bluuebunny/crossref_metadata_2025 huggingface dataset:
Thrombo-Inflammation and Immunological Response in Ischemic Stroke: Focusing on Platelet-Tregs Interaction
Authors: Cui Jieqiong , Li Huayan , Chen Zongning , Dong Ting , He Xiying , Wei Yuanyuan , Li Zhengkun , Duan Jinfeng , Cao Ting , Chen Qian , Ma Dongmei , Zhou Yang , Wang Bo , Shi Mingqin , Zhang Qin , Xiong Lei , Qin Dongdong
Published: June 2022

Strokes are mainly caused by thromboembolic obstruction of a major cerebral artery. Major clinical manifestations include paralysis hemiplegia, aphasia, memory, and learning disorders. In the case of ischemic stroke (IS), hyperactive platelets contribute to advancing an acute thrombotic event progression. Therefore, the principal goal of treatment is to recanalize the occluded vessel and restore cerebral blood flow by thrombolysis or mechanical thrombectomy. However, antiplatelets or thrombolytic therapy may increase the risk of bleeding. Beyond the involvement in thrombosis, platelets also contribute to the inflammatory process induced by cerebral ischemia. Platelet-mediated thrombosis and inflammation in IS lie primarily in the interaction of platelet receptors with endothelial cells and immune cells, including T-cells, monocytes/macrophages, and neutrophils. Following revascularization, intervention with conventional antiplatelet medicines such as aspirin or clopidogrel does not substantially diminish infarct development, most likely due to the limited effects on the thrombo-inflammation process. Emerging evidence has shown that T cells, especially regulatory T cells (Tregs), maintain immune homeostasis and suppress immune responses, playing a critical immunomodulatory role in ischemia-reperfusion injury. Hence, considering the deleterious effects of inflammatory and immune responses, there is an urgent need for more targeted agents to limit the thrombotic-inflammatory activity of platelets and minimize the risk of a cerebral hemorrhage. This review highlights the involvement of platelets in neuroinflammation and the evolving role of Tregs and platelets in IS. In response to all issues, preclinical and clinical strategies should generate more viable therapeutics for preventing and managing IS with immunotherapy targeting platelets and Tregs.
Excessive Visit-to-Visit Small and Dense Low-Density Lipoproteins Elevate Cerebral Small Vessel Disease Progression Risk in the Elderly
Authors: Liu Weike , Xu Jing , Song Huajing , Zhang Chunju , Yao Yanli , Zhang Hua , Li Yue-Chun , Liu Zhendong
Published: June 2022

Objective

Small and dense low-density lipoprotein (sdLDL) elevation may be among the most sensitive early biomarkers for nascent cardiovascular disease. This study, therefore, investigated the association between visit-to-visit changes in sdLDL and cerebral small vessel disease (CSVD) progression in older individuals, and the influence of Apolipoprotein E (APOE) genotype on this association.

Methods

Between April 2007 and July 2009, 1,143 participants ≥60 years old were recruited from the Shandong region of China, and sdLDL was measured at baseline and at each follow-up visit. White matter hyperintensities (WMHs), lacunes, microbleeds, and enlarged perivascular spaces (EPVSs) were assessed by magnetic resonance imaging. The APOE genotype was determined and participants were stratified as ε4-positive or ε4-negative.

Results

During an average follow-up of 86.0 months, 225 participants (19.7%) developed WMH progression, 193 (16.9%) lacune progression, 170 (14.9%) microbleed progression, and 185 (16.2%) EPVS progression. Compared with patients in the first (lowest) tertile of visit-to-visit mean sdLDL, those in the second and third tertiles demonstrated significantly greater risks of WMH progression (53.5 and 105.3% higher), lacune progression (53.3 and 60.8%), microbleed progression (47.2 and 127.6%), and EPVS progression (54.0 and 135.0%) after adjustment for confounders (all adjusted P values for trends <0.001). Compared with patients in the first tertile of visit-to-visit sdLDL SD, those in the second and third tertiles also demonstrated significantly greater risks of WMH progression (49.9% and 143.6%), lacune progression (75.3 and 178.0%), microbleed progression (12.7 and 64.7%), and EPVS progression (41.7 and 114.6%) after adjustment (all P < 0.001). There were significant and positive visit-to-visit mean sdLDL × visit-to-visit sdLDL SD, visit-to-visit mean sdLD×ε4-positive, visit-to-visit sdLDL SD×ε4-positive, and visit-to-visit mean sdLDL×visit-to-visit sdLDL SD×ε4-positive interactions influencing CSVD progression after confounder adjustment (all P < 0.05).

Conclusion

Large and variable visit-to-visit changes in sdLDL are independent predictors of aggressive CSVD progression, and this association is strongly influenced by APOE ε4 allele genotype.
Development and Validation of a Predictive Nomogram for Possible REM Sleep Behavior Disorders
Authors: Lai Hong , Li Xu-Ying , Hu Junya , Li Wei , Xu Fanxi , Zhu Junge , He Raoli , Weng Huidan , Chen Lina , Yu Jiao , Li Xian , Song Yang , Wang Xianling , Wang Zhanjun , Li Wei , Kang Rong , Li Yuling , Xu Junjie , Deng Yuanfei , Ye Qinyong , Wang Chaodong
Published: June 2022

Objectives

To develop and validate a predictive nomogram for idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) in a community population in Beijing, China.

