways (phenylalanine metabolism, glycerophospholipid metabolism, and D-glutamine and D-glutamate metabolism) in the EGFR-TKIs or PD-1/PD-L1 inhibitor-treated groups, all of which were related to lipid and amino acid metabolism. Moreover, there were significant differences in lipid metabolism (glycerophospholipid metabolism and phosphatidylinositol signaling) and amino acid metabolism (tryptophan metabolism) between the EGFR-TKI and PD-1/PD-L1 inhibitor groups.Conclusion: Our results show that EGFR-TKIs and PD-1/PD-L1 inhibitors induce changes in carnitine, amino acids, fatty acids, and lipids and alter related metabolic pathways in NSCLC patients. Endogenous metabolism changes occur due to drug action and might be indicative of antitumor therapeutic effect. These findings will provide new clues for identifying the antitumor mechanism of these two treatments from the perspective of metabolism.