bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunocytochemical Analysis of Endogenous Frizzled-(Co-)Receptor Interactions and Rapid Wnt Pathway Activation in Mammalian Cells
Authors: Neuhaus Jochen , Weimann Annett , Berndt-Paetz Mandy
Published: November 2021

The differential activation of Wnt pathways (canonical: Wnt/β-catenin; non-canonical: planar cell polarity (PCP), Wnt/Ca2+) depends on the cell-specific availability and regulation of Wnt receptors, called Frizzled (FZD). FZDs selectively recruit co-receptors to activate various downstream effectors. We established a proximity ligation assay (PLA) for the detection of endogenous FZD–co-receptor interactions and analyzed time-dependent Wnt pathway activation in cultured cells. Prostate cancer cells (PC-3) stimulated by Wnt ligands (Wnt5A, Wnt10B) were analyzed by Cy3-PLA for the co-localization of FZD6 and co-receptors (canonical: LRP6, non-canonical: ROR1) at the single-cell level. Downstream effector activation was assayed by immunocytochemistry. PLA allowed the specific (siRNA-verified) detection of FZD6–LRP6 and FZD6–ROR1 complexes as highly fluorescent spots. Incubation with Wnt10B led to increased FZD6–LRP6 interactions after 2 to 4 min and resulted in nuclear accumulation of β-catenin within 5 min. Wnt5A stimulation resulted in a higher number of FZD6–ROR1 complexes after 2 min. Elevated levels of phosphorylated myosin phosphatase target 1 suggested subsequent Wnt/PCP activation in PC-3. This is the first study demonstrating time-dependent interactions of endogenous Wnt (co-)receptors followed by rapid Wnt/β-catenin and Wnt/PCP activation in PC-3. In conclusion, the PLA could uncover novel signatures of Wnt receptor activation in mammalian cells and may provide new insights into involved signaling routes.
A UHPLC-Mass Spectrometry View of Human Melanocytic Cells Uncovers Potential Lipid Biomarkers of Melanoma
Authors: Perez-Valle Arantza , Abad-García Beatriz , Fresnedo Olatz , Barreda-Gómez Gabriel , Aspichueta Patricia , Asumendi Aintzane , Astigarraga Egoitz , Fernández José A. , Boyano María Dolores , Ochoa Begoña
Published: November 2021

Melanoma is the deadliest form of skin cancer due to its ability to colonize distant sites and initiate metastasis. Although these processes largely depend on the lipid-based cell membrane scaffold, our understanding of the melanoma lipid phenotype lags behind most other aspects of this tumor cell. Here, we examined a panel of normal human epidermal and nevus melanocytes and primary and metastatic melanoma cell lines to determine whether distinctive cell-intrinsic lipidomes can discern non-neoplastic from neoplastic melanocytes and define their metastatic potential. Lipidome profiles were obtained by UHPLC-ESI mass-spectrometry, and differences in the signatures were analyzed by multivariate statistical analyses. Significant and highly specific changes in more than 30 lipid species were annotated in the initiation of melanoma, whereas less numerous changes were associated with melanoma progression and the non-malignant transformation of nevus melanocytes. Notably, the “malignancy lipid signature” features marked drops in pivotal membrane lipids, like sphingomyelins, and aberrant elevation of ether-type lipids and phosphatidylglycerol and phosphatidylinositol variants, suggesting a previously undefined remodeling of sphingolipid and glycerophospholipid metabolism. Besides broadening the molecular definition of this neoplasm, the different lipid profiles identified may help improve the clinical diagnosis/prognosis and facilitate therapeutic interventions for cutaneous melanoma.
Geographical Distribution and Long-Term Monitoring of Physokermes hellenicus (Hemiptera: Coccomorpha: Coccidae) on Abies spp. (Pinales: Pinaceae) in Greece
Authors: Papanastasiou Iosif , Kavallieratos Nickolas G. , Papadoulis Georgios Th. , Emmanouil Christina , Emmanouel Nikolaos G.
Published: November 2021

The scale Physokermes hellenicus (Kozár & Gounari) (Hemiptera: Coccidae) has been recently included in the Greek entomofauna as a beneficial honeydew species. However, there are no adequate data about its geographical distribution and degree of infestation. Therefore, a study was conducted to examine these parameters in fifteen mountains of Greece. Furthermore, the monitoring of P. hellenicus infestation was carried out over a six-year period with regard to natural enemies and honeydew presence at three mountains (i.e., Menalon, Parnis and Tymfristos) that are traditional honeybee foraging areas. An extensive geographical distribution of the scale was negatively correlated with the latitude. Over the period of the study, P. hellenicus infestation exhibited a decreasing trend in the three mountains, which was more obvious at Menalon. The abundance of natural enemies of P. hellenicus, their effectiveness on honeydew excretion and the fecundity of P. hellenicus are discussed. The reduction in the honey produced at the Menalon mountain (a protected designation of origin product) could be attributed to the reduced presence of P. hellenicus in the fir forest. Among the other identified arthropods, Dreyfusia nordmannianae Eckstein (Hemiptera: Adelgidae) is reported for the first time infesting Abies cephalonica (Pinales: Pinaceae) in Greece. Furthermore, this species is reported for the first time as a co-parasite with P. hellenicus on A. cephalonica in Greece. Since D. nordmannianae is a serious pest, additional research is needed to determine its status in Greek fir forest ecosystems.
Can the Combined Use of the Mirid Predator Nesidiocoris tenuis and a Braconid Larval Endoparasitoid Dolichogenidea gelechiidivoris Improve the Biological Control of Tuta absoluta?
Authors: Aigbedion-Atalor Pascal Osa , Hill Martin P. , Ayelo Pascal Mahukpe , Ndlela Shepard , Zalucki Myron P. , Mohamed Samira A.
Published: November 2021

