bluuebunny/crossref_metadata_2025 huggingface dataset:
Cumulative IgE-levels specific for respiratory allergens as biomarker to predict efficacy of anti-IgE-based treatment of severe asthma
Authors: Naumova Veronika , Beltyukov Evgeny , Niespodziana Katarzyna , Errhalt Peter , Valenta Rudolf , Karaulov Alexander , Kiseleva Darina
Published: September 2022

Molecular therapies, including anti-IgE, biologicals and small molecules are increasingly used for treatment of asthma. The effectiveness of these therapies may be increased with biomarkers. Aim of this study was to assess the value of measuring cumulative IgE levels specific for respiratory allergens to increase the efficacy of anti-IgE therapy for severe bronchial asthma. One hundred and thirty seven patients with severe asthma were recruited from 2016 to 2022. Standard empirical allergy diagnosis (i.e., anamnesis, skin testing, allergen-specific IgE measurement), blood eosinophil counting, measurement of total IgE and of cumulative IgE-specific for respiratory allergens by Phadiatop™ were performed. Thirty four patients with severe allergic asthma, for whom all three diagnostic methods were performed, were then used to analyze the efficacy of anti-IgE treatment in patients stratified in two groups according to cumulative IgE levels specific for respiratory allergens determined by Phadiatop™. Group #1 patients (n = 8) had cumulative specific IgE values ≥ 0.35 and < 1.53 PAU/l while in group #2 patients (n = 26) they were ≥ 1.53 PAU/l. Treatment with Omalizumab was performed for at least 12 months. The level of asthma control (ACT questionnaire), the number of asthma exacerbations, the quality of life (AQLQ questionnaire), the need for systemic corticosteroids, and the respiratory function (FEV1) was determined by “before-after” analysis for each group, followed by a comparison of the dynamics between groups. In group 2 patients with an initial allergen-specific IgE level ≥ 1.53 kUA/L, the efficacy of Omalizumab treatment was better regarding asthma control, number of exacerbations, and quality of life than in group 1 patients. Our study provides evidence that measuring cumulative levels of IgE specific for respiratory allergens could be a useful screening method for detecting an allergic phenotype of severe asthma and may serve as biomarker to enhance the success of IgE-targeted therapy.
Liver mesenchymal stem cells are superior inhibitors of NK cell functions through differences in their secretome compared to other mesenchymal stem cells
Authors: Yigitbilek Furkan , Ozdogan Elif , Abrol Nitin , Park Walter D. , Hansen Michael J. , Dasari Surendra , Stegall Mark D. , Taner Timucin
Published: September 2022

Liver-resident mesenchymal stem cells (L-MSCs) are superior inhibitors of alloreactive T cell responses compared to their counterparts from bone marrow (BM-MSCs) or adipose tissue (A-MSCs), suggesting a role in liver’s overall tolerogenic microenvironment. Whether L-MSCs also impact NK cell functions differently than other MSCs is not known. We generated and characterized L-MSCs, A-MSCs and BM-MSCs from human tissues. The mass spectrometry analysis demonstrated that L-MSC secretome is uniquely different than that of A-MSC/BM-MSC, with enriched protein sets involved in IFNγ responses and signaling. When co-cultured with primary human NK cells, L-MSCs but not other MSCs, decreased surface expression of activating receptors NKp44 and NKG2D. L-MSCs also decreased IFNγ secretion by IL-2-stimulated NK cells more effectively than other MSCs. Cytolytic function of NK cells were reduced significantly when co-cultured with L-MSCs, whereas A-MSCs or BM-MSCs did not have a major impact. Mechanistic studies showed that the L-MSC-mediated reduction in NK cell cytotoxicity is not through changes in secretion of the cytotoxic proteins Perforin, Granzyme A or B, but through increased production of HLA-C1 found in L-MSC secretome that inhibits NK cells by stimulating their inhibitory receptor KIRDL2/3. L-MSCs are more potent inhibitors of NK cell functions than A-MSC or BM-MSC. Combined with their T cell inhibitory features, these results suggest L-MSCs contribute to the tolerogenic liver microenvironment and liver-induced systemic tolerance often observed after liver transplantation.
Emerging roles of circular RNAs in tuberculosis
Authors: Wang Qinglan , Yang Danni , Zuo Yinan , Wang Dan , Li Weimin
Published: September 2022

Tuberculosis (TB) remains a major global health issue, resulting in around 1.5 million people deaths each year. Better diagnostic and therapeutic tools are urgently needed. Circular RNAs (circRNAs) are a new class of noncoding RNAs with a covalently closed structure, and exhibit a tissue-, cell-, and developmental stage-specific expression pattern. Recently, circRNAs were thought to be regulatory molecules implicated in the onset and progression of a series of human diseases including tuberculosis. In tuberculosis, circRNAs have been shown to regulate host anti-TB immune responses, such as decreasing monocyte apoptosis, enhancing autophagy and promoting macrophage polarization. Importantly, circRNAs are physically stable and abundant in several types of body fluids. Therefore they are considered as promising minimally-invasive biomarkers. In this review, we focus on the recent advances in the immune regulatory roles of circRNAs, as well as their potential diagnostic value in TB.
Salt marsh-atmosphere CO2 exchanges in Patos Lagoon Estuary, Southern Brazil
Authors: Souza Ronald B. , Copertino Margareth S. , Fisch Gilberto , Santini Marcelo F. , Pinaya Walter H. D. , Furlan Fabiane M. , Alves Rita de Cássia M. , Möller Osmar O. , Pezzi Luciano P.
Published: September 2022

