bluuebunny/crossref_metadata_2025 huggingface dataset:
From Conflict to Conviviality? Transforming Human–Bear Relations in Bulgaria
Authors: Toncheva Svetoslava , Fletcher Robert
Published: August 2021

The question of how to transform human–wildlife relations from conflict to coexistence, rather than merely mitigating conflicts, has become a central focus of research and practice. In this article, we address this important question by exploring the factors that may contribute to promoting successful coexistence between humans and brown bears within Europe and elsewhere. We do this through comparative analysis of two cases in rural Bulgaria evidencing different degrees of conflict and coexistence between members of the two species. Through this comparison, we highlight the main factors that lead to conflict in our problem case as well as those that might help to instead foster coexistence. We situate this analysis within growing discussion of convivial conservation as a novel approach intended to transform conservation policy and practice throughout the world that emphasizes the importance of attending to the overarching social and political-economic processes encompassing human–wildlife interaction in order to influence the latter. In this way, we contribute to research and discussion concerning how to transform human–wildlife conflict (HWC) into convivial coexistence more broadly by demonstrating how attention to the immediate circumstances of human–wildlife encounter in such efforts should be complemented by promotion of more inclusive, democratic forms of decision-making, and egalitarian distribution of economic resources.
Long Non-coding RNA N1LR Protects Against Myocardial Ischemic/Reperfusion Injury Through Regulating the TGF-β Signaling Pathway
Authors: Du Lin , Chen Jie , Wu Yong , Xia Guangwei , Chen Mingxing , Zhao Pei , Wang Yao , Yao Deshan , Liu Fan , Zhang Lina , Wang Xue , Yang Yi , Wang Liansheng
Published: August 2021

Long non-coding RNAs (lncRNAs) have been shown to play critical roles in various cell biological processes. However, the mechanism of lncRNAs in acute myocardial infarction (AMI) is not fully understood. Previous studies showed that lncRNA N1LR was down-regulated in ischemic cerebral stroke and its up-regulation was protective. The current study was designed to assess the protective effect of N1LR and further to explore potential mechanisms of N1LR in ischemic/reperfusion (I/R) injury after AMI. Male C57BL/6J mice and H9c2 cardiomyocytes were selected to construct in vivo and in vitro pathological models. In H9c2 cell line, N1LR expression was markedly decreased after H2O2 and CoCl2 treatments and N1LR overexpression alleviated apoptosis, inflammation reaction, and LDH release in cardiomyocytes treated with H2O2 and CoCl2. Mouse in vivo study showed that overexpression of N1LR enhanced cardiac function and suppressed inflammatory response and fibrosis. Mechanistically, we found that the expression of transforming growth factor (TGF)-β1 and smads were significantly decreased in the N1LR overexpression group exposed to H2O2. In a summary, our study indicated that N1LR can act as a protective factor against cardiac ischemic-reperfusion injury through regulating the TGF-β/Smads signaling pathway.
Greater Dietary Inflammatory Potential Is Associated With Higher Likelihood of Abdominal Aortic Calcification
Authors: Qin Zheng , Chang Kaixi , Liao Ruoxi , Jiang Luojia , Yang Qinbo , Su Baihai
Published: August 2021

Aims: We aimed to assess the association between dietary inflammation index (DII) and abdominal aortic calcification (AAC) in US adults aged ≥40 years.

Methods: Data were obtained from the 2013–2014 National Health and Nutrition Examination Survey (NHANES). Participants who were <40 years old and missing the data of DII and AAC were excluded. DII was calculated based on a 24-h dietary recall interview for each participant. AAC score was quantified by assessing lateral spine images and severe AAC was defined as AAC score >6. Weighted multivariable regression analysis and subgroup analysis were preformed to estimate the independent relationship between DII with AAC score and severe AAC.

Results: A total of 2,897 participants were included with the mean DII of −0.17 ± 2.80 and the mean AAC score of 1.462 ± 3.290. The prevalence of severe AAC was 7.68% overall, and participants in higher DII quartile tended to have higher rates of severe AAC (Quartile 1: 5.03%, Quartile 2: 7.44%, Quartile 3: 8.38%, Quartile 4: 10.46%, p = 0.0016). A positive association between DII and AAC score was observed (β = 0.055, 95% CI: 0.010, 0.101, p = 0.01649), and higher DII was associated with an increased risk of severe AAC (OR = 1.067, 95% CI: 1.004, 1.134, p = 0.03746). Subgroup analysis indicated that this positive association between DII and AAC was similar in population with differences in gender, age, BMI, hypertension status, and diabetes status and could be appropriate for different population settings.

Conclusion: Higher pro-inflammatory diet was associated with higher AAC score and increased risk of severe AAC. Anti-inflammatory dietary management maybe beneficial to reduce the risk of AAC.
Zirconia Materials for Dental Implants: A Literature Review
Authors: Qu Yinying , Liu Lin
Published: August 2021

Titanium is currently the most commonly used material for manufacturing dental implants. However, its potential toxic effects and the gray color have resulted in increasing requests for metal-free treatment options. Zirconia is a type of ceramic materials that has been extensively used in medicine field, such as implant abutments and various joint replacement appliances. Amounts of clinical evaluations have indicated good biocompatibility for zirconia products. Besides, its toothlike color, low affinity for plaque and outstanding mechanical and chemical properties have made it an ideal candidate for dental implants. The aim of this study is to review the laboratory and clinical papers about several kinds of zirconia materials and zirconia surface modification techniques. Although there are plenty of literatures on these topics, most of the researches focused on the mechanical properties of the materials or based on cell and animal experiments. Randomized clinical trials on zirconia materials are still urgently needed to validate their application as dental implants.
Effects of Metformin on Reproductive, Endocrine, and Metabolic Characteristics of Female Offspring in a Rat Model of Letrozole-Induced Polycystic Ovarian Syndrome With Insulin Resistance
Authors: Xie Yidong , Xiao Li , Li Shangwei
Published: August 2021

