bluuebunny/crossref_metadata_2025 huggingface dataset:
Host autophagy limits Toxoplasma gondii proliferation in the absence of IFN-γ by affecting the hijack of Rab11A-positive vesicles
Authors: Pan Lingtao , Yang Yimin , Chen Xueqiu , Zhao Mingxiu , Yao Chaoqun , Sheng Kaiyin , Yang Yi , Ma Guangxu , Du Aifang
Published: December 2022

Introduction

Autophagy has been recognized as a bona fide immunological process. Evidence has shown that this process in IFN-γ stimulated cells controls Toxoplasma gondii proliferation or eliminates its infection. However, little is known about the effect of T. gondii infection on the host cell autophagy in the absence of IFN-γ.

Methods

Multiple autophagy detection methods and CRISPR/CAS9 technology were used to study T. gondii-induced autophagy in HeLa and several other mammalian cell lines.

Results

Here, we report increased LC3 II, autophagosome-like membrane structures, enhanced autophagic flux, and decreased lysosomes in a range of mammalian cell lines without IFN-γ treatment after T. gondii infection. Specifically, disruption of host atg5 (a necessary gene for autophagy) in HeLa cells promoted the intracellular replication of T. gondii, with the transcript level of rab11a increased, compared with that in wild-type cells. Further, after T. gondii infection, the abundance of Rab11A remained stable in wild-type HeLa cells but decreased in atg5−/− mutant. Disruption of rab11a in the HeLa cells compromised the proliferation of T. gondii, and increased the transcription of gra2 in the parasite. Compared to the T. gondii wild-type RH∆ku80 strain, the ∆gra2 mutant induces enhanced host autophagy in HeLa cells, and results in slower replication of the parasite.

Discussion

Collectively, these results indicate that host cell autophagy can limit T. gondii proliferation in an IFN-γ independent manner, possibly by affecting the hijack of host Rab11A-positive vesicles by the parasite which involved TgGRA2. The findings provide novel insights into T. gondii infection in host cells and toxoplasmosis research.
Mutation-driven evolution of antibacterial function in an ancestral antifungal scaffold: Significance for peptide engineering
Authors: Gu Jing , Isozumi Noriyoshi , Gao Bin , Ohki Shinya , Zhu Shunyi
Published: December 2022

Mutation-driven evolution of novel function on an old gene has been documented in many development- and adaptive immunity-related genes but is poorly understood in immune effector molecules. Drosomycin-type antifungal peptides (DTAFPs) are a family of defensin-type effectors found in plants and ecdysozoans. Their primitive function was to control fungal infection and then co-opted for fighting against bacterial infection in plants, insects, and nematodes. This provides a model to study the structural and evolutionary mechanisms behind such functional diversification. In the present study, we determined the solution structure of mehamycin, a DTAFP from the Northern root-knot nematode Meloidogyne hapla with antibacterial activity and an 18-mer insert, and studied the mutational effect through using a mutant with the insert deleted. Mehamycin adopts an expected cysteine-stabilized α-helix and β-sheet fold in its core scaffold and the inserted region, called single Disulfide Bridge-linked Domain (abbreviated as sDBD), forms an extended loop protruding from the scaffold. The latter folds into an amphipathic architecture stabilized by one disulfide bridge, which likely confers mehamycin a bacterial membrane permeability. Deletion of the sDBD remarkably decreased the ability but accompanying an increase in thermostability, indicative of a structure-function trade-off in the mehamycin evolution. Allosteric analysis revealed an interior interaction between the two domains, which might promote point mutations at some key sites of the core domain and ultimately give rise to the emergence of antibacterial function. Our work may be valuable in guiding protein engineering of mehamycin to improve its activity and stability.
Reintroduction modifies the intraspecific variations of symbiotic microbes in captive bred Chinese giant salamander
Authors: Feng Jianyi , Zhu Wei , Jiang Jianping , Zhao Chunlin , Sun Zijian , Jiang Wansheng , Luo Qinghua , Zhao Tian
Published: December 2022

Microorganisms play as fundamental contributors to maintain hosts’ fitness, which can be shaped by external environment. Moreover, symbiotic microbiome also varied within species (e.g., between sexes and developmental stages). However, we still need more studies to quantify whether the intraspecific variation patterns of symbiotic microbes can be modified with the change of environment. The Chinese giant salamander (CGS; Andrias davidianus) is a Critically Endangered species. Despite quantitative captive bred individuals were released to rebuild wild populations, the effectiveness is limited. More importantly, no studies have revealed the adaptation of released CGSs to the complex field conditions. In the present study, we explored whether reintroduction can reshape the intraspecific variations of symbiotic microbiota in captive bred CGSs using high-throughput amplicon sequencing of the16S rRNA gene. We found no significant difference of symbiotic microbiome in captive bred males and females, but released males and females differed significantly in skin microbiome. Juveniles had higher diversity of microbial symbiont than adults in hatchery, but lower diversity in field. Moreover, dominant bacterial taxa differed between juveniles and adults in both hatchery and field. Importantly, this symbiotic microbiome variations within species can be modified (alpha and beta diversity, and community composition) when captive bred individuals were released to the field. Overall, we observed a lower alpha diversity and higher relative abundance of Chryseobacterium, Plesiomonas, and Acinetobacter in the bacterial community of captive bred individuals. Instead, higher alpha diversity of symbiotic microbiota and higher relative abundance of S24-7 and Lactobacillus was detected in released individuals. These modifications may associate with the change of living environment, as well as the specific behavior within CGSs (e.g., movement patterns and foraging activities). Future studies can incorporate other approaches (e.g., blood physiology) to better evaluate the growth and health of reintroduced CGSs.
Effects of challenge with Clostridium perfringens, Eimeria and both on ileal microbiota of yellow feather broilers
Authors: Feng Xin , Li Tonghao , Zhu Hui , Liu Lidan , Bi Shengqun , Chen Xiaolin , Zhang Huihua
Published: December 2022