Blue carbon ecosystems are recognized as carbon sinks and therefore for their potential for climate mitigation. While carbon stocks and burial rates have been quantified and estimated regionally and globally, there are still many knowledge gaps on carbon fluxes exchanged particularly at the interface vegetation-atmosphere. In this study we measured the atmospheric CO2 concentrations in a salt marsh located in the Patos Lagoon Estuary, southern Brazil. Eddy correlation techniques were applied to account for the CO2 exchange fluxes between the vegetation and the atmosphere. Our dataset refers to two sampling periods spanning from July up to November 2016 and from January to April 2017. By using time series analysis techniques including wavelet and cross-wavelet analysis, our results show the natural cycles of the CO2 exchanges variability and the relationship of these cycles with other environmental variables. We also present the amplitudes of the salt marsh-atmosphere CO2 fluxes’ diurnal cycle for both study periods and demonstrate that the CO2 fluxes are modulated by the passage of transient atmospheric systems and by the level variation of surrounding waters. During daytime, our site was as a CO2 sink. Fluxes were measured as -6.71 ± 5.55 μmol m-2 s-1 and -7.95 ± 6.44 μmol m-2 s-1 for the winter-spring and summer-fall periods, respectively. During nighttime, the CO2 fluxes were reversed and our site behaved as a CO2 source. Beside the seasonal changes in sunlight and air temperature, differences between the two periods were marked by the level of marsh inundation, winds and plant biomass (higher in summer). The net CO2 balance showed the predominance of the photosynthetic activity over community respiration, indicating the role of the salt marsh as a CO2 sink. When considering the yearly-averaged net fluxes integrated to the whole area of the Patos Lagoon Estuary marshes, the total CO2 sink was estimated as -87.6 Mg C yr-1. This paper is the first to measure and study the vegetation-atmosphere CO2 fluxes of a salt marsh environment of Brazil. The results will contribute to the knowledge on the global carbon budget and for marsh conservation and management plans, including climate change policies.
Numerical simulation and analysis of crack disease in tunnel lining structure
Authors: Chen Song , Yang Zhao , Liu Shuo , Li Liufang , Zheng Yibo , Yuan Ying
Published: September 2022

Tunnel construction in China is increasing year by year. With the passage of time, China will usher in the peak period of tunnel engineering repair, and it is vital to study in advance the influential nature of tunnel lining crack disease as well as management measures. By summarising a large amount of relevant literature, this paper analyses the main locations where cracks are generated in tunnel linings. Through the method of finite element numerical analysis, 24 cases of cracks of different widths and depths were modelled and calculated for each location of lining vaults, shoulders and side walls, respectively, to analyse the influence of different cases on the internal forces and deformation of the lining. The study shows that the stress concentration around the crack tip decreases with the increase of the crack width, while the stress concentration around the crack tip increases with the increase of the crack depth. The stresses in the other main parts of the lining increase after the crack is created, which has a deteriorating effect on the load-bearing capacity and stability of the lining structure. With the increase in crack width and depth, the sinking deformation of the vault and the heaving deformation of the back arch increase, especially when the cracks are large, but lining cracking has less effect on the lateral deformation of the lining. Compared to cracks in the top and shoulder of the arch, cracks in the side walls have a more pronounced effect on the distribution of internal forces around the cracks.
Predictors of visual acuity improvement after phacoemulsification cataract surgery
Authors: AlRyalat Saif Aldeen , Atieh Duha , AlHabashneh Ayed , Hassouneh Mariam , Toukan Rama , Alawamleh Renad , Alshammari Taher , Abu-Ameerh Mohammed
Published: September 2022

Purpose

This study aimed to assess preoperative predictors of visual outcome after phacoemulsification cataract surgery in Jordan, a Middle Eastern country.

Methods

This was a retrospective longitudinal study of adult patients who underwent phacoemulsification cataract surgery from January 2019 to July 2021. For each patient, we included only the first operated eye. We obtained pre-operative ocular history, cataract surgery complication risk based on a predesigned score, visual acuity, best correction, and best corrected visual acuity. We recorded intraoperative complications. We also obtained postoperative best corrected visual acuity and refractive error for correction after 1–3 months.

Results

A total of 1,370 patients were included in this study, with a mean age of 66.39 (± 9.48). 48.4% of patients achieved visual acuity ≥ 0.8, and 72.7% achieved visual acuity ≥ 0.5. The mean visual acuity improvement after phacoemulsification cataract surgery was 0.33 (95% CI 0.31–0.35). In the regression model, significant predictors that affected visual acuity improvement included the presence of diabetic retinopathy, glaucoma, and complication risk factors (i.e., high-risk surgery).

