bluuebunny/crossref_metadata_2025 huggingface dataset:
ERBB2 as a prognostic biomarker correlates with immune infiltrates in papillary thyroid cancer
Authors: Jin Yuchen , Qiu Xian , He Ziyan , Wang JunYao , Sa Ri , Chen Libo
Published: November 2022

Epidermal growth factor receptor 2 (ERBB2) is commonly over-expressed in advanced or metastatic tissues of papillary thyroid cancer (PTC) with poor prognosis, while it remains unknown whether ERBB2 plays a role in the progression of PTC. Thus, we analyzed the data derived from online repositories, including TCGA, KEGG, GO, GeneMANIA, and STRING, to explore the relationship between ERBB2 expression and prognosis, tumor phenotypes of interest, and immune infiltrates in PTC. Compared to normal thyroid tissue, ERBB2 was up-regulated in PTC samples (p < 0.001); In comparison with the group with low expression of ERBB2, the group with high expression of ERBB2 had poorer progression-free interval in stage III/IV patients (p = 0.008) and patients aged >45 years (p = 0.019). The up-regulated ERBB2 was associated with iodine metabolism dysfunction, proliferation, metastasis, angiogenesis, and drug resistance. The expression of ERBB2 negatively correlated with enrichment scores of B cells (r = −0.176, p < 0.001), CD8+ T cells (r = −0.160, p < 0.001), cytotoxic cells (r = −0.219, p < 0.001), NK CD56dim cells (r = −0.218, p < 0.001), plasmacytoid dendritic cells (r = −0.267, p < 0.001), T cells (r = −0.164, p < 0.001), T follicular helper cells (r = −0.111, p = 0.012), gamma delta T cells (r = −0.105, p = 0.017), and regulatory T cells (r = −0.125, p = 0.005). In conclusion, ERBB2 may serve as a prognostic biomarker and an immunotherapeutic target in PTC, deserving further exploration.
Causal associations between CD40/CD40L and aortic diseases: A mendelian randomization study
Authors: Cui Xiao , Xuan Tianming , Chen Siyuan , Guo Xiaogang
Published: November 2022

Background: CD40 and CD40L have been reported as associated with aortic dissection (AD) and aortic aneurysm (AA), but the causality of the associations has not been established yet.

Methods: We conducted a two-sample Mendelian randomization (MR) study to assess the causal inference between CD40/CD40L and aortic diseases including AD and AA. The instrumental variables (IVs) for CD40 and CD40L were selected from a high-quality protein quantitative trait loci dataset released by a genomic study involving 30,931 individuals of European ancestry. The genome-wide association studies summary statistics for AD and AA were from the FinnGen Release 7, with 288638 controls for all outcomes of interests, 680 cases for AD and 6,092 cases for AA, also from European ancestry. For AA subtypes, there were 5,881 cases of thoracic AA (TAA) and 2,434 cases of abdominal AA (AAA) respectively. Inverse-variance weighted and Wald ratio were applied for calculating causal estimates. Horizontal pleiotropy and heterogeneity were assessed using MR-Egger regression analysis and Cochran Q test, respectively. Leave-one-out analyses were further performed.

Results: Three single-nucleotide polymorphisms (SNPs) for CD40 and one SNP for CD40L were selected as IVs. We found genetic proxied CD40 levels inversely associated with the risk of AD (odds ratio [OR]: 0.777, 95% confidence interval [CI]: 0.618–0.978, p = 0.031) and AA (OR: 0.905, 95% CI: 0.837–0.978, p = 0.012), consistent across TAA (both p < 0.050). There were trends of increased risks of AD and AA in the presence of CD40L while not reaching statistical significance. No significant horizontal pleiotropy or heterogeneity was observed.

Conclusion: Our MR study provides evidence supporting the causal association between CD40 and the reduced risks of both AD and AA.
SARS-CoV-2-specific humoral and cellular immune responses to BNT162b2 vaccine in Fibrodysplasia ossificans progressiva patients
Authors: Smetanova Jitka , Milota Tomas , Rataj Michal , Hurnakova Jana , Zelena Hana , Horvath Rudolf
Published: November 2022

Introduction

Fibrodysplasia ossificans progressiva (FOP) is characterized by progressive heterotopic ossification triggered by various conditions, such as trauma, infection, including COVID-19 infection, and vaccination. Although SARS-CoV-2 vaccinations prevent poor outcomes in the general population, there is limited evidence on safety, immunogenicity, and efficacy of SARS-CoV-2 vaccines for inpatients with FOP.

Methods

A case series of two patients with FOP focused on humoral, cellular post-vaccination response, and the incidence of adverse events after administration of the BNT162b2 vaccine (Comirnaty).

Results

Injection site reactions, fever, myalgia, and fatigue were the most common adverse events (AE). Neither severe AE (SAE), nor disease flare-ups were observed. No differences between patients with FOP and healthy controls were observed in humoral and cellular responses.

