bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and Validation of the Diagnostic Characteristic Genes of Ovarian Cancer by Bioinformatics and Machine Learning
Authors: Liu Jinya , Liu Leping , Antwi Paul Akwasi , Luo Yanwei , Liang Fang 
Published: June 2022

Background: Ovarian cancer (OC) has a high mortality rate and poses a severe threat to women’s health. However, abnormal gene expression underlying the tumorigenesis of OC has not been fully understood. This study aims to identify diagnostic characteristic genes involved in OC by bioinformatics and machine learning.Methods: We utilized five datasets retrieved from the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA) database, and the Genotype-Tissue Expression (GTEx) Project database. GSE12470 and GSE18520 were combined as the training set, and GSE27651 was used as the validation set A. Also, we combined the TCGA database and GTEx database as validation set B. First, in the training set, differentially expressed genes (DEGs) between OC and non-ovarian cancer tissues (nOC) were identified. Next, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Disease Ontology (DO) enrichment analysis, and Gene Set Enrichment Analysis (GSEA) were performed for functional enrichment analysis of these DEGs. Then, two machine learning algorithms, Least Absolute Shrinkage and Selector Operation (LASSO) and Support Vector Machine-Recursive Feature Elimination (SVM-RFE), were used to get the diagnostic genes. Subsequently, the obtained diagnostic-related DEGs were validated in the validation sets. Then, we used the computational approach (CIBERSORT) to analyze the association between immune cell infiltration and DEGs. Finally, we analyzed the prognostic role of several genes on the KM-plotter website and used the human protein atlas (HPA) online database to analyze the expression of these genes at the protein level.Results: 590 DEGs were identified, including 276 upregulated and 314 downregulated DEGs.The Enrichment analysis results indicated the DEGs were mainly involved in the nuclear division, cell cycle, and IL−17 signaling pathway. Besides, DEGs were also closely related to immune cell infiltration. Finally, we found that BUB1, FOLR1, and PSAT1 have prognostic roles and the protein-level expression of these six genes SFPR1, PSAT1, PDE8B, INAVA and TMEM139 in OC tissue and nOC tissue was consistent with our analysis.Conclusions: We screened nine diagnostic characteristic genes of OC, including SFRP1, PSAT1, BUB1B, FOLR1, ABCB1, PDE8B, INAVA, BUB1, TMEM139. Combining these genes may be useful for OC diagnosis and evaluating immune cell infiltration.
Selective Sphingosine 1-Phosphate Receptor 1 Modulation Augments Thrombolysis of Low-Dose Tissue Plasminogen Activator Following Cerebrovascular Thrombosis
Authors: Li Han-Dong , Li Ran , Kong Ying , Zhang Wenyan , Qi Caiyun , Wang Dan , Hao Hongying , Liu Qiang 
Published: June 2022

BackgroundResults from our recent study demonstrate that sphingosine-1-phosphate receptor 1 (S1PR1) modulation improves microvascular hemodynamics after cerebrovascular thrombosis. This study was to determine the microvascular hemodynamic effects of a sub-thrombolytic dose of tPA combined with a selective S1PR1 modulator ozanimod in a mouse model of cerebrovascular thrombosis.MethodsMicrovascular circulation in mice was monitored in vivo by two-photon microscopy. Thrombosis was induced in cortical arterioles by laser irradiation. Arteriolar flow velocity was measured by line-scanning following plasma-labeling with fluorescein-dextran.ResultsLaser‐induced thrombosis led to a persistent reduction of flow velocity in cortical arterioles. Sub-thrombolytic dose of tPA along with vehicle control did not improve the flow velocity in cortical arterioles following thrombosis. In contrast, a sub-thrombolytic dose of tPA along with ozanimod dramatically restored flow velocity in cortical arterioles following thrombosis. Ozanimod did not affect coagulation and bleeding time. Notably, ozanimod reduced thrombus volume without altering microvascular lumen diameter. In addition, ozanimod reduced leukocyte components within the thrombus.ConclusionsThese findings demonstrate that the thrombolytic effect of a sub-thrombolytic dose of tPA is markedly enhanced by S1PR1 modulation, implying that S1PR1 modulation may improve the therapeutic benefit of low-dose tPA in patients with acute ischemic stroke.
Heterogeneous SARS-CoV-2-Neutralizing Activities After Infection and Vaccination
Authors: Graninger Marianne , Camp Jeremy V. , Aberle Stephan W. , Traugott Marianna T. , Hoepler Wolfgang , Puchhammer-Stöckl Elisabeth , Weseslindtner Lukas , Zoufaly Alexander , Aberle Judith H. , Stiasny Karin 
Published: June 2022

