bluuebunny/crossref_metadata_2025 huggingface dataset:
Testing the Shielding Effect of Intergenerational Contact against Ageism in the Workplace: A Canadian Study
Authors: Lagacé Martine , Donizzetti Anna Rosa , Van de Beeck Lise , Bergeron Caroline D. , Rodrigues-Rouleau Philippe , St-Amour Audrey
Published: April 2022

Negative outcomes of ageism in the context of the Canadian labor market are well documented. Older workers remain the target of age-based stereotypes and attitudes on the part of employers. This study aims at assessing (1) the extent to which quality and quantity intergroup contacts between younger and older workers as well as knowledge-sharing practices reduce ageist attitudes, in turn (2) how a decrease in ageist attitudes increase the level of workers’ engagement and intentions to remain in the organization. Data were collected from 603 Canadian workers (aged 18 to 68 years old) from private and public organizations using an online survey measuring concepts under study. Results of a path analysis suggest that intergroup contacts and knowledge-sharing practices are associated with positive attitudes about older workers. More so, positive attitudes about older workers generate higher levels of work engagement, which in turn are associated with stronger intentions to remain with the organization. However, positive attitudes about older workers had no effect on intentions to remain in the workplace. Results are discussed in light of the intergroup contact theory.
Research on Maternal Service Area and Referral System in Hubei Province, China
Authors: Bai Lingyao , Cheng Yang , Tao Zhuolin , Feng Ling , Wang Shaoshuai , Zeng Yu
Published: April 2022

Hospital service area (HSA) and Hospital referral region (HRR) are significant in organizing maternal care resources in hierarchical medical systems. This quantitative study aims to delineate HAS and HRR by using obstetrics medical record data reflecting patients’ medical behavior to improve the efficiency of the utilization of medical resources. The Dartmouth method and an improved version that considers the administrative division was applied to delineate HSA and HRR by using the obstetrics medical records in Hubei Province of China in 2016. The result shows that 117 Dartmouth HSAs have a strong correlation with the county boundaries and 22 Dartmouth HRRs are highly coincident with the prefecture boundaries in Hubei. In addition, 25 improved Dartmouth HRRs within prefecture boundaries and core areas serving patients across prefecture boundaries have been identified. Based on the above results, two sets of hierarchical healthcare systems were constructed, respectively, which can provide methods and references for delineating HAS and HRR in the hierarchical medical systems in other regions of China and developing countries. The findings of this study shed light on future research and policymaking in the spatial organization of medical resources for improving the efficiency and equity in maternal care delivery.
Effects of Forest-Based Interventions on Mental Health: A Meta-Analysis of Randomized Controlled Trials
Authors: Kang Mi-Jung , Kim Hyun-Sun , Kim Ji-Yeon
Published: April 2022

Forest-based interventions are a promising alternative therapy for enhancing mental health. The current study investigated the effects of forest therapy on anxiety, depression, and negative and positive mental condition through a meta-analysis of recent randomized controlled trials, using the PRISMA guideline. Of 825 articles retrieved from databases including PubMed, EMBASE, CINAHL, Cochrane, and PsycINFO, 6 met the inclusion criteria. The results of this study showed that forest-based interventions improved the mental health of participants in the intervention groups when compared to those in the control groups. Thirty-four outcome variables were analyzed from six studies. The overall effect size of the forest therapy programs was 1.25 (95% CI = 0.93–1.57, p < 0.001), which was large and statistically significant. These findings imply that forest-based interventions can improve mental health as a nonpharmacological intervention. This study is significant in that it is a meta-analysis of mental health that included only high-quality domestic and international RCTs. In future studies, more RCTs related to various forest interventions and studies involving many participants should be undertaken, which will complement heterogeneity in future meta-analysis studies.
Seasonal Distribution, Composition, and Inventory of Plastic Debris on the Yugang Park Beach in Zhanjiang Bay, South China Sea
Authors: Zhang Peng , Wei Shanshan , Zhang Jibiao , Zhong Huifeng , Wang Shujia , Jian Qiying
Published: April 2022

