bluuebunny/crossref_metadata_2025 huggingface dataset:
Unique Angiogenesis From Cardiac Arterioles During Pericardial Adhesion Formation
Authors: Namiguchi Kenji , Sakaue Tomohisa , Okazaki Mikio , Kanno Kaho , Komoda Yuhei , Shikata Fumiaki , Kurata Mie , Ota Noritaka , Kubota Yoshiaki , Kurobe Hirotsugu , Nishimura Takashi , Masumoto Junya , Higashiyama Shigeki , Izutani Hironori
Published: February 2022

Objectives

The molecular mechanisms underlying post-operative pericardial adhesions remain poorly understood. We aimed to unveil the temporal molecular and cellular mechanisms underlying tissue dynamics during adhesion formation, including inflammation, angiogenesis, and fibrosis.

Methods and Results

We visualized cell-based tissue dynamics during pericardial adhesion using histological evaluations. To determine the molecular mechanism, RNA-seq was performed. Chemical inhibitors were administered to confirm the molecular mechanism underlying adhesion formation. A high degree of adhesion formation was observed during the stages in which collagen production was promoted. Histological analyses showed that arterioles excessively sprouted from pericardial tissues after the accumulation of neutrophils on the heart surface in mice as well as humans. The combination of RNA-seq and histological analyses revealed that hyperproliferative endothelial and smooth muscle cells with dedifferentiation appeared in cytokine-exposed sprouting vessels and adhesion tissue but not in quiescent vessels in the heart. SMAD2/3 and ERK activation was observed in sprouting vessels. The simultaneous abrogation of PI3K/ERK or TGF-β/MMP9 signaling significantly decreased angiogenic sprouting, followed by inhibition of adhesion formation. Depleting MMP9-positive neutrophils shortened mice survival and decreased angiogenic sprouting and fibrosis in the adhesion. Our data suggest that TGF-β/matrix metalloproteinase-dependent tissue remodeling and PI3K/ERK signaling activation might contribute to unique angiogenesis with dedifferentiation of vascular smooth muscle cells from the contractile to the synthetic phenotype for fibrosis in the pericardial cavity.

Conclusions

Our findings provide new insights in developing prevention strategies for pericardial adhesions by targeting the recruitment of vascular cells from heart tissues.
EP-PINNs: Cardiac Electrophysiology Characterisation Using Physics-Informed Neural Networks
Authors: Herrero Martin Clara , Oved Alon , Chowdhury Rasheda A. , Ullmann Elisabeth , Peters Nicholas S. , Bharath Anil A. , Varela Marta
Published: February 2022

Accurately inferring underlying electrophysiological (EP) tissue properties from action potential recordings is expected to be clinically useful in the diagnosis and treatment of arrhythmias such as atrial fibrillation. It is, however, notoriously difficult to perform. We present EP-PINNs (Physics Informed Neural Networks), a novel tool for accurate action potential simulation and EP parameter estimation from sparse amounts of EP data. We demonstrate, using 1D and 2D in silico data, how EP-PINNs are able to reconstruct the spatio-temporal evolution of action potentials, whilst predicting parameters related to action potential duration (APD), excitability and diffusion coefficients. EP-PINNs are additionally able to identify heterogeneities in EP properties, making them potentially useful for the detection of fibrosis and other localised pathology linked to arrhythmias. Finally, we show EP-PINNs effectiveness on biological in vitro preparations, by characterising the effect of anti-arrhythmic drugs on APD using optical mapping data. EP-PINNs are a promising clinical tool for the characterisation and potential treatment guidance of arrhythmias.
Effect of Anti-Rheumatic Drugs on Cardiovascular Disease Events in Rheumatoid Arthritis
Authors: Baoqi Yang , Dan Ma , Xingxing Zhao , Xueqing Zhu , Yajing Wang , Ke Xu , Liyun Zhang
Published: February 2022

Rheumatoid arthritis (RA) is an autoimmune disease characterized by erosive arthritis, which can involve multiple systems. Patients with RA may have a variety of comorbidities, including cardiovascular disease (CVD), lung cancer, lymphoma, infection, osteoporosis, fatigue, depression, colon cancer, breast cancer, prostate cancer, and Alzheimer's disease. Among these comorbidities, the incidence of CVD, lung cancer, lymphoma, infection, and osteoporosis is higher. CVD is a serious complication of RA. The risk of CVD and associated mortality rate in patients with RA is high, and the treatment rate is low. In addition to traditional risk factors, such as age, sex, blood pressure, and diabetes, RA is also associated with inflammation. Furthermore, therapeutic drugs for RA, including non-steroidal anti-inflammatory drugs, glucocorticoids, and disease-modifying anti-rheumatic drugs, have beneficial or harmful effects on cardiovascular events in patients with RA. This article discusses the effects of therapeutic drugs for RA on cardiovascular events.
An Investigation Into the Mechanism of Rock Bursts in Mines for Tunnel-Cut Isolated Areas with Multiple Stress Fields
Authors: Zhang Heng , Ouyang Zhenhua , Li Tie , Liu Su , Yi Haiyang , Wang Honglei , Chen Jianqiang , Li Kang
Published: February 2022

