bluuebunny/crossref_metadata_2025 huggingface dataset:
Broadband Transformation Acoustic Waveguide With Anisotropic Density Based on Pentamode Metamaterials
Authors: Chen Xing , Cai Li , Wen Jihong
Published: February 2022

Multiple layer anisotropic fluid medium is critical to the realization of transformation acoustic devices, such as cloak or bend waveguide. Pentamode metamaterials have attracted extensive attention as a solid artificial version with anisotropic modulus to approximate liquids. In this paper, we present an approach to realize fluid-like anisotropic density by using pentamode materials, and an underwater bend acoustic waveguide with anisotropic density is designed and fabricated to demonstrate the effectiveness of it. Simulation results indicate that, compared with anisotropic-modulus design by using pentamode materials, wider bandwidth acoustic modulation effect can be obtained. An in-depth and comprehensive analysis of the mechanisms of the broadband characteristics is provided by calculating the band structure of the pentamode metamaterials constituting the acoustic waveguides and analyzing their vibration modes. Finally, remarkable wavefront manipulation for underwater acoustics based on the acoustic waveguide with anisotropic density is experimentally verified.
High Interleukin-8 Levels Associated With Decreased Survival in Patients With Cirrhosis Following Transjugular Intrahepatic Portosystemic Shunt
Authors: Liu Guofeng , Wang Xiaoze , Yang Tingting , Yan Yuling , Xiang Tong , Yang Li , Luo Xuefeng
Published: February 2022

Background

Serum cytokines—reflecting systemic inflammation has been associated with the risk of decompensation and mortality in patients with cirrhosis. However, the role of systemic inflammation in patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt procedure remains unknown.

Patients and Methods

Patients with cirrhosis who received transjugular intrahepatic portosystemic shunt between June 2015 and September 2017 were included. Portal and hepatic venous blood samples were obtained intraoperatively; serum cytokine levels (IL-10, IL-17A, IL-1RA, IL-8, and CXCL10) were measured in 105 patients. Associations with survival and other outcomes during long-term follow-up (median: 1,564 days) were assessed using logistic regression.

Results

IL-17A and CXCL10 levels were higher in the portal than in the hepatic veins, whereas IL-1RA levels were higher in the hepatic than in the portal veins. However, IL-8 or IL-10 levels between hepatic and portal veins showed no differences. Multivariate analysis demonstrated that Child–Pugh scores (P = 0.017, HR: 1.484, 95% CI: 1.072–2.055) and IL-8 level in hepatic veins (P < 0.001, HR: 1.043, 95% CI: 1.019–1.068) were independent predictors for mortality during long-term follow-up, with an optimal cut-off of 5.87 pg/ml for IL-8 in hepatic veins. Patients with hepatic IL-8 levels < 5.87 pg/ml had significantly higher cumulative survival rates (98.4 vs. 72.9% at 1 year, 98.4 vs. 65.3% at 2 years, 96.7 vs. 60.3% at 3 years, 94.2 vs. 60.3% at 4 years; P < 0.0001).

Conclusions

IL-8 levels in hepatic veins may reflect liver cirrhosis severity. Elevated IL-8 levels suggest shorter survival in patients receiving TIPS.
Comparative Genome Analysis of ‘Candidatus Phytoplasma luffae’ Reveals the Influential Roles of Potential Mobile Units in Phytoplasma Evolution
Authors: Huang Ching-Ting , Cho Shu-Ting , Lin Yu-Chen , Tan Choon-Meng , Chiu Yi-Ching , Yang Jun-Yi , Kuo Chih-Horng
Published: February 2022

Phytoplasmas are insect-transmitted plant pathogens that cause substantial losses in agriculture. In addition to economic impact, phytoplasmas induce distinct disease symptoms in infected plants, thus attracting attention for research on molecular plant-microbe interactions and plant developmental processes. Due to the difficulty of establishing an axenic culture of these bacteria, culture-independent genome characterization is a crucial tool for phytoplasma research. However, phytoplasma genomes have strong nucleotide composition biases and are repetitive, which make it challenging to produce complete assemblies. In this study, we utilized Illumina and Oxford Nanopore sequencing technologies to obtain the complete genome sequence of ‘Candidatus Phytoplasma luffae’ strain NCHU2019 that is associated with witches’ broom disease of loofah (Luffa aegyptiaca) in Taiwan. The fully assembled circular chromosome is 769 kb in size and is the first representative genome sequence of group 16SrVIII phytoplasmas. Comparative analysis with other phytoplasmas revealed that NCHU2019 has a remarkably repetitive genome, possessing a pair of 75 kb repeats and at least 13 potential mobile units (PMUs) that account for ∼25% of its chromosome. This level of genome repetitiveness is exceptional for bacteria, particularly among obligate pathogens with reduced genomes. Our genus-level analysis of PMUs demonstrated that these phytoplasma-specific mobile genetic elements can be classified into three major types that differ in gene organization and phylogenetic distribution. Notably, PMU abundance explains nearly 80% of the variance in phytoplasma genome sizes, a finding that provides a quantitative estimate for the importance of PMUs in phytoplasma genome variability. Finally, our investigation found that in addition to horizontal gene transfer, PMUs also contribute to intra-genomic duplications of effector genes, which may provide redundancy for subfunctionalization or neofunctionalization. Taken together, this work improves the taxon sampling for phytoplasma genome research and provides novel information regarding the roles of mobile genetic elements in phytoplasma evolution.
Isolation, Characterization, and Tea Growth-Promoting Analysis of JW-CZ2, a Bacterium With 1-Aminocyclopropane-1-Carboxylic Acid Deaminase Activity Isolated From the Rhizosphere Soils of Tea Plants
Authors: Liu Hui , Chen Guang-Hui , Sun Jing-Jing , Chen Shu , Fang Yong , Ren Jia-Hong
Published: February 2022

