bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Diet Enriched With Hemp Seeds on Goat Milk Fatty Acids, Transcriptome, and miRNAs
Authors: Cremonesi Paola , Capra Emanuele , Turri Federica , Lazzari Barbara , Chessa Stefania , Battelli Giovanna , Colombini Stefania , Rapetti Luca , Castiglioni Bianca
Published: July 2022

In dairy ruminants, a diet supplemented with feed rich in unsaturated fatty acids can be an effective medium to increase the health-promoting properties of milk, although their effect on the pathways/genes involved in these processes has not been properly and completely defined to date. To improve our knowledge of the cell’s activity in specific conditions, next-generation RNA-sequencing technology was used to allow whole transcriptome characterization under given conditions. In addition to this, microRNAs (miRNAs) have recently been known as post-transcriptional regulators in fatty acid and cholesterol metabolism by targeting lipid metabolism genes. In this study, to analyze the transcriptome and miRNAs in goat milk after a supplemental diet enriched with linoleic acid (hemp seeds), next-generation RNA-sequencing was used in order to point out the general biological mechanisms underlying the effects related to milk fat metabolism. Ten pluriparous Alpine goats were fed with the same pretreatment diet for 40 days; then, they were arranged to two dietary treatments consisting of control (C) and hemp seed (H)-supplemented diets. Milk samples were collected at 40 (time point = T0) and 140 days of lactation (time point = T1). Milk fatty acid (FA) profiles revealed a significant effect of hemp seeds that determined a strong increment in the preformed FA, causing a reduction in the concentration of de-novo FA. Monounsaturated and polyunsaturated n−3 FAs were increased by hemp treatment, determining a reduction in the n−6/n−3 ratio. After removing milk fats and proteins, RNA was extracted from the milk cells and transcriptomic analysis was conducted using Illumina RNA-sequencing. A total of 3,835 genes were highly differentially expressed (p-value < 0.05, fold change > 1.5, and FDR < 0.05) in the H group. Functional analyses evidenced changes in metabolism, immune, and inflammatory responses. Furthermore, modifications in feeding strategies affected also key transcription factors regulating the expression of several genes involved in milk fat metabolism, such as peroxisome proliferator-activated receptors (PPARs). Moreover, 38 (15 known and 23 novel) differentially expressed miRNAs were uncovered in the H group and their potential functions were also predicted. This study gives the possibility to improve our knowledge of the molecular changes occurring after a hemp seed supplementation in the goat diet and increase our understanding of the relationship between nutrient variation and phenotypic effects.
Two Cannulated Screws Provide Sufficient Biomechanical Strength for Prophylactic Fixation in Adult Patients With an Aggressive Benign Femoral Neck Lesion
Authors: Fu Guangtao , Zhong Guoqing , Yang Zehong , Cheng Shi , Ma Limin , Zhang Yu
Published: July 2022

Background: Two cannulated screws were proposed for prophylactic fixation in adult patients with an aggressive benign femoral neck lesion in recent literature. However, the biomechanical properties of this intervention have not yet been investigated.

Methods: After the evaluation of the heterogeneity of bone mineral density and geometry via quantitative computed tomography, 24 embalmed adult human cadaver femurs were randomized into the control, inferior half of the anterior cortical (25%) bone defect, entire anterior cortical (50%) bone defect, and the 50% bone defect and two cannulated screw group. Biomechanical analysis was conducted to compare the stiffness and failure load among the four groups when mimicking a one-legged stance. A CT-based finite element analysis (FEA) was performed to mimic the cortical and cancellous bone defect and the implantation of two cannulated screws of the four groups. Measurements of the maximal displacement and von Mises stress were conducted with the longitudinal load force and boundary conditions being established for a one-leg-standing status.

Results: We noted a significant improvement in the failure load after the insertion of two 6.5 mm cannulated screws in femurs with 50% bone defect (+95%, p = 0.048), and no significant difference was found between the screw group and the intact femur. Similar trends were also found in the measurements of stiffness (+23%, p > 0.05) via biomechanical testing and the von Mises stresses (−71%, p = 0.043) by FEA when comparing the screw group and the 50% bone defect group.

Conclusion: Our findings suggest that two cannulated screws provided sufficient biomechanical strength for prophylactic fixation in adult patients with an aggressive benign femoral neck lesion even when the entire anterior cortical bone is involved.
Self-Assembling Protein Surfaces for In Situ Capture of Cell-Free-Synthesized Proteins
Authors: Thornton Ella Lucille , Paterson Sarah Maria , Gidden Zoe , Horrocks Mathew H. , Laohakunakorn Nadanai , Regan Lynne
Published: July 2022

We present a new method for the surface capture of proteins in cell-free protein synthesis (CFPS). We demonstrate the spontaneous self-assembly of the protein BslA into functionalizable surfaces on the surface of a CFPS reaction chamber. We show that proteins can be covalently captured by such surfaces, using “Catcher/Tag” technology. Importantly, proteins of interest can be captured either when synthesised in situ by CFPS above the BslA surfaces, or when added as pure protein. The simplicity and cost efficiency of this method suggest that it will find many applications in cell-free-based methods.
The Flow-Induced Degradation and Vascular Cellular Response Study of Magnesium-Based Materials
Authors: Shang Tengda , Wang Kebing , Tang Shusheng , Shen Yang , Zhou Lei , Zhang Lu , Zhao Yuancong , Li Xin , Cai Lin , Wang Jin
Published: July 2022