In the poultry industry worldwide,Clostridium perfringenshas been causing major economic loss as it can cause necrotic enteritis (NE). The coccidial infection has been considered as the most important predisposing factor of NE caused byC. perfringens. In this study, we aimed to advance our knowledge on ileal microbiota of yellow feather broilers underC. perfringensand/orEimeriachallenge. Total of 80 healthy day old yellow feather broilers were randomly assigned to four groups including: Control,C. perfringenschallenge group (C. Per),Eimeriachallenge group (Cocc), andC. perfringensplusEimeriachallenge group (Comb). On day 14, the Cocc and Comb group broilers were orally gavaged 1 ml PBS solution containing 25,000 oocysts ofEimeria brunettiand 25,000 oocysts ofEimeria maxima. Starting on day 17, the C. Per and Comb group broilers were orally gavaged 10 mL ofC. perfringensper bird (4 × 107CFU/mL, ATCC®13124™ Strain) every day for 6 days. 16S rRNA gene sequencing was performed on extracted DNA of ileal digesta samples. The results showed thatC. perfringensalone did not affect the alpha diversity of ileal microbiome in yellow feather broilers but co-infection withEimeriasignificantly decreased the diversity of ileal microbiota.C. perfringensandEimeriachallenge also decreased the relative abundance of beneficial bacteria includingBacteroidetesat the phylum level andFaecalibacteriumat the genus level. At the species level, the relative abundance ofCandidatus Arthromituswas significantly decreased in theEimeriachallenged groups. This microbial shift information of ileal microbiota underC. PerfringensandEimeriachallenge provide important reference data for the development of therapeutic approaches to necrotic enteritis in yellow-feather broiler chickens.
Composition and diversity of soil bacterial communities under identical vegetation along an elevational gradient in Changbai Mountains, China
Authors: Li Mengsha , Dai Guanhua , Mu Liqiang
Published: December 2022

Soil bacteria play important roles in biogeochemical cycling and biodiversity in mountain ecosystems. Past studies have investigated the bacterial community composition and diversity in elevation gradations covered by different vegetation types, but for a better assessment of elevation effects, here we studied bacterial communities in soil under identical vegetation cover. High-throughput amplicon sequencing of the V3-V4 region of bacterial 16S rDNA was used to investigate the diversity and composition bacterial communities in soil from 700 to 1,000 m above sea level collected on the north slope of Changbai Mountains, Northeast China. Obviously differences (p < 0.05) in soil physicochemical parameters (i.e., total nitrogen, nitrate and ammonium nitrogen, soil moisture content, available potassium, microbial biomass carbon and nitrogen) were observed at different elevations. Soil bacterial abundance indices (Richness, Chao1, ACE) differed significantly along the elevation gradient, whereas the Shannon index remained unchanged. Principal Coordinates Analysis indicated separated soil bacterial communities of the different elevations. The dominant phyla in all soil samples were Proteobacteria, Acidobacteria, Actinobacteria, Verrucomicrobia, and Bacteroidetes, which in combination reached 80%–85%. Soil pH to some extend related to soil bacterial community along altitude gradations. The relative abundance of a multiple phyla was negatively affected by the soil nutrients, such as ammonium and nitrate nitrogen, available potassium, soil moisture content, available phosphorus, microbial biomass nitrogen and soil organic C. The strongest effects were seen for Proteobacteria. The pH either positively or negatively correlated with specific genera. The soil bacterial function differed significantly among four elevations. The chemoheterotrophy, aerobic chemoheterotrophy and nitrification were the most dominant functions of soil bacteria among four elevations. Overall, the changes in soil physicochemical properties with elevation are important in shaping the bacterial diversity, composition and function in soil with the same above-ground vegetation of Changbai Mountains.
Epidemiological investigation and genetic evolutionary analysis of PRRSV-1 on a pig farm in China
Authors: Li Chao , Xu Hu , Zhao Jing , Gong Bangjun , Sun Qi , Xiang Lirun , Li Wansheng , Guo Zhenyang , Li Jinhao , Tang Yan-dong , Leng Chaoliang , Peng Jinmei , Wang Qian , An Tongqing , Cai Xuehui , Tian Zhi-Jun , Zhou Guohui , Zhang Hongliang
Published: December 2022

