bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic, ventilatory and cardiovascular responses to FES-cycling: A comparison to NMES and passive cycling
Authors: Frazão Murillo , Werlang Luis Augusto , Azevedo Cássio , Kunz Adelar , Peltz Maikel
Published: November 2021

BACKGROUND: Cyclergometry with functional electrical stimulation (FES-cycling) is a feasible method for rehabilitation. The concept is to promote exercise induced by depolarization of the motoneuron and muscular contraction. OBJECTIVE: To measure acute physiological responses to FES-cycling. METHODS: Retrospective study of data from ten healthy volunteers who performed FES-cycling, passive cycling and neuromuscular electrical stimulation (NMES) alone. Metabolic, ventilatory and cardiovascular parameters were analyzed. RESULTS: Oxygen uptake enhanced 97 ± 15% during FES-cycling, with medium effect size compared to NMES and large effect size compared to passive cycling. Energy expenditure enhanced 102 ± 15% during FES-cycling, with medium effect size compared to NMES and large effect size compared to passive cycling. Minute ventilation enhanced 115 ± 26% during FES-cycling, with small effect size compared to NMES and medium effect size compared to passive cycling. Cardiac output enhanced 21 ± 4% during FES-cycling, with medium effect size compared to NMES and passive cycling. Arterial – mixed venous oxygen content difference enhanced 60 ± 8% during FES-cycling, with a medium effect size compared to NMES and large effect size compared to passive cycling. CONCLUSIONS: FES-cycling enhances metabolic, ventilatory and cardiovascular demands and the physiological responses are higher than NMES and passive cycling.
Letalidad por sepsis neonatal, factores de riesgo y características microbiológicas
Authors: López u. Oscar J. , Buriticá H. Héctor M.
Published: November 2021

La sepsis neonatal es una de las principales causas de muerte en esta población y está relacionada con factores gestacionales y perinatales además de características inherentes al recién nacido.Objetivo: Relacionar factores perinatales, neonatales y microbiológicos con letalidad por sepsis.Pacientes y Método: Estudio retrospectivo de casos y controles de recién nacidos hospitalizados con sepsis neonatal confirmada por hemocultivos, desde el 2013 al 2019; los casos fueron definidos como aquellos pacientes con sepsis confirmada que presentaron desenlace mortal y los controles fueron aquellos neonatos con sepsis confirmada sin desenlace fatal. Se compararon los casos y los controles respecto a factores maternos, perinatales, neonatales y microbiológicos para variables cuantitativas, y así identificar la tendencia y la concentración de las variables estudiadas.Resultados: Se identificaron 11 casos y se asignaron aleatoriamente 3 controles por cada caso, estratificados por grupos de edad gestacional. Las medianas de peso al nacer y edad gestaciónal fueron 1.004 g y 28 semanas respectivamente. Se aisló Escherichia coli en un 21%, Candida parapsilosis en 16% y Staphylococcus aureus en 14%. Se encontró asociación estadísticamente significativa entre vía de parto vaginal (P = 0,023), infección antes de 7 días de vida (P = 0,025) y fungemia por Candida parapsilosis (P = 0,049) con letalidad por sepsis. El análisis multivariado determinó asociación estadísticamente significativa entre letalidad por sepsis neonatal con vía del parto vaginal y aislamiento microbiológico de Candida parapsilosis.Conclusión: La letalidad por sepsis neonatal se presentó más en el grupo de prematuros extremos y se identificaron, el antecedente de parto vaginal, aislamiento microbiológico temprano y la infección por Candida parapsilosis como las principales variables asociadas con desenlace mortal.
Manajemen Strategi : Kajian Teori Resource Based View
Authors: Elya Dasuki Rima
Published: November 2021

This paper aims to analyze the framework of the Resource-Based View theory put forward by experts in strategic management, as well as to describe the SWOT framework, especially those related to strengths and weaknesses by identifying what are the strengths and capabilities of the company and avoiding weaknesses for competitive advantage. and is expected to be able to describe the concept of Resource-Based View and analyze the development of Resource-Based View theory in strategic management, and analyze the internal environment from the point of view of strengths and weaknesses that will help the company to be able to take advantage of existing opportunities and be able to avoid possible threats. arise, and analyze the company's capabilities that will affect the final product which includes dynamic skills, capacities, and resources. The research method used is based on a historical approach and literature review from the opinions of experts who discuss the theory of Resource-Based Value, both physical and non-physical in relation to capabilities and competencies in creating superior competitiveness, with the main study based on the opinion of strategic management experts. Mahoney Joseph T, J. Rajendran Pandian, 1992. This paper will be directed to the analysis of various opinions of economists regarding the resource framework that will produce a capability, namely the skills that exist in each individual. competitive of a company
An Active Fraction of Trillium tschonoskii Promotes the Regeneration of Intestinal Epithelial Cells After Irradiation
Authors: Song Feiling , Wang Sihan , Pang Xu , Fan Zeng , Zhang Jie , Chen Xiaojuan , He Lijuan , Ma Baiping , Pei Xuetao , Li Yanhua
Published: November 2021