One of the major mechanisms underlying plant growth-promoting rhizobacteria (PGPR) is the lowering of ethylene level in plants by deamination of 1-aminocyclopropane-1-carboxylic acid (ACC) in the environment. In the present study, using ACC as the sole nitrogen source, we screened seven ACC deaminase-producing bacterial strains from rhizosphere soils of tea plants. The strain with the highest ACC deaminase activity was identified asSerratia marcescensstrain JW-CZ2. Inoculation of this strain significantly increased shoot height and stem diameter of tea seedlings, displaying significant promotive effects. Besides,S. marcescensstrain JW-CZ2 displayed high ACC deaminase activities in wide ranges of ACC concentration, pH, and temperature, suggesting the applicable potential of JW-CZ2 as a biofertilizer. Genome sequencing indicated that clusters of orthologous groups of proteins (COG) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of JW-CZ2 mainly included amino acid transport and metabolism, transcription, carbohydrate transport and metabolism, inorganic ion transport and metabolism, and membrane transport. Moreover, genes in relation to phosphate solubilization, indole acetic acid (IAA) production, and siderophore were observed in the genome of JW-CZ2, and further experimental evidence demonstrated JW-CZ2 could promote solubilization of inorganic phosphate, inhibit growth of pathogenic fungi, and produce IAA and siderophore. These aspects might be major reasons underlying the plant growth-promoting function of JW-CZ2. Overall, this study provides a newS. marcescensstrain, which has applicable potential as a promising biofertilizer.
Heat Stress: Effects on Rumen Microbes and Host Physiology, and Strategies to Alleviate the Negative Impacts on Lactating Dairy Cows
Authors: Kim Seon Ho , Ramos Sonny C. , Valencia Raniel A. , Cho Yong Il , Lee Sang Suk
Published: February 2022

Heat stress (HS) in dairy cows causes considerable losses in the dairy industry worldwide due to reduced animal performance, increased cases of metabolic disorders, altered rumen microbiome, and other health problems. Cows subjected to HS showed decreased ruminal pH and acetate concentration and an increased concentration of ruminal lactate. Heat-stressed cows have an increased abundance of lactate-producing bacteria such as Streptococcus and unclassified Enterobacteriaceae, and soluble carbohydrate utilizers such as Ruminobacter, Treponema, and unclassified Bacteroidaceae. Cellulolytic bacteria, especially Fibrobacteres, increase during HS due to a high heat resistance. Actinobacteria and Acetobacter, both acetate-producing bacteria, decreased under HS conditions. Rumen fermentation functions, blood parameters, and metabolites are also affected by the physiological responses of the animal during HS. Isoleucine, methionine, myo-inositol, lactate, tryptophan, tyrosine, 1,5-anhydro-D-sorbitol, 3-phenylpropionic acid, urea, and valine decreased under these conditions. These responses affect feed consumption and production efficiency in milk yield, growth rate, and reproduction. At the cellular level, activation of heat shock transcription factor (HSF) (located throughout the nucleus and the cytoplasm) and increased expression of heat shock proteins (HSPs) are the usual responses to cope with homeostasis. HSP70 is the most abundant HSP family responsible for the environmental stress response, while HSF1 is essential for increasing cell temperature. The expression of bovine lymphocyte antigen and histocompatibility complex class II (DRB3) is downregulated during HS, while HSP90 beta I and HSP70 1A are upregulated. HS increases the expression of the cytosolic arginine sensor for mTORC1 subunits 1 and 2, phosphorylation of mammalian target of rapamycin and decreases the phosphorylation of Janus kinase-2 (a signal transducer and activator of transcription factor-5). These changes in physiology, metabolism, and microbiomes in heat-stressed dairy cows require urgent alleviation strategies. Establishing control measures to combat HS can be facilitated by elucidating mechanisms, including proper HS assessment, access to cooling facilities, special feeding and care, efficient water systems, and supplementation with vitamins, minerals, plant extracts, and probiotics. Understanding the relationship between HS and the rumen microbiome could contribute to the development of manipulation strategies to alleviate the influence of HS. This review comprehensively elaborates on the impact of HS in dairy cows and introduces different alleviation strategies to minimize HS.
Leveraging Neuroscience to Fight Stigma Around Mental Health
Authors: Almeida Osborne F. X. , Sousa Nuno
Published: February 2022

