bluuebunny/crossref_metadata_2025 huggingface dataset:
Combining autophagy and immune characterizations to predict prognosis and therapeutic response in lung adenocarcinoma
Authors: Li Qiaxuan , Xie Daipeng , Yao Lintong , Qiu Hongrui , You Peimeng , Deng Jialong , Li Congsen , Zhan Weijie , Weng Maotao , Wu Shaowei , Li Fasheng , Zhou Yubo , Zeng Fanjun , Zheng Yong , Zhou Haiyu
Published: September 2022

Background

Autophagy, a key regulator of programmed cell death, is critical for maintaining the stability of the intracellular environment. Increasing evidence has revealed the clinical importance of interactions between autophagy and immune status in lung adenocarcinoma. The present study evaluated the potential of autophagy-immune-derived biomarkers to predict prognosis and therapeutic response in patients with lung adenocarcinoma.

Methods

Patients from the GSE72094 dataset were randomized 7:3 to a training set and an internal validation set. Three independent cohorts, TCGA, GSE31210, and GSE37745, were used for external verification. Unsupervised hierarchical clustering based on autophagy- and immune-associated genes was used to identify autophagy- and immune-associated molecular patterns, respectively. Significantly prognostic autophagy-immune genes were identified by LASSO analysis and by univariate and multivariate Cox regression analyses. Differences in tumor immune microenvironments, functional pathways, and potential therapeutic responses were investigated to differentiate high-risk and low-risk groups.

Results

High autophagy status and high immune status were associated with improved overall survival. Autophagy and immune subtypes were merged into a two-dimensional index to characterize the combined prognostic classifier, with 535 genes defined as autophagy-immune-related differentially expressed genes (DEGs). Four genes (C4BPA, CD300LG, CD96, and S100P) were identified to construct an autophagy-immune-related prognostic risk model. Survival and receiver operating characteristic (ROC) curve analyses showed that this model was significantly prognostic of survival. Patterns of autophagy and immune genes differed in low- and high-risk patients. Enrichment of most immune infiltrating cells was greater, and the expression of crucial immune checkpoint molecules was higher, in the low-risk group. TIDE and immunotherapy clinical cohort analysis predicted that the low-risk group had more potential responders to immunotherapy. GO, KEGG, and GSEA function analysis identified immune- and autophagy-related pathways. Autophagy inducers were observed in patients in the low-risk group, whereas the high-risk group was sensitive to autophagy inhibitors. The expression of the four genes was assessed in clinical specimens and cell lines.

Conclusions

The autophagy-immune-based gene signature represents a promising tool for risk stratification in patients with lung adenocarcinoma, guiding individualized targeted therapy or immunotherapy.
The role of PD-1/PD-L1 and application of immune-checkpoint inhibitors in human cancers
Authors: Tang Qing , Chen Yun , Li Xiaojuan , Long Shunqin , Shi Yao , Yu Yaya , Wu Wanyin , Han Ling , Wang Sumei
Published: September 2022

Programmed cell death protein-1 (PD-1) is a checkpoint receptor expressed on the surface of various immune cells. PD-L1, the natural receptor for PD-1, is mainly expressed in tumor cells. Studies have indicated that PD-1 and PD-L1 are closely associated with the progression of human cancers and are promising biomarkers for cancer therapy. Moreover, the interaction of PD-1 and PD-L1 is one of the important mechanism by which human tumors generate immune escape. This article provides a review on the role of PD-L1/PD-1, mechanisms of immune response and resistance, as well as immune-related adverse events in the treatment of anti-PD-1/PD-L1 immunotherapy in human cancers. Moreover, we summarized a large number of clinical trials to successfully reveal that PD-1/PD-L1 Immune-checkpoint inhibitors have manifested promising therapeutic effects, which have been evaluated from different perspectives, including overall survival, objective effective rate and medium progression-free survival. Finally, we pointed out the current problems faced by PD-1/PD-L1 Immune-checkpoint inhibitors and its future prospects. Although PD-1/PD-L1 immune checkpoint inhibitors have been widely used in the treatment of human cancers, tough challenges still remain. Combination therapy and predictive models based on integrated biomarker determination theory may be the future directions for the application of PD-1/PD-L1 Immune-checkpoint inhibitors in treating human cancers.
Macrophages and neutrophils express IFNλs in granulomas from Mycobacterium tuberculosis-infected nonhuman primates
Authors: Talukdar Priyanka , Junecko Beth F. , Lane Daniel S. , Maiello Pauline , Mattila Joshua T.
Published: September 2022

Granulomas are the hallmark of Mycobacterium tuberculosis (Mtb) infection. Cytokine-mediated signaling can modulate immune function; thus, understanding the cytokine milieu in granulomas is critical for understanding immunity in tuberculosis (TB). Interferons (IFNs) are important immune mediators in TB, and while type 1 and 2 IFNs have been extensively studied, less is known about type 3 IFNs (IFNλs) in TB. To determine if IFNλs are expressed in granulomas, which cells express them, and how granuloma microenvironments influence IFNλ expression, we investigated IFNλ1 and IFNλ4 expression in macaque lung granulomas. We identified IFNλ expression in granulomas, and IFNλ levels negatively correlated with bacteria load. Macrophages and neutrophils expressed IFNλ1 and IFNλ4, with neutrophils expressing higher levels of each protein. IFNλ expression varied in different granuloma microenvironments, with lymphocyte cuff macrophages expressing more IFNλ1 than epithelioid macrophages. IFNλ1 and IFNλ4 differed in their subcellular localization, with IFNλ4 predominantly localizing inside macrophage nuclei. IFNλR1 was also expressed in granulomas, with intranuclear localization in some cells. Further investigation demonstrated that IFNλ signaling is driven in part by TLR2 ligation and was accompanied by nuclear translocation of IFNλR1. Our data indicate that IFNλs are part of the granuloma cytokine milieu that may influence myeloid cell function and immunity in TB.
M2-like tumor-associated macrophage-related biomarkers to construct a novel prognostic signature, reveal the immune landscape, and screen drugs in hepatocellular carcinoma
Authors: Qu Xiaodong , Zhao Xingyu , Lin Kexin , Wang Na , Li Xuezhi , Li Songbo , Zhang Luyao , Shi Yongquan
Published: September 2022

