bluuebunny/crossref_metadata_2025 huggingface dataset:
A Signature-Based Classification of Gastric Cancer That Stratifies Tumor Immunity and Predicts Responses to PD-1 Inhibitors
Authors: Li Song , Gao Jing , Xu Qian , Zhang Xue , Huang Miao , Dai Xin , Huang Kai , Liu Lian
Published: June 2021

Gastric cancer is a leading cause of cancer-related deaths with considerable heterogeneity among patients. Appropriate classifications are essential for prognosis prediction and individualized treatment. Although immunotherapy showed potential efficacy in a portion of patients with gastric cancer, few studies have tried to classify gastric cancer specifically based on immune signatures. In this study, we established a 3-subtype cluster with low (CLIM), medium (CMIM), and high (CHIM) enrichment of immune signatures based on immunogenomic profiling. We validated the classification in multiple independent datasets. The CHIM subtype exhibited a relatively better prognosis and showed features of “hot tumors”, including low tumor purity, high stromal components, overexpression of immune checkpoint molecules, and enriched tumor-infiltrated immune cells (activated T cells and macrophages). In addition, CHIM tumors were also characterized by frequent ARID1A mutation, rare TP53 mutation, hypermethylation status, and altered protein expression (HER2, β-catenin, Cyclin E1, PREX1, LCK, PD-L1, Transglutaminase, and cleaved Caspase 7). By Gene Set Variation Analysis, “TGFβ signaling pathway” and “GAP junction” were enriched in CLIM tumors and inversely correlated with CD8+ and CD4+ T cell infiltration. Of note, the CHIM patients showed a higher response rate to immunotherapy (44.4% vs. 11.1% and 16.7%) and a more prolonged progression-free survival (4.83 vs. 1.86 and 2.75 months) than CMIM and CLIM patients in a microsatellite-independent manner. In conclusion, the new immune signature-based subtypes have potential therapeutic and prognostic implications for gastric cancer management, especially immunotherapy.
Encapsulation and Algicidal Properties of Fermentation Products From Vibrio brasiliensis H115
Authors: Ouyang Liao , Liu Yan , Chen Huirong , Zaynab Madiha , Yang Xuewei , Wang Shilin , Li Shuangfei
Published: June 2021

Algicidal bacteria offer an eco-friendly and promising approach for controlling harmful algae blooms (HABs). In this study, repeated batch fermentation of immobilized algicidal bacterium Vibrio brasiliensis H115 was preformed to enhance the productivity of the algicidal compounds. The highest algicidal efficiency of the fermentation products against Akashiwo sanguinea (100%) was achieved when the fermentation time was decreased from 24 to 14 h. The cell-free fermentation broth was then spray-dried and floating microcapsules were prepared from the dried powder. The optimum preparation conditions for floating microcapsules were: sodium alginate (SA), 3%; CaCO3: SA (mass ratio), 3:4; CaCl2, 3%; citric acid, 4%; ethylcellulose, 2%; crosslinking time, 30 min. Under the optimal conditions, the floating microcapsules displayed efficient A. sanguinea cell lysis ability and the algicidal efficiency increased from 10.62% (4 h) to 100% (24 h). These results suggest that the floating microcapsules could potentially be practically used for controlling the outbreaks of A. sanguinea.
International Quality-Controlled Ocean Database (IQuOD) v0.1: The Temperature Uncertainty Specification
Authors: Cowley Rebecca , Killick Rachel E. , Boyer Tim , Gouretski Viktor , Reseghetti Franco , Kizu Shoichi , Palmer Matthew D. , Cheng Lijing , Storto Andrea , Le Menn Marc , Simoncelli Simona , Macdonald Alison M. , Domingues Catia M.
Published: June 2021

Ocean temperature observations are crucial for a host of climate research and forecasting activities, such as climate monitoring, ocean reanalysis and state estimation, seasonal-to-decadal forecasts, and ocean forecasting. For all of these applications, it is crucial to understand the uncertainty attached to each of the observations, accounting for changes in instrument technology and observing practices over time. Here, we describe the rationale behind the uncertainty specification provided for all in situ ocean temperature observations in the International Quality-controlled Ocean Database (IQuOD) v0.1, a value-added data product served alongside the World Ocean Database (WOD). We collected information from manufacturer specifications and other publications, providing the end user with uncertainty estimates based mainly on instrument type, along with extant auxiliary information such as calibration and collection method. The provision of a consistent set of observation uncertainties will provide a more complete understanding of historical ocean observations used to examine the changing environment. Moving forward, IQuOD will continue to work with the ocean observation, data assimilation and ocean climate communities to further refine uncertainty quantification. We encourage submissions of metadata and information about historical practices to the IQuOD project and WOD.
Temperature Controlled Evolution of Pure Phase Cu9S5 Nanoparticles by Solvothermal Process
Authors: Olatunde Olalekan C. , Onwudiwe Damian C.
Published: June 2021

