bluuebunny/crossref_metadata_2025 huggingface dataset:
No Benefit of a Pediatric Screening in Discovering Reduced Visual Acuity in Children: Experiences from a Cross-Sectional Study in Germany
Authors: Elflein Heike M. , Pokora Roman , Müller Denis F. , Jahn Klaus , Ponto Katharina A. , Pitz Susanne , Pfeiffer Norbert , Schuster Alexander K. , Urschitz Michael S.
Published: May 2020

Background: The newly introduced German pediatric screening examination at the end of the third year of life (U7a) incorporates visual function testing in particular; there is no ophthalmic screening during childhood in Germany. The purpose of this study is to investigate the relationship between participation in U7a and visual function at the preschool health examination (PHE) in the sixth year of life. Methods: This study evaluated PHE data from school enrollment years 2009/2010 to 2014/2015 of Rhineland-Palatinate, Germany. Visual acuity (VA) at PHE was assessed with Rodenstock visual acuity test device (tumbling E) wearing glasses if present. The relationship between participation in U7a and VA <0.7 at PHE was calculated for reduced monocular and binocular VA using multiple logistic regression adjusted for potential confounders. Results: Data from 189,704 children (91,041 girls) in 35 out of 36 districts were included. The first children to participate in U7a were enrolled in 2011/2012 school year. In total, 90,339 children (47.6%) had U7a before PHE, while 99,365 (52.4%) had not. VA <0.7 in at least one eye was measured at PHE in 8429 (4.4%) children, and in both eyes in 4345 (2.3%) children. Participation in U7a was not associated with VA <0.7 at PHE (odds ratio 0.99; 95% confidence interval: 0.94–1.04). Conclusions: The proportion of children with VA <0.7 at PHE was high. No beneficial effect of newly introduced German U7a pediatric screening examination was found for reduced VA at PHE.
Impact of Perinatal Death on the Social and Family Context of the Parents
Authors: Fernández-Sola Cayetano , Camacho-Ávila Marcos , Hernández-Padilla José Manuel , Fernández-Medina Isabel María , Jiménez-López Francisca Rosa , Hernández-Sánchez Encarnación , Conesa-Ferrer María Belén , Granero-Molina José
Published: May 2020

Background: Perinatal death (PD) is a painful experience, with physical, psychological and social consequences in families. Each year, there are 2.7 million perinatal deaths in the world and about 2000 in Spain. The aim of this study was to explore, describe and understand the impact of perinatal death on parents’ social and family life. Methods: A qualitative study based on Gadamer’s hermeneutic phenomenology was used. In-depth interviews were conducted with 13 mothers and eight fathers who had suffered a perinatal death. Inductive analysis was used to find themes based on the data. Results: Seven sub-themes emerged, and they were grouped into two main themes: 1) perinatal death affects family dynamics, and 2) the social environment of the parents is severely affected after perinatal death. Conclusions: PD impacts the family dynamics of the parents and their family, social and work environments. Parents perceive that society trivializes their loss and disallows or delegitimizes their grief. Implications: Social care, health and education providers should pay attention to all family members who have suffered a PD. The recognition of the loss within the social and family environment would help the families to cope with their grief.
School-Based Tobacco Control and Smoking in Adolescents: Evidence from Multilevel Analyses
Authors: Kim Seong Yeon , Jang Myungwha , Yoo Seunghyun , JeKarl Jung , Chung Joo Youn , Cho Sung-il
Published: May 2020

Since 2015, universal comprehensive school-based tobacco control programs have been provided in all primary and secondary schools in Korea. This study explored the association of school-level tobacco control with adolescent smoking, and the interactions to investigate whether gender moderates the impact of school tobacco control programs and school-level norms. Both school- and individual-level data were drawn from the 2015 School-Based Tobacco Prevention Program Survey. Multilevel logistic regression analyses were performed using data from 4631 students (ages 10–18 years) who were nested in 62 secondary schools in Seoul, Korea. Students who participated in more prevention programs were less likely to smoke (OR = 0.47, 95% CI 0.30–0.74). The effect of the programs was significantly moderated by gender. For boys, exposure to a greater number of programs decreased the risk of smoking (OR = 0.32, 95% CI 0.18–0.57) but not for girls. At the school level, the school norm regarding tobacco control regulations was negatively associated with smoking (OR = 0.28, 95% CI 0.11–0.76), and its effect was significant for girls only (OR = 0.35, 95% CI 0.17–0.76). This study highlights how the school environment is associated with adolescent smoking behavior, and the effects of programs and norms are different by gender. The findings suggest the need to develop strategies to enhance school-based tobacco control programs and the school norm considering gender differences.
A Longitudinal Study of a Multicomponent Exercise Intervention with Remote Guidance among Breast Cancer Patients
Authors: Dong Xiaosheng , Yi Xiangren , Ding Meng , Gao Zan , McDonough Daniel J. , Yi Nuo , Qiao Wenzhen
Published: May 2020