The beneficial effects of metformin, especially its capacity to ameliorate insulin resistance (IR) in polycystic ovary syndrome (PCOS), explains why it is widely prescribed. However, its effect on the offspring of patients with PCOS remains uncertain. This study investigated the impact of metformin treatment on the first- and second-generation female offspring born to letrozole-induced PCOS-IR rats. Forty-five female Wistar rats were implanted with continuous-release letrozole pellets or placebo and treated with metformin or vehicle control. Rats exposed to letrozole showed PCOS-like reproductive, endocrine, and metabolic phenotypes in contrast to the controls. Metformin significantly decreased the risk of body weight gain and increased INSR expression in F1 female offspring in PCOS-IR rats, contributing to the improvement in obesity, hyperinsulinemia, and IR. Decreased FSHR expression and increased LHCGR expression were observed in F1 female rats of the PCOS-IR and PCOS-IR+Metformin groups, suggesting that FSHR and LHCGR dysfunction might promote the development of PCOS. Nevertheless, we found no significant differences in INSR, FSHR, and LHCGR expression or other PCOS phenotypes in F2 female offspring of PCOS-IR rats. These findings indicated widespread reproductive, endocrine, and metabolic changes in the PCOS-IR rat model, but the PCOS phenotypes could not be stably inherited by the next generations. Metformin might have contributed to the improvement in obesity, hyperinsulinemia, and IR in F1 female offspring. The results of this study could be used as a theoretical basis in support of using metformin in the treatment of PCOS-IR patients.
The Chlamydia psittaci Inclusion Membrane Protein 0556 Inhibits Human Neutrophils Apoptosis Through PI3K/AKT and NF-κB Signaling Pathways
Authors: He Zhangping , Xiao Jian , Wang Jianye , Lu Simin , Zheng Kang , Yu Maoying , Liu Jie , Wang Chuan , Ding Nan , Liang Mingxing , Wu Yimou
Published: August 2021

Inclusion membrane proteins (Incs) play an important role in the structure and stability of chlamydial inclusion and the interaction betweenChlamydiaspp. and their hosts. Following Chlamydia infection through the respiratory tract, human polymorphonuclear neutrophils (hPMN) not only act as the primary immune cells reaching the lungs, but also serve as reservoir for Chlamydia. We have previously identified aChlamydia psittacihypothetical protein, CPSIT_0556, as a medium expressed inclusion membrane protein. However, the role of inclusion membrane protein, CPSIT_0556 in regulating hPMN functions remains unknown. In the present study, we found that CPSIT_0556 could not only inhibit hPMN apoptosis through the PI3K/Akt and NF-κB signaling pathways by releasing IL-8, but also delays procaspase-3 processing and inhibits caspase-3 activity in hPMN. Up-regulating the expression of anti-apoptotic protein Mcl-1 and down-regulating the expression of pro-apoptotic protein Bax could also inhibit the translocalization of Bax in the cytoplasm into the mitochondria, as well as induce the transfer of p65 NF-κB from the cytoplasm to the nucleus. Overall, our findings demonstrate that CPSIT_0556 could inhibit hPMN apoptosis through PI3K/Akt and NF-κB pathways and provide new insights towards understanding a better understanding of the molecular pathogenesis and immune escape mechanisms ofC. psittaci.
Promising New Tools for Targeting p53 Mutant Cancers: Humoral and Cell-Based Immunotherapies
Authors: Chasov Vitaly , Zaripov Mikhail , Mirgayazova Regina , Khadiullina Raniya , Zmievskaya Ekaterina , Ganeeva Irina , Valiullina Aigul , Rizvanov Albert , Bulatov Emil
Published: August 2021

Transcription factor and oncosuppressor protein p53 is considered as one of the most promising molecular targets that remains a high-hanging fruit in cancer therapy. TP53 gene encoding the p53 protein is known to be the most frequently mutated gene in human cancers. The loss of transcriptional functions caused by mutations in p53 protein leads to deactivation of intrinsic tumor suppressive responses associated with wild-type (WT) p53 and acquisition of new pro-oncogenic properties such as enhanced cell proliferation, metastasis and chemoresistance. Hotspot mutations of p53 are often immunogenic and elicit intratumoral T cell responses to mutant p53 neoantigens, thus suggesting this protein as an attractive candidate for targeted anti-cancer immunotherapies. In this review we discuss the possible use of p53 antigens as molecular targets in immunotherapy, including the application of T cell receptor mimic (TCRm) monoclonal antibodies (mAbs) as a novel powerful approach.
Strategies for Accurate Cell Type Identification in CODEX Multiplexed Imaging Data
Authors: Hickey John W. , Tan Yuqi , Nolan Garry P. , Goltsev Yury
Published: August 2021

