bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluctuaciones bursátiles de las acciones de empresas mineras peruanas durante el Estado de Emergencia Nacional por efecto de la COVID-19
Authors: Ordinola Valdez Andrea Carmen Lidia , Filinich Cutipa José Alejandro
Published: November 2021

El objetivo del trabajo fue describir las repercusiones que se han venido suscitando a partir del Estado de Emergencia Nacional por efectos del coronavirus en las acciones de las empresas mineras peruanas. La investigación fue de enfoque cuantitativo, de nivel explicativo (causal), basada en la cuantificación y el análisis econométrico de las series de tiempo de activos financieros que cotizan en la Bolsa de Valores de Lima (BVL), durante el periodo de cuarentena, iniciada el 16 de marzo y concluida el 30 de junio del 2020, y su comportamiento poscuarentena. La muestra en estudio estuvo conformada por las compañías mineras representativas que se encuentran en el top ten de las más importantes a nivel nacional. Se concluye que la rentabilidad de las mencionadas empresas que cotizan en la BVL, en el periodo estudiado, ha sido negativa.
Efecto de la pandemia de COVID-19 en el comportamiento de la economía del Perú, 2020
Authors: Olivera Cáceres Jesús Amadeo , Loza Ticona Renzi Marilu
Published: November 2021

La pandemia de COVID-19 generó pérdidas severas en las economías del mundo, lo que ocasionó un grave impacto en la economía del Perú, además de un futuro caracterizado por la incertidumbre. La investigación tuvo como propósito analizar el efecto de la pandemia de COVID-19 en el comportamiento de la economía del Perú, correspondiente al período 2020. La metodología se basó en el enfoque cuantitativo, de tipo básico, diseño no experimental, de nivel descriptivo documental. Finalmente, se estableció que la pandemia de COVID-19 tuvo un efecto negativo en el comportamiento de la economía del Perú, al hallarse valores descendientes negativos en el Producto Bruto Interno (PBI) (-11.1 %); importaciones (-14.9 %); oferta y demanda global (-12 %); demanda interna (-10.1 %); y, exportaciones (-19 %). La caída del PBI a -11.1 % en el 2020 representó una pérdida de más de 131 mil millones de soles, lo que semejó a más de 1.2 mil millones de soles diarios. Para aplacar el efecto de la pandemia de COVID-19 en la economía, el Estado peruano realizó la reactivación económica flexibilizando las condiciones para que las empresas retomen sus actividades.
Perfil profesional del contador público colegiado y su influencia en la detección de los actos de corrupción en la región Moquegua
Authors: Arohuanca Antahuanaco Bethy Verlina
Published: November 2021

El objetivo del estudio realizado en el año 2019, fue determinar si el perfil profesional del contador público colegiado influye en la detección de los actos de corrupción en la región Moquegua. Al considerar que, hoy en día, la región Moquegua es una de las regiones con más casos de corrupción a nivel nacional. Al respecto, el Estado y las empresas privadas, han adoptado medidas, sin embargo, no consideran al profesional en Contabilidad para contrarrestar la corrupción, teniendo conocimiento que el Contador se desenvuelve en los escenarios donde se genera en su mayoría los actos de corrupción. A fin de lograr el objetivo planteado, el estudio se situó como una investigación básica de nivel descriptivo y explicativo, no experimental y transversal, utilizando el modelo de regresión logística Logit, donde la variable dependiente es dicotómica y las variables independientes se encuentran en una escala de intervalo. Como resultado, se determinó que el perfil profesional del contador público colegiado, que posee experiencia profesional de seis a diez años, con especialización de Contador General, especialista en Finanzas, Tributaria, Normas Internacionales de Información Financiera, Costos, Presupuestos, Integrador Contable y Auditor, con capacitación constante de 501 a más horas en los últimos cinco años y que se encuentra en el rango de edad de 31 a 45 años, influye significativamente en la detección de actos de corrupción en la región Moquegua.
THE STUDY OF COMPOUNDS DISTILLED WITH WATER VAPOR OF POPULUS ×BEROLINENSIS DIPPEL. LEAFS
Authors:   Zaporizhia State Medical University, Rudnyk A.M. , Trzhetsynskyi S.D. ,   Zaporizhia State Medical University
Published: November 2021

Keywords: populus ×berolinensis Dippel., leafs, compounds distilled with water vapor, gas chromatography-mass spectrometry Continuing the comprehensive pharmacognostic study of raw materials of plants of the genus Poplar, the aim of the study was to study the composition and content of compounds volatile with water vapor, Berlin poplar leaves (populus × berolinensis Dippel), which is widely cultivated in Ukraine. Raw materials for research were harvested from trees growing in the botanical garden of Kharkiv National University. V.N. Karazin (50 ° 01′46 ″ N 36 ° 14′02 ″ E.) in June 2019. It was found that the total content of compounds distilled with water vapor was 2026.4 mg / kg. 51 compounds were identified. Dominated by the content of: β-eudesmol (677.0 mg / kg), γ-eudesmol (234.0 mg / kg), α-bisabolol (125.9 mg / kg), eugenol (217.7 mg / kg), cubenol (92.3 mg / kg), quinesol (39.0 mg / kg). The obtained data indicate the prospects for further study of this type of raw material to assess the possibility of using it as a drug.
The ‘D-Books’ of Daryaganj Sunday Book Market
Authors: Dhingra Kanupriya
Published: November 2021

