bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenotypic and Genotypic Antibiotic Resistance Patterns in Helicobacter pylori Strains From Ethnically Diverse Population in México
Authors: Camorlinga-Ponce Margarita , Gómez-Delgado Alejandro , Aguilar-Zamora Emmanuel , Torres Roberto C. , Giono-Cerezo Silvia , Escobar-Ogaz Antonio , Torres Javier
Published: February 2021

Helicobacter pylori strains carry a range of mutations in genes that confer antimicrobial resistance and restrict the available options to treat the infection. Latin America is a region that conserve a large number of indigenous communities relatively isolated that practice a traditional medicine without consumption of drugs. We hypothesized that rates of antibiotic resistance are lower in these communities. Recent progress in whole-genome sequencing has allowed the study of drug susceptibility by searching for the known mutations associated with antibiotic resistance. The aim of this work was to study trends of antibiotic resistance over a 20-year period in Mexican H. pylori strains and to compare susceptibility between strains from Mexican mestizos and from indigenous population; we also aimed to learn the prevalence of mutational patterns in genes gyrA, gyrB, rdxA, frxA, rpsU, omp11, dppA, and 23S rRNA and its association with phenotypic tests. Resistance to clarithromycin, metronidazole, amoxicillin and levofloxacin was determined in167 H. pylori isolates by E-test, and the occurrence of mutational patterns in specific genes was determined by whole genome sequencing (WGS). The trend of resistance over 20 years in mestizo isolates showed significant resistant increase for clarithromycin and levofloxacin to frequencies that banned its clinical use. Resistance in H. pylori isolates of native communities was lower for all antibiotics tested. Phenotypic resistance showed good to moderate correlation with genotypic tests. Genetic methods for characterizing antibiotic resistance require further validation in each population.
Modulation of Bacterial Fitness and Virulence Through Antisense RNAs
Authors: Millar Jess A. , Raghavan Rahul
Published: February 2021

Regulatory RNAs contribute to gene expression control in bacteria. Antisense RNAs (asRNA) are a class of regulatory RNAs that are transcribed from opposite strands of their target genes. Typically, these untranslated transcripts bind to cognate mRNAs and rapidly regulate gene expression at the post-transcriptional level. In this article, we review asRNAs that modulate bacterial fitness and increase virulence. We chose examples that underscore the variety observed in nature including, plasmid- and chromosome-encoded asRNAs, a riboswitch-regulated asRNA, and asRNAs that require other RNAs or RNA-binding proteins for stability and activity. We explore how asRNAs improve bacterial fitness and virulence by modulating plasmid acquisition and maintenance, regulating transposon mobility, increasing resistance against bacteriophages, controlling flagellar production, and regulating nutrient acquisition. We conclude with a brief discussion on how this knowledge is helping to inform current efforts to develop new therapeutics.
The Association Between Plasma Hyaluronan Level and Plaque Types in ST-Segment–Elevation Myocardial Infarction Patients
Authors: Li Jiannan , Tan Yu , Sheng Zhaoxue , Zhou Peng , Liu Chen , Zhao Hanjun , Song Li , Zhou Jinying , Chen Runzhen , Chen Yi , Yan Hongbing
Published: February 2021

Background: The metabolism of hyaluronan (HA) is widely known to be involved in the process of acute coronary syndrome, but it is unknown how circulating HA levels change in ST-Segment–Elevation Myocardial Infarction (STEMI) patients and whether HA is associated with plaque morphology, including rupture and erosion.

Objectives: This study focused on the changes in the plasma levels of high molecular weight (HMW) HA (>35 kDa) and CD44 in STEMI patients and their relationship with plaque morphology evaluated by optical coherence tomography (OCT).

Methods: We prospectively enrolled 3 cohorts in this study, including 162 patients with STEMI, 34 patients with stable coronary artery disease (S-CAD) and 50 healthy controls. Plaque morphology was detected by OCT analysis, and the plasma levels of HMW HA and CD44 were examined by enzyme-linked immunosorbent assay (ELISA). We compared plasma level of HMW HA and CD44 among STEMI patients, S-CAD patients and healthy controls, as well as in plaque rupture and plaque erosion.

Results: The plasma levels of HMW HA and CD44 were significantly lower in STEMI patients than in healthy controls (p = 0.009 and p < 0.001, respectively). In addition, plasma level of HMW HA in plaque erosion was significantly lower than that in plaque rupture (p = 0.021), whereas no differences were found in plasma level of soluble CD44 between plaque rupture and erosion.

Conclusions: Low levels of circulating HMW HA and CD44 were independently correlated with STEMI, and low levels of HMW HA were associated with plaque erosion compared with rupture. Moreover, plasma HMW HA might be a useful biomarker for identifying plaque erosion to improve the risk stratification and management of STEMI patients.
A Policy and Practice Review of Consumer Protections and Their Application to Hospital-Sourced Data Aggregation and Analytics by Third-Party Companies
Authors: Rahimzadeh Vasiliki
Published: February 2021