Multiplexed imaging is a recently developed and powerful single-cell biology research tool. However, it presents new sources of technical noise that are distinct from other types of single-cell data, necessitating new practices for single-cell multiplexed imaging processing and analysis, particularly regarding cell-type identification. Here we created single-cell multiplexed imaging datasets by performing CODEX on four sections of the human colon (ascending, transverse, descending, and sigmoid) using a panel of 47 oligonucleotide-barcoded antibodies. After cell segmentation, we implemented five different normalization techniques crossed with four unsupervised clustering algorithms, resulting in 20 unique cell-type annotations for the same dataset. We generated two standard annotations: hand-gated cell types and cell types produced by over-clustering with spatial verification. We then compared these annotations at four levels of cell-type granularity. First, increasing cell-type granularity led to decreased labeling accuracy; therefore, subtle phenotype annotations should be avoided at the clustering step. Second, accuracy in cell-type identification varied more with normalization choice than with clustering algorithm. Third, unsupervised clustering better accounted for segmentation noise during cell-type annotation than hand-gating. Fourth, Z-score normalization was generally effective in mitigating the effects of noise from single-cell multiplexed imaging. Variation in cell-type identification will lead to significant differential spatial results such as cellular neighborhood analysis; consequently, we also make recommendations for accurately assigning cell-type labels to CODEX multiplexed imaging.
Cellular and Molecular Effects of SARS-CoV-2 Linking Lung Infection to the Brain
Authors: Francistiová Linda , Klepe Adrián , Curley Géza , Gulya Károly , Dinnyés András , Filkor Kata
Published: August 2021

In December 2019, a new viral disease emerged and quickly spread all around the world. In March 2020, the COVID-19 outbreak was classified as a global pandemic and by June 2021, the number of infected people grew to over 170 million. Along with the patients’ mild-to-severe respiratory symptoms, reports on probable central nervous system (CNS) effects appeared shortly, raising concerns about the possible long-term detrimental effects on human cognition. It remains unresolved whether the neurological symptoms are caused directly by the SARS-CoV-2 infiltration in the brain, indirectly by secondary immune effects of a cytokine storm and antibody overproduction, or as a consequence of systemic hypoxia-mediated microglia activation. In severe COVID-19 cases with impaired lung capacity, hypoxia is an anticipated subsidiary event that can cause progressive and irreversible damage to neurons. To resolve this problem, intensive research is currently ongoing, which seeks to evaluate the SARS-CoV-2 virus’ neuroinvasive potential and the examination of the antibody and autoantibody generation upon infection, as well as the effects of prolonged systemic hypoxia on the CNS. In this review, we summarize the current research on the possible interplay of the SARS-CoV-2 effects on the lung, especially on alveolar macrophages and direct and indirect effects on the brain, with special emphasis on microglia, as a possible culprit of neurological manifestation during COVID-19.
Portraying Gradients of Structural Complexity in Coral Reefs Using Fine-Scale Depth Profiles
Authors: Ribas-Deulofeu Lauriane , Château Pierre-Alexandre , Denis Vianney , Chen Chaolun Allen
Published: August 2021

Structural complexity is an important feature to understand reef resilience abilities, through its role in mediating predator-prey interactions, regulating competition, and promoting recruitment. Most of the current methods used to measure reef structural complexity fail to quantify the contributions of fine and coarse scales of rugosity simultaneously, while other methods require heavy data computation. In this study, we propose estimating reef structural complexity based on high-resolution depth profiles to quantify the contributions of both fine and coarse rugosities. We adapted the root mean square of the deviation from the assessed surface profile (Rq) with polynomials. The efficiency of the proposed method was tested on nine theoretical cases and 50 in situ transects from South Taiwan, and compared to both the chain method and the visual rugosity index commonly employed to characterize reef structural complexity. The Rq indices proposed as rugosity estimators in this study consider multiple levels of reef rugosity, which the chain method and the visual rugosity index fail to apprehend. Furthermore, relationships were found between Rq scores and specific functional groups in the benthic community. Indeed, the fine scale rugosity of the South Taiwan reefs mainly comes from biotic components such as hard corals, while their coarse scale rugosity is essentially provided by the topographic variations that reflect the geological context of the reefs. This approach allows identifying the component of the rugosity that could be managed and which could, ultimately, improve strategies designed for conservation.
Microalgal Diet Influences the Nutritive Quality and Reproductive Investment of the Cyclopoid Copepod Paracyclopina nana
Authors: Dayras Paul , Bialais Capucine , Sadovskaya Irina , Lee Min-Chul , Lee Jae-Seong , Souissi Sami
Published: August 2021

Copepods represent an interesting alternative or a complement live food to brine shrimps and rotifers commonly used in aquaculture. They constitute the natural prey of many fish species and therefore do not require a potential nutritional enrichment. But an optimization of the microalgal diets used to feed copepods is essential to improve their mass culture. This study examined the effects of seven microalgal diets, namely single-species diets of Rhodomonas salina (R), Tisochrysis lutea (T), and Pavlova lutheri (=Diacronema lutheri) (P), two-species diets (R + T, T + P, and R + P), and a three-species diet (R + T + P), on the fatty acid and monosaccharide composition of the cyclopoid copepod Paracyclopina nana as well as its reproductive investment. Experiments were run during 15 days in 10-L beakers; starting with nauplii collected from a large 300-L batch culture. Copepods fatty acid contents were studied, particularly the relative amounts of docosahexaenoic acid (DHA) and eicosa-pentaenoic acid (EPA). The R + T, R, and T diets induced the highest total fatty acid amount in copepods. R + T and R also generated the lowest DHA/EPA ratios in copepods due to high EPA contents. The highest value of total monosaccharides was found in copepods fed with R + T + P. Diets R + T and R induced the greatest prosome volumes and clutch volumes in ovigerous females. Both prosome volume and clutch volume in P. nana ovigerous females were correlated to the individual EPA amount. The results demonstrated that all diets including R. salina enhanced the productivity of P. nana in mass culture, particularly when combined with T. lutea. R. salina, and T. lutea induced complementary fatty acid and monosaccharide profiles, confirming that R + T represents the best microalgae combination for productive culture of P. nana. Conversely, P. lutheri did not enhance the nutritional profile nor the fecundity of P. nana in the culture. This study is the first to demonstrate that R. salina is a suitable microalga for productive mass culture of P. nana for use as live food in aquaculture.
Technical and Social Approaches to Study Shoreline Change of Kuakata, Bangladesh
Authors: Bushra Nazla , Mostafiz Rubayet Bin , Rohli Robert V. , Friedland Carol J. , Rahim Md Adilur
Published: August 2021

