bluuebunny/crossref_metadata_2025 huggingface dataset:
Overload capacity analysis of extra high voltage AC XLPE submarine cable
Authors: Zhang Hao , Ma Guoqing , Li Pengfei , Huang Youcong , He Tongtong , Zheng Yuesheng
Published: June 2023

When submarine cable line fails or other lines need load transfer, it often suffers from emergency ampacity that exceeds the steady-state ampacity. The layout environment of the submarine cable is always complex and changeable, and the overload capacity of the submarine cable in different layout environments is also different. Therefore, it is necessary to analyze the overload capacity of the submarine cable. In this paper, a coupled multi-physical field model by finite element method is established for AC 500 kV XLPE extra high voltage submarine cable in landing section, which is the ampacity bottleneck section of the whole line. The overload capacity of submarine cable in two typical layout environments which are direct buried and within pipeline is analyzed. The results show that the overload capacity of submarine cable in the direct buried environment is much higher than that in the pipeline environment. The allowable emergency time in the direct buried environment is 2–3 times that of the pipeline environment under the same condition. In the two typical layout environments, when the emergency current are 2500 A and 3500 A, the ratio of the emergency time allowed to run in the direct buried environment to that in the pipeline environment is about 5 times under the same initial capacity. The proposed model can provide a reference for dynamic capacity control of the extra high voltage submarine cable.
Administration strategy of energy management in smart grid: system view and optimization path
Authors: Liu Peng , Wang Siyan , Wei Youman
Published: June 2023

Power generation and transmission infrastructure is vulnerable to the interaction of various Distributed Generations (DG), which leads to the imbalance of power system operation, frequent voltage drops or spikes, and even power outages. This phenomenon not only wastes energy, but also affects grid security. The main reason is a delayed feedback of circuit failure and load changes, and the optimization of energy management system and path is an effective way to solve the above problems. In this paper, a method of multi-objective optimization based on ANFIS algorithm is proposed which can help to improve the demand response, energy storage and management of smart power grid, reduce the volatility of DGs, reducing electricity costs and improving energy efficiency. Firstly, based on the ANFIS algorithm, the distributed power generation control mode, inverter control, real-time electricity price calculation method, energy transfer and storage scheme are improved, and the optimization path of the energy management system is defined. Secondly, the advantages of ANFIS algorithm in response speed and running stability are verified by comparing with other algorithms. Finally, a distributed energy microgrid is constructed for simulation verification. The results show that :(1) ANFIS optimization algorithm has good adaptability in smart grid, and has advantages in large amount of data processing and information transmission; (2) The verification model based on ANFIS has strong elasticity and efficient response speed. The research results will help solve various problems in the smart grid, including establishing a clear energy management system path, maintaining the stable operation of the power system, providing users with more reasonable power plans and the lowest cost of electricity.
The construction of an ecological security pattern based on the comprehensive evaluation of the importance of ecosystem service and ecological sensitivity: a case of Yangxin County, Hubei Province
Authors: Xu Hong , Zhang Zhiqi , Yu Xincan , Li Tianyue , Chen Zheng
Published: June 2023

An ecological safety pattern is the basic guarantee for pollution control, ecological environmental protection, economic construction, and sustainable social development, and is an important means of integrated and coordinated development, protection, and governance. This study proposes a research method to identify ecological source sites based on the evaluation of the importance of ecosystem services and ecological sensitivity, and to identify ecological corridors using the minimum cumulative resistance model. The empirical analysis was carried out in Yangxin County, Hubei Province, as an example. The results show that the study area has 16 key corridors and 29 potential corridors, a total of 45 ecological corridors, with a total length of 452 km. In addition, these ecological corridors present a network-like intertwined distribution, connecting various ecological source sites and ensuring the connectivity between ecological source sites, while the well-developed water source sites in the study area provide excellent ecosystem service functions such as water containment for the area.
Green economy studies amongst the global climate change challenge between 2016 and 2022: a bibliometric review
Authors: Zhu Jinsheng Jason , Zhang Ruitian , Kanhalikham Kesone , Liu Zitao , Shen Xiaoping
Published: June 2023

Practical and theoretical advancements have not caught pace with rising scientific researches in the rapidly emerging economy undertaking a shift to a more sustainable and particularly green model. After the UN adopted the 2030 Agenda for Sustainable Development, there has been a surge in interest in the green economy among academics around the world, and the literature on the issue is proliferating. This paper adopts the methodology of bibliometric review and thematic analysis to summarize the relevant literature from 2016 to 2022 on areas related to the theme of green economy. The literature was obtained from the Web of Science database with a total of 1,022 articles. Furthermore, the literature was analyzed using VOSviewer as well as the R language to couple the literature by keywords, country, affiliation, author, and publication. The findings of the current paper show that the green economy has received more academic attention from scholars since 2016. Asia and Europe are leaders in green economy studies. In the context of climate change, future research is anticipated to concentrate on establishing a green economy for global economic growth. This paper makes a substantial contribution to future research on the green economy.
Impact of maternal whole-cell or acellular pertussis primary immunization on neonatal immune response
Authors: Martin Aispuro Pablo , Bottero Daniela , Zurita María Eugenia , Gaillard María Emilia , Hozbor Daniela Flavia
Published: June 2023

