bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and characterization of a CRISPR/Cas9-mediated RAG1 knockout chicken model lacking mature B and T cells
Authors: Lee Kyung Youn , Choi Hyeon Jeong , Park Kyung Je , Woo Seung Je , Kim Young Min , Han Jae Yong
Published: August 2022

Although birds have been used historically as a model animal for immunological research, resulting in remarkable achievements, immune cell development in birds themselves has yet to be fully elucidated. In this study, we firstly generated an immunodeficient chicken model using a CRISPR/Cas9-mediated recombination activating gene 1 (RAG1) knockout, to investigate avian-specific immune cell development. Unlike previously reported immunoglobulin (Ig) heavy chain knockout chickens, the proportion and development of B cells in bothRAG1+/-andRAG1-/-embryos were significantly impaired during B cell proliferation (embryonic day 16 to 18). Our findings indicate that, this is likely due to disordered B cell receptor (BCR)-mediated signaling and interaction of CXC motif chemokine receptor (CXCR4) with CXCL12, resulting from disrupted Ig V(D)J recombination at the embryonic stage. Histological analysis after hatching showed that, unlike wild-type (WT) andRAG1+/-chickens, lymphatic organs in 3-week oldRAG1-/-chickens were severely damaged. Furthermore, relative to WT chickens,RAG1+/-andRAG1-/-birds had reduced serum Igs, fewer mature CD4+and CD8+T lymphocytes. Furthermore, BCR-mediated B cell activation inRAG1+/-chickens was insufficient, leading to decreased expression of the activation-induced deaminase (AID) gene, which is important for Ig gene conversion. Overall, this immunodeficient chicken model underlines the pivotal role ofRAG1in immature B cell development, Ig gene conversion during embryonic stages, and demonstrates the dose-dependent regulatory role ofRAG1during immune cell development. This model will provide ongoing insights for understanding chicken immune system development and applied in the fields of immunology and biomedical science.
Sex-dependent Lupus Blautia (Ruminococcus) gnavus strain induction of zonulin-mediated intestinal permeability and autoimmunity
Authors: Silverman Gregg J. , Deng Jing , Azzouz Doua F.
Published: August 2022

Imbalances in the gut microbiome are suspected contributors to the pathogenesis of Systemic Lupus Erythematosus, and our studies and others have documented that patients with active Lupus nephritis have expansions of the obligate anaerobe, Blautia (Ruminococcus) gnavus (RG). To investigate whether the RG strains in Lupus patients have in vivo pathogenic properties in a gnotobiotic system, we colonized C57BL/6 mice with individual RG strains from healthy adults or those from Lupus patients. These strains were similar in their capacity for murine intestinal colonization of antibiotic-preconditioned specific-pathogen-free, as well as of germ-free adults and of their neonatally colonized litters. Lupus-derived RG strains induced high levels of intestinal permeability that was significantly greater in female than male mice, whereas the RG species-type strain (ATCC29149/VPI C7-1) from a healthy donor had little or no effects. These Lupus RG strain-induced functional alterations were associated with RG translocation to mesenteric lymph nodes, and raised serum levels of zonulin, a regulator of tight junction formation between cells that form the gut barrier. Notably, the level of Lupus RG-induced intestinal permeability was significantly correlated with serum IgG anti RG cell-wall lipoglycan antibodies, and with anti-native DNA autoantibodies that are a biomarker for SLE. Strikingly, gut permeability was completely reversed by oral treatment with larazotide acetate, an octapeptide that is a specific molecular antagonist of zonulin. Taken together, these studies document a pathway by which RG strains from Lupus patients contribute to a leaky gut and features of autoimmunity implicated in the pathogenesis of flares of clinical Lupus disease.
Phenotypic and functional analysis of γδ T cells in the pathogenesis of human T-cell lymphotropic virus type 1 infection
Authors: Ruggieri Matias , Ducasa Nicolás , Juraske Claudia , Polo Virginia Gonzalez , Berini Carolina , Quiroga Maria Florencia , Christopoulos Petros , Minguet Susana , Biglione Mirna , Schamel Wolfgang W.
Published: August 2022

The human T-cell leukemia virus type 1 (HTLV-1) is the cause of serious malignant and inflammatory diseases, including adult T-cell leukemia and lymphoma and tropical spastic paraparesis. The potential protective role of γδ T cells in HTLV-1 infection remains unclear. Here, demonstrate that there is a decrease in the amount of Vγ9Vδ2 T cells in patients with HTLV-1, especially in those with HTLV-1 associated pathologies. This suggests that γδ T cells could be involved in controlling the virus. Indeed, we found that Vγ9Vδ2 T cells, expanded from non-infected individuals, can kill cells expressing the viral proteins HBZ and Tax and this phenotype is reversed in the presence of mevastatin. Cytotoxicity by Vγ9Vδ2 T cells was not associated with an increase of INF-γ production. In sharp contrast, killing by NK cells was reduced by Tax expression. Thus, our study provides initial evidence for a potential protective role of Vγ9Vδ2 T cells against HTLV-1 infection. Therapeutic exploitation of these insights is feasible with current technologies of T-cell therapies and could provide novel tools to prevent and treat HTLV-1-associated malignancies and neurologic complications.
A promising antitumor method: Targeting CSC with immune cells modified with CAR
Authors: Huang Binjie , Miao Lele , Liu Jie , Zhang Jiaxing , Li Yumin
Published: August 2022

