bluuebunny/crossref_metadata_2025 huggingface dataset:
CSR Performance, Firm’s Attributes, and Sustainability Reporting
Authors: Berto Usman
Published: April 2021

This study aims to empirically identify the drivers of sustainability reporting (SR) in Indonesia. Relying on the legitimacy theory, we conjecture that CSR performance and the firm’s attributes are associated with SR. Using the sample from the Indonesian Capital Market (IDX), we run logit regression analysis. Logit regression is performed by employing quarterly data from 37 publicly listed companies, that voluntarily published sustainability reports from the first quarter (Q1) of 2012 to the last quarter (Q4) of 2016 fiscal year. The obtained results show that CSR performance is positively associated with SR. Whilst, firm’s attributes with different surrogate indicators indicate mixed results. Overall, this study provides empirical evidence, in which CSR performance and the firm’s attributes play a pivotal role as the drivers of sustainability reporting.
Earning Management and the Effect Characteristics of Audit Committee, Independent Commissioners: Evidence from Indonesia
Authors: Enny Susilowati Mardjono  , Yahn-Shir Chen
Published: April 2021

This study aimed to investigate the effect of the independent commissioner and of the characteristics of the audit committee (measured by auditor size, independence, expertise, and activities) on the efficient or opportunistic earnings management. In terms of those companies listed on Indonesia Stock Exchange. The sample consists of 186 observations of those manufacturing companies in Indonesia Stock Exchange during the 2013-2018. Using panel regression fixed effect method, independent commissioners are found to have a significant effect on reducing earnings management. Based on The Positive Accounting Theory, the efficient perspective will occur when the compensation contract and internal control system, including monitoring done by the board of commissioners, limit the common view opportunistic manager and motivate the manager to choose the right accounting policy. The effective monitoring conducted by an independent commissioner can reduce agency costs because management prioritizes the best interests of shareholders by maximizing company resources. Furthermore, it was found that audit committee size can reduce earning management. It is due to the wide range of skills possessed by audit committee members to exercise oversight over management. Audit committees with accounting and financial expertise can reduce earnings management. This part of finding indicates that audit committee may tend to uphold conservative as accounting mechanism. Accounting conservatism has an important role to play in restricting opportunistic management behavior.
Impact of Covid-19: Evidence from Malaysian Stock Market
Authors: Kelvin Yong-Ming Lee  , Mohamad Jais  , Chia-Wen Chan
Published: April 2021

Since the first case was reported at the end of 2019, COVID-19 has spread throughout the world resulting in more than 2 million confirmed cases. The World Health Organization (WHO) also declared the COVID-19 disease as pandemic on 11 March 2020. The COVID-19 pandemic has also affected the global financial market, which includes Malaysia. This study aims to investigate the impact of the COVID-19 outbreak on the Malaysian stock market. The dependent variables used in this study were the Kuala Lumpur Composite Index (KLCI) and 13 other sectorial indices. The independent variables were (i) the number of COVID-19 cases in Malaysia, China, and USA; (ii) the number of deaths due to COVID-19 in Malaysia, China, and USA; (iii) the volatility index, and (iv) the Brent oil price. The sample period of this study covered from 31st December 2019 to 18th April 2020. The findings showed that higher numbers of COVID-19 cases in Malaysia tended to adversely affect the performance of the KLCI index and all sectorial indices, except for the Real Estate Investment Fund (REIT) index. The results also showed that the Brent oil price and the volatility index tended to affect the Malaysian stock market performance. The results of this study can help investors understand the impact of COVID-19 on different sectors in Malaysia.
Information Distribution and Informed Trading in Mixed and Islamic Capital Markets
Authors: Rahma Tri Benita  , Siti Damayanti  , Irwan Adi Ekaputra
Published: April 2021

The correlation between volume and frequency with return volatility can explicate the information distribution process and informed traders' transaction behavior in a stock market. In this study, the Indonesian stock market represents the mixed market, while the Saudi Arabian stock market represents the Islamic market. We find that 94% and 96% of sharia-compliant stocks in Indonesia and Saudi Arabia follow the Mixture of Distribution Hypothesis (MDH). Consequently, we may conclude that sharia-compliant stocks in both markets are informationally efficient. However, we find that informed traders tend to behave differently in both markets. In the Indonesian market, informed traders exhibit competitive behavior in 95% of shariacompliant stocks and strategic transaction behavior in only 5% of the stocks. In contrast, in the Saudi Arabian market, we find that informed traders exhibit competitive behavior in only 38% of the stocks and strategic behavior in 62% of the stocks. The findings suggest that social and religious contexts may affect market participants' behavior.
EVALUATION OF THE PERFORMANCE OF WASTE MARBLE DUST AS A MINERAL FILLER IN HOT-MIX ASPHALT CONCRETE
Authors: Sang Levy , Idowu Temitope , Okumu Victoria
Published: April 2021

