bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma lipidomics of primary biliary cholangitis and its comparison with Sjögren’s syndrome
Authors: Li Haolong , Zhan Haoting , Cheng Linlin , Huang Yuan , Li Xiaomeng , Yan Songxin , Liu Yongmei , Wang Li , Li Yongzhe
Published: May 2023

Background

Abnormal lipid metabolism is common in patients with primary biliary cholangitis (PBC). PBC and Sjögren’s syndrome (SS) frequently coexist in clinical practice; however, the lipid characteristics of both diseases are unknown. Therefore, we aimed to analyze the plasma lipid profiles of both diseases.

Methods

Plasma samples from 60 PBC patients, 30 SS patients, and 30 healthy controls (HC) were collected, and untargeted lipidomics was performed using ultrahigh-performance liquid chromatography high-resolution mass spectrometry. Potential lipid biomarkers were screened through an orthogonal projection to latent structure discriminant analysis and further evaluated using receiver operating characteristic (ROC) analysis.

Results

A total of 115 lipids were differentially upregulated in PBC patients compared with HC. Seventeen lipids were positively associated with the disease activity of PBC, and ROC analysis showed that all of these lipids could differentiate between ursodeoxycholic acid (UDCA) responders and UDCA non-responders. The top six lipids based on the area under the curve (AUC) values were glycerophosphocholine (PC) (16:0/16:0), PC (18:1/18:1), PC (42:2), PC (16:0/18:1), PC (17:1/14:0), and PC (15:0/18:1). In comparison with SS, 44 lipids were found to be differentially upregulated in PBC. Additionally, eight lipids were found to have a good diagnostic performance of PBC because of the AUC values of more than 0.9 when identified from SS and HC groups, which were lysophosphatidylcholines (LysoPC) (16:1), PC (16:0/16:0), PC (16:0/16:1), PC (16:1/20:4), PC (18:0/20:3), PC (18:1/20:2), PC (20:0/22:5), and PC (20:1/22:5).

Conclusion

Our study revealed differentially expressed lipid signatures in PBC compared with HC and SS. PC is the main lipid species associated with disease activity and the UDCA response in patients with PBC.
TANK shapes an immunosuppressive microenvironment and predicts prognosis and therapeutic response in glioma
Authors: Li Shasha , Guo Youwei , Hu Huijuan , Gao Na , Yan Xuejun , Zhou Quanwei , Liu Hui
Published: May 2023

Background

Glioma, the most prevalent malignant intracranial tumor, poses a significant threat to patients due to its high morbidity and mortality rates, but its prognostic indicators remain inaccurate. Although TRAF-associated NF-kB activator (TANK) interacts and cross-regulates with cytokines and microenvironmental immune cells, it is unclear whether TANK plays a role in the immunologically heterogeneous gliomas.

Methods

TANK mRNA expression patterns in public databases were analyzed, and qPCR and IHC were performed in an in-house cohort to confirm the clinical significance of TANK. Then, we systematically evaluated the relationship between TANK expression and immune characteristics in the glioma microenvironment. Additionally, we evaluated the ability of TANK to predict treatment response in glioma. TANK-associated risk scores were developed by LASSO-Cox regression and machine learning, and their prognostic ability was tested.

Results

TANK was specifically overexpressed in glioma and enriched in the malignant phenotype, and its overexpression was related to poor prognosis. The presence of a tumor microenvironment that is immunosuppressive was evident by the negative correlations between TANK expression and immunomodulators, steps in the cancer immunity cycle, and immune checkpoints. Notably, treatment for cancer may be more effective when immunotherapy is combined with anti-TANK therapy. Prognosis could be accurately predicted by the TANK-related risk score.

Conclusions

High expression of TANK is associated with the malignant phenotype of glioma, as it shapes an immunosuppressive tumor microenvironment. Additionally, TANK can be used as a predictive biomarker for responses to various treatments and prognosis.
GNPNAT1 is a potential biomarker correlated with immune infiltration and immunotherapy outcome in breast cancer
Authors: Yuan Renjie , Zhang Yulu , Wang Yange , Chen Hongling , Zhang Ruiming , Hu Zhiyuan , Chai Chengsen , Chen Tingmei
Published: May 2023

Background

Glucosamine 6-phosphate N-acetyltransferase (GNPNAT1) is a crucial enzyme involving hexosamine biosynthesis pathway and is upregulated in breast cancer (BRCA). However, its biological function and mechanism on patients in BRCA have not been investigated.

Methods

In this study, the differential expression of GNPNAT1 was analyzed between BRCA tissues and normal breast tissues using the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, which was validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry. Then, the potential clinical value of GNPNAT1 in BRCA was investigated based on TCGA database. Functional enrichment analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Variation Analysis, were performed to explore the potential signaling pathways and biological functions involved in GNPNAT1 in BRCA. Tumor immune infiltration was analyzed using ESTIMATE, CIBERSORT and TISIDB database; and immune therapy response scores were assessed using TIDE. Finally, Western blot, Cell counting kit-8 and Transwell assay were used to determine the proliferation and invasion abilities of breast cancer cells with GNPNAT1 knockdown.