The koinobiont solitary larval endoparasitoid Dolichogenidea gelechiidivoris (Marsh) (Syn.: Apanteles gelechiidivoris) (Hymenoptera: Braconidae) and the predatory bug Nesidiocoris tenuis (Reuter) (Hemiptera: Miridae) are important natural enemies of Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae), a serious pest of tomato. Although N. tenuis preferentially feeds on T.absoluta eggs, it is also recorded as a predator of first and second instar larval stages. Dolichogenidea gelechiidivoris preferentially seeks these early larval stages of T. absoluta for oviposition. The occurrence of intraguild predation between N. tenuis and D. gelechiidivoris and the consequences on the oviposition performance of D. gelechiidivoris were investigated in the laboratory. Regardless of the manner of introduction (i.e., the sequence of combinations with D. gelechiidivoris) or density (i.e., number of N. tenuis combined with D. gelechiidivoris), the presence of N. tenuis did not affect the oviposition performance of D. gelechiidivoris or the parasitoid’s progeny. Combination assays revealed that the efficacy of the combined use of N. tenuis and D. gelechiidivoris in controlling T. absoluta populations was significantly higher than that of either natural enemy alone. Our results highlight the potential of combining mirid predators and koinobiont larval endoparasitoids to control T. absoluta. The findings further contribute to data supporting the release of D. gelechiidivoris in tomato agroecosystems for the control of T. absoluta in Africa, where N. tenuis is widespread and abundant.
GD (Generative Design) Applied to a Plastics Recovery Drone (PRD) Using IDeS (Industrial Design Structure)
Authors: Frizziero Leonardo , Liverani Alfredo , Donnici Giampiero , Conti Enrico , Dello Preite Beatrice , Lamanna Umberto , Leon-Cardenas Christian , Garulli Matteo
Published: November 2021

The evolution of innovative and systematic design methodologies over time has widened the design concept involvement from the product development phase, which also includes the production and start-up phases. Literature findings have presented to accomplish a Generative Design (GD) approach through the application of an innovative method called Industrial Structure Design (IDeS), a systematic design method able to discover the customer’s needs and the fundamental technical solutions to obtain a good innovative product, involving the whole organization for this achievement. Nevertheless, there is a social demand for solutions to the dramatic and growing problem of marine pollution from plastic materials, encouraging the designers to conceive a new innovative drone for waste collection at sea. Therefore, this study aims to merge all the most advanced design technologies with IDeS in an integrated way, by generating a structure that can also be adopted to plan the organization of a production company. The approach is validated with the design of the Recovery Plastic Drone (RPD) obtained with the IDeS methodology, combining Design and Product development phases, leading to a better and innovative solution for the market.
Designing a Block Cipher in Galois Extension Fields for IoT Security
Authors: George Kiernan , Michaels Alan J.
Published: November 2021

This paper focuses on a block cipher adaptation of the Galois Extension Fields (GEF) combination technique for PRNGs and targets application in the Internet of Things (IoT) space, an area where the combination technique was concluded as a quality stream cipher. Electronic Codebook (ECB) and Cipher Feedback (CFB) variations of the cryptographic algorithm are discussed. Both modes offer computationally efficient, scalable cryptographic algorithms for use over a simple combination technique like XOR. The cryptographic algorithm relies on the use of quality PRNGs, but adds an additional layer of security while preserving maximal entropy and near-uniform distributions. The use of matrices with entries drawn from a Galois field extends this technique to block size chunks of plaintext, increasing diffusion, while only requiring linear operations that are quick to perform. The process of calculating the inverse differs only in using the modular inverse of the determinant, but this can be expedited by a look-up table. We validate this GEF block cipher with the NIST test suite. Additional statistical tests indicate the condensed plaintext results in a near-uniform distributed ciphertext across the entire field. The block cipher implemented on an MSP430 offers a faster, more power-efficient alternative to the Advanced Encryption Standard (AES) system. This cryptosystem is a secure, scalable option for IoT devices that must be mindful of time and power consumption.
Cardiac Tissue Engineering for the Treatment of Myocardial Infarction
Authors: Yu Dongmin , Wang Xiaowei , Ye Lei
Published: November 2021

Poor cell engraftment rate is one of the primary factors limiting the effectiveness of cell transfer therapy for cardiac repair. Recent studies have shown that the combination of cell-based therapy and tissue engineering technology can improve stem cell engraftment and promote the therapeutic effects of the treatment for myocardial infarction. This mini-review summarizes the recent progress in cardiac tissue engineering of cardiovascular cells from differentiated human pluripotent stem cells (PSCs), highlights their therapeutic applications for the treatment of myocardial infarction, and discusses the present challenges of cardiac tissue engineering and possible future directions from a clinical perspective.
Two-Stage Exchange Arthroplasty for Periprosthetic Shoulder Infection Is Associated with High Rate of Failure to Reimplant and Mortality
Authors: Akgün Doruk , Wiethölter Mats , Maziak Nina , Paksoy Alp , Karczewski Daniel , Scheibel Markus , Moroder Philipp
Published: November 2021

