bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Isothermal ω Transitional Phase-Assisted Phase Transition From β to α on Room-Temperature Mechanical Performance of a Meta-Stable β Titanium Alloy Ti−10Mo−6Zr−4Sn−3Nb (Ti-B12) for Medical Application
Authors: Cheng Jun , Li Jinshan , Yu Sen , Du Zhaoxin , Zhang Xiaoyong , Zhang Wen , Gai Jinyang , Wang Hongchuan , Song Hongjie , Yu Zhentao
Published: January 2021

The microstructural evolution and tensile performance of a meta-stable β-type biomedical Ti−10Mo−6Zr−4Sn−3Nb (Ti-B12) alloy subjected to one-stage aging (OSA) and two-stage aging (TSA) are investigated in this work. The OSA treatment is performed at 510°C for 8 h. The TSA treatments are composed of low-temperature aging and high-temperature aging. In the first step, low-temperature aging is conducted at 325°C for 2 h. In the second step, the aging temperature is the same as that in the OSA. The result of the microstructure evolution shows that the precipitated secondary phase after aging is mainly influenced by the process of phase transition. There is a marked difference in the microstructure of the Ti-B12 alloy subjected to the OSA and TSA treatments. The needle-shaped α phases are precipitated in the parent β phase after the OSA treatment. Conversely, the short shuttle-like α phases precipitated after the TSA treatment are formed in the β matrix with the aid of the role of the isothermal ω transitional phase-assisted phase transition. The electron backscattered diffraction results indicate that the crystallographic orientation relationship of the α phases precipitated during the TSA treatment is basically analogous to those in the OSA treatment. The relatively higher tensile strength of 1,275 MPa is achieved by strengthening the effect of the short shuttle-like α precipitation with a size of 0.123 μm in length during the TSA treatment, associating with a suitable elongation of 12% at room temperature simultaneously. The fracture surfaces of the samples after the OSA and TSA treatments indicate that preventing the coarsening of the α layers in the grain boundaries is favorable for the enhancement of strength of Ti-B12 at room temperature. MTT test was carried out to evaluate the acute cytotoxicity and biocompatibility of the implanted material using L929 cells. The relative proliferation rates of cytotoxicity levels 0, 1, 2, 3, and 4 are ≥100, 80–99, 50–79, 30–49, and 0–29%, respectively. The cytotoxicity of the Ti-B12 alloy is slightly better than that of the Ti−6Al−4V alloy, which can meet the requirements of medical materials for biomedical materials.
Inactivation of Inulinase and Marination of High-Quality Jerusalem Artichoke (Helianthus tuberosus L.) Pickles With Screened Dominant Strains
Authors: Zhang Li , Liu Wei , Ji Jiahong , Deng Lina , Feng Qian , Shi Wujian , Gao Jian
Published: January 2021

Freshly harvested Jerusalem artichoke tubers contain inulinase, an enzyme that requires inactivation, because of its ability to hydrolysis inulin into fructose, which can be consumed by microorganism during marination. As the traditional pickling process takes 6 months, and involves the addition of a large amount of salt (18–20%), this production strategy is uneconomical and increases the nitrite intake. Additionally, miscellaneous bacteria produced during pickling affect the product taste. In this study, the enzyme inactivation effects of NaCl, NaHCO3, and ultrasound were evaluated. NaHCO3 treatment results in the highest degree of enzyme inactivation; however, the quality and flavor of the obtained Jerusalem artichoke pickles were not ideal. The Jerusalem artichoke pickles in which the enzymes were inactivated using a combination of NaCl and ultrasound exhibited better flavor than those exposed to NaHCO3; further, this combination reduced the inulinase activity of the Jerusalem artichokes to 2.50 U/mL, and maintained the inulin content at 61.22%. The strains LS3 and YS2, identified as Enterococcus faecalis and the salt-tolerant yeast Meyerozyma guilliermondii, respectively, were the dominant microorganisms isolated from the pickle juice. Jerusalem artichokes with inactivated inulinase were pickled with microbial powder, separated, purified, and dried to remove the natural Jerusalem artichoke sauce. This process shortened the fermentation cycle and improved product quality.
Guidelines for Techno-Economic Analysis of Adsorption Processes
Authors: Danaci David , Webley Paul A. , Petit Camille
Published: January 2021

Techno-economic analyses (TEAs) of CO2 capture technologies have risen in popularity, due to growing interest in meeting CO2 emissions reduction targets. Adsorption processes are one of the technologies proposed for CO2 capture, and although difficult, standardization of TEAs for adsorption should be attempted. The reason is that TEAs are often referred to as input data to other forms of modeling, to guide policy, and to act as summaries for those unfamiliar with adsorption processes. Herein, we discuss the aspects that should be considered when conducting TEAs for CO2 adsorption processes, and we present the implications of choices made at the TEA stage and offer guidance on best practice. our aim is to make TEAs of adsorption processes widely accessible to the adsorption community, and more generally to communities engaged in the evaluation of CCS technologies.
Age- and Gender-Related Differences in Speech Alignment Toward Humans and Voice-AI
Authors: Zellou Georgia , Cohn Michelle , Ferenc Segedin Bruno
Published: January 2021