With the introduction of pertussis immunization for pregnant women in many countries, there has been renewed interest in the impact of whole-cell pertussis vaccine (wP) versus acellular vaccine (aP) on disease control, particularly regarding the best approach for priming. To gather evidence on this topic, we analyzed the impact of aP or wP priming on aP vaccination during pregnancy (aPpreg) in mice. Two-mother vaccination schemes were employed (wP-wP-aPpreg and aP-aP-aPpreg), and the immune response in the mothers and their offspring, as well as the protection of the offspring against Bordetella pertussis challenge, were assessed. Pertussis toxin (PTx)-specific IgG responses were detected in mothers after both the second and third doses, with higher titers after the third dose, regardless of the vaccination schedule. However, a significant reduction in PTx-IgG levels was observed after 22 weeks post aPpreg immunization in mothers with the aP-aP-aPpreg scheme but not in the wP-wP-aPpreg immunized mothers. The aP-aP-aPpreg schedule triggered a murine antibody response mainly to a Th2-profile, while wP-wP-aPpreg induced a Th1/Th2 mixed profile. Both immunization schemes administered to the mothers protected the offspring against pertussis, but the wP-wP-aPpreg vaccination conferred offspring protection in all pregnancies at least up to 20 weeks after receiving the aPpreg-dose. In contrast, the immunity induced by aP-aP-aPpreg began to decline in births that occurred 18 weeks after receiving the aPpreg dose. For the aP-aP-aPpreg scheme, pups born from gestations furthest from aPpreg (+22 weeks) had lower PTx-specific IgG levels than those born closer to the application of the dose during pregnancy. In contrast, for pups born to wP-wP-aPpreg vaccinated mothers, the PTx-specific IgG levels were maintained over time, even for those born at the longest time studied (+22 weeks). It is noteworthy that only the pups born from mothers with aP-aP-aPpreg and receiving a neonatal dose of either aP or wP were more susceptible to B. pertussis infection than mice with only maternal immunity, suggesting interference with the induced immunity (p<0.05). However, it should be noted that mice with maternal immunity, whether vaccinated or not with neonatal doses, are better protected against colonization with B. pertussis than mice without maternal immunity but vaccinated with aP or wP.
Immune-checkpoint protein VISTA in allergic, autoimmune disease and transplant rejection
Authors: Zheng Meijun , Zhang Zongliang , Yu Lingyu , Wang Zeng , Dong Yijun , Tong Aiping , Yang Hui
Published: June 2023

Negative checkpoint regulators (NCRs) reduce the T cell immune response against self-antigens and limit autoimmune disease development. V-domain Ig suppressor of T cell activation (VISTA), a novel immune checkpoint in the B7 family, has recently been identified as one of the NCRs. VISTA maintains T cell quiescence and peripheral tolerance. VISTA targeting has shown promising results in treating immune-related diseases, including cancer and autoimmune disease. In this review, we summarize and discuss the immunomodulatory role of VISTA, its therapeutic potential in allergic, autoimmune disease, and transplant rejection, as well as the current therapeutic antibodies, to present a new method for regulating immune responses and achieving durable tolerance for the treatment of autoimmune disease and transplantation.
Enhancing therapeutic effects of murine cancer vaccine by reshaping gut microbiota with Lactobacillus rhamnosus GG and jujube powder
Authors: Jing Nan , Wang Luoyang , Zhuang Huiren , Jiang Guoqiang , Liu Zheng
Published: June 2023

Cancer vaccines have gained widespread attention in recent years as an emerging treatment for tumors. However, most therapeutic cancer vaccines have failed in phase III clinical trials due to faint clinical benefits. In this study, we funded that a specific synbiotic composing Lactobacillus rhamnosus GG (LGG) and jujube powder significantly enhanced the therapeutic effects of whole cells cancer vaccine in MC38 cancer cells bearing-mouse. The utilization of LGG increased the abundance of Muribaculaceae, which is conductive to an enhanced anti-tumor effect, but reduced microbial α-diversity. The use of jujube nursed probiotic microorganisms in Lachnospiaceae and enriched microbial diversity, as indicated by increased Shannon and Chao index. The reshaped gut microbiota by this synbiotic improved lipid metabolism conductive to intensified infiltration of CD8+ T cells in the tumor microenvironment and enhanced the potency of above-mentioned cancer vaccine. These encouraging findings are helpful for further efforts towards enhancing the therapeutic effects of cancer vaccines through nutritional intervention.
Nanopeptide C-I20 as a novel feed additive effectively alleviates detrimental impacts of soybean meal on mandarin fish by improving the intestinal mucosal barrier
Authors: Huo Xingchen , Zhang Qiwei , Chang Jiao , Yang Gang , He Shan , Yang Chunrong , Liang Xufang , Zhang Yongan , Su Jianguo
Published: June 2023

