bluuebunny/crossref_metadata_2025 huggingface dataset:
Desmin Modulates Muscle Cell Adhesion and Migration
Authors: Hakibilen Coralie , Delort Florence , Daher Marie-Thérèse , Joanne Pierre , Cabet Eva , Cardoso Olivier , Bourgois-Rocha Fany , Tian Cuixia , Rivas Eloy , Madruga Marcos , Ferreiro Ana , Lilienbaum Alain , Vicart Patrick , Agbulut Onnik , Hénon Sylvie , Batonnet-Pichon Sabrina
Published: March 2022

Cellular adhesion and migration are key functions that are disrupted in numerous diseases. We report that desmin, a type-III muscle-specific intermediate filament, is a novel cell adhesion regulator. Expression of p.R406W mutant desmin, identified in patients with desmin-related myopathy, modified focal adhesion area and expression of adhesion-signaling genes in myogenic C2C12 cells. Satellite cells extracted from desmin-knock-out (DesKO) and desmin-knock-in-p.R405W (DesKI-R405W) mice were less adhesive and migrated faster than those from wild-type mice. Moreover, we observed mislocalized and aggregated vinculin, a key component of cell adhesion, in DesKO and DesKI-R405W muscles. Vinculin expression was also increased in desmin-related myopathy patient muscles. Together, our results establish a novel role for desmin in cell-matrix adhesion, an essential process for strength transmission, satellite cell migration and muscle regeneration. Our study links the patho-physiological mechanisms of desminopathies to adhesion/migration defects, and may lead to new cellular targets for novel therapeutic approaches.
Profiling Temporal Changes of the Pineal Transcriptomes at Single Cell Level Upon Neonatal HIBD
Authors: Ding Xin , Pan Tao , Tian Qiuyan , Huang Wenxi , Hayashi Lauren S , Liu Qin , Li Fuyong , Xu Li-Xiao , Miao Po , Yang Xiaofeng , Sun Bin , Feng Chen-Xi , Feng Xing , Li Mei , Huang Jian
Published: March 2022

Neonatal hypoxic-ischemic brain damage (HIBD) often results in various neurological deficits. Among them, a common, yet often neglected, symptom is circadian rhythm disorders. Previous studies revealed that the occurrence of cysts in the pineal gland, an organ known to regulate circadian rhythm, is associated with circadian problems in children with HIBD. However, the underlying mechanisms of pineal dependent dysfunctions post HIBD remain largely elusive. Here, by performing 10x single cell RNA sequencing, we firstly molecularly identified distinct pineal cell types and explored their transcriptome changes at single cell level at 24 and 72 h post neonatal HIBD. Bioinformatic analysis of cell prioritization showed that both subtypes of pinealocytes, the predominant component of the pineal gland, were mostly affected. We then went further to investigate how distinct pineal cell types responded to neonatal HIBD. Within pinealocytes, we revealed a molecularly defined β to α subtype conversion induced by neonatal HIBD. Within astrocytes, we discovered that all three subtypes responded to neonatal HIBD, with differential expression of reactive astrocytes markers. Two subtypes of microglia cells were both activated by HIBD, marked by up-regulation ofCcl3. Notably, microglia cells showed substantial reduction at 72 h post HIBD. Further investigation revealed that pyroptosis preferentially occurred in pineal microglia through NLRP3-Caspase-1-GSDMD signaling pathway. Taken together, our results delineated temporal changes of molecular and cellular events occurring in the pineal gland following neonatal HIBD. By revealing pyroptosis in the pineal gland, our study also provided potential therapeutic targets for preventing extravasation of pineal pathology and thus improving circadian rhythm dysfunction in neonates with HIBD.
Activating Transcription Factor 3 (ATF3) is a Highly Conserved Pro-regenerative Transcription Factor in the Vertebrate Nervous System
Authors: Katz Hilary R. , Arcese Anthony A. , Bloom Ona , Morgan Jennifer R.
Published: March 2022

The vertebrate nervous system exhibits dramatic variability in regenerative capacity across species and neuronal populations. For example, while the mammalian central nervous system (CNS) is limited in its regenerative capacity, the CNS of many other vertebrates readily regenerates after injury, as does the peripheral nervous system (PNS) of mammals. Comparing molecular responses across species and tissues can therefore provide valuable insights into both conserved and distinct mechanisms of successful regeneration. One gene that is emerging as a conserved pro-regenerative factor across vertebrates is activating transcription factor 3 (ATF3), which has long been associated with tissue trauma. A growing number of studies indicate that ATF3 may actively promote neuronal axon regrowth and regeneration in species ranging from lampreys to mammals. Here, we review data on the structural and functional conservation of ATF3 protein across species. Comparing RNA expression data across species that exhibit different abilities to regenerate their nervous system following traumatic nerve injury reveals that ATF3 is consistently induced in neurons within the first few days after injury. Genetic deletion or knockdown of ATF3 expression has been shown in mouse and zebrafish, respectively, to reduce axon regeneration, while inducing ATF3 promotes axon sprouting, regrowth, or regeneration. Thus, we propose that ATF3 may be an evolutionarily conserved regulator of neuronal regeneration. Identifying downstream effectors of ATF3 will be a critical next step in understanding the molecular basis of vertebrate CNS regeneration.
The Opportunity of Proteomics to Advance the Understanding of Intra- and Extracellular Regulation of Malignant Hematopoiesis
Authors: Jassinskaja Maria , Hansson Jenny
Published: March 2022