Methods

Based on the validated RBD questionnaire-Hong Kong (RBDQ-HK), we identified 78 individuals with possible RBD (pRBD) in 1,030 community residents from two communities in Beijing. The least absolute shrinkage and selection operator (LASSO) regression was applied to identify candidate features and develop the nomogram. Internal validation was performed using bootstrap resampling. The discrimination of the nomogram was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve, and the predictive accuracy was assessed via a calibration curve. Decision curve analysis (DCA) was performed to evaluate the clinical value of the model.

Results

From 31 potential predictors, 7 variables were identified as the independent predictive factors and assembled into the nomogram: family history of Parkinson's disease (PD) or dementia [odds ratio (OR), 4.59; 95% confidence interval (CI), 1.35–14.45; p = 0.011], smoking (OR, 3.24; 95% CI, 1.84–5.81; p < 0.001), physical activity (≥4 times/week) (OR, 0.23; 95% CI, 0.12–0.42; p < 0.001), exposure to pesticides (OR, 3.73; 95%CI, 2.08–6.65; p < 0.001), constipation (OR, 6.25; 95% CI, 3.58–11.07; p < 0.001), depression (OR, 3.66; 95% CI, 1.96–6.75; p < 0.001), and daytime somnolence (OR, 3.28; 95% CI, 1.65–6.38; p = 0.001). The nomogram displayed good discrimination, with original AUC of 0.885 (95% CI, 0.845–0.925), while the bias-corrected concordance index (C-index) with 1,000 bootstraps was 0.876. The calibration curve and DCA indicated the high accuracy and clinical usefulness of the nomogram.

Conclusions

This study proposed an effective nomogram with potential application in the individualized prediction for pRBD.
Peripheral Hemolysis in Relation to Iron Rim Presence and Brain Volume in Multiple Sclerosis
Authors: Krajnc Nik , Bsteh Gabriel , Kasprian Gregor , Zrzavy Tobias , Kornek Barbara , Berger Thomas , Leutmezer Fritz , Rommer Paulus , Lassmann Hans , Hametner Simon , Dal-Bianco Assunta
Published: June 2022

Background:

Iron rim lesions (IRLs) represent chronic lesion activity and are associated with a more severe disease course in multiple sclerosis (MS). How the iron rims around the lesions arise in patients with MS (pwMS), and whether peripheral hemolysis may be a source of iron in rim associated macrophages, is unclear.

Objective

To determine a potential correlation between peripheral hemolysis parameters and IRL presence in pwMS.

Methods

This retrospective study included pwMS, who underwent a 3T brain MRI between 2015 and 2020 and had a blood sample drawn at ± 2 weeks. Patients with vertigo served as a control group.

Results

We analyzed 75 pwMS (mean age 37.0 years [SD 9.0], 53.3% female) and 43 controls (mean age 38.3 years [SD 9.8], 51.2% female). Median number of IRLs was 1 (IQR 4), 28 (37.3%) pwMS had no IRLs. IRL patients showed significantly higher Expanded Disability Status Scale (EDSS) compared to non-IRL patients (median EDSS 2.3 [IQR 2.9] vs. 1.3 [IQR 2.9], p = 0.017). Number of IRLs correlated significantly with disease duration (rs = 0.239, p = 0.039), EDSS (rs = 0.387, p < 0.001) and Multiple Sclerosis Severity Scale (MSSS) (rs = 0.289, p = 0.014). There was no significant difference in hemolysis parameters between non-IRL, IRL patients (regardless of gender and/or disease type) and controls, nor between hemolysis parameters and the number of IRLs. Total brain volume was associated with fibrinogen (β= −0.34, 95% CI −1.32 to −0.145, p = 0.016), and absolute cortical and total gray matter volumes were associated with hemoglobin (β = 0.34, 95% CI 3.39–24.68, p = 0.011; β = 0.33, 95% CI 3.29–28.95, p = 0.015; respectively).

Conclusion

Our data do not suggest an association between hemolysis parameters and IRL presence despite a significant association between these parameters and markers for neurodegeneration.
Horizons in Human Aging Neuroscience: From Normal Neural Aging to Mental (Fr)Agility
Authors: Ridderinkhof K. Richard , Krugers Harm J.
Published: June 2022

While aging is an important risk factor for neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease, age-related cognitive decline can also manifest without apparent neurodegenerative changes. In this review, we discuss molecular, cellular, and network changes that occur during normal aging in the absence of neurodegenerative disease. Emerging findings reveal that these changes include metabolic alterations, oxidative stress, DNA damage, inflammation, calcium dyshomeostasis, and several other hallmarks of age-related neural changes that do not act on their own, but are often interconnected and together may underlie age-related alterations in brain plasticity and cognitive function. Importantly, age-related cognitive decline may not be reduced to a single neurobiological cause, but should instead be considered in terms of a densely connected system that underlies age-related cognitive alterations. We speculate that a decline in one hallmark of neural aging may trigger a decline in other, otherwise thus far stable subsystems, thereby triggering a cascade that may at some point also incur a decline of cognitive functions and mental well-being. Beyond studying the effects of these factors in isolation, considerable insight may be gained by studying the larger picture that entails a representative collection of such factors and their interactions, ranging from molecules to neural networks. Finally, we discuss some potential interventions that may help to prevent these alterations, thereby reducing cognitive decline and mental fragility, and enhancing mental well-being, and healthy aging.
Necroptosis and Neuroinflammation in Retinal Degeneration
Authors: Tao Yan , Murakami Yusuke , Vavvas Demetrios G. , Sonoda Koh-Hei
Published: June 2022

