bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Surfactant Protein D Binds Spike Protein and Acts as an Entry Inhibitor of SARS-CoV-2 Pseudotyped Viral Particles
Authors: Hsieh Miao-Hsi , Beirag Nazar , Murugaiah Valarmathy , Chou Yu-Chi , Kuo Wen-Shuo , Kao Hui-Fang , Madan Taruna , Kishore Uday , Wang Jiu-Yao
Published: May 2021

Human SP-D is a potent innate immune molecule whose presence at pulmonary mucosal surfaces allows its role in immune surveillance against pathogens. Higher levels of serum SP-D have been reported in the patients with severe acute respiratory syndrome coronavirus (SARS-CoV). Studies have suggested the ability of human SP-D to recognise spike glycoprotein of SARS-CoV; its interaction with HCoV-229E strain leads to viral inhibition in human bronchial epithelial (16HBE) cells. Previous studies have reported that a recombinant fragment of human SP-D (rfhSP-D) composed of 8 Gly-X-Y repeats, neck and CRD region, can act against a range of viral pathogens including influenza A Virus and Respiratory Syncytial Virus in vitro, in vivo and ex vivo. In this context, this study was aimed at examining the likely protective role of rfhSP-D against SARS-CoV-2 infection. rfhSP-D showed a dose-responsive binding to S1 spike protein of SARS-CoV-2 and its receptor binding domain. Importantly, rfhSP-D inhibited interaction of S1 protein with the HEK293T cells overexpressing human angiotensin converting enzyme 2 (hACE2). The protective role of rfhSP-D against SARS-CoV-2 infection as an entry inhibitor was further validated by the use of pseudotyped lentiviral particles expressing SARS-CoV-2 S1 protein; ~0.5 RLU fold reduction in viral entry was seen following treatment with rfhSP-D (10 µg/ml). These results highlight the therapeutic potential of rfhSP-D in SARS-CoV-2 infection and merit pre-clinical studies in animal models.
Serum Interleukin-26 Is a New Biomarker for Disease Activity Assessment in Systemic Lupus Erythematosus
Authors: Brilland Benoit , Bach-Bunner Maxime , Gomes Christopher Nunes , Larochette Vincent , Foucher Etienne , Plaisance Marc , Saulnier Patrick , Costedoat-Chalumeau Nathalie , Ghillani Pascale , Belizna Cristina , Delneste Yves , Augusto Jean-François , Jeannin Pascale
Published: May 2021

Objective

Interleukin-26 (IL-26) has a unique ability to activate innate immune cells due to its binding to circulating double-stranded DNA. High levels of IL-26 have been reported in patients with chronic inflammation. We aimed to investigate IL-26 levels in patients with systemic lupus erythematosus (SLE).

Methods

IL-26 serum levels were quantified by ELISA for 47 healthy controls and 109 SLE patients previously enrolled in the PLUS study. Performance of IL-26 levels and classical markers (autoantibodies or complement consumption) to identify an active SLE disease (SLE disease activity index (SLEDAI) score > 4) were compared.

Results

IL-26 levels were significantly higher in SLE patients than in controls (4.04 ± 11.66 and 0.74 ± 2.02 ng/mL; p = 0.005). IL-26 levels were also significantly higher in patients with active disease than those with inactive disease (33.08 ± 21.06 vs 1.10 ± 3.80 ng/mL, p < 0.0001). IL-26 levels correlated with SLEDAI score and the urine protein to creatinine ratio (uPCR) (p < 0.001). Patients with high IL-26 levels had higher SLEDAI score, anti-DNA antibodies levels, and uPCR (p < 0.05). They presented more frequently with C3 or C4 complement consumption. Lastly, IL-26 showed stronger performance than classical markers (complement consumption or autoantibodies) for active disease identification.

Conclusions

Our results suggest that, in addition to classical SLE serological markers, the measurement of IL-26 levels may be a useful biomarker for active disease identification in SLE patients.
Modifications of the BAFF/BAFF-Receptor Axis in Patients With Pemphigus Treated With Rituximab Versus Standard Corticosteroid Regimen
Authors: Hébert Vivien , Maho-Vaillant Maud , Golinski Marie-Laure , Petit Marie , Riou Gaëtan , Boyer Olivier , Musette Philippe , Calbo Sébastien , Joly Pascal
Published: May 2021

The efficacy of the B-cell-depleting agent rituximab has been reported in immune diseases but relapses are frequent, suggesting the need for repeated infusions. The B-cell activating factor (BAFF) is an important factor for B cell survival, class switch recombination and selection of autoreactive B cells, as well as maintaining long-lived plasma cells. It has been hypothesized that relapses after rituximab might be due to the increase of serum BAFF levels. From the Ritux3 trial, we showed that baseline serum BAFF levels were higher in pemphigus patients than in healthy donors (308 ± 13 pg/mL versus 252 ± 28 pg/mL, p=0.037) and in patients with early relapse compared who didn’t (368 ± 92 vs 297 ± 118 pg/mL, p=0.036). Rituximab and high doses of CS alone have different effects on the BAFF/BAFF-R axis. Rituximab led to an increase of BAFF levels associated to a decreased mRNA (Day 0: 12.3 ± 7.6 AU vs Month 36: 3.3 ± 4.3 AU, p=0.01) and mean fluorescence intensity of BAFF-R in non-autoreactive (Day 0: 3232 vs Month 36: 1527, mean difference: 1705, 95%CI: 624 to 2786; p=0.002) as well as on reappearing autoreactive DSG-specific B cells (Day 0: 3873 vs Month 36: 2688, mean difference: 1185, 95%CI: -380 to 2750; p=0.20). Starting high doses of corticosteroids allowed a transitory decrease of serum BAFF levels that re-increased after doses tapering whereas it did not modify BAFF-R expression in autoreactive and non-autoreactive B cells. Our results suggest that the activation of autoreactive B cells at the onset of pemphigus is likely to be related to the presence of high BAFF serum levels and that the decreased BAFF-R expression after rituximab might be responsible for the delayed generation of memory B cells, resulting in a rather long period of mild pemphigus activity after rituximab therapy. Conversely, the incomplete B cell depletion and persistent BAFF-R expression associated with high BAFF serum levels might explain the high number of relapses in patients treated with CS alone.
A Cancer-Specific Qualitative Method for Estimating the Proportion of Tumor-Infiltrating Immune Cells
Authors: Xiao Huiting , Zhang Jiashuai , Wang Kai , Song Kai , Zheng Hailong , Yang Jing , Li Keru , Yuan Rongqiang , Zhao Wenyuan , Hui Yang
Published: May 2021