Background

M2-like tumor-associated macrophages (M2-like TAMs) have important roles in the progression and therapeutics of cancers. We aimed to detect novel M2-like TAM-related biomarkers in hepatocellular carcinoma (HCC) via integrative analysis of single-cell RNA-seq (scRNA-seq) and bulk RNA-seq data to construct a novel prognostic signature, reveal the “immune landscape”, and screen drugs in HCC.

Methods

M2-like TAM-related genes were obtained by overlapping the marker genes of TAM identified from scRNA-seq data and M2 macrophage modular genes identified by weighted gene co-expression network analysis (WGCNA) using bulk RNA-seq data. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were carried out to screen prognostic genes from M2-like TAM-related genes, followed by a construction of a prognostic signature, delineation of risk groups, and external validation of the prognostic signature. Analyses of immune cells, immune function, immune evasion scores, and immune-checkpoint genes between high- and low-risk groups were done to further reveal the immune landscape of HCC patients. To screen potential HCC therapeutic agents, analyses of gene–drug correlation and sensitivity to anti-cancer drugs were conducted.

Results

A total of 127 M2-like TAM-related genes were identified by integrative analysis of scRNA-seq and bulk-seq data. PDLIM3, PAM, PDLIM7, FSCN1, DPYSL2, ARID5B, LGALS3, and KLF2 were screened as prognostic genes in HCC by univariate Cox regression and LASSO regression analyses. Then, a prognostic signature was constructed and validated based on those genes for predicting the survival of HCC patients. In terms of drug screening, expression of PAM and LGALS3 was correlated positively with sensitivity to simvastatin and ARRY-162, respectively. Based on risk grouping, we predicted 10 anticancer drugs with high sensitivity in the high-risk group, with epothilone B having the lowest half-maximal inhibitory concentration among all drugs tested.

Conclusions

Our findings enhance understanding of the M2-like TAM-related molecular mechanisms involved in HCC, reveal the immune landscape of HCC, and provide potential targets for HCC treatment.
Treating performance of a commercial-scale constructed wetland system for aquaculture effluents from intensive inland Micropterus salmoides farm
Authors: Li Bing , Jia Rui , Hou Yiran , Zhu Jian
Published: September 2022

In intensive inland fish farming, discharge of untreated effluents adversely affects adjacent water bodies and causes water pollution. Thus, it is highly necessary to treat the effluents from inland fish farm. In this study, we built a commercial-scale integrated constructed wetland (CW) system with vertical subsurface flow, and monitored the purifying effect. During fish farming and discharge of effluents periods, the water samples were collected to detected the total nitrogen (TN), total phosphorus (TP), ammonia nitrogen (NH4+-N), nitrate nitrogen (NO3--N), nitrite nitrogen (NO2--N) and chemical oxygen demand (CODMn). Results showed that the system was stable and significantly improved water quality from fish pond. During the fish farming period, the removal efficiency for TN, TP, NH4+-N, NO3--N, NO2--N, and COD was 24.93–43.72%, 61.92–72.18%, 56.29–68.63%, 56.66–64.81%, 56.42–64.19% and 28.37–42.79%, respectively. Similarly, these parameters were also markedly decreased by the integrated CW system during sewage discharge period, and the average total removal rate for TN, TP, NH4+-N, NO3--N, NO2--N, and COD was 50.24%, 64.48%, 61.36%, 62.65%, 56.16% and 37.32%, respectively. It was worth noting that three key parameters for effluents detection TN, TP and COD values were below the threshold values of water quality of Class II in freshwater sewage discharge standard of China (SCT9101-2007). In conclusion, this study evidently demonstrated that application of CW system was an environmental sustainable sewage treatment strategy in intensive inland fish farming.
Transcriptomic and metabolomic insights into the role of fliS in the pathogenicity of Pseudomonas plecoglossicida against Epinephelus coioides
Authors: Wu Wensi , Zhao Lingmin , Huang Lixing , Qin Yingxue , Zhang Jiaonan , Zhang Jiaolin , Yan Qingpi
Published: September 2022

