bluuebunny/crossref_metadata_2025 huggingface dataset:
Black Soldier Fly Larvae Adapt to Different Food Substrates through Morphological and Functional Responses of the Midgut
Authors: Bonelli Marco , Bruno Daniele , Brilli Matteo , Gianfranceschi Novella , Tian Ling , Tettamanti Gianluca , Caccia Silvia , Casartelli Morena
Published: July 2020

Modulation of nutrient digestion and absorption is one of the post-ingestion mechanisms that guarantees the best exploitation of food resources, even when they are nutritionally poor or unbalanced, and plays a pivotal role in generalist feeders, which experience an extreme variability in diet composition. Among insects, the larvae of black soldier fly (BSF), Hermetia illucens, can grow on a wide range of feeding substrates with different nutrient content, suggesting that they can set in motion post-ingestion processes to match their nutritional requirements. In the present study we address this issue by investigating how the BSF larval midgut adapts to diets with different nutrient content. Two rearing substrates were compared: a nutritionally balanced diet for dipteran larvae and a nutritionally poor diet that mimics fruit and vegetable waste. Our data show that larval growth performance is only moderately affected by the nutritionally poor diet, while differences in the activity of digestive enzymes, midgut cell morphology, and accumulation of long-term storage molecules can be observed, indicating that diet-dependent adaptation processes in the midgut ensure the exploitation of poor substrates. Midgut transcriptome analysis of larvae reared on the two substrates showed that genes with important functions in digestion and absorption are differentially expressed, confirming the adaptability of this organ.
Melatonin Induces Melanogenesis in Human SK-MEL-1 Melanoma Cells Involving Glycogen Synthase Kinase-3 and Reactive Oxygen Species
Authors: Perdomo Juan , Quintana Carlos , González Ignacio , Hernández Inmaculada , Rubio Sara , Loro Juan F. , Reiter Russel J. , Estévez Francisco , Quintana José
Published: July 2020

Melatonin is present in all living organisms where it displays a diversity of physiological functions. Attenuation of melanogenesis by melatonin has been reported in some mammals and also in rodent melanoma cells. However, melatonin may also stimulate melanogenesis in human melanoma cells through mechanisms that have not yet been revealed. Using the human melanoma cells SK-MEL-1 as a model, an increase in both tyrosinase activity and melanin was already observed at 24 h after melatonin treatment with maximal levels of both being detected at 72 h. This effect was associated with the induction in the expression of the enzymes involved in the synthesis of melanin. In this scenario, glycogen synthase kinase-3β seems to play a significant function since melatonin decreased its phosphorylation and preincubation with specific inhibitors of this protein kinase (lithium or BIO) reduced the expression and activity of tyrosinase. Blocking of PI3K/AKT pathway stimulated melanogenesis and the effect was suppressed by the inhibitors of glycogen synthase kinase-3β. Although melatonin is a recognized antioxidant, we found that it stimulates reactive oxygen species generation in SK-MEL-1 cells. These chemical species seem to be an important signal in activating the melanogenic process since the antioxidants N-acetyl-l-cysteine and glutathione decreased both the level and activity of tyrosinase stimulated by melatonin. Our results support the view that regulation of melanogenesis involves a cross-talk between several signaling pathways.
Immunomodulatory Effects of Hydroxychloroquine and Chloroquine in Viral Infections and Their Potential Application in Retinal Gene Therapy
Authors: Chandler Laurel , Yusuf Imran , McClements Michelle , Barnard Alun , MacLaren Robert , Xue Kanmin
Published: July 2020

Effective treatment of retinal diseases with adeno-associated virus (AAV)-mediated gene therapy is highly dependent on the proportion of successfully transduced cells. However, due to inflammatory reactions at high vector doses, adjunctive treatment may be necessary to enhance the therapeutic outcome. Hydroxychloroquine and chloroquine are anti-malarial drugs that have been successfully used in the treatment of autoimmune diseases. Evidence suggests that at high concentrations, hydroxychloroquine and chloroquine can impact viral infection and replication by increasing endosomal and lysosomal pH. This effect has led to investigations into the potential benefits of these drugs in the treatment of viral infections, including human immunodeficiency virus and severe acute respiratory syndrome coronavirus-2. However, at lower concentrations, hydroxychloroquine and chloroquine appear to exert immunomodulatory effects by inhibiting nucleic acid sensors, including toll-like receptor 9 and cyclic GMP-AMP synthase. This dose-dependent effect on their mechanism of action supports observations of increased viral infections associated with lower drug doses. In this review, we explore the immunomodulatory activity of hydroxychloroquine and chloroquine, their impact on viral infections, and their potential to improve the efficacy and safety of retinal gene therapy by reducing AAV-induced immune responses. The safety and practicalities of delivering hydroxychloroquine into the retina will also be discussed.
BIM-Based Design for Road Infrastructure: A Critical Focus on Modeling Guardrails and Retaining Walls
Authors: Biancardo Salvatore Antonio , Viscione Nunzio , Cerbone Antonio , Dessì Enzo
Published: July 2020

Although building information modeling (BIM) has been widely adopted in the building industry for several decades, the use of BIM in the context of transportation infrastructure has been slow in terms of both adoption and application. Industry and academia are increasingly making efforts to adopt BIM for other non-building civil infrastructure but, so far, there has not been a comprehensive review of these efforts specifically regarding transportation. This paper explores BIM implementation in an infrastructure design project. An Autodesk ® BIM-based tool, Civil 3D, is proposed as a potential BIM tool platform. This paper also focuses on modeling specific road elements not editable from the standard library, such as guardrails and retaining walls, as well as proposing different solutions using Revit and Subassembly Composer and analyzing the interoperability among BIM-based tools.
Body Size Differences between Foraging and Intranidal Workers of the Monomorphic Ant Lasius niger
Authors: Okrutniak Mateusz , Rom Bartosz , Turza Filip , Grześ Irena M.
Published: July 2020