Purpose: Breast cancer patients in treatment suffer from long-term side effects that seriously influence their physical and mental health. The aim of this study was to examine effectiveness of a 12-week multicomponent exercise (ME) with remote guidance intervention on health-related outcomes after one year among breast cancer patients. Methods: In phases I–III, 60 patients (51.2 ± 7.9 years) with breast cancer (BC) who completed chemotherapy/postoperative radiotherapy within the previous four months to two years were randomly assigned to (1) multicomponent exercise with remote guidance (ME) and (2) usual care (UC). Eligible participants were approached to assess cancer-related quality of life (QOL), muscle strength, cardiorespiratory endurance, and physical activity (PA) barriers after one year. Results: The results demonstrated that, after one year, the ME group reported higher vitality-related QOL (5.776, 95% confidence interval [CI] 0.987, 10.565, effect size [ES] = 0.360), mental health-related QOL (9.938, 95% CI 4.146, 15.729, ES = 0.512), leg strength and endurance (2.880, CI 1.337, 4.423, ES = 0.557), and strength and endurance of upper extremities (2.745, 95% CI 1.076, 4.415, ES = 0.491) and lower physical activity (PA) hindrance (5.120, 95% CI 1.976, 8.264, ES = 0.486) than the UC group. Conclusions: The ME group observed significant differences from the UC group in QOL, muscle strength, cardiopulmonary endurance, and PA participation. These findings suggested that the multicomponent exercise intervention with remote guidance produced long-term health benefits for breast cancer patients.
Objective and Perceived Neighborhood Greenness of Students Differ in Their Agreement in Home and Study Environments
Authors: Loder Alexander Karl Ferdinand , Gspurning Josef , Paier Christoph , van Poppel Mireille Nicoline Maria
Published: May 2020

Research has reported the associations between objective or subjective neighborhood greenness and health, with low agreement between the greenness scores. College students are prone to poor health, and data are lacking on home and university environments. We studied the agreement between greenness parameters and the associations of objective greenness with health in different locations. Three hundred and seventy-seven college students were recruited, with a mean age of 24 years, in the city of Graz, Austria. Objective and perceived greenness was assessed at home and at university. Health measures included the WHO-5 questionnaire for mental health, the IPAQ questionnaire (short) for physical activity and sedentariness, and body mass index. Per location, quintile pairs of objective and perceived greenness were classified into underestimates, correct estimates or overestimates. Interrater reliability and correlation analyses revealed agreement between greenness scores at home but not at university. ANOVA models only showed poorer mental health for students underestimating greenness at university (M = 51.38, SD = 2.84) compared to those with correct estimates (M = 61.03, SD = 1.85). Agreement between greenness scores at home but not at university was obtained, and mental health was related to the perception of greenness at university. We conclude that reliable and corresponding methods for greenness scores need to be developed.
Temporomandibular Joints’ Morphology and Osteoarthritic Changes in Cone-Beam Computed Tomography Images in Patients with and without Reciprocal Clicking—A Case Control Study
Authors: Derwich Marcin , Mitus-Kenig Maria , Pawlowska Elzbieta
Published: May 2020

Background: Patients referred for orthodontic treatment often present symptoms of temporomandibular joints’ disorders (TMD), predominantly clicking. The objective was to analyze the morphology of the temporomandibular joints in cone-beam computed tomography (CBCT) images based on the presence of reciprocal clicking before orthodontic treatment. Methods: 105 participants took part in the study. 210 temporomandibular joints (TMJs) were allocated into one of two groups regarding the presence of reciprocal clicking. Morphology of condyle’s head, glenoid fossa, and articular eminence as well as condylar head position in the glenoid fossa and osteoarthritic changes in the area of the condylar head were examined for each TMJ in the CBCT images. Statistical analysis was performed with STATISTICA version 12.0. The following tests were performed: U-Mann Whitney, Kruskal-Wallis, t-Student, and chi-square. The statistical significance level was p = 0.05 for all the measurements included. Results: Significantly smaller condylar A-P dimension (p = 0.040) characterized temporomandibular joints with reciprocal clicking. Condyles were substantially more often positioned posteriorly (p = 0.043) and were significantly more often accompanied by subcortical cysts and pathologic osteoarthritic bone changes (p < 0.001). Conclusions: The early stages of internal derangements stay with alterations in morphology and position of TMJs as well as with the presence of osteoarthritic changes.
Psychological Distress of Patients Experiencing Different Types of Road Traffic Injuries in Vietnam
Authors: Hoang Chi Linh , Vu Hai Minh , Pham Hai Quang , Nguyen Huong Lan Thi , Vu Linh Gia , Tran Bach Xuan , Latkin Carl A. , Ho Roger C. M. , Ho Cyrus S. H.
Published: May 2020

Road-related injuries are often catastrophic, and the eighth leading cause of all-aged mortality. While psychological problems, including anxiety, driving phobia, and post-traumatic stress have been found to be common among injured survivors, the literature in this area is still limited. This study aimed to evaluate the prevalence of distress between different types of road injuries among 413 patients in Thai Binh hospitals from October to December 2018. The Kessler Psychological Distress Scale (K6) was used to assess mental health status. Sociodemographic and clinical characteristics were also collected. The results of Multiple Logistic and Tobit regression models were utilized. Psychological issues were found in 13.8% of the participants. In terms of K6 profile, nervous, restless/fidgety, and “everything was an effort” were the three most frequently endorsed aspects. Having soft-tissue injuries had a 0.32-time lower likelihood of psychological distress compared to those having other injuries. Additionally, patients who were diagnosed with fractures were 4.5-times more likely to report psychological distress. Our finding highlights the need for psychological screening to reduce disabilities associated with non-fatal injury related to road traffic crashes.
Analysis of Cyclist’s Drag on the Aero Position Using Numerical Simulations and Analytical Procedures: A Case Study
Authors: Forte Pedro , Marinho Daniel A. , Nikolaidis Pantelis T. , Knechtle Beat , Barbosa Tiago M. , Morais Jorge E.
Published: May 2020

