bluuebunny/crossref_metadata_2025 huggingface dataset:
Late Gadolinium Enhancement Cardiovascular Magnetic Resonance Assessment of Substrate for Ventricular Tachycardia With Hemodynamic Compromise
Authors: Whitaker John , Neji Radhouene , Kim Steven , Connolly Adam , Aubriot Thierry , Calvo Justo Juliá , Karim Rashed , Roney Caroline H. , Murfin Brendan , Richardson Carla , Morgan Stephen , Ismail Tevfik F. , Harrison James , de Vos Judith , Aalders Maurice C. G. , Williams Steven E. , Mukherjee Rahul , O'Neill Louisa , Chubb Henry , Tschabrunn Cory , Anter Elad , Camporota Luigi , Niederer Steven , Roujol Sébastien , Bishop Martin J. , Wright Matthew , Silberbauer John , Razavi Reza , O'Neill Mark
Published: October 2021

Background: The majority of data regarding tissue substrate for post myocardial infarction (MI) VT has been collected during hemodynamically tolerated VT, which may be distinct from the substrate responsible for VT with hemodynamic compromise (VT-HC). This study aimed to characterize tissue at diastolic locations of VT-HC in a porcine model.

Methods: Late Gadolinium Enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging was performed in eight pigs with healed antero-septal infarcts. Seven pigs underwent electrophysiology study with venous arterial-extra corporeal membrane oxygenation (VA-ECMO) support. Tissue thickness, scar and heterogeneous tissue (HT) transmurality were calculated at the location of the diastolic electrograms of mapped VT-HC.

Results: Diastolic locations had median scar transmurality of 33.1% and a median HT transmurality 7.6%. Diastolic activation was found within areas of non-transmural scar in 80.1% of cases. Tissue activated during the diastolic component of VT circuits was thinner than healthy tissue (median thickness: 5.5 mm vs. 8.2 mm healthy tissue, p < 0.0001) and closer to HT (median distance diastolic tissue: 2.8 mm vs. 11.4 mm healthy tissue, p < 0.0001). Non-scarred regions with diastolic activation were closer to steep gradients in thickness than non-scarred locations with normal EGMs (diastolic locations distance = 1.19 mm vs. 9.67 mm for non-diastolic locations, p < 0.0001). Sites activated late in diastole were closest to steep gradients in tissue thickness.

Conclusions: Non-transmural scar, mildly decreased tissue thickness, and steep gradients in tissue thickness represent the structural characteristics of the diastolic component of reentrant circuits in VT-HC in this porcine model and could form the basis for imaging criteria to define ablation targets in future trials.
Deep Neural Network to Accurately Predict Left Ventricular Systolic Function Under Mechanical Assistance
Authors: Bonnemain Jean , Zeller Matthias , Pegolotti Luca , Deparis Simone , Liaudet Lucas
Published: October 2021

Characterizing left ventricle (LV) systolic function in the presence of an LV assist device (LVAD) is extremely challenging. We developed a framework comprising a deep neural network (DNN) and a 0D model of the cardiovascular system to predict parameters of LV systolic function. DNN input data were systemic and pulmonary arterial pressure signals, and rotation speeds of the device. Output data were parameters of LV systolic function, including end-systolic maximal elastance (Emax,lv), a variable essential for adequate hemodynamic assessment of the LV. A 0D model of the cardiovascular system, including a wide range of LVAD settings and incorporating the whole spectrum of heart failure, was used to generate data for the training procedure of the DNN. The DNN predicted Emax,lv with a mean relative error of 10.1%, and all other parameters of LV function with a mean relative error of <13%. The framework was then able to retrieve a number of LV physiological variables (i.e., pressures, volumes, and ejection fraction) with a mean relative error of <5%. Our method provides an innovative tool to assess LV hemodynamics under device assistance, which could be helpful for a better understanding of LV-LVAD interactions, and for therapeutic optimization.
Toward the Development of Key Competencies: A Conceptual Framework for the STEM Curriculum Design and a Case Study
Authors: Hu Weiping , Guo Xipei
Published: October 2021

National attention has been given to science, technology, engineering, and mathematics (STEM) education, which is well recognized as an effective way to cultivate the key competencies of 21st-century talents. However, current STEM education falls short of the desired results. The fundamental reason is that there has not been a clearly and structurally explained systematic construction and effective implementation of STEM curricula. Accordingly, this article systematically expounds on the construction of the STEM curricula system from four aspects. Specifically, we first proposed the components of the STEM competencies as the goal of STEM education to provide a guiding direction for other parts of the design of the STEM curricula. Then, we elaborated on how to cultivate the STEM competencies from two aspects: the design principles of the STEM curricula content and the implementation strategies of STEM teaching. Finally, we explained how to effectively evaluate to monitor and improve the implementation of the STEM curriculum. In addition to the above mentioned, we then presented a case study of STEM courses constructed under the guidance of “think-based instruction theory” (TBIT) to help readers further understand the nature of the STEM curricula.
The Utility of Exosomes in Diagnosis and Therapy of Diabetes Mellitus and Associated Complications
Authors: Sun Yaoxiang , Tao Qing , Wu Xueqin , Zhang Ling , Liu Qi , Wang Lei
Published: October 2021