Copper sulphides are one of the most explored semiconductor metal sulphides because of their stoichiometric and morphological dependent optical and electrical properties, which makes them tunable for numerous optoelectronic applications. Stoichiometrically, copper sulphides exist in numerous structures which varies from the copper-rich phase (Cu2S) to the copper-deficient phase (CuS). Within these extreme stoichiometric phases lies numerous non-stoichiometric phases with interesting optical properties. Different solvothermal techniques have been explored for the synthesis of copper sulphides; however, the thermal decomposition of single source precursors provides a facile and tunable route to the synthesis of pure phase copper sulphides of different stoichiometries. In this study, copper (II) dithiocarbamate have been explored as a single source precursor compound to study the evolution of pure phase Cu9S5. Below 240°C, mixed phase of CuS and Cu9S5 were obtained, and as the temperature was increased beyond 240°C, keeping other reaction condition unchanged, the precursor yielded pure phase of Cu9S5. This phase selectivity at high temperature was attributed to the increased reducing ability of oleylamine (used as solvent) which enhance the evolution of the copper rich phase at high temperature. Optical and morphological studies of the pure phase Cu9S5, showed properties that varied considerably with the temperature of synthesis.
Neonatal Sepsis: The Impact of Carbapenem-Resistant and Hypervirulent Klebsiella pneumoniae
Authors: Mukherjee Subhankar , Mitra Shravani , Dutta Shanta , Basu Sulagna
Published: June 2021

The convergence of a vulnerable population and a notorious pathogen is devastating, as seen in the case of sepsis occurring during the first 28 days of life (neonatal period). Sepsis leads to mortality, particularly in low-income countries (LICs) and lower-middle-income countries (LMICs). Klebsiella pneumoniae, an opportunistic pathogen is a leading cause of neonatal sepsis. The success of K. pneumoniae as a pathogen can be attributed to its multidrug-resistance and hypervirulent-pathotype. Though the WHO still recommends ampicillin and gentamicin for the treatment of neonatal sepsis, K. pneumoniae is rapidly becoming untreatable in this susceptible population. With escalating rates of cephalosporin use in health-care settings, the increasing dependency on carbapenems, a “last resort antibiotic,” has led to the emergence of carbapenem-resistant K. pneumoniae (CRKP). CRKP is reported from around the world causing outbreaks of neonatal infections. Carbapenem resistance in CRKP is largely mediated by highly transmissible plasmid-encoded carbapenemase enzymes, including KPC, NDM, and OXA-48-like enzymes. Further, the emergence of a more invasive and highly pathogenic hypervirulent K. pneumoniae (hvKP) pathotype in the clinical context poses an additional challenge to the clinicians. The deadly package of resistance and virulence has already limited therapeutic options in neonates with a compromised defense system. Although there are reports of CRKP infections, a review on neonatal sepsis due to CRKP/ hvKP is scarce. Here, we discuss the current understanding of neonatal sepsis with a focus on the global impact of the CRKP, provide a perspective regarding the possible acquisition and transmission of the CRKP and/or hvKP in neonates, and present strategies to effectively identify and combat these organisms.
Case Report: Metagenomic Next-Generation Sequencing in Diagnosis of Legionella pneumophila Pneumonia in a Patient After Umbilical Cord Blood Stem Cell Transplantation
Authors: Wang Yangyan , Dai Yuanyuan , Lu Huaiwei , Chang Wenjiao , Ma Fan , Wang Ziran , Liu Zhican , Ma Xiaoling
Published: June 2021

We report a case of hospital-acquired Legionella pneumonia that was detected by metagenomic next-generation sequencing (mNGS) of blood from a 7-year-old girl after umbilical cord blood stem cell transplantation (UCBT) with myelodysplastic syndrome. UCBT is traditionally associated with an increased risk of infection, particularly during the first 3 months after transplantation. Controlling interstitial pneumonia and severe infection is the key to reducing patient mortality from infection. Legionella pneumophila can cause a mild cough to rapidly fatal pneumonia. After mNGS confirmed that the pathogen was L. pneumophila, azithromycin, cefoperazone sulbactam, and posaconazole were used for treatment, and the patient's temperature decreased and remained normal. The details of this case highlight the benefits of the timely use of metagenomic NGS to identify pathogens for the survival of immunocompromised patients.
Clinical and Microbiological Characteristics of a Community-Acquired Carbapenem-Resistant Escherichia coli ST410 Isolate Harbouring blaNDM-5-Encoding IncX3-Type Plasmid From Blood
Authors: Gu Ji-Na , Chen Lin , Weng Xing-Bei , Yang Xiao-Yan , Pan Dan-Mei
Published: June 2021

Objectives: The aim of this research was to investigate the clinical and microbiological characteristics of a case of community-acquired carbapenem-resistant Escherichia coli isolated from a patient with a bloodstream infection in China.

Methods:Escherichia coli Huamei202001 was recovered from the first blood culture from a patient hospitalised in China. An antimicrobial susceptibility test was performed, and the genome was sequenced on an Illumina HiSeq X 10 platform with a 150-bp paired-end approach. The generated sequence reads were assembled using Unicycler, and the whole genome sequence data were analysed using bioinformatics tools. Moreover, the patient and her main family members obtained a faecal sample screening test for CRE, the positive strain was further isolated and the identification and antimicrobial susceptibility testing was performed.

Results:Escherichia coli Huamei202001 belonged to sequence type 410. In addition, a blaNDM-5-encoding IncX3-type plasmid was responsible for the spreading of carbapenem resistance. Only the patient was detected as having a positive faecal sample screening test for CRE. Strain Fec01 was identified as E. coli, and the antibiotic susceptibility profile was the same as that of E. coli Huamei202001.