Daryaganj Sunday Book Market, popularly known as Daryaganj Sunday Patri Kitab Bazaar, is a weekly informal market for used, rare, and pirated books that has been operating on the streets of Old Delhi for the past fifty years. In this essay, I focus on one of the circuits that has been flourishing in this market, that of pirated or ‘duplicate’ or D-books. In order to examine the forms in which piracy thrives in the present-day Patri Kitab Bazaar, and the reasons behind it, I compare two types of pirated books found here: a low-price self-help manual in Hindi and a ‘D’ copy of an English novel by popular Indian author Chetan Bhagat. As I examine the essential role that ‘randomness’ plays in the constitution of pirated texts, I suggest that there is organization to this apparent lack of pattern or unpredictability. Such permutation of order and chaos resonates with the location of the bazaar – a site that thrives on the serendipity of the streets.
Assemblages and Co-emergent Corpomaterialities in Postsecondary Education: Pedagogical Lessons from Somatic Psychology and Physical Cultures
Authors: Joseph Janelle , Kerr Ellyn
Published: November 2021

Building on a new materialist ontology, this article explores the significance of viewing the postsecondary institution and learner as assemblages co-emerging in material relationality. Bodies of thought from social cognitive neuroscience, somatic psychotherapy, and physical cultural studies inform an analysis of the evaluation culture predominant in Western postsecondary education. These disciplines are used to interrogate representational performativity and point to new possibilities for material-inclusive learning. A new materialist pedagogy holds possibilities to reconfigure learning architectures to recognise and attend to the corpomaterialities of learners while allowing for new and creative lines of flight in education, as illustrated by physical cultural practices such as sport training, dance, and capoeira.
Environmental Audit Committee Call for Evidence: “Sustainability of the Built Environment”
Authors: Ramage Michael , Shah Darshil U. , Bukauskas Aurimas , Koronaki Antiopi , Colman Anthony , Gatóo Ana , Wiegand Eduardo , Gin Yelda , Debnath Ramit
Published: November 2021

The Centre for Natural Material Innovation in the Department of Architecture at the University of Cambridge is a cross-disciplinary centre, bringing together people and research in plant sciences, biochemistry, chemistry, fluid dynamics, engineering, and architecture. Through innovative research and experimentation, we aim to transform the way we build to achieve zero carbon emissions. Our work enables the substitution of artificial materials such as concrete and steel with nature-based materials such as timber and bamboo, and replacement of structural carbon fibre and glass fibre with hemp and flax-based biocomposites. We collaborate with other leading research institutions globally, including in the USA, China, Australia, Uruguay and others.
Dietary Patterns and Associated Microbiome Changes that Promote Oncogenesis
Authors: Ibragimova Shakhzada , Ramachandran Revathy , Ali Fahad R. , Lipovich Leonard , Ho Samuel B.
Published: November 2021

The recent increases in cancer incidences have been linked to lifestyle changes that result in obesity and metabolic syndrome. It is now evident that these trends are associated with the profound changes that occur in the intestinal microbiome, producing altered microbial population signatures that interact, directly or indirectly, with potentially pro-carcinogenic molecular pathways of transcription, proliferation, and inflammation. The effects of the entire gut microbial population on overall health are complex, but individual bacteria are known to play important and definable roles. Recent detailed examinations of a large number of subjects show a tight correlation between habitual diets, fecal microbiome signatures, and markers of metabolic health. Diets that score higher in healthfulness or diversity such as plant-based diets, have altered ratios of specific bacteria, including an increase in short-chain fatty acid producers, which in turn have been linked to improved metabolic markers and lowered cancer risk. Contrarily, numerous studies have implicated less healthy, lower-scoring diets such as the Western diet with reduced intestinal epithelial defenses and promotion of specific bacteria that affect carcinogenic pathways. In this review, we will describe how different dietary patterns affect microbial populations in the gut and illustrate the subsequent impact of bacterial products and metabolites on molecular pathways of cancer development, both locally in the gut and systemically in distant organs.
Novel Insights Into the Potential Mechanisms of N6-Methyladenosine RNA Modification on Sepsis-Induced Cardiovascular Dysfunction: An Update Summary on Direct and Indirect Evidences
Authors: Wang Yang , Xu Miaomiao , Yue Peng , Zhang Donghui , Tong Jiyu , Li Yifei
Published: November 2021

Sepsis is a life-threatening organ dysfunction caused by a host’s dysfunctional response to infection. As is known to all, septic heart disease occurs because pathogens invading the blood stimulate the activation of endothelial cells, causing a large number of white blood cells to accumulate and trigger an immune response. However, in severe sepsis, the hematopoietic system is inhibited, and there will also be a decline in white blood cells, at which time the autoimmune system will also be suppressed. During the immune response, a large number of inflammatory factors are released into cells to participate in the inflammatory process, which ultimately damages cardiac myocytes and leads to impaired cardiac function. N6-methyladenosine (m6A) is a common RNA modification in mRNA and non-coding RNA that affects RNA splicing, translation, stability, and epigenetic effects of some non-coding RNAs. A large number of emerging evidences demonstrated m6A modification had been involved in multiple biological processes, especially for sepsis and immune disorders. Unfortunately, there are limited results provided to analyze the association between m6A modification and sepsis-induced cardiovascular dysfunction (SICD). In this review, we firstly summarized current evidences on how m6A mediates the pathophysiological process in cardiac development and cardiomyopathy to emphasize the importance of RNA methylation in maintaining heart biogenesis and homeostasis. Then, we clarified the participants of m6A modification in extended inflammatory responses and immune system activation, which are the dominant and initial changes secondary to sepsis attack. After that, we deeply analyzed the top causes of SICD and identified the activation of inflammatory cytokines, endothelial cell dysfunction, and mitochondrial failure. Thus, the highlight of this review is that we systematically collected all the related potential mechanisms between m6A modification and SICD causes. Although there is lack of direct evidences on SICD, indirect evidences had been demonstrated case by case on every particular molecular mechanism and signal transduction, which require further explorations into the potential links among the listed mechanisms. This provides novel insights into the understanding of SICD.
Human Sperm Remain Motile After a Temporary Energy Restriction but do Not Undergo Capacitation-Related Events
Authors: Marín-Briggiler Clara I. , Luque Guillermina M. , Gervasi María G. , Oscoz-Susino Natalia , Sierra Jessica M. , Mondillo Carolina , Salicioni Ana M. , Krapf Darío , Visconti Pablo E. , Buffone Mariano G.
Published: November 2021