Magnesium (Mg)-based materials are considered as potential materials for biodegradable vascular stents, and some Mg-based stents have obtained regulatory approval. However, the development and application of Mg-based stents are still restricted by the rapid degradation rate of Mg and its alloys. In order to screen out the desirable Mg-based materials for stents, the degradation behavior still needs further systematic study, especially the degradation behavior under the action of near-physiological fluid. Currently, the commonly used Mg-based vascular stent materials include pure Mg, AZ31, and WE43. In this study, we systematically evaluated their corrosion behaviors in a dynamic environment and studied the effect of their degradation products on the behavior of vascular cells. The results revealed that the corrosion rate of different Mg-based materials was related to the composition of the elements. The dynamic environment accelerated the corrosion of Mg-based materials. All the same, AZ31 still shows good corrosion resistance. The effect of corrosive products on vascular cells was beneficial to re-endothelialization and inhibition of smooth muscle cell proliferation at the implantation site of vascular stent materials.
Mussel-Inspired Polydopamine-Based Multilayered Coatings for Enhanced Bone Formation
Authors: Wu Hao , Zhao Cancan , Lin Kaili , Wang Xudong
Published: July 2022

Repairing bone defects remains a challenge in clinical practice and the application of artificial scaffolds can enhance local bone formation, but the function of unmodified scaffolds is limited. Considering different application scenarios, the scaffolds should be multifunctionalized to meet specific demands. Inspired by the superior adhesive property of mussels, polydopamine (PDA) has attracted extensive attention due to its universal capacity to assemble on all biomaterials and promote further adsorption of multiple external components to form PDA-based multilayered coatings with multifunctional property, which can induce synergistic enhancement of new bone formation, such as immunomodulation, angiogenesis, antibiosis and antitumor property. This review will summarize mussel-inspired PDA-based multilayered coatings for enhanced bone formation, including formation mechanism and biofunction of PDA coating, as well as different functional components. The synergistic enhancement of multiple functions for better bone formation will also be discussed. This review will inspire the design and fabrication of PDA-based multilayered coatings for different application scenarios and promote deeper understanding of their effect on bone formation, but more efforts should be made to achieve clinical translation. On this basis, we present a critical conclusion, and forecast the prospects of PDA-based multilayered coatings for bone regeneration.
Effects of Transcription-Dependent Physical Perturbations on the Chromosome Dynamics in Living Cells
Authors: Ku Hyeyeong , Park Gunhee , Goo Jiyoung , Lee Jeongmin , Park Tae Lim , Shim Hwanyong , Kim Jeong Hee , Cho Won-Ki , Jeong Cherlhyun
Published: July 2022

Recent studies with single-particle tracking in live cells have revealed that chromatin dynamics are directly affected by transcription. However, how transcription alters the chromatin movements followed by changes in the physical properties of chromatin has not been elucidated. Here, we measured diffusion characteristics of chromatin by targeting telomeric DNA repeats with CRISPR-labeling. We found that transcription inhibitors that directly block transcription factors globally increased the movements of chromatin, while the other inhibitor that blocks transcription by DNA intercalating showed an opposite effect. We hypothesized that the increased mobility of chromatin by transcription inhibition and the decreased chromatin movement by a DNA intercalating inhibitor is due to alterations in chromatin rigidity. We also tested how volume confinement of nuclear space affects chromatin movements. We observed decreased chromatin movements under osmotic pressure and with overexpressed chromatin architectural proteins that compact chromatin.
Loss of α6β4 Integrin-Mediated Hemidesmosomes Promotes Prostate Epithelial Cell Migration by Stimulating Focal Adhesion Dynamics
Authors: Schmidt Anette , Kaakinen Mika , Wenta Tomasz , Manninen Aki
Published: July 2022

Epithelial cell adhesion is mediated by actin cytoskeleton-linked focal adhesions (FAs) and intermediate filament-associated hemidesmosomes (HDs). HDs are formed by α6β4-integrins and mediate stable anchoring to the extracellular matrix (ECM) while FAs containing β1-integrins regulate cell migration. Loss of HDs has been reported in various cancers such as prostate cancer where it correlates with increased invasive migration. Here we have studied cell migration properties and FA dynamics in genetically engineered prostate epithelial cell lines with intact or disrupted HDs. Disruption of HDs by depleting α6- or β4-integrin expression promoted collective cell migration and modulated migratory activity. Dynamic analysis of fluorescent protein-tagged FA marker proteins revealed faster FA assembly and disassembly kinetics in HD-depleted cells. FRAP analysis showed that loss of HDs correlated with faster diffusion rates of focal adhesion kinase (FAK) and vinculin in and out of FAs. These data suggest that loss of α6β4-mediated HDs promote cell migration and FA assembly dynamics by influencing the molecular diffusion rates of FAK.
Identification of UCP1 and UCP2 as Potential Prognostic Markers in Breast Cancer: A Study Based on Immunohistochemical Analysis and Bioinformatics
Authors: Yu Xin , Shi Manman , Wu Qi , Wei Wen , Sun Shengrong , Zhu Shan
Published: July 2022

Background: Uncoupling protein 1 (UCP1) and UCP2 are associated with tumor metabolism and immunity. However, the prognostic value and molecular mechanisms underlying their action in breast cancer (BC) remain unclear.

