bluuebunny/crossref_metadata_2025 huggingface dataset:
Standardization and Validation of Fluorescence-Based Quantitative Assay to Study Human Platelet Adhesion to Extracellular-Matrix in a 384-Well Plate
Authors: Martins Lima Augusto , Saint Auguste Damian S. , Cuenot François , Martins Cavaco Ana C. , Lachkar Tom , Khawand Cindy Marie Elodie , Fraga-Silva Rodrigo A. , Stergiopulos Nikolaos
Published: September 2020

Platelets play a crucial role in the immunological response and are involved in the pathological settings of vascular diseases, and their adhesion to the extracellular matrix is important to bring leukocytes close to the endothelial cells and to form and stabilize the thrombus. Currently there are several methods to study platelet adhesion; however, the optimal parameters to perform the assay vary among studies, which hinders their comparison and reproducibility. Here, a standardization and validation of a fluorescence-based quantitative adhesion assay to study platelet-ECM interaction in a high-throughput screening format is proposed. Our study confirms that fluorescence-based quantitative assays can be effectively used to detect platelet adhesion, in which BCECF-AM presents the highest sensitivity in comparison to other dyes.
Strategies for Using Polydopamine to Induce Biomineralization of Hydroxyapatite on Implant Materials for Bone Tissue Engineering
Authors: Kaushik Neha , Nhat Nguyen Linh , Kim June Hyun , Choi Eun Ha , Kumar Kaushik Nagendra
Published: September 2020

In the field of tissue engineering, there are several issues to consider when designing biomaterials for implants, including cellular interaction, good biocompatibility, and biochemical activity. Biomimetic mineralization has gained considerable attention as an emerging approach for the synthesis of biocompatible materials with complex shapes, categorized organization, controlled shape, and size in aqueous environments. Understanding biomineralization strategies could enhance opportunities for novel biomimetic mineralization approaches. In this regard, mussel-inspired biomaterials have recently attracted many researchers due to appealing features, such as strong adhesive properties on moist surfaces, improved cell adhesion, and immobilization of bioactive molecules via catechol chemistry. This molecular designed approach has been a key point in combining new functionalities into accessible biomaterials for biomedical applications. Polydopamine (PDA) has emerged as a promising material for biomaterial functionalization, considering its simple molecular structure, independence of target materials, cell interactions for adhesion, and robust reactivity for resulting functionalization. In this review, we highlight the strategies for using PDA to induce the biomineralization of hydroxyapatite (HA) on the surface of various implant materials with good mechanical strength and corrosion resistance. We also discuss the interactions between the PDA-HA coating, and several cell types that are intricate in many biomedical applications, involving bone defect repair, bone regeneration, cell attachment, and antibacterial activity.
Enhancing Software Comments Readability Using Flesch Reading Ease Score
Authors: Eleyan Derar , Othman Abed , Eleyan Amna
Published: September 2020

Comments are used to explain the meaning of code and ease communications between programmers themselves, quality assurance auditors, and code reviewers. A tool has been developed to help programmers write readable comments and measure their readability level. It is used to enhance software readability by providing alternatives to both keywords and comment statements from a local database and an online dictionary. It is also a word-finding query engine for developers. Readability level is measured using three different formulas: the fog index, the Flesch reading ease score, and Flesch–Kincaid grade levels. A questionnaire has been distributed to 42 programmers and 35 students to compare the readability aspect between both new comments written by the tool and the original comments written by previous programmers and developers. Programmers stated that the comments from the proposed tool had fewer complex words and took less time to read and understand. Nevertheless, this did not significantly affect the understandability of the text, as programmers normally have quite a high level of English. However, the results from students show that the tool affects the understandability of text and the time taken to read it, while text complexity results show that the tool makes new comment text that is more readable by changing the three studied variables.
Aquatic Insects Are Dramatically Underrepresented in Genomic Research
Authors: Hotaling Scott , Kelley Joanna L. , Frandsen Paul B.
Published: September 2020

Aquatic insects comprise 10% of all insect diversity, can be found on every continent except Antarctica, and are key components of freshwater ecosystems. However, aquatic insect genome biology lags dramatically behind that of terrestrial insects. If genomic effort was spread evenly, one aquatic insect genome would be sequenced for every ~9 terrestrial insect genomes. Instead, ~24 terrestrial insect genomes have been sequenced for every aquatic insect genome. This discrepancy is even more dramatic if the quality of genomic resources is considered; for instance, while no aquatic insect genome has been assembled to the chromosome level, 29 terrestrial insect genomes spanning four orders have. We argue that a lack of aquatic insect genomes is not due to any underlying difficulty (e.g., small body sizes or unusually large genomes), yet it is severely hampering aquatic insect research at both fundamental and applied scales. By expanding the availability of aquatic insect genomes, we will gain key insight into insect diversification and empower future research for a globally important taxonomic group.
Specific and Spillover Effects on Vectors Following Infection of Two RNA Viruses in Pepper Plants
Authors: Gautam Saurabh , Mugerwa Habibu , Sundaraj Sivamani , Gadhave Kiran R. , Murphy John F. , Dutta Bhabesh , Srinivasan Rajagopalbabu
Published: September 2020