The Office of the National Coordinator for Health Information Technology estimates that 96% of all U.S. hospitals use a basic electronic health record, but only 62% are able to exchange health information with outside providers. Barriers to information exchange across EHR systems challenge data aggregation and analysis that hospitals need to evaluate healthcare quality and safety. A growing number of hospital systems are partnering with third-party companies to provide these services. In exchange, companies reserve the rights to sell the aggregated data and analyses produced therefrom, often without the knowledge of patients from whom the data were sourced. Such partnerships fall in a regulatory grey area and raise new ethical questions about whether health, consumer, or health and consumer privacy protections apply. The current opinion probes this question in the context of consumer privacy reform in California. It analyzes protections for health information recently expanded under the California Consumer Privacy Act (“CA Privacy Act”) in 2020 and compares them to protections outlined in the Health Information Portability and Accountability Act (“Federal Privacy Rule”). Four perspectives are considered in this ethical analysis: 1) standards of data deidentification; 2) rights of patients and consumers in relation to their health information; 3) entities covered by the CA Privacy Act; 4) scope and complementarity of federal and state regulations. The opinion concludes that the CCPA is limited in its application when health information is processed by a third-party data aggregation company that is contractually designated as a business associate; when health information is deidentified; and when hospital data are sourced from publicly owned and operated hospitals. Lastly, the opinion offers practical recommendations for facilitating parity between state and federal health data privacy laws and for how a more equitable distribution of informational risks and benefits from the sale of aggregated hospital data could be fostered and presents ways both for-profit and nonprofit hospitals can sustain patient trust when negotiating partnerships with third-party data aggregation companies.
Patent Landscape of Automated Systems for Personalized Health Management (ASHM): Features, Shortcomings, and Implications for Developing an Optimal ASHM
Authors: Martyushev-Poklad Andrey , Yankevich Dmitry
Published: February 2021

The current struggle of national health care systems against global epidemic of non-communicable diseases (NCD) is both clinically ineffective and cost ineffective. On the other hand, rapid development of systems biology, P4 medicine and new digital and communication technologies are good prerequisites for creating an affordable and scalable automated system for personalized health management (ASHM). The current practice of ASHM is better represented in patent literature (36 relevant documents found in Google Patents and USPTO) than in scientific papers (17 documents found in PubMed and Google Scholar). However, only a small fraction of publications disclose a complete self-sufficient system. Problems that authors of ASHM aim to address, methodological approaches, and the most important technical solutions are reviewed and discussed along with shortcomings and limitations. Technical solutions for ASHM currently commercialized or described in literature generally fail to enable practicable, scalable and affordable automated and individualized screening, monitoring, prevention and correction of human health conditions. They also fail to provide a decision support system to patients that would help effectively prevent major NCD and their complications, be accessible and cost effective, consider individual lifestyle factors and involve patients in management of their individual health. Based on analysis of the literature, models of health and care, we propose conceptual framework for developing an ASHM that would be free from the mentioned problems.
Tectonic Fabric, Geochemistry, and Zircon-Monazite Geochronology as Proxies to Date an Orogeny: Example of South Delhi Orogeny, NW India, and Implications for East Gondwana Tectonics
Authors: Singh Subhash , De Waele Bert , Shukla Anjali , Umasankar B. H. , Biswal Tapas Kumar
Published: February 2021

We have dated the South Delhi orogeny, Aravalli-Delhi Mobile Belt (ADMB), NW India, using the tectonic fabric, geochemistry, and zircon-monazite geochronology as the proxies. The South Delhi Terrane (SDT), a passive margin domain in the ADMB, consists of multiply deformed (D1–D4) greenschist facies rocks and several granite plutons. The D1deformation is characterized by pervasive isoclinal recumbent F1fold and axial planar tectonometamorphic fabric, S1, developed in all rock types. The S1minerals belong to peak greenschist facies metamorphism, M1, suggesting syntectonic nature of M1with D1. The age of the D1-M1is constrained by the syncollisional peralkaline S type Sewariya granite which is characterized by magmatic/submagmatic fabric (Sm) coplanar with the S1. The margin of the pluton is turned into quartzofeldspathic gneiss carrying the evidence of high temperature deformation. The age of Sewariya granite is estimated at ca. 878 Ma by zircon geochronology. The D1-M1is further constrained by monazite geochronology of the mica schist at ca. 865–846 Ma. The other granite plutons and metarhyolite are pre-D1and emplaced at ca. 992–946 Ma. The D2deformation produced NE-SW trending open upright F2folds coaxial with the F1, and northwesterly vergent F2–axial planar thrusts. Monazite geochronology constrains the D2at ca. 811–680 Ma. The D3is characterized by small to large scale NW-SE folds, and the D4by faults and fractures marking the brittle deformation in the rocks. The D4is constrained by monazite geochronology at ca. 588–564 Ma. There are upper amphibolitic tectonic slivers along the D2-Phulad thrust, belonging to the pre-Delhi rocks, which show ca. 1,638 Ma metamorphism age. From the above study, it is suggested that the South Delhi orogeny belongs to ca. 878–680 Ma marking the final amalgamation of Marwar Craton with the rest of India. This overlaps the early phase of the Pan-African orogeny (900–630 Ma). The brittle deformation, D4, coincides with Kuunga orogeny (650–500 Ma). Our study implies that India, like other continents in the East Gondwana, underwent amalgamation of internal blocks until the late part of the Neoproterozoic.
Magnetic Susceptibility Properties of Loess From the Willendorf Archaeological Site: Implications for the Syn/Post-Depositional Interpretation of Magnetic Fabric
Authors: Zeeden Christian , Hambach Ulrich
Published: February 2021