Conclusions:Escherichia coli Huamei202001 is defined as community-acquired carbapenem-resistant Enterobacteriaceae. The clone ST410 that harbours the blaNDM-5-encoding IncX3-type plasmid is causing new high-risk clones globally. Thus, infection control measures should be strengthened to curb the dissemination of IncX3.
Assessing METland® Design and Performance Through LCA: Techno-Environmental Study With Multifunctional Unit Perspective
Authors: Peñacoba-Antona Lorena , Senán-Salinas Jorge , Aguirre-Sierra Arantxa , Letón Pedro , Salas Juan José , García-Calvo Eloy , Esteve-Núñez Abraham
Published: June 2021

Conventional wastewater treatment technologies are costly and energy demanding; such issues are especially remarkable when small communities have to clean up their pollutants. In response to these requirements, a new variety of nature-based solution, so-called METland®, has been recently develop by using concepts from Microbial Electrochemical Technologies (MET) to outperform classical constructed wetland regarding wastewater treatment. Thus, the current study evaluates two operation modes (aerobic and aerobic–anoxic) of a full-scale METland®, including a Life Cycle Assessment (LCA) conducted under a Net Environmental Balance perspective. Moreover, a combined technical and environmental analysis using a Net Eutrophication Balance (NEuB) focus concluded that the downflow (aerobic) mode achieved the highest removal rates for both organic pollutant and nitrogen, and it was revealed as the most environmentally friendly design. Actually, aerobic configuration outperformed anaero/aero-mixed mode in a fold-range from 9 to 30%. LCA was indeed recalculated under diverse Functional Units (FU) to determine the influence of each FU in the impacts. Furthermore, in comparison with constructed wetland, METland® showed a remarkable increase in wastewater treatment capacity per surface area (0.6 m2/pe) without using external energy. Specifically, these results suggest that aerobic–anoxic configuration could be more environmentally friendly under specific situations where high N removal is required. The removal rates achieved demonstrated a robust adaptation to influent variations, revealing a removal average of 92% of Biology Oxygen Demand (BOD), 90% of Total Suspended Solids (TSS), 40% of total nitrogen (TN), and 30% of total phosphorus (TP). Moreover, regarding the global warming category, the overall impact was 75% lower compared to other conventional treatments like activated sludge. In conclusion, the LCA revealed that METland® appears as ideal solution for rural areas, considering the low energy requirements and high efficiency to remove organic pollutants, nitrogen, and phosphates from urban wastewater.
Periodontitis Exacerbates and Promotes the Progression of Chronic Kidney Disease Through Oral Flora, Cytokines, and Oxidative Stress
Authors: Li Ling , Zhang Ya-Li , Liu Xing-Yu , Meng Xiang , Zhao Rong-Quan , Ou Lin-Lin , Li Bao-Zhu , Xing Tian
Published: June 2021

Periodontitis is a type of systemic immune inflammation that is caused by the complex infection of a variety of microorganisms in the subgingival plaque and the imbalance of the microbial ecological environment in the mouth. Periodontitis and chronic kidney disease (CKD) share many risk factors, such as obesity, smoking, and age. A growing body of data supports a strong correlation between periodontitis and kidney disease. Evidence supports the role of periodontal inflammation and elevated serum inflammatory mediators in renal atherosclerosis, renal deterioration, and end-stage renal disease (ESRD) development. Periodontitis is a risk factor for kidney disease. However, to our knowledge, there are few studies detailing the possible link between periodontitis and CKD. This review summarizes the possible mechanisms underlying periodontitis and CKD. More importantly, it highlights novel and potential pathogenic factors for CKD, including bacteria, pro-inflammatory mediators and oxidative stress. However, most research on the relationship between periodontitis and systemic disease has not determined causality, and these diseases are largely linked by bidirectional associations. Future research will focus on exploring these links to contribute to new treatments for CKD.
Ecological Divergence Within the Enterobacterial Genus Sodalis: From Insect Symbionts to Inhabitants of Decomposing Deadwood
Authors: Tláskal Vojtěch , Pylro Victor Satler , Žifčáková Lucia , Baldrian Petr
Published: June 2021

The bacterial genus Sodalis is represented by insect endosymbionts as well as free-living species. While the former have been studied frequently, the distribution of the latter is not yet clear. Here, we present a description of a free-living strain, Sodalis ligni sp. nov., originating from decomposing deadwood. The favored occurrence of S. ligni in deadwood is confirmed by both 16S rRNA gene distribution and metagenome data. Pangenome analysis of available Sodalis genomes shows at least three groups within the Sodalis genus: deadwood-associated strains, tsetse fly endosymbionts and endosymbionts of other insects. This differentiation is consistent in terms of the gene frequency level, genome similarity and carbohydrate-active enzyme composition of the genomes. Deadwood-associated strains contain genes for active decomposition of biopolymers of plant and fungal origin and can utilize more diverse carbon sources than their symbiotic relatives. Deadwood-associated strains, but not other Sodalis strains, have the genetic potential to fix N2, and the corresponding genes are expressed in deadwood. Nitrogenase genes are located within the genomes of Sodalis, including S. ligni, at multiple loci represented by more gene variants. We show decomposing wood to be a previously undescribed habitat of the genus Sodalis that appears to show striking ecological divergence.
Rhizobial–Host Interactions and Symbiotic Nitrogen Fixation in Legume Crops Toward Agriculture Sustainability
Authors: Goyal Ravinder K. , Mattoo Autar K. , Schmidt Maria Augusta
Published: June 2021