Pseudomonas plecoglossicida is responsible for visceral white spot disease in economically valuable marine fish such as Larimichthys crocea and Epinephelus coioides. Based on RNA sequencing, we previously showed that P. plecoglossicida fliS gene expression is significantly up-regulated in E. coioides spleens during infection. Here, to explore the role of this gene in pathogenicity, RNA interference (RNAi) was performed to silence fliS in P. plecoglossicida, and the mutant with the best silencing efficiency (89%) was chosen for further studies. Results showed that fliS silencing significantly attenuated motility, chemotaxis, adhesion, and biofilm formation of P. plecoglossicida. Furthermore, E. coioides infected with the fliS-RNAi strain recorded no deaths and showed fewer pathogens in the spleen and fewer white spots on the spleen surface compared to those fish infected with the wild type P. plecoglossicida strain. RNAi of fliS significantly affected the spleen transcriptome and metabolome in infected E. coioides. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the cytokine-cytokine receptor interaction pathway was the most enriched immune-related pathway, and the arginine biosynthesis pathway was the most enriched metabolism-related pathway. These findings suggest that fliS is a virulence gene of P. plecoglossicida and is involved in the regulation of motility, chemotaxis, adhesion, and biofilm formation, as well as the inflammatory and immune responses of E. coioides to P. plecoglossicida infection.
Removal of sulphate and arsenic from wastewater using calcium sulfoaluminate (ye’elimite)
Authors: Nurmesniemi Emma-Tuulia , Huhta Milla , Derkani Maryam , Isteri Visa , Hanein Theodore , Hu Tao , Tanskanen Pekka , Lassi Ulla
Published: September 2022

Chemical precipitation is one of the most widely known methods for treatment of industrial wastewaters with high sulphate content, where sulphate can be precipitated as practically insoluble ettringite (Ca6Al2(SO4)3(OH)12·26H2O). This treatment method is also widely recognised for solidifying hazardous components and toxic elements e.g. arsenic in wastewater. In the ettringite precipitation process, lime and aluminium salts are typically used as starting materials, in stoichiometric amounts to form ettringite from the sulphate-containing water, leading to a pH rise to ∼11.5 and ettringite precipitation. In the current study, for the first time, ye’elimite mineral (Ca4Al6O12SO4), also known as calcium sulfoaluminate (CSA) in cements, is used in order to investigate its suitability to form ettringite precipitate from sulphate and arsenic containing synthetic wastewater and industrial wastewater solutions. The dissolution of ye’elimite prior to dosing, optimal precipitation pH, and arsenic co-precipitation were studied. The effluent and precipitates were characterized using X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM-EDS) and inductively coupled plasma atomic emission spectroscopy (ICP-OES). The results showed that high percentage of sulphate removal (98% in the synthetic wastewater and 87% in the industrial wastewater) can be achieved using ye’elimite as the aluminium source in ettringite precipitation. Additionally, up to 95% arsenic removal was achieved in arsenic co-precipitation experiments from the synthetic wastewater. The current developed technology can be used as a novel ecological and cost-effective approach for removal of sulphate and toxic elements from wastewater.
Pulse pressure and the risk of renal hyperfiltration in young adults: Results from Korea National Health and Nutrition Examination Survey (2010–2019)
Authors: Yang Eunji , Park Sang Ho , Lee Seoyoung , Oh Donghwan , Choi Hoon Young , Park Hyeong Cheon , Jhee Jong Hyun
Published: September 2022

Background

High pulse pressure (PP) is associated with increased risk of decline of kidney function. However, little is known about the association between PP and RHF in young adults. This study aimed to evaluate the association between PP and RHF in healthy young adults.

Methods

Data were retrieved from the Korea National Health and Nutrition Examination Survey from 2010 to 2019. A total of 10,365 participants aged 19–39 years with no hypertension and normal kidney function were analyzed. RHF was defined as logarithm transformed estimated glomerular filtration rate (eGFR) with residuals >90th percentile after adjustment for sex, logarithm transformed age, weight, and height. Participants were divided into tertile based on PP levels.

Results

The prevalence of RHF was higher in higher PP tertile group (6.6, 10.5, and 12.7% in T1, T2, and T3; P for trend < 0.001). In multivariable logistic regression analyses, the risk for RHF was increased in higher PP tertiles compared to the lowest tertile [odds ratio (OR), 1.42; 95% confidence interval (CI), 1.19–1.69 in T2; OR, 1.44; 95% CI, 1.20–1.73 in T3]. When PP levels were treated as continuous variable, the risk of RHF was increased 2.36 per 1.0 increase of PP (P < 0.001). In subgroup analyses stratified sex, histories of diabetes or dyslipidemia, and isolated systolic hypertension or isolated diastolic hypertension, there were no significant interactions with PP for the risk for RHF, suggesting that high PP was associated with increased risk of RHF regardless of subgroups. However, the subgroup with BMI showed significant interaction with PP for the risk of RHF, indicating that participants with BMI ≥ 25 kg/m2 were at higher risk of RHF with increasing PP levels than those with BMI < 25 kg/m2 (OR, 1.89; 95% CI, 1.25–2.87 in BMI < 25 kg/m2; OR, 3.16; 95% CI, 1.74–5.73 in BMI ≥ 25 kg/m2; P for interaction = 0.01).

Conclusion

High PP is associated with an increased risk of RHF in healthy young adults and this association is prominent in obese young adults. The assessment of PP and associated RHF may give benefit to early detect the potential risk of CKD development in young adults.
A novel computed tomography radiomic nomogram for early evaluation of small airway dysfunction development
Authors: Cui Sijia , Shu Zhenyu , Ma Yanqing , Lin Yi , Wang Haochu , Cao Hanbo , Liu Jing , Gong Xiangyang
Published: September 2022