Speech alignment is where talkers subconsciously adopt the speech and language patterns of their interlocutor. Nowadays, people of all ages are speaking with voice-activated, artificially-intelligent (voice-AI) digital assistants through phones or smart speakers. This study examines participants’ age (older adults, 53–81 years old vs. younger adults, 18–39 years old) and gender (female and male) on degree of speech alignment during shadowing of (female and male) human and voice-AI (Apple’s Siri) productions. Degree of alignment was assessed holistically via a perceptual ratings AXB task by a separate group of listeners. Results reveal that older and younger adults display distinct patterns of alignment based on humanness and gender of the human model talkers: older adults displayed greater alignment toward the female human and device voices, while younger adults aligned to a greater extent toward the male human voice. Additionally, there were other gender-mediated differences observed, all of which interacted with model talker category (voice-AI vs. human) or shadower age category (OA vs. YA). Taken together, these results suggest a complex interplay of social dynamics in alignment, which can inform models of speech production both in human-human and human-device interaction.
Cardiac Biomarker Levels and Their Prognostic Values in COVID-19 Patients With or Without Concomitant Cardiac Disease
Authors: Yu Jia-Sheng , Pan Nan-Nan , Chen Ru-Dong , Zeng Ling-Cheng , Yang Hong-Kuan , Li Hua
Published: January 2021

The coronavirus disease 2019 (COVID-19) pandemic has become a global threat. Increases in cardiac biomarkers are common and are associated with adverse outcomes in patients with COVID-19. Although these increases are more likely to occur in cases with concomitant cardiac disease, the differences in cardiac biomarker levels between patients with and without cardiac disease and their associations with in-hospital mortality are largely unknown. A consecutive serial of laboratory-confirmed COVID-19 cases was retrospectively enrolled. Clinical characteristics, laboratory results, and outcome data were collected. The levels of cardiac biomarkers were evaluated and compared by stratifying patients according to concomitant cardiac conditions and clinical classifications. The prognostic efficacy of cardiac biomarker levels on admission was also assessed. Among the overall study population and survived patients, the cardiac biomarker levels at both the early and late stages in cardiac patients were significantly higher than those in non-cardiac patients. However, their concentrations in cardiac patients were comparable to non-cardiac ones among non-survivors. The cardiac biomarker levels at the late stage of the disease were significantly decreased compared to those at the early stage among patients who were alive. Whereas, the late-stage biomarker levels were significantly increased in patients who ultimately died. Subgroup analysis illustrated that increases in cardiac biomarkers were closely related to the severity of the disease, and were prognostic for high risks of in-hospital mortality in non-cardiac, rather than in cardiac patients. Myo and NT-proBNP, rather than Hs-TnI and CK-MB, were independently associated with in-hospital mortality in the overall population and non-cardiac patients. However, these associations were not significant among cardiac patients. In conclusion, our results helped better understand the release pattern and prognostic performance of cardiac biomarkers in patients with COVID-19. Increased levels of Myo and NT-proBNP on admission could be useful markers for early identifying high-risk patients. However, special attention must be paid when implementing the prognostic function for cardiac patients.
MiR-223-3p in Cardiovascular Diseases: A Biomarker and Potential Therapeutic Target
Authors: Zhang Meng-Wan , Shen Yun-Jie , Shi Jing , Yu Jian-Guang
Published: January 2021

Cardiovascular diseases, involving vasculopathy, cardiac dysfunction, or circulatory disturbance, have become the major cause of death globally and brought heavy social burdens. The complexity and diversity of the pathogenic factors add difficulties to diagnosis and treatment, as well as lead to poor prognosis of these diseases. MicroRNAs are short non-coding RNAs to modulate gene expression through directly binding to the 3′-untranslated regions of mRNAs of target genes and thereby to downregulate the protein levels post-transcriptionally. The multiple regulatory effects of microRNAs have been investigated extensively in cardiovascular diseases. MiR-223-3p, expressed in multiple cells such as macrophages, platelets, hepatocytes, and cardiomyocytes to modulate their cellular activities through targeting a variety of genes, is involved in the pathological progression of many cardiovascular diseases. It participates in regulation of several crucial signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B, insulin-like growth factor 1, nuclear factor kappa B, mitogen-activated protein kinase, NOD-like receptor family pyrin domain containing 3 inflammasome, and ribosomal protein S6 kinase B1/hypoxia inducible factor 1 α pathways to affect cell proliferation, migration, apoptosis, hypertrophy, and polarization, as well as electrophysiology, resulting in dysfunction of cardiovascular system. Here, in this review, we will discuss the role of miR-223-3p in cardiovascular diseases, involving its verified targets, influenced signaling pathways, and regulation of cell function. In addition, the potential of miR-223-3p as therapeutic target and biomarker for diagnosis and prediction of cardiovascular diseases will be further discussed, providing clues for clinicians.
Cardiac Mineralocorticoid Receptor and the Na+/H+ Exchanger: Spilling the Beans
Authors: Ennis Irene Lucía , Pérez Néstor Gustavo
Published: January 2021

Current evidence reveals that cardiac mineralocorticoid receptor (MR) activation following myocardial stretch plays an important physiological role in adapting developed force to sudden changes in hemodynamic conditions. Its underlying mechanism involves a previously unknown nongenomic effect of the MR that triggers redox-mediated Na+/H+ exchanger (NHE1) activation, intracellular Na+ accumulation, and a consequent increase in Ca2+ transient amplitude through reverse Na+/Ca2+ exchange. However, clinical evidence assigns a detrimental role to MR activation in the pathogenesis of severe cardiac diseases such as congestive heart failure. This mini review is meant to present and briefly discuss some recent discoveries about locally triggered cardiac MR signals with the objective of shedding some light on its physiological but potentially pathological consequences in the heart.
Current Evidence on Traditional Chinese Exercises for Quality of Life in Patients With Essential Hypertension: A Systematic Review and Meta-Analysis
Authors: Song Yang , Li Jialin , István Bíró , Xuan Rongrong , Wei Sheng , Zhong Guanghui , Gu Yaodong
Published: January 2021