Necroptosis mediates the chronic inflammatory phenotype in neurodegeneration. Receptor-interacting protein kinase (RIPK) plays a pivotal role in the induction of necroptosis in various cell types, including microglia, and it is implicated in diverse neurodegenerative diseases in the central nervous system and the retina. Targeting RIPK has been proven beneficial for alleviating both neuroinflammation and degeneration in basic/preclinical studies. In this review, we discuss the role of necroptosis in retinal degeneration, including (1) the molecular pathways involving RIPK, (2) RIPK-dependent microglial activation and necroptosis, and (3) the interactions between necroptosis and retinal neuroinflammation/degeneration. This review will contribute to a renewed focus on neuroinflammation induced by necroptosis and to the development of anti-RIPK drugs against retinal degeneration.
Structural and Functional Brain Changes in Patients With Classic Trigeminal Neuralgia: A Combination of Voxel-Based Morphometry and Resting-State Functional MRI Study
Authors: Liu Hao , Hou Haiman , Li Fangfang , Zheng Ruiping , Zhang Yong , Cheng Jingliang , Han Shaoqiang
Published: June 2022

Objectives

Brain structural and functional abnormalities have been separately reported in patients with classic trigeminal neuralgia (CTN). However, whether and how the functional deficits are related to the structural alterations remains unclear. This study aims to investigate the anatomical and functional deficits in patients with CTN and explore their association.

Methods

A total of 34 patients with CTN and 29 healthy controls (HCs) with age- and gender-matched were recruited. All subjects underwent structural and resting-state functional magnetic resonance imaging (fMRI) scanning and neuropsychological assessments. Voxel-based morphometry (VBM) was applied to characterize the alterations of gray matter volume (GMV). The amplitude of low-frequency fluctuation (ALFF) method was used to evaluate regional intrinsic spontaneous neural activity. Further correlation analyses were performed between the structural and functional changes and neuropsychological assessments.

Results

Compared to the HCs, significantly reduced GMV was revealed in the right hippocampus, right fusiform gyrus (FFG), and temporal-parietal regions (the left superior/middle temporal gyrus, left operculo-insular gyrus, left inferior parietal lobule, and right inferior temporal gyrus) in patients with CTN. Increased functional activity measured by zALFF was observed mainly in the limbic system (the bilateral hippocampus and bilateral parahippocampal gyrus), bilateral FFG, basal ganglia system (the bilateral putamen, bilateral caudate, and right pallidum), left thalamus, left cerebellum, midbrain, and pons. Moreover, the right hippocampus and FFG were the overlapped regions with both functional and anatomical deficits. Furthermore, GMV in the right hippocampus was negatively correlated with pain intensity, anxiety, and depression. GMV in the right FFG was negatively correlated with illness duration. The zALFF value in the right FFG was positively correlated with anxiety.

Conclusion

Our results revealed concurrent structural and functional changes in patients with CTN, indicating that the CTN is a brain disorder with structural and functional abnormalities. Moreover, the overlapping structural and functional changes in the right hippocampus and FFG suggested that anatomical and functional changes might alter dependently in patients with CTN. These findings highlight the vital role of hippocampus and FFG in the pathophysiology of CTN.
Lactobacillus casei SYF-08 Protects Against Pb-Induced Injury in Young Mice by Regulating Bile Acid Metabolism and Increasing Pb Excretion
Authors: Chen Zhenhui , Tang Ziyu , Kong Jingjing , Chen Lixuan , Liu Jiaxin , Li Yunting , Huang Wanwen , Li Wendan , Wu Junlin , Zhao Wei , Meng Xiaojing , Fan Hongying
Published: June 2022

Pb poisoning affects infant growth and development. However, dimercaptosuccinic acid (DMSA) as the current therapy for Pb poisoning exerts relatively significant toxic side effects in infants. Therefore, identifying a non-toxic treatment in this regard is particularly important. In this study, we aimed to investigate the therapeutic effect of an infant feces-derived probiotic strain, Lactobacillus casei SYF-08 (SYF-08), on Pb poisoning in young mice. The Pb levels in the organisms were detected via inductively coupled plasma mass spectrometry, while the therapeutic effect of SYF-08 on Pb-induced neural system damage was explored via the Morris water maze test, hematoxylin-eosin staining, and immunohistochemistry. Additionally, the molecular mechanisms underlying the protective effects of SYF-08 against Pb-induced intestinal damage were also explored via histological staining, 16S rRNA sequencing, untargeted metabolomics, qRT-PCR, and western blotting. In vivo experiments revealed that SYF-08 reduced blood and bone Pb levels and increased urinary Pb excretion. Additionally, SYF-08 alleviated Pb-induced pathological damage to the brain and ultimately improved the learning and cognitive abilities of the young mice. This treatment also restored intestinal microflora dysbiosis, regulated bile acid metabolism, and inhibited the FXR-NLRP3 signaling pathway. It also resulted in fewer adverse events than the DMSA treatment. In conclusion, our results provided valuable insights into the therapeutic role of SYF-08 in Pb poisoning and also suggested that its administration can significantly alleviate the Pb-induced damage.
Effects of Salinity Stress at Reproductive Growth Stage on Rice (Oryza sativa L.) Composition, Starch Structure, and Physicochemical Properties
Authors: Yao Dongping , Wu Jun , Luo Qiuhong , Zhang Dongmeng , Zhuang Wen , Xiao Gui , Deng Qiyun , Bai Bin
Published: June 2022