Despite significant scientific advances toward the development of safe and effective radiation countermeasures, no drug has been approved for use in the clinic for prevention or treatment of radiation-induced acute gastrointestinal syndrome (AGS). Thus, there is an urgent need to develop potential drugs to accelerate the repair of injured intestinal tissue. In this study, we investigated that whether some fractions of Traditional Chinese Medicine (TCM) have the ability to regulate intestinal crypt cell proliferation and promotes crypt regeneration after radiation. By screening the different supplements from a TCM library, we found that an active fraction of the rhizomes of Trillium tschonoskii Maxim (TT), TT-2, strongly increased the colony-forming ability of irradiated rat intestinal epithelial cell line 6 (IEC-6) cells. TT-2 significantly promoted the proliferation and inhibited the apoptosis of irradiated IEC-6 cells. Furthermore, in a small intestinal organoid radiation model, TT-2 promoted irradiated intestinal organoid growth and increased Lgr5+ intestinal stem cell (ICS) numbers. More importantly, the oral administration of TT-2 remarkably enhanced intestinal crypt cell proliferation and promoted the repair of the intestinal epithelium of mice after abdominal irradiation (ABI). Mechanistically, TT-2 remarkably activated the expression of ICS-associated and proliferation-promoting genes and inhibited apoptosis-related gene expression. Our data indicate that active fraction of TT can be developed into a potential oral drug for improving the regeneration and repair of intestinal epithelia that have intestinal radiation damage.
High-Resolution 3D Reconstruction of Human Oocytes Using Focused Ion Beam Scanning Electron Microscopy
Authors: Trebichalská Zuzana , Javůrek Jakub , Tatíčková Martina , Kyjovská Drahomíra , Kloudová Soňa , Otevřel Pavel , Hampl Aleš , Holubcová Zuzana
Published: November 2021

The egg plays a pivotal role in the reproduction of our species. Nevertheless, its fundamental biology remains elusive. Transmission electron microscopy is traditionally used to inspect the ultrastructure of female gametes. However, two-dimensional micrographs contain only fragmentary information about the spatial organization of the complex oocyte cytoplasm. Here, we employed the Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) to explore human oocyte intracellular morphology in three dimensions (3D). Volume reconstruction of generated image stacks provided an unprecedented view of ooplasmic architecture. Organelle distribution patterns observed in nine donor oocytes, representing three maturational stages, documented structural changes underlying the process by which the egg acquires developmental competence. 3D image segmentation was performed to extract information about distinct organelle populations, and the following quantitative analysis revealed that the mitochondrion occupies ∼ 4.26% of the maturing oocyte cytoplasm. In summary, this proof-of-concept study demonstrates the potential of large volume electron microscopy to study rare samples of delicate female gametes and paves the way for applying the FIB-SEM technique in human oocyte research.
Challenges and Perspective of Recent Biomass Pretreatment Solvents
Authors: Kim Kwang Ho , Yoo Chang Geun
Published: November 2021

The increased demands on renewable and sustainable products require enhancing the current conversion efficiency and expanding the utilization of biomass from a single component (i.e., cellulose) to entire biomass components in the biorefinery concept. Pretreatment solvent plays a critical role in various biorefinery processes. Recent pretreatment solvents such as organic co-solvents, acid hydrotropes, ionic liquids and deep eutectic solvents showed effective biomass fractionation as well as preservation of high-quality cellulose and lignin under mild conditions. Despite these significant enhancements in biomass pretreatment solvent, there are still many challenges, such as feedstock variety, valorization of non-cellulose components, and eco-friendliness of the applied catalyst and solvent. These technical, economic and environmental obstacles should be considered in future biomass pretreatment solvents. In particular, the development of feedstock-agnostic solvent with high fractionation performance for high quality and quantity of all three major components (i.e., cellulose, hemicellulose, and lignin) together would be an ideal direction.
Impact of Nanoparticle Consolidation on Charge Separation Efficiency in Anatase TiO2 Films
Authors: Rettenmaier Karin , Berger Thomas
Published: November 2021

Mesoporous films and electrodes were prepared from aqueous slurries of isolated anatase TiO2 nanoparticles. The resulting layers were annealed in air at temperatures 100°C ≤ T ≤ 450°C upon preservation of internal surface area, crystallite size and particle size. The impact of processing temperature on charge separation efficiency in nanoparticle electrodes was tracked via photocurrent measurements in the presence of methanol as a hole acceptor. Thermal annealing leads to an increase of the saturated photocurrent and thus of the charge separation efficiency at positive potentials. Furthermore, a shift of capacitive peaks in the cyclic voltammograms of the nanoparticle electrodes points to the modification of the energy of deep traps. Population of these traps triggers recombination possibly due to the action of local electrostatic fields attracting photogenerated holes. Consequently, photocurrents saturate at potentials, at which deep traps are mostly depopulated. Charge separation efficiency was furthermore investigated for nanoparticle films and was tracked via the decomposition of hydrogen peroxide. Our observations evidence an increase of charge separation efficiency upon thermal annealing. The effect of particle consolidation, which we associate with minute atomic rearrangements at particle/particle contacts, is attributed to the energetic modification of deep traps and corresponding modifications of charge transport and recombination, respectively.
First Case of Subcutaneous Mycoses Caused by Dirkmeia churashimaensis and a Literature Review of Human Ustilaginales Infections
Authors: Hu Fengming , Wang Chong , Wang Peng , Zhang Lei , Jiang Qing , Al-Hatmi Abdullah M. S. , Blechert Oliver , Zhan Ping
Published: November 2021

Objective

Dirkmeia churashimaensis, belonging to Ustilaginales fungi, has never been reported as clinical pathogenic until very recently. In this study, we report an unusual subcutaneous infection with Dirkmeia churashimaensis and reviewed all human Ustilaginales infections. The aim is to better understand their epidemiology, infection type, risk factors, and the sensitivity to antifungal agents.