Results

GNPNAT1 was up-regulated in BRCA tissues compared with normal tissues which was subsequently verified in different cell lines and clinical tissue samples. Based on TCGA and GEO, the overexpression of GNPNAT1 in BRCA contributed to a significant decline in overall survive and disease specific survive. Functional enrichment analyses indicated that the enriched pathways in high GNPNAT1 expression group included citrate cycle, N-glycan biosynthesis, DNA repair, and basal transcription factors. Moreover, the overexpression of GNPNAT1 was negatively correlated with immunotherapy response and the levels of immune cell infiltration of CD8+ T cells, B cells, natural killer cells, dendritic cells and macrophages. Knockdown of GNPNAT1 impairs the proliferation and invasion abilities of breast cancer cells.

Conclusion

GNPNAT1 is a potential diagnostic, prognostic biomarker and novel target for intervention in BRCA.
Global transmission of monkeypox virus—a potential threat under the COVID-19 pandemic
Authors: Wang Yang , Leng Ping , Zhou Hao
Published: May 2023

Monkeypox virus (MPXV) cases have increased dramatically worldwide since May 2022. The Atlanta Center for Disease Control and Prevention (Atlanta CDC) had reported a total of 85,922 cases as of February 20th, 2023. During the COVID-19 pandemic, MPXV has emerged as a potential public threat. MPXV transmission and prevalence must be closely monitored. In this comprehensive review, we explained the basic characteristics and transmission routes of MPXV, individuals susceptible to it, as well as highlight the impact of the behavior of men who have sex with men (MSM) and airline traveling on recent outbreaks of MPXV. We also describe the clinical implications, the prevention of MPXV, and clinical measures of viral detection.
Establishment of a novel lysosomal signature for the diagnosis of gastric cancer with in-vitro and in-situ validation
Authors: Wang Qi , Liu Ying , Li Zhangzuo , Tang Yidan , Long Weiguo , Xin Huaiyu , Huang Xufeng , Zhou Shujing , Wang Longbin , Liang Bochuan , Li Zhengrui , Xu Min
Published: May 2023

Background

Gastric cancer (GC) represents a malignancy with a multi-factorial combination of genetic, environmental, and microbial factors. Targeting lysosomes presents significant potential in the treatment of numerous diseases, while lysosome-related genetic markers for early GC detection have not yet been established, despite implementing this process by assembling artificial intelligence algorithms would greatly break through its value in translational medicine, particularly for immunotherapy.

Methods

To this end, this study, by utilizing the transcriptomic as well as single cell data and integrating 20 mainstream machine-learning (ML) algorithms. We optimized an AI-based predictor for GC diagnosis. Then, the reliability of the model was initially confirmed by the results of enrichment analyses currently in use. And the immunological implications of the genes comprising the predictor was explored and response of GC patients were evaluated to immunotherapy and chemotherapy. Further, we performed systematic laboratory work to evaluate the build-up of the central genes, both at the expression stage and at the functional aspect, by which we could also demonstrate the reliability of the model to guide cancer immunotherapy.

Results

Eight lysosomal-related genes were selected for predictive model construction based on the inclusion of RMSE as a reference standard and RF algorithm for ranking, namely ADRB2, KCNE2, MYO7A, IFI30, LAMP3, TPP1, HPS4, and NEU4. Taking into account accuracy, precision, recall, and F1 measurements, a preliminary determination of our study was carried out by means of applying the extra tree and random forest algorithms, incorporating the ROC-AUC value as a consideration, the Extra Tree model seems to be the optimal option with the AUC value of 0.92. The superiority of diagnostic signature is also reflected in the analysis of immune features.

Conclusion

In summary, this study is the first to integrate around 20 mainstream ML algorithms to construct an AI-based diagnostic predictor for gastric cancer based on lysosomal-related genes. This model will facilitate the accurate prediction of early gastric cancer incidence and the subsequent risk assessment or precise individualized immunotherapy, thus improving the survival prognosis of GC patients.
A linear B-cell epitope close to the furin cleavage site within the S1 domain of SARS-CoV-2 Spike protein discriminates the humoral immune response of nucleic acid- and protein-based vaccine cohorts
Authors: Lorenz Peter , Steinbeck Felix , Mai Franz , Reisinger Emil C. , Müller-Hilke Brigitte
Published: May 2023

Background

Understanding the humoral immune response towards viral infection and vaccination is instrumental in developing therapeutic tools to fight and restrict the viral spread of global pandemics. Of particular interest are the specificity and breadth of antibody reactivity in order to pinpoint immune dominant epitopes that remain immutable in viral variants.

Methods

We used profiling with peptides derived from the Spike surface glycoprotein of SARS-CoV-2 to compare the antibody reactivity landscapes between patients and different vaccine cohorts. Initial screening was done with peptide microarrays while detailed results and validation data were obtained using peptide ELISA.

Results

Overall, antibody patterns turned out to be individually distinct. However, plasma samples of patients conspicuously recognized epitopes covering the fusion peptide region and the connector domain of Spike S2. Both regions are evolutionarily conserved and are targets of antibodies that were shown to inhibit viral infection. Among vaccinees, we discovered an invariant Spike region (amino acids 657-671) N-terminal to the furin cleavage site that elicited a significantly stronger antibody response in AZD1222- and BNT162b2- compared to NVX-CoV2373-vaccinees.

