bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor-Derived Small Extracellular Vesicles Induce Pro-Inflammatory Cytokine Expression and PD-L1 Regulation in M0 Macrophages via IL-6/STAT3 and TLR4 Signaling Pathways
Authors: Pucci Marzia , Raimondo Stefania , Urzì Ornella , Moschetti Marta , Di Bella Maria Antonietta , Conigliaro Alice , Caccamo Nadia , La Manna Marco Pio , Fontana Simona , Alessandro Riccardo
Published: November 2021

Tumor-associated macrophages play a key role in promoting tumor progression by exerting an immunosuppressive phenotype associated with the expression of programmed cell death ligand 1 (PD-L1). It is well known that tumor-derived small extracellular vesicles (SEVs) affect the tumor microenvironment, influencing TAM behavior. The present study aimed to examine the effect of SEVs derived from colon cancer and multiple myeloma cells on macrophage functions. Non-polarized macrophages (M0) differentiated from THP-1 cells were co-cultured with SEVs derived from a colorectal cancer (CRC) cell line, SW480, and a multiple myeloma (MM) cell line, MM1.S. The expression of PD-L1, interleukin-6 (IL-6), and other inflammatory cytokines as well as of the underlying molecular mechanisms were evaluated. Our results indicate that SEVs can significantly upregulate the expressions of PD-L1 and IL-6 at both the mRNA and protein levels and can activate the STAT3 signaling pathway. Furthermore, we identified the TLR4/NF-kB pathway as a convergent mechanism for SEV-mediated PD-L1 expression. Overall, these preliminary data suggest that SEVs contribute to the formation of an immunosuppressive microenvironment.
Effects of Cynaroside on Cell Proliferation, Apoptosis, Migration and Invasion though the MET/AKT/mTOR Axis in Gastric Cancer
Authors: Ji Juanli , Wang Zhongze , Sun Wei , Li Zekun , Cai Huarui , Zhao Erhu , Cui Hongjuan
Published: November 2021

The Chinese medicine monomer cynaroside (Cy) is a flavonoid glycoside compound that widely exists in plants and has a variety of pharmacological effects, such as its important role in the respiratory system, cardiovascular system and central nervous system. Studies have reported that Cy has varying degrees of anticancer activity in non-small cell lung cancer, cervical cancer, liver cancer, esophageal cancer and other cancers. However, there are no relevant reports about its role in gastric cancer. The MET/AKT/mTOR signaling pathway plays important roles in regulating various biological processes, including cell proliferation, apoptosis, autophagy, invasion and tumorigenesis. In this study, we confirmed that Cy can inhibit the cell growth, migration and invasion and tumorigenesis in gastric cancer. Our finding shows that Cy can block the MET/AKT/mTOR axis by decreasing the phosphorylation level of AKT, mTOR and P70S6K. Therefore, the MET/AKT/mTOR axis may be an important target for Cy. In summary, Cy has anti-cancer properties and is expected to be a potential drug for the treatment of gastric cancer.
Global Transcriptomic Analysis Reveals Differentially Expressed Genes Involved in Embryogenic Callus Induction in Drumstick (Moringa oleifera Lam.)
Authors: Yang Endian , Zheng Mingyang , Zou Xuan , Huang Xiaoling , Yang Heyue , Chen Xiaoyang , Zhang Junjie
Published: November 2021

The plant embryogenic callus (EC) is an irregular embryogenic cell mass with strong regenerative ability that can be used for propagation and genetic transformation. However, difficulties with EC induction have hindered the breeding of drumstick, a tree with diverse potential commercial uses. In this study, three drumstick EC cDNA libraries were sequenced using an Illumina NovaSeq 6000 system. A total of 7191 differentially expressed genes (DEGs) for embryogenic callus development were identified, of which 2325 were mapped to the KEGG database, with the categories of plant hormone signal transduction and Plant-pathogen interaction being well-represented. The results obtained suggest that auxin and cytokinin metabolism and several embryogenesis-labeled genes are involved in embryogenic callus induction. Additionally, 589 transcription factors from 20 different families were differentially expressed during EC formation. The differential expression of 16 unigenes related to auxin signaling pathways was validated experimentally by quantitative real time PCR (qRT-PCR) using samples representing three sequential developmental stages of drumstick EC, supporting their apparent involvement in drumstick EC formation. Our study provides valuable information about the molecular mechanism of EC formation and has revealed new genes involved in this process.
Select Ethical Aspects of Next-Generation Sequencing Tests for Newborn Screening and Diagnostic Evaluation of Critically Ill Newborns
Authors: Sen Kuntal , Harmon Jennifer , Gropman Andrea L.
Published: November 2021

In this review, we analyze medical and select ethical aspects of the increasing use of next-generation sequencing (NGS) based tests in newborn medicine. In the last five years, there have been several studies exploring the role of rapid exome sequencing (ES) and genome sequencing (GS) in critically ill newborns. While the advantages include a high diagnostic yield with potential changes in interventions, there have been ethical dilemmas surrounding consent, information about adult-onset diseases and resolution of variants of uncertain significance. Another active area of research includes a cohort of studies funded under Newborn Sequencing in Genomic Medicine and Public Health pertaining to the use of ES and GS in newborn screening (NBS). While these techniques may allow for screening for several genetic disorders that do not have a detectable biochemical marker, the high costs and long turnaround times of these tests are barriers in their utilization as public health screening tests. Discordant results between conventional NBS and ES-based NBS, as well as challenges with consent, are other potential pitfalls of this approach. Please see the Bush, Al-Hertani and Bodamer article in this Special Issue for the broader scope and further discussion.
Asset Management Method of Industrial IoT Systems for Cyber-Security Countermeasures
Authors: Matsumoto Noritaka , Fujita Junya , Endoh Hiromichi , Yamada Tsutomu , Sawada Kenji , Kaneko Osamu
Published: November 2021