Labels serve as identifiers and convenient descriptors of inanimate and animate objects. In humans, given labels can easily become part of an individual’s self-perceived identity. Negative labels ascribed to a person can result ininternalized stigma, a state that will shape the subject’s biography. This can ultimately impact the person’s mental and physical health sinceperceivedand/oranticipated stigmadiscourages the use of social and health services. Per definition, stigma involves labeling of persons with physical, mental, or social characteristics that do not match the observer’s arbitrarily conditioned and calibrated sense of norms (public stigma); such labeling may eventually become embedded in rules, regulations, and laws (structural stigma). Internalized stigma projects onto a person’s emotions and actions.Public (enacted) stigmaresults from stereotyping (collectively agreed-upon notions about a group of persons that are used to categorize these people) and devaluation, which subsequently leads to social distancing, discrimination, and blatant abuse of human rights. Much of what we know about stigma results from research in the psychosocial sciences and, more recently, from social neuroscience. The stigma around mental health has generated much attention in the field of psychiatry where, to date, most research has focussed on epidemiology and anti-stigma interventions. This essay intends to stimulate thought, debate, and research within the behavioral neuroscience community and, therefore, to inform evidence-based design and implementation of neuroscience-based approaches by other professionals working towards the elimination of the stigma attached to mental illness. The article starts by considering the concept of stigma and the psychological processes that give rise to the phenomenon; it also considers how projected and perceived stigma are multiplied. Finally, after a brief review of the few existing neuroscientific explorations of stigma, gaps in our knowledge of the neurobiological basis of stigma are identified and discussed.
Study Protocol for a Randomized Controlled Trial Assessing the Effectiveness of Personalized Computerized Cognitive Training for Individuals With Insomnia
Authors: Tapia Jose Luis , Puertas Francisco Javier , Duñabeitia Jon Andoni
Published: February 2022

Insomnia is a frequent and heightened pathology in the general population of developed countries, and its condition generally leads to health discomfort and performance drop in daily and work-related tasks. As current pharmacological treatments for insomnia do not always seem sufficient to mitigate impairment, contemporary cognitive approaches might shed light on developing complementary therapies for this population. We propose a cognitive stimulation intervention program based on the importance of cognitive abilities as precipitating and maintenance variables of sleep disturbances. A full phase I-II-III clinical trial is proposed in which the first two studies will serve to assess the safety of the intervention and to identify the maximum tolerated time of the computerized cognitive training (phase I) and the minimum effective number of training sessions (phase II) in the absence of adverse events or side effects. Next, a phase-III double-blind randomized controlled trial design will be set. Sixty individuals with insomnia aged 25 to 55 years will enroll in a home-based personalized computerized cognitive stimulation program for a total time of 8 weeks, training 5 days per week. Sixty insomnia patients matched in a variety of factors will constitute the active control group, where the orthogonal activities will not be cognitively demanding. Sleep, cognitive, emotional, and quality of life variables will be measured before and immediately after training. A linear mixed model and hierarchical regression analysis will be used to investigate intervention effects. The results derived from this study will be precious for future research and treatment in cognitive performance and clinical pathologies.

Clinical Trial Registration: [https://clinicaltrials.gov/], identifier [NCT05050292].
FreeSurfer and 3D Slicer-Assisted SEEG Implantation for Drug-Resistant Epilepsy
Authors: Liu Qiangqiang , Wang Junjie , Wang Changquan , Wei Fang , Zhang Chencheng , Wei Hongjiang , Ye Xiaolai , Xu Jiwen
Published: February 2022

Objective

Our study aimed to develop an approach to improve the speed and resolution of cerebral-hemisphere and lesion modeling and evaluate the advantages and disadvantages of robot-assisted surgical planning software.

Methods

We applied both conventional robot planning software (method 1) and open-source auxiliary software (FreeSurfer and 3D Slicer; method 2) to model the brain and lesions in 19 patients with drug-resistant epilepsy. The patients' mean age at implantation was 21.4 years (range, 6–52 years). Each patient received an average of 12 electrodes (range, 9–16) between May and November 2021. The electrode-implantation plan was designed based on the models established using the two methods. We statistically analyzed and compared the duration of designing the models and planning the implantation using these two methods and performed the surgeries with the implantation plan designed using the auxiliary software.

Results

A significantly longer time was needed to reconstruct a cerebral-hemisphere model using method 1 (mean, 206 s) than using method 2 (mean, 20 s) (p < 0.05). Both methods identified a mean of 1.4 lesions (range, 1–5) in each patient. Overall, using method 1 required longer (mean, 130 s; range, 48–436) than using method 2 (mean, 68.1 s; range, 50–104; p < 0.05). In addition, the clarity of the model based on method 1 was lower than that based on method 2. To devise an electrode-implantation plan, it took 9.1–25.5 min (mean, 16) and 6.6–14.8 min (mean, 10.2) based on methods 1 and 2, respectively (p < 0.05). The average target point error of 231 electrodes amounted to 1.90 mm ± 0.37 mm (range, 0.33–3.61 mm). The average entry point error was 0.89 ± 0.26 mm (range, 0.17–1.67 mm). None of the patients presented with intracranial hemorrhage or infection, and no other serious complications were observed.

Conclusions

FreeSurfer and 3D Slicer-assisted SEEG implantation is an excellent approach to enhance modeling speed and resolution, shorten the electrode-implantation planning time, and boost the efficiency of clinical work. These well-known, trusted open-source programs do not have explicitly restricted licenses. These tools, therefore, seem well suited for clinical-research applications under the premise of approval by an ethics committee, informed consent of the patient, and clinical judgment of the surgeon.
Altered Microstructural Changes Detected by Diffusion Kurtosis Imaging in Patients With Cognitive Impairment After Acute Cerebral Infarction
Authors: Fan Liting , Ibrahim Fatima Elzahra E. M. , Chu Xiaoqi , Fu Yu , Yan Hongting , Wu Zheng , Tao Chunmei , Chen Xuejing , Ma Yue , Guo Yunchu , Dong Yang , Yang Chao , Ge Yusong
Published: February 2022

Objective

To detect the microstructural changes in patients with cognitive impairment after acute cerebral infarction using diffusion kurtosis imaging (DKI).

Materials and Methods

A total of 70 patients with acute cerebral infarction were divided into two groups: 35 patients with cognitive impairment (VCI group), and 35 patients without cognitive impairment (N-VCI group), according to mini-mental state examination (MMSE) score. Healthy individuals (n = 36) were selected as the normal control (NORM) group. DKI parameters from 28 different brain regions of interest (ROIs) were selected, measured, and compared.

