bluuebunny/crossref_metadata_2025 huggingface dataset:
Tenascin-C can Serve as an Indicator for the Immunosuppressive Microenvironment of Diffuse Low-Grade Gliomas
Authors: Zhang Po , Liu Guohao , Hu Jinyang , Chen Sui , Wang Baofeng , Peng Peng , Yu Xingjiang , Guo Dongsheng
Published: March 2022

Purpose

The development and progression of glioma are associated with the tumor immune microenvironment. Diffuse low-grade gliomas (LGGs) with higher immunosuppressive microenvironment tend to have a poorer prognosis. The study aimed to find a biological marker that can reflect the tumor immune microenvironment status and predict prognosis of LGGs.

Methods

The target gene tenascin-C (TNC) was obtained by screening the Chinese Glioma Genome Atlas (CGGA) and the Cancer Genome Atlas (TCGA) databases. Then samples of LGGs were collected for experimental verification with immunohistochemistry, immunofluorescence, immunoblotting, quantitative real-time PCR. ELISA was employed to determine the content of TNC in serum and examine its relationship with the tumor immune microenvironment. Eventually, the sensitivity of immunotherapy was predicted on the basis of the content of TNC in LGGs.

Results

In the high-TNC subgroup, the infiltration of immunosuppressive cells was increased (MDSC: r=0.4721, Treg: r=0.3154, etc.), and immune effector cells were decreased [NKT, γδT, etc. (p<0.05)], immunosuppressive factors were elevated [TGF-β, IL10, etc. (p<0.05)], immunostimulatory factors, such as NKG2D, dropped (p<0.05), hypoxia scores increased (p<0.001), and less benefit from immunotherapy (p<0.05). Serum TNC level could be used to assess the status of tumor immune microenvironment in patients with grade II (AUC=0.8571; 95% CI: 0.6541-1.06) and grade III (AUC=0.8333; 95% CI: 0.6334-1.033) glioma.

Conclusions

Our data suggested that TNC could serve as an indicator for the immunosuppressive microenvironment status and the prognosis of LGGs. Moreover, it could also act as a predictor for the effect of immunotherapy on LGG patients.
CD56-Negative Extranodal Natural Killer/T-Cell Lymphoma: A Retrospective Study in 443 Patients Treated by Chemotherapy With or Without Asparaginase
Authors: Yang Jing , Li Pengfei , Piao Yingshi , Liu Xindi , Wei Liqiang , Sang Wei , Zhang Luo , Wang Liang
Published: March 2022

Objective

Extranodal natural killer/T cell lymphoma (NKTCL) is an aggressive EBV-related lymphoma, originating from NK cells or T cells. Previous study demonstrated that CD56 negative NKTCL should be recognized as a distinct subtype. In this study, the value of CD56 in NKTCL is validated in the era of asparaginase, and genomic analysis was done to dissect the differences between CD56-negative and positive NKTCL.

Methods

443 patients with newly diagnosed NKTCL were enrolled in this retrospective study, and correlation between CD56 positivity and survival outcomes was analyzed. The gene sequencing data was downloaded (http://www.biosino.org/node/project/detail/OEP000498), and bioinformatics analysis was done to delineate the tumor microenvironment and differentially expressed genes.

Results

CD56 was expressed in 337 patients (76.1%). Within a median follow-up time of 51 months, the 5-year overall survival (OS) and progression free survival (PFS) rates were 63.8% and 51.9%, respectively. For the whole cohort, patients who were CD56-positive had superior OS (5-year OS, 86.2% vs. 51.9%, p=0.019) and PFS (5-year PFS, 55.9% vs. 40.1%, p=0.016). For patients in early stage disease, CD56 positivity was associated with superior OS and PFS (p=0.008 and 0.005, respectively). In patients who received non-asparaginase-based chemotherapy, CD56-negative was associated with shorter OS and PFS (p<0.001), and in patients who received asparaginase-based chemotherapy, CD56-negative was not related to inferior OS and PFS (p=0.093 and p=0.829, respectively). The genomic analysis demonstrated that CD56 positive NKTCL probably originated from NK cells and CD56 negative NKTCL originated from T cells. CD56 positive NKTCL had significantly higher proportion of resting NK cells, activated NK cells, and activated CD8+ and CD4+ T cells in the tumor microenvironment.

Conclusions

CD56 negative NKTCL differs from CD56 positive NKTCL in both the tumor microenvironment and survival outcomes, and asparaginase-based treatment may overcome the poor prognosis brought by CD56 negativity.
STING1 in Different Organelles: Location Dictates Function
Authors: Zhang Ruoxi , Kang Rui , Tang Daolin
Published: March 2022

Stimulator of interferon response cGAMP interactor 1 (STING1), also known as TMEM173, is an immune adaptor protein that governs signal crosstalk that is implicated in many physiological and pathological processes. Although it has been established that STING1 traffics from the endoplasmic reticulum (ER) to Golgi apparatus (Golgi) upon DNA-triggered activation, emerging evidence reveals that STING1 can be transported to different organelles, which dictate its immune-dependent (e.g., the production of type I interferons and pro-inflammatory cytokines) and -independent (e.g., the activation of autophagy and cell death) functions. In this brief review, we outline the roles of STING1 in different organelles (including the ER, ER-Golgi intermediate compartment, Golgi, mitochondria, endosomes, lysosomes, and nucleus) and discuss the potential relevance of these roles to diseases and pharmacological interventions.
Plasma Markers of Neutrophil Extracellular Trap Are Linked to Survival but Not to Pulmonary Embolism in COVID-19-Related ARDS Patients
Authors: Prével Renaud , Dupont Annabelle , Labrouche-Colomer Sylvie , Garcia Geoffrey , Dewitte Antoine , Rauch Antoine , Goutay Julien , Caplan Morgan , Jozefowicz Elsa , Lanoix Jean-Philippe , Poissy Julien , Rivière Etienne , Orieux Arthur , Malvy Denis , Gruson Didier , Garçon Loic , Susen Sophie , James Chloé
Published: March 2022

