bluuebunny/crossref_metadata_2025 huggingface dataset:
Acondicionamiento del puente de O'Donnell sobre la M-30 (Madrid, España)
Authors: Sopeña Corvinos Luis , Álvarez Andrés Juan Jesús , Silvo González José Enrique , Corral Moraleda Noemí , Ripa Alonso Tomás
Published: January 2021

Dentro del plan de mantenimiento de infraestructuras de Calle 30, empresa pública del Ayuntamiento de Madrid, se plantea el acondicionamiento del puente que resuelve el cruce de la prolongación de la calle O’Donnell (M-23) sobre la M-30.

Este puente, construido aproximadamente en 1970, está constituido por dos tableros independientes de hormigón pretensado, con pilas y estribos de hormigón armado. Consta de 5 vanos de luces 15 +24 +38 +24 +15 m.

La sección transversal de cada tablero, con una anchura de 20,40 m, está formada por dos losas aligeradas de hormigón pretensado en forma de artesa, con canto variable entre 0,95 y 1,20 m, unidas por la losa superior.

La rehabilitación de la estructura implicó actuaciones en estribos, pilas y tablero, la mayoría consistentes en reparaciones superficiales, pero también fueron necesarias actuaciones más profundas a nivel estructural. A continuación se exponen las 3 principales actuaciones de rehabilitación llevadas a cabo:

1) Sustitución de apoyos de estribos. La principal dificultad fue el pequeño espacio disponible para alojar los gatos y trabajar.

2) Inyección de fisuras: en total, 925 m de tratamiento de fisuras.

3) Instalación de nuevos pretiles. Aplicando la nueva normativa de pretiles y barreras de seguridad, el nivel de contención necesario es H4b. Teniendo en cuenta los criterios de deflexión dinámica y anchura de trabajo, se optó por un pretil metálico anclado químicamente al tablero, previo refuerzo del mismo  a base de un sistema de láminas de CFRP.

Todos los trabajos se realizaron con la premisa de minimizar la afección al tráfico inferior de la M-30, así como manteniendo el tráfico abierto sobre la propia estructura al menos en una de las 2 calzadas.
Diseño y construcción de los Puentes Junín y Leoncio Prado en Lima (Perú)
Authors: Capellán Miguel Guillermo , Alonso Velasco Carlos D. , Pando Anta José Luis , Godoy Ansótegui Alejandro , González Zalduondo Julio
Published: January 2021

La vía expresa del Paseo de la República, es uno de los ejes vertebradores de la ciudad de Lima. Debido a su condición de trinchera, supone un gran obstáculo entre los distritos de Surquillo y Miraflores. Con el fin de facilitar la permeabilidad del tráfico entre ambos barrios, se han construido los puentes de Junín y Leoncio Prado.

Los dos puentes, debido a limitaciones de gálibo y a fin de despejar completamente la vía expresa de pilas intermedias que supongan un peligro constante de accidentes, son puentes arco atirantados por el tablero (“bowstring”), con dos arcos metálicos sin arriostrar que separan el tráfico peatonal del rodado.

El Puente de Leoncio Prado, de 42.8 m de luz entre apoyos, es el arco más rebajado, y se une al nervio inferior por medio de péndolas rígidas. Tanto las anchas aceras, los arcos, los nervios y las vigas de borde siguen un trazado curvo para permitir el abocinamiento de la entrada y de la salida al puente, invitando a peatones y vehículos a cruzar. Aunque los principales elementos, como los arcos y los nervios longitudinales tiene un ancho constante, las aceras tienen un ancho variable que va desde los 4 metros en la entrada, a los 3.30 metros en el centro luz.

En Puente Junín, de 55.50 m de luz entre apoyos, los arcos se unen al tablero mediante péndolas realizadas con barras de acero inoxidable. A pesar de que los nervios inferiores del puente bowstring siguen manteniendo el mismo abocinamiento de entrada y salida, la directriz del arco es completamente recta en planta, por lo que los tirantes forman una superficie tridimensional que cubre a los peatones en su paso sobre el Paseo de la República.
Diseño, Construcción y Capacidades del Large Universal Shell Element Tester
Authors: Alexander Beck , Kaufmann Walter , Karagiannis Demis , Werne Dominik
Published: January 2021

El Large Universal Shell Element Tester (LUSET) es un nuevo dispositivo de ensayos, desarrollado en la ETH Zúrich, el cual facilita el estudio del comportamiento mecánico, a escala real, de elementos lámina de hormigón armado sujetos a solicitaciones en sus tres dimensiones (esfuerzos combinados de elementos tipo losa y membrana). En este artículo se presentan los motivos que condujeron al desarrollo del LUSET y, adicionalmente, se describen sus componentes, el software de control y los sistemas de medición. Finalmente, se presenta una breve descripción de la serie de ensayos usada para validar la funcionalidad del LUSET, así como, un resumen de sus posibilidades.
Depósito de cloruros en el hormigón en las atmósferas de la Isla de Tenerife-España
Authors: Andrade Perdrix María del Carmen , Blanco Peñalver Concepción , Souto Suárez R. , Santana Rodríguez J.J. , Rodríguez Brito N.
Published: January 2021

El efecto del viento sobre la superficie del mar y su oleaje cerca de la costa provoca la formación de un aerosol con un contenido de cloruros y sales que depende de su velocidad. Este aerosol es transportado por el viento hacia el interior de tierra hasta que termina depositándose, y en el caso concrete de las estructuras de hormigón penetra por la red de poros pudiendo provocar la corrosión de la armadura. El alcance hacia el interior de este aerosol ha sido estudiado por numerosos investigadores y existen modelos al igual que se ha estudiado su acumulación en probetas de hormigón situadas al menos en dos atmosferas de Brasil. No existen en cambio estudios similares en España. En el presente trabajo se comunican los contenidos de cloruros que se han recogido con el método de la vela húmeda en cinco estaciones colocadas en diversos emplazamientos de la Isla de Tenerife en España. En la figura 1 y 2 se muestran una estación de ensayo y el dispositivo de la vela húmeda.