Diabetes mellitus and the associated complications are metabolic diseases with high morbidity that result in poor quality of health and life. The lack of diagnostic methods for early detection results in patients losing the best treatment opportunity. Oral hypoglycemics and exogenous insulin replenishment are currently the most common therapeutic strategies, which only yield temporary glycemic control rather than curing the disease and its complications. Exosomes are nanoparticles containing bioactive molecules reflecting individual physiological status, regulating metabolism, and repairing damaged tissues. They function as biomarkers of diabetes mellitus and diabetic complications. Considering that exosomes are bioactive molecules, can be obtained from body fluid, and have cell-type specificity, in this review, we highlight the multifold effects of exosomes in the pathology and therapy of diabetes mellitus and diabetic complications.
Clinical and Pathological Characteristics of Patients With Nonproteinuric Diabetic Nephropathy
Authors: Chang Dong-Yuan , Li Meng-Rui , Yu Xiao-Juan , Wang Su-Xia , Chen Min , Zhao Ming-Hui
Published: October 2021

Introduction

As the most common complication of diabetes mellitus (DM), diabetic nephropathy (DN) was initially considered to begin with proteinuria preceding the progression of renal insufficiency. This clinical paradigm has been questioned in the late decades, as many DM patients without proteinuria have progressive renal insufficiency. However, the characteristics of nonproteinuric DN were not fully clear yet.

Patients and Methods

A total of 390 patients with renal biopsy-proven DN in our center were retrospectively recruited in the current study. Clinical and histopathological data of the patients were analyzed. We used propensity score-matching methods to address the imbalance of age, sex, and diabetes duration for comparative analyses.

Results

Among all the renal biopsy-proven DN patients with renal biopsy proven DN, 18 patients were classified as nonproteinuric DN. Compared with 36 propensity score-matched proteinuric DN patients, diabetic retinopathy (DR) was less frequent in nonproteinuric DN patients (38.9% vs. 66.4%, p<0.05). During the follow-up of 24.0 (12.0–42.0) months, the probability of developing the end-stage renal disease (ESRD) was significantly lower in nonproteinuric DN patients than in proteinuric ones in both the propensity score-matched cohort and overall cohort (log-rank test, p<0.001 and p<0.001, respectively).

Conclusions

Compared with proteinuric DN patients, DR was less frequent in nonproteinuric DN patients. Nonproteinuric DN patients had better renal outcomes than proteinuric DN patients.
How Birds During Migration Maintain (Oxidative) Balance
Authors: McWilliams Scott , Carter Wales , Cooper-Mullin Clara , DeMoranville Kristen , Frawley Abigail , Pierce Barbara , Skrip Megan
Published: October 2021

Animals dynamically adjust their physiology and behavior to survive in changing environments, and seasonal migration is one life stage that demonstrates these dynamic adjustments. As birds migrate between breeding and wintering areas, they incur physiological demands that challenge their antioxidant system. Migrating birds presumably respond to these oxidative challenges by up-regulating protective endogenous systems or accumulating dietary antioxidants at stopover sites, although our understanding of the pre-migration preparations and mid-migration responses of birds to such oxidative challenges is as yet incomplete. Here we review evidence from field and captive-bird studies that address the following questions: (1) Do migratory birds build antioxidant capacity as they build fat stores in preparation for long flights? (2) Is oxidative damage an inevitable consequence of oxidative challenges such as flight, and, if so, how is the extent of damage affected by factors such as the response of the antioxidant system, the level of energetic challenge, and the availability of dietary antioxidants? (3) Do migratory birds ‘recover’ from the oxidative damage accrued during long-duration flights, and, if so, does the pace of this rebalancing of oxidative status depend on the quality of the stopover site? The answer to all these questions is a qualified ‘yes’ although ecological factors (e.g., diet and habitat quality, geographic barriers to migration, and weather) affect how the antioxidant system responds. Furthermore, the pace of this dynamic physiological response remains an open question, despite its potential importance for shaping outcomes on timescales ranging from single flights to migratory journeys. In sum, the antioxidant system of birds during migration is impressively dynamic and responsive to environmental conditions, and thus provides ample opportunities to study how the physiology of migratory birds responds to a changing and challenging world.
Establishment of Prognosis Model in Acute Myeloid Leukemia Based on Hypoxia Microenvironment, and Exploration of Hypoxia-Related Mechanisms
Authors: Zhong Jinman , Wu Hang , Bu Xiaoyin , Li Weiru , Cai Shengchun , Du Meixue , Gao Ya , Ping Baohong
Published: October 2021

Acute myeloid leukemia (AML) is a highly heterogeneous hematologic neoplasm with poor survival outcomes. However, the routine clinical features are not sufficient to accurately predict the prognosis of AML. The expression of hypoxia-related genes was associated with survival outcomes of a variety of hematologic and lymphoid neoplasms. We established an 18-gene signature-based hypoxia-related prognosis model (HPM) and a complex model that consisted of the HPM and clinical risk factors using machine learning methods. Both two models were able to effectively predict the survival of AML patients, which might contribute to improving risk classification. Differentially expressed genes analysis, Gene Ontology (GO) categories, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to reveal the underlying functions and pathways implicated in AML development. To explore hypoxia-related changes in the bone marrow immune microenvironment, we used CIBERSORT to calculate and compare the proportion of 22 immune cells between the two groups with high and low hypoxia-risk scores. Enrichment analysis and immune cell composition analysis indicated that the biological processes and molecular functions of drug metabolism, angiogenesis, and immune cell infiltration of bone marrow play a role in the occurrence and development of AML, which might help us to evaluate several hypoxia-related metabolic and immune targets for AML therapy.
Translational and Clinical Applications of Dental Stem Cell-Derived Exosomes
Authors: Mai Zizhao , Chen Huan , Ye Yu , Hu Ziyu , Sun Wenjuan , Cui Li , Zhao Xinyuan
Published: October 2021