Conclusions

Understanding the exact function of antibodies recognizing amino acid region 657-671 of SARS-CoV-2 Spike glycoprotein and why nucleic acid-based vaccines elicit different responses from protein-based ones will be helpful for future vaccine design.
Global ocean colour trends in biogeochemical provinces
Authors: van Oostende Marit , Hieronymi Martin , Krasemann Hajo , Baschek Burkard
Published: May 2023

Satellite-derived ocean colour data provide continuous, daily measurements of global waters and are an essential tool for monitoring these waters in a changing climate. Merging observations from different satellite sensors is necessary for long-term and continuous climate research because the lifetime of these sensors is limited. A key issue in deriving long-term trends from merged ocean colour data is the inconsistency between the spatiotemporal coverage of the different sensor datasets that can lead to spurious multi-year fluctuations or trends in the time series. This study used the merged ocean colour satellite dataset produced by the Ocean Colour Climate Change Initiative (OC-CCI version 6.0) to infer global and local trends in optically active constituents. We applied a novel correction method to the OC-CCI dataset that results in a spatiotemporally consistent dataset, allowing the examination of long-term trends of optically active constituents with greater accuracy. We included sea surface temperature, salinity, and several climate oscillations in our analysis to gain insight into the underlying processes of derived trends. Our results indicate a significant increase in chlorophyll-a concentration in the polar waters, a decrease in chlorophyll-a concentration in some equatorial waters, and point to ocean darkening, predominantly in the polar waters, due to an increase in non-phytoplankton absorption. This study contributes to broader knowledge of global trends of optically active constituents and their relation to a changing environment.
Impact of anthropogenic sounds (pile driving, drilling and vessels) on the development of model species involved in marine biofouling
Authors: Cervello Gauthier , Olivier Frédéric , Chauvaud Laurent , Winkler Gesche , Mathias Delphine , Juanes Francis , Tremblay Réjean
Published: May 2023

The uncontrolled colonization of benthic organisms on submerged surfaces, also called biofouling, causes severe damage in the shipping and aquaculture industries. Biofouling starts with a benthic biofilm composed of a complex assemblage of microbes, bacteria and benthic diatoms, called microfouling, on which macrofouling invertebrate species settle and grow. Invertebrate larvae may use natural soundscapes to orientate inshore and choose their optimal habitat. Recent studies have demonstrated that ship sounds enhance the larval settlement and growth of several invertebrate species, such as mussels, associated with biofouling. Among invertebrates, effects of sound generated by offshore human activities are still poorly studied. This study aims to assess the effect of pile driving, drilling and vessel sounds on model species associated with micro and macrofouling. First, the biofilm development of Navicula pelliculosa and Amphora coffeaeformis was assessed, then, the larval development of the blue mussel (Mytilus edulis) was evaluated from the D-veliger to the postlarval stage. Mussel larvae and microalgae were exposed 12 h each day in tanks (Larvosonic) adapted to sound experiments under controlled conditions. All anthropogenic sounds induced a thinner N. pelliculosa biofilm coupled with a lower microalgae concentration. The drilling sound had a stronger effect on the biofilm thickness. The drilling sound significantly reduced the pediveliger settlement and the postlarvae clearance rate by 70.4% and tended to diminish settler sizes compared to control sound. Contrary to our expectation, pile driving tended to enhance larval recruitment by 22% (P=0.077) and the boat sound did not stimulate larval settlements or recruitment. Drilling sound generated a stressful acoustic environment for pediveliger settlements and postlarvae seem to maintain their shell valves closed to preserve energy. We identify potential causes and mechanisms involved in these impacts of anthropophony on larval ecology and microfouling dynamics.
Development of an AlphaLISA assay for sensitive and accurate detection of influenza B virus
Authors: Zong Huijun , Zhang Shengwei , Shang Xueyi , Jiang Hua , Zhao Zhongpeng , Chen Shaolong , Wang Xin , Wang Ye , Jiang Yongqiang , Li Xinyu , Tan Lingyun , Liu Peng , Lv Qingyu , Li Yan
Published: May 2023

Objective

Influenza B virus (IBV) is highly contagious, spreads rapidly, and causes seasonal epidemic respiratory disease in the human population, especially in immunocompromised people and young children. Clinical manifestations in this high-risk population are often more severe than in immunocompetent hosts and sometimes atypical. Therefore, rapid, and accurate detection of IBV is important.

Methods

An amplified luminescent proximity homogeneous assay linked immunosorbent assay (AlphaLISA) was developed for detection of IBV by optimizing the ratio of IBV antibody-labeled receptor beads, streptavidin-conjugated donor beads and biotinylated IBV antibody, as well as the optimal temperature and time conditions for incubation. Assay sensitivity, specificity and reproducibility were evaluated. A total of 228 throat swab samples and inactivated influenza B virus were tested by AlphaLISA and lateral flow colloidal gold-based immunoassay (LFIA).

Results

AlphaLISA produced the best results for detection of inactivated influenza B virus when IBV antibody-labeled acceptor beads were 50 μg/ mL, streptavidin-conjugated donor beads were 40 μg/mL, and biotinylated IBV antibody was 0.5 μg/mL at 37°C for 15–10 min. Under these conditions, AlphaLISA had a limit of detection of 0.24 ng/mL for the detection of influenza B nucleoprotein, did not cross react with other common respiratory viruses, and showed good reproducibility with inter-assay coefficient of variation (CV) and intra-assay CV < 5%. The results of 228 clinical throat swab samples showed good agreement between AlphaLISA and LFIA (Kappa = 0.982), and AlphaLISA showed better sensitivity than LFIA for detecting inactivated influenza B virus.

