bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypoxia Constructing the Prognostic Model of Colorectal Adenocarcinoma and Related to the Immune Microenvironment
Authors: Zhang Yuanyuan , Yang Feng , Peng Xiaohong , Li Xiaoyu , Luo Na , Zhu Wenjun , Fu Min , Li Qianxia , Hu Guangyuan
Published: April 2021

Background: Hypoxia is a common phenomenon in solid tumors, which plays an important role in tumor proliferation, apoptosis, angiogenesis, invasion and metastasis, energy metabolism and chemoradiotherapy resistance. However, comprehensive analysis of hypoxia markers in colorectal adenocarcinoma (COAD) is still lacking. And there is a need for mechanism exploration and clinical application.

Methods: The gene expression, mutation and clinical data of COAD were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, respectively. Tumor samples from TCGA were randomly divided into the training and internal validation groups, while tumor samples from GEO were used as the external validation group. Univariate COX—LASSO—multivariate COX method was applied to construct the prognostic model. We clustered all TCGA tumor samples into high, medium and low hypoxia groups, evaluated the correlation between hypoxia degree and immunoactivity, and explored the combined effect of mutation for common target genes and model riskscore on survival in COAD patients. Finally, we developed a dynamic nomograph App online for direct clinical application and carried out multiple validations of the prognostic model.

Results: Our hypoxia-related prognostic model for COAD patients is accurate and has been successfully validated internally and externally. Single Sample Gene Set Enrichment Analysis (ssGSEA) and Gene Set Enrichment Analysis (GSEA) results suggest that for COAD patients with higher hypoxia, the stronger the associated immunosuppressive activity, providing a possible mechanism for the lower survival rate. Finally, the dynamic nomograph App online enhances the clinical translational significance of the study.

Conclusion: In this study, an accurate prognostic model for COAD patients was established and validated. In addition, our innovative findings include correlations between hypoxia levels and immune activity, as well as an in-depth exploration of common target gene mutations.
High Performance Aqueous Li-Ion Flow Capacitor Realized Through Microstructure Design of Suspension Electrode
Authors: Cao Defu , Bai Xiaojie , Wang Junhui , Liu Hao , Liao Libing
Published: April 2021

Suspension electrode is the core of flowable electrochemical energy storage systems, which are considered suitable for large-scale energy storage. Nevertheless, obtaining suspension electrodes with both low viscosity and high conductivity is still a big challenge. In present work, spinel LiMn2O4 was chosen as an example to make suspension with low viscosity and high conductivity through microstructure morphology control of solid particles and the contact mode between active materials and conductive additives in suspension electrode. By coating a thin layer of polyaniline on the surface of spherical spinel LiMn2O4, the resulting suspension showed much higher electronic conductivity (about 10 times) and lower viscosity (about 4.5 times) as compared to irregular and bare spinel LiMn2O4-based suspension counterpart. As a result, the Li-ion flow capacitor based on LiMn2O4 and activated carbon suspensions exhibited a record energy density of 27.4 W h L−1 at a power density of 22.5 W L−1 under static condition to date, and can be smoothly work under an intermittent-flow mode. The strategy reported in this work is an effective way for obtaining suspension electrodes with low viscosity and high electronic conductivity simultaneously. It can not only be used in the flow capacitors, but also can be extended to other flowable electrochemical energy storage systems.
Better Representation Is Needed in U.S. Endangered Species Act Implementation
Authors: Malcom Jacob , Carter Andrew
Published: April 2021

In the United States, the U.S. Fish and Wildlife Service uses the concepts of resilience, redundancy, and representation—often known as the “3Rs”—to guide implementation of the Endangered Species Act, which requires the U.S. government to designate imperiled species as threatened or endangered, and take action to recover them. The Service has done little, however, to relate the 3Rs to the statutory requirements of the Act. Here we focus on interpreting the concept of representation given core tenets of science and conservation policy. We show that the Service's current interpretation, which focuses on a narrow set of characteristics intrinsic to species that facilitate future adaptation, falls far short of a reasonable interpretation from the scientific literature and other policy, and has significant consequences for the conservation of threatened and endangered species, including those found in other countries. To illustrate the shortcomings in practice, we discuss the cases of the Lower 48 gray wolf (Canis lupus) delisting, the proposed Red-cockadedWoodpecker (Picoides borealis) downlisting, and the possible downlisting of the Canada lynx (Lynx canadensis). We then propose an alternative interpretation of representation that accommodates the Service's narrow interpretation and broadens it to include the importance of intraspecific variation for its own sake as well as extrinsic characteristics such as a species' role in ecological communities. We argue that this interpretation better reflects the intent of the Endangered Species Act, the best available science, and policy needs for conserving imperiled wildlife, all of which recognize the importance not only of preventing global extinction but also of preventing ecological extinction and extirpation across significant portions of a species' range.
Outcomes of Patients With ST-Segment Elevation Myocardial Infarction Admitted During COVID-19 Pandemic Lockdown in Germany – Results of a Single Center Prospective Cohort Study
Authors: Rattka Manuel , Stuhler Lina , Winsauer Claudia , Dreyhaupt Jens , Thiessen Kevin , Baumhardt Michael , Markovic Sinisa , Rottbauer Wolfgang , Imhof Armin
Published: April 2021

Objective: Since the outbreak of the COVID-19 pandemic, healthcare professionals reported declining numbers of patients admitted with ST-segment myocardial infarction (STEMI) associated with increased in-hospital morbidity and mortality. However, the effect of lockdown on outcomes of STEMI patients admitted during the COVID-19 crisis has not been prospectively evaluated.