Methods

An 80-year-old female farmer developed extensive plaques and nodules on her left arm within 2 years. Pathological and microbiological examinations identified a new pathological agent, Dirkmeia churashimaensis, as the cause of this infection. The patient was successfully cured by oral itraconazole. We reviewed a total of 31 cases of Ustilaginales cases, among of which only three were skin infections.

Results

Local barrier damage (i.e., surgery, trauma, and basic dermatosis) and systemic immunodeficiency (i.e., preterm and low birthweight, Crohn’s disease, malignant cancer, and chemotherapy) are risk factors for Ustilaginales infection. The D1/D2 and ITS regions are the frequently used loci for identifying the pathogens together with phenotype. Most patients could survive due to antifungal treatment, whereas seven patients died. Amphotericin B, posaconazole, itraconazole, and voriconazole showed good activity against these reported strains, whereas fluconazole, 5-flucytosine, and echinocandins usually showed low susceptibility. Itraconazole had good efficiency for subcutaneous infections.

Conclusions

The present case study and literature review reveal that Ustilaginales can be opportunistic pathogenic normally in immunocompromised and barrier damage people. A proper identification of fungi can be crucial for clinical treatment, and more data of antifungal are needed for choice of medication against this kind of infections.
Circulating Monocyte Subsets Are Associated With Extent of Myocardial Injury but Not With Type of Myocardial Infarction
Authors: Askari Noushin , Lipps Christoph , Voss Sandra , Staubach Nora , Grün Dimitri , Klingenberg Roland , von Jeinsen Beatrice , Wolter Jan Sebastian , Kriechbaum Steffen , Dörr Oliver , Nef Holger , Liebetrau Christoph , Hamm Christian W. , Keller Till
Published: November 2021

Inflammation is a hallmark of the period after a myocardial infarction (MI) that is either promoted or resolved by distinct subtypes of circulating inflammatory cells. The three main monocyte subpopulations play different roles inflammation. This study examined whether the type of MI (type 1 or type 2) or the extent of myocardial injury is associated with differences in monocyte subpopulations. For this purpose, peripheral whole blood from patients with a suspected MI was used for flow cytometric measurements of the monocyte subpopulations, and myocardial injury was classified by cardiac troponin levels in serum. In patients with acute coronary syndrome (n = 82, 62.2% male) similar proportions of the monocyte subsets were associated with the two types of MI, whereas total monocyte counts were increased in patients with substantial myocardial injury vs. those with minor injury (p = 0.045). This was accompanied by a higher proportion of intermediate (p = 0.045) and classical monocytes (p = 0.059); no difference was found for non-classical monocytes (p = 0.772). In patients with chronic coronary syndrome (n = 144, 66.5% male), an independent association with myocardial injury was also observed for classical monocytes (p = 0.01) and intermediate monocytes (p = 0.08). In conclusion, changes in monocyte subpopulation counts, particularly for classical and intermediate monocytes, were related to the extent of myocardial injury in acute and stable coronary artery disease but not to the type of MI.
The Effects of Moderate Alcohol Consumption on Circulating Metabolites and Gut Microbiota in Patients With Coronary Artery Disease
Authors: Zhao Xinyue , Zhou Ruilin , Li Hanyu , Fan Yue , Sun Yueshen , Hu Xiaomin , Zhang Shuyang
Published: November 2021

Background: Epidemiological studies confirmed that moderate alcohol consumption was associated with a reduced risk of adverse cardiovascular events. It is increasingly recognized that the composition of gut microbiota and metabolites is involved in modulating the cardiovascular health of the host. However, the association of moderate alcohol consumption with serum metabolites and gut microbiome and its impact on coronary artery disease (CAD) is not fully investigated.

Method: Serum untargeted metabolomics analysis and fecal 16S rRNA sequencing were performed on 72 male patients with CAD having various alcohol consumption (36 non-drinkers, 18 moderate drinkers, and 18 heavy drinkers) and 17 matched healthy controls. MetaboAnalyst and PICRUSt2 were utilized to analyze the possible involved metabolic pathways. Multi-omics analysis was achieved by Spearman correlation to reveal the interactions of alcohol consumption with gut microbiome and serum metabolites in patients with CAD.

Results: We noted distinct differences between patients with CAD, with varying levels of alcohol consumption and healthy controls in aspects of serum metabolome and the gut microbiome. Moderate alcohol consumption significantly changed the lipidomic profiles, including reductions of sphingolipids and glycerophospholipids in moderate drinkers with CAD when compared with non and heavy drinkers with CAD. Moreover, we also found the reduction of microbial-derived metabolites in moderate drinkers with CAD, such as 2-phenylacetamide and mevalonic acid. To be noted, the gut microbiota of moderate drinkers with CAD tended to resemble that of healthy controls. Compared with non-drinkers, the relative abundance of genus Paraprevotella, Lysinibacillus was significantly elevated in moderate drinkers with CAD, while the genus Bifidobacterium, Megasphaera, and Streptococcus were significantly reduced in moderate drinkers with CAD. Multi-omics analysis revealed that specific metabolites and microbes associated with moderate alcohol consumption were correlated with the severity of CAD.