Background: Resistance acting on a cyclist is a major concern among the cycling fraternity. Most of the testing methods require previous training or expensive equipment and time-consuming set-ups. By contrast, analytical procedures are more affordable and numerical simulations are perfect for manipulating and controlling inputs. The aim of this case study was to compare the drag of a cyclist in the aero position as measured using numerical simulation and analytical procedures. Methods: An elite male cyclist (65 kg in mass and 1.72 m in height) volunteered to take part in this research. The cyclist was wearing his competition gear, helmet and bicycle. A three-dimensional model of the bicycle and cyclist in the aero position was obtained to run the numerical simulations. Computational fluid dynamics (CFD) and a set of analytical procedures were carried out to assess drag, frontal area and drag coefficient, between 1 m/s and 22 m/s, with increments of 1 m/s. The t-test paired samples and linear regression were selected to compare, correlate and assess the methods agreement. Results: No significant differences (t = 2.826; p = 0.275) between CFD and analytical procedures were found. The linear regression showed a very high adjustment for drag (R2 = 0.995; p < 0.001). However, the drag values obtained by the analytical procedures seemed to be overestimated, even though without effect (d = 0.11). Conclusions: These findings suggest that drag might be assessed using both a set of analytical procedures and CFD.
Food Supply without Risk: Multicriteria Analysis of Institutional Conditions of Exporters
Authors: Puertas Rosa , Marti Luisa , Garcia-Alvarez-Coque Jose-Maria
Published: May 2020

International trade in food knows no borders, hence the need for prevention systems to avoid the consumption of products that are harmful to health. This paper proposes the use of multicriteria risk prevention tools that consider the socioeconomic and institutional conditions of food exporters. We propose the use of three decision-making methods—Technique for Order Preference by Similarity to the Ideal Solution (TOPSIS), Elimination et Choix Traduisant la Realité (ELECTRE), and Cross-Efficiency (CE)—to establish a ranking of countries that export cereals to the European Union, based on structural criteria related to the detection of potential associated risks (notifications, food quality, corruption, environmental sustainability in agriculture, and logistics). In addition, the analysis examines whether the wealth and institutional capacity of supplier countries influence their position in the ranking. The research was carried out biannually over the period from 2012–2016, allowing an assessment to be made of the possible stability of the markets. The results reveal that suppliers’ rankings based exclusively on aspects related to food risk differ from importers’ actual choices determined by micro/macroeconomic features (price, production volume, and economic growth). The rankings obtained by the three proposed methods are not the same, but present certain similarities, with the ability to discern countries according to their level of food risk. The proposed methodology can be applied to support sourcing strategies. In the future, food safety considerations could have increased influence in importing decisions, which would involve further difficulties for low-income countries.
Changes of Material Elastic Properties during Healing of Ruptured Achilles Tendons Measured with Shear Wave Elastography: A Pilot Study
Authors: Frankewycz Borys , Henssler Leopold , Weber Johannes , Silva Natascha Platz Batista da , Koch Matthias , Jung Ernst Michael , Docheva Denitsa , Alt Volker , Pfeifer Christian G.
Published: May 2020

Therapy options for ruptured Achilles tendons need to take into account the right balance of timing, amount and intensity of loading to ensure a sufficient biomechanical resilience of the healing tendon on the one hand, and to enable an adequate tensile stimulus on the other hand. However, biomechanical data of human Achilles tendons after rupture during the separate healing stages are unknown. Shear wave elastography is an ultrasound technique that measures material elastic properties non-invasively, and was proven to have a very good correlation to biomechanical studies. Taking advantage of this technology, 12 patients who suffered from an acute Achilles tendon rupture were acquired and monitored through the course of one year after rupture. Nine of these patients were treated non-operatively and were included for the analysis of biomechanical behaviour. A significant increase of material elastic properties was observed within the first six weeks after trauma (up to 80% of baseline value), where it reached a plateau phase. A second significant increase occurred three to six months after injury. This pilot study suggests a time correlation of biomechanical properties with the biological healing phases of tendon tissue. In the reparative phase, a substantial amount of biomechanical resilience is restored already, but the final stage of biomechanical stability is reached in the maturation phase. These findings can potentially be implemented into treatment and aftercare protocols.
Effects of Maternal Resveratrol on Maternal High-Fat Diet/Obesity with or without Postnatal High-Fat Diet
Authors: Hsu Mei-Hsin , Sheen Jiunn-Ming , Lin I-Chun , Yu Hong-Ren , Tiao Mao-Meng , Tain You-Lin , Huang Li-Tung
Published: May 2020