Mixed infection of plant viruses is ubiquitous in nature and can affect virus–plant–vector interactions differently than single virus infection. While several studies have examined virus–virus interactions involving mixed virus infection, relatively few have examined effects of mixed virus infection on vector preference and fitness, especially when multiple vectors are involved. This study explored how single and mixed viral infection of a non-persistently transmitted cucumber mosaic virus (CMV) and propagative and persistently-transmitted tomato spotted wilt orthotospovirus (TSWV) in pepper, Capsicum annum L., influenced the preference and fitness of their vectors, the green peach aphid, Myzus persicae (Sulzer), and the tobacco thrips, Frankliniella fusca (Hinds), respectively. In general, mixed infected plants exhibited severe symptoms compared with individually infected plants. An antagonistic interaction between the two viruses was observed when CMV titer was reduced following mixed infection with TSWV in comparison with the single infection. TSWV titer did not differ between single and mixed infection. Myzus persicae settling preference and median developmental were not significantly different between CMV and/or TSWV-infected and non-infected plants. Moreover, M. persicae fecundity did not differ between CMV-infected and non-infected pepper plants. However, M. persicae fecundity was substantially greater on TSWV-infected plants than non-infected plants. Myzus persicae fecundity on mixed-infected plants was significantly lower than on singly-infected and non-infected plants. Frankliniella fusca fecundity was higher on CMV and/or TSWV-infected pepper plants than non-infected pepper plants. Furthermore, F. fusca-induced feeding damage was higher on TSWV-infected than on CMV-infected, mixed-infected, or non-infected pepper plants. Overall, our results indicate that the effects of mixed virus infection on vectors were not different from those observed following single virus infection. Virus-induced host phenotype-modulated effects were realized on both specific and non-specific vectors, suggesting crosstalk involving all vectors and viruses in this pathosystem. The driving forces of these interactions need to be further examined. The effects of interactions between two viruses and two vectors towards epidemics of one or both viruses also need to be examined.
Ability of Euscelidius variegatus to Transmit Flavescence Dorée Phytoplasma with a Short Latency Period
Authors: Picciau Luca , Orrù Bianca , Mandrioli Mauro , Gonella Elena , Alma Alberto
Published: September 2020

Phytoplasma transmission takes place by insect vectors through an Acquisition Access Period (AAP), Latency Period (LP) and Inoculation Access Period (IAP). Generally, phytoplasmas are believed to be transmitted more efficiently by nymphs because they need a long LP to reach the salivary glands before becoming infective. The transmission can start from adults as well, but in this case a long LP may exceed the insect’s lifespan. However, previous evidence has indicated that adults can undergo a shorter LP, even though little knowledge is available regarding the phytoplasma temporal dynamics during this period. Here, we investigate the minimum time required by the phytoplasma to colonize the vector midgut and salivary glands, and finally to be inoculated into a plant. We used the leafhopper Euscelidius variegatus to investigate the life cycle of flavescence dorée phytoplasma (FDP). Phytoplasma-free E. variegatus adults were left on broad beans (BBs) infected with FDP for an AAP of 7 days. Subsequently, they were individually transferred onto a healthy BB for seven different IAPs, each one lasting 24 h from day 8 to 14. Molecular analyses and fluorescence in situ hybridization were performed for FDP detection. FDP was found in the leafhopper midgut from IAP 1 with an infection rate reaching 50%, whereas in the salivary glands it was found from IAP 2 with an infection rate reaching 30%. FDP was also detected in BBs from IAP 4, with infection rates reaching 10%. Our results represent an important step to further deepen the knowledge of phytoplasma transmission and its epidemiology.
Relationships between Hyalesthes obsoletus, Its Herbaceous Hosts and Bois Noir Epidemiology in Northern Italian Vineyards
Authors: Mori Nicola , Cargnus Elena , Martini Marta , Pavan Francesco
Published: September 2020

Hyalesthes obsoletus is the vector of “Candidatus Phytoplasma (Ca. P.) solani,” the causal agent of grapevine yellows Bois noir (BN). The relationships among the planthopper, its main herbaceous hosts as phytoplasma reservoirs (Convolvolus arvensis and Urtica dioica) and BN spreading were studied in northern Italy. In two areas the relationship between host plants and the phenology and survival of planthopper adults was investigated in potted plants and in field conditions. Moreover, H. obsoletus ecology, newly symptomatic grapevine occurrence and “Ca. P. solani” tuf-types’ presence were studied in two vineyards (2014–2019). An earlier occurrence of H. obsoletus adults on C. arvensis than U. dioica and better adult survival of the originating host were observed. When U. dioica was prevalent, the vector occurred almost exclusively along the ditch outside the vineyard. Hyalesthes obsoletus amount varied widely from year to year and nymphal mortality due to late frosts was supposed. In one vineyard, the amount of newly symptomatic grapevines was significantly correlated with vector abundance in the previous year. The “Ca. P. solani” tuf-type was influenced by vector population levels on the two hosts. Since the abundance of H. obsoletus populations on the two hosts influences BN epidemiology and dynamics and the “Ca. P. solani” tuf-type, this must be considered in BN control strategies.
Evaluation of Mental Health Factors among People with Systemic Lupus Erythematosus during the SARS-CoV-2 Pandemic
Authors: Wańkowicz Paweł , Szylińska Aleksandra , Rotter Iwona
Published: September 2020