Antibacterial peptide has been widely developed in cultivation industry as feed additives. However, its functions in reducing the detrimental impacts of soybean meal (SM) remain unknown. In this study, we prepared nano antibacterial peptide CMCS-gcIFN-20H (C-I20) with excellent sustained-release and anti-enzymolysis, and fed mandarin fish (Siniperca chuatsi) with a SM diet supplemented with different levels of C-I20 (320, 160, 80, 40, 0 mg/Kg) for 10 weeks. 160 mg/Kg C-I20 treatment significantly improved the final body weight, weight gain rate and crude protein content of mandarin fish and reduced feed conversion ratio. 160 mg/Kg C-I20-fed fish maintained appropriate goblet cells number and mucin thickness, as well as improved villus length, intestinal cross-sectional area. Based on these advantageous physiological changes, 160 mg/Kg C-I20 treatment effectively reduced multi-type tissue (liver, trunk kidney, head kidney and spleen) injury. The addition of C-I20 did not change the muscle composition and muscle amino acids composition. Interestingly, dietary 160 mg/Kg C-I20 supplementation prevented the reduction in myofiber diameter and change in muscle texture, and effectively increased polyunsaturated fatty acids (especially DHA + EPA) in muscle. In conclusion, dietary C-I20 in a reasonable concentration supplementation effectively alleviates the negative effects of SM by improving the intestinal mucosal barrier. The application of nanopeptide C-I20 is a prospectively novel strategy for promoting aquaculture development.
Complex interactions of cellular players in chronic Graft-versus-Host Disease
Authors: Gail Laura Marie , Schell Kimberly Julia , Łacina Piotr , Strobl Johanna , Bolton Steven J. , Steinbakk Ulriksen Emilie , Bogunia-Kubik Katarzyna , Greinix Hildegard , Crossland Rachel Emily , Inngjerdingen Marit , Stary Georg
Published: June 2023

Chronic Graft-versus-Host Disease is a life-threatening inflammatory condition that affects many patients after allogeneic hematopoietic stem cell transplantation. Although we have made substantial progress in understanding disease pathogenesis and the role of specific immune cell subsets, treatment options are still limited. To date, we lack a global understanding of the interplay between the different cellular players involved, in the affected tissues and at different stages of disease development and progression. In this review we summarize our current knowledge on pathogenic and protective mechanisms elicited by the major involved immune subsets, being T cells, B cells, NK cells and antigen presenting cells, as well as the microbiome, with a special focus on intercellular communication of these cell types via extracellular vesicles as up-and-coming fields in chronic Graft-versus-Host Disease research. Lastly, we discuss the importance of understanding systemic and local aberrant cell communication during disease for defining better biomarkers and therapeutic targets, eventually enabling the design of personalized treatment schemes.
High infiltration of CD209+ dendritic cells and CD163+ macrophages in the peritumor area of prostate cancer is predictive of late adverse outcomes
Authors: Molina Oscar Eduardo , LaRue Hélène , Simonyan David , Hovington Hélène , Têtu Bernard , Fradet Vincent , Lacombe Louis , Toren Paul , Bergeron Alain , Fradet Yves
Published: June 2023

Introduction

Prostate cancer (PCa) shows considerable variation in clinical outcomes between individuals with similar diseases. The initial host-tumor interaction as assessed by detailed analysis of tumor infiltrating immune cells within the primary tumor may dictate tumor evolution and late clinical outcomes. In this study, we assessed the association between clinical outcomes and dendritic cell (DC) or macrophage (MΦ) tumor infiltration as well as with expression of genes related to their functions.

Methods

Infiltration and localization of immature DC, mature DC, total MΦ and M2-type MΦ was analyzed by immunohistochemistry in 99 radical prostatectomy specimens from patients with 15.5 years median clinical follow-up using antibodies against CD209, CD83, CD68 and CD163, respectively. The density of positive cells for each marker in various tumor areas was determined. In addition, expression of immune genes associated with DC and MΦ was tested in a series of 50 radical prostatectomy specimens by Taqman Low-Density Array with similarly long follow-up. Gene expression was classified as low and high after unsupervised hierarchical clustering. Numbers and ratio of positive cells and levels of gene expression were correlated with endpoints such as biochemical recurrence (BCR), need for definitive androgen deprivation therapy (ADT) or lethal PCa using Cox regression analyses and/or Kaplan-Meier curves.

Results

Positive immune cells were observed in tumor, tumor margin, and normal-like adjacent epithelium areas. CD209+ and CD163+ cells were more abundant at the tumor margin. Higher CD209+/CD83+ cell density ratio at the tumor margin was associated with higher risk of ADT and lethal PCa while higher density of CD163+ cells in the normal-like adjacent epithelium was associated with a higher risk of lethal PCa. A combination of 5 genes expressed at high levels correlated with a shorter survival without ADT and lethal PCa. Among these five genes, expression of IL12A and CD163 was correlated to each other and was associated with shorter survival without BCR and ADT/lethal PCa, respectively.

Conclusion

A higher level of infiltration of CD209+ immature DC and CD163+ M2-type MΦ in the peritumor area was associated with late adverse clinical outcomes.
Case Report: A severe case of immunosuppressant-refractory immune checkpoint inhibitor-mediated colitis rescued by tofacitinib
Authors: Sweep Mark W. D. , Tjan Martijn J. H. , Gorris Mark A. J. , Bol Kalijn F. , Westdorp Harm
Published: June 2023

