bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased histone citrullination in juvenile idiopathic arthritis
Authors: Parackova Zuzana , Zentsova Irena , Malcova Hana , Cebecauerova Dita , Sediva Anna , Horvath Rudolf 
Published: August 2022

ObjectivePosttranslational modifications (PTMs) of proteins are crucial for regulating various biological processes. However, protein alteration via PTMs, and consequently, the creation of new epitopes, can induce abnormal autoimmune responses in predisposed individuals. Immunopathogenesis of several rheumatic diseases, including the most common childhood form, juvenile idiopathic arthritis (JIA), is associated with the generation of autoantibodies against such modified proteins. Dysregulated generation of neutrophil extracellular traps (NETs) can be a source of post-translationally altered proteins. Thus, we investigated the role of PTMs and the presence of NET-associated markers in JIA patients.MethodsWe recruited 30 pediatric patients with JIA (20 with active disease and 10 in remission) and 30 healthy donors. The serum concentrations of citrullinated histone H3 (citH3), peptidyl arginine deiminases (PADs), and NET-related products were detected using ELISA, and the number of citH3+ neutrophils was assessed using flow cytometry.ResultsThe serum levels of citH3 and PADs were higher in active as well as in remission JIA patients than in healthy donors. Similarly, the number of citH3+ neutrophils was higher in the peripheral blood of patients with JIA, implying an enhanced process of NETosis. This was effectively reflected by elevated serum levels of NET-associated products, such as neutrophil elastase, LL37, and cell-free DNA-histone complexes. Additionally, 16.7% of active JIA patients were seropositive for carbamylated autoantibodies, the levels of which declined sharply after initiation of anti-TNFα therapy.ConclusionCollectively, our data suggest that the accelerated process of NETosis and PTMs in JIA may result in the generation of anti-citrullinated/carbamylated autoantibodies against various epitopes later in life, which could be prevented by effectively regulating inflammation using immune therapy.
Relationship between cytokine release and stress hyperglycemia in patients hospitalized with COVID-19 infection
Authors: Da Porto Andrea , Tascini Carlo , Colussi Gianluca , Peghin Maddalena , Graziano Elena , De Carlo Chiara , Bulfone Luca , Antonello Martina , Sozio Emanuela , Fabris Martina , Curcio Francesco , Pucillo Carlo , Catena Cristiana , Sechi Leonardo A. 
Published: August 2022

IntroductionStress hyperglycemia is a frequent finding in patients with COVID-19 infection and could affect the outcome of disease. Cytokines released in response to infection could have adverse effects on insulin sensitivity and pancreatic beta-cell function. The aim of the study was to examine the relationships of stress hyperglycemia with cytokines and clinical outcomes in hospitalized patients with COVID-19.MethodsIn a cross-sectional analysis of 150 patients hospitalized for COVID-19 infection who were included in the GIRA-COVID database, we identified patients with stress hyperglycemia by calculation of the Stress Hyperglycemia Ratio (SHR) and use of a cut-off of 1.14. Plasma levels of cytokines principally involved in COVID-19 infection-related cytokine storm were measured. Outcome variables were use of mechanical ventilation and death within 60 days from hospital admission.ResultsPatients with SHR &gt; 1.14 had significantly higher plasma insulin, HOMA-index, and levels of interleukin-10 (IL-10), interleukin-10/tumor necrosis factor-a ratio (IL-10/TNF-α), and CXC motif chemokine ligand 10 (CXCL10) than patients with SHR ≤ 1.14. IL-10, IL-10/TNF-α ratio, CXCL10, and IFN-γ were significantly and directly related with SHR in univariate analysis and multivariate logistic regression models showed that IL-10, IL-10/TNF-α ratio, and CXCL10 were independently associated with SHR&gt;1.14. In a multivariate logistic model, stress hyperglycemia predicted use of mechanical ventilation (OR 2.453; CI 1.078–6.012) and death (OR 2.281; CI 1.049–7.369) independently of diabetes and other major confounders.ConclusionsIn patients hospitalized for COVID-19 infection, stress hyperglycemia is associated with worse clinical outcomes and is independently related to levels of cytokines that might impair glucose homeostasis.
Computer-based assessment of unilateral spatial neglect: A systematic review
Authors: Giannakou Ioanna , Lin Dan , Punt David 
Published: August 2022