Results

VCI group patients had significantly higher mean diffusion (MD) and significantly lower mean kurtosis (MK) values in most ROIs than those in the N-VCI and NORM groups. DKI parameters in some ROIs correlated significantly with MMSE score. The splenium of corpus callosum MD was most correlated with MMSE score, the correlation coefficient was −0.652, and this parameter had good ability to distinguish patients with VCI from healthy controls; at the optimal cut-off MD value (0.9915), sensitivity was 91.4%, specificity 100%, and the area under the curve value 0.964.

Conclusions

Pathological changes in some brain regions may underlie cognitive impairment after acute cerebral infarction, especially the splenium of corpus callosum. These preliminary results suggest that, in patients with VCI, DKI may be useful for assessing microstructural tissue damage.
A Modified Dura Puncture Procedure to Reduce Brain Shift in Deep Brain Stimulation Surgery: One Institution's Experience
Authors: Wu Yu-Xi , Xiang Wei , Wang Jia-Jing , Liu Xiao-Ming , Yi Dong-Ye , Tian Han , Zhao Hong-Yang , Jiang Xiao-Bing , Fu Peng
Published: February 2022

Objective

The therapeutic effect of deep brain stimulation (DBS) surgery mainly depends on the accuracy of electrode placement and the reduction in brain shift. Among the standard procedures, cerebrospinal fluid (CSF) loss or pneumocephalus caused by dura incision (DI) is thought to be the main reason for brain shift and inaccuracy of electrode placement. In the current study, we described a modified dura puncture (DP) procedure to reduce brain shift and compare it with the general procedure of DBS surgery in terms of electrode placement accuracy.

Materials and Methods

We retrospectively analyzed a series of 132 patients who underwent DBS surgery in Wuhan Union Hospital from December 2015 to April 2021. According to the different surgery procedures, patients were classified into two cohorts: the DI group (DI cohort) had 49 patients who receive the general procedure, and the DP group (DP cohort) had 83 patients who receive the modified procedure. Postoperative pneumocephalus volume (PPV) and CSF loss volume, electrode fusion error (EFE), and trajectory number were calculated. Meanwhile, intraoperative electrophysiological signal length (IESL), electrode implantation duration, and other parameters were analyzed.

Results

In the current study, we introduced an improved electrode implantation procedure for DBS surgery named the DP procedure. Compared with the general DI cohort (n = 49), the modified DP cohort (n = 83) had a shorter electrode implantation duration (p < 0.0001), smaller PPV, lower CSF leakage volume (p < 0.0001), and smaller EFE (p < 0.0001). There was no significant difference in IESL (p > 0.05) or adverse events (perioperative cerebral haematoma, skin erosion, epilepsy, p > 0.05) between the two cohorts.

Conclusion

The DP procedure is a modified procedure that can reduce brain shift and ensure implantation accuracy during DBS surgery without adverse events.
Combined Subthalamic and Nigral Stimulation Modulates Temporal Gait Coordination and Cortical Gait-Network Activity in Parkinson’s Disease
Authors: Wagner Jonas R. , Schaper Miriam , Hamel Wolfgang , Westphal Manfred , Gerloff Christian , Engel Andreas K. , Moll Christian K. E. , Gulberti Alessandro , Pötter-Nerger Monika
Published: February 2022

Background

Freezing of gait (FoG) is a disabling burden for Parkinson’s disease (PD) patients with poor response to conventional therapies. Combined deep brain stimulation of the subthalamic nucleus and substantia nigra (STN+SN DBS) moved into focus as a potential therapeutic option to treat the parkinsonian gait disorder and refractory FoG. The mechanisms of action of DBS within the cortical-subcortical-basal ganglia network on gait, particularly at the cortical level, remain unclear.

Methods

Twelve patients with idiopathic PD and chronically-implanted DBS electrodes were assessed on their regular dopaminergic medication in a standardized stepping in place paradigm. Patients executed the task with DBS switched off (STIM OFF), conventional STN DBS and combined STN+SN DBS and were compared to healthy matched controls. Simultaneous high-density EEG and kinematic measurements were recorded during resting-state, effective stepping, and freezing episodes.

Results

Clinically, STN+SN DBS was superior to conventional STN DBS in improving temporal stepping variability of the more affected leg. During resting-state and effective stepping, the cortical activity of PD patients in STIM OFF was characterized by excessive over-synchronization in the theta (4–8 Hz), alpha (9–13 Hz), and high-beta (21–30 Hz) band compared to healthy controls. Both active DBS settings similarly decreased resting-state alpha power and reduced pathologically enhanced high-beta activity during resting-state and effective stepping compared to STIM OFF. Freezing episodes during STN DBS and STN+SN DBS showed spectrally and spatially distinct cortical activity patterns when compared to effective stepping. During STN DBS, FoG was associated with an increase in cortical alpha and low-beta activity over central cortical areas, while with STN+SN DBS, an increase in high-beta was prominent over more frontal areas.

