bluuebunny/crossref_metadata_2025 huggingface dataset:
Restricted T-Cell Repertoire in the Epicardial Adipose Tissue of Non-ST Segment Elevation Myocardial Infarction Patients
Authors: Pedicino Daniela , Severino Anna , Di Sante Gabriele , De Rosa Maria Cristina , Pirolli Davide , Vinci Ramona , Pazzano Vincenzo , Giglio Ada F. , Trotta Francesco , Russo Giulio , Ruggio Aureliano , Pisano Eugenia , d’Aiello Alessia , Canonico Francesco , Ciampi Pellegrino , Cianflone Domenico , Cianfanelli Lorenzo , Grimaldi Maria Chiara , Filomia Simone , Luciani Nicola , Glieca Franco , Bruno Piergiorgio , Massetti Massimo , Ria Francesco , Crea Filippo , Liuzzo Giovanna
Published: July 2022

Aims

Human epicardial adipose tissue, a dynamic source of multiple bioactive factors, holds a close functional and anatomic relationship with the epicardial coronary arteries and communicates with the coronary artery wall through paracrine and vasocrine secretions. We explored the hypothesis that T-cell recruitment into epicardial adipose tissue (EAT) in patients with non-ST segment elevation myocardial infarction (NSTEMI) could be part of a specific antigen-driven response implicated in acute coronary syndrome onset and progression.

Methods and Results

We enrolled 32 NSTEMI patients and 34 chronic coronary syndrome (CCS) patients undergoing coronary artery bypass grafting (CABG) and 12 mitral valve disease (MVD) patients undergoing surgery. We performed EAT proteome profiling on pooled specimens from three NSTEMI and three CCS patients. We performed T-cell receptor (TCR) spectratyping and CDR3 sequencing in EAT and peripheral blood mononuclear cells of 29 NSTEMI, 31 CCS, and 12 MVD patients. We then used computational modeling studies to predict interactions of the TCR beta chain variable region (TRBV) and explore sequence alignments. The EAT proteome profiling displayed a higher content of pro-inflammatory molecules (CD31, CHI3L1, CRP, EMPRINN, ENG, IL-17, IL-33, MMP-9, MPO, NGAL, RBP-4, RETN, VDB) in NSTEMI as compared to CCS (P < 0.0001). CDR3-beta spectratyping showed a TRBV21 enrichment in EAT of NSTEMI (12/29 patients; 41%) as compared with CCS (1/31 patients; 3%) and MVD (none) (ANOVA for trend P < 0.001). Of note, 11/12 (92%) NSTEMI patients with TRBV21 perturbation were at their first manifestation of ACS. Four patients with the first event shared a distinctive TRBV21-CDR3 sequence of 178 bp length and 2/4 were carriers of the human leukocyte antigen (HLA)-A*03:01 allele. A 3D analysis predicted the most likely epitope able to bind HLA-A3*01 and interact with the TRBV21-CDR3 sequence of 178 bp length, while the alignment results were consistent with microbial DNA sequences.

Conclusions

Our study revealed a unique immune signature of the epicardial adipose tissue, which led to a 3D modeling of the TCRBV/peptide/HLA-A3 complex, in acute coronary syndrome patients at their first event, paving the way for epitope-driven therapeutic strategies.
Targeting Multiple End Organs in Lupus and Other Systemic Rheumatic Diseases by Inhibiting Bruton’s Tyrosine Kinase
Authors: Du Yong , Lei Ling , Ding Huihua , Chen Yanping , Pathak Simanta , Hicks John , Tran Phuongthy T. , Wu Minghua , Chang Betty , Wirtz Uwe , Mohan Chandra
Published: July 2022

Bruton tyrosine kinase (Btk) plays a vital role in activating and differentiating B-cells and regulating signaling in myeloid cells. Indeed, the potential use of Btk inhibitors in preventing lupus has been reported. Here, we extend these observations to 4 additional models of end-organ inflammation: (a) BWF1 lupus nephritis mice, (b) anti-GBM nephritis, (c) bleomycin-induced systemic sclerosis like skin disease, and (d) bleomycin-induced lung disease. In agreement with the previous studies, BTK inhibitor (BTKB66) treatment was effective in treating lupus nephritis in terms of reducing renal damage both functionally and histologically, accompanied by significant decrease in proteinuria. Both low-dose and high-dose BTKB66 profoundly blocked renal disease in the anti-GBM nephritis model, with efficacy that was comparable to that seen with dexamethasone. This study provides the first evidence that BTK inhibition has both therapeutic and preventative effects in bleomycin-induced SSc-like disease, in terms of reducing skin thickness, fibrosis, collagen deposition, and inflammation. Likewise, significantly lower lung inflammatory cell infiltration was observed after treatment with BTKB66. Therapeutic benefit was associated with lower numbers of macrophages, proliferating macrophages and activated T-cells in the respective injured organs. The observation that these immune cells play key roles in driving end organ inflammation in multiple systemic rheumatic diseases have broad implications for the use of BTKB66 in managing patients with systemic rheumatic diseases where multiple end organs are afflicted, including lupus and systemic sclerosis.
A Single Vaccination of Chimeric Bivalent Virus-Like Particle Vaccine Confers Protection Against H9N2 and H3N2 Avian Influenza in Commercial Broilers and Allows a Strategy of Differentiating Infected from Vaccinated Animals
Authors: Sun Yi-xue , Li Zheng-rong , Zhang Peng-ju , Han Jin-hong , Di Hai-yang , Qin Jia-yi , Cong Yan-long
Published: July 2022