At the Willendorf site Upper Paleolithic archeological layers associated to early Aurignacian cultures were found. The environmental conditions of the associated society, potentially co-existing with Neanderthal groups, is still not fully understood. Here, we report on environmental magnetic analyses including anisotropy of the magnetic susceptibility (AMS) carried out on loessic aeolian sediments at the Willendorf site. Data on lineation, foliation and the degree of anisotropy were used to assess depositional and post-depositional magnetic fabric properties and to deduce site-specific environmental processes. Overall, the loess is of aeolian origin and shows magnetic enhancement and magnetic fabric properties similar to those of other European loess geoarchives, but the magnetic mineralogy differs from many ‘dry’ loess sites, insofar as it shows a higher susceptibility during heating. We infer an enhanced neoformation of magnetite during heating due to the presence of organic matter. While at face value the AMS properties are indicative of pure aeolian loess consistent with previous studies, imbrication suggests post-depositional slope movement toward the Danube, which obscures inferences on palaeo-wind direction. It is well possible that these post-depositional magnetic fabric alterations occur at other localities with similar geomorphological settings.
High-Resolution Stable Isotope Paleotopography of the John Day Region, Oregon, United States
Authors: Kukla Tyler , Ibarra Daniel Enrique , Rugenstein Jeremy K. Caves , Gooley Jared T. , Mullins Casey E. , Kramer Samuel , Moragne Danielle Y. , Chamberlain C. Page
Published: February 2021

The John Day region of central Oregon, United States contains ∼50 million years of near-continuous, fossiliferous sedimentation, representing one of the world’s richest archives of Cenozoic terrestrial ecosystems and climate. Stable isotope proxy data from this region are commonly used to infer the elevation history of the Cascades, which intercept westerly moisture in transit to the John Day region. However, the Blue Mountains, which accreted in the Mesozoic, create a region of local high topography that can confound signals of Cascades uplift. John Day deposits, including the John Day Formation, are divided into an eastern facies located within the Blue Mountains and a western facies in the adjacent plains. As a result, the Blue Mountains may have supported gradients in climate and ecology between the eastern and western facies, and constraining these gradients is necessary for reconstructing past topography and ecosystem change. In order to define the Cenozoic extent and magnitude of Blue Mountains topography we use oxygen isotopes in authigenic clay minerals to construct a spatially resolved map of local elevation. We find that the oxygen isotope composition of clay minerals within the Blue Mountains is ∼3‰ lower than in the adjacent high plains, and this offset is mostly constant throughout our record (spanning ∼50 – 5 Ma). We attribute this offset to Blue Mountains topography, either directly from upslope rainout or indirectly through the effect of elevation on local variations in precipitation seasonality. Our results highlight the importance of local topographic features in regional paleotopography reconstructions and provide important biogeographical context for the rich paleo-floral and -faunal records preserved in John Day sediments.
Contradictory Perspectives on Academic Support: Beyond Linear Logic
Authors: Hallett Fiona
Published: February 2021

This paper employs a Square of Opposition as an interpretivist heuristic device in order to interrogate perceptions of academic support. The Square of Opposition is used to move beyond binary explanations of academic development subsumed within learner-/discipline-focussed practices or institutionally /epistemologically constrained systems; an exemplar data set is used to achieve this. The results of this analysis demonstrate that positions that might normally be understood as opposed in fact share common features, at least where some key concepts are concerned. In particular, two “contradictories” are explored: the first of these critiques the differences and similarities between contested meaning-making and knowledge dissemination and the second analyses the disjuncture between skills-focussed instruction and academic literacy as a social practice. This form of analysis offers new insights that directly speak to the ways in which we conceive of, and enact, teaching, personal tutoring and academic advising.
Educator Beliefs Around Supporting Early Self-Regulation: Development and Evaluation of the Self-Regulation Knowledge, Attitudes and Self-Efficacy Scale
Authors: Vasseleu Elena , Neilsen-Hewett Cathrine , Ehrich John , Cliff Ken , Howard Steven James
Published: February 2021

The current study sought to investigate the extent to which early childhood educators’ confidence in knowledge, attitudes and self-efficacy for supporting early self-regulation predicted educator behavior and children’s self-regulation outcomes. Data from a diverse sample of 165 early childhood educators participating in a cluster Randomized Control Trial evaluation of a self-regulation intervention were utilized to evaluate the construct validity, reliability and predictive properties of the Self-Regulation Knowledge, Attitudes and Self-Efficacy scale. Evaluation via traditional (EFA, Cronbach’s Alpha) and modern approaches (Rasch Analysis) yielded a valid and reliable 25-item scale, comprising three distinct yet related subscales (i.e., confidence in knowledge, attitudes, self-efficacy). For educators assigned to the intervention group, self-efficacy significantly predicted educators perceived competency to implement the self-regulation intervention as well as their perceptions around the effectiveness of the intervention to enhance children’s self-regulation. For educators assigned to the control group (i.e., practice as usual), educator attitudes longitudinally predicted children’s end-of-year status and change in self-regulation (over 6 months later). Findings from this study suggest the importance of pre-school educators’ beliefs for fostering early self-regulation and highlight a need to further explore the impact of these beliefs with regard to educator engagement with intervention.
Timing the Juvenile-Adult Neurohormonal Transition: Functions and Evolution
Authors: Barredo Celia G. , Gil-Marti Beatriz , Deveci Derya , Romero Nuria M. , Martin Francisco A.
Published: February 2021