To acquire fertilization competence, mammalian sperm must undergo several biochemical and physiological modifications known as capacitation. Despite its relevance, the metabolic pathways that regulate the capacitation-related events, including the development of hyperactivated motility, are still poorly described. Previous studies from our group have shown that temporary energy restriction in mouse sperm enhanced hyperactivation, in vitro fertilization, early embryo development and pregnancy rates after embryo transfer, and it improved intracytoplasmic sperm injection results in the bovine model. However, the effects of starvation and energy recovery protocols on human sperm function have not yet been established. In the present work, human sperm were incubated for different periods of time in medium containing glucose, pyruvate and lactate (NUTR) or devoid of nutrients for the starving condition (STRV). Sperm maintained in STRV displayed reduced percentages of motility and kinematic parameters compared to cells incubated in NUTR medium. Moreover, they did not undergo hyperactivation and showed reduced levels of ATP, cAMP and protein tyrosine phosphorylation. Similar to our results with mouse sperm, starvation induced increased intracellular Ca2+ concentrations. Starved human sperm were capable to continue moving for more than 27 h, but the incubation with a mitochondrial uncoupler or inhibitors of oxidative phosphorylation led to a complete motility loss. When exogenous nutrients were added back (sperm energy recovery (SER) treatment), hyperactivated motility was rescued and there was a rise in sperm ATP and cAMP levels in 1 min, with a decrease in intracellular Ca2+ concentration and no changes in sperm protein tyrosine phosphorylation. The finding that human sperm can remain motile for several hours under starvation due to mitochondrial use of endogenous metabolites implies that other metabolic pathways may play a role in sperm energy production. In addition, full recovery of motility and other capacitation parameters of human sperm after SER suggests that this treatment might be used to modulate human sperm fertilizing ability in vitro.
Mixing in the NETmix Reactor
Authors: Matos Joana , Santos Ricardo J. , Dias Madalena M. , Lopes José Carlos B.
Published: November 2021

NETmix is a static mixing reactor composed of a network of mixing chambers interconnected by channels. The repetitive mixing pattern inside the reactor enables the use of reduced geometries to represent the NETmix network, such as the ExtendedNUB model, used in this work. Mixing in NETmix is based on the impingement of jets, issuing from channels. Inside the chambers, the jets are engulfed by dynamic vortices which can be quantified using Lagrangian techniques. Batch Lagrangian Mixing Simulation (BLMS) is based on successive injections of particles to measure the fraction of the fluids at the outlet of the mixing chambers. The distribution of the outlet fraction of particles indicates that it is possible to have nearly perfect mixing inside the NETmix chambers, depending on the dimensions of the channels and chambers. The NETmix design is here optimized in relation to the chamber diameter to channel width ratio, D/d. Results from BLMS show that best performance in NETmix occurs for 6.65≤D/d≤6.85.
Case Report: Area of Focus of Myocardial Infarction With Non-obstructive Coronary Arteries in Eosinophilic Granulomatosis With Polyangiitis
Authors: Cui Xiaoxian , Peng Yang , Liu Jun , Dong Yugang , Wu Zexuan , Chen Yili
Published: November 2021

Background: Eosinophilic granulomatosis with polyangitis manifested as myocardial infarction with non-obstructed coronary arteries (MINOCA) is rarely reported.

Case: We report a 43-year-old male patient without any cardiovascular risk factors presenting with acute chest pain. Electrocardiogram was suggestive of acute anterior and inferior myocardial infarction. MINOCA was confirmed based on significant elevated cardiac troponin and normal coronary arteries. Cardiac magnetic resonance (CMR) imaging revealed extended late gadolinium enhancement (LGE). Further diagnosis of eosinophilic granulomatosis with polyangitis (EGPA) was based on clinical manifestations and auxiliary examination. Subsequent immunosuppressive therapy led to regression of symptoms and significant resolution of LGE on CMR.