Immune checkpoint inhibitor therapy for cancer treatment can give rise to a variety of adverse events. Here we report a male patient with metastatic melanoma who experienced life-threatening colitis and duodenitis following treatment with ipilimumab and nivolumab. The patient did not respond to the first three lines of immunosuppressive therapy (corticosteroids, infliximab, and vedolizumab), but recovered well after administration of tofacitinib, a JAK inhibitor. Cellular and transcriptional data on colon and duodenum biopsies shows significant inflammation in the tissue, characterized by a large number of CD8 T cells and high expression of PD-L1. While cellular numbers do decrease during three lines of immunosuppressive therapy, CD8 T cells remain relatively high in the epithelium, along with PD-L1 expression in the involved tissue and expression of colitis-associated genes, indicating an ongoing colitis at that moment. Despite all immunosuppressive treatments, the patient has an ongoing tumor response with no evidence of disease. Tofacitinib might be a good candidate to consider more often for ipilimumab/nivolumab-induced colitis.
Transforming growth factor-β1 and SMAD signalling pathway in the small airways of smokers and patients with COPD: potential role in driving fibrotic type-2 epithelial mesenchymal transition
Authors: Brake Samuel James , Lu Wenying , Chia Collin , Haug Greg , Larby Josie , Hardikar Ashutosh , Singhera Gurpreet K. , Hackett Tillie L. , Eapen Mathew Suji , Sohal Sukhwinder Singh
Published: June 2023

Background

COPD is a common disease characterized by respiratory airflow obstruction. TGF-β1 and SMAD pathway is believed to play a role in COPD pathogenesis by driving epithelial mesenchymal transition (EMT).

Methods

We investigated TGF-β1 signalling and pSmad2/3 and Smad7 activity in resected small airway tissue from patients with; normal lung function and a smoking history (NLFS), current smokers and ex-smokers with COPD GOLD stage 1 and 2 (COPD-CS and COPD-ES) and compared these with normal non-smoking controls (NC). Using immunohistochemistry, we measured activity for these markers in the epithelium, basal epithelium, and reticular basement membrane (RBM). Tissue was also stained for EMT markers E-cadherin, S100A4 and vimentin.

Results

The Staining of pSMAD2/3 was significantly increased in the epithelium, and RBM of all COPD groups compared to NC (p <0.0005). There was a less significant increase in COPD-ES basal cell numbers compared to NC (p= 0.02). SMAD7 staining showed a similar pattern (p <0.0001). All COPD group levels of TGF-β1 in the epithelium, basal cells, and RBM cells were significantly lower than NC (p <0.0001). Ratio analysis showed a disproportionate increase in SMAD7 levels compared to pSMAD2/3 in NLFS, COPD-CS and COPD-ES. pSMAD negatively correlated with small airway calibre (FEF25–75%; p= 0.03 r= -0.36). EMT markers were active in the small airway epithelium of all the pathological groups compared to patients with COPD.

Conclusion

Activation of the SMAD pathway via pSMAD2/3 is triggered by smoking and active in patients with mild to moderate COPD. These changes correlated to decline in lung function. Activation of the SMADs in the small airways is independent of TGF-β1, suggesting factors other than TGF-β1 are driving these pathways. These factors may have implications for small airway pathology in smokers and COPD through the process of EMT, however more mechanistic work is needed to prove these correlations.
Processes controlling the aragonite saturation state in the North Yellow Sea near the Yalu River estuary: contrasting river input effects
Authors: Xu Xuemei , Hu Yingying , He Zongcai , Wang Xinyi , Chen Hong , Han Jianbo
Published: June 2023

Understanding the characteristics of the aragonite saturation state (Ωarag) is necessary for assessing impacts of ocean acidification, especially in coastal oceans. Based upon surveys conducted in August and October 2022, the distribution and controlling processes of Ωarag were investigated in the North Yellow Sea near the Yalu River estuary. Surface water Ωarag values exhibited substantial variations of 1.14 to 3.79 for the input of river-diluted water and community production, whereas bottom water Ωarag values ranged from 1.82 to 2.40 in August. In addition, surface water Ωarag was further reduced to 1.07–2.37 in October due to the combined effects of seawater temperature decreasing and the upwelling of bottom water with low Ωarag values, while Ωarag values lowed to 1.04–2.14 in bottom water. Considerably low Ωarag values during summer and autumn in nearshore areas, especially in the Yalu River estuary, were resulted from the input of river-diluted water, while the net community respiration and remineralization induced the low bottom water Ωarag values in offshore areas. We suggest that integrated and multidisciplinary studies are required to quantify the trends and dynamics of acidification and its synergistic effects on the marine ecosystem in estuarine and coastal oceans.
Innate immune responses in Behçet disease and relapsing polychondritis
Authors: Shimizu Jun , Murayama Masanori A. , Mizukami Yoshihisa , Arimitsu Nagisa , Takai Kenji , Miyabe Yoshishige
Published: June 2023

