bluuebunny/crossref_metadata_2025 huggingface dataset:
SUSTAINABILITY-ORIENTED INNOVATION, TECHNOLOGIES & FINANCE IN CONSTRUCTION: A MULTI-CRITERIA METHODOLOGY
Authors: A. R. Barbosa Adriano , Vilnits Martins , Leal Filho Walter
Published: June 2021

Considering the efforts to adjust the great
demand of the civil construction in the developing
countries and the economic interests of the sector, in line
with current sustainable trends, this article presents a
methodology to support the planning and decision making
of construction companies. An analysis of the elements
involved in the process, their interaction and proposed
application priorities are evaluated using the AHP
(Analytic Hierarchy Process) method as a multi-criteria
decision support tool. The results obtained allow us to
observe the parameters that guide the decision-making of
the managers in the construction sites, the impact of low
productivity and limited investments in innovation and
processes, which still adopts the traditional methods of
construction. However, exists a margin that is sustainable,
without major financial impact, through the management
and encouragement of the environmental awareness of
investors, entrepreneurs and construction workers. The
actions that interfere with the process and its application
priorities in construction are related, within the context of
innovation, technology and finance oriented to
sustainability. Supported by the concepts of management
and SOI (Sustainability-oriented innovation) topics, a
discussion of the civil construction scenario in Brazil is
carried out through the economic, social, technological and
managerial issues typical of developing countries, guided
by the strong trends in the macro-economics adjustments
and rational use of natural resources in the coming
decades. It highlights the main challenges of the sector and
presents a analysis, planning, decision-making approach
and collective impact actions that could support the
development actions of the sector, in order to reduce the
distance from the concepts of environmental awareness
and attitudes existing in developed countries.
K-Pop 4E, azaz a kreatív és kulturális ipari marketing-mix elemeinek bemutatása a dél-koreai popzenében (K-Popban) és filmsorozatoknál (K-drámáknál) használt marketing eszközök példáján keresztül
Authors: Gajzágó Éva Judit
Published: June 2021

Az elmúlt évtizedekben a kreatív és kulturális ipar szerepe felértékelődött, termékeinek és szolgáltatásainak kereslete növekedett. A cikkben ezen növekedés hátterét, illetve a növekedéshez hozzájáruló vállalati marketing eszközöket egy egyre népszerűbb szektor, a dél-koreai zenei- és filmipar példáján keresztül mutatja be a szerző. A 4E marketing-mix modelljét (Experience, Everyplace, Exchange, Evangelism) használva ismerteti azokat az eszközöket, amelyekkel a vállalatok befolyásolják az iparág termékeinek fogyasztását. A cikk második felében egy nemzetközi szekunder kutatás, valamint egy hazai, a koreai kultúra rajongói körében 2018-2019-ben elvégzett primer kutatás eredményeit összegezve a szektor fogyasztónak sajátosságai és preferenciai is bemutatásra kerülnek.
Electrochemical Approach to Measure Physiological Fluid Flow Rates
Authors: Sarathy Srivats , Nino Marco A. , Ghanim Abdulsattar H. , Rajagopal Srinivasan , Mubeen Syed , Raghavan M. L.
Published: June 2021

In vivo measurement of the flow rate of physiological fluids such as the blood flow rate in the heart is vital in critically ill patients and for those undergoing surgical procedures. The reliability of these measurements is therefore quite crucial. However, current methods in practice for measuring flow rates of physiological fluids suffer from poor repeatability and reliability. Here, we assessed the feasibility of a flow rate measurement method that leverages time transient electrochemical behavior of a tracer that is injected directly into a medium (the electrochemical signal caused due to the tracer injectate will be diluted by the continued flow of the medium and the time response of the current—the electrodilution curve—will depend on the flow rate of the medium). In an experimental flow loop apparatus equipped with an electrochemical cell, we used the AC voltammetry technique and tested the feasibility of electrodilution-based measurement of the flow rate using two mediums—pure water and anticoagulated blood—with 0.9 wt% saline as the injectate. The electrodilution curve was quantified using three metrics—change in current amplitude, total time, and change in the total charge for a range of AC voltammetry settings (peak voltages and frequencies). All three metrics showed an inverse relationship with the flow rate of water and blood, with the strongest negative correlation obtained for change in current amplitude. The findings are a proof of concept for the electrodilution method of the flow rate measurement and offer the potential for physiological fluid flow rate measurement in vivo.
Feeling the Beat in an African Tone Language: Rhythmic Mapping Between Language and Music
Authors: Franich Kathryn H. , Lendja Ngnemzué Ange B.
Published: June 2021

Text-setting patterns in music have served as a key data source in the development of theories of prosody and rhythm in stress-based languages, but have been explored less from a rhythmic perspective in the realm of tone languages. African tone languages have been especially under-studied in terms of rhythmic patterns in text-setting, likely in large part due to the ill-understood status of metrical structure and prosodic prominence asymmetries in many of these languages. Here, we explore how language is mapped to rhythmic structure in traditional folksongs sung in Medʉmba, a Grassfields Bantu language spoken in Cameroon. We show that, despite complex and varying rhythmic structures within and across songs, correspondences emerge between musical rhythm and linguistic structure at the level of stem position, tone, and prosodic structure. Our results reinforce the notion that metrical prominence asymmetries are present in African tone languages, and that they play an important coordinative role in music and movement.
Estrogen Protects Vasomotor Functions in Rats During Catecholamine Stress
Authors: Zhang Lin , Li Chenfei , Yang Liting , Adzika Gabriel Komla , Machuki Jeremiah Ong'achwa , Shi Mingjin , Sun Qi , Sun Hong
Published: June 2021