This study aimed to investigate the changes in polished rice composition, starch structure, and physicochemical properties from three rice cultivars treated with medium and high salinity stress at the reproductive growth stage. The results showed that salt stress led to poor milling and appearance quality, higher total starch content, protein content, higher proportion of the medium, and long chains of amylopectin, as well as gelatinization temperature (GT) but lower amylose content and lower proportion of the short chain of amylopectin. Compared with salt-sensitive cultivars, the salt-tolerant cultivars exhibited lower GT and gelatinization enthalpy, better pasting properties, and more stable crystal structure; therefore, their eating and cooking quality (ECQ) was less affected. The above results imply that salt stress at the reproductive growth stage can degrade ECQ and can slightly increase the pasting property of starch from salt-tolerant rice cultivar.
Microencapsulation of Plant Phenolic Extracts Using Complex Coacervation Incorporated in Ultrafiltered Cheese Against AlCl3-Induced Neuroinflammation in Rats
Authors: Soliman Tarek N. , Mohammed Dina Mostafa , El-Messery Tamer M. , Elaaser Mostafa , Zaky Ahmed A. , Eun Jong-Bang , Shim Jae-Han , El-Said Marwa M.
Published: June 2022

Plant-derived phenolic compounds have numerous biological effects, including antioxidant, anti-inflammatory, and neuroprotective effects. However, their application is limited because they are degraded under environmental conditions. The aim of this study was to microencapsulate plant phenolic extracts using a complex coacervation method to mitigate this problem. Red beet (RB), broccoli (BR), and spinach leaf (SL) phenolic extracts were encapsulated by complex coacervation. The characteristics of complex coacervates [zeta potential, encapsulation efficiency (EE), FTIR, and morphology] were evaluated. The RB, BR, and SL complex coacervates were incorporated into an ultrafiltered (UF) cheese system. The chemical properties, pH, texture profile, microstructure, and sensory properties of UF cheese with coacervates were determined. In total, 54 male Sprague–Dawley rats were used, among which 48 rats were administered an oral dose of AlCl3 (100 mg/kg body weight/d). Nutritional and biochemical parameters, including malondialdehyde, superoxide dismutase, catalase, reduced glutathione, nitric oxide, acetylcholinesterase, butyrylcholinesterase, dopamine, 5-hydroxytryptamine, brain-derived neurotrophic factor, and glial fibrillary acidic protein, were assessed. The RB, BR, and SL phenolic extracts were successfully encapsulated. The RB, BR, and SL complex coacervates had no impact on the chemical composition of UF cheese. The structure of the RB, BR, and SL complex coacervates in UF cheese was the most stable. The hardness of UF cheese was progressively enhanced by using the RB, BR, and SL complex coacervates. The sensory characteristics of the UF cheese samples achieved good scores and were viable for inclusion in food systems. Additionally, these microcapsules improved metabolic strategies and neurobehavioral systems and enhanced the protein biosynthesis of rat brains. Both forms failed to induce any severe side effects in any experimental group. It can be concluded that the microencapsulation of plant phenolic extracts using a complex coacervation technique protected rats against AlCl3-induced neuroinflammation. This finding might be of interest to food producers and researchers aiming to deliver natural bioactive compounds in the most acceptable manner (i.e., food).
Chemical Structure and Immune Activation of a Glucan From Rhizoma Acori Tatarinowii
Authors: Zhang Wuxia , He Jiaqi , Hu Yihua , Lu Jingwu , Zhao Jinzhong , Li Peng
Published: June 2022

Rhizoma Acori Tatarinowii is a traditional Chinese herb used to treat depression and coronary heart disease. Studies on its active components mainly focus on small molecular compounds such as asarone and other essential oil components, while the large molecular active components such as polysaccharides are ignored. In this study, we aimed to study the chemical structure and immune activation of polysaccharides from Rhizoma Acori Tatarinowii. In this study, a polysaccharide (RATAPW) was isolated and purified by DEAE-52 cellulose and Sephadex G-100 column chromatography from alkali extraction polysaccharide of Rhizoma Acori Tatarinowii. The average molecular weight of RATAPW was 2.51 × 104 Da, and the total carbohydrate contents of RATAPW were 98.23 ± 0.29%. The monosaccharide composition, methylation, and nuclear magnetic resonance (NMR) analysis results displayed that the polysaccharide was α-1,4-glucan with short α-1,6 branches. Immunofluorescence assay and inhibitor neutralization assay indicated that RATAPW could promote the TNF-α production of RAW264.7 macrophage through the nuclear factor kappa B (NF-κB) molecular signaling pathway. Treatment with 200 μg/ml of RATAPW enhanced a 38.77% rise in the proliferation rate of spleen lymphocytes. RATAPW also enhances ConA-induced T cells and lipopolysaccharide (LPS)-induced B cell proliferation in a dose-dependent effect. Our study lays a foundation for the discovery of natural polysaccharide immune modulators or functional food from Rhizoma Acori Tatarinowii.
Collagen XI Alpha 1 Chain, a Novel Therapeutic Target for Cancer Treatment
Authors: Wu Yi-Hui , Chou Cheng-Yang
Published: June 2022