Background: Patients with a periprosthetic joint infection (PJI) of the shoulder, who fail to undergo reimplantation in an attempted two-stage exchange seem to be neglected in the current literature. The aim of this study was to assess the clinical course of patients after the first stage in the process of an attempted two-stage exchange for shoulder PJI. Methods: After a retrospective review of our institutional database between 2008 and 2018, 49 patients, who were treated with an intended two-stage exchange for shoulder PJI, were identified. Patients’ demographics, laboratory and health status parameters, along with records of clinical outcome were collected. The primary outcome measurements analyzed were infection eradication, successful reimplantation, and patient survival. Results: Reimplantation was completed in only 35 (71%) of 49 cases and eradication of infection was achieved in 85.7% of patients with successful reimplantation after a mean follow-up duration of 5.1 years (1.1 to 10.2 years). Reasons for failure to reimplant were premature death in 36%, high general morbidity in 29%, satisfaction with the current status in 21%, or severe infection with poor bone and soft tissues in 14% of the patients. Of the 14 cases without reimplantation, eradication rate of infection was 57% after a mean follow-up of 5 years (2.6 to 11 years). The overall mortality rate of the entire cohort was 25% at the latest follow-up and 10% within ninety days after implant removal. Patients who deceased or did not undergo reimplantation during the follow-up were significantly older and had a significantly higher Charlson comorbidity index (CCI). Conclusions: While the two-stage exchange arthroplasty can lead to high rates of infection eradication, a considerable subset of patients never undergoes the second stage for a variety of reasons. Shoulder PJI and its treatment are associated with a high risk of mortality, especially in patients with older age and higher CCI.
Factors Associated with Acute Community-Acquired Pyelonephritis Caused by Extended-Spectrum β-Lactamase-Producing Escherichia coli
Authors: Romero Nieto Mónica , Maestre Verdú Sara , Gil Vicente , Pérez Barba Carlos , Quesada Rico Jose Antonio , Pascual Pérez Reyes
Published: November 2021

This study aimed to identify the factors associated with the presence of extended-spectrum ß-lactamase-(ESBL) in patients with acute community-acquired pyelonephritis (APN) caused by Escherechia coli (E. coli), with a view of optimising empirical antibiotic therapy in this context. We performed a retrospective analysis of patients with community-acquired APN and confirmed E. coli infection, collecting data related to demographic characteristics, comorbidities, and treatment. The associations of these factors with the presence of ESBL were quantified by fitting multivariate logistic models. Goodness-of-fit and predictive performance were measured using the ROC curve. We included 367 patients of which 51 presented with ESBL, of whom 90.1% had uncomplicated APN, 56.1% were women aged ≤55 years, 33.5% had at least one mild comorbidity, and 12% had recently taken antibiotics. The prevalence of ESBL-producing E. coli was 13%. In the multivariate analysis, the factors independently associated with ESBL were male sex (OR 2.296; 95% CI 1.043–5.055), smoking (OR 4.846, 95% CI 2.376–9.882), hypertension (OR 3.342, 95% CI 1.423–7.852), urinary incontinence (OR 2.291, 95% CI 0.689–7.618) and recurrent urinary tract infections (OR 4.673, 95% CI 2.271–9.614). The area under the ROC curve was 0.802 (IC 95% 0.7307–0.8736), meaning our model can correctly classify an individual with ESBL-producing E. coli infection in 80.2% of cases.
Relationship between Adipokines and Cardiovascular Ultrasound Parameters in Metabolic-Dysfunction-Associated Fatty Liver Disease
Authors: Ismaiel Abdulrahman , Spinu Mihail , Budisan Livia , Leucuta Daniel-Corneliu , Popa Stefan-Lucian , Chis Bogdan Augustin , Berindan-Neagoe Ioana , Olinic Dan Mircea , Dumitrascu Dan L.
Published: November 2021

(1) Background: The role of adipokines such as adiponectin and visfatin in metabolic-dysfunction-associated fatty liver disease (MAFLD) and cardiovascular disease remains unclear. Therefore, we aim to assess serum adiponectin and visfatin levels in MAFLD patients and associated cardiovascular parameters. (2) Methods: A cross-sectional study involving 80 participants (40 MAFLD patients, 40 controls), recruited between January and September 2020, was conducted, using both hepatic ultrasonography and SteatoTestTM to evaluate hepatic steatosis. Echocardiographic and Doppler parameters were assessed. Serum adipokines were measured using ELISA kits. (3) Results: Adiponectin and visfatin levels were not significantly different in MAFLD vs. controls. Visfatin was associated with mean carotid intima-media thickness (p-value = 0.047), while adiponectin was associated with left ventricular ejection fraction (LVEF) (p-value = 0.039) and E/A ratio (p-value = 0.002) in controls. The association between adiponectin and E/A ratio was significant in the univariate analysis at 95% CI (0.0049–0.1331, p-value = 0.035), but lost significance after the multivariate analysis. Although LVEF was not associated with adiponectin in the univariate analysis, significant values were observed after the multivariate analysis (95% CI (−1.83–−0.22, p-value = 0.015)). (4) Conclusions: No significant difference in serum adiponectin and visfatin levels in MAFLD patients vs. controls was found. Interestingly, although adiponectin levels were not associated with LVEF in the univariate analysis, a significant inversely proportional association was observed after the multivariate analysis.
IRF3 Knockout Results in Partial or Complete Rejection of Murine Mesothelioma
Authors: Aoki Masaya , Wu Licun , Murakami Junichi , Zhao Yidan , Yun Hana , de Perrot Marc
Published: November 2021