Conclusion

Predictors of visual acuity improvement vary between studies. This study was conducted in a developing country; we defined predictors of visual acuity improvement. We also provided a new preoperative phacoemulsification cataract surgery complication risk score.
Extracellular enzyme stoichiometry reveals carbon and nitrogen limitations closely linked to bacterial communities in China’s largest saline lake
Authors: Zhang Weizhen , Liu Yongqin , Geng Mengdie , Chen Ruirui , Wang Jiyi , Xue Bin , Xie Ping , Wang Jianjun
Published: September 2022

Saline lakes possess substantial carbon storage and play essential roles in global carbon cycling. Benthic microorganisms mine and decompose sediment organic matter via extracellular enzymes to acquire limiting nutrients and thus meet their element budgets, which ultimately causes variations in sediment carbon storage. However, current knowledge about microbial nutrient limitation and the associated organic carbon changes especially in saline lake remains elusive. Therefore, we took Qinghai Lake, the largest saline lake of China, as an example to identify the patterns and drivers of microbial metabolic limitations quantified by the vector analyses of extracellular enzyme stoichiometry. Benthic microorganisms were dominantly colimited by carbon (C) and nitrogen (N). Such microbial C limitation was aggravated upon the increases in water salinity and sediment total phosphorus, which suggests that sediment C loss would be elevated when the lake water is concentrated (increasing salinity) and phosphorus becomes enriched under climate change and nutrient pollution, respectively. Microbial N limitation was predominantly intensified by water total nitrogen and inhibited by C limitation. Among the microbial drivers of extracellular enzyme investments, bacterial community structure consistently exerted significant effects on the C, N, and P cycles and microbial C and N limitations, while fungi only altered the P cycle through species richness. These findings advance our knowledge of microbial metabolic limitation in saline lakes, which will provide insights towards a better understanding of global sediment C storage dynamics under climate warming and intensified human activity.
Efficient production of the β-ionone aroma compound from organic waste hydrolysates using an engineered Yarrowia lipolytica strain
Authors: Chen Shuyi , Lu Yanping , Wang Wen , Hu Yunzi , Wang Jufang , Tang Shixing , Lin Carol Sze Ki , Yang Xiaofeng
Published: September 2022

This study demonstrates the feasibility of establishing a natural compound supply chain in a biorefinery. The process starts with the biological or chemical hydrolysis of food and agricultural waste into simple and fermentative sugars, followed by their fermentation into more complex molecules. The yeast strain, Yarrowia lipolytica, was modified by introducing high membrane affinity variants of the carotenoid cleavage dioxygenase enzyme, PhCCD1, to increase the production of the aroma compound, β-ionone. The initial hydrolysis process converted food waste or sugarcane bagasse into nutrient-rich hydrolysates containing 78.4 g/L glucose and 8.3 g/L fructose, or 34.7 g/L glucose and 20.1 g/L xylose, respectively. During the next step, engineered Y. lipolytica strains were used to produce β-ionone from these feedstocks. The yeast strain YLBI3120, carrying a modified PhCCD1 gene was able to produce 4 g/L of β-ionone with a productivity of 13.9 mg/L/h from food waste hydrolysate. This is the highest yield reported for the fermentation of this compound to date. The integrated process described in this study could be scaled up to achieve economical large-scale conversion of inedible food and agricultural waste into valuable aroma compounds for a wide range of potential applications.
First generation of multifunctional peptides derived from latarcin-3a from Lachesana tarabaevi spider toxin
Authors: de Moraes Luiz Filipe Ramalho Nunes , Silva Patrícia Souza e , Pereira Tábata Camila Pereira Leite , Almeida Rodrigues Thiago Antônio , Farias Frihling Breno Emanuel , da Costa Rosiane Andrade , Torquato Heron Fernandes Vieira , Lima Cauê Santos , Paredes-Gamero Edgar Julian , Migliolo Ludovico
Published: September 2022

The need for discovering new compounds that can act selectively on pathogens is becoming increasingly evident, given the number of deaths worldwide due to bacterial infections or tumor cells. New multifunctional biotechnological tools are being sought, including compounds present in spider venoms, which have high biotechnological potential. The present work aims to perform the rational design and functional evaluation of synthetic peptides derived from Lachesana tarabaevi spider toxin, known as latarcin-3a. The antimicrobial activity was tested against Gram-positive and -negative bacteria, with minimum inhibitory concentrations (MIC) between 4 and 128 μg.ml−1. Anti-biofilm tests were then performed to obtain MICs, where the peptides demonstrated activity from 4 to 128 μg.ml−1. In vitro cell cytotoxicity assays were carried out from tumor cell lines, lineages C1498, Kasumi-1, K-562, Jurkat, MOLT4, and Raji. Erythrocyte integrity was evaluated in the presence of synthetic peptides analog, which did not promote hemolysis at 128 μg.ml−1. The peptide that showed the best antibacterial activity was Lt-MAP3 and the best antitumor was Lt-MAP2. In conclusion, rational design of multifunctional antimicrobial peptides may be promising alternative tools in the treatment of emerging diseases such as bacterial infections and tumor cells.
Dietary supplementation with Cyberlindnera jadinii improved growth performance, serum biochemical Indices, antioxidant status, and intestinal health in growing raccoon dogs (Nyctereutes procyonoides)
Authors: Zhao Dehui , Liu Hanlu , Zhang Haihua , Liu Keyuan , Zhang Xinyu , Liu Qian , Wu Yan , Zhang Ting , Zhang Qiaoru
Published: September 2022