Symbiotic nitrogen fixation (SNF) process makes legume crops self-sufficient in nitrogen (N) in sharp contrast to cereal crops that require an external input by N-fertilizers. Since the latter process in cereal crops results in a huge quantity of greenhouse gas emission, the legume production systems are considered efficient and important for sustainable agriculture and climate preservation. Despite benefits of SNF, and the fact that chemical N-fertilizers cause N-pollution of the ecosystems, the focus on improving SNF efficiency in legumes did not become a breeder’s priority. The size and stability of heritable effects under different environment conditions weigh significantly on any trait useful in breeding strategies. Here we review the challenges and progress made toward decoding the heritable components of SNF, which is considerably more complex than other crop allelic traits since the process involves genetic elements of both the host and the symbiotic rhizobial species. SNF-efficient rhizobial species designed based on the genetics of the host and its symbiotic partner face the test of a unique microbiome for its success and productivity. The progress made thus far in commercial legume crops with relevance to the dynamics of host–rhizobia interaction, environmental impact on rhizobial performance challenges, and what collectively determines the SNF efficiency under field conditions are also reviewed here.
A Significantly High Abundance of “Candidatus Liberibacter asiaticus” in Citrus Fruit Pith: in planta Transcriptome and Anatomical Analyses
Authors: Fang Fang , Guo Hengyu , Zhao Anmin , Li Tao , Liao Huihong , Deng Xiaoling , Xu Meirong , Zheng Zheng
Published: June 2021

Huanglongbing, a highly destructive disease of citrus, is associated with the non-culturable phloem-limited α-proteobacterium “Candidatus Liberibacter asiaticus” (CLas). The distribution patterns of CLas in infected plant are variable and not consistent, which make the CLas detection and characterization more challenging. Here, we performed a systemic analysis of CLas distribution in citrus branches and fruits of 14 cultivars. A significantly high concentration of CLas was detected in fruit pith (dorsal vascular bundle) of 14 citrus cultivars collected at fruit maturity season. A 2-year monitoring assay of CLas population in citrus branches of “Shatangju” mandarin (Citrus reticulata Blanco “Shatangju”) revealed that CLas population already exhibited a high level even before the appearance of visual symptoms in the fruit rind. Quantitative analyses of CLas in serial 1.5-cm segments of fruit piths showed the CLas was unevenly distributed within fruit pith and tended to colonize in the middle or distal (stylar end) regions of pith. The use of CLas-abundant fruit pith for dual RNA-seq generated higher-resolution CLas transcriptome data compared with the leaf samples. CLas genes involved in transport system, flagellar assembly, lipopolysaccharide biosynthesis, virulence, stress response, and cell surface structure, as well as host genes involved in biosynthesis of antimicrobial-associated secondary metabolites, was up-regulated in leaf midribs compared with fruit pith. In addition, CLas infection caused the severe collapse in phloem and callose deposition in the plasmodesmata of fruit pith. The ability of fruit pith to support multiplication of CLas to high levels makes it an ideal host tissue for morphological studies and in planta transcriptome analyses of CLas–host interactions.
P23 Acts as Functional RBP in the Macrophage Inflammation Response
Authors: de Vries Sebastian , Benes Vladimir , Naarmann-de Vries Isabel S. , Rücklé Cornelia , Zarnack Katharina , Marx Gernot , Ostareck Dirk H. , Ostareck-Lederer Antje
Published: June 2021

Macrophages exert the primary cellular immune response. Pathogen components like bacterial lipopolysaccharides (LPS) stimulate macrophage migration, phagocytotic activity and cytokine expression. Previously, we identified the poly(A)+RNA interactome of RAW 264.7 macrophages. Of the 402 RNA-binding proteins (RBPs), 32 were classified as unique in macrophages, including nineteen not reported to interact with nucleic acids before. Remarkably, P23 a HSP90 co-chaperone, also known as cytosolic prostaglandin E2 synthase (PTGES3), exhibited differential poly(A)+RNA binding in untreated and LPS-induced macrophages. To identify mRNAs bound by P23 and to elucidate potential regulatory RBP functions in macrophages, we immunoprecipitated P23 from cytoplasmic extracts of cross-linked untreated and LPS-induced cells. RNAseq revealed that enrichment of 44 mRNAs was reduced in response to LPS.Kif15mRNA, which encodes kinesin family member 15 (KIF15), a motor protein implicated in cytoskeletal reorganization and cell mobility was selected for further analysis. Noteworthy, phagocytic activity of LPS-induced macrophages was enhanced by P23 depletion. Specifically, in untreated RAW 264.7 macrophages, decreased P23 results inKif15mRNA destabilization, diminished KIF15 expression and accelerated macrophage migration. We show that the unexpected RBP function of P23 contributes to the regulation of macrophage phagocytotic activity and migration.
Structural Basis of the Function of Yariv Reagent—An Important Tool to Study Arabinogalactan Proteins
Authors: Přerovská Tereza , Pavlů Anna , Hancharyk Dzianis , Rodionova Anna , Vavříková Anna , Spiwok Vojtěch
Published: June 2021

Arabinogalactan proteins are very abundant, heavily glycosylated plant cell wall proteins. They are intensively studied because of their crucial role in plant development as well as their function in plant defence. Research of these biomacromolecules is complicated by the lack of tools for their analysis and characterisation due to their extreme heterogeneity. One of the few available tools for detection, isolation, characterisation, and functional studies of arabinogalactan proteins is Yariv reagents. Yariv reagent is a synthetic aromatic glycoconjugate originally prepared as an antigen for immunization. Later, it was found that this compound can precipitate arabinogalactan proteins, namely, their ß-D-(1→3)-galactan structures. Even though this compound has been intensively used for decades, the structural basis of arabinogalactan protein precipitation by Yariv is not known. Multiple biophysical studies have been published, but none of them attempted to elucidate the three-dimensional structure of the Yariv-galactan complex. Here we use a series of molecular dynamics simulations of systems containing one or multiple molecules of ß-D-galactosyl Yariv reagent with or without oligo ß-D-(1→3)-galactan to predict the structure of the complex. According to our model of Yariv-galactan complexes, Yariv reagent forms stacked oligomers stabilized by π-π and CH/π interactions. These oligomers may contain irregularities. Galactan structures crosslink these Yariv oligomers. The results were compared with studies in literature.
Arginine Methyltransferases as Regulators of RNA-Binding Protein Activities in Pathogenic Kinetoplastids
Authors: Campagnaro Gustavo D. , Nay Edward , Plevin Michael J. , Cruz Angela K. , Walrad Pegine B.
Published: June 2021