Essential hypertension is one of the most common chronic diseases seen in primary human health care that could lead to various health problems and reduce the quality of life (QOL). This study was performed to evaluate the effects of traditional Chinese exercises (TCE) on QOL in patients with essential hypertension. Three English databases and one Chinese database were searched for randomized controlled trials (RCTs) until August 2020. A total of 13 RCTs with 1,361 hypertensive patients met the inclusion criteria, 10 trials employed Tai Chi and 3 trials employed Qigong, including Dongeui Qinggong, Yijinjing, and Wuqinxi. Despite a large heterogeneity within studies, it is demonstrated that TCE may be an effective therapy to improve the QOL of hypertensive patients. More specific, compared with no intervention, the meta-analysis presented that Tai Chi significantly improved both the physical and mental component of the 36-item short-form health survey (SF-36) QOL scale, and it was found that the simplified 24-form Tai Chi with a frequency of 30–50 min per session at five to eight sessions per week was the most commonly used setting. The pooling also revealed that Tai Chi and Qigong had some significantly positive effects on QOL based on other scales. However, more rigorously designed RCTs are warranted for further verification. This systematic review and meta-analysis of RCTs demonstrated that Tai Chi may be an effective therapy to improve the QOL of patients with essential hypertension. All these findings provide helpful information for hypertensive patients and medical personnel.
Fault Pattern and Seismotectonic Style of the Campania – Lucania 1980 Earthquake (Mw 6.9, Southern Italy): New Multidisciplinary Constraints
Authors: Bello S. , de Nardis R. , Scarpa R. , Brozzetti F. , Cirillo D. , Ferrarini F. , di Lieto B. , Arrowsmith R. J. , Lavecchia G.
Published: January 2021

New fault trace mapping and structural survey of the active faults outcropping within the epicentral area of the Campania-Lucania 1980 normal fault earthquake (Mw6.9) are integrated with a revision of pre-existing earthquake data and with an updated interpretation of the CROP-04 near-vertical seismic profile to reconstruct the surface and depth geometry, the kinematics and stress tensor of the seismogenic fault pattern. Three main fault alignments, organized in high-angle en-echelon segments of several kilometers in length, are identified and characterized. The inner and intermediate ones, i.e. Inner Irpinia (InIF) and Irpinia Faults (IF), dip eastward; the outer Antithetic Fault (AFA) dips westward. Both the InIF and the IF strike NW-SE along the northern and central segments and rotate to W-E along the southern segments for at least 16 km. We provide evidence of surface coseismic faulting (up to 1 m) not recognized before along the E-W segments and document coseismic ruptures with maximum vertical displacement up to ∼1 m where already surveyed from other investigators 40 years ago. Fault/slip data from surface data and a new compilation of focal mechanisms (1980 – 2018) were used for strain and stress analyses to show a coherent NNE-directed least principal stress over time and at different crustal depths, with a crustal-scale deviation from the classic SW-NE tensional direction across the Apennines of Italy. The continuation at depth of the outcropping faults is analyzed along the trace of the CROP-04 profile and with available hypocentral distributions. Integrating all information, a 3D seismotectonic model, extrapolated to the base of the seismogenic layer, is built. It outlines a graben-like structure with a southern E-W bend developed at depth shallower than 10–12 km, at the hanging wall of an extensional NE- to E-dipping extensional basal detachment. In our interpretation, such a configuration implies a control in the stress transfer during the 1980 earthquake ruptures and provides a new interpretation of the second sub-event, occurred at 20 s. Our reconstruction suggests that the latter ruptured a hanging wall NNE-dipping splay of the E-W striking main fault segment and possibly also an antithetic SSW-dipping splay, in two in-sequence episodes.
Using Google Earth Images to Extract Dense Landslides Induced by Historical Earthquakes at the Southwest of Ordos, China
Authors: Peng Du , Yueren Xu , Qinjian Tian , Wenqiao Li
Published: January 2021

