bluuebunny/crossref_metadata_2025 huggingface dataset:
ESTUDO DE CASO DA EMPRESA A E EMPRESA B
Authors: Quinaglia Sônia Regina , Caldeira Thiciana Favareto , Marinho Clesio Aparecido
Published: March 2021

O fluxo de informações a que as pessoas estão sujeitas cresce a cada dia. O mesmo acontece nas organizações com relação a informações técnicas, econômicas e financeiras, comportamentais entre outras. Não obstante ao fluxo de informações, a forma como elas são transmitidas pode provocar ruídos e esses ruídos na comunicação podem ocasionar conflitos. O presente trabalho faz uma reflexão e discussão sobre a comunicação assertiva na redução de conflitos nas organizações. Para a realização deste trabalho, são abordados e utilizados conceitos de alguns renomados autores que versam sobre comunicação e gestão de conflitos, bem como pesquisa exploratória com o objetivo de identificar como se dá a comunicação e gestão dos conflitos em diferentes empresas da região de Sertãozinho.
ANÁLISE DAS CARACTERÍSTICAS DE UMA JUNTA SOLDADA, DE UM AÇO INOXIDÁVEL DUPLEX, COM E SEM TRATAMENTOS TÉRMICOS
Authors: Farah Alessandro Fraga , Gomes Marcia Aparecida , Farah Solange Pereira dos Santos , Caetano Junior Marcelo Caetano , Batistela Thiago Teixeira
Published: March 2021

Analisou-se uma amostra de aço inoxidável Duplex UNS 31803, soldada com eletrodos do tipo E309Mol, com a presença de tratamento térmico em diferentes situações de aquecimento e resfriamento, e também, sem qualquer tipo de tratamento para avaliar a influencia na microestrutura e microdureza. Foram selecionadas três amostras das juntas soldadas, sendo que uma amostra foi tratada a 600°C por duas horas e resfriada ao ar, uma amostra foi tratada a 1050°C por duas horas resfriado em água e aquecido novamente a 600°C por duas horas e resfriado ao ar e uma amostra não passou por tratamento térmico. Realizou-se análise metalográfica por microscopia óptica e ensaio de microdureza Vickers. Observou-se que para o tratamento térmico a 600ºC houve variações significativas na microestrutura e microdureza. Para o tratamento térmico a 1050°C houve uma homogeneização na microestrutura e apresentou variação significativa na dureza da zona fundida (ZF). Concluiu-se que os tratamentos térmicos promoveram diminuição na dureza da zona fundida e na zona termicamente afetada pelo calor (ZTA) do aço inoxidável Duplex UNS 31803.
SEDIMENTASI SOSIAL DALAM TINDAKAN KESEHARIAN PENGIKUT PARMALIM, KRISTEN, DAN ISLAM DI DESA PARDOMUAN NAULI LAGUBOTI(Social Sedimentation Parmalim, Christianity, and Islam Adherents’ Daily Action in Pardomuan Nauli Village of Laguboti)
Authors: Tambunan Mispa Sulastri , Pilakoannu Rama Tulus
Published: March 2021

This article studies the social sedimentation in the daily actions of Parmalim, Christian, and Islam adherents in Pardomuan Nauli Village, Laguboti. The multi-religious Batak people adhere to same customs, norms, traditions and cultures. But, in preserving same customs, norms, and culture, in fact, some conflicts still appear among the people. Through social sedimentation, however, people in Pardomuan Nauli can live in harmony and unity. This study employs Erving Goffman’s theory to see the interaction among people in their daily life. It also sees how people still can live in harmony among the religious differences by using social networks theory. The objective of study is to apply the development of qualitative research design and library research. The data were collected by conducting interviews, observation, and theoretical review. This study describes and analyzes how Parmalim, Christian, and Islam people in Batak Toba tribe live up the social sedimentation in their daily lives and also, how do they preserve the cultural values they have amidst religious differences.
RASAN TUE: BUDAYA PERKAWINAN SUKU PASEMAH (Rasan Tue: Marriage Culture of Pasemah Tribe)
Authors: Wardani Wardani
Published: March 2021

This study attempts to describe culture rasan tue marriage in the Padang Guci Bengkulu. The methodology used is a descriptive qualitative method anthropological approach. The research was conducted by observing directly the Pasemah tribe’s marriage culture in the Padang Guci Bengkulu. This study summarizes the phases of rasan tue marriage culture completely. The result shows that marriage with rasan tue culture is held for some reasons: (1) the boy and the girl have a kinship, despite far relative, (2) the boy and the girl are equally shy so that they do not have the courage to express their feelings and need parents’ help to communicate it, (3) both girl and boy have been adult and they have acquaintance with adult boy and girl, and (4) the boy and the girl have wealth so that it was necessary to make the agreement between the two parties by presenting both parents. It can be concluded that the procedure of marriage using rasan tue culture involves, among others: meminang (proposing), miare tunang, nolong tunang, tandang with tunang, ngalih panggilan, setting up marriage time, netak akhi malam, and holding the marriage (wedding) event.
Could Gait Biomechanics Become a Marker of Atypical Neuronal Circuitry in Human Development?—The Example of Autism Spectrum Disorder
Authors: Jequier Gygax Marine , Maillard Anne M. , Favre Julien
Published: March 2021