Behçet disease (BD) and relapsing polychondritis (RP) are chronic multisystem disorders characterized by recurrent flare-ups of tissue inflammation. Major clinical manifestations of BD are oral aphthae, genital aphthous ulcers, skin lesions, arthritis, and uveitis. Patients with BD may develop rare but serious neural, intestinal, and vascular complications, with high relapse rates. Meanwhile, RP is characterized by the inflammation of the cartilaginous tissues of the ears, nose, peripheral joints, and tracheobronchial tree. Additionally, it affects the proteoglycan-rich structures in the eyes, inner ear, heart, blood vessels, and kidneys. The mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome is a common characteristic of BD and RP. The immunopathology of these two diseases may be closely related. It is established that the genetic predisposition to BD is related to the human leukocyte antigen (HLA)-B51 gene. Skin histopathology demonstrates the overactivation of innate immunity, such as neutrophilic dermatitis/panniculitis, in patients with BD. Monocytes and neutrophils frequently infiltrate cartilaginous tissues of patients with RP. Somatic mutations in UBA1, which encodes a ubiquitylation-related enzyme, cause vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome (VEXAS) with severe systemic inflammation and activation of myeloid cells. VEXAS prompts auricular and/or nasal chondritis, with neutrophilic infiltration around the cartilage in 52–60% of patients. Thus, innate immune cells may play an important role in the initiation of inflammatory processes underlying both diseases. This review summarizes the recent advances in our understanding of the innate cell-mediated immunopathology of BD and RP, with a focus on the common and distinct features of these mechanisms.
Computer-aided diagnosis using embedded ensemble deep learning for multiclass drug-resistant tuberculosis classification
Authors: Sethanan Kanchana , Pitakaso Rapeepan , Srichok Thanatkij , Khonjun Surajet , Weerayuth Nantawatana , Prasitpuriprecha Chutinun , Preeprem Thanawadee , Jantama Sirima Suvarnakuta , Gonwirat Sarayut , Enkvetchakul Prem , Kaewta Chutchai , Nanthasamroeng Natthapong
Published: June 2023

Introduction

This study aims to develop a web application, TB-DRD-CXR, for the categorization of tuberculosis (TB) patients into subgroups based on their level of drug resistance. The application utilizes an ensemble deep learning model that classifies TB strains into five subtypes: drug sensitive tuberculosis (DS-TB), drug resistant TB (DR-TB), multidrug-resistant TB (MDR-TB), pre-extensively drug-resistant TB (pre-XDR-TB), and extensively drug-resistant TB (XDR-TB).

Methods

The ensemble deep learning model employed in the TB-DRD-CXR web application incorporates novel fusion techniques, image segmentation, data augmentation, and various learning rate strategies. The performance of the proposed model is compared with state-of-the-art techniques and standard homogeneous CNN architectures documented in the literature.

Results

Computational results indicate that the suggested method outperforms existing methods reported in the literature, providing a 4.0%-33.9% increase in accuracy. Moreover, the proposed model demonstrates superior performance compared to standard CNN models, including DenseNet201, NASNetMobile, EfficientNetB7, EfficientNetV2B3, EfficientNetV2M, and ConvNeXtSmall, with accuracy improvements of 28.8%, 93.4%, 2.99%, 48.0%, 4.4%, and 7.6% respectively.

Conclusion

The TB-DRD-CXR web application was developed and tested with 33 medical staff. The computational results showed a high accuracy rate of 96.7%, time-based efficiency (ET) of 4.16 goals/minutes, and an overall relative efficiency (ORE) of 100%. The system usability scale (SUS) score of the proposed application is 96.7%, indicating user satisfaction and a likelihood of recommending the TB-DRD-CXR application to others based on previous literature.
Multidimensional risk factor analysis of acute low back pain progressing to chronicity: a longitudinal cohort study protocol
Authors: Huang Yilong , Li Chunli , Chen Jiaxin , Jiang Yuanming , Yang Yingjuan , Yang Juntao , Wang Zhongwei , Zhao Derong , Luo Mingbin , Pu Fushun , Zhang Zhenguang , He Bo
Published: June 2023

Introduction

Approximately 40% of patients with acute low back pain (LBP) develop chronic low back pain, which significantly increases the risk of poor prognosis. To reduce the risk of acute LBP becoming chronic, effective preventive strategies are needed. Early identification of risk factors for the development of chronic LBP can help clinicians choose appropriate treatment options and improve patient outcomes. However, previous screening tools have not considered medical imaging findings. The aim of this study is to identify factors that can predict the risk of acute LBP becoming chronic based on clinical information, pain and disability assessment, and MRI imaging findings. This protocol describes the methodology and plan for investigating multidimensional risk factors for acute LBP becoming chronic, in order to better understand the development of acute LBP and prevent chronic LBP.

Methods

This is a prospective multicenter study. We plan to recruit 1,000 adult patients with acute low back pain from four centers. In order to select four representative centers, we find the larger hospitals from different regions in Yunnan Province. The study will use a longitudinal cohort design. Patients will undergo baseline assessments upon admission and will be followed up for 5 years to collect the time of chronicity and associated risk factors. Upon admission, patients will be collected detailed demographic information, subjective and objective pain scores, disability scale, and lumbar spine MRI scanning. In addition, patient’s medical history, lifestyle, psychological factors will be collected. Patients will be followed up at 3 months, 6 months, 1 year, 2 years and up for 5 years after admission to collect the time of chronicity and associated factors. Multivariate analysis will be used to explore the multidimensional risk factors affecting the chronicity of acute LBP patients (such as age, gender, BMI, degree of intervertebral disc degeneration, etc.), and survival analysis will be performed to explore the impact of each factor on the time of chronicity.