As historical earthquake records are simple, determining the source parameters of historical strong earthquakes over an extended period is difficult. There are numerous uncertainties in the study of historical earthquakes based on limited literature records. Co-seismic landslide interpretation combined with historical documents can yield the possibility of reducing these uncertainties. The dense co-seismic landslides can be preserved for hundreds to thousands of years in Loess Plateau, North China; furthermore, there are notable attribute differences between earthquake landslides and rainfall-triggered landslides. Along the southwestern margin of the Ordos Block, only one severe earthquake has been recorded in the past 3,000 years. The records of “Sanchuan exhaustion and Qishan collapse” provide clues for an investigation of the 780 BC Qishan earthquake. In this study, combined with historical documents, current high-resolution Google Earth images were used to extract historical landslides along the southwestern of the Ordos Block. There were 6,876 landslides with a total area of 643 km2. The landslide-intensive areas were mainly distributed along the Longxian–Qishan–Mazhao Fault in the loess valley area on the northeastern side of the fault. Loess tableland and river terraces occur on the southwest side of the fault; dense landslides have not been examined due to the topographical conditions in this area. By analyzing the spatial distribution of historical earthquake damage in this region, comparing the characteristics of rainfall-triggered landslides, and combining existing dating results for bedrock collapse and loess landslides, the interpretation of dense historical landslides can be linked to the Qishan Earthquake. The interpretation results are associated with historical records. Analyses of current earthquake cases show that the distribution of dense landslides triggered by strong earthquakes can indicate the episeismic area of an earthquake. In addition, the non-integrated landslide catalog without small- and medium-scale coseismic landslides can be used to effectively determine the source parameters of historical strong earthquakes and perform quantitative evaluations. This study evaluates the focal parameters of the 780 BC Qishan earthquake based on interpretations of the spatial distribution range of historical landslides as representations of the range of the extreme earthquake zone.
Beyond Ethnic Diversity: The Role of Teacher Care for Interethnic Relations
Authors: Grütter Jeanine , Meyer Bertolt , Philipp Michel , Stegmann Sebastian , van Dick Rolf
Published: January 2021

Drawing on the role of teachers for peer ecologies, we investigated whether students favored ethnically homogenous over ethnically diverse relationships, depending on classroom diversity and perceived teacher care. We specifically studied students' intra- and interethnic relationships in classrooms with different ethnic compositions, accounting for homogeneous subgroups forming on the basis of ethnicity and gender diversity (i.e., ethnic-demographic faultlines). Based on multilevel social network analyses of dyadic networks between 1299 early adolescents in 70 German fourth grade classrooms, the results indicated strong ethnic homophily, particularly driven by German students who favored ethnically homogenous dyads over mixed dyads. As anticipated, the results showed that there was more in-group bias if perceived teacher care was low rather than high. Moreover, stronger faultlines were associated with stronger in-group bias; however, this relation was moderated by teacher care: If students perceived high teacher care, they showed a higher preference for mixed-ethnic dyads, even in classrooms with strong faultlines. These findings highlight the central role of teachers as agents of positive diversity management and the need to consider contextual classroom factors other than ethnic diversity when investigating intergroup relations in schools.
Is Sugarcane a Convenient Feedstock to Provide Ethanol to Oxygenate Gasolines in Mexico? A Process Simulation and Techno-Economic-Based Analysis
Authors: Aburto Jorge , Martínez-Hernández Elías
Published: January 2021

Sugarcane is a major crop produced in many tropical countries including Mexico and has been the basis of a well-established agroindustry. However, the variation in market prices and health concerns over the consumption of sugar are challenging the economics and sustainability of sugarcane growers and mills. This paper presents a techno-economic assessment of using existing production capacity of sugarcane in Mexico and the correspondent Mexican sugarcane mills for producing ethanol as gasoline oxygenate, in comparison to the export of excess sugar production. Using the most recent statistics, we found out that the bioethanol potential is of 849,260,499 L/year which can cover for 100% of the premium and magna gasoline demand in metropolitan area (MA) and 48% of premium gasoline in rest of the country areas (RoCAs) at 5.8% w/v blending (2.7% O2 w/v). This can be done by diverting the 20% sugar production excess to ethanol with the benefit of a higher gross netback of 308.3 USD/ton of sugarcane in comparison to 222.5 USD/ton of sugarcane when it is exported. Furthermore, a minimum ethanol-selling price (MESP) of 0.5211 USD/L was estimated, showing that ethanol might be competitive against methyl tert-butyl ether (0.50 USD/L FOB Gulf price) as gasoline oxygenate agent. Decarbonizing gasoline in Mexico through the use of ethanol might allow the abatement of 5,766.8 kg CO2/day when 20% sugar is used. Concerning the underconstruction Dos Bocas refinery in Tabasco State, southern Mexico, ethanol blend at 5.8% in gasolines might but also contribute to the abatement of 6.1% of CO2 emissions and the required sugarcane was estimated at 1 million tons per year. All these indicate that sugarcane has a great potential as a feedstock to produce first-generation ethanol as a gasoline oxygenate agent in Mexico.
Unsynchronized Driving Mechanisms of Spring and Autumn Phenology Over Northern Hemisphere Grasslands
Authors: Cong Nan , Huang Ke , Zhang Yangjian
Published: January 2021

Global warming has impacted Northern Hemisphere (NH) grassland ecosystems to a great extent. Vegetation growing season length (GSL) has been extended by concurrent advances in spring green-up and postponements in autumn dormancy. However, the driving mechanisms of phenology are unclear as limited factors have been considered so far. Therefore, it is still elusive to what extent phenological changes shaped GSL. In this study, we used remote sensing normalized difference vegetation index (NDVI) to extract spring and autumn phenology of NH grasslands, and further explored the contribution of each phenophase to GSL through the coefficient of variation (CV) and contribution coefficient (CntC). We found that 65% of NH grasslands exhibited advanced start-of-season (SOS) and circa 58% showed delayed end-of-season (EOS) in the three decades. Changes in GSL was regulated more by EOS changes than by SOS changes, as evidenced by their respective 52 vs. 48% CntC. As for the relationship between phenology and environmental elements, the causing factor analysis revealed that climatic factors (temperature, precipitation, and their interactions) played a dominant role in SOS variations, while environmental and internal factors exerted dominant effects on EOS. Also, interactions of temperature and precipitation contributed a higher variation of SOS than either of them individually. The differentiated factors controlling the two bounding ends of the growing season suggested that it is impossible for GSL to continue to extend without limits under global warming.
Characteristics of Genetic Variations Associated With Lennox-Gastaut Syndrome in Korean Families
Authors: Yang Jin Ok , Choi Min-Hyuk , Yoon Ji-Yong , Lee Jeong-Ju , Nam Sang Ook , Jun Soo Young , Kwon Hyeok Hee , Yun Sohyun , Jeon Su-Jin , Byeon Iksu , Halder Debasish , Kong Juhyun , Lee Byungwook , Lee Jeehun , Kang Joon-Won , Kim Nam-Soon
Published: January 2021

