bluuebunny/crossref_metadata_2025 huggingface dataset:
Regular Leisure-Time Physical Activity is Effective in Boosting Neurotrophic Factors and Alleviating Menopause Symptoms
Authors: Kim Boram , Kang Sunghwun
Published: November 2020

Background: The study investigated the effects of regular leisure-time physical activity on the parameters of cognitive function (plasma brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and cathepsin B) and menopausal symptoms (the climacterium, depression, and cognitive impairment) in obese middle-aged women. Methods: All subjects were middle-aged and obese women (n = 52, % body fat > 30%). The participants were divided into premenopausal (PRM) (n = 18, age = 47.56 ± 6.11 years) and postmenopausal (POM) (n = 34, age = 57.79 ± 5.68 years) groups. The participants completed a survey questionnaire related to depression and the climacterium, as well as cognitive tests. Physical activity was performed for 12 weeks. Blood samples from the forearm vein were analyzed after 12 h of fasting. Blood levels of BDNF, NGF, and cathepsin B were analyzed using an R&D kit. Results: Regular leisure-time physical activity had a positive effect on reducing the percentage of body fat in premenopausal and postmenopausal obese women. In addition, the results of the questionnaire showed that regular exercise had a positive effect on body composition caused by lifestyle change and enhanced psychological stability. The BDNF concentration was significantly lower in postmenopausal than in premenopausal obese women. In addition, regular physical activity significantly increased the cathepsin B and NGF levels in postmenopausal obese women. Conclusions: Continuous leisure-time physical activity improved body composition and neurotrophic factors and alleviated menopausal symptoms in obese Korean women.
The Impact of a Household Food Garden Intervention on Food Security in Lesotho
Authors: Walsh Corinna May , Fouché Michelle Shannon , Nel Mariette , Booysen Frederik
Published: November 2020

Food insecurity is a challenge in the developing world, where many are finding healthy food inaccessible due to poverty. A pre-test, post-test design was applied to determine the impact of a vegetable gardening intervention in 25 experimental and 25 control households in Lesotho. Information about sociodemographic conditions and indicators of food security was collected by trained fieldworkers. As evidenced by the Living Poverty Index of 2.5, the sample was characterized by high levels of poverty. Although almost no households were scored very low or low using the Months of Adequate Household Food Provisioning (MAHFP) tool, less than half of households were categorized as food-secure. Household Dietary Diversity (HDD) showed infrequent intake of vegetables and fruits and regular intake of fats and sugar. After intervention, the percentage of households with a low HDD score improved significantly in the intervention group (12%) compared to the control group (40%) (95% CI (2.5%; 50.7%)). Despite this, the percentage of households that consumed vegetables during the previous day was still below 30%. Food gardens have the potential to improve availability of food and frequency of vegetable consumption, but harsh environmental conditions need to be considered.
Towards the Development of an Intervention to Address Social Determinants of Non-Communicable Disease in Kerala, India: A Mixed Methods Study
Authors: Webber Martin , Joubert Jacques , Fendt-Newlin Meredith , Madavanakadu Devassy Saju , Scaria Lorane , Benny Anuja Maria , Joubert Lynette
Published: November 2020

In India, cardiovascular disease (CVD), with hypertension as its foremost risk factor, has the highest prevalence rate of non-communicable diseases (NCDs) and a rising mortality. Previous research has found a clustering of behavioural and social risks pertaining to NCDs, though the latter are infrequently addressed in public health interventions in India. This paper reaches toward the development of a social intervention to address social determinants of NCD relating to hypertension and diabetes. We used Theory of Change (ToC) as a theoretical approach to programme design. Mixed methods were used, including qualitative interviews with community members (n = 20), Accredited Social Health Activists (n = 6) and health professionals (n = 8), and a stakeholder workshop (n = 5 participants). The recruitment of participants from one local area in Kerala enabled us to map service provision and gain a holistic understanding of how to utilise the existing workforce to target social risk factors. The findings suggest that social interventions need to focus on ensuring health behaviour information reaches all parts of the community, and that those with more social risk factors are identified and supported to engage with treatment. Further research is required to test the resulting intervention model.
Supermarkets in Cyberspace: A Conceptual Framework to Capture the Influence of Online Food Retail Environments on Consumer Behavior
Authors: Khandpur Neha , Zatz Laura Y. , Bleich Sara N. , Taillie Lindsey Smith , Orr Jennifer A. , Rimm Eric B. , Moran Alyssa J.
Published: November 2020

The rapid increase in online shopping and the extension of online food purchase and delivery services to federal nutrition program participants highlight the need for a conceptual framework capturing the influence of online food retail environments on consumer behaviors. This study aims to develop such a conceptual framework. To achieve this, mixed methods were used, including: (1) a literature review and development of an initial framework; (2) key informant interviews; (3) pilot testing and refinement of the draft framework; and (4) a group discussion with experts to establish content validity. The resulting framework captures both consumer- and retailer-level influences across the entire shopping journey, as well as the broader social, community, and policy context. It identifies important factors such as consumer demographic characteristics, preferences, past behaviors, and retailer policies and practices. The framework also emphasizes the dynamic nature of personalized marketing by retailers and customizable website content, and captures equity and transparency in retailer policies and practices. The framework draws from multiple disciplines, providing a foundation for understanding the impact of online food retail on dietary behaviors. It can be utilized to inform public health interventions, retailer practices, and governmental policies for creating healthy and equitable online food retail environments.
Crowd Detection in Mass Gatherings Based on Social Media Data: A Case Study of the 2014 Shanghai New Year’s Eve Stampede
Authors: Duan Jiexiong , Zhai Weixin , Cheng Chengqi
Published: November 2020