The incidence of dysfunctional vasomotor diseases has mostly occurred in postmenopausal women but not in premenopausal women. Hence, this study sought to investigate the impact of estrogen deficiency during catecholamine stress on vasomotor function. Also, attempts were made to utilize estrogen replacement therapy to mitigate the adverse effects (pathological remodeling) of stress on the aortic vessels to preserve vasomotor functions. To do this, female Sprague-Dawley (SD) rats were ovariectomized (OVX) along with sham operations (Sham). Day 14 after OVX operation, 17-estradiol (E2) was subcutaneously implanted (OVX+E2). Day 35 after operation, stress was induced by isoproterenol (ISO) subcutaneous injections. Clinically relevant blood pressure indexes (systolic, diastolic, and mean atrial blood pressures) were assessed in the rats. Aortic vascular ring tensions were assessed in vitro to ascertain the impact of E2 on their vasomotor function. Aortic vascular rings (AVRs) from OVX+ISO exhibited a significant increase in contractility in response to phenylephrine than AVRs isolated from Sham+ISO rats. Also, sera levels of nitric oxide (NO) and endothelin-1 (ET-1) and the expression of p-eNOS/eNOS from vascular tissues were ascertained. We demonstrate that, during stress, E2 prevented excessive weight gain and OVX rats had higher blood pressures than those in the Sham group. Further, we showed that E2 decreases ET-1 expressions during stress while upregulating NO expressions via enhancing eNOS activities to facilitate vasomotor functions. Finally, histological assessment revealed the E2 treatments during stress preserved vasomotor functions by preventing excessive intima-media thickening and collagen depositions in the aortic vascular walls.
Mineralization of the Tuwu Porphyry Cu Deposit in Eastern Tianshan, NW China: Insights From In Situ Trace Elements of Chlorite and Pyrite
Authors: Tan Wei , Mao Qigui , Yu Mingjie , Sun Yan , Lv Xiaoqiang
Published: June 2021

The Tuwu porphyry copper deposit is located on the Dananhu-Haerlik island arc in eastern Tianshan, NW China. Based on geology, petrology, and in situ trace element studies of pyrite and chlorite, we redefined the characteristics of hydrothermal fluids and the following three mineralization stages: premineralization stage (stage Ⅰ), porphyry metallogenic stage (stage Ⅱ), and superimposed transformation stage (stage Ⅲ). Pyrite stage Ⅰ (Py-I) has the highest Co/Ni ratios, and the precipitation crystallization of chlorite (Chl-I2) has the similar rare earth element distribution patterns with those of volcanic rocks Carboniferous Qieshan (CQ), indicating intense volcanic hydrothermal activity. The Co/Ni ratios of Py-II1 and Py-II2 (stage Ⅱ) tend to decrease over time. Moreover, the rare earth element (REE) distribution patterns of Chl-II have similar LREE enrichment, and the Eu anomalies in Chl-II1, Chl-II2, and Chl-II3 range from positive to negative. The initial ore-forming fluid was mainly magmatic hydrothermal fluid, and with the late-stage addition of meteoric water and continuous sulfide precipitation, the trace element composition of the fluid changed, and the whole system became more oxidizing. Py-III (stage Ⅲ) has the lowest Co/Ni ratios, and the REE distribution pattern of Chl-III is characterized by LREE enrichment. Moreover, the Chl-III shows obvious shear deformation characteristics. The results indicate that the host rocks experienced intensely superimposed reformation. By combining and integrating our results with the regional evolution processes in the eastern Tianshan, we propose that the Tuwu porphyry deposit has undergone magmatic hydrothermal and metamorphic hydrothermal processes. Volcanism (stage Ⅰ) provided the space and initial conditions for the emplacement of the metallogenic body. With the emplacement of the plagiogranite porphyry (stage Ⅱ), the main copper mineralization occurred in the porphyry and surrounding rocks. After porphyry mineralization (stage Ⅲ), regional ductile shearing and collisional compression led to a copper reaction, and its accumulation along the faults formed an ore shoot.
Toward Green Optoelectronics: Environmental-Friendly Colloidal Quantum Dots Photodetectors
Authors: Miao Sijia , Cho Yuljae
Published: June 2021

Colloidal quantum dots (CQDs) have attracted tremendous research interests in future-generation energy, electronic, optoelectronic, and bio-imaging applications due to their fascinating material properties, such as solution processability at room temperature and under ambient conditions, compatibility with various functional materials, and high photostability as well as photosensitivity. Among the various optoelectronic applications of CQDs, optical light sensors, which convert photonic energy into electrical signals, have been of particular interest because they are one of the key building blocks for modern communication and imaging applications, including medical X-ray and near-infrared imaging, visible light cameras, and machine vision. However, CQDs, which have been widely researched for photodetectors (PDs) so far, contain toxic and hazardous heavy metals, namely, lead (Pb), cadmium (Cd), and mercury (Hg). These substances are extremely toxic and harmful to the environment as well as human beings. Therefore, it is highly desirable to substitute CQDs containing heavy metals with nontoxic and environmentally friendly ones to realize green optoelectronics. In this review article, we introduce various kinds of heavy metal–free CQDs and their PD applications. This article comprehensively includes working mechanisms of PDs, various kinds of nontoxic and environmentally friendly CQD-based PDs, advanced heterojunction PDs, and discussion for future perspectives.
Determination of Optimal Indicators Based on Statistical Analysis for the State of Health Estimation of a Lithium-Ion Battery
Authors: Shi Gaoya , Chen Siqi , Yuan Hao , You Heze , Wang Xueyuan , Dai Haifeng , Wei Xuezhe
Published: June 2021