Tunnels in several mines in Shaanxi Province, China, which are subject to multiple stress fields, are used as case studies to clarify the structural problems associated with rock bursts that occur in high-stress mines. Field studies featuring field measurements and theoretical analysis are used to investigate the modes and mechanisms of failure. The following are the main findings: (1) a model for distributing the dominant pressure features around the goaf was established by analyzing the stress distribution induced by the goafs on both sides of the excavated zone in a coal seam. The model reveals the pressure distribution in the tunnel-cut area, which is the mechanical factor responsible for rockburst. (2) Because of the goafs acting on both sides of the tunnel, an area of concentrated stress was formed, and stress was transferred to the coal seam. The intense tunnel-cutting action can reduce the stability of the coal. The plastic area caused by tunnel mining and a reduction in the elastic area of the tunnel-cut coal pillars in each segment, increase the possibility for rockburst under the application of dynamic-static stress; this process is known as a stabilizing factor. (3) Due to the combined effect of the tunnel-cut and goafs on both sides, most of the microseismic incidents happened in the core area of coal pillar and in the side of tunnels. When the stress applied on coal pillar is more than critical strength, burst and mine earthquake can be induced. Our study focused mainly on rockburst incidents that occurred in coal mines in Shaanxi Province, which were caused by tunnel-cut coal seams that were subject to multiple stress fields. The study has direct implications for developing new and improved guidelines for preventing rockburst in mines.
An Efficient Rock Physics Scheme for Estimating Crack Density and Fluid Saturation of Shale Gas Reservoir
Authors: Jiang Ziran , Qi Qiaomu , Jiang Xudong , Meng Jikun , Wang Xing-Jian
Published: February 2022

We propose a simple rock physics model for the characterization of elastic properties of shale. The model combines a dual-porosity concept and the effective medium theory for constructing the anisotropic elastic tensor of the multimineral organic-rich shale. Based on the model, we address how to estimate two key shale gas evaluation parameters, i.e., crack density and gas saturation from well-log and seismic data. Application to Wufeng-Longmaxi Shale shows that the estimated crack porosity decreases with increasing burial depth and decreasing clay content. The analysis indicates that the microcracks are mainly developed among clay minerals, which is consistent with the results from mercury injection and SEM imaging experiments. More importantly, we show that the velocity of the Wufeng-Longmaxi Shale is primarily controlled by the crack porosity instead of the total porosity. Both P- and S-wave velocities decrease linearly as the volume of microcrack increases. The fluid substitution analysis shows that the Poisson’s ratio and P-impedance of the shale are sensitive to the change of pore-fluid saturation. Based on the above sensitivity analyses, we customize a rock physics template for quantifying crack density, and gas saturation from the shale elastic properties. The interpretation results show that there is an overall good agreement between the measured and predicted petrophysical properties from well-log and seismic data.
Hierarchical Modeling of Carbonate Fault-Controlled Paleokarst Systems: A Case Study of the Ordovician Reservoir in the Tahe Oilfield, Tarim Basin
Authors: Zhang Wenbiao , He Zhiliang , Duan Taizhong , Li Meng , Zhao Huawei
Published: February 2022

As a special type of fracture-cavity carbonate reservoir, fault/fracture-controlled paleokarsts are affected by large strike-slip faults with various storage spaces, irregular geometry, and stochastic spatial distribution, which brings new challenges to their 3D quantitative characterization and geological modeling. Based on multi-scale research data, a hierarchical scheme of a fault-controlled paleokarst is established for the Tahe oilfield, and then a hierarchical modeling method for the paleokarst is proposed based on the principles of hierarchical constraint and genetic control. The results show that the fault-controlled paleokarst hierarchy is divided into four levels according to genesis and scale. These are the strike-slip fault impact zone, the fault-controlled external paleokarst envelope, the fault-controlled internal paleokarst architecture, and the internal karst cave fillings. The strike-slip fault impact zone model is established using deterministic data of the main fault, secondary fault, envelope range, and key geological horizons obtained from seismic interpretation. Based on the seismic FL (Fault Likelihood) attribute, the external envelope model of the fault-controlled paleokarst is established using the deterministic method through automatic attribute segmentation and drilling calibration. With the constraint of the external envelope, the internal architectural elements are classified and modeled. A large-scale karst cave model and mesoscale discrete fracture distribution model are established using the deterministic method based on the seismic texture property and seismic ant property truncation. Taking well data as conditional data and seismic-geological probability cubes as constraint data, the sequential indication simulation and object-based marked point process simulation methods are used to obtain the model of the dissolution pores distribution and the model of the discrete small-scale fractures distribution, respectively. Finally, a typical fault-controlled paleokarst reservoir in the TP area of the Tahe oilfield is taken as an example to test the above modeling method; the 3D integrated model developed in this study can reflect the spatial hierarchy of the fault-controlled paleokarst carbonate reservoir.
Genome-Wide Identification and Expression Analysis of VviYABs Family Reveal Its Potential Functions in the Developmental Switch and Stresses Response During Grapevine Development
Authors: Jiu Songtao , Zhang Yanping , Han Peng , Han Yubo , Xu Yan , Liu Gengsen , Leng Xiangpeng
Published: February 2022

