bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Fusarium verticillioides Fumonisins on Fatty Acids, Sphingolipids, and Oxylipins in Maize Germlings
Authors: Beccaccioli Marzia , Salustri Manuel , Scala Valeria , Ludovici Matteo , Cacciotti Andrea , D’Angeli Simone , Brown Daren W. , Reverberi Massimo
Published: March 2021

Fusarium verticillioides causes multiple diseases of Zea mays (maize) including ear and seedling rots, contaminates seeds and seed products worldwide with toxic chemicals called fumonisins. The role of fumonisins in disease is unclear because, although they are not required for ear rot, they are required for seedling diseases. Disease symptoms may be due to the ability of fumonisins to inhibit ceramide synthase activity, the expected cause of lipids (fatty acids, oxylipins, and sphingolipids) alteration in infected plants. In this study, we explored the impact of fumonisins on fatty acid, oxylipin, and sphingolipid levels in planta and how these changes affect F. verticillioides growth in maize. The identity and levels of principal fatty acids, oxylipins, and over 50 sphingolipids were evaluated by chromatography followed by mass spectrometry in maize infected with an F. verticillioides fumonisin-producing wild-type strain and a fumonisin-deficient mutant, after different periods of growth. Plant hormones associated with defense responses, i.e., salicylic and jasmonic acid, were also evaluated. We suggest that fumonisins produced by F. verticillioides alter maize lipid metabolism, which help switch fungal growth from a relatively harmless endophyte to a destructive necrotroph.
Genetic Profiling of Malignant Melanoma Arising from an Ovarian Mature Cystic Teratoma: A Case Report
Authors: Nakamura Kohei , Aimono Eriko , Takamatsu Reika , Tanishima Shigeki , Tohyama Tomonari , Sasano Katsutoshi , Sakuma Hiroshi , Nishihara Hiroshi
Published: March 2021

Ovarian mature cystic teratomas comprise tissues derived from all three germ layers. In rare cases, malignant tumors arise from ovarian mature cystic teratoma. A variety of tumors can arise from mature cystic teratoma, among which primary malignant melanoma (MM), for which no molecular analyses such as genomic sequencing have been reported to date, is exceedingly rare, thereby limiting possible therapeutic options using precision medicine. We used targeted gene sequencing to analyze the status of 160 cancer-related genes in a patient with MM arising from an ovarian mature cystic teratoma (MM-MCT). KRAS amplification and homozygous deletion in PTEN and RB1 were detected in tumor samples collected from the patient. No KRAS amplification has been previously reported in cutaneous MM, indicating that the carcinogenesis of MM-MCT differs from that of primary cutaneous melanomas. A better understanding of the underlying genetic mechanisms will help clarify the carcinogenesis of MM-MCT. In turn, this will enable treatment with novel targeting agents as well as the initial exploration of gene-based precision oncological therapies, which aim to improve treatment outcomes for patients with this disease.
IL-33 Is Involved in the Anti-Inflammatory Effects of Butyrate and Propionate on TNFα-Activated Endothelial Cells
Authors: Li Meng , van Esch Betty C. A. M. , Henricks Paul A. J. , Garssen Johan , Folkerts Gert
Published: March 2021

Short-chain fatty acids (e.g., butyrate and propionate) are able to diminish endothelial cell activation. The aim of this study was to investigate whether intracellular IL-33 mediates the effects of butyrate and propionate on TNFα-induced IL-8 production and vascular cell adhesion molecule-1 (VCAM-1) expression. In addition, it was investigated whether regulating NF-κB and MAPK signaling pathways are involved. Intracellular IL-33 was measured in human endothelial cells (HUVECs) pre-incubated for 24 h with butyrate (0.1 mM or 5 mM), propionate (0.3 mM or 10 mM), or trichostatin A (TSA, 0.5 μM) prior to TNFα (1 ng/mL) stimulation (24 h). The effects of butyrate, propionate, and TSA on TNFα-induced IL-8, vascular cell adhesion molecule-1 (VCAM-1), NF-κB, and MAPK signaling pathways in normal HUVECs and IL-33 siRNA (siIL-33)-transfected HUVECs were compared to study the role of IL-33 in the protective effects of butyrate and propionate. Endogenous IL-33 was highly expressed in the perinuclear in HUVECs, which was significantly reduced by TNFα stimulation. The TNFα-induced reduction in IL-33 was prevented by pre-incubation with butyrate or propionate. Butyrate (0.1 mM), propionate (0.3 mM), and TSA inhibited the IL-8 production and activation of NF-κB. Interestingly, this effect was not observed in siIL-33-transfected HUVECs. The effects of butyrate (5 mM), propionate (10 mM), and TSA (0.5 μM) on VCAM-1 expression and activation of MAPK signaling pathways were not affected by siIL-33 transfection. In conclusion, we showed that the inhibitory effects of butyrate and propionate on TNFα-induced IL-8 production were mediated by the HDACs/IL-33/NF-κB pathway, while their effects on VCAM-1 expression might be associated with the HDACs/MAPK signaling pathway, independently of IL-33.
A Systems Biology Approach to Investigating the Interaction between Serotonin Synthesis by Tryptophan Hydroxylase and the Metabolic Homeostasis
Authors: Park Suhyeon , Kim Yumin , Lee Jibeom , Lee Jeong Yun , Kim Hail , Lee Sunjae , Oh Chang-Myung
Published: March 2021