Online state of health (SOH) estimation is essential for lithium-ion batteries in a battery management system. As the conventional SOH indicator, the capacity is challenging to be estimated online. Apart from the capacity, various indicators related to the internal resistance are proposed as indicators for the SOH estimation. However, research gaps still exist in terms of optimal resistance-related indicators, online acquisition of indicators, temperature disturbance elimination, and state of charge (SOC) disturbance elimination. In this study, the equivalent circuit model parameters are identified based on recursive least square method in dynamic working conditions in the life span. Statistical analysis methods including multiple stepwise regression analysis and path analysis are introduced to characterize the sensitivity of the parameters to SOH estimation. Based on the above approach, the coupling relationship between the parameters is comprehensively analyzed. Results indicate that the ohmic resistance R0 and the diffusion capacitance Cd are the most suitable parameters for the SOH indication. Furthermore, R0 and Cd are proved to be exponentially correlated to the ambient temperature, while SOC demonstrates a quadratic trend on them. To eliminate the disturbance caused by the ambient temperature and SOC, a compensating method is further proposed. Finally, a mapping relationship between SOH and the indicators under normal operations is established. SOH can be estimated with the maximum error of 2.301%, which proves the reliability and feasibility of the proposed indicators and estimation method.
Properties and Configurations of B-N Co-Doped ZnO Nanorods Fabricated on ITO/PET Substrate
Authors: Jiang Jianchao , Jiang Liyun , Rong Ping , Wu Kechen , Yang Qingqing , Yu Qi
Published: June 2021

Based on flexible materials, optoelectronic devices with optoelectronic technology as the core and flexible electronic devices as the platform are facing new challenges in their applications, including material requirements based on functional electronic devices such as lightness, thinness, and impact resistance. However, there is still a big gap between the current preparation technology of flexible materials and practical applications. At present, the main factors restricting the more commercial development of flexible materials include preparation conditions and performance. In this work, B-N co-doped ZnO nanorod arrays (NRAs) were successfully synthesized on the polyethylene terephthalate (PET) substrate coated with indium tin oxide (ITO) by the hydrothermal method. Based on the density functional theory, the effect of B-N co-doping on the electronic structure of ZnO was calculated; the incorporation of B and N led to an increase in the lattice constant of ZnO. The B-N co-doped ZnO has obvious rectification characteristics with the positive conduction voltage of 2 V in the I–V curve.
Admixture Has Shaped Romani Genetic Diversity in Clinically Relevant Variants
Authors: Font-Porterias Neus , Giménez Aaron , Carballo-Mesa Annabel , Calafell Francesc , Comas David
Published: June 2021

Genetic patterns of inter-population variation are a result of different demographic and adaptive histories, which gradually shape the frequency distribution of the variants. However, the study of clinically relevant mutations has a Eurocentric bias. The Romani, the largest transnational minority ethnic group in Europe, originated in South Asia and received extensive gene flow from West Eurasia. Most medical genetic studies have only explored founder mutations related to Mendelian disorders in this population. Here we analyze exome sequences and genome-wide array data of 89 healthy Spanish Roma individuals to study complex traits and disease. We apply a different framework and focus on variants with both increased and decreased allele frequencies, taking into account their local ancestry. We report several OMIM traits enriched for genes with deleterious variants showing increased frequencies in Roma or in non-Roma (e.g., obesity is enriched in Roma, with an associated variant linked to South Asian ancestry; while non-insulin dependent diabetes is enriched in non-Roma Europeans). In addition, previously reported pathogenic variants also show differences among populations, where some variants segregating at low frequency in non-Roma are virtually absent in the Roma. Lastly, we describe frequency changes in drug-response variation, where many of the variants increased in Roma are clinically associated with metabolic and cardiovascular-related drugs. These results suggest that clinically relevant variation in Roma cannot only be characterized in terms of founder mutations. Instead, we observe frequency differences compared to non-Roma: some variants are absent, while other have drifted to higher frequencies. As a result of the admixture events, these clinically damaging variants can be traced back to both European and South Asian-related ancestries. This can be attributed to a different prevalence of some genetic disorders or to the fact that genetic susceptibility variants are mostly studied in populations of European descent, and can differ in individuals with different ancestries.
Women Deprivation Index and Family Planning Utilisation in Urban Geography of West African Countries
Authors: Akinyemi Akanni Ibukun , Mobolaji Jacob Wale , Abe John Olugbenga , Ibrahim Elhakim , Ikuteyijo Olutoyin
Published: June 2021

