bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive insight into anti-staphylococcal and anti-enterococcal action of brominated and chlorinated pyrazine-based chalcones
Authors: Konečná Klára , Diepoltová Adéla , Holmanová Pavlína , Jand’ourek Ondřej , Vejsová Marcela , Voxová Barbora , Bárta Pavel , Maixnerová Jana , Trejtnar František , Kučerová-Chlupáčová Marta
Published: August 2022

The greatest threat and medicinal impact within gram-positive pathogens are posed by two bacterial genera, Staphylococcus and Enterococcus. Chalcones have a wide range of biological activities and are recognized as effective templates in medicinal chemistry. This study provides comprehensive insight into the anti-staphylococcal and anti-enterococcal activities of two recently published brominated and chlorinated pyrazine-based chalcones, CH-0y and CH-0w. Their effects against 4 reference and 12 staphylococcal and enterococcal clinical isolates were evaluated. Bactericidal action, the activity in combination with selected conventional antibiotics, the study of post-antimicrobial effect (PAE, PAE/SME), and in vitro and in vivo toxicity, were included. In CH-0y, anti-staphylococcal activity ranging from MIC = 15.625 to 62.5 μM, and activity against E. faecium from 31.25 to 62.5 μM was determined. In CH-0w, anti-staphylococcal activity ranging from 31.25 to 125 μM, and activity against E. faecium and E. faecalis (62.5 μM) was revealed. Both CH-0y and CH-0w showed bactericidal action, beneficial impact on bacterial growth delay within PAE and PAE/SME studies, and non/low toxicity in vivo. Compared to CH-0w, CH-0y seems to have higher anti-staphylococcal and less toxic potential. In conclusion, chalcones CH-0y and CH-0w could be considered as structural pattern for future adjuvants to selected antibiotic drugs.
Probiotics or synbiotics addition to sows’ diets alters colonic microbiome composition and metabolome profiles of offspring pigs
Authors: Zhu Qian , Song Mingtong , Azad Md. Abul Kalam , Cheng Yating , Liu Yating , Liu Yang , Blachier François , Yin Yulong , Kong Xiangfeng
Published: August 2022

Little information exists about the effects of maternal probiotics and synbiotics addition on the gut microbiome and metabolome of offspring. The present study evaluated the effects of probiotics or synbiotics addition to sows’ diets on colonic microbiota and their metabolites in offspring using 16S rRNA gene sequencing and metabolome strategy. A total of 64 pregnant Bama mini-pigs were randomly divided into control, antibiotic, probiotics, and synbiotics groups and fed the corresponding experimental diets during pregnancy and lactation. After weaning, two piglets per litter and eight piglets per group were selected and fed a basal diet. The β-diversity analysis showed that the colonic microbiota of offspring had a clear distinction among the four groups at 65 days of age. Maternal probiotics addition increased the Actinobacteria abundance at 65 days of age and Tenericutes and Firmicutes abundances at 95 days of age of offspring compared with the other three groups, whereas maternal antibiotic addition increased Spirochaetes and Proteobacteria abundances at 95 days of age of offspring compared with the other three groups. Metabolomic analysis showed that colonic metabolites were different between the groups, regardless of the days of age. Furthermore, both PICRUSt2 and enrichment analysis of metabolic pathways showed that maternal probiotics and synbiotics addition affected metabolism of carbohydrate, amino acid, cofactors and vitamins in the colonic microbiota. Compared with the control group, the colonic concentration of indole decreased and skatole increased in the probiotics group, whereas indole increased and skatole decreased in the synbiotics group. Maternal probiotics addition increased the colonic concentrations of acetate and butyrate at 65 and 125 days of age, whereas probiotics and synbiotics addition decreased short-chain fatty acids concentrations at 95 days of age. In addition, the colonic concentrations of putrescine, cadaverine, 1,7-heptanediamine, and spermidine were increased in the antibiotic, probiotics, and synbiotics groups compared with the control group at 95 days of age. The correlation analysis showed that Gemmiger, Roseburia, and Faecalibacterium abundances were positively correlated with acetate, propionate, and butyrate concentrations; Gemmiger, Blautia, and Faecalibacterium were positively correlated with putrescine and spermidine; and Faecalibacterium, Blautia, Clostridium, and Streptococcus were positively correlated with (R)-3-hydroxybutyric acid. Collectively, these findings suggest that probiotics and synbiotics addition to sows’ diets exerts effects on offspring pigs by altering gut microbiota composition and their metabolites. The potential beneficial effect on gut health is discussed.
Niche, not phylogeny, governs the response to oxygen availability among diverse Pseudomonas aeruginosa strains
Authors: Shewaramani Sonal , Kassen Rees
Published: August 2022