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) with different resistance levels to existing immunity have recently emerged. Antibodies that recognize the SARS-CoV-2 spike (S) protein and exhibit neutralizing activities are considered the best correlate of protection and an understanding of humoral immunity is crucial for controlling the pandemic. We thus analyzed such antibodies in individuals recovered from infection in 2020 as well as vaccinees after two doses of an mRNA vaccine.MethodsNeutralizing antibody responses against three SARS-CoV-2 variants (D614G, VOCs Beta and Delta) were determined in serum samples from 54 infected individuals (24 non-hospitalized, 30 hospitalized) and 34 vaccinees shortly after symptom onset or second vaccination, respectively, as well as six months later. In addition, the effect of the S sequence of the infecting strain on neutralization was studied.ResultsNon-hospitalized patients had the lowest neutralization titers against all variants, while those of hospitalized patients equaled or exceeded those of vaccinees. Neutralizing activity was lower against the two VOCs and declined significantly in all cohorts after six months. This decrease was more pronounced in hospitalized and vaccinated individuals than in non-hospitalized patients. Of note, the specific neutralizing activity (NT titer/ELISA value ratio) was higher in the infected cohorts than in vaccinees and did not differ between non-hospitalized and hospitalized patients. Patients infected with viral strains carrying mutations in the N-terminal domain of the spike protein were impaired in Beta VOC neutralization.ConclusionsSpecific neutralizing activities were higher in infected than in vaccinated individuals, and no difference in the quality of these antibodies was observed between hospitalized and non-hospitalized patients, despite significantly lower titers in the latter group. Additionally, antibody responses of infected individuals showed greater heterogeneity than those of vaccinees, which was associated with mutations in the spike protein of the infecting strain. Overall, our findings yielded novel insights into SARS-CoV-2-specific neutralizing antibodies, evolving differently after virus infection and COVID-19 vaccination, which is an important issue to consider in ongoing vaccine strategy improvements.
Substantial Biogeochemical and Biomolecular Processing of Dissolved Organic Matter in an Anticyclonic Eddy in the Northern South China Sea Down to Bathypelagic Depths
Authors: Zhang Miao , Li Siyu , Hertkorn Norbert , Harir Mourad , Xu Dongfeng , Schmitt-Kopplin Philippe , Wu Ying 
Published: June 2022

Solid-phase extracted dissolved organic matter (SPE-DOM) was isolated from two depth profiles at the core and at the edge of an anticyclonic eddy (ACE) in the northern South China Sea. Non-target nuclear magnetic resonance (NMR) spectroscopy and Fourier transform ion cyclotron mass spectrometry (FTICR/MS) of SPE-DOM revealed a higher uniformity of DOM molecules within the ACE than at the edge of the ACE. Small-scale upwelling of external nutrients may have contributed to higher productivity and production of fresher DOM, with higher proportions of CHNO and CHNOS compounds and low molecular weight species at the edge of the eddy. Common SPE-DOM molecules of supposedly biological origin such as carbohydrates and olefins were most abundant in the chlorophyll maximum layer in both stations. An unusual suite of ~10 abundant and ~35 less abundant tert-butyl benzene derivatives with potential to act as endocrine disruptors within a marine food chain and ~two dozen ketones of putative bacterial origin was recognized at meso- and bathypelagic depths in single-digit micromolar concentrations, with a distinct maximum at 1000 m depth at the edge of ACE. Downwelling might bring temporary large volumes of productive marine waters into deep waters, with micromolar concentration of abundant, microbial food web-specific metabolites (e.g. 2,4-di-tert-butylphenol et al.). In our study, these eventually added up to one quarter of common background biogeochemical marine organic matter even at bathypelagic depths and beneath and are significant food and energy sources for marine biota. Mesoscale chemical heterogeneity of marine water columns might extend to larger depths than currently anticipated and may create activity hotspots influencing biota, processing of DOM, and cycling of nutrients and trace elements.
Rational Synthesis of Freestanding NaxV2O5-rGO Paper as the Stable Cathode for Sodium Ion Batteries
Authors: Wang Qi , Li Xin , Xu Junmin , Yuan Yueyue , Li Xinyue , Wang Xinchang 
Published: June 2022