Tumor-infiltrating immune cells are important components in the tumor microenvironment (TME) and different types of these cells exert different effects on tumor development and progression; these effects depend upon the type of cancer involved. Several methods have been developed for estimating the proportion of immune cells using bulk transcriptome data. However, there is a distinct lack of methods that are capable of predicting the immune contexture in specific types of cancer. Furthermore, the existing methods are based on absolute gene expression and are susceptible to experimental batch effects, thus resulting in incomparability across different datasets. In this study, we considered two common neoplasms as examples (colorectal cancer [CRC] and melanoma) and introduced the Tumor-infiltrating Immune Cell Proportion Estimator (TICPE), a cancer-specific qualitative method for estimating the proportion of tumor-infiltrating immune cells. The TICPE was based on the relative expression orderings (REOs) of gene pairs within a sample and is notably insensitive to batch effects. Performance evaluation using public expression data with mRNA mixtures, single-cell RNA-Seq (scRNA-Seq) data, immunohistochemistry data, and simulated bulk RNA-seq samples, indicated that the TICPE can estimate the proportion of immune cells with levels of accuracy that are clearly superior to other methods. Furthermore, we showed that the TICPE could effectively detect prognostic signals in patients with tumors and changes in the fractions of immune cells during immunotherapy in melanoma. In conclusion, our work presented a unique novel method, TICPE, to estimate the proportion of immune cells in specific cancer types and explore the effect of the infiltration of immune cells on the efficacy of immunotherapy and the prognosis of cancer. The source code for TICPE is available at https://github.com/huitingxiao/TICPE.
Sterile Injury Repair and Adhesion Formation at Serosal Surfaces
Authors: Zwicky Simone N. , Stroka Deborah , Zindel Joel
Published: May 2021

Most multicellular organisms have a major body cavity containing vital organs. This cavity is lined by a mucosa-like serosal surface and filled with serous fluid which suspends many immune cells. Injuries affecting the major body cavity are potentially life-threatening. Here we summarize evidence that unique damage detection and repair mechanisms have evolved to ensure immediate and swift repair of injuries at serosal surfaces. Furthermore, thousands of patients undergo surgery within the abdominal and thoracic cavities each day. While these surgeries are potentially lifesaving, some patients will suffer complications due to inappropriate scar formation when wound healing at serosal surfaces defects. These scars called adhesions cause profound challenges for health care systems and patients. Therefore, reviewing the mechanisms of wound repair at serosal surfaces is of clinical importance. Serosal surfaces will be introduced with a short embryological and microanatomical perspective followed by a discussion of the mechanisms of damage recognition and initiation of sterile inflammation at serosal surfaces. Distinct immune cells populations are free floating within the coelomic (peritoneal) cavity and contribute towards damage recognition and initiation of wound repair. We will highlight the emerging role of resident cavity GATA6+ macrophages in repairing serosal injuries and compare serosal (mesothelial) injuries with injuries to the blood vessel walls. This allows to draw some parallels such as the critical role of the mesothelium in regulating fibrin deposition and how peritoneal macrophages can aggregate in a platelet-like fashion in response to sterile injury. Then, we discuss how serosal wound healing can go wrong, causing adhesions. The current pathogenetic understanding of and potential future therapeutic avenues against adhesions are discussed.
Influences of Extreme Upwelling on a Coastal Retention Zone
Authors: Harvey Julio B. J. , Ryan John P. , Zhang Yanwu
Published: May 2021

Coastal retention zones occur in the lee of headlands and within bays of coastal upwelling environments. Because retention zones can concentrate and retain communities of coastal planktonic organisms that would otherwise be advected offshore by wind-driven transport, they are ecologically significant. While the consequences of these zones for plankton retention and recruitment have been examined, the degree to which they remain retentive under variable upwelling intensity is less well understood. This aspect of coastal plankton ecology was studied during 2012 in the retentive upwelling shadow of northern Monterey Bay, California. Environmental and biological data show that exceptionally strong upwelling can greatly diminish resident plankton populations in the upwelling shadow. Results indicate that wind-driven circulation, essential to primary productivity and the formation of retention zones, can surpass levels that allow accumulation and retention of plankton communities.
Sepsis—Pathophysiology and Therapeutic Concepts
Authors: Jarczak Dominik , Kluge Stefan , Nierhaus Axel
Published: May 2021