Background: Malignant pleural mesothelioma (MESO) has a poor prognosis despite aggressive treatment with surgery, radiation and chemotherapy, and novel therapeutic approaches are needed. IRF3 is a downstream molecule of the cGAS/STING signaling pathway, but its roles have not been investigated in MESO. Methods: Various murine mesothelioma cell lines were inoculated into wild type (WT) and IRF3 knockout (IRF3KO) mice to compare tumor growth. AE17-bearing mice were treated with local radiotherapy (LRT) to evaluate the effect on tumor growth, and immune cell infiltration was analyzed by flow cytometry 20 days after tumor inoculation. TCGA data were used to examine the relationship between mRNA expression of IRF3 and genes of the cGAS/STING signaling cascade on prognosis in MESO. Correlations between gene expression of IRF3, cGAS/STING signaling pathway, and immune checkpoints were analyzed in TCGA MESO and our scRNA-Seq data from MESO patients. Results: In mouse mesothelioma models, AK7, RN5 and ZiP3 were completely rejected in IRF3KO mice 20 days after the tumor challenge. AE17tumor volume was slightly larger than WT mice around day 10 before shrinking and becoming significantly smaller than WT mice on day 20. LRT accelerated tumor shrinkage of AE17 tumors in IRF3KO mice. Compared with WT mice, the number of macrophages infiltrating the tumor of IRF3KO mice was significantly reduced, and CD4+ T cells and CD8+IFNγ+ T cells were significantly increased. TCGA data showed that IRF3 expression was an unfavorable prognostic factor in MESO patients. IRF3 expression, the cGAS/STING signaling pathway, and immune checkpoints were positively correlated. Conclusion: IRF3 could play a critical role in the tumor immune microenvironment of MESO.
Determining What Changed Japanese Suicide Mortality in 2020 Using Governmental Database
Authors: Matsumoto Ryusuke , Motomura Eishi , Fukuyama Kouji , Shiroyama Takashi , Okada Motohiro
Published: November 2021

The pandemic of 2019 novel coronavirus disease (COVID-19) caused both COVID-19-related health hazards and the deterioration of socioeconomic and sociopsychological status due to governmental restrictions. There were concerns that suicide mortality would increase during the COVID-19 pandemic; however, a recent study reported that suicide mortality did not increase in 21 countries during the early pandemic period. In Japan, suicide mortality was reduced from 2009 to 2019, but both the annual number of suicide victims and the national suicide mortality rates in 2020 increased compared to that in 2019. To clarify the discrepancy of suicide mortality between the first and second half of 2020 in Japan, the present study determines annual and monthly suicide mortality disaggregated by prefectures, gender, age, means, motive, and household factors during the COVID-19 pandemic and pre-pandemic periods using a linear mixed-effects model. Furthermore, the relationship between suicide mortality and COVID-19 data (the infection rate, mortality, and duration of the pandemic) was analysed using hierarchal linear regression with a robust standard error. The average of monthly suicide mortality of both males and females in all 47 prefectures decreased during the first stay-home order (April–May) (females: from 10.1–10.2 to 7.8–7.9; males: from 24.0–24.9 to 21.6 per 100,000 people), but increased after the end of the first stay-home order (July–December) (females: from 7.5–9.5 to 10.3–14.5; males: from 19.9–23.0 to 21.1–26.7 per 100,000 people). Increasing COVID-19-infected patients and victims indicated a tendency of suppression, but the prolongation of the pandemic indicated a tendency of increasing female suicide mortality without affecting that of males. Contrary to the national pattern, in metropolitan regions, decreasing suicide mortality during the first stay-home order was not observed. Decreasing suicide mortality during the first stay-home order was not observed in populations younger than 30 years old, whereas increasing suicide mortality of populations younger than 30 years old after the end of the first stay-home order was predominant. A decrease in suicide mortality of one-person household residents during the first stay-home order was not observed. The hanging suicide mortality of males and females was decreased and increased during and after the end of the first stay-home orders, respectively; however, there was no decrease in metropolitan regions. These results suggest that the suicide mortality in 2020 of females, younger populations, urban residents, and one-person household residents increased compared to those of males, the elderly, rural residents, and multiple-person household residents. Therefore, the unexpected drastic fluctuations of suicide mortality during the COVID-19 pandemic in Japan were probably composed of complicated reasons among various identified factors in this study, and other unknown factors.
Exploring Early Pre-Symptomatic Detection of Influenza Using Continuous Monitoring of Advanced Physiological Parameters during a Randomized Controlled Trial
Authors: Goldstein Nir , Eisenkraft Arik , Arguello Carlos J. , Yang Ge Justin , Sand Efrat , Ishay Arik Ben , Merin Roei , Fons Meir , Littman Romi , Nachman Dean , Gepner Yftach
Published: November 2021