A large number of eukaryotic proteins are processed by single or combinatorial post-translational covalent modifications that may alter their activity, interactions and fate. The set of modifications of each protein may be considered a “regulatory code”. Among the PTMs, arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), can affect how a protein interacts with other macromolecules such as nucleic acids or other proteins. In fact, many RNA-binding (RBPs) proteins are targets of PRMTs. The methylation status of RBPs may affect the expression of their bound RNAs and impact a diverse range of physiological and pathological cellular processes. Unlike most eukaryotes, Kinetoplastids have overwhelmingly intronless genes that are arranged within polycistronic units from which mature mRNAs are generated by trans-splicing. Gene expression in these organisms is thus highly dependent on post-transcriptional control, and therefore on the action of RBPs. These genetic features make trypanosomatids excellent models for the study of post-transcriptional regulation of gene expression. The roles of PRMTs in controlling the activity of RBPs in pathogenic kinetoplastids have now been studied for close to 2 decades with important advances achieved in recent years. These include the finding that about 10% of the Trypanosoma brucei proteome carries arginine methylation and that arginine methylation controls Leishmania:host interaction. Herein, we review how trypanosomatid PRMTs regulate the activity of RBPs, including by modulating interactions with RNA and/or protein complex formation, and discuss how this impacts cellular and biological processes. We further highlight unique structural features of trypanosomatid PRMTs and how it contributes to their singular functionality.
Progressive Phosphorylation Modulates the Self-Association of a Variably Modified Histone H3 Peptide
Authors: Papamokos George V. , Tziatzos George , Papageorgiou Dimitrios G. , Georgatos Spyros , Kaxiras Efthimios , Politou Anastasia S.
Published: June 2021

Protein phosphorylation is a key regulatory mechanism in eukaryotic cells. In the intrinsically disordered histone tails, phosphorylation is often a part of combinatorial post-translational modifications and an integral part of the “histone code” that regulates gene expression. Here, we study the association between two histone H3 tail peptides modified to different degrees, using fully atomistic molecular dynamics simulations. Assuming that the initial conformations are either α-helical or fully extended, we compare the propensity of the two peptides to associate with one another when both are unmodified, one modified and the other unmodified, or both modified. The simulations lead to the identification of distinct inter- and intramolecular interactions in the peptide dimer, highlighting a prominent role of a fine-tuned phosphorylation rheostat in peptide association. Progressive phosphorylation appears to modulate peptide charge, inducing strong and specific intermolecular interactions between the monomers, which do not result in the formation of amorphous or ordered aggregates, as documented by experimental evidence derived from Circular Dichroism and NMR spectroscopy. However, upon complete saturation of positive charges by phosphate groups, this effect is reversed: intramolecular interactions prevail and dimerization of zero-charge peptides is markedly reduced. These findings underscore the role of phosphorylation thresholds in the dynamics of intrinsically disordered proteins. Phosphorylation rheostats might account for the divergent effects of histone modifications on the modulation of chromatin structure.
Sleep in Older Adults and Its Possible Relations With COVID-19
Authors: Pires Gabriel Natan , Ishikura Isabela Antunes , Xavier Sandra Doria , Petrella Caetano , Piovezan Ronaldo Delmonte , Xerfan Ellen Maria Sampaio , Andersen Monica Levy , Tufik Sergio
Published: June 2021

Since the beginning of the COVID-19 pandemic, older adults have been found to be a highly vulnerable group, with a higher prevalence of severe cases and negative outcomes. Research has focused on the reasons why older adults are at greater risk; Sleep-related factors have been suggested as one possible explanation for this. An individual’s sleep pattern undergoes significant changes over the course of their life. In older adults a specific sleep profile can be observed, one characterized by advanced sleep timing, a morningness preference, longer sleep-onset latency, shorter overall sleep duration, increased sleep fragmentation, reduced slow-wave sleep and, increased wake time after sleep onset. Additionally, an increased prevalence of sleep disorders can be observed, such as obstructive sleep apnea and insomnia. Previous research has already linked sleep disorders (especially sleep apnea) with COVID-19, but few studies have focused specifically on the older population. We believe that the intrinsic sleep patterns of older adults, and the prevalence of sleep disorders in this population, may be important factors that could explain why they are at a greater risk of negative COVID-19 outcomes. In this review, we discuss the relationship between sleep and COVID-19 among older adults, focusing on three different aspects: (1) Sleep-related issues that might increase the likelihood of getting infected by SARS-COV-2; (2) Sleep disturbances that might increase the predisposition to worse COVID-19 prognosis and outcomes; and (3) COVID-19-related aspects affecting community-dwelling older adults, such as social isolation, quarantine, and home confinement, among others, that might impact sleep.
Subjective Cognitive Decline May Be Associated With Post-operative Delirium in Patients Undergoing Total Hip Replacement: The PNDABLE Study
Authors: Lin Xu , Liu Fanghao , Wang Bin , Dong Rui , Sun Lixin , Wang Mingshan , Bi Yanlin
Published: June 2021

Objective: Subjective cognitive decline (SCD) is associated with an increased risk of clinical cognitive disorders. Post-operative delirium (POD) is a common complication after total hip replacement. We aimed to investigate the relationship between SCD and POD in patients undergoing total hip replacement.