There are considerable psychological and psychiatric consequences of the pandemic. Researchers have started to take into account the real or perceived sense of social threats that may be expressed, such as anxiety, depression, and sleep disorders. However, analyses on pandemic-related anxiety, depression, and sleep disorders mostly rarely addresses the situation of people with autoimmune diseases. Therefore, the aim of this study was to assess the mental health factors among people with systemic lupus erythematosus by quantifying the severity of anxiety, depression, and sleep disorders during the SARS-CoV-2 pandemic. In total, 723 people took part in the study. The study group consisted of 134 individuals with a systemic lupus erythematosus. The control group consisted of 589 people without systemic lupus erythematosus. The regression adjusted by age, gender, and diagnosis of other chronic diseases showed individuals with systemic lupus erythematosus were at a much higher risk of elevated symptoms of anxiety on the GAD-7 scale (OR = 3.683; p < 0.001), depression on the PHQ-9 scale (OR = 4.183; p < 0.001), and sleep disorders on the Insomnia Severity Index (ISI) scale (OR = 6.781; p < 0.001). Therefore, the mental health of patients with systemic lupus erythematosus in the times of the SARS-CoV-2 pandemic is not only an extremely important medical problem but also a social one and must require special attention.
Safety and Tolerability of Plasma Exchange and Immunoadsorption in Neuroinflammatory Diseases
Authors: Dorst Johannes , Fillies Frank , Dreyhaupt Jens , Senel Makbule , Tumani Hayrettin
Published: September 2020

Plasma exchange (PE) and immunoadsorption (IA) are frequently used for treatment of various autoimmune-mediated neurological diseases, including multiple sclerosis (MS), chronic inflammatory demyelinating polyneuropathy (CIDP), and Guillain–Barré syndrome (GBS). Although both methods are generally regarded as well-tolerated treatment options, evidence for safety and tolerability is low for most indications and largely relies on small case series. In this study, we retrospectively analysed adverse events (AEs) and laboratory changes in 284 patients with various neurological indications who received either PE (n = 65, 113 cycles) or IA (n = 219, 435 cycles) between 2013 and 2020 in our Neurology department. One standard treatment cycle for PE as well as IA consisted of five treatments on five consecutive days. During every treatment, the 2.0–2.5-fold individual plasma volume (PV) was treated in IA, while in PE, the 0.7-fold individual PV was replaced by human albumin solution. Overall, both methods showed an excellent safety profile; no deaths of life-threatening adverse events were recorded. Severe AEs (corresponding to grade 3 on the Common Terminology Criteria for Adverse Events grading scale v5.0) including three patients with sepsis, one pneumonia, and one pneumothorax were present in 5/435 IA cycles (1.1%); in the PE group, no severe AEs were recorded. Furthermore, although advantageous tolerability is generally considered the main advantage of IA over PE, we found that overall frequency of AEs (including grades 1 and 2) was higher in IA (67.1% of all cycles) compared to PE (35.4%; p < 0.001). The low incidence of AEs in PE might be caused by the lower PV exchanged during each treatment (0.7-fold) compared to previous studies which predominantly exchanged the 1.0–1.5-fold PV. In order to verify this hypothesis as well as confirming the efficacy of this lower-dosed scheme, prospective studies comparing different treatment regimens are needed.
A Real-Life Survey of Venous Thromboembolic Events Occurring in Myeloma Patients Treated in Third Line with Second-Generation Novel Agents
Authors: Calafiore Valeria , Giamporcaro Silvia , Conticello Concetta , Romano Alessandra , Parisi Marina , Giuffrida Gaetano , Tibullo Daniele , Di Raimondo Francesco , Signorelli Salvatore Santo
Published: September 2020

Compared to the general population, patients with multiple myeloma (MM) have a nine-fold increased risk of developing venous thromboembolism (VTE). Little is known about VTE prophylaxis in relapsed/refractory (RR) MM patients treated with next generation anti-myeloma drugs, such as pomalidomide (Poma) and carfilzomib (K), and monoclonal antibodies daratumumab (Dara) and elotuzumab (Elo), alone or in combination with dexamethasone at high- (D, 40 mg/week) or low-dose (d, 20 mg/week). Here, we describe the incidence of VTE in a retrospective cohort of 112 consecutive relapsed and refractory myeloma (RRMM) patients who received a third line of treatment from April 2013 to February 2020. Anti-MM regimens included combinations of pomalidomide and dexamethasone (PomaD, N = 61), carfilzomib, lenalidomide and dexamethasone (KRd, N = 31), and elotuzumab, lenalidomide and dexamethasone (EloRd, N = 10), while the remaining 10 patients received daratumumab as a single agent. According to National Comprehnsive Cancer Network (NCCN), International Myeloma Working Group (IMWG) and 2015 European Myeloma Network (EMN) guidelines, 42 patients (38%) were classified as high-risk patients. According to the IMPEDE VTE score, 32 patients (28%) were classified as low-risk, with a score ≤ 3 (most of them in the PomaD and Dara group), 70 (63%) were classified as intermediate-risk, with a score of 4–7 (most of them in PomaD and KRd group), and 10 (9%) were classified as high-risk, with a score ≥8 (most of them in the PomaD group). All patients received a prophylaxis, consisting generally of low-doses of acetylsalicylic acid. VTE was recorded in 9% of our patients, all of them with an intermediate or high-risk IMPEDE score, treated with low doses aspirin (ASA). No VTE occurred in patients treated with daratumumab. Thus, our real-life experience documents that (1) in RRMM patients treated with continuative regimens of third line, the incidence of VTE is similar to the setting of newly-diagnosed patients; (2) many patients in real-life received prophylaxis with ASA, irrespective of the risk classification; (3) the IMPEDE VTE score seems to be more appropriate to define the risk categories. Randomized clinical trials are required to better define the VTE prophylaxis strategy in the RRMM setting.
Peripheral Blood Lymphocyte Subpopulations in Patients Following Small Diameter Metal-On-Metal Total Hip Replacement at Long-Term Follow-Up
Authors: Reiner Tobias , Haubenreisser Hester , Tripel Elena , Rosshirt Nils , Sorbi Reza , Nees Timo Albert , Gotterbarm Tobias , Merle Christian , Moradi Babak , Hagmann Sébastien
Published: September 2020