As the construction industry continues to evolve globally, there is a need to develop best practices geared towards achieving sustainable construction. Asphalt concrete’s demand has been increasing steadily with an estimated global demand of 122.5 million tons in 2019. This is driven primarily by the growth in construction activities in developing countries as each country works towards enhancing its transportation facilities to cater to the ever-expanding population. Hence, there are needs to develop newer and more efficient means of asphalt consumption. One of such is identifying cheaper or waste materials for use in Asphalt production. This study, therefore, examined the viability of waste marble dust (WMD), an industrial waste produced during the shaping and polishing of marble blocks and also during its extraction from the mines, as a mineral filler in Hot-mix asphalt (HMA) concrete. Engineering properties such as Marshall stability and flow, Void characteristics, Indirect tensile strength and Tensile strength ratio properties were examined. It was observed that the addition of WMD steadily increased the Marshall Stability and indirect tensile strength values and lowered the voids percentages. The study’s major finding is that waste marble dust is highly suitable as a mineral filler in HMA and a 3% by volume addition of WMD in HMA at 4.5% binder content produced the most optimal mix for use in road pavements.
Superresolution Microscopy Reveals Distinct Phosphoinositide Subdomains Within the Cilia Transition Zone
Authors: Conduit Sarah E. , Davies Elizabeth M. , Fulcher Alex J. , Oorschot Viola , Mitchell Christina A.
Published: April 2021

Primary cilia are evolutionary conserved microtubule-based organelles that protrude from the surface of most mammalian cells. Phosphoinositides (PI) are membrane-associated signaling lipids that regulate numerous cellular events via the recruitment of lipid-binding effectors. The temporal and spatial membrane distribution of phosphoinositides is regulated by phosphoinositide kinases and phosphatases. Recently phosphoinositide signaling and turnover has been observed at primary cilia. However, the precise localization of the phosphoinositides to specific ciliary subdomains remains undefined. Here we use superresolution microscopy (2D stimulated emission depletion microscopy) to map phosphoinositide distribution at the cilia transition zone. PI(3,4,5)P3 and PI(4,5)P2 localized to distinct subregions of the transition zone in a ring-shape at the inner transition zone membrane. Interestingly, the PI(3,4,5)P3 subdomain was more distal within the transition zone relative to PtdIns(4,5)P2. The phosphoinositide effector kinase pAKT(S473) localized in close proximity to these phosphoinositides. The inositol polyphosphate 5-phosphatase, INPP5E, degrades transition zone phosphoinositides, however, studies of fixed cells have reported recombinant INPP5E localizes to the ciliary axoneme, distant from its substrates. Notably, here using live cell imaging and optimized fixation/permeabilization protocols INPP5E was found concentrated at the cilia base, in a distribution characteristic of the transition zone in a ring-shaped domain of similar dimensions to the phosphoinositides. Collectively, this superresolution map places the phosphoinositides in situ with the transition zone proteins and reveals that INPP5E also likely localizes to a subdomain of the transition zone membrane, where it is optimally situated to control local phosphoinositide metabolism.
Core-Shell Structured PtxMoy@TiO2 Nanoparticles Synthesized by Reverse Microemulsion for Methanol Electrooxidation of Fuel Cells
Authors: Ai Tianyu , Bao Shuo , Lu Jinlin
Published: April 2021

The high price of catalyst and poor durability still restrict the development of fuel cells. In this work, core-shell structured PtxMoy@TiO2 nanoparticles with low Pt content are prepared by a reverse microemulsion method. The morphologies, particle size, structure, and composition of PtxMoy@TiO2 nanoparticles are examined by several techniques such as X-ray Diffraction, X-ray photoelectron spectroscopy and transmission electron microscopy, etc. The PtxMoy@TiO2 electrocatalysts show significantly higher catalytic activity and better durability for methanol oxidation than the commercial Pt/C (ETEK). Compared to Pt/C catalyst, the enhancement of the electrochemical performance of PtxMoy@TiO2 electrocatalysts can be attributed to the core-shell structure and the shift of the d-band center of Pt atoms, which can weaken the adsorption strength toward CO molecules, facilitate the removal of the CO groups and improve electrocatalytic activity. The development of PtxMoy@TiO2 electrocatalysts is promising to reduce the use of noble metal Pt and has a great potential for application in fuel cells.
Heterologous Expression and Biochemical Characterization of the Human Zinc Transporter 1 (ZnT1) and Its Soluble C-Terminal Domain
Authors: Cotrim Camila A. , Jarrott Russell J. , Whitten Andrew E. , Choudhury Hassanul G. , Drew David , Martin Jennifer L.
Published: April 2021

Human zinc transporter 1 (hZnT1) belongs to the cation diffusion facilitator (CDF) family. It plays a major role in transporting zinc (Zn2+) from the cytoplasm across the plasma membrane and into the extracellular space thereby protecting cells from Zn2+ toxicity. Through homology with other CDF family members, ZnT1 is predicted to contain a transmembrane region and a soluble C-terminal domain though little is known about its biochemistry. Here, we demonstrate that human ZnT1 and a variant can be produced by heterologous expression in Saccharomyces cerevisiae cells and purified in the presence of detergent and cholesteryl hemisuccinate. We show that the purified hZnT1 variant has Zn2+/H+ antiporter activity. Furthermore, we expressed, purified and characterized the soluble C-terminal domain of hZnT1 (hZnT1-CTD) in a bacterial expression system. We found that the hZnT1-CTD melting temperature increases at acidic pH, thus, we used an acetate buffer at pH 4.5 for purifications and concentration of the protein up to 12 mg/mL. Small-angle X-ray scattering analysis of hZnT1-CTD is consistent with the formation of a dimer in solution with a V-shaped core.
Metal-Free Direct C–H Functionalization of Quinoxalin-2(1H)-Ones to Produce 3-Vinylated Quinoxalin-2(1H)-Ones in the Presence of Alkenes
Authors: Ding Rongcai , Li Yingxue , Chang Yaoyao , Liu Yue , Yu Jie , Lv Yanna , Hu Jinxing
Published: April 2021

