bluuebunny/crossref_metadata_2025 huggingface dataset:
Génesis y realización del primer radioteatro de ‘Don Quijote’ producido por la BBC en 1947
Authors: Ayuso Elena
Published: July 2021

En 1947 la BBC realiza el primer radioteatro de Don Quijote para celebrar el IV Centenario del nacimiento de Cervantes. Emitido en España y Latinoamérica en 27 capítulos, la BBC lo definió como «el proyecto más ambicioso jamás llevado a cabo». El objetivo era mejorar la reputación de la BBC en España. El radioteatro contó con la participación de actores de Radio Madrid, exiliados españoles en Londres y profesionales latinoamericanos. La BBC se rodeó de expertos para adaptar la narración cervantina al lenguaje radiofónico; tratar la diversidad de acentos del español; y realizar la música que acompañó la versión radiofónica. El Quijote de la BBC difundió la obra de Cervantes por todos los países de habla hispana e impulsó la producción de otros Quijotes radiofónicos en España.
La figura del narrador en la ficción radiofónica seriada: el caso de 'Taxi Key'
Authors: Arias García Elisa
Published: July 2021

A pesar del protagonismo que adquieren los diálogos de los personajes en la creación de una serie, no podemos obviar que la palabra radiofónica puede hallarse representada a su vez por la presencia del narrador. Por ello, en el presente artículo se ha seleccionado como objeto de estudio la emblemática serie policiaca Taxi Key, para poder determinar el porcentaje de aparición de la figura del narrador en los episodios de la serie, la tipología de narrador que prevalece y las principales funciones que desempeña en este producto ficcional. Se trata de un estudio exploratorio en el que se han realizado análisis descriptivos e inferenciales a partir de los guiones radiofónicos originales de Taxi Key. Los resultados del estudio revelan que la presencia de la figura del narrador alcanza la mayoría significativa en los capítulos de la muestra, siendo el narrador autodiegético el que se erige como tipo de narrador más frecuente. Proporcionar información contextual, actuar de nexo y transición entre escenas y caracterizar a los personajes o incorporarlos a escena son las funciones del narrador que prevalecen en este seriado que permaneció casi veinte años en la antena de Radio Barcelona.
Las tres etapas del radioteatro en Chile: de la época dorada al nuevo auge de las series de ficción
Authors: Rodríguez Ortiz Raúl
Published: July 2021

A raíz del aumento, desde 2016, de nuevas series de ficción y no ficción sonora en gran parte de Iberoamérica, gracias al podcast y a la radio on demand, se plantea la tarea de analizar la historia del género del radioteatro en Chile, desde sus raíces y su importancia sociocultural, hasta las nuevas formas de producir y pensar este género en el siglo XXI. Sobre la base de información documental, compuesta por archivos de prensa, audios y libretos de radiodramas y los escasos estudios sobre la radio y el radioteatro, se logra dilucidar tres etapas: la época dorada (1940-1970); el renacimiento del radioteatro (2003-2015) y el periodo de auge actual del género (2016 al presente). Si bien existen ciertas continuidades entre el primer y segundo periodo, pese al salto temporal y tecnológico, en la tercera etapa se da una nueva manera de crear y diseñar estas producciones, con temáticas que responden a luchas sociales y políticas de grupos invisibilizados o discriminados del espacio público, como también en la forma de difundirlos, sin que la antena sea el lugar por excelencia para la transmisión como ocurrió con las antiguas radionovelas.
Radio Theatre in Italy. Storytelling between Public Service Broadcasting and New Digital Spaces
Authors: Gavrila Mihaela
Published: July 2021

This paper analyzes Italian radio theatre evolution and its ability to put itself always in the middle between radio and other expressive media: theater, cinema, comics, daily news, books and Internet. Starting from the analysis of the main evolutionary phases of this complex radio genre, this contribution illustrates the complexity of radio theater as one of the treasures brought to light by media archeology, which lends itself almost naturally to disciplinary and media crossings. In this expressive format, belonging to media proto history, lurks a deeply complex nature and fervent creativity, which rediscovers in the ether an amplifier of the digital, a new space of expressiveness and diversification of its audience.
The Twinning Problem
Authors: Böhmer Christian , Corcoran Luke , Einav Amit , Hall Cameron L. , Harris James P. , Midgley Laura , Negus Michael J. , Peyerimhoff Norbert
Published: July 2021

In the field of crystallography, some crystals are not made of a single component but are instead twinned.In these cases, the observed intensities at some points in the lattice will be far larger than predictions. If we find the rotation associated to the twinned component, we can model this twin and improve our agreement with observations. In this report, we explore many routes to improve the process of identifying twins: Generation of fake data for better understanding and accurate testing. The representation of a rotation as defined by an axis and angle. The representation of a rotation as a quaternion. Using lattice points which must be equidistant from the origin to create our viable rotations. An algorithm focused on restricted possibilities. An exploration of 2D lattices for which twinning is mathematically impossible. We find that there is much to be investigated in the field of twinning.
Inventario de las abejas (Hymenoptera: Apoidea) de la reserva ecológica Sierra de la Güira, Pinar del Río, Cuba
Authors: Breto Dayron
Published: July 2021