Pseudomonas aeruginosa, a ubiquitous opportunistic pathogen, is a leading cause of chronic infection of airways in cystic fibrosis (CF) patients. Chronic infections typically arise from colonization by environmental strains, followed by adaptation of P. aeruginosa to the conditions within the CF airway. It has been suggested that oxygen availability can be an important source of selection causing trait changes associated with the transition to chronic infection, but little data exist on the response of P. aeruginosa to varying levels of oxygen. Here, we use a diverse collection of P. aeruginosa strains recovered from both CF patients and environmental sources to evaluate the role of oxygen availability in driving adaptation to the CF lung while also accounting for phylogenetic relatedness. While we can detect a signal of phylogeny in trait responses to oxygen availability, niche of origin is a far stronger predictor. Specifically, strains isolated from the lungs of CF patients are more sensitive to external oxidative stress but more resistant to antibiotics under anoxic conditions. Additionally, many, though not all, patho-adaptive traits we assayed are insensitive to oxygen availability. Our results suggest that inferences about trait expression, especially those associated with the transition to chronic infection, depend on both the available oxygen and niche of origin of the strains being studied.
Evaluation of two different vaccine platforms for immunization against melioidosis and glanders
Authors: Biryukov Sergei S. , Cote Christopher K. , Klimko Christopher P. , Dankmeyer Jennifer L. , Rill Nathaniel O. , Shoe Jennifer L. , Hunter Melissa , Shamsuddin Zain , Velez Ivan , Hedrick Zander M. , Rosario-Acevedo Raysa , Talyansky Yuli , Schmidt Lindsey K. , Orne Caitlyn E. , Fetterer David P. , Burtnick Mary N. , Brett Paul J. , Welkos Susan L. , DeShazer David
Published: August 2022

Burkholderia pseudomalleiand the closely related species,Burkholderia mallei, produce similar multifaceted diseases which range from rapidly fatal to protracted and chronic, and are a major cause of mortality in endemic regions. Besides causing natural infections, both microbes are Tier 1 potential biothreat agents. Antibiotic treatment is prolonged with variable results, hence effective vaccines are urgently needed. The purpose of our studies was to compare candidate vaccines that target both melioidosis and glanders to identify the most efficacious one(s) and define residual requirements for their transition to the non-human primate aerosol model. Studies were conducted in the C57BL/6 mouse model to evaluate the humoral and cell-mediated immune response and protective efficacy of threeBurkholderiavaccine candidates against lethal aerosol challenges withB. pseudomalleiK96243,B. pseudomalleiMSHR5855, andB. malleiFMH. The recombinant vaccines generated significant immune responses to the vaccine antigens, and the live attenuated vaccine generated a greater immune response to OPS and the whole bacterial cells. Regardless of the candidate vaccine evaluated, the protection of mice was associated with a dampened cytokine response within the lungs after exposure to aerosolized bacteria. Despite being delivered by two different platforms and generating distinct immune responses, two experimental vaccines, a capsule conjugate + Hcp1 subunit vaccine and the liveB. pseudomallei668 ΔilvIstrain, provided significant protection and were down-selected for further investigation and advanced development.
Succession of soil microbial community in a developing mid-channel bar: The role of environmental disturbance and plant community
Authors: Ye Fei , Hong Yiguo , Wu Jiapeng , Yi Xuemei , Op den Camp Huub J. M. , Moore Selina Sterup , Vamerali Teofilo , Wang Yu
Published: August 2022

Succession of microbial and plant communities is crucial for the development and the stability of soil ecological functions. The relative role of plant communities and environmental disturbance in shaping the microbial community in a newly established habitat remains unclear. In this study, a mid-channel bar (MCB) exposed to an environmental disturbance gradient in the Yangtze River was studied to explore the effects of such disturbance and plant community traits on the succession of the soil microbial community. Bulk and rhizospheric soils were collected from the MCB and classified according to their level of exposure to environmental disturbance: head, central and tail. These subsequently underwent high-throughput sequencing and interdomain ecological network (IDEN) analysis to identify and characterize the predominant microbial groups present in the soils at each disturbance level. Furthermore, at each site, the presence and distribution of the plant community was also noted. The present study demonstrated that both bulk soil nutrients and plant community exhibited significant spatial distribution dependent on the level of disturbance and this influenced the composition of the microbial community. In less eroded parts of the MCB, i.e., the central, nutrients accumulated, promoting growths of plants. This in turn encouraged a more diverse microbial community, dominated by the bacterial genusPseudarthrobacter. Plant showed a stronger association with bulk soil microbial communities compared to rhizosphere soil microbial communities. Particularly,Triarrhena saccharifloraandHemarthria altissima, present in sites of low disturbance, exhibiting a more extensive plant-microbe association. They thus played a key role in shaping the soil microbial community. In general, however, plant species did not directly determine the composition of the bacterial community, but instead altered the nutritive state of the soil to promote microbial growth. Such findings are of significant value for conservation practices of newly formed ecosystems, which requires an integrated understanding of the role of environmental disturbance and plants on soil microbial community assemblage.
The l-rhamnose-dependent regulator RhaS and its target promoters from Escherichia coli expand the genetic toolkit for regulatable gene expression in the acetic acid bacterium Gluconobacter oxydans
Authors: Fricke Philipp Moritz , Gries Mandy Lynn , Mürköster Maurice , Höninger Marvin , Gätgens Jochem , Bott Michael , Polen Tino
Published: August 2022