BackgroundTo date, no gold standard exists for the assessment of unilateral spatial neglect (USN), a common post-stroke cognitive impairment, with limited sensitivity provided by currently used clinical assessments. Extensive research has shown that computer-based (CB) assessment can be more sensitive, but these have not been adopted by stroke services yet.ObjectiveWe conducted a systematic review providing an overview of existing CB tests for USN to identify knowledge gaps and positive/negative aspects of different methods. This review also investigated the benefits and barriers of introducing CB assessment tasks to clinical settings and explored practical implications for optimizing future designs.MethodologyWe included studies that investigated the efficacy of CB neglect assessment tasks compared to conventional methods in detecting USN for adults with brain damage. Study identification was conducted through electronic database searches (e.g., Scopus), using keywords and standardized terms combinations, without date limitation (last search: 08/06/2022). Literature review and study selection were based on prespecified inclusion criteria. The quality of studies was assessed with the quality assessment of diagnostic accuracy studies tool (Quadas-2). Data synthesis included a narrative synthesis, a table summarizing the evidence, and vote counting analysis based on a direction of effect plot.ResultsA total of 28 studies met the eligibility criteria and were included in the review. According to our results, 13/28 studies explored CB versions of conventional tasks, 11/28 involved visual search tasks, and 5/28 other types of tasks. The vote counting analysis revealed that 17/28 studies found CB tasks had either equal or higher sensitivity than conventional methods and positive correlation with conventional methods (15/28 studies). Finally, 20/28 studies showed CB tasks effectively detected patients with USN within different patient groups and control groups (17/28).ConclusionsThe findings of this review provide practical implications for the implementation of CB assessment in the future, offering important information to enhance a variety of methodological issues. The study adds to our understanding of using CB tasks for USN assessment, exploring their efficacy and benefits compared to conventional methods, and considers their adoption in clinical environments.
HALP score and GNRI: Simple and easily accessible indexes for predicting prognosis in advanced stage NSCLC patients. The İzmir oncology group (IZOG) study
Authors: Güç Zeynep Gülsüm , Alacacıoğlu Ahmet , Kalender Mehmet Eren , Oflazoğlu Utku , Ünal Sinan , Yıldız Yaşar , Salman Tarık , Küçükzeybek Yüksel , Tarhan Mustafa Oktay 
Published: August 2022

ObjectiveThe Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) Score and the Geriatric Nutrition Risk Index (GNRI) are used as prognostic factors in different types of cancers. In this study we analyzed the prognostic value of the HALP Score and the GNRI calculated prior to first-line treatment in patients diagnosed with de novo metastatic non-small cell lung cancer (mNSCLC).Materials and methodsDe novo mNSCLC patients were retrospectively evaluated from January 2016 to December 2019. Patients with Driver’s mutation, severe comorbidities, active infection, or insufficient organ function, and those receiving anti-inflammatory treatment were excluded from the study. Optimal cut-off points for the HALP score and the GNRI were calculated with the receiver operating characteristic (ROC) curve analysis. Predictive factors for overall survival (OS) were assessed with univariate and multivariate Cox proportional hazard analyses, and OS was studied with the Kaplan–Meier analysis.ResultsThe study included 401 patients in total. In the ROC curve analysis, the cut-off points were found 23.24 (AUC = 0.928; 95% CI: 0.901–0.955, p &lt; 0.001) for HALP, and 53.60 (AUC = 0.932; 95% CI: 0.908–0.955, p &lt; 0.001) for GNRI. Groups with lower HALP scores and lower GNRI had significantly shorter OS compared to those with higher HALP scores and GNRIs. Univariate analysis showed that male gender, smoking, high ECOG score, low HALP score and low GNRI were associated with worse survival rates. Multivariate analysis showed that low HALP score (HR = 2.988, 95% CI: 2.065–4.324, p &lt; 0.001); low GNRI score (HR = 2.901, 95% CI: 2.045–4.114, p &lt; 0.001) and smoking history (HR = 1.447, 95% CI: 1.046–2.001, p = 0.025) were independent factors associated with worse OS rates.ConclusionOur study showed the HALP score and the GNRI to be of prognostic value as simple, cost-effective, and useful markers that predict OS in de novo mNSCLC patients.
Comprehensive analysis of m6A circRNAs identified in colorectal cancer by MeRIP sequencing
Authors: He Feng , Guo Qin , Jiang Guo-xiu , Zhou Yan 
Published: August 2022