H9N2 and H3N2 are the two most important subtypes of low pathogenic avian influenza viruses (LPAIV) because of their ongoing threat to the global poultry industry and public health. Although commercially available inactivated H9N2 vaccines are widely used in the affected countries, endemic H9N2 avian influenza remains uncontrolled. In addition, there is no available avian H3N2 vaccine. Influenza virus-like particles (VLPs) are one of the most promising vaccine alternatives to traditional egg-based vaccines. In this study, to increase the immunogenic content of VLPs to reduce production costs, we developed chimeric bivalent VLPs (cbVLPs) co-displaying hemagglutinin (HA) and neuraminidase (NA) of H9N2 and H3N2 viruses with the Gag protein of bovine immunodeficiency virus (BIV) as the inner core using the Bac-to-Bac baculovirus expression system. The results showed that a single immunization of chickens with 40μg/0.3mL cbVLPs elicited an effective immune response and provided complete protection against H9N2 and H3N2 viruses. More importantly, cbVLPs with accompanying serological assays can successfully accomplish the strategy of differentiating infected animals from vaccinated animals (DIVA), making virus surveillance easier. Therefore, this cbVLP vaccine candidate would be a promising alternative to conventional vaccines, showing great potential for commercial development.
Development and Validation of an ADME-Related Gene Signature for Survival, Treatment Outcome and Immune Cell Infiltration in Head and Neck Squamous Cell Carcinoma
Authors: Tang Xinran , Li Rui , Wu Dehua , Wang Yikai , Zhao Fang , Lv Ruxue , Wen Xin
Published: July 2022

ADME genes are a set of genes which are involved in drug absorption, distribution, metabolism, and excretion (ADME). However, prognostic value and function of ADME genes in head and neck squamous cell carcinoma (HNSCC) remain largely unclear. In this study, we established an ADME-related prognostic model through the least absolute shrinkage and selection operator (LASSO) analysis in the Cancer Genome Atla (TCGA) training cohort and its robustness was validated by TCGA internal validation cohort and a Gene Expression Omnibus (GEO) external cohort. The 14-gene signature stratified patients into high- or low-risk groups. Patients with high-risk scores exhibited significantly poorer overall survival (OS) and disease-free survival (DFS) than those with low-risk scores. Receiver operating characteristic (ROC) curve analysis was used to confirm the signature’s predictive efficacy for OS and DFS. Furthermore, gene ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analyses showed that immune-related functions and pathways were enriched, such as lymphocyte activation, leukocyte cell-cell adhesion and T-helper cell differentiation. The Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) and other analyses revealed that immune cell (especially B cell and T cell) infiltration levels were significantly higher in the low-risk group. Moreover, patients with low-risk scores were significantly associated with immunotherapy and chemotherapy treatment benefit. In conclusion, we constructed a novel ADME-related prognostic and therapeutic biomarker associated with immune cell infiltration of HNSCC patients.
Dynamics of host immune response development during Schistosoma mansoni infection
Authors: Costain Alice H. , Phythian-Adams Alexander T. , Colombo Stefano A. P. , Marley Angela K. , Owusu Christian , Cook Peter C. , Brown Sheila L. , Webb Lauren M. , Lundie Rachel J. , Borger Jessica G. , Smits Hermelijn H. , Berriman Matthew , MacDonald Andrew S.
Published: July 2022

Schistosomiasis is a disease of global significance, with severity and pathology directly related to how the host responds to infection. The immunological narrative of schistosomiasis has been constructed through decades of study, with researchers often focussing on isolated time points, cell types and tissue sites of interest. However, the field currently lacks a comprehensive and up-to-date understanding of the immune trajectory of schistosomiasis over infection and across multiple tissue sites. We have defined schistosome-elicited immune responses at several distinct stages of the parasite lifecycle, in three tissue sites affected by infection: the liver, spleen, and mesenteric lymph nodes. Additionally, by performing RNA-seq on the livers of schistosome infected mice, we have generated novel transcriptomic insight into the development of schistosome-associated liver pathology and fibrosis across the breadth of infection. Through depletion of CD11c+ cells during peak stages of schistosome-driven inflammation, we have revealed a critical role for CD11c+ cells in the co-ordination and regulation of Th2 inflammation during infection. Our data provide an updated and high-resolution account of how host immune responses evolve over the course of murine schistosomiasis, underscoring the significance of CD11c+ cells in dictating host immunopathology against this important helminth infection.
G-Protein-Coupled Receptors in Rheumatoid Arthritis: Recent Insights into Mechanisms and Functional Roles
Authors: Zhao Jianan , Wei Kai , Jiang Ping , Chang Cen , Xu Lingxia , Xu Linshuai , Shi Yiming , Guo Shicheng , He Dongyi
Published: July 2022

Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to joint damage and even disability. Although there are various clinical therapies for RA, some patients still have poor or no response. Thus, the development of new drug targets remains a high priority. In this review, we discuss the role of G-protein-coupled receptors (GPCRs), including chemokine receptors, melanocortin receptors, lipid metabolism-related receptors, adenosine receptors, and other inflammation-related receptors, on mechanisms of RA, such as inflammation, lipid metabolism, angiogenesis, and bone destruction. Additionally, we summarize the latest clinical trials on GPCR targeting to provide a theoretical basis and guidance for the development of innovative GPCR-based clinical drugs for RA.
Single-Cell RNA Sequencing Reveals the Pathogenic Relevance of Intracranial Atherosclerosis in Blood Blister-Like Aneurysms
Authors: Wen Dingke , Wang Xing , Chen Ruiqi , Li Hao , Zheng Jun , Fu Wei , Zhang Tianjie , Yang Mu , You Chao , Ma Lu
Published: July 2022

Background

Intracranial non-branching site blood blister-like aneurysms (BBA) are extremely rare and vicious. Their etiology remains elusive, and no molecular study has been carried out to reveal its pathogenic relevance to intracranial atherosclerosis. To investigate its transcriptomic landscape and underlying potential pathogenesis, we performed single-cell RNA sequencing with extensive pathological validation.