In recent years, shoreline determination has become an issue of increasing importance and concern, especially at the local level, as sea level continues to rise. This study identifies the rates of absolute and net erosion, accretion, and shoreline stabilization along the coast of Kuakata, a vulnerable coastal region in south-central Bangladesh. Shoreline change was detected by applying remote sensing and geographic information system (RS-GIS)-based techniques by using Landsat Thematic Mapper (TM), Landsat 8 Operational Land Imager (OLI) and Thermal Infrared Sensor (TIRS) satellite images at 30-m resolution from 1989, 2003, 2010, and 2020. The band combination (BC) method was used to extract the shoreline (i.e., land-water boundary) due to its improved accuracy over other methods for matching with the existing shoreline position. This study also used participatory rural appraisal (PRA) tools which revealed the societal impacts caused by the shoreline changes. Coupling RS-GIS and PRA techniques provides an enhanced understanding of shoreline change and its impacts because PRA enriches the RS-GIS outcomes by contextualizing the findings. Results show that from 1989 to 2020, a total of 13.59 km2 of coastal land was eroded, and 3.27 km2 of land was accreted, suggesting that land is retreating at about 0.32 km2 yr–1. Results from the PRA tools support this finding and demonstrate that fisheries and tourism are affected by the shoreline change. These results are important in Kuakata, a major tourist spot in Bangladesh, because of the impacts on fisheries, recreation, resource extraction, land use planning, and coastal risk management.
The Effect of Pyrolysis Conditions on the Preparation of Fe2O3 Particles Using Simulated Pickling Liquor in a Venturi Reactor
Authors: Lv Chao , Sun Ming-He , Yin Hong-Xin
Published: August 2021

Large amounts of pickling liquor are produced during the pickling of iron and steel. The Venturi reactor is used during the pyrolysis of pickling liquor to prepare high-purity Fe2O3 particles. Changing the pyrolysis conditions will affect the purity and concentration of Fe2O3 particles. In this paper, physical experiments and numerical simulations were carried out to study the effect of pyrolysis conditions on the Fe2O3 particles, including the pyrolysis temperature, the FeCl2/FeCl3 ratio in the pickling liquor, and the citric acid ratio. The results showed that a product with a higher purity, better crystallinity, and greater concentration was obtained at 923 K. Further increasing the temperature did not change the concentration of Fe2O3 particles. When the ratio of FeCl2/FeCl3 in the pickling liquor was 1:1.5, the maximum concentration of Fe2O3 particles at the outlet was obtained. When the added proportion of citric acid was 1:1, the particle size distribution was more uniform, and when the added proportion was 1:2.5, the maximum concentration of Fe2O3 particles at the outlet was achieved.
Worldwide Assessment of Low- and Middle-Income Countries' Regulatory Preparedness to Approve Medical Products During Public Health Emergencies
Authors: Khadem Broojerdi Alireza , Alfonso Claudia , Ostad Ali Dehaghi Razieh , Refaat Mohamed , Sillo Hiiti Baran
Published: August 2021

Background: Regulatory preparedness for public health emergencies is critical. However, responses to past emergencies, such as the 2009 H1N1 influenza pandemic and medical product shortages, have revealed sizable gaps in countries' regulatory capacity and preparedness. A systematic analysis of the regulatory preparedness of countries around the world has not yet been performed. The purpose of this study was to analyze and document the current regulatory preparedness status, highlight the related gaps and challenges in order to propose strategic, harmonized, and sustainable regulatory solutions to improve future responses to public health emergencies.

Methods: From 2016 to 2020, we used the World Health Organization (WHO)'s Global Benchmarking Tool (GBT), a standardized instrument for identifying national regulatory authorities' strengths and gaps, to analyze the regulatory preparedness of 84 Member States, 95% of which were low- or middle-income countries. We analyzed whether participating Member States had not implemented, displayed ongoing implementation, had partially implemented, or had fully implemented 10 of the GBT's 268 sub-indicators most relevant to regulatory preparedness for public health emergencies.

Findings: Only 10 Member States (12%) that underwent benchmarking had fully implemented all 10 sub-indicators related to regulatory preparedness for public health emergencies; 34 (40%) had fully implemented ≥50% of the emergency sub-indicators, and 20 (24%) had not fully implemented any of the sub-indicators. With regard to individual sub-indicators, regulatory preparedness ranged from 19 Member States (23%) fully implementing reliance on clinical trial decisions of others to 45 (59%) fully implementing legal provisions to fast-track (or expedite) marketing authorization applications.