For regulatable target gene expression in the acetic acid bacterium (AAB) Gluconobacter oxydans only recently the first plasmids became available. These systems solely enable AraC- and TetR-dependent induction. In this study we showed that the l-rhamnose-dependent regulator RhaS from Escherichia coli and its target promoters PrhaBAD, PrhaT, and PrhaSR could also be used in G. oxydans for regulatable target gene expression. Interestingly, in contrast to the responsiveness in E. coli, in G. oxydans RhaS increased the expression from PrhaBAD in the absence of l-rhamnose and repressed PrhaBAD in the presence of l-rhamnose. Inserting an additional RhaS binding site directly downstream from the −10 region generating promoter variant PrhaBAD(+RhaS-BS) almost doubled the apparent RhaS-dependent promoter strength. Plasmid-based PrhaBAD and PrhaBAD(+RhaS-BS) activity could be reduced up to 90% by RhaS and l-rhamnose, while a genomic copy of PrhaBAD(+RhaS-BS) appeared fully repressed. The RhaS-dependent repression was largely tunable by l-rhamnose concentrations between 0% and only 0.3% (w/v). The RhaS-PrhaBAD and the RhaS-PrhaBAD(+RhaS-BS) systems represent the first heterologous repressible expression systems for G. oxydans. In contrast to PrhaBAD, the E. coli promoter PrhaT was almost inactive in the absence of RhaS. In the presence of RhaS, the PrhaT activity in the absence of l-rhamnose was weak, but could be induced up to 10-fold by addition of l-rhamnose, resulting in a moderate expression level. Therefore, the RhaS-PrhaT system could be suitable for tunable low-level expression of difficult enzymes or membrane proteins in G. oxydans. The insertion of an additional RhaS binding site directly downstream from the E. coli PrhaT −10 region increased the non-induced expression strength and reversed the regulation by RhaS and l-rhamnose from inducible to repressible. The PrhaSR promoter appeared to be positively auto-regulated by RhaS and this activation was increased by l-rhamnose. In summary, the interplay of the l-rhamnose-binding RhaS transcriptional regulator from E. coli with its target promoters PrhaBAD, PrhaT, PrhaSR and variants thereof provide new opportunities for regulatable gene expression in G. oxydans and possibly also for simultaneous l-rhamnose-triggered repression and activation of target genes, which is a highly interesting possibility in metabolic engineering approaches requiring redirection of carbon fluxes.
Enhancing control of multidrug-resistant plasmid and its host community with a prolonged thermophilic phase during composting
Authors: Shen Lei , Qiu Tianlei , Guo Yajie , Gao Min , Gao Haoze , Zhao Guozhu , Wang Xuming
Published: August 2022

The plasmid-mediated horizontal transfer of antibiotic resistance genes (ARGs) among bacteria facilitates the evolution and dissemination of antibiotic resistance. Broad-host-range plasmids can be transferred to different bacterial hosts in soil, plant rhizospheres, and wastewater treatment plants. Although composting is an effective way to convert organic waste into fertilizer and reduce some ARGs, few studies have focused on its effects on the spread of ARG-carrying plasmids and their bacterial host communities during composting. In this study, a fluorescently labeled Pseudomonas putida (P. putida) harboring a broad-host-range plasmid RP4 carrying three ARGs was inoculated into a raw material microcosm and composted with different durations of the thermophilic phase. The fate of the donor and RP4 in composting was investigated. The prolonged thermophilic composting removed 95.1% of dsRed and 98.0% of gfp, and it inhibited the rebound of P. putida and RP4 during the maturation phase. The spread potential of RP4 decreased from 10−4 to 10−6 transconjugants per recipient after composting. In addition, we sorted and analyzed the composition of RP4 recipient bacteria using fluorescence-activated cell sorting combined with 16S rRNA gene amplicon sequencing. The recipient bacteria of RP4 belonged to eight phyla, and Firmicutes, accounting for 75.3%–90.1%, was the dominant phylum in the transconjugants. The diversity and richness of the RP4 recipient community were significantly reduced by prolonged thermophilic periods. Overall, these findings provide new insights for assessing the contribution of composting in mitigating the dissemination of plasmid-mediated ARGs, and the prolonged thermophilic phase of composting can limit the transfer of multidrug-resistant plasmids.
Identification of hub genes and immune cell infiltration characteristics in chronic rhinosinusitis with nasal polyps: Bioinformatics analysis and experimental validation
Authors: Pan Yangwang , Wu Linjing , He Shuai , Wu Jun , Wang Tong , Zang Hongrui
Published: August 2022

The aim of our study is to reveal the hub genes related to the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) and their association with immune cell infiltration through bioinformatics analysis combined with experimental validation. In this study, through differential gene expression analysis, 1,516 upregulated and 1,307 downregulated DEG were obtained from dataset GSE136825 of the GEO database. We identified 14 co-expressed modules using weighted gene co-expression network analysis (WGCNA), among which the most significant positive and negative correlations were MEgreen and MEturquoise modules, containing 1,540 and 3,710 genes respectively. After the intersection of the two modules and DEG, two gene sets—DEG-MEgreen and DEG-MEturquoise—were obtained, containing 395 and 1,168 genes respectively. Through GO term analysis, it was found that immune response and signal transduction are the most important biological processes. We found, based on KEGG pathway enrichment analysis, that osteoclast differentiations, cytokine–cytokine receptor interactions, and neuroactive ligand–receptor interactions are the most important in the two gene sets. Through PPI network analysis, we listed the top-ten genes for the concentrated connectivity of the two gene sets. Next, a few genes were verified by qPCR experiments, and FPR2, ITGAM, C3AR1, FCER1G, CYBB in DEG-MEgreen and GNG4, NMUR2, and GNG7 in DEG-MEturquoise were confirmed to be related to the pathogenesis of CRSwNP. NP immune cell infiltration analysis revealed a significant difference in the proportion of immune cells between the NP group and control group. Finally, correlation analysis between target hub genes and immune cells indicated that FPR2 and GNG7 had a positive or negative correlation with some specific immune cells. In summary, the discoveries of these new hub genes and their association with immune cell infiltration are of great significance for uncovering the specific pathogenesis of CRSwNP and searching for disease biomarkers and potential therapeutic targets.
Identification of immune-related ferroptosis prognostic marker and in-depth bioinformatics exploration of multi-omics mechanisms in thyroid cancer
Authors: Fan Xin , Xie Fei , Zhang Lingling , Tong Chang , Zhang Zhiyuan
Published: August 2022