Porcine reproductive and respiratory syndrome virus (PRRSV) has brought serious economic losses to pig industry. PRRSV-1 have existed in China for more than 25 years. The prevalence and features of PRRSV-1 on Chinese farms are unclear. We continuously monitored PRRSV in a pig farm with strict biosafety measures in Henan Province, China, in 2020. The results showed that multiple types of PRRSV coexisted on this single pig farm. PRRSV-1 was one of the main circulating strains on the farm and was responsible for infections throughout nearly the entire epidemic cycle. Phylogenetic analysis showed that PRRSV-1 isolates from this pig farm formed an independent branch, with all isolates belonging to BJEU06-1-like PRRSV. The analysis of selection pressure on ORF5 on this branch identified 5 amino acids as positive selection sites, indicating that PRRSV-1 had undergone adaptive evolution on this farm. According to the analysis of ORF5 of PRRSV-1 on this farm, the evolutionary rate of the BJEU06-1-like branch was estimated to be 1.01 × 10−2 substitutions/site/year. To further understand the genome-wide characteristics of PRRSV-1 on this pig farm, two full-length PRRSV-1 genomes representative of pig farms were obtained. The results of amino acid alignment revealed that although one NSP2 deletion was consistent with BJEU06-1, different new features were found in ORF3 and ORF4. According to the above results, PRRSV-1 has undergone considerable evolution in China. This study is the first to report the prevalence and characteristics of PRRSV-1 on a large farm in mainland China, which will provide a reference for the identification and further prevention and control of PRRSV-1.
Natural products against inflammation and atherosclerosis: Targeting on gut microbiota
Authors: Deng Bing , Tao Liyu , Wang Yiru
Published: December 2022

The gut microbiota (GM) has become recognized as a crucial element in preserving human fitness and influencing disease consequences. Commensal and pathogenic gut microorganisms are correlated with pathological progress in atherosclerosis (AS). GM may thus be a promising therapeutic target for AS. Natural products with cardioprotective qualities might improve the inflammation of AS by modulating the GM ecosystem, opening new avenues for researches and therapies. However, it is unclear what components of natural products are useful and what the actual mechanisms are. In this review, we have summarized the natural products relieving inflammation of AS by regulating the GM balance and active metabolites produced by GM.
Identification of PTK2 as an adverse prognostic biomarker in breast cancer by integrated bioinformatics and experimental analyses
Authors: Chen Yanru , Wang Wei , Fang Lingyu , Zhang Zhenyang , Deng Shishan
Published: December 2022

PTK2 is highly expressed in many cancers and is involved in cell growth, survival, migration, and invasion. However, the prognostic value of PTK2 and its potential function remain unclear in breast cancer. Therefore, we performed a comprehensive analysis of multiple public databases to explore the roles of PTK2. By integrating multiple datasets, we found that PTK2 mRNA expression in breast cancer tissue was higher than that in normal breast tissue or adjacent tissue. High PTK2 expression was associated with lymph node metastasis stage, tumor stage, breast cancer type, age, TP53 mutation, and gender and significantly predicted a poor survival outcome in breast cancer patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) results suggested that PTK2 and co-expressed genes participated in the cell cycle. Immune infiltration analysis clarified that high PTK2 expression was positively correlated with infiltrating levels of CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. The DNA methylation of PTK2 in breast cancer tissues was higher than that in normal tissues, and high PTK2 methylation was correlated with poor prognosis in breast cancer patients. Furthermore, 16 possible ceRNA networks related to PTK2 were constructed for breast cancer. Additionally, PTK2 knockdown could suppress the proliferation and migration ability of MCF-7 cells. These results suggest that PTK2 can be used as a prognostic biomarker for breast cancer.
Exercise improves behavioral dysfunction and inhibits the spontaneous excitatory postsynaptic current of D2-medium spiny neurons
Authors: Zhao Gang , Zhang Danyu , Qiao Decai , Liu Xiaoli
Published: December 2022

The abnormal function of striatal medium spiny neurons (MSNs) leads to the excitation-inhibition imbalance of the basal ganglia, which is an important pathogenic factor of Parkinson’s disease (PD). Exercise improves the dysfunction of basal ganglia through neuroprotective and neuroreparative effects, which may be related to the functional changes of expresses D2 receptors MSNs (D2-MSNs). In this study, D2-Cre mice were selected as the research objects, the PD model was induced by unilateral injection of 6-hydroxydopamine (6-OHDA) in the striatum, and the 4-week treadmill training method was used for exercise intervention. Using optogenetics and behavioral tests, we determined that the average total movement distance of PD and PD + Ex groups was significantly lower than that of the Control group, while that of the PD + Ex and PD + Laser groups was significantly higher than that of the PD group, and the two intervention methods of exercise and optogenetic-stimulation of the D2-MSNs had basically similar effects on improving the autonomic behavior of PD mice. To further investigate the cellular mechanisms, whole-cell patch clamp recordings were carried out on D2-MSNs. We found that exercise decreased the frequency and amplitude of spontaneous excitatory postsynaptic current (sEPSC) and increased the paired-pulse radio of D2-MSNs while leaving basic electrophysiological properties of MSNs unaffected. Combined with behavioral improvement and enhanced D2R protein expression, our findings suggest the inhibited sEPSC of D2-MSNs may contribute to the behavioral improvement after exercise.
Stroke-associated infection in patients with co-morbid diabetes mellitus is associated with in-hospital mortality
Authors: Wei Minping , Huang Qin , Yu Fang , Feng Xianjing , Luo Yunfang , Zhao Tingting , Tu Ruxin , Liao Di , Du Yang , Huang Qing , Gu Wenping , Liu Yunhai , Jiang Yingyu , Gu Hongqiu , Li Zixiao , Xia Jian
Published: December 2022

Background and objective

The association between infection and acute ischemic stroke (AIS) with diabetes mellitus (DM) remains unknown. Therefore, this study aimed to explore the effect of infection on AIS with DM.