To examine the effects of maternal resveratrol in rats borne to dams with gestational high-fat diet (HFD)/obesity with or without postnatal high-fat diet. We first tested the effects of maternal resveratrol intake on placenta and male fetus brain in rats borne to dams with gestational HFD/obesity. Then, we assessed the possible priming effect of a subsequent insult, male offspring were weaned onto either a rat chow or a HFD. Spatial learning and memory were assessed by Morris water maze test. Blood pressure and peripheral insulin resistance were examined. Maternal HFD/obesity decreased adiponectin, phosphorylation alpha serine/threonine-protein kinase (pAKT), sirtuin 1 (SIRT1), and brain-derived neurotrophic factor (BDNF) in rat placenta, male fetal brain, and adult male offspring dorsal hippocampus. Maternal resveratrol treatment restored adiponectin, pAKT, and BDNF in fetal brain. It also reduced body weight, peripheral insulin resistance, increased blood pressure, and alleviated cognitive impairment in adult male offspring with combined maternal HFD and postnatal HFD. Maternal resveratrol treatment restored hippocampal pAKT and BDNF in rats with combined maternal HFD and postnatal HFD in adult male offspring dorsal hippocampus. Maternal resveratrol intake protects the fetal brain in the context of maternal HFD/obesity. It effectively reduced the synergistic effects of maternal HFD/obesity and postnatal HFD on metabolic disturbances and cognitive impairment in adult male offspring. Our data suggest that maternal resveratrol intake may serve as an effective therapeutic strategy in the context of maternal HFD/obesity.
Molecular Analysis of the ABCA4 Gene Mutations in Patients with Stargardt Disease Using Human Hair Follicles
Authors: Ścieżyńska Aneta , Soszyńska Marta , Komorowski Michał , Podgórska Anna , Krześniak Natalia , Nogowska Aleksandra , Smolińska Martyna , Szulborski Kamil , Szaflik Jacek P. , Noszczyk Bartłomiej , Ołdak Monika , Malejczyk Jacek
Published: May 2020

ABCA4 gene mutations are the cause of a spectrum of ABCA4 retinopathies, and the most common juvenile macular degeneration is called Stargardt disease. ABCA4 has previously been observed almost exclusively in the retina. Therefore, studying the functional consequences of ABCA4 variants has required advanced molecular analysis techniques. The aim of the present study was to evaluate whether human hair follicles may be used for molecular analysis of the ABCA4 gene splice-site variants in patients with ABCA4 retinopathies. We assessed ABCA4 expression in hair follicles and skin at mRNA and protein levels by means of real-time PCR and Western blot analyses, respectively. We performed cDNA sequencing to reveal the presence of full-length ABCA4 transcripts and analyzed ABCA4 transcripts from three patients with Stargardt disease carrying different splice-site ABCA4 variants: c.5312+1G>A, c.5312+2T>G and c.5836-3C>A. cDNA analysis revealed that c.5312+1G>A, c.5312+2T>G variants led to the skipping of exon 37, and the c.5836-3C>A variant resulted in the insertion of 30 nucleotides into the transcript. Our results strongly argue for the use of hair follicles as a model for the molecular analysis of the pathogenicity of ABCA4 variants in patients with ABCA4 retinopathies.
Instability of Short Arm of Acrocentric Chromosomes: Lesson from Non-Acrocentric Satellited Chromosomes. Report of 24 Unrelated Cases
Authors: Redaelli Serena , Conconi Donatella , Villa Nicoletta , Sala Elena , Crosti Francesca , Corti Cecilia , Catusi Ilaria , Garzo Maria , Romitti Lorenza , Martinoli Emanuela , Patrizi Antonella , Malgara Roberta , Recalcati Maria Paola , Dalprà Leda , Lavitrano Marialuisa , Riva Paola , Roversi Gaia , Bentivegna Angela
Published: May 2020

Satellited non-acrocentric autosomal chromosomes (ps–qs-chromosomes) are the result of an interchange between sub- or telomeric regions of autosomes and the p arm of acrocentrics. The sequence homology at the rearrangement breakpoints appears to be, among others, the most frequent mechanism generating these variant chromosomes. The unbalanced carriers of this type of translocation may or may not display phenotypic abnormalities. With the aim to understand the causative mechanism, we revised all the ps–qs-chromosomes identified in five medical genetics laboratories, which used the same procedures for karyotype analysis, reporting 24 unrelated cases involving eight chromosomes. In conclusion, we observed three different scenarios: true translocation, benign variant and complex rearrangement. The detection of translocation partners is essential to evaluate possible euchromatic unbalances and to infer their effect on phenotype. Moreover, we emphasize the importance to perform both, molecular and conventional cytogenetics methods, to better understand the behavior of our genome.
Unique Gut Microbiome Signatures Depict Diet-Versus Genetically Induced Obesity in Mice
Authors: Nagpal Ravinder , Mishra Sidharth P , Yadav Hariom
Published: May 2020

The gut microbiome plays an important role in obesity and Type 2 diabetes (T2D); however, it remains unclear whether the gut microbiome could clarify the dietary versus genetic origin of these ailments. Moreover, studies examining the gut microbiome in diet- versus genetically induced obesity/T2D in the same experimental set-up are lacking. We herein characterized the gut microbiomes in three of the most widely used mouse models of obesity/T2D, i.e., genetically induced (leptin-deficient i.e., Lepob/ob; and leptin-receptor-deficient i.e., Lepdb/db) and high-fat diet (HFD)-induced obese (DIO)/T2D mice, with reference to their normal chow-fed (NC) and low-fat-diet-fed (LF) control counterparts. In terms of β-diversity, Lepob/ob and Lepdb/db mice showed similarity to NC mice, whereas DIO and LF mice appeared as distinct clusters. The phylum- and genus-level compositions were relatively similar in NC, Lepob/ob, and Lepdb/db mice, whereas DIO and LF mice demonstrated distinct compositions. Further analyses revealed several unique bacterial taxa, metagenomic functional features, and their correlation patterns in these models. The data revealed that obesity/T2D driven by diet as opposed to genetics presents distinct gut microbiome signatures enriched with distinct functional capacities, and indicated that these signatures can distinguish diet- versus genetically induced obesity/T2D and, if extrapolated to humans, might offer translational potential in devising dietary and/or genetics-based therapies against these maladies.
Nanoliposomes from Agro-Resources as Promising Delivery Systems for Chondrocytes
Authors: Bianchi Arnaud , Velot Émilie , Kempf Hervé , Elkhoury Kamil , Sanchez-Gonzalez Laura , Linder Michel , Kahn Cyril , Arab-Tehrany Elmira
Published: May 2020