Background: Factors such as variations in thyroid carcinoma (THCA) gene characteristics could influence the clinical outcome. Ferroptosis and immunity have been verified to play an essential role in various cancers, and could affect the cancer patients’ prognosis. However, their relationship to the progression and prognosis of many types of THCA remains unclear.

Methods: First, we extracted prognosis-related immune-related genes and ferroptosis-related genes from 2 databases for co-expression analysis to obtain prognosis-related differentially expressed immune-related ferroptosis genes (PR-DE-IRFeGs), and screened BID and CDKN2A for building a prognostic model. Subsequently, multiple validation methods were used to test the model’s performance and compare its performance with other 4 external models. Then, we explored the mechanism of immunity and ferroptosis in the occurrence, development and prognosis of THCA from the perspectives of anti-tumor immunity, CDKN2A-related competitive endogenous RNA regulatory, copy number variations and high frequency gene mutation. Finally, we evaluated this model’s clinical practice value.

Results: BID and CDKN2A were identified as prognostic risk and protective factors, respectively. External data and qRT-PCR experiment also validated their differential expression. The model’s excellent performance has been repeatedly verified and outperformed other models. Risk scores were significantly associated with most immune cells/functions. Risk score/2 PR-DE-IRFeGs expression was strongly associated with BRAF/NRAS/HRAS mutation. Single copy number deletion of CDKN2A is associated with upregulation of CDKN2A expression and worse prognosis. The predicted regulatory network consisting of CYTOR, hsa-miRNA-873-5p and CDKN2A was shown to significantly affect prognosis. The model and corresponding nomogram have been shown to have excellent clinical practice value.

Conclusion: The model can effectively predict the THCA patients’ prognosis and guide clinical treatment. Ferroptosis and immunity may be involved in the THCA’s progression through antitumor immunity and BRAF/NRAS/HRAS mutation. CYTOR-hsa-miRNA-873-5p-CDKN2A regulatory networks and single copy number deletion of CDKN2A may also affect THCA′ progression and prognosis.
Emerging role of ferroptosis in glioblastoma: Therapeutic opportunities and challenges
Authors: Zhuo Shenghua , He Guiying , Chen Taixue , Li Xiang , Liang Yunheng , Wu Wenkai , Weng Lingxiao , Feng Jigao , Gao Zhenzhong , Yang Kun
Published: August 2022

Glioblastoma (GBM) is the most common malignant craniocerebral tumor. The treatment of this cancer is difficult due to its high heterogeneity and immunosuppressive microenvironment. Ferroptosis is a newly found non-apoptotic regulatory cell death process that plays a vital role in a variety of brain diseases, including cerebral hemorrhage, neurodegenerative diseases, and primary or metastatic brain tumors. Recent studies have shown that targeting ferroptosis can be an effective strategy to overcome resistance to tumor therapy and immune escape mechanisms. This suggests that combining ferroptosis-based therapies with other treatments may be an effective strategy to improve the treatment of GBM. Here, we critically reviewed existing studies on the effect of ferroptosis on GBM therapies such as chemotherapy, radiotherapy, immunotherapy, and targeted therapy. In particular, this review discussed the potential of ferroptosis inducers to reverse drug resistance and enhance the sensitivity of conventional cancer therapy in combination with ferroptosis. Finally, we highlighted the therapeutic opportunities and challenges facing the clinical application of ferroptosis-based therapies in GBM. The data generated here provide new insights and directions for future research on the significance of ferroptosis-based therapies in GBM.
5-methylcytosine turnover: Mechanisms and therapeutic implications in cancer
Authors: Turpin Marion , Salbert Gilles
Published: August 2022

DNA methylation at the fifth position of cytosine (5mC) is one of the most studied epigenetic mechanisms essential for the control of gene expression and for many other biological processes including genomic imprinting, X chromosome inactivation and genome stability. Over the last years, accumulating evidence suggest that DNA methylation is a highly dynamic mechanism driven by a balance between methylation by DNMTs and TET-mediated demethylation processes. However, one of the main challenges is to understand the dynamics underlying steady state DNA methylation levels. In this review article, we give an overview of the latest advances highlighting DNA methylation as a dynamic cycling process with a continuous turnover of cytosine modifications. We describe the cooperative actions of DNMT and TET enzymes which combine with many additional parameters including chromatin environment and protein partners to govern 5mC turnover. We also discuss how mathematical models can be used to address variable methylation levels during development and explain cell-type epigenetic heterogeneity locally but also at the genome scale. Finally, we review the therapeutic implications of these discoveries with the use of both epigenetic clocks as predictors and the development of epidrugs that target the DNA methylation/demethylation machinery. Together, these discoveries unveil with unprecedented detail how dynamic is DNA methylation during development, underlying the establishment of heterogeneous DNA methylation landscapes which could be altered in aging, diseases and cancer.
Identification of a prognostic classifier based on EMT-related lncRNAs and the function of LINC01138 in tumor progression for lung adenocarcinoma
Authors: Xiao Lingyan , Huang Yongbiao , Li Qian , Wang Sheng , Ma Li , Fan Zhijie , Tang Zhe , Yuan Xianglin , Liu Bo
Published: August 2022