Se presenta la composición de especies de abejas en seis localidades de la Reserva Ecológica Sierra de La Güira, Pinar del Río. Las observaciones y recolectas se realizaron entre los años 2013 y 2019, en las siguientes formaciones vegetales: bosque semideciduo, pinares, vegetación secundaria y vegetación ruderal. Se registraron 42 especies, correspondientes a 21 géneros y cuatro familias. Las especies endémicas representaron el 26.2 % y se destacan los nuevos registros de Hylaeus royesi y Megachile droegei, ampliándose su distribución hacia Cuba occidental. Se analizó la distribución de las abejas en algunas formaciones vegetales, encontrándose que la vegetación secundaria y el bosque semideciduo albergaron el mayor número de especies.
First record of the genus Oediceroides (Amphipoda: Amphilochidea: Oedicerotidae) for the Gulf of Mexico, with the description of a new species
Authors: Varela Carlos , Bracken-Grissom Heather D.
Published: July 2021

The genus Oediceroides Stebbing, 1888 represents a group of 23 species of amphipods that live from shallow coastal areas to abyssal plains. Most of these species have been collected in deep waters from localities in the South Atlantic and Pacific Oceans, and only one species has been found in the Mediterranean Sea. Many oediceroids inhabit waters more than 200 meters deep with only four species confined to shallow waters. This is the first occasion in which a species belonging to the genus Oediceroides is recorded for the Gulf of Mexico. Here, we describe O. improvisus sp. nov., a species of marine deep-water amphipod collected in 925 meters of water. This species has carapace, mouthpart and pereopodal characters that unite it with other members of the genus. It differs from all other species due to unique rostral and pereopod seven characters, all discussed in detail further in this description. To date, only 20 deep-sea (>200 meters) benthic amphipods have been recorded in the Gulf of Mexico, in comparison with more than 200 species of shallow water representatives from the same region. Our study provides evidence that the deep waters of the Gulf of Mexico still hold undescribed biodiversity.
Macrofauna bentónica asociada a bancos ostrícolas (Crassostrea virginica) en las lagunas de Pueblo Viejo, Tamiahua y Tampamachoco, Veracruz, México
Authors: San Martín-del Ángel Pablo , Cuervo-González Rodrigo , De la Cruz-Francisco Vicencio , Hernández-Herrera Rosa Idalia
Published: July 2021

Los bancos ostrícolas de Crassostrea virginica constituyen hábitats importantes ya que proveen refugio, alimento y áreas de crianza para diversos organismos acuáticos. El objetivo de este trabajo fue estudiar la composición y abundancia de la macrofauna bentónica en los bancos ostrícolas (C. virginica) de las lagunas Pueblo Viejo, Tamiahua y Tampamachoco, Veracruz, México. Se realizaron muestreos mensuales en tres bancos ostrícolas por laguna costera. Los organismos fueron extraídos con el arte de pesca “gafas”. La información obtenida se utilizó para estimar la riqueza de especies, abundancia, equitatividad y diversidad verdadera a nivel mensual por laguna costera. Además, se determinaron diferencias significativas mediante análisis de similitud y ordenación. Se recolectó un total de 1 606 ejemplares del macrobentos en las tres lagunas, identificando 28 especies, 24 familias, 18 órdenes distribuidos en seis grupos zoológicos: Porifera, Platyhelminthes, Annelida, Mollusca, Arthropoda y Bryozoa. Mollusca y Annelida fueron los de mayor riqueza y abundancia de especies. Los bancos ostrícolas de la laguna Tampamachoco fueron más diversos en especies (27 taxa) y abundantes (857 individuos) en comparación a Pueblo Viejo y Tamiahua. Epibiontes filtradores caracterizaron los bancos ostrícolas representados por Brachidontes exustus (en Pueblo Viejo), Amphibalanus eburneus e Hydroides dianthus (ambas en Tampamachoco). Mientras en Tamiahua, las más representativas fueron carnívoros: Nereis oligohalina y Stylochus ellipticus. Para las tres lagunas estudiadas, los valores de la riqueza, abundancia y equitatividad fueron homogéneos en los meses estudiados. Los bancos ostrícolas de cada laguna costera presentan un ensamblaje macrofaunístico propio, dado que se determinaron diferencias significativas con base en la riqueza y abundancia.
Variaciones espaciales de las comunidades de lagartos diurnos en Loma de Cunagua, Ciego de Ávila, Cuba
Authors: Fundora-Caballero Daylon , Arias-Barreto Ángel
Published: July 2021

Una problemática común en nuestro país es conocer cómo influyen las variaciones del área y sus condiciones, en la distribución y abundancia de las comunidades de reptiles. El Refugio de Fauna Loma de Cunagua presenta dos variantes de Bosque Semideciduo (conservada y secundaria). Existen en el área 18 especies, 14 de ellas endémicas, que incluyen dos taxones a nivel subespecífico. Hay predominio de lagartos diurnos, pero sin información sobre el comportamiento de sus poblaciones. Para este estudio se establecieron transectos en las dos variantes de bosque, donde se efectuó un muestreo mensual durante un año y se anotaron las especies y sus datos de hábitat y microhábitat. Se realizó una correlación de Pearson con los valores de riqueza de especies en cada variante de bosque para conocer la influencia del hábitat en la comunidad. Para identificar las tendencias de las variaciones comunitarias se utilizó un Análisis de Correspondencias. Las especies más representadas fueron Anolis sagrei y Anolis lucius, pero todas son dependientes de las características del hábitat. Existe una correlación positiva entre la riqueza de especies y la variante conservada de bosque, probablemente relacionado con la complejidad del hábitat. A mayor número de estratos a usar, mayor número de especies de reptiles. Además, la cobertura de dosel y la insolación son parámetros esenciales en la segregación de las especies.
Coherence Resonance in Random Erdös-Rényi Neural Networks: Mean-Field Theory
Authors: Hutt A. , Wahl T. , Voges N. , Hausmann Jo , Lefebvre J.
Published: July 2021