The Shanghai New Year’s Eve stampede on 31 December 2014, caused 36 deaths and 47 other injuries, generating attention from around the world. This research aims to explore crowd aggregation from the perspective of Sina Weibo check-in data and evaluate the potential of crowd detection based on social media data. We develop a framework using Weibo check-in data in three dimensions: the aggregation level of check-in data, the topic changes in posts and the sentiment fluctuations of citizens. The results show that the numbers of check-ins in all of Shanghai on New Years’ Eve is twice that of other days and that Moran’s I reaches a peak on this date, implying a spatial autocorrelation mode. Additionally, the results of topic modeling indicate that 72.4% of the posts were related to the stampede, reflecting public attitudes and views on this incident from multiple angles. Moreover, sentiment analysis based on Weibo posts illustrates that the proportion of negative posts increased both when the stampede occurred (40.95%) and a few hours afterwards (44.33%). This study demonstrates the potential of using geotagged social media data to analyze population spatiotemporal activities, especially in emergencies.
Reactive Oxygen Species: Modulators of Phenotypic Switch of Vascular Smooth Muscle Cells
Authors: Badran Adnan , Nasser Suzanne A. , Mesmar Joelle , El-Yazbi Ahmed F. , Bitto Alessandra , Fardoun Manal M. , Baydoun Elias , Eid Ali H.
Published: November 2020

Reactive oxygen species (ROS) are natural byproducts of oxygen metabolism in the cell. At physiological levels, they play a vital role in cell signaling. However, high ROS levels cause oxidative stress, which is implicated in cardiovascular diseases (CVD) such as atherosclerosis, hypertension, and restenosis after angioplasty. Despite the great amount of research conducted to identify the role of ROS in CVD, the image is still far from being complete. A common event in CVD pathophysiology is the switch of vascular smooth muscle cells (VSMCs) from a contractile to a synthetic phenotype. Interestingly, oxidative stress is a major contributor to this phenotypic switch. In this review, we focus on the effect of ROS on the hallmarks of VSMC phenotypic switch, particularly proliferation and migration. In addition, we speculate on the underlying molecular mechanisms of these cellular events. Along these lines, the impact of ROS on the expression of contractile markers of VSMCs is discussed in depth. We conclude by commenting on the efficiency of antioxidants as CVD therapies.
Ferroptosis Mechanisms Involved in Neurodegenerative Diseases
Authors: Reichert Cadiele Oliana , de Freitas Fábio Alessandro , Sampaio-Silva Juliana , Rokita-Rosa Leonardo , Barros Priscila de Lima , Levy Debora , Bydlowski Sérgio Paulo
Published: November 2020

Ferroptosis is a type of cell death that was described less than a decade ago. It is caused by the excess of free intracellular iron that leads to lipid (hydro) peroxidation. Iron is essential as a redox metal in several physiological functions. The brain is one of the organs known to be affected by iron homeostatic balance disruption. Since the 1960s, increased concentration of iron in the central nervous system has been associated with oxidative stress, oxidation of proteins and lipids, and cell death. Here, we review the main mechanisms involved in the process of ferroptosis such as lipid peroxidation, glutathione peroxidase 4 enzyme activity, and iron metabolism. Moreover, the association of ferroptosis with the pathophysiology of some neurodegenerative diseases, namely Alzheimer’s, Parkinson’s, and Huntington’s diseases, has also been addressed.
Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases
Authors: Jensen Nicole Jacqueline , Wodschow Helena Zander , Nilsson Malin , Rungby Jørgen
Published: November 2020

Under normal physiological conditions the brain primarily utilizes glucose for ATP generation. However, in situations where glucose is sparse, e.g., during prolonged fasting, ketone bodies become an important energy source for the brain. The brain’s utilization of ketones seems to depend mainly on the concentration in the blood, thus many dietary approaches such as ketogenic diets, ingestion of ketogenic medium-chain fatty acids or exogenous ketones, facilitate significant changes in the brain’s metabolism. Therefore, these approaches may ameliorate the energy crisis in neurodegenerative diseases, which are characterized by a deterioration of the brain’s glucose metabolism, providing a therapeutic advantage in these diseases. Most clinical studies examining the neuroprotective role of ketone bodies have been conducted in patients with Alzheimer’s disease, where brain imaging studies support the notion of enhancing brain energy metabolism with ketones. Likewise, a few studies show modest functional improvements in patients with Parkinson’s disease and cognitive benefits in patients with—or at risk of—Alzheimer’s disease after ketogenic interventions. Here, we summarize current knowledge on how ketogenic interventions support brain metabolism and discuss the therapeutic role of ketones in neurodegenerative disease, emphasizing clinical data.
Physiological Changes in Barley mlo-11 Powdery Mildew Resistance Conditioned by Tandem Repeat Copy Number
Authors: Ge Cynthia , Moolhuijzen Paula , Hickey Lee , Wentzel Elzette , Deng Weiwei , Dinglasan Eric G. , Ellwood Simon R.
Published: November 2020