Flexible NaxV2O5/rGO papers were successfully prepared via hydrothermal method followed by vacuum filtration as a high-performance cathode for SIBs. The as-prepared NaxV2O5/rGO combined flexibility and high conductivity that can buffer stress and facilitate the fast transportation of electrons during the charge-discharge process. As a result, the as-prepared NaxV2O5-rGO paper can exhibit a reversible Na-ion storage capacity of ∼197 mA h g−1 at 100 mA g−1 and a good cycling performance with 81% capacity retention for 400 cycles at a high current density of 500 mA g−1, showing great potential in flexible energy storage devices.
Effect of High Myopia and Cataract Surgery on the Correlation Between Diabetic Retinopathy and Chronic Kidney Disease
Authors: Kong Huiqian , Zang Siwen , Hu Yijun , Lin Zhanjie , Liu Baoyi , Zeng Xiaomin , Xiao Yu , Du Zijing , Guanrong Wu , Ren Yun , Fang Ying , Xiaohong Yang , Yu Honghua 
Published: June 2022

PurposeTo investigate the effect of high myopia and cataract surgery on the grading of diabetic retinopathy (DR) and their roles in the correlation between DR and chronic kidney disease (CKD).MethodsA total of 1,063 eyes of 1,063 diabetic patients were enrolled. We conducted binary and multiple multivariate regressions to analyze the ocular and systemic risk factors of DR. Based on the presence of myopia and history of cataract surgery, we divided the cases into four subgroups, namely those with high myopia, with the history of cataract surgery, with both conditions, and with neither, then determined the correlation between the stages of DR and CKD in each subgroup.ResultsIn the binary analysis, high myopia was identified as the protective factor for DR odds ratio (OR): 0.312 [95% confidence interval (CI): 0.195–0.500, p &lt; 0.001], whereas cataract surgery was one of the independent risk factors for DR [OR: 2.818 (95% CI: 1.507–5.273), p = 0.001]. With increased stages of DR, high myopia played an increasingly protective role [mild non-proliferative DR (NPDR), OR = 0.461, p = 0.004; moderate NPDR OR = 0.217, p = 0.003; severe NPDR, OR = 0.221, p = 0.008; proliferative DR (PDR), OR = 0.125, p = 0.001], whereas cataract surgery became a stronger risk factor, especially in PDR (mild NPDR, OR = 1.595, p = 0.259; moderate NPDR, OR = 3.955, p = 0.005; severe NPDR, OR = 6.836, p &lt; 0.001; PDR, OR = 9.756, p &lt; 0.001). The correlation between the stages of DR and CKD in the group with neither high myopia nor cataract surgery history was the highest among all subgroups.ConclusionHigh myopia was a protective factor, whereas cataract surgery is a risk factor for DR, and both factors showed stronger effects throughout the (natural disease) grading of DR. The stages of DR and CKD showed a higher correlation after adjustment of the ocular confounding factors.
Beyond QuantiFERON-TB Results, the Added Value of a Weak Mitogen Response
Authors: Jacquier Marine , Binquet Christine , Manoha Catherine , Audia Sylvain , Simonet-Lamm Anne-Laure , Casenaz Alice , Sow Amadou-Khalilou , Piroth Lionel , Blot Mathieu 
Published: June 2022

IntroductionWhile QuantiFERON-TB gold (QFT) is frequently used, little attention is paid to the mitogen response. How it could be impacted and associated with outcomes is poorly known.MethodsRetrospective, case-control study in hospitalized patients who underwent QFT testing in two hospitals between 2016 and 2019. We defined two groups of cases with either negative [interferon (IFN)-γ ≤ 0.5 IU/ml, official threshold] or weak (0.5–2 IU/ml) mitogen response, and one group of controls with normal (&gt;2 IU/ml) mitogen response.ResultsA total of 872 patients were included. An ongoing infection was independently associated with both a negative (RR = 4.34; 95% CI = 2.94–6.41) and a weak mitogen response (RR = 2.44; 95% CI = 1.66–3.58). Among tuberculosis patients, a weak mitogen response was associated with a false-negative QFT result (75%) compared to a normal response (20%). Decreasing mitogen response (normal, weak and negative, respectively) was associated with increasing length of hospital stay [median (interquartile range) 5 (3–13), 11 (5–21) and 15 (10–30) days; p &lt; 0.001] and increasing hospital mortality (3, 7, and 15%; p &lt; 0.001).ConclusionClinicians should take notice of the mitogen response since IFN-γ concentrations lower than &lt;2 IU/ml were associated with false-negative QFT results in tuberculosis patients, independently associated with ongoing infections, and could be associated with worse prognosis.
Tuberculous Thoracic Aortic Pseudoaneurysm Associated With Spinal Tuberculosis: A Case Report and Literature Review
Authors: Chen Yurou , Sheng Bo , Li Jia , Lv Furong 
Published: June 2022