Conclusions

The BNT162b2 vaccine induced high humoral and cellular response levels in patients with FOP. Vaccination was not associated with SAE or disease relapse. The AEs spectrum was comparable to that of the general population.
Generation of high affinity ICAM-1-specific nanobodies and evaluation of their suitability for allergy treatment
Authors: Zettl Ines , Ivanova Tatiana , Zghaebi Mohammed , Rutovskaya Marina V. , Ellinger Isabella , Goryainova Oksana , Kollárová Jessica , Villazala-Merino Sergio , Lupinek Christian , Weichwald Christina , Drescher Anja , Eckl-Dorna Julia , Tillib Sergei V. , Flicker Sabine
Published: November 2022

The nasal cavity is an important site of allergen entry. Hence, it represents an organ where trans-epithelial allergen penetration and subsequent IgE-mediated allergic inflammation can potentially be inhibited. Intercellular adhesion molecule 1 (ICAM-1) is highly expressed on the surface of respiratory epithelial cells in allergic patients. It was identified as a promising target to immobilize antibody conjugates bispecific for ICAM-1 and allergens and thereby block allergen entry. We have previously characterized a nanobody specific for the major birch pollen allergen Bet v 1 and here we report the generation and characterization of ICAM-1-specific nanobodies. Nanobodies were obtained from a camel immunized with ICAM-1 and a high affinity binder was selected after phage display (Nb44). Nb44 was expressed as recombinant protein containing HA- and His-tags in Escherichia coli (E.coli) and purified via affinity chromatography. SDS-PAGE and Western blot revealed a single band at approximately 20 kDa. Nb44 bound to recombinant ICAM-1 in ELISA, and to ICAM-1 expressed on the human bronchial epithelial cell line 16HBE14o- as determined by flow cytometry. Experiments conducted at 4°C and at 37°C, to mimic physiological conditions, yielded similar percentages (97.2 ± 1.2% and 96.7 ± 1.5% out of total live cells). To confirm and visualize binding, we performed immunofluorescence microscopy. While Texas Red Dextran was rapidly internalized Nb44 remained localized on the cell surface. Additionally, we determined the strength of Nb44 and ICAM-1 interaction using surface plasmon resonance (SPR). Nb44 bound ICAM-1 with high affinity (10-10 M) and had slow off-rates (10-4 s-1). In conclusion, our results showed that the selected ICAM-1-specific nanobody bound ICAM-1 with high affinity and was not internalized. Thus, it could be further used to engineer heterodimers with allergen-specific nanobodies in order to develop topical treatments of pollen allergy.
Non-replicative antibiotic resistance-free DNA vaccine encoding S and N proteins induces full protection in mice against SARS-CoV-2
Authors: Alcolea Pedro J. , Larraga Jaime , Rodríguez-Martín Daniel , Alonso Ana , Loayza Francisco J. , Rojas José M. , Ruiz-García Silvia , Louloudes-Lázaro Andrés , Carlón Ana B. , Sánchez-Cordón Pedro J. , Nogales-Altozano Pablo , Redondo Natalia , Manzano Miguel , Lozano Daniel , Palomero Jesús , Montoya María , Vallet-Regí María , Martín Verónica , Sevilla Noemí , Larraga Vicente
Published: November 2022

SARS-CoV-2 vaccines currently in use have contributed to controlling the COVID-19 pandemic. Notwithstanding, the high mutation rate, fundamentally in the spike glycoprotein (S), is causing the emergence of new variants. Solely utilizing this antigen is a drawback that may reduce the efficacy of these vaccines. Herein we present a DNA vaccine candidate that contains the genes encoding the S and the nucleocapsid (N) proteins implemented into the non-replicative mammalian expression plasmid vector, pPAL. This plasmid lacks antibiotic resistance genes and contains an alternative selectable marker for production. The S gene sequence was modified to avoid furin cleavage (Sfs). Potent humoral and cellular immune responses were observed in C57BL/6J mice vaccinated with pPAL-Sfs + pPAL-N following a prime/boost regimen by the intramuscular route applying in vivo electroporation. The immunogen fully protected K18-hACE2 mice against a lethal dose (105 PFU) of SARS-CoV-2. Viral replication was completely controlled in the lungs, brain, and heart of vaccinated mice. Therefore, pPAL-Sfs + pPAL-N is a promising DNA vaccine candidate for protection from COVID-19.
Characterization of exosomes derived from IPEC-J2 treated with probiotic Bacillus amyloliquefaciens SC06 and its regulation of macrophage functions
Authors: Xu Xiaogang , Liu Rongrong , Zhou Xuqiang , Zhang Zhongshan , Zhu Tianjun , Huang Yingying , Chai Lan , Wang Yazhen , Zhao Zhenlei , Li Weifen , Mao Genxiang
Published: November 2022

Probiotics can maintain or improve health by modulating the response of immune cells in the gastrointestinal tract. However, the mechanisms by which probiotics promote macrophage (Mφ) activity are poorly understood. Here, we evaluated exosomes derived from intestinal epithelial cells treated with Bacillus amyloliquefaciens SC06 (Ba) and investigated the regulation of Mφ phagocytosis, apoptosis, and polarization. We isolated two exosomes from intestinal porcine epithelial cell lines (IPEC-J2) with or without Ba-treatment, named Ba-Exo and Exo, respectively. They had typical sizes and a cup-shaped morphology, and their surfaces presented typical exosomes-associated proteins, including CD63, ALIX, and TSG101. Ba-Exo and Exo could entrer Mφ (3D4/21 cells) effectively. Moreover, an in vitro phagocytosis assay demonstrated that Ba-Exo can promote phagocytosis of Mφ. Similar to Exo, Ba-Exo had no effect on Mφ apoptosis. Furthermore, Ba-Exo significantly increased inducible nitric oxide synthase (iNOS), declined the expression of arginase 1 (Arg1) in Mφ, and stimulated Mφ polarization to M1. To explore the differences in the regulation of Mφ polarization between Ba-Exo and Exo, we performed reverse transcription quantitative polymerase chain reaction analysis of the small RNAs and found that miR-222 increased in the Ba-Exo group compared to that in the Exo group. These results provide a new perspective on the relationship between probiotics and intestinal immunity.
Splenic protection network revealed by transcriptome analysis in inactivated vaccine-immunized flounder (Paralichthys olivaceus) against Edwardsiella tarda infection
Authors: Wu Xiaoyan , Xing Jing , Tang Xiaoqian , Sheng Xiuzhen , Chi Heng , Zhan Wenbin
Published: November 2022