Introduction

Coronavirus disease 2019 (COVID-19) can cause life-threatening acute respiratory distress syndrome (ARDS). Recent data suggest a role for neutrophil extracellular traps (NETs) in COVID-19-related lung damage partly due to microthrombus formation. Besides, pulmonary embolism (PE) is frequent in severe COVID-19 patients, suggesting that immunothrombosis could also be responsible for increased PE occurrence in these patients. Here, we evaluate whether plasma levels of NET markers measured shorty after admission of hospitalized COVID-19 patients are associated with clinical outcomes in terms of clinical worsening, survival, and PE occurrence.

Patients and Methods

Ninety-six hospitalized COVID-19 patients were included, 50 with ARDS (severe disease) and 46 with moderate disease. We collected plasma early after admission and measured 3 NET markers: total DNA, myeloperoxidase (MPO)–DNA complexes, and citrullinated histone H3. Comparisons between survivors and non-survivors and patients developing PE and those not developing PE were assessed by Mann–Whitney test.

Results

Analysis in the whole population of hospitalized COVID-19 patients revealed increased circulating biomarkers of NETs in patients who will die from COVID-19 and in patients who will subsequently develop PE. Restriction of our analysis in the most severe patients, i.e., the ones who enter the hospital for COVID-19-related ARDS, confirmed the link between NET biomarker levels and survival but not PE occurrence.

Conclusion

Our results strongly reinforce the hypothesis that NETosis is an attractive therapeutic target to prevent COVID-19 progression but that it does not seem to be linked to PE occurrence in patients hospitalized with COVID-19.
Dll1 Can Function as a Ligand of Notch1 and Notch2 in the Thymic Epithelium
Authors: Hirano Ken-ichi , Hosokawa Hiroyuki , Yahata Takashi , Ando Kiyoshi , Tanaka Masayuki , Imai Jin , Yazawa Masaki , Ohtsuka Masato , Negishi Naoko , Habu Sonoko , Sato Takehito , Hozumi Katsuto
Published: March 2022

T-cell development in the thymus is dependent on Notch signaling induced by the interaction of Notch1, present on immigrant cells, with a Notch ligand, delta-like (Dll) 4, on the thymic epithelial cells. Phylogenetic analysis characterizing the properties of the Dll4 molecule suggests that Dll4 emerged from the common ancestor of lobe- and ray-finned fishes and diverged into bony fishes and terrestrial organisms, including mammals. The thymus evolved in cartilaginous fishes before Dll4, suggesting that T-cell development in cartilaginous fishes is dependent on Dll1 instead of Dll4. In this study, we compared the function of both Dll molecules in the thymic epithelium using Foxn1-cre and Dll4-floxed mice with conditional transgenic alleles in which the Dll1 or Dll4 gene is transcribed after the cre-mediated excision of the stop codon. The expression of Dll1 in the thymic epithelium completely restored the defect in the Dll4-deficient condition, suggesting that Dll1 can trigger Notch signaling that is indispensable for T-cell development in the thymus. Moreover, using bone marrow chimeras with Notch1- or Notch2-deficient hematopoietic cells, we showed that Dll1 is able to activate Notch signaling, which is sufficient to induce T-cell development, with both the receptors, in contrast to Dll4, which works only with Notch1, in the thymic environment. These results strongly support the hypothesis that Dll1 regulates T-cell development via Notch1 and/or Notch2 in the thymus of cartilaginous fishes and that Dll4 has replaced Dll1 in inducing thymic Notch signaling via Notch1 during evolution.
Butyrophilins: γδ T Cell Receptor Ligands, Immunomodulators and More
Authors: Herrmann Thomas , Karunakaran Mohindar M.
Published: March 2022

Butyrophilins (BTN) are relatives of the B7 family (e.g., CD80, PD-L1). They fulfill a wide range of functions including immunomodulation and bind to various receptors such as the γδ T cell receptor (γδTCR) and small molecules. One intensively studied molecule is BTN3A1, which binds via its cytoplasmic B30.2 domain, metabolites of isoprenoid synthesis, designated as phosphoantigen (PAg), The enrichment of PAgs in tumors or infected cells is sensed by Vγ9Vδ2 T cells, leading to the proliferation and execution of effector functions to remove these cells. This article discusses the contribution of BTNs, the related BTNL molecules and SKINT1 to the development, activation, and homeostasis of γδ T cells and their immunomodulatory potential, which makes them interesting targets for therapeutic intervention.
Long Distance Runners in the Marine Realm: New Insights Into Genetic Diversity, Kin Relationships and Social Fidelity of Indian Ocean Male Sperm Whales
Authors: Girardet Justine , Sarano Francois , Richard Gaëtan , Tixier Paul , Guinet Christophe , Alexander Alana , Sarano Véronique , Vitry Hugues , Preud’homme Axel , Heuzey René , Garcia-Cegarra Ana M. , Adam Olivier , Madon Bénédicte , Jung Jean-Luc
Published: March 2022