The common respiratory abnormality, small airway dysfunction (fSAD), is easily neglected. Its prognostic factors, prevalence, and risk factors are unclear. This study aimed to explore the early detection of fSAD using radiomic analysis of computed tomography (CT) images to predict fSAD progress. The patients were divided into fSAD and non-fSAD groups and divided randomly into a training group (n = 190) and a validation group (n = 82) at a 7:3 ratio. Lung kit software was used for automatic delineation of regions of interest (ROI) on chest CT images. The most valuable imaging features were selected and a radiomic score was established for risk assessment. Multivariate logistic regression analysis showed that age, radiomic score, smoking, and history of asthma were significant predictors of fSAD (P < 0.05). Results suggested that the radiomic nomogram model provides clinicians with useful data and could represent a reliable reference to form fSAD clinical treatment strategies.
Multichannel stimulation module as a tool for animal studies on cortical neural prostheses
Authors: Hayashida Yuki , Kameda Seiji , Umehira Yuichi , Ishikawa Shinnosuke , Yagi Tetsuya
Published: September 2022

Intracortical microstimulation to the visual cortex is thought to be a feasible technique for inducing localized phosphenes in patients with acquired blindness, and thereby for visual prosthesis. In order to design effective stimuli for the prosthesis, it is important to elucidate relationships between the spatio-temporal patterns of stimuli and the resulting neural responses and phosphenes through pre-clinical animal studies. However, the physiological basis of effective spatial patterns of the stimuli for the prosthesis has been little investigated in the literature, at least partly because that the previously developed multi-channel stimulation systems were designed specifically for the clinical use. In the present, a 64-channel stimulation module was developed as a scalable tool for animal experiments. The operations of the module were verified by not only dry-bench tests but also physiological animal experiments in vivo. The results demonstrated its usefulness for examining the stimulus-response relationships in a quantitative manner, and for inducing the multi-site neural excitations with a multi-electrode array. In addition, this stimulation module could be used to generate spatially patterned stimuli with up to 4,096 channels in a dynamic way, in which the stimulus patterns can be updated at a certain frame rate in accordance with the incoming visual scene. The present study demonstrated that our stimulation module is applicable to the physiological and other future studies in animals on the cortical prostheses.
Receptor-binding domain-anchored peptides block binding of severe acute respiratory syndrome coronavirus 2 spike proteins with cell surface angiotensin-converting enzyme 2
Authors: Wang Ting , Xu Jie , Wang Beibei , Wang Yulian , Zhao Wei , Xiang Bin , Xue Yuhua , Yuan Quan , Wang Yiqiang
Published: September 2022

Background

The COVID-19 pandemic has killed over 6 million people worldwide. Despite the accumulation of knowledge about the causative pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the pathogenesis of this disease, cures remain to be discovered. We searched for certain peptides that might interfere with spike protein (S protein)-angiotensin-converting enzyme 2 (ACE2) interactions.

Methods

Phage display (PhD)-12 peptide library was screened against recombinant spike trimer (S-trimer) or receptor-binding domain (S-RBD) proteins. The resulting enriched peptide sequences were obtained, and their potential binding sites on S-trimer and S-RBD 3D structure models were searched. Synthetic peptides corresponding to these and other reference sequences were tested for their efficacy in blocking the binding of S-trimer protein onto recombinant ACE2 proteins or ACE2-overexpressing cells.

Results

After three rounds of phage selections, two peptide sequences (C2, DHAQRYGAGHSG; C6, HWKAVNWLKPWT) were enriched by S-RBD, but only C2 was present in S-trimer selected phages. When the 3D structures of static monomeric S-RBD (6M17) and S-trimer (6ZGE, 6ZGG, 7CAI, and 7CAK, each with different status of S-RBDs in the three monomer S proteins) were scanned for potential binding sites of C2 and C6 peptides, C6 opt to bind the saddle of S-RBD in both 6M17 and erected S-RBD in S-trimers, but C2 failed to cluster there in the S-trimers. In the competitive S-trimer-ACE2-binding experiments, synthetic C2 and C6 peptides inhibited S-trimer binding onto 293T-ACE2hR cells at high concentrations (50 μM) but not at lower concentrations (10 μM and below), neither for the settings of S-trimer binding onto recombinant ACE2 proteins.

Conclusion

Using PhD methodology, two peptides were generated bearing potentials to interfere with S protein-ACE2 interaction, which might be further exploited to produce peptidomimetics that block the attachment of SARS-CoV-2 virus onto host cells, hence diminishing the pathogenesis of COVID-19.
Novel lineages of single-stranded DNA phages that coevolved with the symbiotic bacteria Rhizobium
Authors: Van Cauwenberghe Jannick , Santamaría Rosa I. , Bustos Patricia , González Víctor
Published: September 2022

This study describes novel single-stranded DNA phages isolated from common bean agriculture soils by infection of the nitrogen-fixing symbiotic bacteria Rhizobium etli and R. phaseoli. A total of 29 phages analyzed have 4.3–6 kb genomes in size and GC 59–60%. They belong to different clades unrelated to other Microviridae subfamilies. Three-dimensional models of the major capsid protein (MCP) showed a conserved β-barrel structural “jelly-roll” fold. A variable-length loop in the MCPs distinguished three Rhizobium microvirus groups. Microviridae subfamilies were consistent with viral clusters determined by the protein-sharing network. All viral clusters, except for Bullavirinae, included mostly microviruses identified in metagenomes from distinct ecosystems. Two Rhizobium microvirus clusters, chaparroviruses, and chicoviruses, were included within large viral unknown clusters with microvirus genomes identified in diverse metagenomes. A third Rhizobium microvirus cluster belonged to the subfamily Amoyvirinae. Phylogenetic analysis of the MCP confirms the divergence of the Rhizobium microviruses into separate clades. The phylogeny of the bacterial hosts matches the microvirus MCP phylogeny, suggesting a coevolutionary history between the phages and their bacterial host. This study provided essential biological information on cultivated microvirus for understanding the evolution and ecological diversification of the Microviridae family in diverse microbial ecosystems.
Identification of a novel aminoglycoside O-nucleotidyltransferase AadA33 in Providencia vermicola
Authors: Feng Chunlin , Gao Mengdi , Jiang Weiyan , Shi Weina , Li Anqi , Liu Shuang , Zhang Lei , Zhang Xueya , Li Qiaoling , Lin Hailong , Lu Junwan , Li Kewei , Zhang Hailin , Hu Yunliang , Bao Qiyu , Lin Xi
Published: September 2022