The protective immune response produced by fish after vaccination is crucial for vaccine effectiveness. Our previous studies have shown inactivated vaccine against Edwardsiella tarda can induce immune response in flounder (Paralichthys olivaceus). To elucidate the protective immune response at the genetic level, in this study, flounder was immunized with inactivated E. tarda for 5 weeks, and then they were challenged with E. tarda. The spleen was dissected at 7th day post immunization, 1st and 7th day post challenge, respectively. Transcriptome analysis showed that average of 46 million clean reads were obtained per library, while percentage of clean reads being mapped to reference genome was more than 89% in all cases, which suggested good quality of samples. As for differentially expressed genes (DEGs) identification in inactivated E. tarda groups, at 7th day post immunization, 1422 DEGs were identified and significantly enriched in innate immune-related pathways, such as Phagosome, Cell adhesion molecules and NF-kappa B signaling pathway; At 1st post challenge day, 1210 DEGs were identified and enriched to Antigen processing and presentation and Cell adhesion molecules, indicating that the pathogen was rapidly recognized and delivered; At 7th post challenge day, 1929 DEGs were identified, belonged to Toll-like receptor signaling pathway, Antigen processing and presentation, Th1 and Th2 cell differentiation and Th17 cell differentiation. Compared to 7th post immunization day, 73 immune-associated DEGs were identified at 1st post challenge day. Protein-protein interaction networks analysis revealed 11 hub genes (TLR7, TLR3, CXCR4, IFIH1, TLR8 etc), associated with recognition of pathogens and activation of innate immunity; while for 7th post challenge day, 141 immune-associated DEGs were identified. 30 hub genes (IL6, STAT1, HSP90A.1, TLR7, IL12β etc) were associated with stimulation of lymphocyte differentiation and activation of cellular immunity. Ten immune-related genes were randomly selected for RT-qPCR validation at each time point. In conclusion, data revealed protection of flounder against E. tarda infection by inactivated vaccine is mediated via immediate recognition of pathogen and subsequently activation of cellular immunity. Results give new aspect for vaccine protection cascades, is good references for vaccine evaluation.
A pilot study for treatment of severe COVID-19 pneumonia by aerosolized formulation of convalescent human immune plasma exosomes (ChipEXO™)
Authors: Gül Fethi , Gonen Zeynep Burcin , Jones Olcay Y. , Taşlı Neslihan Pakize , Zararsız Gökmen , Ünal Ekrem , Özdarendeli Aykut , Şahin Fikrettin , Eken Ahmet , Yılmaz Semih , Karakukçu Musa , Kırbaş Oğuz Kaan , Gökdemir Nur Seda , Bozkurt Batuhan Turhan , Özkul Yusuf , Oktay Burçin Doruk , Uygut Muhammet Ali , Cinel Ismail , Çetin Mustafa
Published: November 2022

This is a single-center prospective, open-label, single arm interventional study to test the safety and efficacy of recently described ChipEXO™ for severe COVID-19 pneumonia. The ChipEXO™ is a natural product derived from convalescent human immune plasma of patients recovered from moderate COVID-19 infection. In September 2021, 13 patients with pending respiratory failure were treated with ChipEXO™ adapted for aerosolized formulation delivered via jet nebulizer. Patients received 1-5x1010 nano vesicle/5 mL in distilled water twice daily for five days as an add-on to ongoing conventional COVID-19 treatment. The primary endpoint was patient safety and survival over a 28-day follow-up. The secondary endpoint was longitudinal assessment of clinical parameters following ChipEXO™ to evaluate treatment response and gain insights into the pharmacodynamics. ChipEXO™ was tolerated well without any allergic reaction or acute toxicity. The survival rate was 84.6% and 11 out of 13 recovered without any sequel to lungs or other organs. ChipEXO™ treatment was effective immediately as shown in arterial blood gas analyses before and two hours after exosome inhalation. During the 5 days of treatment, there was a sustainable and gradual improvement on oxygenation parameters: i.e. respiratory rate (RR) [20.8% (P < 0.05)], oxygen saturation (SpO2) [6,7% (P < 0.05)] and partial pressure of oxygen to the fraction of inspired oxygen (PaO2/FiO2) [127.9% (P < 0.05)] that correlated with steep decrease in the disease activity scores and inflammatory markers, i.e. the sequential organ failure assessment (SOFA) score (75%, p < 0.05), C-reactive protein (46% p < 0.05), ferritin (58% p = 0.53), D-dimer (28% p=0.46). In conclusion, aerosolized ChipEXO™ showed promising safety and efficacy for life-threatening COVID-19 pneumonia. Further studies on larger patient populations are required to confirm our findings and understand the pathophysiology of improvement toward a new therapeutic agent for the treatment of severe COVID-19 pneumonia.
CD8+ T cell/cancer-associated fibroblast ratio stratifies prognostic and predictive responses to immunotherapy across multiple cancer types
Authors: Zheng Xinlong , Jiang Kan , Xiao Weijin , Zeng Dongqiang , Peng Wenying , Bai Jing , Chen Xiaohui , Li Pansong , Zhang Longfeng , Zheng Xiaobin , Miao Qian , Wang Haibo , Wu Shiwen , Xu Yiquan , Xu Haipeng , Li Chao , Li Lifeng , Gao Xuan , Zheng Suya , Li Junhui , Wang Deqiang , Zhou Zhipeng , Xia Xuefeng , Yang Shanshan , Li Yujing , Cui Zhaolei , Zhang Qiuyu , Chen Ling , Lin Xiandong , Lin Gen
Published: November 2022

Background

Cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) are critical for immune suppression by restricting immune cell infiltration in the tumor stromal zones from penetrating tumor islands and changing their function status, particularly for CD8+ T cells. However, assessing and quantifying the impact of CAFs on immune cells and investigating how this impact is related to clinical outcomes, especially the efficacy of immunotherapy, remain unclear.