Methods

In total, 12,245 cells were recovered for single-cell RNA sequencing analysis from 1 BBA and 2 saccular intracranial aneurysms (IAs). Unbiased clustering using Seurat-based pipeline was used for cellular landscape profiling. Cellchat was used to understand intracellular communications. Furthermore, 10 BBAs and 30 IAs were retrospectively collected for pathological validations like scanning electron microscopy, H&E stain, Masson stain, Verhoeff Van Gielson stain, and immunofluorescence.

Results

Single-cell transcriptome profiled 14 total subclusters in 6 major groups, namely, 6 monocyte/macrophage clusters, 2 T&NK clusters, 3 vascular smooth muscle cell (VSMC) clusters, 1 dendritic cell, 1 B cell, and 1 endothelial cell cluster. The only mural cell identified in BBAs was VSMC-2 cluster, while mural cells in IAs comprise most clusters of VSMCs and endothelial cells. Upregulated genes in BBA-derived VSMCs are related to arterial mineralization and atherosclerosis, such as PTX3, SPP1, LOX, etc., whereas vasodilation and physiological regulatory genes such as MGP, ACTA2, and MYL9 were conversely enriched in conventional IA-derived VSMCs. Immune cells in the BBA were predominantly macrophages, with a low fraction of T&NK cells, while conventional IAs had a higher percentage of T&NK. Gene enrichment analysis suggested that macrophages in BBA were highly enriched in lipid metabolism as well as atherosclerosis. Ligand–receptor interaction suggested that secretory phosphoprotein 1 (also known as osteopontin) played a major role in mediating the intracellular communication between VSMC and macrophages, especially in BBA. Pathological experiments corroborate with the bioinformatic findings and further characterized BBAs as a thin-walled thrombotic aneurysm with severe atherosclerotic lesions, where ApoE+ macrophages and OPN+ mural cells are intimately involved in the inflammation process.

Conclusions

The preexisting intracranial atherosclerosis might predispose the parent artery to the pathogenic occurrence of BBAs. These data shed light on the pathophysiology of intracranial aneurysms and might assist in the further resolution of the complexity in aneurysm pathogenesis.
A Novel Ferroptosis-Related Long Non-Coding RNA Prognostic Signature Correlates With Genomic Heterogeneity, Immunosuppressive Phenotype, and Drug Sensitivity in Hepatocellular Carcinoma
Authors: Li Guanghao , Liu Yongheng , Zhang Yanting , Xu Yao , Zhang Jin , Wei Xianfu , Zhang Zhongmin , Zhang Chao , Feng Jinyan , Li Qiang , Wang Guowen
Published: July 2022

Hepatocellular carcinoma (HCC) with high heterogeneity is a common malignancy worldwide, but effective treatments are limited. Ferroptosis plays a critical role in tumors as a novel iron-dependent and reactive oxygen species-reliant type of cell death. Several studies have shown that long non-coding RNAs (lncRNAs) can drive HCC initiation and progression. However, the prognostic value of ferroptosis-related lncRNAs in patients with HCC has not been explored comprehensively. Gene set variation analysis (GSVA) based on gene set and RNA-seq profiles obtained from public databases indicated that ferroptosis is suppressed in HCC patients. Ferroptosis-related differentially expressed lncRNAs were screened by Pearson’s test. Univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression were performed to establish a novel five ferroptosis-related lncRNA signature in the training cohort with 60% patients, which was further verified in the testing cohort with 40% patients. Dimensionality reduction analysis, Kaplan–Meier curve, receiver operating characteristic (ROC) curve, independent prognostic analysis, and stratification analysis confirmed that our signature had a high clinical application value in predicting the overall survival of HCC patients. Compared to the clinicopathological factors and the other four published HCC prognostic signatures, the current risk model had a better predictive value. The comparison results of functional enrichment, tumor immune microenvironment, genomic heterogeneity, and drug sensitivity between the high- and low-risk groups showed that the risk score is associated with extensive genomic alterations, immunosuppressive tumor microenvironment, and clinical treatment response. Finally, cell experiments showed that silencing LNCSRLR expression inhibited the growth, proliferation, migration, and invasion of the HCC cell line. Thus, the model can function as an efficient indicator for predicting clinical prognosis and treatment of anticancer drugs in HCC patients.
Peroxisome Proliferator-Activated Receptors Regulate Hepatic Immunity and Assist in the Treatment of Primary Biliary Cholangitis
Authors: Wang Chang , Shi Ying , Wang Xiaomei , Ma Heming , Liu Quan , Gao Yanhang , Niu Junqi
Published: July 2022