A novel and efficient C3-H vinylation reaction with quinoxalin-2(1H)-one as the substrate, in the presence of alkenes, under metal-free conditions, is reported herein. The reaction leads to the formation of new carbon–carbon bonds that exhibit moderate to good reactivities. The vinylation of quinoxalin-2(1H)-ones, in the presence of alkenes, is an attractive process that can be potentially utilized to produce biologically active 3-vinylated quinoxalin-2(1H)-ones.
Alterations of the Human Gut Microbiota in Intrahepatic Cholestasis of Pregnancy
Authors: Zhan Qitao , Qi Xuchen , Weng Ruopeng , Xi Fangfang , Chen Yuan , Wang Yayun , Hu Wen , Zhao Baihui , Luo Qiong
Published: April 2021

Background and Aims

Women with severe intrahepatic cholestasis of pregnancy (ICP) are at higher risks of fetal complications and without effective treatments. Changes in gut microbiota in pregnancy were found to be related to the altered intestinal bile acid composition, so we aimed to explore the alterations of microbiota in the gut of ICP patients.

Methods

A total of 90 women were recruited, including 45 ICP patients and 45 healthy controls. The gut microbiota communities of ICP group were compared to control group through 16S ribosomal RNA gene sequencing. The results were then confirmed by real-time polymerase chain reaction (PCR) and generalized linear model (GLM). Furthermore, we analyzed the relationships between microbiota and the severity of ICP.

Results

A total of seven genera and nine taxa with differential abundances between the ICP patients and the controls were identified. All of the seven genera were verified through real-time PCR, and three key genera Parabacteroides, Flavonifractor, and Megamonas were confirmed by using the GLM model. Further analysis found that the genera Escherichia_Shigella, Olsenella, and Turicibacter were enriched in the severe ICP group, the microbial gene function related to biosynthesis of unsaturated fatty acids and propanoate metabolism were also increased in them.

Conclusions

Overall, our study was the first in Asia to demonstrate an association between gut microbiota and ICP. Our findings would contribute to a better understanding of the occurrence of ICP.
CRISPR-Based COVID-19 Testing: Toward Next-Generation Point-of-Care Diagnostics
Authors: Ganbaatar Uyanga , Liu Changchun
Published: April 2021

As the COVID-19 pandemic continues, people are becoming infected at an alarming rate, individuals are unknowingly spreading disease, and more lives are lost every day. There is an immediate need for a simple, rapid, early and sensitive point-of-care testing for COVID-19 disease. However, current testing approaches do not meet such need. Recently, clustered regularly interspaced short palindromic repeats (CRISPR)-based detection methods have received substantial attention for nucleic acid-based molecular testing due to their simplicity, high sensitivity and specificity. This review explores the various CRISPR-based COVID-19 detection methods and related diagnostic devices. As with any emerging technology, CRISPR/Cas-based nucleic acid testing methods have several challenges that must be overcome for practical applications in clinics and hospitals. More importantly, these detection methods are not limited to COVID-19 but can be applied to detect any type of pathogen, virus, and fungi that may threaten humans, agriculture, and food industries in resource-limited settings. CRISPR/Cas-based detection methods have the potential to become simpler, more reliable, more affordable, and faster in the near future, which is highly important for achieving point-of-care diagnostics.
Periodontitis Is Associated With Risk of Conventional Stent Restenosis: Pilot Case-Control Study
Authors: Osugue Raphael , Castro dos Santos Nidia C. , Araujo Cassia F. , de Almeida Flavio X. , Feres Magda , Santamaria Mauro P.
Published: April 2021

Objectives: Percutaneous coronary angioplasty with stent implantation has been established as the main form of treatment of atherosclerosis. However, 16 to 44% of patients may evolve with stent restenosis. Periodontitis is an inflammatory condition associated with bacterial infection, that may lead to periodontal tissue destruction and tooth loss. This study aimed to evaluate the association between stent restenosis and periodontitis.

Materials and Methods: Coronary angiography exams presenting stent imaging with and without restenosis were analyzed. Patients meeting the inclusion and exclusion criteria were selected and allocated in 2 groups: case (restenosis) and control (without restenosis). We evaluated if systemic and periodontal variables were predictors of restenosis (primary outcome) using a multivariable stepwise logistic regression. Additionally, we compared clinical and periodontal conditions between the control and case groups (secondary outcomes) using Chi-square test and ANOVA test.

Results: Data from 49 patients (case n = 15; control n = 34) were analyzed. The results showed that stages III and IV periodontitis and lack of physical activity were significant predictors of stent restenosis (OR 5.82 and 5.98, respectively). Comparisons regarding the diagnosis of periodontal conditions between control and case groups did not present significant differences in the incidence of periodontitis and alveolar bone loss.