Interpretation: Many WHO Member States have limited regulatory preparedness for a public health emergency. Strengthening regulatory systems and promoting Good Regulatory Practices and reliance in these countries, to enable efficient response to emergencies, should be a global health priority.
SARS-CoV-2 Accessory Protein ORF7b Mediates Tumor Necrosis Factor-α-Induced Apoptosis in Cells
Authors: Yang Ruiping , Zhao Qiong , Rao Jingjing , Zeng Feng , Yuan Shengren , Ji Manshan , Sun Xiaoguang , Li Jian , Yang Jing , Cui Jingwen , Jin Zhixiong , Liu Long , Liu Zhixin
Published: August 2021

The accessory proteins of coronaviruses are essential for virus–host interactions and the modulation of host immune responses. It has been reported that accessory protein ORF3a encoded by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can induce apoptosis, and accessory protein ORF6 and ORF8 could be inhibitors of the type-I interferon (IFN) signaling pathway. However, the function of accessory protein ORF7b is largely unknown. We investigated the apoptosis-inducing activity of ORF7b in cells. Cytokine levels and host innate immune responses, including expression of interferon regulatory transcription factor (IRF)-3, signal transducer and activator of transcription (STAT)-1, interferon (IFN)-β, tumor necrosis factor (TNF)-α, and interleukin (IL)-6, were also investigated. We found that ORF7b promoted expression of IFN-β, TNF-α, and IL-6, activated type-I IFN signaling through IRF3 phosphorylation, and activated TNFα-induced apoptosis in HEK293T cells and Vero E6 cells. These results could provide deeper understanding about the pathogenicity of SARS-CoV-2 as well as the interaction between the accessory protein ORF7b with host immune responses.
Metagenomic Investigation Uncovers Presence of Probiotic-Type Microbiome in Kalparasa® (Fresh Unfermented Coconut Inflorescence Sap)
Authors: Gopal Murali , Shil Sandip , Gupta Alka , Hebbar K. B. , Arivalagan M.
Published: August 2021

The phloem sap tapped from unopened inflorescence (spadix) of coconut palm using a novel collecting device, “coco-sap chiller,” has been branded Kalparasa® (henceforth as Kalparasa in the text) to distinguish its properties not found in sap harvested by traditional methods. To know its hitherto unidentified microbiome profile, we employed high-throughput sequencing to uncover the bacteriome and mycobiome in fresh and 12-h fermented samples. Fresh Kalparasa had a pH of 7.2, which dropped to 4.5 after 12 h, signifying fermentation of the sap. Diversity analysis indicated fresh Kalparasa having higher bacterial species than the fermented one. Contrary to this, fresh sap had lower fungal/yeast diversity than the fermented sample. Fresh Kalparasa had relatively higher abundance of probiotic-type Leuconostoc genus followed by equal proportions of Gluconobacter, Acetobacter, and Fructobacillus. The 12-h fermented Kalparasa showed a significant increase in Gluconobacter with a sharp decrease in Leuconostoc. Mycobiome data revealed fresh Kalparasa to be preponderant in Saccharomyces and Hanseniaspora genera of yeasts while the fermented sap had higher representation of Hanseniaspora and Cortinarius and lesser Saccharomyces. This suggested that the fermentation of Kalparasa was probably driven by symbiotic culture of bacteria and yeasts (SCOBY), particularly acetic acid bacteria and non-Saccharomyces yeasts. The bacteriome-function predictions highlighted the enrichment of glycerophospholipid, ABC transporters, purine, and pyrimidine metabolisms. Based on our findings, Kalparasa containing large population of Leuconostoc mesenteroides, Fructobacillus fructosus, Saccharomyces cerevisiae, and Hanseniaspora guilliermondii can be promoted as a healthy “unfermented” plant edible food containing live probiotic-type microbiome during its consumption.
Phylotaxogenomics for the Reappraisal of the Genus Roseomonas With the Creation of Six New Genera
Authors: Rai Anusha , Jagadeeshwari Uppada , Deepshikha Gupta , Smita Nandardhane , Sasikala Chintalapati , Ramana Chintalapati Venkata
Published: August 2021

The genus Roseomonas is a significant group of bacteria which is invariably of great clinical and ecological importance. Previous studies have shown that the genus Roseomonas is polyphyletic in nature. Our present study focused on generating a lucid understanding of the phylogenetic framework for the re-evaluation and reclassification of the genus Roseomonas. Phylogenetic studies based on the 16S rRNA gene and 92 concatenated genes suggested that the genus is heterogeneous, forming seven major groups. Existing Roseomonas species were subjected to an array of genomic, phenotypic, and chemotaxonomic analyses in order to resolve the heterogeneity. Genomic similarity indices (dDDH and ANI) indicated that the members were well-defined at the species level. The Percentage of Conserved Proteins (POCP) and the average Amino Acid Identity (AAI) values between the groups of the genus Roseomonas and other interspersing members of the family Acetobacteraceae were below 65 and 70%, respectively. The pan-genome evaluation depicted that the pan-genome was an open type and the members shared 958 core genes. This claim of reclassification was equally supported by the phenotypic and chemotaxonomic differences between the groups. Thus, in this study, we propose to re-evaluate and reclassify the genus Roseomonas and propose six novel genera as Pararoseomonas gen. nov., Falsiroseomonas gen. nov., Paeniroseomonas gen. nov., Plastoroseomonas gen. nov., Neoroseomonas gen. nov., and Pseudoroseomonas gen. nov.
Dodecapeptide Cathelicidins of Cetartiodactyla: Structure, Mechanism of Antimicrobial Action, and Synergistic Interaction With Other Cathelicidins
Authors: Bolosov Ilia A. , Panteleev Pavel V. , Sychev Sergei V. , Sukhanov Stanislav V. , Mironov Pavel A. , Myshkin Mikhail Yu. , Shenkarev Zakhar O. , Ovchinnikova Tatiana V.
Published: August 2021

