bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the consistence between the results of immunoinformatics predictions and real-world animal experiments of a new tuberculosis vaccine MP3RT
Authors: Cheng Peng , Xue Yong , Wang Jie , Jia Zaixing , Wang Liang , Gong Wenping 
Published: November 2022

BackgroundOur previous study developed a novel peptide-based vaccine, MP3RT, to fight against tuberculosis (TB) infection in a mouse model. However, the consistency between the immunoinformatics predictions and the results of real-world animal experiments on the MP3RT vaccine remains unclear.MethodIn this study, we predicted the antigenicity, immunogenicity, physicochemical parameters, secondary structure, and tertiary structure of MP3RT using bioinformatics technologies. The immune response properties of the MP3RT vaccine were then predicted using the C-ImmSim server. Finally, humanized mice were used to verify the characteristics of the humoral and cellular immune responses induced by the MP3RT vaccine.ResultsMP3RT is a non-toxic and non-allergenic vaccine with an antigenicity index of 0.88 and an immunogenicity index of 0.61, respectively. Our results showed that the MP3RT vaccine contained 53.36% α-helix in the secondary structure, and the favored region accounted for 98.22% in the optimized tertiary structure. The binding affinities of the MP3RT vaccine to the human leukocyte antigen (HLA)-DRB1*01:01 allele, toll-like receptor-2 (TLR-2), and TLR-4 receptors were -1234.1 kcal/mol, -1066.4 kcal/mol, and -1250.4 kcal/mol, respectively. The results of the C-ImmSim server showed that the MP3RT vaccine could stimulate T and B cells to produce immune responses, such as high levels of IgM and IgG antibodies, IFN-γ, TNF-α, and IL-2 cytokines. Results from real-world animal experiments showed that the MP3RT vaccine could stimulate the humanized mice to produce high levels of IgG and IgG2a antibodies and IFN-γ+ T lymphocytes. Furthermore, the levels of IFN-γ, IL-2, and IL-6 cytokines in mice immunized with the MP3RT vaccine were significantly higher than those in the control group.ConclusionMP3RT is a highly antigenic and immunogenic potential vaccine that can effectively induce Th1-type immune responses in silico analysis and animal experiments. This study lays the foundation for evaluating the value of computational tools and immunoinformatic techniques in reverse vaccinology research.
Cost analysis of chronic heart failure management in Malaysia: A multi-centred retrospective study
Authors: Ong Siew Chin , Low Joo Zheng , Yew Wing Yee , Yen Chia How , Abdul Kader Muhamad Ali S. K. , Liew Houng Bang , Abdul Ghapar Abdul Kahar 
Published: November 2022

BackgroundEstimation of the economic burden of heart failure (HF) through a complete evaluation is essential for improved treatment planning in the future. This estimation also helps in reimbursement decisions for newer HF treatments. This study aims to estimate the cost of HF treatment in Malaysia from the Ministry of Health’s perspective.Materials and methodsA prevalence-based, bottom-up cost analysis study was conducted in three tertiary hospitals in Malaysia. Chronic HF patients who received treatment between 1 January 2016 and 31 December 2018 were included in the study. The direct cost of HF was estimated from the patients’ healthcare resource utilisation throughout a one-year follow-up period extracted from patients’ medical records. The total costs consisted of outpatient, hospitalisation, medications, laboratory tests and procedure costs, categorised according to ejection fraction (EF) and the New York Heart Association (NYHA) functional classification.ResultsA total of 329 patients were included in the study. The mean ± standard deviation of total cost per HF patient per-year (PPPY) was USD 1,971 ± USD 1,255, of which inpatient cost accounted for 74.7% of the total cost. Medication costs (42.0%) and procedure cost (40.8%) contributed to the largest proportion of outpatient and inpatient costs. HF patients with preserved EF had the highest mean total cost of PPPY, at USD 2,410 ± USD 1,226. The mean cost PPPY of NYHA class II was USD 2,044 ± USD 1,528, the highest among all the functional classes. Patients with underlying coronary artery disease had the highest mean total cost, at USD 2,438 ± USD 1,456, compared to other comorbidities. HF patients receiving angiotensin-receptor neprilysin-inhibitor (ARNi) had significantly higher total cost of HF PPPY in comparison to patients without ARNi consumption (USD 2,439 vs. USD 1,933, p &lt; 0.001). Hospitalisation, percutaneous coronary intervention, coronary angiogram, and comorbidities were the cost predictors of HF.ConclusionInpatient cost was the main driver of healthcare cost for HF. Efficient strategies for preventing HF-related hospitalisation and improving HF management may potentially reduce the healthcare cost for HF treatment in Malaysia.
Test-Retest reliability and preliminary reliable change estimates for Sway Balance tests administered remotely in community-dwelling adults
Authors: Caccese Jaclyn B. , Teel Elizabeth , Van Patten Ryan , Muzeau Mélissa A. , Iverson Grant L. , VanRavenhorst-Bell Heidi A. 
Published: November 2022