Conclusion: Stages III and IV periodontitis increased the incidence of stent restenosis. These findings suggest that advanced stages of periodontal disease might lead to the occurrence of negative outcomes after coronary angioplasty with stent placement.
Radioactive Thoron 220Rn Exhalation From Unfired Mud Building Material Into Room Air of Earthen Dwellings
Authors: Nguyễn Nguyệt Thị Ánh , Nguyễn-Thùy Du’o’ng , Nguyễn-Văn Hu’ó’ng , Nguyễn-Hải Nam , Schimmelmann Arndt
Published: April 2021

Thoron (220Rn), an isotope of radon with a strong α-decay energy, and its short-lived metallic progeny can pose an elevated lung cancer hazard in room air when unfired-soil derived building materials are used in earthen dwellings. Changes in moisture content and density influencing the thoron exhalation rate from earthen materials into room air were studied in the laboratory with terra rossa from a village on the Ðồng Văn Karst Plateau Geopark, Việt Nam, where ethnic minorities construct traditional dwellings with unfired terra rossa walls and floors. Our results show that the thoron exhalation rate from mud surfaces depends on (i) the content of radioactive parental nuclides in mineral components; (ii) the moisture content of mud where ∼5–10 weight % water maximizes the 220Rn exhalation rate; and (iii) the density of dry mud as primarily controlled by internal macroscopic voids, fractures, and porosity. Additional time-series of 220Rn exhalation data from an interior mud wall of a terra rossa-built house under different seasonal and weather conditions show that the temperature is influencing thoron exhalation via the water vapor pressure deficit (VPD) in air and the associated amount of atmospheric moisture adsorbed onto indoor mud surfaces. Our data suggest that occupants of “mud house” earthen dwellings in northern Việt Nam are exposed to an increased thoron geohazard during cooler weather, low VPD, and high relative humidity in air. Detailed studies are needed to evaluate the thoron geohazard for inhabitants of mud-built dwellings in other climates and geological terrains.
Total Scanning Fluorescence Characteristics and Implications of Shale Oil in the Lucaogou Formation, Jimsar Sag, Junggar Basin, NW China
Authors: Zhao Zhongying , Hou Lianhua , Luo Xia , Sun Feifei , Lin Senhu , Zhang Lijun
Published: April 2021

The Lucaogou Formation in the Jimsar Sag is a typical lacustrine shale oil development area where the first large-scale shale oil field in China was discovered, and a large number of studies have been conducted on the genesis and distribution of the shale oil in this formation. However, few detailed studies have been conducted on the comparison between the characteristics of the hydrocarbons in the shale and the adjacent tight reservoirs in the same shale sequence package. In this study, the total scanning fluorescence (TSF) quantitative fluorescence technique, which has been rarely applied to and studied in the Lucaogou Formation in the Jimsar Sag, was used to conduct systematic quantitative fluorescence analysis of the shale, tight reservoirs, and crude oils in the Lucaogou Formation. The geochemical analysis was also carried out for all samples. The results revealed that the shale, tight reservoirs, and oils have similar single-peak TSF spectrograms, and different values of the TSF parameters in the Lucaogou Formation. The TSF parameters R1and R2values of the blocky shale, fractured shale, tight reservoirs, and produced oils are decreased successively. The TSF parameters can be used as indicators of hydrocarbon composition, physical properties, thermal maturity, migration, and oil-producing layers. The values of TSF parameters R1and R2are generally smaller in the upper section of the Lucaogou Formation (P2l2) than in the lower section (P2l1), indicating that the hydrocarbons in the upper section have better physical properties and higher thermal maturity. The distribution of TSF parameters R1and R2in the upper section of the Lucaogou Formation is relatively scattered, indicating that the hydrocarbons have undergone obvious lateral migration. Based on the TSF parameter comparison of core and oil samples, it was preliminarily determined that the shale oil in the upper and lower sections of the Lucaogou Formation was mainly produced from the tight reservoirs in the shale sequence. The results of this study provide new data and ideas for fine studies of the shale oil in the Lucaogou Formation in the Jimsar Sag.
Geochemistry of Surface Sediments From the Emperor Seamount Chain, North Pacific
Authors: Chen Jie , Zou Jianjun , Zhu Aimei , Shi Xuefa , Nürnberg Dirk , Lembke-Jene Lester , Tiedemann Ralf , Wang Kunshan , Wu Yonghua , Dong Zhi , Liu Jianxing , Dou Ruxi
Published: April 2021

Investigating the composition and distribution of pelagic marine sediments is fundamental in the field of marine sedimentology. The spatial distributions of surface sediment are unclear due to limited investigation along the Emperor Seamount Chain of the North Pacific. In this study, a suite of sedimentological and geochemical proxies were analyzed, including the sediment grain size, organic carbon, CaCO3, major and rare earth elements of 50 surface sediment samples from the Emperor Seamount Chain, spanning from ∼33°N to ∼52°N. On the basis of sedimentary components, we divide them into three Zones (I, II, and III) spatially with distinct features. Sediments in Zone I (∼33°N–44°N) and Zone III (49.8°N–53°N) are dominated by clayey silt, and mainly consist of sand and silty sand in Zone II. The mean grain size of the sortable silt shows that the hydrodynamic condition in the study area is significantly stronger than that of the abyssal plain, especially at the water depth of 1,000–2,500 m. The CaCO3 contents in sediments above 4,000 m range from 20 to 84% but decrease sharply to less than 1.5% below 4,000 m, confirming that the water depth of 4,000 m is the carbonate compensation depth of the study area. Strong positive correlations between Al2O3 and Fe2O3, TiO2, MgO, and K2O (R > 0.9) in the bulk sediments indicate pronounced contributions of terrigenous materials from surrounding continent mass to the study area. Furthermore, the eolian dust makes contributions to the composition of bulk sediments as confirmed by rare earth elements. There is no significant correlation between grain size and major and minor elements, which indicates that the sedimentary grain size does not exert important effects on terrigenous components. There is significant negative δCe and positive δEu anomalies at all stations. The negative Ce anomaly mainly exists in carbonate-rich sediments, inheriting the signal of seawater. The positive Eu anomaly indicates widespread volcanism contributions to the study area from active volcanic islands arcs around the North Pacific. The relative contributions of terrestrial, volcanic, and biogenic materials vary with latitude and water depth in the study area.
Exploring the Process of Preservice Teachers’ Diagnostic Activities in a Video-Based Simulation
Authors: Codreanu Elias , Sommerhoff Daniel , Huber Sina , Ufer Stefan , Seidel Tina
Published: April 2021