Cyber-security countermeasures are important for IIoT (industrial Internet of things) systems in which IT (information technology) and OT (operational technology) are integrated. The appropriate asset management is the key to creating strong security systems to protect from various cyber threats. However, the timely and coherent asset management methods used for conventional IT systems are difficult to be implemented for IIoT systems. This is because these systems are composed of various network protocols, various devices, and open technologies. Besides, it is necessary to guarantee reliable and real-time control and save CPU and memory usage for legacy OT devices. In this study, therefore, (1) we model various asset configurations for IIoT systems and design a data structure based on SCAP (Security Content Automation Protocol). (2) We design the functions to automatically acquire the detailed information from edge devices by “asset configuration management agent”, which ensures a low processing load. (3) We implement the proposed asset management system to real edge devices and evaluate the functions. Our contribution is to automate the asset management method that is valid for the cyber security countermeasures in the IIoT systems.
The First Eight Mitogenomes of Leaf-Mining Dactylispa Beetles (Coleoptera: Chrysomelidae: Cassidinae) Shed New Light on Subgenus Relationships
Authors: Zhang Shengdi , Sekerka Lukáš , Liao Chengqing , Long Chengpeng , Xu Jiasheng , Dai Xiaohua , Guo Qingyun
Published: November 2021

The taxonomic classification of Dactylispa, a large genus of leaf-mining beetles, is problematic because it is currently based on morphology alone. Here, the first eight mitochondrial genomes of Dactylispa species, which were used to construct the first molecular phylogenies of this genus, are reported. The lengths of the eight mitogenomes range from 17,189 bp to 20,363 bp. All of the mitochondrial genomes include 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), 2 ribosomal RNA genes (rRNAs), and 1 A + T-rich region. According to the nonsynonymous/synonymous mutation ratio (Ka/Ks) of all PCGs, the highest and the lowest evolutionary rates were found for atp8 and cox1, respectively, which is a common phenomenon among animals. According to relative synonymous codon usage, UUA(L) has the highest frequency. With two Gonophorini species as the outgroup, mitogenome-based phylogenetic trees of the eight Dactylispa species were constructed using maximum likelihood (ML) and Bayesian inference (BI) methods based on the PCGs, tRNAs, and rRNAs. Two DNA-based phylogenomic inferences and one protein-based phylogenomic inference support the delimitation of the subgenera Dactylispa s. str. and Platypriella as proposed in the system of Chen et al. (1986). However, the subgenus Triplispa is not recovered as monophyletic. The placement of Triplispa species requires further verification and testing with more species. We also found that both adult body shape and host plant relationship might explain the subgeneric relationships among Dactylispa beetles to a certain degree.
Outcomes of Patients with and without Malignancy Undergoing Percutaneous Pericardiocentesis for Pericardial Effusion
Authors: Shih Chun-Ting , Lee Wei-Chieh , Fang Hsiu-Yu , Wu Po-Jui , Fang Yen-Nan , Chong Shaur-Zheng
Published: November 2021

(1) Background: This study aimed to evaluate the etiologies and clinical outcomes of patients with pericardial effusion (PE) treated with echo-guided percutaneous pericardiocentesis. (2) Methods: Between July 2010 and December 2020, a total of 502 patients underwent echo-guided percutaneous pericardiocentesis for PE at our hospital. The reasons for PE were malignancy (N = 277), and non-malignancy (N = 225). The comorbidities, complications, and all-cause mortality were compared between the malignancy and non-malignancy groups. (3) Results: In multivariable Cox regression analyses for 1-year mortality, malignancy related PE, nasopharyngeal and oropharyngeal cancer, and metastatic status were positive predictors. A higher incidence of in-hospital and 1-year mortality were observed in patients with malignancy-related PE than with non-malignancy-related PE. In patients with malignancy-related PE, the Kaplan-Meier curve of 1-year all-cause mortality significantly differed between patients with or without metastasis; however, PE with or without malignant cells did not influence the prognosis. (4) Conclusions: In the patients with large PE requiring percutaneous pericardiocentesis, malignancy-related PE, nasopharyngeal and oropharyngeal cancer, and metastatic status were positive predictors of 1-year mortality. In patients with malignancy, a higher incidence of all-cause mortality was noted in patients with metastasis but did not differ between the groups with and without malignant cells in PE.
Autoimmune Myocarditis and Arrhythmogenic Mitral Valve Prolapse: An Unexpected Overlap Syndrome
Authors: Villatore Andrea , Sala Simone , Stella Stefano , Vignale Davide , Busnardo Elena , Esposito Antonio , Basso Cristina , Della Bella Paolo , Mazzone Patrizio , Peretto Giovanni
Published: November 2021