Materials and methods

The data of patients with AIS and DM were extracted from the Chinese Stroke Center Alliance (CSCA) database from August 2015 to July 2019. The association between infections [pneumonia or urinary tract infection (UTI)] and in-hospital mortality was analyzed. Logistic regression models were used to identify the risk factors for in-hospital mortality of patients with infection.

Results

In total, 1,77,923 AIS patients with DM were included in the study. The infection rate during hospitalization was 10.5%, and the mortality rate of infected patients was 3.4%. Stroke-associated infection was an independent risk factor for an early poor functional outcome [odds ratio (OR) = 2.26, 95% confidence interval (CI): 1.97–2.34, P < 0.0001] and in-hospital mortality in AIS patients with DM. The in-hospital mortality after infection was associated with age (OR = 1.02, 95% CI: 1.01–1.03, P < 0.0001), male (OR = 1.39, 95% CI: 1.13–1.71, P = 0.0018), reperfusion therapy (OR = 2.00, 95% CI: 1.56–2.56, P < 0.0001), and fasting plasma glucose at admission (OR = 1.05, 95% CI: 1.03–1.08, P < 0.0001). In contrast, antiplatelet drug therapy (OR = 0.63, 95% CI: 0.50–0.78, P < 0.0001) and hospital stay (OR = 0.96, 95% CI: 0.94–0.97, P < 0.0001) were independent protecting factors against in-hospital mortality of patients with infection.

Conclusion

Infection is an independent risk factor of in-hospital mortality for patients with AIS and DM, and those patients require strengthening nursing management to prevent infection.
Differences in resting state functional connectivity underlie visuomotor performance declines in older adults with a genetic risk (APOE ε4) for Alzheimer’s disease
Authors: Rogojin Alica , Gorbet Diana J. , Hawkins Kara M. , Sergio Lauren E.
Published: December 2022

Introduction

Non-standard visuomotor integration requires the interaction of large networks in the brain. Previous findings have shown that non-standard visuomotor performance is impaired in individuals with specific dementia risk factors (family history of dementia and presence of the APOE ε4 allele) in advance of any cognitive impairments. These findings suggest that visuomotor impairments are associated with early dementia-related brain changes. The current study examined the underlying resting state functional connectivity (RSFC) associated with impaired non-standard visuomotor performance, as well as the impacts of dementia family history, sex, and APOE status.

Methods

Cognitively healthy older adults (n = 48) were tested on four visuomotor tasks where reach and gaze were increasingly spatially dissociated. Participants who had a family history of dementia or the APOE ε4 allele were considered to be at an increased risk for AD. To quantify RSFC within networks of interest, an EPI sequence sensitive to BOLD contrast was collected. The networks of interest were the default mode network (DMN), somatomotor network (SMN), dorsal attention network (DAN), ventral attention network (VAN), and frontoparietal control network (FPN).

Results

Individuals with the ε4 allele showed abnormalities in RSFC between posterior DMN nodes that predicted poorer non-standard visuomotor performance. Specifically, multiple linear regression analyses revealed lower RSFC between the precuneus/posterior cingulate cortex and the left inferior parietal lobule as well as the left parahippocampal cortex. Presence of the APOE ε4 allele also modified the relationship between mean DAN RSFC and visuomotor control, where lower mean RSFC in the DAN predicted worse non-standard visuomotor performance only in APOE ε4 carriers. There were otherwise no effects of family history, APOE ε4 status, or sex on the relationship between RSFC and visuomotor performance for any of the other resting networks.

Conclusion

The preliminary findings provide insight into the impact of APOE ε4-related genetic risk on neural networks underlying complex visuomotor transformations, and demonstrate that the non-standard visuomotor task paradigm discussed in this study may be used as a non-invasive, easily accessible assessment tool for dementia risk.
Precision medicine for Parkinson’s disease: The subtyping challenge
Authors: Frasier Mark , Fiske Brian K. , Sherer Todd B.
Published: December 2022

Despite many pharmacological and surgical treatments addressing the symptoms of Parkinson’s disease, there are no approved treatments that slow disease progression. Genetic discoveries in the last 20 years have increased our understanding of the molecular contributors to Parkinson’s pathophysiology, uncovered many druggable targets and pathways, and increased investment in treatments that might slow or stop the disease process. Longitudinal, observational studies are dissecting Parkinson’s disease heterogeneity and illuminating the importance of molecularly defined subtypes more likely to respond to targeted interventions. Indeed, clinical and pathological differences seen within and across carriers of PD-associated gene mutations suggest the existence of greater biological complexity than previously appreciated and increase the likelihood that targeted interventions based on molecular characteristics will be beneficial. This article offers our current perspective on the promise and current challenges in subtype identification and precision medicine approaches in Parkinson’s disease.
Intelligent air defense task assignment based on hierarchical reinforcement learning
Authors: Liu Jia-yi , Wang Gang , Guo Xiang-ke , Wang Si-yuan , Fu Qiang
Published: December 2022

