bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Diagnosis of Dengue in Patients Presenting With Acute Febrile Illness Using Supervised Machine Learning and Impact of Seasonality
Authors: Ming Damien K. , Tuan Nguyen M. , Hernandez Bernard , Sangkaew Sorawat , Vuong Nguyen L. , Chanh Ho Q. , Chau Nguyen V. V. , Simmons Cameron P. , Wills Bridget , Georgiou Pantelis , Holmes Alison H. , Yacoub Sophie 
Published: March 2022

BackgroundSymptomatic dengue infection can result in a life-threatening shock syndrome and timely diagnosis is essential. Point-of-care tests for non-structural protein 1 and IgM are used widely but performance can be limited. We developed a supervised machine learning model to predict whether patients with acute febrile illnesses had a diagnosis of dengue or other febrile illnesses (OFI). The impact of seasonality on model performance over time was examined.MethodsWe analysed data from a prospective observational clinical study in Vietnam. Enrolled patients presented with an acute febrile illness of &lt;72 h duration. A gradient boosting model (XGBoost) was used to predict final diagnosis using age, sex, haematocrit, platelet, white cell, and lymphocyte count collected on enrolment. Data was randomly split 80/20% into a training and hold-out set, respectively, with the latter not used in model development. Cross-validation and hold out set testing was used, with performance over time evaluated through a rolling window approach.ResultsWe included 8,100 patients recruited between 16th October 2010 and 10th December 2014. In total 2,240 (27.7%) patients were diagnosed with dengue infection. The optimised model from training data had an overall median area under the receiver operator curve (AUROC) of 0.86 (interquartile range 0.84–0.86), specificity of 0.92, sensitivity of 0.56, positive predictive value of 0.73, negative predictive value (NPV) of 0.84, and Brier score of 0.13 in predicting the final diagnosis, with similar performances in hold-out set testing (AUROC of 0.86). Model performances varied significantly over time as a function of seasonality and other factors. Incorporation of a dynamic threshold which continuously learns from recent cases resulted in a more consistent performance throughout the year (NPV &gt;90%).ConclusionSupervised machine learning models are able to discriminate between dengue and OFI diagnoses in patients presenting with an early undifferentiated febrile illness. These models could be of clinical utility in supporting healthcare decision-making and provide passive surveillance across dengue endemic regions. Effects of seasonality and changing disease prevalence must however be taken into account—this is of significant importance given unpredictable effects of human-induced climate change and the impact on health.
Correction of Atmospheric Delay Error of Airborne and Spaceborne GNSS-R Sea Surface Altimetry
Authors: Yan Zhengjie , Zheng Wei , Wu Fan , Wang Cheng , Zhu Huizhong , Xu Aigong 
Published: March 2022

Improving the measurement accuracy is a necessary condition for sea surface altimetry using the Global Navigation Satellite System Reflectometry (GNSS-R). The ionosphere and troposphere delay the transmission of satellite signals, which directly affect the measuring accuracy. The influence of the atmospheric environment on GNSS-R altimetry differs from different platforms. By analyzing and sorting out the altimetry data of airborne and spaceborne platforms, this paper studies the variation law of signal delay in the altimetry process from the point of view of mathematical geometry, which provides an example for improving the precision of GNSS-R altimetry measurements. Firstly, in order to facilitate data analysis, this paper constructed an altimetry model with the GNSS satellite position, specular reflection point position, receiver position as nodes, classified direct signals, and reflected signals. Secondly, calculate ionospheric puncture point coordinates , and interpolate GIM products provided by IGS using time and puncture point coordinates to obtain the VTEC value in the vertical direction of the puncture point, which was converted into the path direction STEC by projection function, the ionospheric delay of each part was obtained in this way. The tropospheric delay of each part is considered for the along-path component and the geometric component, the delay of along-path component was calculated by the UNB3m model, and the delay of geometric component was calculated by the equation provided by Nikolaidou (Nikolaidou et al., 2021). Thirdly, by comparing the sea surface height inversion results with or without atmospheric delay correction with the mean sea surface height provided by DTU15, the measurement accuracy with atmospheric delay correction is obviously improved. The study results of the influence of atmospheric delay on the altimetry experiments precision error of airborne and spaceborne platforms show that the error magnitude is consistent with the existing literature. In the airborne experiment, the influence of the ionosphere is negligible and the troposphere has sub-meter influence on altimetry results, among which the tropospheric along-path delay component occupies a high proportion. The geometric delay component has a high correlation with the satellite elevation angle and its influence on the measurement accuracy decreases with the elevation angle increase. The effect of this factor can be effectively weakened by setting a high satellite cutoff angle. In the spaceborne experiment, the effect of atmospheric delay on altimetry results fluctuates in the range of 3∼5 m when the satellite elevation angle is greater than 60°. In this paper, the method of calculating signal atmospheric delay through geometric relation to improving the measurement accuracy can provide an example for the atmospheric delay correction of GNSS-R ocean altimetry with high precision and spatial resolution in future research.
One-step Synthesis of Biomass-Based Carbon Dots for Detection of Metal Ions and Cell Imaging
Authors: Huang Xiaolin , Liu Jiaheng , Zhao Bin , Bai Yibing , Peng Zhibin , Zhou Jundan , Wang Chenxi , Zhao Xuan , Han Shiyan , Zhang Chunlei 
Published: March 2022