Methods: A prospective, observational study on STEMI patients admitted to our tertiary care center during the COVID-19 pandemic was conducted. Outcomes of patients admitted during lockdown were compared to those patients admitted before and after pandemic-related lockdown.

Results: A total of 147 patients were enrolled in our study, including 57 patients in the pre-lockdown group (November 1, 2019 to March 20, 2020), 16 patients in the lockdown group (March 21 to April 19, 2020), and 74 patients in the post-lockdown group (April 20 to September 30, 2020). Patients admitted during lockdown had significantly longer time to first medical contact, longer door-to-needle-time, higher serum troponin T levels, worse left ventricular end-diastolic pressure, and higher need for circulatory support. After a median follow-up of 142 days, survival was significantly worse in STEMI patients of the lockdown group (log-rank: p = 0.0035).

Conclusions: This is the first prospective study on outcomes of STEMI patients admitted during public lockdown amid the COVID-19 pandemic. Our results suggest that lockdown might deteriorate outcomes of STEMI patients. Public health strategies to constrain spread of COVID-19, such as lockdown, have to be accompanied by distinct public instructions to ensure timely medical care in acute diseases such as STEMI.
Common Variants Associated With OSMR Expression Contribute to Carotid Plaque Vulnerability, but Not to Cardiovascular Disease in Humans
Authors: van Keulen Danielle , van Koeverden Ian D. , Boltjes Arjan , Princen Hans M. G. , van Gool Alain J. , de Borst Gert J. , Asselbergs Folkert W. , Tempel Dennie , Pasterkamp Gerard , van der Laan Sander W.
Published: April 2021

Background and Aims:Oncostatin M (OSM) signaling is implicated in atherosclerosis, however the mechanism remains unclear. We investigated the impact of common genetic variants inOSMand its receptors,OSMRandLIFR, on overall plaque vulnerability, plaque phenotype, intraplaqueOSMRandLIFRexpression, coronary artery calcification burden and cardiovascular disease susceptibility.

Methods and Results:We queried Genotype-Tissue Expression data and found that rs13168867 (C allele) was associated with decreasedOSMRexpression and that rs10491509 (A allele) was associated with increasedLIFRexpression in arterial tissues. No variant was significantly associated withOSMexpression.

We associated these two variants with plaque characteristics from 1,443 genotyped carotid endarterectomy patients in the Athero-Express Biobank Study. After correction for multiple testing, rs13168867 was significantly associated with an increased overall plaque vulnerability (β = 0.118 ± s.e. = 0.040,p= 3.00 × 10−3, C allele). Looking at individual plaque characteristics, rs13168867 showed strongest associations with intraplaque fat (β = 0.248 ± s.e. = 0.088,p= 4.66 × 10−3, C allele) and collagen content (β = −0.259 ± s.e. = 0.095,p= 6.22 × 10−3, C allele), but these associations were not significant after correction for multiple testing. rs13168867 was not associated with intraplaqueOSMRexpression. Neither was intraplaqueOSMRexpression associated with plaque vulnerability and no knownOSMReQTLs were associated with coronary artery calcification burden, or cardiovascular disease susceptibility. No associations were found for rs10491509 in theLIFRlocus.

Conclusions:Our study suggests that rs1316887 in the OSMR locus is associated with increased plaque vulnerability, but not with coronary calcification or cardiovascular disease risk. It remains unclear through which precise biological mechanisms OSM signaling exerts its effects on plaque morphology. However, the OSM-OSMR/LIFR pathway is unlikely to be causally involved in lifetime cardiovascular disease susceptibility.
The Effect of a Computerized Growth-Mindset Intervention on Teaching Students’ Mindset and Cognitive Stress Appraisal
Authors: Montagna Melissa Joy , Marksteiner Tamara , Dickhäuser Oliver
Published: April 2021

The present study assessed the impact of a one-time computerized mindset intervention on teaching students’ cognitive stress appraisal before an upcoming exam. Previous research highlights the long-term effectiveness of growth-mindset interventions. Based on theoretical assumptions derived from the transactional stress theory as well as recent empirical evidence on intelligence mindset and stress, we proposed that changing students’ mindset would also impact their cognitive stress appraisal. In order to test this hypothesis, a sample of teaching students received a one-time computerized growth-mindset intervention aiming to foster viewing abilities as incremental. We found a significant as well as relatively lasting impact on participants’ mindset but no significant effect on participants’ stress appraisal. Nevertheless, an exploratory mediation analysis revealed that the intervention’s effect on participants’ appraisal of their coping ability (as part of the cognitive stress appraisal) was fully mediated by participants’ mindset. The results highlight the effectiveness of the utilized intervention and provide first practical insights into how a person’s mindset and their stress appraisal relate.
Microalgae: The Future Supply House of Biohydrogen and Biogas
Authors: Wang Kexin , Khoo Kuan Shiong , Chew Kit Wayne , Selvarajoo Anurita , Chen Wei-Hsin , Chang Jo-Shu , Show Pau Loke
Published: April 2021