Puberty and metamorphosis are two major developmental transitions linked to the reproductive maturation. In mammals and vertebrates, the central brain acts as a gatekeeper, timing the developmental transition through the activation of a neuroendocrine circuitry. In addition to reproduction, these neuroendocrine axes and the sustaining genetic network play additional roles in metabolism, sleep and behavior. Although neurohormonal axes regulating juvenile-adult transition have been classically considered the result of convergent evolution (i.e., analogous) between mammals and insects, recent findings challenge this idea, suggesting that at least some neuroendocrine circuits might be present in the common bilaterian ancestor Urbilateria. The initial signaling pathways that trigger the transition in different species appear to be of a single evolutionary origin and, consequently, many of the resulting functions are conserved with a few other molecular players being co-opted during evolution.
Assessing CeO2 and TiO2 Nanoparticle Concentrations in the Seine River and Its Tributaries Near Paris
Authors: Phalyvong Karine , Sivry Yann , Pauwels Hélène , Gélabert Alexandre , Tharaud Mickaël , Wille Guillaume , Bourrat Xavier , Ranville James F. , Benedetti Marc F.
Published: February 2021

Motivation for detecting engineered nanoparticles (ENPs) in the environment comes from a need to understand fate and behavior of these materials in natural matrices. The difficulty lies in the low expected ENP particle number concentration (PNC) and the presence of a large and variable background concentration of natural NPs. We report the PNCs and characteristics of cerium-bearing nanoparticles (Ce-NPs) and titanium-bearing nanoparticles (Ti-NPs) in an aquatic matrix (the Seine River and three of its tributaries) with the use of single particle ICP-MS (spICPMS) and electron microscopy (FEG-SEM). Ce-bearing and Ti-bearing particles were observed in suspended particulate matter collected onto 0.2 μm and 1 kDa filters, using FEG-SEM imaging. At Marnay-sur-Seine, the upstream point, PNCs for Ce-NPs and Ti-NPs were 0.47 ± 0.07 × 106 and 1.35 ± 0.17 × 106 particles as measured by spICPMS. The maximum PNC for both Ce-NPs and Ti-NPs, 1.59 ± 0.10 × 106 particles mL−1 and 5.89 ± 0.10 × 106 particles mL−1, respectively, were found in the Marne River, a major tributary to the Seine. It was shown that downstream of each confluence, an increase in the PNC of the Seine is observed, suggesting a significant contribution of the different tributaries. Mass balance of particles flows and elemental ratios of Ce/La showed that in the Marne and the Oise River, a contribution of natural CeO2 NPs exists. The anthropogenic contribution in TiO2 ENPs for the Marne River was further assessed with Ti/Al, Ti/V, and Ti/Y elemental ratios. Near constant element ratios in the Seine below the Orge River and Paris city suggest neither contribute significantly to Ce or Ti NP concentrations. The study provides further investigation of the strengths and limitations of the application of spICPMS to natural samples and contributes data to the currently highly-limited dataset on natural NP backgrounds in rivers, information that is key to assessing the potential for quantifying the input of ENPs to surface waters. Of the total mass of Ce and Ti, 83 and 90%, respectively, could be detected as particles by spICPMS.
Analysis of Information Feedback on Residential Energy Conservation and the Implications: The Case of China
Authors: Li Zhuangai , Cao Xia
Published: February 2021

Household electricity consumption has increased significantly over the last two decades, leading to a series of policy interventions targeting to reduce electricity consumption in the residential sector. Information feedback regarding household electricity consumption is considered a cost-effective approach to promoting energy conservation. Various studies have so far covered the effects of information feedback on electricity consumption, yet the variations in both the types of feedback provided and the research methodologies have made it difficult to draw plausible conclusions. In China’s case, less due regard has been given to the effectiveness of various types of information feedback. This study has compared the effectiveness of information feedback between emailing electricity bills to households and installing smart meters in terms of promoting electricity conservation by employing empirical survey data from the Chinese General Social Survey with the help of the propensity score matching method. The results show that information provision via information bills curtails electricity consumption by around 20%, whereas information feedback via smart meters installation has no positive effects on household electricity conservation due to lack of access and knowledge to understand the displays of advanced meters. In light of the above results, the study suggests that policy-makers stress the importance of information feedback-based initiatives and improve the information feedback capacity of smart meters through training and education.
Long-Term Empirical Studies Highlight Multiple Drivers of Temporal Change in Bird Fauna in the Wet Forests of Victoria, South-Eastern Australia
Authors: Lindenmayer David , Bowd Elle , McBurney Lachlan
Published: February 2021