Materials and methods: In TCGA-BRCA cohort, we investigated the expression characteristics of UCP mRNAs, analyzed their prognostic value by Kaplan-Meier survival analysis, their potential molecular functions by gene set enrichment analysis, and their relationship with immune infiltrating cell types using TIMER and CIBERSORT, along with the assessment of their association with mutational profiles. Kaplan-Meier survival analysis was performed for UCPs in our cohort and their association with BC thermogenesis was assessed by thermal tomography.

Results: High expression of UCP1 and UCP2 were positive prognostic markers for BC. UCP1 was associated with the impaired glucose metabolism, while UCP2 with enhanced anti-tumor immunity. High expressions of UCP1 and UCP2 were associated with CDH1 mutations. High UCP1 expression was associated with a high rate of thermogenesis in BC.

Conclusions: These results implied a key role of UCP1 and UCP2 in prognosis, metabolism, and immune infiltration in BC. Further investigation of the relevant molecular mechanisms may provide new strategies for BC treatment.
Post-Translational Modifications in Atopic Dermatitis: Current Research and Clinical Relevance
Authors: Ma Xin , Ru Yi , Luo Ying , Kuai Le , Chen Qi-Long , Bai Yun , Liu Ye-Qiang , Chen Jia , Luo Yue , Song Jian-Kun , Zhou Mi , Li Bin
Published: July 2022

Atopic dermatitis (AD) is a chronic and relapsing cutaneous disorder characterized by compromised immune system, excessive inflammation, and skin barrier disruption. Post-translational modifications (PTMs) are covalent and enzymatic modifications of proteins after their translation, which have been reported to play roles in inflammatory and allergic diseases. However, less attention has been paid to the effect of PTMs on AD. This review summarized the knowledge of six major classes (including phosphorylation, acetylation, ubiquitination, SUMOylation, glycosylation, o-glycosylation, and glycation) of PTMs in AD pathogenesis and discussed the opportunities for disease management.
Enzymatic Active Release of Violacein Present in Nanostructured Lipid Carrier by Lipase Encapsulated in 3D-Bioprinted Chitosan-Hydroxypropyl Methylcellulose Matrix With Anticancer Activity
Authors: Rivero Berti Ignacio , Rodenak-Kladniew Boris E. , Katz Sergio F. , Arrua Eva Carolina , Alvarez Vera A. , Duran Nelson , Castro Guillermo R.
Published: July 2022

Violacein (Viol) is a bacterial purple water-insoluble pigment synthesized by Chromobacterium violaceum and other microorganisms that display many beneficial therapeutic properties including anticancer activity. Viol was produced, purified in our laboratory, and encapsulated in a nanostructured lipid carrier (NLC). The NLC is composed of the solid lipid myristyl myristate, an oily lipid mixture composed of capric and caprylic acids, and the surfactant poloxamer P188. Dormant lipase from Rhizomucor miehei was incorporated into the NLC-Viol to develop an active release system. The NLC particle size determined by dynamic light scattering brings around 150 nm particle size and ζ≈ −9.0 mV with or without lipase, but the incorporation of lipase increase the PdI from 0.241 to 0.319 (≈32%). For scaffold development, a 2.5 hydroxypropyl methylcellulose/chitosan ratio was obtained after optimization of a composite for extrusion in a 3D-bioprinter developed and constructed in our laboratory. Final Viol encapsulation efficiency in the printings was over 90%. Kinetic release of the biodye at pH = 7.4 from the mesh containing NLC-lipase showed roughly 20% Viol fast release than without the enzyme. However, both Viol kinetic releases displayed similar profiles at pH = 5.0, where the lipase is inactive. The kinetic release of Viol from the NLC-matrices was modeled and the best correlation was found with the Korsmeyer-Peppas model (R2 = 0.95) with n < 0.5 suggesting a Fickian release of Viol from the matrices. Scanning Electron Microscope (SEM) images of the NLC-meshes showed significant differences before and after Viol’s release. Also, the presence of lipase dramatically increased the gaps in the interchain mesh. XRD and Fourier Transform Infrared (FTIR) analyses of the NLC-meshes showed a decrease in the crystalline structure of the composites with the incorporation of the NLC, and the decrease of myristyl myristate in the mesh can be attributed to the lipase activity. TGA profiles of the NLC-meshes showed high thermal stability than the individual components. Cytotoxic studies in A549 and HCT-116 cancer cell lines revealed high anticancer activity of the matrix mediated by mucoadhesive chitosan, plus the biological synergistic activities of violacein and lipase.
Nanomaterials-Mediated Therapeutics and Diagnosis Strategies for Myocardial Infarction
Authors: Lv Qingbo , Ma Boxuan , Li Wujiao , Fu Guosheng , Wang Xiaoyu , Xiao Yun
Published: July 2022

The alarming mortality and morbidity rate of myocardial infarction (MI) is becoming an important impetus in the development of early diagnosis and appropriate therapeutic approaches, which are critical for saving patients’ lives and improving post-infarction prognosis. Despite several advances that have been made in the treatment of MI, current strategies are still far from satisfactory. Nanomaterials devote considerable contribution to tackling the drawbacks of conventional therapy of MI by improving the homeostasis in the cardiac microenvironment via targeting, immune modulation, and repairment. This review emphasizes the strategies of nanomaterials-based MI treatment, including cardiac targeting drug delivery, immune-modulation strategy, antioxidants and antiapoptosis strategy, nanomaterials-mediated stem cell therapy, and cardiac tissue engineering. Furthermore, nanomaterials-based diagnosis strategies for MI was presented in term of nanomaterials-based immunoassay and nano-enhanced cardiac imaging. Taken together, although nanomaterials-based strategies for the therapeutics and diagnosis of MI are both promising and challenging, such a strategy still explores the immense potential in the development of the next generation of MI treatment.
Vanillin: A Promising Biosourced Building Block for the Preparation of Various Heterocycles
Authors: Gendron David
Published: July 2022