Conclusions: Our study revealed that the impact of moderate alcohol consumption on serum metabolites and gut microbiota in patients with CAD seemed to be separated from that of heavy and non-alcohol consumption. Moderate drinking tended to have more positive effects on metabolic profiles and commensal flora, which may explain its beneficial effects on cardiovascular health. Overall, our study provides a novel insight into the effects of moderate alcohol consumption in patients with CAD.
The TsuJal Amphibious Seismic Network: A Passive-Source Seismic Experiment in Western Mexico
Authors: Núñez-Cornú Francisco Javier , Córdoba Barba Diego , Bandy William , Dañobeitia Juan José , Alarcón Salazar José Edgar , Núñez Diana , Suárez Plascencia Carlos
Published: November 2021

The geodynamic complexity in the western Mexican margin is controlled by the multiple interactions between the Rivera, Pacific, Cocos, and North American plates, as evidenced by a high seismicity rate, most of whose hypocenters are poorly located. To mitigate this uncertainty with the aim of improving these hypocentral locations, we undertook the TsuJal Project, a passive seafloor seismic project conducted from April to November 2016. In addition to the Jalisco Seismic Network, 10 LCHEAPO 2000 Ocean Bottom Seismometers (OBSs) were deployed by the BO El Puma in a seafloor array from the Islas Marías Archipelago (Nayarit) to the offshore contact between the states of Colima and Michoacan. We located 445 earthquakes in four or more OBSs within the deployed array. Most of these earthquakes occurred in the contact region of the Rivera, Pacific, and Cocos plates, and a first analysis suggests the existence of three seismogenic zones (West, Center, and East) along the Rivera Transform fault that can be correlated with its morphological expression throughout the three seismogenic zones. The seismicity estimates that the Moho discontinuity is located at 10 km depth and supports earlier works regarding the West zone earthquake distribution. Subcrustal seismicity in the Central zone suggests that the Intra-Transform Spreading Basin domain is an ultra-low spreading ridge. A seismic swarm occurred during May and June 2016 between the eastern tip of the Paleo-Rivera Transform fault and the northern tip of the East Pacific Rise-Pacific Cocos Segment, illuminating some unidentified tectonic feature.
CO2 Adsorption and Desorption by Waste Ion-Exchange Resin–Based Activated Carbon on Fixed Bed
Authors: Wei Mengqi , Zhao Qiuyue
Published: November 2021

The waste ion-exchange resin–based activated carbon (WIRAC) was utilized for CO2 adsorption. The effect of adsorption temperature, gas flow, CO2 concentration, and adsorbent filling content on CO2 adsorption properties of WIRAC and the effect of desorption temperature and sweep gas flow on CO2 desorption performances of WIRAC were researched. In the adsorption process, with the increase of adsorption temperature, the CO2 adsorption capacity and adsorption rate decrease; as the gas flow increases, the CO2 adsorption capacity decreases, but the adsorption rate increases; with the increase of CO2 concentration and adsorbent filling content, the CO2 adsorption capacity and adsorption rate both increase. In the desorption process, the higher the desorption temperature and the smaller the sweep gas flow, the higher the CO2 purity of product gas and the longer the desorption time. In order to make sure the adsorbent be used efficiently and the higher CO2 concentration of product gas, the adsorption and desorption conditions selected should be a suitable choice.
Identification of Wolf-Dog Hybrids in Europe – An Overview of Genetic Studies
Authors: Dziech Arkadiusz
Published: November 2021

Significant development of genetic tools during the last decades provided opportunities for more detailed analyses and deeper understanding of species hybridization. New genetic markers allowed for reliable identification of admixed individuals deriving from recent hybridization events (a few generations) and those originating from crossings up to 19 generations back. Implementation of microsatellites (STRs) together with Bayesian clustering provided abundant knowledge regarding presence of admixed individuals in numerous populations and helped understand the problematic nature of studying hybridization (i.a., defining a reliable thresholds for recognizing individuals as admixed or obtaining well-grounded results representing actual proportion of hybrids in a population). Nevertheless, their utilization is limited to recent crossbreeding events. Single Nucleotide Polymorphisms (SNPs) proved to be more sensible tools for admixture analyses furnishing more reliable knowledge, especially for older generation backcrosses. Small sets of Ancestry Informative Markers (AIMs) of both types of markers were effective enough to implement in monitoring programs, however, SNPs seem to be more appropriate because of their ability to identify admixed individuals up to 3rd generations. The main aim of this review is to summarize abundant knowledge regarding identification of wolf-dog hybrids in Europe and discuss the most relevant problems relating to the issue, together with advantages and disadvantages of implemented markers and approaches.
Associations Between the Purinergic Receptor P2X7 and Leprosy Disease
Authors: Souza Rebeka da Conceição , Louvain de Souza Thaís , Ferreira Cristina dos Santos , Nascimento Letícia Silva , Nahn Edilbert Pellegrini , Peixoto-Rangel Alba Lucínia
Published: November 2021