Lennox-Gastaut syndrome (LGS) is a severe type of childhood-onset epilepsy characterized by multiple types of seizures, specific discharges on electroencephalography, and intellectual disability. Most patients with LGS do not respond well to drug treatment and show poor long-term prognosis. Approximately 30% of patients without brain abnormalities have unidentifiable causes. Therefore, accurate diagnosis and treatment of LGS remain challenging. To identify causative mutations of LGS, we analyzed the whole-exome sequencing data of 17 unrelated Korean families, including patients with LGS and LGS-like epilepsy without brain abnormalities, using the Genome Analysis Toolkit. We identified 14 mutations in 14 genes as causes of LGS or LGS-like epilepsy. 64 percent of the identified genes were reported as LGS or epilepsy-related genes. Many of these variations were novel and considered as pathogenic or likely pathogenic. Network analysis was performed to classify the identified genes into two network clusters: neuronal signal transmission or neuronal development. Additionally, knockdown of two candidate genes with insufficient evidence of neuronal functions, SLC25A39 and TBC1D8, decreased neurite outgrowth and the expression level of MAP2, a neuronal marker. These results expand the spectrum of genetic variations and may aid the diagnosis and management of individuals with LGS.
Sea Urchin as a Universal Model for Studies of Gene Networks
Authors: Adonin Leonid , Drozdov Anatoliy , Barlev Nickolai A.
Published: January 2021

The purple sea urchinStrongylocentrotus purpuratushas been used for over 150 years as a model organism in developmental biology. Using this model species, scientists have been able to describe, in detail, the mechanisms of cell cycle control and cell adhesion, fertilization, calcium signaling, cell differentiation, and death. Massive parallel sequencing of the sea urchin genome enabled the deciphering of the main components of gene regulatory networks during the activation of embryonic signaling pathways. This knowledge helped to extrapolate aberrations in somatic cells that may lead to diseases, including cancer in humans. Furthermore, since many, if not all, developmental signaling pathways were shown to be controlled by non-coding RNAs (ncRNAs), the sea urchin organism represents an attractive experimental model. In this review, we discuss the main discoveries in the genetics, genomics, and transcriptomics of sea urchins during embryogenesis with the main focus on the role of ncRNAs. This information may be useful for comparative studies between different organisms, and may help identify new regulatory networks controlled by ncRNAs.
Immunosuppressive Amino-Acid Catabolizing Enzymes in Multiple Sclerosis
Authors: Correale Jorge
Published: January 2021

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease that affects the central nervous system. Although the pathogenesis of MS is not yet fully elucidated, several evidences suggest that autoimmune processes mediated by Th1, Th17, and B cells play an important role in the development of the disease. Similar to other cells, immune cells need continuous access to amino acids (AA) in order to maintain basal metabolism and maintain vitality. When immune cells are activated by inflammation or antigenic signals, their demand for AA increases rapidly. Although AA deprivation itself may weaken the immune response under certain conditions, cells also have AA sensitive pathways that can activate intense alterations in cell metabolism based on changes in AA levels. Several data indicate that cells expressing enzymes that can degrade AA can regulate the functions of antigen-presenting cells and lymphocytes, revealing that the AA pathways are essential for controlling the function, and survival of immune cells, as well as immune cell gene expression. Basal AA catabolism may contribute to immune homeostasis and prevent autoimmunity, while increased AA catalytic activity may enhance immune suppression. In addition, there is increasing evidence that some downstream AA metabolites are important biological mediators of autoimmune response regulation. Two of the most important AA that modulate the immune response are L-Tryptophan (Trp) and L-Arginine (Arg). Tryptophan is catabolized through 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) 1 and IDO2 enzymes, while three other enzymes catabolize Arg: inducible nitric oxide synthetase (iNOS), and two arginase isoforms (ARG1, ARG2). Genes encoding IDO, iNOS and ARG are induced by inflammatory cues such as cytokines, a key feature that distinguishes them from enzymes that catabolize other AA. Evidence suggests that AA catabolism is decreased in MS patients and that this decrease has functional consequences, increasing pro-inflammatory cytokines and decreasing Treg cell numbers. These effects are mediated by at least two distinct pathways involving serine/threonine kinases: the general control nonderepressible 2 kinase (GCN2K) pathway; and the mammalian target of rapamycin (mTOR) pathway. Similarly, IDO1-deficient mice showed exacerbation of experimental autoimmune encephalomyelitis (EAE), increased Th1 and Th17 cells, and decreased Treg cells. On the contrary, the administration of downstream Trp metabolite 3-HAA, inhibits Th1/Th17 effector cells and promotes Treg response by up-regulating TGF-β production by dendritic cells, thereby improving EAE. Collectively, these observations stand out the significance of AA catabolism in the regulation of the immune responses in MS patients. The molecules related to these pathways deserve further exploration as potential new therapeutic targets in MS
Spatial Organization and Recruitment of Non-Specific T Cells May Limit T Cell-Macrophage Interactions Within Mycobacterium tuberculosis Granulomas
Authors: Millar Jess A. , Butler J. Russell , Evans Stephanie , Grant Nicole L. , Mattila Joshua T. , Linderman Jennifer J. , Flynn JoAnne L. , Kirschner Denise E.
Published: January 2021