In this study, dodecapeptide cathelicidins were shown to be widespread antimicrobial peptides among the Cetruminantia clade. In particular, we investigated the dodecapeptide from the domestic goat Capra hircus, designated as ChDode and its unique ortholog from the sperm whale Physeter catodon (PcDode). ChDode contains two cysteine residues, while PcDode consists of two dodecapeptide building blocks and contains four cysteine residues. The recombinant analogs of the peptides were obtained by heterologous expression in Escherichia coli cells. The structures of the peptides were studied by circular dichroism (CD), FTIR, and NMR spectroscopy. It was demonstrated that PcDode adopts a β-hairpin structure in water and resembles β-hairpin antimicrobial peptides, while ChDode forms a β-structural antiparallel covalent dimer, stabilized by two intermonomer disulfide bonds. Both peptides reveal a significant right-handed twist about 200 degrees per 8 residues. In DPC micelles ChDode forms flat β-structural tetramers by antiparallel non-covalent association of the dimers. The tetramers incorporate into the micelles in transmembrane orientation. Incorporation into the micelles and dimerization significantly diminished the amplitude of backbone motions of ChDode at the picosecond-nanosecond timescale. When interacting with negatively charged membranes containing phosphatidylethanolamine (PE) and phosphatidylglycerol (PG), the ChDode peptide adopted similar oligomeric structure and was capable to form ion-conducting pores without membrane lysis. Despite modest antibacterial activity of ChDode, a considerable synergistic effect of this peptide in combination with another goat cathelicidin – the α-helical peptide ChMAP-28 was observed. This effect is based on an increase in permeability of bacterial membranes. In turn, this mechanism can lead to an increase in the efficiency of the combined action of the synergistic pair ChMAP-28 with the Pro-rich peptide mini-ChBac7.5Nα targeting the bacterial ribosome.
Relative Power Correlates With the Decoding Performance of Motor Imagery Both Across Time and Subjects
Authors: Zhou Qing , Lin Jiafan , Yao Lin , Wang Yueming , Han Yan , Xu Kedi
Published: August 2021

One of the most significant challenges in the application of brain-computer interfaces (BCI) is the large performance variation, which often occurs over time or across users. Recent evidence suggests that the physiological states may explain this performance variation in BCI, however, the underlying neurophysiological mechanism is unclear. In this study, we conducted a seven-session motor-imagery (MI) experiment on 20 healthy subjects to investigate the neurophysiological mechanism on the performance variation. The classification accuracy was calculated offline by common spatial pattern (CSP) and support vector machine (SVM) algorithms to measure the MI performance of each subject and session. Relative Power (RP) values from different rhythms and task stages were used to reflect the physiological states and their correlation with the BCI performance was investigated. Results showed that the alpha band RP from the supplementary motor area (SMA) within a few seconds before MI was positively correlated with performance. Besides, the changes of RP between task and pre-task stage from theta, alpha, and gamma band were also found to be correlated with performance both across time and subjects. These findings reveal a neurophysiological manifestation of the performance variations, and would further provide a way to improve the BCI performance.
Ten Color Multiparameter Flow Cytometry in Bone Marrow and Apheresis Products for Assessment and Outcome Prediction in Multiple Myeloma Patients
Authors: Riebl Veronika , Dold Sandra Maria , Wider Dagmar , Follo Marie , Ihorst Gabriele , Waldschmidt Johannes M. , Jung Johannes , Rassner Michael , Greil Christine , Wäsch Ralph , Engelhardt Monika
Published: August 2021

Objective

In clinical trials (CTs), the assessment of minimal residual disease (MRD) has proven to have prognostic value for multiple myeloma (MM) patients. Multiparameter flow cytometry (MFC) and next-generation sequencing are currently used in CTs as effective tools for outcome prediction. We have previously described 6- and 8-color MFC panels with and without kappa/lambda, which were equally reliable in detecting aberrant plasma cells (aPC) in myeloma bone marrow (BM) specimens. This follow-up study a) established a highly sensitive single-tube 10-color MFC panel for MRD detection in myeloma samples carrying different disease burden (monoclonal gammopathy of unknown significance (MGUS), smoldering multiple myeloma (SMM), MM), b) evaluated additional, rarely used markers included in this panel, and c) assessed MRD levels and the predictive value in apheresis vs. BM samples of MM patients undergoing autologous stem cell transplantation (ASCT).

Methods + Results

The 10-color MFC was performed in BM and apheresis samples of 128 MM and pre-MM (MGUS/SMM) patients. The markers CD28, CD200, CD19, and CD117 underwent closer examination. The analysis revealed distinct differences in these antigens between MM, MGUS/SMM, and patients under treatment. In apheresis samples, the 10-color panel determined MRD negativity in 44% of patients. Absence of aPC in apheresis corresponded with disease burden, cytogenetics, and response to induction. It also determined MRD negativity in BM samples after ASCT and was associated with improved progression-free survival.

Conclusion

These results highlight the significance of the evaluation of both BM and apheresis samples with a novel highly sensitive 10-color MFC panel.
Nicardipine Inhibits Breast Cancer Migration via Nrf2/HO-1 Axis and Matrix Metalloproteinase-9 Regulation
Authors: Chen Yen-Chang , Chen Jia-Hong , Tsai Cheng-Fang , Wu Chen-Teng , Wu Miao-Hsiang , Chang Pei-Chun , Yeh Wei-Lan
Published: August 2021

Background: Metastasis represents an advanced stage of cancers, and matrix metalloproteinases are critical regulators. Calcium signal is crucial for appropriate cell behaviors. The efficacy and effects of calcium channel blockers in treating cancers are individually differ from each other. Here, we attempt to investigate the effects of nicardipine, a FDA-approved calcium channel blocker, in advanced breast cancers.