Biomass-based carbon dots (Bio-CDs) were prepared from dehydroabietic acid using a one-step hydrothermal process. Characterization by TEM, XPS and FTIR spectroscopy showed that the Bio-CDs are spherical nanoparticles containing mainly C, N and O elements, with functional groups such as amino and carbonyl groups on their surface. The optical properties of the Bio-CDs were studied in detail. A solution of Bio-CDs exhibited excitation-dependent blue fluorescence emission. The solution showed excellent photostability under ultraviolet light and the fluorescence intensity could be enhanced by decreasing the temperature. The intensity of fluorescence emission of the solution was essentially unchanged over the pH range 3.91–8.69, and in the presence of different anions and cations, other than Fe3+ and Pb2+. Fe3+ and Pb2+ ions, respectively, quenched and enhanced the intensity of the fluorescence emission of the solution, allowing sensitive and selective detection of Fe3+ (LOD = 2.33 μM, Em = 437 nm) and of Pb2+ (LOD = 0.27 μM, Em = 437 nm and LOD = 0.33 μM, Em = 500 nm). As a further demonstration of potential applications, the Bio-CDs were shown to have low cytotoxicity and to stain cell nuclei as effectively as the commonly used nuclear stain 4′,6-diamino-2-phenylindole (DAPI), demonstrating their promise in the field of cell imaging.
Novel Stemness-Related Gene Signature Predicting Prognosis and Indicating a Different Immune Microenvironment in HNSCC
Authors: Luo Yi , Xu Wei-Bo , Ma Ben , Wang Yu 
Published: March 2022

Background: The head and neck squamous cell carcinomas (HNSCC) is one of the most frequent cancers in the world, with an unfavorable prognosis. Cancer stem cells (CSCs) have been found to be responsible for HNSCC recurrence and therapeutic resistance.Methods: The stemness of HNSCC was measured using a stemness index based on mRNA expression (mRNAsi). Stemness-related genes were discovered using weighted gene co-expression network analysis, least absolute shrinkage and selection operator analysis, and Cox regression, and a stemness-related prognostic index (SPI) was constructed. This research was based on TCGA and GSE65858.Results: Stemness was found upregulated in HNSCC compared with normal tissues. The risk score model including five stemness-related genes exhibited a good accuracy in predicting outcomes. High SPI predicted a shorter overall survival (OS) in HNSCC patients, in the meantime, also demonstrated a lower CD8+ T cell infiltration and a higher enrichment of macrophages and fibroblasts than the low-SPI group, focusing on several up-regulated pathways such as epithelial mesenchymal transition (EMT), MYC targets v1, E2F targets, mTORC1 signaling, hypoxia, MYC targets v2, angiogenesis, G2M checkpoint, and glycolysis.Conclusion: The SPI signature, which includes five stemness-related genes, could be utilized as a prognostic biomarker for HNSCC, implying that stemness may impact HNSCC immunologic profiles and be a feasible therapeutic target.
Familial Hypercholesterolemia: Real-World Data of 1236 Patients Attending a Czech Lipid Clinic. A Retrospective Analysis of Experience in More than 50 years. Part II. Clinical Characteristics
Authors: Altschmiedova Tereza , Todorovova Veronika , Vrablik Michal , Ceska Richard 
Published: March 2022