Tuberculosis (TB) is a worldwide health problem; successful interventions such as vaccines and treatment require a 2better understanding of the immune response to infection withMycobacterium tuberculosis(Mtb). In many infectious diseases, pathogen-specific T cells that are recruited to infection sites are highly responsive and clear infection. Yet in the case of infection with Mtb, most individuals are unable to clear infection leading to either an asymptomatically controlled latent infection (the majority) or active disease (roughly 5%–10% of infections). The hallmark of Mtb infection is the recruitment of immune cells to lungs leading to development of multiple lung granulomas. Non-human primate models of TB indicate that on average <10% of T cells within granulomas are Mtb-responsive in terms of cytokine production. The reason for this reduced responsiveness is unknown and it may be at the core of why humans typically are unable to clear Mtb infection. There are a number of hypotheses as to why this reduced responsiveness may occur, including T cell exhaustion, direct downregulation of antigen presentation by Mtb within infected macrophages, the spatial organization of the granuloma itself, and/or recruitment of non-Mtb-specific T cells to lungs. We use a systems biology approach pairing data and modeling to dissect three of these hypotheses. We find that the structural organization of granulomas as well as recruitment of non-specific T cells likely contribute to reduced responsiveness.
Interferon Receptor Trafficking and Signaling: Journey to the Cross Roads
Authors: Zanin Natacha , Viaris de Lesegno Christine , Lamaze Christophe , Blouin Cedric M.
Published: January 2021

Like most plasma membrane proteins, type I interferon (IFN) receptor (IFNAR) traffics from the outer surface to the inner compartments of the cell. Long considered as a passive means to simply control subunits availability at the plasma membrane, an array of new evidence establishes IFNAR endocytosis as an active contributor to the regulation of signal transduction triggered by IFN binding to IFNAR. During its complex journey initiated at the plasma membrane, the internalized IFNAR complex, i.e. IFNAR1 and IFNAR2 subunits, will experience post-translational modifications and recruit specific effectors. These finely tuned interactions will determine not only IFNAR subunits destiny (lysosomal degradation vs. plasma membrane recycling) but also the control of IFN-induced signal transduction. Finally, the IFNAR system perfectly illustrates the paradigm of the crosstalk between membrane trafficking and intracellular signaling. Investigating the complexity of IFN receptor intracellular routes is therefore necessary to reveal new insight into the role of IFNAR membrane dynamics in type I IFNs signaling selectivity and biological activity.
Intestinal Stem Cells and Immune Cell Relationships: Potential Therapeutic Targets for Inflammatory Bowel Diseases
Authors: Hou Qihang , Huang Jingxi , Ayansola Hammed , Masatoshi Hori , Zhang Bingkun
Published: January 2021

The mammalian intestine is the largest immune organ that contains the intestinal stem cells (ISC), differentiated epithelial cells (enterocytes, Paneth cells, goblet cells, tuft cells, etc.), and gut resident-immune cells (T cells, B cells, dendritic cells, innate lymphoid cell, etc.). Inflammatory bowel disease (IBD), a chronic inflammatory disease characterized by mucosa damage and inflammation, threatens the integrity of the intestine. The continuous renewal and repair of intestinal mucosal epithelium after injury depend on ISCs. Inflamed mucosa healing could be a new target for the improvement of clinical symptoms, disease recurrence, and resection-free survival in IBD treated patients. The knowledge about the connections between ISC and immune cells is expanding with the development of in vitro intestinal organoid culture and single-cell RNA sequencing technology. Recent findings implicate that immune cells such as T cells, ILCs, dendritic cells, and macrophages and cytokines secreted by these cells are critical in the regeneration of ISCs and intestinal epithelium. Transplantation of ISC to the inflamed mucosa may be a new therapeutic approach to reconstruct the epithelial barrier in IBD. Considering the links between ISC and immune cells, we predict that the integration of biological agents and ISC transplantation will revolutionize the future therapy of IBD patients.
Molecular Systematics of the Long-Snouted Deep Water Dogfish (Centrophoridae, Deania) With Implications for Identification, Taxonomy, and Conservation
Authors: Stefanni Sergio , Catarino Diana , Ribeiro Pedro A. , Freitas Mafalda , Menezes Gui M. , Neat Francis , Stanković David
Published: January 2021

