bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct Radiotherapy-Induced Effects on Dental Hard Tissue in Combination With Bleaching Procedure
Authors: Klarić Sever Eva , Tarle Andro , Soče Majana , Grego Timor
Published: September 2021

Introduction: The aim of this study was to evaluate the effects of radiation and tooth bleaching on the physical and morphological properties of enamel and dentin on permanent teeth.

Materials and Methods: Eighty fresh, non-carious third molars were used in this study. Before cutting the crown in half, the teeth samples were randomly allocated to treatment and control groups by using a lottery method. The first group (n = 20) underwent standard radiation protocol (2 Gy/fraction/day, 5 days/week) with bleaching treatment afterward using 16% carbamide peroxide gel, the second group (n = 20) underwent standard radiation protocol with afterward bleaching treatment using 38% hydrogen peroxide, the third group (n = 20) underwent a short, one strong, experimental dose of 70 Gy with afterward bleaching treatment using 16% carbamide peroxide gel, and the fourth group (n = 20) underwent one strong, experimental dose of 70 Gy with afterward bleaching treatment using 38% hydrogen peroxide gel. Groups 5–8 (n = 20) served as control as they underwent only bleaching treatment. Vickers microhardness and surface roughness were performed before (initial) and after irradiation and before bleaching or after only bleaching. The effects of irradiation and bleaching on microhardness (or roughness) of enamel and dentin were analyzed in the repeated-measures ANOVA model.

Results: Enamel microhardness after experimental single 70-Gy irradiation or after standard radiation protocol and bleaching with 16 or 38% gel was not statistically significant from microhardness in the control group (p > 0.05). There was a statistically significantly greater reduction in the average microhardness of enamel and dentin during bleaching with 38% gel compared to 16% for both radiation protocols (p < 0.001). After experimental 70-Gy irradiation and bleaching, a 16% statistically significant increase in surface roughness was found for enamel (p = 0.006) and dentin (p = 0.018), while this was not recorded for 38% gel. There was a statistically significantly greater increase in the average roughness of enamel and dentin during bleaching with 38% gel compared to 16% (p < 0.001) for both radiation protocols.

Conclusions: Directly induced radiation leads to potential damage of hard dental tissues, which can be further damaged by additional bleaching. If teeth whitening is necessary after irradiation, it is suggested to use lower concentrations of whitening gels.
Review of Electrical Resistivity Measurements and Calculations of Fe and Fe-Alloys Relating to Planetary Cores
Authors: Berrada Meryem , Secco Richard A.
Published: September 2021

There is a considerable amount of literature on the electrical resistivity of iron at Earth’s core conditions, while only few studies have considered iron and iron-alloys at other planetary core conditions. Much of the total work has been carried out in the past decade and a review to collect data is timely. High pressures and temperatures can be achieved with direct measurements using a diamond-anvil cell, a multi-anvil press or shock compression methods. The results of direct measurements can be used in combination with first-principle calculations to extrapolate from laboratory temperature and pressure to the relevant planetary conditions. This review points out some discrepancies in the electrical resistivity values between theoretical and experimental studies, while highlighting the negligible differences arising from the selection of pressure and temperature values at planetary core conditions. Also, conversions of the reported electrical resistivity values to thermal conductivity via the Wiedemann-Franz law do not seem to vary significantly even when the Sommerfeld value of the Lorenz number is used in the conversion. A comparison of the rich literature of electrical resistivity values of pure Fe at Earth’s core-mantle boundary and inner-core boundary conditions with alloys of Fe and light elements (Si, S, O) does not reveal dramatic differences. The scarce literature on the electrical resistivity at the lunar core suggests the effect of P on a wt% basis is negligible when compared to that of Si and S. On the contrary, studies at Mercury’s core conditions suggest two distinct groups of electrical resistivity values but only a few studies apply to the inner-core boundary. The electrical resistivity values at the Martian core-mantle boundary conditions suggest a negligible contribution of Si, S and O. In contrast, Fe-S compositions at Ganymede’s core-mantle boundary conditions result in large deviations in electrical resistivity values compared to pure Fe. Contour maps of the reported values illustrate ρ(P, T) for pure Fe and its alloys with Ni, O and Si/S and allow for estimates of electrical resistivity at the core-mantle boundary and inner-core boundary conditions for the cores of terrestrial-like planetary bodies.
Effects of Whole SST Anomaly in the Tropical Indian Ocean on Summer rainfall Over Central Asia
Authors: Meng Lixia , Zhao Yong , Li Mingang
Published: September 2021

The effects of sea surface temperature (SST) anomaly in the tropical Indian Ocean (IO) on summer rainfall over central Asia (CA) are investigated using NCEP/NCAR reanalysis circulation data, Hadley Centre SST data, and GPCC gridded precipitation data for 1971–2016. Results show that the SST anomalies over the whole tropical IO play important roles in modulating summer rainfall over southeast CA via the subtropical westerly jet. When the SSTs in the tropical IO are in positive phases, the south Asian monsoon is weakened, which reduces summer rainfall in the Indian monsoon regions corresponding to less release of latent heat. There is an anomalous anticyclone over the Indian Peninsula and an anomalous cyclone in the upper troposphere over CA, corresponding to a shift of the subtropical westerly jet farther south over CA. The southward shift of westerly jet would be responded to anomalous cyclone at 500 hPa over CA and water vapor transported into CA through two steps from the Arabian Sea, above both contribute to more summer rainfall over CA.
Principals’ Leadership of Mathematics Teachers’ Professional Development
Authors: Braseth Eskil Ahn
Published: September 2021