Tumors pose a great threat to human health; as a subgroup of tumor cells, cancer stem cells (CSCs) contribute to the genesis, development, metastasis, and recurrence of tumors because of their enhanced proliferation and multidirectional differentiation. Thus, a critical step in tumor treatment is to inhibit CSCs. Researchers have proposed many methods to inhibit or reduce CSCs, including monoclonal antibodies targeting specific surface molecules of CSCs, signal pathway inhibitors, and energy metabolic enzyme inhibitors and inducing differentiation therapy. Additionally, immunotherapy with immune cells engineered with a chimeric antigen receptor (CAR) showed favorable results. However, there are few comprehensive reviews in this area. In this review, we summarize the recent CSC targets used for CSC inhibition and the different immune effector cells (T cells, natural killer (NK) cells, and macrophages) which are engineered with CAR used for CSC therapy. Finally, we list the main challenges and options in targeting CSC with CAR-based immunotherapy. The design targeting two tumor antigens (one CSC antigen and one mature common tumor antigen) should be more reasonable and practical; meanwhile, we highlight the potential of CAR-NK in tumor treatment.
An enhanced level of VCAM in transplant preservation fluid is an independent predictor of early kidney allograft dysfunction
Authors: Baboudjian Michael , Gondran-Tellier Bastien , Boissier Romain , Ancel Patricia , Marjollet Juline , Lyonnet Luc , François Pauline , Sabatier Florence , Lechevallier Eric , Dutour Anne , Paul Pascale
Published: August 2022

Background

We aimed to evaluate whether donor-related inflammatory markers found in kidney transplant preservation fluid can associate with early development of kidney allograft dysfunction.

Methods

Our prospective study enrolled 74 consecutive donated organs who underwent kidney transplantation in our center between September 2020 and June 2021. Kidneys from 27 standard criteria donors were allocated to static cold storage and kidneys from 47 extended criteria donors to hypothermic machine perfusion. ELISA assessment of inflammatory biomarkers (IL-6, IL6-R, ICAM, VCAM, TNFα, IFN-g, CXCL1 and Fractalkine) was analyzed in view of a primary endpoint defined as the occurrence of delayed graft function or slow graft function during the first week following transplantation.

Results

Soluble VCAM levels measured in transplant conservation fluid were significantly associated with recipient serum creatinine on day 7. Multivariate stepwise logistic regression analysis identified VCAM as an independent non-invasive predictor of early graft dysfunction, both at 1 week (OR: 3.57, p = .04, 95% CI: 1.06-12.03) and 3 Months (OR: 4.039, p = .034, 95% CI: 1.11-14.73) after transplant surgery.

Conclusions

This prospective pilot study suggests that pre-transplant evaluation of VCAM levels could constitute a valuable indicator of transplant health and identify the VCAM-CD49d pathway as a target to limit donor-related vascular injury of marginal transplants.
New insights into the archives of redox conditions in seep carbonates from the northern South China Sea
Authors: Liang Qianyong , Huang Huiwen , Sun Yuedong , Gong Shanggui , Wang Xudong , Xiao Xi , Dong Yifei , Feng Junxi , Feng Dong
Published: August 2022

Modern cold seeps are of fluctuant flux, which could result in variabilities of geochemical archives through intensively influencing the redox condition in pore fluids. However, the geochemical archives are not fully understood when the redox condition changes. Here, tubular carbonates from the Shenhu Sea Area were used to reconstruct the formation environment and redox conditions. The moderately negative δ13C values of the carbonates (−40.1‰ to −30.8‰, VPDB) indicate a mixed carbon source of thermogenic and biogenic methane. The low δ18O values (−2.7‰ to 1.0‰, VPDB) suggest a type of 18O-depleted pore fluid possibly influenced by gas hydrate formation. Co-variation of MoEF, WEF, CoEF, and CrEF suggests that high Fe contents in the rims of samples R1 and R2 are induced by Fe (oxyhydr)oxidation enrichment, while the positive correlation between MoEF and Mn/Al ratio indicates that high Mn contents in the rims of samples R3 and R4 are induced by Mn (oxyhydr)oxidation enrichment. The occurrence of Fe or Mn enrichment in the rims and the absence of Fe/Mn enrichment in the cores suggest Fe/Mn (oxyhydr)oxides forming in pore fluid rather than in bottom seawater. The carbonate phases of the rims enriched in Fe (oxyhydr)oxides are dominated by high magnesium calcite, while those of the rims enriched in Mn (oxyhydr)oxides are dominated by aragonite. The occurrence of Fe or Mn (oxyhydr)oxides corresponds to the previously proposed formation depth for the carbonate phase. The occurrence of dissolution textures in these rims indicates episodic oxic conditions, which would facilitate Fe2+/Mn2+ oxidation. We suppose that the Fe2+ and Mn2+ could be supplied through fluid seepage or diffusion from underlying sediments when the flux decreased. Similar archives may be applied to qualitatively reflect the changes of redox conditions in seep systems. Similar scenarios may help us understand the geochemical records in seeps of fluctuant flux.
Quantifying baseline costs and cataloging potential optimization strategies for kelp aquaculture carbon dioxide removal
Authors: Coleman Struan , Dewhurst Tobias , Fredriksson David W. , St. Gelais Adam T. , Cole Kelly L. , MacNicoll Michael , Laufer Eric , Brady Damian C.
Published: August 2022