Conclusions

STN+SN DBS improved temporal aspects of parkinsonian gait impairment compared to conventional STN DBS and differentially affected cortical oscillatory patterns during regular locomotion and freezing suggesting a potential modulatory effect on dysfunctional cortical-subcortical communication in PD.
Quercetin Mitigates Methamphetamine-Induced Anxiety-Like Behavior Through Ameliorating Mitochondrial Dysfunction and Neuroinflammation
Authors: Chen Fengrong , Sun Jiaxue , Chen Cheng , Zhang Yongjin , Zou Lei , Zhang Zunyue , Chen Minghui , Wu Hongjin , Tian Weiwei , Liu Yu , Xu Yu , Luo Huayou , Zhu Mei , Yu Juehua , Wang Qian , Wang Kunhua
Published: February 2022

Methamphetamine (MA) abuse results in neurotoxic outcomes, including increased anxiety and depression. Studies have reported an association between MA exposure and anxiety, nonetheless, the underlying mechanism remains elusive. In the present study, we developed a mouse model of anxiety-like behavior induced by MA administration. RNA-seq was then performed to profile the gene expression patterns of hippocampus (HIPP), and the differentially expressed genes (DEGs) were significantly enriched in signaling pathways related to psychiatric disorders and mitochondrial function. Based on these, mitochondria was hypothesized to be involved in MA-induced anxiety. Quercetin, as a mitochondrial protector, was used to investigate whether to be a potential treatment for MA-induced anxiety; accordingly, it alleviated anxiety-like behavior and improved mitochondrial impairment in vivo. Further experiments in vitro suggested that quercetin alleviated the dysfunction and morphological abnormalities of mitochondria induced by MA, via decreasing the levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and increasing the oxygen consumption rate (OCR) and ATP production. Moreover, the study examined the effect of quercetin on astrocytes activation and neuroinflammation, and the results indicated that it significantly attenuated the activation of astrocytes and reduced the levels of IL-1β, TNFα but not IL-6. In light of these findings, quantitative evidence is presented in the study supporting the view that MA can evoke anxiety-like behavior via the induction of mitochondrial dysfunction. Quercetin exerted antipsychotic activity through modulation of mitochondrial function and neuroinflammation, suggesting its potential for further therapeutic development in MA-induced anxiety.
Integrated Microbiomic and Metabolomic Dynamics of Fermented Corn and Soybean By-Product Mixed Substrate
Authors: Wang Cheng , Wei Siyu , Jin Mingliang , Liu Bojing , Yue Min , Wang Yizhen
Published: February 2022

Microbes and their metabolites produced in fermented food have been considered as critical contributors to the quality of the final products, but the comprehensive understanding of the microbiomic and metabolomic dynamics in plant-based food during solid-state fermentation remains unclear. Here, the probiotics of Bacillus subtilis and Enterococcus faecalis were inoculated into corn and defatted soybean to achieve the two-stage solid-state fermentation. A 16S sequencing and liquid chromatography–tandem mass spectrometry were applied to investigate the dynamics of microbiota, metabolites, and their integrated correlations during fermentation. The results showed that the predominant bacteria changed from Streptophyta and Rickettsiales at 0 h to Bacillus and Pseudomonas in aerobic stage and then to Bacillus, Enterococcus, and Pseudomonas in anaerobic stage. In total, 229 notably different metabolites were identified at different fermentation times, and protein degradation, amino acid synthesis, and carbohydrate metabolism were the main metabolic pathways during the fermentation. Notably, phenylalanine metabolism was the most important metabolic pathway in the fermentation process. Further analysis of the correlations among the microbiota, metabolites, and physicochemical characteristics indicated that Bacillus spp. was significantly correlated with amino acids and carbohydrate metabolism in aerobic stage, and Enterococcus spp. was remarkably associated with amino acids metabolism and lactic acid production in the anaerobic stage. The present study provides new insights into the dynamic changes in the metabolism underlying the metabolic and microbial profiles at different fermentation stages, and are expected to be useful for future studies on the quality of fermented plant-based food.
Efficacy and Safety of Cellular Immunotherapy by Local Infusion for Liver Tumor: A Systematic Review and Meta-Analysis
Authors: Chen Shanshan , Chen Hualei , Zhang Yongchao , Li Wei
Published: February 2022

Background

Cellular immunotherapy has become a new and promising treatment for patients with liver tumor. However, as most immune cells are delivered by intravenous injection, the effect is limited and is likely to produce systemic toxicity. Here, the objective was to investigate the efficacy and safety of cellular immunotherapy by local infusion, which seems to be a promising approach and has not been well-studied.

Methods

The PubMed, Web of Science, Embase, and Cochrane Library databases were searched to obtain literature. The overall response rate (ORR), overall survival (OS) rates, and adverse events were investigated to evaluate the effectiveness and safety of locoregional therapy. The methodological quality of the articles was assessed using the methodological index for non-randomized studies (MINORS) score. The meta-analysis was performed using Stata 15.0.

Results

The eligible 17 studies involved a total of 318 patients. The random-effects model demonstrated that the ORR of local cell infusion therapy was 48% (95% confidence interval [CI]: 26%–70%). The pooled OS rate was 94% (95% CI: 83%–100%) at 6 months, 87% (95% CI: 74%–96%) at 12 months, and 42% (95% CI: 16%–70%) at 24 months. Subgroup analyses suggested that minimally invasive treatment and absence of metastasis were significantly associated with better ORR. Fourteen studies reported a variety of adverse events related to cell therapy by local perfusion. The most common complications after regional infusion of immune cells were myelosuppression (66%), fever (50%), gastrointestinal toxicity (22%), hepatic dysfunction (15%), and pleural effusion and/or ascites (14%).