Leadership has long been recognized for having a significant impact on teacher learning. While research on development programs for mathematics teachers has suggested a change in focus from teachers being passive participants to becoming active learners in practice-based development programs, little is said about how this change in focus affects the principals’ role as leaders of teachers’ professional development (PD). In response to this, the presented study investigates how a Norwegian school management team facilitates and supports its mathematics teacher’s PD in their first year of participation in a particular practice-based development program. Findings from the study show that supporting teachers’ PD is easier said than done. The study highlights the importance of building teachers’ sense of ownership and having a shared overarching goal for participating in a practice-based development program. Moreover, there must be a structure and a practice for development work at school if a plan for development in practice is to be successfully implemented and fulfill teachers’ need for continuous development support. Based on the findings from this study and the use of cultural historical activity theory (CHAT) and the activity system, the article suggests that at least two prerequisites must be present for practice-based development programs to serve as mediating artifacts for teachers’ PD. First, the roles involved in the development work must be defined so that the work or goal-directed actions divided between the people in the shared community act towards the same object. Second, the school leader needs support in his work as a leader of teachers’ PD.
Flash Pyrolysis Kinetics of Extracted Lignocellulosic Biomass Components
Authors: Pielsticker Stefan , Gövert Benjamin , Umeki Kentaro , Kneer Reinhold
Published: September 2021

Biomass is a complex material mainly composed of the three lignocellulosic components: cellulose, hemicellulose and lignin. The different molecular structures of the individual components result in various decomposition mechanisms during the pyrolysis process. To understand the underlying reactions in more detail, the individual components can be extracted from the biomass and can then be investigated separately. In this work, the pyrolysis kinetics of extracted and purified cellulose, hemicellulose and lignin are examined experimentally in a small-scale fluidized bed reactor (FBR) under N2 pyrolysis conditions. The FBR provides high particle heating rates (approx. 104 K/s) at medium temperatures (573–973 K) with unlimited reaction time and thus complements typically used thermogravimetric analyzers (TGA, low heating rate) and drop tube reactors (high temperature and heating rate). Based on the time-dependent gas concentrations of 22 species, the release rates of these species as well as the overall rate of volatiles released are calculated. A single first-order (SFOR) reaction model and a 2-step model combined with Arrhenius kinetics are calibrated for all three components individually. Considering FBR and additional TGA experiments, different reaction regimes with different activation energies could be identified. By using dimensionless pyrolysis numbers, limits due to reaction kinetics and heat transfer could be determined. The evaluation of the overall model performance revealed model predictions within the ±2σ standard deviation band for cellulose and hemicellulose. For lignin, only the 2-step model gave satisfying results. Modifications to the SFOR model (yield restriction to primary pyrolysis peak or the assumption of distributed reactivity) were found to be promising approaches for the description of flash pyrolysis behavior, which will be further investigated in the future.
Long-Term Changes in the Abundance of Benthic Foraging Birds in a Restored Wetland
Authors: Mander Lucas , Scapin Luca , Thaxter Chris B. , Forster Rodney M. , Burton Niall H. K.
Published: September 2021

Estuaries have historically been subject to considerable habitat loss, and continue to be subjected to such in areas where the natural landward migration of intertidal habitats is constrained by hard coastal defences. Thus, in estuaries where direct (e.g., port development) or indirect (e.g., sea level rise) processes are predicted to threaten intertidal habitats and associated waterbird species, there is a regulatory requirement to produce compensatory intertidal habitats. Managed realignment (MR) is a shoreline management practise that is undertaken to build sustainable coastal defences and create intertidal habitats in estuaries. This nature-based solution brings multiple benefits in the form of carbon storage, increased resilience to flooding, and, potentially, the formation of new habitats, which is the topic of this study. A 75-ha site at the Paull Holme Strays (Humber Estuary, United Kingdom) was monitored over a 10-year period following MR to examine the change in the abundance of waterbirds in the chosen site in response to the physical processes occurring there. Using digital terrain models (DTMs) collected via light detection and ranging (LiDAR), we examined how four compensatory target species responded to changes in elevation after the creation of the site. It was shown that the very rapid accretion of estuarine sediment occurred in the first decade of the new re-created intertidal, which, over time, led to changes in the numbers of benthic foraging birds supported. Furthermore, elevation change was also driven by this sediment accretion, the rate of which depended on the initial bed elevation of the sectors within the site. Ten years after the recreation of the habitat, the spatial heterogeneity in the bed elevation remained high; however, the sectors with the lowest elevations accreted the most over the 10-year period. The foraging number of the four waterbird species that colonised the MR site significantly declined above a certain elevation, with this effect being most pronounced for the Eurasian curlew (Numenius arquata). The number of common shelducks (Tadorna tadorna), dunlins (Calidris alpina), and common redshanks (Tringa totanus) declined significantly after initial peaks 5–7 years after the creation of the site, reflecting the ongoing elevation changes. Thus, this study highlighted the need for long-term studies to understand how species respond to large-scale habitat construction. It can also aid in predicting the suitability of an MR site for waterbirds in the medium and long term.
Data Management and Sharing for Collaborative Science: Lessons Learnt From the Euromammals Initiative
Authors: Urbano Ferdinando , Cagnacci Francesca ,   Euromammals Collaborative Initiative
Published: September 2021