Ethics and dissemination

The study has been approved by the institutional research ethics committee of each study center (main center number: 2022-L-305). Results will be disseminated through scientific conferences and peer-reviewed publications, as well as meetings with stakeholders.
Case report: A successfully treated case of community-acquired urinary tract infection due to Klebsiella aerogenes in Bangladesh
Authors: Mazumder Razib , Hussain Arif , Bhadra Bithika , Phelan Jody , Campino Susana , Clark Taane G. , Mondal Dinesh
Published: June 2023

Klebsiella aerogenes, a nosocomial pathogen, is increasingly associated with extensive drug resistance and virulence profiles. It is responsible for high morbidity and mortality. This report describes the first successfully treated case of community-acquired urinary tract infection (UTI) caused by Klebsiella aerogenes in an elderly housewife with Type-2 diabetes (T2D) from Dhaka, Bangladesh. The patient was empirically treated with intravenous ceftriaxone (500 mg/8 h). However, she did not respond to the treatment. The urine culture and sensitivity tests, coupled with bacterial whole-genome sequencing (WGS) and analysis, revealed the bacteria to be K. aerogenes which was extensively drug-resistant but was susceptible to carbapenems and polymyxins. Based on these findings, meropenem (500 mg/8 h) was administered to the patient, who then responded to the treatment and recovered successfully without having a relapse. This case raises awareness of the importance of diagnosis of not-so-common etiological agents, correct identification of the pathogens, and targeted antibiotic therapy. In conclusion, correctly identifying etiological agents of UTI using WGS approaches that are otherwise difficult to diagnose could help improve the identification of infectious agents and improve the management of infectious diseases.
Unrecognized diversity and distribution of soil algae from Maritime Antarctica (Fildes Peninsula, King George Island)
Authors: Rybalka Nataliya , Blanke Matthias , Tzvetkova Ana , Noll Angela , Roos Christian , Boy Jens , Boy Diana , Nimptsch Daniel , Godoy Roberto , Friedl Thomas
Published: June 2023

Introduction

Eukaryotic algae in the top few centimeters of fellfield soils of ice-free Maritime Antarctica have many important effects on their habitat, such as being significant drivers of organic matter input into the soils and reducing the impact of wind erosion by soil aggregate formation. To better understand the diversity and distribution of Antarctic terrestrial algae, we performed a pilot study on the surface soils of Meseta, an ice-free plateau mountain crest of Fildes Peninsula, King George Island, being hardly influenced by the marine realm and anthropogenic disturbances. It is openly exposed to microbial colonization from outside Antarctica and connected to the much harsher and dryer ice-free zones of the continental Antarctic. A temperate reference site under mild land use, SchF, was included to further test for the Meseta algae distribution in a contrasting environment.

Methods

We employed a paired-end metabarcoding analysis based on amplicons of the highly variable nuclear-encoded ITS2 rDNA region, complemented by a clone library approach. It targeted the four algal classes, Chlorophyceae, Trebouxiophyceae, Ulvophyceae, and Xanthophyceae, representing key groups of cold-adapted soil algae.

Results

A surprisingly high diversity of 830 algal OTUs was revealed, assigned to 58 genera in the four targeted algal classes. Members of the green algal class Trebouxiophyceae predominated in the soil algae communities. The major part of the algal biodiversity, 86.1% of all algal OTUs, could not be identified at the species level due to insufficient representation in reference sequence databases. The classes Ulvophyceae and Xanthophyceae exhibited the most unknown species diversity. About 9% of the Meseta algae species diversity was shared with that of the temperate reference site in Germany.

Discussion

In the small portion of algal OTUs for which their distribution could be assessed, the entire ITS2 sequence identity with references shows that the soil algae likely have a wide distribution beyond the Polar regions. They probably originated from soil algae propagule banks in far southern regions, transported by aeolian transport over long distances. The dynamics and severity of environmental conditions at the soil surface, determined by high wind currents, and the soil algae’s high adaptability to harsh environmental conditions may account for the high similarity of soil algal communities between the northern and southern parts of the Meseta.
The fungus Clonostachys epichloë alters the influence of the Epichloë endophyte on seed germination and the biomass of Puccinellia distans grass
Authors: Górzyńska Karolina , Olejniczak Paweł , Węgrzyn Ewa
Published: June 2023

The fungal grass endophyte Epichloë typhina (Pers.) Tul. & C. Tul. (Ascomycota: Clavicipitaceae) grows intercellulary in aerial plant parts and reproduces asexually by invading host seeds. In this phase, it enhances seed production and germination, which accelerates its vertical spread. This relationship may be distorted by other seed-born fungi, whose spread is not so directly dependent on the success of the grass. Recently, the fungus Clonostachys epichloë Schroers has been observed on Puccinellia distans (Jacq.) Parl seeds originating from grass clumps infested with stromata, sexual structures of Epichloë typhina that are formed in spring on some host culms, preventing flower and seed development (‘choke disease’). C. epichloë shows mycoparasitic activity toward Epichloë stromata by reducing the production of ascospores, which are responsible for horizontal transmission of the fungus. The aim of this study was to investigate the effect of seed-borne C. epichloë on seed germination, as well as the size and weight of P. distans seedlings and to examine whether C. epichloë alters the influence of Epichloë in the early developmental stages of P. distans. The results showed that if C. epichloë acts on seeds together with E. typhina endophytes, the seeds were negatively affected due to the elimination of the positive effect of the latter in terms of both seed germination rate and seedling length. At the same time, C. epichloë increased the proportion of E. typhina-untreated germinated seeds. Additionally, only the joint action of the two fungi, E. typhina and C. epichloë, effectively stimulated seedling dry mass; the presence of E. typhina alone was not sufficient to noticeably affect seedling size. Based on the increasing commonality of C. epichloë on Epichloë stromata, as well as its potential to be used in biocontrol of ‘choke disease’, we should take a closer look at this fungus, not only in terms of its mycoparasitic ability, but also in terms of its cumulative impact on the whole Epichloë-grass system.
Comparative genomics of the Liberibacter genus reveals widespread diversity in genomic content and positive selection history
Authors: Batarseh Tiffany N. , Batarseh Sarah N. , Morales-Cruz Abraham , Gaut Brandon S.
Published: June 2023