Wild barley accessions have evolved broad-spectrum defence against barley powdery mildew through recessive mlo mutations. However, the mlo defence response is associated with deleterious phenotypes with a cost to yield and fertility, with implications for natural fitness and agricultural productivity. This research elucidates the mechanism behind a novel mlo allele, designated mlo-11(cnv2), which has a milder phenotype compared to standard mlo-11. Bisulphite sequencing and histone ChIP-seq analyses using near-isogenic lines showed pronounced repression of the Mlo promoter in standard mlo-11 compared to mlo-11(cnv2), with repression governed by 24 nt heterochromatic small interfering RNAs. The mlo-11(cnv2) allele appears to largely reduce the physiological effects of mlo while still endorsing a high level of powdery mildew resistance. RNA sequencing showed that this is achieved through only partly restricted expression of Mlo, allowing adequate temporal induction of defence genes during infection and expression close to wild-type Mlo levels in the absence of infection. The two mlo-11 alleles showed copy number proportionate oxidase and peroxidase expression levels during infection, but lower amino acid and aromatic compound biosynthesis compared to the null allele mlo-5. Examination of highly expressed genes revealed a common WRKY W-box binding motif (consensus ACCCGGGACTAAAGG) and a transcription factor more highly expressed in mlo-11 resistance. In conclusion, mlo-11(cnv2) appears to significantly mitigate the trade-off between mlo defence and normal gene expression.
Management of Iron Overload in Beta-Thalassemia Patients: Clinical Practice Update Based on Case Series
Authors: Pinto Valeria , Forni Gian
Published: November 2020

Thalassemia syndromes are characterized by the inability to produce normal hemoglobin. Ineffective erythropoiesis and red cell transfusions are sources of excess iron that the human organism is unable to remove. Iron that is not saturated by transferrin is a toxic agent that, in transfusion-dependent patients, leads to death from iron-induced cardiomyopathy in the second decade of life. The availability of effective iron chelators, advances in the understanding of the mechanism of iron toxicity and overloading, and the availability of noninvasive methods to monitor iron loading and unloading in the liver, heart, and pancreas have all significantly increased the survival of patients with thalassemia. Prolonged exposure to iron toxicity is involved in the development of endocrinopathy, osteoporosis, cirrhosis, renal failure, and malignant transformation. Now that survival has been dramatically improved, the challenge of iron chelation therapy is to prevent complications. The time has come to consider that the primary goal of chelation therapy is to avoid 24-h exposure to toxic iron and maintain body iron levels within the normal range, avoiding possible chelation-related damage. It is very important to minimize irreversible organ damage to prevent malignant transformation before complications set in and make patients ineligible for current and future curative therapies. In this clinical case-based review, we highlight particular aspects of the management of iron overload in patients with beta-thalassemia syndromes, focusing on our own experience in treating such patients. We review the pathophysiology of iron overload and the different ways to assess, quantify, and monitor it. We also discuss chelation strategies that can be used with currently available chelators, balancing the need to keep non-transferrin-bound iron levels to a minimum (zero) 24 h a day, 7 days a week and the risk of over-chelation.
Responses of DNA Mismatch Repair Proteins to a Stable G-Quadruplex Embedded into a DNA Duplex Structure
Authors: Pavlova Anzhela V. , Monakhova Mayya V. , Ogloblina Anna M. , Andreeva Natalia A. , Laptev Gennady Yu. , Polshakov Vladimir I. , Gromova Elizaveta S. , Zvereva Maria I. , Yakubovskaya Marianna G. , Oretskaya Tatiana S. , Kubareva Elena A. , Dolinnaya Nina G.
Published: November 2020

DNA mismatch repair (MMR) plays a crucial role in the maintenance of genomic stability. The main MMR protein, MutS, was recently shown to recognize the G-quadruplex (G4) DNA structures, which, along with regulatory functions, have a negative impact on genome integrity. Here, we studied the effect of G4 on the DNA-binding activity of MutS from Rhodobacter sphaeroides (methyl-independent MMR) in comparison with MutS from Escherichia coli (methyl-directed MMR) and evaluated the influence of a G4 on the functioning of other proteins involved in the initial steps of MMR. For this purpose, a new DNA construct was designed containing a biologically relevant intramolecular stable G4 structure flanked by double-stranded regions with the set of DNA sites required for MMR initiation. The secondary structure of this model was examined using NMR spectroscopy, chemical probing, fluorescent indicators, circular dichroism, and UV spectroscopy. The results unambiguously showed that the d(GGGT)4 motif, when embedded in a double-stranded context, adopts a G4 structure of a parallel topology. Despite strong binding affinities of MutS and MutL for a G4, the latter is not recognized by E. coli MMR as a signal for repair, but does not prevent MMR processing when a G4 and G/T mismatch are in close proximity.
Lipodystrophies—Disorders of the Fatty Tissue
Authors: Knebel Birgit , Müller-Wieland Dirk , Kotzka Jorg
Published: November 2020