Early detection of influenza may improve responses against outbreaks. This study was part of a clinical study assessing the efficacy of a novel influenza vaccine, aiming to discover distinct, highly predictive patterns of pre-symptomatic illness based on changes in advanced physiological parameters using a novel wearable sensor. Participants were frequently monitored 24 h before and for nine days after the influenza challenge. Viral load was measured daily, and self-reported symptoms were collected twice a day. The Random Forest classifier model was used to classify the participants based on changes in the measured parameters. A total of 116 participants with ~3,400,000 data points were included. Changes in parameters were detected at an early stage of the disease, before the development of symptomatic illness. Heart rate, blood pressure, cardiac output, and systemic vascular resistance showed the greatest changes in the third post-exposure day, correlating with viral load. Applying the classifier model identified participants as flu-positive or negative with an accuracy of 0.81 ± 0.05 two days before major symptoms appeared. Cardiac index and diastolic blood pressure were the leading predicting factors when using data from the first and second day. This study suggests that frequent remote monitoring of advanced physiological parameters may provide early pre-symptomatic detection of flu.
Post-COVID-19 Sydrome and Decrease in Health-Related Quality of Life in Kidney Transplant Recipients after SARS-COV-2 Infection—A Cohort Longitudinal Study from the North of Poland
Authors: Malinowska Agnieszka , Muchlado Marta , Ślizień Zuzanna , Biedunkiewicz Bogdan , Heleniak Zbigniew , Dębska-Ślizień Alicja , Tylicki Leszek
Published: November 2021

Introduction: Patients after SARS-CoV-2 infection frequently face “Post-COVID-19 Syndrome”, defined by symptoms that develop during or after COVID-19, continue for more than 12 weeks, and are not explained by an alternative diagnosis. We aimed to evaluate the presence of post-COVID-19 syndrome and its predictors in kidney transplant recipients (KTR) 6 months after the disease. Materials and Methods: A total of 67 KTR (38 m) with a mean age of 53.6 ± 14 years, 7.3 ± 6.4 years post-transplant were included in the cohort longitudinal study. Thirty-nine (58.2%) of them were hospitalized, but not one required invasive ventilation therapy. They were interviewed 6 months after being infected, with a series of standardized questionnaires: a self-reported symptoms questionnaire, the modified British Medical Research Council (mMRC) dyspnea scale, EQ-5D-5L questionnaire, and EQ-VAS scale. Results: Post-COVID-19 syndrome was diagnosed in 70.1% of KTR and 26.9% of them reported at least three persistent symptoms. The most common symptoms were fatigue (43.3%), hair loss (31.3%), memory impairment (11.9%), muscle aches, and headaches (11.9%). Dyspnea with an mMRC scale grade of at least 1 was reported by 34.3% patients vs. 14.9% before infection; 47.8% stated that they still feel worse than before the disease. Mean EQ-VAS scores were 64.83 vs. 73.34 before infection. The persistent symptoms are more frequent in older patients and those with greater comorbidity. Conclusions: Persistent symptoms of post-COVID-19 syndrome are present in the majority of KTR, which highlights the need for long-term follow-up as well as diagnostic and rehabilitation programs.
Long-Term Safety and Efficacy of Subcutaneous Cladribine Used in Increased Dosage in Patients with Relapsing Multiple Sclerosis: 20-Year Observational Study
Authors: Rejdak Konrad , Zasybska Adriana , Pietruczuk Aleksandra , Baranowski Dariusz , Szklener Sebastian , Kaczmarek Magda , Stelmasiak Zbigniew
Published: November 2021

Cladribine is currently registered as a 10-milligram tablet formulation with a fixed cumulative dosage of 3.5 mg/kg over 2 years. It is important to investigate if an increased dosage may lead to further clinical stability with preserved safety. This study used an off-label subcutaneous (s.c.) formulation of cladribine and compared outcomes (Expanded Disability Status Scale (EDSS) scores and disease progression) between 52 relapsing multiple sclerosis (RMS) patients receiving different s.c. dosing regimens with up to 20 years of follow-up. The study group received induction therapy with s.c. cladribine (1.8 mg/kg cumulative dose; consistent with 3.5 mg/kg of cladribine tablets). Patients were subsequently offered maintenance therapy (repeated courses of 0.3 mg/kg s.c. cladribine during 5–20-year follow-up). Forty-one patients received an increased cumulative dose (higher than the induction dose of 1.8 mg/kg); 11 received the standard induction dose. Risk of progression on the EDSS correlated with lower cumulative dose (p < 0.05) and more advanced disability at treatment initiation (p < 0.05) as assessed by EDSS change between year 1 and years 5 and 10 as the last follow-up. Maintenance treatment was safe and well-tolerated, based on limited source data. Subcutaneous cladribine with increased cumulative maintenance dosage was associated with disease stability and favorable safety over a prolonged period of follow-up (up to 20 years) in RMS patients.
Adenine Nucleotide Metabolites in Uremic Erythrocytes as Metabolic Markers of Chronic Kidney Disease in Children
Authors: Piechowicz Joanna , Gamian Andrzej , Zwolińska Danuta , Polak-Jonkisz Dorota
Published: November 2021