Purpose: This study aimed to develop a prognostic indicator based on epithelial-mesenchymal transition (EMT)-related long noncoding RNAs (lncRNAs) and explore the function of EMT-related lncRNAs in malignant progression in lung adenocarcinoma (LUAD).

Materials and methods: A LUAD dataset was acquired from The Cancer Genome Atlas (TCGA) to identify prognostic EMT-related lncRNAs via differential expression analysis and univariate Cox regression analysis. Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis was utilized for variable selection and model construction. The EMT-related prognostic index (ERPI) was calculated according to the model and served as a classifier to divide LUAD individuals into high-ERPI and low-ERPI groups. A nomogram incorporating ERPI and clinicopathological variables was constructed. TCGA-LUAD, GSE50081, and GSE31210 were used to test the predictive capacity of the ERPI and nomogram. The characteristics of the tumor microenvironment (TME) were evaluated via the ESTIMATE, TIMER, and ssGSEA algorithms. Gene set variation analysis (GSVA) and ssGSEA were used to annotate the functions of the high-ERPI and low-ERPI groups. CCK8, transwell assay, wound-healing assay, and clone formation assay were conducted to clarify the biological functions of prognostic EMT-related lncRNAs.

Results: Ninety-seven differentially expressed EMT-related lncRNAs were identified, 15 of which were related to overall survival (OS). A prognostic signature was constructed based on 14 prognostic EMT-related lncRNAs to calculate the ERPI of each patient, and the predictive ability of ERPI was verified in TCGA, GSE50081, and GSE31210. The low-ERPI group survived longer and had a lower percentage of patients in advanced stage than the high-ERPI group. The nomogram had the highest predictive accuracy, followed by ERPI and stage. Patients with low ERPI had higher infiltration degree of immune cells and stronger immune responses than those with high ERPI. A series of in vitro experiments demonstrated that knockdown of LINC01138 dampened variability, proliferation, and motility of A549 and H460 cells.

Conclusion: Our study developed a prognostic classifier with robust prognostic performance and clarified the biological functions of LINC01138 in LUAD, aiding in making individual treatments for patients with LUAD and dissecting the mechanism of oncogenesis.
The Age-adjusted Charlson Comorbidity Index predicts post-operative delirium in the elderly following thoracic and abdominal surgery: A prospective observational cohort study
Authors: Liu Jing , Li Jianli , He Jinhua , Zhang Huanhuan , Liu Meinv , Rong Junfang
Published: August 2022

Background

Post-operative delirium (POD) presents as a serious neuropsychiatric syndrome in the elderly undergoing thoracic and abdominal surgery, which is mostly associated with poor prognosis. The Age-adjusted Charlson Comorbidity Index (ACCI) has been widely recognized as an independently predictive factor for overall survival rate and mortality in various surgeries. However, no studies demonstrated the potential relationship between ACCI and POD. The current study was to explore the correlation between ACCI and POD, and determine the predictive effect of ACCI on POD in the elderly after thoracic and abdominal surgery.

Materials and methods

Total 184 patients (≥60 years) who underwent thoracic and abdominal surgery from 2021.10 to 2022.5 were enrolled in this prospective observational cohort study. ACCI was calculated by weighting comorbidities and age. POD was diagnosed using Confusion Assessment Method (CAM) twice a day in the first 3 days after surgery. The Visual Analog Scale (VAS) was applied to measure pre-operative and post-operative pain at rest and in motion. All demographic and perioperative data were compared in patients with POD and without POD. ACCI and other variables were analyzed by univariate and multivariate logistic regression analysis. The characteristic curve of receiver operating characteristic (ROC) was used to further evaluate the accuracy of ACCI to predict POD.

Results

Post-operative delirium was diagnosed in 36 of 184 patients included in our study. The prevalence of POD in the elderly after thoracic and abdominal surgery was 19.6%. The outcomes by multivariate regression analysis showed the independent risk factors for POD were ACCI (OR: 1.834; 95%CI: 1.434–2.344; P < 0.001), pre-operative Mini-Mental State Examination (MMSE) scores (OR: 0.873; 95%CI: 0.767–0.994; P = 0.040), serum albumin (OR: 0.909; 95%CI: 0.826–1.000; P = 0.049) and pain scores in the post-operative third day (OR: 2.013; 95%CI: 1.459–2.778; P < 0.001). ACCI can predict POD more accurately with the largest area under curve (AUC) of 0.794 and sensitivity of 0.861, respectively.