Adult male sperm whales (Physeter macrocephalus) are long distance runners of the marine realm, feeding in high latitudes and mating in tropical and subtropical waters where stable social groups of females and immatures live. Several areas of uncertainty still limit our understanding of their social and breeding behavior, in particular concerning the potential existence of geographical and/or social fidelities. In this study, using underwater observation and sloughed-skin sampling, we looked for male social fidelity to a specific matrilineal sperm whale group near Mauritius. In addition, we captured a wider picture of kin relationships and genetic diversity of male sperm whales in the Indian Ocean thanks to biopsies of eight individuals taken in a feeding ground near the Kerguelen and Crozet Archipelagos (Southern Indian Ocean). Twenty-six adult male sperm whales were identified when socializing with adult females and immatures off Mauritius. Sloughed-skin samples were taken from thirteen of them for genetic analysis. Long-term underwater observation recorded several noteworthy social interactions between adult males and adult females and/or immatures. We identified seven possible male recaptures over different years (three by direct observation, and four at the gametic level), which supports a certain level of male social fidelity. Two probable first- and thirty second-degree kin relationships were highlighted between members of the social unit and adult males, confirming that some of the adult males observed in Mauritian waters are reproductive. Male social philopatry to their natal group can be excluded, as none of the males sampled shared the haplotype characteristic of the matrilineal social group. Mitochondrial DNA control region haplotype and nucleotide diversities calculated over the 21 total male sperm whales sampled were similar to values found by others in the Indian Ocean. Our study strongly supports the existence of some levels of male sperm whale social fidelity, not directed to their social group of birth, in the Indian Ocean. Males sampled in breeding and feeding grounds are linked by kin relationships. Our results support a model of male mediated gene flow occurring at the level of the whole Indian Ocean, likely interconnected with large-scale geographical fidelity to ocean basin, and a small-scale social fidelity to matrilineal social groups.
Offshore Freshwater Pathways in the Northern Gulf of Mexico: Impacts of Modeling Choices
Authors: Liu Guangpeng , Bracco Annalisa , Sun Daoxun
Published: March 2022

The Gulf of Mexico is a very productive and economically important system where riverine runoff acts as a linkage between the continental shelf and the open ocean, providing nutrients in addition to freshwater. This work investigates the three-dimensional transport and pathway structure of this river runoff offshore the continental shelf using ensembles of numerical simulations with different configurations regarding grid resolution (mesoscale resolving and submesoscale permitting) and river setup using suites of 5-months long integrations covering nearly 3 years. The riverine forcing is applied only at the surface over an area around the river mouth, a strategy often adopted in numerical studies, or as a meridional flux with a vertical extension. The simulated flow captures the southward offshore transport of river runoff driven by its interaction with the largest mesoscale circulations in the basin, the Loop Current and Loop Current eddies. This pathway is strong and well-document during summer but also active and relevant in winter, despite a less obvious surface signature. The most intense transport occurs primarily at the peripheries of the Loop Current and the detached eddies, and the freshwater is subducted as deep as 600 m around the mesoscale anticyclonic eddies. Submesoscale motions strengthen slightly the spread of freshwater plumes in summer but their contribution is negligible, if not negative, in winter. Differences in the freshwater distribution and transport volume among runs are small and generally less than 10% among ensembles, with overall slightly higher volume of freshwater transported off-shore and at depth in submesoscale permitting runs that include a velocity flux in their riverine input representation.
Changes in Transcriptome and Ultrastructure Reveal Salinity Tolerance of Obscure Puffer Takifugu obscurus
Authors: Wang Jun , Zhu Xuexia , Sun Yunfei , Gu Lei , Wu Yaping , Chen Yafen , Yang Zhou
Published: March 2022

Fish can maintain a stable intracellular concentration of ions in environments of variable salinities through osmoregulation. In this study, we focused on obscure puffer Takifugu obscurus (T. obscurus), an anadromous fish with high commercial value and rapid depression of wide populations, to investigate changes at molecular and physiological levels underlying salinity tolerance through multifaceted analyses integrating transcriptomics and micrography. We found that with the increase of salinity, the structure of the three main osmoregulation organs, i.e., gill, intestine, and kidney had remarkable changes. The results of transcriptome demonstrated that the ATP-binding box transporter and cyclic adenosine monophosphate (cAMP) signaling pathway in the gill and kidney were significantly reduced. Growth hormone, prolactin, and cortisol regulated more transporters of body composition and stimulated chloride cell proliferation and differentiation, which change the capacity for membrane transport between ion and water molecules. Adenosine-activating protein kinase and thyroid hormone signaling pathway were also significantly upregulated. These transcriptional levels changes of T. obscurus combined with ultrastructure in response to salinity increase indicated that osmoregulation is a complex process involving multiple organs and signaling pathways. Overall, this study can deepen the understanding of osmotic regulation during fish migration.
Relationship Between Endothelial and Angiogenesis Biomarkers Envisage Mortality in a Prospective Cohort of COVID-19 Patients Requiring Respiratory Support
Authors: Maldonado Felipe , Morales Diego , Díaz-Papapietro Catalina , Valdés Catalina , Fernandez Christian , Valls Nicolas , Lazo Marioli , Espinoza Carolina , González Roberto , Gutiérrez Rodrigo , Jara Álvaro , Romero Carlos , Cerda Oscar , Cáceres Mónica
Published: March 2022

Purpose

Endothelial damage and angiogenesis are fundamental elements of neovascularisation and fibrosis observed in patients with coronavirus disease 2019 (COVID-19). Here, we aimed to evaluate whether early endothelial and angiogenic biomarkers detection predicts mortality and major cardiovascular events in patients with COVID-19 requiring respiratory support.

Methods

Changes in serum syndecan-1, thrombomodulin, and angiogenic factor concentrations were analysed during the first 24 h and 10 days after COVID-19 hospitalisation in patients with high-flow nasal oxygen or mechanical ventilation. Also, we performed an exploratory evaluation of the endothelial migration process induced by COVID-19 in the patients' serum using an endothelial cell culture model.