Investigations in cartilage biology have been hampered by the limited capacity of chondrocytes, especially in rats and humans, to be efficiently transfected. Liposomes are a promising delivery system due to their lipid bilayer structure similar to a biological membrane. Here we used natural rapeseed lecithin, which contains a high level of mono- and poly-unsaturated fatty acids, to evaluate the cytocompatibility of these phospholipids as future potential carriers of biomolecules in joint regenerative medicine. Results show that appropriate concentrations of nanoliposome rapeseed lecithin under 500 µg/mL were safe for chondrocytes and did not induce any alterations of their phenotype. Altogether, these results sustain that they could represent a novel natural carrier to deliver active substances into cartilage cells.
Improving Anti-Neurodegenerative Benefits of Acetylcholinesterase Inhibitors in Alzheimer’s Disease: Are Irreversible Inhibitors the Future?
Authors: Moss Donald E.
Published: May 2020

Decades of research have produced no effective method to prevent, delay the onset, or slow the progression of Alzheimer’s disease (AD). In contrast to these failures, acetylcholinesterase (AChE, EC 3.1.1.7) inhibitors slow the clinical progression of the disease and randomized, placebo-controlled trials in prodromal and mild to moderate AD patients have shown AChE inhibitor anti-neurodegenerative benefits in the cortex, hippocampus, and basal forebrain. CNS neurodegeneration and atrophy are now recognized as biomarkers of AD according to the National Institute on Aging-Alzheimer’s Association (NIA-AA) criteria and recent evidence shows that these markers are among the earliest signs of prodromal AD, before the appearance of amyloid. The current AChE inhibitors (donepezil, rivastigmine, and galantamine) have short-acting mechanisms of action that result in dose-limiting toxicity and inadequate efficacy. Irreversible AChE inhibitors, with a long-acting mechanism of action, are inherently CNS selective and can more than double CNS AChE inhibition possible with short-acting inhibitors. Irreversible AChE inhibitors open the door to high-level CNS AChE inhibition and improved anti-neurodegenerative benefits that may be an important part of future treatments to more effectively prevent, delay the onset, or slow the progression of AD.
Anti-Inflammatory Effects of Lasia spinosa Leaf Extract in Lipopolysaccharide-Induced RAW 264.7 Macrophages
Authors: Nguyen Thanh Q. C. , Duy Binh Tran , Pham Tuan L. A. , Nguyen Yen D. H. , Thi Xuan Trang Dai , Nguyen Trong Tuan , Kanaori Kenji , Kamei Kaeko
Published: May 2020

Lasia spinosa (L.) Thwaites was used as a traditional medicine to treat many inflammatory diseases for centuries. However, its effects on the inflammatory response are not yet characterized. In this study, we investigated the anti-inflammatory activities of L. spinosa leaf extract in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. We found that ethanol extracts of L. spinosa leaves showed anti-oxidant activity due to the presence of high levels of polyphenolic compounds. Treatment with the leaf extract significantly repressed the production of inflammatory mediators such as nitric oxide and reactive oxygen species and the expression of pro-inflammatory cytokines in the LPS-stimulated RAW 264.7 cells. Moreover, L. spinosa leaf extract treatment prevented activation of the nuclear factor-kappa B pathway by inhibiting nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) degradation. Furthermore, the mitogen-activated kinase and phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathways were suppressed upon treatment with the leaf extract. In addition to suppressing inflammatory factors, the extract also activated the nuclear factor erythroid 2-related factor 2/heme-oxygenase-1 pathway. We propose that L. spinosa leaf extract has the potential as an effective therapeutic agent for alleviating oxidative stress and excessive inflammation.
Enhanced Clearance of Neurotoxic Misfolded Proteins by the Natural Compound Berberine and Its Derivatives
Authors: Rusmini Paola , Cristofani Riccardo , Tedesco Barbara , Ferrari Veronica , Messi Elio , Piccolella Margherita , Casarotto Elena , Chierichetti Marta , Cicardi Maria Elena , Galbiati Mariarita , Geroni Cristina , Lombardi Paolo , Crippa Valeria , Poletti Angelo
Published: May 2020

Background: Accumulation of misfolded proteins is a common hallmark of several neurodegenerative disorders (NDs) which results from a failure or an impairment of the protein quality control (PQC) system. The PQC system is composed by chaperones and the degradative systems (proteasome and autophagy). Mutant proteins that misfold are potentially neurotoxic, thus strategies aimed at preventing their aggregation or at enhancing their clearance are emerging as interesting therapeutic targets for NDs. Methods: We tested the natural alkaloid berberine (BBR) and some derivatives for their capability to enhance misfolded protein clearance in cell models of NDs, evaluating which degradative pathway mediates their action. Results: We found that both BBR and its semisynthetic derivatives promote degradation of mutant androgen receptor (ARpolyQ) causative of spinal and bulbar muscular atrophy, acting mainly via proteasome and preventing ARpolyQ aggregation. Overlapping effects were observed on other misfolded proteins causative of amyotrophic lateral sclerosis, frontotemporal-lobar degeneration or Huntington disease, but with selective and specific action against each different mutant protein. Conclusions: BBR and its analogues induce the clearance of misfolded proteins responsible for NDs, representing potential therapeutic tools to counteract these fatal disorders.
Comprehensive Comparison of Clinically Relevant Grain Proteins in Modern and Traditional Bread Wheat Cultivars
Authors: Lakhneko Olha , Danchenko Maksym , Morgun Bogdan , Kováč Andrej , Majerová Petra , Škultéty Ľudovit
Published: May 2020