The preparation of heterocyclic compounds often involves the use of petroleum-based or non-renewable sources. Considering the actual societal and environmental awareness towards sustainable chemistry, new and green sources of organic carbon are sought. In this regard, vanillin is a molecular building block that can be obtained from the depolymerization of lignin. Due to its different functional groups (hydroxyl, aldehyde, and methoxy) vanillin can undergo a variety of reactions leading to various heterocycles such as pyrimidines, quinoxalines, imidazoles or thiazoles to name a few. This mini-review will focus on the preparation of accessible heterocycles building blocks from the vanillin moiety in regard to the medicinal, pharmaceutical, and material fields.
The Lack of the TetR-Like Repressor Gene BCG_2177c (Rv2160A) May Help Mycobacteria Overcome Intracellular Redox Stress and Survive Longer Inside Macrophages When Surrounded by a Lipid Environment
Authors: García-Morales Lázaro , Del Portillo Patricia , Anzola Juan M. , Ares Miguel A. , Helguera-Repetto Addy C. , Cerna-Cortes Jorge F. , Méndez-Tenorio Alfonso , García María J. , Otal Isabel , Martín Carlos , Gonzalez-y-Merchand Jorge A. , Rivera-Gutiérrez Sandra
Published: July 2022

Mycobacteria, like other microorganisms, survive under different environmental variations by expressing an efficient adaptive response, oriented by regulatory elements, such as transcriptional repressors of the TetR family. These repressors in mycobacteria also appear to be related to cholesterol metabolism. In this study, we have evaluated the effect of a fatty acid (oleic–palmitic–stearic)/cholesterol mixture on some phenotypic and genotypic characteristics of a tetR-mutant strain (BCG_2177cmutated gene) ofM. bovisBCG, a homologous ofRv2160AofM. tuberculosis. In order to accomplish this, we have analyzed the global gene expression of this strain by RNA-seq and evaluated its neutral-lipid storage capacity and potential to infect macrophages. We have also determined the macrophage response by measuring some pro- and anti-inflammatory cytokine expressions. In comparison with wild-type microorganisms, we showed that the mutation in theBCG_2177cgene did not affect the growth ofM. bovisBCG in the presence of lipids but it probably modified the structure/composition of its cell envelope. Compared to with dextrose, an overexpression of the transcriptome of the wild-type and mutant strains was observed when these mycobacteria were cultured in lipids, mainly at the exponential phase. Twelve putative intracellular redox balance maintenance genes and four others coding for putative transcriptional factors (including WhiB6 and three TetR-like) were the main elements repeatedly overexpressed when cultured in the presence of lipids. These genes belonged to the central part of what we called the “genetic lipid signature” forM. bovisBCG. We have also found that all these mycobacteria genotypic changes affected the outcome of BCG-infected macrophages, being the mutant strain most adapted to persist longer inside the host. This high persistence result was also confirmed when mutant-infected macrophages showed overexpression of the anti-inflammatory cytokine TGF-β versus pro-inflammatory cytokines. In summary, the lack of this TetR-like repressor expression, within a lipid environment, may help mycobacteria overcome intracellular redox stress and survive longer inside their host.
Comprehensive Analysis of circRNA-miRNA-mRNA Regulatory Network and Novel Potential Biomarkers in Acute Myocardial Infarction
Authors: Wu Jiahe , Li Chenze , Lei Zhe , Cai Huanhuan , Hu Yushuang , Zhu Yanfang , Zhang Tong , Zhu Haoyan , Cao Jianlei , Hu Xiaorong
Published: July 2022

Background

Circular RNA (circRNA) plays an important role in the regulation of gene expression and the occurrence of human diseases. However, studies on the role of circRNA in acute myocardial infarction (AMI) are limited. This study was performed to explore novel circRNA-related regulatory networks in AMI, aiming to better understand the molecular mechanism of circRNAs involvement in AMI and provide basis for further scientific research and clinical decision-making.

Methods

The AMI-related microarray datasets GSE160717 (circRNA), GSE31568 (miRNA), GSE61741 (miRNA), and GSE24519 (mRNA) were obtained from the Gene Expression Omnibus (GEO) database. After differential expression analysis, the regulatory relationships between these DERNAs were identified by online databases circBank, circInteractome, miRDB, miRWalk, Targetscan, and then two circRNA-miRNA-mRNA regulatory networks were constructed. Differentially expressed genes (DEGs) in this network were selected followed by enrichment analysis and protein–protein interaction (PPI) analysis. Hub genes were identified using Cytohubba plug-in of Cytoscape software. Hub genes and hub gene-related miRNAs were used for receiver operating characteristic curve (ROC) analysis to identify potential biomarkers. The relative expression levels of these biomarkers were further assessed by GSE31568 (miRNA) and GSE66360 (mRNA). Finally, on the basis of the above analysis, myocardial hypoxia model was constructed to verify the expression of Hub genes and related circRNAs.