Plastic debris contamination in marine environments is a global problem that poses a considerable threat to the sustainability and health of coastal ecosystems. Marine beaches, as the key zones where terrestrial plastic debris reach coastal waters, are faced with the increasing pressures of human activities. In this study, we explored the distribution, composition, and inventory of plastic debris over seasonal and tidal zones at the Yugang Park Beach (YPB) in Zhanjiang Bay, South China Sea, to provide a baseline for plastic debris on a marine beach. The results showed mean abundance of plastic debris in summer (6.00 ± 2.10 items/m2) was significantly greater than that in winter (3.75 ± 2.12 items/m2). In addition, the composition of plastic debris ranged in size mainly from 1 to 5 mm and 0.5 to 2.5 cm in winter and summer, respectively. In terms of composition, white plastic debris was the most common (81.1%), and foam was the most abundant (64.4%). Moreover, there was a significant relationship between the abundance of plastic debris and sand grain size fraction (p < 0.05), implying the abundances of microplastic debris were more easily impacted by sand grain size (>2 mm). In total inventory, there were about 1.18 × 105 and 2.95 × 105 items of plastic debris on the YPB in winter and summer, respectively. The tidal variation and human activities are responsible for the plastic debris accumulation. This study provided a method to quantify the inventory of plastic debris on a beach and could be helpful to consider regional tidal variations and critical source areas for effective plastic debris clean-up.
White-Tailed Deer Spatial Distribution in Relation to ‘4-Poster’ Tick Control Devices in Suburbia
Authors: Roden-Reynolds Patrick , Kent Cody M. , Li Andrew Y. , Mullinax Jennifer M.
Published: April 2022

Deer are keystone hosts for adult ticks and have enabled the spread of tick distributions. The ‘4-Poster’ deer bait station was developed by the United States Department of Agriculture to control ticks feeding on free-ranging deer. Although effective in certain scenarios, ‘4-Poster’ deer treatment stations require the use of bait to attract deer to one location, which may cause increased deer disease transmission rates and habitat damage. To better understand and manage the impact of baited ‘4-Poster’ stations on deer movements, we captured and GPS-monitored 35 deer as part of an integrated pest management project. Fifteen ‘4-Poster’ stations were deployed among three suburban county parks to control ticks. To quantify the effects of ‘4-Poster’ stations, we calculated deer movement metrics before and after feeders were filled with whole kernel corn, and we gathered information on visitation rates to feeders. Overall, 83.3% of collared deer visited a feeder and revisited approximately every 5 days. After feeders were refilled, collared deer were ~5% closer to feeders and conspecifics than before filling. Males used a higher percentage of available feeders and visited them more throughout the deployment periods. Although these nuanced alterations in behavior may not be strong enough to increase local deer abundance, in light of infectious diseases affecting deer populations and effective ‘4-Poster’ densities, the core range shifts and clustering after refilling bait may be a cause for concern. As such, trade-offs between conflicting management goals should be carefully considered when deploying ‘4-Poster’ stations.
A Gas Pressure Prediction Model of the Excavation Face Based on Gas Emission
Authors: Chen Liang , Liu Qi
Published: April 2022

Gas pressure is one of the important factors related to the occurrence of coal and gas outburst disasters. The accurate gas pressure forecasting is of significance for the prevention and control of a gas disaster. In this work, a gas pressure prediction model based on the sources of gas emissions was established. The verified results show that the predicted gas pressure was roughly consistent with the actual situation. This model could meet the needs of engineering projects. Coal and gas outburst dynamic phenomenon are successfully predicted in an engineering application using the model. Overall, the prediction of coal and gas outburst using the gas pressure model achieves a continuous and dynamic effect. The model can overcome both the static and sampling shortcomings of traditional methods and solve the difficulty of coal and gas outburst prediction at the excavation face. With its broad applicability and potential prospects, the model is of great importance for guiding gas drainage, and the prevention of coal and gas outburst disasters.
Regulation of Th17/Treg Balance by 27-Hydroxycholesterol and 24S-Hydroxycholesterol Correlates with Learning and Memory Ability in Mice
Authors: Wang Tao , Cui Shanshan , Hao Ling , Liu Wen , Wang Lijing , Ju Mengwei , Feng Wenjing , Xiao Rong
Published: April 2022