Conclusion: Our case highlights that EGPA can be a rare cause of MINOCA. CMR is useful for differentiation diagnosis and evaluation of cardiac involvement.
Smartphones and Video Cameras: Future Methods for Blood Pressure Measurement
Authors: Steinman Joe , Barszczyk Andrew , Sun Hong-Shuo , Lee Kang , Feng Zhong-Ping
Published: November 2021

Regular blood pressure (BP) monitoring enables earlier detection of hypertension and reduces cardiovascular disease. Cuff-based BP measurements require equipment that is inconvenient for some individuals and deters regular home-based monitoring. Since smartphones contain sensors such as video cameras that detect arterial pulsations, they could also be used to assess cardiovascular health. Researchers have developed a variety of image processing and machine learning techniques for predicting BP via smartphone or video camera. This review highlights research behind smartphone and video camera methods for measuring BP. These methods may in future be used at home or in clinics, but must be tested over a larger range of BP and lighting conditions. The review concludes with a discussion of the advantages of the various techniques, their potential clinical applications, and future directions and challenges. Video cameras may potentially measure multiple cardiovascular metrics including and beyond BP, reducing the risk of cardiovascular disease.
Exploring Reliability and Factorial Validity of Responsible Talk and its Impact on Cooperative Classrooms
Authors: Pons Rosa M. , Reyes Vicente
Published: November 2021

The aim of this study was to validate an instrument which enables the evaluation of talk which maximizes student performance during different segments of interaction-interactivity throughout a complete learning sequence. Based on works developed by the Learning and Research Development Center of the University of Pittsburgh, a scale was developed that gathered the most relevant behaviors of each proposed dimension by researchers from this university center. The scale was used to develop a core subject for a final year Bachelor of Arts degree in Primary Education at a university in Spain and was applied to the 65 students (M = 19, F = 46) taking the subject. The data analysis used an exploratory factor analysis (EFA) that yielded a reliability of α = 0.922. EFA revealed a final interpretable three-factor structure, and the factorial solution comprised 87.86% of total variance. Results show that the talk that students use has three purposes: to constitute an effective group for learning, to build knowledge and to verify its acquisition. The results are discussed in terms of input from the Center for Research in Education and Educational Technologies at the Open University and the Learning Research and Development Center of the University of Pittsburgh.
The Retina in Patients With Triple A Syndrome: A Window Into Neurodegeneration?
Authors: Ulgiati Fiorenza , Lhoir Sophie , Balikova Irina , Tenoutasse Sylvie , Boros Emese , Vilain Catheline , Heinrichs Claudine , Brachet Cécile
Published: November 2021

Objective

Experimental evidence suggests that the clinical manifestations of Triple A syndrome result from oxidative stress. Several conditions caused by oxidative stress display retinal involvement. Our objective was to assess the retina and optic nerve involvement in children with Triple A syndrome.

Methods

Eleven patients with genetically proven Triple A syndrome followed-up in our centre were approached for study participation. The main outcome was the measurement of the thicknesses of the different retinal layers by Optical Coherence Tomography (OCT).

Results

9 patients with triple A syndrome had OCT measurements. 7 patients were children and 2 were adults; 4 were females and 5 were males. The 7 paediatric patients had at least two OCT measured at a mean interval of 7.9 months after the first one. The average Retinal Nerve Fibre Layer thickness was 74 ± 10 µm in patients compared to the paediatric reference range of 100 ± 2 µm (p<0.05).

Conclusions and Relevance

This is the first study to document retinal layer thicknesses in a series of patients with Triple A syndrome. Nearly all retinal thickness and peripapillary RNFL measurements were very significantly inferior to the reference range in Triple A patients, whatever their age. RNFL thinning was more marked at the temporal part of the optic nerve. OCT being non-invasive, it represents a promising tool to assess the severity of neurodegeneration in patients with Triple A syndrome.
Influence of Particle Composition and Size on the Accuracy of Low Cost PM Sensors: Findings From Field Campaigns
Authors: Gramsch E. , Oyola P. , Reyes F. , Vásquez Y. , Rubio M. A. , Soto C. , Pérez P. , Moreno F. , Gutiérrez N.
Published: November 2021

In the last decade, many low-cost monitoring sensors and sensor-networks have been used as an alternative air quality assessment method. It is also well known that these low cost monitors have calibration, accuracy and long term variation problems which require various calibration techniques. In this work PM2.5and PM10low cost sensors (Plantower and Nova Fitness) have been tested in five cities under different environmental conditions and compared with collocated standard instruments. Simultaneously, particle composition (organic and black carbon, sulfate, nitrate, chloride, ammonium, and chemical elements) has been measured in the same places to study its influence on the accuracy. The results show a very large variability in the correlation between the low cost sensors and collocated standard instruments depending on the composition and size of particles present in the site. The PM10correlation coefficient (R2) between the low cost sensor and a collocated regulatory instrument varied from to 0.95 in Temuco to 0.04 in Los Caleos. PM2.5correlation varied from 0.97 to 0.68 in the same places. It was found that sites that had higher proportion of large particles had lower correlation between the low cost sensor and the regulatory instrument. Sites that had higher relative concentration of organic and black carbon had better correlation because these species are mostly below the 1 μm size range. Sites that had higher sulfate, nitrate or SiO2concentrations in PM2.5or PM10had low correlation most likely because these particles have a scattering coefficients that depends on its size or composition, thus they can be classified incorrectly.
Southern Ocean Food Web Modelling: Progress, Prognoses, and Future Priorities for Research and Policy Makers
Authors: McCormack Stacey A. , Melbourne-Thomas Jessica , Trebilco Rowan , Griffith Gary , Hill Simeon L. , Hoover Carie , Johnston Nadine M. , Marina Tomás I. , Murphy Eugene J. , Pakhomov Evgeny A. , Pinkerton Matt , Plagányi Éva , Saravia Leonardo A. , Subramaniam Roshni C. , Van de Putte Anton P. , Constable Andrew J.
Published: November 2021