Results

In 43 patients, mean syndecan-1 concentration was 40.96 ± 106.9 ng/mL with a 33.9% increase (49.96 ± 58.1 ng/mL) at day 10. Both increases were significant compared to healthy controls (Kruskal–Wallis p < 0.0001). We observed an increase in thrombomodulin, Angiopoietin-2, human vascular endothelial growth factor (VEGF), and human hepatocyte growth factor (HGF) concentrations during the first 24 h, with a decrease in human tissue inhibitor of metalloproteinases-2 (TIMP-2) that remained after 10 days. An increase in human Interleukin-8 (IL-8) on the 10th day accompanied by high HGF was also noted. The incidence of myocardial injury and pulmonary thromboembolism was 55.8 and 20%, respectively. The incidence of in-hospital deaths was 16.3%. Biomarkers showed differences in severity of COVID-19. Syndecan-1, human platelet-derived growth factor (PDGF), VEGF, and Ang-2 predicted mortality. A multiple logistic regression model with TIMP-2 and PDGF had positive and negative predictive powers of 80.9 and 70%, respectively, for mortality. None of the biomarkers predicted myocardial injury or pulmonary thromboembolism. A proteome profiler array found changes in concentration in a large number of biomarkers of angiogenesis and chemoattractants. Finally, the serum samples from COVID-19 patients increased cell migration compared to that from healthy individuals.

Conclusion

We observed that early endothelial and angiogenic biomarkers predicted mortality in patients with COVID-19. Chemoattractants from patients with COVID-19 increase the migration of endothelial cells. Trials are needed for confirmation, as this poses a therapeutic target for SARS-CoV-2.
Modified Intraperitoneal Chemotherapy Without Bevacizumab as a First-Line Therapy for Newly Diagnosed Advanced Epithelial Ovarian Cancer-Two Centers Experiences
Authors: Shen Yuanming , Tang Sangsang , Xu Junfen , Xie Xing , Chen Zhongbo
Published: March 2022

Objectives

To evaluate whether the modified intraperitoneal plus intravenous chemotherapy regimen as a first-line therapy for advanced epithelial ovarian cancer (EOC) in China can be well-tolerated or confer any potential benefit on survival.

Methods

We evaluated the outcomes of women with newly diagnosed advanced-stage III-IV EOC treated with optimal cytoreductive surgery (<1 cm) and subsequent intraperitoneal plus intravenous chemotherapy or intravenous chemotherapy from January 2005 to December 2017 at two Gynecologic Oncology Centers in China. Kaplan-Meier survival analysis and Cox regression multivariate analysis models were performed to determine the toxicities and survival outcomes.

Results

A total of 463 patients with stage III-IV EOC were enrolled. According to the propensity scores (1:2), 85 patients who received intraperitoneal plus intravenous chemotherapy (group A) were matched to 170 patients who received intravenous chemotherapy (group B). The median follow-up time was 41 months (range 6–155 months). However, there was no statistically significant difference in the median progression-free survival (PFS) (20 vs. 22 months, P = 0.351) or 3-year overall survival (OS) rate (80 vs. 78%, P = 0.749) between the two groups. R0 primary cytoreductive surgery was the only factor related to PFS (P = 0.028) and OS (P = 0.005) by Cox regression analysis. The incidence of grade 3/4 adverse events did not significantly differ between the two groups.

Conclusion

The efficacy of intraperitoneal chemotherapy mainly comes from the intraperitoneal drug dose intensity and cumulative dose. High-efficiency and low-toxicity intraperitoneal chemotherapy regimens still need to be found and validated.
Unraveling Anaerobic Metabolisms in a Hypersaline Sediment
Authors: Solchaga Juan Ignacio , Busalmen Juan Pablo , Nercessian Débora
Published: March 2022

The knowledge on the microbial diversity inhabiting hypersaline sediments is still limited. In particular, existing data about anaerobic hypersaline archaea and bacteria are scarce and refer to a limited number of genera. The approach to obtain existing information has been almost exclusively attempting to grow every organism in axenic culture on the selected electron acceptor with a variety of electron donors. Here, a different approach has been used to interrogate the microbial community of submerged hypersaline sediment of Salitral Negro, Argentina, aiming at enriching consortia performing anaerobic respiration of different electron acceptor compounds, in which ecological associations can maximize the possibilities of successful growth. Growth of consortia was demonstrated on all offered electron acceptors, including fumarate, nitrate, sulfate, thiosulfate, dimethyl sulfoxide, and a polarized electrode. Halorubrum and Haloarcula representatives are here shown for the first time growing on lactate, using fumarate or a polarized electrode as the electron acceptor; in addition, they are shown also growing in sulfate-reducing consortia. Halorubrum representatives are for the first time shown to be growing in nitrate-reducing consortia, probably thanks to reduction of N2O produced by other consortium members. Fumarate respiration is indeed shown for the first time supporting growth of Halanaeroarchaeum and Halorhabdus belonging to the archaea, as well as growth of Halanaerobium, Halanaerobaculum, Sporohalobacter, and Acetohalobium belonging to the bacteria. Finally, evidence is presented suggesting growth of nanohaloarchaea in anaerobic conditions.
Appraisal of Cinnamaldehyde Analogs as Dual-Acting Antibiofilm and Anthelmintic Agents
Authors: Khadke Sagar Kiran , Lee Jin-Hyung , Kim Yong-Guy , Raj Vinit , Lee Jintae
Published: March 2022