Formative assessment of student learning is a challenging task in the teaching profession. Both teachers’ professional vision and their pedagogical content knowledge of specific subjects such as mathematics play an important role in assessment processes. This study investigated mathematics preservice teachers’ diagnostic activities during a formative assessment task in a video-based simulation. It examined which mathematical content was important for the successful assessment of the simulated students’ mathematical argumentation skills. Beyond that, the preservice teachers’ use of different diagnostic activities was assessed and used as an indicator of their knowledge-based reasoning during the assessment situation. The results showed that during the assessment, the mathematical content focused on varied according to the level of the simulated students’ mathematical argumentation skills. In addition, explaining what had been noticed was found to be the most difficult activity for the participants. The results suggest that the examined diagnostic activities are helpful in detecting potential challenges in the assessment process of preservice teachers that need to be further addressed in teacher education. In addition, the findings illustrate that a video-based simulation may have the potential to train specific diagnostic activities by means of additional instructional support.
Review: Obesity and COVID-19: A Detrimental Intersection
Authors: Gammone Maria Alessandra , D’Orazio Nicolantonio
Published: April 2021

Obesity has been recognized as an independent risk factor for critical illness and major severity in subjects with coronavirus disease 2019 (COVID-19). The role of fat distribution, particularly visceral fat (often linked to metabolic abnormalities), is still unclear. The adipose tissue represents a direct source of cytokines responsible for the pathological modifications occurring within adipose tissue in obese subjects. Adipokines are a crucial connection between metabolism and immune system: their dysregulation in obesity contributes to chronic low-grade systemic inflammation and metabolic comorbidities. Therefore the increased amount of visceral fat can lead to a proinflammatory phenotypic shift. This review analyzes the interrelation between obesity and COVID-19 severity, as well as the cellular key players and molecular mechanisms implicated in adipose inflammation, investigating if adipose tissue can constitute a reservoir for viral spread, and contribute to immune activation and cytokines storm. Targeting the underlying molecular mechanisms might have therapeutic potential in the management of obesity-related complications in COVID-19 patients.
Hypothalamus-Pituitary Dysfunction as an Independent Risk Factor for Postoperative Central Nervous System Infections in Patients With Sellar Region Tumors
Authors: Wen Junxian , Yin Rui , Chen Yihao , Chang Jianbo , Ma Baitao , Zuo Wei , Zhang Xiao , Ma Xiaojun , Feng Ming , Wang Renzhi , Ma Wenbin , Wei Junji
Published: April 2021

Objective

The purpose of this study was to verify that hypothalamus-pituitary dysfunction is one of the risk factors for postoperative central nervous system infections (PCNSIs).

Method

We performed a retrospective analysis of all patients with sellar region lesions who underwent surgery between January 2016 and November 2019 at Peking Union Medical College Hospital. In total, 44 age− and sex-matched controls were enrolled. Univariate and multivariate analyses were performed to identify risk factors for PCNSIs.

Result

We enrolled 88 patients, 44 of whom had PCNSIs. Surgical approach (TCS) (P<0.001), previous surgery on the same site (P=0.001), intraoperative cerebral spinal fluid (CSF) leakage (P<0.001), postoperative adrenal insufficiency (P=0.017), postoperative DI (P=0.004) and the maximum Na+ levels(<0.001) correlated significantly with PCNSIs. Multivariate analysis showed that Surgery approach (TCS)(OR: 77.588; 95%CI: 7.981-754.263; P<0.001), intraoperative CSF leakage (OR: 12.906; 95%CI: 3.499-47.602; P<0.001), postoperative DI (OR: 6.999; 95%CI:1.371-35.723; P=0.019) and postoperative adrenal insufficiency (OR: 6.115; 95%CI: 1.025-36.469; P=0.047) were independent influencing factors for PCNSIs.

Conclusion

TCS, intraoperative CSF leakage, postoperative DI and postoperative adrenal insufficiency are risk factors for PCNSIs in patients with sellar region tumors.
Sequence and Structure Characteristics of 22 Deletion Breakpoints in Intron 44 of the DMD Gene Based on Long-Read Sequencing
Authors: Geng Chang , Tong Yuanren , Zhang Siwen , Ling Chao , Wu Xin , Wang Depeng , Dai Yi
Published: April 2021

Purpose: Exon deletions make up to 80% of mutations in the DMD gene, which cause Duchenne and Becker muscular dystrophy. Exon 45-55 regions were reported as deletion hotspots and intron 44 harbored more than 25% of deletion start points. We aimed to investigate the fine structures of breakpoints in intron 44 to find potential mechanisms of large deletions in intron 44.