Materials and methods

The TME was characterized using immunohistochemical (IHC) analysis using a large-scale sample size of gene expression profiles. The CD8+ T cell/CAF ratio (CFR) association with survival was investigated in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) lung cancer cohorts. The correlation between CFR and immunotherapeutic efficacy was computed in five independent cohorts. The correlation between CFR and objective response rates (ORRs) following pembrolizumab monotherapy was investigated in 20 solid tumor types. To facilitate clinical translation, the IHC-detected CD8/α-SMA ratio was applied as an immunotherapeutic predictive biomarker in a real-world lung cancer cohort.

Results

Compared with normal tissue, CAFs were enriched in cancer tissue, and the amount of CAFs was overwhelmingly higher than that in other immune cells. CAFs are positively correlated with the extent of immune infiltration. A higher CFR was strongly associated with improved survival in lung cancer, melanoma, and urothelial cancer immunotherapy cohorts. Within most cohorts, there was no clear evidence for an association between CFR and programmed death-ligand 1 (PD-L1) or tumor mutational burden (TMB). Compared with TMB and PD-L1, a higher correlation coefficient was observed between CFR and the ORR following pembrolizumab monotherapy in 20 solid tumor types (Spearman’s r = 0.69 vs. 0.44 and 0.21). In a real-world cohort, patients with a high CFR detected by IHC benefited considerably from immunotherapy as compared with those with a low CFR (hazard ratio, 0.37; 95% confidence interval, 0.19–0.75; p < 0.001).

Conclusions

CFR is a newly found and simple parameter that can be used for identifying patients unlikely to benefit from immunotherapy. Future studies are needed to confirm this finding.
Efferocytosis drives myeloid NLRP3 dependent inflammasome signaling secretion of IL-1β to promote tumor growth
Authors: Lang Cara , Roy Sohini , Wang Yu , Graves Diana , Xu Yaomin , Serezani C. Henrique , Korrer Michael , Kim Young J.
Published: November 2022

Caspase-1 signaling in myeloid suppressor cells can promote T-cell independent cancer progression, but the regulation of inflammasome signaling within the highly heterogeneous myeloid population in the tumor milieu remains elusive. To resolve this complexity, single cell transcriptomic profile of Head and Neck Squamous Cell Carcinoma (HNSCC) identified distinct inflammasome-associated genes within specific clusters of tumor-infiltrating myeloid cells. Among these myeloid cells, the sensor protein, NLRP3, and downstream effector IL-1β transcripts were enriched in discreet monocytic and macrophage subtypes in the TME. We showed that deletion of NLRP3, but not AIM2, phenocopied caspase-1/IL-1β dependent tumor progression in vivo. Paradoxically, we found myeloid-intrinsic caspase-1 signaling increased myeloid survival contrary to what would be predicted from the canonical pyroptotic function of caspase-1. This myeloid NLRP3/IL-1β signaling axis promotion of tumor growth was found to be gasdermin D independent. Mechanistically, we found that phagocyte-mediated efferocytosis of dying tumor cells in the TME directly activated NLRP3-dependent inflammasome signaling to drive IL-1β secretion. Subsequently we showed that NLRP3-mediated IL-1β production drives tumor growth in vivo. Dynamic RNA velocity analysis showed a robust directional flow from efferocytosis gene-set high macrophages to an inflammasome gene-set high macrophage population. We provide a novel efferocytosis-dependent inflammasome signaling pathway which mediates homeostatic tumor cell apoptosis that characterizes chronic inflammation-induced malignancy.
A systematic review and meta-analysis of cognitive and behavioral tests in rodents treated with different doses of D-ribose
Authors: Song Ying , Du Yage , An Yu , Zheng Jie , Lu Yanhui
Published: November 2022

Background

D-ribose is an aldehyde sugar and a necessary component of all living cells. Numerous reports have focused on D-ribose intervention in animal models to assess the negative effects of D-ribose on cognition. However, the results across these studies are inconsistent and the doses and actual effects of D-ribose on cognition remain unclear. This systematic review aimed to evaluate the effect of D-ribose on cognition in rodents.

Methods

The articles from PubMed, Embase, Sciverse Scopus, Web of Science, the Chinese National Knowledge Infrastructure, SinoMed, Wanfang, and Cqvip databases were screened. The results from the abstract on cognitive-related behavioral tests and biochemical markers from the included articles were extracted and the reporting quality was assessed.

Results

A total of eight trials involving 289 rodents met the eligibility criteria, and both low- and high-dose groups were included. Meta-analyses of these studies showed that D-ribose could cause a significant decrease in the number of platform crossings (standardized mean difference [SMD]: –0.80; 95% CI: –1.14, –0.46; p < 0.00001), percentage of distance traversed in the target quadrant (SMD: –1.20; 95% CI: –1.47, –0.92; p < 0.00001), percentage of time spent in the target quadrant (SMD: –0.93; 95% CI: –1.18, –0.68; p < 0.00001), and prolonged escape latency (SMD: 0.41; 95% CI: 0.16, 0.65; p = 0.001) in the Morris water maze test. Moreover, D-ribose intervention increased the levels of advanced glycation end products (AGEs) in the brain (SMD: 0.49; 95% CI: 0.34, 0.63; p < 0.00001) and blood (SMD: 0.50; 95% CI: 0.08, 0.92; p = 0.02). Subsequently, subgroup analysis for the dose of D-ribose intervention revealed that high doses injured cognitive function more significantly than low D-ribose doses.