The non-renewable nature of fossil energy and the environmental pollution caused by its use, such as haze, make it very urgent to develop clean and efficient renewable energy. By using microalgae biomass as an alternative raw material energy sources like biohydrogen, methane can be produced through fermentation and photosynthesis. Unlike solar energy, which has the disadvantages of low energy density, instability and difficulty in storage, biohydrogen and biogas are one of the novel ideal energy sources at present. The utilization of microalgae has various attractive prospects in their production due to its cost-effectiveness, renewable biomass and ease of scaling-up technology. This paper discusses the latest microalgae biomass biohydrogen and biogas production technology including integrated biorefinery systems, co-production or mixed production techniques and puts forward the key problems to be solved in the development of microalgae biohydrogen production technology.
Spatial Distribution Characteristic of Antimony in Typical Paddy Soil of Eastern Hunan Province, China
Authors: Wang ChenRan , Wan DaJuan , Cao XueYing , Wang Huan , Chen JiaQi , Ouyang NingXiang , Zhang YangZhu , Tan ChangYin
Published: April 2021

Considering the eastern part of Hunan Province as the research area, 34 sampling sites were set up, 198 samples were collected from representative paddy soil, the distribution characteristics of antimony (Sb) were studied. The results showed that: (1) The content of Sb on the surface of paddy soil ranging from 0.07 to 11.00 mg/kg and the geometric mean was 1.56 mg/kg. (2) The distribution of contents of Sb in paddy soil in different areas was shown as Yueyang > Changsha > Zhuzhou > Xiangtan. (3) Sb showed a strong migration in paddy soil in the research area and its content increased initially and then decreased or gradually decreased with the increase of profile depth. (4) The content of Sb in the substratum was significantly affected by parent materials.
Inter-Individual Diversity Scaling Analysis of the Human Virome With Classic Diversity-Area Relationship (DAR) Modeling
Authors: Xiao Wanmeng , Ma Zhanshan (Sam)
Published: April 2021

The human virome is a critical component of the human microbiome, and it is believed to hold the richest diversity within human microbiomes. Yet, the inter-individual scaling (changes) of the human virome has not been formally investigated to the best of our knowledge. Here we fill the gap by applying diversity-area relationship (DAR) modeling (a recent extension to the classic species-area law in biodiversity and biogeography research) for analyzing four large datasets of the human virome with three DAR profiles: DAR scaling (z)—measuring the inter-individual heterogeneity in virome diversity, MAD (maximal accrual diversity: Dmax) and LGD ratio (ratio of local diversity to global diversity)—measuring the percentage of individual to population level diversity. Our analyses suggest: (i) The diversity scaling parameter (z) is rather resilient against the diseases as indicated by the lack of significant differences between the healthy and diseased treatments. (ii) The potential maximal accrual diversity (Dmax) is less resilient and may vary between the healthy and diseased groups or between different body sites. (iii) The LGD ratio of bacterial communities is much smaller than for viral communities, and relates to the comparatively greater heterogeneity between local vs. global diversity levels found for bacterial-biomes.
Luminal A Breast Cancer Co-expression Network: Structural and Functional Alterations
Authors: García-Cortés Diana , Hernández-Lemus Enrique , Espinal-Enríquez Jesús
Published: April 2021

Luminal A is the most common breast cancer molecular subtype in women worldwide. These tumors have characteristic yet heterogeneous alterations at the genomic and transcriptomic level. Gene co-expression networks (GCNs) have contributed to better characterize the cancerous phenotype. We have previously shown an imbalance in the proportion of intra-chromosomal (cis-) over inter-chromosomal (trans-) interactions when comparing cancer and healthy tissue GCNs. In particular, for breast cancer molecular subtypes (Luminal A included), the majority of high co-expression interactions connect gene-pairs in the same chromosome, a phenomenon that we have called loss of trans- co-expression. Despite this phenomenon has been described, the functional implication of this specific network topology has not been studied yet. To understand the biological role that communities of co-expressed genes may have, we constructed GCNs for healthy and Luminal A phenotypes. Network modules were obtained based on their connectivity patterns and they were classified according to their chromosomal homophily (proportion of cis-/trans- interactions). A functional overrepresentation analysis was performed on communities in both networks to observe the significantly enriched processes for each community. We also investigated possible mechanisms for which the loss of trans- co-expression emerges in cancer GCN. To this end we evaluated transcription factor binding sites, CTCF binding sites, differential gene expression and copy number alterations (CNAs) in the cancer GCN. We found that trans- communities in Luminal A present more significantly enriched categories than cis- ones. Processes, such as angiogenesis, cell proliferation, or cell adhesion were found in trans- modules. The differential expression analysis showed that FOXM1, CENPA, and CIITA transcription factors, exert a major regulatory role on their communities by regulating expression of their target genes in other chromosomes. Finally, identification of CNAs, displayed a high enrichment of deletion peaks in cis- communities. With this approach, we demonstrate that network topology determine, to at certain extent, the function in Luminal A breast cancer network. Furthermore, several mechanisms seem to be acting together to avoid trans- co-expression. Since this phenomenon has been observed in other cancer tissues, a remaining question is whether the loss of long distance co-expression is a novel hallmark of cancer.
Genetic Characterization of Mutations Related to Conidiophore Stalk Length Development in Aspergillus niger Laboratory Strain N402
Authors: Demirci Ebru , Arentshorst Mark , Yilmaz Baran , Swinkels Aram , Reid Ian D. , Visser Jaap , Tsang Adrian , Ram Arthur F. J.
Published: April 2021