Fetal and adult hematopoiesis are regulated by largely distinct sets of cell-intrinsic gene regulatory networks as well as extracellular cues in their respective microenvironment. These ontogeny-specific programs drive hematopoietic stem and progenitor cells (HSPCs) in fetus and adult to divergent susceptibility to initiation and progression of hematological malignancies, such as leukemia. Elucidating how leukemogenic hits disturb the intra- and extracellular programs in HSPCs along ontogeny will provide a better understanding of the causes for age-associated differences in malignant hematopoiesis and facilitate the improvement of strategies for prevention and treatment of pediatric and adult acute leukemia. Here, we review current knowledge of the intrinsic and extrinsic programs regulating normal and malignant hematopoiesis, with a particular focus on the differences between infant and adult acute leukemia. We discuss the recent advances in mass spectrometry-based proteomics and its opportunity for resolving the interplay of cell-intrinsic and niche-associated factors in regulating malignant hematopoiesis.
Polyoxometalate Functionalized Sensors: A Review
Authors: Veríssimo Marta I. S. , Evtuguin Dmitry V. , Gomes M. Teresa S. R.
Published: March 2022

Polyoxometalates (POMs) are a class of metal oxide complexes with a large structural diversity. Effective control of the final chemical and physical properties of POMs could be provided by fine-tuning chemical modifications, such as the inclusion of other metals or non-metal ions. In addition, the nature and type of the counterion can also impact POM properties, like solubility. Besides, POMs may combine with carbon materials as graphene oxide, reduced graphene oxide or carbon nanotubes to enhance electronic conductivity, with noble metal nanoparticles to increase catalytic and functional sites, be introduced into metal-organic frameworks to increase surface area and expose more active sites, and embedded into conducting polymers. The possibility to design POMs to match properties adequate for specific sensing applications turns them into highly desirable chemicals for sensor sensitive layers. This review intends to provide an overview of POM structures used in sensors (electrochemical, optical, and piezoelectric), highlighting their main functional features. Furthermore, this review aims to summarize the reported applications of POMs in sensors for detecting and determining analytes in different matrices, many of them with biochemical and clinical relevance, along with analytical figures of merit and main virtues and problems of such devices. Special emphasis is given to the stability of POMs sensitive layers, detection limits, selectivity, the pH working range and throughput.
Platelet Membrane Biomimetic Nanoparticles Combined With UTMD to Improve the Stability of Atherosclerotic Plaques
Authors: Zhou Jia , Niu Chengcheng , Huang Biying , Chen Sijie , Yu Caigui , Cao Sheng , Pei Wenjing , Guo Ruiqiang
Published: March 2022

Although research on the treatment of atherosclerosis has progressed recently, challenges remain in developing more effective, safer and transformative strategies for the treatment of atherosclerosis. Nanomaterials have recently played a unique role in many fields, including atherosclerosis treatment. Platelets are common component in the blood. Due to their inherent properties, platelets can target and adhere to atherosclerotic plaques. Ultrasound-targeted microbubble destruction (UTMD) shows great prospects in promoting the efficiency of drug delivery in treating solid tumors. In this study, we explored the possibility that UTMD assists platelet biomimetic rapamycin (RAP)-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (RAP@PLT NPs) in the treatment of atherosclerosis. The biomimetic nano-formulations exhibit better targeting ability to plaques when administered in vivo. Targeted destruction of Sonovue™ in the aortic area further improved the efficiency of targeting plaques. Moreover, the progression of atherosclerotic plaques was inhibited, and the stability of plaques was improved. Together, our study established a novel strategy for targeted delivery of nanoparticles in atherosclerotic plaques, by combining the advantages of the ultrasonic cavitation effect and biomimicking nanoparticles in drug delivery.
Exosome-Derived From Sepsis Patients' Blood Promoted Pyroptosis of Cardiomyocytes by Regulating miR-885-5p/HMBOX1
Authors: Tu Guo-wei , Ma Jie-fei , Li Jia-kun , Su Ying , Luo Jing-chao , Hao Guang-wei , Luo Ming-hao , Cao Yi-rui , Zhang Yi , Luo Zhe
Published: March 2022

Background

Septic myocardial depression has been associated with increased morbidity and mortality. miR-885-5p has been shown to regulate cell growth, senescence, and/or apoptosis. Published studies demonstrated that Homeobox-containing protein 1 (HMBOX1) inhibits inflammatory response, regulates cell autophagy, and apoptosis. However, the role of miR-885-5p/HMBOX1 in sepsis and septic myocardial depression and the underlying mechanism is not fully understood.

Materials and Methods

Exosomes (exos) derived from sepsis patients (sepsis-exos) were isolated using ultracentrifugation. Rats were subjected to cecal ligation and puncture surgery and treated with sepsis-exos. HMBOX1 was knocked down or overexpressed in AC16 cells using lentiviral plasmids carrying short interfering RNAs targeting human HMBOX1 or carrying HMBOX1 cDNA. Cell pyroptosis was measured by flow cytometry. The secretion of IL-1β and IL-18 was examined by ELISA kits. Quantitative polymerase chain reaction (PCR) or western blot was used for gene expression.

Results

Sepsis-exos increased the level of miR-885-5p, decreased HMBOX1, elevated IL-1β and IL-18, and promoted pyroptosis in AC16 cells. Septic rats treated with sepsis-exos increased the serum inflammatory cytokines is associated with increased pyroptosis-related proteins of hearts. MiR-885-5p bound to the three prime untranslated regions of HMBOX1 to negatively regulate its expression. Overexpressing HMBOX1 reversed miR-885-5p-induced elevation of inflammatory cytokines and upregulation of NLRP3, caspase-1, and GSDMD-N in AC16 cells. The mechanistic study indicated that the effect of HMBOX1 was NF-κB dependent.