This study was conducted to investigate whether different dietary Cyberlindnera jadinii levels affect growth performance, serum immunity, antioxidant capacity, and intestinal microbiota in growing raccoon dogs. Forty-five healthy male raccoon dogs were randomly assigned to three treatment groups, with 15 raccoon dogs per group. Each raccoon dog was housed in an individual cage. The raccoon dogs in the three groups were fed diets supplemented with Cyberlindnera jadinii at dosages of 0 (N group), 1 × 109 (L group) and 5 × 109 CFU/g (H group). A 7-day pretest period preceded a formal test period of 30 days. The results showed that Cyberlindnera jadinii in the L and H groups improved average daily gain (ADG) (P < 0.05) and decreased the ratio of feed to weight (F/G) (P < 0.05). Serum immunoglobulins A and G levels were increased in the L and H groups compared to the N group (P < 0.05). Cyberlindnera jadinii in the L and H groups increased serum superoxide dismutase activity (P < 0.05), and serum glutathione peroxidase activity was increased in the L group compared to the N group (P < 0.05). The relative abundance of Firmicutes and Actinobacteriota were increased, and the relative abundance of Bacteroidota was decreased in the L and H groups compared to the N group (P < 0.05). The relative abundance of Proteobacteria and Cyanobacteria was increased in the H group compared to the other two groups (P < 0.05). The ratio of Firmicutes to Bacteroidetes in the Cyberlindnera jadinii supplementation groups increased compared with the N group (P < 0.05). The relative abundance of Megasphaera and Bifidobacterium were increased, and the relative abundance of Prevotella was decreased in the L and H groups compared to the N group (P < 0.05). The relative abundance of Dialister was increased, while the relative abundance of Blautia was decreased in the H group compared to the other two groups (P < 0.05). The relative abundance of Agathobacter was decreased in the H group compared to the N group (P < 0.05). In conclusion, dietary supplementation with Cyberlindnera jadinii increased growth performance, serum immunity, antioxidant capacity, and improved intestinal microbiota in growing raccoon dogs. Cyberlindnera jadinii can therefore be used as a growth promoter in raccoon dogs.
Biotreatment of oily sludge by a bacterial consortium: Effect of bioprocess conditions on biodegradation efficiency and bacterial community structure
Authors: Hentati Dorra , Abed Raeid M. M. , Abotalib Nasser , El Nayal Ashraf M. , Ashraf Ijaz , Ismail Wael
Published: September 2022

We studied the biodegradation of oily sludge generated by a petroleum plant in Bahrain by a bacterial consortium (termed as AK6) under different bioprocess conditions. Biodegradation of petroleum hydrocarbons in oily sludge (C11-C29) increased from 24% after two days to 99% after 9 days of incubation in cultures containing 5% (w/v) of oily sludge at 40°C. When the nitrogen source was excluded from the batch cultures, hydrocarbon biodegradation dropped to 45% within 7 days. The hydrocarbon biodegradation decreased also by increasing the salinity to 3% and the temperature above 40°C. AK6 tolerated up to 50% (w/v) oily sludge and degraded 60% of the dichloromethane-extractable oil fraction. Illumina-MiSeq analyses revealed that the AK6 consortium was mainly composed of Gammaproteobacteria (ca. 98% of total sequences), with most sequences belonging to Klebsiella (77.6% of total sequences), Enterobacter (16.7%) and Salmonella (5%). Prominent shifts in the bacterial composition of the consortium were observed when the temperature and initial sludge concentration increased, and the nitrogen source was excluded, favoring sequences belonging to Pseudomonas and Stenotrophomonas. The AK6 consortium is endowed with a strong oily sludge tolerance and biodegradation capability under different bioprocess conditions, where Pseudomonas spp. appear to be crucial for hydrocarbon biodegradation.
Nutritional immunomodulation of Atlantic salmon response to Renibacterium salmoninarum bacterin
Authors: Emam Mohamed , Eslamloo Khalil , Caballero-Solares Albert , Lorenz Evandro Kleber , Xue Xi , Umasuthan Navaneethaiyer , Gnanagobal Hajarooba , Santander Javier , Taylor Richard G. , Balder Rachel , Parrish Christopher C. , Rise Matthew L.
Published: September 2022

We investigated the immunomodulatory effect of varying levels of dietary ω6/ω3 fatty acids (FA) on Atlantic salmon (Salmo salar) antibacterial response. Two groups were fed either high-18:3ω3 or high-18:2ω6 FA diets for 8 weeks, and a third group was fed for 4 weeks on the high-18:2ω6 diet followed by 4 weeks on the high-18:3ω3 diet and termed “switched-diet”. Following the second 4 weeks of feeding (i.e., at 8 weeks), head kidney tissues from all groups were sampled for FA analysis. Fish were then intraperitoneally injected with either a formalin-killedRenibacterium salmoninarumbacterin (5 × 107cells mL−1) or phosphate-buffered saline (PBS control), and head kidney tissues for gene expression analysis were sampled at 24 h post-injection. FA analysis showed that the head kidney profile reflected the dietary FA, especially for C18FAs. The qPCR analyses of twenty-three genes showed that both the high-ω6 and high-ω3 groups had significant bacterin-dependent induction of some transcripts involved in lipid metabolism (ch25haandlipe), pathogen recognition (clec12bandtlr5), and immune effectors (znrf1andcish).In contrast, these transcripts did not significantly respond to the bacterin in the “switched-diet” group. Concurrently, biomarkers encoding proteins with putative roles in biotic inflammatory response (tnfrsf6b) and dendritic cell maturation (ccl13) were upregulated, and a chemokine receptor (cxcr1) was downregulated with the bacterin injection regardless of the experimental diets. On the other hand, an inflammatory regulator biomarker,bcl3, was only significantly upregulated in the high-ω3 fed group, and a C-type lectin family member (clec3a) was only significantly downregulated in the switched-diet group with the bacterin injection (compared with diet-matched PBS-injected controls). Transcript fold-change (FC: bacterin/PBS) showed thattlr5was significantly over 2-fold higher in the high-18:2ω6 diet group compared with other diet groups. FC and FA associations highlighted the role of DGLA (20:3ω6; anti-inflammatory) and/or EPA (20:5ω3; anti-inflammatory) vs. ARA (20:4ω6; pro-inflammatory) as representative of the anti-inflammatory/pro-inflammatory balance between eicosanoid precursors. Also, the correlations revealed associations of FA proportions (% total FA) and FA ratios with several eicosanoid and immune receptor biomarkers (e.g., DGLA/ARA significant positive correlation withpgds,5loxa,5loxb,tlr5, andcxcr1). In summary, dietary FA profiles and/or regimens modulated the expression of some immune-relevant genes in Atlantic salmon injected withR. salmoninarumbacterin. The modulation of Atlantic salmon responses to bacterial pathogens and their associated antigens using high-ω6/high-ω3 diets warrants further investigation.
A comprehensive next generation sequencing tissue assay for Asian-prevalent cancers—Analytical validation and performance evaluation with clinical samples
Authors: Ng Cedric Chuan-Young , Lim Sandy , Lim Abner Herbert , Md Nasir Nur Diyana , Zhang Jingxian , Rajasegaran Vikneswari , Lee Jing Yi , Kok Jessica Sook Ting , Thike Aye Aye , Lim Johnathan Xiande , Weng Ruifen , Yee Sidney , Choudhury Yukti , Chan Jason Yongsheng , Tan Puay Hoon , Tan Min-Han , Teh Bin Tean
Published: September 2022