Results

A total of 83 DEcircRNAs, 109 CoDEmiRNAs and 1204 DEGs were significantly differentially expressed in these datasets. The up-regulated circRNAs and down-regulated circRNAs were used to construct a circRNA-miRNA-mRNA regulatory network respectively. These circRNA-related DEGs were mainly enriched in the terms of “FOXO signaling pathway,” “T cell receptor signaling pathway,” “MAPK signaling pathway,” “Insulin resistance,” “cAMP signaling pathway,” and “mTOR signaling pathway.” The top 10 hub genes ATP2B2, KCNA1, GRIN2A, SCN2B, GPM6A, CACNA1E, HDAC2, SRSF1, ANK2, and HNRNPA2B1 were identified from the PPI network. Hub genes GPM6A, SRSF1, ANK2 and hub gene-related circRNAs hsa_circ_0023461, hsa_circ_0004561, hsa_circ_0001147, hsa_circ_0004771, hsa_circ_0061276, and hsa_circ_0045519 were identified as potential biomarkers in AMI.

Conclusion

In this study, the potential circRNAs associated with AMI were identified and two circRNA-miRNA-mRNA regulatory networks were constructed. This study explored the mechanism of circRNA involvement in AMI and provided new clues for the selection of new diagnostic markers and therapeutic targets for AMI.
Case Report: Tetralogy of Fallot in a Chinese Family Caused by a Novel Missense Variant of MYOM2
Authors: Wang Jing , Wang Chunyan , Xie Haiyang , Feng Xiaoyuan , Wei Lei , Wang Binbin , Li Tengyan , Pi Mingan , Gong Li
Published: July 2022

Background

Rare genetic variants have been identified to be important contributors to the risk of Tetralogy of Fallot (TOF), the most common cyanotic congenital heart disease (CHD). But relatively limited familial studies with small numbers of TOF cases have been reported to date. In this study, we aimed to identify novel pathogenic genes and variants that caused TOF in a Chinese family using whole exome sequencing (WES).

Methods

A Chinese family whose twins were affected by TOF were recruited for this study. A WES was performed for the affected twins, their healthy brother, and parents to identify the potential pathogenic mutated gene(s). Heterozygous variants carried by the twins, but not the unaffected brother, were retained. Public databases were used to assess the frequencies of the selected variants, and online prediction tools were accessed to predict the influences of these variants on protein function. The final candidate variant was further confirmed by Sanger sequencing in other members of the family.

Results

After several filtering processes, a heterozygous missense variant in the MYOM2 gene (NM_003970.4:c.3097C>T:p.R1033C) was identified and confirmed by Sanger sequencing in the affected twins and their unaffected father, suggesting an inheritance pattern with incomplete penetrance. The variant was found to be extremely rare in the public databases. Furthermore, the mutated site was highly conserved among mammals, and as shown using multiple online prediction tools, this variant was predicted to be a detrimental variant.

Conclusion

We assessed a family with TOF caused by a rare heterozygous missense variant of MYOM2. Our findings not only further confirm the significant role of genetics in the incidence of TOF but also expand the spectrum of the gene variants that lead to TOF.
Plaque Structural Stress: Detection, Determinants and Role in Atherosclerotic Plaque Rupture and Progression
Authors: Gu Sophie Z. , Bennett Martin R.
Published: July 2022

Atherosclerosis remains a major cause of death worldwide, with most myocardial infarctions being due to rupture or erosion of coronary plaques. Although several imaging modalities can identify features that confer risk, major adverse cardiovascular event (MACE) rates attributable to each plaque are low, such that additional biomarkers are required to improve risk stratification at plaque and patient level. Coronary arteries are exposed to continual mechanical forces, and plaque rupture occurs when plaque structural stress (PSS) exceeds its mechanical strength. Prospective studies have shown that peak PSS is correlated with acute coronary syndrome (ACS) presentation, plaque rupture, and MACE, and provides additional prognostic information to imaging. In addition, PSS incorporates multiple variables, including plaque architecture, plaque material properties, and haemodynamic data into a defined solution, providing a more detailed overview of higher-risk lesions. We review the methods for calculation and determinants of PSS, imaging modalities used for modeling PSS, and idealized models that explore structural and geometric components that affect PSS. We also discuss current experimental and clinical data linking PSS to the natural history of coronary artery disease, and explore potential for refining treatment options and predicting future events.
Histopathological Examination of an Explanted Heart in a Long-Term Responder to Cardiac Stereotactic Body Radiotherapy (STereotactic Arrhythmia Radioablation)
Authors: Miszczyk Marcin , Sajdok Mateusz , Nożyński Jerzy , Cybulska Magdalena , Bednarek Jacek , Jadczyk Tomasz , Latusek Tomasz , Kurzelowski Radoslaw , Dolla Łukasz , Wojakowski Wojciech , Dyla Agnieszka , Zembala Michał , Drzewiecka Anna , Kaminiów Konrad , Kozub Anna , Chmielik Ewa , Grza̧dziel Aleksandra , Bekman Adam , Gołba Krzysztof Stanisław , Blamek Sławomir
Published: July 2022