Fibrates, which are agonists of peroxisome proliferator-activated receptor alpha, have received increasing attention in the treatment of primary biliary cholangitis. Reduced alkaline phosphatase levels and improved clinical outcomes were observed in patients with primary biliary cholangitis with an inadequate response to ursodeoxycholic acid (UDCA) monotherapy4 when treated with bezafibrate or fenofibrate combined with UDCA. In contrast to obeticholic acid, which exacerbates pruritus in patients, fibrates have been shown to relieve pruritus. Clinical trial outcomes show potential for the treatment of primary biliary cholangitis by targeting peroxisome proliferator-activated receptors. It is currently agreed that primary biliary cholangitis is an autoimmune-mediated cholestatic liver disease, and peroxisome proliferator-activated receptor is a nuclear receptor that regulates the functions of multiple immune cells, thus playing an important role in regulating innate and adaptive immunity. Therefore, this review focuses on the immune disorder of primary biliary cholangitis and summarizes the regulation of hepatic immunity when peroxisome proliferator-activated receptors are targeted for treating primary biliary cholangitis.
Malaria Transmission and Vector Resistance to Insecticides in a Changing Environment: Case of Simbock in Yaoundé-City, Cameroon
Authors: Mbakop Lili R. , Awono-Ambene Parfait H. , Ekoko Wolfgang E. , Mandeng Stanislas E. , Nwane Philippe , Fesuh Betrand N. , Toto Jean-Claude , Alenou Léo D. , Onguina Hugues G. , Piameu Michael , Fomena Abraham , Etang Josiane
Published: July 2022

Ecological upheavals resulting from uncontrolled urbanization can lead to significant changes in vector borne diseases’ profiles, thus requiring a thorough revision of their prevention and control strategies. The current study aimed at characterizing malaria vector populations in the Simbock neighborhood of Yaoundé-city (Cameroon), in relation to its urbanization scheme. Adult mosquitoes were captured by human landing catches (HLC) in- and outdoors prior to (2000–2006) and during infrastructural development (2014–2016). Anophelines were morphologically identified and analyzed for Plasmodium (P.) falciparum circumsporozoite protein detection using the ELISA technique. Species of the Anopheles (An.) gambiae complex were identified using SINE-PCR. Adult An. gambiae s.l. from larvae collected between 2014 and 2017 were tested for susceptibility to insecticides (0.1% bendiocarb, 4% DDT, 0.75% permethrin and 0.05% deltamethrin) with or without piperonyl butoxide (PBO) synergist, using WHO standard bioassays. The Hot Oligonucleotide Ligation Assay was used to detect the knockdown resistance (kdr) L995F/S mutations. Overall, nine malaria vector species were identified in 2000-2006, mostly An. moucheti (49%), An. nili (13.5%) and An. gambiae s.l. (12%); the six remaining species were represented at less than 3% each. However, only three species were found in 2014-2016, with increasing proportions of An. gambiae s.l. (67%) and An. funestus (32%) (P<0.0001). An. gambiae s.l. consisted An. coluzzii (> 85%) and An. gambiae (<15%) species during the two study periods. Plasmodium falciparum infection rates were 2.1% and 1.0% in 2000-2006 and 2014-2016 respectively (P=0.4), with decreasing entomological inoculation rates (EIR) from 0.34 infective bites per man per night (ib/m/n) to 0.02 ib/m/n (P<0.0001). Anopheles gambiae s.l. was resistant to DDT and permethrin [<40% mortality rates (MR)], and deltamethrin (65-89% MR), but fully susceptible to bendiocarb (100% MR). Pre-exposure of mosquitoes to PBO resulted in 90-100% MR to deltamethrin but not to permethrin. Furthermore, the two kdr L995F/S resistance alleles were recorded at 0.64 and 0.006 frequencies respectively. This study highlights a shift from rural to urban malaria transmission in Simbock, coupled with DDT and pyrethroid resistance in An. gambiae s.l. Combination vector control interventions, e.g., PBO nets and bendiocarb indoor residual spraying are needed in such areas.
Fluid-Driven Instabilities in Granular Media: From Viscous Fingering and Dissolution Wormholes to Desiccation Cracks and Ice Lenses
Authors: Liu Qi , Santamarina J. Carlos
Published: July 2022

Single and multi-phase fluids fill the pore space in sediments; phases may include gases (air, CH4, CO2, H2, and NH3), liquids (aqueous solutions or organic compounds), and even ice and hydrates. Fluids can experience instabilities within the pore space or trigger instabilities in the granular skeleton. Then, we divided fluid-driven instabilities in granular media into two categories. Fluid instabilities at constant fabric take place within the pore space without affecting the granular skeleton; these can result from hysteresis in contact angle and interfacial tension (aggravated in particle-laden flow), fluid compressibility, changes in pore geometry along the flow direction, and contrasting viscosity among immiscible fluids. More intricate fluid instabilities with fabric changes take place when fluids affect the granular skeleton, thus the evolving local effective stress field. We considered several cases: 1) open-mode discontinuities driven by drag forces, i.e., hydraulic fracture; 2) grain-displacive invasion of immiscible fluids, such as desiccation cracks, ice and hydrate lenses, gas and oil-driven openings, and capillary collapse; 3) hydro-chemo-mechanically coupled instabilities triggered by mineral dissolution during the injection of reactive fluids, from wormholes to shear band formation; and 4) instabilities associated with particle transport (backward piping erosion), thermal changes (thermo-hydraulic fractures), and changes in electrical interparticle interaction (osmotic-hydraulic fractures and contractive openings). In all cases, we seek to identify the pore and particle-scale positive feedback mechanisms that amplify initial perturbations and to identify the governing dimensionless ratios that define the stable and unstable domains. A [N/m] Contact line adhesion
Clonal Dissemination of Aeromonas hydrophila With Binary Carriage of blaKPC-2-Bearing Plasmids in a Chinese Hospital
Authors: Xu Zhijiang , Shen Weiyi , Zhang Rong , Cai Jiachang
Published: July 2022