To keep global surface warming below 1.5°C by 2100, the portfolio of cost-effective CDR technologies must expand. To evaluate the potential of macroalgae CDR, we developed a kelp aquaculture bio-techno-economic model in which large quantities of kelp would be farmed at an offshore site, transported to a deep water “sink site”, and then deposited below the sequestration horizon (1,000 m). We estimated the costs and associated emissions of nursery production, permitting, farm construction, ocean cultivation, biomass transport, and Monitoring, Reporting, and Verification (MRV) for a 1,000 acre (405 ha) “baseline” project located in the Gulf of Maine, USA. The baseline kelp CDR model applies current systems of kelp cultivation to deep water (100 m) exposed sites using best available modeling methods. We calculated the levelized unit costs of CO2eq sequestration (LCOC; $ tCO2eq-1). Under baseline assumptions, LCOC was $17,048 tCO2eq-1. Despite annually sequestering 628 tCO2eq within kelp biomass at the sink site, the project was only able to net 244 C credits (tCO2eq) each year, a true sequestration “additionality” rate (AR) of 39% (i.e., the ratio of net C credits produced to gross C sequestered within kelp biomass). As a result of optimizing 18 key parameters for which we identified a range within the literature, LCOC fell to $1,257 tCO2eq-1 and AR increased to 91%, demonstrating that substantial cost reductions could be achieved through process improvement and decarbonization of production supply chains. Kelp CDR may be limited by high production costs and energy intensive operations, as well as MRV uncertainty. To resolve these challenges, R&D must (1) de-risk farm designs that maximize lease space, (2) automate the seeding and harvest processes, (3) leverage selective breeding to increase yields, (4) assess the cost-benefit of gametophyte nursery culture as both a platform for selective breeding and driver of operating cost reductions, (5) decarbonize equipment supply chains, energy usage, and ocean cultivation by sourcing electricity from renewables and employing low GHG impact materials with long lifespans, and (6) develop low-cost and accurate MRV techniques for ocean-based CDR.
Mesoscale eddy effects on sea-air CO2 fluxes in the northern Philippine Sea
Authors: Kim Dongseon , Lee Seon-Eun , Cho Sosul , Kang Dong-Jin , Park Geun-Ha , Kang Sok Kuh
Published: August 2022

To determine the effects of mesoscale eddies on sea-air CO2 flux, we investigated the surface fugacity of CO2 (surface fCO2) distribution in the northern Philippine Sea, where mesoscale eddies are common. Surface fCO2 showed large spatial variations, such that values were high in the non-eddy and cyclonic eddy regions, while they were low within the anticyclonic eddy. The maximum fCO2 was observed in the non-eddy region; higher fCO2 values were observed in the area surrounding the cyclonic eddy than at the center of the cyclonic eddy. Within the cyclonic eddy, the contribution of dissolved inorganic carbon (DIC) enrichment because of upwelling was considerably offset by cooling. In the non-eddy region, the contribution of DIC enrichment from upwelling was rarely offset by cooling; thus, the maximum fCO2 was observed in the non-eddy region. Surface fCO2 showed a robust correlation with sea surface temperature (SST) within the cyclonic and anticyclonic eddies, but it did not display any correlation in the non-eddy region. Temperature was a major factor that controlled surface fCO2 in the anticyclonic eddy, but this effect was absent in the cyclonic eddy. Temperature-normalized fCO2 exhibited a clear negative relationship with SST in the cyclonic eddy and the non-eddy region, indicating that surface fCO2 was considerably affected by the upwelling of high-fCO2 deep water in both regions. Sea-air CO2 fluxes ranged from 0.011 to 9.92 mmol m-2 day-1 and all values were positive, indicating that the entire study area acted as a CO2 source during the research period. The estimated mean sea-air CO2 fluxes in the cyclonic eddy, anticyclonic eddy, and non-eddy region were 1.10 ± 0.75, 0.64 ± 0.66, and 1.42 ± 1.12 mmol m-2 day-1, respectively. The sea-air CO2 fluxes considerably varied according to eddy type; they were almost twofold higher in the cyclonic eddy than in the anticyclonic eddy. In the cyclonic eddy and non-eddy regions, upwelling caused surface fCO2 to increase, thereby increasing sea-air CO2 flux.
Comparative analysis reveals distinctive genomic features of Taiwan hot-spring cyanobacterium Thermosynechococcus sp. TA-1
Authors: Cheng Yen-I , Lin Yu-Chen , Leu Jyh-Yih , Kuo Chih-Horng , Chu Hsiu-An
Published: August 2022

Thermosynechococcus is a genus of thermophilic unicellular cyanobacteria that dominates microbial mats in Asian non-acidic hot springs. These cyanobacteria are the major primary producers in their ecological niches and are promising sources of thermostable enzymes for biotechnology applications. To improve our understanding of these organisms, we conducted whole-genome sequencing of a novel strain for comparative analysis with other representatives in the same genus. This newly characterized strain, Thermosynechococcus sp. TA-1, was isolated from the Taian hot springs in Taiwan. Analyses based on average nucleotide identity (ANI) and genome-scale phylogeny suggested that TA-1 and another Taiwanese strain CL-1 belong to a novel species-level taxon. Two metagenome-assembled genomes (MAGs) originated from India represent the sister group, and Thermosynechococcus elongatus PKUAC-SCTE542 from China is the next closest lineage. All cultivated strains and MAGs from Japan form a separate monophyletic clade and could be classified into two species-level taxa. Intriguingly, although TA-1 and CL-1 share 97.0% ANI, the genome alignment identified at least 16 synteny breakpoints that are mostly associated with transposase genes, which illustrates the dynamic nature of their chromosomal evolution. Gene content comparisons identified multiple features distinct at species- or strain-level among these Thermosynechococcus representatives. Examples include genes involved in bicarbonate transportation, nitric oxide protection, urea utilization, kanamycin resistance, restriction-modification system, and chemotaxis. Moreover, we observed the insertion of type II inteins in multiple genes of the two Taiwanese strains and inferred putative horizontal transfer of an asparagine synthase gene (asnB) associated with exopolysaccharides gene cluster. Taken together, while previous work suggested that strains in this genus share a highly conserved genomic core and no clear genetic differentiation could be linked to environmental factors, we found that the overall pattern of gene content divergence is largely congruent with core genome phylogeny. However, it is difficult to distinguish between the roles of phylogenetic relatedness and geographic proximity in shaping the genetic differentiation. In conclusion, knowledge of the genomic differentiation among these strains provides valuable resources for future functional characterization.
Autoinducer-2 promotes Pseudomonas aeruginosa PAO1 acute lung infection via the IL-17A pathway
Authors: Li Hongdong , Li Xingyuan , Ai Qing , Tan Liping
Published: August 2022