Plant-specific YABBY (YAB) transcription factors play multiple roles in plant growth and development process. However, no comprehensive study has been performed in grapevines, especially to determine their roles in berry development and abiotic stress response. A total of seven VviYABs allocated to six chromosomal positions in grapevines were identified and classified into five subfamilies based on phylogenetic and structural analysis. Promoter element analysis and tissue-specific transcriptional response of VviYABs suggested that VviYABs might play vital roles in plant growth and development. VviYAB1, 2, 3, and 5 showed significantly higher expression levels in vegetative/green organs than in mature/woody tissues, implying that VviYABs might be involved in the regulatory switch from immature to mature developmental phases. The expression of VviYAB1, 2, 3, and VviFAS were gradually downregulated during berry developmental and ripening, which can be considered as putative molecular biomarkers between vegetative/green and mature/woody samples, and were used to identify key developmental and metabolic processes in grapevines. Furthermore, VviYAB1 expression was not markedly increased by gibberellic acid (GA3) treatment alone, but displayed significant upregulation when GA3 in combination with N-(2-chloro-4-pyridyl)-N′-phenylurea (CPPU) were applied, suggesting an involvement of VviYAB1 in fruit expansion by mediating cytokinin signaling pathway. Additionally, microarray and RNA-seq data suggested that VviYABs showed transcriptional regulation in response to various abiotic and biotic stresses, including salt, drought, Bois Noir, Erysiphe necator, and GLRaV-3 infection. Overall, our results provide a better understanding of the classification and functions of VviYABs during berry development and in response to abiotic and biotic stresses in grapevines.
HLA-C*04:01 Affects HLA Class I Heterozygosity and Predicted Affinity to SARS-CoV-2 Peptides, and in Combination With Age and Sex of Armenian Patients Contributes to COVID-19 Severity
Authors: Hovhannisyan Anahit , Madelian Vergine , Avagyan Sevak , Nazaretyan Mihran , Hyussyan Armine , Sirunyan Alina , Arakelyan Rubina , Manukyan Zorayr , Yepiskoposyan Levon , Mayilyan Karine R. , Jordan Frieda
Published: February 2022

The novel SARS-CoV-2 coronavirus infection has become a global health concern, causing the COVID-19 pandemic. The disease symptoms and outcomes depend on the host immunity, in which the human leukocyte antigen (HLA) molecules play a distinct role. The HLA alleles have an inter-population variability, and understanding their link to the COVID-19 in an ethnically distinct population may contribute to personalized medicine. The present study aimed at detecting associations between common HLA alleles and COVID-19 susceptibility and severity in Armenians. In 299 COVID-19 patients (75 asymptomatic, 102 mild/moderate, 122 severe), the association between disease severity and classic HLA-I and II loci was examined. We found that the advanced age, male sex of patients, and sex and age interaction significantly contributed to the severity of the disease. We observed that an age-dependent effect of HLA-B*51:01 carriage [odds ratio (OR)=0.48 (0.28-0.80), Pbonf <0.036] is protective against severe COVID-19. Contrary, the HLA-C*04:01 allele, in a dose-dependent manner, was associated with a significant increase in the disease severity [OR (95% CI) =1.73 (1.20-2.49), Pbonf <0.021] and an advancing age (P<0.013). The link between HLA-C*04:01 and age was secondary to a stronger association between HLA-C*04:01 and disease severity. However, HLA-C*04:01 exerted a sex-dependent differential distribution between clinical subgroups [females: P<0.0012; males: P=0.48]. The comparison of HLA-C*04:01 frequency between subgroups and 2,781 Armenian controls revealed a significant incidence of HLA-C*04:01 deficiency in asymptomatic COVID-19. HLA-C*04:01 homozygous genotype in patients blueprinted a decrease in heterozygosity of HLA-B and HLA class-I loci. In HLA-C*04:01 carriers, these changes translated to the SARS-CoV-2 peptide presentation predicted inefficacy by HLA-C and HLA class-I molecules, simultaneously enhancing the appropriate HLA-B potency. In patients with clinical manifestation, due to the high prevalence of HLA-C*04:01, these effects provided a decrease of the HLA class-I heterozygosity and an ability to recognize SARS-CoV-2 peptides. Based on our observations, we developed a prediction model involving demographic variables and HLA-C*04:01 allele for the identification of potential cases with the risk of hospitalization (the area under the curve (AUC) = 86.2%) or severe COVID-19 (AUC =71%).
Transplacental and Breast Milk Transfer of IgG1 Are Both Required for Prolonged Protection of Offspring Against Influenza A Infection
Authors: Chronopoulos Julia , Martin James G. , Divangahi Maziar
Published: February 2022

The immune system during pregnancy teeters between maintaining fetal tolerance and providing protection against pathogens. Due to this delicate balance, pregnant women and their offspring often have increased susceptibilities to infection. During the first year of life, infant immunity against infection is mainly mediatedviapassively transferred maternal antibodies. However, our understanding of the route of transfer of the maternal antibodies for conferring protection to influenza A virus (IAV) infection in offspring is incomplete. Here we have demonstrated that offspring from IAV-infected mice were significantly protected against IAV infection. This remarkable increase in survival is mediatedviathe elevated maternal serum IgG1. By cross-fostering, we further showed that this enhanced host resistance was only achieved in mice born to and nursed by IAV-infected mothers. Collectively, our data suggest that the prolonged protection of offspring against IAV infection requires maternal IgG1 from both the placenta and breast milk.
Compound-Specific Nitrogen Isotope Analysis of Amino Acids in Eye Lenses as a New Tool to Reconstruct the Geographic and Trophic Histories of Fish
Authors: Harada Yota , Ito Shin-ichi , Ogawa Nanako O. , Yoshikawa Chisato , Ishikawa Naoto F. , Yoneda Michio , Ohkouchi Naohiko
Published: February 2022