Cinnamaldehyde has a broad range of biological activities, which include antibiofilm and anthelmintic activities. The ever-growing problem of drug resistance and limited treatment options have created an urgent demand for natural molecules with antibiofilm and anthelmintic properties. Hence, we hypothesized that molecules with a scaffold structurally similar to that of cinnamaldehyde might act as dual inhibitors against fungal biofilms and helminths. In this regard, eleven cinnamaldehyde analogs were tested to determine their effects on fungal Candida albicans biofilm and nematode Caenorhabditis elegans. α-Methyl and trans-4-methyl cinnamaldehydes efficiently inhibited C. albicans biofilm formation (>90% inhibition at 50 μg/mL) with minimum inhibitory concentrations (MICs) of ≥ 200 μg/mL and 4-bromo and 4-chloro cinnamaldehydes exhibited anthelmintic property at 20 μg/mL against C. elegans. α-Methyl and trans-4-methyl cinnamaldehydes inhibited hyphal growth and cell aggregation. Scanning electron microscopy was employed to determine the surface architecture of C. albicans biofilm and cuticle of C. elegans, and confocal laser scanning microscopy was used to determine biofilm characteristics. The perturbation in gene expression of C. albicans was investigated using qRT-PCR analysis and α-methyl and trans-4-methyl cinnamaldehydes exhibited down-regulation of ECE1, IFD6, RBT5, UCF1, and UME6 and up-regulation of CHT4 and YWP1. Additionally, molecular interaction of these two molecules with UCF1 and YWP1 were revealed by molecular docking simulation. Our observations collectively suggest α-methyl and trans-4-methyl cinnamaldehydes are potent biofilm inhibitors and that 4-bromo and 4-chloro cinnamaldehydes are anthelmintic agents. Efforts are required to determine the range of potential therapeutic applications of cinnamaldehyde analogs.
A Plasmid With Conserved Phage Genes Helps Klebsiella pneumoniae Defend Against the Invasion of Transferable DNA Elements at the Cost of Reduced Virulence
Authors: Cai Mufeng , Pu Bingchun , Wang Yue , Lv Lin , Jiang Chunyu , Fu Xiaomei , Zhang Yan , Zhao Wei , Dong Ke , Yang Yi , Liu Yangming , Wei Yalu , Zhang Zhengyue , Li Jianhui , Guo Xiaokui , Liu Chang , Qin Jinhong
Published: March 2022

Klebsiella pneumoniae exhibits extensive phenotypic and genetic diversity. Higher plasmid loads in the cell were supposed to play an key role in its genome diversity. Although some plasmids are widely distributed in Kp populations, they are poorly recognized. A plasmid named p2 in strain Kp1604 was predicted to be an intact prophage like Salmonella phage SSU5. However, our study showed that p2 was specifically packaged into membrane vesicles (MVs) rather than phage particles triggered by mitomycin C and subinhibitory concentrations of antibiotics. p2-minus mutant Kp1604Δp2 did not affect MV production. Compared with Kp1604, the capacity of plasmid uptake and the amount of phage burst of Kp1604Δp2 were improved. Moreover, virulence of Kp1604Δp2 also increased. Our results indicated that p2 could contribute to the host defense against the invasion of transferable DNA elements at the cost of reduced virulence. Further study on the mechanism will help us understand how it provides adaptive phenotypes to host evolution.
Antimicrobial Resistance Profiles of Non-typhoidal Salmonella From Retail Meat Products in California, 2018
Authors: Lee Katie Yen , Atwill Edward Robert , Pitesky Maurice , Huang Anny , Lavelle Kurtis , Rickard Maribel , Shafii Marzieh , Hung-Fan Melody , Li Xunde
Published: March 2022

Non-typhoidal Salmonella remains a leading cause of foodborne illness in the United States, with food animal products serving as a key conduit for transmission. The emergence of antimicrobial resistance (AMR) poses an additional public health concern warranting better understanding of its epidemiology. In this study, 958 retail meat samples collected from January to December 2018 in California were tested for Salmonella. From multivariable logistic regression, there was a 6.47 (90% CI 2.29–18.27), 3.81 (90% CI 1.29–11.27), and 3.12 (90% CI 1.03–9.45) higher odds of contamination in samples purchased in the fall, spring, and summer than in winter months, respectively, and a 3.70 (90% CI 1.05–13.07) higher odds in ground turkey compared to pork samples. Fourteen distinct serotypes and 17 multilocus sequence types were identified among the 43 isolates recovered, with S. Kentucky (25.58%), S. Reading (18.60%), S. Infantis (11.63%), and S. Typhimurium (9.30%) comprising the top serotypes. High prevalence of resistance was observed in retail chicken isolates for streptomycin (12/23, 52.17%) and tetracycline (12/23, 52.17%), in ground turkey isolates for ampicillin (8/15, 53.34%), and in ground beef isolates for nalidixic acid (2/3, 66.67%). Fourteen (32.56%) were susceptible to all antimicrobials tested, 11 (25.58%) were resistant to one drug, and 12 (27.91%) were resistant to two drugs. The remaining six isolates (13.95%) were multidrug-resistant (MDR, ≥3 drug classes) S. Infantis (n = 4), S. Reading (n = 1), and S. Kentucky (n = 1). Whole-genome sequencing (WGS) identified 16 AMR genes and 17 plasmid replicons, including blaCTX–M–65 encoding ceftriaxone resistance and a D87Y mutation in gyrA conferring resistance to nalidixic acid and reduced susceptibility to ciprofloxacin. The IncFIB(pN55391) replicon previously identified in connection to the worldwide dissemination of pESI-like mega plasmid carriage in an emerged S. Infantis clone was detected in four of the six MDR isolates. Genotypes from WGS showed high concordance with phenotype with overall sensitivity and specificity of 95.31% and 100%, respectively. This study provides insight into the AMR profiles of a diversity of Salmonella serotypes isolated from retail meat products in California and highlights the value of routine retail food surveillance for the detection and characterization of AMR in foodborne pathogens.
Mycorrhizosphere Bacteria, Rahnella sp. HPDA25, Promotes the Growth of Armillaria gallica and Its Parasitic Host Gastrodia elata
Authors: Liu Tianrui , Hua Zhongyi , Han Pengjie , Zhao Yuyang , Zhou Junhui , Jin Yan , Li Xiaolin , Huang Luqi , Yuan Yuan
Published: March 2022