Aspergillus nigeris an important filamentous fungus in industrial biotechnology for the production of citric acid and enzymes. In the late 1980s, theA. nigerN400/NRRL3 strain was selected for both fundamental and applied studies in relation to several processes including gluconic acid and protein production. To facilitate handling ofA. niger, the N400 wild-type strain was UV mutagenized in two consecutive rounds to generate N401 and N402. N402 was used as a reference laboratory strain and exhibits the phenotypes with reduced conidiophore stalk length and reduced radial growth. The conidiophore stalk length and radial growth ofA. nigerstrain N400 were determined and compared to N401 and N402. The length of N400 conidiophore stalks (2.52 ± 0.40 mm) was reduced in N401 and N402 to 0.66 ± 0.14 mm and 0.34 ± 0.06 mm, respectively. Whereas N400 reached a colony diameter of 6.7 ± 0.2 cm after 7 days, N401 and N402 displayed reduced radial growth phenotype (4.3 ± 0.1 and 4.1 ± 0.1, respectively). To identify the mutations (dubbedcspAandcspB) responsible for the phenotypes of N401 and N402, the genomes were sequenced and compared to the N400 genome sequence. A parasexual cross was performed between N400 and N402 derivatives to isolate segregants which allowed cosegregation analysis of single nucleotide polymorphisms and insertions and deletions among the segregants. The shorter conidiophore stalk and reduced radial growth in N401 (cspA) was found to be caused by a 9-kb deletion on chromosome III and was further narrowed down to a truncation of NRRL3_03857 which encodes a kinesin-like protein homologous to theA. nidulansUncA protein. The mutation responsible for the further shortening of conidiophore stalks in N402 (cspB) was found to be caused by a missense mutation on chromosome V in a hitherto unstudied C2H2 transcription factor encoded by the gene NRRL3_06646. The importance of these two genes in relation to conidiophore stalk length and radial growth was confirmed by single and double gene deletion studies. The mutations in the laboratory strain N402 should be taken into consideration when studying phenotypes in the N402 background.
Gene Expression Classifier Reveals Prognostic Osteosarcoma Microenvironment Molecular Subtypes
Authors: Song Yi-Jiang , Xu Yanyang , Deng Chuangzhong , Zhu Xiaojun , Fu Jianchang , Chen Hongmin , Lu Jinchang , Xu Huaiyuan , Song Guohui , Tang Qinglian , Wang Jin
Published: April 2021

Osteosarcoma (OSA) is the most common bone malignancy and displays high heterogeneity of molecular phenotypes. This study aimed to characterize the molecular features of OSA by developing a classification system based on the gene expression profile of the tumor microenvironment. Integrative analysis was performed using specimens and clinical information for OSA patients from the TARGET program. Using a matrix factorization method, we identified two molecular subtypes significantly associated with prognosis, S1 (infiltration type) and S2 (escape type). Both subtypes displayed unique features of functional significance features and cellular infiltration characteristics. We determined that immune and stromal infiltrates were abundant in subtype S1 compare to that in subtype S2. Furthermore, higher expression of immune checkpoint PDCD1LG2 and HAVCR2 was associated with improved prognosis, while a preferable chemotherapeutic response was associated with FAP-positive fibroblasts in subtype S1. Alternatively, subtype S2 is characterized by a lack of effective cytotoxic responses and loss of major histocompatibility complex class I molecule expression. A gene classifier was ultimately generated to enable OSA classification and the results were confirmed using the GSE21257 validation set. Correlations between the percentage of fibroblasts and/or fibrosis and CD8+ cells, and their clinical responses to chemotherapy were assessed and verified based on 47 OSA primary tumors. This study established a new OSA classification system for stratifying OSA patient risk, thereby further defining the genetic diversity of OSA and allowing for improved efficiency of personalized therapy.
Vaccine Inoculation Route Modulates Early Immunity and Consequently Antigen-Specific Immune Response
Authors: Rosenbaum Pierre , Tchitchek Nicolas , Joly Candie , Rodriguez Pozo André , Stimmer Lev , Langlois Sébastien , Hocini Hakim , Gosse Leslie , Pejoski David , Cosma Antonio , Beignon Anne-Sophie , Dereuddre-Bosquet Nathalie , Levy Yves , Le Grand Roger , Martinon Frédéric
Published: April 2021

Vaccination is one of the most efficient public healthcare measures to fight infectious diseases. Nevertheless, the immune mechanisms induced in vivo by vaccination are still unclear. The route of administration, an important vaccination parameter, can substantially modify the quality of the response. How the route of administration affects the generation and profile of immune responses is of major interest. Here, we aimed to extensively characterize the profiles of the innate and adaptive response to vaccination induced after intradermal, subcutaneous, or intramuscular administration with a modified vaccinia virus Ankara model vaccine in non-human primates. The adaptive response following subcutaneous immunization was clearly different from that following intradermal or intramuscular immunization. The subcutaneous route induced a higher level of neutralizing antibodies than the intradermal and intramuscular vaccination routes. In contrast, polyfunctional CD8+ T-cell responses were preferentially induced after intradermal or intramuscular injection. We observed the same dichotomy when analyzing the early molecular and cellular immune events, highlighting the recruitment of cell populations, such as CD8+ T lymphocytes and myeloid-derived suppressive cells, and the activation of key immunomodulatory gene pathways. These results demonstrate that the quality of the vaccine response induced by an attenuated vaccine is shaped by early and subtle modifications of the innate immune response. In this immunization context, the route of administration must be tailored to the desired type of protective immune response. This will be achieved through systems vaccinology and mathematical modeling, which will be critical for predicting the efficacy of the vaccination route for personalized medicine.
Behind the Scenes for the Designation of the Corales de Profundidad National Natural Park of Colombia
Authors: Alonso David , Vides-Casado Martha , Arias-Isaza Francisco , Zambrano Hernando , Rodriguez Emilio , Rocha-Gutierrez Venus , Herron Pilar , Castillo Anny
Published: April 2021