Additive noise is known to tune the stability of nonlinear systems. Using a network of two randomly connected interacting excitatory and inhibitory neural populations driven by additive noise, we derive a closed mean-field representation that captures the global network dynamics. Building on the spectral properties of Erdös-Rényi networks, mean-field dynamics are obtained via a projection of the network dynamics onto the random network’s principal eigenmode. We consider Gaussian zero-mean and Poisson-like noise stimuli to excitatory neurons and show that these noise types induce coherence resonance. Specifically, the stochastic stimulation induces coherent stochastic oscillations in the γ-frequency range at intermediate noise intensity. We further show that this is valid for both global stimulation and partial stimulation, i.e. whenever a subset of excitatory neurons is stimulated only. The mean-field dynamics exposes the coherence resonance dynamics in the γ-range by a transition from a stable non-oscillatory equilibrium to an oscillatory equilibrium via a saddle-node bifurcation. We evaluate the transition between non-coherent and coherent state by various power spectra, Spike Field Coherence and information-theoretic measures.
One-Time Optimization of Advanced T Cell Culture Media Using a Machine Learning Pipeline
Authors: Grzesik Paul , Warth Sebastian C.
Published: July 2021

The growing application of cell and gene therapies in humans leads to a need for cell type-optimized culture media. Design of Experiments (DoE) is a successful and well known tool for the development and optimization of cell culture media for bioprocessing. When optimizing culture media for primary cells used in cell and gene therapy, traditional DoE approaches that depend on interpretable models will not always provide reliable predictions due to high donor variability. Here we present the implementation of a machine learning pipeline into the DoE-based design of cell culture media to optimize T cell cultures in one experimental step (one-time optimization). We applied a definitive screening design from the DoE toolbox to screen 12 major media components, resulting in 25 (2k + 1) media formulations. T cells purified from a set of four human donors were cultured for 6 days and cell viability on day 3 and cell expansion on day 6 were recorded as response variables. These data were used as a training set in the machine learning pipeline. In the first step, individual models were created for each donor, evaluated and selected for each response variable, resulting in eight final statistical models (R2 > 0.92, RMSE < 1.5). These statistical models were used to predict T cell viability and expansion for 105 random in silico-generated media formulations for each donor in a grid search approach. With the aim of identifying similar formulations in all donors, the 40 best performing media formulations of each response variable were pooled from all donors (n = 320) and subjected to unsupervised clustering using the k-means algorithm. The median of each media component in each cluster was defined as the cluster media formulation. When these formulations were tested in a new set of donor cells, they not only showed a higher T cell expansion than the reference medium, but also precisely matched the average expansion predicted from the donor models of the training set. In summary, we have shown that the introduction of a machine learning pipeline resulted in a one-time optimized T cell culture medium and is advantageous when working with heterogeneous biological material.
3D Printing Experimental Validation of the Finite Element Analysis of the Maxillofacial Model
Authors: Shu Jingheng , Luo Haotian , Zhang Yuanli , Liu Zhan
Published: July 2021

Contacts used in finite element (FE) models were considered as the best simulation for interactions in the temporomandibular joint (TMJ). However, the precision of simulations should be validated through experiments. Three-dimensional (3D) printing models with the high geometric and loading similarities of the individuals were used in the validation. This study aimed to validate the FE models of the TMJ using 3D printing models. Five asymptomatic subjects were recruited in this study. 3D models of mandible, disc, and maxilla were reconstructed according to cone-beam CT (CBCT) image data. PLA was chosen for 3D printing models from bottom to top. Five pressure forces corresponding to the central occlusion were applied to the 3D printing models. Ten strain rosettes were distributed on the mandible to record the horizontal and vertical strains. Contact was used in the FE models with the same geometries, material properties, loadings, and boundary conditions as 3D printing models to simulate the interaction of the disc-condyle, disc-temporal bone, and upper-lower dentition. The differences of the simulated and experimental results for each sample were less than 5% (maximum 4.92%) under all five loadings. In conclusion, it was accurate to use contact to simulate the interactions in TMJs and upper-lower dentition.
Tree Canopies Influence Ground Level Atmospheric Electrical and Biogeochemical Variability
Authors: Hunting Ellard R. , England Sam J. , Robert Daniel
Published: July 2021

Static electric fields in the atmosphere are increasingly recognized as interacting with various organisms over several levels of biological organization. Recently, a link between atmospheric electrical variations and biogeochemical processes has been established in the context of open fields, yet biological structures like trees produce substantial alterations in atmospheric electric properties. Here, we assess whether these structural changes affect the dynamics of the electrical landscape and its relation to geochemical processes. To this end, we theoretically assess how trees alter their surrounding electric fields and empirically compare the temporal dynamics of atmospheric potential gradients, positive ions in the near-ground level atmosphere and soil electrochemical properties in an open field and under a tree. The developed model of electric fields around trees provides insight into the extent to which trees shield the underlying electric landscape, revealing that a substantial increase in atmospheric potential gradient only marginally affects the electric field under the canopy. We further show that soil electrochemical properties are tied to the temporal dynamics of positive ion in the near-ground level atmosphere, and that the presence of a tree reduces the temporal variability in both ground level positive ion concentrations and soil redox potential. This suggests that a tree can alter the temporal variability in atmospheric electricity and soil electro-chemistry, thereby likely indirectly influencing soil microorganisms and processes as well as electro-sensitive organisms that perceive and utilize atmospheric electric fields.
Narratives of Systemic Barriers and Accessibility: Poverty, Equity, Diversity, Inclusion, and the Call for a Post-Pandemic New Normal
Authors: Ciuffetelli Parker Darlene , Conversano Palmina
Published: July 2021