Dissemination of the Klebsiella pneumoniae carbapenemase (KPC)-encoding gene among Enterobacterales is common but relatively rare in Aeromonas spp. In this study, we characterized two KPC-2-producing Aeromonas hydrophila strains (Ah2101 and Ah2111), each isolated from a patient in different intensive care units (ICUs) of a Chinese hospital. Whole-genome sequencing (WGS) revealed simultaneous carriage of the blaKPC−2 and imiH genes, both of which encode high-level carbapenem resistance in these two A. hydrophila isolates. The two isolates were shown to be clonally related and each isolate harbored two distinguishable blaKPC−2-bearing plasmids, only one of which was transferrable to A. hydrophila, but not Escherichia coli EC600 via conjugation. The genetic element that contains blaKPC−2 in these two plasmids, namely ISKpn27-ΔblaTEM−1-blaKPC−2-ISKpn6, was structurally identical, commonly detected in Enterobacterales, and associated with Tn3-based transposons. In addition, more than sixty putative genes that encode various virulence factors were identified in these two A. hydrophila isolates. This is the first study that reports clonal dissemination of carbapenem-resistant A. hydrophila strains carrying structurally different blaKPC−2-bearing plasmids. Further investigation is warranted to monitor the future transmission of blaKPC−2-bearing plasmids in A. hydrophila in clinical settings.
Pedunculopontine Nucleus Dysconnectivity Correlates With Gait Impairment in Parkinson’s Disease: An Exploratory Study
Authors: Joza Stephen , Camicioli Richard , Martin W. R. Wayne , Wieler Marguerite , Gee Myrlene , Ba Fang
Published: July 2022

Background

Gait impairment is a debilitating and progressive feature of Parkinson’s disease (PD). Increasing evidence suggests that gait control is partly mediated by cholinergic signaling from the pedunculopontine nucleus (PPN).

Objective

We investigated whether PPN structural connectivity correlated with quantitative gait measures in PD.

Methods

Twenty PD patients and 15 controls underwent diffusion tensor imaging to quantify structural connectivity of the PPN. Whole brain analysis using tract-based spatial statistics and probabilistic tractography were performed using the PPN as a seed region of interest for cortical and subcortical target structures. Gait metrics were recorded in subjects’ medication ON and OFF states, and were used to determine if specific features of gait dysfunction in PD were related to PPN structural connectivity.

Results

Tract-based spatial statistics revealed reduced structural connectivity involving the corpus callosum and right superior corona radiata, but did not correlate with gait measures. Abnormalities in PPN structural connectivity in PD were lateralized to the right hemisphere, with pathways involving the right caudate nucleus, amygdala, pre-supplementary motor area, and primary somatosensory cortex. Altered connectivity of the right PPN-caudate nucleus was associated with worsened cadence, stride time, and velocity while in the ON state; altered connectivity of the right PPN-amygdala was associated with reduced stride length in the OFF state.

Conclusion

Our exploratory analysis detects a potential correlation between gait dysfunction in PD and a characteristic pattern of connectivity deficits in the PPN network involving the right caudate nucleus and amygdala, which may be investigated in future larger studies.
Structural Brain Network Abnormalities in Parkinson’s Disease With Freezing of Gait
Authors: Jin Chaoyang , Yang Lei , Qi Shouliang , Teng Yueyang , Li Chen , Yao Yudong , Ruan Xiuhang , Wei Xinhua
Published: July 2022

Objective

Diffusion tensor imaging (DTI) studies have investigated white matter (WM) integrity abnormalities in Parkinson’s disease (PD). However, little is known about the topological changes in the brain network. This study aims to reveal these changes by comparing PD without freezing of gait (FOG) (PD FOG–), PD with FOG (PD FOG+), and healthy control (HC).

Methods

21 PD FOG+, 34 PD FOG-, and 23 HC were recruited, and DTI images were acquired. The graph theoretical analysis and network-based statistical method were used to calculate the topological parameters and assess connections.

Results

PD FOG+ showed a decreased normalized clustering coefficient, small-worldness, clustering coefficient, and increased local network efficiency compared with HCs. PD FOG+ showed decreased centrality, degree centrality, and nodal efficiency in the striatum, frontal gyrus, and supplementary motor area (SMA). PD FOG+ showed decreased connections in the frontal gyrus, cingulate gyrus, and caudate nucleus (CAU). The between centrality of the left SMA and left CAU was negatively correlated with FOG questionnaire scores.

Conclusion

This study demonstrates that PD FOG+ exhibits disruption of global and local topological organization in structural brain networks, and the disrupted topological organization can be potential biomarkers in PD FOG+. These new findings may provide increasing insight into the pathophysiological mechanism of PD FOG+.
Modular Organization of Signal Transmission in Primate Somatosensory Cortex
Authors: Mir Yaqub , Zalányi László , Pálfi Emese , Ashaber Mária , Roe Anna W. , Friedman Robert M. , Négyessy László
Published: July 2022