Sepsis is a life-threatening condition and a global disease burden. Today, the heterogeneous syndrome is defined as severe organ dysfunction caused by a dysregulated host response to infection, with renewed emphasis on immune pathophysiology. Despite all efforts of experimental and clinical research during the last three decades, the ability to positively influence course and outcome of the syndrome remains limited. Evidence-based therapy still consists of basic causal and supportive measures, while adjuvant interventions such as blood purification or targeted immunotherapy largely remain without proof of effectiveness so far. With this review, we aim to provide an overview of sepsis immune pathophysiology, to update the choice of therapeutic approaches targeting different immunological mechanisms in the course of sepsis and septic shock, and to call for a paradigm shift from the pathogen to the host response as a potentially more promising angle.
The Association Between the Baseline and the Change in Neutrophil-to-Lymphocyte Ratio and Short-Term Mortality in Patients With Acute Respiratory Distress Syndrome
Authors: Zhang Wei , Wang Yadan , Li Weijie , Wang Guizuo
Published: May 2021

Background: Two previous studies have shown that increased neutrophil to lymphocyte ratio (NLR) is associated with short-term prognosis in patients with acute respiratory distress syndrome (ARDS), but it is usually assessed as a single threshold value at baseline. We investigated the relationship between the baseline and the early change in NLR and 30-day mortality in patients with ARDS to evaluate the prognostic value of NLR baseline and NLR changes during the first 7 days after ICU admission.

Methods: This is a retrospective cohort study, with all ARDS patients diagnosed according to the Berlin definition from the Medical Information Mart for Intensive Care III (MIMIC-III) database. We calculated the NLR by dividing the neutrophil count by the lymphocyte count. The multivariable logistic regression analysis was used to investigate the relationship between the baseline NLR and short-term mortality. Then the generalized additive mixed model was used to compare trends in NLR over time among survivors and non-survivors after adjusting for potential confounders.

Results: A total of 1164 patients were enrolled in our study. Multivariable logistic regression analysis showed that after adjusting for confounders, elevated baseline NLR was a significant risk factor predicting 30-day mortality (OR 1.02, 95%CI 1.01, 1.03, P = 0.0046) and hospital mortality (OR 1.02, 95%CI 1.01, 1.03, P = 0.0003). The result of the generalized additive mixed model showed that the NLR decreased in the survival group and increased in the non-survival group gradually within 7 days after ICU admission. The difference between the two groups showed a trend of increase gradually and the difference increased by an average of 0.67 daily after adjusting for confounders.

Conclusions: We confirmed that there was a positive correlation between baseline NLR and short-term mortality, and we found significant differences in NLR changes over time between the non-survival group and the survival group. The early increase in NLR was associated with short-term mortality in ARDS patients.
Challenges and Issues of Anti-SARS-CoV-2 Vaccines
Authors: Blumental Sophie , Debré Patrice
Published: May 2021

At the beginning of 2021, anti-SARS-CoV-2 vaccination campaigns had been launched in almost 60 countries with more than 500 million doses having been distributed. In addition to the few vaccines already in use, many other candidates are in preclinical phases or experimental stages in humans. Despite the fact that the availability of anti-SARS-CoV-2 vaccine constitutes a major advance and appear to be the only way to control the pandemic, some investigation remains to be carried out, and this is notably concerning the impact on transmissibility, the duration of the conferred protection in the mid- and long term, the effectiveness against present and future viral mutants, or the ideal schedule that should be applied. In this paper, we review the circumstances that facilitated such a rapid development of anti-SARS-CoV-2 vaccines and summarize the different vaccine platforms under investigation as well as their present results and perspectives in different settings. We also discuss the indications of vaccination under special conditions, such as a history of previous COVID-19 infection or belonging to extreme age categories like children and elderly. Overall, this review highlights the multiple challenges to face if aiming to find a global solution to the pandemic through high vaccination coverage all over the world.
Mortality Rate and Characteristics of Deaths Following COVID-19 Vaccination
Authors: Lv Gang , Yuan Jing , Xiong Xiaomo , Li Minghui
Published: May 2021

Background: The emergency use authorization for coronavirus disease 2019 (COVID-19) vaccines brought both hopes and concerns to the Americans and others. We aimed to estimate the mortality rate of COVID-19 vaccination and presented characteristics of deaths following COVID-19 vaccination.

Methods: Data on deaths following COVID-19 vaccination were obtained from the Vaccine Adverse Event Reporting System (VAERS) from December 11, 2020 through January 8, 2021. The Centers for Disease Control and Prevention (CDC) COVID Data Tracker was used to identify the total number of people receiving COVID-19 vaccines during the same period to estimate the mortality rate. Stratified analysis was conducted by the location of vaccination.

Results: As of January 8, 2021, 55 deaths were reported, and the mortality rate of COVID-19 vaccination was 8.2 per million population. A total of 37 deaths were reported among long-term care facility residents, and the mortality rate was 53.4 per million population. Top reported comorbidities associated with deaths included hypertension, dementia, chronic obstructive pulmonary disease (COPD), diabetes, and heart failure. In addition, dementia was more likely to be associated with deaths vaccinated at long-term care facilities than at other locations.