The extracellular matrix (ECM) plays an important role in the progression of cancer. Collagen is the most abundant component in ECM, and is involved in the biological formation of cancer. Although type XI collagen is a minor fibrillar collagen, collagen XI alpha 1 chain (COL11A1) expression has been found to be upregulated in a variety of human cancers including colorectal, esophagus, glioma, gastric, head and neck, lung, ovarian, pancreatic, salivary gland, and renal cancers. High levels of COL11A1 usually predict poor prognosis, owing to its association with angiogenesis, invasion, and drug resistance in cancer. However, little is known about the specific mechanism through which COL11A1 regulates tumor progression. Here, we have organized and summarized recent developments regarding the interactions between COL11A1 and intracellular signaling pathways and selected therapeutic agents targeting COL11A1, as these indicate its potential as a target for treatment of cancers, especially epithelial ovarian cancer.
Patterns of Treatment and Outcomes in Older Men With Penile Cancer: A SEER Dataset Analysis
Authors: Bourlon Maria T. , Verduzco-Aguirre Haydee , Molina Elizabeth , Meyer Elisabeth , Kessler Elizabeth , Kim Simon P. , Spiess Philippe E. , Flaig Thomas
Published: June 2022

Purpose

To evaluate clinicopathologic and treatment characteristics from a population-based cohort of penile cancer, with an emphasis in older adults, due to incomplete evidence to guide therapy in this age subgroup.

Materials and Methods

Patients with malignant penile tumors diagnosed 2004-2016 were identified in the Surveillance, Epidemiology and End Results Program (SEER)-18 dataset. Demographic and treatment characteristics were obtained. Population was analyzed by age at diagnosis (<65 vs ≥65 years). We examined univariate associations between age groups with Chi-square analysis. To study survival, we calculated Kaplan-Meier survival curves, but due to the high number of competing events, we also performed a univariate competing risk analysis using the cumulative incidence function, and a multivariate analysis using the Fine-Gray method. We also described competing mortality due to penile cancer and other causes of death.

Results

We included 3,784 patients. Median age was 68 years, 58.7% were aged ≥65. Older patients were less likely to have received chemotherapy (p<0.001), primary site surgery (p = 0.002), or therapeutic regional surgery (p <0.001). Median overall survival (OS) in patients <65 years was not reached (95% CI incalculable) vs 49 months in those ≥65 years (95% CI 45-53, p <0.0001). On univariate analysis, age was associated with a lower incidence of penile cancer death. On multivariate analysis, stage at diagnosis, and receipt of primary site surgery were associated with a higher incidence of penile cancer death. Estimated penile cancer-specific mortality was higher in patients <65 years in stages II-IV. Estimated mortality due to other causes was higher in older patients across all stages.

Conclusions

Older patients are less likely to receive surgery, chemotherapy and radiotherapy for penile cancer. Primary surgical resection was associated with better penile cancer-specific mortality on multivariate analysis. Competing mortality risks are highly relevant when considering OS in older adults with penile cancer. Factors associated with undertreatment of older patients with penile cancer need to be studied, in order to develop treatment strategies tailored for this population.
Case Report: The Value of Genomic Analysis in a Case of Megakaryoblastic Leukemia With Atypical Initial Manifestation
Authors: Gutiérrez-Jimeno Miriam , Panizo-Morgado Elena , Calvo-Imirizaldu Marta , Galán-Gómez Víctor , Escudero-López Adela , Patiño-García Ana
Published: June 2022

We report the case of a 7-month-old female patient who developed acute megakaryoblastic leukemia 6 months after the appearance of skull bone lesions. Initial evaluation and diagnosis of this patient were challenging and only achieved thanks to genomic analysis by NGS (next generation sequencing). It is unusual for the initial manifestation of acute megakaryoblastic leukemia to be a skull bone lesion. Extramedullary acute myeloid leukemia (eAML), also known as myeloid sarcoma (MS), often occurs simultaneously with acute myeloid leukemia (AML), although it may precede AML. Genomic analysis based on a NGS panel (Oncomine Childhood Cancer Research Assay) detected a RBM15::MKL1 fusion, a consequence of a t (1;22)(p13;q13) translocation, establishing the diagnosis of acute megakaryoblastic leukemia and enabling disease follow-up by qPCR. A diagnosis of eAML is built up from various findings in radiological, histological, immunophenotypic and genomic studies; when the tumor appears de novo, diagnosis is more complicated. We emphasize the importance of a multidisciplinary team in the initial approach to rare tumors and the use of genomic studies to contribute to the knowledge of these neoplasms, risk stratification and treatment planning.
Association Between Methylmalonic Acid and Cognition: A Systematic Review and Meta-Analysis
Authors: Wang Chao , Zhang Ying , Shu Jianbo , Gu Chunyu , Yu Yuping , Liu Wei
Published: June 2022

Background

Methylmalonic acid (MMA) is an intermediate metabolite of human body. The content of MMA in the blood of healthy people is very low, and its concentration will increase in some diseases and elderly people. Recent studies have shown that MMA has a variety of biological functions. The correlation between MMA and cognition, one of the important functions of the nervous system, is still uncertain.

Objective

Meta-analyses were performed to assess whether elevated MMA was associated with the risk of cognitive decline.

Materials and Methods

Cross-sectional studies, randomized controlled studies, and case-control studies on the relationship between MMA and cognition were obtained by searching PubMed, Web of Science, EMBASE, ProQuest, WANFANG MED ONLINE, China National Knowledge Infrastructure (CNKI) and Chongqing VIP until May 2022. Two researchers independently selected studies according to inclusion and exclusion criteria, evaluated study quality and extracted data. Meta-analyses were performed using Review Manager 5.4 software. The sensitivity analysis of meta-analysis was performed by One by one exclusion method.