Conclusion

Sepsis-exos promoted the pyroptosis of AC16 cells through miR-885-5p via HMBOX1. The results show the significance of the miR-885-5p/HMBOX1 axis in myocardial cell pyroptosis and provide new directions for the treatment of septic myocardial depression.
Dynamics and Functional Interplay of Nonhistone Lysine Crotonylome and Ubiquitylome in Vascular Smooth Muscle Cell Phenotypic Remodeling
Authors: Cao Shan-Hu , Chen Zhi-Huan , Ma Ru-Yuan , Yue Lin , Jiang Han-Mei , Dong Li-Hua
Published: March 2022

Background

The crotonylation of histones is discovered of late as one of the post-translational modifications (PTMs) that can regulate gene expression. However, the function of crotonylation on nonhistone proteins in vascular smooth muscle cells (VSMCs) is unclear. Here, we aim to find the cellular characteristics of crotonylated nonhistone proteins and the cross talk with ubiquitinated proteins in VSMC phenotypic remodeling using the modified omics and proteomic analysis.

Methods

We performed the modified omics and proteomic analysis of VSMCs before and after the stimulation with platelet-derived growth factor-BB (PDGF-BB). The crotonylated and ubiquitinated pan-antibody was used to enrich proteins and then subjected to a high-throughput mass spectrometry analysis. The enrichment analysis was performed within differentially modified proteins in regard to GO terms, KEGG, and protein domains.

Results

As a result, there were 2,138 crotonylation sites in 534 proteins and 1,359 ubiquitination sites corresponding to 657 proteins. These crotonylated proteins detected after PDGF-BB stimulation might be involved in various vital cellular pathways and carry out important functions in VSMCs. Some of them closely took part in significant physiological processes of VSMC phenotypic remodeling, including glycolysis/gluconeogenesis, vascular smooth muscle contraction, and the PI3K-Akt signaling pathway. Furthermore, the KEGG pathway enrichment analysis showed the involvement of ubiquitinated proteins in the physiological processes of VSMC phenotypic remodeling, including glycolysis/gluconeogenesis, vascular smooth muscle contraction, RAS signaling pathway, or the PI3K-Akt signaling pathway. A cross talk analysis showed that there were 199 sites within the 177 proteins modified by crotonylation and ubiquitination simultaneously. Protein–protein interaction (PPI) network analysis indicated that crotonylated and ubiquitinated proteins play an important role in cellular bioprocess commonly and possibly have a synergistic effect.

Conclusion

In summary, our bioinformatics analysis shows that the crotonylation and ubiquitination of nonhistone proteins play an essential role in VSMC phenotypic transformation induced by PDGF-BB stimulation. The cross talk between crotonylation and ubiquitination in glycolysis is possibly a novel mechanism during VSMC phenotypic remodeling.
The Efficacy and Safety of Phase I Cardiac Rehabilitation in Patients Hospitalized in Cardiac Intensive Care Unit With Acute Decompensated Heart Failure: A Study Protocol for a Randomized, Controlled, Clinical Trial
Authors: Wu Linjing , Li Jiahua , Chen Linjian , Xue Mengmeng , Zheng Yamin , Meng Fanqi , Jiang Hongfei , Shi Zaixing , Zhang Peng , Dai Cuilian
Published: March 2022

Background

Cardiac rehabilitation (CR) improves outcomes in patients with heart failure. However, data on CR efficacy in patients with acute decompensated heart failure is limited. This study is designed to assess the efficacy and safety of CR in patients hospitalized in cardiac intensive care unit (CICU) with acute decompensated heart failure (ADHF).

Methods

This is a single-center, randomized controlled, single-blind clinical trial. A total of 120 participants hospitalized in CICU with ADHF will be randomly allocated in the ratio of 1:1 to two groups: CR group and control group. Participants will receive tailored and progressive CR intervention or attention control. The CR intervention include personalized breathing training, small muscle group resistance training, and aerobic endurance training based on the physical fitness assessment results. The subjects will receive the CR training for 5 days and will be followed up for 6 months. The primary endpoints are the score of the short physical performance battery (SPPB) and 6-month all-cause rehospitalization. The secondary endpoints include cardio-pulmonary function, activities of daily living (ADL), in-hospital mortality rate and 6-month all-cause mortality rate.

Discussion

This randomized, controlled, clinical trial will assess whether CR improves physical function and reduces rehospitalization in patients hospitalized in CICU with ADHF. The results will provide further research-based evidence for the clinical application of CR in patients with ADHF.

Trial Registration

Chinese Clinical Trial Registry ChiCTR2100050151. Registered on 19 August 2021.
Analysis of Vascular Architecture and Parenchymal Damage Generated by Reduced Blood Perfusion in Decellularized Porcine Kidneys Using a Gray Level Co-occurrence Matrix
Authors: Pantic Igor V. , Shakeel Adeeba , Petroianu Georg A. , Corridon Peter R.
Published: March 2022