Obesity has become a global public health and economic problem. Obesity is a major risk factor for a number of complications, such as type 2 diabetes, cardiovascular disease, fatty liver disease, and cancer. Serotonin (5-hydroxytryptamine [5-HT]) is a biogenic monoamine that plays various roles in metabolic homeostasis. It is well known that central 5-HT regulates appetite and mood. Several 5-HT receptor agonists and selective serotonin receptor uptake inhibitors (SSRIs) have shown beneficial effects on appetite and mood control in clinics. Although several genetic polymorphisms related to 5-HT synthesis and its receptors are strongly associated with obesity, there is little evidence of the role of peripheral 5-HT in human metabolism. In this study, we performed a systemic analysis of transcriptome data from the Genotype-Tissue Expression (GTEX) database. We investigated the expression of 5-HT and tryptophan hydroxylase (TPH), the rate-limiting enzyme of 5-HT biosynthesis, in the human brain and peripheral tissues. We also performed differential gene expression analysis and predicted changes in metabolites by comparing gene expressions of tissues with high TPH expression to the gene expressions of tissues with low TPH expression. Our analyses provide strong evidence that serotonin plays an important role in the regulation of metabolic homeostasis in humans.
Secreted Signaling Molecules at the Neuromuscular Junction in Physiology and Pathology
Authors: Ohkawara Bisei , Ito Mikako , Ohno Kinji
Published: March 2021

Signal transduction at the neuromuscular junction (NMJ) is affected in many human diseases, including congenital myasthenic syndromes (CMS), myasthenia gravis, Lambert–Eaton myasthenic syndrome, Isaacs’ syndrome, Schwartz–Jampel syndrome, Fukuyama-type congenital muscular dystrophy, amyotrophic lateral sclerosis, and sarcopenia. The NMJ is a prototypic cholinergic synapse between the motor neuron and the skeletal muscle. Synaptogenesis of the NMJ has been extensively studied, which has also been extrapolated to further understand synapse formation in the central nervous system. Studies of genetically engineered mice have disclosed crucial roles of secreted molecules in the development and maintenance of the NMJ. In this review, we focus on the secreted signaling molecules which regulate the clustering of acetylcholine receptors (AChRs) at the NMJ. We first discuss the signaling pathway comprised of neural agrin and its receptors, low-density lipoprotein receptor-related protein 4 (Lrp4) and muscle-specific receptor tyrosine kinase (MuSK). This pathway drives the clustering of acetylcholine receptors (AChRs) to ensure efficient signal transduction at the NMJ. We also discuss three secreted molecules (Rspo2, Fgf18, and connective tissue growth factor (Ctgf)) that we recently identified in the Wnt/β-catenin and fibroblast growth factors (FGF) signaling pathways. The three secreted molecules facilitate the clustering of AChRs by enhancing the agrin-Lrp4-MuSK signaling pathway.
Comparison of the Efficacy of Two Novel Antitubercular Agents in Free and Liposome-Encapsulated Formulations
Authors: Kósa Nikoletta , Zolcsák Ádám , Voszka István , Csík Gabriella , Horváti Kata , Horváth Lilla , Bősze Szilvia , Herenyi Levente
Published: March 2021

Tuberculosis is one of the top ten causes of death worldwide, and due to the appearance of drug-resistant strains, the development of new antituberculotic agents is a pressing challenge. Employing an in silico docking method, two coumaran (2,3-dihydrobenzofuran) derivatives—TB501 and TB515—were determined, with promising in vitro antimycobacterial activity. To enhance their effectiveness and reduce their cytotoxicity, we used liposomal drug carrier systems. Two types of small unilamellar vesicles (SUV) were prepared: multicomponent pH-sensitive stealth liposome (SUVmixed) and monocomponent conventional liposome. The long-term stability of our vesicles was obtained by the examination of particle size distribution with dynamic light scattering. Encapsulation efficiency (EE) of the two drugs was determined from absorption spectra before and after size exclusion chromatography. Cellular uptake and cytotoxicity were determined on human MonoMac-6 cells by flow cytometry. The antitubercular effect was characterized by the enumeration of colony-forming units on Mycobacterium tuberculosis H37Rv infected MonoMac-6 cultures. We found that SUVmixed + TB515 has the best long-term stability. TB515 has much higher EE in both types of SUVs. Cellular uptake for native TB501 is extremely low, but if it is encapsulated in SUVmixed it appreciably increases; in the case of TB515, quasi total uptake is accessible. It is concluded that SUVmixed + TB501 seems to be the most efficacious antitubercular formulation given the presented experiments; to find the most promising antituberculotic formulation for therapy further in vivo investigations are needed.
The Novel Benzamide Derivative, VKNG-2, Restores the Efficacy of Chemotherapeutic Drugs in Colon Cancer Cell Lines by Inhibiting the ABCG2 Transporter
Authors: Narayanan Silpa , Gujarati Nehaben A. , Wang Jing-Quan , Wu Zhuo-Xun , Koya Jagadish , Cui Qingbin , Korlipara Vijaya L. , Ashby Charles R. , Chen Jr.
Published: March 2021