Background: both myocarditis and mitral valve prolapse (MVP) are known uncommon causes of ventricular arrhythmias in young patients. Aim: to report the first clinical case of endomyocardial biopsy (EMB)-proven autoimmune myocarditis and associated arrhythmogenic MVP in a patient with recurrent ventricular fibrillation (VF) episodes. Methods: myocarditis was diagnosed both by cardiac magnetic resonance (CMR) and EMB. Arrhythmogenic MVP was documented by transthoracic echocardiogram, CMR, and electroanatomical mapping of the trigger premature ventricular contractions (PVCs). Results: a 22-year-old woman underwent immunosuppressive therapy after EMB-proven diagnosis of autoimmune myocarditis with VF onset and early implantable cardioverter defibrillator (ICD) placement. Three years later, she experienced two VF recurrences and persistent PVCs, despite no signs of myocarditis recurrence. An echocardiogram revealed bileaflet MVP with high arrhythmic risk features. Finally, electroanatomical mapping and ablation of the trigger PVC were successfully performed. Conclusion: in patients with recurrent VF episodes despite evidence-based medical treatment for myocarditis, MVP should be considered as an alternative arrhythmogenic substrate, and warrants early ICD implant and PVC-targeted therapy.
Obesity and Risk of Diabetes Mellitus by Menopausal Status: A Nationwide Cohort Study
Authors: Lee Han Rim , Shin Jungeun , Han Kyungdo , Chang Jiwon , Jeong Su-Min , Chon Seung Joo , Choi Soo Jung , Shin Dong Wook
Published: November 2021

Although both obesity and menopause are associated with increased risk of diabetes mellitus (DM), the association between obesity and DM according to menopausal status remains uncertain. Therefore, we conducted a study to examine the relationship between obesity and incidence of diabetes mellitus (DM) in premenopausal and postmenopausal women. Total of 926,196 premenopausal and 1,193,881 postmenopausal women who underwent health examinations from 2009 to 2014 were identified using the database of the Korean National Health Insurance Service. We compared the incidence and risk of DM according to body mass index (BMI) and waist circumference (WC) in the two groups of women. Cox proportional hazards analyses were performed to evaluate the association between the presence of obesity and risk of DM according to menopausal state. During the 7.8-year follow-up period, 37,736 (4.1%) premenopausal women and 121,102 (10.1%) postmenopausal women were diagnosed with DM. Compared to the reference group (BMI 18.5–23), a stronger association between obesity and risk of DM was observed in both pre- and postmenopausal women: multivariable-adjusted hazard ratios and 95% confidence intervals for BMI subgroups <18.5, 23–25, 25–30, and >30 were 0.62 (0.54, 0.70), 1.91 (1.85, 1.97), 3.38 (3.28, 3.47), and 6.25 (6.02, 6.48), respectively (p trend < 0.001) in premenopausal women and 0.87 (0.82, 0.92), 1.44 (1.41, 1.46), 2.00 (1.97, 2.03), and 2.96 (2.89, 3.02) in postmenopausal women (p trend < 0.001, p-interaction < 0.001). A similar trend was observed for WC. Subgroup analyses of women aged 45 to 55 also showed a stronger association with DM in premenopausal than in postmenopausal women. In conclusion, the association between obesity and DM was stronger in premenopausal women than in postmenopausal women. As estrogens are synthesized in adipose tissue by aromatization of androgens after menopause, increased estrogen levels in obese postmenopausal might have a protective effect against DM.
Cytokine Release Syndrome in the Immunotherapy of Hematological Malignancies: The Biology behind and Possible Clinical Consequences
Authors: Tvedt Tor Henrik Anderson , Vo Anh Khoi , Bruserud Øystein , Reikvam Håkon
Published: November 2021

Cytokine release syndrome (CRS) is an acute systemic inflammatory syndrome characterized by fever and multiple organ dysfunction associated with (i) chimeric antigen receptor (CAR)-T cell therapy, (ii) therapeutic antibodies, and (iii) haploidentical allogeneic stem cell transplantation (haplo-allo-HSCT). Severe CRS can be life-threatening in some cases and requires prompt management of those toxicities and is still a great challenge for physicians. The pathophysiology of CRS is still not fully understood, which also applies to the identifications of predictive biomarkers that can forecast these features in advance. However, a broad range of cytokines are involved in the dynamics of CRS. Treatment approaches include both broad spectrum of immunosuppressant, such as corticosteroids, as well as more specific inhibition of cytokine release. In the present manuscript we will try to review an update regarding pathophysiology, etiology, diagnostics, and therapeutic options for this serious complication.
Modified ELISA for Ultrasensitive Diagnosis
Authors: Tsurusawa Naoko , Chang Jyunhao , Namba Mayuri , Makioka Daiki , Yamura Sou , Iha Kanako , Kyosei Yuta , Watabe Satoshi , Yoshimura Teruki , Ito Etsuro
Published: November 2021

An enzyme-linked immunosorbent assay (ELISA) can be used for quantitative measurement of proteins, and improving the detection sensitivity to the ultrasensitive level would facilitate the diagnosis of various diseases. In the present review article, we first define the term ‘ultrasensitive’. We follow this with a survey and discussion of the current literature regarding modified ELISA methods with ultrasensitive detection and their application for diagnosis. Finally, we introduce our own newly devised system for ultrasensitive ELISA combined with thionicotinamide adenine dinucleotide cycling and its application for the diagnosis of infectious diseases and lifestyle-related diseases. The aim of the present article is to expand the application of ultrasensitive ELISAs in the medical and biological fields.
Diet and Chronic Non-Cancer Pain: The State of the Art and Future Directions
Authors: Brain Katherine , Burrows Tracy L. , Bruggink Laura , Malfliet Anneleen , Hayes Chris , Hodson Fiona J. , Collins Clare E.
Published: November 2021