Pseudomonas aeruginosa is an opportunistic pathogenic bacterium that causes various acute and chronic lung infections in immunocompromised patients. We previously found that a quorum sensing (QS) signal, namely, autoinducer-2 (AI-2), facilitates the pathogenicity of the wild-type (WT) P. aeruginosa PAO1 strain in vitro and in vivo. However, the immunological mechanism that leads to pulmonary injury remains to be elucidated. In this study, we aimed to investigate the effects of AI-2 on interleukin-17A (IL-17A) production during acute P. aeruginosa PAO1 lung infection using a mouse model, with an emphasis on the underlying immunological mechanism. Compared to infection with P. aeruginosa PAO1 alone, infection with P. aeruginosa PAO1 combined with AI-2 treatment resulted in significantly increased levels of IL-17A, numbers of Th17 cells and levels of STAT3 in the lung tissues of WT mice (P < 0.05), as well as more serious lung damage. In contrast, the concentrations of the proinflammatory cytokines IL-1α, IL-1β, and IL-6 and the chemokine keratinocyte-derived chemokine (KC) were significantly reduced during P. aeruginosa lung infection in IL-17A−/− mice compared with WT mice (P < 0.05), and no effects were observed after AI-2 treatment (P > 0.05). Furthermore, the level of IL-17A in the lungs of WT mice was significantly reduced following infection with a P. aeruginosa strain harboring mutations in the QS genes lasR and rhlR compared with the level of IL-17A following infection with P. aeruginosa PAO1. Our data suggest that AI-2 promotes P. aeruginosa PAO1 acute lung infection via the IL-17A pathway by interfering with the QS systems of P. aeruginosa. IL-17A may be a therapeutic target for the treatment of acute P. aeruginosa lung infections in the clinic.
Root rot a silent alfalfa killer in China: Distribution, fungal, and oomycete pathogens, impact of climatic factors and its management
Authors: Abbas Aqleem , Mubeen Mustansar , Sohail Muhammad Aamir , Solanki Manoj Kumar , Hussain Babar , Nosheen Shaista , Kashyap Brijendra Kumar , Zhou Lei , Fang Xiangling
Published: August 2022

Alfalfa plays a significant role in the pasture ecosystems of China’s north, northeast, and northwest regions. It is an excellent forage for livestock, improves soil structure, prevents soil erosion, and has ecological benefits. Presently root rot is a significant threat to the alfalfa productivity because of the survival of the pathogens as soil-borne and because of lack of microbial competition in the impoverished nutrient-deficient soils and resistant cultivars. Furthermore, these regions’ extreme ecological and environmental conditions predispose alfalfa to root rot. Moisture and temperature, in particular, have a considerable impact on the severity of root rot. Pathogens such as Fusarium spp. and Rhizoctonia solani are predominant, frequently isolated, and of major concern. These pathogens work together as disease complexes, so finding a host genotype resistant to disease complexes is challenging. Approaches to root rot control in these regions include mostly fungicides treatments and cultural practices and very few reports on the usage of biological control agents. As seed treatment, fungicides such as carbendazim are frequently used to combat root rot; however, resistance to fungicides has arisen. However, breeding and transgenic approaches could be more efficient and sustainable long-term control strategies, especially if resistance to disease complexes may be identified. Yet, research in China is mainly limited to field investigation of root rot and disease resistance evaluation. In this review, we describe climatic conditions of pastoral regions and the role of alfalfa therein and challenges of root rot, the distribution of root rot in the world and China, and the impact of root rot pathogens on alfalfa in particular R. solani and Fusarium spp., effects of environmental factors on root rot and summarize to date disease management approach.
Plant growth-promoting bacteria in metal-contaminated soil: Current perspectives on remediation mechanisms
Authors: Wang Yue , Narayanan Mathiyazhagan , Shi Xiaojun , Chen Xinping , Li Zhenlun , Natarajan Devarajan , Ma Ying
Published: August 2022

Heavy metal contamination in soils endangers humans and the biosphere by reducing agricultural yield and negatively impacting ecosystem health. In recent decades, this issue has been addressed and partially remedied through the use of “green technology,” which employs metal-tolerant plants to clean up polluted soils. Furthermore, the global climate change enhances the negative effects of climatic stressors (particularly drought, salinity, and extreme temperatures), thus reducing the growth and metal accumulation capacity of remediating plants. Plant growth-promoting bacteria (PGPB) have been widely introduced into plants to improve agricultural productivity or the efficiency of phytoremediation of metal-contaminated soils via various mechanisms, including nitrogen fixation, phosphate solubilization, phytohormone production, and biological control. The use of metal-tolerant plants, as well as PGPB inoculants, should hasten the process of moving this technology from the laboratory to the field. Hence, it is critical to understand how PGPB ameliorate environmental stress and metal toxicity while also inducing plant tolerance, as well as the mechanisms involved in such actions. This review attempts to compile the scientific evidence on this topic, with a special emphasis on the mechanism of PGPB involved in the metal bioremediation process [plant growth promotion and metal detoxification/(im)mobilization/bioaccumulation/transformation/translocation] and deciphering combined stress (metal and climatic stresses) tolerance.
Synergistic effect of co-culture rhizosphere Streptomyces: A promising strategy to enhance antimicrobial activity and plant growth-promoting function
Authors: Li Jing , Zhang Lin , Yao Gan , Zhu Lixiang , Lin Jingling , Wang Chengqiang , Du Binghai , Ding Yanqin , Mei Xiangui
Published: August 2022