This perspective paper presents converging recent knowledge in neurosciences (motor neurophysiology, neuroimaging and neuro cognition) and biomechanics to outline the relationships between maturing neuronal network, behavior, and gait in human development. Autism Spectrum Disorder (ASD) represents a particularly relevant neurodevelopmental disorder (NDD) to study these convergences, as an early life condition presenting with sensorimotor and social behavioral alterations. ASD diagnosis relies solely on behavioral criteria. The absence of biological marker in ASD is a main challenge, and hampers correlations between behavioral development and standardized data such as brain structure alterations, brain connectivity, or genetic profile. Gait, as a way to study motor system development, represents a well-studied, early life ability that can be characterized through standardized biomechanical analysis. Therefore, developmental gait biomechanics might appear as a possible motor phenotype and biomarker, solid enough to be correlated to neuronal network maturation, in normal and atypical developmental trajectories—like in ASD.
Man/Cel5B, a Bifunctional Enzyme Having the Highest Mannanase Activity in the Hyperthermic Environment
Authors: Sadaqat Beenish , Sha Chong , Rupani Parveen Fatemeh , Wang Hongcheng , Zuo Wanbing , Shao Weilan
Published: March 2021

Thermotoga maritima (Tma) contains genes encoding various hyperthermophilic enzymes with great potential for industrial applications. The gene TM1752 in Tma genome has been annotated as cellulase gene encoding protein Cel5B. In this work, the gene TM1752 was cloned and expressed in Escherichia coli, and the recombinant enzyme was purified and characterized. Interestingly, the purified enzyme exhibited specific activities of 416 and 215 U/mg on substrates galactomannan and carboxy methyl cellulose, which is the highest among thermophilic mannanases. However, the putative enzyme did not show sequence homology with any of the previously reported mannanases; therefore, the enzyme Cel5B was identified as bifunctional mannanase and cellulase and renamed as Man/Cel5B. Man/Cel5B exhibited maximum activity at 85°C and pH 5.5. This enzyme retained more than 50% activity after 5 h of incubation at 85°C, and retained up to 80% activity after incubated for 1 h at pH 5–8. The Km and Vmax of Man/Cel5B were observed to be 4.5 mg/mL galactomannan and 769 U/mg, respectively. Thin layer chromatography depicted that locust bean gum could be efficiently degraded to mannobiose, mannotriose, and mannooligosaccharides by Man/Cel5B. These characteristics suggest that Man/Cel5B has attractive applications for future food, feed, and biofuel industries.
Tumor Hypoxia Drives Genomic Instability
Authors: Tang Ming , Bolderson Emma , O’Byrne Kenneth J. , Richard Derek J.
Published: March 2021

Cancer is a leading cause of death worldwide. As a common characteristic of cancer, hypoxia is associated with poor prognosis due to enhanced tumor malignancy and therapeutic resistance. The enhanced tumor aggressiveness stems at least partially from hypoxia-induced genomic instability. Therefore, a clear understanding of how tumor hypoxia induces genomic instability is crucial for the improvement of cancer therapeutics. This review summarizes recent developments highlighting the association of tumor hypoxia with genomic instability and the mechanisms by which tumor hypoxia drives genomic instability, followed by how hypoxic tumors can be specifically targeted to maximize efficacy.
Deciphering Epitranscriptome: Modification of mRNA Bases Provides a New Perspective for Post-transcriptional Regulation of Gene Expression
Authors: Kumar Suresh , Mohapatra Trilochan
Published: March 2021

Gene regulation depends on dynamic and reversibly modifiable biological and chemical information in the epigenome/epitranscriptome. Accumulating evidence suggests that messenger RNAs (mRNAs) are generated in flashing bursts in the cells in a precisely regulated manner. However, the different aspects of the underlying mechanisms are not fully understood. Cellular RNAs are post-transcriptionally modified at the base level, which alters the metabolism of mRNA. The current understanding of epitranscriptome in the animal system is far ahead of that in plants. The accumulating evidence indicates that the epitranscriptomic changes play vital roles in developmental processes and stress responses. Besides being non-genetically encoded, they can be of reversible nature and involved in fine-tuning the expression of gene. However, different aspects of base modifications in mRNAs are far from adequate to assign the molecular basis/functions to the epitranscriptomic changes. Advances in the chemogenetic RNA-labeling and high-throughput next-generation sequencing techniques are enabling functional analysis of the epitranscriptomic modifications to reveal their roles in mRNA biology. Mapping of the common mRNA modifications, including N6-methyladenosine (m6A), and 5-methylcytidine (m5C), have enabled the identification of other types of modifications, such as N1-methyladenosine. Methylation of bases in a transcript dynamically regulates the processing, cellular export, translation, and stability of the mRNA; thereby influence the important biological and physiological processes. Here, we summarize the findings in the field of mRNA base modifications with special emphasis on m6A, m5C, and their roles in growth, development, and stress tolerance, which provide a new perspective for the regulation of gene expression through post-transcriptional modification. This review also addresses some of the scientific and technical issues in epitranscriptomic study, put forward the viewpoints to resolve the issues, and discusses the future perspectives of the research in this area.
The Role of the Interplay Between Autophagy and NLRP3 Inflammasome in Metabolic Disorders
Authors: Lv Shuangyu , Wang Honggang , Li Xiaotian
Published: March 2021

Autophagy is an important and conserved cellular pathway in which cells transmit cytoplasmic contents to lysosomes for degradation. It plays an important role in maintaining the balance of cell composition synthesis, decomposition and reuse, and participates in a variety of physiological and pathological processes. The nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome can induce the maturation and secretion of Interleukin-1 beta (IL-1β) and IL-18 by activating caspase-1. It is involved in many diseases. In recent years, the interplay between autophagy and NLRP3 inflammasome has been reported to contribute to many diseases including metabolic disorders related diseases. In this review, we summarized the recent studies on the interplay between autophagy and NLRP3 inflammasome in metabolic disorders to provide ideas for the relevant basic research in the future.
Therapeutic Effects of Mesenchymal Stromal Cell-Derived Small Extracellular Vesicles in Oxygen-Induced Multi-Organ Disease: A Developmental Perspective
Authors: Fernandez-Gonzalez Angeles , Willis Gareth R. , Yeung Vincent , Reis Monica , Liu Xianlan , Mitsialis S. Alex , Kourembanas Stella
Published: March 2021