Nutrition plays an important role in pain management. Healthy eating patterns are associated with reduced systemic inflammation, as well as lower risk and severity of chronic non-cancer pain and associated comorbidities. The role of nutrition in chronic non-cancer pain management is an emerging field with increasing interest from clinicians and patients. Evidence from a number of recent systematic reviews shows that optimising diet quality and incorporating foods containing anti-inflammatory nutrients such as fruits, vegetables, long chain and monounsaturated fats, antioxidants, and fibre leads to reduction in pain severity and interference. This review describes the current state of the art and highlights why nutrition is critical within a person-centred approach to pain management. Recommendations are made to guide clinicians and highlight areas for future research.
Detection of Human Papillomavirus DNA in Paired Peripheral Blood and Cervix Samples in Patients with Cervical Lesions and Healthy Individuals
Authors: Conceição Gomes Nascimento Kamylla , Gonçalves Lima Élyda , Mota Nunes Zhilbelly , Rêgo Barros Júnior Marconi , de Aragão Batista Marcus Vinícius , Lucena Araujo Antonio Roberto , da Costa Silva Neto Jacinto , Simas Chagas Bárbara , Almeida Diniz Gurgel Ana Pavla , de Freitas Antonio Carlos
Published: November 2021

This study evaluated the presence of Human Papillomavirus (HPV) DNA in the cervix and peripheral blood of women with cervical intraepithelial neoplasia (CIN I, II, and III) and healthy individuals. Overall, 139 paired peripheral blood and cervix samples of healthy women and women with CIN I, II, and III (n = 68) were tested for HPV DNA by using standard procedures. Polymerase chain reaction (PCR) sequencing determined HPV types. Quantification of HPV16 E6 and E2 genes was performed to determine viral load and physical state. HPV DNA was detected in the cervix (21.1% in healthy individuals; 48.8–55.5% in CIN patients), blood (46.4% in healthy individuals; 44.1–77.7% in CIN patients) and paired peripheral blood and cervix samples (24% in healthy individuals; 32.5–44.4% in CIN patients). The most frequent types found in the cervix were HPV16, 18, 31, 33, 58, and 70, while HPV16, 18, 33, 58, and 66 were the most frequent types found in the blood. HPV DNA in the cervix was associated with previous sexually transmitted infections (STIs) (p = 0.023; OR: 2.978; CI:1.34–7.821), HPV DNA in the blood (p = 0.000; OR: 8.283; CI:3.700–18.540), and cervical lesions (CIN I/II or III) (p = 0.007). Binomial logistic regression showed that HPV DNA in the blood (p = 0.000; OR: 9.324; CI:3.612–24.072) and cervical lesions (p = 0.011; OR: 3.622; CI:1.338–9.806) were associated with HPV DNA in the cervix. However, we did not find an association between HPV DNA in the blood and cervical lesions (p = 0.385). Our results showed that only HPV DNA found in the cervix was associated with cervical lesions.
Recovering the Magnetic Image of Mars from Satellite Observations
Authors: Kolotov Igor , Lukyanenko Dmitry , Stepanova Inna , Wang Yanfei , Yagola Anatoly
Published: November 2021

One of the possible approaches to reconstructing the map of the distribution of magnetization parameters in the crust of Mars from the data of the Mars MAVEN orbiter mission is considered. Possible ways of increasing the accuracy of reconstruction of the magnetic image of Mars are discussed.
Effects of Second-Order Hydrodynamics on the Dynamic Responses and Fatigue Damage of a 15 MW Floating Offshore Wind Turbine
Authors: Mei Xuan , Xiong Min
Published: November 2021

In order to investigate the effects of second-order hydrodynamic loads on a 15 MW floating offshore wind turbine (FOWT), this study employs a tool that integrates AQWA and OpenFAST to conduct fully coupled simulations of the FOWT subjected to wind and wave loadings. The load cases covering normal and extreme conditions are defined based on the met-ocean data observed at a specific site. The results indicate that the second-order wave excitations activate the surge mode of the platform. As a result, the surge motion is increased for each of the examined load case. In addition, the pitch, heave, and yaw motions are underestimated when neglecting the second-order hydrodynamics under the extreme condition. First-order wave excitation is the major contributor to the tower-base bending moments. The fatigue damage of the tower-base under the extreme condition is underestimated by 57.1% if the effect of second-order hydrodynamics is ignored. In addition, the accumulative fatigue damage over 25 years at the tower-base is overestimated by 16.92%. Therefore, it is suggested to consider the effects of second-order wave excitations of the floating platform for the design of the tower to reduce the cost of the FOWT.
Mixed-Fidelity Design Optimization of Hull Form Using CFD and Potential Flow Solvers
Authors: Grigoropoulos Gregory J. , Bakirtzoglou Christos , Papadakis George , Ntouras Dimitrios
Published: November 2021