Deep-water environments make up 64% of the world’s oceans (nearly 202 million km2). In the past, the belief that this environment represented one of the most stable and unproductive ecosystems on the planet has been refuted by scientific research and the interest of potential productive sectors evaluating seabed resources. Human activities that threaten the health of deep-sea threats are uncontrolled and unregulated fishing, deep-sea mining, oil spills, marine litter, and climate change. With recent advances in technology, the study of deep-sea coral communities is a growing subject. The deep-sea corals are long-lived, slow-growing, and fragile systems, making them especially vulnerable to physical damage. In the last 40 years, Colombia has discovered these communities’ existence scarcely distributed in its territorial waters. A representative and irreplaceable sample of deep-sea coral formations triggered in 2013 the establishment of the Corales de Profundidad National Natural Park, a Marine Protected Area (MPA), which holds 40% of the marine biodiversity known in the Colombian Caribbean continental shelf-slope break. The MPA’s essential ecological value is theMadracis myriasterspecies’ presence as a primary habitat-forming organism, a unique habitat for the Caribbean and the world. Here we describe the MPA creation process in three phases. Firstly, in the provisioning phase, three main threats from human activities are identified. Secondly, in the preparation phase, the area’s conservation objectives and management category are defined, and the negotiation process with the fishing, communications, and oil and gas economic sectors is described. Lastly, in the designation phase, three MPA scenario proposals were evaluated, assessing the minimum distance, the possible effects of activities in the area as the main criteria for the buffer zone and the management of possible future impacts. As a result, the most extended boundary was adopted, guaranteeing these communities’ conservation despite the limited information to carry out a complete planning process. The MPA designation is considered the first experience of deep communities in the Southern Caribbean and an example that it is possible to have effective conservation agreements with economic sectors.
Magneto-Induced Normal Stress of Magnetorheological Gel Under Quasi-Statically Monotonic and Periodically Cyclic Loading
Authors: Mao Runsong , Ye Xudan , Wang Huixing , Zhang Guang , Wang Jiong
Published: April 2021

Magnetorheological (MR) gel, an analog of MR fluid, is a novel kind of magnetic-responsive material. In this article, the influence of quasi-statically monotonic loading and periodically cyclic loading on the normal stress behavior of MR gel (MRG) is systemically investigated. Firstly, carbonyl iron powder (CIP) and soft polymer were adopted for the fabrication of MRG. Then, the variations of normal stress with shear strain were tested under different excited magnetic fields, shear rates, CIP contents, and shear strain amplitudes. It was found that the normal stress behavior of MRG exhibits three prominent stages: a sudden rise at the beginning, followed by a rapid decrease, and then a final steady-state value. The experiments also indicated that the excited magnetic field, compared with other influencing factors, has the most critical effect on the normal stress behavior of MRG. The corresponding mechanisms of various phenomena were methodically discussed. Furthermore, the ratio of shear stress to normal stress was proposed to better comprehend the mechanism of the evolution of internal microstructures of MRG and MR effects from a novel perspective. The results implied that the ratio has a close relation to the excited magnetic field and CIP content of MRG. The increase of normal stress is helpful for the fabrication of MRG with a high-efficiency MR effect.
Chemical Synthesis and Antipseudomonal Activity of Al-Doped NiO Nanoparticles
Authors: Irum Sidra , Andleeb Saadia , Sardar Sumbal , Mustafa Zeeshan , Ghaffar Ghazanfar , Mumtaz M. , Mubasher  , Arslan Muhammad , Abbas Mudassar
Published: April 2021

Synthesis of efficient antibacterial agents has become extremely important due to the emergence of antibiotic resistant bacteria. This is especially true for Pseudomonas aeruginosa, an opportunistic pathogen having ability to rapidly develop resistance to multiple classes of antibiotics thus limiting the efficacy of antibiotics approved for clinical use. Aluminum (Al)-doped NiO nanoparticles are of special interest due to their enhanced antipseudomonal properties at certain Al-doping levels. The composite hydroxide mediated (CHM) approach was opted for the synthesis of pure nickel oxide (NiO) and Al-doped nickel oxide (Ni1–xAlxO; x = 5, 10, 15, 20, 25, and 30 wt.%) nanoparticles. X-ray diffraction (XRD) technique was used for structural analysis of these nanoparticles. Morphology and elemental composition of these nanoparticles were investigated by scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy, respectively. The optical properties were investigated by using UV-visible spectroscopy and Kubelka-Munk Theory and Tauc relation were employed for energy bandgap calculation of these nanoparticles. The antibacterial activity of representative Al-doped NiO nanoparticles was assessed on multidrug-resistant clinical P. aeruginosa strains. The agar well and disc-diffusion methods were used to assess the antibacterial efficacy of (Al)-doped NiO compared to pure NiO nanoparticles. Interestingly, a gradual increase in the antibacterial activity was observed with increasing Al-doping concentration and the highest antibacterial activity was observed at x = 15 wt.% Al-doping concentration. The antipseudomonal efficacy of Ni1–xAlxO nanoparticles was comparable to aztreonam antibiotic, primarily used for Gram-negative bacterial infections. Hence, it is proposed that these nanoparticles can be used for coating surgical devices, bone prostheses, medical implants, antibacterial clothing and in pharmaceutical formulations as burn ointments to produce the antimicrobial effect.
First Report of a Foodborne Salmonella enterica Serovar Gloucester (4:i:l,w) ST34 Strain Harboring blaCTX–M–55 and qnrS Genes Located in IS26-Mediated Composite Transposon
Authors: Li Lili , Olsen Rikke Heidemann , Song Anhua , Xiao Jian , Wang Chong , Meng Hecheng , Shi Lei
Published: April 2021