Conclusion

Age-adjusted Charlson Comorbidity Index, pre-operative MMSE scores, serum albumin and post-operative pain were independently associated with POD in geriatric patients following thoracic and abdominal surgery. Moreover, ACCI may become an accurate indicator to predict POD early.
Consensus recommendations on therapeutic hypothermia after minimally invasive intracerebral hemorrhage evacuation from the hypothermia for intracerebral hemorrhage (HICH) working group
Authors: Baker Turner S. , Kellner Christopher P. , Colbourne Frederick , Rincon Fred , Kollmar Rainer , Badjatia Neeraj , Dangayach Neha , Mocco J. , Selim Magdy H. , Lyden Patrick , Polderman Kees , Mayer Stephan
Published: August 2022

Background and purpose

Therapeutic hypothermia (TH), or targeted temperature management (TTM), is a classic treatment option for reducing inflammation and potentially other destructive processes across a wide range of pathologies, and has been successfully used in numerous disease states. The ability for TH to improve neurological outcomes seems promising for inflammatory injuries but has yet to demonstrate clinical benefit in the intracerebral hemorrhage (ICH) patient population. Minimally invasive ICH evacuation also presents a promising option for ICH treatment with strong preclinical data but has yet to demonstrate functional improvement in large randomized trials. The biochemical mechanisms of action of ICH evacuation and TH appear to be synergistic, and thus combining hematoma evacuation with cooling therapy could provide synergistic benefits. The purpose of this working group was to develop consensus recommendations on optimal clinical trial design and outcomes for the use of therapeutic hypothermia in ICH in conjunction with minimally invasive ICH evacuation.

Methods

An international panel of experts on the intersection of critical-care TH and ICH was convened to analyze available evidence and form a consensus on critical elements of a focal cooling protocol and clinical trial design. Three focused sessions and three full-group meetings were held virtually from December 2020 to February 2021. Each meeting focused on a specific subtopic, allowing for guided, open discussion.

Results

These recommendations detail key elements of a clinical cooling protocol and an outline for the roll-out of clinical trials to test and validate the use of TH in conjunction with hematoma evacuation as well as late-stage protocols to improve the cooling approach. The combined use of systemic normothermia and localized moderate (33.5°C) hypothermia was identified as the most promising treatment strategy.

Conclusions

These recommendations provide a general outline for the use of TH after minimally invasive ICH evacuation. More research is needed to further refine the use and combination of these promising treatment paradigms for this patient population.
Simultaneous PET/MRI: The future gold standard for characterizing motor neuron disease—A clinico-radiological and neuroscientific perspective
Authors: Juengling Freimut D. , Wuest Frank , Kalra Sanjay , Agosta Federica , Schirrmacher Ralf , Thiel Alexander , Thaiss Wolfgang , Müller Hans-Peter , Kassubek Jan
Published: August 2022

Neuroimaging assessment of motor neuron disease has turned into a cornerstone of its clinical workup. Amyotrophic lateral sclerosis (ALS), as a paradigmatic motor neuron disease, has been extensively studied by advanced neuroimaging methods, including molecular imaging by MRI and PET, furthering finer and more specific details of the cascade of ALS neurodegeneration and symptoms, facilitated by multicentric studies implementing novel methodologies. With an increase in multimodal neuroimaging data on ALS and an exponential improvement in neuroimaging technology, the need for harmonization of protocols and integration of their respective findings into a consistent model becomes mandatory. Integration of multimodal data into a model of a continuing cascade of functional loss also calls for the best attempt to correlate the different molecular imaging measurements as performed at the shortest inter-modality time intervals possible. As outlined in this perspective article, simultaneous PET/MRI, nowadays available at many neuroimaging research sites, offers the perspective of a one-stop shop for reproducible imaging biomarkers on neuronal damage and has the potential to become the new gold standard for characterizing motor neuron disease from the clinico-radiological and neuroscientific perspectives.
Neurological and psychological effects of long COVID in a young population: A cross-sectional study
Authors: Guido Cristiana Alessia , Lucidi Fabio , Midulla Fabio , Zicari Anna Maria , Bove Elena , Avenoso Federica , Amedeo Ilaria , Mancino Enrica , Nenna Raffaella , De Castro Giovanna , Capponi Martina , Cinicola Bianca Laura , Brindisi Giulia , Grisoni Flavia , Murciano Manuel , Spalice Alberto ,   the Long-Covid Group of Department of Maternal Sciences
Published: August 2022

Aim

We evaluated the long-term clinical status of pediatric patients after testing positive for COVID-19. We hypothesized that there are similar symptoms to those that have been described in adults and children and that pediatric patients with neurophysiologic symptoms still present 3–5 months after infection have psychological consequences that interfere with their adaptive functioning.

Method

We recruited 322 COVID-19-positive pediatric patients, between 1.5 and 17 years old, from the outpatient clinic for COVID-19 follow-up. Neurological symptoms were analyzed at onset, after 1 month, and after 3–5 months. A psychological assessment with standardized questionnaires was also conducted to determine the impact of the disease.

Results

At the onset of COVID-19, 60% of the total sample exhibited symptoms; this decreased after 1 month (20%) but stabilized 3–5 months after disease onset (22%). Prevailing long-COVID neurological symptoms were headache, fatigue, and anosmia. In the 1.5–5-year-old subgroup, internalizing problems emerged in 12% of patients. In the 6–18-year-old subgroup, anxiety and post-traumatic stress showed significant associations with neurological symptoms of long COVID.