The present paper proposes a new mixed-fidelity method to optimize the shape of ships using genetic algorithms (GA) and potential flow codes to evaluate the hydrodynamics of variant hull forms, enhanced by a surrogate model based on an Artificial Neural Network (ANN) to account for viscous effects. The performance of the variant hull forms generated by the GA is evaluated for calm water resistance using potential flow methods which are quite fast when they run on modern computers. However, these methods do not take into account the viscous effects which are dominant in the stern region of the ship. Solvers of the Reynolds-Averaged Navier-Stokes Equations (RANS) should be used in this respect, which, however, are too time-consuming to be used for the evaluation of some hundreds of variants within the GA search. In this study, a RANS solver is used prior to the execution of the GA to train an ANN in modeling the effect of stern design geometrical parameters only. Potential flow results, accounting for the geometrical design parameters of the rest of the hull, are combined with the aforementioned trained meta-model for the final hull form evaluation. This work concentrates on the provision of a more reliable framework for the evaluation of hull form performance in calm water without a significant increase of the computing time.
Metabolic Syndrome Increases the Risk of Kidney Stone Disease: A Cross-Sectional and Longitudinal Cohort Study
Authors: Chang Che-Wei , Ke Hung-Lung , Lee Jia-In , Lee Yung-Chin , Jhan Jhen-Hao , Wang Hsun-Shuan , Shen Jung-Tsung , Tsao Yao-Hsuan , Huang Shu-Pin , Geng Jiun-Hung
Published: November 2021

We aimed to examine the association between metabolic syndrome and the risk of kidney stone development in a large-scale community-based cohort. A total of 121,579 participants enrolled in the Taiwan Biobank were analyzed. They were divided into two groups on the basis of presence of metabolic syndrome. The presence of kidney stone disease was defined by self-reported history of kidney stones. The mean age of participants was 50 years old, and self-reported kidney stones were observed in 3446 (10%) and 4292 (5%) participants with metabolic syndrome and without metabolic syndrome, respectively. Higher prevalence of kidney stone disease was found in participants with metabolic syndrome compared to those without metabolic syndrome (odds ratio (OR), 1.32; 95% confidence interval (95% CI), 1.25 to 1.39). In addition, the risk of incident kidney stone development was analyzed in a longitudinal cohort of 25,263 participants without kidney stones at baseline during a mean follow-up of 47 months. Multivariable Cox regression analysis revealed that the risk for incident kidney stone disease was higher in participants with metabolic syndrome than those without metabolic syndrome (hazard ratio, 1.24; 95% CI, 1.04 to 1.49). Our study suggests that metabolic syndrome does increase the risk of kidney stones.
Interventions to Promote a Healthy Sexuality among School Adolescents: A Scoping Review
Authors: Loureiro Fernanda , Ferreira Margarida , Sarreira-de-Oliveira Paula , Antunes Vanessa
Published: November 2021

Schools are particularly suitable contexts for the implementation of interventions focused on adolescent sexual behavior. Sexual education and promotion have a multidisciplinary nature. Nurses’ role and the spectrum of the carried-out interventions is not clear. We aimed to identify interventions that promote a healthy sexuality among school adolescents. Our review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews and was registered in the Open Science Framework. Published articles on sexuality in adolescents in school contexts were considered. The research limitations included primary studies; access in full text in English, Spanish, or Portuguese; and no data publication limitation. Research was carried out on the EBSCOhost, PubMed, SciELO, and Web of Science platforms; gray literature and the bibliographies of selected articles were also searched. A total of 56 studies were included in the sample. The studies used a broad range of research methods, and 10 types of interventions were identified. Multi-interventional programs and socio-emotional interventions showed a greater impact on long-term behavioral changes, and continuity seemed to be a key factor. Long-term studies are needed to reach a consensus on the effectiveness of interventions. Nurses’ particular role on the multidisciplinary teams was found to be a gap in the research, and must be further explored.
Improved In Vivo Delivery of Small RNA Based on the Calcium Phosphate Method
Authors: Wu Xin , Yokoyama Yuhki , Takahashi Hidekazu , Kouda Shihori , Yamamoto Hiroyuki , Wang Jiaqi , Morimoto Yoshihiro , Minami Kazumasa , Hata Tsuyoshi , Shamma Awad , Inoue Akira , Ohtsuka Masahisa , Shibata Satoshi , Kobayashi Shogo , Akai Shuji , Yamamoto Hirofumi
Published: November 2021

In the past few years, we have demonstrated the efficacy of a nanoparticle system, super carbonate apatite (sCA), for the in vivo delivery of siRNA/miRNA. Intravenous injection of sCA loaded with small RNAs results in safe, high tumor delivery in mouse models. To further improve the efficiency of tumor delivery and avoid liver toxicity, we successfully developed an inorganic nanoparticle device (iNaD) via high-frequency ultrasonic pulverization combined with PEG blending during the production of sCA. Compared to sCA loaded with 24 μg of miRNA, systemic administration of iNaD loaded with 0.75 μg of miRNA demonstrated similar delivery efficiency to mouse tumors with little accumulation in the liver. In the mouse therapeutic model, iNaD loaded with 3 μg of the tumor suppressor small RNA MIRTX resulted in an improved anti-tumor effect compared to sCA loaded with 24 μg. Our findings on the bio-distribution and therapeutic effect of iNaD provide new perspectives for future nanomedicine engineering.
An Empirical Investigation into Alarming Signals Ignored by the U.S. Multi-Brand Retailer J. Crew Incorporation during COVID-19 Pandemic
Authors: Bhavani Ganga , Agrawal Reena , Mendon Suhan , Spulbar Cristi , Birau Ramona
Published: November 2021