This paper captures the intimate, intensely lived, and storied experiences during the pandemic, on teachers’ narratives of teaching and education. The narratives illuminate deep knowledge and insight into pre-existing school systemic barriers prior to the pandemic, and how those same barriers are magnified during the pandemic in what has become a global watershed moment that calls for equity reform in school systems. A narrative theoretical framework is used, as well as an ethic of care framework that informs the study. Issues of poverty, diversity, equity, and inclusion are illuminated, with further focus on topics of technology access, streaming, resilience, and teacher-student identity and relationship. Recommendations to eradicate systemic barriers in schools are explored, highlighting suggestions for equity reform in areas that include: enhancing professional practice; building a school culture of care, and; developing partnerships and relationships.
Comparative Transcriptome and Weighted Gene Co-expression Network Analysis Identify Key Transcription Factors of Rosa chinensis ‘Old Blush’ After Exposure to a Gradual Drought Stress Followed by Recovery
Authors: Jia Xin , Feng Hui , Bu Yanhua , Ji Naizhe , Lyu Yingmin , Zhao Shiwei
Published: July 2021

Rose is one of the most fundamental ornamental crops, but its yield and quality are highly limited by drought. The key transcription factors (TFs) and co-expression networks during rose’s response to drought stress and recovery after drought stress are still limited. In this study, the transcriptomes of leaves of 2-year-old cutting seedlings of Rosa chinensis ‘Old Blush’ from three continuous droughted stages (30, 60, 90 days after full watering) and rewatering were analyzed using RNA sequencing. Weighted gene co-expression network analysis (WGCNA) was used to construct a co-expression network, which was associated with the physiological traits of drought response to discovering the hub TFs involved in drought response. More than 45 million high-quality clean reads were generated from the sample and used for comparison with the rose reference genome. A total of 46433 differentially expressed genes (DEGs) were identified. Gene Ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that drought stress caused significant changes in signal transduction, plant hormones including ABA, auxin, brassinosteroid (BR), cytokinin, ethylene (ET), jasmonic acid (JA) and salicylic acid (SA), primary and secondary metabolism, and a certain degree of recovery after rewatering. Gene co-expression analysis identified 18 modules, in which four modules showed a high degree of correlation with physiological traits. In addition, 42 TFs including members of NACs, WRKYs, MYBs, AP2/ERFs, ARFs, and bHLHs with high connectivity in navajowhite1 and blue modules were screened. This study provides the transcriptome sequencing report of R. chinensis ‘Old Blush’ during drought stress and rewatering process. The study also identifies the response of candidate TFs to drought stress, providing guidelines for improving the drought tolerance of the rose through molecular breeding in the future.
Identification and Characterization of the Succinate Dehydrogenase Complex Iron Sulfur Subunit B Gene in the Oriental River Prawn, Macrobrachium nipponense
Authors: Jin Shubo , Hu Yuning , Fu Hongtuo , Jiang Sufei , Xiong Yiwei , Qiao Hui , Zhang Wenyi , Gong Yongsheng , Wu Yan
Published: July 2021

Previous studies have revealed that SDHB has potential functions in the male sexual differentiation and development in M. nipponense through providing ATP. In this study, the functions of Mn-SDHB were further analyzed in depth using quantitative polymerase chain reaction (qPCR), in situ hybridization, western-blot, and RNA interference (RNAi), combined with the histological observations. The full-genome sequence of Mn-SDHB was 54,608 bp at Chromosome 34, including 7 introns and 6 exons. The full-length cDNA sequence of Mn-SDHB was 1,268 base pairs (bp) long with an open reading frame of 807 bp, encoding for 268 amino acids. The highest expression level of Mn-SDHB in different tissues was observed in the testis, and male prawns at post-larval developmental stage 25 during different developmental stages, indicating that SDHB was potentially involved in the male sexual development in M. nipponense. In situ hybridization and western-blot analysis indicated that SDHB plays essential roles in the testis development. The in situ hybridization analysis also implies the potential roles of Mn-SDHB in ovarian development. The expressions of Mn-IAG were decreased after Mn-SDHB dsRNA injection, indicating SDHB has the positive regulatory effects on IAG in M. nipponese. Thus, SDHB was involved in the mechanism of the male sexual development. The testis development was inhibited, and sperms were rarely observed after 10 days of Mn-SDHB dsRNA injection, indicating SDHB has positive effects on the male sexual development in M. nipponense. This study highlights the functions of SDHB in M. nipponense, which provide new insights for the future studies of the male sexual development in other crustacean species.
Comprehensive Profiling of Inflammatory Factors Revealed That Growth Differentiation Factor-15 Is an Indicator of Disease Severity in COVID-19 Patients
Authors: Teng Xiangyun , Zhang Jiaqi , Shi Yaling , Liu Yuntao , Yang Yanqing , He Jinyong , Luo Shuhong , Huang Yile , Liu Yanxia , Liu Dongdong , Li Yizhe , Zhang Shuangzhe , Huang Ruo-Pan , Wang Dawei , Xu Jianhua
Published: July 2021