Cardiac stereotactic body radiotherapy is an emerging treatment method for recurrent ventricular tachycardia refractory to invasive treatment methods. The single-fraction delivery of 25 Gy was assumed to produce fibrosis, similar to a post-radiofrequency ablation scar. However, the dynamics of clinical response and recent preclinical findings suggest a possible different mechanism. The data on histopathological presentation of post-radiotherapy hearts is scarce, and the authors provide significantly different conclusions. In this article, we present unique data on histopathological examination of a heart explanted from a patient who had a persistent anti-arrhythmic response that lasted almost a year, until a heart failure exacerbation caused a necessity of a heart transplant. Despite a complete treatment response, there was no homogenous transmural fibrosis in the irradiated region, and the overall presentation of the heart was similar to other transplanted hearts of patients with advanced heart failure. In conclusion, our findings support the theorem of functional changes as a source of the anti-arrhythmic mechanism of radiotherapy and show that durable treatment response can be achieved in absence of transmural fibrosis of the irradiated myocardium.
Outcome of Patients Supported by Large Impella Systems After Re-implantation Due to Continued or Recurrent Need of Temporary Mechanical Circulatory Support
Authors: Sugimura Yukiharu , Bauer Sebastian , Immohr Moritz Benjamin , Mehdiani Arash , Rellecke Philipp , Westenfeld Ralf , Aubin Hug , Boeken Udo , Lichtenberg Artur , Akhyari Payam
Published: July 2022

Despite the growing utilization of a large microaxial pump, i. e., Impella 5.0 or 5.5 (Abiomed Inc., Danvers, MA, USA) (Impella 5+) for patients with cardiogenic shock (CS), adverse events including the necessity of re-implantation have not been well discussed. In all 67 patients, in-hospital mortality was 52.2% (n = 35). Explantation of Impella 5+ was performed in 39 patients (58.2%), 22 of whom (32.8%) recovered under Impella 5+, and ten further patients (14.9%) survived after a successful transition to permanent mechanical circulatory support. Embolic events were considerable complications in each access. They occurred in the right arm after the removal of Impella 5+ via a subclavian artery (SA) (n = 3, 9.1%) or in the form of leg ischemia in patients with Impella 5+ via femoral artery (FA) (n = 2, 33.3%). Re-implantation was necessary for 10 patients (14.9%) due to 1) recurrent CS (n = 3), 2) pump thrombosis (n = 5), or 3) pump dislocation (n = 2), all of which were successfully performed via the same access route. In univariate analysis, FA access was a significant risk factor for Impella dysfunction compared to SA access (FA vs. SA, 42.9% vs. 9.8%, p < 0.05, odds ratio 6.88). No statistical difference of overall mortality was observed in patients with Impella 5+ re-implantation (n = 10) compared to patients with primary Impella 5+ support (n = 57) (80.0% (n = 8/10) vs. 47.4% (n = 27/57), p = 0.09). Our results suggested the acceptable clinical outcome of Impella 5+ despite a 15% re-implantation rate. Our observational data may merit further analysis of anticoagulation strategies, including risk stratification for embolic events.
Extended-Range Luminescence Dating of Central and Eastern Amazonia Sandy Terrains
Authors: Rodrigues Fernanda Costa G. , Porat Naomi , Mineli Thays Desiree , Del Río Ian , Niyonzima Pontien , Nogueira Luciana , Pupim Fabiano do Nascimento , Silva Cleverson Guizan , Baker Paul , Fritz Sherilyn , Wahnfried Ingo , Kiefer Gustavo , Sawakuchi André Oliveira
Published: July 2022

The Amazonia biome hosts upland closed and open vegetation ecosystems, in which the current biogeographical patterns relate to the evolution of the physical landscape. Therefore, understanding the origin and timing of the substrates supporting different ecosystems is indispensable for better comprehension of Amazonian biogeography. Here we used quartz optically stimulated luminescence (OSL) and thermally transferred optically stimulated luminescence (TT-OSL) for dating sandy substrates of closed and open vegetation environments in Central and Eastern Amazonia, from both outcrop and drill core samples (Autazes core: PBAT-15-43). These sandy substrates present ages ranging from 1 ka up to almost 2 Ma, that were primarily interpreted as depositional ages of fluvial terraces. Moreover, ages are discussed in terms of potential geomorphic processes leading to the formation of substrates, such as soil mixing and apparent age of quartz from the parent bedrock. The coupling between OSL and TT-OSL techniques allow us to date sedimentary deposits covering the whole Quaternary, which implies a new time window for the Amazonia history.
Kinematic Analysis of the 2020 Elliot Creek Landslide, British Columbia, Using Remote Sensing Data
Authors: Donati Davide , Stead Doug , Geertsema Marten , Bendle Jacob M. , Menounos Brian , Borgatti Lisa
Published: July 2022

The 2020 Elliot Creek landslide-tsunami-flood cascade originated from an 18.3 Mm3 rock slope failure in quartz diorite bedrock in a valley undergoing rapid glacial retreat. We used airborne LiDAR and optical imagery to characterize the slope and its surroundings. Using the LiDAR, we determined that two rockslides (2020 and an older undated one) occurred on this slope and shared a common basal rupture surface. We mapped two main sets of lineaments that represent structures that controlled the orientation of the lateral and rear release surfaces. Analysis of the topographic profile indicates a wedge-shaped failure block and a stepped rupture surface. Further topographic profile analysis indicates the possibility of a structurally controlled geomorphic step in the valley that corresponds with a change in the orientation of the valley. The rapid retreat of the West Grenville Glacier and the positions of the rupture surfaces suggest glacial retreat played a role in the landslides.
Seismic Tomography of the Trans-North China Orogen and Its Dynamic Implications
Authors: Xu Xiaoming , Ding Zhifeng , Guo Huili , Li Xinfu
Published: July 2022