Conclusion

AlphaLISA showed higher sensitivity and throughput in the detection of IBV and can be used for IBV diagnosis and epidemic control.
Case report: Open water swimming as a possible treatment for asthma
Authors: Greenfield Kirsty , Verling William , Larcombe Thomas , Connett Gary James
Published: May 2023

Asthma is a complex medical problem for which currently available treatment can be incompletely effective. This case report describes a 49 year old woman who had suffered from asthma since her teenage years that resolved after she took up regular open water swimming. After sharing this case report with an international open water swimming community on social media, over one hundred people with asthma commented that their symptoms had also improved after taking up this activity. The mechanism whereby open water swimming might alleviate asthma has not been established. Possibilities include benefits to mental health, anti-inflammatory effects, being more fit, improved immune function and suppression of the bronchoconstrictive component of the diving reflex. Further research might usefully confirm or refute these clinical observations.
Implications of gut microbiota dysbiosis and fecal metabolite changes in psychologically stressed mice
Authors: Zhang Yi , Zhang Jing , Wu Jianmin , Zhu Qinwen , Chen Changrong , Li Yanning
Published: May 2023

Introduction

Psychological stress can induce affective disorders. Gut microbiota plays a vital role in emotional function regulation; however, the association between gut microbiota and psychological stress is poorly understood. We investigated effects of psychological stress on the gut microbiome and fecal metabolites and assessed the relationship between affective disorder behavior and altered fecal microbiota.

Methods

A psychological stress model was established in C57BL/6J mice using a communication box. Sucrose preference test, forced swim test, and open field test helped assess anxiety- and depression-like behaviors. Fecal microbiota transplantation (FMT) was conducted using fecal samples from stressed and non-stressed mice. Moreover, 16S rRNA gene sequencing and untargeted metabolomics were performed

Results

After stress exposure for 14 days, a significant increase in anxiety- and depression-like behaviors was observed. FMT of “affective disorder microbiota” from psychologically stressed mice increased stress sensitivity relative to FMT of “normal microbiota” from non-stressed mice. 16S rRNA gene sequencing revealed decreased abundance of Bacteroides, Alistipes, and Lactobacillus and increased abundance of Parasutterella and Rikenellaceae_RC9_gut_group in stressed mice; furthermore, stressed mice showed differential metabolite profiles. KEGG pathway analysis indicated that differential metabolites were chiefly involved in the downregulated pathways of α-linolenic acid metabolism, taste transduction, and galactose metabolism. Alistipes and Bacteroides were mainly positively correlated and Parasutterella was mainly negatively correlated with diverse metabolites.

Discussion

Our findings suggest that gut microbiome dysbiosis contributes to affective disorder development in response to psychological stress.
Phosphocholine cytidylyltransferase MoPct1 is crucial for vegetative growth, conidiation, and appressorium-mediated plant infection by Magnaporthe oryzae
Authors: Xu Zhe , Tong Qi , Lv Wuyun , Xiao Yu , Wang Zhengyi
Published: May 2023

Phosphatidylcholine (PC) plays crucial biological roles in eukaryotic cells. In Saccharomyces cerevisiae, apart from phosphatidylethanolamine (PE) methylation pathway, PC is also synthesized via CDP–choline pathway. Phosphocholine cytidylyltransferase Pct1 is the rate-limiting enzyme to catalyze the conversion from phosphocholine to CDP–choline in this pathway. Here, we report the identification and functional characterization of an ortholog of the budding yeast PCT1 in Magnaporthe oryzae, named MoPCT1. Targeted gene deletion mutants of MoPCT1 were impaired in vegetative growth, conidiation, appressorium turgor accumulation and cell wall integrity. Also, the mutants were severely compromised in appressorium-mediated penetration, infectious growth and pathogenicity. Western blot analysis revealed that cell autophagy was activated by the deletion of MoPCT1 under nutrient-rich conditions. Moreover, we found several key genes in PE methylation pathway, such as MoCHO2, MoOPI3, and MoPSD2, were significantly up-regulated in the ΔMopct1 mutants, indicating that a pronounced compensation effect exists between the two PC biosynthesis pathways in M. oryzae. Interestingly, in the ΔMopct1 mutants, histone H3 was hypermethylated and expression levels of several methionine cycling-related genes were significantly up-regulated, suggesting that MoPCT1 is involved in histone H3 methylation and methionine metabolism. Taken together, we conclude that the phosphocholine cytidylyltransferase coding gene MoPCT1 plays important roles in vegetative growth, conidiation and appressorium-mediated plant infection by M. oryzae.
Comparative genomics and transcriptomics insight into myxobacterial metabolism potentials and multiple predatory strategies
Authors: Wang Chunling , Xiao Yi , Wang Yong , Liu Yumin , Yao Qing , Zhu Honghui
Published: May 2023

Myxobacteria are part of the phylum Myxococcota, encompassing four orders. Most of them display complex lifestyles and broad predation profiles. However, metabolic potential and predation mechanisms of different myxobacteria remains poorly understood. Herein, we used comparative genomics and transcriptomics to analyze metabolic potentials and differentially expressed gene (DEG) profiles of Myxococcus xanthus monoculture (Mx) compared to coculture with Escherichia coli (MxE) and Micrococcus luteus (MxM) prey. The results showed that myxobacteria had conspicuous metabolic deficiencies, various protein secretion systems (PSSs) and the common type II secretion system (T2SS). RNA-seq data demonstrated that M. xanthus overexpressed the potential predation DEGs, particularly those encoding T2SS, the tight adherence (Tad) pilus, different secondary metabolites (myxochelin A/B, myxoprincomide, myxovirescin A1, geosmin and myxalamide), glycosyl transferases and peptidase during predation. Furthermore, the myxalamide biosynthesis gene clusters, two hypothetical gene clusters and one arginine biosynthesis clusters were highly differential expressed in MxE versus MxM. Additionally, homologue proteins of the Tad (kil) system and five secondary metabolites were in different obligate or facultative predators. Finally, we provided a working model for exhibiting multiple predatory strategies when M. xanthus prey on M. luteus and E. coli. These results might spur application-oriented research on the development of novel antibacterial strategies.
Biochemical characterization of an acetylesterase from Bacillus subtilis and its application for 7-aminocephalosporanic acid deacetylation
Authors: Wang Xiaoliang , Nong Sujin , Li Jiayi , Liu Yan , Wu Qian , Huang Zunxi , Xu Bo , Ding Junmei
Published: May 2023