The overexpression of ATP-binding cassette transporter, ABCG2, plays an important role in mediating multidrug resistance (MDR) in certain types of cancer cells. ABCG2-mediated MDR can significantly attenuate or abrogate the efficacy of anticancer drugs by increasing their efflux from cancer cells. In this study, we determined the efficacy of the novel benzamide derivative, VKNG-2, to overcome MDR due to the overexpression of the ABCG2 transporter in the colon cancer cell line, S1-M1-80. In vitro, 5 μM of VKNG-2 reversed the resistance of S1-M1-80 cell line to mitoxantrone (70-fold increase in efficacy) or SN-38 (112-fold increase in efficacy). In contrast, in vitro, 5 μM of VKNG-2 did not significantly alter either the expression of ABCG2, AKT, and PI3K p110β protein or the subcellular localization of the ABCG2 protein compared to colon cancer cells incubated with the vehicle. Molecular docking data indicated that VKNG-2 had a high docking score (-10.2 kcal/mol) for the ABCG2 transporter substrate-drug binding site whereas it had a low affinity on ABCB1 and ABCC1 transporters. Finally, VKNG-2 produced a significant concentration-dependent increase in ATPase activity (EC50 = 2.3 µM). In conclusion, our study suggests that in vitro, VKNG-2 reverses the resistance of S1-M1-80, a cancer cell line resistant to mitoxantrone and SN-38, by inhibiting the efflux function of the ABCG2 transporter.
Nutraceuticals in the Prevention of Viral Infections, including COVID-19, among the Pediatric Population: A Review of the Literature
Authors: Parisi Giuseppe Fabio , Carota Giuseppe , Castruccio Castracani Carlo , Spampinato Mariarita , Manti Sara , Papale Maria , Di Rosa Michelino , Barbagallo Ignazio , Leonardi Salvatore
Published: March 2021

In recent years, there has been a growth in scientific interest in nutraceuticals, which are those nutrients in foods that have beneficial effects on health. Nutraceuticals can be extracted, used for food supplements, or added to foods. There has long been interest in the antiviral properties of nutraceuticals, which are especially topical in the context of the ongoing COVID-19 pandemic. Therefore, the purpose of this review is to evaluate the main nutraceuticals to which antiviral roles have been attributed (either by direct action on viruses or by modulating the immune system), with a focus on the pediatric population. Furthermore, the possible applications of these substances against SARS-CoV-2 will be considered.
Inhibition of Inducible Nitric Oxide Synthase Prevents IL-1β-Induced Mitochondrial Dysfunction in Human Chondrocytes
Authors: Eitner Annett , Müller Sylvia , König Christian , Wilharm Arne , Raab Rebecca , Hofmann Gunther O. , Kamradt Thomas , Schaible Hans-Georg
Published: March 2021

Interleukin (IL)-1β is an important pro-inflammatory cytokine in the progression of osteoarthritis (OA), which impairs mitochondrial function and induces the production of nitric oxide (NO) in chondrocytes. The aim was to investigate if blockade of NO production prevents IL-1β-induced mitochondrial dysfunction in chondrocytes and whether cAMP and AMP-activated protein kinase (AMPK) affects NO production and mitochondrial function. Isolated human OA chondrocytes were stimulated with IL-1β in combination with/without forskolin, L-NIL, AMPK activator or inhibitor. The release of NO, IL-6, PGE2, MMP3, and the expression of iNOS were measured by ELISA or Western blot. Parameters of mitochondrial respiration were measured using a seahorse analyzer. IL-1β significantly induced NO release and mitochondrial dysfunction. Inhibition of iNOS by L-NIL prevented IL-1β-induced NO release and mitochondrial dysfunction but not IL-1β-induced release of IL-6, PGE2, and MMP3. Enhancement of cAMP by forskolin reduced IL-1β-induced NO release and prevented IL-1β-induced mitochondrial impairment. Activation of AMPK increased IL-1β-induced NO production and the negative impact of IL-1β on mitochondrial respiration, whereas inhibition of AMPK had the opposite effects. NO is critically involved in the IL-1β-induced impairment of mitochondrial respiration in human OA chondrocytes. Increased intracellular cAMP or inhibition of AMPK prevented both IL-1β-induced NO release and mitochondrial dysfunction.
Calcium-Sensing Receptor (CaSR), Its Impact on Inflammation and the Consequences on Cardiovascular Health
Authors: Sundararaman Sai Sahana , van der Vorst Emiel P. C.
Published: March 2021

The calcium Sensing Receptor (CaSR) is a cell surface receptor belonging to the family of G-protein coupled receptors. CaSR is mainly expressed by parathyroid glands, kidneys, bone, skin, adipose tissue, the gut, the nervous system, and the cardiovascular system. The receptor, as its name implies is involved in sensing calcium fluctuations in the extracellular matrix of cells, thereby having a major impact on the mineral homeostasis in humans. Besides calcium ions, the receptor is also activated by other di- and tri-valent cations, polypeptides, polyamines, antibiotics, calcilytics and calcimimetics, which upon binding induce intracellular signaling pathways. Recent studies have demonstrated that CaSR influences a wide variety of cells and processes that are involved in inflammation, the cardiovascular system, such as vascular calcification, atherosclerosis, myocardial infarction, hypertension, and obesity. Therefore, in this review, the current understanding of the role that CaSR plays in inflammation and its consequences on the cardiovascular system will be highlighted.
Management of Onion Thrips (Thrips tabaci) in Organic Onion Production Using Multiple IPM Tactics
Authors: Iglesias Lindsy , Havey Michael J. , Nault Brian A.
Published: March 2021