Birds are high profile elements of the vertebrate biota in almost all terrestrial ecosystems worldwide. Many studies have uncovered evidence of a decline in bird biodiversity, but temporal patterns of change vary among ecosystems and among bird species with different life history traits. Ecosystem-specific, long-term studies are critical for identifying patterns of temporal change in bird biodiversity and the drivers of that change. Here we present a case study of drivers of temporal change in the bird fauna of the Mountain Ash and Alpine Ash eucalypt forests of south-eastern Australia. Using insights from observational studies and experiments conducted over the past 18 years, we discuss the direct and interactive effects of fire and logging on birds. The extent and severity of wildfires have major negative effects on almost all bird species, and have persisted for more than a decade after the last major conflagration (in 2009). Logging has markedly different effects on birds than those quantified for fire, and may have resulted in elevated levels of site occupancy in remaining uncut areas in the landscape. Both fire and logging have led to marked losses in the extent of old growth forest in Mountain Ash and Alpine Ash ecosystems. This is a concern given the strong association of most species of birds with old forest relative to younger age cohorts. Based on an understanding of the effects of fire and logging as drivers of change, we propose a series of inter-related management actions designed to enhance the conservation of avifauna in Mountain Ash and Alpine Ash ecosystems. A particular focus of management must be on increasing the interval between fires and limiting the spatial extent of wildfires and, in turn, significantly expanding the extent of old growth forest. This is because old growth forest is where most bird species are most likely to occur, and in the event of future wildfires, where fire severity will be lowest. Expansion of the old growth estate will require commercial logging operations to be excluded from large parts of Mountain Ash and Alpine Ash forests.
Linkage Between Site Features and Soil Characteristics Within a Mediterranean Volcanic Area
Authors: Panico Speranza Claudia , Memoli Valeria , Santorufo Lucia , Esposito Francesco , De Marco Anna , Barile Rossella , Maisto Giulia
Published: February 2021

Altitude, exposure, and plant cover may have a significant impact on the soil system, affecting its abiotic characteristics and, in turn, soil microbial composition and activity. In the Mediterranean area, the relationships among environmental features and soil characteristics are still scarcely investigated. The present study aimed to evaluate the effects of altitude, slope exposure, and plant cover on soil abiotic characteristics and the responses of the soil microbial community. Surface soil was sampled at 32 field points of the Vesuvius Mountain (Southern Italy) at two slope exposures (North and South), two altitudes (600 and 900 m a.s.l), and under two different plant covers (pines and shrubs), and it was analyzed for soil abiotic and biotic characteristics. The results showed that soil characteristics mainly differed according to site altitude, but some characteristics also changed according to site exposure and plant cover. The soil organic carbon (Corg) showed significant high values at low altitude, south exposure, and under pines and played a role in influencing the soil microbial community. In soil covered by pines, the greatest soil Corg amount matched with the highest values of C/N ratio and fungal biomass. Finally, high Corg and water availability significantly enhanced the microbial activities.
Effects of Circular RNA of Chicken Growth Hormone Receptor Gene on Cell Proliferation
Authors: Xu Haidong , Leng Qiying , Zheng Jiahui , Adu-Asiamah Patricia , Lin Shudai , Li Ting , Wang Zhang , An Lilong , Zhao Zhuihui , Zhang Li
Published: February 2021

Animal growth and development are regulated by neural and endocrine growth axes, in which cell proliferation plays key roles. Recently, many research showed that circular RNAs were involved in hepatocyte and myoblast proliferation. Previously, we identified a circular RNA derived from the chicken GHR gene, named circGHR. However, the function of circGHR is unclear. The objective of this study was to investigate circGHR expression pattern and its roles in cell proliferation. Results indicated that circGHR was a closed-loop structure molecule, and it was richer in the nucleus of hepatocytes and myoblast. Real-time PCR showed that circGHR was increased from E13 to the 7th week in the liver but decreased in the thigh and breast muscle. The CCK-8 assay displayed that circGHR promoted cell proliferation. Simultaneously, the biomarker genes PCNA, CCND1, and CDK2 and the linear transcripts GHR and GHBP were upregulated when circGHR was overexpressed. Altogether, these data exhibited that circGHR could promote cell proliferation possibly by regulating GHR mRNA and GHBP expression.
Coupling of Co-expression Network Analysis and Machine Learning Validation Unearthed Potential Key Genes Involved in Rheumatoid Arthritis
Authors: Xiao Jianwei , Wang Rongsheng , Cai Xu , Ye Zhizhong
Published: February 2021

Rheumatoid arthritis (RA) is an incurable disease that afflicts 0.5–1.0% of the global population though it is less threatening at its early stage. Therefore, improved diagnostic efficiency and prognostic outcome are critical for confronting RA. Although machine learning is considered a promising technique in clinical research, its potential in verifying the biological significance of gene was not fully exploited. The performance of a machine learning model depends greatly on the features used for model training; therefore, the effectiveness of prediction might reflect the quality of input features. In the present study, we used weighted gene co-expression network analysis (WGCNA) in conjunction with differentially expressed gene (DEG) analysis to select the key genes that were highly associated with RA phenotypes based on multiple microarray datasets of RA blood samples, after which they were used as features in machine learning model validation. A total of six machine learning models were used to validate the biological significance of the key genes based on gene expression, among which five models achieved good performances [area under curve (AUC) >0.85], suggesting that our currently identified key genes are biologically significant and highly representative of genes involved in RA. Combined with other biological interpretations including Gene Ontology (GO) analysis, protein–protein interaction (PPI) network analysis, as well as inference of immune cell composition, our current study might shed a light on the in-depth study of RA diagnosis and prognosis.
Abiotic Stress-Responsive miRNA and Transcription Factor-Mediated Gene Regulatory Network in Oryza sativa: Construction and Structural Measure Study
Authors: Sharma Rinku , Upadhyay Shashankaditya , Bhattacharya Sudeepto , Singh Ashutosh
Published: February 2021