Fish migration has always played an essential role in marine conservation and fisheries management. However, migration patterns are changing globally alongside changing ocean conditions. This affects the spatial scale of required governance and, consequently, our food supply. Technological advances in the bio-tracer approach using isotopes would make it possible to monitor fish migration differently from the conventional bio-logging method. Eye lenses of fish are incrementally grown and metabolically inert. Therefore, stable isotope analysis of eye lenses can reconstruct the geographic and trophic histories of fish. However, it is difficult to distinguish between the two pieces of information: migration and changing trophic relationships with the conventional bulk stable isotope approach. In this study, we measured the nitrogen isotope ratios of individual amino acids in eye lenses of chub mackerel (n = 3) from the western North Pacific to test whether the two pieces of information could be distinguished. A maximum of 34 growth layers was obtained from a single eye lens. For assigning the isotopic trends observed in lens tissues to specific life stages or size classes, we established a relationship between lens size and fork length (FL) as a reference framework. The reconstructed nitrogen isotope chorology of chub mackerel showed an increase in trophic position of about 1 unit from juvenile (FL ∼30 mm) to adult stages (FL ∼300 mm). The variation in nitrogen isotope ratios of phenylalanine (a source amino acid) in the eye lenses was –3 to 5‰. This baseline variability could be used for estimating fish movements. This study proposed compound-specific nitrogen isotope analysis of amino acids in eye lenses as a new tool capable of reconstructing the geographic and trophic histories of migratory fish.
Classifications and Characteristics of Marine Heatwaves in the Northern South China Sea
Authors: Wang Yinxia , Zeng Jisheng , Wei Zheng , Li Shan , Tian Song , Yang Fan , Chen Qidong , He Yinghui
Published: February 2022

The classifications and associated characteristics of marine heatwaves (MHWs) in the northern South China Sea (SCS) have been investigated. Based on the ratio of the area with MHWs to the total area of the northern SCS, the MHWs are divided into three categories, i.e., narrow coverage, moderate coverage, and wide coverage. Different kinds of MHWs (i.e., narrow coverage, moderate coverage, and wide coverage) contribute around 64, 28, and 8% to the total days with MHWs, respectively. Narrow coverage MHW scatters over the northern SCS continental shelf, and moderate (wide) coverage MHWs are concentrated east of Hainan Island (mid of northern SCS continental shelf). Wide coverage MHWs contribute more than 50% to the total MHW cumulative sea surface temperature (SST) anomalies. The cumulative days and temperature anomalies of all kinds of MHWs exhibit significant long-term trends and decadal variability.
Optimizing Barium Titanate Nanocomposite Bone Scaffolds for Biomineralization in Dynamic Compression Bioreactors Using Time-Lapsed Microstructural Imaging and Smart Thresholding
Authors: Schädli Gian Nutal , David Helena , de Leeuw Anke M. , Carlson Franklin , Tenisch Lara , Muff Pascal , Rubert Marina , Müller Ralph
Published: February 2022

Bone scaffolds made of calcium phosphate polymer nanocomposites have limited osteoinductive properties. Piezoelectric materials have attracted considerable interest in bone tissue engineering due to their potential to promote osteogenesis through additional electrical stimulation. Time-lapsed micro-CT imaging is a time-effective tool for in vitro optimization of such scaffolds but is challenged by nanocomposites with a high attenuation coefficient, such as one containing high amounts of piezoelectric barium titanate. We used high-resolution end-point micro-CT scans combined with histology and Raman spectroscopy to screen polydopamine functionalized nanocomposites containing 3–27 vol% barium titanate for collagenous extracellular matrix formation and mineralization. All compositions showed well-connected extracellular matrix and birefringent matured collagen after seven weeks of static human mesenchymal stem cell cultures. Nevertheless, high-resolution micro-CT analysis combined with smart thresholding during image processing enabled us to observe modest differences in ECM mineralization between groups suggesting that a volume fraction of 9–21% barium titanate facilitated the formation of dense mineral clusters in the pores even in the absence of mechanical stimuli, further corroborated by Raman spectroscopy. The same image processing approach facilitated the analysis of time-lapsed micro-CT images of scaffold cultures in dynamic compression bioreactors where 9 vol% barium titanate was the best nanocomposite composition, resulting in a significant twofold increased maturation rate under dynamic conditions. On the other hand, barium titanate content of ≥15 vol% did not improve mineralization. At 27 vol%, the biomineralization of the collagenous extracellular matrix was even impeded in the nanocomposite scaffolds, as evidenced by histology stainings. Overall, our approach enables time-lapsed quantitative assessment of high X-ray absorbing nanocomposite scaffolds for biomineralization under dynamic compression, facilitating the optimization of such mechanically responsive scaffolds.
Sexual Health Dysfunction After Radiotherapy for Gynecological Cancer: Role of Physical Rehabilitation Including Pelvic Floor Muscle Training
Authors: Barcellini Amelia , Dominoni Mattia , Dal Mas Francesca , Biancuzzi Helena , Venturini Sara Carla , Gardella Barbara , Orlandi Ester , Bø Kari
Published: February 2022

Introduction

The present study aims to describe: 1. How the side effects of radiotherapy (RT) could impact sexual health in women; 2. The effectiveness of physical rehabilitation including pelvic floor muscle training (PFMT) in the management of sexual dysfunction after RT.