Axonal patches are known as the major sites of synaptic connections in the cerebral cortex of higher order mammals. However, the functional role of these patches is highly debated. Patches are formed by populations of nearby neurons in a topographic manner and are recognized as the termination fields of long-distance lateral connections within and between cortical areas. In addition, axons form numerous boutons that lie outside the patches, whose function is also unknown. To better understand the functional roles of these two distinct populations of boutons, we compared individual and collective morphological features of axons within and outside the patches of intra-areal, feedforward, and feedback pathways by way of tract tracing in the somatosensory cortex of New World monkeys. We found that, with the exception of tortuosity, which is an invariant property, bouton spacing and axonal convergence properties differ significantly between axons within patch and no-patch domains. Principal component analyses corroborated the clustering of axons according to patch formation without any additional effect by the type of pathway or laminar distribution. Stepwise logistic regression identified convergence and bouton density as the best predictors of patch formation. These findings support that patches are specific sites of axonal convergence that promote the synchronous activity of neuronal populations. On the other hand, no-patch domains could form a neuroanatomical substrate to diversify the responses of cortical neurons.
Study of Antidepressant-Like Effects of Albiflorin and Paeoniflorin Through Metabolomics From the Perspective of Cancer-Related Depression
Authors: Zhao Danping , Zhang Jianjun , Zhu Yingli , He Cheng , Fei Wenting , Yue Na , Wang Chenglong , Wang Linyuan
Published: July 2022

Mental health has become a new challenge in cancer treatment, with a high prevalence of depression in patients with cancer. Albiflorin (AF) and paeoniflorinn (PF) are isomers extracted from the root of Paeoniae Radix Alba (Baishao in Chinese), belonging to the monoterpene glycosides, and multiple studies have been conducted on their antidepression and anti-cancer effects. However, the effects of AF and PF on cancer-related depression are unclear. Therefore, the current study aims to investigate whether the two isomers are able to exert antidepressant-like effects and understand the underlying mechanisms in a rat model, established by combining irradiation with chronic restraint stress and solitary confinement. Our results demonstrate a significant regulation of AF and PF in the pharmacodynamic index, including the peripheral blood, organ index, behavioral traits, and HPA axis, relative to control rats. In serum and cerebral cortex metabonomics analysis, AF and PF showed a significantly restorative trend in abnormal biomarkers and regulating ether lipid metabolism, alanine, aspartate, glutamate metabolism, tryptophan metabolism, carnitine metabolism, arachidonic acid metabolism, arginine and proline metabolism pathway. Eight potential biomarkers were further screened by means of receiver operating characteristic (ROC) analysis. The data indicate that AF and PF could effectively ameliorate a depression-like state in the model rats, and the mechanism may be associated with the regulation of the neuroendocrine immune system and disrupted metabolic pathways. Further experiments are warranted to comprehensively evaluate the antidepressant effects of AF and PF in cancer-related depression. This study provides a better insight into the action mechanisms of antidepression of TCM, and provides a new perspective for the therapy of cancer-related depression.
Global Trend in the Research and Development of Acupuncture Treatment on Parkinson's Disease From 2000 to 2021: A Bibliometric Analysis
Authors: Li Xiaoping , Wei Wan , Wang Yuan , Wang Qiang , Liu Zhibin
Published: July 2022

Background

Acupuncture has been widely used in the treatment of patients with Parkinson's disease (PD) in the world. Despite we have an in-depth understanding of acupuncture in this field over the past years, there is no available literature on bibliometric analysis on the development of acupuncture on PD. This study was designed to explore the global trend in the research of acupuncture on PD in the recent 20 years by the software CiteSpace (5.8.R3) and VOSviewer (1.6.14).

Methods

Publications regarding acupuncture therapy for PD from 2000 to 2021 were retrieved from the Web of Science Core Collection database. CiteSpace and VOSviewer were used to analyze the number of publications, the contribution of countries, institutions, journals, authors, references, and keywords.

Results

A total of 217 studies were extracted from the database. The outputs of the publications in this field showed an upward trend during the past two decades. The country and institutions with the most publications in this field are China, South Korea, and the USA. They were the main contributors to the research. Kyung Hee University and Capital Medical University were the two most productive organizations. Hi-Joon Park had made the greatest contributions to the field. Evidence-based Complementary and Alternative Medicine was the most popular journals in this field. “Electroacupuncture” and “Bee venom acupuncture” were emerging research hotspots.

Conclusion

The research on acupuncture on PD is potential. Authors from different countries/regions and organizations need to remove the language and academic barriers to enhance global cooperation and communications. Scholars in this field need to publish their research findings in high-quality journals to gain more attention worldwide. This study indicated that the mechanism leading to the non-motor symptoms of PD, the establishment of appropriate models that fully reflects the non-motor features of human PD, and the efficacy and safety of promising therapies for patients with PD will remain research frontiers in the future.
Clinical Effect of Electroacupuncture on Acute Sleep Deprivation and Event-Related Potential Affecting the Inhibition Control of the Brain: Study Protocol for a Randomized Controlled Trial
Authors: Li Haiping , Wang Mengyu , Wu Yiming , Chen Xinwang , Xue Cong , Liu Peidong , Zhang Run , Liao Ziyun
Published: July 2022

Background

Acute sleep deprivation (ASD) can effect mood, attention, memory, alertness and metabolism. Especially, it is often accompanied by cognitive impairment of the brain. Acupuncture is safe and effective for improving cognitive function, but its underlying mechanism is not fully understood. In this study, an event-related potential (ERP) technique will be employed to measure the behavioral, cognitive, and physiological changes produced by electroacupuncture intervention after ASD.

Methods

We will recruit 60 healthy subjects. The participants will be randomly divided into a treatment group, a control group, a sham electroacupuncture group and a blank group, at a 1:1:1:1 ratio. The primary outcome will be determined by the change from baseline to 36 h in the MoCA score. The secondary results include the amplitude and latency of ERP N2 and P3, Go-hit rates, Go-RTs, No-Go-FA rates, the WCST, the Digit Span Subtest of the WAIS, the ESS score and FS-14. The 15 healthy subjects will not receive acupuncture treatment and ASD, but will receive EEG records and cognition functions test at the beginning and end of the experiment. Electroacupuncture intervention will be performed for 30 min once every 12 h, a total of three times. ERP measurements and other tests will be performed after baseline and ASD, and the statistician and outcome evaluator will be blinded to treatment allocation.