This study investigated the financial signals that have been ignored or have failed to be controlled by J. Crew Inc. from 2013 until 2019. Exploratory research is carried out with the help of secondary data which was collected from the downloaded formal documents submitted by J. Crew Inc. to the Securities Exchange Commission (SEC). Researchers analyzed these documents and prepared statements on vertical income statement, vertical balance sheet, horizontal income statement, horizontal balance sheet, trend analysis of income statement, and trend analysis of balance sheet, as well as ratio analysis on liquidity, long-term solvency, profitability, and turnover ratios with the help of excel. This paper has identified total of 15 alarming signs that companies either ignored, could not control, or did not act with alertness towards to stop the business being taken out of hands. In this research paper, the establishment of J. Crew Inc. was presented in four sections: Crew Retail Stores, Crew Factory Stores, Crew Mercantile Stores, and Crew Madewell Stores. The results of this study show that it was not the COVID-19 pandemic that pushed this retail giant into bankruptcy, but numerous reasons and financial turbulences. J. Crew’s financial performance gave plenty of alarming signals that the showed the company was not on track, but these were ignored by the company. Right from net profit, operating expenses, total revenue, goodwill, return on assets, liquidity, and solvency, all 15 indicators were not meeting the industry ideal standard for a continuous period of 5 years. Whether or not the organization can rebuild and contend in a post-pandemic world, is not yet clear.
Addressing Peatland Rewetting in Russian Federation Climate Reporting
Authors: Sirin Andrey , Medvedeva Maria , Korotkov Vladimir , Itkin Victor , Minayeva Tatiana , Ilyasov Danil , Suvorov Gennady , Joosten Hans
Published: November 2021

Rewetting is the most effective way to reduce greenhouse gas (GHG) emissions from drained peatlands and must significantly contribute to the implementation of the Paris Agreement on Climate within the land sector. In 2010–2013, more than 73 thousand hectares of fire-prone peatlands were rewetted in the Moscow Region (the hitherto largest rewetting program in the Northern Hemisphere). As the Russian Federation has no national accounting of rewetted areas yet, this paper presents an approach to detect them based on multispectral satellite data verified by ground truthing. We propose that effectively rewetted areas should minimally include areas with wet grasslands and those covered with water (cf. the IPCC categories “rewetted organic soils” and “flooded lands”). In 2020, these lands amounted in Moscow Region to more than 5.3 and 3.6 thousand hectares, respectively. Assuming that most rewetted areas were former peat extraction sites and using IPCC default GHG emission factors, an overall GHG emission reduction of over 36,000 tCO2-eq year−1 was calculated. We furthermore considered the uncertainty of calculations. With the example of a 1535 ha large rewetted peatland, we illustrate the estimation of GHG emission reductions for the period up to 2050. The approach presented can be used to estimate GHG emission reductions by peatland rewetting on the national, regional, and object level.
Modeling the Size of Protection Zones of Cultural Heritage Sites Based on Factors of the Historical and Cultural Assessment of Lands
Authors: Bykowa Elena , Dyachkova Irina
Published: November 2021

This article addresses the global issue of preserving cultural heritage, which is associated, among other things, with the lack of provision for boundaries of protection zones for cultural heritage sites. This paper analyzes the worldwide experience in the field of establishing protection zones for cultural heritage sites, identifies the issues of preserving cultural heritage in Russia, as well as imperfections in the management of lands containing cultural heritage sites. To improve the management of such lands, a method of historical and cultural assessment of territories has been developed, which, on the basis of evaluative factors, makes it possible to characterize the historical and cultural value of a territory. In this article, based on this list of factors, a method for mathematical substantiation of the boundaries of protection zones of cultural heritage sites has been developed; this method includes seven stages. Using mathematical and statistical methods, models were obtained to determine the area of the protection (buffer) zone and the development control zone, the analysis of which revealed differentiation between the factors of historical and cultural assessment that characterize the urban environment, depending on the type of zones. The interpretation of the obtained models and the fields of their use are given.
Assessing the Climate Resilience of Sub-Saharan Africa (SSA): A Metric-Based Approach
Authors: Sono Douglas , Wei Ye , Jin Ying
Published: November 2021

The impacts of climate change have resulted in the emergence of resilience as the de factor framework for countries seeking to capture the differential and uneven ability to prepare, react, respond and cope with volatile and rapid changes of climate-related stresses. Despite being considered by many researchers the most vulnerable region to the negative effects of climate change, the climate resilience of Sub-Saharan Africa has not been extensively studied. Using countries in Sub-Saharan Africa (SSA) as a study area, this paper constructed a pragmatically based resilience metric called the composite national climate resilience index (CNCRI) that can be used as a tool for the policy word. The inherent variables used to construct the CNCRI were justified and used to measure the resilience of countries in SSA based on five different dimensions. The result indicates that the CNCRI score, 1.05 (least resilient) to 44.8 (most resilient), and the island countries of Mauritius, Seychelles, and Cape Verde are comparatively more resilient than the rest of the countries in the study area. Regionally, Southern Africa is more resilient compared to East, West, and Central Africa. The vulnerability and readiness metric suggested that Cape Verde is the only country in SSA to have low vulnerability and high readiness, while most countries have high vulnerability and low readiness, making them the least resilient countries needing urgent mitigation and adaptation actions. Lastly, finding from this study could provide the policy world with insight for improving the overall ability to prepare and respond to the negative impacts of climate in the study area.
Cropland Abandonment and Influencing Factors in Chongqing, China
Authors: Li Han , Song Wei
Published: November 2021