Inequalities in health care utilisation and outcomes vary significantly across geographies. Though available evidence suggests disparity in contraceptive uptake in favour of urban compared with rural geographies, there are unassessed nuances among women in urban communities. This study examines some of these disparities within the context of socioeconomic deprivations and family planning utilisation among urban women in West Africa. A secondary analysis of the most recent Demographic and Health Survey dataset of five selected West African countries was conducted, using pooled data of 21,641 women aged 15–49 years. Associations between family planning utilisation and women's deprivation status were investigated using a binary logistic regression model. The findings show that more than one-quarter of the women were severely deprived across the countries except Senegal (17.4%), and the severely deprived consistently have relatively low contraceptive prevalence rates (CPR) (16.0–24.3%) compared with women with no/low deprivation across the countries except Senegal (39.8%). The results for long-acting reversible contraceptives (LARC) were not consistent across the five countries: whereas, LARC utilisation was lower among severely deprived women in Nigeria (9.1%), Guinea (9.6%), and Mali (19.3%), utilisation was similar across the deprivation groups in Benin and Senegal. In the multivariable analyses, the log-odds of modern contraceptive utilisation decreases by 0.27 among the moderately deprived (ß = −0.27, SE = 0.05, p < 0.01) and by 0.75 among the severely deprived women (ß = −0.75, SE = 0.05, p < 0.01) compared with those with no/low deprivation, with variations across the countries. Similarly, the log-odds of LARC utilisation decreases by 0.44–0.72 among the severely deprived women compared with those with no/low deprivation across the countries except Senegal. This study concluded that family planning intervention programmes and policies need to underscore the deprivation context of urban geographies, particularly among women living in informal settlements.
Investigation of Genetic Determinants of Glioma Immune Phenotype by Integrative Immunogenomic Scale Analysis
Authors: Zhao Binghao , Wang Yuekun , Wang Yaning , Dai Congxin , Wang Yu , Ma Wenbin
Published: June 2021

The immunosuppressive mechanisms of the surrounding microenvironment and distinct immunogenomic features in glioblastoma (GBM) have not been elucidated to date. To fill this gap, useful data were extracted from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), GSE16011, GSE43378, GSE23806, and GSE12907. With the ssGSEA method and the ESTIMATE and CIBERSORT algorithms, four microenvironmental signatures were used to identify glioma microenvironment genes, and the samples were reasonably classified into three immune phenotypes. The molecular and clinical features of these phenotypes were characterized via key gene set expression, tumor mutation burden, fraction of immune cell infiltration, and functional enrichment. Exhausted CD8+ T cell (GET) signature construction with the predictive response to commonly used antitumor drugs and peritumoral edema assisted in further characterizing the immune phenotype features. A total of 2,466 glioma samples with gene expression profiles were enrolled. Tumor purity, ESTIMATE, and immune and stromal scores served as the 4 microenvironment signatures used to classify gliomas into immune-high, immune-middle and immune-low groups, which had distinct immune heterogeneity and clinicopathological characteristics. The immune-H phenotype had higher expression of four immune signatures; however, most checkpoint molecules exhibited poor survival. Enriched pathways among the subtypes were related to immunity. The GET score was similar among the three phenotypes, while immune-L was more sensitive to bortezomib, cisplatin, docetaxel, lapatinib, and rapamycin prescriptions and displayed mild peritumor edema. The three novel immune phenotypes with distinct immunogenetic features could have utility for understanding glioma microenvironment regulation and determining prognosis. These results contribute to classifying glioma subtypes, remodeling the immunosuppressive microenvironment and informing novel cancer immunotherapy in the era of precision immuno-oncology.
Impact of Interleukin 10 Deficiency on Intestinal Epithelium Responses to Inflammatory Signals
Authors: Papoutsopoulou Stamatia , Pollock Liam , Walker Catherine , Tench William , Samad Sakim Shakh , Bergey François , Lenzi Luca , Sheibani-Tezerji Raheleh , Rosenstiel Phillip , Alam Mohammad Tauqeer , Martins Dos Santos Vitor A. P. , Müller Werner , Campbell Barry J.
Published: June 2021

Interleukin 10 (IL-10) is a pleiotropic, anti-inflammatory cytokine that has a major protective role in the intestine. Although its production by cells of the innate and adaptive immune system has been extensively studied, its intrinsic role in intestinal epithelial cells is poorly understood. In this study, we utilised both ATAC sequencing and RNA sequencing to define the transcriptional response of murine enteroids to tumour necrosis factor (TNF). We identified that the key early phase drivers of the transcriptional response to TNF within intestinal epithelium were NFκB transcription factor dependent. Using wild-type and Il10−/− enteroid cultures, we showed an intrinsic, intestinal epithelium specific effect of IL-10 deficiency on TNF-induced gene transcription, with significant downregulation of identified NFκB target genes Tnf, Ccl20, and Cxcl10, and delayed overexpression of NFκB inhibitor encoding genes, Nfkbia and Tnfaip3. IL-10 deficiency, or immunoblockade of IL-10 receptor, impacted on TNF-induced endogenous NFκB activity and downstream NFκB target gene transcription. Intestinal epithelium-derived IL-10 appears to play a crucial role as a positive regulator of the canonical NFκB pathway, contributing to maintenance of intestinal homeostasis. This is particularly important in the context of an inflammatory environment and highlights the potential for future tissue-targeted IL-10 therapeutic intervention.
Satellite Observations Are Needed to Understand Ocean Acidification and Multi-Stressor Impacts on Fish Stocks in a Changing Arctic Ocean
Authors: Green Hannah L. , Findlay Helen S. , Shutler Jamie D. , Land Peter E. , Bellerby Richard G. J.
Published: June 2021