Materials and Methods

Search keys on PubMed, Web of Science, Scopus, PEDro, and Cochrane were used to identify studies on women treated with radical or adjuvant RT and/or brachytherapy for gynecological cancers with an emphasis on vulvo-vaginal toxicities and PFMT studies on sexual dysfunction for this group of women.

Results

Regarding the first key question, we analyzed 19 studies including a total of 2,739 women who reported vaginal dryness, stenosis, and pain as the most common side effects. Reports of dosimetric risk factors and dose-effect data for vaginal and vulvar post-RT toxicities are scant. Only five studies, including three randomized controlled trials (RCTs), were found to report the effect of PFMT alone or in combination with other treatments. The results showed some evidence for the effect of training modalities including PFMT, but to date, there is insufficient evidence from high-quality studies to draw any conclusion of a possible effect.

Conclusions

Gynecological toxicities after RT are common, and their management is challenging. The few data available for a rehabilitative approach on post-actinic vulvo-vaginal side effects are encouraging. Large and well-designed RCTs with the long-term follow-up that investigate the effect of PFMT on vulvo-vaginal tissues and pelvic floor muscle function are needed to provide further guidance for clinical management.
Conditional Drug Approval as a Path to Market for Oncology Drugs in Canada: Challenges and Recommendations for Assessing Eligibility and Regulatory Responsiveness
Authors: McPhail Melanie , Weiss Emma , Bubela Tania
Published: February 2022

International drug regulators use conditional drug approval mechanisms to facilitate faster patient access to drugs based on a lower evidentiary standard typically required of drug approvals. Faster and earlier access is justified by limiting eligibility to drugs intended for serious and life-threatening diseases and by requiring post-market evidence collection to confirm clinical benefit. One such mechanism in Canada, the Notice of Compliance with Conditions (NOC/c) policy, was introduced in 1998. Today, most of the drugs approved under the NOC/c policy are for oncology indications. We analyze oncology drugs approvals under the NOC/c policy to inform discussions of two tradeoffs applied to conditional drug approvals, eligibility criteria and post-market evidence. Our analysis informs recommendations for Canada's proposed regulatory reforms approach to conditional approvals pathways. Our analysis demonstrates that under the current policy, eligibility criteria are insufficiently defined, resulting in their inconsistent application by Health Canada. Regulatory responsiveness to post-market evidence from post-market clinical trial and foreign jurisdiction regulatory decisions is slow and insufficient. In the absence of sufficient regulatory responsiveness, physicians and patients must make clinical decisions without the benefit of the best available evidence. Together, our analysis of the two core tradeoffs in Canada's conditional drug approval provides insight to inform the further development of Canada's proposed agile regulatory approach to drugs and devices that will expand the use of terms and conditions.
COVID-19-Triggered Acute Exacerbation of IPF, an Underdiagnosed Clinical Entity With Two-Peaked Respiratory Failure: A Case Report and Literature Review
Authors: Goto Yosuke , Sakamoto Koji , Fukihara Jun , Suzuki Atsushi , Omote Norihito , Ando Akira , Shindo Yuichiro , Hashimoto Naozumi
Published: February 2022

Because severe coronavirus disease 2019 (COVID-19) affects the respiratory system and develops into respiratory failure, patients with pre-existing chronic lung disorders, such as idiopathic pulmonary fibrosis (IPF), are thought to be at high risk of death. Patients with IPF often suffer from a lethal complication, acute exacerbation (AE), a significant part of which is assumed to be triggered by respiratory viral infection. However, whether mild to moderate COVID-19 can trigger AE in patients with IPF remains unknown. This is the case report of a 60-year-old man with a 4-year history of IPF who successfully recovered from moderate COVID-19 but subsequently developed more severe respiratory failure, which was considered to be a COVID-19-triggered acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). It is important to be aware of the risk of AE-IPF after COVID-19 and to properly manage this deadly complication of IPF. Recent literature reporting cases with chronic interstitial lung diseases which developed respiratory failure by complications with COVID-19 is also reviewed and discussed.
New Insight Into the Interspecies Shift of Anammox Bacteria Ca. “Brocadia” and Ca. “Jettenia” in Reactors Fed With Formate and Folate
Authors: Kallistova Anna , Nikolaev Yury , Grachev Vladimir , Beletsky Alexey , Gruzdev Evgeny , Kadnikov Vitaly , Dorofeev Alexander , Berestovskaya Julia , Pelevina Anna , Zekker Ivar , Ravin Nikolai , Pimenov Nikolai , Mardanov Andrey
Published: February 2022