Methods: Our study recruited 214 cognitively intact individuals from the Perioperative Neurocognitive Disorder And Biomarker Lifestyle (PNDABLE) study in the final analysis. SCD was diagnosed with Subjective Cognitive Decline Scale (SCDS), Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA). The incidence of POD was evaluated by using Confusion Assessment Method (CAM), and POD severity was measured by using the Memorial Delirium Assessment Scale (MDAS). Preoperative cerebrospinal fluid (CSF) Aβ40, Aβ42, T-tau, and P-tau levels were measured by enzyme-linked immune-sorbent assay (ELISA).

Results: Overall, the incidence of POD was 26.64% (57/214), including 32.43% (36/111) in the SCD group and 20.39% (21/103) in the NC group. With the increase of age, the incidence of POD in all age groups increased (P < 0.05). Logistic regression analysis showed that after adjusting for SCD, Aβ42, Aβ40, P-tau, and T-tau, SCD (OR 2.32, CI 1.18–4.55, P = 0.01) and the increased CSF level of P-tau (OR 1.04, CI 1.01–1.06, P < 0.001) were risk factors for POD, while the level of aβ42 (OR 0.99, CI 0.99–1.00, P < 0.001) was a protective factor for POD.

Conclusion: SCD is one of the preoperative risk factors for POD.

Clinical Trial Registration: This study was registered at China Clinical Trial Registry (Chictr200033439).
A Sensitive Homecage-Based Novel Object Recognition Task for Rodents
Authors: Wooden Jessica I. , Spinetta Michael J. , Nguyen Teresa , O’Leary Charles I. , Leasure J. Leigh
Published: June 2021

The recognition of novel objects is a common cognitive test for rodents, but current paradigms have limitations, such as low sensitivity, possible odor confounds and stress due to being performed outside of the homecage. We have developed a paradigm that takes place in the homecage and utilizes four stimuli per trial, to increase sensitivity. Odor confounds are eliminated because stimuli consist of inexpensive, machined wooden beads purchased in bulk, so each experimental animal has its own set of stimuli. This paradigm consists of three steps. In Step 1, the sampling phase, animals freely explore familiar objects (FO). Novel Objects (NO1 and NO2) are soiled with bedding from the homecage, to acquire odor cues identical to those of the FO. Steps 2 and 3 are test phases. Herein we report results of this paradigm from neurologically intact adult rats and mice of both sexes. Identical procedures were used for both species, except that the stimuli used for the mice were smaller. As expected in Step 2 (NO1 test phase), male and female rats and mice explored NO1 significantly more than FO. In Step 3 (NO2 test phase), rats of both sexes demonstrated a preference for NO2, while this was seen only in female mice. These results indicate robust novelty recognition during Steps 2 and 3 in rats. In mice, this was reliably seen only in Step 2, indicating that Step 3 was difficult for them under the given parameters. This paradigm provides flexibility in that length of the sampling phase, and the delay between test and sampling phases can be adjusted, to tailor task difficulty to the model being tested. In sum, this novel object recognition test is simple to perform, requires no expensive supplies or equipment, is conducted in the homecage (reducing stress), eliminates odor confounds, utilizes 4 stimuli to increase sensitivity, can be performed in both rats and mice, and is highly flexible, as sampling phase and the delay between steps can be adjusted to tailor task difficulty. Collectively, these results indicate that this paradigm can be used to quantify novel object recognition across sex and species.
Effect of Neonatal Treatment With the NMDA Receptor Antagonist, MK-801, During Different Temporal Windows of Postnatal Period in Adult Prefrontal Cortical and Hippocampal Function
Authors: Plataki Maria E. , Diskos Konstantinos , Sougklakos Christos , Velissariou Marouso , Georgilis Alexandros , Stavroulaki Vasiliki , Sidiropoulou Kyriaki
Published: June 2021

The neonatal MK-801 model of schizophrenia has been developed based on the neurodevelopmental and NMDA receptor hypofunction hypotheses of schizophrenia. This animal model is generated with the use of the NMDA receptor antagonist, MK-801, during different temporal windows of postnatal life of rodents leading to behavioral defects in adulthood. However, no studies have examined the role of specific postnatal time periods in the neonatal MK-801 (nMK-801) rodent model and the resulting behavioral and neurobiological effects. Thus, the goal of this study is to systematically investigate the role of NMDA hypofunction, during specific temporal windows in postnatal life on different cognitive and social behavioral paradigms, as well as various neurobiological effects during adulthood. Both female and male mice were injected intraperitoneally (i.p.) with MK-801 during postnatal days 7–14 (p7–14) or 11–15 (p11–15). Control mice were injected with saline during the respective time period. In adulthood, mice were tested in various cognitive and social behavioral tasks. Mice nMK-801-treated on p7–14 show impaired performance in the novel object, object-to-place, and temporal order object recognition (TOR) tasks, the sociability test, and contextual fear extinction. Mice nMK-801-treated on p11–15 only affects performance in the TOR task, the social memory test, and contextual fear extinction. No differences were identified in the expression of NMDA receptor subunits, the synapsin or PSD-95 proteins, either in the prefrontal cortex (PFC) or the hippocampus (HPC), brain regions significantly affected in schizophrenia. The number of parvalbumin (PV)-expressing cells is significantly reduced in the PFC, but not in the HPC, of nMK-801-treated mice on p7–14 compared to their controls. No differences in PV-expressing cells (PFC or HPC) were identified in nMK-801-treated mice on p11–15. We further examined PFC function by recording spontaneous activity in a solution that allows up state generation. We find that the frequency of up states is significantly reduced in both nMK-801-treated mice on p7–14 and p11–15 compared to saline-treated mice. Furthermore, we find adaptations in the gamma and high gamma activity in nMK-801-treated mice. In conclusion, our results show that MK-801 treatment during specific postnatal temporal windows has differential effects on cognitive and social behaviors, as well as on underlying neurobiological substrates.
Characteristics of Objective Sleep and Its Related Risk Factors Among Parkinson's Disease Patients With and Without Restless Legs Syndrome
Authors: Sun Shuyu , Zhao Xianchao , Ren Jiafeng , Cheng Jinxiang , Zhou Junying , Su Changjun
Published: June 2021