Lipodystrophies are a heterogeneous group of physiological changes characterized by a selective loss of fatty tissue. Here, no fat cells are present, either through lack of differentiation, loss of function or premature apoptosis. As a consequence, lipids can only be stored ectopically in non-adipocytes with the major health consequences as fatty liver and insulin resistance. This is a crucial difference to being slim where the fat cells are present and store lipids if needed. A simple clinical classification of lipodystrophies is based on congenital vs. acquired and generalized vs. partial disturbance of fat distribution. Complications in patients with lipodystrophy depend on the clinical manifestations. For example, in diabetes mellitus microangiopathic complications such as nephropathy, retinopathy and neuropathy may develop. In addition, due to ectopic lipid accumulation in the liver, fatty liver hepatitis may also develop, possibly with cirrhosis. The consequences of extreme hypertriglyceridemia are typically acute pancreatitis or eruptive xanthomas. The combination of severe hyperglycemia with dyslipidemia and signs of insulin resistance can lead to premature atherosclerosis with its associated complications of coronary heart disease, peripheral vascular disease and cerebrovascular changes. Overall, lipodystrophy is rare with an estimated incidence for congenital (<1/1.000.000) and acquired (1–9/100.000) forms. Due to the rarity of the syndrome and the phenotypic range of metabolic complications, only studies with limited patient numbers can be considered. Experimental animal models are therefore useful to understand the molecular mechanisms in lipodystrophy and to identify possible therapeutic approaches.
Sleep Apnoea Adverse Effects on Cancer: True, False, or Too Many Confounders?
Authors: Gozal David , Almendros Isaac , Phipps Amanda I. , Campos-Rodriguez Francisco , Martínez-García Miguel A. , Farré Ramon
Published: November 2020

Obstructive sleep apnoea (OSA) is a prevalent disorder associated with increased cardiovascular, metabolic and neurocognitive morbidity. Recently, an increasing number of basic, clinical and epidemiological reports have suggested that OSA may also increase the risk of cancer, and adversely impact cancer progression and outcomes. This hypothesis is convincingly supported by biological evidence linking certain solid tumours and hypoxia, as well as by experimental studies involving cell and animal models testing the effects of intermittent hypoxia and sleep fragmentation that characterize OSA. However, the clinical and epidemiological studies do not conclusively confirm that OSA adversely affects cancer, even if they hold true for specific cancers such as melanoma. It is likely that the inconclusive studies reflect that they were not specifically designed to test the hypothesis or because of the heterogeneity of the relationship of OSA with different cancer types or even sub-types. This review critically focusses on the extant basic, clinical, and epidemiological evidence while formulating proposed directions on how the field may move forward.
The Search for New Anticonvulsants in a Group of (2,5-Dioxopyrrolidin-1-yl)(phenyl)Acetamides with Hybrid Structure—Synthesis and In Vivo/In Vitro Studies
Authors: Abram Michał , Jakubiec Marcin , Rapacz Anna , Mogilski Szczepan , Latacz Gniewomir , Kamiński Rafał M. , Kamiński Krzysztof
Published: November 2020

Epilepsy belongs to the most common and debilitating neurological disorders with multifactorial pathophysiology and a high level of drug resistance. Therefore, with the aim of searching for new, more effective, and/or safer therapeutics, we discovered a focused series of original hybrid pyrrolidine-2,5-dione derivatives with potent anticonvulsant properties. We applied an optimized coupling reaction yielding several hybrid compounds that showed broad-spectrum activity in widely accepted animal seizure models, namely, the maximal electroshock (MES) test and the psychomotor 6 Hz (32 mA) seizure model in mice. The most potent anticonvulsant activity and favorable safety profile was demonstrated for compound 30 (median effective dose (ED50) MES = 45.6 mg/kg, ED50 6 Hz (32 mA) = 39.5 mg/kg, median toxic dose (TD50) (rotarod test) = 162.4 mg/kg). Anticonvulsant drugs often show activity in pain models, and compound 30 was also proven effective in the formalin test of tonic pain, the capsaicin-induced pain model, and the oxaliplatin (OXPT)-induced neuropathic pain model in mice. Our studies showed that the most plausible mechanism of action of 30 involves inhibition of calcium currents mediated by Cav1.2 (L-type) channels. Importantly, 30 revealed high metabolic stability on human liver microsomes, negligible hepatotoxicity, and relatively weak inhibition of CYP3A4, CYP2D6, and CYP2C9 isoforms of cytochrome P450, compared to reference compounds. The promising in vivo activity profile and drug-like properties of compound 30 make it an interesting candidate for further preclinical development.
Diagnostic and Therapeutic Implications of microRNAs in Non-Small Cell Lung Cancer
Authors: Ahn Young-Ho , Ko Yoon Ho
Published: November 2020

microRNAs (miRNAs), endogenous suppressors of target mRNAs, are deeply involved in every step of non-small cell lung cancer (NSCLC) development, from tumor initiation to progression and metastasis. They play roles in cell proliferation, apoptosis, angiogenesis, epithelial-to-mesenchymal transition, migration, invasion, and metastatic colonization, as well as immunosuppression. Due to their versatility, numerous attempts have been made to use miRNAs for clinical applications. miRNAs can be used as cancer subtype classifiers, diagnostic markers, drug-response predictors, prognostic markers, and therapeutic targets in NSCLC. Many challenges remain ahead of their actual clinical application; however, when achieved, the use of miRNAs in the clinic is expected to enable great progress in the diagnosis and treatment of patients with NSCLC.
Genetic Background Underlying 5-HT1A Receptor Functioning Affects the Response to Fluoxetine
Authors: Kondaurova Elena M. , Rodnyy Alexander Ya. , Ilchibaeva Tatiana V. , Tsybko Anton S. , Eremin Dmitry V. , Antonov Yegor V. , Popova Nina K. , Naumenko Vladimir S.
Published: November 2020