A novel chromosome-encoded aminoglycoside O-nucleotidyltransferase AadA33 was identified in Providencia vermicola strain P13. The AadA33 shares the highest amino acid identity of 51.28% with the function characterized AadA31. Antibiotic susceptibility testing and enzyme kinetics analysis revealed that the function of AadA33 is to mediate spectinomycin and streptomycin resistance. The recombinant strain harboring aadA33 (pUCP20-aadA33/Escherichia coli DH5α) displayed >256- and 128-fold increases in the minimum inhibitory concentration levels to spectinomycin and streptomycin, respectively, compared with the control strains pUCP20/DH5α. Enzyme kinetic parameters manifested the substrate of AadA33 including spectinomycin and streptomycin, with kcat/Km of 3.28 × 104 (M−1 s−1) and 3.37 × 104 (M−1 s−1), respectively. Bioinformatics analysis revealed its structural mechanism of antimicrobial resistance, genetic context, and phylogenetic relationship with other aminoglycoside O-nucleotidyltransferases. This study of AadA33 contributed to understanding the function and resistance mechanism of aminoglycoside O-nucleotidyltransferase.
From ensembles to meta-ensembles: Specific reward encoding by correlated network activity
Authors: Körber Christoph , Sommer Wolfgang H.
Published: September 2022

Neuronal ensembles are local, sparsely distributed populations of neurons that are reliably re-activated by a specific stimulus, context or task. Such discrete cell populations can be defined either functionally, by electrophysiological recordings or in vivo calcium imaging, or anatomically, using the expression of markers such as the immediate early gene cFos. A typical example of tasks that involve the formation of neuronal ensembles is reward learning, such as the cue-reward pairing during operant conditioning. These ensembles are re-activated during cue-presentation and increasing evidence suggests that this re-activation is the neurophysiological basis for the execution of reward-seeking behavior. Whilst the pursuit of rewards is a common daily activity, it is also related to the consumption of drugs, such as alcohol, and may result in problematic behaviors including addiction. Recent research has identified neuronal ensembles in several reward-related brain regions that control distinct aspects of a conditioned response, e.g., contextual information about the availability of a specific reward or the actions needed to retrieve this reward under the given circumstances. Here, we review studies using the activity marker cFos to identify and characterize neuronal ensembles related to alcohol and non-drug rewards with a special emphasis on the discrimination between different rewards by meta-ensembles, i.e., by dynamic co-activation of multiple ensembles across different brain areas.
Brain-Inspired Domain-Incremental Adaptive Detection for Autonomous Driving
Authors: Liang Weihao , Gan Lu , Wang Pengfei , Meng Wei
Published: September 2022

Most existing methods for unsupervised domain adaptation (UDA) only involve two domains, i.e., source domain and the target domain. However, such trained adaptive models have poor performance when applied to a new domain without learning. Moreover, using UDA methods to adapt from the source domain to the new domains will lead to catastrophic forgetting of the previous target domain. To handle these issues, inspired by the ability to balance the maintenance of old knowledge and learning new knowledge of the human brain, in this article, we propose a new incremental learning framework for domain-incremental cases, which can harmonize the memorability and discriminability of the existing and the novel domains. By this means, the model can imitate the learning process of the human brain and, thus, improve its adaptability. To evaluate the effectiveness of the proposed methods, we conduct two groups of experiments, including virtual-to-real and diverse-weather cases. The experimental results demonstrate that our approach can avoid catastrophic forgetting, mitigate performance degradation in the previous domains, and improve the object detection accuracy of the novel target domain significantly.
Predicting task performance for intelligent human-machine interactions
Authors: Heard Jamison , Baskaran Prakash , Adams Julie A.
Published: September 2022

Human-machine teams are deployed in a diverse range of task environments and paradigms that may have high failure costs (e.g., nuclear power plants). It is critical that the machine team member can interact with the human effectively without reducing task performance. These interactions may be used to manage the human's workload state intelligently, as the overall workload is related to task performance. Intelligent human-machine teaming systems rely on a facet of the human's state to determine how interaction occurs, but typically only consider the human's state at the current time step. Future task performance predictions may be leveraged to determine if adaptations need to occur in order to prevent future performance degradation. An individualized task performance prediction algorithm that relies on a multi-faceted human workload estimate is shown to predict a supervisor's task performance accurately. The analysis varies the prediction time frame (from 0 to 300 s) and compares results to a generalized algorithm.
The multiple faces of extracellular vesicles released by microglia: Where are we 10 years after?
Authors: Gabrielli Martina , Raffaele Stefano , Fumagalli Marta , Verderio Claudia
Published: September 2022

As resident component of the innate immunity in the central nervous system (CNS), microglia are key players in pathology. However, they also exert fundamental roles in brain development and homeostasis maintenance. They are extremely sensitive and plastic, as they assiduously monitor the environment, adapting their function in response to stimuli. On consequence, microglia may be defined a heterogeneous community of cells in a dynamic equilibrium. Extracellular vesicles (EVs) released by microglia mirror the dynamic nature of their donor cells, exerting important and versatile functions in the CNS as unbounded conveyors of bioactive signals. In this review, we summarize the current knowledge on EVs released by microglia, highlighting their heterogeneous properties and multifaceted effects.
Case report: Dueling etiologies: Longitudinally extensive spinal cord lesion mimicking spinal cord infarct with simultaneous positive Lyme serology and amphiphysin antibody
Authors: Kalaszi Marianna , Donlon Eoghan , Ahmad Marzuki Wan , Mohamed Abdirahman Sheikh , Boers Peter
Published: September 2022

Background

Longitudinally extensive spinal cord lesions are challenging diagnostic entities as they are uncommon, but various etiologies can cause them.