It is widely projected that under future climate scenarios the economic importance of Arctic Ocean fish stocks will increase. The Arctic Ocean is especially vulnerable to ocean acidification and already experiences low pH levels not projected to occur on a global scale until 2100. This paper outlines how ocean acidification must be considered with other potential stressors to accurately predict movement of fish stocks toward, and within, the Arctic and to inform future fish stock management strategies. First, we review the literature on ocean acidification impacts on fish, next we identify the main obstacles that currently preclude ocean acidification from Arctic fish stock projections. Finally, we provide a roadmap to describe how satellite observations can be used to address these gaps: improve knowledge, inform experimental studies, provide regional assessments of vulnerabilities, and implement appropriate management strategies. This roadmap sets out three inter-linked research priorities: (1) Establish organisms and ecosystem physiochemical baselines by increasing the coverage of Arctic physicochemical observations in both space and time; (2) Understand the variability of all stressors in space and time; (3) Map life histories and fish stocks against satellite-derived observations of stressors.
Staphylococcus epidermidis Has Growth Phase Dependent Affinity for Fibrinogen and Resulting Fibrin Clot Elasticity
Authors: Vitale Carolyn , Ma Tianhui Maria , Sim Janice , Altheim Christopher , Martinez-Nieves Erika , Kadiyala Usha , Solomon Michael J. , VanEpps J. Scott
Published: June 2021

Bacterial infection and thrombosis are highly correlated, especially in patients with indwelling medical devices. Coagulase-negative staphylococci, typified by Staphylococcus epidermidis, are a common cause of medical device infections owing to their biofilm forming capacity which provides protection from antibiotics and host immune response. Attention has been drawn to the interaction between S. epidermidis and host proteins, specifically fibrinogen. However, little is known regarding the impact of the transition from planktonic to biofilm forming phenotype on this interaction. Here we investigate the growth phase dependence of bacteria-fibrinogen interaction and the resulting effect on fibrin clot formation, structure, and mechanics. Flow cytometry demonstrated growth phase dependent affinity for fibrinogen. To mimic intravascular device seeding, we quantified the adhesion of S. epidermidis to a fibrinogen coated surface under continuous flow conditions in vitro. The bacterial deposition rate onto fibrinogen was significantly greater for stationary (5,360 ± 1,776 cells/cm2s) versus exponential phase (2,212 ± 264, cells/cm2 s). Furthermore, the expression of sdrG–a cell surface adhesion protein with specificity for fibrinogen–was upregulated ∼twofold in the stationary versus the exponential phase. Rheometry and confocal microscopy demonstrated that stationary phase S. epidermidis slows clot formation and generates a more heterogeneous fibrin network structure with greater elasticity (G′ = 5.7 ± 1.0 Pa) compared to sterile fibrinogen (G′ = l.5 ± 0.2 Pa), while exponential phase cells had little effect. This work contributes to the current understanding of the growth phase dependent regulation of bacterial virulence factors and the correlation between bacterial infection and thrombosis.
Bifidobacterium breve Exopolysaccharide Blocks Dendritic Cell Maturation and Activation of CD4+ T Cells
Authors: Hickey Ana , Stamou Panagiota , Udayan Sreeram , Ramón-Vázquez Ana , Esteban-Torres Maria , Bottacini Francesca , Woznicki Jerzy Adam , Hughes Owen , Melgar Silvia , Ventura Marco , Van Sinderen Douwe , Rossini Valerio , Nally Ken
Published: June 2021

Exopolysaccharide (EPS) is a bacterial extracellular carbohydrate moiety which has been associated with immunomodulatory activity and host protective effects of several gut commensal bacteria. Bifidobacterium breve are early colonizers of the human gastrointestinal tract (GIT) but the role of EPS in mediating their effects on the host has not been investigated for many strains. Here, we characterized EPS production by a panel of human B. breve isolates and investigated the effect of EPS status on host immune responses using human and murine cell culture-based assay systems. We report that B. breve EPS production is heterogenous across strains and that immune responses in human THP-1 monocytes are strain-specific, but not EPS status-specific. Using wild type and isogenic EPS deficient mutants of B. breve strains UCC2003 and JCM7017 we show that EPS had strain-specific divergent effects on cytokine responses from murine bone marrow derived macrophages (BMDMs) and dendritic cells (BMDCs). The B. breve UCC2003 EPS negative (EPS–) strain increased expression of cytokine genes (Tnfa, Il6, Il12a, and Il23a) relative to untreated BMDCs and BMDCs treated with wild type strain. B. breve UCC2003 and JCM7017 EPS– strains increased expression of dendritic cell (DC) activation and maturation marker genes (Cd80, Cd83, and Cd86) relative to untreated BMDCs. Consistent with this, BMDCs co-cultured with B. breve UCC2003 and JCM7017 EPS– strains engineered to express OVA antigen activated OVA-specific OT-II CD4+ T-cells in a co-culture antigen-presentation assay while EPS proficient strains did not. Collectively, these data indicate that B. breve EPS proficient strains use EPS to prevent maturation of DCs and activation of antigen specific CD4+ T cells responses to B. breve. This study identifies a new immunomodulatory role for B. breve EPS and suggests it may be important for immune evasion of adaptive immunity by B. breve and contribute to host-microbe mutualism.
Therapeutic Drug Monitoring of Tigecycline in 67 Infected Patients and a Population Pharmacokinetics/Microbiological Evaluation of A. baumannii Study
Authors: Yang Tianli , Mei Hekun , Wang Jin , Cai Yun
Published: June 2021

Background

The widespread use of antibiotics has led to the emergence of multidrug-resistant (MDR) bacteria such as multidrug-resistant Acinetobacter baumannii (AB). Tigecycline (TGC), as the first glycylcycline antibiotic approved by FDA, is a broad-spectrum antibiotic which remains highly effective to treat AB infections.