Extended-spectrum β-lactamases (ESBLs) production and (fluoro)quinolone (FQ) resistance among Salmonella pose a public health threat. The objective of this study was the phenotypic and genotypic characterization of an ESBL-producing and nalidixic acid-resistant Salmonella enterica serovar Gloucester isolate (serotype 4:i:l,w) of sequence type 34 (ST34) from ready-to-eat (RTE) meat products in China. Whole-genome short and long read sequencing (HiSeq and MinION) results showed that it contained blaCTX–M–55, qnrS1, and tetB genes, with blaCTX–M–55 and qnrS1 located in chromosomal IS26-mediated composite transposon (IS26–qnrS1–IS3–Tn3–orf–blaCTX–M–55–ISEcp1–IS26). The same genetic structure was found in the chromosome of S. enterica subsp. enterica serovar Typhimurium strain and in several plasmids of Escherichia coli, indicating that the IS26-mediated composite transposon in the chromosome of S. Gloucester may originate from plasmids of E. coli and possess the ability to disseminate to Salmonella and other bacterial species. Besides, the structural unit qnrS1–IS3–Tn3–orf–blaCTX–M–55 was also observed to be linked with ISKpn19 in both the chromosomes and plasmids of various bacteria species, highlighting the contribution of the insertion sequences (IS26 and ISKpn19) to the co-dissemination of blaCTX–M–55 and qnrS1. To our knowledge, this is the first description of chromosomal blaCTX–M–55 and qnrS in S. Gloucester from RTE meat products. Our work expands the host range and provides additional evidence of the co-transfer of blaCTX–M–55 and qnrS1 among different species of Salmonella through the food chain.
Exploring the Antibiotic Resistance Burden in Livestock, Livestock Handlers and Their Non-Livestock Handling Contacts: A One Health Perspective
Authors: Hickman Rachel A. , Leangapichart Thongpan , Lunha Kamonwan , Jiwakanon Jatesada , Angkititrakul Sunpetch , Magnusson Ulf , Sunde Marianne , Järhult Josef D.
Published: April 2021

Antibiotics are freqeuently used in the livestock sector in low- and middle-income countries for treatment, prophylaxis, and growth promotion. However, there is limited information into the zoonotic prevalence and dissemination patterns of antimicrobial resistance (AMR) within these environments. In this study we used pig farming in Thailand as a model to explore AMR; 156 pig farms were included, comprising of small-sized (<50 sows) and medium-sized (≥100 sows) farms, where bacterial isolates were selectively cultured from animal rectal and human fecal samples. Bacterial isolates were subjected to antimicrobial susceptibility testing (AST), and whole-genome sequencing. Our results indicate extensive zoonotic sharing of antibiotic resistance genes (ARGs) by horizontal gene transfer. Resistance to multiple antibiotics was observed with higher prevalence in medium-scale farms. Zoonotic transmission of colistin resistance in small-scale farms had a dissemination gradient from pigs to handlers to non-livestock contacts. We highly recommend reducing the antimicrobial use in animals’ feeds and medications, especially the last resort drug colistin.
Role of Virally Encoded Circular RNAs in the Pathogenicity of Human Oncogenic Viruses
Authors: Avilala Janardhan , Becnel David , Abdelghani Ramsy , Nanbo Asuka , Kahn Jacob , Li Li , Lin Zhen
Published: April 2021

Human oncogenic viruses are a group of important pathogens that etiologically contribute to at least 12% of total cancer cases in the world. As an emerging class of non-linear regulatory RNA molecules, circular RNAs (circRNAs) have gained increasing attention as a crucial player in the regulation of signaling pathways involved in viral infection and oncogenesis. With the assistance of current circRNA enrichment and detection technologies, numerous novel virally-encoded circRNAs (vcircRNAs) have been identified in the human oncogenic viruses, initiating an exciting new era of vcircRNA research. In this review, we discuss the current understanding of the roles of vcircRNAs in the respective viral infection cycles and in virus-associated pathogenesis.
Pseudmonas cannabina pv. alisalensis TrpA Is Required for Virulence in Multiple Host Plants
Authors: Sakata Nanami , Ishiga Takako , Ishiga Yasuhiro
Published: April 2021