ObjectiveImpaired balance and postural stability can occur with advanced age, following traumatic brain injury, in association with neurological disorders and diseases, and as the result of acute or chronic orthopedic problems. The remote assessment of balance and postural stability could be of value in clinical practice and research. We examined the test-retest reliability and reliable change estimates for Sway Balance Mobile Application tests (Sway Medical, Tulsa OK, USA) administered remotely from the participant's home.MethodPrimarily young, healthy community-dwelling adults completed Sway Balance Mobile Application tests remotely on their personal mobile devices once per week for three consecutive weeks while being supervised with a video-based virtual connection. Sway Balance tests include five stances (i.e., feet together, tandem right foot forward, tandem left foot forward, single leg right foot, single leg left foot), which are averaged to compute a Sway Balance composite score from 0 to 100, with higher scores indicating better postural stability. We examined test-retest reliability (measured with intraclass correlation coefficients, ICCs) and preliminary reliable change estimates for 70%, 80%, and 90% confidence intervals.ResultsParticipants included 55 healthy adults (ages = 26.7 ± 9.9 years, interquartile range = 20–30, range = 18–58; 38 [69%] women). Test-retest reliability for the Sway Balance composite score across three weeks was.88. Test-retest reliability for individual stances ranged from 62 to 83 (all ps &lt; 0.001). At the 80% confidence interval, preliminary reliable changes estimates were 9 points for the Sway Balance composite score.ConclusionsFor a remote administration, test–retest reliability was moderate-to-good for all Sway Balance stances, as well as for the Sway Balance composite score. Reliable change estimates may allow clinicians to determine whether an improvement or decline in performance is greater than the expected improvement or decline due to measurement error in young adults.
The hypoglycaemia error grid: A UK-wide consensus on CGM accuracy assessment in hyperinsulinism
Authors: Worth Chris , Dunne Mark J. , Salomon-Estebanez Maria , Harper Simon , Nutter Paul W. , Dastamani Antonia , Senniappan Senthil , Banerjee Indraneel 
Published: November 2022

ObjectiveContinuous Glucose Monitoring (CGM) is gaining in popularity for patients with paediatric hypoglycaemia disorders such as Congenital Hyperinsulinism (CHI), but no standard measures of accuracy or associated clinical risk are available. The small number of prior assessments of CGM accuracy in CHI have thus been incomplete. We aimed to develop a novel Hypoglycaemia Error Grid (HEG) for CGM assessment for those with CHI based on expert consensus opinion applied to a large paired (CGM/blood glucose) dataset.Design and methodsPaediatric endocrinology consultants regularly managing CHI in the two UK centres of excellence were asked to complete a questionnaire regarding glucose cutoffs and associated anticipated risks of CGM errors in a hypothetical model. Collated information was utilised to mathematically generate the HEG which was then approved by expert, consensus opinion. Ten patients with CHI underwent 12 weeks of monitoring with a Dexcom G6 CGM and self-monitored blood glucose (SMBG) with a Contour Next One glucometer to test application of the HEG and provide an assessment of accuracy for those with CHI.ResultsCGM performance was suboptimal, based on 1441 paired values of CGM and SMBG showing Mean Absolute Relative Difference (MARD) of 19.3% and hypoglycaemia (glucose &lt;3.5mmol/L (63mg/dL)) sensitivity of only 45%. The HEG provided clinical context to CGM errors with 15% classified as moderate risk by expert consensus when data was restricted to that of practical use. This provides a contrasting risk profile from existing diabetes error grids, reinforcing its utility in the clinical assessment of CGM accuracy in hypoglycaemia.ConclusionsThe Hypoglycaemia Error Grid, based on UK expert consensus opinion has demonstrated inadequate accuracy of CGM to recommend as a standalone tool for routine clinical use. However, suboptimal accuracy of CGM relative to SMBG does not detract from alternative uses of CGM in this patient group, such as use as a digital phenotyping tool. The HEG is freely available on GitHub for use by other researchers to assess accuracy in their patient populations and validate these findings.
Clinical value of FNA puncture feeling in the diagnosis of non-diagnostic and indeterminate thyroid nodules
Authors: Wu Jintao , Li Yingying , Zhang Mingbo 
Published: November 2022