Onion thrips (Thrips tabaci Lindeman) is a major pest in organic onion production and effective integrated pest management strategies are lacking. Our objective was to evaluate combinations of semi-glossy (“Rossa di Milano” and B5336AxB5351C) and waxy (“Bradley”) onion cultivars with reflective mulch, with or without biopesticides (spinosad + neem oil tank mix), to manage T. tabaci in organic onion production. Thrips densities were assessed weekly and bulbs graded and weighed at harvest. Onions sprayed with spinosad + neem oil had fewer T. tabaci (adults: 74% (2019); larvae: 40% (2018), 84% (2019) and produced higher yields (13% (2018), 23% (2019)) than onions that were unsprayed, regardless of mulch type or onion cultivar. “Rossa di Milano” had relatively fewer adult and larval thrips populations compared with “Bradley” (21% (2018), 32% (2019)) and B5336AxB5351C. However, “Rossa di Milano” had the lowest marketable yield in both years. Reflective mulch reduced densities on certain dates in both years compared to white mulch, but the largest and most consistent reduction only occurred in 2019. Reflective mulch had no impact on bulb yield. While spinosad + neem oil reduced thrips numbers and increased yield alone, none of the treatment combinations were effective at suppressing populations of thrips. Future T. tabaci management in organic onions will require optimization of the available effective biopesticides.
A New High-Throughput Focused MeV Ion-Beam Analysis Setup
Authors: Möller Sören , Höschen Daniel , Kurth Sina , Esser Gerwin , Hiller Albert , Scholtysik Christian , Dellen Christian , Linsmeier Christian
Published: March 2021

The analysis of material composition by ion-beam analysis (IBA) is becoming a standard method, similar to electron microscopy. A pool of IBA methods exists, from which the combination of particle-induced-X-ray emission (PIXE), particle induced gamma-ray analysis (PIGE), nuclear-reaction-analysis (NRA), and Rutherford-backscattering-spectrometry (RBS) provides the most complete analysis over the whole periodic table in a single measurement. Yet, for a highly resolved and accurate IBA analysis, a sophisticated technical setup is required integrating the detectors, beam optics, and sample arrangement. A new end-station developed and installed in Forschungszentrum Jülich provides these capabilities in combination with high sample throughput and result accuracy. Mechanical tolerances limit the device accuracy to 3% for RBS. Continuous pumping enables 5 × 10−8 mbar base pressure with vibration amplitudes < 0.1 µm. The beam optics achieves a demagnification of 24–34, suitable for µ-beam analysis. An in-vacuum manipulator enables scanning 50 × 50 mm² sample areas with 10 nm accuracy. The setup features the above-mentioned IBA detectors, enabling a broad range of analysis applications such as the operando analysis of batteries or the post-mortem analysis of plasma-exposed samples with up to 3000 discrete points per day. Custom apertures and energy resolutions down to 11 keV enable separation of Fe and Cr in RBS. This work presents the technical solutions together with the quantification of these challenges and their success in the form of a technical reference.
From Nonalcoholic Fatty Liver Disease (NAFLD) to Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)—New Terminology in Pediatric Patients as a Step in Good Scientific Direction?
Authors: Flisiak-Jackiewicz Marta , Bobrus-Chociej Anna , Wasilewska Natalia , Lebensztejn Dariusz Marek
Published: March 2021

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, which predispose to more serious hepatic conditions. It ranges from simple liver steatosis to nonalcoholic steatohepatitis (NASH), which may progress to cirrhosis, and even end-stage liver disease. Since obesity became one of the most important health concerns wordwide, a considerable increase in the prevalance of NAFLD and other metabolic implications has been observed, both in adults and children. Due to the coexistence of visceral obesity, insulin resistance, dyslipidemia, NAFLD is considered to be the hepatic manifestation of metabolic syndrome (MetS). These relationships between NAFLD and MetS led to the set up in adults of a new term combining both of these conditions, called metabolic dysfunction-associated fatty liver disease (MAFLD). Based on these findings, we propose a set of criteria, which may be useful to diagnose MAFLD in children and adolescents.
Walk and Run Test in Patients with Degenerative Compression of the Cervical Spinal Cord
Authors: Kadanka Zdenek , Kadanka Zdenek , Skutil Tomas , Vlckova Eva , Bednarik Josef
Published: March 2021

Impaired gait is one of the cardinal symptoms of degenerative cervical myelopathy (DCM) and frequently its initial presentation. Quantitative gait analysis is therefore a promising objective tool in the disclosure of early cervical cord impairment in patients with degenerative cervical compression. The aim of this cross-sectional observational cohort study was to verify whether an objective and easily-used walk and run test is capable of detecting early gait impairment in a practical proportion of non-myelopathic degenerative cervical cord compression (NMDCC) patients and of revealing any correlation with severity of disability in DCM. The study group consisted of 45 DCM patients (median age 58 years), 126 NMDCC subjects (59 years), and 100 healthy controls (HC) (55.5 years), all of whom performed a standardized 10-m walk and run test. Walking/running time/velocity, number of steps and cadence of walking/running were recorded; analysis disclosed abnormalities in 66.7% of NMDCC subjects. The DCM group exhibited significantly more pronounced abnormalities in all walk/run parameters when compared with the NMDCC group. These were apparent in 84.4% of the DCM group and correlated closely with disability as quantified by the modified Japanese Orthopaedic Association scale. A standardized 10-m walk/run test has the capacity to disclose locomotion abnormalities in NMDCC subjects who lack other clear myelopathic signs and may provide a means of classifying DCM patients according to their degree of disability.
Common Genetic Variation in MC4R Does Not Affect Atherosclerotic Plaque Phenotypes and Cardiovascular Disease Outcomes
Authors: Blauw Lisanne L. , Noordam Raymond , van der Laan Sander W. , Trompet Stella , Kooijman Sander , van Heemst Diana , Jukema Johan Wouter , van Setten Jessica , de Borst Gert J. , Tybjærg-Hansen Anne , Pasterkamp Gerard , Berbée Jimmy F. P. , Rensen Patrick C. N.
Published: March 2021