To systematically explore potential biomarkers which can predict disease severity in COVID-19 patients and prevent the occurrence or development of severe COVID-19, the levels of 440 factors were analyzed in patients categorized according to COVID-19 disease severity; including asymptomatic, mild, moderate, severe, convalescent and healthy control groups. Factor candidates were validated by ELISA and functional relevance was uncovered by bioinformatics analysis. To identify potential biomarkers of occurrence or development of COVID-19, patient sera from three different severity groups (moderate, severe, and critical) at three time points (admission, remission, and discharge) and the expression levels of candidate biomarkers were measured. Eleven differential factors associated with disease severity were pinpointed from 440 factors across 111 patients of differing disease severity. The dynamic changes of GDF15 reflect the progression of the disease, while the other differential factors include TRAIL R1, IGFBP-1, IGFBP-4, VCAM-1, sFRP-3, FABP2, Transferrin, GDF15, IL-1F7, IL-5Rα, and CD200. Elevation of white blood cell count, neutrophil count, neutrophil-lymphocyte ratio (NLR), Alanine aminotransferase and Aspartate aminotransferase, low lymphocyte and eosinophil counts in the severe group were associated with the severity of COVID-19. GDF15 levels were observed to be associated with the severity of COVID-19 and the dynamic change of GDF15 levels was closely associated with the COVID-19 disease progression. Therefore, GDF15 might serve as an indicator of disease severity in COVID-19 patients.
Identification and Validation of Immune Molecular Subtypes in Pancreatic Ductal Adenocarcinoma: Implications for Prognosis and Immunotherapy
Authors: Li Ruiyu , He Yangzhige , Zhang Hui , Wang Jing , Liu Xiaoding , Liu Hangqi , Wu Huanwen , Liang Zhiyong
Published: July 2021

Background

Pancreatic ductal adenocarcinoma (PDAC) remains treatment refractory. Immunotherapy has achieved success in the treatment of multiple malignancies. However, the efficacy of immunotherapy in PDAC is limited by a lack of promising biomarkers. In this research, we aimed to identify robust immune molecular subtypes of PDAC to facilitate prognosis prediction and patient selection for immunotherapy.

Methods

A training cohort of 149 PDAC samples from The Cancer Genome Atlas (TCGA) with mRNA expression data was analyzed. By means of non-negative matrix factorization (NMF), we virtually dissected the immune-related signals from bulk gene expression data. Detailed immunogenomic and survival analyses of the immune molecular subtypes were conducted to determine their biological and clinical relevance. Validation was performed in five independent datasets on a total of 615 samples.

Results

Approximately 31% of PDAC samples (46/149) had higher immune cell infiltration, more active immune cytolytic activity, higher activation of the interferon pathway, a higher tumor mutational burden (TMB), and fewer copy number alterations (CNAs) than the other samples (all P < 0.001). This new molecular subtype was named Immune Class, which served as an independent favorable prognostic factor for overall survival (hazard ratio, 0.56; 95% confidence interval, 0.33-0.97). Immune Class in cooperation with previously reported tumor and stroma classifications had a cumulative effect on PDAC prognostic stratification. Moreover, programmed cell death-1 (PD-1) inhibitors showed potential efficacy for Immune Class (P = 0.04). The robustness of our immune molecular subtypes was further verified in the validation cohort.

Conclusions

By capturing immune-related signals in the PDAC tumor microenvironment, we reveal a novel molecular subtype, Immune Class. Immune Class serves as an independent favorable prognostic factor for overall survival in PDAC patients.
Immunopathogenesis of Different Emerging Viral Infections: Evasion, Fatal Mechanism, and Prevention
Authors: Yang Betsy , Yang Kuender D.
Published: July 2021

Different emerging viral infections may emerge in different regions of the world and pose a global pandemic threat with high fatality. Clarification of the immunopathogenesis of different emerging viral infections can provide a plan for the crisis management and prevention of emerging infections. This perspective article describes how an emerging viral infection evolves from microbial mutation, zoonotic and/or vector-borne transmission that progresses to a fatal infection due to overt viremia, tissue-specific cytotropic damage or/and immunopathology. We classified immunopathogenesis of common emerging viral infections into 4 categories: 1) deficient immunity with disseminated viremia (e.g., Ebola); 2) pneumocytotropism with/without later hyperinflammation (e.g., COVID-19); 3) augmented immunopathology (e.g., Hanta); and 4) antibody-dependent enhancement of infection with altered immunity (e.g., Dengue). A practical guide to early blocking of viral evasion, limiting viral load and identifying the fatal mechanism of an emerging viral infection is provided to prevent and reduce the transmission, and to do rapid diagnoses followed by the early treatment of virus neutralization for reduction of morbidity and mortality of an emerging viral infection such as COVID-19.
T Cell Response in Ischemic Stroke: From Mechanisms to Translational Insights
Authors: Zhang Dianhui , Ren Jiaxin , Luo Yun , He Qianyan , Zhao Ruoyu , Chang Junlei , Yang Yi , Guo Zhen-Ni
Published: July 2021

Ischemic stroke, caused by a sudden disruption of blood flow to the brain, is a leading cause of death and exerts a heavy burden on both patients and public health systems. Currently available treatments for ischemic stroke are very limited and are not feasible in many patients due to strict time windows required for their administration. Thus, novel treatment strategies are keenly required. T cells, which are part of the adaptive immune system, have gained more attention for its effects in ischemic stroke. Both preclinical and clinical studies have revealed the conflicting roles for T cells in post-stroke inflammation and as potential therapeutic targets. This review summarizes the mediators of T cell recruitment, as well as the temporal course of its infiltration through the blood-brain-barrier, choroid plexus, and meningeal pathways. Furthermore, we describe the mechanisms behind the deleterious and beneficial effects of T cells in the brain, in both antigen-dependent and antigen-independent manners, and finally we specifically focus on clinical and preclinical studies that have investigated T cells as potential therapeutic targets for ischemic stroke.
Cryptococcal Meningitis and Post-Infectious Inflammatory Response Syndrome in a Patient With X-Linked Hyper IgM Syndrome: A Case Report and Review of the Literature
Authors: Romani Lorenza , Williamson Peter Richard , Di Cesare Silvia , Di Matteo Gigliola , De Luca Maia , Carsetti Rita , Figà-Talamanca Lorenzo , Cancrini Caterina , Rossi Paolo , Finocchi Andrea
Published: July 2021