Los resultados encontrados confirman el descenso exponencial de la deposición de cloruros con la distancia a la costa (figura 3) y con la velocidad del viento (figura 4)

Solo en una de las estaciones los cloruros depositados han tenido relevancia desde la perspectiva de la durabilidad de la armadura, ya que en las demás la cantidad depositada ha sido muy pequeña. La relación entre la distancia y el depósito de cloruros ha sido de tipo exponencial al igual que la relación con la velocidad del viento. En el trabajo se comparan estos resultados con los propuestos por Meira, no encontrándose una completa concordancia, posiblemente debido al irregular régimen del viento en el presente caso y a que la velocidad en la isla de Tenerife es mayor que la registrada por Meira que fue de alrededor de 3 m/s. Es precisamente para velocidades mayores de 3 m/s cuando existen divergencias en la literatura debido al mayor arrastre del aerosol por las mayores velocidades. Las cantidades que penetran en el hormigón, son función de su calidad como era esperable. En el presente trabajo se dan los datos encontrados con los hormigones ensayados.

 

REFERENCIAS

Caracterización climática de las Islas Canarias para la aplicación del código técnico de la Edificación, CLIMCAN-010 y de su aplicación informática complementaria, CTE-DR/008/11. Gobierno de Canarias, Santa Cruz de Tenerife, 2011.

G.R. Meira, C. Andrade, C. Alonso, I.J. Padaratz, J.C. Borba, Modelling sea-salt transport and deposition in marine atmosphere zone – A tool for corrosion studies, Corros. Sci. 50 (2008) 2724-2731.

G.R. Meira, C. Andrade, C. Alonso, I.J. Padaratz, J.C. Borba Jr, Salinity of marine aerosols in a Brazilian coastal area—Influence of wind regime, Atmos. Environ. 41 (2007) 8431-8441.

M. Morcillo, B. Chico, L. Mariaca, E. Otero, Salinity in marine atmospheric corrosion: its dependence on the wind regime existing in the site, Corros. Sci. 42 (2000) 91-104.
ÇOCUK EDEBİYATI ÜRÜNLERİNDE FARKLI SANATLARIN VARLIĞINA VE SUNULUŞ BİÇİMİNE İLİŞKİN BİR İNCELEME
Authors: ASLAN Canan , BAYRAKTAR Ayşegül
Published: January 2021

Okulöncesi dönemden başlayarak öğretimin her aşamasında çocukların farklı sanatlarla buluşturulması çocuğun sanat eğitimi süreci açısından önemli ve gereklidir. Çocuğun farklı sanatlarla buluştuğu ortamlardan biri de çocuk edebiyatı ürünleridir. Bu nitelikteki ürünler görsel ve dilsel metinler yoluyla çocukları öteki sanatlarla buluşturur, doğal kurgusu içinde bu sanatların önemini ve gerekliliğini duyumsatır ve böylece çocukların bütüncül bir sanat eğitiminden geçmesine katkıda bulunur. Çocuk edebiyatı ürünleri gerek içerik ve tasarım özellikleri açısından gerekse başka açılardan birçok çalışmanın konusu olmuş; ancak bu nitelikteki ürünlerin çocuğu öteki sanatlarla buluşturma işlevini ortaya koymak amacıyla gerçekleştirilen bir çalışmaya rastlanmamıştır. Bu çalışmanın amacı, çocuk edebiyatı adı altında çok satılan kitaplarda çocukları sanatın farklı dallarıyla buluşturacak, onlara bu sanatların önemini duyumsatacak anlatımların olup olmadığını belirlemektir. Araştırma, nitel araştırma yaklaşımıyla gerçekleştirilmiştir. Araştırmanın inceleme nesnesi, nitel araştırma yaklaşımı içinde yer alan amaçlı örnekleme yöntemlerinden “ölçüt örnekleme” yoluyla belirlenmiştir. Çalışma kapsamında incelenecek kitaplar «Idefix Online Kitabevi» adlı kitap satış sitesinin ve “D&R Kitabevi”nin çok satılan çocuk kitapları sayfalarından alınmıştır. Bu amaçla her iki sitenin listesinde ortaklık gösteren 20 kitap incelenmek üzere seçilmiştir. Çalışma sonucunda çok satılan çocuk kitaplarının farklı sanatların olanaklarını yazınsal bir biçimde yansıttığı, çocukta bu sanatlara karşı farkındalık yaratacak nitelikte olduğu görülmüştür.
The Microbiome and Alzheimer’s Disease: Potential and Limitations of Prebiotic, Synbiotic, and Probiotic Formulations
Authors: Arora Karan , Green Miranda , Prakash Satya
Published: January 2021