The influence of genetic background on sensitivity to drugs represents a topical problem of personalized medicine. Here, we investigated the effect of chronic (20 mg/kg, 14 days, i.p.) antidepressant fluoxetine treatment on recombinant B6-M76C mice, differed from control B6-M76B mice by CBA-derived 102.73–110.56 Mbp fragment of chromosome 13 and characterized by altered sensitivity of 5-HT1A receptors to chronic 8-OH-DPAT administration and higher 5-HT1A receptor mRNA levels in the frontal cortex and hippocampus. Significant changes in the effects of fluoxetine treatment on behavior and brain 5-HT system in recombinant B6-M76C mice were revealed. In contrast to B6-M76B mice, in B6-M76C mice, fluoxetine produced pro-depressive effects, assessed in a forced swim test. Fluoxetine decreased 5-HT1A receptor mRNA levels in the cortex and hippocampus, reduced 5-HT1A receptor protein levels and increased receptor silencer Freud-1 protein levels in the hippocampus of B6-M76C mice. Fluoxetine increased mRNA levels of the gene encoding key enzyme for 5-HT synthesis in the brain, tryptophan hydroxylase-2, but decreased tryptophan hydroxylase-2 protein levels in the midbrain of B6-M76B mice. These changes were accompanied by increased expression of the 5-HT transporter gene. Fluoxetine reduced 5-HT and 5-HIAA levels in cortex, hippocampus and midbrain of B6-M76B and in cortex and midbrain of B6-M76C; mice. These data demonstrate that changes in genetic background may have a dramatic effect on sensitivity to classic antidepressants from the Selective Serotonin Reuptake Inhibitors family. Additionally, the results provide new evidence confirming our idea on the disrupted functioning of 5-HT1A autoreceptors in the brains of B6-M76C mice, suggesting these mice as a model of antidepressant resistance.
Synthesis of Novel Tetra(µ3-Methoxo) Bridged with [Cu(II)-O-Cd(II)] Double-Open-Cubane Cluster: XRD/HSA-Interactions, Spectral and Oxidizing Properties
Authors: Titi Abderrahim , Messali Mouslim , Touzani Rachid , Fettouhi Mohammed , Zarrouk Abdelkader , Al-Zaqri Nabil , Alsalme Ali , Alharthi Fahad A. , Alsyahi Amjad , Warad Ismail
Published: November 2020

A new double-open-cubane core Cd(II)-O-Cu(II) bimetallic ligand mixed cluster of type [Cl2Cu4Cd2(NNO)6(NN)2(NO3)2].CH3CN was made available in EtOH/CH3CN solution. The 1-hydroxymethyl-3,5-dimethylpyrazole (NNOH) and 3,5-dimethylpyrazole (NNH) act as N,O-polydentate anion ligands in coordinating the Cu(II) and Cd(II) centers. The structure of the cluster in the solid state was proved by XRD study and confirmed in the liquid state by UV-vis analysis. The XRD result supported the construction of two octahedral and one square pyramid geometries types around the four Cu(II) centers and only octahedral geometry around Cd(II) two centers. Interestingly, NNOH ligand acts as a tetra-µ3-oxo and tri-µ2-oxo ligand; meanwhile, the N-N in NNH acts as classical bidentate anion/neutral ligands. The interactions in the lattice were detected experimentally by the XRD-packing result and computed via Hirschfeld surface analysis (HSA). The UV-vis., FT-IR and Energy Dispersive X-ray (EDX), supported the desired double-open cubane cluster composition. The oxidation potential of the desired cluster was evaluated using a 3,5-DTB-catechol 3,5-DTB-quinone as a catecholase model reaction.
Changes in microRNA Expression in the Cochlear Nucleus and Inferior Colliculus after Acute Noise-Induced Hearing Loss
Authors: Park Sohyeon , Han Seung Hee , Kim Byeong-Gon , Suh Myung-Whan , Lee Jun Ho , Oh Seung Ha , Park Moo Kyun
Published: November 2020

Noise-induced hearing loss (NIHL) can lead to secondary changes that induce neural plasticity in the central auditory pathway. These changes include decreases in the number of synapses, the degeneration of auditory nerve fibers, and reorganization of the cochlear nucleus (CN) and inferior colliculus (IC) in the brain. This study investigated the role of microRNAs (miRNAs) in the neural plasticity of the central auditory pathway after acute NIHL. Male Sprague–Dawley rats were exposed to white band noise at 115 dB for 2 h, and the auditory brainstem response (ABR) and morphology of the organ of Corti were evaluated on days 1 and 3. Following noise exposure, the ABR threshold shift was significantly smaller in the day 3 group, while wave II amplitudes were significantly larger in the day 3 group compared to the day 1 group. The organ of Corti on the basal turn showed evidence of damage and the number of surviving outer hair cells was significantly lower in the basal and middle turn areas of the hearing loss groups relative to controls. Five and three candidate miRNAs for each CN and IC were selected based on microarray analysis and quantitative reverse transcription PCR (RT-qPCR). The data confirmed that even short-term acoustic stimulation can lead to changes in neuroplasticity. Further studies are needed to validate the role of these candidate miRNAs. Such miRNAs may be used in the early diagnosis and treatment of neural plasticity of the central auditory pathway after acute NIHL.
Short Disordered Epitope of CRTAM Ig-Like V Domain as a Potential Target for Blocking Antibodies
Authors: Vázquez-Martínez Julio Angel , Gómez-Lim Miguel Angel , Morales-Ríos Edgar , Gonzalez-y-Merchand Jorge Alberto , Ortiz-Navarrete Vianney
Published: November 2020