Pseudomonas cannabina pv. alisalensis (Pcal) causes bacterial leaf spot and blight of Brassicaceae and Poaceae. We previously identified several potential Pcal virulence factors with transposon mutagenesis. Among these a trpA mutant disrupted the tryptophan synthase alpha chain, and had an effect on disease symptom development and bacterial multiplication. To assess the importance of TrpA in Pcal virulence, we characterized the trpA mutant based on inoculation test and Pcal gene expression profiles. The trpA mutant showed reduced virulence when dip- and syringe-inoculated on cabbage and oat. Moreover, epiphytic bacterial populations of the trpA mutant were also reduced compared to the wild-type (WT). These results suggest that TrpA contributes to bacterial multiplication on the leaf surface and in the apoplast, and disease development. Additionally, several Brassicaceae (including Japanese radish, broccoli, and Chinese cabbage) also exhibited reduced symptom development when inoculated with the trpA mutant. Moreover, trpA disruption led to downregulation of bacterial virulence genes, including type three effectors (T3Es) and the phytotoxin coronatine (COR), and to upregulation of tryptophan biosynthesis genes. These results indicate that a trade-off between virulence factor production and Pcal multiplication with tryptophan might be regulated in the infection processes.
Isolation and Identification of a Recombinant Porcine Epidemic Diarrhea Virus With a Novel Insertion in S1 Domain
Authors: Li Dongliang , Li Yongtao , Liu Yunchao , Chen Yumei , Jiao Wenqiang , Feng Hua , Wei Qiang , Wang Jucai , Zhang Yuhang , Zhang Gaiping
Published: April 2021

Porcine epidemic diarrhea virus (PEDV) is the major pathogen that causes diarrhea and high mortality in newborn piglets with devastating impact to the pig industry. Recombination and mutation are the main driving forces of viral evolution and genetic diversity of PEDV. In 2016, an outbreak of diarrhea in piglets occurred in an intensive pig farm in Central China. A novel PEDV isolate (called HNAY) was successfully isolated from clinical samples. Sequence analysis and alignment showed that HNAY possessed 21-nucleotide (nt) insertion in its S1 gene, which has never been reported in other PEDV isolates. Moreover, the sequence of the insertion was identical with the sequence fragment in PEDV N gene. Notably, the HNAY strain exhibited two unique mutations (T500A and L521Y) in the neutralizing epitopes of the S1 protein that were different from those of other PEDV variant strains and CV777-based vaccine strains. Additionally, PEDV HNAY might be derived from a natural recombination between two Chinese variant PEDV strains. Animal experiments demonstrated that HNAY displayed higher pathogenicity compared with two other clinical isolates. This study lays the foundation for better understanding of the genetic evolution and molecular pathogenesis of PEDV.
Elevated Neutrophil to Lymphocyte Ratio Associated With Increased Risk of Recurrent Vascular Events in Older Minor Stroke or TIA Patients
Authors: Chan Ka Lung , Feng Xueyan , Ip Bonaventure , Huang Shangmeng , Ma Sze Ho , Fan Florence S. Y. , Ip Hing Lung , Huang Li’an , Mok Vincent C. T. , Soo Yannie O. Y. , Leung Thomas W. , Leng Xinyi
Published: April 2021

Background

The risk of recurrent stroke following a minor stroke or transient ischemic attack (TIA) is high, when inflammation might play an important role. We aimed to evaluate the value of neutrophil to lymphocyte ratio (NLR) in predicting composite cardiovascular events in patients with minor stroke and TIA.

Methods

Consecutive patients with acute minor stroke or TIA admitted within 24 h of symptoms onset during a 5-year period in a prospective stroke registry were analyzed. We calculated the NLR dividing absolute neutrophil count by absolute lymphocyte count tested within 24 h of admission. NLR ≥4th quartile was defined as high NLR. A composite outcome was defined as stroke, acute coronary syndrome or vascular death within 1 year. We investigated associations between NLR and the composite outcome in univariate and multivariate analyses, among all patients and in those aged over 60 years (i.e., older patients).

Results

Overall, 841 patients (median age 68 years; 60.4% males) were recruited. No significant independent association was found between NLR and the composite outcome in multivariate analysis in the overall cohort. Among the 612 older patients (median age 73 years; 59.2% males), the median NLR was 2.76 (interquartile range 1.96−4.00) and 148 (24.2%) patients had high NLR. The composite outcome occurred in 77 (12.6%) older patients, who were more likely to have a high NLR (39.0% versus 22.1%; p = 0.001) than those without a composite outcome. In multivariate logistic regression, high NLR (adjusted odds ratio 2.00; 95% confidence interval 1.07−3.75; p = 0.031) was independently associated with the composite outcome in older patients.

Conclusion

In older (aged ≥60 years) patients with acute minor stroke or TIA, a higher NLR, a marker of systemic inflammation that can be easily obtained in routine blood tests, is an independent predictor of subsequent cardiovascular events.
Application of the Mirror Technique for Three-Dimensional Electron Microscopy of Neurochemically Identified GABA-ergic Dendrites
Authors: Talapka Petra , Kocsis Zsolt , Marsi Lívia Diána , Szarvas Vera Etelka , Kisvárday Zoltán F.
Published: April 2021

In the nervous system synaptic input arrives chiefly on dendrites and their type and distribution have been assumed pivotal in signal integration. We have developed an immunohistochemistry (IH)-correlated electron microscopy (EM) method – the “mirror” technique – by which synaptic input to entire dendrites of neurochemically identified interneurons (INs) can be mapped due preserving high-fidelity tissue ultrastructure. Hence, this approach allows quantitative assessment of morphometric parameters of synaptic inputs along the whole length of dendrites originating from the parent soma. The method exploits the fact that adjoining sections have truncated or cut cell bodies which appear on the common surfaces in a mirror fashion. In one of the sections the histochemical marker of the GABAergic subtype, calbindin was revealed in cell bodies whereas in the other section the remaining part of the very same cell bodies were subjected to serial section EM to trace and reconstruct the synaptology of entire dendrites. Here, we provide exemplary data on the synaptic coverage of two dendrites belonging to the same calbindin-D28K immunopositive IN and determine the spatial distribution of asymmetric and symmetric synapses, surface area and volume of the presynaptic boutons, morphometric parameters of synaptic vesicles, and area extent of the active zones.
The Effect of Surface Coating of Iron Oxide Nanoparticles on Magnetic Resonance Imaging Relaxivity
Authors: Ahmadpoor Fatemeh , Masood Atif , Feliu Neus , Parak Wolfgang J. , Shojaosadati Seyed Abbas
Published: April 2021