Rhizosphere Streptomyces is one of the important types of rhizosphere microorganisms that plays an important role in promoting plant growth and controlling plant diseases to maintain agricultural ecosystem balance and green ecological agriculture development as beneficial bacteria. Microbial co-culture simulates the complex biocommunity in nature, which has more advantages than the monoculture with a synergistic effect. As the key signal mediums of microorganisms, plants, and their interactions, microbial metabolites are of great significance in revealing their functional mechanism. In this study, two potential plant growth-promoting rhizobacteria, Streptomyces albireticuli MDJK11, and Streptomyces alboflavus MDJK44, were selected to explore the effects of co-culture and monoculture on plant growth promotion and disease prevention, and the metabolic material basis was analyzed by metabonomics. Results showed that Streptomyces MDJK11, MDJK44 monoculture, and co-culture condition all showed good growth promoting and antimicrobial effects. Moreover, as compared to the monoculture, the co-culture showed the advantage of a synergistic enhancement effect. LC-MS-based metabonomics analysis showed the metabolic material bases of Streptomyces for plant growth promotion and disease prevention were mainly plant hormone and antibiotics and the co-culture condition could significantly stimulate the production of plant hormone promoters and macrolide, cyclic peptide, and aminoglycoside antibiotics. The study proved that the co-cultures of S. albireticuli MDJK11 and S. alboflavus MDJK44 have great potential in crop growth promotion and disease prevention.
Increased expressions of CD123, CD63, CD203c, and Fc epsilon receptor I on blood leukocytes of allergic asthma
Authors: Xie Hua , Chen Liping , Zhang Huiyun , Wang Junling , Zang Yanyan , Zhan Mengmeng , Gu Fangqiu , Wang Shunlan , He Shaoheng
Published: August 2022

Background: Altered basophil identification markers have been discovered to associate with allergic asthma (AA) in recent years. However, little is known about the expression of basophil markers in blood granulocytes.

Aim: To parallel test blood basophils in peripheral blood mononuclear cell (PBMC) and granulocyte populations of patients with AA and AA combined with allergic rhinitis (ARA)

Methods: The expressions of surface molecules were determined via flow cytometry. CD123 expressing cells in blood were isolated using a cell sorting technique, and mouse AA models were employed for in vivo study.

Results: The numbers of CD123+HLA-DR− cells in the granulocytes of AA and ARA patients markedly increased. However, only 49.7% of CD123+HLA-DR− cells in granulocytes and 99.0% of CD123+HLA-DR− cells in PBMCs were basophils. Almost all CD123+HLA-DR− cells expressed CD63 regardless in granulocytes or PBMC. The numbers of CD63, Fc epsilon receptor I (FcεRI), and CD203c expressing cells markedly enhanced in CD123+HLA-DR− granulocytes of AA and ARA patients. Mean fluorescence intensity (MFI) of CD63 and CD203c expressions on CD123+HLA-DR− PBMC and granulocytes of AA and ARA patients dramatically elevated. House dust mite extract (HDME) and Artemisia sieversiana wild allergen extract (ASWE) enhanced the numbers of CD63+CD123+HLA-DR− granulocytes and PBMC and the MFI of CD203c expression on CD123+HLA-DR− granulocyte of AA and ARA patients. Histamine, tryptase, and PGD2 enhanced proportions of CD123+ KU812 cells. ASWE- and HDME-induced AA mice showed upregulated CD63 expression on basophils. In conclusion, upregulated expressions of CD123, CD203c, CD63, and FcεRIα in PBMC and granulocytes of patients with AA and ARA suggest that CD123+HLA-DR− cells may contribute to the development of AA and ARA.
The effect of age on electroencephalogram measures of anesthesia hypnosis: A comparison of BIS, Alpha Power, Lempel-Ziv complexity and permutation entropy during propofol induction
Authors: Biggs Daniela , Boncompte Gonzalo , Pedemonte Juan C. , Fuentes Carlos , Cortinez Luis I.
Published: August 2022

Background

Improving anesthesia administration for elderly population is of particular importance because they undergo considerably more surgical procedures and are at the most risk of suffering from anesthesia-related complications. Intraoperative brain monitors electroencephalogram (EEG) have proved useful in the general population, however, in elderly subjects this is contentious. Probably because these monitors do not account for the natural differences in EEG signals between young and older patients. In this study we attempted to systematically characterize the age-dependence of different EEG measures of anesthesia hypnosis.

Methods

We recorded EEG from 30 patients with a wide age range (19–99 years old) and analyzed four different proposed indexes of depth of hypnosis before, during and after loss of behavioral response due to slow propofol infusion during anesthetic induction. We analyzed Bispectral Index (BIS), Alpha Power and two entropy-related EEG measures, Lempel-Ziv complexity (LZc), and permutation entropy (PE) using mixed-effect analysis of variances (ANOVAs). We evaluated their possible age biases and their trajectories during propofol induction.

Results

All measures were dependent on anesthesia stages. BIS, LZc, and PE presented lower values at increasing anesthetic dosage. Inversely, Alpha Power increased with increasing propofol at low doses, however this relation was reversed at greater effect-site propofol concentrations. Significant group differences between elderly patients (>65 years) and young patients were observed for BIS, Alpha Power, and LZc, but not for PE.