The Microbiome has generated significant attention for its impacts not only on gastrointestinal health, but also on signaling pathways of the enteric and central nervous system via the microbiome gut–brain axis. In light of this, microbiome modulation may be an effective therapeutic strategy for treating or mitigating many somatic and neural pathologies, including neurodegenerative disorders. Alzheimer’s disease (AD) is a chronic neurodegenerative disease that interferes with cerebral function by progressively impairing memory, thinking and learning through the continuous depletion of neurons. Although its etiopathogenesis remains uncertain, recent literature endorses the hypothesis that probiotic, prebiotic and synbiotic supplementation alters AD-like symptoms and improves many of its associated disease biomarkers. Alternatively, a dysfunctional microbiota impairs the gut epithelial barrier by inducing chronic gastric inflammation, culminating in neuroinflammation and accelerating AD progression. The findings in this review suggest that probiotics, prebiotics or synbiotics have potential as novel biological prophylactics in treatment of AD, due to their anti-inflammatory and antioxidant properties, their ability to improve cognition and metabolic activity, as well as their capacity of producing essential metabolites for gut and brain barrier permeability.
DJ-1 Regulates Microglial Polarization Through P62-Mediated TRAF6/IRF5 Signaling in Cerebral Ischemia-Reperfusion
Authors: Wang Tingting , Zhao Na , Peng Li , Li Yumei , Huang Xiaohuan , Zhu Jin , Chen Yanlin , Yu Shanshan , Zhao Yong
Published: January 2021

The polarization of microglia/macrophage, the resident immune cells in the brain, plays an important role in the injury and repair associated with ischemia-reperfusion (I/R). Previous studies have shown that DJ-1 has a protective effect in cerebral I/R. We found that DJ-1 regulates the polarization of microglial cells/macrophages after cerebral I/R and explored the mechanism by which DJ-1 mediates microglial/macrophage polarization in cerebral I/R. Middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen and glucose deprivation/reoxygenation (OGD/R) models were used to simulate cerebral I/R in vivo and in vitro, respectively. DJ-1 siRNA and the DJ-1-based polypeptide ND13 were used to produce an effect on DJ-1, and the P62-specific inhibitor XRK3F2 was used to block the effect of P62. Enhancing the expression of DJ-1 induced anti-inflammatory (M2) polarization of microglia/macrophage, and the expression of the anti-inflammatory factors IL-10 and IL-4 increased. Interference with DJ-1 expression induced pro-inflammatory (M1) polarization of microglia/macrophage, and the expression of the proinflammatory factors TNF-α and IL-1β increased. DJ-1 inhibited the expression of P62, impeded the interaction between P62 and TRAF6, and blocked nuclear entry of IRF5. In subsequent experiments, XRK3F2 synergistically promoted the effect of DJ-1 on microglial/macrophage polarization, further attenuating the interaction between P62 and TRAF6.
Photobleaching Imprinting Enhanced Background Rejection in Line-Scanning Temporal Focusing Microscopy
Authors: Zhuang Chaowei , Li Xinyang , Zhang Yuanlong , Kong Lingjie , Xie Hao , Dai Qionghai
Published: January 2021

Compared with two-photon point-scanning microscopy, two-photon temporal focusing microscopy (2pTFM) provides a parallel high-speed imaging strategy with optical sectioning capability. Owing to out-of-focus fluorescence induced by scattering, 2pTFM suffers deteriorated signal-to-background ratio (SBR) for deep imaging in turbid tissue, Here, we utilized the photobleaching property of fluorophore to eliminate out-of-focus fluorescence. According to different decay rates in different focal depth, we extract the in-focus signals out of backgrounds through time-lapse images. We analyzed the theoretical foundations of photobleaching imprinting of the line-scanning temporal focusing microscopy, simulated implementation for background rejection, and demonstrated the contrast enhancement in MCF-10A human mammary epithelial cells and cleared Thy1-YFP mouse brains. More than 50% of total background light rejection was achieved, providing higher SBR images of the MCF-10A samples and mouse brains. The photobleaching imprinting method can be easily adapted to other fluorescence dyes or proteins, which may have application in studies involving relatively large and nontransparent organisms.
Audiovisual Science Communication on TV and YouTube. How Recipients Understand and Evaluate Science Videos
Authors: Boy Bettina , Bucher Hans-Jürgen , Christ Katharina
Published: January 2021

With the emergence of the Internet, social media and video platforms are gaining considerable influence on the traditional media landscape in general and on science communication in particular. This has changed the role of science journalists as gatekeepers because many platforms are based on a participatory culture, in which passive consumers can become active participants. In addition to scientists, non-scientific actors also act as experts and participate in the communication process between science and the public. In contrast to the relevance of YouTube for science communication there is a lack of research focusing on the questions of how internet users receive YouTube videos to acquire information about science, how successful audiovisual media function in knowledge transfer, and what effects it has on the epistemic regime of a society. Therefore, this study combines a discourse analysis with the aim to create a typology of YouTube videos—the independent variables—and an audience study for investigating knowledge transfer—the dependent variables. In the first step, this article presents the results of a systematic analysis and categorization of 400 German science videos, from which four types of audiovisual science communication on YouTube were derived: presentation films, expert films, animation films, and narrative explanatory films. In order to clarify how powerful these new forms of science communication are in terms of knowledge transfer, attitudes, and trust toward the presentation of science, a discourse analysis of the videos is combined with a multi-level reception study and an online survey. The reception study included eye-tracking to investigate the allocation of attention and two different methods of knowledge tests (recognition and recall) of which the multiple-choice test was also applied in the online survey. The results show that the type of video has an important impact on knowledge transfer and para-social effects. One of the central results of the audience study is that the videos' gaze guidance, the recipients' allocation of attention, and the results of knowledge testing are closely intertwined. The correlation of data from eye-tracking and the two knowledge tests prove in principle that the more homogeneous the gaze patterns of the recipients are, the better they score in the multiple-choice test as well as in the concept mapping test.
Academic Leadership During a Pandemic: Department Heads Leading With a Focus on Equity
Authors: Kruse Sharon D. , Hackmann Donald G. , Lindle Jane Clark
Published: January 2021