ObjectiveThe aim of this study was to explore the clinical diagnostic value of puncture feeling during fine-needle aspiration (FNA) for non-diagnostic and indeterminate thyroid nodules.MethodsA retrospective analysis was performed on 176 patients (196 nodules) diagnosed with Bethesda I or III by FNA cytology at the ultrasound department of our hospital between January 2017 and January 2020. Comparisons were made on the differences in puncture feeling (including stiffness and grittiness) between benign and malignant thyroid nodules, and their diagnostic performance was analyzed.ResultsThere were significant differences between benign and malignant nodules with respect to the puncture stiffness and puncture grittiness (P &lt; 0.001). The presence of a hard stiffness and grittiness demonstrated comparable levels of diagnostic performance for malignant thyroid nodules, with sensitivities, specificities, accuracies, positive predictive values, and negative predicative values of 55.56% and 63.89%, 87.10% and 78.22%, 75.51% and 72.96%, 71.43% and 63.01%, and 77.14% and 78.86%, respectively. The diagnostic performance was most optimal in the presence of at least one puncture feeling (area under the receiver operating characteristic curve: 0.771), exhibiting a sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 79.17%, 75.00%, 76.53%, 64.77, and 86.11%%, respectively.ConclusionsPuncture feeling adds clinical value in the diagnosis of thyroid nodules with indeterminate FNA findings.
Implications of m6A-associated snRNAs in the prognosis and immunotherapeutic responses of hepatocellular carcinoma
Authors: Zhang Cheng , Zhang Wangjian , Shui Yongjie , Li Ping , Tian Zhifeng , Duan Shiwei , Wei Qichun 
Published: November 2022

BackgroundHepatocellular carcinoma (HCC) is the most prevalent pathological type of liver cancer worldwide with high mortality and poor prognosis. N6-methyladenosine (m6A) can modify RNAs such as mRNA, lncRNA, miRNA, and tRNA, thereby playing a critical role in the pathogenesis of HCC. However, the role of m6A-associated small nuclear RNA (snRNA) in the prognostic value and immunotherapeutic response in HCC remains unclear.Materials and methodsIn this study, snRNA expression data, gene mutation data, and clinical data of HCC patients were acquired from The Cancer Genome Atlas (TCGA) database. We used the least absolute shrinkage and selection operator (LASSO) Cox regression analysis to identify significant prognostic m6A-associated snRNAs, and then developed a multivariate Cox model based on the selected snRNAs. HCC patients were split into low- and high-risk groups based on the median risk score. We subsequently performed Kaplan-Meier curve analysis to estimate overall survival (OS) by clinicopathological characteristics and tumor mutational burden (TMB) status in low- and high-risk HCC patients. Finally, we compared the immunotherapeutic response as represented by tumor immune dysfunction and exclusion (TIDE) scores between the two risk groups.ResultsEight m6A-associated snRNAs were selected as independent predictors to develop the risk model. Our results revealed that the OS of HCC patients in the high-risk group was significantly worse than that in the low-risk group on clinicopathologic characteristics, including age (≤65 years and &gt;65 years), gender (male), grade (G I-II and G III-IV) and TNM staging (Stage I-II and Stage III-IV). In addition, the OS of low-TMB and low-risk group was longer than that of high-TMB and high-risk group. The TIDE score indicated that HCC patients in the high-risk group were more susceptible to immunotherapy.ConclusionOur study suggests that m6A-associated snRNAs may be useful biomarkers for the prognosis of HCC and that m6A-associated snRNA models can predict the effect of immunotherapy in HCC patients.
Dynamic changes in kynurenine pathway metabolites in multiple sclerosis: A systematic review
Authors: Fathi Mobina , Vakili Kimia , Yaghoobpoor Shirin , Tavasol Arian , Jazi Kimia , Mohamadkhani Ashraf , Klegeris Andis , McElhinney Alyssa , Mafi Zahedeh , Hajiesmaeili Mohammadreza , Sayehmiri Fatemeh 
Published: November 2022