The sensitivity of anaerobic ammonium-oxidizing (anammox) bacteria to environmental fluctuations is a frequent cause of reactor malfunctions. It was hypothesized that the addition of formate and folate would have a stimulating effect on anammox bacteria, which in turn would lead to the stability of the anammox process under conditions of a sharp increase in ammonium load, i.e., it helps overcome a stress factor. The effect of formate and folate was investigated using a setup consisting of three parallel sequencing batch reactors equipped with a carrier. Two runs of the reactors were performed. The composition of the microbial community was studied by the 16S rRNA gene profiling and metagenomic analysis. Among anammox bacteria, Ca. “Brocadia” spp. dominated during the first run. A stimulatory effect of folate on the daily nitrogen removal rate (dN) was identified. The addition of formate led to progress in dissimilatory nitrate reduction and stimulated the growth of Ca. “Jettenia” spp. The spatial separation of two anammox species was observed in the formate reactor: Ca. “Brocadia” occupied the carrier and Ca. “Jettenia”—the walls of the reactors. Biomass storage at low temperature without feeding led to an interspecies shift in anammox bacteria in favor of Ca. “Jettenia.” During the second run, a domination of Ca. “Jettenia” spp. was recorded along with a stimulating effect of formate, and there was no effect of folate on dN. A comparative genome analysis revealed the patterns suggesting different strategies used by Ca. “Brocadia” and Ca. “Jettenia” spp. to cope with environmental changes.
Three Month Follow-Up of Patients With COVID-19 Pneumonia Complicated by Pulmonary Embolism
Authors: Calabrese Cecilia , Annunziata Anna , Flora Martina , Mariniello Domenica Francesca , Allocca Valentino , Palma Maria Ilaria , Coppola Antonietta , Meoli Ilernando , Pafundi Pia Clara , Fiorentino Giuseppe
Published: February 2022

Background: Previous studies have demonstrated persistent dyspnoea and impairment of respiratory function in the follow-up of patients who have recovered from COVID-19 pneumonia. However, no studies have evaluated the clinical and functional consequences of COVID-19 pneumonia complicated by pulmonary embolism.

Objective: The aim of our study was to assess the pulmonary function and exercise capacity in COVID-19 patients 3 months after recovery from pneumonia, either complicated or not by pulmonary embolism.

Methods: This was a retrospective, single-centre, observational study involving 68 adult COVID-19 patients with a positive/negative clinical history of pulmonary embolism (PE) as a complication of COVID-19 pneumonia. Three months after recovery all patients underwent spirometry, diffusion capacity of the lungs for carbon monoxide (DLCO), and 6 minute walk test (6MWT). In addition, high-resolution computed tomography (HRCT) of the lung was carried out and CT-pulmonary angiography was conducted only in the PE+ subgroup. Patients with a previous diagnosis of PE or chronic lung diseases were excluded from the study.

Results: Of the 68 patients included in the study, 24 had previous PE (PE+) and 44 did not (PE−). In comparison with the PE− subgroup, PE+ patients displayed a FVC% predicted significantly lower (87.71 ± 15.40 vs 98.7 ± 16.7, p = 0.009) and a significantly lower DLCO% predicted (p = 0.023). In addition, a higher percentage of patients were dyspnoeic on exercise, as documented by a mMRC score ≥1 (75% vs 54.3%, p < 0.001) and displayed a SpO2 <90% during 6MWT (37.5% vs 0%, p < 0.001). HRCT features suggestive of COVID-19 pneumonia resolution phase were present in both PE+ and PE− subjects without any significant difference (p = 0.24) and abnormalities at CT pulmonary angiography were detected in 57% of the PE+ subgroup.

Conclusion: At the 3 month follow-up, the patients who recovered from COVID-19 pneumonia complicated by PE showed more dyspnoea and higher impairment of pulmonary function tests compared with those without PE.
Susceptibility to Metabolic Diseases in COVID-19: To be or Not to be an Issue
Authors: Kaviani Maryam , Keshtkar Somayeh , Soleimanian Saeede , Sabet Sarvestani Fatemeh , Azarpira Negar , Pakbaz Sara
Published: February 2022

Despite the passage of more than 17 months from the beginning of the COVID-19 pandemic, challenges regarding the disease and its related complications still continue in recovered patients. Thus, various studies are underway to assay the long-term effects of COVID-19. Some patients, especially those with severe symptoms, experience susceptibility to a range of diseases and substantial organ dysfunction after recovery. Although COVID-19 primarily affects the lungs, multiple reports exist on the effect of this infection on the kidneys, cardiovascular system, and gastrointestinal tract. Studies have also indicated the increased risk of severe COVID-19 in patients with diabetes. On the other hand, COVID-19 may predispose patients to diabetes, as the most common metabolic disease. Recent studies have shown that Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) binds to Angiotensin-Converting Enzyme 2 (ACE2) receptors, which are expressed in the tissues and organs involved in regulating the metabolic status including pancreas, adipose tissue, gastrointestinal tract, and kidneys. Therefore, SARS-CoV-2 may result in metabolic disturbance. However, there are still many unknowns about SARS-CoV-2, which are required to be explored in basic studies. In this context, special attention to molecular pathways is warranted for understanding the pathogenesis of the disease and achieving therapeutic opportunities. Hence, the present review aims to focus on the molecular mechanisms associated with the susceptibility to metabolic diseases amongst patients recovered from COVID-19.
Invariable Ribosome Stoichiometry During Murine Erythroid Differentiation: Implications for Understanding Ribosomopathies
Authors: Papagiannopoulos Christos I. , Kyritsis Konstantinos A. , Psatha Konstantina , Mavridou Dimitra , Chatzopoulou Fani , Orfanoudaki Georgia , Aivaliotis Michalis , Vizirianakis Ioannis S.
Published: February 2022