Introduction: Patients with familial hypercholesterolemia (FH) are at increased risk of premature atherosclerotic cardiovascular disease (ASCVD).Aim of study: To perform a retrospective analysis of data to assess the effects of individual lipoproteins and other risk factors (RFs) on the development of ASCVD and to compare these parameters in individuals with versus without ASCVD.Patients and methods: Our study group included a total of 1,236 patients with FH (395 men and 841 women with a mean age of 44.8 ± 16.7 years) attending a single lipid clinic. The diagnosis of FH was established using the Dutch Lipid Clinic Network score (DLCN). Among the 1236 FH patients, 1,008 of them [854 suspected with LDL receptor-mediated FH and 154 with familial defective apolipoprotein B-100 (FDB)] were genetically analysed. Their RFs were assessed based on the patients’ clinical characteristics.Results: While patients with ASCVD had higher baseline LDL-C, TC, TG and Lp(a) compared with patients without this diagnosis, this ratio was just the opposite by the follow-up. The highest statistically significant differences were seen in the baseline levels of Lp(a) and, quite surprisingly, TG. Except for Lp(a), the levels of all lipid parameters declined significantly over time. While the incidence of diabetes and arterial hypertension was not higher in our group compared with the general population, these patients were at a more significant risk of ASCVD.Conclusion: Familial hypercholesterolemia is a major RF for the development of ASCVD. While our analysis confirmed the important role of LDL-C, it also corroborated a strong correlation between ASCVD and other lipid parameters, and Lp(a) and TG in particular. Familial hypercholesterolemia is not the only RF and, to reduce cardiovascular risk of their patients, physicians have to search for other potential RFs. Patients diagnosed to have FH benefit from attending a specialized lipid clinic perse.
A Link Between Mitochondrial Dysfunction and the Immune Microenvironment of Salivary Glands in Primary Sjogren’s Syndrome
Authors: Li Ning , Li Yusi , Hu Jiawei , Wu Yicheng , Yang Jie , Fan Hongmei , Li Lei , Luo Danyang , Ye Yulin , Gao Yiming , Xu Haimin , Hai Wangxi , Jiang Liting 
Published: March 2022

BackgroundPrimary Sjogren’s syndrome (pSS) is a slowly progressive, inflammatory autoimmune disease characterized by lymphocytic infiltration into salivary and lacrimal glands. It becomes more recognized that morphology alterations of epithelial mitochondria are involved in altered cellular bioenergetics in pSS patients. The integrated analysis of the mitochondrial role in the pathogenesis and aberrant immune microenvironment in pSS remains unknown.MethodsThe mitochondria-related genes and gene expression data were downloaded from the MitoMiner, MitoCarta, and NCBI GEO databases. We performed novel transcriptomic analysis and constructed a network between the mitochondrial function and immune microenvironment in pSS-salivary glands by computer-aided algorithms. Subsequently, real-time PCR was performed in clinical samples in order to validate the bioinformatics results. Histological staining and transmission electron microscopy (TEM) were further studied on labial salivary gland samples of non-pSS and pSS patients characterized for mitochondria-related phenotypic observation in the different stages of the disease.ResultsThe bioinformatic analysis revealed that the expression of several mitochondria-related genes was altered in pSS. Quantitative real-time PCR showed that four hub genes, CD38, CMPK2, TBC1D9, and PYCR1, were differentially expressed in the pSS clinical samples. These hub genes were associated with the degree of immune cell infiltration in salivary glands, the mitochondrial respiratory chain complexes, mitochondrial metabolic pathway in gluconeogenesis, TCA cycle, and pyruvate/ketone/lipid/amino acid metabolism in pSS. Clinical data revealed that the gene expression of fission (Fis1, DRP1, and MFF) and fusion (MFN1, MFN2, and OPA1) was downregulated in pSS samples, consistent with the results from the public validation database. As the disease progressed, cytochrome c and Bcl-2 proteins were regionally distributed in salivary glands from pSS patients. TEM revealed cytoplasmic lipid droplets and progressively swollen mitochondria in salivary epithelial cells.ConclusionOur study revealed cross talk between mitochondrial dysfunction and the immune microenvironment in salivary glands of pSS patients, which may provide important insights into SS clinical management based on modulation of mitochondrial function.
Anti-Nuclear Antibodies Patterns in Patients With Systemic Lupus Erythematosus and Their Correlation With Other Diagnostic Immunological Parameters
Authors: Al-Mughales Jamil A. 
Published: March 2022