Methods: We analyzed the influence of nicardipine on the colony-forming ability of triple negative breast cancer cell lines. Using cell culture inserts, cell migration was also examined. The expression of regulatory proteins was evaluated by real-time PCR, Western blot, and ELISA.

Results: We have confirmed that nicardipine inhibits the breast cancer cells migration and colony formation. In addition, we also revealed that nicardipine increases the Nrf2 and HO-1 expression. The inhibition of HO-1 abrogates nicardipine-reduced matrix metalloproteinase-9 expression. Moreover, the end products of HO-1, namely, CO, Fe2+, and biliverdin (will converted to bilirubin), also decreases the expression of matrix metalloproteinase-9.

Conclusion: These findings suggest that nicardipine-mediated matrix metalloproteinase-9 reduction is regulated by Nrf2/HO-1 axis and its catalytic end products. Therefore, nicardipine may be a potential candidate for repurposing against advanced breast cancers.
Assessing the Accuracy of Sales Forecasts Submitted by Pharmaceutical Companies Applying for Reimbursement in Austria
Authors: Kossmeier Michael , Themanns Madeleine , Hatapoglu Lena , Kogler Bernhard , Keuerleber Simon , Lichtenecker Jutta , Sauermann Robert , Bucsics Anna , Freissmuth Michael , Zebedin-Brandl Eva
Published: August 2021

Objectives:Reimbursement decisions on new medicines require an assessment of their value. In Austria, when applying for reimbursement of new medicines, pharmaceutical companies are also obliged to submit forecasts of future sales. We systematically examined the accuracy of these pharmaceutical sales forecasts and hence the usefulness of these forecasts for reimbursement evaluations.Methods:We retrospectively analyzed reimbursement applications of 102 new drugs submitted between 2005 and 2014, which were accepted for reimbursement outside of hospitals, and for which actual reimbursed sales were available for at least 3 years. The main outcome variable was the accuracy ratio, defined as the ratio of forecasted sales submitted by pharmaceutical companies when applying for reimbursement to actual sales from reimbursement data.Results:The median accuracy ratio [95% confidence interval] was 1.33 [1.03; 1.74, range 0.15–37.5], corresponding to a median overestimation of actual sales by 33%. Forecasts of actual sales for 55.9% of all examined products either overestimated actual sales by more than 100% or underestimated them by more than 50%. The accuracy of sales forecasts did not show systematic change over the analyzed decade nor was it discernibly influenced by reimbursement status (restricted or unrestricted), the degree of therapeutic benefit, or the therapeutic area of the pharmaceutical product. Sales forecasts of drugs with a higher degree of innovation and those within a dynamic market tended to be slightly more accurate.Conclusions:The majority of sales forecasts provided by applicants for reimbursement evaluations in Austria were highly inaccurate and were on average too optimistic. This is in line with published results for other jurisdictions and highlights the need for caution when using such forecasts for reimbursement procedures.
A Multiple Step Active Stiffness Integration Scheme to Couple a Stochastic Cross-Bridge Model and Continuum Mechanics for Uses in Both Basic Research and Clinical Applications of Heart Simulation
Authors: Yoneda Kazunori , Okada Jun-ichi , Watanabe Masahiro , Sugiura Seiryo , Hisada Toshiaki , Washio Takumi
Published: August 2021

In a multiscale simulation of a beating heart, the very large difference in the time scales between rapid stochastic conformational changes of contractile proteins and deterministic macroscopic outcomes, such as the ventricular pressure and volume, have hampered the implementation of an efficient coupling algorithm for the two scales. Furthermore, the consideration of dynamic changes of muscle stiffness caused by the cross-bridge activity of motor proteins have not been well established in continuum mechanics. To overcome these issues, we propose a multiple time step scheme called the multiple step active stiffness integration scheme (MusAsi) for the coupling of Monte Carlo (MC) multiple steps and an implicit finite element (FE) time integration step. The method focuses on the active tension stiffness matrix, where the active tension derivatives concerning the current displacements in the FE model are correctly integrated into the total stiffness matrix to avoid instability. A sensitivity analysis of the number of samples used in the MC model and the combination of time step sizes confirmed the accuracy and robustness of MusAsi, and we concluded that the combination of a 1.25 ms FE time step and 0.005 ms MC multiple steps using a few hundred motor proteins in each finite element was appropriate in the tradeoff between accuracy and computational time. Furthermore, for a biventricular FE model consisting of 45,000 tetrahedral elements, one heartbeat could be computed within 1.5 h using 320 cores of a conventional parallel computer system. These results support the practicality of MusAsi for uses in both the basic research of the relationship between molecular mechanisms and cardiac outputs, and clinical applications of perioperative prediction.
Research on the Method of Predicting Fractional Flow Reserve Based on Multiple Independent Risk Factors
Authors: Zhang Honghui , Li Gaoyang , Hou Qianwen , Yang Yinlong , Wei Hongge , Yang Yujia , Qu Zhuoran , Xie Jinjie , Qiao Aike
Published: August 2021