Leprosy is an infectious disease still highly prevalent in Brazil, having been detected around 27,863 new cases in 2019. Exposure to Mycobacterium leprae may not be sufficient to trigger the disease, which seems to be influenced by host immunogenetics to determine resistance or susceptibility. The purinergic receptor P2X7 plays a crucial role in immunity, inflammation, neurological function, bone homeostasis, and neoplasia and is associated with several infectious and non-infectious diseases. Here, we first compare the P2RX7 expression in RNA-seq experiments from 16 leprosy cases and 16 healthy controls to establish the magnitude of allele-specific expression for single-nucleotide polymorphisms of the gene P2RX7 and to determine the level of gene expression in healthy and diseased skin. In addition, we also evaluated the association of two P2RX7 single-nucleotide polymorphisms (c.1513A>C/rs3751143 and c.1068A>G/rs1718119) with leprosy risk. The expression of P2RX7 was found significantly upregulated at macrophage cells from leprosy patients compared with healthy controls, mainly in macrophages from lepromatous patients. Significant risk for leprosy disease was associated with loss function of rs3751143 homozygous mutant CC [CC vs. AA: p = 0.001; odds ratio (OR) = 1.676, 95% CI = 1.251–2.247] but not with heterozygous AC (AC vs. AA: p = 0.001; OR = 1.429, 95% CI = 1.260–1.621). Contrary, the polymorphic A allele from the gain function of rs1718119 was associated with protection for the development of leprosy, as observed in the dominant model (AA + AG × GG p = 0.0028; OR = 0.03516; CI = 0.1801–0.6864). So, our results suggest that the functional P2X7 purinergic receptor may exert a key role in the Mycobacterium death inside macrophages and inflammatory response, which is necessary to control the disease.
USH2A Mutation is Associated With Tumor Mutation Burden and Antitumor Immunity in Patients With Colon Adenocarcinoma
Authors: Sun Yuanyuan , Li Long , Yao Wenchao , Liu Xuxu , Yang Yang , Ma Biao , Xue Dongbo
Published: November 2021

Colon adenocarcinoma (COAD) is one of the diseases with the highest morbidity and mortality in the world. At present, immunotherapy has become a valuable method for the treatment of COAD. Tumor mutational burden (TMB) is considered to be the most common biomarker for predicting immunotherapy. According to reports, the mutation rate of COAD ranks third. However, whether these gene mutations are related to TMB and immune response is still unknown. Here, COAD somatic mutation data were downloaded from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Bioinformatics methods were used to study the relationships among gene mutations, COAD survival prognosis, and tumor immune response. A total of 22 of the top 40 mutations in TCGA and ICGC databases were the same. Among them, the USH2A mutation was associated with high TMB and poor clinical prognosis. According to Gene Set Enrichment Analysis (GSEA) and the CIBERSORT algorithm, we determined that the USH2A mutation upregulates signaling pathways involved in the immune system and the antitumor immune response. In cases with a USH2A mutation, the immune score and MSI score of TCGA samples increased, the expression of immune checkpoint genes decreased significantly, and the TIDE score decreased significantly. Dependent on the presence or absence of a USH2A mutation, TCGA COAD samples were analyzed for differentially expressed genes, 522 of which were identified. Using a univariate Cox analysis and LASSO COX analysis of these differential genes, a prediction model was established, which established significant differences in the infiltration of immune cells, immune checkpoint gene expression, immune score, MSI score, TMB, and TIDE in patients in high- and low-risk groups. In conclusion, mutation of USH2A is frequent in COAD and is related to an increase in TMB and the antitumor immunity. The differential genes screened by USH2A mutation allowed the construction of a risk model for predicting the survival and prognosis of cancer patients, in addition to providing new ideas for COAD immunotherapy.
High Larval Concentrations and Onshore Transport of Barnacle Cyprids Associated With Thermal Stratification
Authors: Yamhure Gabriela M. , Reyns Nathalie , Pineda Jesús
Published: November 2021

To better understand the hydrodynamic and hydrographic conditions experienced by larvae in the nearshore (within 1 km of shore), and the role that larval behavior plays in mediating shoreward transport to adult benthic habitats, we examined the vertical distribution and concentration of barnacle cyprids in a shallow, nearshore region in southern California, United States. We collected high-resolution physical measurements of currents and temperature at 3 stations (8, 5, and 4 m depths), and high-frequency measurements of barnacle larvae at a 4 m deep station ∼300 m from shore. Larvae were sampled from distinct 1 m depth intervals between the surface and the bottom (0–1 m, 1–2 m, 2–3 m, 3 m-bottom), each hour for overnight periods that ranged between 13 to 24 h in five cruises during the summers of 2017 and 2018. Barnacle cyprids of Chthamalus fissus predominated in all samples. Thermal stratification decreased closer to shore, but when the nearshore-most station remained stratified (Δ°C m–1 ≥ 0.1), C. fissus cyprid concentrations were high to extremely abundant (exceeding 200 and 4,000 individuals m–3, respectively). There were significant positive correlations between thermal stratification and the log-transformed C. fissus concentration at cruise-to-cruise scales, and between stratification and vertical variability in the high-frequency cross-shore currents at 2-day scales. Additionally, estimated larval transport was relatively high and shoreward when nearshore thermal stratification was greatest. Significant, albeit small, diel differences in cyprid distributions were also observed, with the proportion of cyprids increasing near the surface at night, and concentrations greater during the day than at night. Collectively, these results suggest that thermal stratification increases larval supply to the nearshore, and may enhance onshore larval transport to augment chances of successful settlement and recruitment to the intertidal adult habitat.
Ontogenetic δ15N Trends and Multidecadal Variability in Shells of the Bivalve Mollusk, Arctica islandica
Authors: Schöne Bernd R. , Huang Qian
Published: November 2021