Climate changes and environmental stresses have a consequential association with crop plant growth and yield, meaning it is necessary to cultivate crops that have tolerance toward the changing climate and environmental disturbances such as water stress, temperature fluctuation, and salt toxicity. Recent studies have shown that trans-acting regulatory elements, including microRNAs (miRNAs) and transcription factors (TFs), are emerging as promising tools for engineering naive improved crop varieties with tolerance for multiple environmental stresses and enhanced quality as well as yield. However, the interwoven complex regulatory function of TFs and miRNAs at transcriptional and post-transcriptional levels is unexplored inOryza sativa. To this end, we have constructed a multiple abiotic stress responsive TF-miRNA-gene regulatory network forO. sativausing a transcriptome and degradome sequencing data meta-analysis approach. The theoretical network approach has shown the networks to be dense, scale-free, and small-world, which makes the network stable. They are also invariant to scale change where an efficient, quick transmission of biological signals occurs within the network on extrinsic hindrance. The analysis also deciphered the existence of communities (cluster of TF, miRNA, and genes) working together to help plants in acclimatizing to multiple stresses. It highlighted that genes, TFs, and miRNAs shared by multiple stress conditions that work as hubs or bottlenecks for signal propagation, for example, during the interaction between stress-responsive genes (TFs/miRNAs/other genes) and genes involved in floral development pathways under multiple environmental stresses. This study further highlights how the fine-tuning feedback mechanism works for balancing stress tolerance and how timely flowering enable crops to survive in adverse conditions. This study developed the abiotic stress-responsive regulatory network, APRegNet database (http://lms.snu.edu.in/APRegNet), which may help researchers studying the roles of miRNAs and TFs. Furthermore, it advances current understanding of multiple abiotic stress tolerance mechanisms.
Identification of Prognostic Stromal-Immune Score–Based Genes in Hepatocellular Carcinoma Microenvironment
Authors: Liu Shanshan , Yu Guangchuang , Liu Li , Zou Xuejing , Zhou Lang , Hu Erqiang , Song Yang
Published: February 2021

A growing amount of evidence has suggested the clinical importance of stromal and immune cells in the liver cancer microenvironment. However, reliable prognostic signatures based on assessments of stromal and immune components have not been well-established. This study aimed to identify stromal-immune score–based potential prognostic biomarkers for hepatocellular carcinoma. Stromal and immune scores were estimated from transcriptomic profiles of a liver cancer cohort from The Cancer Genome Atlas using the ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumors using Expression data) algorithm. Least absolute shrinkage and selection operator (LASSO) algorithm was applied to select prognostic genes. Favorable overall survivals and progression-free interval were found in patients with high stromal score and immune score, and 828 differentially expressed genes were identified. Functional enrichment analysis and protein–protein interaction networks further showed that these genes mainly participated in immune response, extracellular matrix, and cell adhesion. MMP9 (matrix metallopeptidase 9) was identified as a prognostic tumor microenvironment–associated gene by using LASSO and TIMER (Tumor IMmune Estimation Resource) algorithms and was found to be positively correlated with immunosuppressive molecules and drug response.
Characterizing the Leaf Transcriptome of Chrysanthemum rhombifolium (Ling et C. Shih), a Drought Resistant, Endemic Plant From China
Authors: Zhang Wenjie , Xu Hongyuan , Duan Xiaxia , Hu Jing , Li Jingjing , Zhao Liang , Ma Yueping
Published: February 2021

Chrysanthemum rhombifolium (Ling et C. Shih), an endemic plant that is extremely well-adapted to harsh environments. However, little is known about its molecular biology of the plant's resistant traits against stress, or even its molecular biology of overall plant. To investigate the molecular biology of C. rhombifolium and mechanism of stress adaptation, we performed transcriptome sequencing of its leaves using an Illumina platform. A total of 130,891 unigenes were obtained, and 97,496 (~74.5%) unigenes were annotated in the public protein database. The similarity search indicated that 40,878 and 74,084 unigenes showed significant similarities to known proteins from NCBI non-redundant and Swissprot protein databases, respectively. Of these, 56,213 and 42,005 unigenes were assigned to the Gene Ontology (GO) database and Cluster of Orthologous Groups (COG), respectively, and 38,918 unigenes were mapped into five main categories, including 18 KEGG pathways. Metabolism was the largest category (23,128, 59.4%) among the main KEGG categories, suggesting active metabolic processes in C. rhombifolium. About 2,459 unigenes were annotated to have a role in defense mechanism or stress tolerance. Transcriptome analysis of C. rhombifolium revealed the presence of 12,925 microsatellites in 10,524 unigenes and mono, trip, and dinucleotides having higher polymorphism rates. The phylogenetic analysis based on GME gene among related species confirmed the reliability of the transcriptomic data. This work is the first genetic study of C. rhombifolium as a new plant resource of stress-tolerant genes. This large number of transcriptome sequences enabled us to comprehensively understand the basic genetics of C. rhombifolium and discover novel genes that will be helpful in the molecular improvement of chrysanthemums.
An Improved Genome-Wide Polygenic Score Model for Predicting the Risk of Type 2 Diabetes
Authors: Liu Wei , Zhuang Zhenhuang , Wang Wenxiu , Huang Tao , Liu Zhonghua
Published: February 2021