Conclusion

D-ribose treatment caused cognitive impairment, and cognition deteriorated with increasing dose. Furthermore, the increase in AGEs in the blood and brain confirmed that D-ribose may be involved in cognitive impairment through non-enzymatic glycosylation resulting in the generation of AGEs. These findings provide a new research idea for unveiling basic mechanisms and prospective therapeutic targets for the prevention and treatment of patients with cognitive impairment.
Time-varying caloric vestibular stimulation for the treatment of neurodegenerative disease
Authors: Black Robert D. , Chaparro Eduardo
Published: November 2022

Time-varying caloric vestibular stimulation (tvCVS) is a new form of non-invasive neuromodulation similar to, but different from, diagnostic caloric vestibular stimulation (CVS). Using a non-invasive, solid-state delivery device, tvCVS has been successfully used in a human clinical trial with Parkinson’s disease (PD) subjects. Additionally, the effects of tvCVS on brain activation have been studied in healthy human subjects using transcranial Doppler sonography (TCD) and functional magnetic resonance imaging (BOLD fMRI). A novel finding in the TCD and fMRI studies was the induction of cerebral blood flow velocity (CBFv) oscillations. How such oscillations might lead to the observed clinical effects seen in PD subjects will be discussed. Enabling studies of tvCVS with rodents is an attractive goal in support of explorations of the mechanism of action. Male Wistar rats were used in a proof-of-concept study described herein. Rats were anesthetized (isoflurane) and ventilated for the duration of the tvCVS runs. Time-varying thermal stimuli were administered using a digital temperature controller to modulate Peltier-type heater/cooler devices. Blunt ear bars conveyed the thermal stimulus to the external ear canals of the rats. Different thermal waveform combinations were evaluated for evidence of successful induction of the CVS effect. It was found that bilateral triangular thermal waveforms could induce oscillations in CBFv both during and after the application of tvCVS. These oscillations were similar to, but different from those observed in awake human subjects. The establishment of a viable animal model for the study of tvCVS will augment ongoing clinical investigations of this new form of neuromodulation in patients with neurodegenerative disease.
Cognitive impairments in patients with subacute coronavirus disease: Initial experiences in a post-coronavirus disease clinic
Authors: Chang Jhin Goo , Ha Eun-Hye , Lee Wangjun , Lee Su Young
Published: November 2022

Background

A significant number of patients experience persistent cognitive impairment after coronavirus disease (COVID-19). This study aimed to investigate the cognitive function of patients in the subacute phase of COVID-19 and to identify the clinical factors associated with cognitive sequelae.

Materials and methods

Data from patients who visited the psychiatric department of our post-COVID clinic between March and May 2022 were analyzed. The results of neuropsychiatric function tests, including the digit span forward (attention/processing speed) and backward (working memory) tests, the trail making test part A (attention/processing speed) and part B (executive functioning), and the Stroop word color interference test (executive functioning), as well as clinical data from 40 patients in the subacute phase of COVID-19 were analyzed. We calculated the frequency of impairments in each cognitive measure, defined as a z-score of ≤−1.5 standard deviations below measure-specific age- and sex-adjusted norms.

Results

Of the participants, 72.5% (n = 29) had impairments in at least one cognitive domain. Impairment in executive function was the most frequent (64.9%), followed by impairments in processing speed/attention (52.5%) and working memory (42.5%). Age was inversely correlated with T scores in all cognitive function tests.

Conclusion

Regular examination of cognitive function is needed, especially in elderly individuals, regardless of the subjective symptom manifestations.
Biological and disease hallmarks of Alzheimer’s disease defined by Alzheimer’s disease genes
Authors: Murakami Shin , Lacayo Patricia
Published: November 2022

An increasing number of genes associated with Alzheimer’s disease (AD genes) have been reported. However, there is a lack of an overview of the genetic relationship between AD and age-related comorbidities, such as hypertension, myocardial infarction, and diabetes, among others. Previously, we used Reactome analysis in conjunction with the AD genes to identify both the biological pathways and the neurological diseases. Here we provide systematic updates on the genetic and disease hallmarks defined by AD genes. The analysis identified 50 pathways (defined as biological hallmarks). Of them, we have successfully compiled them into a total of 11 biological hallmarks, including 6 existing hallmarks and 5 newly updated hallmarks. The AD genes further identified 20 diverse diseases (defined as disease hallmarks), summarized into three major categories: (1) existing hallmarks, including neurological diseases; (2) newly identified hallmarks, including common age-related diseases such as diabetes, hypertension, other cardiovascular diseases, and cancers; (3) and other health conditions; note that cancers reportedly have an inverse relation with AD. We previously suggested that a single gene is associated with multiple neurological diseases, and we are further extending the finding that AD genes are associated with common age-related comorbidities and others. This study indicates that the heterogeneity of Alzheimer’s disease predicts complex clinical presentations in people living with AD. Taken together, the genes define AD as a part of age-related comorbidities with shared biological mechanisms and may raise awareness of a healthy lifestyle as potential prevention and treatment of the comorbidities.
Research on the multi-granularity method of role engineering
Authors: Jiao Yongmei , Zhang Menghan , Wu Yu
Published: November 2022