We present a high-resolution S wave velocity model of the Trans-North China Orogen (TNCO) and its adjacent areas derived from S wave traveltime residuals of teleseismic waveforms recorded by the dense ChinArray seismic network. Our model reveals S wave velocity anomalies beneath the study area, suggesting the strong lateral heterogeneities of the upper mantle structures. The upper mantle of the Datong volcano is dominated by the significant low velocity anomalies. In addition to the low-velocity zone rooted in the mantle transition zone beneath the Datong volcano region, two low velocity layers extend northwestward to the Hetao graben and southwestward to the southern TNCO within depths of 100–300 km, respectively. Based on these low-velocity anomalies, we provide new insights into the origin of the Datong volcano, which may be related to the asthenospheric upwelling originated from the water-rich mantle transition zone and horizontal mantle flows driven by the extrusion northeastward of the Tibetan plateau. A clear velocity contrast in the upper mantle above 300 km depth beneath the Ordos block and the TNCO implies that the Ordos block still preserves thick cratonic root while the lithosphere of the TNCO is modified. We propose that the asthenospheric upwelling and northeastward push of the Tibetan plateau account for the lithospheric deformation of the TNCO and its adjacent areas.
In Enhancing Preservice Teachers’ Assessment Literacy: Focus on Knowledge Base, Conceptions of Assessment, and Teacher Learning
Authors: Atjonen Päivi , Pöntinen Susanna , Kontkanen Sini , Ruotsalainen Päivi
Published: July 2022

Assessment has a critical and time-consuming role in the teaching profession. However, teachers generally possess low levels of assessment knowledge and skills, with their understanding more about the culturally and historically established summative compared to formative assessment. Therefore, developing assessment literacy in preservice teacher education (PsTE) is important. In the present study, a special study module of assessment was designed for PsTE to examine Finnish student teachers’ assessment literacy. Deductive and inductive content analyses of students’ (N = 168) written diaries were conducted applying a conceptual framework of teacher’s assessment literacy in practice (TALiP). Based on the results, the students’ assessment knowledge base and assessment conceptions were promisingly versatile and indicated a rich awareness of the broad nature of assessment. However, the key findings also suggest that assessment is not an easy topic for student teachers to discuss with peers. It can be concluded that even short PsTE assessment courses can enhance student teachers’ views of versatile pedagogical inputs and outputs of assessment.
The Training Needs of In-Service Teachers for the Teaching of Historical Thinking Skills in Compulsory Secondary Education and the Baccalaureate Level
Authors: Guerrero-Romera Catalina , Perez-Ortiz Antonio Luis
Published: July 2022

In a context of change such as that which is currently taking place in the field of social sciences education, the ongoing training of in-service teachers is an essential element. Only by bringing about a true change in their teaching practice can teaching approaches and the processes of history education be improved. The present paper aims to contrast a theoretical model with a questionnaire designed to identify the training needs of secondary and baccalaureate teachers with regard to the teaching of the historical thinking skills. A quantitative research methodology has been employed with a non-experimental design in which an exploratory and confirmatory factor analysis and a hierarchical clustering analysis have been carried out. After carrying out and applying the analysis, a questionnaire (NFPA) was elaborated. Its construct validity and reliability were satisfactory and appropriate. The results will make it possible to detect and identify needs and deficiencies in ongoing teacher training. Furthermore, it will become possible to discover new elements in order to improve training processes from the point of view of in-service teachers.
Congenital Hyperinsulinism: Current Laboratory-Based Approaches to the Genetic Diagnosis of a Heterogeneous Disease
Authors: Hewat Thomas I. , Johnson Matthew B. , Flanagan Sarah E.
Published: July 2022

Congenital hyperinsulinism is characterised by the inappropriate release of insulin during hypoglycaemia. This potentially life-threatening disorder can occur in isolation, or present as a feature of syndromic disease. Establishing the underlying aetiology of the hyperinsulinism is critical for guiding medical management of this condition especially in children with diazoxide-unresponsive hyperinsulinism where the underlying genetics determines whether focal or diffuse pancreatic disease is present. Disease-causing single nucleotide variants affecting over 30 genes are known to cause persistent hyperinsulinism with mutations in the KATP channel genes (ABCC8 and KCNJ11) most commonly identified in children with severe persistent disease. Defects in methylation, changes in chromosome number, and large deletions and duplications disrupting multiple genes are also well described in congenital hyperinsulinism, further highlighting the genetic heterogeneity of this condition. Next-generation sequencing has revolutionised the approach to genetic testing for congenital hyperinsulinism with targeted gene panels, exome, and genome sequencing being highly sensitive methods for the analysis of multiple disease genes in a single reaction. It should though be recognised that limitations remain with next-generation sequencing with no single application able to detect all reported forms of genetic variation. This is an important consideration for hyperinsulinism genetic testing as comprehensive screening may require multiple investigations.
Structural and Electrical Remodeling of the Sinoatrial Node in Diabetes: New Dimensions and Perspectives
Authors: Al Kury Lina T. , Chacar Stephanie , Alefishat Eman , Khraibi Ali A. , Nader Moni
Published: July 2022