The COVID-19 pandemic has created an unprecedented crisis with momentous challenges for higher education institutions. Academic leaders have been charged with restructuring their systems, ensuring instructional quality while operating with significantly diminished resources. For department heads of units with leadership preparation programs, the complexity of this crisis is layered upon fundamental scholarship about leadership, which reports the effectiveness of leadership as a collective incorporating the shared and diverse talents of faculty, students, and program stakeholders. This work of educational leadership rests on a public and democratic ethic promoting social justice and equity as the practices and outcomes for schooling at any level. In this article, three department heads of educational leadership units in major research universities use dialogic inquiry to reflect on our responses to complex demands brought forth by the pandemic. We share insights into our decision making, as we have led with a focus on equity. We address dilemmas and conflicts that we have addressed as departmental leaders during this critical period of institutional challenges, changing institutional policies and practices, and declining resources, as we have worked to ensure equitable access and distribution of resources for students, faculty, and staff. We conclude with implications for department heads who strive to maintain a focus on equity during times of sweeping organizational change.
Fabrication and Optimization of Nanocatalyst for Biodiesel Production: An Overview
Authors: Bano Sayfa , Ganie Adil Shafi , Sultana Saima , Sabir Suhail , Khan Mohammad Zain
Published: January 2021

Necessity and exploitation of fossil fuel products are implacable in serving the needs of humanity despite being a finite and limited resource. To meet the thrust of energy, biofuels derived from varieties of renewable resources are imperative in fulfilling the demand of renewable fuels on a large scale without creating environmental concerns. Biofuels are inevitably the result of the carbon fixation process which stores chemical energy, ultimately reducing the total amount of carbon dioxide. Different kinds of biofuels like bioethanol, biomethanol, biogas, and biodiesel are derived depending on varieties of feedstock materials. Among these, production of biodiesel augments the progression of clean and renewable fuel. In this review, we have discussed the production of biodiesel derived from various feedstock and using several processes like pyrolysis, direct blending, micro-emulsion, and trans-esterification, with critical discussion focussing on increasing biodiesel production using nanocatalysts. Biodiesel production mainly proceeds through homogenous and heterogeneous catalysis via trans-esterification method. The review further discusses the significance of nanocatalyst in heterogeneous catalysis based trans-esterification for large scale biodiesel production. With the advent of nanotechnology, designing and modification of nanocatalyst gives rise to attractive properties such as increased surface area, high thermal stability, and enhanced catalytic activity. The role of nanocatalysts have been extensively studied and investigated in regard to the increased biodiesel production. Along with the modification of nanocatalysts, we have briefly discussed the physico-chemical properties and the role of the optimization parameters as it plays a pivotal role in enhancing the biodiesel production commercially.
Remnants of Native Vegetation Surrounding Do Not Affect the Diversity and Density of Birds in Brazilian Grassland-Restoration Sites
Authors: Silva Thaiane Weinert da , Fontana Carla Suertegaray
Published: January 2021

Since in general the surrounding landscape influences the species diversity and abundance in fragments of native vegetation, an amount of native-vegetation cover nearby may also positively affect communities in restored areas, regardless of the sizes of individual habitat patches. We investigated for the first time whether the species richness, total abundance, and density of grassland birds in restoration sites are influenced by the amount of native grassland in the surrounding landscape in the Brazilian Pampa. We sampled birds by point counts in five restoration sites in the most representative area of grasslands in Brazil. We established an outer buffer zone with a 1 km-radius around the point-count areas in each site, and calculated the percentage of native grassland vegetation in the surrounding landscape. Bird species richness and abundance did not show a significant response to the amount of neighboring native grassland in restored areas. Individual analyses of the density of seven bird species associated to grassland also showed similar pattern. We believe the vegetation structure in these restoration sites may already been sufficiently re-established to provide necessary resources and a suitable habitat for the birds. Even so, we assume that previously existing landscape features were important for recovery of the vegetation structure, as continuous native grassland in the surroundings. Thus, we recommend consider the landscape context as an additional issue in studies dealing with conservation strategies for recovery of grasslands in Brazil.
A Review on Fish Sensory Systems and Amazon Water Types With Implications to Biodiversity
Authors: Borghezan Elio de Almeida , Pires Tiago Henrique da Silva , Ikeda Takehide , Zuanon Jansen , Kohshima Shiro
Published: January 2021