(1) Background: The objective of the present study was to investigate peripheral blood lymphocyte subpopulations in patients with small diameter metal-on-metal total hip arthroplasty (MoM THA) and elevated blood metal ion concentrations at long-term follow-up. The hypothesis was that increased blood metal ion levels or the presence of adverse local tissue reactions (ALTR) would be associated with changes in the peripheral expression of lymphocyte subpopulations, which could potentially serve as early diagnostic markers for metal wear related complications. (2) Methods: Peripheral blood samples were analyzed for leucocyte subgroups (CD3+, CD4+, CD8+, CD14+, CD16+/CD56+, CD25+/CD127−, CD19+, IFN-γ+, IL-4+ and IL-17A+ cells) in 34 patients with elevated blood metal ion levels (combined cobalt and chromium levels >2 µg/L) following small head MoM THA at a mean follow-up of 15.6 years. Fifteen patients with small head MoM THA and blood metal ion levels within the normal range and 15 patients with conventional ceramic-on-polyethylene THA served as control groups. In addition, blood metal ion levels and leucocyte subpopulations were compared between patients with and without adverse local tissue reactions (ALTR), which was investigated by MRI in 27 patients of the study cohort. (3) Results: There was a significant decrease in the levels of IFN-γ+ Type-1 T helper cells (Th1) in patients with MoM THA compared to the ceramic-on-polyethylene control group (p < 0.001). No statistically significant differences in the cell counts of other lymphocyte subpopulations were found between the three groups. Cobalt ion levels were significantly higher in patients with ALTR (p < 0.001) compared to the non-ALTR group, but no differences in the levels of lymphocyte subsets were found between the two groups. (4) Conclusions: No adverse systemic effects with respect to peripheral blood leucocyte subpopulations could be detected in the present study in patients following THA with a small diameter MoM articulation at long-term follow-up. We found a significant decrease of IFN-γ+ Th1 cells in patients with MoM THA compared to the control group, but no differences in the peripheral expression of leucocyte subpopulations were seen between patients with and without ALTR. Future studies with larger patient cohorts and additional histopathological investigations could help to better understand the role of Th1 cells and other cell lines of the adaptive immune system in the development of metal wear related complications after total joint replacement.
Challenges in Antifungal Therapy in Diabetes Mellitus
Authors: Mohd Sazlly Lim Sazlyna , Sinnollareddy Mahipal , Sime Fekade Bruck
Published: September 2020

Diabetic patients have an increased propensity to Candida sp. infections due to disease-related immunosuppression and various other physiological alterations. The incidence of candidiasis has increased in number over the years and is linked to significant morbidity and mortality in critically ill and immunosuppressed patients. Treatment of infection in diabetic patients may be complicated due to the various disease-related changes to the pharmacokinetics and pharmacodynamics (PK/PD) of a drug, including antifungal agents. Application of PK/PD principles may be a sensible option to optimise antifungal dosing regimens in this group of patients. Further studies on PK/PD of antifungals in patients with diabetes mellitus are needed as current data is limited or unavailable.
Feasibility and Acceptability Findings of an Energy Balance Data Repository of Children, Adolescents, and Young Adults with Cancer
Authors: Swartz Maria C. , Teague Alaina K. , Wells Stephanie J. , Honey Theresa , Fu Min , Mahadeo Kris M. , Kabiri Laura S. , Chandra Joya , Moody Karen , Schadler Keri
Published: September 2020