Chronic kidney disease (CKD) is associated with multifaceted pathophysiological lesions including metabolic pathways in red blood cells (RBC). The aim of the study was to determine the concentration of adenine nucleotide metabolites, i.e., nicotinamide adenine dinucleotide (NAD)-oxidized form, nicotinamide adenine dinucleotide hydrate (NADH)-reduced form, nicotinic acid mononucleotide (NAMN), β-nicotinamide mononucleotide (NMN), nicotinic acid adenine dinucleotide (NAAD), nicotinic acid (NA) and nicotinamide (NAM) in RBC and to determine a relationship between NAD metabolites and CKD progression. Forty-eight CKD children and 33 age-matched controls were examined. Patients were divided into groups depending on the CKD stages (Group II-stage II, Group III- stage III, Group IV- stage IV and Group RRT children on dialysis). To determine the above-mentioned metabolites concentrations in RBC liquid chromatography-mass spectrometry was used. Results: the only difference between the groups was shown concerning NAD in RBC, although the values did not differ significantly from controls. The lowest NAD values were found in Group II (188.6 ± 124.49 nmol/mL, the highest in group IV (324.94 ± 63.06 nmol/mL. Between Groups II and IV, as well as III and IV, the differences were statistically significant (p < 0.032, p < 0.046 respectively). Conclusions. CKD children do not have evident abnormalities of RBC metabolism with respect to adenine nucleotide metabolites. The significant differences in erythrocyte NAD concentrations between CKD stages may suggest the activation of adaptive defense mechanisms aimed at erythrocyte metabolic stabilization. It seems that the implementation of RRT has a positive impact on RBC NAD metabolism, but further research performed on a larger population is needed to confirm it.
Preliminary Finite Element Analysis and Flight Simulations of a Modular Drone Built through Fused Filament Fabrication
Authors: Brischetto Salvatore , Torre Roberto
Published: November 2021

This paper discusses the architecture and preliminary design of an Unmanned Aerial Vehicle (UAV), whose actual operative scenario and required performances drive its flying configuration. The UAV is a multirotor and can be adapted to be used as a tricopter, a quadcopter, a hexacopter, and an octocopter: the number (and consequent arrangement) of the arms modify its performance. Customization is combined with the concept of additive manufacturing, as all components are designed to be produced in Fused Filament Fabrication (FFF). This approach does not limit the application scenarios of the drone; it is instead a further push in the direction of customization, as it permits continuous upgrades over time. The paper simulates four scenarios and discusses how to optimize performances such as payload, thrust-to-weight ratio, efficiency, flight time, and maximum speed through suitable configurations. Avionic components already available on the market integrate into a customizable and adaptable frame. This analysis reveals the most severe conditions for the structure, and conducts a structural validation of its performance. Validating the functional use of FFF-produced parts is challenging due to the anisotropic behavior of the parts. However, some structural elements are thin-walled and enjoy being printed with a 100% linear infill. A simplified approach to those elements has already been proposed and validated through a parallel with UniDirectional Composites, whose 2D testing procedures and methodologies have been derived and adapted. An FEA of some elements of the frame is conducted, using shell elements to discretize the geometry. A proper definition of their mechanical response is possible because the constitutive model is not isotropic a priori but reflects the behavior of the finished parts. The tensile strength variability in the material reference system is high: a component-by-component comparison proves the design to be adequate and measured to the surrounding conditions; however, it highlights the absence of a defined failure criterion.
Illuminating the Imperceptible, Researching Mina’i Ceramics with Digital Imaging Techniques
Authors: Norris Dana , Watson Oliver
Published: November 2021

Mina’i ceramics dating to the late 12th and early 13th century made in the Kashan region of Iran represent a novel period of overglaze enamelling technology in ceramic history. New colours were used to produce stylistically attractive and dynamic polychrome motifs. Due to their archaeological context, and popularity in the art market since the mid-20th century, these objects often have complex conditions involving reconstruction and overpainting. The aesthetic and technological significance of these pieces warrants further study, but in practice, removing restorations can lead to structural destabilisation, requiring time-consuming and potentially unplanned for conservation treatment. To determine if it is possible to gain useful information from the study of these artworks without disturbing existing restorations, a group of objects were drawn from the Sarikhani and Ashmolean Museum of Art and Archaeology collections. The objective of this project was twofold, first to assess the merits of the imaging techniques for understanding condition, and second to propose a protocol for imaging with the aim of encouraging collaborative projects with international partners. The techniques used in this study include digital photography under visible and ultraviolet light, infrared reflectography, and radiography. The results show that important information invisible to the naked eye can be obtained about the decorative surfaces, using ultraviolet light and infrared reflectography. Digital radiography proved to be equally effective when studying the condition of the ceramic body. The results of this project were used to produce guidance on these techniques as a collaborative documentation package for the study of Mina’i ceramics.
Effect of Electric Current on SPS Densification of Spherical Copper Powder
Authors: Collet Romaric , Le Gallet Sophie , Charlot Frédéric , Lay Sabine , Chaix Jean-Marc , Bernard Frédéric
Published: November 2021

When a current is involved, as in spark plasma sintering, metallic powders are heated by the Joule effect through both tool and specimen. Other mechanisms might occur, but it is difficult to separate the role of the temperature from the role of the current inside the sample as, in most cases, the two parameters are not controlled independently. In this paper, the consolidation and the densification of a pure copper powder were studied in three configurations for obtaining different electric current paths: (i) current flowing through both the powder and the die, (ii) current forced into the powder and (iii) no current allowed in the powder. Electrical conductivity measurements showed that even low-density samples displayed higher conductivities than graphite by several orders of magnitude. FEM simulations confirmed that these copper specimens were mainly heated by the graphite punches. No modification of the microstructure by the flow of current could be observed. However, the absence of current in the specimen led to a decrease in densification. No significant temperature difference was modeled between the configurations, suggesting that differences are not linked to a thermal cause but rather to a current effect.
Verification of Forecast Performance of a Rapid Refresh Wave Model Based on Wind–Wave Interaction Effect
Authors: Roh Min , La Nary , Oh Sang-Myeong , Kang Kiryong , Oh Youjung , Kim Hyung-Suk
Published: November 2021