Mesenchymal stem cells (MSCs) are promising seed cells in tissue repair and regeneration due to their featured properties of self-renewal and multipotency. However, a growing body of evidence has demonstrated that MSCs exert biological functions mainly through secreting exosomes. Exosomes, which contain RNA, proteins, lipids, and metabolites, are new players in regulating many fundamental processes and play important roles in regenerative medicine. Exosomes not only mimic the effects of their parent cells but also possess many advantages such as high drug loading capacity, low immunogenicity, excellent biocompatibility, and low side effects. Currently, a total of 6 different dental stem cells (DSCs) including dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHEDs), periodontal ligament stem cells (PDLSCs), dental follicle progenitor cells (DFPCs), stem cells from apical papilla (SCAPs) and gingival mesenchymal stem cells (GMSCs) have been isolated and identified. DSC-derived exosomes (DSC-Exos) are actively involved in intercellular communication, anti-inflammation, osteogenesis, angiogenesis, immunomodulation, nurturing neurons, and promoting tumor cell apoptosis. In this review, we will critically review the emerging role and clinical application potential of DSC-Exos.
RAB11FIP1: An Indicator for Tumor Immune Microenvironment and Prognosis of Lung Adenocarcinoma from a Comprehensive Analysis of Bioinformatics
Authors: Zhang Wenyi , Chen Ting , Liu Jun , Yu Shali , Liu Lei , Zheng Miaosen , Liu Yifei , Zhang Hongbing , Bian Tingting , Zhao Xinyuan
Published: October 2021

Lung adenocarcinoma (LUAD) was the first one all over the world. RAB11FIP1 was found to be expressed differently in a critical way among different cancers. However, the prognostic value and immune infiltration of RAB11FIP1 expression in LUAD are unclear. In this study, the expression of RAB11FIP1 in LUAD was investigated in the Oncomine, TCGA, GEO, and UALCAN databases. Kaplan-Meier analysis was chosen to compare the association between RAB11FIP1 expression and overall survival (OS) in LUAD patients. The dataset of TCGA was used to analyze the pertinence between RAB11FIP1 and clinicpathological factors. GO, KEGG, and network analysis of protein-protein interactions (PPI) were conducted to investigate the potential mechanism of RAB11FIP1. In the end, the relevance of RAB11FIP1 to cancer-immune infiltrates was investigated. RAB11FIP1 was found to be down-regulated by tumors compared with adjacent normal tissue in multiple LUAD cohorts. RAB11FIP1 is an independent prognostic factor in lung adenocarcinoma. There was a high correlation between low RAB11FIP1 in tumors and worse OS in LUAD. Functional network analysis suggested that RAB11FIP1 was associated with multiple pathways. Besides, the expression of RAB11FIP1 was closely related to the infiltration levels of B cell, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. RAB11FIP1 expression in LUAD occurred with a variety of immune markers. Our findings suggest that RAB11FIP1 is related to prognosis and immune infiltrates in LUAD.
Immune-Related Genes to Construct a Novel Prognostic Model of Breast Cancer: A Chemosensitivity-Based Study
Authors: Deng Zhi-Min , Hu Wei , Dai Fang-Fang , Yuan Meng-Qin , Hu Min , Cheng Yan-Xiang
Published: October 2021

Chemotherapy combined with surgery is effective for patients with breast cancer (BC). However, chemoresistance restricts the effectiveness of BC treatment. Immune microenvironmental changes are of pivotal importance for chemotherapy responses. Thus, we sought to construct and validate an immune prognostic model based on chemosensitivity status in BC. Here, immune-related and chemosensitivity-related genes were obtained from GSE25055. Then, univariate analysis was employed to identify prognostic-related gene pairs from the intersection of the two parts of the genes, and modified least absolute shrinkage and selection operator (LASSO) analysis was performed to build a prognostic model. Furthermore, we investigated the efficiency of this model from various perspectives, and further validation was performed using the Cancer Genome Atlas (TCGA) cohorts. We identified seven immune and chemosensitivity-related gene pairs and incorporated them into the Cox regression model. After multilevel validation, the risk model was found to be closely related to the survival rate, various clinical characteristics, tumor mutation burden (TMB) score, immune checkpoints, and response to chemotherapeutic drugs. In addition, the model was verified to exhibit predictive capacity as an independent factor over other candidate clinical features. Notably, the constructed nomogram was more accurate than any single factor. Altogether, the risk score model and the nomogram have potential predictive value and may have important practical implications.
Following the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progression
Authors: Souza Flávia dos Santos , Freitas Nicole Lardini , Gomes Yago Côrtes Pinheiro , Torres Rafael Carvalho , Echevarria-Lima Juliana , Silva-Filho Isaac Lima da , Leite Ana Claudia Celestino Bezerra , Lima Marco Antonio Sales Dantas de , Silva Marcus Tulius Teixeira da , Araújo Abelardo de Queiroz Campos , Espíndola Otávio Melo
Published: October 2021

Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease due to axonal damage of the corticospinal secondary to an inflammatory response against infected T-cells. In the present work, we aimed to evaluate biomarkers of neurodegeneration and neuroinflammation in the definition of HAM/TSP prognosis. Neurofilament light (NfL) and phosphorylated heavy (pNfH) chains, total Tau protein, cellular prion protein (PrPc), inflammatory chemokines, and neopterin were quantified in paired cerebrospinal fluid (CSF) and serum samples from HAM/TSP patients (n=21), HTLV-1 asymptomatic carriers (AC) (n=13), and HTLV-1 seronegative individuals with non-inflammatory non-degenerative neurological disease (normal-pressure hydrocephalus) (n=9) as a control group. HTLV-1 proviral load in peripheral blood mononuclear cells and the expression of chemokine receptors CCR4, CCR5, and CXCR3 in infected CD4+ T-cells (HTLV-1 Tax+ cells) were also assessed. CSF levels of Tau, NfL, and pNfH were similar between groups, but PrPc and neopterin were elevated in HAM/TSP patients. Most individuals in the control group and all HTLV-1 AC had CSF/serum neopterin ratio < 1.0, and two-thirds of HAM/TSP patients had ratio values > 1.0, which positively correlated with the speed of disease progression and pNfH levels, indicating active neuroinflammation. HAM/TSP patients showed high serum levels of CXCR3-binding chemokines (CXCL9, CXCL10, and CXCL11) and elevated CSF levels of CCL2, CCL3, CCL4, CCL17, CXCL5, CXCL10, and CXCL11. Indeed, CXCL10 concentration in CSF of HAM/TSP patients was 5.8-fold and 8.7-fold higher in than in HTLV-1 AC and controls, respectively, and correlated with CSF cell counts. HAM/TSP patients with typical/rapid disease progression had CSF/serum CXCL10 ratio > 1.0 and a higher frequency of CXCR3+Tax+CD4+ T-cells in blood, which indicated a positive gradient for the migration of infected cells and infiltration into the central nervous system. In conclusion, the slow progression of HAM/TSP abrogates the usefulness of biomarkers of neuronal injury for the disease prognosis. Thus, markers of inflammation provide stronger evidence for HAM/TSP progression, particularly the CSF/serum neopterin ratio, which may contribute to overcome differences between laboratory assays.
S100A9 Activates the Immunosuppressive Switch Through the PI3K/Akt Pathway to Maintain the Immune Suppression Function of Testicular Macrophages
Authors: Fan Zun Pan , Peng Mei Lin , Chen Yuan Yao , Xia Yu Ze , Liu Chun Yan , Zhao Kai , Zhang Hui Ping
Published: October 2021

Macrophages are functionally plastic and can thus play different roles in various microenvironments. Testis is an immune privileged organ, and testicular macrophages (TMs) show special immunosuppressive phenotype and low response to various inflammatory stimuli. However, the underlying mechanism to maintain the immunosuppressive function of TMs remains unclear. S100A9, a small molecular Ca2+ binding protein, is associated with the immunosuppressive function of macrophages. However, no related research is available about S100A9 in mouse testis. In the present study, we explored the role of S100A9 in TMs. We found that S100A9 was expressed in TMs from postnatal to adulthood and contributed to maintaining the immunosuppressive phenotype of TMs, which is associated with the activation of PI3K/Akt pathway. S100A9 treatment promotes the polarization of bone marrow-derived macrophages from M0 to M2 in vitro. S100A9 was significantly increased in TMs following UPEC-infection and elevated S100A9 contributed to maintain the M2 polarization of TMs. Treatment with S100A9 and PI3K inhibitor decreased the proportion of M2-type TMs in control and UPEC-infected mouse. Our findings reveal a crucial role of S100A9 in maintaining the immunosuppressive function of TMs through the activation of PI3K/Akt pathway, and provide a reference for further understanding the mechanism of immunosuppressive function of TMs.
Synthesis of Thresholds of Ocean Acidification Impacts on Decapods
Authors: Bednaršek Nina , Ambrose Richard , Calosi Piero , Childers Richard K. , Feely Richard A. , Litvin Steven Y. , Long W. Christopher , Spicer John I. , Štrus Jasna , Taylor Jennifer , Kessouri Faycal , Roethler Miranda , Sutula Martha , Weisberg Stephen B.
Published: October 2021

Assessing decapod sensitivity to regional-scale ocean acidification (OA) conditions is limited because of a fragmented understanding of the thresholds at which they exhibit biological response. To address this need, we undertook a three-step data synthesis: first, we compiled a dataset composed of 27,000 datapoints from 55 studies of decapod responses to OA. Second, we used statistical threshold analyses to identify OA thresholds using pH as a proxy for 13 response pathways from physiology to behavior, growth, development and survival. Third, we worked with the panel of experts to review these thresholds, considering the contributing datasets based on quality of the study, and assign a final thresholds and associated confidence scores based on quality and consistency of findings among studies. The duration-dependent thresholds were within a pH range from 7.40 to 7.80, ranging from behavioral and physiological responses to mortality, with many of the thresholds being assigned medium-to-high confidence. Organism sensitivity increased with the duration of exposure but was not linked to a specific life-stage. The thresholds that emerge from our analyses provide the foundation for consistent interpretation of OA monitoring data or numerical ocean model simulations to support climate change marine vulnerability assessments and evaluation of ocean management strategies.
Higher Incidence of Chronic Thromboembolic Pulmonary Hypertension After Acute Pulmonary Embolism in Asians Than in Europeans: A Meta-Analysis
Authors: Pang Wenyi , Zhang Zhu , Wang Zenghui , Zhen Kaiyuan , Zhang Meng , Zhang Yunxia , Gao Qian , Zhang Shuai , Tao Xincao , Wan Jun , Xie Wanmu , Zhai Zhenguo
Published: October 2021

Aim: To summarize the incidence of right heart catheter diagnosed chronic thromboembolic pulmonary hypertension (CTEPH) after acute pulmonary embolism (PE) in a meta-analysis.