There is no cure for kidney failure, but a bioartificial kidney may help address this global problem. Decellularization provides a promising platform to generate transplantable organs. However, maintaining a viable vasculature is a significant challenge to this technology. Even though angiography offers a valuable way to assess scaffold structure/function, subtle changes are overlooked by specialists. In recent years, various image analysis methods in radiology have been suggested to detect and identify subtle changes in tissue architecture. The aim of our research was to apply one of these methods based on a gray level co-occurrence matrix (Topalovic et al.) computational algorithm in the analysis of vascular architecture and parenchymal damage generated by hypoperfusion in decellularized porcine. Perfusion decellularization of the whole porcine kidneys was performed using previously established protocols. We analyzed and compared angiograms of kidneys subjected to pathophysiological arterial perfusion of whole blood. For regions of interest Santos et al. covering kidney medulla and the main elements of the vascular network, five major GLCM features were calculated: angular second moment as an indicator of textural uniformity, inverse difference moment as an indicator of textural homogeneity, GLCM contrast, GLCM correlation, and sum variance of the co-occurrence matrix. In addition to GLCM, we also performed discrete wavelet transform analysis of angiogram ROIs by calculating the respective wavelet coefficient energies using high and low-pass filtering. We report statistically significant changes in GLCM and wavelet features, including the reduction of the angular second moment and inverse difference moment, indicating a substantial rise in angiogram textural heterogeneity. Our findings suggest that the GLCM method can be successfully used as an addition to conventional fluoroscopic angiography analyses of micro/macrovascular integrity following in vitro blood perfusion to investigate scaffold integrity. This approach is the first step toward developing an automated network that can detect changes in the decellularized vasculature.
Association Between Non-alcoholic Fatty Liver Disease and Risk of Stroke: A Systematic Review and Meta-Analysis
Authors: Wang Meng , Zhou Ben-Gang , Zhang Yi , Ren Xi-Fang , Li Ling , Li Bo , Ai Yao-Wei
Published: March 2022

Background/Objectives

Recent observational studies have explored the association between non-alcoholic fatty liver disease (NAFLD) and stroke with controversial results. We therefore performed a meta-analysis to investigate this possible association.

Methods

PubMed, EMBASE and Web of Science database were searched from inception until December 2019, and updated on May 2021. Random-effects meta-analyses were performed by generic inverse variance method. Subgroup and sensitivity analyses were also conducted. The PROSPERO registered number of this study is CRD42020167330.

Results

Twenty observational (15 cohort, 4 cross-sectional, and 1 case-control) studies with 17,060,388 participants were included in the meta-analysis. Meta-analysis of data from 18 studies with 17,031,672 participants has shown that NAFLD was associated with mildly increased risk of stroke (OR = 1.18, 95% CI: 1.08–1.30, P = 0.0005). Similar results were observed in most of the subgroup analyses we performed. Sensitivity analyses did not alter these findings. Meta-analysis of data from 3 studies with 29,614 participants has shown that insufficient evidence to support the proposed association between NAFLD-fibrosis and an increased risk of stroke.

Conclusions

We found that NAFLD was associated with increased risk of stroke. However, there was insufficient evidence to support the proposed association between NAFLD-fibrosis and an increased risk of stroke. To better understand any association, future well-designed prospective studies that take fully account of specific population, type of stroke, and confounding factors are warranted.

Systematic Review Registration

Unique Identifier: CRD42020167330.
Trends in Transcatheter Edge-to-Edge Mitral Valve Repair Over a Decade: Data From the MiTra ULM Registry
Authors: Nita Nicoleta , Schneider Leonhard , Dahme Tilman , Markovic Sinisa , Keßler Mirjam , Rottbauer Wolfang , Tadic Marijana
Published: March 2022

Objective

This study sought to determine the potential change in trends in the baseline characteristics of patients with symptomatic severe mitral regurgitation who underwent transcatheter edge-to-edge mitral valve repair (M-TEER) over the last decade in a high-volume center.

Methodology

The investigation included 942 symptomatic patients with moderate-to-severe and severe mitral regurgitation who underwent transcatheter edge-to-edge repair (TEER) at our institution between January 2010 and March 2021. Patients were divided into quintiles and compared separately.

Results

Patients treated in the last quintile had significantly lower surgical risk (Euro Score 7.2 ± 6.8% in the last quintile vs. 10.9 ± 9.4% in the first quintile, p < 0.001), better New York Heart Association (NYHA) status (NYHA IV 14% in the last quintile vs. 40% in the first quintile, p < 0.001), lower NT-pro-BNP, and smaller left ventricle diameter than patients who were treated in the first quintile. There was no difference in age between quintiles. However, an invasive hemodynamic assessment did not show significant changes over the last decade (sPAP 51.35 ± 16.2 mmHg in the first quintile vs. 51.02 ± 14.5 mmHg in the last quintile, p = 0.90, pulmonary capillary wedge V wave 30.7 ± 14.8 mmHg in the first quintile vs. 27.4 ± 10.3 mmHg in the last quintile, p = 0.40). There is a significant trend of a gradually increasing proportion of patients with degenerative mitral regurgitation (MR) over the last 10 years (p < 0.001). The experience gained in the M-TEER procedure brought a significant reduction in fluoroscopy time and hospitalization duration. Medical therapy significantly changed over the last decade in terms of higher use of angiotensin receptor blockers (ARBs), lower use of angiotensin-converting enzyme inhibitors (ACEIs), and the introduction of angiotensin receptor-neprilysin inhibitors (ARNIs).