The Amazon has the highest richness of freshwater organisms in the world, which has led to a multitude of hypotheses on the mechanisms that generated this biodiversity. However, most of these hypotheses focus on the spatial distance of populations, a framework that fails to provide an explicit mechanism of speciation. Ecological conditions in Amazon freshwaters can be strikingly distinct, as it has been recognized since Alfred Russel Wallace’s categorization into black, white, and blue (= clear) waters. Water types reflect differences in turbidity, dissolved organic matter, electrical conductivity, pH, amount of nutrients and lighting environment, characteristics that directly affect the sensory abilities of aquatic organisms. Since natural selection drives evolution of sensory systems to function optimally according to environmental conditions, the sensory systems of Amazon freshwater organisms are expected to vary according to their environment. When differences in sensory systems affect chances of interbreeding between populations, local adaptations may result in speciation. Here, we briefly present the limnologic characteristics of Amazonian water types and how they are expected to influence photo-, chemical-, mechano-, and electro-reception of aquatic organisms, focusing on fish. We put forward that the effect of different water types on the adaptation of sensory systems is an important mechanism that contributed to the evolution of fish diversity. We point toward underexplored research perspectives on how divergent selection may act on sensory systems and thus contribute to the origin and maintenance of the biodiversity of Amazon aquatic environments.
Epstein-Barr Virus and Multiple Sclerosis
Authors: Houen Gunnar , Trier Nicole Hartwig , Frederiksen Jette Lautrup
Published: January 2021

Multiple sclerosis (MS) is a neurologic disease affecting myelinated nerves in the central nervous system (CNS). The disease often debuts as a clinically isolated syndrome, e.g., optic neuritis (ON), which later develops into relapsing-remitting (RR) MS, with temporal attacks or primary progressive (PP) MS. Characteristic features of MS are inflammatory foci in the CNS and intrathecal synthesis of immunoglobulins (Igs), measured as an IgG index, oligoclonal bands (OCBs), or specific antibody indexes. Major predisposing factors for MS are certain tissue types (e.g., HLA DRB1*15:01), vitamin D deficiency, smoking, obesity, and infection with Epstein-Barr virus (EBV). Many of the clinical signs of MS described above can be explained by chronic/recurrent EBV infection and current models of EBV involvement suggest that RRMS may be caused by repeated entry of EBV-transformed B cells to the CNS in connection with attacks, while PPMS may be caused by more chronic activity of EBV-transformed B cells in the CNS. In line with the model of EBV’s role in MS, new treatments based on monoclonal antibodies (MAbs) targeting B cells have shown good efficacy in clinical trials both for RRMS and PPMS, while MAbs inhibiting B cell mobilization and entry to the CNS have shown efficacy in RRMS. Thus, these agents, which are now first line therapy in many patients, may be hypothesized to function by counteracting a chronic EBV infection.
A TP53-Associated Immune Prognostic Signature for the Prediction of Overall Survival and Therapeutic Responses in Muscle-Invasive Bladder Cancer
Authors: Wu Xiangkun , Lv Daojun , Cai Chao , Zhao Zhijian , Wang Ming , Chen Wenzhe , Liu Yongda
Published: January 2021

Background

TP53 gene mutation is one of the most common mutations in human bladder cancer (BC) and has been implicated in the progression and prognosis of BC.

Methods

RNA sequencing data and TP53 mutation data in different populations and platforms were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database to determine and validate a TP53-associated immune prognostic signature (TIPS) based on differentially expressed immune-related genes (DEIGs) between muscle-invasive bladder cancer (MIBC) patients with and without TP53 mutations.

Results

A total of 99 DEIGs were identified based on TP53 mutation status. TIPS including ORM1, PTHLH, and CTSE were developed and validated to identify high-risk prognostic group who had a poorer prognosis than low-risk prognostic group in TCGA and GEO database. The high-risk prognostic group were characterized by a higher abundance of regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages than the low-risk prognostic group. Moreover, they exhibited a lower abundance of CD56bright NK cells, higher expression of CTLA4, LAG3, PDCD1, TIGIT, and HAVCR2, as well as being more likely to respond to anti–PD-1, and neoadjuvant chemotherapy than the low-risk prognostic group. Based on TIPS and other clinical characteristics, a nomogram was constructed for clinical use.

Conclusion

TIPS derived from TP53 mutation status is a potential prognostic signature or therapeutic target but additional prospective studies are necessary to confirm this potential.
PD-L1 and PD-L2 Expression in Cervical Cancer: Regulation and Biomarker Potential
Authors: Rotman Jossie , Otter Leontine A. S. den , Bleeker Maaike C. G. , Samuels Sanne S. , Heeren A. Marijne , Roemer Margaretha G. M. , Kenter Gemma G. , Zijlmans Henry J. M. A. A. , van Trommel Nienke E. , de Gruijl Tanja D. , Jordanova Ekaterina S.
Published: January 2021