Graphical Abstract

Graphical summary of multiple aspects of Southern Ocean food web structure and function including alternative energy pathways through pelagic food webs, climate change and fisheries impacts and the importance of microbial networks and benthic systems.
Research on Mental Stress Recognition of Depressive Disorders in Patients With Androgenic Alopecia Based on Machine Learning and Fuzzy K-Means Clustering
Authors: Li Yulong , Wu Baojin , Li Xiujun , Zhou Qin , Yang Xin , Li Yufei
Published: November 2021

Under the new trend of industry 4.0 software-defined network, the value of meta heuristic algorithm was explored in the recognition of depression in patients with androgenic alopecia (AGA), and there was an analysis on the effect of comprehensive psychological interventions in the rehabilitation of AGA patients. Based on the meta heuristic algorithm, the Filter and Wrapper algorithms were combined in this study to form a new feature selection algorithm FAW-FS. Then, the classification accuracy of FAW-FS and the ability to identify depression disorders were verified under different open data sets. 54 patients with AGA who went to the Medical Cosmetic Center of Tongji Hospital were selected as the research objects and rolled into a control group (routine psychological intervention) and an intervention group (routine + comprehensive psychological interventions) according to different psychological intervention methods, with 27 cases in each group. The differences of the self-rating anxiety scale (SAS), self-rating depression scale (SDS), Hamilton depression scale (HAMD), and physical, psychological, social, and substance function scores before and after intervention were compared between the two groups of AGA patients, and the depression efficacy and compliance of the two groups were analyzed after intervention. The results showed that the classification accuracy of FAW-FS algorithm was the highest in logistic regression (LR), decision tree (DT), K-nearest neighbor (KNN) algorithm, support vector machine (SVM) algorithm, and random forest (RF) algorithm, which was 80.87, 79.24, 80.42, 83.07, and 81.45%, respectively. The LR algorithm had the highest feature selection accuracy of 82.94%, and the classification accuracy of depression disorder in RF algorithm was up to 73.01%. Besides, the SDS, SAS, and HAMD scores of the intervention group were lower sharply than the scores of the control group (p < 0.05). The physical function, psychological function, social function, and substance function scores of the intervention group were higher markedly than those of the control group (p < 0.05). In addition, the proportions of cured, markedly effective, total effective, full compliance, and total compliance patients in the intervention group increased obviously in contrast to the proportions of the control group (p < 0.05). Therefore, it indicated that the FAW-FS algorithm established in this study had significant advantages in the recognition of depression in AGA patients, and comprehensive psychological intervention had a positive effect in the rehabilitation of depression in AGA patients.
Identification of lncRNA–miRNA–mRNA Networks Linked to Non-small Lung Cancer Resistance to Inhibitors of Epidermal Growth Factor Receptor
Authors: Wang Ting , Yang Chengliang , Li Bing , Xing Ying , Huang Jian , Zhang Yangping , Bu Shanshan , Ge Hong
Published: November 2021

Background: Tyrosine kinase inhibitors that act against epidermal growth factor receptor (EGFR) show strong efficacy against non-small cell lung cancer (NSCLC) involving mutated EGFRs. However, most such patients eventually develop resistance to EGFR-TKIs. Numerous researches have reported that messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs) may be involved in EGFR-TKI resistance, but the comprehensive expression profile and competitive endogenous RNA (ceRNA) regulatory network between mRNAs and ncRNAs in EGFR-TKI resistance of NSCLC are incompletely known. We aimed to define a ceRNA regulatory network linking mRNAs and non-coding RNAs that may mediate this resistance.

Methods: Using datasets GSE83666, GSE75309 and GSE103352 from the Gene Expression Omnibus, we identified long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs differentially expressed between NSCLC cells that were sensitive or resistant to EGFR-TKIs. The potential biological functions of the corresponding differentially expressed genes were analyzed based KEGG pathways. We combined interactions among lncRNAs, miRNAs and mRNAs in the RNAInter database with KEGG pathways to generate transcriptional regulatory ceRNA networks associated with NSCLC resistance to EGFR-TKIs. Kaplan-Meier analysis was used to assess the ability of core ceRNA regulatory sub-networks to predict the progression-free interval and overall survival of NSCLC. The expression of two core ceRNA regulatory sub-networks in NSCLC was validated by quantitative real-time PCR.

Results: We identified 8,989 lncRNAs, 1,083 miRNAs and 3,191 mRNAs that were differentially expressed between patients who were sensitive or resistant to the inhibitors. These DEGs were linked to 968 biological processes and 31 KEGG pathways. Pearson analysis of correlations among the DEGs of lncRNAs, miRNAs and mRNAs identified 12 core ceRNA regulatory sub-networks associated with resistance to EGFR-TKIs. The two lncRNAs ABTB1 and NPTN with the hsa-miR-150–5p and mRNA SERPINE1 were significantly associated with resistance to EGFR-TKIs and survival in NSCLC. These lncRNAs and the miRNA were found to be down-regulated, and the mRNA up-regulated, in a resistant NSCLC cell line relative to the corresponding sensitive cells.