Conclusions

Immune cell therapy through local perfusion is effective for patients with liver cancer, with manageable toxicity. It demonstrates better prognosis when combined with minimally invasive therapy. Considering the potential limitations, more randomized controlled trials are needed to provide solid evidence for our findings.
Circular RNAs are Potential Prognostic Markers of Head and Neck Squamous Cell Carcinoma: Findings of a Meta-Analysis Study
Authors: Nath Moumita , Roy Dibakar , Choudhury Yashmin
Published: February 2022

Background

Several studies have reported the role of circRNAs in the pathogenesis, diagnosis and prognosis of different cancers. This meta-analysis study aimed to evaluate the potential of using circRNAs as prognostic biomarkers of head and neck squamous cell carcinoma (HNSCC).

Methods

816 relevant articles were retrieved from PubMed and Science Direct databases, out of which 17 met the inclusion criteria. These 17 studies were assessed for quality by the Newcastle-Ottawa Scale (NOS) system, and 9 high quality studies (NOS>7) were included in the meta-analysis. Cochran Q test and the I square (I2) metric were calculated to detect potential heterogeneity among studies. Sensitivity analysis was performed to validate the credibility of outcomes, and publication bias was determined using Begg’s funnel plot and Egger’s test. Hazard ratio (HR) and 95% Confidence Intervals (CIs) were used to evaluate overall survival (OS) of HNSCC patients by univariate and multivariate analyses.

Results

The dysregulated levels of 9 circRNAs (circPVT1, circCORO1C, circ_0000199, circCUX1, circPARD3, circMYC, circ_0102272, circ_0092125 and circ_00072387) were inversely related to OS of HNSCC patients [upregulated circRNA (univariate analysis: HR = 3.40, 95% CI: 2.66-4.36, p < 0.0001, I2 = 0%; multivariate analysis: HR = 3.33, 95% CI: 2.54-4.38, p < 0.0001, I2 = 0%), downregulated circRNA (univariate analysis: HR = 2.83, 95% CI: 1.73-4.65, p < 0.0001, I2 = 57.8%; multivariate analysis: HR = 2.35, 95% CI: 1.42-3.89, p = 0.0009, I2 = 0%)]. The individual HR for these 9 circRNAs indicated inverse relation to OS, validating the overall HR. The dyregulated levels of these circRNAs were also associated with poor clinicopathological outcomes such as primary tumor size, lymph node metastasis, distant metastasis and poor tumor (T), nodes (N), metastases (M); i.e TNM staging, and six of these circRNAs regulated diverse micro RNAs, revealing their role in tumorigenesis and cancer progression.

Conclusion

Nine different circRNAs dysregulated in HNSCC tumors may serve as potential prognostic markers of HNSCC. These markers are associated with reduced OS and poor clinicopathological outcomes of HNSCC patients. They are also involved in the pathogenesis and progression of HNSCC through diverse mechanisms.
Case Report: Toripalimab Combined With Anlotinib in a Patient With Metastatic Upper Tract Urothelial Carcinoma After Pembrolizumab Failure
Authors: Zan Ning , Zhang Xuan , Du Lingyan , Lin Zhiyu , Yu Danfei , Liu Juan , Gou Fusheng
Published: February 2022

Urothelial carcinoma is the most common primary upper tract urinary carcinoma. If surgery, chemotherapy, and immunotherapy fail, the prognosis for upper tract urinary carcinoma is extremely poor. Immunotherapy combined with antiangiogenesis therapy is a new therapeutic regimen with a synergistic antitumor effect. We present a case of metastatic upper tract urinary carcinoma in which the patient underwent surgery and treatment with gemcitabine combined with platinum-based chemotherapy. Radiotherapy and second-line immunotherapy (pembrolizumab) were administered after the cancer had progressed to the left lymph node of the abdominal aorta in the umbilical plane. However, the patient developed liver metastases while being treated with pembrolizumab. He was administered off-label immunotherapy (toripalimab) combined with antiangiogenesis therapy (anlotinib) and achieved a long-term clinical response for over 25 months. Toripalimab combined with anlotinib has potential therapeutic value for locally advanced or metastatic upper tract urinary carcinoma in patients who had previously received platinum-based chemotherapy and had disease progression or after treatment with a PD-1 inhibitor.
An Overview of Epigenetic Methylation in Pancreatic Cancer Progression
Authors: Zhao Yuhao , Yang Mao , Wang Shijia , Abbas Sk Jahir , Zhang Junzhe , Li Yongsheng , Shao Rong , Liu Yingbin
Published: February 2022

Over the past decades, the aberrant epigenetic modification, apart from genetic alteration, has emerged as dispensable events mediating the transformation of pancreatic cancer (PC). However, the understanding of molecular mechanisms of methylation modifications, the most abundant epigenetic modifications, remains superficial. In this review, we focused on the mechanistic insights of DNA, histone, and RNA methylation that regulate the progression of PC. The methylation regulators including writer, eraser and reader participate in the modification of gene expression associated with cell proliferation, invasion and apoptosis. Some of recent clinical trials on methylation drug targeting were also discussed. Understanding the novel regulatory mechanisms in the methylation modification may offer alternative opportunities to improve therapeutic efficacy to fight against this dismal disease.
Identification of CXCL10 as a Prognostic Biomarker for Clear Cell Renal Cell Carcinoma
Authors: Qu Genyi , Wang Hao , Yan Huiqin , Liu Genlin , Wu Min
Published: February 2022

Background

One of the widespread forms of kidney tumor is clear cell renal cell carcinoma (ccRCC), with poor prognosis and insensitivity to radio chemotherapy as there is limited capacity to understand the disease mechanism. This study aims at identifying potential biomarkers and the underlying processes of ccRCC using bioinformatics analysis.