Bulk stable nitrogen isotope values of the carbonate-bound organic matrix in bivalve shells (δ15NCBOM) are increasingly used to assess past food web dynamics, track anthropogenic nitrogen pollution and reconstruct hydrographic changes. However, it remains unresolved if the δ15NCBOM values are also affected by directed ontogenetic trends which can bias ecological and environmental interpretations. This very aspect is tested here with modern and fossil specimens of the long-lived ocean quahog, Arctica islandica, collected from different sites and water depths in the NE Atlantic Ocean. As demonstrated, δ15NCBOM values from the long chronologies show a general decrease through lifetime by −0.006‰ per year. The most likely reason for the observed δ15NCBOM decline is a change in the type of proteins synthesized at different stages of life, i.e., a gradual shift from proteins rich in strongly fractionating, trophic amino acids during youth toward proteins rich in source amino acids during adulthood. Aside from this ontogenetic trend, distinct seasonal to multidecadal δ15NCBOM variations (ca. 50 to 60 years; up to 2.90‰) were identified. Presumably, the latter were governed by fluctuations in nutrient supply mediated by the Atlantic Multidecadal Variation (AMV) and Atlantic Meridional Overturning Circulation (AMOC) combined with changes in nitrate utilization by photoautotrophs and associated Rayleigh fractionation processes. Findings underline the outstanding potential of bivalve shells in studies of trophic ecology, oceanography and pollution, but also highlight the need for compound-specific isotope analyses.
Novel Targets for Drug Use in Eosinophilic Granulomatosis With Polyangiitis
Authors: Uzzo Martina , Regola Francesca , Trezzi Barbara , Toniati Paola , Franceschini Franco , Sinico Renato Alberto
Published: November 2021

Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare autoimmune disease characterized by medium and small vessels inflammation. Cardiac vasculitic involvement is one of the most severe manifestations with a significant impact on patients' long-term prognosis: anyway, a specific therapeutic approach for heart involvement in EGPA has not been explored yet. Current regimen consists of a long-term therapy with high dose of glucocorticoids, causing the well-known related-adverse events; immunosuppressive drugs are used in patients with severe manifestations, with some limitations. New therapeutic approaches are needed for patients with refractory disease or contraindications to conventional therapies. The quest for the ideal therapy is going toward a more and more personalized approach: on the one hand, efforts are made to use already existing therapies in the most appropriate way; on the other hand, new insights into EGPA pathogenesis allow the discovery of new targets, as demonstrated by mepolizumab and rituximab, targeting eosinophils, and B-cell compartments. This review summarizes the emerging therapies used in EGPA, focusing on the most recent studies on biologics and analyzing their efficacy and safety.
pH Stress Mediated Alteration in Protein Composition and Reduction in Cytotoxic Potential of Gardnerella vaginalis Membrane Vesicles
Authors: Shishpal Parul , Patel Vainav , Singh Dipty , Bhor Vikrant M.
Published: November 2021

The vagina of healthy women is predominantly colonized by lactobacilli but it also harbors a limited proportion of certain anaerobes such as Gardnerella vaginalis. An increase in G. vaginalis along with other anaerobes on account of perturbation in the vaginal microbiota is associated with bacterial vaginosis (BV). Although strategies adopted by G. vaginalis for survival and pathogenesis in a conducive environment (i.e., high vaginal pH, characteristic of BV) have been previously studied, the approaches potentially employed for adaptation to the low pH of the healthy vagina are unknown. In the present study, we investigated the effect of acidic stress on the modulation of the production and function of membrane vesicles (MVs) of G. vaginalis. pH stress led to a distortion of the bacterial cell morphology as well as an altered biogenesis of MVs, as revealed by transmission electron microscopy (TEM). Both qualitative and quantitative differences in protein content of MVs produced in response to pH stress were observed by flow cytometry. A significant change in the protein composition characterized by presence of chaperones despite a reduction in number of proteins was also noted in the stress induced MVs. Further, these changes were also reflected in the reduced cytotoxic potential toward vaginal epithelial cells. Although, these findings need to be validated in the in vivo settings, the modulation of G. vaginalis MV biogenesis, composition and function appears to reflect the exposure to acidic conditions prevailing in the host vaginal mileu in the absence of vaginal infection.
Top-Down Enrichment Strategy to Co-cultivate Lactic Acid and Lignocellulolytic Bacteria From the Megathyrsus maximus Phyllosphere
Authors: Díaz-García Laura , Chaparro Dayanne , Jiménez Hugo , Gómez-Ramírez Luis Fernando , Bernal Adriana J. , Burbano-Erazo Esteban , Jiménez Diego Javier
Published: November 2021