Deacetyl-7-aminocephalosporanic acid (D-7-ACA), which could be converted from 7-aminocephalosporanic acid (7-ACA), is a crucial starting material that is used for synthesizing industrial semisynthetic β-lactam antibiotics. Enzymes involved in the conversion from 7-ACA to D-7-ACA present critical resources in the pharmaceutical industry. In the present study, a putative acetylesterase, EstSJ, identified from Bacillus subtilis KATMIRA1933, was first heterologously expressed in Escherichia coli BL21(DE3) cells and biochemically characterized. EstSJ belongs to carbohydrate esterase family 12 and is active on short-chain acyl esters from p-NPC2 to p-NPC6. Multiple sequence alignments showed that EstSJ was also an SGNH family esterase with a typical GDS(X) motif at its N-terminal end and a catalytic triad composed of Ser186-Asp354-His357. The purified EstSJ displayed the highest specific activity of 1,783.52 U mg–1 at 30°C and pH 8.0, and was stable within the pH range of 5.0–11.0. EstSJ can deacetylate the C3′ acetyl group of 7-ACA to generate D-7-ACA, and the deacetylation activity was 4.50 U mg–1. Based on the structural and molecular docking with 7-ACA, the catalytic active sites (Ser186-Asp354-His357) together with four substrate-binding residues (Asn259, Arg295, Thr355, and Leu356) of EstSJ are revealed. This study provided a promising 7-ACA deacetylase candidate that could be applied to produce D-7-ACA from 7-ACA in the pharmaceutical industry.
Molecular epidemiology of enterically colonizing Escherichia coli with resistance against third-generation cephalosporins isolated from stool samples of European soldiers with concomitant diarrhea on deployment in Western African Mali
Authors: Hoffmann Katharina , Riediger Matthias , Tersteegen Aljoscha , Marquardt Pauline , Kahlfuß Sascha , Kaasch Achim J. , Hagen Ralf Matthias , Frickmann Hagen , Zautner Andreas E.
Published: May 2023

Extended spectrum beta-lactamases (ESBL) are frequently found in Enterobacterales isolates from Western Africa. However, information on the molecular epidemiology of regional ESBL-positive Enterobacterales strains is scarce. In order to provide epidemiological information, ESBL-positive Escherichia coli isolates from stool samples of European soldiers with diarrhea deployed to a field camp in Mali were subjected to whole-genome sequencing (Illumina MiSeq and Oxford Nanopore MinION) and antimicrobial susceptibility testing. With two exemptions, sequence-based analysis suggested an absence of transmission events between soldiers as indicated by a high genetic diversity of isolates and sequence types, confirming previous rep-PCR results. Third-generation cephalosporin resistance was associated with the presence of blaCTX-M-15 genes with (n = 14) and without (n = 5) co-occurring blaTEM-1b genes. Between 0 and 6 virulence and resistance plasmids per isolate were recorded. The detected resistance plasmids could be categorized into five types, which, in turn, share different sequence-identical segments, representing particular antimicrobial resistance gene-associated mobile genetic elements (MGEs). Phenotypic resistance rates within the 19 assessed isolates that showed distinguishable colony morphologies were 94.7% (18/19) against ampicillin-sulbactam and trimethoprim/sulfamethoxazole, 68.4% (13/19) against moxifloxacin, 31.6% (6/19) against ciprofloxacin, 42.1% (8/19) against gentamicin, 31.6% (6/19) against tobramycin, and 21.1% (4/19) against piperacillin-tazobactam and fosfomycin. Virulence-associated genes mediating infectious gastroenteritis were rarely detected. The gene aggR, which is characteristic for enteroaggregative E. coli, was only detected in one single isolate. In summary, we found a variety of different strains and clonal lineages of ESBL-carrying E. coli. Transmission either between soldiers or from common contaminated sources was demonstrated in two cases and played only a minor role in this military field camp, while there were indications that resistance gene bearing MGEs had been exchanged between antimicrobial resistance gene-(ARG-)carrying plasmids.
Mobile genetic elements carrying aminoglycoside resistance genes in Acinetobacter baumannii isolates belonging to global clone 2
Authors: Naderi Ghazal , Talebi Malihe , Gheybizadeh Roghayeh , Seifi Arash , Ghourchian Sedigheh , Rahbar Mohammad , Abdollahi Alireza , Naseri Abdolhossein , Eslami Parisa , Douraghi Masoumeh
Published: May 2023