Despite major advances in neonatal intensive care, infants born at extremely low birth weight still face an increased risk for chronic illness that may persist into adulthood. Pulmonary, retinal, and neurocognitive morbidities associated with preterm birth remain widespread despite interventions designed to minimize organ dysfunction. The design of therapeutic applications for preterm pathologies sharing common underlying triggers, such as fluctuations in oxygen supply or in the inflammatory state, requires alternative strategies that promote anti-inflammatory, pro-angiogenic, and trophic activities—ideally as a unitary treatment. Mesenchymal stem/stromal cell-derived extracellular vesicles (MEx) possess such inherent advantages, and they represent a most promising treatment candidate, as they have been shown to contribute to immunomodulation, homeostasis, and tissue regeneration. Current pre-clinical studies into the MEx mechanism of action are focusing on their restorative capability in the context of preterm birth-related pathologies, albeit not always with a multisystemic focus. This perspective will discuss the pathogenic mechanisms underlying the multisystemic lesions resulting from early-life disruption of normal physiology triggered by high oxygen exposures and pro-inflammatory conditions and introduce the application of MEx as immunomodulators and growth-promoting mediators for multisystem therapy.
CARD-Associated Risk Score Features the Immune Landscape and Predicts the Responsiveness to Anti-PD-1 Therapy in IDH Wild-Type Gliomas
Authors: Li Depei , Hu Wanming , Lin Xiaoping , Zhang Ji , He Zhenqiang , Zhong Sheng , Wen Xia , Zhang Peiyu , Jiang Xiaobing , Duan Hao , Guo Chengcheng , Wang Jian , Zeng Jing , Chen Zhongping , Mou Yonggao , Sai Ke
Published: March 2021

Background

Proteins containing the caspase recruitment domain (CARD) play critical roles in cell apoptosis and immunity. However, the impact of CARD genes in tumor immune cell infiltration, responsiveness to checkpoint immunotherapy, and clinical outcomes of gliomas remains unclear. Here, we explore using CARD genes to depict the immune microenvironment and predict the responsiveness of gliomas to anti-PD-1 therapy.

Methods

The genome and transcriptome data of 231 patients with isocitrate dehydrogenase wild-type (IDH-wt) gliomas were retrieved from The Cancer Genome Atlas (TCGA) database to screen CARD genes associated with T lymphocyte infiltration in gliomas. Weighted co-expression network and LASSO penalized regression were employed to generate a CARD-associated risk score (CARS). Two independent and publicly available datasets were used to validate the effectiveness of CARS.

Results

The CARS divided the 231 glioma patients into high- and low-risk subgroups with distinct immune microenvironment and molecular features. The high-risk group had high CARS and was characterized by enrichment of dysfunctional T lymphocytes in a profound immunosuppressive microenvironment, whereas the low-risk group had low CARS and exhibited an immune exclusion genotype. Moreover, signaling aberrations including upregulation of PI3K/Akt/mTOR, NF-κB, and TGF-β were found in the high-risk group. In contrast, the activated WNT pathway was more evident in the low-risk group. Furthermore, we found that an elevated CARS indicated a decreased overall survival for IDH-wt gliomas under standard care but a clinical benefit from checkpoint immunotherapy.

Conclusion

This study developed an immune- and prognosis-relevant risk score, which could be used to enhance our understanding of the heterogeneity of immune microenvironment of gliomas and facilitate to identify patients who will benefit from checkpoint immunotherapy.
Diluted Aqueous Dispersed Systems of 4-Aminopyridine: The Relationship of Self-Organization, Physicochemical Properties, and Influence on the Electrical Characteristics of Neurons
Authors: Ryzhkina Irina , Murtazina Lyaisan , Gainutdinov Khalil , Konovalov Alexander
Published: March 2021

A variety of physicochemical methods were used to examine the self-organization, physicochemical, UV absorption, and fluorescent properties of diluted aqueous solutions (calculated concentrations from 1·10−20 to 1·10−2 M) of the membrane voltage-dependent potassium channels blocker 4-aminopyridine (4-AP). Using the dynamic light scattering method, it was shown that 4-AP solutions at concentrations in the range of 1·10−20–1·10−6 M are dispersed systems in which domains and nanoassociates of hundreds of nm in size are formed upon dilution. An interrelation between the non-monotonic concentration dependencies of the size of the dispersed phase, the fluorescence intensity (λex 225 nm, λem 340 nm), specific electrical conductivity, and pH has been established. This allows us to predict the bioeffects of the 4-AP systems at low concentrations. The impact of these diluted aqueous systems on the electrical characteristics of identified neurons of Helix lucorum snails was studied. Incubation of neurons in the 4-AP systems for which the formation of domains and nanoassociates had been established lead to a nonmonotonic decrease of the resting potential by 7–13%. An analysis of the obtained results and published data allows for a conclusion that a consistent change in the nature and parameters of the dispersed phase, as well as the pH of the medium, apparently determines the nonmonotonic nature of the effect of the 4-AP systems in a 1·10−20–1·10−6 M concentration range on the resting membrane potential of neurons. It was found that the pre-incubation of neurons in the 4-AP system with a concentration of 1·10−12 M led to a 17.0% synergistic decrease in the membrane potential after a subsequent treatment with 1·10−2 M 4-AP solution. This finding demonstrates a significant modifying effect of self-organized dispersed systems of 4-AP in low concentrations on the neurons’ sensitivity to 4-AP.
The Role of Neutrophils and Neutrophil Elastase in Pneumococcal Pneumonia
Authors: Domon Hisanori , Terao Yutaka
Published: March 2021