Introduction: A well-validated diagnostic assay with curated biomarkers complements clinicopathological factors to facilitate early diagnosis and ensure timely treatment delivery. This study focuses on an Asian-centric cancer diagnostic assay designed and thoroughly validated against commercially available standard references and a cohort of over 200 clinical specimens spanning 12 diverse Asian-centric cancer types.

Methods: The assay uses hybrid-capture probes capable of profiling DNA aberrations from 572 cancer-related genes and 91 RNA fusion partners. The panel can detect clinically-tractable biomarkers such as microsatellite instability (MSI) and tumor mutation burden (TMB).

Results: Analytical evaluation demonstrated 100% specificity and 99.9% sensitivity within a ≥5% VAF limit of detection (LoD) for SNV/Indels. RNA-based fusion features an LoD of ≥5 copies per nanogram input when evaluated against commercial references. Excellent linearity and concordance were observed when benchmarking against orthogonal methods in identifying MSI status, TMB scores and RNA fusions. Actionable genetic alterations were identified in 65% of the clinical samples.

Conclusion: These results demonstrate a molecular diagnostic assay that accurately detects genomic alterations and complex biomarkers. The data also supports an excellent performance of this assay for making critical diagnoses and well-informed therapeutic decisions in Asian prevalent cancers.
Preoperative homocysteine modifies the association between postoperative C-reactive protein and postoperative delirium
Authors: Ma Xin , Mei Xinchun , Tang Tianyi , Wang Meijuan , Wei Xiaoyi , Zheng Hailin , Cao Jing , Zheng Hui , Cody Kathryn , Xiong Lize , Marcantonio Edward R. , Xie Zhongcong , Shen Yuan
Published: September 2022

Background

Homocysteine and C-reactive protein (CRP) may serve as biomarkers of postoperative delirium. We set out to compare the role of blood concentration of homocysteine versus CRP in predicting postoperative delirium in patients.

Materials and methods

In this prospective observational cohort study, the plasma concentration of preoperative homocysteine and postoperative CRP was measured. Delirium incidence and severity within 3 days postoperatively were determined using the Confusion Assessment Method and Confusion Assessment Method-Severity algorithm.

Results

Of 143 participants [69% female, median (interquartile range, 25th–75th) age of 71 (67–76) years] who had knee or hip surgery under general anesthesia, 44 (31%) participants developed postoperative delirium. Postoperative plasma concentration of CRP was associated with postoperative delirium incidence [adjusted odds ratio (OR) per one standard deviation change in CRP: 1.51; 95% Confidence Interval (CI): 1.05, 2.16;P= 0.026], and severity [in which each one standard deviation increase in postoperative CRP was associated with a 0.47 point (95% CI: 0.18–0.76) increase in the severity of delirium,P= 0.002] after adjusting age, sex, preoperative Mini-Mental State Examination score and the days when postoperative CRP was measured. A statistically significant interaction (adjustedP= 0.044) was also observed, in which the association between postoperative plasma concentration of CRP and postoperative delirium incidence was stronger in the participants with lower preoperative plasma concentrations of homocysteine compared to those with higher preoperative levels.