Bread wheat (Triticum aestivum L.) is one of the most valuable cereal crops for human consumption. Its grain storage proteins define bread quality, though they may cause food intolerances or allergies in susceptible individuals. Herein, we discovered a diversity of grain proteins in three Ukrainian wheat cultivars: Sotnytsia, Panna (both modern selection), and Ukrainka (landrace). Firstly, proteins were isolated with a detergent-containing buffer that allowed extraction of various groups of storage proteins (glutenins, gliadins, globulins, and albumins); secondly, the proteome was profiled by the two-dimensional gel electrophoresis. Using multi-enzymatic digestion, we identified 49 differentially accumulated proteins. Parallel ultrahigh-performance liquid chromatography separation followed by direct mass spectrometry quantification complemented the results. Principal component analysis confirmed that differences among genotypes were a major source of variation. Non-gluten fraction better discriminated bread wheat cultivars. Various accumulation of clinically relevant plant proteins highlighted one of the modern genotypes as a promising donor for the breeding of hypoallergenic cereals.
Rubrofusarin Attenuates Chronic Restraint Stress-Induced Depressive Symptoms
Authors: Yi Jee Hyun , Jeon Jieun , Kwon Huiyoung , Cho Eunbi , Yun Jeanho , Lee Young Choon , Ryu Jong Hoon , Park Se Jin , Cho Jong Hyun , Kim Dong Hyun
Published: May 2020

The aim of this study was to examine whether rubrofusarin, an active ingredient of the Cassia species, has an antidepressive effect in chronic restraint stress (CRS) mouse model. Although acute treatment using rubrofusarin failed, chronic treatment using rubrofusarin ameliorated CRS-induced depressive symptoms. Rubrofusarin treatment significantly reduced the number of Fluoro-Jade B-positive cells and caspase-3 activation within the hippocampus of CRS-treated mice. Moreover, rubrofusarin treatment significantly increased the number of newborn neurons in the hippocampus of CRS-treated mice. CRS induced activation of glycogen synthase kinase-3β and regulated development and DNA damage responses, and reductions in the extracellular-signal-regulated kinase pathway activity were also reversed by rubrofusarin treatment. Microglial activation and inflammasome markers, including nod-like receptor family pyrin domain containing 3 and adaptor protein apoptosis-associated speck-like protein containing CARD, which were induced by CRS, were ameliorated by rubrofusarin. Synaptic plasticity dysfunction within the hippocampus was also rescued by rubrofusarin treatment. Within in vitro experiments, rubrofusarin blocked corticosterone-induced long-term potentiation impairments. These were blocked by LY294002, which is an Akt inhibitor. Finally, we found that the antidepressant effects of rubrofusarin were blocked by an intracerebroventricular injection of LY294002. These results suggest that rubrofusarin ameliorated CRS-induced depressive symptoms through PI3K/Akt signaling.
Corin Overexpression Reduces Myocardial Infarct Size and Modulates Cardiomyocyte Apoptotic Cell Death
Authors: Sullivan Ryan D. , Houng Aiilyan K. , Gladysheva Inna P. , Fan Tai-Hwang M. , Tripathi Ranjana , Reed Guy L. , Wang Dong
Published: May 2020

Altered expression of corin, a cardiac transmembrane serine protease, has been linked to dilated and ischemic cardiomyopathy. However, the potential role of corin in myocardial infarction (MI) is lacking. This study examined the outcomes of MI in wild-type vs. cardiac-specific overexpressed corin transgenic (Corin-Tg) mice during pre-MI, early phase (3, 24, 72 h), and late phase (1, 4 weeks) post-MI. Corin overexpression significantly reduced cardiac cell apoptosis (p < 0.001), infarct size (p < 0.001), and inhibited cleavage of procaspases 3, 9, and 8 (p < 0.05 to p < 0.01), as well as altered the expression of Bcl2 family proteins, Bcl-xl, Bcl2 and Bak (p < 0.05 to p < 0.001) at 24 h post-MI. Overexpressed cardiac corin also significantly modulated heart function (ejection fraction, p < 0.0001), lung congestion (lung weight to body weight ratio, p < 0.0001), and systemic extracellular water (edema, p < 0.05) during late phase post-MI. Overall, cardiac corin overexpression significantly reduced apoptosis, infarct size, and modulated cardiac expression of key members of the apoptotic pathway in early phase post-MI; and led to significant improvement in heart function and reduced congestion in late phase post-MI. These findings suggest that corin may be a useful target to protect the heart from ischemic injury and subsequent post-infarction remodeling.
MiR-519d-3p in Trophoblastic Cells: Effects, Targets and Transfer to Allogeneic Immune Cells via Extracellular Vesicles
Authors: Chaiwangyen Wittaya , Murrieta-Coxca José M. , Favaro Rodolfo R. , Photini Stella M. , Gutiérrez-Samudio Ruby N. , Schleussner Ekkehard , Markert Udo R. , Morales-Prieto Diana M.
Published: May 2020