Conclusions

These data demonstrate that long COVID presents various broad-spectrum symptoms, including psychological and long-lasting cognitive issues. If not treated, these symptoms could significantly compromise the quality of life of children and adolescents.
Closed-loop motor imagery EEG simulation for brain-computer interfaces
Authors: Shin Hyonyoung , Suma Daniel , He Bin
Published: August 2022

In a brain-computer interface (BCI) system, the testing of decoding algorithms, tasks, and their parameters is critical for optimizing performance. However, conducting human experiments can be costly and time-consuming, especially when investigating broad sets of parameters. Attempts to utilize previously collected data in offline analysis lack a co-adaptive feedback loop between the system and the user present online, limiting the applicability of the conclusions obtained to real-world uses of BCI. As such, a number of studies have attempted to address this cost-wise middle ground between offline and live experimentation with real-time neural activity simulators. We present one such system which generates motor imagery electroencephalography (EEG) via forward modeling and novel motor intention encoding models for conducting sensorimotor rhythm (SMR)-based continuous cursor control experiments in a closed-loop setting. We use the proposed simulator with 10 healthy human subjects to test the effect of three decoder and task parameters across 10 different values. Our simulated approach produces similar statistical conclusions to those produced during parallel, paired, online experimentation, but in 55% of the time. Notably, both online and simulated experimentation expressed a positive effect of cursor velocity limit on performance regardless of subject average performance, supporting the idea of relaxing constraints on cursor gain in online continuous cursor control. We demonstrate the merits of our closed-loop motor imagery EEG simulation, and provide an open-source framework to the community for closed-loop SMR-based BCI studies in the future. All code including the simulator have been made available on GitHub.
Cumulant expansion with localization: A new representation of the diffusion MRI signal
Authors: Afzali Maryam , Pieciak Tomasz , Jones Derek K. , Schneider Jürgen E. , Özarslan Evren
Published: August 2022

Diffusion MR is sensitive to the microstructural features of a sample. Fine-scale characteristics can be probed by employing strong diffusion gradients while the low b-value regime is determined by the cumulants of the distribution of particle displacements. A signal representation based on the cumulants, however, suffers from a finite convergence radius and cannot represent the ‘localization regime' characterized by a stretched exponential decay that emerges at large gradient strengths. Here, we propose a new representation for the diffusion MR signal. Our method provides not only a robust estimate of the first three cumulants but also a meaningful extrapolation of the entire signal decay.
Protocol for randomized controlled trial to evaluate the safety and feasibility of a novel helmet to deliver transcranial light emitting diodes photobiomodulation therapy to patients with Parkinson’s disease
Authors: McGee Claire , Liebert Ann , Herkes Geoffrey , Bicknell Brian , Pang Vincent , McLachlan Craig S. , Kiat Hosen
Published: August 2022

Introduction

Parkinson’s disease (PD) is the second most common, progressive, and debilitating neurodegenerative disease associated with aging and the most common movement disorder. Photobiomodulation (PBM), the use of non-thermal light for therapeutic purposes using laser or light emitting diodes (LED) is an emerging non-invasive treatment for a diverse range of neurological conditions. The main objectives of this clinical trial are to investigate the feasibility, safety, tolerability, and efficacy of a novel transcranial LED helmet device (the “PDNeuro”) in the alleviation of symptoms of PD.

Methods and analysis

This is a 24-week, two-arm, triple-blinded randomized placebo-controlled clinical trial of a novel transcranial “PDNeuro” LED Helmet, comparing an active helmet to a sham helmet device. In a survey, 40 PD participants with Hoehn and Yahr Stage I–III during ON periods will be enrolled and randomly assigned into two groups. Both groups will be monitored weekly for the safety and tolerability of the “PDNeuro” LED Helmet. Clinical signs and symptoms assessed will include mobility, fine motor skills and cognition, with data collected at baseline, 12 weeks, and 24 weeks. Assessment tools include the TUG, UPDRS, and MoCA all validated for use in PD patients. Patient’s adherence to the device usage and participant drop out will be monitored weekly. At 12 weeks both placebo and treatment groups will crossover and placebo participants offered the treatment. The main indicator for clinical efficacy of the “PDneuro” Helmet is evidence of sustained improvements in motor and non-motor symptoms obtained from participant self-reported changes, carer reporting of changes and objective reassessment by the investigators. The outcomes will assist in a future larger randomized trial design.