Class-I Restricted T Cell-Associated Molecule (CRTAM) is a protein that is expressed after T cell activation. The interaction of CRTAM with its ligand, nectin-like 2 (Necl2), is required for the efficient production of IL-17, IL-22, and IFNγ by murine CD4 T cells, and it plays a role in optimal CD8 T and NK cell cytotoxicity. CRTAM promotes the pro-inflammatory cytokine profile; therefore, it may take part in the immunopathology of autoimmune diseases such as diabetes type 1 or colitis. Thus, antibodies that block the interaction between CRTAM and Necl2 would be useful for controlling the production of these inflammatory cytokines. In this work, using bioinformatics predictions, we identified three short disordered epitopes (sDE1-3) that are located in the Ig-like domains of murine CRTAM and are conserved in mammalian species. We performed a structural analysis by molecular dynamics simulations of sDE1 (QHPALKSSKY, Ig-like V), sDE2 (QRNGEKSVVK, Ig-like C1), and sDE3 (CSTERSKKPPPQI, Ig-like C1). sDE1, which is located within a loop of the contact interface of the heterotypic interaction with Nectl2, undergoes an order–disorder transition. On the contrary, even though sDE2 and sDE3 are flexible and also located within loops, they do not undergo order–disorder transitions. We evaluated the immunogenicity of sDE1 and sDE3 through the expression of these epitopes in chimeric L1 virus-like particles. We confirmed that sDE1 induces polyclonal antibodies that recognize the native folding of CRTAM expressed in activated murine CD4 T cells. In contrast, sDE3 induces polyclonal antibodies that recognize the recombinant protein hCRTAM-Fc, but not the native CRTAM. Thus, in this study, an exposed disordered epitope in the Ig-like V domain of CRTAM was identified as a potential site for therapeutic antibodies.
Rbm38 Reduces the Transcription Elongation Defect of the SMEK2 Gene Caused by Splicing Deficiency
Authors: Muraoka Shintaro , Fukumura Kazuhiro , Hayashi Megumi , Kataoka Naoyuki , Mayeda Akila , Kaida Daisuke
Published: November 2020

Pre-mRNA splicing is an essential mechanism for ensuring integrity of the transcriptome in eukaryotes. Therefore, splicing deficiency might cause a decrease in functional proteins and the production of nonfunctional, aberrant proteins. To prevent the production of such aberrant proteins, eukaryotic cells have several mRNA quality control mechanisms. In addition to the known mechanisms, we previously found that transcription elongation is attenuated to prevent the accumulation of pre-mRNA under splicing-deficient conditions. However, the detailed molecular mechanism behind the defect in transcription elongation remains unknown. Here, we showed that the RNA binding protein Rbm38 reduced the transcription elongation defect of the SMEK2 gene caused by splicing deficiency. This reduction was shown to require the N- and C-terminal regions of Rbm38, along with an important role being played by the RNA-recognition motif of Rbm38. These findings advance our understanding of the molecular mechanism of the transcription elongation defect caused by splicing deficiency.
Genetically Encoded Red Photosensitizers with Enhanced Phototoxicity
Authors: Gorbachev Dmitry A. , Staroverov Dmitry B. , Lukyanov Konstantin A. , Sarkisyan Karen S.
Published: November 2020

Genetically encoded photosensitizers are increasingly used as optogenetic tools to control cell fate or trigger intracellular processes. A monomeric red fluorescent protein called SuperNova has been recently developed, however, it demonstrates suboptimal characteristics in most phototoxicity-based applications. Here, we applied directed evolution to this protein and identified SuperNova2, a protein with S10R substitution that results in enhanced brightness, chromophore maturation and phototoxicity in bacterial and mammalian cell cultures.
Contribution of Extensive Farming Practices to the Supply of Floral Resources for Pollinators
Authors: Langlois Alban , Jacquemart Anne-Laure , Piqueray Julien
Published: November 2020

Intensification of agricultural practices leads to a loss of floral resources and drives pollinator decline. Extensive agricultural practices are encouraged in Europe and contribute to the preservation of biodiversity. We compared three agricultural landscapes without extensive farming practices with three adjacent landscapes containing organic crops and extensively managed grasslands in Belgium. Nectar resource availability and plant–pollinator interactions were monitored from April to June. Flower density per plant species and plant–pollinator interactions were recorded in different landscape elements. In April, the main nectar resources were provided by linear elements such as hedgerows and forest edges. Nectar production peaked in May, driven by intensive grasslands and mass-flowering crops. Occurrence of extensive grasslands and organic crops significantly alleviated the nectar resource gap observed in June. Our results underscore the importance of maintaining landscape heterogeneity for continuous flower resources and highlight the specific role of extensive grasslands and organic crops in June.
Hospital Resources May Be an Important Aspect of Mortality Rate among Critically Ill Patients with COVID-19: The Paradigm of Greece
Authors: Routsi Christina , Magira Eleni , Kokkoris Stelios , Siembos Ilias , Vrettou Charikleia , Zervakis Dimitris , Ischaki Eleni , Malahias Sotiris , Sigala Ioanna , Asimakos Andreas , Daidou Theodora , Kaltsas Panagiotis , Douka Evangelia , Sotiriou Adamandia , Markaki Vassiliki , Temberikidis Prodromos , Koroneos Apostolos , Politis Panagiotis , Mastora Zafiria , Dima Efrosini , Tsoutsouras Theodoros , Papahatzakis Ioannis , Gioni Panagiota , Strilakou Athina , Maragouti Aikaterini , Mizi Eleftheria , Kanavou Ageliki , Sarri Aikaterini , Gavrielatou Evdokia , Mentzelopoulos Spyros , Kalomenidis Ioannis , Papastamopoulos Vassilios , Kotanidou Anastasia , Zakynthinos Spyros
Published: November 2020