Methods: Cohort studies reporting the incidence of CTEPH after acute PE were identified via search of Medline, Embase, China National Knowledge Infrastructure and WanFang databases.

Results: Twenty-two cohort studies with 5,834 acute PE patients were included. Pooled results showed that the overall incidence of CTEPH was 2.82% (95% CI: 2.11–3.53%). Subgroup analyses showed higher incidence of CTEPH in Asians than Europeans (5.08 vs. 1.96%, p = 0.01), in retrospective cohorts than prospective cohorts (4.75 vs. 2.47%, p = 0.02), and in studies with smaller sample size than those with larger sample size (4.57 vs. 1.71%, p < 0.001). Stratified analyses showed previous venous thromboembolic events and unprovoked PE were both significantly associated with increased risk of CTEPH (OR = 2.57 and 2.71, respectively; both p < 0.01).

Conclusions: The incidence of CTEPH after acute PE is ~3% and the incidence is higher in Asians than Europeans. Efforts should be made for the early diagnosis and treatment of CTEPH in PE patients, particularly for high-risk population.
The Misattributed and Silent Causes of Poor COVID-19 Outcomes Among Pregnant Women
Authors: Machluf Yossy , Rosenfeld Sherman , Ben Shlomo Izhar , Chaiter Yoram , Dekel Yaron
Published: October 2021

Abundant evidence strongly suggests that the condition of pregnancy makes women and their fetuses highly vulnerable to severe Corona-virus 2019 (COVID-19) complications. Here, two novel hypoxia-related conditions are proposed to play a pivotal role in better understanding the relationship between COVID-19, pregnancy and poor health outcomes. The first condition, “misattributed dyspnea (shortness of breath)” refers to respiratory symptoms common to both advanced pregnancy and COVID-19, which are mistakenly perceived as related to the former rather than to the latter; as a result, pregnant women with this condition receive no medical attention until the disease is in an advanced stage. The second condition, “silent hypoxia”, refers to abnormally low blood oxygen saturation levels in COVID-19 patients, which occur in the absence of typical respiratory distress symptoms, such as dyspnea, thereby also leading to delayed diagnosis and treatment. The delay in diagnosis and referral to treatment, due to either “misattributed dypsnea” or “silent hypoxia”, may lead to rapid deterioration and poor health outcome to both the mothers and their fetuses. This is particularly valid among women during advanced stages of pregnancy as the altered respiratory features make the consequences of the disease more challenging to cope with. Studies have demonstrated the importance of monitoring blood oxygen saturation by pulse oximetry as a reliable predictor of disease severity and outcome among COVID-19 patients. We propose the use of home pulse oximetry during pregnancy as a diagnostic measure that, together with proper medical guidance, may allow early diagnosis of hypoxia and better health outcomes.
Peripheral Immune Cells Exhaustion and Functional Impairment in Patients With Chronic Hepatitis B
Authors: Jin Xin , Yan Zhi-han , Lu Lingna , Lu Shengjia , Zhang Guoping , Lin Wei
Published: October 2021

After infection of hepatitis B virus (HBV), the virus induces a variety of immune disorders in the host, leading to immune escape and, finally, the chronicity of the disease. This study investigated immune cell defects and functional impairment in patients with chronic hepatitis B (CHB). We analyzed the percentage, function, and phenotypes of various immune cell subpopulations in the peripheral blood along with the concentrations of cytokines in the plasma. We compared the results between patients with CHB and healthy individuals. It was found that in patients with CHB, the cell function was impaired and, there was increased expression of inhibitory receptors, such as NKG2A and PD-1 in both NK and T cells. The impairment of function was mainly in cytokine secretion, and the cytotoxicity was not significantly diminished. We also found that the proportion of dendritic cells (DC) decreased and regulatory B cells (Breg) increased in CHB. In addition, the Breg cells were negatively correlated with T cell cytokine and positively correlated with ALT and HBV viral load. Taken together, various disorders and functional impairments were found in the immune cells of peripheral blood in CHB patients, especially NK and T cells. These cells showed exhaustion and the increase of regulatory B cells may be one of the reasons for this phenomenon.
Functional Characterization of the Nep1-Like Protein Effectors of the Necrotrophic Pathogen – Alternaria brassicae
Authors: Duhan Deepak , Gajbhiye Shivani , Jaswal Rajdeep , Singh Ravindra Pal , Sharma Tilak Raj , Rajarammohan Sivasubramanian
Published: October 2021

Alternaria brassicae is an important necrotrophic pathogen that infects the Brassicaceae family. A. brassicae, like other necrotrophs, also secretes various proteinaceous effectors and metabolites that cause cell death to establish itself in the host. However, there has been no systematic study of A. brassicae effectors and their roles in pathogenesis. The availability of the genome sequence of A. brassicae in public domain has enabled the search for effectors and their functional characterization. Nep1-like proteins (NLPs) are a superfamily of proteins that induce necrosis and ethylene biosynthesis. They have been reported from a variety of microbes including bacteria, fungi, and oomycetes. In this study, we identified two NLPs from A. brassicae viz. AbrNLP1 and AbrNLP2 and functionally characterized them. Although both AbrNLPs were found to be secretory in nature, they localized differentially inside the plant. AbrNLP2 was found to induce necrosis in both host and non-host species, while AbrNLP1 could not induce necrosis in both species. Additionally, AbrNLP2 was shown to induce pathogen-associated molecular pattern (PAMP)-triggered immunity in both host and non-host species. Overall, our study indicates that AbrNLPs are functionally and spatially (subcellular location) distinct and may play different but important roles during the pathogenesis of A. brassicae.
Mechanism and Potential of Extracellular Vesicles Derived From Mesenchymal Stem Cells for the Treatment of Infectious Diseases
Authors: You Jingyi , Fu Zhou , Zou Lin
Published: October 2021