‘Candidatus Liberibacter’ is a group of bacterial species that are obligate intracellular plant pathogens and cause Huanglongbing disease of citrus trees and Zebra Chip in potatoes. Here, we examined the extent of intra- and interspecific genetic diversity across the genus using comparative genomics. Our approach examined a wide set of Liberibacter genome sequences including five pathogenic species and one species not known to cause disease. By performing comparative genomics analyses, we sought to understand the evolutionary history of this genus and to identify genes or genome regions that may affect pathogenicity. With a set of 52 genomes, we performed comparative genomics, measured genome rearrangement, and completed statistical tests of positive selection. We explored markers of genetic diversity across the genus, such as average nucleotide identity across the whole genome. These analyses revealed the highest intraspecific diversity amongst the ‘Ca. Liberibacter solanacearum’ species, which also has the largest plant host range. We identified sets of core and accessory genes across the genus and within each species and measured the ratio of nonsynonymous to synonymous mutations (dN/dS) across genes. We identified ten genes with evidence of a history of positive selection in the Liberibacter genus, including genes in the Tad complex, which have been previously implicated as being highly divergent in the ‘Ca. L. capsica’ species based on high values of dN.
Slipped-strand mispairing within a polycytidine tract in transcriptional regulator mga leads to M protein phase variation and Mga length polymorphism in Group A Streptococcus
Authors: Lei Benfang , Hanks Tracey S. , Bao Yunjuan , Liu Mengyao
Published: June 2023

The M protein, a major virulence factor of Group A Streptococcus (GAS), is regulated by the multigene regulator Mga. An unexplained phenomena frequently occurring with in vitro genetic manipulation or culturing of M1T1 GAS strains is the loss of M protein production. This study was aimed at elucidating the basis for the loss of M protein production. The majority of M protein-negative (M−) variants had one C deletion at a tract of 8 cytidines starting at base 1,571 of the M1 mga gene, which is designated as c.1571C[8]. The C deletion led to a c.1571C[7] mga variant that has an open reading frame shift and encodes a Mga-M protein fusion protein. Transformation with a plasmid containing wild-type mga restored the production of the M protein in the c.1571C[7] mga variant. Isolates producing M protein (M+) were recovered following growth of the c.1571C[7] M protein-negative variant subcutaneously in mice. The majority of the recovered isolates with reestablished M protein production had reverted back from c.1571C[7] to c.1571C[8] tract and some M+ isolates lost another C in the c.1571C[7] tract, leading to a c.1571C[6] variant that encodes a functional Mga with 13 extra amino acid residues at the C-terminus compared with wild-type Mga. The nonfunctional c.1571C[7] and functional c.1571C[6] variants are present in M1, M12, M14, and M23 strains in NCBI genome databases, and a G-to-A nonsense mutation at base 1,657 of M12 c.1574C[7] mga leads to a functional c.1574C[7]/1657A mga variant and is common in clinical M12 isolates. The numbers of the C repeats in this polycytidine tract and the polymorphism at base 1,657 lead to polymorphism in the size of Mga among clinical isolates. These findings demonstrate the slipped-strand mispairing within the c.1574C[8] tract of mga as a reversible switch controlling M protein production phase variation in multiple GAS common M types.
Association of brain morphology and phenotypic profile in patients with unruptured intracranial aneurysm
Authors: Li Jianyu , Tan Zeming , Yi Xiaoping , Fu Yan , Zhu Liping , Zeng Feiyue , Han Zaide , Ren Zhanbing , Zhang Yuanchao , Chen Bihong T.
Published: June 2023

Introduction

Studies have found a varying degree of cognitive, psychosocial, and functional impairments in patients with unruptured intracranial aneurysms (UIAs), whereas the neural correlates underlying these impairments remain unknown.

Methods

To examine the brain morphological alterations and white matter lesions in patients with UIA, we performed a range of structural analyses to examine the brain morphological alterations in patients with UIA compared with healthy controls (HCs). Twenty-one patients with UIA and 23 HCs were prospectively enrolled into this study. Study assessment consisted of a brain magnetic resonance imaging (MRI) scan with high-resolution T1-weighted and T2-weighted imaging data, a Montreal Cognitive Assessment (MoCA), and laboratory tests including blood inflammatory markers and serum lipids. Brain MRI data were processed for cortical thickness, local gyrification index (LGI), volume and shape of subcortical nuclei, and white matter lesions.

Results

Compared to the HCs, patients with UIA showed no significant differences in cortical thickness but decreased LGI values in the right posterior cingulate cortex, retrosplenial cortex, cuneus, and lingual gyrus. In addition, decreased LGI values correlated with decreased MoCA score (r = 0.498, p = 0.021) and increased white matter lesion scores (r = −0.497, p = 0.022). The LGI values were correlated with laboratory values such as inflammatory markers and serum lipids. Patients with UIA also showed significant regional atrophy in bilateral thalami as compared to the HCs. Moreover, the LGI values were significantly correlated with thalamic volume in the HCs (r = 0.4728, p = 0.0227) but not in the patients with UIA (r = 0.11, p = 0.6350).