Conclusion

Pending validation studies, these data suggest that preoperative plasma concentration of homocysteine modifies the established association between postoperative plasma concentration of CRP and postoperative delirium incidence.
Astroglial and microglial pathology in Down syndrome: Focus on Alzheimer's disease
Authors: García Octavio , Flores-Aguilar Lisi
Published: September 2022

Down syndrome (DS) arises from the triplication of human chromosome 21 and is considered the most common genetic cause of intellectual disability. Glial cells, specifically astroglia and microglia, display pathological alterations that might contribute to DS neuropathological alterations. Further, in middle adulthood, people with DS develop clinical symptoms associated with premature aging and Alzheimer's disease (AD). Overexpression of the amyloid precursor protein (APP) gene, encoded on chromosome 21, leads to increased amyloid-β (Aβ) levels and subsequent formation of Aβ plaques in the brains of individuals with DS. Amyloid-β deposition might contribute to astroglial and microglial reactivity, leading to neurotoxic effects and elevated secretion of inflammatory mediators. This review discusses evidence of astroglial and microglial alterations that might be associated with the AD continuum in DS.
Identification of feature genes and pathways for Alzheimer's disease via WGCNA and LASSO regression
Authors: Sun Hongyu , Yang Jin , Li Xiaohui , Lyu Yi , Xu Zhaomeng , He Hui , Tong Xiaomin , Ji Tingyu , Ding Shihan , Zhou Chaoli , Han Pengyong , Zheng Jinping
Published: September 2022

While Alzheimer's disease (AD) can cause a severe economic burden, the specific pathogenesis involved is yet to be elucidated. To identify feature genes associated with AD, we downloaded data from three GEO databases: GSE122063, GSE15222, and GSE138260. In the filtering, we used AD for search keywords, Homo sapiens for species selection, and established a sample size of > 20 for each data set, and each data set contains Including the normal group and AD group. The datasets GSE15222 and GSE138260 were combined as a training group to build a model, and GSE122063 was used as a test group to verify the model's accuracy. The genes with differential expression found in the combined datasets were used for analysis through Gene Ontology (GO) and The Kyoto Encyclopedia of Genes and Genome Pathways (KEGG). Then, AD-related module genes were identified using the combined dataset through a weighted gene co-expression network analysis (WGCNA). Both the differential and AD-related module genes were intersected to obtain AD key genes. These genes were first filtered through LASSO regression and then AD-related feature genes were obtained for subsequent immune-related analysis. A comprehensive analysis of three AD-related datasets in the GEO database revealed 111 common differential AD genes. In the GO analysis, the more prominent terms were cognition and learning or memory. The KEGG analysis showed that these differential genes were enriched not only in In the KEGG analysis, but also in three other pathways: neuroactive ligand-receptor interaction, cAMP signaling pathway, and Calcium signaling pathway. Three AD-related feature genes (SST, MLIP, HSPB3) were finally identified. The area under the ROC curve of these AD-related feature genes was greater than 0.7 in both the training and the test groups. Finally, an immune-related analysis of these genes was performed. The finding of AD-related feature genes (SST, MLIP, HSPB3) could help predict the onset and progression of the disease. Overall, our study may provide significant guidance for further exploration of potential biomarkers for the diagnosis and prediction of AD.
Made to measure—Selecting outcomes in aneurysmal subarachnoid hemorrhage research
Authors: Andersen Christopher R. , English Shane W. , Delaney Anthony
Published: September 2022

There has been limited new high-level evidence generated to guide aneurysmal subarachnoid hemorrhage (aSAH) management in the past decade. The choice of outcome measures used in aSAH clinical trials may be one of the factors hindering progress. In this narrative review we consider the current process for determining “what” to measure in aSAH and identify some of the shortcomings of these approaches. A consideration of the unique clinical course of aSAH is then discussed and how this impacts on selecting the best timepoints to assess change in the chosen constructs. We also review the how to critically appraise different measurement instruments and some of the issues with how these are applied in the context of aSAH. We conclude with current initiatives to improve outcome selection in aSAH and future directions in the research agenda.
Cerebral protection by remote ischemic post-conditioning in patients with ischemic stroke: A systematic review and meta-analysis of randomized controlled trials
Authors: Lu Meng , Wang Yujiao , Yin Xin , Li Yuanyuan , Li Hongyan
Published: September 2022

Background

There is evidence that remote limb ischemic postconditioning (RIPostC) can reduce ischemia-reperfusion injury (IRI) and improve the prognosis of patients with ischemic stroke. However, so far, only few relevant clinical studies have been conducted. Therefore, we carried out a meta-analysis of eligible randomized controlled trials to compare the RIPostC group with a control group (no intervention or sham surgery) in patients with ischemic stroke.

Methods

Four English-language publication databases, PubMed, Cochrane, Embase, and Web of Science, were systematically searched up to March 2022. The data were analyzed using Review Manager fixed-effects and random-effects models.

Results

A total of 12 studies were included, and 11 of those were analyzed quantitatively. Compared to controls, The RIPostC group showed significantly reduced NIHHS scores in patients with ischemic stroke, (MD: −1.09, 95% confidence interval [CI]: −1.60, −0.57, P < 0.0001) and improved patients' Montreal Cognitive Assessment (MoCA) scores, (MD: 1.89, 95% CI: 0.78, 3.00, P = 0.0009), Our results showed that RIPostC is safe, (RR = 0.81, 95%CI: 0.61, 1.08, P = 0.15).

Conclusion

Our meta-analysis showed that RIPostC is safe and effective and has a positive cerebral protective effect in patients with ischemic stroke, which is safe and effective, and future large-sample, multicenter trials are needed to validate the cerebral protective effect of RIPostC.
Mental health and quality of life in patients with craniofacial movement disorders: A cross-sectional study
Authors: Yi Ming , Li Jing , Liu Gang , Ou Zilin , Liu Yanmei , Li Jing , Chen Yicong , Guo Yaomin , Wang Ying , Zhang Weixi , Zeng Jinsheng , Dang Chao
Published: September 2022

Background

Facial appearance and expressions influence social interaction. Hemifacial spasm (HFS), blepharospasm (BPS), and blepharospasm-oromandibular dystonia (BOD) are common forms of craniofacial movement disorders. Few studies have focused on the mental burden and quality of life (QoL) in patients with craniofacial movement disorders. Therefore, this study investigated mental health and QoL in these patients.