Cancer patients suffer changes in energy balance (EB), the combination of energy intake (nutrition) and energy expenditure (physical activity (PA)), which may influence cancer-related morbidity, mortality, and quality of life. Significant gaps remain in our understanding of the frequency and magnitude of these EB changes. Herein, we report on the feasibility and acceptability of a longitudinal repository of EB outcomes in children, adolescents and young adults (AYA) with cancer along the cancer continuum to fill these gaps. This EB repository includes PA, nutrition, and physical function (PF) parameters. PA data were gathered through activity trackers. Nutritional data were gathered through food diaries and micronutrient labs. PF was assessed with validated objective and patient-reported measures. Feasibility was achieved with >50% enrollment of eligible patients (n = 80, Mage = 18.1 ± 7.5); 26 were children with cancer and 54 were AYAs with cancer. An 88.75% retention rate indicated acceptability. Despite COVID-19 disruptions, >50% of participants provided completed data for PA and micronutrient labs as of April 2020. Food diaries and PF data collection experienced disruptions. Methodological adaptations are in progress to minimize future disruptions. Overall, our findings demonstrate that prospective EB assessments are feasible and acceptable among children and AYAs with cancer.
Therapeutic Strategies Targeting DUX4 in FSHD
Authors: Le Gall Laura , Sidlauskaite Eva , Mariot Virginie , Dumonceaux Julie
Published: September 2020

Facioscapulohumeral muscular dystrophy (FSHD) is a common muscle dystrophy typically affecting patients within their second decade. Patients initially exhibit asymmetric facial and humeral muscle damage, followed by lower body muscle involvement. FSHD is associated with a derepression of DUX4 gene encoded by the D4Z4 macrosatellite located on the subtelomeric part of chromosome 4. DUX4 is a highly regulated transcription factor and its expression in skeletal muscle contributes to multiple cellular toxicities and pathologies ultimately leading to muscle weakness and atrophy. Since the discovery of the FSHD candidate gene DUX4, many cell and animal models have been designed for therapeutic approaches and clinical trials. Today there is no treatment available for FSHD patients and therapeutic strategies targeting DUX4 toxicity in skeletal muscle are being actively investigated. In this review, we will discuss different research areas that are currently being considered to alter DUX4 expression and toxicity in muscle tissue and the cell and animal models designed to date.
Applicability and Eligibility of the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) for Patients who Underwent Revascularization with Percutaneous Coronary Intervention
Authors: Niimi Nozomi , Sawano Mitsuaki , Ikemura Nobuhiro , Nagai Toshiyuki , Nakano Shintaro , Shoji Satoshi , Shiraishi Yasuyuki , Ueda Ikuko , Numasawa Yohei , Suzuki Masahiro , Noma Shigetaka , Fukuda Keiichi , Kohsaka Shun
Published: September 2020

In the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial, an early invasive strategy did not decrease mortality compared to a conservative strategy for stable ischemic heart disease (SIHD) patients with moderate-to-severe ischemia, and the role of revascularization would be revised. However, the applicability and potential influence of this trial in daily practice remains unclear. Our objective was to assess the eligibility and representativeness of the ISCHEMIA trial on the patients with percutaneous coronary intervention (PCI). From a multicenter registry, we extracted a consecutive 13,223 SIHD patients with PCI (baseline cohort). We applied ISCHEMIA eligibility criteria and compared the baseline characteristics between the eligible patients and the actual study participants (randomized controlled trial (RCT) patients). In 3463 patients with follow-up information (follow-up cohort), the 2 year composite of major adverse cardiac events was evaluated between the eligible patients and RCT patients, as well as eligible and non-eligible patients in the registry. In the baseline cohort, 77.3% of SIHD patients with moderate-to-severe ischemia were eligible for the ISCHEMIA. They were comparable with RCT patients for baseline characteristics and outcomes unlike the non-eligible patients. In conclusion, the trial results seem applicable for the majority of PCI patients with moderate-to-severe ischemia except for the non-eligible patients.
Phenoconversion of Cytochrome P450 Metabolism: A Systematic Review
Authors: Klomp Sylvia D. , Manson Martijn L. , Guchelaar Henk-Jan , Swen Jesse J.
Published: September 2020

Phenoconversion is the mismatch between the individual’s genotype-based prediction of drug metabolism and the true capacity to metabolize drugs due to nongenetic factors. While the concept of phenoconversion has been described in narrative reviews, no systematic review is available. A systematic review was conducted to investigate factors contributing to phenoconversion and the impact on cytochrome P450 metabolism. Twenty-seven studies met the inclusion criteria and were incorporated in this review, of which 14 demonstrate phenoconversion for a specific genotype group. Phenoconversion into a lower metabolizer phenotype was reported for concomitant use of CYP450-inhibiting drugs, increasing age, cancer, and inflammation. Phenoconversion into a higher metabolizer phenotype was reported for concomitant use of CYP450 inducers and smoking. Moreover, alcohol, pregnancy, and vitamin D exposure are factors where study data suggested phenoconversion. The studies reported genotype–phenotype discrepancies, but the impact of phenoconversion on the effectiveness and toxicity in the clinical setting remains unclear. In conclusion, phenoconversion is caused by both extrinsic factors and patient- and disease-related factors. The mechanism(s) behind and the extent to which CYP450 metabolism is affected remain unexplored. If studied more comprehensively, accounting for phenoconversion may help to improve our ability to predict the individual CYP450 metabolism and personalize drug treatment.
Maternal Cardiovascular Dysfunction is Associated with Hypoxic Cerebral and Umbilical Doppler Changes
Authors: Masini Giulia , Tay Jasmine , McEniery Carmel M , Wilkinson Ian B , Valensise Herbert , Tiralongo Grazia M , Farsetti Daniele , Gyselaers Wilfried , Vonck Sharona , Lees Christoph C.
Published: September 2020