The current and future consequences of anthropogenic impacts such as climate change and habitat loss on ecosystems will be better understood and therefore addressed if diverse ecological data from multiple environmental contexts are more effectively shared. Re-use requires that data are readily available to the scientific scrutiny of the research community. A number of repositories to store shared data have emerged in different ecological domains and developments are underway to define common data and metadata standards. Nevertheless, the goal is far from being achieved and many challenges still need to be addressed. The definition of best practices for data sharing and re-use can benefit from the experience accumulated by pilot collaborative projects. The Euromammals bottom-up initiative has pioneered collaborative science in spatial animal ecology since 2007. It involves more than 150 institutes to address scientific, management and conservation questions regarding terrestrial mammal species in Europe using data stored in a shared database. In this manuscript we present some key lessons that we have learnt from the process of making shared data and knowledge accessible to researchers and we stress the importance of data management for data quality assurance. We suggest putting in place a pro-active data review before data are made available in shared repositories via robust technical support and users’ training in data management and standards. We recommend pursuing the definition of common data collection protocols, data and metadata standards, and shared vocabularies with direct involvement of the community to boost their implementation. We stress the importance of knowledge sharing, in addition to data sharing. We show the crucial relevance of collaborative networking with pro-active involvement of data providers in all stages of the scientific process. Our main message is that for data-sharing collaborative efforts to obtain substantial and durable scientific returns, the goals should not only consist in the creation of e-infrastructures and software tools but primarily in the establishment of a network and community trust. This requires moderate investment, but over long-term horizons.
Effect of MAP3K8 on Prognosis and Tumor-Related Inflammation in Renal Clear Cell Carcinoma
Authors: Hao Jiatao , Cao Yumeng , Yu Hui , Zong Lu , An Ruifang , Xue Yan
Published: September 2021

Background: MAPK kinase kinase 8 (MAP3K8) is involved in the regulation of MAPK cascades and immune responses. Differential expression of MAP3K8 is closely correlated with tumorigenesis. In this study, we used bioinformatics tools to explore expression level, prognostic values, and interactive networks of MAP3K8 in renal clear cell carcinoma (ccRCC).

Methods: Differential expression of MAP3K8 was determined by TIMER2.0, UALCAN, and Oncomine Platform. For exploration of MAP3K8 mutation profile, TIMER2.0, DriverDBv3, and cBioPortal were used. The survival module of GEPIA, UALCAN, and DriverDBv3 was used to examine the prognostic value of MAP3K8. Immune infiltration was estimated by TIMER, TIDE, CIBERSORT, CIBERSORT-ABS, QUANTISEQ, XCELL, MCPCOUNTER, and EPIC algorithms. PPI networks and functional enrichment analysis were constructed using GeneMANIA, Cytoscape, and Metascape. The co-expression module in cBioPortal was used to find genes that are correlated with MAP3K8 in mRNA expression.

Results: Compared to normal renal samples, ccRCC (3.08-fold change, P = 1.50E-7; 1.10-fold change, P = 3.00E-3), papillary RCC (2.24-fold change, P = 1.86E-4), and hereditary ccRCC (1.98-fold change, P = 1.69E-9) have significantly higher levels of MAP3K8 expression. Compared to Grade 1 ccRCC samples, Grade 2 (P = 1.28E-3) and Grade 3 (P = 7.41E-4) cases have higher levels of MAP3K8 methylation. Percentage of patients harboring MAP3K8 mutation is 0.3% from TIMER2.0 and 0.2 to 11.5% from cBioPortal. High levels of MAP3K8 expression were associated with poorer overall survival (OS) in ccRCC (GEPIA: Log-rank P = 0.60E-2, HR = 1.5; DriverDBv3: Log-rank P = 1.68E-7, HR = 2.21; UALCAN: P = 0.20E-2). MAP3K8 was positively correlated with the presence of T cell regulatory (Tregs) (QUANTISEQ: Rho = 0.33, P = 1.59E-13). PPI network and functional enrichment analyses revealed that MAP3K8 correlated with NFKBIZ, MIAT, PARP15, CHFR, MKNK1, and ERMN, which was mainly involved in I-kappaB kinase/NF-kappaB and toll-like receptor signaling pathways.

Conclusion: MAP3K8 overexpression was correlated with damaged survival in ccRC and may play a crucial role in cancer-related inflammation via I-kappaB kinase/NF-kappaB and toll-like receptor signaling pathways.
Hepatitis B Vaccine Non-Responders Show Higher Frequencies of CD24highCD38high Regulatory B Cells and Lower Levels of IL-10 Expression Compared to Responders
Authors: Körber Nina , Pohl Laureen , Weinberger Birgit , Grubeck-Loebenstein Beatrix , Wawer Andrea , Knolle Percy A. , Roggendorf Hedwig , Protzer Ulrike , Bauer Tanja
Published: September 2021

Background

The cellular mechanisms involved in the lack of protective antibody response after hepatitis B vaccination are still rather unclear. Regulatory B cells (Breg) known as modulators of B-and T-cell responses may contribute to poor vaccine responsiveness. The current study aimed to investigate the role of regulatory B cells (Breg) in hepatitis B vaccine non-responsiveness after immunization with second- or third-generation hepatitis B vaccines.

Method

We performed comparative phenotypic and frequency analysis of Breg subsets (CD24+CD27+ and CD24highCD38high Breg) in second-generation hepatitis B vaccine non-responders (2nd HBvac NR, n = 11) and responders (2nd HBvac R, n = 8) before (d0), on day 7 (d7), and 28 (d28) after booster vaccination. Cryopreserved peripheral blood mononuclear cells were stimulated ex vivo with a combination of CpG, PMA, and Ionomycin (CpG+P/I) and analyzed for numbers and IL-10 expression levels of Breg by flow cytometry-based analyses.