Conclusion: The benefits of COVID-19 vaccines outweigh the potential risks in older frail populations, and our findings do not support actions to exclude older adults from being vaccinated. However, continued monitoring of COVID-19 vaccination is still warranted.
The Relationship Between Lower Respiratory Tract Microbiome and Allergic Respiratory Tract Diseases in Children
Authors: Cui Jinghua , Zhang Yuanyuan , Zhao Hanqing , Sun Xuemei , Chen Zhen , Zhang Qun , Yan Chao , Xue Guanhua , Li Shaoli , Feng Yanling , Liu Han , Xie Xianghui , Yuan Jing
Published: May 2021

Similar to those in the upper respiratory tract, there are microbes present in the healthy human lower respiratory tract (LRT), including the lungs and bronchus. To evaluate the relationship between LRT microbiome and allergic respiratory diseases in children, we enrolled 68 children who underwent bronchoscopy from January 2018 to December 2018 in the affiliated hospital of the Capital Institute of Pediatrics. Using the total IgE (TIgE) values, children were divided into two groups: allergy sensitivity (AS) group and non-allergy sensitivity (NAS) group. Nucleic acid was extracted from samples of bronchoalveolar lavage fluid (BALF) from the two groups of children taken during bronchoscopy treatment and the 16S rDNA gene was sequenced and analyzed. The results showed that Haemophilus, Moraxella, Streptococcus, Prevotella, Neisseria, and Rothia were detected in all patients. There was a statistically significant difference in the composition and distribution of microbiota between the AS and NAS groups (p < 0.01). Analysis of the correlation of clinical indices and microbiome showed that TIgE was positively correlated with Bacteroidetes and negatively correlated with Streptococcus. Absolute lymphocyte count showed a relationship with Streptococcus, and the absolute neutrophil count or percentage of neutrophils showed a relationship with Cardiobacterium. The LRT microbiome functioned similarly to the intestinal microbiome. That is, the decrease in microbial diversity and the change in composition could lead to an increase in allergic symptoms. The microbiome of the LRT in children, especially that of Bacteriodetes and Streptococcus, showed a correlation with respiratory allergic diseases.
Development and Application of a Fast Method to Acquire the Accurate Whole-Genome Sequences of Human Adenoviruses
Authors: Zhao Shan , Guan Wenyi , Ma Kui , Yan Yuqian , Ou Junxian , Zhang Jing , Yu Zhiwu , Wu Jianguo , Zhang Qiwei
Published: May 2021

The whole-genome sequencing (WGS) of human adenoviruses (HAdVs) plays an important role in identifying, typing, and mutation analysis of HAdVs. Nowadays, three generations of sequencing have been developed. The accuracy of first-generation sequencing is up to 99.99%, whereas this technology relies on PCR and is time consuming; the next-generation sequencing (NGS) is expensive and not cost effective for determining a few special samples; and the third-generation sequencing technology has a higher error rate. In this study, first, we developed an efficient HAdV genomic DNA extraction method. Using the complete genomic DNA instead of the PCR amplicons as the direct sequencing template and a set of walking primers, we developed the HAdV WGS method based on first-generation sequencing. The HAdV whole genomes were effectively sequenced by a set of one-way sequencing primers designed, which reduced the sequencing time and cost. More importantly, high sequence accuracy is guaranteed. Four HAdV strains (GZ01, GZ02, HK35, and HK91) were isolated from children with acute respiratory diseases (ARDs), and the complete genomes were sequenced using this method. The accurate sequences of the whole inverted terminal repeats (ITRs) at both ends of the HAdV genomes were also acquired. The genome sequence of human adenovirus type 14 (HAdV-B14) strain GZ01 acquired by this method is identical to the sequence released in GenBank, which indicates that this novel sequencing method has high accuracy. The comparative genomic analysis identified that strain GZ02 isolated in September 2010 had the identical genomic sequence with the HAdV-B14 strain GZ01 (October 2010). Therefore, strain GZ02 is the first HAdV-B14 isolate emergent in China (September 2010; GenBank acc no. MW692349). The WGS of HAdV-C2 strain HK91 and HAdV-E4 strain HK35 isolated from children with acute respiratory disease in Hong Kong were also determined by this sequencing method. In conclusion, this WGS method is fast, accurate, and universal for common human adenovirus species B, C, and E. The sequencing strategy may also be applied to the WGS of the other DNA viruses.
Evaluating Cross-Resistance to Cry and Vip Toxins in Four Strains of Helicoverpa armigera With Different Genetic Mechanisms of Resistance to Bt Toxin Cry1Ac
Authors: Qi Liangxuan , Dai Hanyang , Jin Zeng , Shen Huiwen , Guan Fang , Yang Yihua , Tabashnik Bruce E. , Wu Yidong
Published: May 2021

Evolution of resistance by pests has diminished the efficacy of transgenic crops producing insecticidal proteins from Bacillus thuringiensis (Bt). In China, where transgenic cotton producing Bt toxin Cry1Ac has been planted since 1997, field control failures have not been reported but the frequency of resistance to Cry1Ac has increased in the cotton bollworm, Helicoverpa armigera. This provides incentive to switch to multi-toxin Bt cotton, which is grown in many other countries. Previous work created four laboratory strains of H. armigera with >100-fold resistance to Cry1Ac, with the genetic basis of resistance known in all but the LF256 strain. Here, we analyzed the genetic basis of resistance in Cry1Ac in LF256 and evaluated cross-resistance of all four strains to three toxins produced by widely planted multi-toxin Bt cotton: Cry1Fa, Cry2Ab, and Vip3Aa. DNA sequencing revealed that LF256 lacked the mutations in three genes (HaTSPAN1, HaABCC2, and HaABCC3) that confer resistance to Cry1Ac in two other strains of H. armigera we analyzed. Together with previous results, the data reported here show that each of the four strains examined has a different genetic basis of resistance to Cry1Ac. Significant positive cross-resistance occurred to Cry1Fa in three of the four strains tested but not to Cry2Ab or Vip3Aa in any strain. Thus, Cry2Ab and Vip3Aa are likely to be especially valuable for increasing the efficacy and durability of Bt cotton against H. armigera populations that have some resistance to Cry1Ac.
Metabolomics Reveals Differences in Aqueous Humor Composition in Patients With and Without Pseudoexfoliation Syndrome
Authors: Dmuchowska Diana Anna , Pietrowska Karolina , Krasnicki Pawel , Kowalczyk Tomasz , Misiura Magdalena , Grochowski Emil Tomasz , Mariak Zofia , Kretowski Adam , Ciborowski Michal
Published: May 2021