Methods: Twenty-two dystrophinopathy patients whose deletion started in intron 44 were sequenced using long-read sequencing of a DMD gene capture panel. Sequence homology, palindromic sequences, and polypyrimidine sequences were searched at the breakpoint junctions. RepeatMasker was used to analyze repetitive elements and Mfold was applied to predict secondary DNA structure.

Results: With a designed DMD capture panel, 22 samples achieved 2.25 gigabases and 1.28 million reads on average. Average depth was 308× and 99.98% bases were covered at least 1×. The deletion breakpoints in intron 44 were scattered and no breakpoints clustered in any region less than 500 bp. A total of 72.7% of breakpoints located in distal 100 kb of intron 44 and more repetitive elements were found in this region. Microhomologies of 0–1 bp were found in 36.4% (8/22) of patients, which corresponded with non-homologous end-joining. Microhomologies of 2–20 bp were found in 59.1% (13/22) of patients, which corresponded with microhomology-mediated end-joining. Moreover, a 7 bp insertion was found in one patient, which might be evidence of aberrant replication origin firing. Palindromic sequences, polypyrimidine sequences, and small hairpin loops were found near several breakpoint junctions. No evidence of large hairpin loop formation in deletion root sequences was observed.

Conclusion: This study was the first to explore possible mechanisms underlying exon deletions starting from intron 44 of the DMD gene based on long-read sequencing. Diverse mechanisms might be associated with deletions in the DMD gene.
GNA14, GNA11, and GNAQ Mutations Are Frequent in Benign but Not Malignant Cutaneous Vascular Tumors
Authors: Jansen Philipp , Müller Hansgeorg , Lodde Georg C. , Zaremba Anne , Möller Inga , Sucker Antje , Paschen Annette , Esser Stefan , Schaller Jörg , Gunzer Matthias , Standl Fabian , Bauer Sebastian , Schadendorf Dirk , Mentzel Thomas , Hadaschik Eva , Griewank Klaus G.
Published: April 2021

Cutaneous vascular tumors consist of a heterogeneous group of benign proliferations, including a range of hemangiomas and vascular malformations, as well as heterogeneous groups of both borderline and malignant neoplasms such as Kaposi’s sarcoma and angiosarcomas. The genetics of these tumors have been assessed independently in smaller individual cohorts making comparisons difficult. In our study, we analyzed a representative cohort of benign vascular proliferations observed in a clinical routine setting as well as a selection of malignant vascular proliferations. Our cohort of 104 vascular proliferations including hemangiomas, malformations, angiosarcomas and Kaposi’s sarcoma were screened by targeted next-generation sequencing for activating genetic mutations known or assumed to be potentially relevant in vascular proliferations. An association analysis was performed for mutation status and clinico-pathological parameters. Frequent activating hotspot mutations in GNA genes, including GNA14 Q205, GNA11 and GNAQ Q209 were identified in 16 of 64 benign vascular tumors (25%). GNA gene mutations were particularly frequent (52%) in cherry (senile) hemangiomas (13 of 25). In angiosarcomas, activating RAS mutations (HRAS and NRAS) were identified in three samples (16%). No activating GNA or RAS gene mutations were identified in Kaposi’s sarcomas. Our study identifies GNA14 Q205, GNA11 and GNAQ Q209 mutations as being the most common and mutually exclusive mutations in benign hemangiomas. These mutations were not identified in malignant vascular tumors, which could be of potential diagnostic value in distinguishing these entities.
SIns: A Novel Insertion Detection Approach Based on Soft-Clipped Reads
Authors: Yan Chaokun , He Junyi , Luo Junwei , Wang Jianlin , Zhang Ge , Luo Huimin
Published: April 2021

As a common type of structural variation, an insertion refers to the addition of a DNA sequence into an individual genome and is usually associated with some inherited diseases. In recent years, many methods have been proposed for detecting insertions. However, the accurate calling of insertions is also a challenging task. In this study, we propose a novel insertion detection approach based on soft-clipped reads, which is called SIns. First, based on the alignments between paired reads and the reference genome, SIns extracts breakpoints from soft-clipped reads and determines insertion locations. The insert size information about paired reads is then further clustered to determine the genotype, and SIns subsequently adopts Minia to assemble the insertion sequences. Experimental results show that SIns can achieve better performance than other methods in terms of the F-score value for simulated and true datasets.
Anti-HIV-1 ADCC and HIV-1 Env Can Be Partners in Reducing Latent HIV Reservoir
Authors: Suryawanshi Poonam , Bagul Rajani , Shete Ashwini , Thakar Madhuri
Published: April 2021

Background

Persistence of HIV reservoir even in suppressive ART is the key obstacle in HIV-1 cure. We evaluated the ability of HIV-1 C Env to reactivate the latently infected resting memory CD4 cells and the ability of polyclonal HIV antibodies mediating ADCC to lyse the reactivated targets.

Methodology

HIV-1 antibodies from 25 HIV infected individuals (14 ADCC responders and 11 non-responders) were tested against the Env-C reactivated primary cells; CD4+ and CD4+CD45RO+ memory T cells in the presence of autologous or heterologous effector cells using multicolor flow cytometry. The frequencies of p24+ve target cells were measured to determine the reactivation and antibody mediated lysis.

Results

Increase in the frequency of p24 expressing cells (P < 0.01 in all cases) after Env-C stimulation of target cells indicated reactivation. When these reactivated targets were mixed with effector cells and HIV-1 antibodies, the frequencies of p24 expressing targets were decreased significantly when the ADCC mediating antibodies (P < 0.01 in all cases) were added but not when the antibodies from ADCC non-responders or HIV negative individuals were added. In parallel, the NK cell activation was also increased only when ADCC mediating antibodies were added.