Aminoglycosides are used to treat infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) strains. However, resistance to aminoglycosides has increased remarkably in the last few years. Here, we aimed to determine the mobile genetic elements (MGEs) associated with resistance to aminoglycosides in the global clone 2 (GC2) A. baumannii. Among the 315 A. baumannii isolates, 97 isolates were identified as GC2, and 52 of GC2 isolates (53.6%) were resistant to all the aminoglycosides tested. The AbGRI3s carrying armA were detected in 88 GC2 isolates (90.7%), and of them, 17 isolates (19.3%) carried a new variant of AbGRI3 (AbGRI3ABI221). aphA6 was located in TnaphA6 of 30 isolates out of 55 aphA6-harboring isolates, and 20 isolates were found to harbor TnaphA6 on a RepAci6 plasmid. Tn6020 carrying aphA1b was detected in 51 isolates (52.5%), which was located within AbGRI2 resistance islands. The pRAY* carrying the aadB gene was detected in 43 isolates (44.3%), and no isolate was found to contain a class 1 integron harboring this gene. The GC2 A. baumannii isolates contained at least one MGE carrying the aminoglycoside resistance gene, located mostly either in the chromosome within AbGRIs or on the plasmids. Thus, it is likely that these MGEs play a role in the dissemination of aminoglycoside resistance genes in GC2 isolates from Iran.
Pyrroloquinoline-quinone to reduce fat accumulation and ameliorate obesity progression
Authors: Mohamad Ishak Nur Syafiqah , Ikemoto Kazuto
Published: May 2023

Obesity is a major health concern worldwide, and its prevalence continues to increase in several countries. Pyrroloquinoline quinone (PQQ) is naturally found in some foods and is available as a dietary supplement in its disodium crystal form. The potential health benefits of PQQ have been studied, considering its antioxidant and anti-inflammatory properties. Furthermore, PQQ has been demonstrated to significantly influence the functions of mitochondria, the organelles responsible for energy production within cells, and their dysfunction is associated with various health conditions, including obesity complications. Here, we explore PQQ properties that can be exploited in obesity treatment and highlight the underlying molecular mechanisms. We review animal and cell culture studies demonstrating that PQQ is beneficial for reducing the accumulation of visceral and hepatic fat. In addition to inhibiting lipogenesis, PQQ can increase mitochondria number and function, leading to improved lipid metabolism. Besides diet-induced obesity, PQQ ameliorates programing obesity of the offspring through maternal supplementation and alters gut microbiota, which reduces obesity risk. In obesity progression, PQQ mitigates mitochondrial dysfunction and obesity-associated inflammation, resulting in the amelioration of the progression of obesity co-morbidities, including non-alcoholic fatty liver disease, chronic kidney disease, and Type 2 diabetes. Overall, PQQ has great potential as an anti-obesity and preventive agent for obesity-related complications. Although human studies are still lacking, further investigations to address obesity and associated disorders are still warranted.
Exergaming in older adults: the effects of game characteristics on brain activity and physical activity
Authors: Müller Helen , Baumeister Jochen , Bardal Ellen Marie , Vereijken Beatrix , Skjæret-Maroni Nina
Published: May 2023

Introduction

Exergames are increasingly used in rehabilitation settings for older adults to train physical and cognitive abilities. To meet the potential that exergames hold, they need to be adapted to the individual abilities of the player and their training objectives. Therefore, it is important to know whether and how game characteristics affect their playing. The aim of this study is to investigate the effect of two different kinds of exergame (step game and balance game) played at two difficulty levels on brain activity and physical activity.

Methods

Twenty-eight older independently living adults played two different exergames at two difficulty levels each. In addition, the same movements as during gaming (leaning sideways with feet in place and stepping sideways) were performed as reference movements. Brain activity was recorded using a 64-channel EEG system to assess brain activity, while physical activity was recorded using an accelerometer at the lower back and a heart rate sensor. Source-space analysis was applied to analyze the power spectral density in theta (4 Hz–7 Hz) and alpha-2 (10 Hz–12 Hz) frequency bands. Vector magnitude was applied to the acceleration data.

Results

Friedman ANOVA revealed significantly higher theta power for the exergaming conditions compared to the reference movement for both games. Alpha-2 power showed a more diverse pattern which might be attributed to task-specific conditions. Acceleration decreased significantly from the reference movement to the easy condition to the hard condition for both games.

Discussion

The results indicate that exergaming increases frontal theta activity irrespective of type of game or difficulty level, while physical activity decreases with increasing difficulty level. Heart rate was found to be an inappropriate measure in this population older adults. These findings contribute to understanding of how game characteristics affect physical and cognitive activity and consequently need to be taken into account when choosing appropriate games and game settings for exergame interventions.
Interhemispheric neural characteristics of noxious mechano-nociceptive stimulation in the anterior cingulate cortex
Authors: Aminitabar Amir , Mirmoosavi Mahnoosh , Ghodrati Mohammad Taghi , Shalchyan Vahid
Published: May 2023

Background

Pain is an unpleasant sensory and emotional experience. One of the most critical regions of the brain for pain processing is the anterior cingulate cortex (ACC). Several studies have examined the role of this region in thermal nociceptive pain. However, studies on mechanical nociceptive pain have been very limited to date. Although several studies have investigated pain, the interactions between the two hemispheres are still not clear. This study aimed to investigate nociceptive mechanical pain in the ACC bilaterally.

Methods

Local field potential (LFP) signals were recorded from seven male Wistar rats’ ACC regions of both hemispheres. Mechanical stimulations with two intensities, high-intensity noxious (HN) and non-noxious (NN) were applied to the left hind paw. At the same time, the LFP signals were recorded bilaterally from awake and freely moving rats. The recorded signals were analyzed from different perspectives, including spectral analysis, intensity classification, evoked potential (EP) analysis, and synchrony and similarity of two hemispheres.