Objective

To confirm the TGC treatment dosage and effectiveness to treat AB infections in the Chinese population by performing therapeutic drug monitoring (TDM).

Methods

This study was performed from October 2018 through March 2019 at the PLA General Hospital. A high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was validated and employed to determine the plasma concentrations of TGC in patients with infectious diseases. The minimum inhibitory concentration (MIC) of TGC to clinically isolated AB was determined by broth microdilution method, agar dilution method, and disk diffusion method. Moreover, a model of population pharmacokinetics/pharmacodynamics (PPK/PD) was constructed.

Results

A total of 186 plasma samples from 67 patients were detected by the validated HPLC-MS/MS method. The MIC values determined by the broth microdilution method were more sensitive and accurate than the other two methods. The microbial and clinical PK/PD breakpoints were reached when the maintenance dose of TGC was 100 mg.

Conclusion

Our study established a validated HPLC-MS/MS method to monitor the plasma concentrations of TGC. In view of the MIC range to AB isolates in our hospital and the PPK/PD modeling results, we recommend a relatively high dose of 100 mg q12h regimen to achieve the optimal clinical efficacy and antimicrobial response.
Highly Prevalent Multidrug-Resistant Campylobacter spp. Isolated From a Yellow-Feathered Broiler Slaughterhouse in South China
Authors: Bai Jie , Chen Zhengquan , Luo Kaijian , Zeng Fanliang , Qu Xiaoyun , Zhang Hongxia , Chen Kaifeng , Lin Qijie , He Haishan , Liao Ming , Zhang Jianmin
Published: June 2021

The purpose of this study was to investigate the prevalence, antimicrobial resistance, virulence genes, and genetic diversity of Campylobacter spp. along the yellow-feathered broiler slaughtering line in Southern China from December 2018 to June 2019. A total of 157 Campylobacter spp. isolates were identified from 1,102 samples (including 53.6% (75/140) of live chicken anal swab samples, 27.5% (44/160) of defeathering samples, 18.1% (29/160) of evisceration samples, 2.1% (3/140) of washing samples, 1.4% (2/140) of chilling samples, and 1.1% (4/362) of environmental samples). The prevalence of Campylobacter spp. was 14.2%, including 43.9% Campylobacter jejuni, 53.5% Campylobacter coli, and 2.5% other Campylobacter species. The highest antimicrobial resistance rate was found to be against sulfamethoxazole (138/157, 87.9%), and 90.4% (142/157) of the isolates were multidrug resistant (MDR). Examination of resistance-related genes revealed the double base mutated Thr-86-Ile, which informed ACA-TTA, with an Arg-79-Lys substitution in gyrA. Eleven virulence-associated genes (cadF, cdtA, cdtB, ciaB, flaA, imaA, dnaJ, plaA, virB11, racR, and cdtC) were also detected by a polymerase chain reaction (PCR) analysis, and cadF (81.5%) was the most prevalent. Based on an analysis of pulsed-field gel electrophoresis (PFGE) results, we found that Campylobacter spp. could be cross-contaminated throughout the entire slaughtering line. These results show that it is imperative to study the Campylobacter spp. from the yellow-feathered broiler along the slaughtering line in China to develop preventative and treatment measures for the poultry industry, as well as food safety and public health.
SmgGDS: An Emerging Master Regulator of Prenylation and Trafficking by Small GTPases in the Ras and Rho Families
Authors: Brandt Anthony C. , Koehn Olivia J. , Williams Carol L.
Published: June 2021

Newly synthesized small GTPases in the Ras and Rho families are prenylated by cytosolic prenyltransferases and then escorted by chaperones to membranes, the nucleus, and other sites where the GTPases participate in a variety of signaling cascades. Understanding how prenylation and trafficking are regulated will help define new therapeutic strategies for cancer and other disorders involving abnormal signaling by these small GTPases. A growing body of evidence indicates that splice variants of SmgGDS (gene name RAP1GDS1) are major regulators of the prenylation, post-prenylation processing, and trafficking of Ras and Rho family members. SmgGDS-607 binds pre-prenylated small GTPases, while SmgGDS-558 binds prenylated small GTPases. This review discusses the history of SmgGDS research and explains our current understanding of how SmgGDS splice variants regulate the prenylation and trafficking of small GTPases. We discuss recent evidence that mutant forms of RabL3 and Rab22a control the release of small GTPases from SmgGDS, and review the inhibitory actions of DiRas1, which competitively blocks the binding of other small GTPases to SmgGDS. We conclude with a discussion of current strategies for therapeutic targeting of SmgGDS in cancer involving splice-switching oligonucleotides and peptide inhibitors.
Vitamins in Cereals: A Critical Review of Content, Health Effects, Processing Losses, Bioaccessibility, Fortification, and Biofortification Strategies for Their Improvement
Authors: Garg Monika , Sharma Anjali , Vats Shreya , Tiwari Vandita , Kumari Anita , Mishra Vibhu , Krishania Meena
Published: June 2021