Conclusion

The study showed that the HIV-1 Env could act as latency reversal agent (LRA), and only ADCC mediating antibodies could lyse the reactivated HIV reservoirs. The short stimulation cycle used in this study could be useful in testing LRAs as well as immune mediated lysis of reactivated reservoirs. The observations have further implication in designing antibody mediated immunotherapy for eradication of latent HIV reservoir.
Impact of Smoking on Women During the Covid-19 Pandemic
Authors: Mihaltan Florin Dumitru , Rajnoveanu Armand-Gabriel , Rajnoveanu Ruxandra-Mioara
Published: April 2021

The coronavirus disease 2019 (COVID-19) brought in 2020 an important challenge for health-care systems and authorities. Smoking and its influence on this disease remain, after months of the pandemic, one of the debatable risk factors. From the literature point of view, the focus of most articles is on smoking as a possible general risk factor for all analyzed populations. Women tend to represent a more significant population in exposed occupations. In our mini-review, we try to dig deeper, looking for gender-related health effects of smoking in this pandemic context, its effects on the infection with this novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), on illness severity, and on the rate of hospitalization and mortality. Despite the fact that the male gender is reported in many articles as a predictor of a poor outcome, we suggest that further research is needed to confirm or deny these relationships. Moreover, studies focusing specifically on women in these study populations are required.
Novel TNIP2 and TRAF2 Variants Are Implicated in the Pathogenesis of Pulmonary Arterial Hypertension
Authors: Pienkos Shaun , Gallego Natalia , Condon David F. , Cruz-Utrilla Alejandro , Ochoa Nuria , Nevado Julián , Arias Pedro , Agarwal Stuti , Patel Hiral , Chakraborty Ananya , Lapunzina Pablo , Escribano Pilar , Tenorio-Castaño Jair , de Jesús Pérez Vinicio A.
Published: April 2021

Background: Pulmonary arterial hypertension (PAH) is a rare disease characterized by pulmonary vascular remodeling and right heart failure. Specific genetic variants increase the incidence of PAH in carriers with a family history of PAH, those who suffer from certain medical conditions, and even those with no apparent risk factors. Inflammation and immune dysregulation are related to vascular remodeling in PAH, but whether genetic susceptibility modifies the PAH immune response is unclear. TNIP2 and TRAF2 encode for immunomodulatory proteins that regulate NF-κB activation, a transcription factor complex associated with inflammation and vascular remodeling in PAH.

Methods: Two unrelated families with PAH cases underwent whole-exome sequencing (WES). A custom pipeline for variant prioritization was carried out to obtain candidate variants. To determine the impact of TNIP2 and TRAF2 in cell proliferation, we performed an MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay on healthy lung pericytes transfected with siRNA specific for each gene. To measure the effect of loss of TNIP2 and TRAF2 on NF-kappa-beta (NF-κB) activity, we measured levels of Phospho-p65-NF-κB in siRNA-transfected pericytes using western immunoblotting.

Results: We discovered a novel missense variant in the TNIP2 gene in two affected individuals from the same family. The two patients had a complex form of PAH with interatrial communication and scleroderma. In the second family, WES of the proband with PAH and primary biliary cirrhosis revealed a de novo protein-truncating variant in the TRAF2. The knockdown of TNIP2 and TRAF2 increased NF-κB activity in healthy lung pericytes, which correlated with a significant increase in proliferation over 24 h.

Conclusions: We have identified two rare novel variants in TNIP2 and TRAF2 using WES. We speculate that loss of function in these genes promotes pulmonary vascular remodeling by allowing overactivation of the NF-κB signaling activity. Our findings support a role for WES in helping identify novel genetic variants associated with dysfunctional immune response in PAH.
Gene Expression Profiling of Pseudomonas aeruginosa Upon Exposure to Colistin and Tobramycin
Authors: Cianciulli Sesso Anastasia , Lilić Branislav , Amman Fabian , Wolfinger Michael T. , Sonnleitner Elisabeth , Bläsi Udo
Published: April 2021

Pseudomonas aeruginosa (Pae) is notorious for its high-level resistance toward clinically used antibiotics. In fact, Pae has rendered most antimicrobials ineffective, leaving polymyxins and aminoglycosides as last resort antibiotics. Although several resistance mechanisms of Pae are known toward these drugs, a profounder knowledge of hitherto unidentified factors and pathways appears crucial to develop novel strategies to increase their efficacy. Here, we have performed for the first time transcriptome analyses and ribosome profiling in parallel with strain PA14 grown in synthetic cystic fibrosis medium upon exposure to polymyxin E (colistin) and tobramycin. This approach did not only confirm known mechanisms involved in colistin and tobramycin susceptibility but revealed also as yet unknown functions/pathways. Colistin treatment resulted primarily in an anti-oxidative stress response and in the de-regulation of the MexT and AlgU regulons, whereas exposure to tobramycin led predominantly to a rewiring of the expression of multiple amino acid catabolic genes, lower tricarboxylic acid (TCA) cycle genes, type II and VI secretion system genes and genes involved in bacterial motility and attachment, which could potentially lead to a decrease in drug uptake. Moreover, we report that the adverse effects of tobramycin on translation are countered with enhanced expression of genes involved in stalled ribosome rescue, tRNA methylation and type II toxin-antitoxin (TA) systems.
Mechanistic Understanding of Candida albicans Biofilm Formation and Approaches for Its Inhibition
Authors: Atriwal Tanu , Azeem Kashish , Husain Fohad Mabood , Hussain Afzal , Khan Muhammed Nadeem , Alajmi Mohamed F. , Abid Mohammad
Published: April 2021