Results

By using spectro-temporal features and support vector machine (SVM) classifier, HN vs. no-stimulation (NS), NN vs. NS, and HN vs. NN were classified with accuracies of 89.6, 71.1, and 84.7%, respectively. Analyses of the signals from the two hemispheres showed that the EPs in the two hemispheres were very similar and occurred simultaneously; however, the correlation and phase locking value (PLV) between the two hemispheres changed significantly after HN stimulation. These variations persisted for up to 4 s after the stimulation. In contrast, variations in the PLV and correlation for NN stimulation were not significant.

Conclusions

This study showed that the ACC area was able to distinguish the intensity of mechanical stimulation based on the power activities of neural responses. In addition, our results suggest that the ACC region is activated bilaterally due to nociceptive mechanical pain. Additionally, stimulations above the pain threshold (HN) significantly affect the synchronicity and correlation between the two hemispheres compared to non-noxious stimuli.
Cognitive reserve index and long-term disability in patients with severe traumatic brain injury discharged from the intensive rehabilitation unit
Authors: Hakiki Bahia , Pancani Silvia , Romoli Anna Maria , Draghi Francesca , Maccanti Daniela , Mannini Andrea , Cecchi Francesca
Published: May 2023

Objectives

The “cognitive reserve” (CR) theory posits that higher premorbid cognitive activities can mitigate the effects of brain damage. This study aimed to investigate the association between CR and long-term functional autonomy in patients surviving a severe traumatic brain injury (sTBI).

Setting

Data were collected from the database of inpatients with severe acquired brain injury in a rehabilitation unit admitted from August 2012 to May 2020.

Participants

Patients that had incurred an sTBI, aged 18+ years, completing the phone Glasgow Outcome Scale-Expanded at follow-up (pGOS-E) in absence of previous brain trauma or neurological disease, or cognitive disorders were included. Patients with severe brain injury from non-traumatic etiologies were not included in the study.

Design

In this longitudinal study, all patients underwent a multidimensional assessment including the cognitive reserve index questionnaire (CRIq), the coma recovery scale-revised, the level of cognitive functioning, the Disability Rating Scale (DRS), and the Galveston Orientation and Amnesia Test at admission. At discharge, functional scales were administered again together with the Glasgow Outcome Scale. The pGOS-E was assessed at follow-up.

Main measures

pGOS-E.

Results

A total of 106 patients/caregivers underwent the pGOS-E after 5.8 [3.6] years from the event. Among them, 46 (43.4%) died after discharge, and 60 patients [men: 48 (80%); median age: 54 years; median time post-onset: 37 days; median education level: 10 years; median CRIq total score: 91] were included in the analysis exploring the association between pGOS-E and demographic data, cognitive reserve surrogates, and clinical variables at admission and discharge from the rehabilitation unit. A younger age (B = −0.035, p = 0.004) and a lower DRS category at discharge (B = −0.392, p = 0.029) were significantly related to a higher long-term functional autonomy in the multivariate analysis.

Conclusion

Long-term functional autonomy was not influenced by CR as assessed through the educational level and the CRIq.
Case report: Persistent hypogammaglobulinemia in thymoma-associated myasthenia gravis: the impact of rituximab or Good's syndrome?
Authors: Ren Jingru , Wang Jianchun , Liu Ran , Guo Jing , Yao Yan , Luo Jingjing , Hao Hongjun , Gao Feng
Published: May 2023

Introduction

Rituximab (RTX) showed good efficacy and safety for patients with myasthenia gravis. However, the percentage of peripheral CD20+ B cell may be absent for years after low dose of RTX treatment. Persistent hypogammaglobulinemia and opportunistic infection may occur in patients under treatment of RTX with thymoma relapse.

Case representation

We report a case of refractory myasthenia gravis. After two doses of 100 mg rituximab, the patient developed transient neutropenia. The peripheral blood CD20+ B cell percentage was 0 more than 3 years. Eighteen months later, the patient's symptoms relapsed with thymoma recurred. She had persistent hypogammaglobulinemia and multiple opportunistic infections.

Conclusion

In MG patient under B cell depletion therapy had thymoma relapse, Good's syndrome may induce prolonged B cell depletion, hypogammaglobulinemia and opportunistic infections.
Case report: An overlooked complication of the dural suture after craniotomy: pseudoaneurysm of the middle meningeal artery with endovascular resolution
Authors: Xu Yao , Li Xiangdong
Published: May 2023

Aneurysms of the middle meningeal artery (MMA) are exceedingly uncommon and mainly result from traumatic brain damage, but this report describes a case of MMA aneurysm induced by cranial surgery. Surgery was performed on a 34-year-old male with cerebrovascular malformation and cerebral hemorrhage. Cerebral angiography revealed no MMA aneurysm before craniocerebral surgery; however, a postoperative angiogram revealed a new MMA aneurysm. Aneurysms of the MMA are uncommon consequences of brain surgery. Based on our findings, the MMA as well as other meningeal arteries should be avoided while suturing the dura mater tent to prevent aneurysms.
Remotely supervised at-home tDCS for veterans with persistent post-traumatic headache: a double-blind, sham-controlled randomized pilot clinical trial
Authors: Charvet Leigh , Harrison Adam T. , Mangold Kiersten , Moore Robert Davis , Guo Siyuan , Zhang Jiajia , Datta Abhishek , Androulakis X. Michelle
Published: May 2023

Background

Currently, there are no FDA approved therapies for persistent post-traumatic headache (PPTH) secondary to traumatic brain injury (TBI). As such neither headache nor TBI specialists have an effective means to manage PPTH. Thus, the objective of the present pilot trial was to evaluate the feasibility and preliminary efficacy of a four-week at-home remotely supervised transcranial direct current stimulation (RS-tDCS) intervention for veterans with PPTH.