In this study, we constructed a rapid refresh wave forecast model using sea winds from the Korea Local Analysis and Prediction System as input forcing data. The model evaluated the changes in forecast performance considering the influence of input wind–wave interaction, which is an important factor that determines forecast performance. The forecast performance was evaluated by comparing the forecast results of the wave model with the significant wave height, wave period, and wave direction provided by moored buoy observations. During the typhoon season, the model tended to underestimate the conditions, and the root mean square error (RMSE) was reduced by increasing the wind and wave interaction parameter. The best value of the interaction parameter that minimizes the RMSE was determined based on the results of the numerical experiments performed during the typhoon season. The forecast error in the typhoon season was higher than that observed in the analysis results of the non-typhoon season. This can be attributed to the variations of the wave energy caused by the relatively strong typhoon wind field considered in the wave model.
A Hybrid Model for Vessel Traffic Flow Prediction Based on Wavelet and Prophet
Authors: Wang Dangli , Meng Yangran , Chen Shuzhe , Xie Cheng , Liu Zhao
Published: November 2021

Accurate vessel traffic flow prediction is significant for maritime traffic guidance and control. According to the characteristics of vessel traffic flow data, a new hybrid model, named DWT–Prophet, is proposed based on the discrete wavelet decomposition and Prophet framework for the prediction of vessel traffic flow. First, vessel traffic flow was decomposed into a low-frequency component and several high-frequency components by wavelet decomposition. Second, Prophet was trained to predict the components, respectively. Finally, the prediction results of the components were reconstructed to complete the prediction. The experimental results demonstrate that the hybrid DWT–Prophet outperformed the single Prophet, long short-term memory, random forest, and support vector regression (SVR). Moreover, the practicability of the new forecasting method was improved effectively.
Three-Dimensional Modelling of Non-Linear Wave-Induced Seabed Response around Offshore Open-Ended Pile
Authors: Liu Junwei , Chen Shuiyue , Li Xin , Liang Zuodong
Published: November 2021

This paper analyses the fluid–seabed–structure interactions (FSSI) around the open-ended pile by applying the in-house solver established on the open-source Computational Fluid Dynamics (CFD) platform. The Reynolds-averaged Navier–Stokes (RANS) equations are solved to simulate the hydrodynamic interactions between waves and open-ended piles. Biot’s poro-elastic theory (quasi-static model) is used to reproduce the wave-induced seabed responses. The parameter analysis indicates that the wave period, degree of saturation of seabed and pile diameter have a great influence on the development of the transient seabed liquefaction depth around the pile. In addition, the distribution of the pore water pressure vs soil depth in the inner zone of the pile presents a “V” shape rotated 90 degrees counterclockwise.
Synchronization Control of Dynamic Positioning Ships Using Model Predictive Control
Authors: Liu Cheng , Sun Ting , Hu Qizhi
Published: November 2021

Underway replenishment is essential for ships performing long-term missions at sea, which can be formulated into the problem of leader-tracking configuration. Not only the position and orientation but also the velocities are required to be controlled for ensuring the synchronization; additionally, the control inputs are constrained. On this basis, in this paper, a novel synchronization controller on account of model predictive control (MPC) for dynamic positioning (DP) ships is devised to achieve underway replenishment. Firstly, a novel synchronization controller based on MPC is devised to ensure the synchronization of not only the position and orientation but the velocities; furthermore, it is a beneficial solution for its advantages in handling the control input constraints ignored in most studies of underway replenishment. Secondly, a neurodynamic optimization system is applied to the implementation of MPC, which can improve the computational efficiency and shorten the simulation time. Thirdly, stability, frequently neglected by traditional MPC, is ensured by the means of adding a terminal cost function exported from the Lyapunov equation into the objective function. Finally, the effectiveness and advantages of the proposed control design are illustrated by extensive simulations.
Insights on Lulworthiales Inhabiting the Mediterranean Sea and Description of Three Novel Species of the Genus Paralulworthia
Authors: Poli Anna , Prigione Valeria , Bovio Elena , Perugini Iolanda , Varese Giovanna Cristina
Published: November 2021

The order Lulworthiales, with its sole family Lulworthiaceae, consists of strictly marine genera found on a wide range of substrates such as seagrasses, seaweeds, and seafoam. Twenty-one unidentified Lulworthiales were isolated in previous surveys aimed at broadening our understanding of the biodiversity hosted in the Mediterranean Sea. Here, these organisms, mostly found in association with Posidonia oceanica and with submerged woods, were examined using thorough multi-locus phylogenetic analyses and morphological observations. Maximum-likelihood and Bayesian phylogeny based on nrITS, nrSSU, nrLSU, and four protein-coding genes led to the introduction of three novel species of the genus Paralulworthia: P. candida, P. elbensis, and P. mediterranea. Once again, the marine environment is a confirmed huge reservoir of novel fungal lineages with an under-investigated biotechnological potential waiting to be explored.
A Novel Deoxynivalenol-Activated Wheat Arl6ip4 Gene Encodes an Antifungal Peptide with Deoxynivalenol Affinity and Protects Plants against Fusarium Pathogens and Mycotoxins
Authors: Liu Gang , Zuo Dong-Yun , Yang Peng , He Wei-Jie , Yang Zheng , Zhang Jing-Bo , Wu Ai-Bo , Yi Shu-Yuan , Li He-Ping , Huang Tao , Liao Yu-Cai
Published: November 2021