Streptococcus pneumoniae, also known as pneumococcus, is a Gram-positive diplococcus and a major human pathogen. This bacterium is a leading cause of bacterial pneumonia, otitis media, meningitis, and septicemia, and is a major cause of morbidity and mortality worldwide. To date, studies onS. pneumoniaehave mainly focused on the role of its virulence factors including toxins, cell surface proteins, and capsules. However, accumulating evidence indicates that in addition to these studies, knowledge of host factors and host-pathogen interactions is essential for understanding the pathogenesis of pneumococcal diseases. Recent studies have demonstrated that neutrophil accumulation, which is generally considered to play a critical role in host defense during bacterial infections, can significantly contribute to lung injury and immune subversion, leading to pneumococcal invasion of the bloodstream. Here, we review bacterial and host factors, focusing on the role of neutrophils and their elastase, which contribute to the progression of pneumococcal pneumonia.
RIPK3-Dependent Necroptosis Is Induced and Restricts Viral Replication in Human Astrocytes Infected With Zika Virus
Authors: Wen Chunxia , Yu Yufeng , Gao Chengfeng , Qi Xian , Cardona Carol J. , Xing Zheng
Published: March 2021

Apoptosis, pyroptosis and necroptosis are regulated processes of cell death which can be crucial for viral disease outcomes in hosts because of their effects on viral pathogenicity and host resistance. Zika virus (ZIKV) is a mosquito-borne flavivirus, which infects humans and can cause neurological disorders. Neural developmental disorders and microcephaly could occur in infected fetuses. Several types of nervous cells have been reported to be susceptible to ZIKV infection. Human astrocytes play important roles in the nutritional support and defense of neurons. In this study, we show that human astrocytes are susceptible to ZIKV infection and undergo progressive cell death after infection. In infected astrocytes we detected no cleavage or activation of pro-caspase-3 and pro-caspase-1. Apoptotic substrates and increased secretion of interleukin (IL)-1β or IL-18 were not detected, either. These ruled out the occurrence of apoptosis or pyroptosis in ZIKV-infected astrocytes. We detected, however, an increase of phosphorylated receptor-interacting serine/threonine-protein kinase (RIPK)1, RIPK3, and mixed lineage kinase domain-like (MLKL) protein, indicating that programmed necrosis, or necroptosis, was induced in infected astrocytes. The phosphorylation and cell death were inhibited in cells pre-treated with GSK’872, an inhibitor of RIPK3, while inhibition of RIPK1 with an inhibitor, Necrostatin-1, had no effect, suggesting that ZIKV-induced necroptosis was RIPK1-independent in astrocytes. Consistent with this finding, the inhibition of RIPK1 had no effect on the phosphorylation of MLKL. We showed evidence that MLKL phosphorylation was RIPK3-dependent and ZBP-1, which could stimulate RIPK3, was upregulated in ZIKV-infected astrocytes. Finally, we demonstrated that in GSK’872-pre-treated astrocytes, viral replication increased significantly, which indicates that necroptosis may be protective against viral replication in astrocytes. Our finding that astrocytes uniquely underwent necroptosis in response to ZIKV infection provides insight and helps us better understand the viral pathogenesis in the ZIKV-infected central nervous system.
Are We Ready for Nosocomial Candida auris Infections? Rapid Identification and Antifungal Resistance Detection Using MALDI-TOF Mass Spectrometry May Be the Answer
Authors: De Carolis Elena , Marchionni Federica , La Rosa Marilisa , Meis Jacques F. , Chowdhary Anuradha , Posteraro Brunella , Sanguinetti Maurizio
Published: March 2021

The occurrence of multidrug-resistant Candida auris isolates and the increased mortality associated with invasive infections or outbreaks due to this Candida species have been reported in many healthcare settings. Therefore, accurate and rapid identification at the species level of clinical C. auris isolates as well as their timely differentiation as susceptible or resistant to antifungal drugs is mandatory. Aims of the present study were to implement the MALDI-TOF mass spectrometry (MS) Bruker Daltonics Biotyper® database with C. auris spectrum profiles and to develop a fast and reproducible MS assay for detecting anidulafungin (AFG) resistance in C. auris isolates. After creation of main C. auris spectra, a score-oriented dendrogram was generated from hierarchical cluster analysis, including spectra of isolates from C. auris and other Candida (C. glabrata, C. guilliermondii, C. haemulonii, C. lusitaniae, and C. parapsilosis) or non-Candida (Rhodotorula glutinis) species. Cluster analysis allowed to group and classify the isolates according to their species designation. Then, a three-hour incubation antifungal susceptibility testing (AFST) assay was developed. Spectra obtained at null, intermediate, or maximum AFG concentrations were used to create composite correlation index matrices for eighteen C. auris isolates included in the study. All six resistant C. auris isolates were detected as resistant whereas 11 of 12 susceptible C. auris isolates were detected as susceptible by the MS-AFST assay. In conclusion, our MS-based assay offers the possibility of rapidly diagnosing and appropriately treating patients with C. auris infection.
Establishment of a Novel Mouse Model for Atherosclerotic Vulnerable Plaque
Authors: Wang Xueyu , Fu Yahong , Xie Zulong , Cao Muhua , Qu Wenbo , Xi Xiangwen , Zhong Shan , Piao Minghui , Peng Xiang , Jia Ying , Meng Lingbo , Tian Jinwei
Published: March 2021

Background and Aims:Acute coronary syndrome (ACS) is a group of clinical syndromes characterized by rupture or erosion of atherosclerotic unstable plaques. Effective intervention for vulnerable plaques (VP) is of great significance to reduce adverse cardiovascular events.