Around the world, cereals are stapled foods and good sources of vitamins A, B, and E. As cereals are inexpensive and consumed in large quantities, attempts are being made to enrich cereals using fortification and biofortification in order to address vitamin deficiency disorders in a vulnerable population. The processing and cooking of cereals significantly affect vitamin content. Depending on grain structure, milling can substantially reduce vitamin content, while cooking methods can significantly impact vitamin retention and bioaccessibility. Pressure cooking has been reported to result in large vitamin losses, whereas minimal vitamin loss was observed following boiling. The fortification of cereal flour with vitamins B1, B2, B3, and B9, which are commonly deficient, has been recommended; and in addition, region-specific fortification using either synthetic or biological vitamins has been suggested. Biofortification is a relatively new concept and has been explored as a method to generate vitamin-rich crops. Once developed, biofortified crops can be utilized for several years. A recent cereal biofortification success story is the enrichment of maize with provitamin A carotenoids.
A Non-Coding RNA Network Involved in KSHV Tumorigenesis
Authors: Naipauer Julián , García Solá Martín E. , Salyakina Daria , Rosario Santas , Williams Sion , Coso Omar , Abba Martín C. , Mesri Enrique A. , Lacunza Ezequiel
Published: June 2021

Regulatory pathways involving non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non-coding RNAs (lncRNA), have gained great relevance due to their role in the control of gene expression modulation. Using RNA sequencing of KSHV Bac36 transfected mouse endothelial cells (mECK36) and tumors, we have analyzed the host and viral transcriptome to uncover the role lncRNA-miRNA-mRNA driven networks in KSHV tumorigenesis. The integration of the differentially expressed ncRNAs, with an exhaustive computational analysis of their experimentally supported targets, led us to dissect complex networks integrated by the cancer-related lncRNAs Malat1, Neat1, H19, Meg3, and their associated miRNA-target pairs. These networks would modulate pathways related to KSHV pathogenesis, such as viral carcinogenesis, p53 signaling, RNA surveillance, and cell cycle control. Finally, the ncRNA-mRNA analysis allowed us to develop signatures that can be used to an appropriate identification of druggable gene or networks defining relevant AIDS-KS therapeutic targets.
Disparity in Access to Oncology Precision Care: A Geospatial Analysis of Driving Distances to Genetic Counselors in the U.S.
Authors: Bellaiche Mathias M. J. , Fan Winnie , Walbert Harold John , McClave Egan H. , Goodnight Bradley L. , Sieling Fred H. , Moore Rebekah A. , Meng Weilin , Black Christopher M.
Published: June 2021

In the US, the growing demand for precision medicine, particularly in oncology, continues to put pressure on the availability of genetic counselors to meet that demand. This is especially true in certain geographic locations due to the uneven distribution of genetic counselors throughout the US. To assess these disparities, access to genetic counselors of all specialties is explored by geography, cancer type, and social determinants of health. Geospatial technology was used to combine and analyze genetic counselor locations and cancer incidence at the county level across the US, with a particular focus on tumors associated with BRCA mutations including ovarian, pancreatic, prostate and breast. Access distributions were quantified, and associations with region, cancer type, and socioeconomic variables were investigated using correlational tests. Nationally, in 2020, there were 4,813 genetic counselors, or 1.49 genetic counselors per 100,000 people, varying between 0.17 to 5.7 per 100,000 at the state level. Seventy-one percent of U.S. residents live within a 30-minute drive-time to a genetic counselor. Drive-times, however, are not equally distributed across the country – while 82% of people in metropolitan areas are 30 minutes from a genetic counselor, only 6% of people in nonmetro areas live within 30 minutes’ drive time. There are statistically significant differences in access across geographical regions, socioeconomics and cancer types. Access to genetic counselors for cancer patients differs across groups, including regional, socioeconomic, and cancer type. These findings highlight areas of the country that may benefit from increased genetic counseling provider supply, by increasing the number of genetic counselors in a region or by expanding the use of telegenetics a term used to describe virtual genetic counseling consults that occur via videoconference. Policy intervention to allow genetic counselors to bill for their services may be an effective route for increasing availability of genetic counselors’ services However, genetic counselors in direct patient care settings also face other challenges such as salary, job satisfaction, job recognition, overwork/burnout, and appropriate administrative/clinical support, and addressing these issues should also be considered along with policy support. These results could support targeted policy reform and alternative service models to increase access to identified pockets of unmet need, such as telemedicine. Data and analysis are available to the public through an interactive dashboard1.
Enhanced Skin Incisional Wound Healing With Intracellular ATP Delivery via Macrophage Proliferation and Direct Collagen Production
Authors: Sarojini Harshini , Bajorek Alexander , Wan Rong , Wang Jianpu , Zhang Qunwei , Billeter Adrian T. , Chien Sufan
Published: June 2021