Modern air defense battlefield situations are complex and varied, requiring high-speed computing capabilities and real-time situational processing for task assignment. Current methods struggle to balance the quality and speed of assignment strategies. This paper proposes a hierarchical reinforcement learning architecture for ground-to-air confrontation (HRL-GC) and an algorithm combining model predictive control with proximal policy optimization (MPC-PPO), which effectively combines the advantages of centralized and distributed approaches. To improve training efficiency while ensuring the quality of the final decision. In a large-scale area air defense scenario, this paper validates the effectiveness and superiority of the HRL-GC architecture and MPC-PPO algorithm, proving that the method can meet the needs of large-scale air defense task assignment in terms of quality and speed.
Predicted molecules and signaling pathways for regulating seizures in the hippocampus in lithium-pilocarpine induced acute epileptic rats: A proteomics study
Authors: Wang Peng , Yang Lu , Yang Rang , Chen Zhangping , Ren Xiaofan , Wang Fangjiao , Jiao Yan , Ding Yuxin , Yang Fengyuan , Sun Tao , Ma Huisheng
Published: December 2022

Seizures in rodent models that are induced by lithium-pilocarpine mimic human seizures in a highly isomorphic manner. The hippocampus is a brain region that generates and spreads seizures. In order to understand the early phases of seizure events occurring in the hippocampus, global protein expression levels in the hippocampus on day 1 and day 3 were analyzed in lithium-pilocarpine induced acute epileptic rat models using a tandem mass tag-based proteomic approach. Our results showed that differentially expressed proteins were likely to be enhanced rather than prohibited in modulating seizure activity on days 1 and 3 in lithium-pilocarpine induced seizure rats. The differentially regulated proteins differed on days 1 and 3 in the seizure rats, indicating that different molecules and pathways are involved in seizure events occurring from day 1 to day 3 following lithium-pilocarpine administration. In regard to subcellular distribution, the results suggest that post-seizure cellular function in the hippocampus is possibly regulated in a differential manner on seizure progression. Gene ontology annotation results showed that, on day 1 following lithium-pilocarpine administration, it is likely necessary to regulate macromolecular complex assembly, and cell death, while on day 3, it may be necessary to modulate protein metabolic process, cytoplasm, and protein binding. Protein metabolic process rather than macromolecular complex assembly and cell death were affected on day 3 following lithium-pilocarpine administration. The extracellular matrix, receptors, and the constitution of plasma membranes were altered most strongly in the development of seizure events. In a KEGG pathway enrichment cluster analysis, the signaling pathways identified were relevant to sustained angiogenesis and evading apoptosis, and complement and coagulation cascades. On day 3, pathways relevant to Huntington’s disease, and tumor necrosis factor signaling were most prevalent. These results suggest that seizure events occurring in day 1 modulate macromolecular complex assembly and cell death, and in day 3 modulate biological protein metabolic process. In summary, our study found limited evidence for ongoing seizure events in the hippocampus of lithium-pilocarpine induced animal models; nevertheless, evaluating the global differential expression of proteins and their impacts on bio-function may offer new perspectives for studying epileptogenesis in the future.
Eye tracking for classification of concussion in adults and pediatrics
Authors: Samadani Uzma , Spinner Robert J. , Dynkowski Gerard , Kirelik Susan , Schaaf Tory , Wall Stephen P. , Huang Paul
Published: December 2022

Introduction

In order to obtain FDA Marketing Authorization for aid in the diagnosis of concussion, an eye tracking study in an intended use population was conducted.

Methods

Potentially concussed subjects recruited in emergency department and concussion clinic settings prospectively underwent eye tracking and a subset of the Sport Concussion Assessment Tool 3 at 6 sites. The results of an eye tracking-based classifier model were then validated against a pre-specified algorithm with a cutoff for concussed vs. non-concussed. The sensitivity and specificity of eye tracking were calculated after plotting of the receiver operating characteristic curve and calculation of the AUC (area under curve).

Results

When concussion is defined by SCAT3 subsets, the sensitivity and specificity of an eye tracking algorithm was 80.4 and 66.1%, The AUC was 0.718. The misclassification rate (n = 282) was 31.6%.

Conclusion

A pre-specified algorithm and cutoff for diagnosis of concussion vs. non-concussion has a sensitivity and specificity that is useful as a baseline-free aid in diagnosis of concussion. Eye tracking has potential to serve as an objective “gold-standard” for detection of neurophysiologic disruption due to brain injury.
Bibliometric and visual analysis of transcranial direct current stimulation in the web of science database from 2000 to 2022 via CiteSpace
Authors: Sun Weiming , Song JingJing , Dong Xiangli , Kang Xizhen , He Binjun , Zhao Wentao , Li Zhaoting , Feng Zhen , Chen Xiuping
Published: December 2022

Objective

This study aimed to evaluate the current research hotspots and development tendency of Transcranial Direct Current Stimulation (tDCS) in the field of neurobiology from a bibliometric perspective by providing visualized information to scientists and clinicians.

Materials and methods

Publications related to tDCS published between 2000 and 2022 were retrieved from the Web of Science Core Collection (WOSCC) on May 5, 2022. Bibliometric features including the number of publications and citations, citation frequency, H-index, journal impact factors, and journal citation reports were summarized using Microsoft Office Excel. Co-authorship, citation, co-citation, and co-occurrence analyses among countries, institutions, authors, co-authors, journals, publications, references, and keywords were analyzed and visualized using CiteSpace (version 6.1.R3).