Results

Flow cytometry-based analyses revealed elevated frequencies of CD24+CD27+ Breg at all time points and significantly higher frequencies of CD24highCD38high Breg on d0 (p = 0.004) and 28 (p = 0.012) in 2nd HBvac NR compared to 2nd HBvac R. In parallel, we observed significantly lower levels of CpG+P/I-induced IL-10 expression levels of CD24+CD27+ and CD24highCD38high Breg (d0: p < 0.0001; d7: p = 0.0004; d28: p = 0.0003 and d0: p = 0.016; d7: p = 0.016, respectively) in 2nd HBvac NR compared to 2nd HBvac R before and after booster immunization.

Frequencies of CD24+CD27+ and CD24highCD38high Breg significantly decreased after third-generation hepatitis B booster vaccination (d7: p = 0.014; d28: p = 0.032 and d7: p = 0.045, respectively), whereas IL-10 expression levels of both Breg subsets remained stable.

Conclusion

Here we report significantly higher frequencies of CD24highCD38high Breg in parallel with significantly lower IL-10 expression levels of CD24+CD27+ and CD24highCD38high Breg in 2nd HBvac NR compared to 2nd HBvac R. Anti-HBs seroconversion accompanied by a decrease of Breg numbers after booster immunization with a third-generation hepatitis B vaccine could indicate a positive effect of third-generation hepatitis B vaccines on Breg-mediated immunomodulation in hepatitis B vaccine non-responders.
Evaluation of the Diagnostic Value of Non-criteria Antibodies for Antiphospholipid Syndrome Patients in a Chinese Cohort
Authors: Hu Chaojun , Li Siting , Xie Zhijuan , You Hanxiao , Jiang Hui , Shi Yu , Qi Wanting , Zhao Jiuliang , Wang Qian , Tian Xinping , Li Mengtao , Zhao Yan , Zeng Xiaofeng
Published: September 2021

Objective

Although specific anti-phospholipid antibodies (aPLs) have been used in the diagnosis of the antiphospholipid syndrome (APS) for years, new biomarkers are required to increase its diagnostic and risk-predictive power. This study aimed to explore the value of several non-criteria aPLs in a Chinese cohort.

Methods

A total of 312 subjects, namely, 100 patients diagnosed with primary APS, 51 with APS secondary to SLE, 71 with SLE, and 90 healthy controls, were recruited. Serum anticardiolipin (aCL) IgG/IgM/IgA, anti-β2-glycoprotein I (aβ2GPI) IgG/IgM/IgA, anti-phosphatidylserine/prothrombin antibodies (aPS/PT) IgG/IgM, and anti-annexin A5 antibodies (aAnxV) IgG/IgM were tested using ELISA kits.

Results

Of the total number of patients, 30.46% and 6.62% with APS were positive for aCL or aβ2GPI IgA, respectively, while 39.07% and 24.50% were positive for aAnxV or aPS/PT for at least one antibody (IgG or IgM). The addition test of aCL IgA and aAnxV IgM assists in identifying seronegative APS patients, and IgG aPS/PT was linked to stroke.

Conclusion

Detection of aCL IgA, aβ2GPI IgA, aAnxV IgG/M, and aPS/PT IgG/M as a biomarker provides additive value in APS diagnosis and would help in risk prediction for APS patients in medical practice.
Complement Alternative and Mannose-Binding Lectin Pathway Activation Is Associated With COVID-19 Mortality
Authors: Defendi Federica , Leroy Corentin , Epaulard Olivier , Clavarino Giovanna , Vilotitch Antoine , Le Marechal Marion , Jacob Marie-Christine , Raskovalova Tatiana , Pernollet Martine , Le Gouellec Audrey , Bosson Jean-Luc , Poignard Pascal , Roustit Matthieu , Thielens Nicole , Dumestre-Pérard Chantal , Cesbron Jean-Yves
Published: September 2021

Background

The SARS-CoV-2 infection triggers excessive immune response resulting in increased levels of pro-inflammatory cytokines, endothelial injury, and intravascular coagulopathy. The complement system (CS) activation participates to this hyperinflammatory response. However, it is still unclear which activation pathways (classical, alternative, or lectin pathway) pilots the effector mechanisms that contribute to critical illness. To better understand the immune correlates of disease severity, we performed an analysis of CS activation pathways and components in samples collected from COVID-19 patients hospitalized in Grenoble Alpes University Hospital between 1 and 30 April 2020 and of their relationship with the clinical outcomes.

Methods

We conducted a retrospective, single-center study cohort in 74 hospitalized patients with RT-PCR-proven COVID-19. The functional activities of classical, alternative, and mannose-binding lectin (MBL) pathways and the antigenic levels of the individual components C1q, C4, C3, C5, Factor B, and MBL were measured in patients’ samples during hospital admission. Hierarchical clustering with the Ward method was performed in order to identify clusters of patients with similar characteristics of complement markers. Age was included in the model. Then, the clusters were compared with the patient clinical features: rate of intensive care unit (ICU) admission, corticoid treatment, oxygen requirement, and mortality.

Results

Four clusters were identified according to complement parameters. Among them, two clusters revealed remarkable profiles: in one cluster (n = 15), patients exhibited activation of alternative and lectin pathways and low antigenic levels of MBL, C4, C3, Factor B, and C5 compared to all the other clusters; this cluster had the higher proportion of patients who died (27%) and required oxygen support (80%) or ICU care (53%). In contrast, the second cluster (n = 19) presented inflammatory profile with high classical pathway activity and antigenic levels of complement components; a low proportion of patients required ICU care (26%) and no patient died in this group.