Extracellular vesicles (EVs) are nano-sized membrane vesicles secreted by cells. EVs serve as a mediator for cell-to-cell communication by regulating the exchange of genetic materials and proteins between the donor and surrounding cells. Current studies have explored the therapeutic value of mesenchymal stem cells-derived EVs (MSC-EVs) for the treatment of infectious diseases extensively. MSC-EVs can eliminate the pathogen, regulate immunity, and repair tissue injury in contagious diseases through the secretion of antimicrobial factors, inhibiting the replication of pathogens and activating the phagocytic function of macrophages. MSC-EVs can also repair tissue damage associated with the infection by upregulating the levels of anti-inflammatory factors, downregulating the pro-inflammatory factors, and participating in the regulation of cellular biological behaviors. The purpose of this mini-review is to discuss in detail the various mechanisms of MSC-EV treatment for infectious diseases including respiratory infections, sepsis, and intestinal infections, as well as challenges for implementing MSC-EVs from bench to bedside.
Imaging Predictors for Endovascular Recanalization of Non-acute Occlusion of Internal Carotid Artery Based on 3D T1-SPACE MRI and DSA
Authors: Chao Liu , Qingbin Meng , Haowen Xu , Shanshan Xie , Qichang Fu , Zhen Chen , Sheng Guan
Published: October 2021

Objectives: To investigate the predictive factors for successful recanalization based on digital subtraction angiography and three-dimensional T1W sampling perfection with application-optimized contrasts using different flip angle evolutions (3D T1-SPACE) high-resolution magnetic resonance imaging (MRI) signal features.

Methods: Consecutive internal carotid artery occlusion cases with ipsilateral ischemic stroke refractory to therapy who visited our institution between February 2017 and August 2020 were retrospectively analyzed. Epidemiology, symptomatology, imaging morphology on angiography and MRI, peri-procedural complications, technical success rate, and follow-up results were summarized. Factors related to technical success were analyzed using univariate and multivariate analyses.

Results: In total, 75 cases (53 men, mean age 57.51 ± 9.71 years) were included. The total successful recanalization rate was 72.00% (54/75), with a complication rate of 13.33% (9/75). Through multivariate analysis, first ischemic stroke in <3 months (OR: 2.57; 95% CI: 1.13–4.58), tapered stump (OR: 4.31; 95% CI: 1.37–13.55), reversed flow of the ophthalmic artery (OR: 2.99; 95% CI: 1.06–8.49), high intraluminal signal on unenhanced T1-SPACE sequence (OR: 16.15; 95% CI: 3.40–76.72), no vessel wall collapse (OR: 17.00; 95% CI: 3.57–81.02), short occlusion length (OR: 9.87; 95% CI: 2.09–46.64), and primary occlusion site at the cervical internal carotid artery (OR: 8.42; 95% CI: 1.04–68.19) were associated with successful recanalization.

Conclusion: Besides traditional features such as short ischemic event time, tapered stump, and distal ICA reconstitution by the ophthalmic artery, our study demonstrates that luminal and mural changes determined by 3D SPACE high-resolution MRI could also predict successful endovascular recanalization. Endovascular recanalization for non-acute internal carotid artery occlusion is feasible, but prudent case selection is mandatory considering the high periprocedural complication rate.
Role of the Cervical Anterior Spinal Artery in the Endovascular Treatment of Vascular Diseases: Bystander, Accomplice, Victim, or Friend?
Authors: Zhang Kun , Li Chao , Hou Kun , Yu Jinlu
Published: October 2021

The cervical anterior spinal artery (ASA) is a very important artery arising from the intracranial vertebral artery (VA). It can play different roles in endovascular treatment (EVT) of spinal vascular diseases. The current understanding of these roles is incomplete; therefore, we performed this review. We found that cervical ASA can be involved in many spinal vascular diseases, such as arteriovenous fistula (AVF), arteriovenous malformation (AVM), and aneurysm, and can serve as a collateral channel in proximal VA occlusion. In AVF and AVM, when the cervical ASA is involved, it often plays the role of an accomplice or victim because it acts as the feeder or as a bystander that does not provide blood flow to the AVF and AVM. In cervical ASA aneurysm, the ASA is a victim. During EVT of VA aneurysms or stenoses, the cervical ASA ostia can be covered or occluded, resulting in ASA ischemia. In this situation, the ASA is a victim. In VA occlusion or the subclavian steal phenomenon, the cervical ASA can serve as a collateral channel to provide blood flow to the posterior circulation. In this case, the ASA plays the role of a friend. According to the role of the cervical ASA in spinal vascular diseases, EVT should be determined “case by case.” Most importantly, when EVT is performed to treat these diseases, the cervical ASA axis must be preserved. Therefore, understanding the role of the cervical ASA in spinal vascular diseases is crucial.
Epidural Spinal Electrogram Provides Direct Spinal Recordings in Awake Human Participants
Authors: Burke John F. , Kunwar Nikhita , Yaroshinsky Maria S. , Louie Kenneth H. , Shirvalkar Prasad , Su Paul , Henry Melanie , Pasvankas George , Poree Lawrence , Jacques Lines , Wang Doris D.
Published: October 2021