BackgroundMultiple sclerosis (MS) is a debilitating neurodegenerative disorder characterized by axonal damage, demyelination, and perivascular inflammatory lesions in the white matter of the central nervous system (CNS). Kynurenine pathway (KP), which is the major route of tryptophan (TRP) metabolism, generates a variety of neurotoxic as well as neuroprotective compounds, affecting MS pathology and the severity of impairments. Alterations in KP have been described not only in MS, but also in various psychiatric and neurodegenerative diseases. The purpose of this systematic review is to investigate the previously reported dysregulation of KP and differences in its metabolites and enzymes in patients with MS compared to healthy control subjects.MethodElectronic databases of PubMed, Scopus, Cochrane Database of Systematic Reviews, and Web of Science were searched to identify studies measuring concentrations of KP metabolites and enzymes in MS patients and control subjects. The following metabolites and enzymes implicated in the KP were investigated: TRP, kynurenine (KYN), kynurenic acid (KYNA), quinolinic acid (QUIN), picolinic acid (PIC), hydroxyindoleacetic acid (HIAA), indoleamine 2,3-dioxygenase (IDO), kynurenine aminotransferase (KAT), and their related ratios.ResultTen studies were included in our systematic review. Our review demonstrates that IDO expression is reduced in the peripheral blood mononuclear cells (PBMCs) of MS patients compared to healthy controls. Also, increased levels of QUIN and QUIN/KYNA in the serum and cerebrospinal fluid (CSF) of MS patients is observed. Differences in levels of other metabolites and enzymes of KP are also reported in some of the reviewed studies, however there are discrepancies among the included reports.ConclusionThe results of this investigation suggest a possible connection between alterations in the levels of KP metabolite or enzymes and MS. QUIN levels in CSF were higher in MS patients than in healthy controls, suggesting that QUIN may be involved in the pathogenesis of MS. The data indicate that differences in the serum/blood or CSF levels of certain KP metabolites and enzymes could potentially be used to differentiate between MS patients and control subjects.
Untargeted metabolomics identified kynurenine as a predictive prognostic biomarker in acute myocardial infarction
Authors: Zhang Xiaolin , Cai Yi , Su Xu , Jing Quanmin , Liu Haiwei , Na Kun , Qiu Miaohan , Tian Xiaoxiang , Liu Dan , Wu Tianxiao , Yan Chenghui , Han Yaling 
Published: November 2022

ObjectiveThe occurrence of cardiovascular adverse events in the first year after ST-acute myocardial infarction (STEMI) remains high; therefore, identification of patients with poor prognosis is essential for early intervention. This study aimed to evaluate the prognostic value of metabolomics-based biomarkers in STEMI patients and explore their functional mechanisms.MethodsMetabolite profiling was performed using nuclear magnetic resonance. The plasma concentration of Kynurenine (Kyn) was measured using ultraperformance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry. Major adverse cardiac and cerebral events were assessed for 1 year. A functional metabolomics strategy was proposed for investigating the role of Kyn in both vitro and vivo models.ResultsThe adjusted hazard ratios in STEMI patients for Kyn in the 4th quartile 7.12(5.71-10.82) was significantly higher than that in the 3rd quartile 3.03(2.62-3.74), 2nd quartile 1.86(1.70-2.03), and 1st quartile 1.20(0.93-1.39).The incidence of MACCE was significantly different among Kyn quartiles and the highest incidence of MACCE was observed in the 4th quartile when compared with the 1st quartile (9.84% vs.2.85%, P&lt;0.001).Immunofluorescence staining indicated that indoleamine-pyrrole 2,3-dioxygenase (IDO1) was located in the CD68 positive staining area of thrombi from STEMI patients and Kyn was induced in the early phase after myocardial infarction. Kyn could trigger inflammation and oxidative stress of macrophage cells by activation of the Sirt3-acSOD2/IL-1β signaling pathway in vitro.ConclusionsPlasma Kyn levels were positively associated with the occurrence of STEMI. Kyn could induce macrophage cells inflammation and oxidative stress by activating the Sirt3-acSOD2/IL-1β pathway following myocardial ischemia injury. Kyn could be a robust biomarker for STEMI prognosis and reduction of Kyn could be beneficial in STEMI patients.
An experimental study on the impact resistance of a new three-wave beam steel guardrail
Authors: Guo Kai , Wang Chenghu , Shen Linlin 
Published: November 2022