Methods

Twenty-five (m = 46.6 ± 8.7 years) veterans with PPTH were randomized into two groups and received either active (n = 12) or sham (n = 13) RS-tDCS, with anodal stimulation over left dlPFC and cathodal over occipital pole. Following a four-week baseline, participants completed 20–sessions of active or sham RS-tDCS with real-time video monitoring over a period of four-weeks. Participants were assessed again at the end of the intervention and at four-weeks post-intervention. Primary outcomes were overall adherence rate (feasibility) and change in moderate-to-severe headache days per month (efficacy). Secondary outcomes were changes in total number of headache days, and PPTH-related functional outcomes.

Results

Adherence rate was high with 88% of participants (active = 10/12; sham = 12/13) fully completing tDCS interventions. Importantly, there was no significant difference in adherence between active and sham groups (p = 0.59). Moderate-to-severe headache days were significantly reduced within the active RS-tDCS group (p = 0.004), compared to sham during treatment (−2.5 ± 3.5 vs. 2.3 ± 3.4), and 4-week follow-up (−3.9 ± 6.4 vs. 1.2 ± 6.5). Total number of headache days was significantly reduced within the active RS-tDCS (p = 0.03), compared to sham during-treatment (−4.0 ± 5.2 vs. 1.5 ± 3.8), and 4-week follow-up (−2.1 ± 7.2 vs. −0.2 ± 4.4).

Conclusion

The current results indicate our RS-tDCS paradigm provides a safe and effective means for reducing the severity and number of headache days in veterans with PPTH. High treatment adherence rate and the remote nature of our paradigm indicate RS-tDCS may be a feasible means to reduce PPTH, especially for veterans with limited access to medical facilities.

Clinical Trial Registration: ClinicalTrials.gov, identifier [NCT04012853].
β-glucans: a potential source for maintaining gut microbiota and the immune system
Authors: Singh Ravindra Pal , Bhardwaj Aditi
Published: May 2023

The human gastrointestinal (GI) tract holds a complex and dynamic population of microbial communities, which exerts a marked influence on the host physiology during homeostasis and disease conditions. Diet is considered one of the main factors in structuring the gut microbiota across a lifespan. Intestinal microbial communities play a vital role in sustaining immune and metabolic homeostasis as well as protecting against pathogens. The negatively altered gut bacterial composition has related to many inflammatory diseases and infections. β-glucans are a heterogeneous assemblage of glucose polymers with a typical structure comprising a leading chain of β-(1,4) and/or β-(1,3)-glucopyranosyl units with various branches and lengths as a side chain. β-glucans bind to specific receptors on immune cells and initiate immune responses. However, β-glucans from different sources differ in their structures, conformation, physical properties, and binding affinity to receptors. How these properties modulate biological functions in terms of molecular mechanisms is not known in many examples. This review provides a critical understanding of the structures of β-glucans and their functions for modulating the gut microbiota and immune system.
Nitric oxide modulates folate-mediated one-carbon metabolism and mitochondrial energy levels of peaches during cold storage
Authors: Yang Zhifeng , Zhu Shuhua , Wang Xiaoyu , Chen Changbao , Huang Dandan , Feng Jianrong
Published: May 2023

Folate-mediated one-carbon metabolism (FOCM) is closely associated with postharvest preservation. This study investigated the effects of exogenous nitric oxide (NO) on FOCM, storage quality, energy metabolism, and mitochondrial membrane integrity in cold-storage peach fruit. In this experiment, peaches were soaked with 1.5 mmol L−1S-nitrosoglutathione (GSNO) as NO donor, and the negative treatment (NT) solution containing 5 μmol L−1 carboxy-PTIO (c-PTIO, NO scavenger), 200 μmol L−1 NG-Nitro-L-arginine methyl ester (L-NAME, NO synthase-like enzyme inhibitor), and 200 μmol L−1 sodium tungstate dihydrate (nitrate reductase inhibitor) and stored at 0°C. The results showed that NO decreased the activity of S-adenosylmethionine synthase and S-adenosylhomocysteine hydrolase and increased the activity of methionine sulfoxide reductase A, as well as the content of N5-methyl-THF, the ratio of tetrahydrofolate (THF), homocysteine, methionine, S-adenosylmethionine (SAM), and SAM to S-adenosylhomocysteine compared with the control, indicating that NO effectively increased FOCM flux by affecting the activity of FOCM enzymes. Meanwhile, NO increased the activities of H+-ATPase, Ca2+-ATPase, cytochrome c oxidase, succinate dehydrogenase, and the contents of adenosine triphosphate and adenosine diphosphate, and maintained high energy charge in peaches during storage. NO retarded the increase in mitochondrial permeability transition, reactive oxygen species content, and the decrease in mitochondrial membrane fluidity, membrane potential, and swelling. NT treatment exhibited the opposite results. In conclusion, these results suggested that NO could induce the accumulation of folate and FOCM flux and maintain mitochondrial energy levels, which might be responsible for maintaining the quality of peaches during cold storage.