Gastrodia elata is an entirely heterotrophic plant, the growth of which is completely reliant on Armillaria gallica, an orchid mycorrhizal fungus. To avoid damaging ecosystems, G. elata cultivation is shifting from woodland to farmland. However, whether the microbial community structure remains stable during this conversation is unknown. Here, we cultivated G. elata in woodland or farmland and found that woodland-cultivated G. elata produced a greater yield and larger tuber size. The relative abundance of Rahnella was 22.84- and 122.25-fold higher in woodland- and farmland-cultivated soil samples, respectively, than that in uncultivated soil samples. To investigate how Rahnella impacts the growth of G. elata and establishes symbiosis with Armillaria gallica, three Rahnella spp. strains (HPDA25, SBD3, and SBD11) were isolated from mycorrhizosphere soil samples. It was found that these strains, especially HPDA25, promoted the growth of A. gallica. Ultra-performance liquid chromatography coupled to a triple quadrupole mass spectrometry analysis detected the indole-3-acetic acid with 16.24 ng/ml in HPDA25 fermentation solution. Co-culturing with the strain HPDA25 or exogenous indole-3-acetic acid increased the branching and fresh weight of rhizomorphs and the growth rate and extracellular laccase activity of A. gallica, compared with A. gallica cultured alone. The results of RNA-seq and quantitative real-time polymerase chain reaction analysis showed that co-culturing A. gallica with HPDA25 increased the expression level of the genes including hydrophobin, SUR7/PalI family, and pectin methylesterase, whereas decreased the expression levels of glycolysis-related genes. Furthermore, co-culturing with the strain HPDA25, A. gallica promotes the growth of G. elata and enhances the tuber size of G. elata. These results provide new insights into an orchid mycorrhizal symbiosis and the cultivation of G. elata.
Time Window of the Critical Period for Neuroplasticity in S1, V1, and A1 Sensory Areas of Small Rodents: A Systematic Review
Authors: Pedrosa Laís Resque Russo , Coimbra Gabriele dos Santos , Corrêa Márcio Gonçalves , Dias Ivanira Amaral , Bahia Carlomagno Pacheco
Published: March 2022

The plasticity of the central nervous system (CNS) allows the change of neuronal organization and function after environmental stimuli or adaptation after sensory deprivation. The so-called critical period (CP) for neuroplasticity is the time window when each sensory brain region is more sensitive to changes and adaptations. This time window is usually different for each primary sensory area: somatosensory (S1), visual (V1), and auditory (A1). Several intrinsic mechanisms are also involved in the start and end of the CP for neuroplasticity; however, which is its duration in S1, VI, and A1? This systematic review evaluated studies on the determination of these time windows in small rodents. The careful study selection and methodological quality assessment indicated that the CP for neuroplasticity is different among the sensory areas, and the brain maps are influenced by environmental stimuli. Moreover, there is an overlap between the time windows of some sensory areas. Finally, the time window duration of the CP for neuroplasticity is predominant in S1.
The zebrafish Multivariate Concentric Square Field: A Standardized Test for Behavioral Profiling of Zebrafish (Danio rerio)
Authors: Vossen Laura E. , Brunberg Ronja , Rådén Pontus , Winberg Svante , Roman Erika
Published: March 2022

The zebrafish (Danio rerio) is an important model organism in the study of the neurobiological basis of human mental disorders. Yet the utility of this species is limited by the quality of the phenotypical characterization tools available. Here, we present a complex testing environment for the quantification of explorative behavior in adult zebrafish, the zebrafish Multivariate Concentric Square Field™ (zMCSF), adapted from the rodent equivalent that has been used in > 40 studies. The apparatus consists of a central open area which is surrounded by a dark corner with a roof (DCR), corridors, and an inclined ramp. These areas differ in illumination, water depth, and are sheltered or exposed to different degrees. We quantified behavior of male and female wild-caught and AB strain zebrafish in the zMCSF (day 1) and cross-validated these results using the novel tank diving test (NTDT) (day 2). To assess the effect of repeated testing, AB zebrafish we tested a second time in both tests 1 week later (on days 7 and 8). We detected strong differences between the strains, with wild zebrafish swimming faster and spending more time in the corridors and on the ramp, while they avoided the open area in the center. AB zebrafish were less hesitant to enter the center but avoided the ramp, and often left one or more zones unexplored. No major sex differences in exploratory behavior were detected in either strain, except for a slightly higher velocity of AB males which has been reported before. Importantly, the zMCSF was largely resilient to repeated testing. The diving test revealed only one difference confined to one sex; wild females paid more visits to the top third than AB females. In isolation, this finding could lead to the conclusion that wild zebrafish are more risk-taking, which is incorrect given this strain’s avoidance of open areas. To conclude, our results suggest that the zMCSF presents a sophisticated behavioral tool that can distinguish between different magnitudes and types of risk, allowing the user to create an intricate behavioral profile of individual adult zebrafish.
Signal Detection Theory as a Novel Tool to Understand Cognitive Fatigue in Individuals With Multiple Sclerosis
Authors: Román Cristina A. F. , DeLuca John , Yao Bing , Genova Helen M. , Wylie Glenn R.
Published: March 2022