Conclusion

These findings argue in favor of prominent activation of the alternative and MBL complement pathways in severe COVID-19, but the spectrum of complement involvement seems to be heterogeneous requiring larger studies.
Transcriptional Responses of Flavin-Containing Monooxygenase Genes in Scallops Exposed to PST-Producing Dinoflagellates Implying Their Involvements in Detoxification
Authors: Kong Lingling , Liu Pingping , Li Moli , Wang Huizhen , Shi Jiaoxia , Hu Jingjie , Li Yueru , Hu Xiaoli
Published: September 2021

Flavin-containing monooxygenase (FMO) is one of the most prominent xenobiotic metabolic enzymes. It can catalyze the conversion of heteroatom-containing chemicals to polar, readily excretable metabolites and is considered an efficient detoxification system for xenobiotics. Bivalves can accumulate paralytic shellfish toxins (PSTs) produced by dinoflagellates, especially during outbreaks of harmful algal blooms. Exploring FMO genes in bivalves may contribute to a better understanding of the adaptation of these species and the mechanisms of PSTs bioavailability. Therefore, through genome screening, we examined the expansion of FMO genes in two scallops (Patinopecten yessoensis and Chlamys farreri) and found a new subfamily (FMO_like). Our expression analyses revealed that, in both scallops, members of the FMO_N-oxide and FMO_like subfamilies were mainly expressed from the D-stage larvae to juveniles, whereas the FMO_GS-OX subfamily genes were mainly expressed at and prior to the trochophore stage. In adult organs, higher expressions of FMOs were observed in the kidney and hepatopancreas than in other organs. After exposure to PST-producing algae, expression changes in FMOs occurred in hepatopancreas and kidney of both scallops, with more members being up-regulated in hepatopancreas than in kidney for Alexandrium catenella exposure, while more up-regulated FMOs were found in kidney than in hepatopancreas of C. farreri exposed to A. minutum. Our findings suggest the adaptive functional diversity of scallop FMO genes in coping with the toxicity of PST-producing algae.
Asthma Patients Benefit More Than Chronic Obstructive Pulmonary Disease Patients in the Coronavirus Disease 2019 Pandemic
Authors: Xiong Ruoyan , Zhao Zhiqi , Lu Huanhuan , Ma Yiming , Zeng Huihui , Chen Yan
Published: September 2021

Background: Coronavirus disease 2019 (COVID-19) has raised many questions about the role of underlying chronic diseases on disease outcomes. However, there is limited information about the effects of COVID-19 on chronic airway diseases. Therefore, we conducted the present study to investigate the impact of COVID-19 on patients with asthma or chronic obstructive pulmonary disease (COPD) and ascertain risk factors for acute exacerbations (AEs).

Methods: This single-center observational study was conducted at the Second Xiangya Hospital of Central South University, involving asthma or COPD patients who had been treated with inhaled combination corticosteroids (ICSs), such as budesonide, and one long-acting beta-2-agonist (LABA), such as formoterol, for at least a year before the COVID-19 pandemic. We conducted telephone interviews to collect demographic information and clinical data between January 1, 2019, and December 31, 2020, focusing on respiratory and systemic symptoms, as well as times of exacerbations. Data for asthma and COPD were then compared, and the risk factors for AEs were identified using logistic regression analysis.

Results: A total of 251 patients were enrolled, comprising 162 (64.5%) who had asthma and 89 who had COPD, with none having COPD/asthma overlap. Frequency of AEs among asthma patients was significantly lower in 2020 than in 2019 (0.82 ± 3.33 vs. 1.00 ± 3.16; P < 0.05). Moreover, these patients visited the clinic less (0.37 ± 0.93 vs. 0.49 ± 0.94; P < 0.05) and used emergency drugs less (0.01 ± 0.11 vs. 007 ± 0.38; P < 0.05) during the COVID-19 pandemic. In contrast, among COPD patients, there were no significant differences in AE frequency, clinic visits, or emergency drug use. Furthermore, asthma patients visited clinics less frequently during the pandemic than those with COPD. Logistic regression analysis also showed that a history of at least one AE within the last 12 months was associated with increased AE odds for both asthma and COPD during the COVID-19 pandemic (odds ratio: 13.73, 95% CI: 7.04–26.77; P < 0.01).

Conclusion: During the COVID-19 pandemic, patients with asthma showed better disease control than before, whereas patients with COPD may not have benefited from the pandemic. For both diseases, at least one AE within the previous 12 months was a risk factor for AEs during the pandemic. Particularly, among asthma patients, the risk factors for AE during the COVID-19 pandemic were urban environment, smoking, and lower asthma control test scores.
Case Report: Diagnosis of Klebsiella pneumoniae Invasive Liver Abscess Syndrome With Purulent Meningitis in a Patient From Pathogen to Lesions
Authors: Zeng Sheng , Yan Wei-qian , Wu Xiao-mei , Zhang Hai-nan
Published: September 2021