We investigate the relationship between maternal cardiovascular (CV) function and fetal Doppler changes in healthy pregnancies and those with pre-eclampsia (PE), small for gestational age (SGA) or fetal growth restriction (FGR). This was a three-centre prospective study, where CV assessment was performed using inert gas rebreathing, continuous Doppler or impedance cardiography. Maternal cardiac output (CO) and peripheral vascular resistance (PVR) were analysed in relation to the uterine artery, umbilical artery (UA) and middle cerebral artery (MCA) pulsatility indices (PI, expressed as z-scores by gestational week) using polynomial regression analyses, and in relation to the presence of absent/reversed end diastolic (ARED) flow in the UA. We included 81 healthy controls, 47 women with PE, 65 with SGA/FGR and 40 with PE + SGA/FGR. Maternal CO was inversely related to fetal UA PI and positively related to MCA PI; the opposite was observed for PVR, which was also positively associated with increased uterine artery impedance. CO was lower (z-score 97, p = 0.02) and PVR higher (z-score 2.88, p = 0.02) with UA ARED flow. We report that maternal CV dysfunction is associated with fetal vascular changes, namely raised impedance in the fetal-placental circulation and low impedance in the fetal cerebral vessels. These findings are most evident with critical UA Doppler changes and represent a potential mechanism for therapeutic intervention.
Application of an Innovative Jet Pump System for the Sediment Management in a Port Channel: Techno-Economic Assessment based on Experimental Measurements
Authors: Pellegrini Marco , Preda Giovanni , Saccani Cesare
Published: September 2020

The realization of infrastructures in coastal environment modifies water and sediment natural current regime. In particular, sediment can be entrained and accumulated in port infrastructure like docks, haling basins, or port entrances and channels, creating problems for navigation and limiting the human activities. The result is that marine basins and approaches are frequently silted and require maintenance dredging. Dredging is a consolidated and proven technology which implies relevant drawbacks, like high environmental impact on marine flora and fauna, mobility and diffusion of contaminants, and pollutants already present on the seabed, limitations to navigation, relatively high and low predictable costs. Starting from 2001 an innovative plant for sediment management, alternative to maintenance dredging, has been developed and tested. The core of the plant is the “ejector”, an open jet pump fed by pressurized water that is able to suck and convey in a pipeline the sediment that may accumulate in a certain area. On August 2018, a pilot plant has been installed in the haling basin of Cattolica (Italy), as part of a pilot initiative included in the Interreg-Med project “Promoting the co-evolution of human activities and natural systems for the development of sustainable coastal and maritime tourism” (CO-EVOLVE). The aim of the specific experimental activity was to test and monitor the efficacy of the technology applied in a port channel and working with sediments like silt and clay instead of sand. The paper shows the results of the monitoring campaign carried out by the University of Bologna from August 2018 to July 2019.
Dynamic Stability of an Ocean Current Turbine System
Authors: Lin Shueei-Muh , Chen Yang-Yih , Hsu Hung-Chu , Li Meng-Syue
Published: September 2020

This paper presents a theoretical solution for the dynamic stability of the ocean current turbine system developed in Taiwan. This system is tethered to the sea floor and uses the Kuroshio Current to produce electricity. To maintain the performance of the turbine system in the presence of the Kuroshio Current, the stability of the surfaced turbine needs to be considered. The proposed system is composed of a turbine, a buoyance platform, a traction rope, and a mooring foundation. The two-dimensional theoretical solutions treat the turbine as a rigid body with a movable structure that is moored with two cables. In this model, the gravity, buoyancy, and drag force generated by the wave on the turbine structure are considered. In addition, an analytical solution is proposed for the general system. Finally, the effects of the wave on the pitch motion and dynamical stability of the ocean current turbine system are investigated.
Experimental Investigation of Horizontal Wave Pressure on the Caisson Protected by Armor Blocks on the Rubble-Mounted Core
Authors: Oh Sang-Ho , Lee Jae-Sung
Published: September 2020

The horizontal wave pressure on the front wall of the caisson protected by armor blocks on the rubble-mounted core is investigated by carrying out physical experiments. There have been few previous studies regarding this type of structure, and the characteristics of horizontal wave pressure on the structure are still unclear. Considering this, a series of experiments were performed by changing the configuration of the coverage rate in front of the caisson and the shoulder width of the armor blocks. For each of the different configurations of the model setup, wave pressure on the caisson was measured under 20 regular waves of different wave periods and heights. By analyzing the obtained experimental data, it was possible to quantify the effects of the coverage rate and the shoulder width on the wave pressure. The wave pressure tended to increase up to maximally 1.5 to 2 times at the exposed part of the caisson if it was incompletely protected. In addition, the wave pressure at the top part of the caisson was substantially reduced with the increase of the shoulder width of the armor layer. Based on these results, adjustment factors for evaluating such effects have been suggested, which can be applicable for the practical design of the caisson covered with armor blocks on the rubble-mounted core.
Microglial Response to Aspergillus flavus and Candida albicans: Implications in Endophthalmitis
Authors: Gandhi Jaishree , Naik Poonam , Kaur Inderjeet , Kumar Ashok , Joseph Joveeta
Published: September 2020