Conclusion

Patients undergoing the M-TEER procedure nowadays have lower surgical risk and are treated before they develop a significant left ventricular (LV) remodeling than before. The increasing expertise on the procedure over the last decade led to a rising number of patients with complex degenerative pathology being treated.
Pak2 Regulation of Nrf2 Serves as a Novel Signaling Nexus Linking ER Stress Response and Oxidative Stress in the Heart
Authors: Binder Pablo , Nguyen Binh , Collins Lucy , Zi Min , Liu Wei , Christou Foteini , Luo Xiaojing , Hille Susanne S. , Frey Norbert , Cartwright Elizabeth J. , Chernoff Jonathan , Müller Oliver J. , Guan Kaomei , Wang Xin
Published: March 2022

Endoplasmic Reticulum (ER) stress and oxidative stress have been highly implicated in the pathogenesis of cardiac hypertrophy and heart failure (HF). However, the mechanisms involved in the interplay between these processes in the heart are not fully understood. The present study sought to determine a causative link between Pak2-dependent UPR activation and oxidative stress via Nrf2 regulation under pathological ER stress. We report that sustained ER stress and Pak2 deletion in cardiomyocytes enhance Nrf2 expression. Conversely, AAV9 mediated Pak2 delivery in the heart leads to a significant decrease in Nrf2 levels. Pak2 overexpression enhances the XBP1-Hrd1 UPR axis and ameliorates tunicamycin induced cardiac apoptosis and dysfunction in mice. We found that Pak2 deletion and altered proteostasis render Nrf2 detrimental by switching from its antioxidant role to renin-angiotensin aldosterone system (RAAS) gene regulator. Mechanistically, Pak2 mediated Hrd1 expression targets Nrf2 for ubiquitination and degradation thus preventing its aberrant activation. Moreover, we find a significant increase in Nrf2 with a decrease in Pak2 in human myocardium of dilated heart disease. Using human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), we find that Pak2 is able to ameliorate Nrf2 induced RAAS activation under ER stress. These findings demonstrate that Pak2 is a novel Nrf2 regulator in the stressed heart. Activation of XBP1-Hrd1 is attributed to prevent ER stress-induced Nrf2 RAAS component upregulation. This mechanism explains the functional dichotomy of Nrf2 in the stressed heart. Thus, Pak2 regulation of Nrf2 homeostasis may present as a potential therapeutic route to alleviate detrimental ER stress and heart failure.
Echocardiographic Parameters to Predict Atrial Fibrillation in Clinical Routine—The EAHsy-AF Risk Score
Authors: Sieweke Jan-Thorben , Hagemus Jan , Biber Saskia , Berliner Dominik , Grosse Gerrit M. , Schallhorn Sven , Pfeffer Tobias Jonathan , Derda Anselm A. , Neuser Jonas , Bauersachs Johann , Bavendiek Udo
Published: March 2022

Background

Echocardiographic parameters representing impaired left atrial (LA) function and remodeling are of high value to predict atrial fibrillation (AF). This study aimed to develop a prediction model for AF easily to apply in clinical routine containing echocardiographic parameters associated with LA remodeling and—function.

Methods and Results

This monocentric, semi-blinded, controlled analysis included 235 patients to derive a prediction model. This prediction model was tested in a validation cohort encompassing 290 cardiovascular inpatients. The derivation and validation cohort included 54 (23%) and 66 (23%) patients with AF, respectively. Transthoracic echocardiography, comprising parameters indicating left atrial remodeling [septal/lateral total atrial conduction time (s/l PA-TDI)] and left atrial volume indexed to a' (LAVI/a') was performed in each patient. Based on multivariable regressions analysis, four variables were enclosed into the EAHsy (Echocardiography, Age, Hypertension)-AF risk score for AF prediction: Hypertension, Age, LAVI/a‘ and septal PA-TDI. In the validation cohort discrimination was strong (C-statistic 0.987, 95%CI 0.974–0.991) with an adequately performed calibration. The EAHsy-AF risk score was associated with a more precise prediction of AF in comparison to commonly used AF-scores (CHADS2-, ATLAS-, ARIC-, CHARGE-AF score).

Conclusion

The EAHsy-AF-Score containing age, hypertension and echocardiographic parameters of atrial dysfunction and remodeling precisely predicts the incidence of AF in a general population of patients with cardiovascular disease. The EAHsy-AF risk score may enable more selective rhythm monitoring in specific patients at high risk for AF.
Pulmonary Embolism and Pregnancy—Challenges in Diagnostic and Therapeutic Decisions in High-Risk Patients
Authors: Hobohm Lukas , Farmakis Ioannis T. , Münzel Thomas , Konstantinides Stavros , Keller Karsten
Published: March 2022

Diagnosis of acute PE in pregnant women with haemodynamic instability is following the general integrated risk-adapted diagnostic algorithm and starts with bedside echocardiography to assess RV function. If RV dysfunction is identified, a prompt and immediate reperfusion without further imaging should be initiated. Although pregnancy is listed as a relative contraindication of systemic thrombolysis, in pregnant women with acute PE and haemodynamic instability thrombolysis must be considered. In those cases, other treatment strategies as surgical embolectomy or catheter-directed low-dose thromboylysis or percutaneous thrombectomy should be taken into consideration as well. A multidisciplinary team with experience of PE management in pregnancy should be consulted to reach consensus on the best treatment approach.
Analysis of Corner Effect of Diaphragm Wall of Special-Shaped Foundation Pit in Complex Stratum
Authors: Li Yaodong , Wang Chongxiao , Sun Yang , Wang Ruicai , Shao Guojian , Yu Jie
Published: March 2022