This study sought to use a newly developed intracellular ATP delivery to enhance incisional wound healing to reduce surgical wound dehiscence and to explore possible mechanism for this effect. Thirty-five adult New Zealand white rabbits were used. Skin incisions were made on the back and closed. ATP-vesicles were mixed with a neutral cream for one side of the wounds while the neutral cream alone was used on the other side of the wounds. Laser speckle contrast imaging (LSCI), biomechanical, histological, and immunohistochemical analyses were performed 7 and 14 days after surgery, and macrophage culture was used to test the enhanced collagen production ability. Among them, 10 were used for wound perfusion study and 25 were used for wound biomechanical and histological/immunohistochemical studies. Wound tissue perfusion was reduced after surgery especially in early days. Wound tissue tensile strength, breaking stress, and elasticity were all much higher in the ATP-vesicle treated group than in the cream treated group at days 7 and 14. The healing was complemented by earlier macrophage accumulation, in situ proliferation, followed by direct collagen production. The results were further confirmed by human macrophage culture. It was concluded that intracellular ATP delivery enhanced healing strength of incisional wounds via multiple mechanisms.
Gut Microbiota: A Novel Regulator of Cardiovascular Disease and Key Factor in the Therapeutic Effects of Flavonoids
Authors: Li Qinyu , Gao Bing , Siqin Bateer , He Qian , Zhang Ru , Meng Xiangxi , Zhang Naiheng , Zhang Na , Li Minhui
Published: June 2021

Cardiovascular disease is the main cause of death worldwide, and traditional cardiovascular risk factors cannot fully explain the occurrence of the disease. In recent years, the relationship between gut microbiota and its metabolites and cardiovascular disease has been a hot study topic. The changes in gut microbiota and its metabolites are related to the occurrence and development of atherosclerosis, myocardial infarction, heart failure, and hypertension. The mechanisms by which gut microbiota and its metabolites influence cardiovascular disease have been reported, although not comprehensively. Additionally, following ingestion, flavonoids are decomposed into phenolic acids that are more easily absorbed by the body after being processed by enzymes produced by intestinal microorganisms, which increases flavonoid bioavailability and activity, consequently affecting the onset of cardiovascular disease. However, flavonoids can also inhibit the growth of harmful microorganisms, promote the proliferation of beneficial microorganisms, and maintain the balance of gut microbiota. Hence, it is important to study the relationship between gut microbiota and flavonoids to elucidate the protective effects of flavonoids in cardiovascular diseases. This article will review the role and mechanism of gut microbiota and its metabolites in the occurrence and development of atherosclerosis, myocardial infarction, heart failure, and hypertension. It also discusses the potential value of flavonoids in the prevention and treatment of cardiovascular disease following their transformation through gut microbiota metabolism.
Mechanical Principles Governing the Shapes of Dendritic Spines
Authors: Alimohamadi Haleh , Bell Miriam K. , Halpain Shelley , Rangamani Padmini
Published: June 2021

Dendritic spines are small, bulbous protrusions along the dendrites of neurons and are sites of excitatory postsynaptic activity. The morphology of spines has been implicated in their function in synaptic plasticity and their shapes have been well-characterized, but the potential mechanics underlying their shape development and maintenance have not yet been fully understood. In this work, we explore the mechanical principles that could underlie specific shapes using a minimal biophysical model of membrane-actin interactions. Using this model, we first identify the possible force regimes that give rise to the classic spine shapes—stubby, filopodia, thin, and mushroom-shaped spines. We also use this model to investigate how the spine neck might be stabilized using periodic rings of actin or associated proteins. Finally, we use this model to predict that the cooperation between force generation and ring structures can regulate the energy landscape of spine shapes across a wide range of tensions. Thus, our study provides insights into how mechanical aspects of actin-mediated force generation and tension can play critical roles in spine shape maintenance.
An in silico hiPSC-Derived Cardiomyocyte Model Built With Genetic Algorithm
Authors: Akwaboah Akwasi D. , Tsevi Bright , Yamlome Pascal , Treat Jacqueline A. , Brucal-Hallare Maila , Cordeiro Jonathan M. , Deo Makarand
Published: June 2021

The formulation of in silico biophysical models generally requires optimization strategies for reproducing experimentally observed phenomena. In electrophysiological modeling, robust nonlinear regressive methods are often crucial for guaranteeing high fidelity models. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), though nascent, have proven to be useful in cardiac safety pharmacology, regenerative medicine, and in the implementation of patient-specific test benches for investigating inherited cardiac disorders. This study demonstrates the potency of heuristic techniques at formulating biophysical models, with emphasis on a hiPSC-CM model using a novel genetic algorithm (GA) recipe we proposed. The proposed GA protocol was used to develop a hiPSC-CM biophysical computer model by fitting mathematical formulations to experimental data for five ionic currents recorded in hiPSC-CMs. The maximum conductances of the remaining ionic channels were scaled based on recommendations from literature to accurately reproduce the experimentally observed hiPSC-CM action potential (AP) metrics. Near-optimal parameter fitting was achieved for the GA-fitted ionic currents. The resulting model recapitulated experimental AP parameters such as AP durations (APD50, APD75, and APD90), maximum diastolic potential, and frequency of automaticity. The outcome of this work has implications for validating the biophysics of hiPSC-CMs in their use as viable substitutes for human cardiomyocytes, particularly in cardiac safety pharmacology and in the study of inherited cardiac disorders. This study presents a novel GA protocol useful for formulating robust numerical biophysical models. The proposed protocol is used to develop a hiPSC-CM model with implications for cardiac safety pharmacology.