As a determinant human pathogen, Klebsiella pneumoniae is known to cause rare K. pneumoniae liver abscess syndrome (KLAS) which was more common in Asia in early-stage and reported increasingly outside Asia now. Patients with KLAS who have septic metastatic ocular or central nervous system (CNS) lesions are associated with high morbidity and mortality. Relatively infrequent adult community-acquired K. pneumoniae meningitis have been documented and most were with poor prognosis. In this paper, we reported a case of KLAS presenting purulent meningitis as disease onset. While negative results were obtained in the bacterial culture of CSF, blood, or liver pus, metagenomic next-generation sequencing (mNGS) of CSF, and blood samples which were synchronously performed demonstrated Klebsiella pneumoniae as the pathogenic microorganism (13,470 and 5,318 unique reads, respectively). The ultimately cured patient benefited from rapid pathogen diagnosis, early percutaneous drainage of the abscess, and prompt appropriate antibiotic administration. Our case highlights the importance of clinicians using mNGS for early pathogen diagnosis of this disease.
Dnj1 Promotes Virulence in Cryptococcus neoformans by Maintaining Robust Endoplasmic Reticulum Homeostasis Under Temperature Stress
Authors: Horianopoulos Linda C. , Lee Christopher W. J. , Hu Guanggan , Caza Mélissa , Kronstad James W.
Published: September 2021

The capacity of opportunistic fungal pathogens such as Cryptococcus neoformans to cause disease is dependent on their ability to overcome an onslaught of stresses including elevated temperature under mammalian host conditions. Protein chaperones and co-chaperones play key roles in thermotolerance. In this study, we characterized the role of the endoplasmic reticulum (ER) J-domain containing co-chaperone, Dnj1, in the virulence of C. neoformans. A strain expressing a Dnj1-GFP fusion protein was used to confirm localization to the ER, and a dnj1∆ deletion mutant was shown to be hypersensitive to the ER stress caused by tunicamycin (TM) or 4μ8C. Dnj1 and another ER chaperone, calnexin were found to coordinately maintain ER homeostasis and contribute to maintenance of cell wall architecture. Dnj1 also contributed to thermotolerance and increased in abundance at elevated temperatures representative of febrile patients (e.g., 39°C) thus highlighting its role as a temperature-responsive J domain protein. The elaboration of virulence factors such as the polysaccharide capsule and extracellular urease activity were also markedly impaired in the dnj1∆ mutant when induced at human body temperature (i.e., 37°C). These virulence factors are immunomodulatory and, indeed, infection with the dnj1∆ mutant revealed impaired induction of the cytokines IL-6, IL-10, and MCP-1 in the lungs of mice compared to infection with wild type or complemented strains. The dnj1∆ mutant also had attenuated virulence in an intranasal murine model of cryptococcosis. Altogether, our data indicate that Dnj1 is crucial for survival and virulence factor production at elevated temperatures. The characterization of this co-chaperone also highlights the importance of maintaining homeostasis in the ER for the pathogenesis of C. neoformans.
Aberrant DNA Methylation-Mediated FOXF2 Dysregulation Is a Prognostic Risk Factor for Gastric Cancer
Authors: Zhang Cheng , Li Yong-Zhi , Dai Dong-Qiu
Published: September 2021

Background: The prognosis of gastric cancer (GC) patients is poor. The effect of aberrant DNA methylation on FOXF2 expression and the prognostic role of FOXF2 methylation in GC have not yet been identified.

Methods: The RNA-Seq and gene methylation HM450 profile data were used for analyzing FOXF2 expression in GC and its association with methylation level. Bisulfite sequencing PCR (BSP) was performed to measure the methylation level of the FOXF2 promoter region in GC cell lines and normal GES-1 cells. The cells were treated with the demethylation reagent 5-Aza-dC, and the mRNA and protein expression levels of FOXF2 were then measured by qRT-PCR and western blot assays. The risk score system from SurvivalMeth was calculated by integrating the methylation level of the cg locus and the corresponding Cox regression coefficient.

Results: FOXF2 was significantly downregulated in GC cells and tissues. On the basis of RNA-Seq and Illumina methylation 450 data, FOXF2 expression was significantly negatively correlated with the FOXF2 methylation level (Pearson’s R = −0.42, p < 2.2e−16). The FOXF2 methylation level in the high FOXF2 expression group was lower than that in the low FOXF2 expression group. The BSP assay indicated that the methylation level of the FOXF2 promoter region in GC cell lines was higher than that in GES-1 cells. The qRT-PCR and western blot assay showed that FOXF2 mRNA and protein levels were increased in GC cells following treatment with 5-Aza-Dc. The methylation risk score model indicated that patients in the high risk group had poorer survival probability than those in the low risk group (HR = 1.84 (1.11–3.07) and p = 0.0068). FOXF2 also had a close transcriptional regulation network with four miRNAs and their corresponding target genes. Functional enrichment analysis of the target genes revealed that these genes were significantly related to several important signaling pathways.

Conclusion: FOXF2 was downregulated due to aberrant DNA methylation in GC, and the degree of methylation in the promoter region of FOXF2 was related to the prognosis of patients. The FOXF2/miRNAs/target genes axis may play a vital biological regulation role in GC.
Dynamic Functional Connectivity Signifies the Joint Impact of Dance Intervention and Cognitive Reserve
Authors: Mitterová Kristína , Lamoš Martin , Mareček Radek , Pupíková Monika , Šimko Patrik , Grmela Roman , Skotáková Alena , Vaculíková Pavlína , Rektorová Irena
Published: September 2021