Conclusion: In this study, we provide new insights into the pathogenesis of NSCLC and the emergence of resistance to EGFR-TKIs, based on a lncRNA-miRNA-mRNA network.
Genome-wide Identification and Analysis of Splicing QTLs in Multiple Sclerosis by RNA-Seq Data
Authors: He Yijie , Huang Lin , Tang Yaqin , Yang Zeyuan , Han Zhijie
Published: November 2021

Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelinating lesions in the central nervous system. Recently, the dysregulation of alternative splicing (AS) in the brain has been found to significantly influence the progression of MS. Moreover, previous studies demonstrate that many MS-related variants in the genome act as the important regulation factors of AS events and contribute to the pathogenesis of MS. However, by far, no genome-wide research about the effect of genomic variants on AS events in MS has been reported. Here, we first implemented a strategy to obtain genomic variant genotype and AS isoform average percentage spliced-in values from RNA-seq data of 142 individuals (51 MS patients and 91 controls). Then, combing the two sets of data, we performed a cis-splicing quantitative trait loci (sQTLs) analysis to identify the cis-acting loci and the affected differential AS events in MS and further explored the characteristics of these cis-sQTLs. Finally, the weighted gene coexpression network and gene set enrichment analyses were used to investigate gene interaction pattern and functions of the affected AS events in MS. In total, we identified 5835 variants affecting 672 differential AS events. The cis-sQTLs tend to be distributed in proximity of the gene transcription initiation site, and the intronic variants of them are more capable of regulating AS events. The retained intron AS events are more susceptible to influence of genome variants, and their functions are involved in protein kinase and phosphorylation modification. In summary, these findings provide an insight into the mechanism of MS.
Utilizing CRISPR-Cas in Tropical Crop Improvement: A Decision Process for Fitting Genome Engineering to Your Species
Authors: Joo Kathleen A. , Muszynski Michael G. , Kantar Michael B. , Wang Ming-Li , He Xiaoling , Del Valle Echevarria Angel R.
Published: November 2021

Adopting modern gene-editing technologies for trait improvement in agriculture requires important workflow developments, yet these developments are not often discussed. Using tropical crop systems as a case study, we describe a workflow broken down into discrete processes with specific steps and decision points that allow for the practical application of the CRISPR-Cas gene editing platform in a crop of interest. While we present the steps of developing genome-edited plants as sequential, in practice parts can be done in parallel, which are discussed in this perspective. The main processes include 1) understanding the genetic basis of the trait along with having the crop’s genome sequence, 2) testing and optimization of the editing reagents, development of efficient 3) tissue culture and 4) transformation methods, and 5) screening methods to identify edited events with commercial potential. Our goal in this perspective is to help any lab that wishes to implement this powerful, easy-to-use tool in their pipeline, thus aiming to democratize the technology.
The Significance of RHD Genotyping and Characteristic Analysis in Chinese RhD Variant Individuals
Authors: Ying Yanling , Zhang Jingjing , Hong Xiaozhen , Xu Xianguo , He Ji , Zhu Faming
Published: November 2021

Background

RhD is the most important and complex blood group system because of its highly polymorphic and immunogenic nature. RhD variants can induce immune response by allogeneic transfusion, organ transplantation, and fetal immunity. The transfusion strategies are different for RhD variants formed by various alleles. Therefore, extensive investigation of the molecular mechanism underlying RhD variants is critical for preventing immune-related blood transfusion reactions and fetal immunity.

Methods

RhD variants were collected from donors and patients in Zhejiang Province, China. The phenotypes were classified using the serologic method. The full coding regions of RHD gene were analyzed using the PCR-SBT method. The multiplex ligation-dependent probe amplification (MLPA) assay was used to analyze the genotype and gene copy number. SWISS-MODLE and PyMOL software were used to analyze 3D structures of RhD caused by the variant alleles. The effect of non-synonymous substitutions was predicted using Polymorphism Phenotyping algorithm (PolyPhen-2), Sorting Intolerant From Tolerant (SIFT), and Protein Variation Effect Analyzer (PROVEAN) software.

Results

In the collected RhD variants, 28 distinct RHD variant alleles were identified, including three novel variant alleles. RH-MLPA assay is advantageous for determining the copy number of RHD gene. 3D homology modeling predicted that protein conformation was disrupted and may explain RhD epitope differential expression. A total of 14 non-synonymous mutations were determined to be detrimental to the protein structure.

Discussion

We revealed the diversity of RHD alleles present in eastern Chinese RhD variants. The bioinformatics of these variant alleles extended our knowledge of RhD variants, which was crucial for evaluating their impact to guide transfusion support and avoid immune-related blood transfusion reactions.
Metallothionein 3-Zinc Axis Suppresses Caspase-11 Inflammasome Activation and Impairs Antibacterial Immunity
Authors: Chowdhury Debabrata , Gardner Jason C. , Satpati Abhijit , Nookala Suba , Mukundan Santhosh , Porollo Aleksey , Landero Figueroa Julio A. , Subramanian Vignesh Kavitha
Published: November 2021

Non-canonical inflammasome activation by mouse caspase-11 (or human CASPASE-4/5) is crucial for the clearance of certain gram-negative bacterial infections, but can lead to severe inflammatory damage. Factors that promote non-canonical inflammasome activation are well recognized, but less is known about the mechanisms underlying its negative regulation. Herein, we identify that the caspase-11 inflammasome in mouse and human macrophages (Mϕ) is negatively controlled by the zinc (Zn2+) regulating protein, metallothionein 3 (MT3). Upon challenge with intracellular lipopolysaccharide (iLPS), Mϕ increased MT3 expression that curtailed the activation of caspase-11 and its downstream targets caspase-1 and interleukin (IL)-1β. Mechanistically, MT3 increased intramacrophage Zn2+ to downmodulate the TRIF-IRF3-STAT1 axis that is prerequisite for caspase-11 effector function. In vivo, MT3 suppressed activation of the caspase-11 inflammasome, while caspase-11 and MT3 synergized in impairing antibacterial immunity. The present study identifies an important yin-yang relationship between the non-canonical inflammasome and MT3 in controlling inflammation and immunity to gram-negative bacteria.
Vitamin C, From Supplement to Treatment: A Re-Emerging Adjunct for Cancer Immunotherapy?
Authors: Kouakanou Léonce , Peters Christian , Brown Christine E. , Kabelitz Dieter , Wang Leo D.
Published: November 2021