Aspergillus flavus is the most common etiology of fungal endophthalmitis in India, while Candida albicans is the causative agent in the West. In this study, we determined the role of microglial cells in evoking an inflammatory response following an infection with A. flavus and C. albicans strains isolated from patients with endophthalmitis. Microglia (CHME-3) cells were infected with A. flavus and C. albicans and the expression of Toll-Like Receptors (TLRs), cytokines and Matrix metalloproteinases (MMPs) were assessed at various time intervals. A. flavus infected cells induced higher expressions of TLR-1, -2, -5, -6, -7 and -9 and cytokines such as IL-1α, IL-6, IL-8, IL-10 and IL-17. In contrast, C. albicans infected microglia induced only TLR-2 along with the downregulation of IL-10 and IL-17. The expression of MMP-9 (Matrix metalloproteinase-9) was however upregulated in both A. flavus and C. albicans infected microglia. These results indicate that microglial cells have the ability to incite an innate response towards endophthalmitis causing fungal pathogens via TLRs and inflammatory mediators. Moreover, our study highlights the differential responses of microglia towards yeast vs. filamentous fungi.
Stochastic Volatility and GARCH: Do Squared End-of-Day Returns Provide Similar Information?
Authors: Allen David Edmund
Published: September 2020

The paper examines the relative performance of Stochastic Volatility (SV) and GARCH(1,1) models fitted to twenty plus years of daily data for three indices. As a benchmark, I use the realized volatility (RV) for the S&P 500, DOW JONES and STOXX50 indices, sampled at 5-minute intervals, taken from the Oxford Man Realised Library. Both models demonstrate comparable performance and are correlated to a similar extent with the RV estimates, when measured by OLS. However, a crude variant of Corsi’s (2009) Heterogenous Auto-Regressive (HAR) model, applied to squared demeaned daily returns on the indices, appears to predict the daily RV of the series, better than either of the two base models. The base SV model was then enhanced by adding a regression matrix including the first and second moments of the demeaned return series. Similarly, the GARCH(1,1) model was augmented by adding a vector of demeaned squared returns to the mean equation. The augmented SV model showed a marginal improvement in explanatory power. This leads to the question of whether we need either of the two standard volatility models, if the simple expedient of using lagged squared demeaned daily returns provides a better RV predictor, at least in the context of the indices in the sample. The paper thus explores whether simple rules of thumb match the volatility forecasting capabilities of more sophisticated models.
Aging Promotes Mitochondria-Mediated Apoptosis in Rat Hearts
Authors: No Mi-Hyun , Choi Youngju , Cho Jinkyung , Heo Jun-Won , Cho Eun-Jeong , Park Dong-Ho , Kang Ju-Hee , Kim Chang-Ju , Seo Dae Yun , Han Jin , Kwak Hyo-Bum
Published: September 2020

Aging represents a major risk for developing cardiac disease, including heart failure. The gradual deterioration of cell quality control with aging leads to cell death, a phenomenon associated with mitochondrial dysfunction in the heart. Apoptosis is an important quality control process and a necessary phenomenon for maintaining homeostasis and normal function of the heart. However, the mechanism of mitochondria-mediated apoptosis in aged hearts remains poorly understood. Here, we used male Fischer 344 rats of various ages, representing very young (1 month), young (4 months), middle-aged (12 months), and old (20 months) rats, to determine whether mitochondria-mediated apoptotic signals and apoptosis in the left ventricle of the heart are altered notably with aging. As the rats aged, the extramyocyte space and myocyte cross-sectional area in their left ventricle muscle increased, while the number of myocytes decreased. Additionally, mitochondrion-mediated apoptotic signals and apoptosis increased remarkably during aging. Therefore, our results demonstrate that aging promotes remarkable morphological changes and increases the degree of mitochondrion-mediated apoptosis in the left ventricle of rat hearts.
Potential for Applying Continuous Directed Evolution to Plant Enzymes: An Exploratory Study
Authors: García-García Jorge D. , Joshi Jaya , Patterson Jenelle A. , Trujillo-Rodriguez Lidimarie , Reisch Christopher R. , Javanpour Alex A. , Liu Chang C. , Hanson Andrew D.
Published: September 2020

Plant evolution has produced enzymes that may not be optimal for maximizing yield and quality in today’s agricultural environments and plant biotechnology applications. By improving enzyme performance, it should be possible to alleviate constraints on yield and quality currently imposed by kinetic properties or enzyme instability. Enzymes can be optimized more quickly than naturally possible by applying directed evolution, which entails mutating a target gene in vitro and screening or selecting the mutated gene products for the desired characteristics. Continuous directed evolution is a more efficient and scalable version that accomplishes the mutagenesis and selection steps simultaneously in vivo via error-prone replication of the target gene and coupling of the host cell’s growth rate to the target gene’s function. However, published continuous systems require custom plasmid assembly, and convenient multipurpose platforms are not available. We discuss two systems suitable for continuous directed evolution of enzymes, OrthoRep in Saccharomyces cerevisiae and EvolvR in Escherichia coli, and our pilot efforts to adapt each system for high-throughput plant enzyme engineering. To test our modified systems, we used the thiamin synthesis enzyme THI4, previously identified as a prime candidate for improvement. Our adapted OrthoRep system shows promise for efficient plant enzyme engineering.
“Primum Non Nocere” in Interventional Oncology for Liver Cancer: How to Reduce the Risk for Complications?
Authors: Iezzi Roberto , Bilhim Tiago , Crocetti Laura , Peynircioglu Bora , Goldberg Shraga , Bilbao Josè Ignacio , Sami Ahmed , Akhan Okan , Scalise Paola , Giuliante Felice , Pompili Maurizio , Valentini Vincenzo , Gasbarrini Antonio , Colosimo Cesare , Manfredi Riccardo
Published: September 2020