Case report

We report a case of a 55-year-old man with a past medical history of hypertension. He is an ex-smoker. He presented with chest pain, followed by right lower limb weakness, preceded by 2 weeks of constipation and voiding dysfunction. The examination revealed right lower limb mild flaccid paresis, absent reflexes, reduced anal tone, and urinary retention. His symptoms deteriorated over 24 h, and he developed severe flaccid paraparesis with impaired pinprick sensation below the T4 level. MRI spine showed an abnormal, non-enhancing signal in the anterior aspect of the spinal cord extending from the T4 level to the conus without associated edema. He was commenced on intravenous steroids and had significant improvement after one dose. The imaging was felt to be consistent with spinal cord infarction, and aspirin was started. The cerebrospinal fluid analysis showed elevated protein (0.8 mg/ml). Investigations for stroke and autoimmune pathologies were negative. The Lyme immunoblot confirmed intrathecal production of IgG to Borrelia antigens. The patient was started on ceftriaxone. The paraneoplastic screen identified amphiphysin antibodies. CT-TAP and PET-CT did not identify occult malignancy. The patient had a significant improvement over 2 months, strength was almost fully recovered, and autonomic functions returned to normal.

Conclusion

We describe an unusual steroid-responsive, longitudinally extensive spinal cord lesion with radiological features of spinal cord infarct and a simultaneous finding of intrathecal Lyme antibodies and serum amphiphysin antibodies.
The efficacy of intravaginal electrical stimulation (IVES) in treating female with urinary incontinence symptom from meta-analysis of nine randomized controlled trials
Authors: Yao Huibao , Zhang Xiaofei , Sun Fengze , Tang Gonglin , Wu Jitao , Zhou Zhongbao
Published: September 2022

Background

Urinary incontinence (UI) is a common disease in the middle-aged and elderly women, and physical therapy has gradually become the mainstream treatment of UI. We conducted a meta-analysis to evaluate the efficacy of intravaginal electrical stimulation (IVES) in the treatment of UI.

Methods

From January 2006 to December 2021, we finally selected nine randomized controlled trials (RCTs) including 657 participants from PubMed, EMBASE, and Cochrane databases to evaluate the efficacy of IVES in the treatment of female UI. Continuous data were represented by mean difference and 95% CI, while dichotomous data were represented by odds ratio and 95% CI. All the data were analyzed by the Review Manager Version 5.4.

Results

Compared with the control group, there were significant improvements in urine pad test (P = 0.01), urinary incontinence frequency (P = 0.04), some indicators in the incontinence quality of life questionnaire and King's health questionnaires, and subjective feeling of cure (P = 0.009) in the IVES group. However, in other indicators reflecting UI, there was no significant difference between the IVES group and the control group. In addition, subgroup analysis showed that IVES and IVES combined with training could significantly reduce the weight of the urine pad, which reflected the improvement of urine leakage.

Conclusion

This meta-analysis proved that IVES can partially improve the symptoms of female patients with UI compared with the control group. However, it still needs to be further evaluated through more high-quality research in the future.
Case report: Multiple brain tuberculomas after in vitro fertilization, embryo transfer, and abortion
Authors: Shi Zhaobo , Sun Yong
Published: September 2022

Background

Multiple brain tuberculomas (MBT), characterized by disseminated tuberculous granulomas in the brain, is a rare disease like tuberculosis encountered after in vitro fertilization, embryo transfer (IVF-ET), and abortion. This study aimed to investigate the clinical characteristics, diagnostic methods, and therapeutic strategies of MBT after IVF-ET and abortion.

Methods

A retrospective analysis was performed on the data of two patients who suffered from MBT after IVF-ET and abortion.

Results

Both patients manifested headache and vomiting, which are the common symptoms of intracranial hypertension, accompanied by tuberculous meningitis. Besides, case 1 was affected by fever and epilepsy. In terms of imaging characteristics, T2-weighted imaging (T2WI) displayed multiple intracranial punctate or patchy high-intensity signals, some of which were presented as “target sign” or enhanced-like disseminated nodules, similar to miliary tuberculosis. Regular anti-tuberculosis therapy with isoniazid, rifampicin, pyrazinamide, and ethambutol was administered but failed to achieve a significant effect in the initial stage. The symptoms were gradually relieved, and the brain lesions in MRI were significantly alleviated after combining with intrathecal injections of isoniazid, dexamethasone, and chymotrypsin.