For critically ill patients with coronavirus disease 2019 (COVID-19) who require intensive care unit (ICU) admission, extremely high mortality rates (even 97%) have been reported. We hypothesized that overburdened hospital resources by the extent of the pandemic rather than the disease per se might play an important role on unfavorable prognosis. We sought to determine the outcome of such patients admitted to the general ICUs of a hospital with sufficient resources. We performed a prospective observational study of adult patients with COVID-19 consecutively admitted to COVID—designated ICUs at Evangelismos Hospital, Athens, Greece. Among 50 patients, ICU and hospital mortality was 32% (16/50). Median PaO2/FiO2 was 121 mmHg (interquartile range (IQR), 86–171 mmHg) and most patients had moderate or severe acute respiratory distress syndrome (ARDS). Hospital resources may be an important aspect of mortality rates, since severely ill COVID-19 patients with moderate and severe ARDS may have understandable mortality, provided that they are admitted to general ICUs without limitations on hospital resources.
One-Stage Extension Shortening Osteotomy for Syndromic Camptodactyly
Authors: Park Byoung Kyu , Kim Hyun Woo , Park Hoon , Park Min Jung , Hong Kee-Bum , Park Kun Bo
Published: November 2020

Syndromic camptodactyly often affects multiple fingers, and severe deformities are common compared to idiopathic camptodactyly. This study aimed to evaluate the use of a one-stage extension shortening osteotomy of the proximal phalanx for patients with syndromic camptodactyly without tendon surgery. Forty-nine cases of syndromic camptodactyly were included. Forty fingers (81.6%) were associated with arthrogryposis multiplex congenita, and nine (18.4%) with other syndromes. Six fingers presented with a moderate form (30° to 60°) of camptodactyly, whereas 43 fingers manifested the severe form (>60°). The mean age at the time of surgery was 8.5 years, and the patients were followed for a mean of 3.9 years. The mean length of the shortening of the proximal phalanx was 4.9 mm, which averaged 17.8% of the proximal phalanx’s original preoperative length. The mean operative time was 25.8 min, and the PIP joint was fixed using Kirschner wires with an average flexion position of 7.6°. The mean flexion contracture improved from 76° preoperatively to 41° postoperatively. The mean preoperative active arc of motion was 23°, which improved to 49° postoperatively. A one-stage extension shortening osteotomy is a straightforward and effective technique for the improvement of finger function through the indirect lengthening of volar structures without the flexor tendon lengthening. The osteotomy could simultaneously correct bony abnormalities. This simple procedure is especially suitable for surgery on multiple fingers in patients with syndromic camptodactyly.
Tomotherapy as an Alternative Irradiative Treatment for Complicated Keloids
Authors: Lin Yu-Fang , Shueng Pei-Wei , Roan Tyng-Luen , Chang Dun-Hao , Yu Yen-Chen , Chang Che-Wei , Kuo An-Ta , Chen Yo-Shen , Hsiao Hsiu-Wen , Tien Hui-Ju , Hsieh Chen-Hsi
Published: November 2020

The aim of this study was to investigate the treatment of complicated keloids with helical tomotherapy (HT) and electron beam radiotherapy. From July 2018 to September 2018, 11 patients with 23 keloid lesions treated with HT were enrolled. Additionally, 11 patients with 20 lesions treated with electron beam radiotherapy in the same period were enrolled. Patients in both groups were treated within 24 h after surgical excision of the keloid lesion with 13.5 Gy in three consecutive daily fractions. The median follow-up period was 15 months. The local control rate was 91.3% and 80% in the HT group and the electron beam group, respectively. No acute adverse effects were observed in either group, but most patients exhibited pigmentation. No radiation-induced cancer occurred in these patients up to the time of this report. Pain and pruritus improved for all patients and more obviously for three patients with complicated keloids treated with HT. The measured surface dose was 103.7–112.5% and 92.8–97.6% of the prescribed dose in the HT group and the electron beam group, respectively. HT can be considered an alternative in cases where it is not feasible to use multiple electron fields, due to encouraging clinical outcomes.
The Body I Live in. Perceptions and Meanings of Body Dissatisfaction in Young Transgender Adults: A Qualitative Study
Authors: Mirabella Marta , Giovanardi Guido , Fortunato Alexandro , Senofonte Giulia , Lombardo Francesco , Lingiardi Vittorio , Speranza Anna Maria
Published: November 2020

Body dissatisfaction in individuals with Gender Incongruence (GI) represents a primary source of suffering. Several studies have highlighted how this suffering has psychological, physical, and biological implications. This work aims to explore experiences related to body dissatisfaction and investigate the issues associated with living in a body perceived as incongruent for individuals with GI. Thirty-six individuals, aged between 18 and 30 years old and at stage T0 of hormone treatment, participated in the study. Body dissatisfaction and experiences related to it were investigated using the Clinical Diagnostic Interview. The Consensual Qualitative Research methodology was applied to the transcripts of the interviews. Several themes emerged: experiences with GI development, experiences with puberty and bodily changes, perception of one’s body, psychological problems and complex behavioral patterns related to body dissatisfaction. Results pointed out the complexity implied in the relationship with one’s body for individuals with GI, highlighting specific aspects of body dissatisfaction among these individuals (e.g., eating disorders, sexual difficulties, social withdrawal). This study underlines the need for a deeper understanding of some aspects of GI to better define guidelines for a correct assessment of it. In this way it will be easier to avoid negative outcomes for the psychological and general health of transgender people.
Optimization of a Multiple Injection System in a Marine Diesel Engine through a Multiple-Criteria Decision-Making Approach
Authors: Lamas Maria Isabel , Castro-Santos Laura , Rodriguez Carlos G.
Published: November 2020