The association between the division of labour and worker body size of ants is typical for species that maintain physical castes. Some studies showed that this phenomenon can be also observed in the absence of distinct morphological subcastes among workers. However, the general and consistent patterns in the size-based division of labour in monomorphic ants are largely unidentified. In this study, we performed a field experiment to investigate the link between worker body size and the division of labour of the ant Lasius niger (Linnaeus, 1758), which displays limited worker size variation. We demonstrated that the body size of workers exploring tuna baits is slightly but significantly smaller than the size of workers located in the upper parts of the nest. Comparing the present results with existing studies, large workers do not seem to be dedicated to work outside the nest. We suggest that monomorphic workers of certain body sizes are flexible in the choice of task they perform, and food type may be the important determinant of this choice.
Efficacy of a Novel Metaldehyde Application Method to Control the Brown Garden Snail, Cornu aspersum (Helicidae), in South Africa
Authors: Pieterse Annika , Malan Antoinette Paula , Ross Jenna Louise
Published: July 2020

Baitchain is a novel molluscicide system that consists of metaldehyde pellets arranged on a cord and is designed to be tied around the base of tree trunks and act as a physical and chemical control method for molluscs. In this study, Baitchain is tested in a South African apple orchard and compared with traditional metaldehyde pellets (Sluggit) applied to the soil surface to determine the efficacy of the products against the brown garden snail, Cornu aspersum (Helicidae). The products were applied at two different concentrations, including 15 g/kg (Baitchain 15 and Sluggit 15) and 40 g/kg (Baitchain 40 and Sluggit 40) metaldehyde, and the products were either applied on their own, or in combination. Both treatments at 40 g/kg metaldehyde caused significant snail mortality when applied either on their own or in combination. However, significant mortality was also achieved by Baitchain 15 when applied on its own as well as in combination with Sluggit 15. The increased efficacy achieved by using Baitchain, even at the lower concentration, indicates that this novel method offers a viable physical and chemical control option for molluscs and could be incorporated as part of an integrated pest management strategy in South Africa, as well as other parts of the world.
Oral Ingestion of Bacterially Expressed dsRNA Can Silence Genes and Cause Mortality in a Highly Invasive, Tree-Killing Pest, the Emerald Ash Borer
Authors: Leelesh Ramya Shanivarsanthe , Rieske Lynne K.
Published: July 2020

RNA interference (RNAi) is a naturally occurring process inhibiting gene expression, and recent advances in our understanding of the mechanism have allowed its development as a tool against insect pests. A major challenge for deployment in the field is the development of convenient and efficient methods for production of double stranded RNA (dsRNA). We assessed the potential for deploying bacterially produced dsRNA as a bio-pesticide against an invasive forest pest, the emerald ash borer (EAB). EAB feeds on the cambial tissue of ash trees (Fraxinus spp.), causing rapid death. EAB has killed millions of trees in North America since its discovery in 2002, prompting the need for innovative management strategies. In our study, bacterial expression and synthesis of dsRNA were performed with E. coli strain HT115 using the L4440 expression vector. EAB-specific dsRNAs (shi and hsp) over-expressed in E. coli were toxic to neonate EAB after oral administration, successfully triggering gene silencing and subsequent mortality; however, a non-specific dsRNA control was not included. Our results suggest that ingestion of transformed E. coli expressing dsRNAs can induce an RNAi response in EAB. To our knowledge, this is the first example of an effective RNAi response induced by feeding dsRNA-expressing bacteria in a forest pest.
Evaluation of a Non-Chemical Compared to a Non-Chemical Plus Silica Gel Approach to Bed Bug Management
Authors: Abbar Salehe , Wang Changlu , Cooper Richard
Published: July 2020

Bed bug resistance to commonly used pesticide sprays has led to exploring new pesticides and other strategies for bed bug management. Non-chemical methods are effective in bed bug management; however, they do not provide residual protection. Compared to insecticide sprays, dust formulations are considered to provide longer residual control. We evaluated two bed bug management programs in apartment buildings. A building-wide inspection was initially conducted to identify bed bug infested apartments. Selected apartments were divided into two treatment groups: non-chemical plus silica gel dust treatment (10 apartments) and non-chemical treatment (11 apartments). After initial treatment, apartments were re-visited monthly for up to 6 months. During each visit, the total bed bug count per apartment was obtained by examining interceptor traps placed in the apartments and conducting a visual inspection. Mean bed bug count was reduced by 99% and 89% in non-chemical plus silica gel dust and non-chemical treatment, respectively. Non-chemical plus silica gel dust treatment caused significantly higher bed bug count reduction than the non-chemical treatment at 6 months. Bed bugs were eradicated from 40% and 36% of apartments treated with non-chemical plus silica gel dust treatment and non-chemical treatment, respectively.
Hybrid Polyetheretherketone (PEEK)–Acrylic Resin Prostheses and the All-on-4 Concept: A Full-Arch Implant-Supported Fixed Solution with 3 Years of Follow-Up
Authors: de Araújo Nobre Miguel , Moura Guedes Carlos , Almeida Ricardo , Silva António , Sereno Nuno
Published: July 2020