Research on dance interventions (DIs) in the elderly has shown promising benefits to physical and cognitive outcomes. The effect of DIs on resting-state functional connectivity (rs-FC) varies, which is possibly due to individual variability. In this study, we assessed the moderation effects of residual cognitive reserve (CR) on DI-induced changes in dynamic rs-FC and their association on cognitive outcomes. Dynamic rs-FC (rs-dFC) and cognitive functions were evaluated in non-demented elderly subjects before and after a 6-month DI (n = 36) and a control group, referred to as the life-as-usual (LAU) group (n = 32). Using linear mixed models and moderation, we examined the interaction effect of DIs and CR on changes in the dwell time and coverage of rs-dFC. Cognitive reserve was calculated as the residual difference between the observed memory performance and the performance predicted by brain state. Partial correlations accounting for CR evaluated the unique association between changes in rs-dFC and cognition in the DI group. In subjects with lower residual CR, we observed DI-induced increases in dwell time [t(58) = –2.14, p = 0.036] and coverage [t(58) = –2.22, p = 0.030] of a rs-dFC state, which was implicated in bottom-up information processing. Increased dwell time was also correlated with a DI-induced improvement in Symbol Search (r = 0.42, p = 0.02). In subjects with higher residual CR, we observed a DI-induced increase in coverage [t(58) = 2.11, p = 0.039] of another rs-dFC state, which was implicated in top-down information processing. The study showed that DIs have a differential and behaviorally relevant effect on dynamic rs-dFC, but these benefits depend on the current CR level.
Integrated Bioinformatics Analysis of Potential mRNA and miRNA Regulatory Networks in Mice With Ischemic Stroke Treated by Electroacupuncture
Authors: Wu Chunxiao , Zhao Lijun , Li Xinrong , Xu Yingshan , Guo Hongji , Huang Zifeng , Wang Qizhang , Liu Helu , Chen Dongfeng , Zhu Meiling
Published: September 2021

Background: The complicated molecular mechanisms underlying the therapeutic effect of electroacupuncture (EA) on ischemic stroke are still unclear. Recently, more evidence has revealed the essential role of the microRNA (miRNA)–mRNA networks in ischemic stroke. However, a systematic analysis of novel key genes, miRNAs, and miRNA–mRNA networks regulated by EA in ischemic stroke is still absent.

Methods: We established a middle cerebral artery occlusion (MCAO) mouse model and performed EA therapy on ischemic stroke mice. Behavior tests and measurement of infarction area were applied to measure the effect of EA treatment. Then, we performed RNA sequencing to analyze differentially expressed genes (DEGs) and functional enrichment between the EA and control groups. In addition, a protein–protein interaction (PPI) network was built, and hub genes were screened by Cytoscape. Upstream miRNAs were predicted by miRTarBase. Then hub genes and predicted miRNAs were verified as key biomarkers by RT-qPCR. Finally, miRNA–mRNA networks were constructed to explore the potential mechanisms of EA in ischemic stroke.

Results: Our analysis revealed that EA treatment could significantly alleviate neurological deficits in the affected limbs and reduce infarct area of the MCAO model mice. A total of 174 significant DEGs, including 53 upregulated genes and 121 downregulated genes, were identified between the EA and control groups. Functional enrichment analysis showed that these DEGs were associated with the FOXO signaling pathway, NF-kappa B signaling pathway, T-cell receptor signaling pathway, and other vital pathways. The top 10 genes with the highest degree scores were identified as hub genes based on the degree method, but only seven genes were verified as key genes according to RT-qPCR. Twelve upstream miRNAs were predicted to target the seven key genes. However, only four miRNAs were significantly upregulated and indicated favorable effects of EA treatment. Finally, comprehensive analysis of the results identified the miR-425-5p-Cdk1, mmu-miR-1186b-Prc1, mmu-miR-434-3p-Prc1, and mmu-miR-453-Prc1 miRNA–mRNA networks as key networks that are regulated by EA and linked to ischemic stroke. These networks might mainly take place in neuronal cells regulated by EA in ischemic stroke.

Conclusion: In summary, our study identified key DEGs, miRNAs, and miRNA–mRNA regulatory networks that may help to facilitate the understanding of the molecular mechanism underlying the effect of EA treatment on ischemic stroke.
Primary Brainstem Hemorrhage: A Review of Prognostic Factors and Surgical Management
Authors: Chen Danyang , Tang Yingxin , Nie Hao , Zhang Ping , Wang Wenzhi , Dong Qiang , Wu Guofeng , Xue Mengzhou , Tang Yuping , Liu Wenjie , Pan Chao , Tang Zhouping
Published: September 2021

Primary brainstem hemorrhage (PBSH) is the most fatal subtype of intracerebral hemorrhage and is invariably associated with poor prognosis. Several prognostic factors are involved, of which the two most predominant and consistent are the initial level of consciousness and hemorrhage size. Other predictors, such as age, hyperthermia, and hydrocephalus, are generally not dependable indicators for making prognoses. Scoring systems have now been developed that can predict mortality and functional outcomes in patients suffering from PBSH, which can thus guide treatment decision-making. A novel grading scale, entitled “the new primary pontine hemorrhage (PPH) score,” represents the latest approach in scoring systems. In this system, patients with a score of 2–3 points appear to benefit from surgical management, although this claim requires further verification. The four main surgical options for the treatment of PBSH are craniotomy, stereotactic hematoma puncture and drainage, endoscopic hematoma removal, and external ventricular drainage. Nevertheless, the management of PBSH still primarily involves conservative treatment methods and surgery is generally not recommended, according to current practice. However, the ongoing clinical trial, entitled Safety and Efficacy of Surgical Treatment in Severe Primary Pontine Hemorrhage Evacuation (STIPE), should provide additional evidence to support the surgical treatment of PBSH. Therefore, we advocate the update of epidemiological data and re-evaluation of PBSH treatment in a contemporary context.
Vibration of the Whole Foot Soles Surface Using an Inexpensive Portable Device to Investigate Age-Related Alterations of Postural Control
Authors: Lauzier Lydiane , Kadri Mohamed Abdelhafid , Bouchard Emilie , Bouchard Kevin , Gaboury Sébastien , Gagnon Jean-Michel , Girard Marie-Pier , Larouche Andréanne , Robert Roxane , Lapointe Patrick , da Silva Rubens A. , Beaulieu Louis-David
Published: September 2021