PurposeTo characterize the entire profile of m6A modifications and differential expression patterns for circRNAs in colorectal cancer (CRC).MethodsFirst, High-throughput MeRIP-sequencing and RNA-sequencing was used to determine the difference in m6A methylome and expression of circRNA between CRC tissues and tumor-adjacent normal control (NC) tissues. Then, GO and KEGG analysis detected pathways involved in differentially methylated and differentially expressed circRNAs (DEGs). The correlations between m6A status and expression level were calculated using a Pearson correlation analysis. Next, the networks of circRNA-miRNA-mRNA were visualized using the Target Scan and miRanda software. Finally, We describe the relationship of distance between the m6A peak and internal ribosome entry site (IRES) and protein coding potential of circRNAs.ResultsA total of 4340 m6A peaks of circRNAs in CRC tissue and 3216 m6A peaks of circRNAs in NC tissues were detected. A total of 2561 m6A circRNAs in CRC tissues and 2129 m6A circRNAs in NC tissues were detected. Pathway analysis detected that differentially methylated and expressed circRNAs were closely related to cancer. The conjoint analysis of MeRIP-seq and RNA-seq data discovered 30 circRNAs with differentially m6A methylated and synchronously differential expression. RT-qPCR showned circRNAs (has_circ_0032821, has_circ_0019079, has_circ_0093688) were upregulated and circRNAs (hsa_circ_0026782, hsa_circ_0108457) were downregulated in CRC. In the ceRNA network, the 10 hyper-up circRNAs were shown to be associated with 19 miRNAs and regulate 16 mRNAs, 14 hypo-down circRNAs were associated with 30 miRNAs and regulated 27 mRNAs. There was no significant correlation between the level of m6A and the expression of circRNAs. The distance between the m6A peak and IRES was not significantly related to the protein coding potential of circRNAs.ConclusionOur study found that there were significant differences in the m6A methylation patterns of circRNAs between CRC and NC tissues. M6A methylation may affect circRNA-miRNA-mRNA co-expression in CRC and further affect the regulation of cancer-related target genes.
The etiology and clinical features of non-CAH primary adrenal insufficiency in children
Authors: Liu Ziqin , Liu Yi , Gao Kang , Chen Xiaobo 
Published: August 2022

BackgroundThe most common cause of primary adrenal insufficiency (PAI) in children is congenital adrenal hyperplasia; however, other genetic causes occur. There is limited epidemiological and clinical information regarding non-CAH PAI.MethodsData for patients diagnosed from January 2015 to December 2021 at a tertiary hospital in northern China were retrospectively analyzed. We excluded those with CAH, which is the most common pathogenic disease among PAI patients. Next-generation sequencing was used for genetic analysis.ResultsThis retrospective study included 16 children (14 males and 2 females) with PAI. A genetic diagnosis was obtained for 14/16 (87.5%) individuals. Pathogenic variants occurred in 6 genes, including ABCD1 (6/16, 37.5%), NR0B1 (4/16, 25.0%), NR5A1/steroidogenic factor-1 (2/16; 12.5%), AAAS (1/16, 6.25%), and NNT (1/16, 6.25%). No genetic cause of PAI diagnosis was found in 2 girls (2/16, 12.5%).ConclusionsCauses of PAI in children are diverse and predominantly affect males. Most PAI in children is congenital, and ABCD1 gene defects account for the largest proportion of PAI cases. Whole-exome sequencing is a tool for diagnosis. However, diagnoses are unclear in some cases.
Anti-tumour necrosis factor-alpha agent therapy, compared with conventional therapy, reduces the relapse of uveitis in patients with behçet’s disease: A systematic review of controlled trials
Authors: Zhou Xinwei , Shi Xianghui , Ren Yanxia , Yan Tingting , Ye Qiao 
Published: August 2022