Little is known about the electrophysiological activity of the spinal cord during voluntary movement control in humans. We present a novel method for recording electrophysiological activity from the human spinal cord using implanted epidural electrodes during naturalistic movements including overground walking. Spinal electrograms (SEGs) were recorded from epidural electrodes implanted as part of a test trial for patients with chronic pain undergoing evaluation for spinal cord stimulation. Externalized ends of the epidural leads were connected to an external amplifier to capture SEGs. Electromyographic and accelerometry data from the upper and lower extremities were collected using wireless sensors and synchronized to the SEG data. Patients were instructed to perform various arm and leg movements while SEG and kinematic data were collected. This study proves the safety and feasibility of performing epidural spinal recordings from human subjects performing movement tasks.
Vascular Risk Factors and Cognition in Multiple System Atrophy
Authors: Zhang Lingyu , Hou Yanbing , Cao Bei , Wei Qian-Qian , Ou Ruwei , Liu Kuncheng , Lin Junyu , Yang Tianmi , Xiao Yi , Zhao Bi , Shang HuiFang
Published: October 2021

Objective: Vascular risk factors have been reported to be associated with cognitive impairment (CI) in the general population, but their role on CI in multiple system atrophy (MSA) is unclear. This study aimed to explore the relationship between vascular risk factors and CI in patients with MSA.

Methods: The clinical data and vascular risk factors were collected. The Montreal Cognitive Assessment tool was used to test the cognitive function of patients with MSA. Binary logistic regression was used to analyze the correlation between vascular risk factors and CI.

Results: A total of 658 patients with MSA with a mean disease duration of 2.55 ± 1.47 years were enrolled. In MSA patients, hypertension was recorded in 20.2%, diabetes mellitus in 10.3%, hyperlipidemia in 10.2%, smoking in 41.2%, drinking in 34.8%, and obesity in 9.6%. The prevalence of CI in patients with MSA, MSA with predominant parkinsonism (MSA-P), and MSA with predominant cerebellar ataxia (MSA-C) was 45.0, 45.1, and 44.9%, respectively. In the binary logistic regression model, patients with more than one vascular risk factors were significantly more likely to have CI in MSA (OR = 4.298, 95% CI 1.456–12.691, P = 0.008) and MSA-P (OR = 6.952, 95% CI 1.390–34.774, P = 0.018), after adjusting for age, sex, educational years, disease duration, and total Unified multiple system atrophy rating scale scores.

Conclusion: Multiple vascular risk factors had a cumulative impact on CI in MSA. Therefore, the comprehensive management of vascular risk factors in MSA should not be neglected.
Sex-Disparity in the Association Between Birthweight and Cardiovascular Parameters in 4-Year-Old Children: A Chinese Cohort Study
Authors: Wang Hualin , Du Bowen , Wu Yujian , Li Zhuoyan , Niu Yiwei , Ouyang Fengxiu , Wang Jian , Chen Sun , Sun Kun
Published: October 2021

Background: Sex-related differences in cardiovascular parameters have been well documented in adults, and the impact of birthweight on cardiovascular health in later life has been acknowledged. However, data was limited regarding the association between birthweight and cardiovascular outcomes at an early age, and the sex-disparity in the association remained unclear.

Objective: To investigate the association between birthweight and cardiovascular parameters in 4-year-old children. Furthermore, to explore whether sex-disparity exist in this association or in cardiovascular risk.

Methods: Follow-up data from the Shanghai Birth Cohort (SBC) was analyzed. Detailed perinatal information including both maternal and offspring datum were recorded. Blood pressure, echocardiography, and anthropometry assessment were conducted during the follow-up of 4-year-old children. Linear regression models were used to analyze the association between birthweight and left ventricle (LV) structure and function changes in each sex and birthweight category. Multivariable logistic regression models were used to compare risk of left ventricular hypertrophy (LVH) in different birthweight subgroups.

Results: Overall, macrosomia was significantly associated with thickened LV posterior wall thickness in systole [LVPWs, (β = 0.26, 95% CI: 0.06, 0.45)] and diastole [LVPWd, (β = 0.18, 95% CI: 0.06, 0.30)], and thickened interventricular septal thickness in diastole [IVSd, (β = 0.16, 95% CI: 0.05, 0.28)]. Boys with macrosomia showed a higher left ventricle mass index [LVMI, (β = 1.29, 95% CI: 0.14, 2.43)], thickened LVPWs (β = 0.30, 95% CI: 0.05, 0.56) and LVPWd (β = 0.21, 95% CI: 0.06, 0.36), and thickened IVSd (β = 0.23, 95% CI: 0.09, 0.36). However, no significant association of structural changes was found in girls. Furthermore, an increased risk of LVH was found solely in macrosomic boys (OR = 2.79, 95% CI: 1.17, 6.63).