Iron oxide nanoparticles (IONPs) with acceptable biocompatibility and size-dependent magnetic properties can be used as efficient contrast agents in magnetic resonance imaging (MRI). Herein, we have investigated the impact of particle size and surface coating on the proton relaxivity of IONPs, as well as engineering of small IONPs' surface coating as a strategy for achieving gadolinium-free contrast agents. Accordingly, polymer coating using poly(isobutylene-alt-maleic anhydride) (PMA) with overcoating of the original ligands was applied for providing colloidal stability to originally oleic acid–capped IONPs in aqueous solution. In case of replacement of the original ligand shell, the polymer had been modified with dopamine. Furthermore, the colloidal stability of the polymer-coated IONPs was evaluated in NaCl and bovine serum albumin (BSA) solutions. The results indicate that the polymer-coated IONPs which involved replacement of the original ligands exhibited considerably better colloidal stability and higher proton relaxivity in comparison to polymer-coated IONPs with maintained ligand shell. The highest r2/r1 we obtained was around 300.
The Ototoxicity of Antimalarial Drugs—A State of the Art Review
Authors: Jozefowicz-Korczynska Magdalena , Pajor Anna , Lucas Grzelczyk Weronika
Published: April 2021

This review summarizes current knowledge about the occurrence of hearing and balance disorders after antimalarial drugs treatment. It also examines the clinical applications of antimalarials, their mechanisms behind this ototoxicity and how it can be monitored. It includes studies with larger numbers of patients and those in which auditory function was assessed using audiological tests. Some antimalarials have been repurposed for other conditions like autoimmune disorders, rheumatic diseases, some viral diseases and cancers. While old antimalarial drugs, such as quinoline derivatives, are known to demonstrate ototoxicity, a number of new synthetic antimalarial agents particularly artemisinin derivatives, demonstrate unknown ototoxicity. Adverse audiovestibular effects vary depending on the medication itself, its dose and route of administration, as well as the drug combination, treated disease and individual predispositions of the patient. Dizziness was commonly reported, while vestibular symptoms, hearing loss and tinnitus were observed much less frequently, and most of these symptoms were reversible. As early identification of ototoxic hearing loss is critical to introducing possible alternative treatments with less ototoxic medications, therefore monitoring systems of those drugs ototoxic side effects are much needed.
Influence of Early Enteral Nutrition on Clinical Outcomes in Neurocritical Care Patients With Intracerebral Hemorrhage
Authors: Peng Jianhua , Volbers Bastian , Sprügel Maximilian I. , Hoelter Philip , Engelhorn Tobias , Jiang Yong , Kuramatsu Joji B. , Huttner Hagen B. , Dörfler Arnd , Schwab Stefan , Gerner Stefan T.
Published: April 2021

Objective: Early enteral nutrition (EEN) represents the current standard of care for patients treated in general intensive care units (ICU). Specific nutritional recommendations for patients receiving dedicated neurocritical care are not established. This study investigated associations of EEN with clinical outcomes for patients suffering from intracerebral hemorrhage treated at a neurological ICU (NICU).

Methods: This retrospective cohort study included patients admitted to the NICU with atraumatic ICH over a 4-year period. Nutritional data, demographic, clinical, radiological, and laboratory characteristics were assessed. EEN was defined as any enteral nutrition within 48 hours after admission. Comparisons were undertaken for patients with EEN vs. those without, further propensity score (PS) matching (caliper 0.2; one: many) was used to account for baseline imbalances. Primary outcome was the modified Rankin Scale (0–3 = favorable, 4–6 = unfavorable) at 12 months, secondary outcomes comprised perihemorrhagic edema (PHE) volume, infectious complications during the hospital stay, and mRS at 3 months, as well as mortality rates at 3 and 12 months.

Results: Of 166 ICH-patients treated at the NICU, 51 (30.7%) patients received EEN, and 115 (69.3%) patients received no EEN (nEEN). After propensity score matching, calories delivered from enteral nutrition (EEN 161.4 [106.4–192.3] kcal/day vs. nEEN 0.0 [0.0–0.0], P < 0.001) and the total calories (EEN 190.0 [126.0–357.0] kcal/day vs. nEEN 33.6 [0.0–190.0] kcal/day, P < 0.001) were significantly different during the first 48 h admitted in NICU. Functional outcome at 12 months (mRS 4–6, EEN 33/43 [76.7%] vs. nEEN, 49/64 [76. 6%]; P = 1.00) was similar in the two groups. There were neither differences in mRS at 3 months, nor in mortality rates at 3 and 12 months between the two groups. EEN did not affect incidence of infective complications or gastrointestinal adverse events during the hospital stay; however, EEN was associated with significantly less extent of PHE evolution [maximum absolute PHE (OR 0.822, 95% CI 0.706–0.957, P = 0.012); maximum relative PHE (OR 0.784, 95% CI 0.646–0.952, P = 0.014)].

Conclusion: In our study, EEN was associated with reduced PHE in ICH-patients treated at a NICU. However, this observation did not translate into improved survival or functional outcome at 3 and 12 months.