Members of the placenta-specific miRNA cluster C19MC, including miR-519d, are secreted by fetal trophoblast cells within extracellular vesicles (EVs). Trophoblast-derived EVs can be internalized by the autologous trophoblast and surrounding maternal immune cells, resulting in coordination of cellular responses. The study of functions and targets of placental miRNAs in the donor and recipient cells may contribute to the understanding of the immune tolerance essential in pregnancy. Here, we report that miR-519d-3p levels correlate positively with cell proliferation and negatively with migration in trophoblastic cell lines. Inhibition of miR-519d-3p in JEG-3 cells increases caspase-3 activation and apoptosis. PDCD4 and PTEN are targeted by miR-519d-3p in a cell type-specific manner. Transfection of trophoblastic cell lines with miR-519d mimic results in secretion of EVs containing elevated levels of this miRNA (EVmiR-519d). Autologous cells enhance their proliferation and decrease their migration ability when treated with EVmiR-519d. NK92 cells incorporate EV-delivered miR-519d-3p at higher levels than Jurkat T cells. EVmiR-519d increases the proliferation of Jurkat T cells but decreases that of NK92 cells. Altogether, miR-519d-3p regulates pivotal trophoblast cell functions, can be transferred horizontally via EVs to maternal immune cells and exerts functions therein. Vesicular miRNA transfer from fetal trophoblasts to maternal immune cells may contribute to the immune tolerance in pregnancy.
Autoantibody and Cytokine Profiles during Treatment with Belimumab in Patients with Systemic Lupus Erythematosus
Authors: Parodis Ioannis , Åkerström Emil , Sjöwall Christopher , Sohrabian Azita , Jönsen Andreas , Gomez Alvaro , Frodlund Martina , Zickert Agneta , Bengtsson Anders A , Rönnelid Johan , Gunnarsson Iva
Published: May 2020

We investigated whether belimumab treatment impacts on levels of autoantibodies and cytokines of interest in systemic lupus erythematosus (SLE). Longitudinally collected serum samples from 78 belimumab-treated Swedish SLE patients were analysed. Serum cytokine levels were determined using Luminex xMAP technology, and nuclear antigen autoantibody specificities using addressable laser bead immunoassay. In patients with detectable levels at baseline, interferon (IFN)-α2 levels were lower at month 6 (median; interquartile range (IQR): 8.9; 1.5–54.9 pg/mL) versus baseline (28.4; 20.9–100.3 pg/mL; p = 0.043). Interleukin (IL)-6 (baseline: 7.1; 2.9–16.1 pg/mL) decreased from month 6 (0.5; 0.5–6.3 pg/mL; p = 0.018) and throughout a 24 month follow-up. IL-10 (baseline: 12.6; 2.8–29.7 pg/mL) showed more rapid decreases from month 3 (1.8; 0.6–9.1 pg/mL; p = 0.003). Levels of anti-dsDNA (p < 0.001), anti-Smith antigen (Sm) (p = 0.002), anti-U1 small nuclear ribonucleoprotein (U1RNP) (p < 0.001), anti-Sm-U1RNP complex (p = 0.028), and anti-ribosomal P (p = 0.012) antibodies decreased from month 3 and remained decreased. Anti-Sm positivity at baseline was associated with higher probability and/or shorter time to achieve sustained SLE responder index-4 response (hazard ratio (HR): 2.52; 95% CI: 1.20–5.29; p = 0.015), independently of other factors. Decline of IL-6 levels through month 3 was greater in responders. In summary, belimumab treatment lowered IFN-α2, IL-6, and IL-10 levels, as well as levels of multiple autoantibodies, however after different time spans. Notably, anti-Sm positivity and early decline in IL-6 levels were associated with favorable treatment outcome.
Galactofuranose-Related Enzymes: Challenges and Hopes
Authors: Seničar Mateja , Lafite Pierre , Eliseeva Svetlana V. , Petoud Stéphane , Landemarre Ludovic , Daniellou Richard
Published: May 2020

Galactofuranose is a rare form of the well-known galactose sugar, and its occurrence in numerous pathogenic micro-organisms makes the enzymes responsible for its biosynthesis interesting targets. Herein, we review the role of these carbohydrate-related proteins with a special emphasis on the galactofuranosidases we recently characterized as an efficient recombinant biocatalyst.
EDEM1 Drives Misfolded Protein Degradation via ERAD and Exploits ER-Phagy as Back-Up Mechanism When ERAD Is Impaired
Authors: Chiritoiu Marioara , Chiritoiu Gabriela N. , Munteanu Cristian V. A. , Pastrama Florin , Ivessa N. Erwin , Petrescu Stefana M.
Published: May 2020

Endoplasmic reticulum (ER)-associated degradation (ERAD) is the main mechanism of targeting ER proteins for degradation to maintain homeostasis, and perturbations of ERAD lead to pathological conditions. ER-degradation enhancing α-mannosidase-like (EDEM1) was proposed to extract terminally misfolded proteins from the calnexin folding cycle and target them for degradation by ERAD. Here, using mass-spectrometry and biochemical methods, we show that EDEM1 is found in auto-regulatory complexes with ERAD components. Moreover, the N-terminal disordered region of EDEM1 mediates protein–protein interaction with misfolded proteins, whilst the absence of this domain significantly impairs their degradation. We also determined that overexpression of EDEM1 can induce degradation, even when proteasomal activity is severely impaired, by promoting the formation of aggregates, which can be further degraded by autophagy. Therefore, we propose that EDEM1 maintains ER homeostasis and mediates ERAD client degradation via autophagy when either dislocation or proteasomal degradation are impaired.
Increased Level of Vascular Endothelial Growth Factors by 4-hexylresorcinol is Mediated by Transforming Growth Factor-β1 and Accelerates Capillary Regeneration in the Burns in Diabetic Animals
Authors: Kim Dae-Won , Jo You-Young , Garagiola Umberto , Choi Je-Yong , Kang Yei-Jin , Oh Ji-Hyeon , Kim Seong-Gon
Published: May 2020