The sinoatrial node (SAN) is composed of highly specialized cells that mandate the spontaneous beating of the heart through self-generation of an action potential (AP). Despite this automaticity, the SAN is under the modulation of the autonomic nervous system (ANS). In diabetes mellitus (DM), heart rate variability (HRV) manifests as a hallmark of diabetic cardiomyopathy. This is paralleled by an impaired regulation of the ANS, and by a pathological remodeling of the pacemaker structure and function. The direct effect of diabetes on the molecular signatures underscoring this pathology remains ill-defined. The recent focus on the electrical currents of the SAN in diabetes revealed a repressed firing rate of the AP and an elongation of its tracing, along with conduction abnormalities and contractile failure. These changes are blamed on the decreased expression of ion transporters and cell-cell communication ports at the SAN (i.e., HCN4, calcium and potassium channels, connexins 40, 45, and 46) which further promotes arrhythmias. Molecular analysis crystallized the RGS4 (regulator of potassium currents), mitochondrial thioredoxin-2 (reactive oxygen species; ROS scavenger), and the calcium-dependent calmodulin kinase II (CaMKII) as metabolic culprits of relaying the pathological remodeling of the SAN cells (SANCs) structure and function. A special attention is given to the oxidation of CaMKII and the generation of ROS that induce cell damage and apoptosis of diabetic SANCs. Consequently, the diabetic SAN contains a reduced number of cells with significant infiltration of fibrotic tissues that further delay the conduction of the AP between the SANCs. Failure of a genuine generation of AP and conduction of their derivative waves to the neighboring atrial myocardium may also occur as a result of the anti-diabetic regiment (both acute and/or chronic treatments). All together, these changes pose a challenge in the field of cardiology and call for further investigations to understand the etiology of the structural/functional remodeling of the SANCs in diabetes. Such an understanding may lead to more adequate therapies that can optimize glycemic control and improve health-related outcomes in patients with diabetes.
Characterizing Photosynthetic Biofuel Production: Isotopically Non-Stationary 13C Metabolic Flux Analysis on Limonene Producing Synechococcus sp. PCC 7002
Authors: Newman Darrian M. , Sake Cara L. , Metcalf Alexander J. , Davies Fiona K. , Cano Melissa , Krishnan Anagha , Boyle Nanette R.
Published: July 2022

Synechococcus sp. PCC 7002 is a unicellular cyanobacterium capable of fast growth and tolerance to high light intensity and high salinity. These attributes along with genetic tractability make Synechococcus sp. PCC 7002 an attractive candidate for industrial scale production of specialty and commodity chemicals. Synechococcus sp. PCC 7002 LS (Davies et al., Front Bioeng Biotechnol, 2014, 2, 21–11) produces limonene, an energy dense diesel jet fuel drop-in additive, at a titer of 4 mg/L over a 4-day incubation period. In this study, we use the state-of-the-art whole-cell characterization tool, isotopically non-stationary 13C metabolic flux analysis (INST-13CMFA) to determine intracellular fluxes through the pathways of central metabolism for the limonene producing strain and wild type strain of Synechococcus sp. PCC 7002. We find similar flux distribution in the Calvin-Benson-Bassham cycle, photorespiration, oxidative pentose phosphate pathway, and oxidative tricarboxylic acid cycle. The key difference between strains is observed in the production of pyruvate. The limonene producing strain displays significantly higher flux through the amphibolic pathways of phosphoenolpyruvate carboxylase and the malic enzyme to synthesize pyruvate, while the wild type strain uses pyruvate kinase in a single step. Our findings suggest that this flux distribution is a mechanism to recover a physiologically optimal ratio of ATP to NADPH. The upregulation of this amphibolic pathway may act to restore the physiological ATP:NADPH ratio that has been disturbed by limonene biosynthesis. This study demonstrates the value of INST-13CMFA as a tool for cyanobacterial strain engineering and provides new avenues of research for improving limonene production in Synechococcus.
A Non-Scheduled Multi-Stage Decision-Making Approach to Control Cascading Failures
Authors: Liu Yumeng , Wang Tao , Guo Jiayi
Published: July 2022

The control research on cascading failures is critical to ensure the reliability of power supply. A path-driven multi-stage corrective control model for the whole process of cascading failures is established to eliminate the risk of cascading failure. For the cascading failure process caused by overloading, the selection criterion for subsequent outage is defined according to the mechanism of propagation of cascading failures. The path-driven constraints and power relaxation constraints are extracted based on the selection criterion for a subsequent outage. A model coupled with non-scheduled multi-stage decision-making is designed by considering the flexibility of control action implementation to optimize the sum of control cost and load-shedding risk for elimination of cascading failures. The verification results show that the proposed method can reduce the probability of outages of tripped branches and successfully eliminate cascading failure.
Numerical Simulation of Tritium Diffusion Behavior in FeCrAl Cladding
Authors: Yin Chunyu , Liu Rong , Jiao Yongjun , Liu Shengyu , Duan Zhengang , Gao Shixin , He Liang , Chen Ping
Published: July 2022

In this article, a simulation code for tritium diffusion behavior analysis in FeCrAl cladding is developed based on the COMSOL platform. The simulated results are in good agreement with experimental and theoretical results. The effects of different concentrations of tritium and temperature distributions on the diffusion behavior of tritium in FeCrAl cladding were further investigated. Finally, the optimal effect of different coating schemes on the tritium resistance of the FeCrAl cladding was investigated. The results show that higher temperatures lead to higher cladding diffusion coefficients, which will further lead to higher fluxes of tritium into and out of the cladding, which is found to further result in a higher tritium flux into and out of the cladding, as well as shorter tritium diffusion times. It is found that higher temperature will lead to more tritium flux into and out of the cladding and shorter time for the tritium flux to reach a steady state on the right side of the cladding. At the same time, the higher tritium partial pressure on the fuel side of the cladding will lead to a longer time for the tritium flux to reach a steady state on the water side of the cladding. The longer time to reach the steady state on the water side of the cladding increases the tritium flux into the cladding.