Results

A total of 4,756 publications on tDCS fulfilled the criteria we designed and then were extracted from the WOSCC. The United States (1,190 publications, 25.02%) and Harvard University (185 publications, 3.89%) were the leading contributors among all the countries and institutions, respectively. NITSCHE MA and FREGNI F, two key researchers, have made great achievements in tDCS. Brain Stimulation (306 publications) had the highest number of publications relevant to tDCS and the highest number of citations (4,042 times). In terms of potential hotspots, we observed through reference co-citation analysis timeline viewer related to tDCS that “depression”#0, “Sensorimotor network”#10, “working memory”#11, and “Transcranial magnetic stimulation”#9 might be the future research hotspots, while keywords with the strong burst and still ongoing were “intensity” (2018–2022), “impairment” (2020–2022), “efficacy” (2020–2022), and “guideline” (2020–2022).

Conclusion

This was the first-ever study of peer-reviewed publications relative to tDCS using several scientometric and visual analytic methods to quantitatively and qualitatively reveal the current research status and trends in the field of tDCS. Through the bibliometric method, we gained an in-depth understanding of the current research status and development trend on tDCS. Our research and analysis results might provide some practical sources for academic scholars and clinicians.
Transcriptional profiles in the mouse amygdala after a cognitive judgment bias test largely depend on the genotype
Authors: Herrera-Rivero Marisol , Bohn Lena , Witten Anika , Jüngling Kay , Kaiser Sylvia , Richter S. Helene , Stoll Monika , Sachser Norbert
Published: December 2022

Background:The amygdala is crucial for emotional cognitive processing. Affective or emotional states can bias cognitive processes, including attention, memory, and decision-making. This can result in optimistic or pessimistic behaviors that are partially driven by the activation of the amygdala. The resulting emotional cognitive bias is a common feature of anxiety and mood disorders, both of which are interactively influenced by genetic and environmental factors. It is also known that emotional cognitive biases can be influenced by environmental factors. However, little is known about the effects of genetics and/or gene-environment interactions on emotional cognitive biases. We investigated the effects of the genetic background and environmental enrichment on the transcriptional profiles of the mouse amygdala following a well-established cognitive bias test.

Methods:Twenty-four female C57BL/6J and B6D2F1N mice were housed either in standard (control) conditions or in an enriched environment. After appropriate training, the cognitive bias test was performed on 19 mice that satisfactorily completed the training scheme to assess their responses to ambiguous cues. This allowed us to calculate an “optimism score” for each mouse. Subsequently, we dissected the anterior and posterior portions of the amygdala to perform RNA-sequencing for differential expression and other statistical analyses.

Results:In general, we found only minor changes in the amygdala’s transcriptome associated with the levels of optimism in our mice. In contrast, we observed wide molecular effects of the genetic background in both housing environments. The C57BL/6J animals showed more transcriptional changes in response to enriched environments than the B6D2F1N mice. We also generally found more dysregulated genes in the posterior than in the anterior portion of the amygdala. Gene set overrepresentation analyses consistently implicated cellular metabolic responses and immune processes in the differences observed between mouse strains, while processes favoring neurogenesis and neurotransmission were implicated in the responses to environmental enrichment. In a correlation analysis, lipid metabolism in the anterior amygdala was suggested to influence the levels of optimism.

Conclusions:Our observations underscore the importance of selecting appropriate animal models when performing molecular studies of affective conditions or emotional states, and suggest an important role of immune and stress responses in the genetic component of emotion regulation.
Factors influencing implementation of food and food-related waste audits in hospital foodservices
Authors: Cook Nathan , Collins Jorja , Goodwin Denise , Porter Judi
Published: December 2022

Background

Designing a food waste audit tool for novel hospital foodservice practice does not guarantee uptake. Intended users must be consulted to understand the tool’s feasibility and face validity. This study aimed to identify the perspectives of staff involved in the operation of hospital foodservices on (1) how an evidenced based consensus pathway food waste audit tool is perceived to translate into practice, and (2) to determine the factors that influence the completion of food and food-related waste audits within this setting.

Materials and methods

Purposeful sampling was used to recruit staff with knowledge on the operation/governance of foodservices within hospitals in Victoria, Australia. Semi-structured interviews (n = 20) were conducted via Zoom to explore barriers and enablers to completing food and food-related waste audits and a previously published food waste audit tool. NVivo was used for inductive thematic analysis.

Results

Three factors determined the completion of food and food-related waste audits in hospital foodservices, and each factor could be a barrier or an enabler; (1) capacity: the availability of time, labour and materials to complete an audit (2) change: staff resistance to audit procedures and how to gain their buy-in (3) processes, governance, and leadership: the opportunity for high level support, policy and structure to encourage waste audits if present. The consensus tool appeared to have face validity. Planning audit operations, conducting stakeholder meetings, providing education/training to foodservice team members, and facilitating communication between managers and staff were described to support consensus tool use and audit completion.