We analyzed the effects of the common BMI-increasing melanocortin 4 receptor (MC4R) rs17782313-C allele with a minor allele frequency of 0.22–0.25 on (1) cardiovascular disease outcomes in two large population-based cohorts (Copenhagen City Heart Study and Copenhagen General Population Study, n = 106,018; and UK Biobank, n = 357,426) and additionally in an elderly population at risk for cardiovascular disease (n = 5241), and on (2) atherosclerotic plaque phenotypes in samples of patients who underwent endarterectomy (n = 1439). Using regression models, we additionally analyzed whether potential associations were modified by sex or explained by changes in body mass index. We confirmed the BMI-increasing effects of +0.22 kg/m2 per additional copy of the C allele (p < 0.001). However, we found no evidence for an association of common MC4R genetic variation with coronary artery disease (HR 1.03; 95% CI 0.99, 1.07), ischemic vascular disease (HR 1.00; 95% CI 0.98, 1.03), myocardial infarction (HR 1.01; 95% CI 0.94, 1.08 and 1.02; 0.98, 1.07) or stroke (HR 0.93; 95% CI 0.85, 1.01), nor with any atherosclerotic plaque phenotype. Thus, common MC4R genetic variation, despite increasing BMI, does not affect cardiovascular disease risk in the general population or in populations at risk for cardiovascular disease.
Validation of the Monitoring Efficacy of Neurogenic Bowel Treatment on Response (MENTOR) Tool in a Japanese Rehabilitation Setting
Authors: Nomi Masashi , Sengoku Atsushi , Krogh Klaus , Emmanuel Anton , Christiansen Albert Bohn
Published: March 2021

Study design: Prospective observational study. Objective: To validate the Monitoring Efficacy of NBD Treatment On Response (MENTOR) tool in individuals with a spinal cord injury (SCI) or spina bifida, suffering from neurogenic bowel dysfunction (NBD) in a rehabilitation center in Japan. Methods: First, the MENTOR tool was translated from English to Japanese using a validated translation process. Second, the MENTOR tool was validated in a rehabilitation clinic in Japan. Participants completed the MENTOR tool prior to a consultation with an expert physician. According to the results of the tool, each participant was allocated to one of three categories regarding change in treatment: “adequately treated,” “further discussion,” and “recommended change.” The results of the MENTOR tool were compared with the treatment decision made by an expert physician, who was blinded to the results of the MENTOR tool. Results: A total of 60 participants completed the MENTOR tool. There was an acceptable concordance between individuals allocated as respectively, being adequately treated (100%) and recommended change in treatment (61%) and the physicians’ decision on treatment. The concordance was lower for individuals allocated as requiring further discussion (48%). Conclusions: In this study the MENTOR tool was successfully validated in a Japanese rehab setting. The tool will help identify individuals with SCI that need further treatment of their NBD symptoms.
The Effect of Stress, Anxiety and Depression on In Vitro Fertilization Outcome in Kazakhstani Public Clinical Setting: A Cross-Sectional Study
Authors: Bapayeva Gauri , Aimagambetova Gulzhanat , Issanov Alpamys , Terzic Sanja , Ukybassova Talshyn , Aldiyarova Aidana , Utepova Gulnara , Daribay Zhanibek , Bekbossinova Gulnara , Balykov Askhat , Laganà Antonio Simone , Terzic Milan
Published: March 2021

Although it is clear that infertility leads to heightened stress for patients, the impact of depressed mood and anxiety on treatment outcome is inconsistently reported. The aim of this study was to evaluate the effect of stress, depression and anxiety on in vitro fertilization (IVF) outcomes in Kazakhstani public assisted reproductive technology (ART) clinics. The prospective cohort study was performed between June 2019 and September 2020 using questionnaires to assess psychological stress, depressed mood and anxiety in women referred to IVF clinics in two public clinical centers in Kazakhstan, Nur-Sultan and Aktobe. Our study sample comprised 142 women with the average age of 33.9 ± 4.9 years, and infertility duration 6.0 ± 3.5 years. More than half of respondents had Center for Epidemiological Studies Depression Scale (CES-D) scores higher than 16, indicating their risk of developing clinical depression. Ninety-one percent of women from Aktobe city were at risk for clinical depression (p < 0.001). Aktobe city respondents had higher stress subscale scores and anxiety scale scores (p < 0.001) than Nur-Sultan respondents. Statistical analysis showed that IVF outcome was not significantly associated with depression and stress, while the higher anxiety scale scores were negatively associated with clinical pregnancy after IVF.
Discordance between Body-Mass Index and Body Adiposity Index in the Classification of Weight Status of Elderly Patients with Stable Coronary Artery Disease
Authors: Hudzik Bartosz , Nowak Justyna , Szkodzinski Janusz , Danikiewicz Aleksander , Korzonek-Szlacheta Ilona , Zubelewicz-Szkodzińska Barbara
Published: March 2021