Discussion

This study is expected to investigate the effectiveness of electroacupuncture in improving cognition for ASD.

Trial Registration

ChiCTR2200055999.
The Spatiotemporal Dynamics of Cerebral Autoregulation in Functional Magnetic Resonance Imaging
Authors: Whittaker Joseph R. , Steventon Jessica J. , Venzi Marcello , Murphy Kevin
Published: July 2022

The thigh-cuff release (TCR) maneuver is a physiological challenge that is widely used to assess dynamic cerebral autoregulation (dCA). It is often applied in conjunction with Transcranial Doppler ultrasound (TCD), which provides temporal information of the global flow response in the brain. This established method can only yield very limited insights into the regional variability of dCA, whereas functional MRI (fMRI) has the ability to reveal the spatial distribution of flow responses in the brain with high spatial resolution. The aim of this study was to use whole-brain blood-oxygenation-level-dependent (BOLD) fMRI to characterize the spatiotemporal dynamics of the flow response to the TCR challenge, and thus pave the way toward mapping dCA in the brain. We used a data driven approach to derive a novel basis set that was then used to provide a voxel-wise estimate of the TCR associated haemodynamic response function (HRFTCR). We found that the HRFTCR evolves with a specific spatiotemporal pattern, with gray and white matter showing an asynchronous response, which likely reflects the anatomical structure of cerebral blood supply. Thus, we propose that TCR challenge fMRI is a promising method for mapping spatial variability in dCA, which will likely prove to be clinically advantageous.
A Co-driven Functional Electrical Stimulation Control Strategy by Dynamic Surface Electromyography and Joint Angle
Authors: Xu Rui , Zhao Xinyu , Wang Ziyao , Zhang Hengyu , Meng Lin , Ming Dong
Published: July 2022

Functional electrical stimulation (FES) is widely used in neurorehabilitation to improve patients’ motion ability. It has been verified to promote neural remodeling and relearning, during which FES has to produce an accurate movement to obtain a good efficacy. Therefore, many studies have focused on the relationship between FES parameters and the generated movements. However, most of the relationships have been established in static contractions, which leads to an unsatisfactory result when applied to dynamic conditions. Therefore, this study proposed a FES control strategy based on the surface electromyography (sEMG) and kinematic information during dynamic contractions. The pulse width (PW) of FES was determined by a direct transfer function (DTF) with sEMG features and joint angles as the input. The DTF was established by combing the polynomial transfer functions of sEMG and joint torque and the polynomial transfer functions of joint torque and FES. Moreover, the PW of two FES channels was set based on the muscle synergy ratio obtained through sEMG. A total of six healthy right-handed subjects were recruited in this experiment to verify the validity of the strategy. The PW of FES applied to the left arm was evaluated based on the sEMG of the right extensor carpi radialis (ECR) and the right wrist angle. The coefficient of determination (R2) and the normalized root mean square error (NRMSE) of FES-included and voluntary wrist angles and torques were used to verify the performance of the strategy. The result showed that this study achieved a high accuracy (R2 = 0.965 and NRMSE = 0.047) of joint angle and a good accuracy (R2 = 0.701 and NRMSE = 0.241) of joint torque reproduction during dynamic movements. Moreover, the DTF in real-time FES system also had a nice performance of joint angle fitting (R2 = 0.940 and NRMSE = 0.071) and joint torque fitting (R2 = 0.607 and NRMSE = 0.303). It is concluded that the proposed strategy is able to generate proper FES parameters based on sEMG and kinematic information for dynamic movement reproduction and can be used in a real-time FES system combined with bilateral movements for better rehabilitation.
Sex Differences in the Behavioural Outcomes of Prenatal Nicotine and Tobacco Exposure
Authors: Sikic Anita , Frie Jude A. , Khokhar Jibran Y. , Murray Jennifer E.
Published: July 2022

Smoking remains the leading cause of preventable death worldwide. A combination of biological and environmental risk factors make women especially vulnerable to nicotine addiction, making it harder for them to quit smoking. Smoking during pregnancy, therefore, is still a major health concern, with epidemiological data suggesting a role for gestational nicotine exposure in the development of several behavioural disorders. Given there are significant sex-specific behavioural outcomes related to smoking in adolescence and adulthood, it is probable that the behavioural outcomes following gestational nicotine or tobacco exposure are similarly sex-dependent. This is an especially relevant topic as the current landscape of nicotine use shifts toward vaping, a mode of high doses of nicotine delivery that is largely believed to be a safer alternative to cigarettes among the public as well as among pregnant women. Here we review existing clinical and preclinical findings regarding the sex-dependent behavioural outcomes of prenatal nicotine exposure. We also highlight the challenges within this literature, particularly those areas in which further research is necessary to improve consistency within, and between, clinical and preclinical findings.
Sports Bras Improve Chest Keloids but Outcomes Are Dependent on Breast Size: A Retrospective Analysis
Authors: Zhu Yanting , Zhang Qiguo , Gong Ting , Zhang Peng , Cheng Bo , Liu Jian , Ji Chao
Published: July 2022