Methods

Transcriptome data of relevant samples were downloaded from The Cancer Genome Atlas (TCGA) database. R software was used to screen differentially expressed genes (DEGs) using the “edgeR” package. Two types of analysis—Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment—were accomplished by applying Database for Annotation, Visualization, and Integrated Discovery (DAVID) and Search Tool for the Retrieval of Interacting Genes database (STRING) online bioinformatics tools. A protein–protein interaction (PPI) network of the identified DEGs was constructed using Cytoscape software, and hub genes were subsequently selected via the Cytohubba plug-in. The selected genes were input into Oncomine for verification. Finally, selected hub genes were analyzed by doing survival analysis to notice the relationship between survival (OS) rate and the selected genes’ level of expression.

Results

There were 1,855 DEGs found connected to ccRCC, with 1,207 upregulated genes and 648 downregulated genes. G-protein-coupled receptor signaling pathway, integral component of membrane, calcium ion binding, and cytokine–cytokine receptor interaction were among the DEGs discovered. Oncomine confirmed the top six hub genes from the PPI network (C3, CXCR3, CXCL10, CCR5, CCL4, and CCL5). A high level of expression of CXCL10, one of these hub genes, was linked to a poor prognosis in individuals with ccRCC. The results of survival analysis showed that the expression level of CXCL10 was significantly correlated with the prognosis of ccRCC patients (p < 0.05).

Conclusions

From the analysis, the following results were drawn: CXCL10 might be a potential prognostic biomarker and novel therapeutic target for ccRCC.
Case Report: Unusual Aggregation of Different Glomerulopathies in a Family Resolved by Genetic Testing and Reverse Phenotyping
Authors: Kumar Reeti , Keskinyan Vahakn , Stangl Megan Chryst , Lane Brandon M. , Buckley Anne F. , Barisoni Laura , Howell David N. , Gbadegesin Rasheed A.
Published: February 2022

Glomerular diseases (GDs) are a major cause of chronic kidney disease in children. The conventional approach to diagnosis of GDs includes clinical evaluation and, in most cases, kidney biopsy to make a definitive diagnosis. However, in many cases, clinical presentations of different GDs can overlap, leading to uncertainty in diagnosis and management even after renal biopsy. In this report, we identify a family with clinical diagnoses of postinfectious glomerulonephritis and IgA nephropathy in a parent and two children. Renal biopsies were initially inconclusive; however, genetic testing showed that the two individuals diagnosed at different points with IgA nephropathy carried novel segregating pathogenic variants in COL4A5 gene. We were only able to make the final diagnoses in each of the family members after genetic testing and reverse phenotyping. This case highlights the utility of genetic testing and reverse phenotyping in resolving clinical diagnosis in families with unusual constellations of different glomerulopathies. We propose that clustering of different glomerular disease phenotypes in a family should be an indication for genetic testing followed by reverse phenotyping.
Dysmotility in Eosinophilic Esophagitis
Authors: Chai Charmaine , Krishnan Usha
Published: February 2022

Eosinophilic esophagitis (EoE) is an immune mediated chronic inflammatory disease resulting from antigen exposure and is characterized by mucosal inflammation with eosinophils. Diagnosis is based on the histological finding of at least 15 eosinophils per high power field in esophageal biopsy specimens from upper gastrointestinal endoscopies. These endoscopies are usually performed in the setting of esophageal dysfunction, however, EoE can occasionally be incidentally diagnosed during endoscopies performed for other indications like coeliac disease. The eosinophilia is in the absence of other causes of esophageal eosinophilia (e.g., parasitic infection, esophageal leiomyomatosis or Crohn's disease). Presentation can be wide ranging and often varies according to age. Infants and younger children can present with choking/gagging, feed refusal, failure to thrive, irritability and vomiting. Older children and adults commonly present with dysphagia, chest pain or food bolus obstruction. EoE was first described in the 1970s, but was only recognized as a distinct disease entity in the 1990s. It has been rising in incidence and prevalence, with reported prevalence ranging between 1 in 2,500 and 1 in 10,000. Although the diagnosis of EoE is dependent on clear histopathologic diagnostic criteria, there is a disconnect between the degree of esophageal eosinophilia and symptom severity especially that of reported dysphagia. Multiple anatomical changes can be seen in the spectrum of presentations of EoE which explain dysphagia, including isolated strictures, diffuse trachealisation, fixed rings, including Schatzki, as well as tissue remodeling and fibrotic changes. However, a majority of EoE patients do not have any of these findings and will still often report ongoing dysphagia. Some will report ongoing dysphagia despite histological remission. This suggests an underlying esophageal dysmotilty which cannot be assessed with endoscopy or correlated with histological changes seen in biopsies. This review will describe the types of motor disturbances seen and their prevalence, the pathophysiological basis of dysmotility seen in EoE, how best to investigate esophageal dysfunction in EoE and the role of manometry in the management of EoE.
The Pharmacological and Structural Basis of the AahII–NaV1.5 Interaction and Modulation by the Anti-AahII Nb10 Nanobody
Authors: Hmaidi Riadh , Ksouri Ayoub , Benabderrazek Rahma , Antonietti Viviane , Sonnet Pascal , Gautier Mathieu , Bouhaouala-Zahar Balkiss , Ouadid-Ahidouch Halima
Published: February 2022