The role-based access control model (RBAC) is an access control approach oriented to enterprise security policy, which plays a leading role in the field of access control due to its good applicability and flexibility. However, as the scale of access subjects and access objects expands, it becomes more difficult to develop a role engineering system that meets security requirements. Particle size calculation can reduce or improve the particle size of the problem and improve efficiency on the premise of obtaining satisfactory solutions. In this study, the granularity calculation method was introduced into the role formulation process of RBAC, which can effectively reduce the complexity of the problem and improve the efficiency of the RBAC role engineer. At the same time, the concept lattice reduction method was used to reduce the role concept lattice and reduce the workload of the system security administrator.
Subclinical alterations of resting state functional brain network for adjunctive bright light therapy in nonseasonal major depressive disorder: A double blind randomized controlled trial
Authors: Huang Chun-Chao , Huang Hui-Chun , Lin Chen-Ju , Hsu Chien-Chi , Lee Chau-Shoun , Hsu Yu-Hsin , Chen Ting-Lin , Liao Wei-Hsin , Wu Yun-Hsiang , Yang Fan-Pei Gloria , Liu Shen-Ing
Published: November 2022

Introduction

The treatment effect of bright light therapy (BLT) on major depressive disorder (MDD) has been proven, but the underlying mechanism remains unclear. Neuroimaging biomarkers regarding disease alterations in MDD and treatment response are rarely focused on BLT. This study aimed to identify the modulatory mechanism of BLT in MDD using resting-state functional magnetic resonance imaging (rfMRI).

Materials and methods

This double-blind, randomized controlled clinical trial included a dim red light (dRL) control group and a BLT experimental group. All participants received light therapy for 30 min every morning for 4 weeks. The assessment of the Hamilton Depression Rating Scale-24 (HAMD-24) and brain MRI exam were performed at the baseline and the 4-week endpoint. The four networks in interest, including the default mode network (DMN), frontoparietal network (FPN), salience network (SN), and sensorimotor network (SMN), were analyzed. Between-group differences of the change in these four networks were evaluated.

Results

There were 22 and 21 participants in the BLT and dRL groups, respectively. Age, sex, years of education, baseline severity, and improvement in depressive symptoms were not significantly different between the two groups. The baseline rfMRI data did not show any significant functional connectivity differences within the DMN, FPN, SN, and SMN between the two groups. Compared with the dRL group, the BTL group showed significantly increased functional connectivity after treatment within the DMN, FPN, SN, and SMN. Graph analysis of the BLT group demonstrated an enhancement of betweenness centrality and global efficiency.

Conclusion

BLT can enhance intra-network functional connectivity in the DMN, FPN, SN, and SMN for MDD patients. Furthermore, BLT improves the information processing of the whole brain.

Clinical trial registration

The ClinicalTrials.gov identifier was NCT03941301.
No sex difference was found in the safety and efficacy of intravenous alteplase before endovascular therapy
Authors: Fang Min , Xu Chenhaoyi , Ma Lan , Sun Yue , Zhou Xiaoyu , Deng Jiangshan , Liu Xueyuan
Published: November 2022

Background and purpose

Prior studies on sex disparities were post-hoc analyses, had limited treatment modalities, and had controversial findings. Our study aimed to examine whether sex difference modifies the effect of intravenous alteplase before endovascular therapy.

Methods

We conducted a multicenter prospective cohort study of 850 eligible patients with acute ischemic stroke who underwent endovascular therapy. A propensity score was utilized as a covariate to achieve approximate randomization of alteplase pretreatment. The baseline characteristics of women and men were compared. Logistic regression with interaction terms, adjusted for potential confounders, was used to investigate the effect of sex on the prognosis of bridging therapy.

Results

In comparison to men, women were older [78.00 (70.00–84.00) vs. 67 (61.00–74.00), P < 0.001], had more atrial fibrillation (61.4 vs. 35.2%, P < 0.001), had a lower ASPECTS [10.00 (8.00–10.00) vs. 10 (9.00–10.00), P = 0.0047], and had a higher NIHSS score [17.00 (14.00–20.00) vs. 16 (13.00–19.00), P = 0.005]. Women tended to receive less bridging therapy (26.3 vs. 33%, P = 0.043) and more retrieval attempts [2.00 (1.00–2.00) vs. 1 (1.00–2.00), P = 0.026]. There was no sex difference in functional independence at 90 days after bridging therapy (OR 0.968, 95% CI 0.575–1.63), whereas men benefited more after EVT alone (OR 0.654, 95% CI 0.456–0.937). There were no sex-treatment interactions observed regardless of the location of the occlusion. There were no significant sex differences in all safety outcomes.

Conclusion

Our study could not confirm that sex modifies the treatment effect of intravenous alteplase before endovascular therapy. At the same time, we advocate for women to seek timely medical treatment.
Cerebello-brainstem dominant form of X-linked adrenoleukodystrophy with intrafamilial phenotypic variability
Authors: Choi Jae-Hwan , Kim Hyun Sung , Oh Eun Hye , Lee Jae Hyeok , Cheon Chong Kun
Published: November 2022

Objectives

This study aimed to describe the clinical and radiological characteristics of a cerebello-brainstem dominant form of X-linked adrenoleukodystrophy (X-ALD).

Methods

Three affected members from a family with cerebellar ataxia received full neurological, laboratory and radiological examinations. Genetic diagnoses were confirmed using whole-exome sequencing and protein structural modeling.

Results

All affected members presented with slurred speech, ataxia, and spasticity, but showed obvious differences in phenotypic severity and radiological findings. The levels of very long-chain fatty acids (VLCFA) were elevated in each member, while only one had adrenal dysfunction. Genetic analysis identified a hemizygous missense mutation (c.887A>G, p.Tyr296Cys) of the ATP-binding cassette subfamily D member 1 gene (ABCD1) in all affected members, which is likely to destabilize the overall structure of the ABCD1 protein.