Our study is a retrospective medical record review performed on 95 female keloid patients with the standard therapy combining complete surgical excision with superficial X-ray radiation. We aimed to analyze the relationship between breast size and treatment outcomes as well as the benefits of sports bras in the postoperative management of keloids. The results showed that the keloid score of no sports bra group was significantly worse than the score of sports bra group at 1-year follow-up. In addition, the large breast size group showed more significant improvement of keloid score when wearing sports bras. Our study highlights that continuous wearing a sports bra effectively reduces the skin tension of the postoperative incision and promotes recovery, especially for patients with large breast size.
Silenced LINC01134 Enhances Oxaliplatin Sensitivity by Facilitating Ferroptosis Through GPX4 in Hepatocarcinoma
Authors: Kang Xiaofeng , Huo Yan , Jia Songhao , He Fuliang , Li Huizi , Zhou Qing , Chang Nijia , Liu Donghui , Li Rongkuan , Hu Yi , Zhang Ping , Xu An
Published: July 2022

Purpose

Recently, long noncoding RNA LINC01134 has been shown to reduce cell viability and apoptosis via the antioxidant stress pathway, thereby enhancing OXA resistance in hepatocellular carcinoma. However, the association of LINC01134 with ferroptosis and the underlying molecular mechanisms remain to be elucidated.

Methods

Bioinformatics analysis was employed to screen lncRNAs positively correlated with GPX4 and poor clinical prognosis. And Western blot and RT-PCR analysis in HCC cells confirmed the effect of LINC01134 on GPX4 expression. In addition, LINC01134 siRNA was transfected in HCC cells to detect the changes in cell viability, ROS, lipid peroxidation, MDA levels and GSH/GSSG levels. CCK-8, colony formation and apoptosis assays were performed to determine the effect of LINC01134 on cell death. The effect of LINC01134 and OXA on Nrf2 transcriptional binding to GPX4 was analyzed using dual luciferase reporter assay and CHIP. The expression of GPX4 and Nrf2 in HCC tissues was detected by FISH and IHC.

Results

LINC01134 is a novel lncRNA positively correlated with GPx4 and associated with poor clinical prognosis. Silenced LINC01134 conferred OXA sensitivity by enhancing total ROS, lipid ROS, MDA levels and decreasing GSH/GSSG ratio. Mechanistically, LINC01134 and OXA could promote Nrf2 recruitment to the GPX4 promoter region to exert transcriptional regulation of GPX4. Clinically, LINC01134 was positively correlated with GPX4 or Nrf2, demonstrating the clinical significance of LINC01134, Nrf2 and GPX4 in OXA resistance of HCC.

Conclusions

We identified LINC01134/Nrf2/GPX4 as a novel and critical axis to regulate HCC growth and progression. Targeting GPX4, knocking down LINC01134 or Nrf2 could be a potential therapeutic strategy for HCC.
Chronic Lung Disease Following Neonatal Extracorporeal Membrane Oxygenation: A Single-Center Experience
Authors: Perez Ortiz Alba , Glauner Anna , Dittgen Felix , Doniga Thalia , Hetjens Svetlana , Schaible Thomas , Rafat Neysan
Published: July 2022

Objective

To assess the incidence and severity of chronic lung disease (CLD) after neonatal extracorporeal membrane oxygenation (ECMO) and to identify factors associated with its development.

Methods

A retrospective observational study in a neonatal ECMO center was conducted. All neonates who received support with ECMO in our institution between January 2019 and October 2021 were included and their pulmonary outcome was investigated.

Results

A total of 91 patients [60 with congenital diaphragmatic hernia (CDH), 26 with meconium aspiration syndrome, and 5 with other diagnoses] were included in this study. Sixty-eight (75%) neonates survived. Fifty-two (76%) ECMO survivors developed CLD. There was no statistical difference between patients with and without CLD with regard to gender or gestational age. Patients with CLD had lower birth weight, were younger at the initiation of ECMO, and required longer ECMO runs. Patients with CDH developed CLD more often than infants with other underlying diseases (94 vs. 60%). Seventeen ECMO survivors (25%) developed severe CLD.

Conclusion

The incidence of CLD after neonatal ECMO is substantial. Risk factors for its development include CDH as an underlying condition, the necessity for early initiation of ECMO, and the need for ECMO over 7 days.
Factors Surrounding the Healthcare Transition From Pediatric to Adult Care in 5p- Syndrome: A Survey Among Healthcare Professionals
Authors: Ishizaki Yuko , Matsuo Mari , Saito Kayoko , Fujihira Yoko
Published: July 2022

Background

The 5p- syndrome is associated with intellectual disturbance and physical complications from infancy, and patients continue treatment into adulthood. This study aimed to clarify the factors that facilitate and prevent healthcare transition from pediatric to adult care by conducting a questionnaire survey among medical professionals.

Subjects

The survey included 81 medical professionals nominated by an association of families of 5p- patients in Japan. The questions involved medical care for 5p- syndrome in adulthood, experience of transition, and factors facilitating a patient’s transition. Responses were obtained from 32 participants, with 27 answers eligible for analysis.

Results

The questionnaire items involved physical symptoms and concerns regarding support and welfare prompting consult. The most common physical symptom was constipation. Regarding support and welfare, all participants had an experience of receiving consultation about care for the siblings of patients. Three (11.1%) participants had an experience of transition. Regarding the transition of patients with rare diseases or intellectual disturbance, only four (14.8%) believed that progress was being made in the transition.

Discussion

Only 11% of the respondents experienced the transition of patients with 5p- syndrome. Because it is difficult for highly specialized adult care providers to deal with multidisciplinary complications of 5p- syndrome and information on prognosis and natural history is not known, it is presumed that the transition of 5p- syndrome did not progress. Factors to improve the transition of patients with 5p- syndrome and are likely to be effective for the transition of patients with other rare diseases or intellectual disabilities.