BackgroundThoracic aortic pseudoaneurysm associated with spinal tuberculosis is a rare but fatal condition. The risk of pseudoaneurysm rupture is extremely high and this disease needs greater awareness. The present study reported a case of thoracic aortic pseudoaneurysm caused by paravertebral cold abscess with spinal tuberculosis.Case presentationA 35-year-old woman with back pain was diagnosed with thoracic aortic pseudoaneurysm with spinal tuberculosis, and endovascular aneurysm repair (EVAR) was performed. The patient's symptoms disappeared after EVAR, following which she was discharged.ConclusionsThe case highlighted that in cases where non-enhanced computed tomography (CT) revealed that the aortic vessel was surrounded by a paravertebral abscess, magnetic resonance imaging (MRI) should be performed to confirm whether the presence of a pseudoaneurysm. Upon diagnosis of pseudoaneurysm, surgery should be performed immediately. In recent times, EVAR has emerged as a promising alternative to open surgery.
Structural Characterization of Mycobacterium abscessus Phosphopantetheine Adenylyl Transferase Ligand Interactions: Implications for Fragment-Based Drug Design
Authors: Thomas Sherine E. , McCarthy William J. , El Bakali Jamal , Brown Karen P. , Kim So Yeon , Blaszczyk Michal , Mendes Vítor , Abell Chris , Floto R. Andres , Coyne Anthony G. , Blundell Tom L. 
Published: June 2022

Anti-microbial resistance is a rising global healthcare concern that needs urgent attention as growing number of infections become difficult to treat with the currently available antibiotics. This is particularly true for mycobacterial infections like tuberculosis and leprosy and those with emerging opportunistic pathogens such as Mycobacterium abscessus, where multi-drug resistance leads to increased healthcare cost and mortality. M. abscessus is a highly drug-resistant non-tuberculous mycobacterium which causes life-threatening infections in people with chronic lung conditions such as cystic fibrosis. In this study, we explore M. abscessus phosphopantetheine adenylyl transferase (PPAT), an enzyme involved in the biosynthesis of Coenzyme A, as a target for the development of new antibiotics. We provide structural insights into substrate and feedback inhibitor binding modes of M. abscessus PPAT, thereby setting the basis for further chemical exploration of the enzyme. We then utilize a multi-dimensional fragment screening approach involving biophysical and structural analysis, followed by evaluation of compounds from a previous fragment-based drug discovery campaign against M. tuberculosis PPAT ortholog. This allowed the identification of an early-stage lead molecule exhibiting low micro molar affinity against M. abscessus PPAT (Kd 3.2 ± 0.8 µM) and potential new ways to design inhibitors against this enzyme. The resulting crystal structures reveal striking conformational changes and closure of solvent channel of M. abscessus PPAT hexamer providing novel strategies of inhibition. The study thus validates the ligandability of M. abscessus PPAT as an antibiotic target and identifies crucial starting points for structure-guided drug discovery against this bacterium.
Comparison of Electroencephalography in Patients With Seizures Caused by Neurosyphilis and Viral Encephalitis
Authors: Zheng Li-Li , Chen Jing-Zhen , Zhuang Xiao-Rong , Miao Jia-Yin 
Published: June 2022

BackgroundNeurosyphilis (NS) lacks specificity in clinical and imaging features, and patients are frequently misdiagnosed as viral encephalitis when they present with seizures. This study aimed to compare electroencephalography (EEG) in patients with seizures resulting from the two diseases and provide guidance for differential diagnosis.MethodsA retrospective study on patients diagnosed with neurosyphilis and viral encephalitis with seizures in the Department of Neurology, Zhongshan Hospital, Xiamen University from 2012 to 2020.ResultsA total of 39 patients with seizures caused by neurosyphilis and 40 patients with seizures caused by viral encephalitis were included. Chi-square test analysis showed that compared with patients with viral encephalitis, patients with neurosyphilis mainly developed in middle-aged and elderly people (p &lt; 0.001), were more likely to have temporal epileptiform discharges (p &lt; 0.001), and less likely to have status epilepticus (SE) (p = 0.029). There was difference between two groups in the EEG performance of lateralized periodic discharges (LPDs) (p = 0.085). The two groups were matched for age and sex by case-control matching, and 25 cases in each group were successfully matched. Patients with neurosyphilis were more likely to have temporal epileptiform discharges than those with viral encephalitis (p = 0.002), and there were no significant differences in LPDs (p = 0.077) and SE (p = 0.088) between two groups.ConclusionWhen EEG shows temporal epileptiform discharges, especially in the form of LPDs, we should consider the possibility of neurosyphilis.
Increased Magnetic Susceptibility in the Deep Gray Matter Nuclei of Wilson's Disease: Have We Been Ignoring Atrophy?
Authors: Jing Xiao-Zhong , Yuan Xiang-Zhen , Li Gai-Ying , Chen Jia-Lin , Wu Rong , Yang Ling-Li , Zhang Shu-Yun , Wang Xiao-Ping , Li Jian-Qi 
Published: June 2022