Background: The aim of this three-year prospective study was to examine the outcome of a solution for full-arch rehabilitation through a fixed implant-supported hybrid prosthesis (polyetheretherketone (PEEK)-acrylic resin) used in conjunction with the All-on-4 concept. Methods: Thirty-seven patients (29 females, 8 males), with an age range of 38 to 78 years (average: 59.8 years) were rehabilitated with 49 full-arch implant-supported prostheses (12 maxillary rehabilitations, 13 mandibular rehabilitations and 12 bimaxillary rehabilitations). The primary outcome measure was prosthetic survival. Secondary outcome measures were marginal bone loss, plaque and bleeding scores, veneer adhesion issues, biological complications, mechanical complications, and the patients’ subjective evaluation. Results: There were two patients (maxillary rehabilitations) lost to follow-up, while one patient withdrew (maxillary rehabilitation). One patient with bimaxillary rehabilitation fractured the mandibular PEEK framework, rendering a 98% prosthetic survival rate. Implant survival was 100%. Average (standard deviation) marginal bone loss at 3-years was 0.40 mm (0.73 mm). Veneer adhesion was the only technical complication (n = 8 patients), resolved for all patients. Nine patients (n = 11 prostheses) experienced mechanical complications (all resolved): fracture of acrylic resin crowns (n = 3 patients), prosthetic and abutment screw loosening (n = 4 patients and 3 patients, respectively), abutment wearing (n = 1 patient). One patient experienced a biological complication (peri-implant pathology), resolved through non-surgical therapy. A 90% satisfaction rate was registered for the patients’ subjective evaluation. Conclusions: Based on the results, the three-year outcome suggests the proposed rehabilitation solution as a legitimate treatment option, providing a potential shock-absorbing alternative that could benefit the implant biological outcome.
Utility of Insulin Resistance in Estimating Cardiovascular Risk in Subjects with Type 1 Diabetes According to the Scores of the Steno Type 1 Risk Engine
Authors: Cano Albert , Llauradó Gemma , Albert Lara , Mazarico Isabel , Astiarraga Brenno , González-Sastre Montserrat , Martínez Laia , Fernández-Veledo Sonia , Simó Rafael , Vendrell Joan , González-Clemente José-Miguel
Published: July 2020

Background: We sought to assess the potential of insulin resistance (IR) for estimating cardiovascular disease (CVD) risk in adults with type 1 diabetes (T1DM) according to the scores of the Steno Type 1 Risk Engine (ST1RE). Methods: A total of 179 adults with T1DM (50.8% men, age 41.2 ± 13.1 years, duration of T1DM 16 (12–23) years) without established CVD were evaluated. IR was assessed by the estimation of insulin sensitivity (eIS) using two validated prediction equations: the estimated insulin sensitivity developed from the Pittsburgh Epidemiology of Diabetes Complications Study (eIS-EDC) and the estimated insulin sensitivity developed from Coronary Artery Calcification in T1DM Study (eIS-CACTI) ST1RE was used to estimate 10-year CVD risk and to classify subjects into three groups according to their risk: low (<10%; n = 105), moderate (10–20%; n = 53), and high (≥20%; n = 21). Results: Both eIS-EDC and eIS-CACTI correlated negatively with ST1RE scores (eIS-EDC: r = −0.636, p < 0.001; eIS-CACTI: r = −0.291, p < 0.001). The C-statistic for predicting moderate/high risk and high risk was 0.816 (95% confidence interval (CI): 0.754–0.878) and 0.843 (95% CI: 0.772–0.913), respectively, for the eIS-EDC equation, and was 0.686 (95% CI: 0.609–0.763) and 0.646 (95% CI: 0.513–0.778), respectively, for the eIS-CACTI equation. The eIS-EDC equation had a significantly higher C-statistic both for moderate-/high-risk (p = 0.001) and high-risk (p = 0.007) subjects. Two cut-off points of eIS-EDC were identified for detecting moderate/high risk (8.52 mg·kg−1·min−1; sensitivity 74% and specificity 76%) and high risk (8.08 mg·kg−1·min−1; sensitivity 65% and specificity 95%) with potential applicability in clinical practice. Conclusions: eIS negatively correlates with the score of CVD risk in the ST1RE. Two cut-off points of eIS are reported with potential utility in clinical practice for detecting adults with T1DM with the highest CVD risk.
Effects of Elastic Resistance Exercise on Postoperative Outcomes Linked to the ICF Core Sets for Osteoarthritis after Total Knee Replacement in Overweight and Obese Older Women with Sarcopenia Risk: A Randomized Controlled Trial
Authors: Liao Chun-De , Chiu Yen-Shuo , Ku Jan-Wen , Huang Shih-Wei , Liou Tsan-Hon
Published: July 2020