Methods

This cross-sectional study included 90 patients with craniofacial movement disorders (HFS, BPS, and BOD; 30 patients per group) and 30 healthy individuals without craniofacial movement disorders (control group) recruited from October 2019 to November 2020. All participants underwent QoL and mental health evaluations for depression, anxiety, and stigma using the 36-item Short Form Health Survey (SF-36), Hamilton Anxiety Rating Scale (HAMA), Hamilton Rating Scale for Depression-24 (HAMD-24) and a questionnaire related to stigma.

Results

Depression was diagnosed in 37 (41.11%) patients, whereas 30 patients (33.33%) had anxiety. HAMA scores were significantly higher in the BPS and BOD groups than in the control group. Nineteen patients (21.11%) experienced stigma and SF-36 scores were lower in various dimensions in the movement disorders groups compared to healthy controls. The role-physical and social function scores were significantly lower in the movement disorders groups than in the control group all p < 0.05. The vitality scores of the BPS group and mental health scores of the BPS and BOD groups were significantly lower than those of the control group. Correlation analysis showed that the eight dimensions of SF-36 correlated with education level, disease duration, HAMD score, and HAMA score (all p < 0.05). Regression analysis demonstrated that the HAMD score correlated with general health, vitality, social function, role-emotional, and mental health (all p < 0.05). The HAMA score correlated with body pain after adjusting for education level and disease duration.

Conclusion

This study highlights the significant frequency of mental symptoms, including depression, anxiety, and stigma, which lower QoL in patients with craniofacial movement disorders.
Progressive 3D biomedical image registration network based on deep self-calibration
Authors: Sun Rui , Wu Jun , Miao Yongchun , Ouyang Lei , Qu Lei
Published: September 2022

Three dimensional deformable image registration (DIR) is a key enabling technique in building digital neuronal atlases of the brain, which can model the local non-linear deformation between a pair of biomedical images and align the anatomical structures of different samples into one spatial coordinate system. And thus, the DIR is always conducted following a preprocessing of global linear registration to remove the large global deformations. However, imperfect preprocessing may leave some large non-linear deformations that cannot be handled well by existing DIR methods. The recently proposed cascaded registration network gives a primary solution to deal with such large non-linear deformations, but still suffers from loss of image details caused by continuous interpolation (information loss problem). In this article, a progressive image registration strategy based on deep self-calibration is proposed to deal with the large non-linear deformations without causing information loss and introducing additional parameters. More importantly, we also propose a novel hierarchical registration strategy to quickly achieve accurate multi-scale progressive registration. In addition, our method can implicitly and reasonably implement dynamic dataset augmentation. We have evaluated the proposed method on both optical and MRI image datasets with obtaining promising results, which demonstrate the superior performance of the proposed method over several other state-of-the-art approaches for deformable image registration.
Implications for blinding in clinical trials with THC-containing cannabinoids based on the CANNA-TICS trial
Authors: Müller-Vahl Kirsten R. , Jakubovski Ewgeni , Fremer Carolin , Lenz-Ziegenbein Martina , Großhennig Anika , Klages Carolin , Koch Armin , Haas Martina , Pisarenko Anna
Published: September 2022

Randomized double-blind placebo-controlled trials (RCTs) are regarded as the gold standard for clinical trials. While there are established standards to avoid unblinding, in RCTs using tetrahydrocannabinol (THC) containing cannabinoids, however, accidental unblinding and intentional self-unbinding must be considered as a particular issue, since THC tests are widely available. To investigate unblinding rates in an RCT using a THC-containing cannabinoid, we re-contacted 54 out of 97 participants of the CANNA-TICS trial who had participated in our study center in Hannover. Of the 54 participants, 53 could be reached. Of these, one participant (2%) stated that she had unblinded herself intentionally during the treatment phase, and another three patients (6%) reported intentional unblinding after the end of the treatment. Noteworthy, two patients provided discrepant information and denied self-unblinding during the interview, although during study/clinic visits they had reported having done so. Thus, based on all available information, three participants (6%) unblinded themselves intentionally during the treatment phase and another three (6%) after the end of the treatment. Accidental unblinding during the treatment phase was reported by 4/54 participants (7%) (during study visits). Since one participant reported both intentional self-unblinding (during the interview) and accidental unblinding (during a study visit), the total unblinding rate was 17% (n = 9). Of these, seven participants (13%) reported unblinding during the treatment phase. When asked in the interview whether they knew that self-unblinding would have been possible, only 34% (n = 18/53) of participants stated that they had been aware of this possibility. Thus, altogether 33% (n = 6/18) of those being informed about the possibility of self-unblinding did so and half of them (3/18, 17 %) during the treatment phase. It can be expected that in parallel to increasing knowledge of medicinal and recreational use of cannabinoids, more and more people will also be informed about the availability of THC tests. Hence, in future RCTs using THC-containing cannabinoids, researchers have to take the possibility of accidental and intentional unblinding into consideration, when designing the study.
Resting-state brain network in Parkinson’s disease with different degrees of depression
Authors: Liu Qinru , Mao Zhenni , Tan Changlian , Cai Sainan , Shen Qin , Wang Min , Li Junli , Zhang Lin , Zhou Fan , Song Chendie , Yuan Jiaying , Liu Yujing , Liu Jun , Liao Haiyan
Published: September 2022

Objective

The aim of this study is to explore the neural network mechanism of Parkinson’s disease (PD) with different degrees of depression using independent component analysis (ICA) of the functional connectivity changes in the forehead, limbic system, and basal ganglia regions.