BackgroundHistopathological studies in Wilson's disease (WD) have revealed increased copper and iron concentrations in the deep gray matter nuclei. However, the commonly used mean bulk susceptibility only reflects the regional metal concentration rather than the total metal content, and regional atrophy may affect the assessment of mean bulk susceptibility. Our study aimed to quantitatively assess the changes of metal concentration and total metal content in deep gray matter nuclei by quantitative susceptibility mapping to distinguish patients with neurological and hepatic WD from healthy controls.MethodsQuantitative susceptibility maps were obtained from 20 patients with neurological WD, 10 patients with hepatic WD, and 25 healthy controls on a 3T magnetic resonance imaging system. Mean bulk susceptibility, volumes, and total susceptibility of deep gray matter nuclei in different groups were compared using a linear regression model. The area under the curve (AUC) was calculated by receiver characteristic curve to analyze the diagnostic capability of mean bulk susceptibility and total susceptibility.ResultsMean bulk susceptibility and total susceptibility of multiple deep gray matter nuclei in patients with WD were higher than those in healthy controls. Compared with patients with hepatic WD, patients with neurological WD had higher mean bulk susceptibility but similar total susceptibility in the head of the caudate nuclei, globus pallidus, and putamen. Mean bulk susceptibility of putamen demonstrated the best diagnostic capability for patients with neurological WD, the AUC was 1, and the sensitivity and specificity were all equal to 1. Total susceptibility of pontine tegmentum was most significant for the diagnosis of patients with hepatic WD, the AUC was 0.848, and the sensitivity and specificity were 0.7 and 0.96, respectively.ConclusionBrain atrophy may affect the assessment of mean bulk susceptibility in the deep gray matter nuclei of patients with WD, and total susceptibility should be an additional metric for total metal content assessment. Mean bulk susceptibility and total susceptibility of deep gray matter nuclei may be helpful for the early diagnosis of WD.
Study Protocol of tDCS Based Pain Modulation in Head and Neck Cancer Patients Under Chemoradiation Therapy Condition: An fNIRS-EEG Study
Authors: de Souza Moura Brenda , Hu Xiao-Su , DosSantos Marcos F. , DaSilva Alexandre F. 
Published: June 2022

BackgroundMultiple therapeutic strategies have been adopted to reduce pain, odynophagia, and oral mucositis in head and neck cancer patients. Among them, transcranial direct current stimulation (tDCS) represents a unique analgesic modality. However, the details of tDCS mechanisms in pain treatment are still unclear.Aims(1) to study the analgesic effects of a protocol that encompassed supervised-remote and in-clinic tDCS sessions applied in head and neck patients undergoing chemoradiation therapy; (2) to explore the underlining brain mechanisms of such modulation process, using a novel protocol that combined functional near-infrared spectroscopy (fNIRS), and electroencephalograph (EEG), two distinct neuroimaging methods that bring information regarding changes in the hemodynamic as well as in the electrical activity of the brain, respectively.MethodsThis proof-of-concept study was performed on two subjects. The study protocol included a 7-week-long tDCS stimulation procedure, a pre-tDCS baseline session, and two post-tDCS follow-up sessions. Two types of tDCS devices were used. One was used in the clinical setting and the other remotely. Brain imaging was obtained in weeks 1, 2, 5, 7, 8, and after 1 month.ResultsThe protocol implemented was safe and reliable. Preliminary results of the fNIRS analysis in weeks 2 and 7 showed a decrease in functional connections between the bilateral prefrontal cortex (PFC) and the primary sensory cortex (S1) (p &lt; 0.05, FDR corrected). Changes in EEG power spectra were found in the PFC when comparing the seventh with the first week of tDCS.ConclusionThe protocol combining remote and in-clinic administered tDCS and integrated fNIRS and EEG to evaluate the brain activity is feasible. The preliminary results suggest that the mechanisms of tDCS in reducing the pain of head and neck cancer patients may be related to its effects on the connections between the S1 and the PFC.