(1) Background: Knee osteoarthritis (KOA) and aging are associated with high sarcopenia risk; sarcopenia may further affect outcomes after total knee replacement (TKR). Elastic resistance exercise training (RET) limits muscle attenuation in older adults. We aimed to identify the effects of post-TKR elastic RET on lean mass (LM) and functional outcomes in overweight and obese older women with KOA by using the brief International Classification of Functioning, Disability and Health Core Set for osteoarthritis (Brief-ICF-OA). (2) Methods: Eligible women aged ≥60 years who had received unilateral primary TKR were randomly divided into an experimental group (EG), which received postoperative RET twice weekly for 12 weeks, and a control group (CG), which received standard care. The primary and secondary outcome measures were LM and physical capacity, respectively, and were linked to the Brief-ICF-OA. The assessment time points were 2 weeks prior to surgery (T0) and postoperative at 1 month (T1; before RET) and 4 months (T2; upon completion of RET) of follow-up. An independent t test with an intention-to-treat analysis was conducted to determine the between-group differences in changes of outcome measures at T1 and T2 from T0. (3) Results: Forty patients (age: 70.9 ± 7.3 years) were randomly assigned to the EG (n = 20) or CG (n = 20). At T2, the EG exhibited significantly greater improvements in leg LM (mean difference (MD) = 0.86 kg, p = 0.004) and gait speed (MD = 0.26 m/s, p = 0.005) compared with the CG. Furthermore, the EG generally obtained significantly higher odds ratios than the CG for treatment success for most Brief-ICF-OA categories (all p < 0.001). Conclusions: Early intervention of elastic RET after TKR yielded positive postoperative outcomes based on the Brief-ICF-OA. The findings of this study may facilitate clinical decision-making regarding the optimal post-TKR rehabilitation strategy for older women with KOA.
Environmental, Health and Sociodemographic Determinants Related to Common Mental Disorders in Adults: A Spanish Country-Wide Population-Based Study (2006–2017)
Authors: Cebrino Jesús , Portero de la Cruz Silvia
Published: July 2020

Common mental disorders (CMD) represent a serious, growing public health concern, especially in women. The aims of this study were to report the prevalence of CMD among the adult population in Spain, to analyze the time trends from 2006 to 2017 and to explore the associations between CMD and gender, in relation to the perceived environmental and sociodemographic problems and clinical factors. A nationwide cross-sectional study was conducted including 48,505 participants aged 16 to 64 years old who had participated in the Spanish National Health Surveys in 2006, 2011/2012 and 2017. A logistic regression analysis was performed to identify the variables associated with CMD by gender. The prevalence of CMD was 20.4% in 2006, 20.8% in 2011/2012 and 16.9% in 2017 (p = 0.36). In women, the probability of having a CMD was higher in widowed or separated/divorced compared with single individuals and as the perception of distressing noise levels from outside the home increased. The probability of CMD was lower as the level of education increased in men. Foreigners and those with limitations due to health problems, chronic conditions and worse perceived health were more likely to suffer from a CMD in both women and men.
Direct Oral Anticoagulants and Timing of Hip Fracture Surgery
Authors: Tarrant Seth M. , Catanach Michael J. , Sarrami Mahsa , Clapham Matthew , Attia John , Balogh Zsolt J.
Published: July 2020

Timely surgical intervention in hip fracture has been linked to improved outcomes. Direct Oral Anticoagulants (DOACs) are an emerging class of anticoagulants without evidence-based guidelines on surgical timing. This study aims to investigate how DOACs affect surgical timing and hence perioperative outcomes. A retrospective database/registry review was conducted for geriatric hip fracture patients aged 65 and over between 2011 and 2018. Primary outcome was 30-day mortality. Secondary outcomes included serious adverse events (SAE), transfusion and postoperative day (POD) 1 haemoglobin (Hb) levels. From a cohort of 3264 patients, 112 admitted subjects were taking DOACs; the annual proportion on DOACs increased over time. Mean time to surgery from last dose (Ts) was 2.2 (±1.0 SD) days. The primary outcome, 30-day mortality, occurred in 16 (14%) patients with secondary outcomes of SAEs in 25 (22%) patients and transfusion in 30 (27%) patients. Ts (days) did not significantly affect 30-day mortality (odds ratio (OR): 1.37, 95% confidence interval (CI): 0.80–2.33; p = 0.248), SAE (hazard ratio (HR): 1.03, 95% CI: 0.70–1.52; p = 0.885), transfusion (OR: 0.72 95% CI: 0.45 to 1.16; p = 0.177) or POD 1 Hb (OR: 1.99, 95% CI: −0.59 to 4.57; p = 0.129). Timing of surgery does not influence common surgical outcomes such as 30-day mortality, SAE, transfusion, and POD1 Hb in patients taking DOACs on admission.
Special Issue on Clinical Medicine for Healthcare and Sustainability
Authors: Meen Teen-Hang , Matsumoto Yusuke , Lee Kuan-Han
Published: July 2020

Recently, due to the advancement of network technology, big data and artificial intelligence, the healthcare industry has undergone many sector-wide changes. Medical care has not only changed from passive and hospital-centric to preventative and personalized, but also from disease-centric to health-centric. Healthcare systems and basic medical research are becoming more intelligent and being implemented in biomedical engineering. This Special Issue on “Clinical Medicine for Healthcare and Sustainability” selected 30 excellent papers from 160 papers presented in IEEE ECBIOS 2019 on the topic of clinical medicine for healthcare and sustainability. Our purpose is to encourage scientists to propose their experiments and theoretical researches to facilitate the scientific prediction and influential assessment of global change and development.
Early Arterial Intimal Thickening and Plaque Is Related with Treatment Regime and Cardiovascular Disease Risk Factors in Young Adults Following Childhood Hematopoietic Stem Cell Transplantation
Authors: Sundholm Johnny K. M. , Suominen Anu , Sarkola Taisto , Jahnukainen Kirsi
Published: July 2020