Conclusion

BIS, Alpha Power, and LZc show important age-related biases during slow propofol induction. These should be considered when interpreting and designing EEG monitors for clinical settings. Interestingly, PE did not present significant age differences, which makes it a promising candidate as an age-independent measure of hypnotic depth to be used in future monitor development.
Deep learning of MRI contrast enhancement for mapping cerebral blood volume from single-modal non-contrast scans of aging and Alzheimer's disease brains
Authors: Liu Chen , Zhu Nanyan , Sun Haoran , Zhang Junhao , Feng Xinyang , Gjerswold-Selleck Sabrina , Sikka Dipika , Zhu Xuemin , Liu Xueqing , Nuriel Tal , Wei Hong-Jian , Wu Cheng-Chia , Vaughan J. Thomas , Laine Andrew F. , Provenzano Frank A. , Small Scott A. , Guo Jia
Published: August 2022

While MRI contrast agents such as those based on Gadolinium are needed for high-resolution mapping of brain metabolism, these contrast agents require intravenous administration, and there are rising concerns over their safety and invasiveness. Furthermore, non-contrast MRI scans are more commonly performed than those with contrast agents and are readily available for analysis in public databases such as the Alzheimer's Disease Neuroimaging Initiative (ADNI). In this article, we hypothesize that a deep learning model, trained using quantitative steady-state contrast-enhanced structural MRI datasets, in mice and humans, can generate contrast-equivalent information from a single non-contrast MRI scan. The model was first trained, optimized, and validated in mice, and was then transferred and adapted to humans. We observe that the model can substitute for Gadolinium-based contrast agents in approximating cerebral blood volume, a quantitative representation of brain activity, at sub-millimeter granularity. Furthermore, we validate the use of our deep-learned prediction maps to identify functional abnormalities in the aging brain using locally obtained MRI scans, and in the brain of patients with Alzheimer's disease using publicly available MRI scans from ADNI. Since it is derived from a commonly-acquired MRI protocol, this framework has the potential for broad clinical utility and can also be applied retrospectively to research scans across a host of neurological/functional diseases.
Abnormal cerebellar network and effective connectivity in sudden and long-term sensorineural hearing loss
Authors: Hua Jin-Chao , Xu Xiao-Min , Xu Zhen-Gui , Xue Yuan , Xu Jin-Jing , Hu Jing-Hua , Wu Yuanqing , Chen Yu-Chen
Published: August 2022

Sudden sensorineural hearing loss (SSNHL) is a common otology emergency and some SSNHL will develop into a long-term hearing loss (LSNHL). However, whether SSNHL and LSNHL have similar psychiatric patterns remains unknown, as well as the neural substrates. Increasing evidence has proved that the cerebellar network plays a vital role in hearing, cognition processing, and emotion control. Thus, we recruited 20 right SSNHL (RSSNHL), 20 right LSNHL (RLSNHL), and 24 well-matched healthy controls to explore the cerebellar patterns among the three groups. Every participant underwent pure tone audiometry tests, neuropsychological evaluations, and MRI scanning. Independent component analysis (ICA) was carried out on the MRI data and the cerebellar network was extracted. Granger causality analysis (GCA) was conducted using the significant cerebellar region as a seed. Pearson’s correlation analysis was computed between imaging characteristics and clinical features. ICA found the effect of group on right cerebellum lobule V for the cerebellar network. Then, we found decreased outflow from right cerebellum lobule V to right middle orbitofrontal cortex, inferior frontal gyrus, anterior cingulate cortex, superior temporal gyrus, and dorsal lateral prefrontal cortex in RSSNHL group in GCA analysis. No significance was found in RLSNHL subjects. Additionally, the RSSNHL group showed increased effective connectivity from the right middle frontal gyrus (MFG) and the RLSNHL group showed increased effective connectivity from the right insula and temporal pole to the right cerebellum lobule V. Moreover, connections between right cerebellum lobule V and mean time series of the cerebellar network was negatively correlated with anxiety score in RSSNHL and negatively correlated with depression scores in RLSNHL. Effective connectivity from right MFG to right cerebellum lobule V could predict anxiety status in RSSNHL subjects. Our results may prove potential imaging biomarkers and treatment targets for hearing loss in future work.
Using machine learning algorithms for predicting cognitive impairment and identifying modifiable factors among Chinese elderly people
Authors: Wang Shuojia , Wang Weiren , Li Xiaowen , Liu Yafei , Wei Jingming , Zheng Jianguang , Wang Yan , Ye Birong , Zhao Ruihui , Huang Yu , Peng Sixiang , Zheng Yefeng , Zeng Yanbing
Published: August 2022

Objectives: This study firstly aimed to explore predicting cognitive impairment at an early stage using a large population-based longitudinal survey of elderly Chinese people. The second aim was to identify reversible factors which may help slow the rate of decline in cognitive function over 3 years in the community.

Methods: We included 12,280 elderly people from four waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), followed from 2002 to 2014. The Chinese version of the Mini-Mental State Examination (MMSE) was used to examine cognitive function. Six machine learning algorithms (including a neural network model) and an ensemble method were trained on data split 2/3 for training and 1/3 testing. Parameters were explored in training data using 3-fold cross-validation and models were evaluated in test data. The model performance was measured by area-under-curve (AUC), sensitivity, and specificity. In addition, due to its better interpretability, logistic regression (LR) was used to assess the association of life behavior and its change with cognitive impairment after 3 years.