Vitamin C (VitC), in addition to its role as a general antioxidant, has long been considered to possess direct anti-cancer activity at high doses. VitC acts through oxidant and epigenetic mechanisms, which at high doses can exert direct killing of tumor cells in vitro and delay tumor growth in vivo. Recently, it has also been shown that pharmacologic-dose VitC can contribute to control of tumors by modulating the immune system, and studies have been done interrogating the role of physiologic-dose VitC on novel adoptive cellular therapies (ACTs). In this review, we discuss the effects of VitC on anti-tumor immune cells, as well as the mechanisms underlying those effects. We address important unanswered questions concerning both VitC and ACTs, and outline challenges and opportunities facing the use of VitC in the clinical setting as an adjunct to immune-based anti-cancer therapies.
Variability of the Red River Plume in the Gulf of Tonkin as Revealed by Numerical Modeling and Clustering Analysis
Authors: Nguyen-Duy Tung , Ayoub Nadia K. , Marsaleix Patrick , Toublanc Florence , De Mey-Frémaux Pierre , Piton Violaine , Herrmann Marine , Duhaut Thomas , Tran Manh Cuong , Ngo-Duc Thanh
Published: November 2021

We study the daily to interannual variability of the Red River plume in the Gulf of Tonkin from numerical simulations at high resolution over 6 years (2011–2016). Compared with observational data, the model results show good performance. To identify the plume, passive tracers are used in order to (1) help distinguish the freshwater coming from different continental sources, including the Red River branches, and (2) avoid the low salinity effect due to precipitation. We first consider the buoyant plume formed by the Red River waters and three other nearby rivers along the Vietnamese coast. We show that the temporal evolution of the surface coverage of the plume is correlated with the runoff (within a lag), but that the runoff only cannot explain the variability of the river plume; other processes, such as winds and tides, are involved. Using a K-means unsupervised machine learning algorithm, the main patterns of the plume and their evolution in time are analyzed and linked to different environmental conditions. In winter, the plume is narrow and sticks along the coast most of the time due to the downcoast current and northeasterly wind. In early summer, the southwesterly monsoon wind makes the plume flow offshore. The plume reaches its highest coverage in September after the peak of runoff. Vertically, the plume thickness also shows seasonal variations. In winter, the plume is narrow and mixed over the whole water depth, while in summer, the plume can be detached both from the bottom and the coast. The plume can deepen offshore in summer, due to strong wind (in May, June) or specifically to a recurrent eddy occurring near 19°N (in August). This first analysis of the variability of the Red River plume can be used to provide a general picture of the transport of materials from the river to the ocean, for example in case of anthropogenic chemical substances leaked to the river. For this purpose, we provide maps of the receiving basins for the different river systems in the Gulf of Tonkin.
Influence of Persistent Inflammation in Follow-Up Biopsies After Antibody-Mediated Rejection in Kidney Transplantation
Authors: Piñeiro Gaston J. , Montagud-Marrahi Enrique , Ríos José , Ventura-Aguiar Pedro , Cucchiari David , Revuelta Ignacio , Lozano Miquel , Cid Joan , Cofan Frederic , Esforzado Nuria , Palou Eduard , Oppenheimer Federico , Campistol Josep M. , Bayés-Genís Beatriu , Rovira Jordi , Diekmann Fritz
Published: November 2021

Background: Despite recent advances in immunosuppression treatment, antibody-mediated rejection (ABMR) remains the leading cause of kidney graft loss. Information about prognostic markers and the efficacy of treatment is scarce.

Methods: Retrospective study with kidney recipients diagnosed an active ABMR from January 1, 2004 to December 31, 2019 to explore the influence of persistent inflammation in follow-up biopsies on graft survival after ABMR treatment.

Results: About 116 patients were included. Active ABMR were treated with a combination of plasma exchange (PE), intravenous immunoglobulin (IVIg), rituximab, and steroids. At 6 months of treatment, 63 (54.3%) patients presented a stabilization or improvement in kidney-graft function. The effectiveness varied depending on the timepoint of the presentation between transplantation and rejection, which is lower for those with late ABMR (63 vs. 21% for early vs. late ABMR, respectively). Ninety patients (77%) underwent a control biopsy after ABMR treatment, from which 46 (51%) responded to the treatment. Microvascular inflammation (MVI) persisted in 64 (71%) biopsies, whereas tubulitis persisted in 17 (19%) biopsies. Death-censored graft survival at 1 year was significantly lower in patients with persistent MVI (86% vs. 95% without persistent MVI, P = 0.002), or with persistent tubulitis (44% vs. 66% without tubulitis, P = 0.02). In the Cox Regression analysis, the persistence of MVI [hazard ratio (HR), 4.50 (95%CI, 1.35–14.96), P = 0.01] and tubulitis [HR 2.88 95%CI (1.24–6.69), P = 0.01) in follow-up biopsies significantly increased the risk of graft failure.