According to the most recent taxonomical revision, the deep-sea dogfish genusDeaniaencompasses four species. Three of them,D. calcea, D. profundorum, andD. hystricosa, occur in the North Atlantic. WhilstD. profundorumcan be identified by the presence of a subcaudal keel, the other two species are not easily visually distinguished. Uncertainties over identification raises concerns over stock units and whether management plans are adequate. In this study we compared onboard visual identification ofDeaniaspecimens, with morphological inspection of skin denticles under stereo microscope and with independent molecular taxonomical assignment using two molecular markers. Particular emphasis was paid to specimens identified asD. calceaandD. hystricosain the NE Atlantic where these species potentially occur sympatrically and may be easily confused. In the past the species have been discriminated on the basis of the size of skin denticles (skin roughness), but our study showed that the crown length of skin denticles covaries with size (and sex), irrespective of species, and therefore this is not a reliable morphological character and should not be used to discriminate between the two species. Phylogenetic analyses did not indicate thatD. hystricosato be a distinct lineage fromD. calcea. Interestingly, however four individuals (specimens from: UK, Azores Is., Madeira Is. and Seine seamount) formed a well-defined sub-clade nested within theD. calceaclade, possibly a signature of a past vicariance event or a result of coalescent stochasticity.
The Clinical Characteristics and Outcomes of Adult Patients With Pneumonia Related to Three Paramyxoviruses
Authors: Chen Liang , Han Xiudi , Li YanLi , Zhang Chunxiao , Xing Xiqian
Published: January 2021

Background: Respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and human parainfluenza virus (hPIV) are paramyxoviruses (PMVs) that are important etiologies of community-acquired pneumonia. However, current knowledge about the clinical features and outcomes of PMV-related pneumonia (PMV-p) is limited. We aimed to investigate the clinical characteristics and disease severity in immunocompetent adults hospitalized with hMPV-related pneumonia (hMPV-p), hPIV-related pneumonia (hPIV-p), or RSV-related pneumonia (RSV-p).

Methods: We retrospectively recruited 488 patients with PMV-p (153 with RSV-p, 137 with hMPV-p, and 198 with hPIV-p) from five teaching hospitals in China during 2011–2019. Univariate and multivariate analyses were performed to identify predictors to distinguish hMPV-p/hPIV-p from RSV-p and evaluate the effects of virus types on the clinical outcomes.

Results: Compared with RSV-p, sputum production [odds ratio (OR) 5.029, 95% confidence interval (CI) 2.452–10.312, P < 0.001] was positively associated with hMPV-p, while solid malignant tumor (OR 0.346, 95% CI 0.126–0.945, P = 0.038), nasal congestion (OR 0.102, 95% CI 0.041–0.251, P < 0.001), and respiratory rate ≥ 30 breaths/min (OR 0.296, 95% CI 0.136–0.640, P = 0.002) were negatively related to hMPV-p. Sputum production (OR 13.418, 95% CI 6.769–26.598, P < 0.001) was positively associated with hPIV-p, while nasal congestion (OR 0.194, 95% CI 0.098–0.387, P < 0.001), dyspnea (OR 0.469, 95% CI 0.272–0.809, P < 0.001), and respiratory rate ≥30 breaths/min (OR 0.090, 95% CI 0.032–0.257, P < 0.001) on admission were negatively related to hPIV-p. After adjustment for confounders, multivariate logistic regression analysis suggested that hMPV-p (OR 0.355, 95% CI 0.135–0.932, P = 0.035) and hPIV-p (OR 0.311, 95% CI 0.121–0.784, P = 0.013) were associated with decreased 30-day mortality compared with RSV-p. RSV infection (OR 4.183, 95% CI 1.709–10.236, P = 0.002) was identified as an independent predictor of 30-day mortality in patients with PMV-p.

Conclusion: RSV-p caused more severe disease than hMPV-p and hPIV-p. Although some clinical features are helpful for distinguishing the diseases, etiologic diagnosis is critical in the management of the PMV-p.
Antibiotics in Bone Cements Used for Prosthesis Fixation: An Efficient Way to Prevent Staphylococcus aureus and Staphylococcus epidermidis Prosthetic Joint Infection
Authors: Cara Andréa , Ballet Mathilde , Hemery Claire , Ferry Tristan , Laurent Frédéric , Josse Jérôme
Published: January 2021