Multiple Sclerosis (MS) affects 2.8 million persons worldwide. One of the most persistent, pervasive, and debilitating symptoms of MS is cognitive fatigue. While this has been known for over a century, cognitive fatigue has been difficult to study because patients’ subjective (self-reported) cognitive fatigue has consistently failed to correlate with more objective measures, such as reaction time (RT) and accuracy. Here, we investigated whether more nuanced metrics of performance, specifically the metrics of Signal Detection Theory (SDT), would show a relationship to cognitive fatigue even if RT and accuracy did not. We also measured brain activation to see whether SDT metrics were related to activation in brain areas that have been shown to be sensitive to cognitive fatigue. Fifty participants (30 MS, 20 controls) took part in this study and cognitive fatigue was induced using four blocks of a demanding working memory paradigm. Participants reported their fatigue before and after each block, and their performance was used to calculate SDT metrics (Perceptual Certainty and Criterion) and RT and accuracy. The results showed that the SDT metric of Criterion (i.e., response bias) was positively correlated with subjective cognitive fatigue. Moreover, the activation in brain areas previously shown to be related to cognitive fatigue, such as the striatum, was also related to Criterion. These results suggest that the metrics of SDT may represent a novel tool with which to study cognitive fatigue in MS and other neurological populations. These results hold promise for characterizing cognitive fatigue in MS and developing effective interventions in the future.
Ultrastructure of Rat Rostral Nucleus of the Solitary Tract Terminals in the Parabrachial Nucleus and Medullary Reticular Formation
Authors: Park Sook Kyung , Cho Yi Sul , Kim Jong Ho , Kim Yun Sook , Bae Yong Chul
Published: March 2022

Neurons in the rostral nucleus of the solitary tract (rNST) receive taste information from the tongue and relay it mainly to the parabrachial nucleus (PBN) and the medullary reticular formation (RF) through two functionally different neural circuits. To help understand how the information from the rNST neurons is transmitted within these brainstem relay nuclei in the taste pathway, we examined the terminals of the rNST neurons in the PBN and RF by use of anterograde horseradish peroxidase (HRP) labeling, postembedding immunogold staining for glutamate, serial section electron microscopy, and quantitative analysis. Most of the anterogradely labeled, glutamate-immunopositive axon terminals made a synaptic contact with only a single postsynaptic element in PBN and RF, suggesting that the sensory information from rNST neurons, at the individual terminal level, is not passed to multiple target cells. Labeled terminals were usually presynaptic to distal dendritic shafts in both target nuclei. However, the frequency of labeled terminals that contacted dendritic spines was significantly higher in the PBN than in the RF, and the frequency of labeled terminals that contacted somata or proximal dendrites was significantly higher in the RF than in the PBN. Labeled terminals receiving axoaxonic synapses, which are a morphological substrate for presynaptic modulation frequently found in primary sensory afferents, were not observed. These findings suggest that the sensory information from rNST neurons is processed in a relatively simple manner in both PBN and RF, but in a distinctly different manner in the PBN as opposed to the RF.
Multichannel Transcranial Direct Current Stimulation Combined With Treadmill Gait Training in Patients With Parkinson's Disease: A Pilot Study
Authors: Na Yoonju , Kim Jinuk , Lee Su-Hyun , Kim Jihye , Lee Jungsoo , Shin Se Young , Chang Won Hyuk , Cho Jin Whan , Kim Yun-Hee
Published: March 2022

Background

Gait problems are critical impairments in Parkinson's disease (PD) and are related to increased risk of fall and negatively impact activities of daily life. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that can modify the cortical excitability of gait-related brain regions. In this study, we investigated whether multichannel tDCS with simultaneous treadmill gait training could improve gait in PD.

Methods

Twenty-four patients with PD were assigned randomly to a real or sham tDCS group. Before intervention, one patient of the real tDCS group was dropped out, leaving 23 patients to be analyzed in this study. Each patient underwent 30 min of treadmill gait training for 10 sessions over four consecutive weeks. Multichannel 4x1 tDCS was applied using five 6-cm-diameter round electrodes. One anode was placed on the CZ, and four cathodes were positioned symmetrically over the FZ, C5, C6, and PZ. Anodal tDCS (2mA) and sham tDCS were delivered for 20 min. The secondary outcomes were gait performance, as measured by the timed up and go test (TUG) and freezing of gait questionnaire (FOG-Q), and balance was assessed using the dynamic gait index (DGI), Berg balance scale (BBS), and functional reach test (FRT). Motor and non-motor performance of patients with PD were assessed using the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Participants were assessed before the intervention, immediately after the intervention, and 4 weeks after completion of the intervention.

Results

The real tDCS group showed a significant improvement in the 10-m walk test, but the sham group did not. Among the secondary outcome measures, MDS-UPDRS part II, TUG, and BBS were improved only in the real tDCS group. Particularly, MDS-UPDRS part II showed a significant group*time interaction effect, indicating that real tDCS demonstrated a better effect on the activities of daily living patients with PD.

Conclusions

The results of this pilot study suggest that multichannel tDCS applied on the leg motor cortex during treadmill gait training is a safe and effective means to improve gait velocity in patients with PD. Additional rigorous, large-sample, multicenter, randomized controlled trials are needed to confirm the effect of tDCS as a therapeutic adjunct for gait rehabilitation of patients with PD.
Posterior Circulation ASPECTS on CT Angiography Predicts Futile Recanalization of Endovascular Thrombectomy for Acute Basilar Artery Occlusion
Authors: Ouyang Keni , Kang Zhiming , Liu Zhengxing , Hou Botong , Fang Jiabing , Xie Yu , Liu Yumin
Published: March 2022

Background

Acute basilar artery occlusion (BAO) is the most potentially disastrous outcome and has a high risk of recurrence stroke in posterior circulation infarction (PCI). However, the rate of futile recanalization remains high despite successful recanalization. The objective of this study was to investigate 90 days functional outcomes among patients with BAO who underwent endovascular thrombectomy (EVT) and to identify the risk factors associated with futile recanalization.