Conclusion: Children with macrosomia developed cardiovascular changes as early as 4 years of age. Macrosomia was associated with LV structural changes and higher LVH risk in pre-school-aged boys, while no association was found in girls.
The Role of the Immune Response in Brain Metastases: Novel Imaging Biomarkers for Immunotherapy
Authors: Zakaria Rasheed , Radon Mark , Mills Samantha , Mitchell Drew , Palmieri Carlo , Chung Caroline , Jenkinson Michael D.
Published: October 2021

Brain metastases are a major clinical problem, and immunotherapy offers a novel treatment paradigm with the potential to synergize with existing focal therapies like surgery and radiosurgery or even replace them in future. The brain is a unique microenvironment structurally and immunologically. The immune response is likely to be crucial to the adaptation of systemic immune modulating agents against this disease. Imaging is frequently employed in the clinical diagnosis and management of brain metastasis, so it is logical that brain imaging techniques are investigated as a source of biomarkers of the immune response in these tumors. Current imaging techniques in clinical use include structural MRI (post-contrast T1W sequences, T2, and FLAIR), physiological sequences (perfusion- and diffusion-weighted imaging), and molecular imaging (MR spectroscopy and PET). These are reviewed for their application to predicting and measuring the response to immunotherapy in brain metastases.
Upregulation of HSPA1A/HSPA1B/HSPA7 and Downregulation of HSPA9 Were Related to Poor Survival in Colon Cancer
Authors: Guan Yufeng , Zhu Xianjun , Liang Junjie , Wei Min , Huang Shan , Pan Xiaofen
Published: October 2021

The human HSP70 family is a type of heat shock protein (HSP), consisting of 13 members encoded by the HSPA genes. HSPs play important roles in regulating cellular responses and functions during carcinogenesis, but their relationship with colon cancer is unclear. In our study, we found that the expressions of HSPA1B, HSPA4, HSPA5, HSPA6, HSPA8, HSPA9, HSPA13, and HSPA14 were significantly increased, while those of HSPA1A, HSPA2, HSPA7, and HSPA12B were significantly decreased in colon cancer tissues. The expression of HSPA gene family members was associated with some clinicopathological characteristics, including age, gender, TNM stage, pathological stage, and CEA level. Furthermore, the Kaplan–Meier method and Cox regression analysis showed that high HSPA1A, HSPA1B, and HSPA7 expressions were related to unfavorable survival, and high HSPA9 was associated with favorable survival. The relationships between HSPA1A and HSPA9 expression and survival were validated in the GEO dataset, and the HSPA1A and HSPA9 protein expression differences between colon cancer tissues and normal tissues were validated in the UALCAN database. Methylation of HSPA1A and HSPA9 was also analyzed, and it was found that the methylation of the HSPA1A promoter was significantly increased, and the methylation of the HSPA9 promoter was significantly decreased in colon cancer tissues. Increasing the methylation level of the HSPA1A gene and decreasing the methylation level of HSPA9 were related to favorable prognosis. The expression difference of HSPA1A/HSPA1B/HSPA7/HSPA9 was verified in colon cancer cell lines and colonic epithelial cells. Gene ontology analysis was used to screen signal pathways related to HSPA1A-, HSPA1B-, HSPA7-, and HSPA9- high phenotype. In summary, the increased expressions of HSPA1A1, HSPA1B, and HSPA7 were associated with poor prognosis, while that of HSPA9 was related to favorable prognosis for colon cancer patients.
Wide-Field Pixel Super-Resolution Colour Lensfree Microscope for Digital Pathology
Authors: Zeng Guang , He Jiahui , Qin Wenjian
Published: October 2021

Whole slide imaging enables scanning entire stained-glass slides with high resolution into digital images for the tissue morphology/molecular pathology assessment and analysis, which has increased in adoption for both clinical and research applications. As an alternative to conventional optical microscopy, lensfree holography imaging, which offers high resolution and a wide field of view (FOV) with digital focus, has been widely used in various types of biomedical imaging. However, accurate colour holographic imaging with pixel super-resolution reconstruction has remained a great challenge due to its coherent characteristic. In this work, we propose a wide-field pixel super-resolution colour lensfree microscopy by performing wavelength scanning pixel super-resolution and phase retrieval simultaneously on the three channels of red, green and blue (RGB), respectively. High-resolution RGB three-channel composite colour image is converted to the YUV space for separating the colour component and the brightness component, keeping the brightness component unchanged as well as enhancing the colour component through average filter, which not only eliminates the common rainbow artifacts of holographic colour reconstruction but also maintains the high-resolution details collected under different colour illuminations. We conducted experiments on the reconstruction of a USAF1951, stained lotus root and red bone marrow smear for performance evaluation of the spatial resolution and colour reconstruction with an imaging FOV >40 mm2.
An Updated Insight Into Molecular Mechanism of Hydrogen Sulfide in Cardiomyopathy and Myocardial Ischemia/Reperfusion Injury Under Diabetes
Authors: Sun Hai-Jian , Wu Zhi-Yuan , Nie Xiao-Wei , Wang Xin-Yu , Bian Jin-Song
Published: October 2021

Cardiovascular diseases are the most common complications of diabetes, and diabetic cardiomyopathy is a major cause of people death in diabetes. Molecular, transcriptional, animal, and clinical studies have discovered numerous therapeutic targets or drugs for diabetic cardiomyopathy. Within this, hydrogen sulfide (H2S), an endogenous gasotransmitter alongside with nitric oxide (NO) and carbon monoxide (CO), is found to play a critical role in diabetic cardiomyopathy. Recently, the protective roles of H2S in diabetic cardiomyopathy have attracted enormous attention. In addition, H2S donors confer favorable effects in myocardial infarction, ischaemia-reperfusion injury, and heart failure under diabetic conditions. Further studies have disclosed that multiplex molecular mechanisms are responsible for the protective effects of H2S against diabetes-elicited cardiac injury, such as anti-oxidative, anti-apoptotic, anti-inflammatory, and anti-necrotic properties. In this review, we will summarize the current findings on H2S biology and pharmacology, especially focusing on the novel mechanisms of H2S-based protection against diabetic cardiomyopathy. Also, the potential roles of H2S in diabetes-aggravated ischaemia-reperfusion injury are discussed.