The use of diameter stenosis (DS), as revealed by coronary angiography, for predicting fractional flow reserve (FFR) usually results in a high error rate of detection. In this study, we investigated a method for predicting FFR in patients with coronary stenosis based on multiple independent risk factors. The aim of the study was to improve the accuracy of detection. First, we searched the existing literature to identify multiple independent risk factors and then calculated the corresponding odds ratios. The improved analytic hierarchy process (IAHP) was then used to determine the weighted value of each independent risk factor, based on the corresponding odds ratio. Next, we developed a novel method, based on the top seven independent risk factors with the highest weighted values, to predict FFR. This model was then used to predict the FFR of 253 patients with coronary stenosis, and the results were then compared with previous methods (DS alone and a simplified scoring system). In addition to DS, we identified a range of other independent risk factors, with the highest weighted values, for predicting FFR, including gender, body mass index, location of stenosis, type of coronary artery distribution, left ventricular ejection fraction, and left myocardial mass. The area under the receiver-operating characteristic curve (AUC) for the newly developed method was 84.3% (95% CI: 79.2–89.4%), which was larger than 65.3% (95% CI: 61.5–69.1%) of DS alone and 74.8% (95% CI: 68.4–81.2%) of the existing simplified scoring system. The newly developed method, based on multiple independent risk factors, effectively improves the prediction accuracy for FFR.
Spanish Versions of the Outcome Rating Scale and the Session Rating Scale: Normative Data, Reliability, and Validity
Authors: Andrade-González Nelson , Rodrigo-Holgado Irene , Fernández-Rozas Jesús , Cáncer Pablo F. , Lahera Guillermo , Fernández-Liria Alberto , Rubio Gabriel , Miller Scott D.
Published: August 2021

Routine outcome monitoring (ROM) uses standardized measures to both track and inform mental health service delivery. Use of ROM has been shown to improve the outcome of psychotherapy when applied to different types of patients. The present research was designed to determine the reliability and validity of the Outcome Rating Scale (ORS) and the Session Rating Scale (SRS) in a sample of Spanish patients. After a controlled process of translation into the Spanish that is spoken and written in Spain (i.e., in Europe, as distinct from, e.g., Latin American Spanish), both measures were completed by patients of an outpatient mental health unit during eight sessions of psychotherapy. Sixty mental health patients filled out the ORS and 59 the SRS. In addition, the ORS was completed by 33 people who constituted the non-clinical sample. The cut-off of the ORS was 24.52 points, and the Reliable Change Index (RCI) was 9.15 points. ORS and SRS scores exhibited excellent internal consistency. The temporal stability of the SRS was adequate. The convergent and discriminant validity of the two measures were adequate. Regarding the factorial validity of the ORS and the SRS, in the third psychotherapy session, confirmatory factor analyses evidenced the existence of a unifactorial model. The predictive validity of SRS was acceptable. The ORS was sensitive to changes in patients’ symptoms. In conclusion, compared to the original English versions of the ORS and SRS measures, the Spanish versions of the measures are also reliable and valid.
Lock-Down Effect on the Mental Health Status of Healthcare Workers During COVID-19 Pandemic
Authors: Fageera Weam , Babtain Fawzi , Alzahrani Ahmad S. , Khrad Hussain M.
Published: August 2021

Background: The psychological impact that outbreaks and pandemics could inflict on healthcare workers has been widely studied; yet, little is known about the impact of the lockdown measures.

Objectives: To assess the magnitude of depression and anxiety among healthcare professionals before and after lifting of the lockdown restrictions in Saudi Arabia.

Methods: Surveys targeting healthcare workers were circulated twice: during the lockdown, and 8 weeks after lifting of lockdown. Anxiety and depressive symptoms were assessed using Generalized Anxiety Disorder (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) scales.

Results: A total of 947 healthcare workers, with the mean age of (37 ± 8.9) responded to the surveys. Among these, 23–27% respondents reported clinically significant levels of anxiety and depression. Whereas, easing of the lockdown restrictions was shown to be associated with decreasing mean scores of PHQ-9 and GAD-7. The noted burden fell heavily on female workers, those with a current or a history of psychiatric disorders, suffering from chronic diseases, being in workplaces with high exposure to COVID-19 or in contact with COVID-19 patients, nurses, as well as those who were living with elderly and perceived their physical and mental health as “much worse” compared to the time before the pandemic.

Conclusion: Our findings identified several predictors for anxiety and depression at different time-points of the pandemic. Thus, priority to psychological support measures might be needed for these groups.
Application of Near-Infrared Spectroscopy for Understanding Spontaneous Brain Activity During Resting State in Schizophrenia: A Mini Review
Authors: Yanagi Masaya , Shirakawa Osamu
Published: August 2021

Spontaneous brain activity occurs at rest, as represented by the default mode network. A resting paradigm is suitable for investigating brain function of patients with psychiatric diseases who may have difficulties adhering to goal-oriented tasks. Evidence accumulated in neuroimaging studies using functional magnetic resonance imaging has shown that the resting cerebral blood flow is impaired in psychiatric diseases. Near-infrared spectroscopy (NIRS), a simple neuroimaging modality, is an optimal tool for the resting paradigm, because it can offer a comfortable environment for measurement. Recent NIRS studies have demonstrated some promising data of altered resting activity in the prefrontal cortex of patients with schizophrenia, which may be exploited to develop further applications of NIRS in clinical psychiatry. Based on these findings, we emphasize the benefits of NIRS for assessing the prefrontal pathophysiology during the resting state and some methodological issues to be noted while analyzing cerebral blood flow using NIRS; moreover, we focus on interpreting these changes based on the complex nature of the spontaneous brain activity during resting state.