BackgroundAntinuclear antibodies (ANA) are major immunodiagnostic tools in systemic lupus erythematosus (SLE); however, their clinical and pathogenic roles are not yet elucidated and are a subject of controversy.ObjectivesThe aim of the study is to explore the pathogenic significance of ANA patterns among SLE patients, by analyzing their association with ANA titers, complement levels and other pathogenic immune markers, namely, anti-double-stranded DNA (anti-dsDNA), complements C3 and C4, rheumatoid factor (RF), anticardiolipin antibodies IgG (ACL IgG) and IgM (ACL IgM), Beta-2 Glycoprotein 1 Antibodies (β2-GP) IgG (β2-IgM) and IgM (β2-IgM), and lupus anticoagulant (LA).MethodA comparative cross-sectional study was conducted among 495 SLE patients, who were diagnosed and classified by consultant rheumatologists according to the new European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 criteria. SLE immunodiagnostic profiles were analyzed including the following parameters: ANA antibody titers and staining patterns, anti-dsDNA, C3 and C4 levels, aCL, and anti-β2-GP and LA.ResultThe most frequently observed ANA patterns were the speckled (52.1%) and homogeneous (35.2%) patterns, while other patterns were rare representing less than 7% of the patients each. ANA titers were highest in patients with mixed pattern followed by the speckled pattern. Of all the investigated patterns, the peripheral pattern showed the most pathogenic immune profile, namely, highest levels of anti-dsDNA, lowest levels of C4, and highest levels of aCL and β2-GP IgG and IgM.ConclusionThis retrospective study showed that speckled followed by homogeneous ANA patterns were predominant accounting for 52.1 and 35.2% of the patients. The ANA pattern showed several associations with other immune markers that are documented to have significant clinical implications in SLE. Peripheral, mixed, and speckled patterns were associated with higher profiles of immune markers indicative of a potential prognostic value of these patterns in SLE.
Who Is at Risk of Poor Mental Health Following Coronavirus Disease-19 Outpatient Management?
Authors: Hüfner Katharina , Tymoszuk Piotr , Ausserhofer Dietmar , Sahanic Sabina , Pizzini Alex , Rass Verena , Galffy Matyas , Böhm Anna , Kurz Katharina , Sonnweber Thomas , Tancevski Ivan , Kiechl Stefan , Huber Andreas , Plagg Barbara , Wiedermann Christian J. , Bellmann-Weiler Rosa , Bachler Herbert , Weiss Günter , Piccoliori Giuliano , Helbok Raimund , Loeffler-Ragg Judith , Sperner-Unterweger Barbara 
Published: March 2022

BackgroundCoronavirus Disease-19 (COVID-19) convalescents are at risk of developing a de novo mental health disorder or worsening of a pre-existing one. COVID-19 outpatients have been less well characterized than their hospitalized counterparts. The objectives of our study were to identify indicators for poor mental health following COVID-19 outpatient management and to identify high-risk individuals.MethodsWe conducted a binational online survey study with adult non-hospitalized COVID-19 convalescents (Austria/AT: n = 1,157, Italy/IT: n = 893). Primary endpoints were positive screening for depression and anxiety (Patient Health Questionnaire; PHQ-4) and self-perceived overall mental health (OMH) and quality of life (QoL) rated with 4 point Likert scales. Psychosocial stress was surveyed with a modified PHQ stress module. Associations of the mental health and QoL with socio-demographic, COVID-19 course, and recovery variables were assessed by multi-parameter Random Forest and Poisson modeling. Mental health risk subsets were defined by self-organizing maps (SOMs) and hierarchical clustering algorithms. The survey analyses are publicly available (https://im2-ibk.shinyapps.io/mental_health_dashboard/).ResultsDepression and/or anxiety before infection was reported by 4.6% (IT)/6% (AT) of participants. At a median of 79 days (AT)/96 days (IT) post-COVID-19 onset, 12.4% (AT)/19.3% (IT) of subjects were screened positive for anxiety and 17.3% (AT)/23.2% (IT) for depression. Over one-fifth of the respondents rated their OMH (AT: 21.8%, IT: 24.1%) or QoL (AT: 20.3%, IT: 25.9%) as fair or poor. Psychosocial stress, physical performance loss, high numbers of acute and sub-acute COVID-19 complaints, and the presence of acute and sub-acute neurocognitive symptoms (impaired concentration, confusion, and forgetfulness) were the strongest correlates of deteriorating mental health and poor QoL. In clustering analysis, these variables defined subsets with a particularly high propensity of post-COVID-19 mental health impairment and decreased QoL. Pre-existing depression or anxiety (DA) was associated with an increased symptom burden during acute COVID-19 and recovery.ConclusionOur study revealed a bidirectional relationship between COVID-19 symptoms and mental health. We put forward specific acute symptoms of the disease as “red flags” of mental health deterioration, which should prompt general practitioners to identify non-hospitalized COVID-19 patients who may benefit from early psychological and psychiatric intervention.Clinical Trial Registration[ClinicalTrials.gov], identifier [NCT04661462].
Isolated Components From Spider Venom Targeting Human Glioblastoma Cells and Its Potential Combined Therapy With Rapamycin
Authors: Caballero Marcus , Barreto Natalia , Bonfanti Amanda Pires , Munhoz Jaqueline , Rocha e Silva Thomaz , Sutti Rafael , Verinaud Liana , Pinheiro de Mato Felipe Cezar , Lanfredi Guilherme Pauperio , Rapôso Catarina 
Published: March 2022