Conclusion: Persistent inflammation in follow-up biopsies after ABMR treatment was associated with an increased risk of graft loss, even without meeting Banff rejection criteria.

Study Registration: Agencia Española de Medicamentos y Productos Sanitarios (AEMPS): 14566/RG 24161. Study code: UTRINM-2017-01.
DHAV-1 Blocks the Signaling Pathway Upstream of Type I Interferon by Inhibiting the Interferon Regulatory Factor 7 Protein
Authors: Lai Yalan , Xia Xiaoyan , Cheng Anchun , Wang Mingshu , Ou Xumin , Mao Sai , Sun Di , Zhang Shaqiu , Yang Qiao , Wu Ying , Zhu Dekang , Jia Renyong , Chen Shun , Liu Mafeng , Zhao Xin-Xin , Huang Juan , Gao Qun , Tian Bin , Liu Yunya , Yu Yanling , Zhang Ling , Pan Leichang
Published: November 2021

Duck hepatitis A virus (DHAV), which mainly infects 1- to 4-week-old ducklings, has a fatality rate of 95% and poses a huge economic threat to the duck industry. However, the mechanism by which DHAV-1 regulates the immune response of host cells is rarely reported. This study examined whether DHAV-1 contains a viral protein that can regulate the innate immunity of host cells and its specific regulatory mechanism, further exploring the mechanism by which DHAV-1 resists the host immune response. In the study, the dual-luciferase reporter gene system was used to screen the viral protein that regulates the host innate immunity and the target of this viral protein. The results indicate that the DHAV-1 3C protein inhibits the pathway upstream of interferon (IFN)-β by targeting the interferon regulatory factor 7 (IRF7) protein. In addition, we found that the 3C protein inhibits the nuclear translocation of the IRF7 protein. Further experiments showed that the 3C protein interacts with the IRF7 protein through its N-terminus and that the 3C protein degrades the IRF7 protein in a caspase 3-dependent manner, thereby inhibiting the IFN-β-mediated antiviral response to promote the replication of DHAV-1. The results of this study are expected to serve as a reference for elucidating the mechanisms of DHAV-1 infection and pathogenicity.
Insignificant Response of Bacterioplankton Community to Elevated pCO2 During a Short-Term Microcosm Experiment in a Subtropical Eutrophic Coastal Ecosystem
Authors: Yang Yunlan , Zhang Fei , Chen Xiaowei , Li Huifang , Jiao Nianzhi , Zhang Rui
Published: November 2021

Ocean acidification, as one of the major consequences of global climate change, markedly affects multiple ecosystem functions in disparate marine environments from coastal habitats to the deep ocean. Evaluation of the responses of marine microbial community to the increasing partial pressure of CO2 (pCO2) is crucial to explore the microbe-driven biogeochemical processes in the future ocean. In this study, a microcosm incubation of eutrophic coastal water from Xiamen Bay under elevated pCO2 (about 1,000 μatm) and control (ambient air, about 380–410 μatm) conditions was conducted to investigate the effect of ocean acidification on the natural bacterioplankton community. During the 5-day incubation period, the chlorophyll a concentration and bacterioplankton abundance were not significantly affected by increased pCO2. Hierarchical clustering and non-metric multidimensional scaling analysis based on Bray-Curtis similarity among the bacterioplankton community derived from the 16S rRNA genes revealed an inconspicuous impact of elevated pCO2 on the bacterial community. During the incubation period, Proteobacteria, Bacteroidetes, Actinobacteria, Cyanobacteria, and Epsilonbacteraeota were predominant in all microcosms. Despite the distinct temporal variation in the composition of the bacterioplankton community during the experimental period, statistical analyses showed that no significant difference was found on bacterioplankton taxa between elevated pCO2 and control, indicating that the bacterioplankton at the population-level were also insensitive to elevated pCO2. Our results therefore suggest that the bacterioplankton communities in the fluctuating and eutrophic coastal ecosystems appear to be adaptable to the short-term elevated pCO2.
Plant Growth Promotion Diversity in Switchgrass-Colonizing, Diazotrophic Endophytes
Authors: Gushgari-Doyle Sara , Schicklberger Marcus , Li Yifan V. , Walker Robert , Chakraborty Romy
Published: November 2021

Endophytic nitrogen-fixing (diazotrophic) bacteria are essential members of the microbiome of switchgrass (Panicum virgatum), considered to be an important commodity crop in bioenergy production. While endophytic diazotrophs are known to provide fixed atmospheric nitrogen to their host plant, there are many other plant growth-promoting (PGP) capabilities of these organisms to be demonstrated. The diversity of PGP traits across different taxa of switchgrass-colonizing endophytes is understudied, yet critical for understanding endophytic function and improving cultivation methods of important commodity crops. Here, we present the isolation and characterization of three diazotrophic endophytes: Azospirillum agricola R1C, Klebsiella variicola F10Cl, and Raoultella terrigena R1Gly. Strains R1C and F10Cl were isolated from switchgrass and strain R1Gly, while isolated from tobacco, is demonstrated herein to colonize switchgrass. Each strain exhibited highly diverse genomic and phenotypic PGP capabilities. Strain F10Cl and R1Gly demonstrated the highest functional similarity, suggesting that, while endophyte community structure may vary widely based on host species, differences in functional diversity are not a clearly delineated. The results of this study advance our understanding of diazotrophic endophyte diversity, which will allow us to design robust strategies to improve cultivation methods of many economically important commodity crops.