Conclusions

In vitro fertilization, embryo transfer (IVF-ET) may be a risk factor for MBT, the common manifestations of which are intracranial hypertension. In addition to multiple nodular enhancement on brain MRI, the “target sign” on T2WI is likely to be another typical feature of MBT. Provided that there is no obvious effect of regular anti-tuberculosis therapy (ATT), intrathecal injections of isoniazid, dexamethasone, and chymotrypsin are considered to produce a favorable prognosis, but further studies are still needed to confirm the efficacy.
Dynamic nomogram for predicting acute kidney injury in patients with acute ischemic stroke: A retrospective study
Authors: Zhu Ganggui , Fu Zaixiang , Jin Taian , Xu Xiaohui , Wei Jie , Cai Lingxin , Yu Wenhua
Published: September 2022

Background

This study sought to develop and validate a dynamic nomogram chart to assess the risk of acute kidney injury (AKI) in patients with acute ischemic stroke (AIS).

Methods

These data were drawn from the Medical Information Mart for Intensive Care III (MIMIC-III) database, which collects 47 clinical indicators of patients after admission to the hospital. The primary outcome indicator was the occurrence of AKI within 48 h of intensive care unit (ICU) admission. Independent risk factors for AKI were screened from the training set using univariate and multifactorial logistic regression analyses. Multiple logistic regression models were developed, and nomograms were plotted and validated in an internal validation set. Based on the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) to estimate the performance of this nomogram.

Results

Nomogram indicators include blood urea nitrogen (BUN), creatinine, red blood cell distribution width (RDW), heart rate (HR), Oxford Acute Severity of Illness Score (OASIS), the history of congestive heart failure (CHF), the use of vancomycin, contrast agent, and mannitol. The predictive model displayed well discrimination with the area under the ROC curve values of 0.8529 and 0.8598 for the training set and the validator, respectively. Calibration curves revealed favorable concordance between the actual and predicted incidence of AKI (p > 0.05). DCA indicates the excellent net clinical benefit of nomogram in predicting AKI.

Conclusion

In summary, we explored the incidence of AKI in patients with AIS during ICU stay and developed a predictive model to help clinical decision-making.
Self-perceived burden and associated factors in Chinese adult epilepsy patients: A cross-sectional study
Authors: Tang Binmi , Fu Yaqian , Liu Birong , Yi Qifeng
Published: September 2022

Objectives

Epilepsy requires long-term or lifelong treatment, and patients are prone to financial, emotional and psychological burdens that can cause psychological changes during the treatment process. This study aimed to describe the prevalence and associated factors of Self-Perceived Burden (SPB) in Chinese adult epilepsy patients, informing the treatment and nursing of epilepsy.

Methods

A total of 143 adult epilepsy patients were included in this study, and the clinical questionnaire survey was conducted at the Third Xiangya Hospital of Central South University in Hunan, China, from March 2022 to June 2022. The sociodemographic and clinical characteristics of adult epilepsy patients were collected using a self-developed questionnaire, and the data on SPB, stigma and quality of life were collected through the Self-Perceived Burden Scale (SPBS), Kilifi Stigma Scale for Epilepsy (KSSE) and Quality of Life in Epilepsy Inventory-31 (QOLIE-31). Multiple linear regression analysis was used to determine the associated factors influencing SPB in adult epilepsy patients.

Results

The average score of SPBS for the 143 adult epilepsy patients was 30.77 (SD = 9.06), and 89.5% of them had obvious SPB. The results of the univariate analysis showed that residence, monthly household income, duration of epilepsy, type of medication and electroencephalogram finding were associated with SPB (P < 0.05). In Spearman correlation analysis indicated that SPBS score were positively correlated with KSSE score (r = 0.510, P < 0.05) while negatively correlated with QOLIE-31 score (r = −0.506, P < 0.05). Multiple linear regression analysis revealed that factors such as KSSE, type of medication, residence and electroencephalogram finding accounted for 32.8% of the factors influencing SPB in adult epilepsy patients.

Conclusion

89.5% of adult epilepsy patients have varying degrees of SPB, which is associated with high stigma and poor quality of life. Therefore, during the treatment and nursing of adult epilepsy patients, clinical staff should pay attention to the psychological status of patients, help them reduce their psychological burden, and guide them to develop a healthy lifestyle.
A novel EEG decoding method for a facial-expression-based BCI system using the combined convolutional neural network and genetic algorithm
Authors: Li Rui , Liu Di , Li Zhijun , Liu Jinli , Zhou Jincao , Liu Weiping , Liu Bo , Fu Weiping , Alhassan Ahmad Bala
Published: September 2022

Multiple types of brain-control systems have been applied in the field of rehabilitation. As an alternative scheme for balancing user fatigue and the classification accuracy of brain–computer interface (BCI) systems, facial-expression-based brain control technologies have been proposed in the form of novel BCI systems. Unfortunately, existing machine learning algorithms fail to identify the most relevant features of electroencephalogram signals, which further limits the performance of the classifiers. To address this problem, an improved classification method is proposed for facial-expression-based BCI (FE-BCI) systems, using a convolutional neural network (CNN) combined with a genetic algorithm (GA). The CNN was applied to extract features and classify them. The GA was used for hyperparameter selection to extract the most relevant parameters for classification. To validate the superiority of the proposed algorithm used in this study, various experimental performance results were systematically evaluated, and a trained CNN-GA model was constructed to control an intelligent car in real time. The average accuracy across all subjects was 89.21 ± 3.79%, and the highest accuracy was 97.71 ± 2.07%. The superior performance of the proposed algorithm was demonstrated through offline and online experiments. The experimental results demonstrate that our improved FE-BCI system outperforms the traditional methods.
Nanoscopic distribution of VAChT and VGLUT3 in striatal cholinergic varicosities suggests colocalization and segregation of the two transporters in synaptic vesicles
Authors: Cristofari Paola , Desplanque Mazarine , Poirel Odile , Hébert Alison , Dumas Sylvie , Herzog Etienne , Danglot Lydia , Geny David , Gilles Jean-François , Geeverding Audrey , Bolte Susanne , Canette Alexis , Trichet Michaël , Fabre Véronique , Daumas Stéphanie , Pietrancosta Nicolas , El Mestikawy Salah , Bernard Véronique
Published: September 2022