In this work, a numerical model was developed to analyze the performance and emissions of a marine diesel engine, the Wärtsilä 6L 46. This model was validated using experimental measurements and was employed to analyze several pre-injection parameters such as pre-injection rate, duration, and starting instant. The modification of these parameters may lead to opposite effects on consumption and/or emissions of nitrogen oxides (NOx), carbon monoxide (CO), and hydrocarbons (HC). According to this, the main goal of the present work is to employ a multiple-criteria decision-making (MCDM) approach to characterize the most appropriate injection pattern. Since determining the criteria weights significantly influences the overall result of a MCDM problem, a subjective weighting method was compared with four objective weighting methods: entropy, CRITIC (CRiteria Importance Through Intercriteria Correlation), variance, and standard deviation. The results showed the importance of subjectivism over objectivism in MCDM analyses. The CRITIC, variance, and standard deviation methods assigned more importance to NOx emissions and provided similar results. Nevertheless, the entropy method assigned more importance to consumption and provided a different injection pattern.
Dynamic Regulation of Peroxisomes and Mitochondria during Fungal Development
Authors: Navarro-Espíndola Raful , Suaste-Olmos Fernando , Peraza-Reyes Leonardo
Published: November 2020

Peroxisomes and mitochondria are organelles that perform major functions in the cell and whose activity is very closely associated. In fungi, the function of these organelles is critical for many developmental processes. Recent studies have disclosed that, additionally, fungal development comprises a dynamic regulation of the activity of these organelles, which involves a developmental regulation of organelle assembly, as well as a dynamic modulation of the abundance, distribution, and morphology of these organelles. Furthermore, for many of these processes, the dynamics of peroxisomes and mitochondria are governed by common factors. Notably, intense research has revealed that the process that drives the division of mitochondria and peroxisomes contributes to several developmental processes—including the formation of asexual spores, the differentiation of infective structures by pathogenic fungi, and sexual development—and that these processes rely on selective removal of these organelles via autophagy. Furthermore, evidence has been obtained suggesting a coordinated regulation of organelle assembly and dynamics during development and supporting the existence of regulatory systems controlling fungal development in response to mitochondrial activity. Gathered information underscores an important role for mitochondrial and peroxisome dynamics in fungal development and suggests that this process involves the concerted activity of these organelles.
Biomarkers for Alzheimer’s Disease: Where Do We Stand and Where Are We Going?
Authors: Villa Chiara
Published: November 2020

Alzheimer’s disease (AD) is an age-related neurodegenerative and progressive disorder representing the most common form of dementia in older adults [...]
Fault Detection Based on Parity Equations in Multiple Lane Road Car-Following Models Using Bayesian Lane Change Estimation
Authors: Pop Mădălin-Dorin , Proștean Octavian , Proștean Gabriela
Published: November 2020

One of the current topics of interest in transportation science is the use of intelligent computation and IoT (Internet of Things) technologies. Researchers have proposed many approaches using these concepts, but the most widely used concept in road traffic modeling at the microscopic level is the car-following model. Knowing that the standard car-following model is single lane-oriented, the purpose of this paper is to present a fault detection analysis of the extension to a multiple lane car-following model that uses the Bayesian reasoning concept to estimate lane change behavior. After the application of the latter model on real traffic data retrieved from inductive loops placed on a road network, fault detection using parity equations was used. The standard car-following model applied separately for each lane showed the ability to perform a lane change action and to incorporate a new vehicle into the current lane. The results will highlight the advantages and the critical points of influence in the use of a multiple lane car-following model based on probabilistic estimated lane changes. Additionally, this research applied fault detection based on parity equations for the proposed model. The purpose was to deliver an overview of the faults introduced by the behavior of vehicles in adjacent lanes on the behavior of the target vehicle.
Analysis of Human Mutations in the Supernumerary Subunits of Complex I
Authors: Dang Quynh-Chi L. , Phan Duong H. , Johnson Abigail N. , Pasapuleti Mukund , Alkhaldi Hind A. , Zhang Fang , Vik Steven B.
Published: November 2020

Complex I is the largest member of the electron transport chain in human mitochondria. It comprises 45 subunits and requires at least 15 assembly factors. The subunits can be divided into 14 “core” subunits that carry out oxidation–reduction reactions and proton translocation, as well as 31 additional supernumerary (or accessory) subunits whose functions are less well known. Diminished levels of complex I activity are seen in many mitochondrial disease states. This review seeks to tabulate mutations in the supernumerary subunits of humans that appear to cause disease. Mutations in 20 of the supernumerary subunits have been identified. The mutations were analyzed in light of the tertiary and quaternary structure of human complex I (PDB id = 5xtd). Mutations were found that might disrupt the folding of that subunit or that would weaken binding to another subunit. In some cases, it appeared that no protein was made or, at least, could not be detected. A very common outcome is the lack of assembly of complex I when supernumerary subunits are mutated or missing. We suggest that poor assembly is the result of disrupting the large network of subunit interactions that the supernumerary subunits typically engage in.