Heterogeneity of the main ribosomal composition represents an emerging, yet debatable, mechanism of gene expression regulation with a purported role in ribosomopathies, a group of disorders caused by mutations in ribosomal protein genes (RPs). Ribosomopathies, mysteriously relate with tissue-specific symptoms (mainly anemia and cancer predisposition), despite the ubiquitous expression and necessity of the associated RPs. An outstanding question that may shed light into disease pathogenicity and provide potential pharmacological interventions, is whether and how the ribosomal composition is modified during, the highly affected by RP mutations, process of erythroid differentiation. To address this issue, we analyzed ribosome stoichiometry using an established model of erythroid differentiation, through sucrose gradient ultracentrifugation and quantitative proteomics. We found that differentiation associates with an extensive reprogramming of the overall ribosomal levels, characterized by an increase in monosomes and a decrease in polysomes. However, by calculating a stoichiometry score for each independent ribosomal protein, we found that the main ribosomal architecture remained invariable between immature and differentiated cells. In total, none of the 78 Ribosomal Proteins (RPs- 74 core RPs, Rack1, Fau and 2 paralogs) detected was statistically different between the samples. This data was further verified through antibody-mediated quantification of 6 representative RPs. Moreover, bioinformatic analysis of whole cell proteomic data derived out of 4 additional models of erythropoiesis revealed that RPs were co-regulated across these cell types, too. In conclusion, ribosomes maintain an invariant protein stoichiometry during differentiation, thus excluding ribosome heterogeneity from a potential mechanism of toxicity in ribosomopathies and other erythroid disorders.
An Eigenvalues-Based Covariance Matrix Bootstrap Model Integrated With Support Vector Machines for Multichannel EEG Signals Analysis
Authors: Al-Hadeethi Hanan , Abdulla Shahab , Diykh Mohammed , Deo Ravinesh C. , Green Jonathan H.
Published: February 2022

Identification of alcoholism is clinically important because of the way it affects the operation of the brain. Alcoholics are more vulnerable to health issues, such as immune disorders, high blood pressure, brain anomalies, and heart problems. These health issues are also a significant cost to national health systems. To help health professionals to diagnose the disease with a high rate of accuracy, there is an urgent need to create accurate and automated diagnosis systems capable of classifying human bio-signals. In this study, an automatic system, denoted as (CT-BS- Cov-Eig based FOA-F-SVM), has been proposed to detect the prevalence and health effects of alcoholism from multichannel electroencephalogram (EEG) signals. The EEG signals are segmented into small intervals, with each segment passed to a clustering technique-based bootstrap (CT-BS) for the selection of modeling samples. A covariance matrix method with its eigenvalues (Cov-Eig) is integrated with the CT-BS system and applied for useful feature extraction related to alcoholism. To select the most relevant features, a nonparametric approach is adopted, and to classify the extracted features, a radius-margin-based support vector machine (F-SVM) with a fruit fly optimization algorithm (FOA), (i.e., FOA-F-SVM) is utilized. To assess the performance of the proposed CT-BS model, different types of evaluation methods are employed, and the proposed model is compared with the state-of-the-art models to benchmark the overall effectiveness of the newly designed system for EEG signals. The results in this study show that the proposed CT-BS model is more effective than the other commonly used methods and yields a high accuracy rate of 99%. In comparison with the state-of-the-art algorithms tested on identical databases describing the capability of the newly proposed FOA-F-SVM method, the study ascertains the proposed model as a promising medical diagnostic tool with potential implementation in automated alcoholism detection systems used by clinicians and other health practitioners. The proposed model, adopted as an expert system where EEG data could be classified through advanced pattern recognition techniques, can assist neurologists and other health professionals in the accurate and reliable diagnosis and treatment decisions related to alcoholism.
Combining Plant Proteins to Achieve Amino Acid Profiles Adapted to Various Nutritional Objectives—An Exploratory Analysis Using Linear Programming
Authors: Dimina Laurianne , Rémond Didier , Huneau Jean-François , Mariotti François
Published: February 2022

Although plant proteins are often considered to have less nutritional quality because of their suboptimal amino acid (AA) content, the wide variety of their sources, both conventional and emerging, suggests potential opportunities from complementarity between food sources. This study therefore aimed to explore whether, and to what extent, combinations of protein ingredients could reproduce an AA profile set as a nutritional objective, and to identify theoretical solutions and limitations. We collected compositional data on protein ingredients and raw plant foods (n = 151), and then ran several series of linear optimization to identify protein ingredient mixes that maximized the content in indispensable AA and reproduced various objective profiles: a “balanced profile,” based on AA requirements for adults; “animal profiles” corresponding to conventional animal protein compositions, and a “cardioprotective profile,” which has been associated with a lower cardiovascular risk. We assumed a very good digestibility of plant protein isolates. As expected, obtaining a balanced profile was obvious, but we also identified numerous plant protein mixtures that met demanding AA profiles. Only for particularly demanding profiles, such as mimicking a particular animal protein, did solutions require the use of protein fractions from more specific sources such as pea or canola. Optimal plant blends could mimic animal proteins such as egg white, cow milk, chicken, whey or casein with a similarity reaching 94.2, 98.8, 86.4, 92.4, and 98.0%, respectively. The limiting constraints were mainly isoleucine, lysine, and histidine target contents. These different solutions offer potential for the formulation of mixtures adapted to specific populations or the design of plant-based substitutes. Some ingredients are not commercially available but they could be developed.
Mission Bambini and the “Children's Heart Program”: The Challenge of Congenital Heart Disease Among Emergency and Education
Authors: Marianeschi Stefano M. , Albano Giulia , Viola Nicola , Barenghi Alberto , Gusella Alex
Published: February 2022