PD-1/PD-L1 immune checkpoint inhibitors show potential for cervical cancer treatment. However, low response rates suggest that patient selection based on PD-L1 protein expression is not optimal. Here, we evaluated different PD-L1 detection methods and studied transcriptional regulation of PD-L1/PD-L2 expression by The Cancer Genome Atlas (TCGA) mRNAseq analysis. First, we determined the copy number of the PD-L1/PD-L2 locus by fluorescence in situ hybridization (FISH), PD-L1 mRNA expression by RNA in situ hybridization (RNAish), and PD-L1/PD-L2 protein expression by immunohistochemistry (IHC) on tissue microarrays containing a cohort of 60 patients. Additionally, distribution of PD-L1/PD-L2 was visualized based on flow cytometry analysis of single-cell suspensions (n = 10). PD-L1/PD-L2 locus amplification was rare (2%). PD-L1 mRNA expression in tumor cells was detected in 56% of cases, while 41% expressed PD-L1 protein. Discordant scores for PD-L1 protein expression on tumor cells between cores from one patient were observed in 27% of cases. Interestingly, with RNAish, PD-L1 heterogeneity was observed in only 11% of the cases. PD-L2 protein expression was found in 53%. PD-L1 mRNA and protein expression on tumor cells were strongly correlated (p < 0.001). PD-L1 and PD-L2 protein expression showed no correlation on tumor cells (p = 0.837), but a strong correlation on cells in stromal fields (p < 0.001). Co-expression of PD-L1 and PD-L2 on macrophage-like populations was also observed with flow cytometry analysis. Both PD-L1 and PD-L2 TCGA transcript levels strongly correlated in the TCGA data, and both PD-L1 and PD-L2 strongly correlated with interferon gamma (IFNG) expression/transcript levels (p < 0.0001). Importantly, patients with high PD-L1/PD-L2/IFNG transcript levels had a survival advantage over patients with high PD-L1/PD-L2 and low IFNG expression. Based on these findings, we conclude that PD-L1/PD-L2 expression in cervical cancer is mainly associated with interferon induction and not gene amplification, which makes FISH unsuitable as biomarker. The heterogeneous PD-L1 and PD-L2 expression patterns suggest IHC unreliable for patient selection. RNAish, in conjunction with interferon signaling evaluation, seems a promising technique for immune checkpoint detection. These results warrant further investigation into their prognostic and predictive potential.
Increased Frequency of Memory CD4+ T-Cell Responses in Individuals With Previously Treated Extrapulmonary Tuberculosis
Authors: Barreto-Duarte Beatriz , Sterling Timothy R. , Fiske Christina T. , Almeida Alexandre , Nochowicz Cynthia H. , Smith Rita M. , Barnett Louise , Warren Christian , Blackman Amondrea , Lapa e Silva Jose Roberto , Andrade Bruno B. , Kalams Spyros A.
Published: January 2021

Extrapulmonary TB (EPTB) occurs with increased frequency in persons with underlying immunodeficiency. Even after recovery from acute illness, differences in immune phenotype and activation persist. Studies defining characteristics of immune responses after recovery from extrapulmonary TB may provide insights into factors that increase TB risk. We performed two case-control studies (in the United States and Brazil) among HIV-seronegative adults with previous EPTB (n = 9; 25), previous pulmonary TB (n = 7; 25), latent M. tuberculosis (Mtb) infection (n = 11; 25), and uninfected TB contacts (n = 10; 25). We assessed the frequency of dual CD4+ interferon-γ and tumor necrosis factor-α responses after stimulation with overlapping Mtb peptides from ESAT-6 or CFP-10, or gamma-irradiated Mtb H37Rv, proliferative responses to Mtb antigens, T-regulatory cell (Treg) frequency and phenotype. In both study populations, individuals with prior EPTB had the highest frequency of intracellular cytokine-producing cells in response to Mtb antigens (p < 0.05; p <.0001). Persons with prior EPTB in Brazil had the highest levels of CD4 proliferation to Mtb antigens (p < 0.0001), and the highest expression of CD39 on Tregs (p < 0.0001). Individuals with treated EPTB maintained high frequencies of Mtb-specific memory responses and active Treg cells, suggesting that susceptibility to EPTB occurs despite the ability to develop and maintain enhanced adaptive immune responses.
Stimulation of Mytilus galloprovincialis Hemocytes With Different Immune Challenges Induces Differential Transcriptomic, miRNomic, and Functional Responses
Authors: Moreira Rebeca , Romero Alejandro , Rey-Campos Magalí , Pereiro Patricia , Rosani Umberto , Novoa Beatriz , Figueras Antonio
Published: January 2021

Mediterranean mussels (Mytilus galloprovincialis) are marine bivalve molluscs with high resilience to biotic and abiotic stress. This resilience is one of the reasons why this species is such an interesting model for studying processes such as the immune response. In this work, we stimulated mussel hemocytes with poly I:C, β-glucans, and LPS and then sequenced hemocyte mRNAs (transcriptome) and microRNAs (miRNome) to investigate the molecular basis of the innate immune responses against these pathogen-associated molecular patterns (PAMPs). An immune transcriptome comprising 219,765 transcripts and an overview of the mussel miRNome based on 5,175,567 non-redundant miRNA reads were obtained. The expression analyses showed opposite results in the transcriptome and miRNome; LPS was the stimulus that triggered the highest transcriptomic response, with 648 differentially expressed genes (DEGs), while poly I:C was the stimulus that triggered the highest miRNA response, with 240 DE miRNAs. Our results reveal a powerful immune response to LPS as well as activation of certain immunometabolism- and ageing/senescence-related processes in response to all the immune challenges. Poly I:C exhibited powerful stimulating properties in mussels, since it triggered the highest miRNomic response and modulated important genes related to energy demand; these effects could be related to the stronger activation of these hemocytes (increased phagocytosis, increased NO synthesis, and increased velocity and accumulated distance). The transcriptome results suggest that after LPS stimulation, pathogen recognition, homeostasis and cell survival processes were activated, and phagocytosis was induced by LPS. β-glucans elicited a response related to cholesterol metabolism, which is important during the immune response, and it was the only stimulus that induced the synthesis of ROS. These results suggest a specific and distinct response of hemocytes to each stimulus from a transcriptomic, miRNomic, and functional point of view.
What Works When Treating Granulomatous Disease in Genetically Undefined CVID? A Systematic Review
Authors: van Stigt Astrid C. , Dik Willem A. , Kamphuis Lieke S. J. , Smits Bas M. , van Montfrans Joris M. , van Hagen P. Martin , Dalm Virgil A. S. H. , IJspeert Hanna
Published: January 2021