Background and Aims: Body-mass index (BMI) is a popular method implemented to define weight status. However, describing obesity by BMI may result in inaccurate assessment of adiposity. The Body Adiposity Index (BAI) is intended to be a directly validated method of estimating body fat percentage. We set out to compare body weight status assessment by BMI and BAI in a cohort of elderly patients with stable coronary artery disease (CAD). Methods: A total of 169 patients with stable CAD were enrolled in an out-patient cardiology clinic. The National Research Council (US) Committee on Diet and Health classification was used for individuals older than 65 years as underweight BMI < 24 kg/m2, normal weight BMI 24–29 kg/m2, overweight BMI 29–35 kg/m2, and obesity BMI > 35 kg/m2. In case of BAI, we used sex- and age-specific classification of weight status. In addition, body fat was estimated by bioelectrical impedance analysis (BImpA). Results: Only 72 out of 169 patients (42.6%) had concordant classification of weight status by both BMI and BAI. The majority of the patients had their weight status either underestimated or overestimated. There were strong positive correlations between BMI and BImpA (FAT%) (R = 0.78 p < 0.001); BAI and BImpA (FAT%) (R = 0.79 p < 0.001); and BMI and BAI (R = 0.67 p < 0.001). BMI tended to overestimate the rate of underweight, normal weight or overweight, meanwhile underestimating the rate of obesity. Third, BMI exhibited an average positive bias of 14.4% compared to the reference method (BImpA), whereas BAI exhibited an average negative bias of −8.3% compared to the reference method (BImpA). Multivariate logistic regression identified independent predictors of discordance in assessing weight status by BMI and BAI: BImpA (FAT%) odds ratio (OR) 1.29, total body water (%) OR 1.61, fat mass index OR 2.62, and Controlling Nutritional Status (CONUT) score OR 1.25. Conclusions: There is substantial rate of misclassification of weight status between BMI and BAI. These findings have significant implications for clinical practice as the boundary between health and disease in malnutrition is crucial to accurately define criteria for intervention. Perhaps BMI cut-offs for classifying weight status in the elderly should be revisited.
Difficult Cases of Paroxysmal Nocturnal Hemoglobinuria: Diagnosis and Therapeutic Novelties
Authors: Fattizzo Bruno , Serpenti Fabio , Giannotta Juri Alessandro , Barcellini Wilma
Published: March 2021

Paroxysmal nocturnal hemoglobinuria (PNH) is an intriguing disease that can pose many difficulties to physicians, as well as to hematologists, who are unfamiliar with it. Research regarding its pathophysiologic, diagnostic, and therapeutic aspects is still ongoing. In the last ten years, new flow cytometry techniques with high sensitivity enabled us to detect PNH clones as small as <1% of a patient’s hematopoiesis, resulting in increasing incidence but more difficult data interpretation. Particularly, the clinical significance of small PNH clones in patients with bone marrow failures, including aplastic anemia and myelodysplastic syndromes, as well as in uncommon associations, such as myeloproliferative disorders, is still largely unknown. Besides current treatment with the anti-C5 eculizumab, which reduced PNH-related morbidity and mortality, new complement inhibitors will likely fulfill unmet clinical needs in terms of patients’ quality of life and better response rates (i.e., responses in subjects with C5 polymorphisms; reduction of extravascular hemolysis and breakthrough hemolysis episodes). Still, unanswered questions remain for these agents regarding their use in mono- or combination therapy, when to treat, and which drug is the best for which patient. Lastly, long-term safety needs to be assessed in real-life studies. In this review, we describe some clinical vignettes illustrating practical aspects of PNH diagnosis and management; moreover, we discuss recent advances in PNH diagnostic and therapeutic approaches.
Emerging Medical Treatment for Hypertrophic Cardiomyopathy
Authors: Argirò Alessia , Zampieri Mattia , Berteotti Martina , Marchi Alberto , Tassetti Luigi , Zocchi Chiara , Iannone Luisa , Bacchi Beatrice , Cappelli Francesco , Stefàno Pierluigi , Marchionni Niccolò , Olivotto Iacopo
Published: March 2021

Hypertrophic cardiomyopathy (HCM) is a common myocardial disease characterized by otherwise unexplained left ventricular hypertrophy. The main cause of disabling symptoms in patients with HCM is left ventricular outflow tract (LVOT) obstruction. This phenomenon is multifactorial, determined both by anatomical and functional abnormalities: myocardial hypercontractility is believed to represent one of its major determinants. The anatomical anomalies are targeted by surgical interventions, whereas attenuating hypercontractility is the objective of old and new drugs including the novel class of allosteric myosin inhibitors. This review summarizes the current treatment modalities and discusses the emerging therapeutical opportunities focusing on the recently developed cardiac myosin ATPase inhibitors Mavacamten and CK-274. Novel surgical and interventional approaches are also discussed.
Lung Transplantation for Pleuroparenchymal Fibroelastosis
Authors: Shiiya Haruhiko , Sato Masaaki
Published: March 2021

Pleuroparenchymal fibroelastosis (PPFE), a new disease entity associated with interstitial pneumonia, is characterized by fibrosis and elastosis involving the pleura and subpleural lung parenchyma, predominantly in the upper lobe. As the awareness of this disease entity has increased, many studies have revealed the prevalence and incidence, clinical and pathological characteristics, and disease course of PPFE. Patients with PPFE reportedly have several unique clinical characteristics—including an extremely low body mass index with a slender body and chest wall deformity, known as “flat chest”. As this disease progresses, shrinking of the lungs often causes life-threatening complications, such as pneumothorax, and associated air leak syndrome. Lung transplantation is considered the only effective treatment for patients with advanced PPFE; however, little is known about the influences of the characteristics of PPFE on the outcome of lung transplantation. This review focuses on the unique clinicopathologic characteristics of PPFE and associated outcomes of lung transplantation for these patients.
Experiential and Strategic Emotional Intelligence Are Implicated When Inhibiting Affective and Non-Affective Distractors: Findings from Three Emotional Flanker N-Back Tasks
Authors: Lim Ming D. , Birney Damian P.
Published: March 2021