Conclusion

The consensus tool can be used to support hospital foodservices to complete food and food-related waste audits, although it may need to be customised to be fit for purpose. Optimising the capacity, change management and processes, governance and leadership of the foodservice department may improve the experience and success of a food and food-related waste audit.
Identification of a novel gene signature of lung adenocarcinoma based on epidermal growth factor receptor-tyrosine kinase inhibitor resistance
Authors: Zhou E. , Wu Feng , Guo Mengfei , Yin Zhengrong , Li Yumei , Li Minglei , Xia Hui , Deng Jingjing , Yang Guanghai , Jin Yang
Published: December 2022

Introduction

Tyrosine kinase inhibitors (TKIs) that target epidermal growth factor receptor (EGFR) mutations are commonly administered to EGFR-positive lung cancer patients. However, resistance to EGFR-TKIs (mostly gefitinib and erlotinib) is presently a significant problem. Limited studies have focused on an EGFR-TKI resistance-related gene signature (ERS) in lung adenocarcinoma (LUAD).

Methods

Gefitinib and erlotinib resistance-related genes were obtained through the differential analyses of three Gene Expression Omnibus datasets. These genes were investigated further in LUAD patients from The Cancer Genome Atlas (TCGA). Patients in the TCGA-LUAD cohort were split into two groups: one for training and one for testing. The training cohort was used to build the ERS, and the testing cohort was used to test it. GO and KEGG analyses were explored for the enriched pathways between the high-risk and low-risk groups. Various software, mainly CIBERSORT and ssGSEA, were used for immune infiltration profiles. Somatic mutation and drug sensitivity analyses were also explored.

Results

An ERS based on five genes (FGD3, PCDH7, DEPDC1B, SATB2, and S100P) was constructed and validated using the TCGA-LUAD cohort, resulting in the significant stratification of LUAD patients into high-risk and low-risk groups. Multivariable Cox analyses confirmed that ERS had an independent prognostic value in LUAD. The pathway enrichment analyses showed that most of the genes that were different between the two risk groups were related to the immune system. Further immune infiltration results revealed that a lower immune infiltration score was observed in high-risk patients, and that various leukocytes were significantly related to the ERS. Importantly, samples from the high-risk group showed lower levels of PD-1, PD-L1, and CTLA-4, which are important biomarkers for immunotherapy responses. Patients in the high-risk group also had more gene mutation changes and were more sensitive to chemotherapy drugs like docetaxel and sorafenib. The ERS was also validated in the GSE30219, GSE11969 and GSE72094, and showed a favorable prognostic value for LUAD patients.

Discussion

The ERS established during this study was able to predict a poor prognosis for LUAD patients and had great potential for predicting drug responses.
Cerebrospinal fluid interleukin-6 is a potential diagnostic biomarker for central nervous system involvement in adult acute myeloid leukemia
Authors: Gu Jiayan , Huang Xin , Zhang Yi , Bao Chenhui , Zhou Ziyang , Tong Hongyan , Jin Jie
Published: December 2022

Objective

We evaluated the correlation between cerebrospinal fluid (CSF) cytokine levels and central nervous system (CNS) involvement in adult acute myeloid leukemia (AML).

Methods

The study sample consisted of 90 patients diagnosed with AML and 20 with unrelated CNS involvement. The AML group was divided into two sub-groups: those with (CNS+, n=30) and without CNS involvement (CNS-, n=60). We used a cytometric bead assay to measure CSF interleukin (IL)-2, IL-4, IL-6, and IL-10, tumor necrosis factor-α, interferon-γ, and IL-17A. We used receiver operating characteristic curves to evaluate the ability of CSF cytokine levels to identify CNS involvement in adult AML.

Results

CSF IL-6 levels were significantly higher in CNS+adult AML patients and positively correlated with the lactate dehydrogenase levels (r=0.738, p<0.001) and white blood cell (WBC) count (r=0.455, p=0.012) in the blood, and the protein (r=0.686, p<0.001) as well as WBC count in the CSF (r=0.427, p=0.019). Using a CSF IL-6 cut-off value of 8.27 pg/ml yielded a diagnostic sensitivity and specificity was 80.00% and 88.46%, respectively (AUC, 0.8923; 95% CI, 0.8168–0.9678). After treating a subset of tested patients, their CSF IL-6 levels decreased. Consequently, the elevated CSF IL-6 levels remaining in CNS+ adult AML patients post-treatment were associated with disease progression.

Conclusion

CSF IL-6 is a promising marker for the diagnosis of adult AML with CNS involvement and a crucial dynamic indicator for therapeutic response.
Contrast-enhanced ultrasonography for early prediction of response of neoadjuvant chemotherapy in breast cancer
Authors: Guo Jiabao , Wang Bao-Hua , He Mengna , Fu Peifen , Yao Minya , Jiang Tian’an
Published: December 2022