Pseudoexfoliation syndrome (XFS) is stress- or inflammation-induced elastosis accompanied by excessive production of microfibrils and their deposition in the anterior segment of the eye. Approximately 60–70 million people are affected by XFS worldwide. It is a component of a systemic disorder, considered a major risk factor for accelerated cataract formation, cataract surgery complications and development of glaucoma, which untreated or inadequately treated may lead to blindness. Moreover, XFS has been associated with cardiovascular and cerebrovascular morbidity, dementia, sensorineural hearing loss and pelvic organ prolapse. The pathogenesis of XFS has not been fully elucidated yet. Aqueous humor (AH) is a transparent fluid filling the anterior and posterior chambers of the eye. Determination of AH metabolites that are characteristic for XFS may provide valuable information about the molecular background of this ocular disorder. The aim of this study was to compare the composition of AH in XFS and non-XFS patients undergoing cataract surgery. The AH samples from 34 patients (15 with XFS and 19 without) were analyzed using liquid chromatography coupled to a Quadrupole Time-of-Flight mass spectrometer (LC-QTOF-MS). The obtained metabolic fingerprints were analyzed using multivariate statistics. Eleven statistically significant metabolites were identified. Compared with the non-XFS group, the AH of patients with XFS contained significantly lower levels of amino acids and their derivatives, for example, arginine (−31%, VIP = 2.38) and homo-arginine (−19%, VIP = 1.38). Also, a decrease in the levels of two acylcarnitines, hydroxybutyrylcarnitine (−29%, VIP = 1.24) and decatrienoylcarnitine (−46%, VIP = 1.89), was observed. However, the level of indoleacetaldehyde in XFS patients was significantly higher (+96%, VIP = 2.64). Other significant metabolites were two well-recognized antioxidants, ascorbic acid (−33%, VIP = 2.11) and hydroxyanthranilic acid (−33%, VIP = 2.25), as well as S-adenosylmethionine, a compound with anti-inflammatory properties (−29%, VIP = 1.93). Metabolic pathway analysis demonstrated that the identified metabolites belonged to eight metabolic pathways, with cysteine and methionine metabolism as well as arginine and proline metabolism being the most frequently represented. XFS can be associated with enhanced oxidative stress and inflammation, as well as with the disturbances of cellular respiration and mitochondrial energy production. Implementation of non-targeted metabolomics provided a better insight into the still not fully understood pathogenesis of XFS.
Acupuncture for Mild Cognitive Impairment and Dementia: An Overview of Systematic Reviews
Authors: He Wenbo , Li Meixuan , Han Xuemei , Zhang Wei
Published: May 2021

Background: Dementia is a gradual decline in cognitive ability and is becoming more common in our elderly population. Mild cognitive impairment (MCI) is defined as a slight clinical deterioration of memory capacity, below the level of normal aging, but does not constitute a clinical diagnosis of dementia. To date, no interventions have been proven to cure MCI and dementia fully.

Purpose: To evaluate the potential effectiveness and safety of acupuncture for mild cognitive impairment (MCI) and dementia and evaluate the methodological quality of systematic reviews (SRs).

Methods: We conducted a literature search for SRs with meta-analyses in seven Chinese and international databases through October 1, 2020. The basic characteristics of the included SRs/meta-analyses and the basic information of the original included randomized controlled trials were extracted by three reviewers independently. A meta-analysis of the original randomized controlled trials from the included SRs/meta-analyses was performed using Stata 12.0 software. The Assessing the Methodological Quality of Systematic Reviews 2 was used to assess the methodological quality of the included SRs/meta-analyses, and the Grading of Recommendations, Assessment, Development, and Evaluation was used to rate the quality of evidence.

Results: A total of 35 SRs/meta-analyses were included, and the majority showed that acupuncture was more effective than western medicine or conventional therapy for MCI and dementia [odds ratio =1.39; 95% confidence interval (CI): 1.24, 1.56]. There was a statistically significant difference in the Mini-Mental State Examination score (weighted mean difference = 1.23; 95% CI: 0.78, 1.68; p < 0.00001), and there was no significant improvement in the activities of daily living score (weighted mean difference = 1.58; 95% CI: −0.02, 3.18; p = 0.053). The assessment results of Assessing the Methodological Quality of Systematic Reviews 2 showed that the methodological quality of most included SRs/meta-analyses was critically low; the lowest scores were items 2, 7, and 10. For Grading of Recommendations, Assessment, Development, and Evaluation, of the 73 outcomes, 50 (68.5%) outcomes were low or very low quality, and 23 (31.5%) outcomes were moderate quality.