Conclusions

We report a cerebello-dominant form of X-ALD caused by a missense variant in ABCD1. This report highlights intrafamilial phenotypic variability in X-ALD.
Brian2Loihi: An emulator for the neuromorphic chip Loihi using the spiking neural network simulator Brian
Authors: Michaelis Carlo , Lehr Andrew B. , Oed Winfried , Tetzlaff Christian
Published: November 2022

Developing intelligent neuromorphic solutions remains a challenging endeavor. It requires a solid conceptual understanding of the hardware's fundamental building blocks. Beyond this, accessible and user-friendly prototyping is crucial to speed up the design pipeline. We developed an open source Loihi emulator based on the neural network simulator Brian that can easily be incorporated into existing simulation workflows. We demonstrate errorless Loihi emulation in software for a single neuron and for a recurrently connected spiking neural network. On-chip learning is also reviewed and implemented, with reasonable discrepancy due to stochastic rounding. This work provides a coherent presentation of Loihi's computational unit and introduces a new, easy-to-use Loihi prototyping package with the aim to help streamline conceptualization and deployment of new algorithms.
Neuroaesthetic exploration on the cognitive processing behind repeating graphics
Authors: Qin Yuan , Ma Lan , Kujala Tuomo , Silvennoinen Johanna , Cong Fengyu
Published: November 2022

Repeating graphics are common research objects in modern design education. However, we do not exactly know the attentional processes underlying graphic artifacts consisting of repeating rhythms. In this experiment, the event-related potential, a neuroscientific measure, was used to study the neural correlates of repeating graphics within graded orderliness. We simulated the competitive identification process of people recognizing artifacts with graded repeating rhythms from a scattered natural environment with the oddball paradigm. In the earlier attentional processing related to the P2 component around the Fz electrode within the 150−250 ms range, a middle-grade repeating rhythm (Target 1) did not show a difference from a high-grade repeating rhythm (Target 2). However, in the later cognitive processes related to the P3b component around the Pz electrode within the 300−450 ms range, Target 1 had longer peak latency than Target 2, based on similar waveforms. Thus, we may suppose that the arrangement of the repeating graphics did not influence the earlier attentional processing but affected the later cognitive part, such as the categorization task in the oddball paradigm. Furthermore, as evidenced by the standard deviation wave across the trials, we suggest that the growing standard deviation value might represent the gradual loss of attentional focus to the task after the stimulus onset and that the zero-growth level may represent similar brain activity between trials.
Multi-modal feature selection with anchor graph for Alzheimer's disease
Authors: Li Jiaye , Xu Hang , Yu Hao , Jiang Zhihao , Zhu Lei
Published: November 2022

In Alzheimer's disease, the researchers found that if the patients were treated at the early stage of the disease, it could effectively delay the development of the disease. At present, multi-modal feature selection is widely used in the early diagnosis of Alzheimer's disease. However, existing multi-modal feature selection algorithms focus on learning the internal information of multiple modalities. They ignore the relationship between modalities, the importance of each modality and the local structure in the multi-modal data. In this paper, we propose a multi-modal feature selection algorithm with anchor graph for Alzheimer's disease. Specifically, we first use the least square loss and l2,1−norm to obtain the weight of the feature under each modality. Then we embed a modal weight factor into the objective function to obtain the importance of each modality. Finally, we use anchor graph to quickly learn the local structure information in multi-modal data. In addition, we also verify the validity of the proposed algorithm on the published ADNI dataset.
Risk factors and a Bayesian network model to predict ischemic stroke in patients with dilated cardiomyopathy
Authors: Fan Ze-Xin , Wang Chao-Bin , Fang Li-Bo , Ma Lin , Niu Tian-Tong , Wang Ze-Yi , Lu Jian-Feng , Yuan Bo-Yi , Liu Guang-Zhi
Published: November 2022

Objective

This study aimed to identify risk factors and create a predictive model for ischemic stroke (IS) in patients with dilated cardiomyopathy (DCM) using the Bayesian network (BN) approach.

Materials and methods

We collected clinical data of 634 patients with DCM treated at three referral management centers in Beijing between 2016 and 2021, including 127 with and 507 without IS. The patients were randomly divided into training (441 cases) and test (193 cases) sets at a ratio of 7:3. A BN model was established using the Tabu search algorithm with the training set data and verified with the test set data. The BN and logistic regression models were compared using the area under the receiver operating characteristic curve (AUC).

Results

Multivariate logistic regression analysis showed that hypertension, hyperlipidemia, atrial fibrillation/flutter, estimated glomerular filtration rate (eGFR), and intracardiac thrombosis were associated with IS. The BN model found that hyperlipidemia, atrial fibrillation (AF) or atrial flutter, eGFR, and intracardiac thrombosis were closely associated with IS. Compared to the logistic regression model, the BN model for IS performed better or equally well in the training and test sets, with respective accuracies of 83.7 and 85.5%, AUC of 0.763 [95% confidence interval (CI), 0.708–0.818] and 0.822 (95% CI, 0.748–0.896), sensitivities of 20.2 and 44.2%, and specificities of 98.3 and 97.3%.