Results: Support vector machine and multi-layer perceptron were found to be the best performing algorithms with AUC of 0.8267 and 0.8256, respectively. Fusing the results of all six single models further improves the AUC to 0.8269. Playing more Mahjong or cards (OR = 0.49,95% CI: 0.38–0.64), doing more garden works (OR = 0.54,95% CI: 0.43–0.68), watching TV or listening to the radio more (OR = 0.67,95% CI: 0.59–0.77) were associated with decreased risk of cognitive impairment after 3 years.

Conclusions: Machine learning algorithms especially the SVM, and the ensemble model can be leveraged to identify the elderly at risk of cognitive impairment. Doing more leisure activities, doing more gardening work, and engaging in more activities combined were associated with decreased risk of cognitive impairment.
Vitamin D level is associated with rupture of intracranial aneurysm in patients with subarachnoid hemorrhage
Authors: Wei Sen , Yuan Xin , Li Dongdong , Fan Feng , Guo Xinbin , Xu Yuming , Guan Sheng
Published: August 2022

Background

Increasing evidence supports the relationship between vitamin D levels and stroke. However, there are few studies on the association between vitamin D levels and subarachnoid hemorrhage (SAH), especially in patients with aneurysmal SAH. The present study investigated the association between vitamin D level and rupture of intracranial aneurysm in a cohort of patients with SAH.

Methods

The data of patients diagnosed with SAH at our hospital between September 2019 and December 2020 were retrospectively reviewed. Patients' information was collected, and serum vitamin D levels were measured. Computed tomography was performed to confirm SAH diagnosis, and digital subtraction angiography was performed to determine whether SAH was caused by rupture of an intracranial aneurysm. Multivariate logistic regression analyses were performed to investigate the association between vitamin D level and aneurysmal SAH.

Results

Overall, 193 patients with SAH were evaluated; 160 with aneurysmal SAH (age 55.86 ± 12.30 years, 63.15% female) and 33 with non-aneurysmal SAH (age 56.21 ± 9.92 years, 45.45% female). Univariate analysis showed that the vitamin D level in aneurysmal SAH was lower than that in non-aneurysmal SAH (16.95 ± 8.69 vs. 22.74 ± 9.12 ng/ml, p = 0.001). In addition, there were more patients with hypertension in aneurysmal SAH group than in non-aneurysmal SAH group (53.75 vs. 24.24%, p = 0.002). Notably, there was still a strong correlation between vitamin D level and aneurysmal SAH after adjusting for confounders in the multivariate model [OR (odds ratio), 0.935; 95% CI (confidence interval), 0.890–0.983; p = 0.008].

Conclusion

Vitamin D level is associated with rupture of intracranial aneurysm in patients with SAH. Patients with aneurysmal SAH have lower vitamin D levels than those with non-aneurysmal SAH.
Bioinformatics analysis to identify potential biomarkers and therapeutic targets for ST-segment–elevation myocardial infarction-related ischemic stroke
Authors: Feng Shuo , Li Rui , Zhou Qingqing , Qu Fengling , Hu Wei , Liu Xinfeng
Published: August 2022

Background

Acute myocardial infarction (AMI) is one of the major causes of mortality and disability worldwide, and ischemic stroke (IS) is a serious complication after AMI. In particular, patients with ST-segment–elevation myocardial infarction (STEMI) are more susceptible to IS. However, the interrelationship between the two disease mechanisms is not clear. Using bioinformatics tools, we investigated genes commonly expressed in patients with STEMI and IS to explore the relationship between these diseases, with the aim of uncovering the underlying biomarkers and therapeutic targets for STEMI-associated IS.

Methods

Differentially expressed genes (DEGs) related to STEMI and IS were identified through bioinformatics analysis of the Gene Expression Omnibus (GEO) datasets GSE60993 and GSE16561, respectively. Thereafter, we assessed protein-protein interaction networks, gene ontology term annotations, and pathway enrichment for DEGs using various prediction and network analysis methods. The predicted miRNAs targeting the co-expressed STEMI- and IS-related DEGs were also evaluated.

Results

We identified 210 and 29 DEGs in GSE60993 and GSE16561, respectively. CD8A, TLR2, TLR4, S100A12, and TREM1 were associated with STEMI, while the hubgenes, IL7R, CCR7, FCGR3B, CD79A, and ITK were implicated in IS. In addition, binding of the transcripts of the co-expressed DEGs MMP9, ARG1, CA4, CRISPLD2, S100A12, and GZMK to their corresponding predicted miRNAs, especially miR-654-5p, may be associated with STEMI-related IS.

Conclusions

STEMI and IS are related and MMP9, ARG1, CA4, CRISPLD2, S100A12, and GZMK genes may be underlying biomarkers involved in STEMI-related IS.
Case report: An EEG captured case of migralepsy/migraine aura-triggered seizures
Authors: Hareem Anam , Pahlavanzadeh Mahsa , Calvo Nicholas E. , Monjazeb Sanaz , Anyanwu Chinekwu
Published: August 2022

Introduction

Migraine and epilepsy are common chronic neurological disorders presenting with paroxysmal attacks of transient cerebral dysfunction, followed by subsequent return to baseline between episodes. The term “migralepsy” has been proposed to define migraine-triggered epileptic seizures classified by the ICHD-III as a complication of migraine with an aura.

Case

A 55-year-old man with a 30-year history of migraine without aura presented with a new onset left parietal pain accompanied by visual disturbances occurring up to 20 times per day. His visual distortions included kaleidoscopic vision, flashes of shadows, and a right superior quadrantanopia lasting 20 min. He described discrete 2-min episodes of scintillating scotomas in his right visual field. Ictal EEG demonstrated a left occipital onset focal aware seizure with his clinical symptoms. The patient was started on valproic Acid and has remained asymptomatic.