Background

Granulomatous disease is reported in at least 8–20% of patients with common variable immunodeficiency (CVID). Granulomatous disease mainly affects the lungs, and is associated with significantly higher morbidity and mortality. In half of patients with granulomatous disease, extrapulmonary manifestations are found, affecting e.g. skin, liver, and lymph nodes. In literature various therapies have been reported, with varying effects on remission of granulomas and related clinical symptoms. However, consensus recommendations for optimal management of extrapulmonary granulomatous disease are lacking.

Objective

To present a literature overview of the efficacy of currently described therapies for extrapulmonary granulomatous disease in CVID (CVID+EGD), compared to known treatment regimens for pulmonary granulomatous disease in CVID (CVID+PGD).

Methods

The following databases were searched: Embase, Medline (Ovid), Web-of-Science Core Collection, Cochrane Central, and Google Scholar. Inclusion criteria were 1) CVID patients with granulomatous disease, 2) treatment for granulomatous disease reported, and 3) outcome of treatment reported. Patient characteristics, localization of granuloma, treatment, and association with remission of granulomatous disease were extracted from articles.

Results

We identified 64 articles presenting 95 CVID patients with granulomatous disease, wherein 117 different treatment courses were described. Steroid monotherapy was most frequently described in CVID+EGD (21 out of 53 treatment courses) and resulted in remission in 85.7% of cases. In CVID+PGD steroid monotherapy was described in 15 out of 64 treatment courses, and was associated with remission in 66.7% of cases. Infliximab was reported in CVID+EGD in six out of 53 treatment courses and was mostly used in granulomatous disease affecting the skin (four out of six cases). All patients (n = 9) treated with anti-TNF-α therapies (infliximab and etanercept) showed remission of extrapulmonary granulomatous disease. Rituximab with or without azathioprine was rarely used for CVID+EGD, but frequently used in CVID+PGD where it was associated with remission of granulomatous disease in 94.4% (17 of 18 treatment courses).

Conclusion

Although the number of CVID+EGD patients was limited, data indicate that steroid monotherapy often results in remission, and that anti-TNF-α treatment is effective for granulomatous disease affecting the skin. Also, rituximab with or without azathioprine was mainly described in CVID+PGD, and only in few cases of CVID+EGD.
Activated Platelets Convert CD14+CD16- Into CD14+CD16+ Monocytes With Enhanced FcγR-Mediated Phagocytosis and Skewed M2 Polarization
Authors: Lee Su Jeong , Yoon Bo Ruem , Kim Hee Young , Yoo Su-Jin , Kang Seong Wook , Lee Won-Woo
Published: January 2021

Monocytes are important cellular effectors of innate immune defense. Human monocytes are heterogeneous and can be classified into three distinct subsets based on CD14 and CD16 expression. The expansion of intermediate CD14+CD16+ monocytes has been reported in chronic inflammatory diseases including rheumatoid arthritis (RA). However, the mechanism underlying induction of CD16 and its role in monocytes remains poorly understood. Here, we demonstrate that activated platelets are important for induction of CD16 on classical CD14+CD16- monocytes by soluble factors such as cytokines. Cytokine neutralization and signaling inhibition assays reveal that sequential involvement of platelet-derived TGF-β and monocyte-derived IL-6 contribute to CD16 induction on CD14+CD16- monocytes. Activated platelet-induced CD16 on monocytes participates in antibody-dependent cellular phagocytosis (ADCP) and its level is positively correlated with phagocytic activity. CD14+CD16- monocytes treated with activated platelets preferentially differentiate into M2 macrophages, likely the M2c subset expressing CD163 and MerTK. Lastly, the amount of sCD62P, a marker of activated platelets, is significantly elevated in plasma of RA patients and positively correlates with clinical parameters of RA. Our findings suggest an important role of activated platelets in modulating phenotypical and functional features of human monocytes. This knowledge increases understanding of the immunological role of CD14+CD16+ cells in chronic inflammatory diseases.
A Novel Subset of CD95+ Pro-Inflammatory Macrophages Overcome miR155 Deficiency and May Serve as a Switch From Metabolically Healthy Obesity to Metabolically Unhealthy Obesity
Authors: Johnson Candice , Drummer IV Charles , Shan Huimin , Shao Ying , Sun Yu , Lu Yifan , Saaoud Fatma , Xu Keman , Nanayakkara Gayani , Fang Pu , Bagi Zsolt , Jiang Xiaohua , Choi Eric T. , Wang Hong , Yang Xiaofeng
Published: January 2021