The long-term vascular effects following childhood hematopoietic stem cell transplantation (HSCT) are not well characterized. We compared arterial wall morphology and function using very-high resolution ultrasound (25–55 MHz) in 62 patients following autologous (n = 19) or allogenic (n = 43) HSCT for childhood malignancies and hematological disease (median age 25.9 years, IQR 21.1–30.1; median follow-up time 17.5 years IQR 14.1–23.0) with an age matched healthy control group (n = 44). Intima-media thickness of carotid (CIMT 0.49 ± 0.11 vs. 0.42 ± 0.06 mm, p < 0.001), brachial, femoral, radial arteries, and local carotid stiffness, but not adventitial thickness, were increased (p < 0.001). Diffuse intimal thickening (>0.06 mm) of femoral or radial arteries (n = 17) and subclinical carotid or femoral plaques (n = 18) were more common (p < 0.001). Radiation predicted plaques (p < 0.001) and local carotid stiffness (p < 0.001), but not intimal thickening. CIMT was predicted by age, BMI >30 kg/m2, hsCRP >2.5 mg/L, hypertension, HbA1c > 42 mmol/L, and cumulative anthracycline >150 mg/m2. Cumulative metabolic syndrome criteria and cardiovascular disease (CVD) risk factors were more common among HSCT and related with CIMT (p < 0.001), but CIMT was similar among controls and HSCT without CVD risk factors. Long-term childhood HSCT survivors show early arterial aging related with radiation, metabolic, and CVD risk factors. Prevention of risk factors could potentially decelerate early arterial wall thickening.
[99mTc]Sestamibi SPECT Can Predict Proliferation Index, Angiogenesis, and Vascular Invasion in Parathyroid Patients: A Retrospective Study
Authors: Urbano Nicoletta , Scimeca Manuel , Di Russo Carmela , Mauriello Alessandro , Bonanno Elena , Schillaci Orazio
Published: July 2020

The aim of this study was to evaluate the possible association among sestamibi uptake and the main histopathological characteristics of parathyroid lesions related to aggressiveness such as the proliferation index (Ki67 expression and mitosis), angiogenesis (number of vessels), and vascular invasion in hyperparathyroidism patients. To this end, 26 patients affected by primary hyperparathyroidism subjected to both scintigraphy with [99mTc]Sestamibi and surgery/bioptic procedure were retrospectively enrolled. Hyperfunctioning of the parathyroid was detected in 19 patients. Our data showed a significant positive association among the sestamibi uptake and the proliferation index histologically evaluated both in terms of the number of Ki67 positive cells and mitosis. According to these data, lesions with a higher valuer of L/N (lesion to nonlesion ratio) frequently showed several vessels in tumor areas and histological evidence of vascular invasion. It is noteworthy that among patients with negative scintigraphy, 2 patients showed a neoplastic lesion after surgery (histological analysis). However, it is important to highlight that these lesions displayed very low proliferation indexes, which was evaluated in terms of number of both mitosis and Ki67-positive cells, some/rare vessels in the main lesion, and no evidence of vascular invasion. In conclusion, data obtained on patients with positive or negative scintigraphy support the hypothesis that sestamibi can be a tracer that is capable of predicting some biological characteristics of parathyroid tumors such as angiogenesis, proliferation indexes, and the invasion of surrounding tissues or vessels.
Plasma Metabolomic Profiling Associates Bicuspid Aortic Valve Disease and Ascending Aortic Dilation with a Decrease in Antioxidant Capacity
Authors: Martínez-Micaelo Neus , Ligero Carme , Antequera-González Borja , Junza Alexandra , Yanes Oscar , Alegret Josep
Published: July 2020

Background: The bicuspid aortic valve (BAV) is the most common cardiac congenital disease and is associated with an increased risk of developing ascending aorta dilation; which can have fatal consequences. Currently; no established risk biomarkers exist to facilitate the diagnosis and prognosis of BAV. Methods: Using an untargeted metabolomic approach; we identified the levels of metabolites in plasma samples and compared them depending on the bicuspid or tricuspid morphology of the aortic valve. Including those patients with ascending aortic dilation and/or aortic stenosis (n = 212), we analyzed the role possibly played by alpha-Tocopherol in BAV disease; considering its association with the pathophysiological characteristics of BAV and biomarkers related to inflammation, oxidative stress and endothelial damage, as well as characteristics related to alpha-Tocopherol functionality and metabolism. Results: We found that BAV patients; especially those with ascending aortic dilation; presented lower antioxidant capacity; as determined by decreased plasma levels of alpha-Tocopherol; paraoxonase 1 and high-density lipoprotein (HDL), as well as increased levels of C-reactive protein (CRP; a biomarker of inflammation) and endothelial microparticles (EMPs; an endothelial damage biomarker). By applying random forest analyses; we evaluated the significant screening capacity of alpha-Tocopherol; CRP and EMPs to classify patients depending on the morphology of the aortic valve. Discussion: Our findings support the role of decreased antioxidant capacity; increased inflammation and endothelial damage in the pathogenesis of BAV and the progression of aortic dilation. Moreover; determining the plasma levels of alpha-Tocopherol; CRP and EMPs could improve BAV diagnosis in large populations.
Rapid Whole-Exome Sequencing as a Diagnostic Tool in a Neonatal/Pediatric Intensive Care Unit
Authors: Śmigiel Robert , Biela Mateusz , Szmyd Krzysztof , Błoch Michal , Szmida Elżbieta , Skiba Paweł , Walczak Anna , Gasperowicz Piotr , Kosińska Joanna , Rydzanicz Małgorzata , Stawiński Piotr , Biernacka Anna , Zielińska Marzena , Gołębiowski Waldemar , Jalowska Agnieszka , Ohia Grażyna , Głowska Bożena , Walas Wojciech , Królak-Olejnik Barbara , Krajewski Paweł , Sykut-Cegielska Jolanta , Sąsiadek Maria M. , Płoski Rafał
Published: July 2020