Methods:Fbn1C1039G+/−mice were crossbred with LDLR−/−mice to obtain a novel model for atherosclerotic VP. After the mice were fed with a high-fat diet (HFD) for 12 or 24 weeks, pathological staining and immunohistochemistry analyses were employed to evaluate atherosclerotic lesions.

Results:Compared to control mice, Fbn1C1039G+/−LDLR−/−mice developed more severe atherosclerotic lesions, and the positive area of oil red O staining in the aortic sinus was significantly increased after 12 weeks (21.7 ± 2.0 vs. 6.3 ± 2.1) and 24 weeks (32.6 ± 2.5 vs. 18.7 ± 2.6) on a HFD. Additional vulnerable plaque characteristics, including significantly larger necrotic cores (280 ± 19 vs. 105 ± 7), thinner fiber caps (14.0 ± 2.8 vs. 32.6 ± 2.7), apparent elastin fiber fragmentation and vessel dilation (3,010 ± 67 vs. 1,465 ± 49), a 2-fold increase in macrophage number (8.5 ± 1.0 vs. 5.0 ± 0.6), obviously decreased smooth muscle cell number (0.6 ± 0.1 vs. 2.1 ± 0.2) and an ~25% decrease in total collagen content (33.6 ± 0.3 vs. 44.9 ± 9.1) were observed in Fbn1C1039G+/−LDLR−/−mice compared with control mice after 24 weeks. Furthermore, spontaneous plaque rupture, neovascularization, and intraplaque hemorrhage were detected in the model mouse plaque regions but not in those of the control mice.

Conclusions:Plaques in Fbn1C1039G+/−LDLR−/−mice fed a HFD show many features of human advanced atherosclerotic unstable plaques. These results suggest that the Fbn1C1039G+/−LDLR−/−mouse is a novel model for investigating the pathological and physiological mechanisms of advanced atherosclerotic unstable plaques.
Echocardiographic Characteristics and Outcome in Patients With COVID-19 Infection and Underlying Cardiovascular Disease
Authors: Li Yuman , Fang Lingyun , Zhu Shuangshuang , Xie Yuji , Wang Bin , He Lin , Zhang Danqing , Zhang Yongxing , Yuan Hongliang , Wu Chun , Li He , Sun Wei , Zhang Yanting , Li Meng , Cui Li , Cai Yu , Wang Jing , Yang Yali , Lv Qing , Zhang Li , Johri Amer M. , Xie Mingxing
Published: March 2021

Background: The cardiac manifestations of coronavirus disease 2019 (COVID-19) patients with cardiovascular disease (CVD) remain unclear. We aimed to investigate the prognostic value of echocardiographic parameters in patients with COVID-19 infection and underlying CVD.

Methods: One hundred fifty-seven consecutive hospitalized COVID-19 patients were enrolled. The left ventricular (LV) and right ventricular (RV) structure and function were assessed using bedside echocardiography.

Results: Eighty-nine of the 157 patients (56.7%) had underlying CVD. Compared with patients without CVD, those with CVD had a higher mortality (22.5 vs. 4.4%, p = 0.002) and experienced more clinical events including acute respiratory distress syndrome, acute heart injury, or deep vein thrombosis. CVD patients presented with poorer LV diastolic and RV systolic function compared to those without CVD. RV dysfunction (30.3%) was the most frequent, followed by LV diastolic dysfunction (9.0%) and LV systolic dysfunction (5.6%) in CVD patients. CVD patients with high-sensitivity troponin I (hs-TNI) elevation or requiring mechanical ventilation therapy demonstrated worsening RV function compared with those with normal hs-TNI or non-intubated patients, whereas LV systolic or diastolic function was similar. Impaired RV function was associated with elevated hs-TNI level. RV function and elevated hs-TNI level were independent predictors of higher mortality in COVID-19 patients with CVD.

Conclusions: Patients with COVID-19 infection and underlying CVD displayed impaired LV diastolic and RV function, whereas LV systolic function was normal in most patients. Importantly, RV function parameters are predictive of higher mortality.
Development and Interplay of Two Orthogonal Fault Systems in the NW Qaidam Basin, Northern Tibetan Plateau
Authors: Huang Kai , Wu Lei , Zhao Haifeng , Zhang Junyong , Zhang Yongshu , Xiao Ancheng , Chen Yan , Chen Hanlin
Published: March 2021

How fold and thrust belts (FTBs) evolve over time and space in a transpressional regime remains poorly understood. Based on high-resolution 3D seismic reflection data and remote sensing images, we herein present a detailed structural analysis of the Cenozoic faults in the NW margin of the Qaidam Basin that is bounded to the north by the left-reverse Altyn Tagh fault system. Two sets of orthogonal, basement-involved faults with contrasting geometries, kinematics, and temporal development are identified. One set consists of generally E-W-striking, N-dipping, reverse faults with a component of sinistral shear. They are parallel or subparallel to the Altyn Tagh fault system, led to southward tilting of the basement, and formed a local unconformity between the middle Miocene Shangyoushashan formation and underlying strata. They developed in an out-of-sequence order, and were mostly active during 43.8–15.3 Ma but in relatively tectonic quiescence with limited weak reactivation since then. The second set is mainly composed of the NNW-striking reverse faults with dextral shear components. They are approximately perpendicular to the Altyn Tagh fault system, and intensively active since ∼15.3 Ma, much later than the initiation of the E-W-striking faults. Together with published results, we ascribe the development of these two sets of orthogonal faults as the transition from transpression to left lateral slip on the central segment of the Altyn Tagh fault system. The two fault sets interplayed with each other in two ways: 1) the older E-W-striking faults were offset by younger NNW-striking faults, and 2) the younger NNW-striking faults curved to link with the preexisting E-W-striking faults. Our findings reveal that transpressional-dominated FTBs evolve in a more complicated way than the contractional-dominated ones, and more site-based case studies are needed to reveal the underlying primary principles.
Tracking Magma Storage: New Perspectives From 40 Years (1980–2020) of Ground Deformation Source Modeling on Etna Volcano
Authors: Bonaccorso Alessandro , Aloisi Marco
Published: March 2021