Discussion

The decreased cortical gyrification, increased white matter lesions, and regional thalamic atrophy in patients with UIA might be potential neural correlates of cognitive changes in UIA.
In silico-in vitro modeling to uncover cues involved in establishing microglia identity: TGF-β3 and laminin can drive microglia signature gene expression
Authors: Timmerman Raissa , Zuiderwijk-Sick Ella Alwine , Baron Wia , Bajramovic Jeffrey John
Published: June 2023

Microglia are the resident macrophages of the central nervous system (CNS) and play a key role in CNS development, homeostasis, and disease. Good in vitro models are indispensable to study their cellular biology, and although much progress has been made, in vitro cultures of primary microglia still only partially recapitulate the transcriptome of in vivo microglia. In this study, we explored a combination of in silico and in vitro methodologies to gain insight into cues that are involved in the induction or maintenance of the ex vivo microglia reference transcriptome. First, we used the in silico tool NicheNet to investigate which (CNS-derived) cues could underlie the differences between the transcriptomes of ex vivo and in vitro microglia. Modeling on basis of gene products that were found to be upregulated in vitro, predicted that high mobility group box 2 (HMGB2)- and interleukin (IL)-1β-associated signaling pathways were driving their expression. Modeling on basis of gene products that were found to be downregulated in vitro, did not lead to predictions on the involvement of specific signaling pathways. This is consistent with the idea that in vivo microenvironmental cues that determine microglial identity are for most part of inhibitory nature. In a second approach, primary microglia were exposed to conditioned medium from different CNS cell types. Conditioned medium from spheres composed of microglia, oligodendrocytes, and radial glia, increased the mRNA expression levels of the microglia signature gene P2RY12. NicheNet analyses of ligands expressed by oligodendrocytes and radial glia predicted transforming growth factor beta 3 (TGF-β3) and LAMA2 as drivers of microglia signature gene expression. In a third approach, we exposed microglia to TGF-β3 and laminin. In vitro exposure to TGF-β3 increased the mRNA expression levels of the microglia signature gene TREM2. Microglia cultured on laminin-coated substrates were characterized by reduced mRNA expression levels of extracellular matrix-associated genes MMP3 and MMP7, and by increased mRNA expression levels of the microglia signature genes GPR34 and P2RY13. Together, our results suggest to explore inhibition of HMGB2- and IL-1β-associated pathways in in vitro microglia. In addition, exposure to TGF-β3 and cultivation on laminin-coated substrates are suggested as potential improvements to current in vitro microglia culture protocols.
Axo-axonic cells in neuropsychiatric disorders: a systematic review
Authors: Vivien Juliette , El Azraoui Anass , Lheraux Cloé , Lanore Frederic , Aouizerate Bruno , Herry Cyril , Humeau Yann , Bienvenu Thomas C. M.
Published: June 2023

Imbalance between excitation and inhibition in the cerebral cortex is one of the main theories in neuropsychiatric disorder pathophysiology. Cortical inhibition is finely regulated by a variety of highly specialized GABAergic interneuron types, which are thought to organize neural network activities. Among interneurons, axo-axonic cells are unique in making synapses with the axon initial segment of pyramidal neurons. Alterations of axo-axonic cells have been proposed to be implicated in disorders including epilepsy, schizophrenia and autism spectrum disorder. However, evidence for the alteration of axo-axonic cells in disease has only been examined in narrative reviews. By performing a systematic review of studies investigating axo-axonic cells and axo-axonic communication in epilepsy, schizophrenia and autism spectrum disorder, we outline convergent findings and discrepancies in the literature. Overall, the implication of axo-axonic cells in neuropsychiatric disorders might have been overstated. Additional work is needed to assess initial, mostly indirect findings, and to unravel how defects in axo-axonic cells translates to cortical dysregulation and, in turn, to pathological states.
Redistribution of the astrocyte phenotypes in the medial vestibular nuclei after unilateral labyrinthectomy
Authors: Li Jie , Wang Pengjun , Wang Lu-Yang , Wu Yaqin , Wang Jiping , Yu Dongzhen , Chen Zhengnong , Shi Haibo , Yin Shankai
Published: June 2023

Astrocytes are highly heterogeneous and involved in different aspects of fundamental functions in the central nervous system (CNS). However, whether and how this heterogeneous population of cells reacts to the pathophysiological challenge is not well understood. To investigate the response status of astrocytes in the medial vestibular nucleus (MVN) after vestibular loss, we examined the subtypes of astrocytes in MVN using single-cell sequencing technology in a unilateral labyrinthectomy mouse model. We discovered four subtypes of astrocytes in the MVN with each displaying unique gene expression profiles. After unilateral labyrinthectomy, the proportion of the astrocytic subtypes and their transcriptional features on the ipsilateral side of the MVN differ significantly from those on the contralateral side. With new markers to detect and classify the subtypes of astrocytes in the MVN, our findings implicate potential roles of the adaptive changes of astrocyte subtypes in the early vestibular compensation following peripheral vestibular damage to reverse behavioral deficits.