Traditionally, starting inoculants have been applied to improve ensiling of forage used for livestock feed. Here, we aimed to build up a bioinoculant composed of lactic acid-producing and lignocellulolytic bacteria (LB) derived from the Megathyrsus maximus (guinea grass) phyllosphere. For this, the dilution-to-stimulation approach was used, including a sequential modification of the starting culture medium [Man, Rogosa, and Sharpe (MRS) broth] by addition of plant biomass (PB) and elimination of labile carbon sources. Along 10 growth-dilution steps (T1–T10), slight differences were observed in terms of bacterial diversity and composition. After the sixth subculture, the consortium started to degrade PB, decreasing its growth rate. The co-existence of Enterobacteriales (fast growers and highly abundance), Actinomycetales, Bacillales, and Lactobacillales species was observed at the end of the selection process. However, a significant structural change was noticed when the mixed consortium was cultivated in higher volume (500ml) for 8days, mainly increasing the proportion of Paenibacillaceae populations. Interestingly, Actinomycetales, Bacillales, and Lactobacillales respond positively to a pH decrease (4–5), suggesting a relevant role within a further silage process. Moreover, gene-centric metagenomic analysis showed an increase of (hemi)cellulose-degrading enzymes (HDEs) during the enrichment strategy. Reconstruction of metagenome-assembled genomes (MAGs) revealed that Paenibacillus, Cellulosimicrobium, and Sphingomonas appear as key (hemi)cellulolytic members (harboring endo-glucanases/xylanases, arabinofuranosidases, and esterases), whereas Enterococcus and Cellulosimicrobium have the potential to degrade oligosaccharides, metabolize xylose and might produce lactic acid through the phosphoketolase (PK) pathway. Based on this evidence, we conclude that our innovative top-down strategy enriched a unique bacterial consortium that could be useful in biotechnological applications, including the development/design of a synthetic bioinoculant to improve silage processes.
Dextran Sulfate Sodium Salt-Induced Colitis Aggravates Gut Microbiota Dysbiosis and Liver Injury in Mice With Non-alcoholic Steatohepatitis
Authors: Shen Bo , Wang Junjun , Guo Yuecheng , Gu Tianyi , Shen Zhenyang , Zhou Cui , Li Binghang , Xu Xianjun , Li Fei , Zhang Qidi , Cai Xiaobo , Dong Hui , Lu Lungen
Published: November 2021

Objective: Inflammatory bowel disease (IBD) is characterized by gut microbiota dysbiosis, which is also frequently observed in patients with non-alcoholic fatty liver disease. Whether gut microbiota dysbiosis in IBD patients promotes the development of non-alcoholic steatohepatitis (NASH) remains unclear. We aimed to explore the role of gut microbiota dysbiosis in the development of NASH in mice with dextran sulfate sodium salt (DSS) induced colitis.

Design: Dextran sulfate sodium salt was used to induce colitis, and high fat (HF), in combination with a high-fructose diet, was used to induce NASH in C57BL/6J male mice. Mice were treated with (1%) DSS to induce colitis in cycles, and each cycle consisted of 7 days of DSS administration followed by a 10-day interval. The cycles were repeated throughout the experimental period of 19 weeks. Pathological alterations in colitis and NASH were validated by hematoxylin and eosin (H&E), oil red O, Sirius red staining, and immunofluorescence. Gut microbiota was examined by 16S rRNA sequencing, and gene expression profiles of hepatic non-parenchymal cells (NPCs) were detected by RNA sequencing.

Results: Dextran sulfate sodium salt administration enhanced the disruption of the gut–vascular barrier and aggravated hepatic inflammation and fibrosis in mice with NASH. DSS-induced colitis was accompanied by gut microbiota dysbiosis, characterized by alteration in the core microbiota composition. Compared with the HF group, the abundance of p_Proteobacteria and g_Bacteroides increased, while that of f_S24-7 decreased in the DSS + HF mice. Specifically, gut microbiota dysbiosis was characterized by enrichment of lipopolysaccharide producing bacteria and decreased abundance of short-chain fatty acid-producing bacteria. Gene expression analysis of liver NPCs indicated that compared with the HF group, genes related to both inflammatory response and angiocrine signaling were altered in the DSS + HF group. The expression levels of inflammation-related and vascular development genes correlated significantly with the abundance of p_Proteobacteria, g_Bacteroides, or f_S24-7 in the gut microbiota, implying that gut microbiota dysbiosis induced by DSS might aggravate hepatic inflammation and fibrosis by altering the gene expression in NPCs.

Conclusion: Dextran sulfate sodium salt-induced colitis may promote the progression of liver inflammation and fibrosis by inducing microbiota dysbiosis, which triggers an inflammatory response and disrupts angiocrine signaling in liver NPCs. The abundance of gut microbiota was associated with expression levels of inflammation-related genes in liver NPCs and may serve as a potential marker for the progression of NASH.
Integrative Analysis of LGR5/6 Gene Variants, Gut Microbiota Composition and Osteoporosis Risk in Elderly Population
Authors: Di Dong-sheng , Li Can , Dai Yu , Wei Mu-hong , Wang Shan-shan , Song Wen-jing , Zhou Hao-long , Cui Yuan , Zhang Ru-yi , Huang Qin , Wang Qi
Published: November 2021

Objective: This study aimed to explore the relationships between the common variants of R-spondin/Wnt signaling genes, gut microbiota composition, and osteoporosis (OP) risk in elderly Chinese Han population.

Design: Dual-energy X-ray absorptiometry was used to obtain the OP-associated measurements at multiple skeleton sites among all 1,168 participants. Genotyping data was obtained by using the next-generation sequencing in the discovery stage (n = 400, 228 OP patients) and SNPscan technology in the replication stage (n = 768, 356 OP patients). Bioinformatic analysis was performed to provide more evidence for the genotype-OP associations. The 16S ribosomal RNA gene high-throughput sequencing technology was adopted to explore OP-associated gut microbiota variations.