Results

A total of 11 studies were included, including six cross-sectional studies, two randomized controlled studies, and three case-control studies, with a sample of 16,533 subjects. Meta-analysis showed that there was no significant difference in cognitive level between high-level MMA subjects and low-level MMA subjects in the general population [SMD = −2.19, 95% CI (−4.76 ∼ 0.38), Z = 1.67, P = 0.09]. In the population supplemented with VitB12, the increase of MMA level caused by VitB12 supplementation was not related to the change of cognition [SMD = 0.32, 95% CI (−0.19 ∼ 0.84) z = 1.22, P = 0.22]. There was also no significant difference in MMA levels between patients with dementia and the control group [WMD = 20.89, 95% CI (−5.13 ∼ 46.92), z = 1.57, P = 0.12].

Conclusion

In the general population, whether VitB12 is supplemented or not, there is no correlation between the increase of MMA level and the decrease of cognitive level. In dementia diseases, the level of MMA did not change significantly. High levels of MMA may not be a risk factor for cognitive impairment. The exact relationship between MMA and cognition needs further research.

Systematic Review Registration

[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021266310], identifier [CRD42021266310].
Effectiveness and Safety of Cystic Fibrosis Transmembrane Conductance Regulator Modulators in Children With Cystic Fibrosis: A Meta-Analysis
Authors: Li Qiyu , Liu Siyuan , Ma Xuemei , Yu Jiaping
Published: June 2022

Background and Aim

Cystic fibrosis (CF) is a genetic disease that is difficult to treat and caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Small molecules have been used to treat the symptom caused by CFTR mutations by restoring CFTR protein function. However, the data on children with CF are scarce. This meta-analysis aimed to evaluate the effectiveness and safety of this therapy in children diagnosed with CF.

Materials and Methods

Relevant studies were identified through searching medical databases before April 1, 2022. The primary outcomes of ppFEV1, lung clearance index2.5 (LCI2.5), sweat chloride concentration (SwCI), and Cystic Fibrosis Questionnaire-Revised (CFQ-R) score were pooled and analyzed. The secondary outcomes were nutritional status (weight, BMI, stature, and their z-score) and adverse events under therapy.

Results

A total of twelve studies were included. Compared with the placebo group, the pooled outcome of the ppFEV1, LCI2.5, SwCI, and CFQ-R score were improved by 7.91 {[95% confidence interval (CI), 3.71–12.12], –1.00 (95% CI, –1.38 to –0.63), –35.22 (95% CI, –55.51 to –14.92), and 4.45 (95% CI, 2.31–6.59), respectively}. Compared with the placebo group, the pooled result of the change in weight was improved by 1.53 (95% CI, 0.42–2.63). All the aforementioned results were also improved in single-arm studies. No clear differences in adverse events were found between CFTR modulator therapy and the placebo group.

Conclusion

CFTR modulators could improve multiaspect function in children with CF and result in comparable adverse events.
Pharmacological and Genetic Inhibition of HDAC4 Alleviates Renal Injury and Fibrosis in Mice
Authors: Shen Fengchen , Hou Xiying , Li Tingting , Yu Jianjun , Chen Huizhen , Liu Na , Qiu Andong , Zhuang Shougang
Published: June 2022

Histone deacetylase 4 (HDAC4) has been shown to be involved in cell proliferation, differentiation, and migration and is associated with a variety of cancers. However, the role of HDAC4 in renal fibrogenesis and its mechanisms are unclear. We assessed the role of HDAC4 and possible mechanisms of fibrosis in a murine model of kidney injury induced by unilateral ureteral obstruction (UUO) using tasquinimod, a highly selective HDAC4 inhibitor, and knockout mice with depletion of HDAC4 in renal tubular cells. UUO injury resulted in increased expression of HDAC4 and fibrotic proteins fibronectin and α-smooth muscle actin, while treatment with tasquinimod or knockout of HDAC4 significantly reduced their expression. Pharmacological and genetic inhibition of HDAC4 also decreased tubular epithelial cell arrest in the G2/M phase of the cell cycle, expression of transforming growth factor-β1 and phosphorylation of Smad3, signal transducer and activator of transcription 3, and extracellular signal-regulated kinase 1/2 in the injured kidney. Moreover, tasquinimod treatment or HDAC4 deletion inhibited UUO-induced renal tubular cell injury and apoptosis as indicated by reduced expression of neutrophil gelatinase–associated lipocalin, Bax, and inhibition of caspase-3. Finally, administration of tasquinimod or knockdown of HDAC4 prevented injury-related repression of Klotho, a renoprotective protein. Our results indicate that HDAC4 is critically involved in renal tubular injury and fibrosis and suggest that HDAC4 is a potential therapeutic target for treatment of chronic fibrotic kidney disease.
Underwater Transmitted Wavefront Manipulation Based on Bubble-Arrayed Acoustic Metasurfaces
Authors: Li Zhimin , Lin Zibin , Zeng Longsheng , Wu Hao , Zhu Xue-Feng
Published: June 2022