The hyper IgM syndromes are a rare group of primary immunodeficiency. The X-linked Hyper IgM syndrome (HIGM), due to a gene defect in CD40L, is the commonest variant; it is characterized by an increased susceptibility to a narrow spectrum of opportunistic infection. A few cases of HIGM patients with Cryptococcal meningoencephalitis (CM) have been described in the literature. Herein we report the case of a young male diagnosed in infancy with HIGM who developed CM complicated by a post-infectious inflammatory response syndrome (PIIRS), despite regular immunoglobulin replacement therapy and appropriate antimicrobial prophylaxis. The patient was admitted because of a headache and CM was diagnosed through detection of Cryptococcus neoformans in the cerebrospinal fluid. Despite the antifungal therapy resulting to negative CSF culture, the patient exhibited persistent headaches and developed diplopia. An analysis of inflammatory cytokines on CSF, as well as the brain MRI, suggested a diagnosis of PIIRS. Therefore, a prolonged corticosteroids therapy was started obtaining a complete resolution of symptoms without any relapse.
Mechanical Modification of Nanomaterials on Fully Saturated Concrete in Groundwater Reservoir Under Long-Term Water Immersion
Authors: Hao XianJie , Wei Yingnan , Chen Zeyu , Zhang Honglan , Niu Yifan , Chen Kai , Huang Ruilai
Published: July 2021

With the increasing number of hydraulic structures in service, many scholars have investigated the performance of saturated concrete, however, there are few studies on the influences of different contents and types of nanomaterials on the performance of fully saturated concrete. In this paper, a series of experiments on concrete with different contents of nano SiO2, nano Al2O3 and nano TiO2 are performed, such as electron mirror scanning, uniaxial compression, acoustic emission, etc., and the microstructure, mechanical properties of samples are compared and analyzed. The results show that: 1) By the addition of various kinds of nanomaterials to saturated concrete, the microstructure of saturated concrete is significantly improved, and the compactness and integrity of the slurry are improved 2) The mechanical properties of saturated concrete are significantly improved by the addition of 3 wt% nanomaterials. And the compressive strength of the saturated concrete sample containing 3 wt% nano-Al2O3 is the largest and the deformation modulus of the saturated concrete sample containing 6 wt% nano-Al2O3 is the largest. 3) Compared with dry concrete, when the concrete is saturated, the modifying effect of nanomaterials on the mechanical properties of concrete is weakened. The results of this study have important guiding significance for the study of the nano-modification and the safe operation of hydraulic structures.
Predictors of Failed Intrauterine Balloon Tamponade in the Management of Severe Postpartum Hemorrhage
Authors: Liu Congcong , Gao Jinsong , Liu Juntao , Wang Xietong , He Jing , Sun Jingxia , Liu Xiaowei , Liao Shixiu
Published: July 2021

To identify the factors predicting intrauterine balloon tamponade (IUBT) failure for severe postpartum hemorrhage (PPH) after delivery, we conducted a retrospective cohort study of women who underwent IUBT for severe PPH after delivery from October 1, 2016 until September 30, 2017. The failure of IUBT was defined as the need of additional surgical procedures or uterine embolization. A total of 99,650 deliveries occurred during the study period. Among the patients, 106 cases of severe PPH were managed with IUBT, and the global success rate was 70.8% (75/106). Least absolute shrinkage and selection operator (LASSO) regression was performed to select the potential risk factors predicting IUBT failure. The associated risk factors—obesity, multiple gestation, cesarean delivery, estimated blood loss (EBL), and placenta accreta spectrum (PAS)—were included in multivariate logistic models. Ultimately, these models identified multiple gestation, EBL, and PAS as independent risk factors for IUBT failure. In conclusion, IUBT is an effective method for severe PPH. The presence of factors affecting IUBT failure should be recognized early, and other modalities of management should be anticipated.
Fine-Tuning of Alkaline Residues on the Hydrophilic Face Provides a Non-toxic Cationic α-Helical Antimicrobial Peptide Against Antibiotic-Resistant ESKAPE Pathogens
Authors: Luo Xudong , Ye Xiangdong , Ding Li , Zhu Wen , Yi Pengcheng , Zhao Zhiwen , Gao Huanhuan , Shu Zhan , Li Shan , Sang Ming , Wang Jue , Zhong Weihua , Chen Zongyun
Published: July 2021