Congenital heart disease is defined as abnormality in the cardiovascular structure or function that is present at birth and it is the most common cause of congenital anomalies. Approximately 90% of more than 1,000,000 children born per year with congenital heart disease worldwide receive suboptimal care or have no access to care at all. Furthermore, the mortality is likely underreported in Low-and Middle-Income Countries. Mission Bambini Foundation is an Italian NGO founded in 2000, aiming at “helping and supporting children who are poor, sick, without education or physically and morally abused” in Italy and worldwide. In 20 years, through 1.700 projects, 1.4 million children have been supported in 75 Countries. In 2005, Mission Bambini launched the “Children's Heart Program,” based on long-term partnerships and on medical/surgical volunteering, in order to provide multidisciplinary education and training and technical support.
An In Silico Study of Electrophysiological Parameters That Affect the Spiral-Wave Frequency in Mathematical Models for Cardiac Tissue
Authors: Mulimani Mahesh Kumar , Zimik Soling , Pandit Rahul
Published: February 2022

Spiral waves of excitation in cardiac tissue are associated with life-threatening cardiac arrhythmias. It is, therefore, important to study the electrophysiological factors that affect the dynamics of these spiral waves. By using an electrophysiologically detailed mathematical model of a myocyte (cardiac cell), we study the effects of cellular parameters, such as membrane-ion-channel conductances, on the properties of the action-potential (AP) of a myocyte. We then investigate how changes in these properties, specifically the upstroke velocity and the AP duration (APD), affect the frequency ω of a spiral wave in the mathematical model that we use for human-ventricular tissue. We find that an increase (decrease) in this upstroke-velocity or a decrease (increase) in the AP duration increases (decreases) ω. We also study how other intercellular factors, such as the fibroblast-myocyte coupling, diffusive coupling strength, and the effective number of neighboring myocytes and fibroblasts, modulate ω. Finally, we demonstrate how a spiral wave can drift to a region with a high density of fibroblasts. Our results provide a natural explanation for the anchoring of spiral waves in highly fibrotic regions in fibrotic hearts.
Myricanol Inhibits Platelet Derived Growth Factor-BB-Induced Vascular Smooth Muscle Cells Proliferation and Migration in vitro and Intimal Hyperplasia in vivo by Targeting the Platelet-Derived Growth Factor Receptor-β and NF-κB Signaling
Authors: Fan Siyuan , Wang Cheng , Huang Kai , Liang Minglu
Published: February 2022

The abnormal proliferation and migration of Vascular smooth muscle cells (VSMCs) are related to many cardiovascular diseases, including atherosclerosis, restenosis after balloon angioplasty, hypertension, etc. Myricanol is a diarylheptanoid that can be separated from the bark of Myrica rubra. It has been reported that myricanol can anti-inflammatory, anti-cancer, anti-neurodegenerative, promote autophagic clearance of tau and prevent muscle atrophy. But its potential role in the cardiovascular field remains unknown. In this study, we investigated the effect of myricanol on the proliferation and migration of VSMCs in vitro and on the intimal hyperplasia in vivo. In vitro experiments, we found myricanol can inhibit the proliferation and migration of VSMCs induced by PDGF-BB. In terms of mechanism, the preincubation of myricanol can suppress the PDGF-BB induced phosphorylation of PDGFRβ and its downstream such as PLCγ1, Src, and MAPKs. In addition, NF-kB p65 translocation was also suppressed by myricanol. In vivo experiments, we found myricanol can suppress the intimal hyperplasia after wire ligation of the carotid artery in mice. These results may provide a new strategy for the prevention and treatment of coronary atherosclerosis and post-stent stenosis in the future.
Role of Myostatin in Muscle Degeneration by Random Positioning Machine Exposure: An in vitro Study for the Treatment of Sarcopenia
Authors: Cariati Ida , Scimeca Manuel , Bonanni Roberto , Triolo Rebecca , Naldi Valerio , Toro Giuseppe , Marini Mario , Tancredi Virginia , Iundusi Riccardo , Gasbarra Elena , Tarantino Umberto
Published: February 2022

Several scientific evidence have shown that exposure to microgravity has a significant impact on the health of the musculoskeletal system by altering the expression of proteins and molecules involved in bone–muscle crosstalk, which is also observed in the research of microgravity effect simulation. Among these, the expression pattern of myostatin appears to play a key role in both load-free muscle damage and the progression of age-related musculoskeletal disorders, such as osteoporosis and sarcopenia. Based on this evidence, we here investigated the efficacy of treatment with anti-myostatin (anti-MSTN) antibodies on primary cultures of human satellite cells exposed to 72 h of random positioning machine (RPM). Cell cultures were obtained from muscle biopsies taken from a total of 30 patients (controls, osteoarthritic, and osteoporotic) during hip arthroplasty. The Pax7 expression by immunofluorescence was carried out for the characterization of satellite cells. We then performed morphological evaluation by light microscopy and immunocytochemical analysis to assess myostatin expression. Our results showed that prolonged RPM exposure not only caused satellite cell death, but also induced changes in myostatin expression levels with group-dependent variations. Surprisingly, we observed that the use of anti-MSTN antibodies induced a significant increase in cell survival after RPM exposure under all experimental conditions. Noteworthy, we found that the negative effect of RPM exposure was counteracted by treatment with anti-MSTN antibodies, which allowed the formation of numerous myotubes. Our results highlight the role of myostatin as a major effector of the cellular degeneration observed with RPM exposure, suggesting it as a potential therapeutic target to slow the muscle mass loss that occurs in the absence of loading.