Dysregulation of cholesterol metabolism and its oxidative products—oxysterols—in the brain is known to be associated with neurodegenerative diseases. It is well-known that 27-hydroxycholesterol (27-OHC) and 24S-hydroxycholesterol (24S-OHC) are the main oxysterols contributing to the pathogenesis of Alzheimer’s disease (AD). However, the molecular mechanism of how 27-OHC and 24S-OHC cause cognitive decline remains unclear. To verify whether 27-OHC and 24S-OHC affect learning and memory by regulating immune responses, C57BL/6J mice were subcutaneously injected with saline, 27-OHC, 24S-OHC, 27-OHC+24S-OHC for 21 days. The oxysterols level and expression level of related metabolic enzymes, as well as the immunomodulatory factors were measured. Our results indicated that 27-OHC-treated mice showed worse learning and memory ability and higher immune responses, but lower expression level of interleukin-10 (IL-10) and interferon (IFN-λ2) compared with saline-treated mice, while 24S-OHC mice performed better in the Morris water maze test than control mice. No obvious morphological lesion was observed in these 24S-OHC-treated mice. Moreover, the expression level of interleukin-17A (IL-17A), granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage inflammatory protein 3α (MIP-3α) were significantly decreased after 24S-OHC treatment. Notably, compared with 27-OHC group, mice treated with 27-OHC+24S-OHC showed higher brain 24S-OHC level, accompanied by increased CYP46A1 expression level while decreased CYP7B1, retinoic acid-related orphan receptor gamma t (RORγt) and IL-17A expression level. In conclusion, our study indicated that 27-OHC is involved in regulating the expression of RORγt, disturbing Th17/Treg balance-related immune responses which may be associated with the learning and memory impairment in mice. In contrast, 24S-OHC is neuroprotective and attenuates the neurotoxicity of 27-OHC.
Plasma Proteomic Profile of Patients with Tick-Borne Encephalitis and Co-Infections
Authors: Gęgotek Agnieszka , Moniuszko-Malinowska Anna , Groth Monika , Pancewicz Sławomir , Czupryna Piotr , Dunaj Justyna , Atalay Sinemyiz , Radziwon Piotr , Skrzydlewska Elżbieta
Published: April 2022

Despite the increasing number of patients suffering from tick-borne encephalitis (TBE), Lyme disease, and their co-infection, the mechanisms of the development of these diseases and their effects on the human body are still unknown. Therefore, the aim of this study was to evaluate the changes in the proteomic profile of human plasma induced by the development of TBE and to compare it with changes in TBE patients co-infected with other tick-borne pathogens. The results obtained by proteomic analysis using a nanoLC-Q Exactive HF mass spectrometer showed that the most highly elevated groups of proteins in the plasma of TBE patients with co-infection were involved in the pro-inflammatory response and protein degradation, while the antioxidant proteins and factors responsible for protein biosynthesis were mainly downregulated. These results were accompanied by enhanced GSH- and 4-HNE-protein adducts formation, observed in TBE and co-infected patients at a higher level than in the case of patients with only TBE. In conclusion, the differences in the proteomic profiles between patients with TBE and co-infected patients indicate that these diseases are significantly diverse and, consequently, require different treatment, which is particularly important for further research, including the development of novel diagnostics tools.
The Result of Vitamin C Treatment of Patients with Cancer: Conditions Influencing the Effectiveness
Authors: Hunyady János
Published: April 2022

Vitamin C (ascorbic acid, AA) is a weak sugar acid structurally related to glucose. All known physiological and biochemical functions of AA are due to its action as an electron donor. Ascorbate readily undergoes pH-dependent autoxidation creating hydrogen peroxide (H2O2). In vitro evidence suggests that vitamin C functions at low concentrations as an antioxidant while high concentration is pro-oxidant. Thus, both characters of AA might be translated into clinical benefits. In vitro obtained results and murine experiments consequently prove the cytotoxic effect of AA on cancer cells, but current clinical evidence for high-dose intravenous (i.v.) vitamin C’s therapeutic effect is ambiguous. The difference might be caused by the missing knowledge of AA’s actions. In the literature, there are many publications regarding vitamin C and cancer. Review papers of systematic analysis of human interventional and observational studies assessing i.v. AA for cancer patients’ use helps the overview of the extensive literature. Based on the results of four review articles and the Cancer Information Summary of the National Cancer Institute’s results, we analyzed 20 publications related to high-dose intravenous vitamin C therapy (HAAT). The analyzed results indicate that HAAT might be a useful cancer-treating tool in certain circumstances. The AA’s cytotoxic effect is hypoxia-induced factor dependent. It impacts only the anoxic cells, using the Warburg metabolism. It prevents tumor growth. Accordingly, discontinuation of treatment leads to repeated expansion of the tumor. We believe that the clinical use of HAAT in cancer treatment should be reassessed. The accumulation of more study results on HAAT is desperately needed.
Natural Products for the Prevention and Treatment of Oral Mucositis—A Review
Authors: Ferreira Ana Sofia , Macedo Catarina , Silva Ana Margarida , Delerue-Matos Cristina , Costa Paulo , Rodrigues Francisca
Published: April 2022