Background: Standing on a foam surface is used to investigate how aging affect the ability to keep balance when somatosensory inputs from feet soles become unreliable. However, since standing on foam also affects the efficacy of postural adjustments, the respective contributions of sensory and motor components are impossible to separate. This study tested the hypothesis that these components can be untangled by comparing changes of center of pressure (CoP) parameters induced by standing on a foam pad vs. a novel vibration (VIB) platform developed by our team and targeting feet soles’ mechanoreceptors.

Methods: Bipedal postural control of young (n = 20) and healthy elders (n = 20) was assessed while standing barefoot on a force platform through 3 randomized conditions: (1) Baseline (BL); (2) VIB; and (3) Foam. CoP Amplitude and Velocity in the antero-posterior/medio-lateral (AP/ML) directions and COP Surface were compared between conditions and groups.

Findings: Both VIB and Foam increased CoP parameters compared to BL, but Foam had a significantly greater impact than VIB for both groups. Young and Old participants significantly differed for all three Conditions. However, when correcting for BL levels of postural performance, VIB-related increase of COP parameters was no longer different between groups, conversely to Foam.

Interpretation: Although both VIB and Foam highlighted age-related differences of postural control, their combined use revealed that “motor” and “sensory” components are differently affected by aging, the latter being relatively unaltered, at least in healthy/active elders. The combined used of these methods could provide relevant knowledge to better understand and manage postural impairments in the aging population.
Refractory and Super-Refractory Status Epilepticus in Nerve Agent-Poisoned Rats Following Application of Standard Clinical Treatment Guidelines
Authors: Morgan Julia E. , Wilson Sara C. , Travis Benjamin J. , Bagri Kathryn H. , Pagarigan Kathleen T. , Belski Hannah M. , Jackson Cecelia , Bounader Kevin M. , Coppola Jessica M. , Hornung Eden N. , Johnson James E. , McCarren Hilary S.
Published: September 2021

Nerve agents (NAs) induce a severe cholinergic crisis that can lead to status epilepticus (SE). Current guidelines for treatment of NA-induced SE only include prehospital benzodiazepines, which may not fully resolve this life-threatening condition. This study examined the efficacy of general clinical protocols for treatment of SE in the specific context of NA poisoning in adult male rats. Treatment with both intramuscular and intravenous benzodiazepines was entirely insufficient to control SE. Second line intervention with valproate (VPA) initially terminated SE in 35% of rats, but seizures always returned. Phenobarbital (PHB) was more effective, with SE terminating in 56% of rats and 19% of rats remaining seizure-free for at least 24 h. The majority of rats demonstrated refractory SE (RSE) and required treatment with a continuous third-line anesthetic. Both ketamine (KET) and propofol (PRO) led to high levels of mortality, and nearly all rats on these therapies had breakthrough seizure activity, demonstrating super-refractory SE (SRSE). For the small subset of rats in which SE was fully resolved, significant improvements over controls were observed in recovery metrics, behavioral assays, and brain pathology. Together these data suggest that NA-induced SE is particularly severe, but aggressive treatment in the intensive care setting can lead to positive functional outcomes for casualties.
Valproic Acid: A Promising Therapeutic Agent in Glioma Treatment
Authors: Han Wei , Guan Wei
Published: September 2021

Glioma, characterized by infiltrative growth and treatment resistance, is regarded as the most prevalent intracranial malignant tumor. Due to its poor prognosis, accumulating investigation has been performed for improvement of overall survival (OS) and progression-free survival (PFS) in glioma patients. Valproic acid (VPA), one of the most common histone deacetylase inhibitors (HDACIs), has been detected to directly or synergistically exert inhibitory effects on glioma in vitro and in vivo. In this review, we generalize the latest advances of VPA in treating glioma and its underlying mechanisms and clinical implications, providing a clearer profile for clinical application of VPA as a therapeutic agent for glioma.
The Key Gene Expression Patterns and Prognostic Factors in Malignant Transformation from Enchondroma to Chondrosarcoma
Authors: Wu Junqing , Huang Yue , Yu Chengxuan , Li Xia , Wang Limengmeng , Hong Jundong , Lin Daochao , Han Xiaoping , Guo Guoji , Hu Tianye , Huang He
Published: September 2021

Enchondroma (EC) is a common benign bone tumor. It has the risk of malignant transformation to Chondrosarcoma (CS). However, the underlying mechanism is unclear. The gene expression profile of EC and CS was obtained from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified using GEO2R. We conducted the enrichment analysis and constructed the gene interaction network using the DEGs. We found that the epithelial-mesenchymal transition (EMT) and the VEGFA-VEGF2R signaling pathway were more active in CS. The CD8+ T cell immunity was enhanced in CS I. We believed that four genes (MFAP2, GOLM1, STMN1, and HN1) were poor predictors of prognosis, while two genes (CAB39L and GAB2) indicated a good prognosis. We have revealed the mechanism in the tumor progression and identified the key genes that predicted the prognosis. This study provided new ideas for the diagnosis and treatment of EC and CS.