In recent years, the demand for novel antifungal therapies has increased several- folds due to its potential to treat severe biofilm-associated infections. Biofilms are made by the sessile microorganisms attached to the abiotic or biotic surfaces, enclosed in a matrix of exopolymeric substances. This results in new phenotypic characteristics and intrinsic resistance from both host immune response and antimicrobial drugs. Candida albicans biofilm is a complex association of hyphal cells that are associated with both abiotic and animal tissues. It is an invasive fungal infection and acts as an important virulent factor. The challenges linked with biofilm-associated diseases have urged scientists to uncover the factors responsible for the formation and maturation of biofilm. Several strategies have been developed that could be adopted to eradicate biofilm-associated infections. This article presents an overview of the role of C. albicans biofilm in its pathogenicity, challenges it poses and threats associated with its formation. Further, it discusses strategies that are currently available or under development targeting prostaglandins, quorum-sensing, changing surface properties of biomedical devices, natural scaffolds, and small molecule-based chemical approaches to combat the threat of C. albicans biofilm. This review also highlights the recent developments in finding ways to increase the penetration of drugs into the extracellular matrix of biofilm using different nanomaterials against C. albicans.
Mefloquine, a Potent Anti-severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Drug as an Entry Inhibitor in vitro
Authors: Shionoya Kaho , Yamasaki Masako , Iwanami Shoya , Ito Yusuke , Fukushi Shuetsu , Ohashi Hirofumi , Saso Wakana , Tanaka Tomohiro , Aoki Shin , Kuramochi Kouji , Iwami Shingo , Takahashi Yoshimasa , Suzuki Tadaki , Muramatsu Masamichi , Takeda Makoto , Wakita Takaji , Watashi Koichi
Published: April 2021

Coronavirus disease 2019 (COVID-19) has caused serious public health, social, and economic damage worldwide and effective drugs that prevent or cure COVID-19 are urgently needed. Approved drugs including Hydroxychloroquine, Remdesivir or Interferon were reported to inhibit the infection or propagation of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), however, their clinical efficacies have not yet been well demonstrated. To identify drugs with higher antiviral potency, we screened approved anti-parasitic/anti-protozoal drugs and identified an anti-malarial drug, Mefloquine, which showed the highest anti-SARS-CoV-2 activity among the tested compounds. Mefloquine showed higher anti-SARS-CoV-2 activity than Hydroxychloroquine in VeroE6/TMPRSS2 and Calu-3 cells, with IC50 = 1.28 μM, IC90 = 2.31 μM, and IC99 = 4.39 μM in VeroE6/TMPRSS2 cells. Mefloquine inhibited viral entry after viral attachment to the target cell. Combined treatment with Mefloquine and Nelfinavir, a replication inhibitor, showed synergistic antiviral activity. Our mathematical modeling based on the drug concentration in the lung predicted that Mefloquine administration at a standard treatment dosage could decline viral dynamics in patients, reduce cumulative viral load to 7% and shorten the time until virus elimination by 6.1 days. These data cumulatively underscore Mefloquine as an anti-SARS-CoV-2 entry inhibitor.
Biphenyl 2,3-Dioxygenase in Pseudomonas alcaliphila JAB1 Is Both Induced by Phenolics and Monoterpenes and Involved in Their Transformation
Authors: Zubrova Andrea , Michalikova Klara , Semerad Jaroslav , Strejcek Michal , Cajthaml Tomas , Suman Jachym , Uhlik Ondrej
Published: April 2021

The involvement of bacterial aromatic ring-hydroxylating dioxygenases (ARHDs) in the degradation of aromatic pollutants, such as polychlorinated biphenyls (PCBs), has been well studied. However, there is considerable speculation as to the origin of this ability. One hypothesis is centered on a connection between the ability to degrade aromatic pollutants and the necessity of soil bacteria to cope with and/or utilize secondary plant metabolites (SPMs). To investigate this connection, we researched the involvement of biphenyl 2,3-dioxygenase (BPDO), an ARHD essential for the degradation of PCBs, in the metabolism of SPMs in the soil bacterium Pseudomonas alcaliphila JAB1, a versatile degrader of PCBs. We demonstrated the ability of the strain JAB1 to transform a variety of SPMs, namely the flavonoids apigenin, flavone, flavanone, naringenin, fisetin, quercetin, morin, and catechin, caffeic acid, trans-cinnamic acid, and the monoterpenes (S)-limonene and (R)-carvone. Of those, the transformation of flavone, flavanone, and (S)-limonene was conditioned by the activity of JAB1-borne BPDO and thus was researched in more detail, and we found evidence for the limonene monooxygenase activity of the BPDO. Furthermore, the bphA gene in the strain JAB1 was demonstrated to be induced by a wide range of SPMs, with monoterpenes being the strongest inducers of the SPMs tested. Thus, our findings contribute to the growing body of evidence that ARHDs not only play a role in the catabolism of aromatic pollutants, but also of natural plant-derived aromatics, and this study supports the hypothesis that ARHDs participate in ecological processes mediated by SPMs.