Antibiotic-resistant ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) has become a serious threat to public health worldwide. Cationic α-helical antimicrobial peptides (CαAMPs) have attracted much attention as promising solutions in post-antibiotic era. However, strong hemolytic activity and in vivo inefficacy have hindered their pharmaceutical development. Here, we attempt to address these obstacles by investigating BmKn2 and BmKn2-7, two scorpion-derived CαAMPs with the same hydrophobic face and a distinct hydrophilic face. Through structural comparison, mutant design and functional analyses, we found that while keeping the hydrophobic face unchanged, increasing the number of alkaline residues (i.e., Lys + Arg residues) on the hydrophilic face of BmKn2 reduces the hemolytic activity and broadens the antimicrobial spectrum. Strikingly, when keeping the total number of alkaline residues constant, increasing the number of Lys residues on the hydrophilic face of BmKn2-7 significantly reduces the hemolytic activity but does not influence the antimicrobial activity. BmKn2-7K, a mutant of BmKn2-7 in which all of the Arg residues on the hydrophilic face were replaced with Lys, showed the lowest hemolytic activity and potent antimicrobial activity against antibiotic-resistant ESKAPE pathogens. Moreover, in vivo experiments indicate that BmKn2-7K displays potent antimicrobial efficacy against both the penicillin-resistant S. aureus and the carbapenem- and multidrug-resistant A. baumannii, and is non-toxic at the antimicrobial dosages. Taken together, our work highlights the significant functional disparity of Lys vs Arg in the scorpion-derived antimicrobial peptide BmKn2-7, and provides a promising lead molecule for drug development against ESKAPE pathogens.
Comprehensive Deep Mutational Scanning Reveals the Immune-Escaping Hotspots of SARS-CoV-2 Receptor-Binding Domain Targeting Neutralizing Antibodies
Authors: Tsai Keng-Chang , Lee Yu-Ching , Tseng Tien-Sheng
Published: July 2021

The rapid spread of SARS-CoV-2 has caused the COVID-19 pandemic, resulting in the collapse of medical care systems and economic depression worldwide. To combat COVID-19, neutralizing antibodies have been investigated and developed. However, the evolutions (mutations) of the receptor-binding domain (RBD) of SARS-CoV-2 enable escape from neutralization by these antibodies, further impairing recognition by the human immune system. Thus, it is critical to investigate and predict the putative mutations of RBD that escape neutralizing immune responses. Here, we employed computational analyses to comprehensively investigate the mutational effects of RBD on binding to neutralizing antibodies and angiotensin-converting enzyme 2 (ACE2) and demonstrated that the RBD residues K417, L452, L455, F456, E484, G485, F486, F490, Q493, and S494 were consistent with clinically emerging variants or experimental observations of attenuated neutralizations. We also revealed common hotspots, Y449, L455, and Y489, that exerted comparable destabilizing effects on binding to both ACE2 and neutralizing antibodies. Our results provide valuable information on the putative effects of RBD variants on interactions with neutralizing antibodies. These findings provide insights into possible evolutionary hotspots that can escape recognition by these antibodies. In addition, our study results will benefit the development and design of vaccines and antibodies to combat the newly emerging variants of SARS-CoV-2.
Impact of Weaning and Maternal Immune Activation on the Metabolism of Pigs
Authors: Southey Bruce R. , Bolt Courtni R. , Rymut Haley E. , Keever Marissa R. , Ulanov Alexander V. , Li Zhong , Rund Laurie A. , Johnson Rodney W. , Rodriguez-Zas Sandra L.
Published: July 2021

Weaning wields environmental, social, and nutritional stresses that are detectable in the blood metabolite levels of the offspring. Prenatal stress in the form of maternal immune activation (MIA) in response to infection, which is associated with health and behavior disorders, also elicits prolonged changes in blood and brain cytokine and metabolite levels of the offspring. The goal of this study was to investigate the effects of weaning and MIA on the offspring’s liver function to advance the understanding of the impact of stressors on peripheral and central nervous systems, physiology, and health. Gas chromatography–mass spectrometry analysis was used to compare the level of hepatic metabolites from 22-day-old pigs (n = 48) evenly distributed among weaning (nursed or weaned), viral MIA exposure (yes or no), and sexes. Weaning effects were detected on 38 metabolites at p-value < 0.05 (28 metabolites at FDR p-value < 0.05), and sex-dependent MIA effects were detected on 11 metabolites. Multiple intermediate and final products of the enriched (FDR p-value < 0.05) glycolysis and gluconeogenesis and pentose phosphate pathways were over-abundant in nursed relative to weaned pigs. The enriched pathways confirm the impact of weaning on hepatic metabolic shift, oxidative stress, and inflammation. Higher levels of the glucogenic amino acid histidine are observed in pigs exposed to MIA relative to controls, suggesting that the role of this metabolite in modulating inflammation may supersede the role of this amino acid as an energy source. The lower levels of cholesterol detected in MIA pigs are consistent with hypocholesterolemia profiles detected in individuals with MIA-related behavior disorders. Our findings underline the impact of weaning and MIA stressors on hepatic metabolites that can influence peripheral and central nervous system metabolic products associated with health and behavior disorders.
Understanding the Clinical Implications of Intracranial Arterial Calcification Using Brain CT and Vessel Wall Imaging
Authors: Yang Wen-Jie , Wasserman Bruce A. , Zheng Lu , Huang Zhong-Qing , Li Jia , Abrigo Jill , Wong Simon Sin-man , Ying Michael Tin-cheung , Chu Winnie Chiu-Wing , Wong Lawrence Ka-sing , Leung Thomas Wai-Hong , Chen Xiang-Yan
Published: July 2021

Background and Purpose: Intracranial arterial calcification (IAC) has been the focus of much attention by clinicians and researchers as an indicator of intracranial atherosclerosis, but correlations of IAC patterns (intimal or medial) with the presence of atherosclerotic plaques and plaque stability are still a matter of debate. Our study aimed to assess the associations of IAC patterns identified on computed tomography (CT) with the presence of plaque detected on vessel wall magnetic resonance imaging and plaque stability.