4-Hexyl resorcinol (4HR) is an organic compound and has been used in skin care application. 4HR is an M2-type macrophage activator and elevates vascular endothelial growth factor (VEGF) expression via the hypoxia-inducible factor (HIF)-independent pathway. As endothelial cells are important in wound healing, the human umbilical vein endothelial cells (HUVECs) were treated with 4HR, and changes in VEGF-A, -C, and transforming growth factor-β1 (TGF-β1) expression were investigated. The administration of 4HR increased the expression level of VEGF-A, -C, and TGF-β1. The application of TGF-β1 protein also increased the expression level of VEGF-A and -C. Knockdown with small interfering RNA (siRNA) targeting to TGF-β1 and the selective chemical inhibition (A83-01) to ALK5 confirmed the involvement of the TGF-β signaling pathway in the 4-HR-mediated VEGFs expression. 4HR application in a burn model of diabetic rats demonstrated an increased level of angiogenic proteins with wound healing. Compared to sericin application, the 4HR application group showed more prominent capillary regeneration. Collectively, 4HR activated TGF-β1/ALK5/VEGFs signaling in endothelial cells and induced vascular regeneration and remodeling for wound healing.
Forcing Pulsations by Means of a Siren for Gas Turbine Applications
Authors: Giuliani Fabrice , Stütz Markus , Paulitsch Nina , Andracher Lukas
Published: May 2020

A siren is a robust fast-valve that generates effective flow pulsations and powerful noise levels under well-controlled conditions. It operates under the inlet flow conditions of a gas turbine combustor. Its principle is based on a sonic air jet periodically sheared by a cogged wheel rotating at a given speed. It is used as an alternative to loudspeakers in combustion laboratories when the use of these is made difficult by aggressive flow conditions, such as hot air under pressure, possibly containing impurities. It is also a serious candidate as an effective flow actuator to be deployed on power gas turbine fleets. The authors have gathered more than twenty years of knowledge on siren technology. This pulsator was originally developed for research on thermoacoustics. By scanning through a given frequency range, one detects the acoustic resonance of specific parts of the combustor assembly, or possibly triggers a combustion instability during a sensitivity analysis of a flame to small perturbations. In 2010, Giuliani et al. developed a novel siren model with the capacity to vary the amplitude of pulsation independently from the frequency. In this contribution, the physics, the metrics, and the resulting parameters of the pulsator are discussed. Technical solutions are unveiled about visiting large frequency ranges (currently 6 kHz) and achieving elevated pressure fluctuations (150 dB SPL proven, possibly up to 155 dB SPL) with a compact device. A multimodal excitation is available with this technology, one idea being to dissipate the acoustic energy on nearby peaks. The contribution ends with a summary of the applications performed so far and the perspective of an industrial application.
Modeling Popularity and Reliability of Sources in Multilingual Wikipedia
Authors: Lewoniewski Włodzimierz , Węcel Krzysztof , Abramowicz Witold
Published: May 2020

One of the most important factors impacting quality of content in Wikipedia is presence of reliable sources. By following references, readers can verify facts or find more details about described topic. A Wikipedia article can be edited independently in any of over 300 languages, even by anonymous users, therefore information about the same topic may be inconsistent. This also applies to use of references in different language versions of a particular article, so the same statement can have different sources. In this paper we analyzed over 40 million articles from the 55 most developed language versions of Wikipedia to extract information about over 200 million references and find the most popular and reliable sources. We presented 10 models for the assessment of the popularity and reliability of the sources based on analysis of meta information about the references in Wikipedia articles, page views and authors of the articles. Using DBpedia and Wikidata we automatically identified the alignment of the sources to a specific domain. Additionally, we analyzed the changes of popularity and reliability in time and identified growth leaders in each of the considered months. The results can be used for quality improvements of the content in different languages versions of Wikipedia.
Gear Fault Diagnosis through Vibration and Acoustic Signal Combination Based on Convolutional Neural Network
Authors: Yu Liya , Yao Xuemei , Yang Jing , Li Chuanjiang
Published: May 2020

Equipment condition monitoring and diagnosis is an important means to detect and eliminate mechanical faults in real time, thereby ensuring safe and reliable operation of equipment. This traditional method uses contact measurement vibration signals to perform fault diagnosis. However, a special environment of high temperature and high corrosion in the industrial field exists. Industrial needs cannot be met through measurement. Mechanical equipment with complex working conditions has various types of faults and different fault characterizations. The sound signal of the microphone non-contact measuring device can effectively adapt to the complex environment and also reflect the operating state of the device. For the same workpiece, if it can simultaneously collect its vibration and sound signals, the two complement each other, which is beneficial for fault diagnosis. One of the limitations of the signal source and sensor is the difficulty in assessing the gear state under different working conditions. This study proposes a method based on improved evidence theory method (IDS theory), which uses convolutional neural network to combine vibration and sound signals to realize gear fault diagnosis. Experimental results show that our fusion method based on IDS theory obtains a more accurate and reliable diagnostic rate than the other fusion methods.