Striatal cholinergic interneurons (CINs) use acetylcholine (ACh) and glutamate (Glut) to regulate the striatal network since they express vesicular transporters for ACh (VAChT) and Glut (VGLUT3). However, whether ACh and Glut are released simultaneously and/or independently from cholinergic varicosities is an open question. The answer to that question requires the multichannel detection of vesicular transporters at the level of single synaptic vesicle (SV). Here, we used super-resolution STimulated Emission Depletion microscopy (STED) to characterize and quantify the distribution of VAChT and VGLUT3 in CINs SVs. Nearest-neighbor distances analysis between VAChT and VGLUT3-immunofluorescent spots revealed that 34% of CINs SVs contain both VAChT and VGLUT3. In addition, 40% of SVs expressed only VAChT while 26% of SVs contain only VGLUT3. These results suggest that SVs from CINs have the potential to store simultaneously or independently ACh and/or Glut. Overall, these morphological findings support the notion that CINs varicosities can signal with either ACh or Glut or both with an unexpected level of complexity.
Persistent or new symptoms 1 year after a single high dose of vitamin D3 in patients with moderate to severe COVID-19
Authors: Fernandes Alan L. , Sales Lucas P. , Santos Mayara D. , Caparbo Valeria F. , Murai Igor H. , Pereira Rosa M. R.
Published: September 2022

Purpose

The aim of this study was to investigate the reported persistent or new symptoms 1 year after a single dose of 200,000 IU of vitamin D3 and hospitalization in patients with moderate to severe COVID-19.

Methods

This is a post-hoc, exploratory analysis from a multicenter, double-blind, placebo-controlled, randomized clinical trial from two hospitals in São Paulo, Brazil, registered in ClinicalTrials.gov, NCT04449718. Discharged patients were followed for up to 1 year and evaluated by telephone interviews at 6 and 12 months. The primary and secondary outcomes were previously published. These post-hoc exploratory secondary outcomes are the persistent or new symptoms and quality of life (QoL) at the post-viral stage of COVID-19. Generalized estimating equations (GEE) for repeated measures with Bonferroni’s adjustment were used for testing outcomes.

Results

Between 2 June and 27 August 2020, we randomized 240 patients of which 144 were included in this study [the vitamin D3 (n = 71) or placebo (n = 73) group]. The mean (SD) age was 54.3 (13.1) years, and body mass index (BMI) was 32.4 (6.5) kg/m2. Fever demonstrated a significant main effect of time (P < 0.001) with a reduction from baseline to 6 (52–0) and 12 months (52–0). No significant differences between groups were observed for fever, cough, fatigue, fever, myalgia, joint pain, runny nose, nasal congestion, sore throat, hypertension, diabetes, cardiovascular disease, rheumatic disease, asthma, chronic obstructive pulmonary, chronic kidney disease, QoL, and new or persistent symptoms up to 1-year of follow-up.

Conclusion

The findings do not support the use of 200,000 IU of vitamin D3 compared to placebo for the management of persistence or new symptoms, and QoL reported by moderate to severe patients after hospitalization for COVID-19.
A detection panel of novel methylated DNA markers for malignant pleural effusion
Authors: Liang Chaonan , Liu Nan , Zhang Qin , Deng Mingming , Ma Jiangwei , Lu Jingwen , Yin Yan , Wang Jian , Miao Yuan , She Bin , Li Qingchang , Hou Gang
Published: September 2022

Background

Cytology remains the gold standard for the detection of malignant cells in pleural effusion. However, its sensitivity is limited. The aim of this study was to establish a novel panel of cancer-specific methylated genes for the differential diagnosis of malignant pleural effusion (MPE).

Methods

A cohort of 100 cancer patients (68 lung cancer, 32 other malignant tumors) and 48 patients with benign disease presenting with pleural effusion was prospectively enrolled. Pleural effusion was evaluated by means of cytopathological investigation and DNA methylation of SHOX2, RASSF1A, SEPTIN9 and HOXA9 in the cellular fraction. DNA methylation in bisulfite-converted DNA was determined using quantitative methylation-specific real-time PCR (MS-PCR). Cytopathological and DNA methylation results were evaluated with regard to the final clinical diagnosis.

Results

The LungMe® SHOX2 and RASSF1A Assay (Tellgen Corporation, China) has been reported to be highly sensitive and specific for lung cancer using bronchial aspirates. As expected, LungMe® detected metastases of lung cancer (sensitivity: 76.5%) as well as metastases of other malignant tumors (sensitivity: 68.8%). OncoMe, a novel combination of SHOX2, RASSF1A, SEPTIN9 and HOXA9 methylation, led to an additional 11% increase in the detection rate of MPE, resulting in a sensitivity of 85% and a specificity of 96%. Overall, OncoMe showed a higher positive detection rate in SCLC (100%), LUAC (87%), OC (100%), BC (92.9%), GC (80.0%), and MESO (80%) than in LUSC (50%). Cytopathological analyses only detected 23 positive samples, which were all positively measured by both LungMe® and OncoMe.

Conclusion

OncoMe has potential for use as a biomarker for the detection of MPE, even not limited to lung cancer.