Objective: This study aimed to investigate the objective sleep characteristics and their related risk factors among Parkinson's disease (PD) patients with and without restless legs syndrome (RLS).

Methods: A total of 125 patients with PD who underwent overnight polysomnography (PSG) were recruited consecutively. Eighty-one patients, including 27 PD with RLS (PD-RLS) and 54 PD without RLS (PD-NRLS), were included in the final analysis after 1:2 propensity score matching. Demographic, clinical, and polysomnographic data were compared between PD patients with and without RLS. The risk factors for sleep quality were examined using a multiple linear regression model.

Results: The prevalence of RLS among PD patients was 28.0% (35/125). The PD-RLS group exhibited a higher score for the Unified Parkinson Disease Rating Scale (UPDRS) III than the PD-NRLS group. Also, the PD-RLS patients displayed significantly shorter total sleep times, worse sleep quality, decreased stage 3 duration, a longer wake time after sleep onset, and a higher arousal index than those without RLS (all p < 0.05). In the multiple linear regression model, PD duration (β = −0.363, 95% CI: −0.652 to −0.074; p = 0.016), UPDRS-III (β = −0.356, 95% CI: −0.641 to −0.071; p = 0.016), and periodic limb movement index (PLMI) (β = −0.472, 95% CI: −0.757 to −0.187; p = 0.002) were determined to be the risk factors influencing sleep quality in PD-RLS patients. The UPDRS-III (β = −0.347, 95% CI: −0.590 to −0.104; p = 0.006) and HAMD scores (β = −0.343, 95% CI: −0.586 to −0.100; p = 0.007) were significantly associated with sleep quality after adjusting for confounding factors in PD-NRLS patients, respectively.

Conclusions: PD-RLS patients exhibited more disturbed and fragmented sleep in objective sleep architecture than PD-NRLS patients. The severity of motor symptoms in PD was significantly associated with poor sleep quality in both PD-RLS and PD-NRLS patients. Notably, our findings indicated that periodic limb movements during sleep (PLMS) was the risk factor that influenced the objective sleep quality in PD patients with RLS.
High PYGL Expression Predicts Poor Prognosis in Human Gliomas
Authors: Zhao Chang-yi , Hua Chun-hui , Li Chang-hua , Zheng Rui-zhe , Li Xin-yuan
Published: June 2021

Background: PYGL has been reported as a glycogen degradation-related gene, which is up-regulated in many tumors. This study was designed to investigate the predictive value of high PYGL expression in patients with gliomas through bioinformatics analysis of the gene transcriptome and the single-cell sequencing data.

Methods: The gene transcriptome data of 595 glioma patients from the TCGA database and the single-cell RNA sequencing data of 7,930 GBM cells from the GEO database were included in the study. Differential analysis was used to find the distribution of expression of PYGL in different groups of glioma patients. OS analysis was used to assess the influence of the high expression of PYGL on the prognosis of patients. The reliability of its prediction was evaluated by the AUC of ROC and the C-index. The GSEA be used to reveal potential mechanisms. The single-cell analysis was used to observe the high expression of PYGL in different cell groups to further analyze the mechanism of its prediction.

Results: Differential analysis identified the expression level of PYGL is positively associated with glioma malignancy. OS analysis and Cox regression analyses showed high expression of PYGL was an independent factor for poor prognosis of gliomas (p < 0.05). The AUC values were 0.838 (1-year ROC), 0.864 (3-year ROC) and 0.833 (5-year ROC). The C index was 0.81. The GSEA showed that gene sets related to MTORC1 signaling, glycolysis, hypoxia, PI3K/AKT/mTOR signaling, KRAS signaling up and angiogenesis were differentially enriched in the high PYGL expression phenotype. The single-cell sequencing data analysis showed TAMs and malignant cells in GBM tissues expressed a high level of PYGL.

Conclusion: The high expression of PYGL is an independent predictor of poor prognosis in patients with glioma.
New Prehospital Triage for Stroke Patients Significantly Reduces Transport Time of EVT Patients Without Delaying IVT
Authors: Cabal Martin , Machova Linda , Vaclavik Daniel , Jasso Petr , Holes David , Volny Ondrej , Bar Michal
Published: June 2021

Background and Purpose: Ischemic stroke is a leading cause of mortality and morbidity worldwide. The time from stroke onset to treatment impacts clinical outcome. Here, we examined whether changing a triage model from “drip and ship” to “mothership” yielded significant reductions of onset-to-groin time (OGT) in patients receiving EVT and onset-to-needle time (ONT) in IVT-treated patients, compared to before FAST-PLUS test implementation. We also investigated whether the new triage improved clinical outcomes.