Materials and Methods: Patients with stroke or transient ischemic attack and intracranial artery stenosis were recruited. IAC was detected and localized (intima or media) on non-contrast CT images. Intracranial atherosclerotic plaques were identified using vessel wall magnetic resonance imaging and matched to corresponding CT images. Associations between IAC patterns and culprit atherosclerotic plaques were assessed by using multivariate regression.

Results: Seventy-five patients (mean age, 63.4 ± 11.6 years; males, 46) were included. Two hundred and twenty-one segments with IAC were identified on CT in 66 patients, including 86 (38.9%) predominantly intimal calcifications and 135 (61.1%) predominantly medial calcifications. A total of 72.0% of intimal calcifications coexisted with atherosclerotic plaques, whereas only 10.2% of medial calcifications coexisted with plaques. Intimal calcification was more commonly shown in non-culprit plaques than culprit plaques (25.9 vs. 9.4%, P = 0.008). The multivariate mixed logistic regression adjusted for the degree of stenosis showed that intimal calcification was significantly associated with non-culprit plaques (OR, 2.971; 95% CI, 1.036–8.517; P = 0.043).

Conclusion: Our findings suggest that intimal calcification may indicate the existence of a stable form of atherosclerotic plaque, but plaques can exist in the absence of intimal calcification especially in the middle cerebral artery.
Forecasting Seizure Likelihood With Wearable Technology
Authors: Stirling Rachel E. , Grayden David B. , D'Souza Wendyl , Cook Mark J. , Nurse Ewan , Freestone Dean R. , Payne Daniel E. , Brinkmann Benjamin H. , Pal Attia Tal , Viana Pedro F. , Richardson Mark P. , Karoly Philippa J.
Published: July 2021

The unpredictability of epileptic seizures exposes people with epilepsy to potential physical harm, restricts day-to-day activities, and impacts mental well-being. Accurate seizure forecasters would reduce the uncertainty associated with seizures but need to be feasible and accessible in the long-term. Wearable devices are perfect candidates to develop non-invasive, accessible forecasts but are yet to be investigated in long-term studies. We hypothesized that machine learning models could utilize heart rate as a biomarker for well-established cycles of seizures and epileptic activity, in addition to other wearable signals, to forecast high and low risk seizure periods. This feasibility study tracked participants' (n = 11) heart rates, sleep, and step counts using wearable smartwatches and seizure occurrence using smartphone seizure diaries for at least 6 months (mean = 14.6 months, SD = 3.8 months). Eligible participants had a diagnosis of refractory epilepsy and reported at least 20 seizures (mean = 135, SD = 123) during the recording period. An ensembled machine learning and neural network model estimated seizure risk either daily or hourly, with retraining occurring on a weekly basis as additional data was collected. Performance was evaluated retrospectively against a rate-matched random forecast using the area under the receiver operating curve. A pseudo-prospective evaluation was also conducted on a held-out dataset. Of the 11 participants, seizures were predicted above chance in all (100%) participants using an hourly forecast and in ten (91%) participants using a daily forecast. The average time spent in high risk (prediction time) before a seizure occurred was 37 min in the hourly forecast and 3 days in the daily forecast. Cyclic features added the most predictive value to the forecasts, particularly circadian and multiday heart rate cycles. Wearable devices can be used to produce patient-specific seizure forecasts, particularly when biomarkers of seizure and epileptic activity cycles are utilized.
Functional Cortical Connectivity Related to Postural Control in Patients Six Weeks After Anterior Cruciate Ligament Reconstruction
Authors: Lehmann Tim , Büchel Daniel , Mouton Caroline , Gokeler Alli , Seil Romain , Baumeister Jochen
Published: July 2021

Whereas initial findings have already identified cortical patterns accompanying proprioceptive deficiencies in patients after anterior cruciate ligament reconstruction (ACLR), little is known about compensatory sensorimotor mechanisms for re-establishing postural control. Therefore, the aim of the present study was to explore leg dependent patterns of cortical contributions to postural control in patients 6 weeks following ACLR. A total of 12 patients after ACLR (25.1 ± 3.2 years, 178.1 ± 9.7 cm, 77.5 ± 14.4 kg) and another 12 gender, age, and activity matched healthy controls participated in this study. All subjects performed 10 × 30 s. single leg stances on each leg, equipped with 64-channel mobile electroencephalography (EEG). Postural stability was quantified by area of sway and sway velocity. Estimations of the weighted phase lag index were conducted as a cortical measure of functional connectivity. The findings showed significant group × leg interactions for increased functional connectivity in the anterior cruciate ligament (ACL) injured leg, predominantly including fronto−parietal [F(1, 22) = 8.41, p ≤ 0.008, η2 = 0.28], fronto−occipital [F(1, 22) = 4.43, p ≤ 0.047, η2 = 0.17], parieto−motor [F(1, 22) = 10.30, p ≤ 0.004, η2 = 0.32], occipito−motor [F(1, 22) = 5.21, p ≤ 0.032, η2 = 0.19], and occipito−parietal [F(1, 22) = 4.60, p ≤ 0.043, η2 = 0.17] intra−hemispherical connections in the contralateral hemisphere and occipito−motor [F(1, 22) = 7.33, p ≤ 0.013, η2 = 0.25] on the ipsilateral hemisphere to the injured leg. Higher functional connectivity in patients after ACLR, attained by increased emphasis of functional connections incorporating the somatosensory and visual areas, may serve as a compensatory mechanism to control postural stability of the injured leg in the early phase of rehabilitation. These preliminary results may help to develop new neurophysiological assessments for detecting functional deficiencies after ACLR in the future.