Neoadjuvant chemotherapy (NAC) is widely accepted as a primary treatment for inoperable or locally advanced breast cancer before definitive surgery. However, not all advanced breast cancers are sensitive to NAC. Contrast-enhanced ultrasonography (CEUS) has been considered to assess tumor response to NAC as it can effectively reflect the condition of blood perfusion and lesion size. Therefore, this study aimed to evaluate the diagnostic performance of CEUS to predict early response in different regions of interest in breast tumors under NAC treatment. This prospective study included 82 patients with advanced breast cancer. Parameters of TIC (time-intensive curve) between baseline and after the first cycle of NAC were calculated for the rate of relative change (Δ), including Δpeak, ΔTTP (time to peak), ΔRBV (regional blood volume), ΔRBF (regional blood flow) and ΔMTT (mean transit time). The responders and non-responders were distinguished by the Miller-Payne Grading (MPG) system and parameters from different regions of tumors were compared in these two groups. For ROI 1(the greatest enhancement area in the central region of the tumor), there were significant differences in Δpeak1, ΔRBV1 and ΔRBF1 between responders and non-responders. For ROI 2 (the greatest enhancement area on edge of the tumor), there were significant differences in Δpeak2 and ΔRBF2 between the groups. The Δpeak1 and ΔRBF2 showed good prediction (AUC 0.798-0.820, p ≤ 0.02) after the first cycle of NAC. When the cut-off value was 0.115, the ΔRBF2 had the highest diagnostic accuracy and the maximum NPV. Quantitative TIC parameters could be effectively used to evaluate early response to NAC in advanced breast cancer.
Predicting the grade of meningiomas by clinical–radiological features: A comparison of precontrast and postcontrast MRI
Authors: Yao Yuan , Xu Yifan , Liu Shihe , Xue Feng , Wang Bao , Qin Shanshan , Sun Xiubin , He Jingzhen
Published: December 2022

Objectives

Postcontrast magnetic resonance imaging (MRI) is important for the differentiation between low-grade (WHO I) and high-grade (WHO II/III) meningiomas. However, nephrogenic systemic fibrosis and cerebral gadolinium deposition are major concerns for postcontrast MRI. This study aimed to develop and validate an accessible risk-scoring model for this differential diagnosis using the clinical characteristics and radiological features of precontrast MRI.

Methods

From January 2019 to October 2021, a total of 231 meningioma patients (development cohort n = 137, low grade/high grade, 85/52; external validation cohort n = 94, low-grade/high-grade, 60/34) were retrospectively included. Fourteen types of demographic and radiological characteristics were evaluated by logistic regression analyses in the development cohort. The selected characteristics were applied to develop two distinguishing models using nomograms, based on full MRI and precontrast MRI. Their distinguishing performances were validated and compared using the external validation cohort.

Results

One demographic characteristic (male), three precontrast MRI features (intratumoral cystic changes, lobulated and irregular shape, and peritumoral edema), and one postcontrast MRI feature (absence of a dural tail sign) were independent predictive factors for high-grade meningiomas. The area under the receiver operating characteristic (ROC) curve (AUC) values of the two distinguishing models (precontrast–postcontrast nomogram vs. precontrast nomogram) in the development cohort were 0.919 and 0.898 and in the validation cohort were 0.922 and 0.878. DeLong’s test showed no statistical difference between the AUC values of the two distinguishing models (p = 0.101).

Conclusions

An accessible risk-scoring model based on the demographic characteristics and radiological features of precontrast MRI is sufficient to distinguish between low-grade and high-grade meningiomas, with a performance equal to that of a full MRI, based on radiological features.
The value of intravoxel incoherent motion model-based diffusion-weighted imaging for predicting long-term outcomes in nasopharyngeal carcinoma
Authors: Qin Yuhui , Chen Chen , Chen Haotian , Gao Fabao
Published: December 2022

Objective

The aim of this study was to evaluate the prognostic value for survival of parameters derived from intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in patients with nasopharyngeal carcinoma (NPC).

Materials

Baseline IVIM-DWI was performed on 97 newly diagnosed NPC patients in this prospective study. The relationships between the pretreatment IVIM-DWI parametric values (apparent diffusion coefficient (ADC), D, D*, and f) of the primary tumors and the patients’ 3-year survival were analyzed in 97 NPC patients who received chemoradiotherapy. The cutoff values of IVIM parameters for local relapse-free survival (LRFS) were identified by a non-parametric log-rank test. The local-regional relapse-free survival (LRRFS), LRFS, regional relapse-free survival (RRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were calculated by using the Kaplan–Meier method. A Cox proportional hazards model was used to explore the independent predictors for prognosis.

Results

There were 97 participants (mean age, 48.4 ± 10.5 years; 65 men) analyzed. Non-parametric log-rank test results showed that the optimal cutoff values of ADC, D, D*, and f were 0.897 × 10−3 mm2/s, 0.699 × 10−3 mm2/s, 8.71 × 10−3 mm2/s, and 0.198%, respectively. According to the univariable analysis, the higher ADC group demonstrated significantly higher OS rates than the low ADC group (p = 0.036), the higher D group showed significantly higher LRFS and OS rates than the low D group (p = 0.028 and p = 0.017, respectively), and the higher D* group exhibited significantly higher LRFS and OS rates than the lower D* group (p = 0.001 and p = 0.002, respectively). Multivariable analyses indicated that ADC and D were the independent prognostic factors for LRFS (p = 0.041 and p = 0.037, respectively), D was an independent prognostic factor for LRRFS (p = 0.045), D* and f were the independent prognostic factors for OS (p = 0.019 and 0.029, respectively), and f acted was an independent prognostic factor for DMFS (p = 0.020).

Conclusions

Baseline IVIM-DWI perfusion parameters ADC and D, together with diffusion parameter D*, could act as useful factors for predicting long-term outcomes and selecting high-risk patients with NPC.