Deoxynivalenol (DON) is one of the most widespread trichothecene mycotoxins in contaminated cereal products. DON plays a vital role in the pathogenesis of Fusarium graminearum, but the molecular mechanisms of DON underlying Fusarium–wheat interactions are not yet well understood. In this study, a novel wheat ADP-ribosylation factor-like protein 6-interacting protein 4 gene, TaArl6ip4, was identified from DON-treated wheat suspension cells by suppression subtractive hybridization (SSH). The qRT-PCR result suggested that TaArl6ip4 expression is specifically activated by DON in both the Fusarium intermediate susceptible wheat cultivar Zhengmai9023 and the Fusarium resistant cultivar Sumai3. The transient expression results of the TaARL6IP4::GFP fusion protein indicate that TaArl6ip4 encodes a plasma membrane and nucleus-localized protein. Multiple sequence alignment using microscale thermophoresis showed that TaARL6IP4 comprises a conserved DON binding motif, 67HXXXG71, and exhibits DON affinity with a dissociation constant (KD) of 91 ± 2.6 µM. Moreover, TaARL6IP4 exhibited antifungal activity with IC50 values of 22 ± 1.5 µM and 25 ± 2.6 µM against Fusarium graminearum and Alternaria alternata, respectively. Furthermore, TaArl6ip4 interacted with the plasma membrane of Fusarium graminearum spores, resulting in membrane disruption and the leakage of cytoplasmic materials. The heterologous over-expression of TaArl6ip4 conferred greater DON tolerance and Fusarium resistance in Arabidopsis. Finally, we describe a novel DON-induced wheat gene, TaArl6ip4, exhibiting antifungal function and DON affinity that may play a key role in Fusarium–wheat interactions.
Spatio-Temporal Profiling of Metarhizium anisopliae—Responsive microRNAs Involved in Modulation of Plutella xylostella Immunity and Development
Authors: Zafar Junaid , Zhang Yuxin , Huang Junlin , Freed Shoaib , Shoukat Rana Fartab , Xu Xiaoxia , Jin Fengliang
Published: November 2021

Metarhizium anisopliae, a ubiquitous pathogenic fungus, regulates a wide array of the insect pest population. The fungus has been employed to control Plutella xylostella, an insecticide-resistant destructive lepidopteran pest, which causes substantial economic losses in crops worldwide. Integration of modern gene-silencing technologies in pest control strategies has become more crucial to counter pesticide-resistant insects. MicroRNAs (miRNA) play essential roles in the various biological process via post-transcriptional gene regulation. In the present study, RNA-seq analysis of control (CK36h, CK72h) and fungal-infected (T36h, T72h) midguts was performed to reveal underlying molecular mechanisms occurring in larval midgut at different time courses. We aimed at exploring M. anisopliae-responsive miRNAs and their target genes involved in development and immunity. After data filtration, a combined set of 170 miRNAs were identified from all libraries. Interestingly, miR-281, miR-263, miR-1, miR-6094 and miR-8 were listed among the most abundantly expressed conserved miRNAs. Furthermore, we experimentally studied the role of differentially expressed miR-11912-5p in regulating corresponding target trypsin-like serine proteinase (Px_TLSP). The luciferase assay (in vitro) revealed that miRNA-11912-5p significantly downregulated its target gene, suggesting it might play a crucial role in defense mechanism of P. xylostella against M.+ anisopliae infection. We used synthetic miRNA mimic/inhibitor (in vivo), to overexpress/silence miRNA, which showed harmful effects on larval duration, survival and adult fecundity. Additionally, fungal application in the presence of mimics revealed enhanced sensitivity of P. xylostella to infection. Our finding provides an insight into the relatively obscure molecular mechanisms involved in insect midgut during the fungal infection.
An Investigation into the Sources of Depreciations in Mongolian Tugrik Exchange Rate: A Structural VAR Approach
Authors: Ganbayar Gunbileg
Published: November 2021

This paper empirically investigates the sources of fluctuations in real and nominal Mongolian Tugrik (MNT) exchange rates by estimating the structural vector autoregressive (SVAR) model over the period January 1994–May 2021 and decomposing the exchange rate series into stochastic components induced by real and nominal shocks under the assumption of the long-run neutrality of nominal shocks on the real exchange rate level. The empirical results show that the real MNT exchange rate movements are primarily due to the real shocks, while the nominal shocks have a major role in explaining nominal exchange rate movements in the short and long run. The nominal exchange rate shows a delayed over-shooting occurring between one and three years after a nominal shock hits the economy. The long-run effect of a monthly one standard deviation nominal shock on nominal MNT exchange rate is 2.5%, which results in a permanent divergence between real and nominal MNT exchange rate and causes non-cointegrated relation between real and nominal MNT exchange rates. The historical decomposition of forecast error indicates that the nominal shock plays a significant role in explaining the depreciation in nominal MNT exchange rate over the last three decades. Our recommendation is to stop “cash handling” policy, minimize monetary shock, and coordinate fiscal and monetary policies to avoid large nominal depreciation.