Conclusions: Acupuncture can be considered as an alternative for the treatment of MCI and dementia when western medicine or other therapies are contraindicated. More high-quality evidence is needed to determine further the effectiveness of acupuncture.
Validation of Predictive Models for Autoimmune Encephalitis-Related Antibodies to Cell-Surface Proteins Expressed in Neurons: A Retrospective Study Based in a Hospital
Authors: Ding Siqi , Gong Jiaoni , Lin Jiahe , Wang Yi , Hua Yingjie , Li Xueying , Du Yanru , Xia Niange , Zhu Zhenguo , Wang Xinshi , Zheng Rongyuan , Xu Huiqin
Published: May 2021

Objective: Autoimmune encephalitis (AE) is a severe but treatable autoimmune disorder that is diagnosed by antibody (Ab) testing. However, it is unrealistic to obtain an early diagnosis in some areas since the Ab status cannot be immediately determined due to time and technology restrictions. In our study, we aimed to validate the Antibody Prevalence in Epilepsy and Encephalopathy (APE2) score among patients diagnosed with possible AE as a predictive model to screen AE patients with antibodies to cell-surface proteins expressed in neurons.

Methods: A total of 180 inpatients were recruited, and antibodies were detected through serological and/or cerebrospinal fluid (CSF) evaluations. The APE2 score was used to validate the predictive models of AE with autoantibodies.

Results: The mean APE2 score in the Ab-positive cases was 7.25, whereas the mean APE2 score in the Ab-negative cases was 3.18 (P < 0.001). The APE2 score had a receiver operating characteristic (ROC) area under the curve of 0.924 [P < 0.0001, 95% confidence interval (CI) = 0.875–0.973]. With a cutoff score of 5, the APE2 score had the best psychometric properties, with a sensitivity of 0.875 and a specificity of 0.791.

Conclusion: The APE2 score is a predictive model for AE with autoantibodies to cell-surface proteins expressed in neurons and was validated and shown to have high sensitivity and specificity in our study. We suggest that such a model should be used in patients with a suspected diagnosis of AE, which could increase the detection rate of Abs, reduce testing costs, and help patients to benefit from treatment quickly.
Pre-operative MRI Radiomics for the Prediction of Progression and Recurrence in Meningiomas
Authors: Ko Ching-Chung , Zhang Yang , Chen Jeon-Hor , Chang Kai-Ting , Chen Tai-Yuan , Lim Sher-Wei , Wu Te-Chang , Su Min-Ying
Published: May 2021

Objectives: A subset of meningiomas may show progression/recurrence (P/R) after surgical resection. This study applied pre-operative MR radiomics based on support vector machine (SVM) to predict P/R in meningiomas.

Methods: From January 2007 to January 2018, 128 patients with pathologically confirmed WHO grade I meningiomas were included. Only patients who had undergone pre-operative MRIs and post-operative follow-up MRIs for more than 1 year were studied. Pre-operative T2WI and contrast-enhanced T1WI were analyzed. On each set of images, 32 first-order features and 75 textural features were extracted. The SVM classifier was utilized to evaluate the significance of extracted features, and the most significant four features were selected to calculate SVM score for each patient.

Results: Gross total resection (Simpson grades I–III) was performed in 93 (93/128, 72.7%) patients, and 19 (19/128, 14.8%) patients had P/R after surgery. Subtotal tumor resection, bone invasion, low apparent diffusion coefficient (ADC) value, and high SVM score were more frequently encountered in the P/R group (p < 0.05). In multivariate Cox hazards analysis, bone invasion, ADC value, and SVM score were high-risk factors for P/R (p < 0.05) with hazard ratios of 7.31, 4.67, and 8.13, respectively. Using the SVM score, an AUC of 0.80 with optimal cutoff value of 0.224 was obtained for predicting P/R. Patients with higher SVM scores were associated with shorter progression-free survival (p = 0.003).

Conclusions: Our preliminary results showed that pre-operative MR radiomic features may have the potential to offer valuable information in treatment planning for meningiomas.
Pre-surgical fMRI Localization of the Hand Motor Cortex in Brain Tumors: Comparison Between Finger Tapping Task and a New Visual-Triggered Finger Movement Task
Authors: Ciavarro Marco , Grande Eleonora , Pavone Luigi , Bevacqua Giuseppina , De Angelis Michelangelo , di Russo Paolo , Morace Roberta , Committeri Giorgia , Grillea Giovanni , Bartolo Marcello , Paolini Sergio , Esposito Vincenzo
Published: May 2021

Introduction:Pre-surgical mapping is clinically essential in the surgical management of brain tumors to preserve functions. A common technique to localize eloquent areas is functional magnetic resonance imaging (fMRI). In tumors involving the peri-rolandic regions, the finger tapping task (FTT) is typically administered to delineate the functional activation of hand-knob area. However, its selectivity may be limited. Thus, here, a novel cue-induced fMRI task was tested, the visual-triggered finger movement task (VFMT), aimed at eliciting a more accurate functional cortical mapping of the hand region as compared with FTT.

Method:Twenty patients with glioma in the peri-rolandic regions underwent pre-operative mapping performing both FTT and VFMT. The fMRI data were analyzed for surgical procedures. When the craniotomy allowed to expose the motor cortex, the correspondence with intraoperative direct electrical stimulation (DES) was evaluated through sensitivity and specificity (mean sites = 11) calculated as percentage of true-positive and true-negative rates, respectively.

Results:Both at group level and at single-subject level, differences among the tasks emerged in the functional representation of the hand-knob. Compared with FTT, VFMT showed a well-localized activation within the hand motor area and a less widespread activation in associative regions. Intraoperative DES confirmed the greater specificity (97%) and sensitivity (100%) of the VFMT in determining motor eloquent areas.