Cropland abandonment occurs frequently in many countries and regions around the world, particularly in those with poor environmental conditions, such as mountainous regions. In Chongqing county, China, over 76% of the total area is mountainous. Due to the lack of reliable remote sensing monitoring and identification methods, the spatial and temporal distribution of abandoned cropland areas and its underlying causes are poorly understood. Thus, the extent of cropland abandonment in Chongqing, since 2001, was estimated using land use trajectories. The following results were obtained: (1) the cropland abandonment rate was 12.2–15.4% from 2001 to 2020, with an average of 13.3%; (2) hotspots of abandoned cropland were concentrated in the north and southeast. Cropland abandonment was clustered in the northern, southeastern, and southwestern areas; (3) socio-economic factors (including gross domestic product density, population density, and road density) had a greater impact on the spatial distribution of abandoned cropland than environmental factors. Based on the results, the government should strive to reduce production costs associated with poor agricultural infrastructure, sporadic cropland, and higher labor costs by providing grain subsidies, undertaking cropland consolidation, encouraging land transfer, and improving agricultural infrastructure.
Cholemic Nephropathy as Cause of Acute and Chronic Kidney Disease. Update on an Under-Diagnosed Disease
Authors: Tinti Francesca , Umbro Ilaria , D’Alessandro Mariadomenica , Lai Silvia , Merli Manuela , Noce Annalisa , Di Daniele Nicola , Mazzaferro Sandro , Mitterhofer Anna Paola
Published: November 2021

Cholemic nephropathy (CN) is a recognized cause of acute kidney injury (AKI) in patients with severe hyperbilirubinemia (sHyb) and jaundice. Pathophysiological mechanisms of CN are not completely understood, but it seems caused both by direct toxicity of cholephiles and bile casts formation in nephrons enhanced by prolonged exposure to sHyb, particularly in the presence of promoting factors, as highlighted by a literature reviewed and by personal experience. The aim of our update is to retrace CN in its pathophysiology, risk factors, diagnosis and treatment, underlining the role of sHyb, promoting factors, and CN-AKI diagnostic criteria in the different clinical settings associated with this often-concealed disease. Our purpose is to focus on clinical manifestation of CN, exploring the possible transition to CKD. Cholemic nephropathy is an overlooked clinical entity that enters differential diagnosis with other causes of AKI. Early diagnosis and treatment are essential because renal injury could be fully reversible as rapidly as bilirubin levels are reduced. In conclusion, our proposal is to introduce an alert for considering CN in diagnostic and prognostic scores that include bilirubin and/or creatinine with acute renal involvement, with the aim of early diagnosis and treatment of sHyb to reduce the burden on renal outcome.
Detection of Material Degradation of a Composite Cylinder Using Mode Shapes and Convolutional Neural Networks
Authors: Miller Bartosz , Ziemiański Leonard
Published: November 2021

This paper presents a numerical study of the feasibility of using vibration mode shapes to identify material degradation in composite structures. The considered structure is a multilayer composite cylinder, while the material degradation zone is, for simplicity, considered a square section of the lateral surface of the cylinder. The material degradation zone size and location along the cylinder axis are identified using a deep learning approach (convolutional neural networks, CNNs, are applied) on the basis of previously identified vibration mode shapes. The different numbers and combinations of identified mode shapes used to assess the damaged zone size and location were analyzed in detail. The final selection of mode shapes considered in the identification procedure yielded high accuracy in the identification of the degradation zone.
Diflunisal Targeted Delivery Systems: A Review
Authors: Snetkov Petr , Morozkina Svetlana , Olekhnovich Roman , Uspenskaya Mayya
Published: November 2021

Diflunisal is a well-known drug for the treatment of rheumatoid arthritis, osteoarthritis, primary dysmenorrhea, and colon cancer. This molecule belongs to the group of nonsteroidal anti-inflammatory drugs (NSAID) and thus possesses serious side effects such as cardiovascular diseases risk development, renal injury, and hepatic reactions. The last clinical data demonstrated that diflunisal is one of the recognized drugs for the treatment of cardiac amyloidosis and possesses a survival benefit similar to that of clinically approved tafamidis. Diflunisal stabilizes the transthyretin (TTR) tetramer and prevents the misfolding of monomers and dimers from forming amyloid deposits in the heart. To avoid serious side effects of diflunisal, the various delivery systems have been developed. In the present review, attention is given to the recent development of diflunisal-loaded delivery systems, its technology, release profiles, and effectiveness.
Bond Strength of Self-Adhesive Flowable Composites and Glass Ionomer Cements to Primary Teeth: A Systematic Review and Meta-Analysis of In Vitro Studies
Authors: Iaculli Flavia , Salucci Alessandro , Di Giorgio Gianni , Luzzi Valeria , Ierardo Gaetano , Polimeni Antonella , Bossù Maurizio
Published: November 2021

Background: Conventional composites are largely used in pediatric restorative dentistry and demonstrate successful clinical outcomes. However, the need for simplification of operative steps in young or uncooperative children demands reliable alternatives. Therefore, the aim of the present systematic review and meta-analysis was to evaluate the in vitro bond strength of glass ionomer cements (GICs) and self-adhesive flowable composites (SFCs) on deciduous teeth. Methods: A comprehensive literature search according to the PRISMA checklist was manually and electronically performed by two independent reviewers through the following databases: MEDLINE/PubMed, Google Scholar, Scopus, and Embase, to include in vitro studies comparing GICs and SFCs bond strength values of restorations on primary teeth. In addition, three groups of meta-analyses were conducted using random-effects models. Results: Three articles meeting the inclusion criteria were selected and subjected to both qualitative and quantitative assessment. No statistically significant difference was found between SFC versus GIC; however, both groups significantly differed with conventional flowable composites (CFs). Conclusions: Despite the absence of significant difference in bond strength values, SFCs may be considered a valid alternative to GICs in the restoration of deciduous teeth, although CFs proved better in vitro performances.
Materials Selection and Design Options Analysis for a Centrifugal Fan Impeller in a Horizontal Conveyor Dryer
Authors: Zinchenko Andrii , Baiul Kostiantyn , Krot Pavlo , Khudyakov Aleksander , Vashchenko Sergii , Banasiewicz Aleksandra , Wróblewski Adam
Published: November 2021