Emotional intelligence (EI) refers to a set of competencies to process, understand, and reason with affective information. Recent studies suggest ability measures of experiential and strategic EI differentially predict performance on non-emotional and emotionally laden tasks. To explore cognitive processes underlying these abilities further, we varied the affective context of a traditional letter-based n-back working-memory task. In study 1, participants completed 0-, 2-, and 3-back tasks with flanking distractors that were either emotional (fearful or happy faces) or non-emotional (shapes or letters stimuli). Strategic EI, but not experiential EI, significantly influenced participants’ accuracy across all n-back levels, irrespective of flanker type. In Study 2, participants completed 1-, 2-, and 3-back levels. Experiential EI was positively associated with response times for emotional flankers at the 1-back level but not other levels or flanker types, suggesting those higher in experiential EI reacted slower on low-load trials with affective context. In Study 3, flankers were asynchronously presented either 300 ms or 1000 ms before probes. Results mirrored Study 1 for accuracy rates and Study 2 for response times. Our findings (a) provide experimental evidence for the distinctness of experiential and strategic EI and (b) suggest that each are related to different aspects of cognitive processes underlying working memory.
Edge Grinding Characteristics of Display Glass Substrate
Authors: Wee Keong Neo Dennis , Liu Kui , Huang Rui , Wu Hu
Published: March 2021

Display glass substrate as a brittle material is very challenging to machine due to its excellent physical, mechanical, electrical, and optical properties such as high hardness, high strength, high wear resistance, good fracture toughness, good chemical stability, and good thermal stability. On the basis of Griffith fracture mechanics, our theoretical analysis indicated that edge grinding of the display glass substrate is under brittle mode when grinding with the given conditions, which was verified by the experimental studies of ground glass edge surface topography and fractured surface obtained. Grinding force (Fy) in the vertical direction was much larger than grinding force (Fx) in the horizontal direction, causing a large compressive stress acting on the grinding glass edge. Grinding torque was slightly increased with the increase of grinding speed. Grinding temperature was very high when measured under dry grinding compared with measurement under high-pressure coolant. Grinding of glass substrate edge was performed partially under ductile mode machining in the experimental conditions, which can be attributed to and contributed by those micro cutting edges generated by the fractured diamond grit on the grinding wheel surface.
Effect of Cutting Ratio and Catch on Drag Characteristics and Fluttering Motions of Midwater Trawl Codend
Authors: Liu Wei , Tang Hao , You Xinxing , Dong Shuchuang , Xu Liuxiong , Hu Fuxiang
Published: March 2021

The codend of a trawl net is the rearmost and crucial part of the net for selective fish catch and juvenile escape. To ensure efficient and sustainable midwater trawl fisheries, it is essential to better understand the drag characteristics and fluttering motions of a midwater trawl codend. These are generally affected by catch, cutting ratio, mesh size, and twine diameter. In this study, six nylon codend models with different cutting ratios (no cutting, 6:1, 5:1, 4:1, 7:2, and 3:1) were designed and tested in a professional flume tank under two conditions (empty codends and codends with catch) and five current speeds to obtain the drag force, spatial geometry, and movement trend. As the cutting ratio of empty codends decreased, the drag force decreased, and the drag coefficient increased. The unfolding degree of codend netting and the height of empty codends were found to be directly proportional to the current speed and inversely proportional to the cutting ratio. The positional amplitude of codend with cutting ratio 4:1 was the smallest for catch. The drag force of codends with catch increased as the current speed increased, and first decreased and then increased as the cutting ratio decreased. To ensure the best stability and minimum drag force of the codend, it is recommended to use the 4:1 cutting ratio codend.
Unmanned Marine Vehicles
Authors: Bruzzone Gabriele , Ferretti Roberta , Odetti Angelo
Published: March 2021

Water covers nearly 70% of the Earth’s surface, and throughout history, oceans, seas, lakes, rivers, etc [...]
PNPLA3 and SERPINA1 Variants Are Associated with Severity of Fatty Liver Disease at First Referral to a Tertiary Center
Authors: Semmler Georg , Balcar Lorenz , Oberkofler Hannes , Zandanell Stephan , Strasser Michael , Niederseer David , Feldman Alexandra , Stickel Felix , Strnad Pavel , Datz Christian , Paulweber Bernhard , Aigner Elmar
Published: March 2021

Single nucleotide polymorphisms (SNPs), including PNPLA3 rs738409 and SERPINA1 rs17580, have been identified as risk modifiers in the progression fatty liver disease (alcoholic (ALD) or non-alcoholic (NAFLD)). While PNPLA3 has been studied in various settings, the value of both SNPs has so far not been addressed in a real-world cohort of subjects referred for a diagnostic work-up of liver disease. Thus, liver disease severity was assessed in 1257 consecutive patients with suspected ALD or NAFLD at the time of referral to a tertiary center. Advanced chronic liver disease (ACLD) was present in 309 (24.6%) patients and clinically significant portal hypertension (CSPH) was present in 185 (14.7%) patients. The PNPLA3 G-allele was independently associated with a higher liver stiffness measurement (LSM; adjusted B: 2.707 (1.435–3.979), p < 0.001), and higher odds of ACLD (adjusted odds ratio (aOR): 1.971 (1.448–2.681), p < 0.001) and CSPH (aOR: 1.685 (1.180–2.406), p = 0.004). While the SERPINA1 Z-allele was not associated with a higher LSM or the presence of ACLD, it was independently associated with higher odds of CSPH (aOR: 2.122 (1.067–4.218), p = 0.032). Associations of the PNPLA3 G-allele and the SERPINA1 Z-allele with CSPH were maintained independently of each other. The presence of both risk variants further increased the likelihood of ACLD and CSPH.
Advancing Personalized Medicine in Common Forms of Parkinson’s Disease through Genetics: Current Therapeutics and the Future of Individualized Management
Authors: Reed Xylena , Schumacher-Schuh Artur , Hu Jing , Bandres-Ciga Sara
Published: March 2021