Cancer, a major world public health problem, is associated with chemotherapy treatments whose administration leads to secondary concerns, such as oral mucositis (OM). The OM disorder is characterized by the presence of ulcers in the oral mucosa that cause pain, bleeding, and difficulty in ingesting fluids and solids, or speaking. Bioactive compounds from natural sources have arisen as an effective approach for OM. This review aims to summarize the new potential application of different natural products in the prevention and treatment of OM in comparison to conventional ones, also providing a deep insight into the most recent clinical studies. Natural products, such as Aloe vera, Glycyrrhiza glabra, Camellia sinensis, Calendula officinalis, or honeybee crops, constitute examples of sources of bioactive compounds with pharmacological interest due to their well-reported activities (e.g., antimicrobial, antiviral, anti-inflammatory, analgesic, or wound healing). These activities are associated with the bioactive compounds present in their matrix (such as flavonoids), which are associated with in vivo biological activities and minimal or absent toxicity. Finally, encapsulation has arisen as a future opportunity to preserve the chemical stability and the drug bioa vailability of bioactive compounds and, most importantly, to improve the buccal retention period and the therapeutic effects.
Nutrient Sensing and Biofilm Modulation: The Example of L-arginine in Pseudomonas
Authors: Scribani Rossi Chiara , Barrientos-Moreno Laura , Paone Alessio , Cutruzzolà Francesca , Paiardini Alessandro , Espinosa-Urgel Manuel , Rinaldo Serena
Published: April 2022

Bacterial biofilm represents a multicellular community embedded within an extracellular matrix attached to a surface. This lifestyle confers to bacterial cells protection against hostile environments, such as antibiotic treatment and host immune response in case of infections. The Pseudomonas genus is characterised by species producing strong biofilms difficult to be eradicated and by an extraordinary metabolic versatility which may support energy and carbon/nitrogen assimilation under multiple environmental conditions. Nutrient availability can be perceived by a Pseudomonas biofilm which, in turn, readapts its metabolism to finally tune its own formation and dispersion. A growing number of papers is now focusing on the mechanism of nutrient perception as a possible strategy to weaken the biofilm barrier by environmental cues. One of the most important nutrients is amino acid L-arginine, a crucial metabolite sustaining bacterial growth both as a carbon and a nitrogen source. Under low-oxygen conditions, L-arginine may also serve for ATP production, thus allowing bacteria to survive in anaerobic environments. L-arginine has been associated with biofilms, virulence, and antibiotic resistance. L-arginine is also a key precursor of regulatory molecules such as polyamines, whose involvement in biofilm homeostasis is reported. Given the biomedical and biotechnological relevance of biofilm control, the state of the art on the effects mediated by the L-arginine nutrient on biofilm modulation is presented, with a special focus on the Pseudomonas biofilm. Possible biotechnological and biomedical applications are also discussed.
Application of Ultrasound Combined with Microbubbles for Cancer Therapy
Authors: Sharma Deepa , Leong Kai Xuan , Czarnota Gregory J.
Published: April 2022

At present, cancer is one of the leading causes of death worldwide. Treatment failure remains one of the prime hurdles in cancer treatment due to the metastatic nature of cancer. Techniques have been developed to hinder the growth of tumours or at least to stop the metastasis process. In recent years, ultrasound therapy combined with microbubbles has gained immense success in cancer treatment. Ultrasound-stimulated microbubbles (USMB) combined with other cancer treatments including radiation therapy, chemotherapy or immunotherapy has demonstrated potential improved outcomes in various in vitro and in vivo studies. Studies have shown that low dose radiation administered with USMB can have similar effects as high dose radiation therapy. In addition, the use of USMB in conjunction with radiotherapy or chemotherapy can minimize the toxicity of high dose radiation or chemotherapeutic drugs, respectively. In this review, we discuss the biophysical properties of USMB treatment and its applicability in cancer therapy. In particular, we highlight important preclinical and early clinical findings that demonstrate the antitumour effect combining USMB and other cancer treatment modalities (radiotherapy and chemotherapy). Our review mainly focuses on the tumour vascular effects mediated by USMB and these cancer therapies. We also discuss several current limitations, in addition to ongoing and future efforts for applying USMB in cancer treatment.
Highly Efficient Bioconversion of trans-Resveratrol to δ-Viniferin Using Conditioned Medium of Grapevine Callus Suspension Cultures
Authors: Park Su Hyun , Jeong Yu Jeong , Park Sung-Chul , Kim Soyoung , Kim Yong-Goo , Shin Gilok , Jeong Hyung Jae , Ryu Young Bae , Lee Jiyoung , Lee Ok Ran , Jeong Jae Cheol , Kim Cha Young
Published: April 2022