Conclusion:The study provides a novel, external-triggered fMRI task for pre-surgical motor mapping. Compared with the traditional FTT, the new VFMT may have potential implications in clinical fMRI and surgical management due to its focal identification of the hand-knob region and good correspondence to intraoperative DES.
Elevated Inter-Brain Coherence Between Subjects With Concordant Stances During Discussion of Social Issues
Authors: Richard Christian , Karić Marija Stevanović , McConnell Marissa , Poole Jared , Rupp Greg , Fink Abigail , Meghdadi Amir , Berka Chris
Published: May 2021

Social media platforms offer convenient, instantaneous social sharing on a mass scale with tremendous impact on public perceptions, opinions, and behavior. There is a need to understand why information spreads including the human motivations, cognitive processes, and neural dynamics of large-scale sharing. This study introduces a novel approach for investigating the effect social media messaging and in-person discussion has on the inter-brain dynamics within small groups of participants. The psychophysiological impact of information campaigns and narrative messaging within a closed social media environment was assessed using 24-channel wireless EEG. Data were acquired from three- or four-person groups while subjects debated contemporary social issues framed by four scenarios of varying controversy: (a) investing in ethical vs. unethical corporations, (b) selecting travel destination based on social awareness, (c) determining verdict in a murder trial and the punishment of life in prison or death penalty, and (d) decision to vaccinate. Pre-/post-scenario questionnaires assess the effects of the social media information. Inter-brain coherence between subject pairs on each social issue discussed by subjects was analyzed by concordance, agreement vs. disagreement, and by group unanimity, unanimous vs. not unanimous. Subject pairs that agreed on the social issues raised in the scenarios had significantly greater inter-brain coherence in gamma frequency range than disagreeing pairs over cortical regions known to be involved in social interactions. These effects were magnified when comparing groups where subject pairs were unanimous in their stance on the social issues for some but not all scenarios. While there was considerable overlap between scenarios in what EEG channels were significant, there was enough variability to indicate the possibility of scenario-specific effects on inter-brain coherence.
Sleep and Memory Consolidation Dysfunction in Psychiatric Disorders: Evidence for the Involvement of Extracellular Matrix Molecules
Authors: Gisabella Barbara , Babu Jobin , Valeri Jake , Rexrode Lindsay , Pantazopoulos Harry
Published: May 2021

Sleep disturbances and memory dysfunction are key characteristics across psychiatric disorders. Recent advances have revealed insight into the role of sleep in memory consolidation, pointing to key overlap between memory consolidation processes and structural and molecular abnormalities in psychiatric disorders. Ongoing research regarding the molecular mechanisms involved in memory consolidation has the potential to identify therapeutic targets for memory dysfunction in psychiatric disorders and aging. Recent evidence from our group and others points to extracellular matrix molecules, including chondroitin sulfate proteoglycans and their endogenous proteases, as molecules that may underlie synaptic dysfunction in psychiatric disorders and memory consolidation during sleep. These molecules may provide a therapeutic targets for decreasing strength of reward memories in addiction and traumatic memories in PTSD, as well as restoring deficits in memory consolidation in schizophrenia and aging. We review the evidence for sleep and memory consolidation dysfunction in psychiatric disorders and aging in the context of current evidence pointing to the involvement of extracellular matrix molecules in these processes.
Neurostimulation for Stroke Rehabilitation
Authors: Ting Windsor Kwan-Chun , Fadul Faïza Abdou-Rahaman , Fecteau Shirley , Ethier Christian
Published: May 2021

Neurological injuries such as strokes can lead to important loss in motor function. Thanks to neuronal plasticity, some of the lost functionality may be recovered over time. However, the recovery process is often slow and incomplete, despite the most effective conventional rehabilitation therapies. As we improve our understanding of the rules governing activity-dependent plasticity, neuromodulation interventions are being developed to harness neural plasticity to achieve faster and more complete recovery. Here, we review the principles underlying stimulation-driven plasticity as well as the most commonly used stimulation techniques and approaches. We argue that increased spatiotemporal precision is an important factor to improve the efficacy of neurostimulation and drive a more useful neuronal reorganization. Consequently, closed-loop systems and optogenetic stimulation hold theoretical promise as interventions to promote brain repair after stroke.
Ameliorative Role of Cerium Oxide Nanoparticles Against Fipronil Impact on Brain Function, Oxidative Stress, and Apoptotic Cascades in Albino Rats
Authors: Elshony Norhan , Nassar Atef M. K. , El-Sayed Yasser S. , Samak Dalia , Noreldin Ahmed , Wasef Lamiaa , Saleh Hamida , Elewa Yaser H. A. , Tawfeek Shereen E. , Saati Abdullah A. , Batiha Gaber El-Saber , Tomczyk Michał , Umezawa Masakazu , Shaheen Hazem M.
Published: May 2021