Parkinson’s disease (PD) is a condition with heterogeneous clinical manifestations that vary in age at onset, rate of progression, disease course, severity, motor and non-motor symptoms, and a variable response to antiparkinsonian drugs. It is considered that there are multiple PD etiological subtypes, some of which could be predicted by genetics. The characterization and prediction of these distinct molecular entities provides a growing opportunity to use individualized management and personalized therapies. Dissecting the genetic architecture of PD is a critical step in identifying therapeutic targets, and genetics represents a step forward to sub-categorize and predict PD risk and progression. A better understanding and separation of genetic subtypes has immediate implications in clinical trial design by unraveling the different flavors of clinical presentation and development. Personalized medicine is a nascent area of research and represents a paramount challenge in the treatment and cure of PD. This manuscript summarizes the current state of precision medicine in the PD field and discusses how genetics has become the engine to gain insights into disease during our constant effort to develop potential etiological based interventions.
Teaching Fieldwork in Landscape Architecture in European Context; Some Backgrounds and Organisation
Authors: Fekete Albert , van den Toorn Martin
Published: March 2021

Fieldwork is an intrinsic part of landscape architecture education because it confronts the students with the landscape in real life, shows realised projects, enables different experiences, and provides a direct confrontation with the historical context of the discipline. Here the main goal is to give a first overview of teaching of fieldwork, compare that with other publications, and analyse pedagogical and didactic backgrounds in landscape architectural education in Europe. This study is based mainly on existing publications and complemented with our own experiences with fieldwork in teaching. The research method is based on accumulating existing knowledge on the subject and the principles of case study research. After a short overview of pedagogy and didactics in the context of teaching in design disciplines and how this relates to teaching landscape architecture, we work out the organisation of teaching in the outdoors. The conclusions focus on what can be learned in the outdoors that you cannot be learned indoors. Learning to see, to experience the landscape in real is part of “learning by doing” in which drawing, sketching, measuring plays a key role. In the long run pedagogy and didactics of fieldwork should be developed as domain-specific field of knowledge as part of design education in general.
Mapping Rural Settlements from Landsat and Sentinel Time Series by Integrating Pixel- and Object-Based Methods
Authors: Xu Ru
Published: March 2021

Rural settlements account for 45% of the world’s population and are targeted places for poverty eradication. However, compared to urban footprints, the distribution of rural settlements is not well characterized in most existing land use and land cover maps because of their patchy and scattered organization and relative stability over time. In this study, we proposed a pixel- and object-based method to map rural settlements by employing spectral-texture-temporal information from Landsat and Sentinel time series. Spectral indices (maximum normalized difference vegetation index (NDVI) and minimum normalized difference built-up index (NDBI composite) and texture indices (vertical transmit and vertical receive (VV) polarization of mean synthetic aperture radar (SAR) composite) were calculated from all available Landsat and Sentinel-1A data from 1 January 2016 to 31 December 2018. These features were then stacked for segmentation to extract potential rural settlement objects. To better differentiate settlements from bare soil, the gradient of annual NDVI maximum (namely, gradient of change, use gradient for simplicity) from 1 January 1987 to 31 December 2018 was used. The rural training samples were selected from global urban footprint (GUF) products with a post filtering process to remove sample noise. Scatter plots between pixel- and object-based values per feature were delineated by t-distribution ellipses to determine the thresholds. Finally, pixel- and object-based thresholds were applied to four features (NDVI, NDBI, VV, gradient) in Google Earth Engine (GEE) to obtain the distribution of rural settlements in eight selected Asian regions. The derived maps of rural settlements showed consistent accuracy, with a producer’s accuracy (PA) of 0.87, user’s accuracy (UA) of 0.93 and overall accuracy (OA) reaching 90% in different landscape conditions, which are better than existing land cover products.
Development of 3D Spatial Database Enabled IT Framework for Land Agencies: Case Studies of Delhi, India and Prague, Czech Republic
Authors: Ghawana Tarun , Janečka Karel , Zlatanova Sisi
Published: March 2021

Rapid urbanization has led vertical infrastructural growth in different countries with differing economic development levels and social systems. The two cities, Prague and Delhi, are the capital cities of their respective countries and have significant vertical developments. However, the two cities represent the urban areas from countries having different economic development levels. The land agencies need to keep monitoring and managing the developments in a city. The paper proposes a conceptual 3D spatial database enabled IT framework for land agencies. A monostrand multiple case study approach reviews the current practices, existing spatial data systems and programmes with 3D components, initiatives taken to create digital spatial database and potential for 3D spatial database in the two cities. The policy drivers for creation and use of 3D spatial database for land agencies are presented. The current legal and planning landscape and the institutional arrangements related to land and property development have been studied considering the scope for the development of 3D data. Further, a conceptual 3D spatial database enabled IT framework for better land administration, planning, development and management functioning is proposed. The proposed framework can make a difference providing interconnectivity, ease of access and usage, time and cost efficiency, enhanced organizational coordination and spatial data information-based decision-making process.