Polygenic risk score (PRS) has been shown to be predictive of disease risk such as type 2 diabetes (T2D). However, the existing studies on genetic prediction for T2D only had limited predictive power. To further improve the predictive capability of the PRS model in identifying individuals at high T2D risk, we proposed a new three-step filtering procedure, which aimed to include truly predictive single-nucleotide polymorphisms (SNPs) and avoid unpredictive ones into PRS model. First, we filtered SNPs according to the marginal association p-values (p≤ 5× 10−2) from large-scale genome-wide association studies. Second, we set linkage disequilibrium (LD) pruning thresholds (r2) as 0.2, 0.4, 0.6, and 0.8. Third, we set p-value thresholds as 5× 10−2, 5× 10−4, 5× 10−6, and 5× 10−8. Then, we constructed and tested multiple candidate PRS models obtained by the PRSice-2 software among 182,422 individuals in the UK Biobank (UKB) testing dataset. We validated the predictive capability of the optimal PRS model that was chosen from the testing process in identifying individuals at high T2D risk based on the UKB validation dataset (n = 274,029). The prediction accuracy of the PRS model evaluated by the adjusted area under the receiver operating characteristics curve (AUC) showed that our PRS model had good prediction performance [AUC = 0.795, 95% confidence interval (CI): (0.790, 0.800)]. Specifically, our PRS model identified 30, 12, and 7% of the population at greater than five-, six-, and seven-fold risk for T2D, respectively. After adjusting for sex, age, physical measurements, and clinical factors, the AUC increased to 0.901 [95% CI: (0.897, 0.904)]. Therefore, our PRS model could be useful for population-level preventive T2D screening.
Research on the Mechanism of Soybean Resistance to Phytophthora Infection Using Machine Learning Methods
Authors: Chi Junxia , Song Shizeng , Zhang Hao , Liu Yuanning , Zhao Hengyi , Dong Liyan
Published: February 2021

Since the emergence of the Phytophthora sojae infection, economic losses of 10–20 billion U.S. dollars have been annually reported. Studies have revealed that P. sojae works by releasing effect factors such as small RNA in the process of infecting soybeans, but research on the interaction mechanism between plants and fungi at the small RNA level remains vague and unclear. For this reason, studying the resistance mechanism of the hosts after P. sojae invades soybeans has critical theoretical and practical significance for increasing soybean yield. The present article is premised on the high-throughput data published by the National Center of Biotechnology Information (NCBI). We selected 732 sRNA sequences through big data analysis whose expression level increased sharply after soybean was infected by P. sojae and 36 sRNA sequences with massive expression levels newly generated after infection. This article analyzes the resistance mechanism of soybean to P. sojae from two aspects of plant’s own passive stress and active resistance. These 768 sRNA sequences are targeted to soybean mRNA and P. sojae mRNA, and 2,979 and 1,683 targets are obtained, respectively. The PageRank algorithm was used to screen the core functional clusters, and 50 core nodes targeted to soybeans were obtained, which were analyzed for functional enrichment, and 12 KEGG_Pathway and 18 Go(BP) were obtained. The node targeted to P. sojae was subjected to functional enrichment analysis to obtain 11 KEGG_Pathway. The results show that there are multiple Go(BP) and KEGG_Pathway related to soybean growth and defense and reverse resistance of P. sojae. In addition, by comparing the small RNA prediction model of soybean resistance with Phytophthora pathogenicity constructed by the three machine learning methods of random forest, support vector machine, and XGBoost, about the accuracy, precision, recall rate, and F-measure, the results show that the three models have satisfied classification effect. Among the three models, XGBoost had an accuracy rate of 86.98% in the verification set.
Optimized Culture Conditions for Improved Growth and Functional Differentiation of Mouse and Human Colon Organoids
Authors: Wilson Sarah S. , Mayo Martha , Melim Terry , Knight Heather , Patnaude Lori , Wu Xiaoming , Phillips Lucy , Westmoreland Susan , Dunstan Robert , Fiebiger Edda , Terrillon Sonia
Published: February 2021

Background & Aims

Diligent side-by-side comparisons of how different methodologies affect growth efficiency and quality of intestinal colonoids have not been performed leaving a gap in our current knowledge. Here, we summarize our efforts to optimize culture conditions for improved growth and functional differentiation of mouse and human colon organoids.

Methods

Mouse and human colon organoids were grown in four different media. Media-dependent long-term growth was measured by quantifying surviving organoids via imaging and a cell viability readout over five passages. The impact of diverse media on differentiation was assessed by quantifying the number of epithelial cell types using markers for enterocytes, stem cells, Goblet cells, and enteroendocrine cells by qPCR and histology upon removal of growth factors.

Results

In contrast to Wnt3a-conditioned media, media supplemented with recombinant Wnt3a alone did not support long-term survival of human or mouse colon organoids. Mechanistically, this observation can be attributed to the fact that recombinant Wnt3a did not support stem cell survival or proliferation as demonstrated by decreased LGR5 and Ki67 expression. When monitoring expression of markers for epithelial cell types, the highest level of organoid differentiation was observed after combined removal of Wnt3a, Noggin, and R-spondin from Wnta3a-conditioned media cultures.