The number of special-shaped foundation pits is increasing fast because of the continuous utilization of underground spaces in urban areas. Based on the deep foundation pit of Maluan North Station of Xiamen Metro Line 2 in Xiamen, China, the deformation characteristics of the supporting structure of special-shaped foundation pits are researched by field observation and numerical simulation. Meanwhile, the depth of the concrete supports and steel supports is considered, respectively. The results show that the lateral deformation of the diaphragm wall at the corner of the pit shows obvious corner effect, and the maximum lateral displacement of the long-side diaphragm wall is slightly larger than the short-side diaphragm wall. Changing the position of the second layer of steel support has almost no effect on the lateral deformation of the corner diaphragm wall. Changing the position of the second layer of concrete support has a greater impact on the lateral displacement of the diaphragm wall, but the path of the maximum lateral displacement of the diaphragm wall and the depth of the point of maximum lateral displacement remain unchanged.
All-Solid-State High-Voltage Supercapacitors Using an Ionic Plastic Crystal-Based Electrolyte
Authors: Yoshizawa-Fujita Masahiro , Kubota Satoshi , Ishimoto Shuichi
Published: March 2022

Recently, ionic plastic crystals (IPCs) have been actively investigated to develop all-solid-state rechargeable batteries, such as lithium-ion batteries. Herein, we report supercapacitors assembled with mesoporous carbon electrodes and an IPC electrolyte, N-ethyl-N-methylpyrrolidinium bis(fluorosulfonyl)amide ([C2mpyr][FSA]). [C2mpyr][FSA] with a 10 mol% lithium bis(fluorosulfonyl)amide (LiFSA) dopant was used as the solid electrolyte in the supercapacitors. The charge–discharge tests of the supercapacitors were performed at various C-rates in the voltage range of 0–2.5 V at 25°C. The capacitance of the cells was 12.3 Fg−1 at a lower C rate (1 C = 8.9 mA g−1). The capacitance retention of the supercapacitors was maintained at approximately 100% up to 20 C, which was comparable to that of the cells containing organic electrolyte solutions. The advantage of using solid electrolytes was the fabrication of bipolar cells using two pairs of mesoporous carbon electrodes and a [C2mpyr][FSA]/LiFSA composite. The charge–discharge tests of the bipolar cells were also performed in the voltage range of 0–5.0 V at 25°C. The capacitance of the bipolar cells was 6.4 Fg−1 at a lower C rate. The bipolar cells exhibited a typical charge–discharge profile for 1,000 cycles, confirming their stable cyclic performance. Thus, IPC electrolytes are interesting materials for developing all-solid-state high-voltage supercapacitors.
Financial Annexation, Green Innovation and Carbon Neutrality in China
Authors: Sun Yunpeng , Li Ying , Wang Yujing , Bao Qun
Published: March 2022

This article used data from 1980 to 2019 to examine the relationship between financial annexation, financial development, green innovation, and CO2 emissions in China. This review provides vital information to policymakers on how to go to preventative and therapeutic measures to reduce CO2 discharges in many sectors and demonstrates that innovation in the energy sector may help alleviate environmental change through energy productivity. The review used an autoregressive disseminated slack (ARDL) model to determine the dynamic coefficients for both the study’s long- and short-term periods. This study used the autoregressive circulated slack (ARDL) approach since it performs better than any alternative strategies in small cases, as was the case in this research. The ARDL and DARDL models show that CO2 emissions in China are increasing as a result of increased energy consumption and economic growth. Based on the findings, it is advised that China’s approach creators take on such sustainable power sources and improve them so that they may help meet the growing need for energy by replacing outdated traditional energy sources like coal, gas, and oil with them.
Contributions of Open Biomass Burning and Crop Straw Burning to Air Quality: Current Research Paradigm and Future Outlooks
Authors: Mehmood Khalid , Bao Yansong , Saifullah  , Bibi Sadia , Dahlawi Saad , Yaseen Muhammad , Abrar Muhammad Mohsin , Srivastava Prashant , Fahad Shah , Faraj Turki Kh.
Published: March 2022

Since open biomass burning (OBB) and open crop straw burning (OCSB) could pose a great risk to human health via altering the air quality, these practices have grabbed considerable attention from the scientific community and policymakers in recent years. In order to have a greater and deeper understanding of the contributions of both OBB and OCSB on air quality, a bibliometric analysis was performed using the Web of Science core collection to understand the research developments and future perspectives of these issues between 1991 and 2021. VOSviewer software 1.6.15 and R version 4.0.3 were employed to determine the annual scientific production trend and the role of countries, institutions, authors, and journal metrics network analysis. The findings showed that the interest in the study of OBB and OCSB pollution related to air quality has increased significantly over the last decade. A total of 1,021 publications were retrieved, with English as the most preferably used language. Among all documents, research articles were the most commonly appearing document type, and the researchers mainly emphasized environmental science, meteorology, atmospheric sciences, energy fuels, and environmental engineering fields. In terms of article analysis, Atmospheric Chemistry Physics, followed by Atmospheric Environment, was found to be the leading journal in this research domain, whereas the most frequently utilized keywords in the documents were biomass, biomass burning, and PM2.5. In terms of countries, the United States emerged as the leader with the highest publication rate, followed by China and India. The Chinese Academy of Sciences was ranked first in the list of most productive institutions, followed by the University of Montana and the US Forest Service. Based on the analysis, the finer spatial and temporal resolution and the characterization and understanding of the complex processes that are occurring in the atmosphere, such as clustering, oxidation, surface chemistry, and their impact on air quality, need to be explored in depth. Our research analysis can provide a baseline for future studies in air quality.
Coupling the TEB and Surfatm Models for Heat Flux Modelling in Urban Area: Comparison With Flux Measurements in Strasbourg (France)
Authors: Le Mentec S. , Stella P. , Najjar G. , Kastendeuch P. , Saudreau M. , Ngao J. , Améglio T. , Colin J. , Flick D. , Personne E.
Published: March 2022