Genetic disorders are the leading cause of infant morbidity and mortality. Due to the large number of genetic diseases, molecular and phenotype heterogeneity and often severe course, these diseases remain undiagnosed. In infants with a suspected acute monogenic disease, rapid whole-exome sequencing (R-WES) can be successfully performed. R-WES (singletons) was performed in 18 unrelated infants with a severe and/or progressing disease with the suspicion of genetic origin hospitalized in an Intensive Care Unit (ICU). Blood samples were also collected from the parents. The results from the R-WES were available after 5–14 days. A conclusive genetic diagnosis was obtained in 13 children, corresponding to an overall diagnostic yield of 72.2%. For nine patients, R-WES was used as a first-tier test. Eight patients were diagnosed with inborn errors of metabolism, mainly mitochondrial diseases. In two patients, the disease was possibly caused by variants in genes which so far have not been associated with human disease (NARS1 and DCAF5). R-WES proved to be an effective diagnostic tool for critically ill infants in ICUs suspected of having a genetic disorder. It also should be considered as a first-tier test after precise clinical description. The quickly obtained diagnosis impacts patient’s medical management, and families can receive genetic counseling.
Assessment of Mortality and Factors Affecting Outcome of Use of Paclitaxel-Coated Stents and Bare Metal Stents in Femoropopliteal PAD
Authors: Falkowski Aleksander , Bogacki Hubert , Szemitko Marcin
Published: July 2020

The use of drug-coated devices in intravascular therapy is aimed at preventing neointimal hyperplasia caused by excessive proliferation of vascular smooth muscle and thereby restenosis. Although its use seemed initially promising, a recent publication has shown an increased risk of mortality with paclitaxel-coated devices, and there is an urgent need to reaffirm assessments of drug-eluting stents (DES). Objective: The aim of the study was to compare mortality and effectiveness of paclitaxel-coated stents and bare-metal stents (BMS) in the treatment of peripheral arterial disease (PAD) with long-term follow-up. Materials and methods: In a single center randomized study, 256 patients with PAD were treated intravascularly with stent implantation. Patients were randomized into two groups: the first (n = 126) were treated with DES, and the second (n = 130) were treated with BMS. The study included evaluation after the procedure, after about 6 months and 36 months. Co-morbidities, with risks for atherosclerosis, were analyzed in all patients. Patients were evaluated for clinical outcome, restenosis frequency, and safety (complications and total mortality). Results: Clinical benefit at the end of the investigation was statistically significantly better in the DES group compared with the BMS group: 85.7% versus 66.2% (p = 0.0003), respectively. Restenosis occurred significantly less frequently in patients with DES: 16.0% versus BMS: 35.0%, p = 0.012. There was no significant effect of comorbidities on the frequency of restenoses. There were no differences in all-cause mortality over the three years with paclitaxel and no-paclitaxel stents cohorts (8.7% versus 7.1%; long-rank p = 0.575). No association was found with mortality and treatment with DES or BMS. Conclusions: The use of paclitaxel-coated stents gave good clinical benefit and caused a significantly lower frequency of restenosis compared to bare-metal stents. The use of paclitaxel-coated stents did not increase mortality.
Deciphering the Molecular Landscape of Cutaneous Squamous Cell Carcinoma for Better Diagnosis and Treatment
Authors: Lazar Andreea D. , Dinescu Sorina , Costache Marieta
Published: July 2020

Cutaneous squamous cell carcinoma (cSCC) is a common type of neoplasia, representing a terrible burden on patients’ life and clinical management. Although it seldom metastasizes, and most cases can be effectively treated with surgical intervention, once metastatic cSCC displays considerable aggressiveness leading to the death of affected individuals. No consensus has been reached as to which features better characterize the aggressive behavior of cSCC, an achievement hindered by the high mutational burden caused by chronic ultraviolet light exposure. Even though some subtypes have been recognized as high risk variants, depending on certain tumor features, cSCC that are normally thought of as low risk could pose an increased danger to the patients. In light of this, specific genetic and epigenetic markers for cutaneous SCC, which could serve as reliable diagnostic markers and possible targets for novel treatment development, have been searched for. This review aims to give an overview of the mutational landscape of cSCC, pointing out established biomarkers, as well as novel candidates, and future possible molecular therapies for cSCC.
Comparison of a Significant Decline in the Glomerular Filtration Rate between Ileal Conduit and Ileal Neobladder Urinary Diversions after Radical Cystectomy: A Propensity Score-Matched Analysis
Authors: Yu Jihion , Hong Bumsik , Park Jun-Young , Lee Yongsoo , Hwang Jai-Hyun , Kong Yu-Gyeong , Kim Young-Kug
Published: July 2020