Scorpion α-toxins are neurotoxins that target the fast inactivation mechanism of voltage-gated sodium (NaV) channels leading to several neuro- and cardiotoxic effects in mammals. The toxin AahII is the most active α-toxin from the North African scorpionAndroctonus australis Hectorthat slows the fast inactivation of NaVchannels. To fight scorpion envenomation, an anti-AahII nanobody named NbAahII10 (Nb10) was developed. The efficiency of this nanobody has been evaluatedin vivoon mice, but its mechanism of action at the cellular level remains unknown. Here we have shown that AahII toxin slows the fast inactivation of the adult cardiac NaV1.5 channels, expressed in HEK293 cells, in a dose-dependent manner, while current amplitude was not affected. The inactivation of NaV1.5 is slower by a factor of 4, 7, and 35 in the presence of [AahII] at 75, 150, and 300 nM, respectively. The washout partially reversed the toxin effect on inactivation from 8.3 ± 0.9 ms to 5.2 ± 1.2 ms at 75 nM. We have also demonstrated that the highly neutralizing Nb10 can fully reverse the effect of AahII toxin on the channel inactivation kinetics even at the 1:1 M ratio. However, the 1:0.5 M ratio is not able to neutralize completely the AahII effect. Therefore, the application of Nb10 promotes a partial abolishment of AahII action. Bioinformatic analysis and prediction of NaV1.5-driven docking with AahII show that Ala39 and Arg62 of AahII play a crucial role to establish a stable interaction through H-bound interactions with Gln1615 and Lys1616 (S3–S4 extracellular loop) and Asp1553 (S1–S2 loop) from the voltage-sensing domain IV (VSD4) of NaV1.5, respectively. From this, we notice that AahII shares the same contact surface with Nb10. This strongly suggests that Nb10 dynamically replaces AahII toxin from its binding site on the NaV1.5 channel. At the physiopathological level, Nb10 completely neutralized the enhancement of breast cancer cell invasion induced by AahII. In summary, for the first time, we made an electrophysiological and structural characterization of the neutralization potent of Nb10 against the α-scorpion toxin AahII in a cellular model overexpressing NaV1.5 channels.
Palatability Assessment of Carbocysteine Oral Solution Strawberry Taste Versus Carbocysteine Oral Solution Mint Taste: A Blinded Randomized Study
Authors: Peng Yaguang , Zhang Huan , Gao Liucun , Wang Xiaoling , Peng Xiaoxia
Published: February 2022

Objective: To compare and evaluate the palatability of two carbocysteine oral solutions (strawberry vs. mint taste) among healthy children aged 2–12 years.

Methods: A randomized, triple-blind, crossover, palatability trial in 42 children aged 2–12 years. All subjects received two preparations of carbocysteine oral solutions (strawberry vs. mint) according to randomized administration sequences, and the administration process was recorded by video. The palatability assessed by emotional valences was performed using a facial action coding system by FaceReader™, which reflected the quantification degree of emotion; a positive value represents positive emotion, and a negative value represents negative emotion. At the same time, a face-to-face interview was conducted for 5- to 12-year-old participants. Then, the taste preferential rates were compared to assess the palatability of two carbocysteine oral solutions.

Results: Forty-two children were enrolled in this study. Twenty children first tasted the carbocysteine oral solution mint taste and then the strawberry taste preparation (M-S sequence), while 22 children tasted the strawberry preparation first and then the mint one (S-M sequence). The emotional valence of mint preparation (−0.9 in M-S and −1.2 in S-M) was both relatively lower than that of strawberry taste (both −0.7 in M-S and S-M) in two sequences; 69.0% (29/42) of participants’ emotional valences for strawberry preparation were higher than those for mint preparation. Among 27 participants aged ≥5 years, the taste preference rate was 88.5% (23/26) for the strawberry preparation (one missing value for the taste preference), and 77.8% of participants (21/27) chose the strawberry preparation if they had to take the medicine one more time.

Conclusion: The carbocysteine oral solution with strawberry taste is an appealing preparation since it was better received by children. The facial action coding system could be an effective alternative for palatability assessment of pediatric pharmaceutical products.
Activation of CNR1/PI3K/AKT Pathway by Tanshinone IIA Protects Hippocampal Neurons and Ameliorates Sleep Deprivation-Induced Cognitive Dysfunction in Rats
Authors: Li Zi-Heng , Cheng Li , Wen Chun , Ding Li , You Qiu-Yun , Zhang Shun-Bo
Published: February 2022

Sleep deprivation is commonplace in modern society, Short periods of continuous sleep deprivation (SD) may negatively affect brain and behavioral function and may lead to vehicle accidents and medical errors. Tanshinone IIA (Tan IIA) is an important lipid-soluble component of Salvia miltiorrhiza, which could exert neuroprotective effects. The aim of this study was to investigate the mechanism of neuroprotective effect of Tan IIA on acute sleep deprivation-induced cognitive dysfunction in rats. Tan IIA ameliorated behavioral abnormalities in sleep deprived rats, enhanced behavioral performance in WMW and NOR experiments, increased hippocampal dendritic spine density, and attenuated atrophic loss of hippocampal neurons. Tan IIA enhanced the expression of CB1, PI3K, AKT, STAT3 in rat hippocampus and down-regulated the expression ratio of Bax to Bcl-2. These effects were inhibited by cannabinoid receptor 1 antagonist (AM251). In conclusion, Tan IIA can play a neuroprotective role by activating the CNR1/PI3K/AKT signaling pathway to antagonize apoptosis in the hippocampus and improve sleep deprivation-induced spatial recognition and learning memory dysfunction in rats. Our study suggests that Tan IIA may be a candidate for the prevention of sleep deprivation-induced dysfunction in spatial recognition and learning memory.