Interventional oncology represents a relatively new clinical discipline based upon minimally invasive therapies applicable to almost every human organ and disease. Over the last several decades, rapidly evolving research developments have introduced a newer generation of treatment devices, reagents, and image-guidance systems to expand the armamentarium of interventional oncology across a wide spectrum of disease sites, offering potential cure, control, or palliative care for many types of cancer patients. Due to the widespread use of locoregional procedures, a comprehensive review of the methodologic and technical considerations to optimize patient selection with the aim of performing a safe procedure is mandatory. This article summarizes the expert discussion and report from the Mediterranean Interventional Oncology Live Congress (MIOLive 2020) held in Rome, Italy, integrating evidence-reported literature and experience-based perceptions as a means for providing guidance on prudent ways to reduce complications. The aim of the paper is to provide an updated guiding tool not only to residents and fellows but also to colleagues approaching locoregional treatments.
Machine Learning Approach to Raman Spectrum Analysis of MIA PaCa-2 Pancreatic Cancer Tumor Repopulating Cells for Classification and Feature Analysis
Authors: Mandrell Christopher T. , Holland Torrey E. , Wheeler James F. , Esmaeili Sakineh M. A. , Amar Kshitij , Chowdhury Farhan , Sivakumar Poopalasingam
Published: September 2020

A machine learning approach is applied to Raman spectra of cells from the MIA PaCa-2 human pancreatic cancer cell line to distinguish between tumor repopulating cells (TRCs) and parental control cells, and to aid in the identification of molecular signatures. Fifty-one Raman spectra from the two types of cells are analyzed to determine the best combination of data type, dimension size, and classification technique to differentiate the cell types. An accuracy of 0.98 is obtained from support vector machine (SVM) and k-nearest neighbor (kNN) classifiers with various dimension reduction and feature selection tools. We also identify some possible biomolecules that cause the spectral peaks that led to the best results.
Manufacturing Aluminum/Multiwalled Carbon Nanotube Composites via Laser Powder Bed Fusion
Authors: Lee Eo Ryeong , Shin Se Eun , Takata Naoki , Kobashi Makoto , Kato Masaki
Published: September 2020

This study provides a novel approach to fabricating Al/C composites using laser powder bed fusion (LPBF) for a wide range of structural applications utilizing Al-matrix composites in additive manufacturing. We investigated the effects of LPBF on the fabrication of aluminum/multiwalled carbon nanotube (Al/MWCNT) composites under 25 different conditions, using varying laser power levels and scan speeds. The microstructures and mechanical properties of the specimens, such as elastic modulus and nanohardness, were analyzed, and trends were identified. We observed favorable sintering behavior under laser conditions with low energy density, which verified the suitability of Al/MWCNT composites for a fabrication process using LPBF. The size and number of pores increased in specimens produced under high energy density conditions, suggesting that they are more influenced by laser power than scan speed. Similarly, the elastic modulus of a specimen was also more affected by laser power than scan speed. In contrast, scan speed had a greater influence on the final nanohardness. Depending on the laser power used, we observed a difference in the crystallographic orientation of the specimens by a laser power during LPBF. When energy density is high, texture development of all samples tended to be more pronounced.
Evolution of SLA-Based Al2O3 Microstructure During Additive Manufacturing Process
Authors: Chugunov Svyatoslav , Adams Nikolaus A. , Akhatov Iskander
Published: September 2020

Evolution of additively manufactured (AM) ceramics’ microstructure between manufacturing stages is a hardly explored topic. These data are of high demand for advanced numerical modeling. In this work, 3D microstructural models of Al2O3 greenbody, brownbody and sintered material are presented and analyzed, for ceramic samples manufactured with SLA-based AM workflow, using a commercially available ceramic paste and 3D printer. The novel data, acquired at the micro- and mesoscale, using Computed Tomography (CT), Scanning Electron Microscopy (SEM) and Focused Ion-Beam SEM (FIB/SEM) techniques, allowed a deep insight into additive ceramics characteristics. We demonstrated the spatial 3D distribution of ceramic particles, an organic binder and pores at every stage of AM workflow. The porosity of greenbody samples (1.6%), brownbody samples (37.3%) and sintered material (4.9%) are analyzed. Pore distribution and possible originating mechanisms are discussed. The location and shape of pores and ceramic particles are indicative of specific physical processes driving the ceramics manufacturing. We will use the presented microstructural 3D models as input and verification data for advanced numerical simulations developed in the project.