Fipronil (FIP) is an N-phenylpyrazole insecticide that is used extensively in public health and agriculture against a wide range of pests. Exposure to FIP is linked to negative health outcomes in humans and animals including promoting neuronal cell injury, which results in apoptosis through the production of reactive oxygen species (ROS). Therefore, the purpose of the current study was to investigate the neuroprotective effects of cerium oxide nanoparticles (CeNPs) on neuronal dysfunction induced by FIP in albino rats. Male rats were randomly classified into four groups: control, FIP (5 mg/kg bwt), CeNPs (35 mg/kg bwt), and FIP + CeNPs (5 (FIP) + 35 (CeNPs) mg/kg bwt), which were treated orally once daily for 28 consecutive days. Brain antioxidant parameters, histopathology, and mRNA expression of genes related to brain function were evaluated. The results revealed oxidative damage to brain tissues in FIP-treated rats indicated by the elevated levels of malondialdehyde (MDA) and nitric oxide (NO) levels and reduced activities of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx). On the other hand, the FIP’s group that was treated with CeNPs showed decrease in MDA and NO levels and increase in SOD and GPx enzymes activity. Besides, FIP-treated rats showed decreased butyrylcholinesterase (BuChE) activity in comparison to the FIP + CeNPs group. Moreover, FIP caused up-regulation of the expression of neuron-specific enolase (NSE), caspase-3, and glial fibrillary acidic protein (GFAP) but down-regulation of B-cell lymphoma-2 (BCL-2) expression. But the FIP + CeNPs group significantly down-regulated the GFAP, NSE, and caspase-3 and up-regulated the gene expression of BCL-2. Additionally, the FIP-treated group of rats had clear degenerative lesions in brain tissue that was reversed to nearly normal cerebral architecture by the FIP + CeNPs treatment. Immunohistochemical examination of brain tissues of rats-treated with FIP showed abundant ionized calcium-binding adaptor molecule 1 (Iba-1) microglia and caspase-3 and apoptotic cells with nearly negative calbindin and synaptophysin reaction, which were countered by FIP + CeNPs treatment that revealed a critical decrease in caspase-3, Iba-1 reaction with a strong calbindin positive reaction in most of the Purkinje cells and strong synaptophysin reaction in the cerebrum and cerebellum tissues. Based on reported results herein, CeNPs treatment might counteract the neurotoxic effect of FIP pesticide via an antioxidant-mediated mechanism.
Comparison of Age-Related Pigmentary Changes in the Auditory and Vestibular Systems Within Mouse and Human Temporal Bones
Authors: Andresen Nicholas S. , Coreas Sarah , Villavisanis Dillan F. , Lauer Amanda M.
Published: May 2021

Background

Melanin pigmentation is present within the auditory and vestibular systems of the mammalian inner ear and may play a role in maintaining auditory and vestibular function. Melanocytes within the stria vascularis (SV) are necessary for the generation of the endocochlear potential (EP) and decreased EP has been linked to age-related hearing loss. Melanocytes and pigment-containing “dark cells” are present within the vestibular system, but have a less well-defined role. African–American individuals have increased pigmentation within the SV and vestibular system, which is hypothesized to be related to lower rates of age-related hearing loss and vestibular dysfunction. It remains unclear if increased pigmentation confers lifelong protection against hearing loss and vestibular dysfunction.

Methods

Mouse temporal bones were collected from juvenile (3–4 week) and aged (20–32 months) CBA/CaJ mice. Pediatric and adult human temporal bones from Caucasian or African–American individuals were examined from the Johns Hopkins Temporal Bone Collection. Information regarding Fitzpatrick skin type were unavailable, and self-identified race/ethnicity was used as a proxy. Images were taken using light microscopy at 20× magnification. ImageJ software (v1.53) was used to measure pigment within the SV and vestibular system.

Results

In mouse temporal bones pigmentation within the SV increased with age, but pigmentation within the vestibular system did not increase with age. In human temporal bones pigmentation within the SV increased with age and pigmentation within the vestibular system increased within the wall of the utricle, but not other regions of the vestibular system. African–American individuals had higher amounts of pigment within the SV and vestibular system, among both pediatric and adult populations.

Conclusion

Stria vascularis pigmentation increases with age in mouse and human temporal bones. Pigmentation within the vestibular system did not increase with age in mouse specimens and only increased within the utricular wall with age in human specimens. Individuals who identified as African–American had higher pigment content within the SV and vestibular system, both as children and as adults. These results highlight how similar age-related pigmentary changes occur in the auditory and vestibular systems across species and underscore the importance of racial/ethnic diversity in human temporal bone studies.
Food Sources Contributing to Intake of Choline and Individual Choline Forms in a Norwegian Cohort of Patients With Stable Angina Pectoris
Authors: Van Parys Anthea , Karlsson Therese , Vinknes Kathrine J. , Olsen Thomas , Øyen Jannike , Dierkes Jutta , Nygård Ottar , Lysne Vegard
Published: May 2021

Background: Choline is an essential nutrient involved in a wide range of physiological functions. It occurs in water- and lipid-soluble forms in the body and diet. Foods with a known high choline content are eggs, beef, chicken, milk, fish, and selected plant foods. An adequate intake has been set in the US and Europe, however, not yet in the Nordic countries. A higher intake of lipid-soluble choline forms has been associated with increased risk of acute myocardial infarction, highlighting the need for knowledge about food sources of the individual choline forms. In general, little is known about the habitual intake and food sources of choline, and individual choline forms.

Objective: Investigate foods contributing to the intake of total choline and individual choline forms.

Design: The study population consisted of 1,929 patients with stable angina pectoris from the Western Norway B Vitamin Intervention Trial. Dietary intake data was obtained through a 169-item food frequency questionnaire. Intake of total choline and individual choline forms was quantified using the USDA database, release 2.

Results: The geometric mean (95% prediction interval) total choline intake was 287 (182, 437) mg/d. Phosphatidylcholine accounted for 42.5% of total choline intake, followed by free choline (25.8%) and glycerophosphocholine (21.2%). Phosphocholine and sphingomyelin contributed 4.2 and 4.5%, respectively. The main dietary choline sources were eggs, milk, fresh vegetables, lean fish, and bread. In general, animal food sources were the most important contributors to choline intake.

Conclusion: This study is, to the best of our knowledge, the first to assess the intake of all choline forms and their dietary sources in a European population. Most choline was consumed in the form of phosphatidylcholine and animal food sources contributed most to choline intake. There is a need for accurate estimates of the dietary intake of this essential nutrient to issue appropriate dietary recommendations.