Results: The genetic variants of rs10920362 in the LGR6 gene (P-FDR = 1.19 × 10–6) and rs11178860 in the LGR5 gene (P-FDR = 1.51 × 10–4) were found to associate with OP risk significantly. Several microbial taxa were associated with the BMDs and T-scores at multiple skeleton sites. The associations between rs10920362 and BMD-associated microbiota maintained significance after adjusting confounders. The rs10920362 CT/TT genotype associated with a decreased relative abundance of Actinobacteria (β = −1.32, P < 0.001), Bifidobacteriaceae (β = −1.70, P < 0.001), and Bifidobacterium (β = −1.70, P < 0.001) compared to the CC genotype.

Conclusion: Our findings suggested that the variants loci of LGR6 may be associate with OP pathogenesis via gut microbiota modifications. The relationship between host genetics and gut microbiome provides new perspectives about OP prevention and treatment.
Environmental Water and Sediment Microbial Communities Shape Intestine Microbiota for Host Health: The Central Dogma in an Anthropogenic Aquaculture Ecosystem
Authors: Huang Zhijian , Hou Dongwei , Zhou Renjun , Zeng Shenzheng , Xing Chengguang , Wei Dongdong , Deng Xisha , Yu Lingfei , Wang Hao , Deng Zhixuan , Weng Shaoping , Ning Daliang , Xiao Chuanle , Yan Qingyun , Zhou Jizhong , He Zhili , He Jianguo
Published: November 2021

From increasing evidence has emerged a tight link among the environment, intestine microbiota, and host health status; moreover, the microbial interaction in different habitats is crucial for ecosystems. However, how the environmental microbial community assembly governs the intestinal microbiota and microbial communities of multiple habitats contribute to the metacommunity remain elusive. Here, we designed two delicate experiments from temporal and spatial scales in a shrimp culture pond ecosystem (SCPE). Of the SCPE metacommunity, the microbial diversity was mainly contributed to by the diversity of–βIntraHabitats and βInterHabitats, and water and sediment communities had a large contribution to the shrimp intestine community as shown by SourceTracker and Sloan neutral community model analyses. Also, phylogenetic bin-based null model results show that microbial assembly of three habitats in the SCPE appeared to be largely driven by stochastic processes. These results enrich our understanding of the environment–intestinal microbiota–host health closely linked relationship, making it possible to be the central dogma for an anthropogenic aquaculture ecosystem. Our findings enhance the mechanistic understanding of microbial assembly in the SCPE for further analyzing metacommunities, which has important implications for microbial ecology and animal health.
MicroRNA-124: A Key Player in Microglia-Mediated Inflammation in Neurological Diseases
Authors: Zhao Jiuhan , He Zhenwei , Wang Jialu
Published: November 2021

Neurological disorders are mainly characterized by progressive neuron loss and neurological deterioration, which cause human disability and death. However, many types of neurological disorders have similar pathological mechanisms, including the neuroinflammatory response. Various microRNAs (miRs), such as miR-21, miR-124, miR-146a, and miR-132 were recently shown to affect a broad spectrum of biological functions in the central nervous system (CNS). Microglia are innate immune cells with important roles in the physiological and pathological activities of the CNS. Recently, abnormal expression of miR-124 was shown to be associated with the occurrence and development of various diseases in CNS via regulating microglia function. In addition, miR-124 is a promising biomarker and therapeutic target. Studies on the role of miR-124 in regulating microglia function involved in pathogenesis of neurological disorders at different stages will provide new ideas for the use of miR-124 as a therapeutic target for different CNS diseases.
Eculizumab Pharmacokinetics and Pharmacodynamics in Patients With Generalized Myasthenia Gravis
Authors: Monteleone Jonathan P. R. , Gao Xiang , Kleijn Huub Jan , Bellanti Francesco , Pelto Ryan
Published: November 2021

Objective: To investigate the pharmacokinetics, pharmacodynamics, and exposure–response of the approved 900/1,200 mg dosing regimen for the terminal complement component 5 (C5) inhibitor eculizumab in patients with generalized myasthenia gravis (gMG).

Methods: The analysis used data from 62 patients aged ≥ 18 years with anti-acetylcholine receptor (AChR) antibody-positive refractory gMG who received eculizumab during the REGAIN study (ClinicalTrials.gov: NCT01997229). One- and two-compartment population-pharmacokinetic models were evaluated, and the impact of covariates on pharmacokinetic parameters was assessed. Relationships between eculizumab exposure and free C5 concentration, in vitro hemolytic activity, clinical response, and tolerability were characterized.

Results: Steady-state serum eculizumab concentrations were achieved by Week 4 and were sustained throughout the 26-week treatment period. The eculizumab pharmacokinetic data were well-described by a two-compartment model with first-order elimination, including effects of body weight on pharmacokinetic parameters and plasma-exchange events on clearance. Complete inhibition of terminal complement was achieved in nearly all patients at the time of trough and peak eculizumab concentrations at all post-dose timepoints assessed (free C5 < 0.5 μg/ml in 92% of patients; in vitro hemolysis < 20% in 87% of patients). Serum eculizumab concentrations of ≥116 μg/ml achieved free C5 concentrations of < 0.5 μg/ml. Clinical efficacy and tolerability were consistent across the eculizumab exposure range.

Conclusions: Rigorous, quantitative, model-based exposure–response analysis of serum eculizumab concentration and response data demonstrated that the approved eculizumab dosing (900/1,200 mg) for adults with anti-AChR antibody-positive refractory gMG rapidly achieved complete inhibition of terminal complement activation and provided sustained clinical efficacy across the eculizumab exposure range.