Glioblastomas (GBs) are responsible for a higher mortality rate among gliomas, corresponding to more than 50% of them and representing a challenge in terms of therapy and prognosis. Peptide-based antineoplastic therapy is a vast and promising field, and these molecules are one of the main classes present in spider venoms. Recently, our research group demonstrated the cytotoxic effects ofPhoneutria nigriventerspider venom (PnV) in GBs. The present study aimed to select the purified PnV-components with potential antineoplastic effects, as well as to compare different metabolic conditions. Human GB (NG97) cells were treated with the PnV fractions: F1 (less than 3 kDa), F2 (between 3 and 10 kDa), and F3 (greater than 10 kDa). After treatments, viability (MTT), proliferation (CFSE), death (Annexin V/propidium iodide-PI), and cell cycle (PI) assays were performed. The F1 and F2 fractions in acute periods (1 and 5 h) and low concentrations (0.1 and 1 μg/ml) showed more relevant effects and were repurified in subfractions (SF1–SF11); from these, SF3 and SF4 showed the most significant effects. The previous inhibition of mTOR by rapamycin had a synergistic effect with SFs, reducing cell viability even more significantly than the untreated control. Taken together, the results point to components present in SF3 and SF4 as potential prototypes for the development of new drugs for GB treatment and stimulate studies to use these compounds in combination therapy with a rapamycin-like activity. Future studies will be conducted to characterize, synthesize the molecules, and to evaluate the efficacy and safety in preclinical models.
High Serum Levels of Otolin-1 in Patients With Benign Paroxysmal Positional Vertigo Predict Recurrence
Authors: Fan Zhenyi , Hu Zhizhou , Han Weiwei , Lu Xiaoxiong , Liu Xiaoxia , Zhou Min , Yan Wang , Wu Yunqin 
Published: March 2022

BackgroundOtolin-1 is an inner ear-specific protein that is exclusively expressed in otoconia and vestibule and cochlea cells. Recent investigations reported that otolin-1 can cross the blood-labyrinthine barrier and that the levels in serum well-reflected otolith status. Serum otolin-1 levels in patients with benign paroxysmal positional vertigo (BPPV) are significantly elevated compared with healthy controls. We aimed to explore whether otolin-1 can also serve as a biomarker for predicting BPPV recurrence.MethodPatients at our institution with new-onset of idiopathic BPPV between May, 2017 and May, 2018 were recruited and followed up for 2 years. All demographic data of the patients were collected, and serum levels of otolin-1 and other laboratory indicators were measured and compared according to the recurrence status.ResultsA total of 74 patients, who met the inclusion criteria were enrolled in this study, of which 27 (36.5%) patients had suffered one or more episodes of recurrence after undergoing canal repositioning treatments during the study. The serum levels of otolin-1 in patients with recurrent BPPV were significantly higher than those in patients without recurrent BPPV (363.9 vs. 309.8 pg/ml, p = 0.001). In multivariate analysis comparing the second to fourth quartiles (Q2–Q4) against the first quartile (Q1) of otolin-1, the level of otolin-1 in Q4 could significantly predict BPPV recurrence, and the odds ratio (OR) was elevated by approximately 812% (OR = 9.12; 95% confidence interval [CI]: 1.44–57.9; p = 0.019).ConclusionHigh serum levels of otolin-1 were associated with an increased risk of BPPV recurrence, and further investigation is required to confirm this association and clarify the exact mechanism.