Comparative strength analysis of two popular options of the radial centrifugal fan impeller design used in horizontal conveyor dryer for fine-grained raw materials is presented. Three types of materials for impeller manufacturing—ASTM A36 steel, Hardox 450 steel and aluminium alloy 6061-T6 are considered. The finite element method (FEM) has been used to investigate stresses and deformations of the impeller within the operational speed range. Analysis shows that the better design is the impeller made of Hardox 450 steel with a central disk. Although the maximum stress is slightly higher in the blades slot for central disk fitting for this design option, it has greatly reduced stresses in contact edges with two other disks (by 22–38%) and blades bending deformation (by 51%). For this design, the maximum operational rotation speed is 1135 min−1 according to the yield strength with a 15% safety factor, while for basic design, it is 1225 min−1. The rational choice of material depends on maximum value of the yield stress to density ratio as well as taking into account the operating conditions and required fan performance. Recommendations for manufacturing the centrifugal fan impeller related to chosen material are given.
In Situ Determination of Droplet and Nanoparticle Size Distributions in Spray Flame Synthesis by Wide-Angle Light Scattering (WALS)
Authors: Aßmann Simon , Münsterjohann Bettina , Huber Franz J. T. , Will Stefan
Published: November 2021

The investigation of droplet and nanoparticle formation in spray flame synthesis requires sophisticated measurement techniques, as often both are present simultaneously. Here, wide-angle light scattering (WALS) was applied to determine droplet and nanoparticle size distributions in spray flames from a standardized liquid-fed burner setup. Solvents of pure ethanol and a mixture of ethanol and titanium isopropoxide, incepting nanoparticle synthesis, were investigated. A novel method for the evaluation of scattering data from droplets between 2 µm and 50 µm was successfully implemented. Applying this, we could reveal the development of a bimodal droplet size distribution for the solvent/precursor system, probably induced by droplet micro-explosions. To determine nanoparticle size distributions, an appropriate filter and the averaging of single-shot data were applied to ensure scattering from a significant amount of nanoparticles homogeneously distributed in the measurement volume. From the multivariate analysis of the scattering data, the presence of spherical particles and fractal aggregates was derived, which was confirmed by analysis of transmission electron microscopy images. Monte Carlo simulations allowed determining the distribution parameters for both morphological fractions in three heights above the burner. The results showed relatively wide size distributions, especially for the spherical fraction, and indicated an ongoing sintering, from fractal to spherical particles.
Rational Design and Characterization of Symmetry-Breaking Organic Semiconductors in Polymer Solar Cells: A Theory Insight of the Asymmetric Advantage
Authors: Liang Zezhou , Yan Lihe , Si Jinhai , Gong Pingping , Li Xiaoming , Liu Deyu , Li Jianfeng , Hou Xun
Published: November 2021

Asymmetric molecule strategy is considered an effective method to achieve high power conversion efficiency (PCE) of polymer solar cells (PSCs). In this paper, nine oligomers are designed by combining three new electron-deficient units (unitA)—n1, n2, and n3—and three electron-donating units (unitD)—D, E, and F—with their π-conjugation area extended. The relationships between symmetric/asymmetric molecule structure and the performance of the oligomers are investigated using the density functional theory (DFT) and time-dependent density functional theory (TD–DFT) calculations. The results indicate that asymmetry molecule PEn2 has the minimum dihedral angle in the angle between two planes of unitD and unitA among all the molecules, which exhibited the advantages of asymmetric structures in molecular stacking. The relationship of the values of ionization potentials (IP) and electron affinities (EA) along with the unitD/unitA π-extend are revealed. The calculated reorganization energy results also demonstrate that the asymmetric molecules PDn2 and PEn2 could better charge the extraction of the PSCs than other molecules for their lower reorganization energy of 0.180 eV and 0.181 eV, respectively.
Preliminary Process and Microstructure Examination of Flux-Cored Wire Arc Additive Manufactured 18Ni-12Co-4Mo-Ti Maraging Steel
Authors: Pańcikiewicz Krzysztof
Published: November 2021

The production of large-size elements using additive manufacturing is a constantly evolving field that includes technological and material solutions. There is a need for a detailed analysis of the process and the products thus manufactured. In line with this trend, the flux-cored wire arc additive manufactured process and the part made of 18Ni-12Co-4Mo-Ti maraging steel were examined. The interpass temperature below 150 °C, the variation of the starting point and the gas flow of 12 L/min with a pre-flow of 2 s ensure the correct shape of the layers. The manufactured part underwent chemical composition analysis, macro- and microscopic examination and hardness measurements; in addition thermodynamic calculations were performed. The part is divided into a light-etched area (bottom part of the sample) with a hardness of 375 ± 12 HV10 and a dark-etched area (top part of the sample) with a hardness of 525 ± 11 HV10. Microscopic observations in the last layers showed supersaturated martensite with primary precipitates of μ-phase intermetallic compounds in intercellular spaces. In the earlier layers aging martensite with austenite and primary precipitates of intermetallic compounds were revealed. The share of austenite was 11.435 ± 1.313%.