Manipulating underwater acoustic waves along the prescribed trajectory has great potential for various applications. Traditional metasurfaces for underwater acoustic modulation usually have complex structural designs and are complicated to manufacture. Here, we propose a simple strategy of embedding air bubbles of different sizes inside the polymer to freely manipulate the transmitted underwater acoustic wavefields. The transmitted phase shift covers the entire 2π range by adjusting the diameter of the bubbles. Utilizing the air-bubble array with precisely designed phase profiles, the abnormal refraction, self-bending beams, and bottle beams are univocally demonstrated based on the generalized Snell’s law. Our study can be used for designing waterborne metasurfaces with simple structures to freely manipulate the transmitted wavefronts and inspire lots of applications for underwater explorations.
Analysis of Worldwide Time-Series Data Reveals Some Universal Patterns of Evolution of the SARS-CoV-2 Pandemic
Authors: Mitrović Dankulov Marija , Tadić Bosiljka , Melnik Roderick
Published: June 2022

Predicting the evolution of the current epidemic depends significantly on understanding the nature of the underlying stochastic processes. To unravel the global features of these processes, we analyse the world data of SARS-CoV-2 infection events, scrutinising two 8-month periods associated with the epidemic’s outbreak and initial immunisation phase. Based on the correlation-network mapping, K-means clustering, and multifractal time series analysis, our results reveal several universal patterns of infection dynamics, suggesting potential predominant drivers of the pandemic. More precisely, the Laplacian eigenvectors localisation has revealed robust communities of different countries and regions that break into clusters according to similar profiles of infection fluctuations. Apart from quantitative measures, the immunisation phase differs significantly from the epidemic outbreak by the countries and regions constituting each cluster. While the similarity grouping possesses some regional components, the appearance of large clusters spanning different geographic locations is persevering. Furthermore, characteristic cyclic trends are related to these clusters; they dominate large temporal fluctuations of infection evolution, which are prominent in the immunisation phase. Meanwhile, persistent fluctuations around the local trend occur in intervals smaller than 14 days. These results provide a basis for further research into the interplay between biological and social factors as the primary cause of infection cycles and a better understanding of the impact of socio-economical and environmental factors at different phases of the pandemic.
Pathogenic Role of MicroRNA Dysregulation in Podocytopathies
Authors: Liu Feng , Chen Jiefang , Luo Changqing , Meng Xianfang
Published: June 2022

MicroRNAs (miRNAs) participate in the regulation of various important biological processes by regulating the expression of various genes at the post-transcriptional level. Podocytopathies are a series of renal diseases in which direct or indirect damage of podocytes results in proteinuria or nephrotic syndrome. Despite decades of research, the exact pathogenesis of podocytopathies remains incompletely understood and effective therapies are still lacking. An increasing body of evidence has revealed a critical role of miRNAs dysregulation in the onset and progression of podocytopathies. Moreover, several lines of research aimed at improving common podocytopathies diagnostic tools and avoiding invasive kidney biopsies have also identified circulating and urine miRNAs as possible diagnostic and prognostic biomarkers for podocytopathies. The present review mainly aims to provide an updated overview of the recent achievements in research on the potential applicability of miRNAs involved in renal disorders related to podocyte dysfunction by laying particular emphasis on focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous nephropathy (MN), diabetic kidney disease (DKD) and IgA nephropathy (IgAN). Further investigation into these dysregulated miRNAs will not only generate novel insights into the mechanisms of podocytopathies, but also might yield novel strategies for the diagnosis and therapy of this disease.
An Analysis Based on Japonica Rice Root Characteristics and Crop Growth Under the Interaction of Irrigation and Nitrogen Methods
Authors: Wang Zhuoqian , Jia Yan , Fu Jinxu , Qu Zhaojun , Wang Xinpeng , Zou Detang , Wang Jingguo , Liu Hualong , Zheng Hongliang , Wang Jin , Yang Liang , Xu Huimin , Zhao Hongwei
Published: June 2022

Water shortages and nitrogen (N) fertilizer overuse limit japonica rice production in Northeastern China. The interactions between water-saving irrigation and nitrogen management on rice root and shoot growth is still our research focus. Here, japonica rice (DN425) was subjected to the irrigation methods W1 (flooding irrigation), W2 [mild alternate wetting and drying irrigation (AWD); −10 kPa], W3 (severe AWD; −30 kPa), and different N fertilizer ratios were applied in different growth stages, namely, N1 (6:3:1:0), N2 (5:3:1:1), and N3 (4:3:2:1). From jointing to full heading stages, the highest photosynthate production capacity and root activity were obtained under W1N2. AWD markedly affected the root system and resulted in root senescence at later growth stages. Grain yield and N utilization efficiency were closely and positively correlated with the relative water content, crop growth rate (CGR), leaf area duration (LAD), the increase rate of root length density, root surface area density, and root volume density (RVD) from the jointing to full heading stages. This positive correlation was also observed in the increased rate of root bleeding sap (RBS) under W1N2 and CGR under W2N3. From full heading to maturity stages, N2 could promote root growth, LAD, and CGR under AWD to a greater extent than those under the other treatments. Water use efficiency (WUE) and N uptake efficiency (NUpE) were both negatively associated with the decreased rate of RVD, root dry weight (RDW), and RBS. They were closely and positively correlated with the increased rate of RDW and CGR. Our results suggested that W2N2 treatment delayed root senescence, maintained leaf photosynthesis, optimized the crop growth rate from full heading to maturity stages, and improved grain yield. The optimal grain yield, WUE, and NUpE were achieved at the irrigation water amount and topdressing fertilizer ratio of 41.40–50.34 × 102 and 31.20–34.83 kg ha–1, respectively.
Antecedents of Employee Green Behavior in the Hospitality Industry
Authors: Khan Noor Ullah , Cheng Jie , Yasir Muhammad , Saufi Roselina Ahmad , Nawi Noorshella Che , Bazkiaei Hanieh Alipour
Published: June 2022