A key issue on active volcanoes is to investigate the position and characteristics of the magma reservoirs over time. The aim is to better understand the crustal magma transfer, therefore also to define the volcanic hazard and plan the mitigation strategies. Mt. Etna volcano is characterized by a lively eruptive activity with frequent major flank eruptions that can be both purely effusive and explosive-effusive. This volcano has been monitored over 40 years by ground deformation measurements. The studies and modeling of the eruptive processes through these data have mainly concerned single eruptions and the recharge phases that preceded them. In this study, for the first time, we present four decades of numerous recharge periods modeled over time by using the same typology of measurements (geodetic baselines) and the same modeling method. This uniform approach enables tracking the location of magma storage in a robust and unambiguous way during its recharging, which causes the volcano to inflate. In particular, the recharging periods that preceded the main eruptive activities were investigated. The tracking of the source positions contributes to update the representation of the shallow-intermediate plumbing system (last 10 km). Moreover, as a new result, we highlight that the recharges preceding the explosive eruptions are accompanied by a deepening over time of the centroid of the pressure source. This result opens up new scenarios on the relationship between the position of the recharging storage and the subsequent eruptive style.
A Historical Earthquake-Induced Landslide Damming Event at the Qiaojia Reach of the Jinsha River, SE Tibetan Plateau: Implication for the Seismic Hazard of the Xiaojiang Fault
Authors: Hu Mengmeng , Wu Zhonghai , Reicherter Klaus , Ali Sajid , Huang Xiaolong , Zuo Jiameng
Published: March 2021

In bedrock mountainous areas where active faults and deep river valleys interact, earthquake-induced landslides can be used to explore local seismic hazards. The intersection of the highly active Xiaojiang Fault and the Jinsha River and its main tributaries in southwest China is a site of abundant earthquake-induced landslides. We found some boulders inappropriately scattered on the east bank of the Qiaojia reach of the Jinsha River, where the Qiaojia Segment of the Xiaojiang Fault passes through. We investigated the lithology and topography nearby and confirmed its source area, as well as the existence of a landslide damming event in the field. A high-resolution Digital Surface Model (DSM) generated from Unmanned Aerial Vehicle (UAV) images was used to analyze its characteristics and calculate its parameters. Optically Stimulated Luminescence (OSL) and14C dating methods on the related dammed lake sand shows the age of the landslide, which is not later than 878 AD. The characteristics of large size with limited depositional extent, spatial relevance between the landslide and Xiaojiang Fault, and temporal-coincidence of the landslide with 624 AD earthquake support the seismic origin of this landslide. Moreover, the 624 AD earthquake was reanalyzed for its magnitude and macro-epicenter based on the coseismic displacement of the Heishui River floodplain. It was calculated to be Mw7.7 or Ms7.9 and relocated to the Qiaojia area. No M ≥ 7 earthquakes have occurred on the Qiaojia Segment for nearly 1,400 years since 624 AD. The elapsed time is close to the average recurrence interval of large earthquakes on the Qiaojia Segment. Therefore, the seismic hazard of the Qiaojia area should be considered in the future.
Sonographic Characteristics of Papillary Thyroid Carcinoma With Coexistent Hashimoto’s Thyroiditis in the Preoperative Prediction of Central Lymph Node Metastasis
Authors: Chen Sijie , Niu Chengcheng , Peng Qinghai , Tang Kui
Published: March 2021

The purpose of this study was to evaluate the usefulness of the sonographic characteristics of papillary thyroid carcinoma (PTC) with Hashimoto’s thyroiditis (HT) for predicting central lymph node metastasis (CLNM). One hundred thirty-three patients who underwent thyroidectomy and central cervical lymph node dissection for PTC with coexistent HT were retrospectively analyzed. All PTCs with HT were preoperatively evaluated by ultrasound (US) regarding their nodular number, size, component, shape, margin, echogenicity, calcification, capsule contact with protrusion, vascularity and contrast enhanced ultrasound (CEUS) parameters. Univariate analysis demonstrated that patients with PTCs with HT and CLNM more frequently had age ≤ 45 years, size > 10 mm, a wider than tall shape, microcalcification, hypo-enhancement and peak intensity index < 1 than those without CLNM (all p<0.05). Binary logistic regression analysis demonstrated that size > 10 mm and CEUS hypo-enhancement were independent characteristics for the presence of CLNM. Our study indicated that preoperative US characteristics could offer help in predicting CLNM in PTCs with coexistent HT.
The Double Edge Sword of Testosterone’s Role in the COVID-19 Pandemic
Authors: Younis Johnny S. , Skorecki Karl , Abassi Zaid
Published: March 2021