Conclusion

Our study defined Wnt3a-containing conditioned media as optimal for growth and survival of human and mouse organoids. Furthermore, we established that the combined removal of Wnt3a, Noggin, and R-spondin results in optimal differentiation. This study provides a step forward in optimizing conditions for intestinal organoid growth to improve standardization and reproducibility of this model platform.
Hepatitis B Virus Infection Among Leprosy Patients: A Case for Polymorphisms Compromising Activation of the Lectin Pathway and Complement Receptors
Authors: Boldt Angelica Beate Winter , Oliveira-Toré Camila de Freitas , Kretzschmar Gabriela Canalli , Weinschutz Mendes Hellen , Stinghen Sérvio Túlio , Andrade Fabiana Antunes , Bumiller-Bini Valéria , Gonçalves Letícia Boslooper , Braga Anna Carolina de Moraes , Stahlke Ewalda von Rosen Seeling , Velavan Thirumalaisamy P. , Thiel Steffen , de Messias-Reason Iara José Taborda
Published: February 2021

Thousands of leprosy patients not only suffer from physical deformities, but also either have or have had hepatitis B virus (HBV) coinfection. Polymorphisms of the complement system modulate susceptibility to leprosy, but genetic susceptibility to past or present HBV infection is unknown. We used sequencing and multiplex sequence-specific PCR to genotype 72 polymorphisms of seven genes (MBL2,FCN1, FCN2, FCN3, MASP1, MASP2, C3) encoding components of the lectin pathway, and two genes encoding complement receptors (CR1, VSIG4) in 190 patients, of which 74 were positive for HBsAg and/or anti-HBc (HBV+, 93.2% with a resolved infection) and 116 lepromatous patients, and 408 HBV-blood donors. In addition, we tested for levels of proteins of the lectin pathway. We found no difference between serum concentrations of mannan-binding lectin (MBL), MBL-associated serine proteins (MASP-1, MASP-2, MASP-3, MAp44), ficolin-3 (FCN-3), soluble complement receptor 1 (sCR1) and MBL mediated C4 activation, measured by ELISA or TRIFMA in up to 167 HBV+ and HBV− patients. Haplotypes lowering protein levels or encoding dysfunctional proteins increased susceptibility to HBV infection:MBL2*LYQC(OR = 3.4, p = 0.02),MASP1*AC_CC(OR = 4.0, p = 0.015) andMASP2*1C2-l(OR = 5.4, p = 0.03). Conversely,FCN1*3C2haplotype, associated with higher gene expression, was protective (OR = 0.56, P = 0.033). Other haplotypes associated with HBV susceptibility were:MASP2*2B1-i(OR = 19.25, P = 0.003),CR1*3A(OR = 2.65, P = 0.011) andVSIG4*TGGRCG(OR = 12.55, P = 0.014). Some polymorphisms in ficolin genes associated with lower protein levels increased susceptibility to leprosy/HBV infection:FCN*1(OR = 1.66, P = 0.029),FCN2*GGGCAC(OR = 6.73, P = 0.008), andFCN3*del_del_C(OR = 12.54, P = 0.037), and to lepromatous disease/HBV infection:FCN2*TA(OR = 2.5, P = 0.009), whereasFCN2*MAGwas associated with increased FCN-2 expression and resistance against coinfection (OR = 0.29, P = 0.026). These associations were independent of demographic factors and did not increase susceptibility to leprosyper se, exceptMASP2*1C2-l. Associations forFCN2, FCN3, MASP1, MASP2, andVSIG4variants were also independent of each other. In conclusion, polymorphisms compromising activation of the lectin pathway of complement increase susceptibility to HBV infection, with ficolin polymorphisms playing a major role in modulating the susceptibility among leprosy patients.
Microarray-Based Allergy Diagnosis: Quo Vadis?
Authors: Huang Huey-Jy , Campana Raffaela , Akinfenwa Oluwatoyin , Curin Mirela , Sarzsinszky Eszter , Karsonova Antonina , Riabova Ksenja , Karaulov Alexander , Niespodziana Katarzyna , Elisyutina Olga , Fedenko Elena , Litovkina Alla , Smolnikov Evgenii , Khaitov Musa , Vrtala Susanne , Schlederer Thomas , Valenta Rudolf
Published: February 2021

More than 30% of the world population suffers from allergy. Allergic individuals are characterized by the production of immunoglobulin E (IgE) antibodies against innocuous environmental allergens. Upon allergen recognition IgE mediates allergen-specific immediate and late-phase allergic inflammation in different organs. The identification of the disease-causing allergens by demonstrating the presence of allergen-specific IgE is the key to precision medicine in allergy because it allows tailoring different forms of prevention and treatment according to the sensitization profiles of individual allergic patients. More than 30 years ago molecular cloning started to accelerate the identification of the disease-causing allergen molecules and enabled their production as recombinant molecules. Based on recombinant allergen molecules, molecular allergy diagnosis was introduced into clinical practice and allowed dissecting the molecular sensitization profiles of allergic patients. In 2002 it was demonstrated that microarray technology allows assembling large numbers of allergen molecules on chips for the rapid serological testing of IgE sensitizations with small volumes of serum. Since then microarrayed allergens have revolutionized research and diagnosis in allergy, but several unmet needs remain. Here we show that detection of IgE- and IgG-reactivity to a panel of respiratory allergens microarrayed onto silicon elements is more sensitive than glass-based chips. We discuss the advantages of silicon-based allergen microarrays and how this technology will allow addressing hitherto unmet needs in microarray-based allergy diagnosis. Importantly, it described how the assembly of silicon microarray elements may create different microarray formats for suiting different diagnostic applications such as quick testing of single patients, medium scale testing and fully automated large scale testing.