Organizations are increasingly adopting green human resource management policies to encourage environmentally friendly behaviors. Research shows that adopting green policies and procedures is beneficial for the hospitality industry. However, limited empirical evidence exists on the association between environmental-specific ethical leadership, psychological green climate, and employees’ green behavior. Therefore, this study intends to examine psychological green climate (PGC) as a mediator between the relationship of environmental-specific ethical leadership (ESEL) and employees’ green behavior (EGB), specifically in the hotel industry of Pakistan. Data from 224 non-managerial position employees in the understudy sector was collected using a convenient sampling technique. Structural equation modeling (SEM) was utilized to examine the direct and indirect effects among the variables using the Smart PLS 3.3.3 version. This study showed that ESEL is positively related to PGC and EGB. Moreover, PGC is positively associated with EGB, and PGC mediated in the relationship between ESEL and EGB. Thus, current research highlights the significance of environmental-specific ethical leadership behavior, which assists in establishing a green psychological climate, thereby fostering employees’ green behavior in the hotel industry of Pakistan.
Love Is Blind! Exploring the Impact of Brand Love on eWOM in Chinese Hospitality Industry
Authors: Bilal Muhammad , Akram Umair , Zhang Yunfeng , Cai Shukai , Wang Zhuliang
Published: June 2022

The rising penetration and value of online information reviews in the hospitality industry have been extensively examined. People are increasingly interacting on interactive online media, prompting firms to create online communities to share electronic word-of-mouth (eWOM) with them and with one another in order to increase brand love. This study seeks to discover what drives consumers to participate in these online brand communities. To examine the research model, an online survey was conducted on 508 consumers who had shared eWOM on social networking sites (SNS). Structural equation modeling (SEM) was employed to test all hypotheses. The findings show that each of the variables has a high impact on brand love, with information quality and virtual interaction having the most significant impact. As a result of brand love, eWOM is significantly increased. Additionally, findings show that the gender gap in the online setting is increasing, as the influence of all characteristics then reward of online brand communities on brand love was adaptable among both male and female associates. Considering the effects of online features (information quality, system quality, virtual interaction, and reward) on online brand communities' impact on brand love and eWOM. Online hotels manager is advised to carefully develop their marketing strategies to retain and attract new consumers. Furthermore, online hotels manager can use the findings from this study to understand the consequences when eWOM is strongly influenced by online brand communities' features. This study is one of the first to illustrate and empirically confirm insight into how online features affect brand lovers in online brand communities. The study adds to the body of knowledge concerning the effectiveness of social media marketing in the Chinese hotel sector.
EEG Evidence of Altered Functional Connectivity and Microstate in Children Orphaned by HIV/AIDS
Authors: Gu Huang , Shan Xueke , He Hui , Zhao Junfeng , Li Xiaoming
Published: June 2022

Children orphaned by HIV/AIDS (“AIDS orphans”) suffer numerous early-life adverse events which have a long-lasting effect on brain function. Although previous studies found altered electroencephalography (EEG) oscillation during resting state in children orphaned by HIV/AIDS, data are limited regarding the alterations in connectivity and microstate. The current study aimed to investigate the functional connectivity (FC) and microstate in children orphaned by HIV/AIDS with resting-state EEG data. Data were recorded from 63 children orphaned by HIV/AIDS and 65 non-orphan controls during a close-eyes resting state. The differences in phase-locking value (PLV) of global average FC and temporal dynamics of microstate were compared between groups. For functional connectivity, children orphaned by HIV/AIDS showed decreased connectivity in alpha, beta, theta, and delta band compared with non-orphan controls. For microstate, EEG results demonstrated that children orphaned by HIV/AIDS show increased duration and coverage of microstate C, decreased occurrence and coverage of microstate B, and decreased occurrence of microstate D than non-orphan controls. These findings suggest that the microstate and functional connectivity has altered in children orphaned by HIV/AIDS compared with non-orphan controls and provide additional evidence that early life stress (ELS) would alter the structure and function of the brain and increase the risk of psychiatric disorders.
Vortioxetine Modulates the Regional Signal in First-Episode Drug-Free Major Depressive Disorder at Rest
Authors: Xiong Shihong , Li Wei , Zhou Yang , Ren Hongwei , Lin Guorong , Zhang Sheng , Xiang Xi
Published: June 2022

Background

Previous studies on brain functional alterations associated with antidepressants for major depressive disorder (MDD) have produced conflicting results because they involved short treatment periods and a variety of compounds.

Methods

Resting-state functional magnetic resonance imaging scans were obtained from 25 first-episode drug-free patients with MDD and 25 healthy controls. The patients, who were treated with vortioxetine for 8 weeks, were scanned at two-time points (baseline and week 8 of treatment). The amplitude of low-frequency fluctuation (ALFF) in the imaging data was used to analyze local brain signal alterations associated with antidepressant treatment.

Results

Compared with the controls, the patients at baseline showed decreased ALFF values in the right inferior temporal gyrus and increased ALFF values in the left inferior cerebellum, right cingulate gyrus and postcentral gyrus. After 8 weeks of vortioxetine treatment, patients showed increased ALFF values in the bilateral cingulate gyrus, middle temporal gyrus, medial superior frontal gyrus, and inferior cerebellum.

Conclusion

This study provided evidence that vortioxetine modulates brain signals in MDD sufferers. These findings contribute to the understanding of how antidepressants effect brain function.