Urinary diversion after radical cystectomy is associated with a risk of renal function impairment. A significant decline in the glomerular filtration rate (GFR) (i.e., a ≥30% decline in baseline GFR after 12 months) is associated with long-term renal function impairment. We compared the significant GFR decline between ileal conduit and ileal neobladder urinary diversions 12 months after radical cystectomy. We retrospectively included radical cystectomy patients. Propensity score-matched analysis was performed. The primary outcome was the incidence of a significant GFR decline in ileal conduit urinary diversion (ileal conduit group) and ileal neobladder urinary diversion (ileal neobladder group) 12 months after radical cystectomy. The secondary outcomes were the change of GFR and the incidence of end-stage renal disease (ESRD) in the two groups. After propensity score matching, the ileal conduit and neobladder groups had 117 patients each. The incidence of a significant GFR decline was not significantly different between ileal conduit and ileal neobladder groups (12.0% vs. 13.7%, p = 0.845). The change of GFR and ESRD incidence were not significantly different between the two groups (−8.4% vs. −9.7%, p = 0.480; 4.3% vs. 5.1%, p > 0.999, respectively). These results can provide important information on appropriate selection of the urinary diversion type in radical cystectomy.
Cerebellar Morphology and Behavioral Profiles in Mice Lacking Heparan Sulfate Ndst Gene Function
Authors: Lewejohann Lars , Pallerla Srinivas R. , Schreiber Rebecca S. , Gerula Joanna , Grobe Kay
Published: July 2020

Disruption of the Heparan sulfate (HS)-biosynthetic gene N-acetylglucosamine N-Deacetylase/N-sulfotransferase 1 (Ndst1) during nervous system development causes malformations that are composites of those caused by mutations of multiple HS binding growth factors and morphogens. However, the role of Ndst function in adult brain physiology is less explored. Therefore, we generated mice bearing a Purkinje-cell-specific deletion in Ndst1 gene function by using Cre/loxP technology under the control of the Purkinje cell protein 2 (Pcp2/L7) promotor, which results in HS undersulfation. We observed that mutant mice did not show overt changes in the density or organization of Purkinje cells in the adult cerebellum, and behavioral tests also demonstrated normal cerebellar function. This suggested that postnatal Purkinje cell development and homeostasis are independent of Ndst1 function, or that impaired HS sulfation upon deletion of Ndst1 function may be compensated for by other Purkinje cell-expressed Ndst isoforms. To test the latter possibility, we additionally deleted the second Purkinje-cell expressed Ndst family member, Ndst2. This selectively abolished reproductive capacity of compound mutant female, but not male, mice, suggesting that ovulation, gestation, or female reproductive behavior specifically depends on Ndst-dependent HS sulfation in cells types that express Cre under Pcp2/L7 promotor control.
Search for the Optimal Build Direction in Additive Manufacturing Technologies: A Review
Authors: Di Angelo Luca , Di Stefano Paolo , Guardiani Emanuele
Published: July 2020

By additive manufacturing technologies, an object is produced deposing material layer by layer. The piece grows along the build direction, which is one of the main manufacturing parameters of Additive Manufacturing (AM) technologies to be set-up. This process parameter affects the cost, quality, and other important properties of the manufactured object. In this paper, the Objective Functions (OFs), presented in the literature for the search of the optimal build direction, are considered and reviewed. The following OFs are discussed: part quality, surface quality, support structure, build time, manufacturing cost, and mechanical properties. All of them are distinguished factors that are affected by build direction. In the first part of the paper, a collection of the most significant published methods for the estimation of the factors that most influence the build direction is presented. In the second part, a summary of the optimization techniques adopted from the reviewed papers is presented. Finally, the advantages and disadvantages are briefly discussed and some possible new fields of exploration are proposed.
Buckling Analysis of an AUV Pressure Vessel with Sliding Stiffeners
Authors: Siqueira Nóbrega de Freitas Artur , Alfonso Alvarez Alexander , Ramos Roberto , de Barros Ettore Apolonio
Published: July 2020

The structure of an autonomous underwater vehicle (AUV), usually composed of a cylindrical shell, may be exposed to high hydrostatic pressures where buckling collapse occurs before yield stress failure. In conventional submarines, welded stiffeners increase the buckling resistance, however, in small AUVs, they reduce the inner space and cause residual stresses. This work presents an innovative concept for the structural design of an AUV, proposing the use of sliding stiffeners that are part of the structure used to accommodate the electronics inside it. Since the sliding stiffeners are not welded to the shell, there are no residual stresses due to welding, the AUV fabrication process is simplified, enabling a reduction of the manufacturing cost, and the inner space is available to accommodate the equipment needed for the AUV mission. Moreover, they provide a higher buckling resistance when compared to that of an unstiffened cylindrical shell. A comparative analysis of the critical buckling loads for different shell designs was carried out considering the following: (i) the unstiffened shell, (ii) the shell with ring stiffeners, and (iii) the shell with sliding stiffeners. Results evidenced that major advantages were obtained by using the latter alternative against buckling.
Causes of and Preventive Measures for Complacency as Viewed by Officers in Charge of the Engineering Watch
Authors: Bielić Toni , Čulin Jelena , Poljak Igor , Orović Josip
Published: July 2020

Complacency has been recognised as a cause of maritime accidents, and there is a need to develop and execute relevant preventive measures. The effectiveness of preventive actions depends on the contribution of the seafarers. Therefore, the purpose of this study was to identify causes and elicit proposals for preventing complacency by officers in charge of the engineering watch. A total of 63 Croatian engineering officers participated in four deliberative workshops, facilitated by an expert in the teaching of leadership and management. As causes of complacency, intensive workload, poor knowledge/understanding of the equipment, steep authority gradient, lack of collaboration, poor communication, efficiency-thoroughness trade-off, crewing strategies, and lack of organisational justice were identified. Efficient training on workload management, adequate familiarisation, reporting issues with technology, producing one’s own manuals, more effective leadership courses, more emphasis on non-technical skills as criteria for a promotion, joint workshops on teamwork for land-based managers and seafarers, open and objective performance evaluation, and direct communication between land-based managers and seafarers were proposed as feasible preventive measures. Human-centred design and standardisation of the equipment were evaluated as unlikely to be feasible. Some practical implications from the findings were discussed.
Modeling Approaches Reveal New Regulatory Networks in Aspergillus fumigatus Metabolism
Authors: Acerbi Enzo , Hortova-Kohoutkova Marcela , Choera Tsokyi , Keller Nancy , Fric Jan , Stella Fabio , Romani Luigina , Zelante Teresa
Published: July 2020