Clinical Trial Registration

[https://www.anzctr.org.au], identifier [12621001722886].
Under or Absent Reporting of Light Stimuli in Testing of Anxiety-Like Behaviors in Rodents: The Need for Standardization
Authors: Neuwirth Lorenz S. , Verrengia Michael T. , Harikinish-Murrary Zachary I. , Orens Jessica E. , Lopez Oscar E.
Published: August 2022

Behavioral neuroscience tests such as the Light/Dark Test, the Open Field Test, the Elevated Plus Maze Test, and the Three Chamber Social Interaction Test have become both essential and widely used behavioral tests for transgenic and pre-clinical models for drug screening and testing. However, as fast as the field has evolved and the contemporaneous involvement of technology, little assessment of the literature has been done to ensure that these behavioral neuroscience tests that are crucial to pre-clinical testing have well-controlled ethological motivation by the use of lighting (i.e., Lux). In the present review paper, N = 420 manuscripts were examined from 2015 to 2019 as a sample set (i.e., n = ~20–22 publications per year) and it was found that only a meager n = 50 publications (i.e., 11.9% of the publications sampled) met the criteria for proper anxiogenic and anxiolytic Lux reported. These findings illustrate a serious concern that behavioral neuroscience papers are not being vetted properly at the journal review level and are being released into the literature and public domain making it difficult to assess the quality of the science being reported. This creates a real need for standardizing the use of Lux in all publications on behavioral neuroscience techniques within the field to ensure that contributions are meaningful, avoid unnecessary duplication, and ultimately would serve to create a more efficient process within the pre-clinical screening/testing for drugs that serve as anxiolytic compounds that would prove more useful than what prior decades of work have produced. It is suggested that improving the standardization of the use and reporting of Lux in behavioral neuroscience tests and the standardization of peer-review processes overseeing the proper documentation of these methodological approaches in manuscripts could serve to advance pre-clinical testing for effective anxiolytic drugs. This report serves to highlight this concern and proposes strategies to proactively remedy them as the field moves forward for decades to come.
Corilagin prevents non-alcoholic fatty liver disease via improving lipid metabolism and glucose homeostasis in high fat diet-fed mice
Authors: Liao Mingjuan , Zhang Rong , Wang Yongling , Mao Ziming , Wu Jing , Guo Huaqi , Zhang Kaiwen , Jing Yu , Zhang Caoxu , Song Huaidong , Chen Xia , Wei Gang
Published: August 2022

Non-alcoholic fatty liver disease (NAFLD) has been considered to be one of the most common chronic liver diseases. However, no validated pharmacological therapies have been officially proved in clinic due to its complex pathogenesis. The purpose of this study was to examine the protective effects of Corilagin (referred to Cori) against NAFLD in mice under a high fat diet (HFD) condition. Mice were fed either a normal control diet (NCD) or HFD with or without Cori (5 or 10 mg/kg body weight) for 15 weeks. In our results, Cori treatment significantly attenuated HFD-induced hepatic steatosis, high NAFLD activity score (NAD) and liver injury. Consistently, Cori treatment remarkably alleviated HFD-induced hepatic lipid accumulation (e.g., triglycerides (TG) and total cholesterol (TC) contents in liver), and improved plasma lipid concentrations (e.g., plasma TG, TC, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c)). Moreover, Cori treatment ameliorated NAFLD associated metabolic disorders such as glucose intolerance and insulin resistance in HFD-fed mice. Additionally, Cori treatment dramatically changed HFD-induced liver gene expression profiles, and identified overlapped differentially expressed genes (DEGs) between NCD vs. HFD group and HFD vs. HCR (high fat diet plus treatment with Cori) group. With these DEGs, we observed a marked enrichment of Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, which were closely associated with the metabolic balance in liver. Particularly, we found several potential hub proteins against NAFLD development with analyses of protein-protein interaction (PPI) network and qPCR assays. Collectively, our results revealed the important protective effects of Cori against the progress of NAFLD, which was probably mediated through improving dysregulated lipid metabolism and insulin resistance in HFD-fed mice. Additionally, Cori-dependent overlapped DEGs might serve as a featured NAFLD-associated gene expression signature for the diagnosis, treatment, as well as drug discovery and development of NAFLD in the near future.
Treatment, pathological characteristics, and prognosis of pulmonary inflammatory myofibroblastic tumor–a retrospective study of 8 cases
Authors: Zhu Xiao , Chen Wen-Bang , Xing Fu-Bao , Zhou Shao , Tang Zhen , Li Xiao-Jun , Zhang Lei , Huang Yu-Chen
Published: August 2022

Objective

Inflammatory myofibroblastic tumor (IMT) is a rare disease. We reviewed data from eight patients diagnosed with pulmonary IMT (PIMT) at our hospital with the aim of summarizing and analyzing the characteristics of PIMT to improve our understanding of the disease.

Methods

From January 2012 to December 2019, eight patients underwent surgical intervention for PIMT at The First Affiliated Hospital of Bengbu Medical College. Resected tumors were subjected to pathological and immunohistochemical analyses. The follow-up duration for all patients ranged from 2 years and 3 months to 9 years and 9 months (median: 6 years and 9 months).

Results

The male:female ratio was 5:3, and the mean age was 48.50 years (21–74 years). Two patients (25%) with lung disease discovered via chest computed tomography during physical examinations had not experienced any symptoms. Six patients (75%) presented at the hospital because of cough, expectoration, blood in sputum, and chest tightness. Lesions from all eight patients were surgically removed, and PIMT was confirmed based on pathological examinations and immunohistochemical results. No patient received additional treatment after discharge. All cases have been followed up to the time of writing, without any tumor recurrence or distant metastasis.

Conclusion

The age of onset of PIMT is usually over 40 years, and its clinical symptoms are easily confused with those of lung cancer. PIMT can only be diagnosed by histopathology and immunohistochemistry. Complete surgical resection is the preferred treatment, as patients undergoing surgery require no additional treatment, such as chemotherapy, and the survival rate is good.