Metabolically healthy obesity (MHO) accounts for roughly 35% of all obese patients. There is no clear consensus that has been reached on whether MHO is a stable condition or merely a transitory period between metabolically healthy lean and metabolically unhealthy obesity (MUO). Additionally, the mechanisms underlying MHO and any transition to MUO are not clear. Macrophages are the most common immune cells in adipose tissues and have a significant presence in atherosclerosis. Fas (or CD95), which is highly expressed on macrophages, is classically recognized as a pro-apoptotic cell surface receptor. However, Fas also plays a significant role as a pro-inflammatory molecule. Previously, we established a mouse model (ApoE-/-/miR155-/-; DKO mouse) of MHO, based on the criteria of not having metabolic syndrome (MetS) and insulin resistance (IR). In our current study, we hypothesized that MHO is a transition phase toward MUO, and that inflammation driven by our newly classified CD95+CD86- macrophages is a novel mechanism for this transition. We found that, with extended (24 weeks) high-fat diet feeding (HFD), MHO mice became MUO, shown by increased atherosclerosis. Mechanistically, we found the following: 1) at the MHO stage, DKO mice exhibited increased pro-inflammatory markers in adipose tissue, including CD95, and serum; 2) total adipose tissue macrophages (ATMs) increased; 3) CD95+CD86- subset of ATMs also increased; and 4) human aortic endothelial cells (HAECs) were activated (as determined by upregulated ICAM1 expression) when incubated with conditioned media from CD95+-containing DKO ATMs and human peripheral blood mononuclear cells-derived macrophages in comparison to respective controls. These results suggest that extended HFD in MHO mice promotes vascular inflammation and atherosclerosis via increasing CD95+ pro-inflammatory ATMs. In conclusion, we have identified a novel molecular mechanism underlying MHO transition to MUO with HFD. We have also found a previously unappreciated role of CD95+ macrophages as a potentially novel subset that may be utilized to assess pro-inflammatory characteristics of macrophages, specifically in adipose tissue in the absence of pro-inflammatory miR-155. These findings have provided novel insights on MHO transition to MUO and new therapeutic targets for the future treatment of MUO, MetS, other obese diseases, and type II diabetes.
Is Oligotrophy an Equalizing Factor Driving Microplankton Species Functional Diversity Within Agulhas Rings?
Authors: Cesar-Ribeiro Caio , Piedras Fernanda R. , da Cunha Leticia C. , de Lima Domênica T. , Pinho Luana Q. , Moser Gleyci A. O.
Published: January 2021

From the southwestern termination of the Agulhas current, anticyclonic eddies are emitted and drift across the South Atlantic Ocean. This study is based on a FORSA (Following Ocean Rings in the South Atlantic) oceanographic cruise, from Cape Town (South AFRica) to Arraial do Cabo (Brazil) in June 2015, during which three eddies of different ages (E1, 7 months; E3, 11 months; E5, 24 months) from the Agulhas current were sampled for microplankton identification and determination of functional traits. The stations where sampling occurred at each eddy included a control outside the eddy and three stations inside the eddy—border, midway (between the border and center), and center (identified through satellite images of sea level anomaly—SLA). Functional traits were determined based on microscopic observations and consultation of the literature. An evident decay in the Agulhas eddies toward the west was observed, and each eddy proved to be different. E1 represented a younger and more robust structure. At the same time, the other eddies, E3 and E5, were more alike with similar physical, chemical, and ecological characteristics and almost the same indices values of functional diversity, demonstrating that although their species compositions were different, the strategies used by the species were the same. The most crucial ecological trait for microplankton was nutrition mode. The microplankton contained mainly mixotrophic dinoflagellates and cyanobacteria adapted to oligotrophic conditions. The functional strategy of microplankton did not differ among the eddies and stations, with mixotrophy being the most striking trait. Therefore, the older eddies’ microplankton community fits the neutrality theory, whereby species perform similar ecological functions, and the younger eddy fits in the niche complementarity. Even with the species composition being different in each eddy and/or within the same eddy, the functional strategy was the same, with scarce resources and species selected that best use any source of nutrients or use evolutionary advantages to live in an oligotrophic environment.
Pathogen Infection and Host-Resistance Interactively Affect Root-Associated Fungal Communities in Watermelon
Authors: Xu Lihui , Nicolaisen Mogens , Larsen John , Zeng Rong , Gao Shigang , Dai Fuming
Published: January 2021

Interactions of pathogen infection, host plant resistance, and fungal communities are poorly understood. Although the use of resistant watermelon cultivars is an effective control measure of watermelon wilt disease, fungal communities may also have significant effects on the development of the soil-borne pathogen complexes. We characterized the root and rhizosphere fungal communities associated with healthy and diseased watermelons of three different cultivars with different susceptibilities toward wilt disease by paired-end Illumina MiSeq sequencing. Thirty watermelon plants including highly wilt-resistant, moderately resistant, and susceptible cultivars were collected from a greenhouse, half of which showing clear wilt symptoms and the other half with no symptoms. Patterns of watermelon wilt disease and the response of the fungal communities varied among the three cultivars. The amount of the pathogenFusarium oxysporumf. sp.niveumwas higher in diseased root and rhizosphere samples, particularly in the susceptible cultivar, and was significantly positively correlated with the disease index of Fusarium wilt. Plant health had significant effects on root-associated fungal communities, whereas only the highly resistant cultivar had significant effects only on the rhizosphere fungal communities. Co-occurrence networks revealed a higher complexity of fungal communities in the symptom-free roots compared to diseased roots. In addition, networks from roots of the highly resistant plants showing symptoms had a higher complexity compared to the susceptible cultivars. Keystone species were identified for the plants with different symptom severity and the different cultivars in the root and rhizosphere, such asFusarium oxysporum, Monosporascus cannonballus, andMortierella alpina. Overall, the most important factor determining fungal communities in the roots was plant symptom severity, whereas in the rhizosphere, plant genotype was the most important factor determining fungal communities.