Purpose: Anti-tumour necrosis factor-alpha (TNF-α) agents are often used for Behçet’s disease (BD) in clinical practice, but they have not been validated by a high level of evidence. We systematically reviewed published controlled trials to investigate the efficacy and safety of anti-TNF-α therapy and summarize the efficacy of anti-TNF-α therapy relative to the available therapeutic options.Methods: A systematic database search was conducted (PubMed, Embase and Cochrane) using specific search terms. All controlled studies of anti-TNF-α treatment of BD patients prior to December 2021 were included. Single-arm studies were excluded. The decision of whether to incorporate data into the meta-analysis or summarize the data by qualitative synthesis was based on the results of the literature screening.Results: Of 4389 screened studies, 13 (total 778 patients) were included in accordance with our retrieval strategy, comprising 1 randomized controlled trial, 1 prospective study, 10 retrospective studies, and 1 multicentre open-label study. Ten studies (76.9%) involved Behçet’s uveitis (BU), 1 involved intestinal BD, and the other studies had undefined subtypes. Subgroup reviews were conducted according to the control drug. Four studies involving 167 participants reported relapse rates. Meta-analysis of three of these studies demonstrated that, compared with traditional immunosuppressant (TIS) therapy, anti-TNF-α therapy reduced the relapse rates in patients with BU. In targeted drug comparison studies, the efficacy appeared to be similar between the anti-TNF-α agent and interferon in BU patients. The rates of adverse events were comparable between a variety of different therapeutic controls. Serious adverse events were not observed in 53.8% (7/13) of the studies.Conclusions: Compared with TIS therapy, anti-TNF-a therapy reduces the relapse of uveitis in patients with BD. However, the evidence regarding anti-TNF-α therapy is very limited for the full spectrum of BD subtypes, which calls for caution.
Acacia sieberiana (Fabaceae) attenuates paracetamol and Bile Duct Ligation-Induced hepatotoxicity via modulation of biochemical and oxidative stress biomarkers
Authors: Watafua Miriam , Ejiofor Jane I. , Musa Aminu , Ahmad Mubarak Hussaini 
Published: August 2022

Background: The plant Acacia sieberiana (Fabaceae) is traditionally used to manage hepatitis. This research work aims to investigate the hepatoprotective effectiveness of root bark extract of Acacia sieberiana (ASE) against paracetamol (PCM) and bile duct ligation (BDL)-induced hepatotoxicity. The phytochemical and median lethal dose (LD50) investigations were conducted. The rats were pre-treated with the ASE (250, 750, and 1,500 mg/kg) once daily via oral route for 7 consecutive days. On the 8th day, liver injury was initiated by PCM administration (2 g/kg). Similarly, in the BDL-induced liver injury, the animals were administered ASE (125, 250, and 380 mg/kg) intraperitoneally for 7 consecutive days. After 24 h, blood samples and hepatic tissues were obtained for biochemical and histopathological investigations.Results: Phytocomponents determination revealed glycosides, triterpenes, glycosides, saponins, tannins, flavonoids and alkaloids. The oral and intraperitoneal LD50 values of the ASE were &gt;5,000 and 1,300 mg/kg, respectively. The ASE efficiently (p &lt; 0.05) decreased the alanine transaminase (ALT) and aspartate transaminase (AST) levels and elevated the albumin and total protein (TP) levels. The direct bilirubin effectively (p &lt; 0.05) decreased at 750 mg/kg. Besides, the extract efficiently elevated the glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) in relation to the PCM hepatotoxic group. Also, the malondialdehyde (MDA) concentration was reduced by the ASE. Meanwhile, in the BDL–induced liver injury, the ASE remarkably (p &lt; 0.05) declined the AST, ALP, bilirubin,and MDA. Besides, there was effective (p &lt; 0.05) elevation in SOD, GPx and CAT in the ASE-treated groups. The morphology of liver tissue was preserved at 125 and 250 mg/kg ASE groups from BDL-induced necrosis and vascular congestion.Conclusion: The study shows that the ASE has hepatoprotective actions against liver damage by possible modulation of biochemical and oxidative stress biomarkers.
Apolipoprotein A-I mimetic peptides (ApoAI MP) improve oxidative stress and inflammatory responses in Parkinson’s disease mice
Authors: Jiang Hongfang , Bai Xue 
Published: August 2022