Methods

A total of 106 patients with PD were divided into three groups: PD with moderate-severe depression (PDMSD, n = 42), PD with mild depression (PDMD, n = 29), and PD without depression (PDND, n = 35). Fifty gender- and age-matched healthy subjects were recruited as a control group (HC). Three-dimensional T1-weighted image and resting-state functional magnetic resonance imaging (RS-fMRI) data were collected.

Results

Different functional connectivity was observed in the left precentral gyrus, right precuneus, right inferior frontal gyrus, right medial and paracingulate gyrus, left supplementary motor area, right brain insula, and the inferior frontal gyrus of the left orbit among the four groups (ANOVA, P < 0.05, Voxel size > 5). Both PDMD and PDMSD exhibited increased functional connectivity in the superior-posterior default-mode network (spDMN) and left frontoparietal network (LFPN); they also exhibited a decreased functional connectivity in the interior Salience Network (inSN) when compared with the PDND group. The functional connectivity within the inSN network was decreased in the PDMSD group when compared with the PDMD group (Alphasim correction, P < 0.05, voxel size > 5).

Conclusion

PD with different degrees of depression has abnormal functional connectivity in multiple networks, which is an important neurobiological basis for the occurrence and development of depression in PD. The degree of decreased functional connectivity in the inSN network is related to the degree of depression in patients with PD-D, which can be an imaging marker for PD to judge the severity of depression.
How facial masks alter the interaction of gaze direction, head orientation, and emotion recognition
Authors: Thomas Lea , von Castell Christoph , Hecht Heiko
Published: September 2022

The COVID-19 pandemic has altered the way we interact with each other: mandatory mask-wearing obscures facial information that is crucial for emotion recognition. Whereas the influence of wearing a mask on emotion recognition has been repeatedly investigated, little is known about the impact on interaction effects among emotional signals and other social signals. Therefore, the current study sought to explore how gaze direction, head orientation, and emotional expression interact with respect to emotion perception, and how these interactions are altered by wearing a face mask. In two online experiments, we presented face stimuli from the Radboud Faces Database displaying different facial expressions (anger, fear, happiness, neutral, and sadness), gaze directions (−13°, 0°, and 13°), and head orientations (−45°, 0°, and 45°) – either without (Experiment 1) or with mask (Experiment 2). Participants categorized the displayed emotional expressions. Not surprisingly, masks impaired emotion recognition. Surprisingly, without the mask, emotion recognition was unaffected by averted head orientations and only slightly affected by gaze direction. The mask strongly interfered with this ability. The mask increased the influence of head orientation and gaze direction, in particular for the emotions that were poorly recognized with mask. The results suggest that in case of uncertainty due to ambiguity or absence of signals, we seem to unconsciously factor in extraneous information.
Activity-regulated E3 ubiquitin ligase TRIM47 modulates excitatory synapse development
Authors: Sharma Gourav , Banerjee Sourav
Published: September 2022

The Ubiquitin Proteasome System (UPS) has been shown to regulate neuronal development and synapse formation. Activity-dependent regulation of E3 ligase, a component of the UPS that targets specific proteins for proteasome-mediated degradation, is emerging as a pivotal player for the establishment of functional synapses. Here, we identified TRIM47 as a developmentally regulated E3 ligase that is expressed in rat hippocampus during the temporal window of synapse formation. We have demonstrated that the expression of TRIM47 is regulated by the glutamate-induced synaptic activity of hippocampal neurons in culture. In addition, the activity-dependent enhancement of TRIM47 expression is recapitulated following the object location test, a hippocampus-dependent spatial memory paradigm. We observed that this enhancement of TRIM47 expression requires NMDA receptor activation. The knockdown of TRIM47 leads to an enhancement of spine density without affecting dendritic complexity. Furthermore, we observed an increase in excitatory synapse development upon loss of TRIM47 function. Comprehensively, our study identified an activity-regulated E3 ligase that drives excitatory synapse formation in hippocampal neurons.
Effects of low molecular weight peptides from monkfish (Lophius litulon) roe on immune response in immunosuppressed mice
Authors: Ren Zhexin , Yang Fei , Yao Sijia , Bi Lijun , Jiang Guanqin , Huang Ju , Tang Yunping
Published: September 2022

This study aimed to investigate the immunomodulatory activation of low-molecular-weight peptides from monkfish (Lophius litulon) roe (named MRP) on cyclophosphamide (CTX)-induced immunosuppressed mice. Our results indicated that MRP (100 mg/kg/d BW) could significantly increase the body weight and immune organ index, and improve the morphological changes in the spleen and thymus of mice. These effects subsequently enhance the serum levels of interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, and immunoglobulin (Ig) A, IgM, and IgG. Furthermore, MRP could also improve CTX-induced oxidative stress, and activate the NF-κB and MAPK pathways in the spleen tissues. The findings reported herein indicate that MRP has a good immunomodulatory activation toward immunosuppressed mice, hence can potentially be developed as an immune adjuvant or functional food.