This study presents the coupling of TEB (Town Energy Balance) and Surfatm models developed for energy exchange estimates for urban impervious and vegetation surfaces, respectively. Once coupled, the TEB-Surfatm model allows the estimate of radiative, sensible (H), and latent heat (LE) fluxes in urban areas accounting for urban vegetation. The modelled fluxes were compared with measurements performed in an urban garden. The model was able to reproduce the energy fluxes, but its performance varied. The variability of the model accuracy depended on the measurement footprint in link with the heterogeneity of the site characteristics: while the measurement footprint fitted with the area characteristics considered by the TEB-Surfatm model, the modelled H and LE fluxes presented a good agreement with the measurements. In the other cases, some overestimation and underestimation occurred, in link with different fractions of impervious surfaces or green spaces. The validation of the TEB-Surfatm model for energy fluxes is a first step, the second will be to include the pollutant exchanges since Surfatm is able to quantify the atmosphere-biosphere fluxes for numerous pollutants. It will allow the TEB-Surfatm model to quantify the impact of urban greening on the assessment of air quality in urban areas.
First Spatial Reconstruction of Past Fires in Temperate Europe Suggests Large Variability of Fire Sizes and an Important Role of Human-Related Ignitions
Authors: Zin Ewa , Kuberski Łukasz , Drobyshev Igor , Niklasson Mats
Published: March 2022

The spatial component of past forest fires in temperate Europe has been little studied, despite the value of such data in quantifying human and natural factors driving fire activity and associated forest dynamics. Changes in fire regimes reported across a range of ecosystems call for a better understanding of variability in historic fires and may help define reference points that can be relied upon when discussing climate change effects. We provide the first dendrochronological reconstruction of historical fire sizes in Central Europe and analyze the minimum extent of fires during the last four centuries in a 9.2 km2 (920 ha) conifer-dominated section of Białowieża Forest, one of the largest continuous lowland forests of the subcontinent. We recorded 82 fires between 1666 and 1946, using 275 sample trees, while 92% of fires (76 out of 82) spread beyond the studied area. Fires varied considerably in size, from events recorded at only one site (1–200 ha) to fires recorded in more than half of the studied area, thus exceeding 500 ha in size. The fire cycle was 11 years over the whole study period, with three distinct periods revealed by the regime shift analysis. In the years 1670–1750, the fire cycle averaged 12 years. It shortened to 7 years between 1755–1840 and increased to 22 years over the 1845–1955 period. In comparison with present day data, the reconstructed fire density of 3.2 fires per 100 km2 (10 000 ha) and year exceeded lightning ignition density by one to two orders of magnitude, suggesting a significant contribution of human-related ignitions. Our results highlight the important role of fire disturbance in Białowieża Forest and provide critical baseline information to design biological conservation strategies for European forests.
Community Engagement With Proactive Wildfire Management in British Columbia, Canada: Perceptions, Preferences, and Barriers to Action
Authors: Copes-Gerbitz Kelsey , Dickson-Hoyle Sarah , Ravensbergen Sarah L. , Hagerman Shannon M. , Daniels Lori D. , Coutu Jemina
Published: March 2022

Wildfires in the wildland-urban interface (WUI) are increasingly threatening lives and livelihoods. These growing impacts have prompted a paradigm shift toward proactive wildfire management that prioritizes prevention and preparedness instead of response. Despite this shift, many communities remain unprepared for wildfires in the WUI due to diverse individual and social-political factors influencing engagement with proactive management approaches. The catastrophic fire seasons of 2017, 2018, and 2021 in British Columbia (BC), Canada, highlighted just how vulnerable communities continue to be and the urgent need to understand the factors limiting engagement to future resilience to wildfire. Our study, conducted prior to the catastrophic fire season in 2017, surveyed 77 community leaders across BC to better understand the factors driving engagement, including risk perception, preferences and support for approaches, and key barriers limiting progress. We demonstrate that wildfire risk is an urgent issue facing communities across BC, but a range of factors drive variable community engagement with proactive wildfire management. First Nations and smaller (≤5,000 residents) communities were less likely to have developed a community wildfire plan, even though First Nations were significantly more concerned than municipalities/regional districts about certain values (such as drinking water and biodiversity) that were at risk from wildfire. In general, proactive approaches that were considered effective were also the most supported. The most highly supported approaches included enforcement of regulations and education, both of which are considered provincial responsibility in BC and are unlikely to alter community values in the WUI. In contrast, approaches involving prescribed burning of the understory had the highest levels of opposition. Despite variability in these individual factors, social-political barriers related to financial and social (time and expertise) capacity primarily limited engagement with proactive wildfire management, including provincial and federal funding programs. However, these barriers are not equally felt across community groups; First Nations identified social capacity (such as expertise on government-sponsored approaches and awareness of funding programs) as significantly more limiting than municipalities/regional districts. Our study illustrates the limitations of implementing a “shared responsibility” of proactive wildfire management in the WUI in BC without targeted supports to address unequal capacity barriers.
Benchmarking the Effectiveness and Accuracy of Multiple Mitochondrial DNA Variant Callers: Practical Implications for Clinical Application
Authors: Ip Eddie K. K. , Troup Michael , Xu Colin , Winlaw David S. , Dunwoodie Sally L. , Giannoulatou Eleni
Published: March 2022