Conclusion

Hypertension, hyperlipidemia, AF or atrial flutter, low eGFR, and intracardiac thrombosis were good predictors of IS in patients with DCM. The BN model was superior to the traditional logistic regression model in predicting IS in patients with DCM and is, therefore, more suitable for early IS detection and diagnosis, and could help prevent the occurrence and recurrence of IS in this patient cohort.
Hepatoprotective effect of hydroalcoholic extract from root of Sechium edule (Jacq.) Sw. over hepatic injury induced by chronic application of angiotensin II
Authors: Alvarado-Ojeda Zimri Aziel , Coset Mejia Alejandro , Arrellin Rosas Gerardo , Jiménez-Ferrer Jesús Enrique , Zamilpa Alejandro , Trejo-Moreno Celeste , Castro Martínez Gabriela , Méndez Martínez Marisol , Cervantes Torres Jacquelynne , Báez Reyes Juan Carlos , Fragoso Gladis , Rosas Salgado Gabriela
Published: November 2022

Liver damage is characterized by lipid accumulation in the liver, a prooxidant/proinflammatory state, necrosis, and fibrosis. Given the multifactorial conditions and complexity of the disease and the contribution of oxidative stress and inflammation in its development, phytomedicine is a good option for its control. Liver damage was induced in male C57BL/6J mice by chronic administration of angiotensin II (ANGII) (0.01 μg/kg/day, administered daily intraperitoneally). A hydroalcoholic extract of Sechium edule root (rSe-HA), standardized for its cinnamic acid content, was used to control the incidence of liver damage in mice (11 mg/kg/day of rSe-HA, administered orally). After 11 weeks, the mice were sacrificed and adipose tissue, serum, and liver were obtained. Hepatic cytokine and triglyceride (TG) concentrations were determined, and any histopathological changes were recorded. Meanwhile, ANGII treatment increased serum TG concentration (62.8%), alanine aminotransaminase (GPT/ALT) levels (206%), as well as TG accumulation (82.7%), hepatomegaly (32.1%), inflammation (measured by TNFα (70%), IL-1β (103%), IL-6 (92%), and TGFβ (203%) levels, along with inflammatory cell recruitment), and fibrosis with respect to untreated controls. rSe-HA prevented these increases, maintaining all parameters evaluated at values similar to those of the control group. Overall, our results support the hepatoprotective effects of rSe-HA against NAFLD and NASH, which are often the gateway to more severe pathologies.
Time-restricted feeding and cognitive function in sedentary and physically active elderly individuals: Ramadan diurnal intermittent fasting as a model
Authors: Boujelbane Mohamed Ali , Trabelsi Khaled , Jahrami Haitham A. , Masmoudi Liwa , Ammar Achraf , Khacharem Aïmen , Boukhris Omar , Puce Luca , Garbarino Sergio , Scoditti Egeria , Khanfir Saber , Msaad Aymen , Msaad Amine , Akrout Soulaimane , Hakim Ahmed , Bragazzi Nicola Luigi , Bryk Kelsey , Glenn Jordan M. , Chtourou Hamdi
Published: November 2022

Objectives

This study aimed to investigate the effects of Ramadan diurnal intermittent fasting (RDIF) on cognitive performance, sleep quality, daytime sleepiness, and insomnia in physically active and sedentary elderly individuals.

Methods

A total of 58 participants (62.93 ± 3.99 years) were assigned to one of the following two groups: a sedentary group (control group) who observed Ramadan (n = 32) and a physically active group (n = 26) who continued to train while observing Ramadan. Participants were assessed 2 weeks before Ramadan and during the fourth week of Ramadan. On each occasion, participants completed a digital assessment of their cognitive performance and responded to the Pittsburgh sleep quality index (PSQI), the insomnia severity index (ISI) and the Epworth sleepiness scale (ESS) questionnaires to assess sleep parameters.

Results

Compared to before Ramadan, performance in executive function (p = 0.035), attention (p = 0.005), inhibition (p = 0.02), associative memory (p = 0.041), and recognition memory (p = 0.025) increased significantly during Ramadan in the physically active group. For the sedentary group, associative learning performance decreased (p = 0.041), whilst performances in the remaining domains remained unchanged during Ramadan. Global PSQI, ISI, and ESS scores indicated both groups suffered from poor sleep quality and excessive daytime sleepiness, with significantly higher negative effects of RDIF observed in the sedentary group.

Conclusion

Older adults who continue to train at least three times per week during Ramadan may improve their cognitive performance, despite the impairment of sleep quality. Future studies in older adults during Ramadan including objective measures of sleep (e.g., polysomnography, actigraphy) and brain function (e.g., functional magnetic resonance imaging) are warranted.
Drying methods affect physicochemical and functional characteristics of Clanis Bilineata Tingtauica Mell protein
Authors: Wang Shuya , Niu Liqiong , Zhou Bin , Peng Yao , Yang Xinquan , Shen Yingbin , Li Shugang
Published: November 2022

Clanis Bilineata Tingtauica Mell Protein (CBTMP) was a kind of natural full-price protein which has a bright application prospect in the food industry. Since the functional properties of protein can be significantly affected by drying method, this study aims to explore the effect of different drying methods, namely freeze drying (FD), vacuum drying (VD),and hot-air drying (HD) on the structure and functional properties of CBTMP. The results showed that the degree of oxidation of CBTMP was found to be in the following order: HD > VD > FD. Functional characteristics revealed that the CBTMP prepared by VD had relatively high foaming ability (150.24 ± 5.34°C) among three drying methods. However, the stability of emulsion and rheological properties prepared by FD was superior to other samples. Differential scanning calorimeter (DSC) showed CBTMP made by HD had the relatively good thermal stability (Tp = 91.49 ± 0.19 °C), followed by VD and FD. Digestive properties reflected that heating treatment could significantly increase its degree of hydrolysis in vitro. To sum up, the research could provide experimental guidance and theoretical support for the preparation method and utilization of CBTMP.