COVID-19 is a complex disease with a multifaceted set of disturbances involving several mechanisms of health and disease in the human body. Sex hormones, estrogen, and testosterone, seem to play a major role in its pathogenesis, development, spread, severity, and mortalities. Examination of factors such as age, gender, ethnic background, genetic prevalence, and existing co-morbidities, may disclose the mechanisms underlying SARS-CoV-2 infection, morbidity, and mortality, paving the way for COVID-19 amelioration and substantial flattening of the infection curve. In this mini-review, we focus on the role of testosterone through a discussion of the intricate mechanisms of disease development and deterioration. Accumulated evidence suggests that there are links between high level (normal male level) as well as low level (age-related hypogonadism) testosterone in disease progression and expansion, supporting its role as a double-edged sword. Unresolved questions point to the essential need for further targeted studies to substantiate these contrasting mechanisms.
Role of Adipokines and Perivascular Adipose Tissue in Abdominal Aortic Aneurysm: A Systematic Review and Meta-Analysis of Animal and Human Observational Studies
Authors: Thanigaimani Shivshankar , Golledge Jonathan
Published: March 2021

Improved understanding of abdominal aortic aneurysms (AAA) pathogenesis is required to identify treatment targets. This systematic review summarized evidence from animal studies and clinical research examining the role of adipokines and perivascular adipose tissue (PVAT) in AAA pathogenesis. Meta-analyses suggested that leptin (Standardized mean difference [SMD]: 0.50 [95% confidence interval (CI): −1.62, 2.61]) and adiponectin (SMD: −3.16 [95% CI: −7.59, 1.28]) upregulation did not significantly affect AAA severity within animal models. There were inconsistent findings and limited studies investigating the effect of resistin-like molecule-beta (RELMβ) and PVAT in animal models of AAA. Clinical studies suggested that circulating leptin (SMD: 0.32 [95% CI: 0.19, 0.45]) and resistin (SMD: 0.63 [95% CI 0.50, 0.76]) concentrations and PVAT to abdominal adipose tissue ratio (SMD: 0.56 [95% CI 0.33, 0.79]) were significantly greater in people diagnosed with AAA compared to controls. Serum adiponectin levels were not associated with AAA diagnosis (SMD: −0.62 [95% CI −1.76, 0.52]). One, eight, and one animal studies and two, two, and four human studies had low, moderate, and high risk-of-bias respectively. These findings suggest that AAA is associated with higher circulating concentrations of leptin and resistin and greater amounts of PVAT than controls but whether this plays a role in aneurysm pathogenesis is unclear.
New Insights Into the Pathologic Roles of the Platelet-Activating Factor System
Authors: Travers Jeffrey B. , Rohan Joyce G. , Sahu Ravi P.
Published: March 2021

Described almost 50 years ago, the glycerophosphocholine lipid mediator Platelet-activating factor (PAF) has been implicated in many pathologic processes. Indeed, elevated levels of PAF can be measured in response to almost every type of pathology involving inflammation and cell damage/death. In this review, we provide evidence for PAF involvement in pathologic processes, with focus on cancer, the nervous system, and in photobiology. Importantly, recent insights into how PAF can generate and travelviabioactive extracellular vesicles such as microvesicle particles (MVP) are presented. What appears to be emerging from diverse pathologies in different organ systems is a common theme where pro-oxidative stressors generate oxidized glycerophosphocholines with PAF agonistic effects, which then trigger more enzymatic PAF synthesisviathe PAF receptor. A downstream consequence of PAF receptor activation is the generation and release of MVP which provide a mechanism to transmit PAF as well as other bioactive agents. The knowledge gaps which when addressed could result in novel therapeutic strategies are also discussed. Taken together, an enhanced understanding of the PAF family of lipid mediators is essential in our improved comprehension of the relationship amongst the diverse cutaneous, cancerous, neurologic and systemic pathologic processes.
The Vbeta13 T Cell Receptor Monoclonal Antibody Reduces Hyaluronan and CD68+, CD3+, and CD8+ Cell Infiltrations to Delay Diabetes in Congenic BB DRLyp/Lyp Rats
Authors: Bogdani Marika , Faxius Linda , Fex Malin , Ramelius Anita , Wernersson Anya , Mordes John P. , Blankenhorn Elizabeth P. , Lernmark Åke
Published: March 2021

The depleting Vβ13a T cell receptor monoclonal antibody (mAb) 17D5 prevents both induced and spontaneous autoimmune diabetes in BB rats. Here it was tested in congenic DRLyp/Lyp rats, all of which spontaneously developed diabetes. Starting at 40 days of age, rats were injected once weekly with either saline, His42 Vβ16 mAb, or 17D5 mAb and monitored for hyperglycemia. Diabetes occurred in 100% (n = 5/5) of saline-treated rats (median age, 66 days; range 55–73), and in 100% (n = 6/6) of His42-treated rats (median age, 69 days; range 59–69). Diabetes occurred in fewer (n = 8/11, 73%) 17D5-treated rats at a later age (median 76 days, range 60–92). Three (27%) of the 17D5-treated rats were killed at 101–103 days of age without diabetes (17D5 no-diabetes rats). Survival analysis demonstrated that 17D5 mAb delayed diabetes onset. Saline- and His42-treated rats had severely distorted islets with substantial loss of insulin-positive cells. These rats exhibited prominent hyaluronan (HA) staining, with the intra-islet HA+ accumulations measuring 5,000 ± 2,400 µm2 and occupying 36 ± 12% of islet area, and severe (grade 4) insulitis with abundant infiltration by CD68+, CD3+, and CD8+ cells. The 17D5 mAb-treated rats with delayed diabetes onset exhibited less severe insulitis (predominantly grade 3). In contrast, the 17D5 no-diabetes rats had mostly normal islets, with insulin+ cells representing 76 ± 3% of islet cells. In these rats, the islet HA deposits were significantly smaller than in the diabetic rats; the intra-islet HA+ areas were 1,200 ± 300 µm2 and accounted for 8 ± 1% of islet area. Also, islet-associated CD68+ and CD3+ cells occurred less frequently (on average in 60 and 3% of the islets, respectively) than in the diabetes rats (present in >95% of the islets). No CD8+ cells were detected in islets in all 17D5 no-diabetes rats. We conclude that mAb 17D5 delayed diabetes in DRLyp/Lyp rats and markedly reduced expression of HA and concomitant infiltration of CD68+, CD3+, and CD8+ cells. Our findings underscore the importance of refining immune suppression in prevention or intervention clinical trials to use mAb reagents that are directed against specific T cell receptors.
Neonatal Hypoglycemia and Brain Vulnerability
Authors: De Angelis Laura Costanza , Brigati Giorgia , Polleri Giulia , Malova Mariya , Parodi Alessandro , Minghetti Diego , Rossi Andrea , Massirio Paolo , Traggiai Cristina , Maghnie Mohamad , Ramenghi Luca Antonio
Published: March 2021