Methods

We retrospectively analyzed 72 patients with acute BAO who received EVT from January 2018 to June 2021. CT angiography source images posterior circulation Acute Stroke Prognosis Early CT Score (CTA-SI pc-ASPECTS) evaluated the extensive hypoattenuation in patients with BAO. Futile recanalization defined an modified Rankin Scale (mRS) of 3-6 at 90 days despite a successful recanalization. Logistic regression analysis was performed to investigate the predictors of futile recanalization.

Results

Our sample included a total of 55 eligible patients. Patients with poor outcomes showed that the pc-ASPECTS score was lower in patients with poor outcomes than that in patients with good outcomes (P = 0.017). Longer time from symptoms onset-to-the puncture (P = 0.014) and elevation of leucocytes (P = 0.012) were associated with poor outcomes. The multivariable logistic analysis showed that pc-ASPECTS and onset-to-puncture time (OPT) were independent predictors of futile recanalization.

Conclusions

This study suggested that pc-ASPECTS and OPT are independent predictors of futile recanalization after EVT in patients with BAO. The lower pc-ASPECTS score and longer puncture time will have a poor clinical outcome.
Systematic Review - Combining Neuroprotection With Reperfusion in Acute Ischemic Stroke
Authors: Vos E. M. , Geraedts V. J. , van der Lugt A. , Dippel D. W. J. , Wermer M. J. H. , Hofmeijer J. , van Es A. C. G. M. , Roos Y. B. W. E. M. , Peeters-Scholte C. M. P. C. D. , van den Wijngaard I. R.
Published: March 2022

Background

Clinical trials of neuroprotection in acute ischemic stroke (AIS) have provided disappointing results. Reperfusion may be a necessary condition for positive effects of neuroprotective treatments. This systematic review provides an overview of efficacy of neuroprotective agents in combination with reperfusion therapy in AIS.

Methods

A literature search was performed on the following databases, namely PubMed, Embase, Web of Science, Cochrane Library, Emcare. All databases were searched up to September 23rd 2021. All randomized controlled trials in which patients were treated with neuroprotective strategies within 12 h of stroke onset in combination with intravenous thrombolysis (IVT), endovascular therapy (EVT), or both were included.

Results

We screened 1,764 titles/abstracts and included 30 full reports of unique studies with a total of 16,160 patients. In 15 studies neuroprotectants were tested for clinical efficacy, where all patients had to receive reperfusion therapies, either IVT and/or EVT. Heterogeneity in reported outcome measures was observed. Treatment was associated with improved clinical outcome for: 1) uric acid in patients treated with EVT and IVT, 2) nerinetide in patients who underwent EVT without IVT, 3) imatinib in stroke patients treated with IVT with or without EVT, 4) remote ischemic perconditioning and IVT, and 5) high-flow normobaric oxygen treatment after EVT, with or without IVT.

Conclusion

Studies specifically testing effects of neuroprotective agents in addition to IVT and/or EVT are scarce. Future neuroprotection studies should report standardized functional outcome measures and combine neuroprotective agents with reperfusion therapies in AIS or aim to include prespecified subgroup analyses for treatment with IVT and/or EVT.
Glial Fibrillary Acidic Protein in Blood as a Disease Biomarker of Neuromyelitis Optica Spectrum Disorders
Authors: Kim Hyunjin , Lee Eun-Jae , Lim Young-Min , Kim Kwang-Kuk
Published: March 2022

Glial fibrillary acidic protein (GFAP) is a type III intermediate filament protein found in astrocytes in the brain. Damaged astrocytes release GFAP into cerebrospinal fluid and blood. Thus, GFAP levels in these body fluids may reflect the disease state of neuromyelitis optica spectrum disorder (NMOSD), which includes astrocytopathy, characterized by pathogenic antibodies against aquaporin 4 located on astrocytes. Recently, single-molecule array technology that can detect these synaptic proteins in blood, even in the subfemtomolar range, has been developed. Emerging evidence suggests that GFAP protein is a strong biomarker candidate for NMOSD. This mini-review provides basic information about GFAP protein and innovative clinical data that show the potential clinical value of blood GFAP levels as a biomarker for NMOSD.
A Zero-Padding Frequency Domain Convolutional Neural Network for SSVEP Classification
Authors: Gao Dongrui , Zheng Wenyin , Wang Manqing , Wang Lutao , Xiao Yi , Zhang Yongqing
Published: March 2022

The brain-computer interface (BCI) of steady-state visual evoked potential (SSVEP) is one of the fundamental ways of human-computer communication. The main challenge is that there may be a nonlinear relationship between different SSVEP in other states. For improving the performance of SSVEP BCI, a novel CNN algorithm model is proposed in this study. Based on the discrete Fourier transform to calculate the signal's power spectral density (PSD), we perform zero-padding in the signal's time domain to improve its performance on the PSD and make it more refined. In this way, the frequency point interval in the PSD of the SSVEP is consistent with the minimum gap between the stimulation frequency. Combining the nonlinear transformation capabilities of CNN in deep learning, a zero-padding frequency domain convolutional neural network (ZPFDCNN) model is proposed. Extensive experiments based on the SSVEP dataset validate the effectiveness of our method. The study verifies that the proposed ZPFDCNN method can improve the effectiveness of the SSVEP-based high-speed BCI ITR. It has massive potential in the application of BCI.