Systems biology approaches are extensively used to model and reverse-engineer gene regulatory networks from experimental data. Indoleamine 2,3-dioxygenases (IDOs)—belonging in the heme dioxygenase family—degrade l-tryptophan to kynurenines. These enzymes are also responsible for the de novo synthesis of nicotinamide adenine dinucleotide (NAD+). As such, they are expressed by a variety of species, including fungi. Interestingly, Aspergillus may degrade l-tryptophan not only via IDO but also via alternative pathways. Deciphering the molecular interactions regulating tryptophan metabolism is particularly critical for novel drug target discovery designed to control pathogen determinants in invasive infections. Using continuous time Bayesian networks over a time-course gene expression dataset, we inferred the global regulatory network controlling l-tryptophan metabolism. The method unravels a possible novel approach to target fungal virulence factors during infection. Furthermore, this study represents the first application of continuous-time Bayesian networks as a gene network reconstruction method in Aspergillus metabolism. The experiment showed that the applied computational approach may improve the understanding of metabolic networks over traditional pathways.
A Relational Approach to Landscape Stewardship: Towards a New Perspective for Multi-Actor Collaboration
Authors: Cockburn Jessica , Rosenberg Eureta , Copteros Athina , Cornelius Susanna Francina (Ancia) , Libala Notiswa , Metcalfe Liz , van der Waal Benjamin
Published: July 2020

Landscape stewardship is increasingly understood within the framing of complex social-ecological systems. To consider the implications of this, we focus on one of the key characteristics of complex social-ecological systems: they are relationally constituted, meaning that system characteristics emerge out of dynamic relations between system components. We focus on multi-actor collaboration as a key form of relationality in landscapes, seeking a more textured understanding of the social relations between landscape actors. We draw on a set of ‘gardening tools’ to analyse the boundary-crossing work of multi-actor collaboration. These tools comprise three key concepts: relational expertise, common knowledge, and relational agency. We apply the tools to two cases of landscape stewardship in South Africa: the Langkloof Region and the Tsitsa River catchment. These landscapes are characterised by economically, socio-culturally, and politically diverse groups of actors. Our analysis reveals that history and context strongly influence relational processes, that boundary-crossing work is indeed difficult, and that doing boundary-crossing work in smaller pockets within a landscape is helpful. The tools also helped to identify three key social-relational practices which lend a new perspective on boundary-crossing work: 1. belonging while differing, 2. growing together by interacting regularly and building common knowledge, and 3. learning and adapting together with humility and empathy.
On the Design and Lubrication of Water-Lubricated, Rubber, Cutlass Bearings Operating in the Soft EHL Regime
Authors: Smith Edward H.
Published: July 2020

All propeller-driven ships employ a drive shaft supported by journal bearings. To avoid water pollution, these bearings are generally lubricated by the surrounding water, removing the need for a rear seal. Such bearings, commonly referred to as Cutlass bearings, usually have an inner grooved nitrile rubber lining. The grooves (called flutes) allow debris to be flushed out and the bearing surface to be cooled. The remaining area is divided into a number of load-carrying areas called staves. At present, no rigorous design guide exists for these bearings. This paper presents a methodology to predict the minimum film thickness between the journal and the most heavily-loaded stave, an approach not hitherto reported in the literature. The method includes a new, 3D, finite element (FE) approach for soft elasto-hydrodynamic (EHL) predictive modelling of generated pressures in cutlass bearings. Model predictions compare favourably with experimental data. It is shown that the modulus of elasticity of the rubber has no influence on the minimum film thickness. An equation relating dimensionless film thickness to dimensionless load, clearance ratio and numbers of staves is presented. For a nominally circular bearing, increasing the clearance ratio or increasing the numbers of staves reduces load-carrying capacity. It is shown that distortion due to loading can increase load-carrying capacity.
Sodium N-(3,5-Bis(ethoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine-4-carbonyl)-l-methioninate
Authors: Bisenieks Egils , Poikans Janis , Plotniece Aiva , Bernotiene Eiva , Tsai Wei-Bor , Sobolev Arkadij
Published: July 2020

The development of the methods for amide bond formation is important for various uses in the laboratory and industrial applications. The compounds combined in their structures 1,4-dihydroisonicotinic acids and amino acids linked with an amide bond can be considered as “privileged structures” due to their broad range of biological activities. Herein, the formation of amide bond between 1,4-dihydroisonicotinic acid and l-methionine is reported. The coupling of l-methionine with pentafluorophenyl active ester of 1,4-dihydroisonicotinic acid appears to be a convenient and effective method for amide bond formation. Sodium N-(3,5-bis(ethoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine-4-carbonyl)-l-methioninate has been successfully synthesized via a procedure where the key step is amide formation from 5-diethyl 4-(perfluorophenyl) 2,6-dimethyl-1,4-dihydropyridine-3,4,5-tricarboxylate and l-methionine. Sodium salt formation was performed to improve physicochemical properties, such as solubility of the l-methionine-derived 1,4-dihydroisonicotinamide. The obtained target compound was fully characterized by UV, IR, 1H NMR, 13C NMR, MS, and microanalysis.