It is crucial to examine the impact resistance of W-beam guardrails on both sides of the highway in order to limit the severity of impact incidents and safeguard passengers. Given its importance, this article investigates the impact resistance of the new three-wave steel guardrail. To be specific, the study uses ANSYS to establish the vehicle impact barrier model in which the guardrail is embedded in concrete and soil column. The new accurate model of the three-wave beam guardrail collision stimulates the deformation degree of the guardrail under the impact of vehicles with different masses and speeds. According to the simulation analysis’ findings, the guardrail with the post embedded in the concrete had a maximum displacement of 568.48 mm, which was less than the specification’s maximum dynamic deformation of 750 mm and met the requirements for Grade 8 protection. In contrast, the guardrail with the post embedded in the soil had a maximum displacement of 679.466 mm, which was less than the specification’s maximum dynamic deformation of 750 mm.
Identification and immune characteristics of molecular subtypes related to protein glycosylation in Alzheimer’s disease
Authors: Ma Zhaotian , Yang Fan , Fan Jiajia , Li Xin , Liu Yuanyuan , Chen Wei , Sun Honghao , Ma Tengfei , Wang Qiongying , Maihaiti Yueriguli , Ren Xiaoqiao 
Published: November 2022

BackgroundProtein glycosylation has been confirmed to be involved in the pathological mechanisms of Alzheimer’s disease (AD); however, there is still a lack of systematic analysis of the immune processes mediated by protein glycosylation-related genes (PGRGs) in AD.Materials and methodsTranscriptomic data of AD patients were obtained from the Gene Expression Omnibus database and divided into training and verification datasets. The core PGRGs of the training set were identified by weighted gene co-expression network analysis, and protein glycosylation-related subtypes in AD were identified based on k-means unsupervised clustering. Protein glycosylation scores and neuroinflammatory levels of different subtypes were compared, and functional enrichment analysis and drug prediction were performed based on the differentially expressed genes (DEGs) between the subtypes. A random forest model was used to select important DEGs as diagnostic markers between subtypes, and a line chart model was constructed and verified in other datasets. We evaluated the differences in immune cell infiltration between the subtypes through the single-sample gene set enrichment analysis, analyzed the correlation between core diagnostic markers and immune cells, and explored the expression regulation network of the core diagnostic markers.ResultsEight core PGRGs were differentially expressed between the training set and control samples. AD was divided into two subtypes with significantly different biological processes, such as vesicle-mediated transport in synapses and neuroactive ligand-receptor interactions. The high protein glycosylation subtype had a higher level of neuroinflammation. Riluzole and sulfasalazine were found to have potential clinical value in this subtype. A reliable construction line chart model was constructed based on nine diagnostic markers, and SERPINA3 was identified as the core diagnostic marker. There were significant differences in immune cell infiltration between the two subtypes. SERPINA3 was found to be closely related to immune cells, and the expression of SERPINA3 in AD was found to be regulated by a competing endogenous RNA network that involves eight long non-coding RNAs and seven microRNAs.ConclusionProtein glycosylation and its corresponding immune process play an important role in the occurrence and development of AD. Understanding the role of PGRGs in AD may provide a new potential therapeutic target for AD.