Methods: In a before/after multicenter study, we evaluated the effects of changing the prehospital triage system for suspected stroke patients in the Moravian–Silesian region, Czech Republic. In the new system, the validated FAST PLUS test is used to differentiate patients with suspected large vessel occlusion and triage-positive patients are transported directly to the CSC. Time metrics and patient data were obtained from the regional EMS database and SITS database.

Results: For EVT patients, the median OGT was 213 min in 2015 and 142 min in 2018, and the median TT was 142 min in 2015 and 47 min in 2018. For tPA patients, the median ONT was 110 min in 2015 and 109 min in 2018, and the median TT was 41 min in 2015 and 48 min in 2018. Clinical outcome did not significantly change. The percentages of patients with favorable clinical outcome (mRS 0–2) were comparable between 2015 and 2018: 60 vs. 59% in tPA patients and 40 vs. 44% in EVT patients.

Conclusions: The new prehospital triage has yielded shorter OGTs for EVT patients. No changes were found in the onset-to-needle time for IVT-treated patients, or in the clinical outcome at 3 months after stroke onset.
Wearable Devices for Assessment of Tremor
Authors: Vescio Basilio , Quattrone Andrea , Nisticò Rita , Crasà Marianna , Quattrone Aldo
Published: June 2021

Tremor is an impairing symptom associated with several neurological diseases. Some of such diseases are neurodegenerative, and tremor characterization may be of help in differential diagnosis. To date, electromyography (EMG) is the gold standard for the analysis and diagnosis of tremors. In the last decade, however, several studies have been conducted for the validation of different techniques and new, non-invasive, portable, or even wearable devices have been recently proposed as complementary tools to EMG for a better characterization of tremors. Such devices have proven to be useful for monitoring the efficacy of therapies or even aiding in differential diagnosis. The aim of this review is to present systematically such new solutions, trying to highlight their potentialities and limitations, with a hint to future developments.
Physical Activity as a Treatment for Social Anxiety in Clinical and Non-clinical Populations: A Systematic Review and Three Meta-Analyses for Different Study Designs
Authors: Zika Maya A. , Becker Linda
Published: June 2021

The fear of being in the focus of attention in social situations can develop into a social anxiety disorder (SAD). The classical treatment for SAD is cognitive behavioral therapy, which is in many cases accompanied by drug treatments. A promising alternative treatment is physical activity (PA) interventions, because regular PA has been shown to be suitable for reducing anxiety in general. We conducted a pre-registered systematic review and meta-analysis (PROSPERO registration no. CRD42020191181) as well as two additional searches. Our aim was to investigate whether PA interventions are a suitable treatment for SAD and whether PA is suitable for reducing social anxiety (SA) in general. For studies with randomized controlled trial designs, a not statistically significant effect of medium size toward lower general SA symptomatology was found in the PA group in comparison with the control group (d= −0.24,p= 0.377). For studies with longitudinal designs, significantly lower SA symptoms were found after PA treatments (d= −0.22,p= 0.001). The effect of PA on SA was stronger for adults than for children and adolescents (p= 0.003). For cross-sectional studies, a small negative association between SA symptoms and the amount of PA was found, i.e., lower SA was found for people who were more physically active (r= −0.12,p= 0.003). We conclude that PA is a promising means for the (additional) treatment of SAD or to reduce SA in general in non-clinical samples, but more research in which high-quality studies with randomized controlled trial designs are used is needed. Furthermore, open questions with respect to moderating variables (e.g., age, sex, BMI, type of intervention, stress, amount of regular PA before the intervention, and comorbidities) remain still open.
Disrupted Spontaneous Neural Activity in Patients With Thyroid-Associated Ophthalmopathy: A Resting-State fMRI Study Using Amplitude of Low-Frequency Fluctuation
Authors: Chen Wen , Wu Qian , Chen Lu , Zhou Jiang , Chen Huan-Huan , Xu Xiao-Quan , Hu Hao , Wu Fei-Yun
Published: June 2021

Purpose

The purpose of the study was to investigate the brain functional alteration in patients with thyroid-associated ophthalmopathy (TAO) by evaluating the spontaneous neural activity changes using resting-state functional magnetic resonance imaging (rs-fMRI) with the amplitude of low-frequency fluctuation (ALFF) method.

Materials and Methods

The rs-fMRI data of 30 TAO patients (15 active and 15 inactive) and 15 healthy controls (HCs) were included for analyses. The ALFF values were calculated and compared among groups. Correlations between ALFF values and clinical metrics were assessed.

Results

Compared with HCs, active TAOs showed significantly decreased ALFF values in the left middle occipital gyrus, superior occipital gyrus, and cuneus. Compared with inactive TAOs, active TAOs showed significantly increased ALFF values in the bilateral precuneus. Additionally, inactive TAOs showed significantly decreased ALFF values in the left middle occipital gyrus, superior occipital gyrus, cuneus, and bilateral precuneus than HCs. The ALFF value in the right precuneus of TAOs was positively correlated with clinical activity score (r = 0.583, P < 0.001) and Mini-Mental State Examination (MMSE) score (r = 0.377, P = 0.040), and negatively correlated with disease duration (r = −0.382, P = 0.037). Moreover, the ALFF value in the left middle occipital gyrus of TAOs was positively correlated with visual acuity (r = 0.441, P = 0.015).

Conclusion

TAO patients had altered spontaneous brain activities in the left occipital lobe and bilateral precuneus. The neuropsychological aspect of the disease should be noticed during clinical diagnosis and treatment.