Discussion

The diagnostic criteria as set out by the ICHD-III for migralepsy and other syndromes with migrainous and ictal features remain confusing for practitioners as there is much overlap in clinical manifestations of these entities. EEG should be obtained when ictal features are noted among patients presenting with headache.
Progressive volume reduction and long-term aneurysmal collapse following flow diversion treatment of giant and symptomatic cerebral aneurysms
Authors: Sirakova Kristina , Penkov Marin , Matanov Svetozar , Minkin Krasimir , Ninov Kristian , Hadzhiyanev Asen , Karakostov Vasil , Ivanova Irena , Sirakov Stanimir
Published: August 2022

Background

The primary goal of conventional endovascular and microvascular approaches is the clinical and radiological resolution of the symptomatic aneurysm-induced mass effect. This study assessed the volume changes and mass effect reduction due to sac shrinkage after treatment with flow diverter stents (FD) for unruptured cerebral aneurysms.

Methods

We analyzed retrospectively 36 symptomatic aneurysms that were larger or equal to 25 mm in diameter in patients treated at our center from January 2016 to April 2022. Radiological and clinical outcomes were analyzed, including aneurysmal volume changes and resolution of aneurysm-related symptoms.

Results

At 6 months, 25 aneurysms decreased in size, 2 remained unchanged, and 9 aneurysms demonstrated a post-treatment dimensional increase. At 12 months, 30 aneurysms showed a progressive radiological volume reduction. Either no change or negligible shrinkage was observed in the remaining six aneurysms. At 24 months, 32 aneurysms showed aneurysmal shrinkage by a mean 47% volume loss with respect to baseline. At the last follow-up, all 13 patients who had presented with third cranial nerve palsy showed improvements. Complete reversal of the pretreatment edematous changes was confirmed in all cases. The overall post-treatment complication rate was 8.3%, as 3 patients experienced non-fatal delayed rupture of their aneurysm. There was no mortality in this study.

Conclusion

Flow diversion could effectively induce progressive aneurysmal shrinkage and resolution of the mass effect associated with giant symptomatic cerebral aneurysms.
The steady state visual evoked potential (SSVEP) tracks “sticky” thinking, but not more general mind-wandering
Authors: Yang Hang , Paller Ken A. , van Vugt Marieke
Published: August 2022

For a large proportion of our daily lives, spontaneously occurring thoughts tend to disengage our minds from goal-directed thinking. Previous studies showed that EEG features such as the P3 and alpha oscillations can predict mind-wandering to some extent, but only with accuracies of around 60%. A potential candidate for improving prediction accuracy is the Steady-State Visual Evoked Potential (SSVEP), which is used frequently in single-trial contexts such as brain-computer interfaces as a marker of the direction of attention. In this study, we modified the sustained attention to response task (SART) that is usually employed to measure spontaneous thought to incorporate the SSVEP elicited by a 12.5-Hz flicker. We then examined whether the SSVEP could track and allow for the prediction of the stickiness and task-relatedness dimensions of spontaneous thought. Our results show that the SSVEP evoked by flickering words was able to distinguish between more and less sticky thinking but not between whether a participant was on- or off-task. This suggests that the SSVEP is able to track spontaneous thinking when it is strongly disengaged from the task (as in the sticky form of off-task thinking) but not off-task thought in general. Future research should determine the exact dimensions of spontaneous thought to which the SSVEP is most sensitive.
Preconditioning prefrontal connectivity using transcranial direct current stimulation and transcranial magnetic stimulation
Authors: Alkhasli Isabel , Mottaghy Felix M. , Binkofski Ferdinand , Sakreida Katrin
Published: August 2022

Transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) have been shown to modulate functional connectivity. Their specific effects seem to be dependent on the pre-existing neuronal state. We aimed to precondition frontal networks using tDCS and subsequently stimulate the left dorsolateral prefrontal cortex (lDLPFC) using TMS. Thirty healthy participants underwent excitatory, inhibitory, or sham tDCS for 10 min, as well as an excitatory intermittent theta-burst (iTBS) protocol (600 pulses, 190 s, 20 × 2-s trains), applied over the lDLPFC at 90% of the individual resting motor threshold. Functional connectivity was measured in three task-free resting state fMRI sessions, immediately before and after tDCS, as well as after iTBS. Testing the whole design did not yield any significant results. Analysis of the connectivity between the stimulation site and all other brain voxels, contrasting only the interaction effect between the experimental groups (excitatory vs. inhibitory) and the repeated measure (post-tDCS vs. post-TMS), revealed significantly affected voxels bilaterally in the anterior cingulate and paracingulate gyri, the caudate nuclei, the insula and operculum cortices, as well as the Heschl’s gyrus. Post-hoc ROI-to-ROI analyses between the significant clusters and the striatum showed post-tDCS, temporo-parietal-to-striatal and temporo-parietal-to-fronto-cingulate differences between the anodal and cathodal tDCSgroup, as well as post-TMS, striatal-to-temporo-parietal differences between the anodal and cathodal groups and frontostriatal and interhemispheric temporo-parietal cathodal-sham group differences. Excitatory iTBS to a tDCS-inhibited lDLPFC thus yielded more robust functional connectivity to various areas as compared to excitatory iTBS to a tDCS-enhanced DLPFC. Even considering reduced statistical power due to low subject numbers, results demonstrate complex, whole-brain stimulation effects. They are possibly facilitated by cortical homeostatic control mechanisms and show the feasibility of using tDCS to modulate subsequent TMS effects. This proof-of-principle study might stimulate further research into the principle of preconditioning that might be useful in the development of protocols using DLPFC as a stimulation site for the treatment of depression.