Purpose: Parkinson’s disease (PD) is closely associated with oxidative stress and inflammatory situation. Apolipoprotein A-I mimetic peptides (ApoAI MP) have antioxidant and anti-inflammatory properties. We aimed to study the therapeutic effect of ApoAI MP on PD mice, and to explore the related mechanisms.Methods: PD mice were induced by using 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP). The model mice were treated with different concentrations of ApoAI MP. The open-field behavioral test assesses the total distance moved, the rest time, and the number of crossings and Rota-rod was used to evaluate motor coordination. Oxidative stress was identified by measuring the levels of superoxide dismutase (SOD), catalase (CAT), glutathionperoxidase (GSH-Px), malondialdehyde, ROS and H2O2. Inflammatory situation was analyzed by measuring the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Meanwhile, the scavenging activities of ApoAI MP for ABTS, DPPH, hydroxyl radical and superoxide anion, and the effects of the peptide on neurotransmitters were evaluated.Results: PD model establishment increased oxidative stress and inflammatory status by increasing the concentrations of ROS and H2O2 production, and the levels of TNF-α, IL-1β and IL-6 (p &lt; 0.05). ApoAI MP intervention improved PD symptoms by reducing the total moved distance and the number of passes (p &lt; 0.01), and the falling times from Rota-rod, and increasing rest time (p &lt; 0.05). ApoAI MP increased antioxidant properties by increasing the activities of SOD, CAT and GSH-Px, and reducing MDA concentration (p &lt; 0.05). ApoAI MP addition reduced oxidative stress by scavenging ABTS, DPPH, hydroxyl radicals and superoxide anion and reducing the concentrations of ROS and H2O2 production (p &lt; 0.05). ApoAI MP treatment increased anti-inflammatory capacities by reducing the concentrations of TNF-α, IL-1β and IL-6 (p &lt; 0.05). HPLC analysis showed that the peptide treatment improved neurotransmitters.Conclusion: ApoAI MP can improve the behavioral performance of PD mice by improving antioxidant and anti-inflammatory capacities.
Integrative physiological study of adaptations induced by aerobic physical training in hypertensive hearts
Authors: Vieira Suenimeire , Aguilar Bruno A. , Veiga Ana Catarine , Philbois Stella V. , Freitas Ana Caroline S. , Rodrigues Karine P. , Tank Jens , Souza Hugo C. D. 
Published: August 2022

Aerobic physical training reduces arterial pressure in patients with hypertension owing to integrative systemic adaptations. One of the key factors is the decrease in cardiac sympathetic influence. Thus, we hypothesized that among other causes, cardiac sympathetic influence reduction might be associated with intrinsic cardiac adaptations that provide greater efficiency. Therefore, 14 spontaneously hypertensive rats (SHR group) and 14 normotensive Wistar Kyoto rats (WKY group) were used in this study. Half of the rats in each group were trained to swim for 12 weeks. All animals underwent the following experimental protocols: double blockade of cardiac autonomic receptors with atropine and propranolol; echocardiography; and analysis of coronary bed reactivity and left ventricle contractility using the Langendorff technique. The untrained SHR group had a higher sympathetic tone, cardiac hypertrophy, and reduced ejection fraction compared with the untrained WKY group. In addition, reduced coronary bed reactivity due to increased flow, and less ventricular contractile response to dobutamine and salbutamol administration were observed. The trained SHR group showed fewer differences in echocardiographic parameters as the untrained SHR group. However, the trained SHR group showed a reduction in the cardiac sympathetic influence, greater coronary bed reactivity, and increased left intraventricular pressure. In conclusion, aerobic physical training seems to reduce cardiac sympathetic influence and increase contractile strength in SHR rats, besides the minimal effects on cardiac morphology. This reduction suggests intrinsic cardiac adaptations resulting in beneficial adjustments of coronary bed reactivity associated with greater left ventricular contraction.
Rapid endothermal development of juvenile pacific bluefin tuna
Authors: Kitagawa Takashi , Abe Takaaki K. , Kubo Keitaro , Fujioka Ko , Fukuda Hiromu , Tanaka Yosuke 
Published: August 2022

An important trait of Pacific bluefin tuna (PBT) is their ability to maintain their body temperature above the ambient temperature, which allows them to occupy a wider ecological niche. However, the size at which this ability in nature develops is unclear. Therefore, this study aimed to clarify this point by monitoring the body temperature and the surrounding ambient temperature as the fish grew. PBT with fork lengths (FLs) ranging from 19.5 to 28.0 cm were implanted with archival electronic tags and released into the ocean. Data from 41 fish were obtained (recorded body and water temperatures, light level, and swimming depth (pressure) at 30-s intervals) and analyzed to elucidate the development of the ability of PBT to maintain a high body temperature. Body temperature of a PBT (&lt; FL of ca. 40 cm) decreased in response to a vertical movement down to cooler depths, but higher body temperatures were maintained as the fish grew. The body temperature was then continuously maintained above ambient temperatures and fluctuated independently when fish attained more than 40 cm FL. Estimation of the whole-body heat-transfer coefficient and heat-production rate indicated that the latter decreased slowly with growth, while the former decreased by one order of magnitude when tuna reached 52 cm FL. Additionally, in the daytime, the whole-body heat-transfer coefficient was significantly higher than that at nighttime. Unlike other fishes including other Thunnus species, inhabiting tropical/subtropical waters, PBT rapidly acquire higher thermo-conservation ability when young, allowing capture of high-quality prey abundant in temperate waters to support high growth rates during early life.