Neonatal hypoglycemia is a common condition. A transient reduction in blood glucose values is part of a transitional metabolic adaptation following birth, which resolves within the first 48 to 72 h of life. In addition, several factors may interfere with glucose homeostasis, especially in case of limited metabolic stores or increased energy expenditure. Although the effect of mild transient asymptomatic hypoglycemia on brain development remains unclear, a correlation between severe and prolonged hypoglycemia and cerebral damage has been proven. A selective vulnerability of some brain regions to hypoglycemia including the second and the third superficial layers of the cerebral cortex, the dentate gyrus, the subiculum, the CA1 regions in the hippocampus, and the caudate-putamen nuclei has been observed. Several mechanisms contribute to neuronal damage during hypoglycemia. Neuronal depolarization induced by hypoglycemia leads to an elevated release of glutamate and aspartate, thus promoting excitotoxicity, and to an increased release of zinc to the extracellular space, causing the extensive activation of poly ADP-ribose polymerase-1 which promotes neuronal death. In this review we discuss the cerebral glucose homeostasis, the mechanisms of brain injury following neonatal hypoglycemia and the possible treatment strategies to reduce its occurrence.
A Systematic Review of Collective Evidences Investigating the Effect of Diabetes Monitoring Systems and Their Application in Health Care
Authors: Kamusheva Maria , Tachkov Konstantin , Dimitrova Maria , Mitkova Zornitsa , García-Sáez Gema , Hernando M. Elena , Goettsch Wim , Petrova Guenka
Published: March 2021

Introduction

Diabetes monitoring systems (DMS) are a possible approach for regular control of glucose levels in patients with Type 1 or 2 diabetes in order to improve therapeutic outcomes or to identify and modify inappropriate patient behaviors in a timely manner. Despite the significant number of studies observing the DMS, no collective evidence is available about the effect of all devices.

Goal

To review and consolidate evidences from multiple systematic reviews on the diabetes monitoring systems and the outcomes achieved.

Materials and methods

Internet-based search in PubMed, EMBASE, and Cochrane was performed to identify all studies relevant to the research question. The data regarding type of intervention, type of diabetes mellitus, type of study, change in clinical parameter(s), or another relevant outcome were extracted and summarized.

Results

Thirty-three out of 1,495 initially identified studies, involving more than 44,100 patients with Type 1, Type 2, or gestational diabetes for real-time or retrospective Continuous Glucose Monitoring (CGMS), Sensor Augmented Pump Therapy (SAPT), Self-monitoring Blood Glucose (SMBG), Continuous subcutaneous insulin infusion (CSII), Flash Glucose Monitoring (FGM), Closed-loop systems and telemonitoring, were included. Most of the studies observed small nominal effectiveness of DMS. In total 11 systematic reviews and 15 meta-analyses, with most focusing on patients with Type 1 diabetes (10 and 6, respectively), reported a reduction in glycated hemoglobin (HbA1c) levels from 0.17 to 0.70% after use of DMS.

Conclusion

Current systematic review of already published systematic reviews and meta-analyses suggests that no statistically significant difference exists between the values of HbA1c as a result of application of any type of DMS. The changes in HbA1c values, number and frequency of hypoglycemic episodes, and time in glucose range are the most valuable for assessing the appropriateness and effectiveness of DMS. Future more comprehensive studies assessing the effectiveness, cost-effectiveness, and comparative effectiveness of DMS are needed to stratify them for the most suitable diabetes patients’ subgroups.
Versatile Functions of Somatostatin and Somatostatin Receptors in the Gastrointestinal System
Authors: Shamsi Bilal Haider , Chatoo Mahanand , Xu Xiao Kang , Xu Xun , Chen Xue Qun
Published: March 2021

Somatostatin (SST) and somatostatin receptors (SSTRs) play an important role in the brain and gastrointestinal (GI) system. SST is produced in various organs and cells, and the inhibitory function of somatostatin-containing cells is involved in a range of physiological functions and pathological modifications. The GI system is the largest endocrine organ for digestion and absorption, SST-endocrine cells and neurons in the GI system are a critical effecter to maintain homeostasis via SSTRs 1-5 and co-receptors, while SST-SSTRs are involved in chemo-sensory, mucus, and hormone secretion, motility, inflammation response, itch, and pain via the autocrine, paracrine, endocrine, and exoendocrine pathways. It is also a power inhibitor for tumor cell proliferation, severe inflammation, and post-operation complications, and is a first-line anti-cancer drug in clinical practice. This mini review focuses on the current function of producing SST endocrine cells and local neurons SST-SSTRs in the GI system, discusses new development prognostic markers, phosphate-specific antibodies, and molecular imaging emerging in diagnostics and therapy, and summarizes the mechanism of the SST family in basic research and clinical practice. Understanding of endocrines and neuroendocrines in SST-SSTRs in GI will provide an insight into advanced medicine in basic and clinical research.