Prosthetic joint infections (PJIs) are one of the most frequent reasons for arthroplasty revision. These infections are mostly associated with the formation of biofilm, notably by staphylococci, such as Staphylococcus aureus and Staphylococcus epidermidis. To minimize the rates of PJIs following primary or revision total joint arthroplasty, antibiotic-loaded bone cements (ALBCs) can be used for prosthesis fixation. However, its use is still debated. Indeed, various studies reported opposite results. In this context, we aimed to compare the prophylactic anti-biofilm activity of ALBCs loaded with two antibiotics with ALBC loaded with only one antibiotic. We compared commercial ready-to-use cements containing gentamicin alone, gentamicin plus vancomycin, and gentamicin plus clindamycin to plain cement (no antibiotic), investigating staphylococcal biofilm formation for 10 strains of S. aureus and S. epidermidis with specific resistance to gentamicin, vancomycin, or clindamycin. Firstly, we performed disk diffusion assays with the elution solutions. We reported that only the cement containing gentamicin and clindamycin was able to inhibit bacterial growth at Day 9, whereas cements with gentamicin only or gentamicin and vancomycin lost their antibacterial activity at Day 3. Then, we observed that all the tested ALBCs can inhibit biofilm formation by methicillin-susceptible staphylococci without other antibiotic resistance ability. Similar results were observed when we tested vancomycin-resistant or clindamycin-resistant staphylococci, with some strain-dependent significant increase of efficacy for the two antibiotic ALBCs when compared with gentamicin-loaded cement. However, adding vancomycin or clindamycin to gentamicin allows a better inhibition of biofilm formation when gentamicin-resistant strains were used. Our in vitro results suggest that using commercially available bone cements loaded with gentamicin plus vancomycin or clindamycin for prosthesis fixation can help in preventing staphylococcal PJIs following primary arthroplasties, non-septic revisions or septic revisions, especially to prevent PJIs caused by gentamicin-resistant staphylococci.
Effects of Environmental Factors on Severity and Mortality of COVID-19
Authors: Kifer Domagoj , Bugada Dario , Villar-Garcia Judit , Gudelj Ivan , Menni Cristina , Sudre Carole , Vučković Frano , Ugrina Ivo , Lorini Luca F. , Posso Margarita , Bettinelli Silvia , Ughi Nicola , Maloberti Alessandro , Epis Oscar , Giannattasio Cristina , Rossetti Claudio , Kalogjera Livije , Peršec Jasminka , Ollivere Luke , Ollivere Benjamin J. , Yan Huadong , Cai Ting , Aithal Guruprasad P. , Steves Claire J. , Kantele Anu , Kajova Mikael , Vapalahti Olli , Sajantila Antti , Wojtowicz Rafal , Wierzba Waldemar , Krol Zbigniew , Zaczynski Artur , Zycinska Katarina , Postula Marek , Lukšić Ivica , Čivljak Rok , Markotić Alemka , Brachmann Johannes , Markl Andreas , Mahnkopf Christian , Murray Benjamin , Ourselin Sebastien , Valdes Ana M. , Horcajada Juan P. , Castells Xavier , Pascual Julio , Allegri Massimo , Primorac Dragan , Spector Tim D. , Barrios Clara , Lauc Gordan
Published: January 2021

Background:Most respiratory viruses show pronounced seasonality, but for SARS-CoV-2, this still needs to be documented.

Methods:We examined the disease progression of COVID-19 in 6,914 patients admitted to hospitals in Europe and China. In addition, we evaluated progress of disease symptoms in 37,187 individuals reporting symptoms into the COVID Symptom Study application.

Findings:Meta-analysis of the mortality risk in seven European hospitals estimated odds ratios per 1-day increase in the admission date to be 0.981 (0.973–0.988,p< 0.001) and per increase in ambient temperature of 1°C to be 0.854 (0.773–0.944,p= 0.007). Statistically significant decreases of comparable magnitude in median hospital stay, probability of transfer to the intensive care unit, and need for mechanical ventilation were also observed in most, but not all hospitals. The analysis of individually reported symptoms of 37,187 individuals in the UK also showed the decrease in symptom duration and disease severity with time.

Interpretation:Severity of COVID-19 in Europe decreased significantly between March and May and the seasonality of COVID-19 is the most likely explanation.
Genetic Diversity, Biochemical Properties, and Detection Methods of Minor Carbapenemases in Enterobacterales
Authors: Bonnin Rémy A. , Jousset Agnès B. , Emeraud Cécile , Oueslati Saoussen , Dortet Laurent , Naas Thierry
Published: January 2021

Gram-negative bacteria, especially Enterobacterales, have emerged as major players in antimicrobial resistance worldwide. Resistance may affect all major classes of anti-gram-negative agents, becoming multidrug resistant or even pan-drug resistant. Currently, β-lactamase-mediated resistance does not spare even the most powerful β-lactams (carbapenems), whose activity is challenged by carbapenemases. The dissemination of carbapenemases-encoding genes among Enterobacterales is a matter of concern, given the importance of carbapenems to treat nosocomial infections. Based on their amino acid sequences, carbapenemases are grouped into three major classes. Classes A and D use an active-site serine to catalyze hydrolysis, while class B (MBLs) require one or two zinc ions for their activity. The most important and clinically relevant carbapenemases are KPC, IMP/VIM/NDM, and OXA-48. However, several carbapenemases belonging to the different classes are less frequently detected. They correspond to class A (SME-, Nmc-A/IMI-, SFC-, GES-, BIC-like…), to class B (GIM, TMB, LMB…), class C (CMY-10 and ACT-28), and to class D (OXA-372). This review will address the genetic diversity, biochemical properties, and detection methods of minor acquired carbapenemases in Enterobacterales.
A Novel Bipolar Polypectomy Snare Can Be an Alternative Choice for Endoscopic Resection
Authors: Chen Shengsen , Zhou Danping , Ruan Rongwei , Yu Jiangping , Li Yandong , Liu Yuanshun , Wang Shi
Published: January 2021

Objective:Endoscopic resection (ER) is more difficult and has a higher rate of complications, such as perforation and bleeding. The aim of this study was to evaluate the safety and feasibility of a bipolar polypectomy snare for ER.

Methods:Initial ER procedures in live pigs were carried out. Then, a human feasibility study was performed in patients with colorectal polyps. Finally, the finite element method was used to evaluate the safety and effectiveness of the new bipolar snare.

Results:In the live animal model, there were no significant differences in wound size and cutting time between monopolar and bipolar groups. The histological results (histological scores) of the two groups in porcine experiments were almost the same except that the incision flatness of bipolar group was better than that of the monopolar group. Incidence of bleeding and perforation was similar between the two groups in pigs' and patients' study. At last, the finite element model showed that the vertical thermal damage depth produced by bipolar snare system was approximately 71–76% of that produced by monopolar snare system at the same power.

Conclusions:The novel bipolar snare is feasible in patients with colorectal polyps and can be an alternative choice for ERs.