Mitochondrial DNA (mtDNA) mutations contribute to human disease across a range of severity, from rare, highly penetrant mutations causal for monogenic disorders to mutations with milder contributions to phenotypes. mtDNA variation can exist in all copies of mtDNA or in a percentage of mtDNA copies and can be detected with levels as low as 1%. The large number of copies of mtDNA and the possibility of multiple alternative alleles at the same DNA nucleotide position make the task of identifying allelic variation in mtDNA very challenging. In recent years, specialized variant calling algorithms have been developed that are tailored to identify mtDNA variation from whole-genome sequencing (WGS) data. However, very few studies have systematically evaluated and compared these methods for the detection of both homoplasmy and heteroplasmy. A publicly available synthetic gold standard dataset was used to assess four mtDNA variant callers (Mutserve, mitoCaller, MitoSeek, and MToolBox), and the commonly used Genome Analysis Toolkit “best practices” pipeline, which is included in most current WGS pipelines. We also used WGS data from 126 trios and calculated the percentage of maternally inherited variants as a metric of calling accuracy, especially for homoplasmic variants. We additionally compared multiple pathogenicity prediction resources for mtDNA variants. Although the accuracy of homoplasmic variant detection was high for the majority of the callers with high concordance across callers, we found a very low concordance rate between mtDNA variant callers for heteroplasmic variants ranging from 2.8% to 3.6%, for heteroplasmy thresholds of 5% and 1%. Overall, Mutserve showed the best performance using the synthetic benchmark dataset. The analysis of mtDNA pathogenicity resources also showed low concordance in prediction results. We have shown that while homoplasmic variant calling is consistent between callers, there remains a significant discrepancy in heteroplasmic variant calling. We found that resources like population frequency databases and pathogenicity predictors are now available for variant annotation but still need refinement and improvement. With its peculiarities, the mitochondria require special considerations, and we advocate that caution needs to be taken when analyzing mtDNA data from WGS data.
Network Crosstalk as a Basis for Drug Repurposing
Authors: Guala Dimitri , Sonnhammer Erik L. L.
Published: March 2022

The need for systematic drug repurposing has seen a steady increase over the past decade and may be particularly valuable to quickly remedy unexpected pandemics. The abundance of functional interaction data has allowed mapping of substantial parts of the human interactome modeled using functional association networks, favoring network-based drug repurposing. Network crosstalk-based approaches have never been tested for drug repurposing despite their success in the related and more mature field of pathway enrichment analysis. We have, therefore, evaluated the top performing crosstalk-based approaches for drug repurposing. Additionally, the volume of new interaction data as well as more sophisticated network integration approaches compelled us to construct a new benchmark for performance assessment of network-based drug repurposing tools, which we used to compare network crosstalk-based methods with a state-of-the-art technique. We find that network crosstalk-based drug repurposing is able to rival the state-of-the-art method and in some cases outperform it.
Machine-Learning Algorithm-Based Prediction of Diagnostic Gene Biomarkers Related to Immune Infiltration in Patients With Chronic Obstructive Pulmonary Disease
Authors: Zhang Yuepeng , Xia Rongyao , Lv Meiyu , Li Zhiheng , Jin Lingling , Chen Xueda , Han Yaqian , Shi Chunpeng , Jiang Yanan , Jin Shoude
Published: March 2022

Objective

This study aims to identify clinically relevant diagnostic biomarkers in chronic obstructive pulmonary disease (COPD) while exploring how immune cell infiltration contributes towards COPD pathogenesis.

Methods

The GEO database provided two human COPD gene expression datasets (GSE38974 and GSE76925; n=134) along with the relevant controls (n=49) for differentially expressed gene (DEG) analyses. Candidate biomarkers were identified using the support vector machine recursive feature elimination (SVM-RFE) analysis and the LASSO regression model. The discriminatory ability was determined using the area under the receiver operating characteristic curve (AUC) values. These candidate biomarkers were characterized in the GSE106986 dataset (14 COPD patients and 5 controls) in terms of their respective diagnostic values and expression levels. The CIBERSORT program was used to estimate patterns of tissue infiltration of 22 types of immune cells. Furthermore, the in vivo and in vitro model of COPD was established using cigarette smoke extract (CSE) to validated the bioinformatics results.

Results

80 genes were identified via DEG analysis that were primarily involved in cellular amino acid and metabolic processes, regulation of telomerase activity and phagocytosis, antigen processing and MHC class I-mediated peptide antigen presentation, and other biological processes. LASSO and SVM-RFE were used to further characterize the candidate diagnostic markers for COPD, SLC27A3, and STAU1. SLC27A3 and STAU1 were found to be diagnostic markers of COPD in the metadata cohort (AUC=0.734, AUC=0.745). Their relevance in COPD were validated in the GSE106986 dataset (AUC=0.900 AUC=0.971). Subsequent analysis of immune cell infiltration discovered an association between SLC27A3 and STAU1 with resting NK cells, plasma cells, eosinophils, activated mast cells, memory B cells, CD8+, CD4+, and helper follicular T-cells. The expressions of SLC27A3 and STAU1 were upregulated in COPD models both in vivo and in vitro. Immune infiltration activation was observed in COPD models, accompanied by the enhanced expression of SLC27A3 and STAU1. Whereas, the knockdown of SLC27A3 or STAU1 attenuated the effect of CSE on BEAS-2B cells.

Conclusion

STUA1 and SLC27A3 are valuable diagnostic biomarkers of COPD. COPD pathogenesis is heavily influenced by patterns of immune cell infiltration. This study provides a molecular biology insight into COPD occurrence and in exploring new therapeutic means useful in COPD.