δ-Viniferin is a resveratrol dimer that possesses potent antioxidant properties and has attracted attention as an ingredient for cosmetic and nutraceutical products. Enzymatic bioconversion and plant callus and cell suspension cultures can be used to produce stilbenes such as resveratrol and viniferin. Here, δ-viniferin was produced by bioconversion from trans-resveratrol using conditioned medium (CM) of grapevine (Vitis labruscana) callus suspension cultures. The CM converted trans-resveratrol to δ-viniferin immediately after addition of hydrogen peroxide (H2O2). Peroxidase activity and bioconversion efficiency in CM increased with increasing culture time. Optimized δ-viniferin production conditions were determined regarding H2O2 concentration, incubation time, temperature, and pH. Maximum bioconversion efficiency reached 64% under the optimized conditions (pH 6.0, 60 °C, 30 min incubation time, 6.8 mM H2O2). In addition, in vitro bioconversion of trans-resveratrol was investigated using CM of different callus suspension cultures, showing that addition of trans-resveratrol and H2O2 to the CM led to production of δ-viniferin via extracellular peroxidase-mediated oxidative coupling of two molecules of trans-resveratrol. We thus propose a simple and low-cost method of δ-viniferin production from trans-resveratrol using CM of plant callus suspension cultures, which may constitute an alternative approach for in vitro bioconversion of valuable molecules.
Ostarine-Induced Myogenic Differentiation in C2C12, L6, and Rat Muscles
Authors: Leciejewska Natalia , Kołodziejski Paweł A. , Sassek Maciej , Nogowski Leszek , Małek Emilian , Pruszyńska-Oszmałek Ewa
Published: April 2022

Ostarine (also known as enobosarm or Gtx-024) belongs to the selective androgen receptor modulators (SARMs). It is a substance with an aryl-propionamide structure, classified as a non-steroidal compound that is not subjected to the typical steroid transformations of aromatization and reduction by α5 reductase. Despite ongoing research on ostarine, knowledge about it is still limited. Earlier studies indicated that ostarine may affect the metabolism of muscle tissue, but this mechanism has not been yet described. We aimed to investigate the effect of ostarine on the differentiation and metabolism of muscle. Using C2C12 and L6 cells, as well as muscles obtained from rats administered ostarine, we showed that ostarine stimulates C2C12 and L6 proliferation and cell viability and that this effect is mediated by androgen receptor (AR) and ERK1/2 kinase activation (p < 0.01). We also found that ostarine stimulates muscle cell differentiation by increasing myogenin, MyoD, and MyH expression in both types of cells (p < 0.01). Moreover, pharmacological blocking of AR inhibits the stimulatory effect of ostarine. We further demonstrated that 30 days of ostarine administration increases myogenin, MyoD, and MyH expression, as well as muscle mass, in rats (p < 0.01). Based on our research, we conclude that ostarine stimulates muscle tissue proliferation and differentiation via the androgen receptor.
Changes in the Cardiotoxic Effects of Lead Intoxication in Rats Induced by Muscular Exercise
Authors: Klinova Svetlana V. , Minigalieva Ilzira A. , Protsenko Yuri L. , Sutunkova Marina P. , Gurvich Vladimir B. , Ryabova Julia V. , Valamina Irene E. , Gerzen Oksana P. , Nabiev Salavat R. , Balakin Alexander A. , Lookin Oleg N. , Lisin Ruslan V. , Kuznetsov Daniil A. , Privalova Larisa I. , Panov Vladimir G. , Katsnelson Leonid B. , Nikitina Larisa V. , Katsnelson Boris A.
Published: April 2022

Exposure to lead is associated with an increased risk of cardiovascular diseases. Outbred white male rats were injected with lead acetate intraperitoneally three times a week and/or were forced to run at a speed of 25 m/min for 10 min 5 days a week. We performed noninvasive recording of arterial pressure, electrocardiogram and breathing parameters, and assessed some biochemical characteristics. Electrophoresis in polyacrylamide gel was used to determine the ratio of myosin heavy chains. An in vitro motility assay was employed to measure the sliding velocity of regulated thin filaments on myosin. Isolated multicellular preparations of the right ventricle myocardium were used to study contractility in isometric and physiological modes of contraction. Exercise under lead intoxication normalized the level of calcium and activity of the angiotensin-converting enzyme in the blood serum, normalized the isoelectric line voltage and T-wave amplitude on the electrocardiogram, increased the level of creatine kinase-MB and reduced the inspiratory rate. Additionally, the maximum sliding velocity and the myosin heavy chain ratio were partly normalized. The effect of exercise under lead intoxication on myocardial contractility was found to be variable. In toto, muscular loading was found to attenuate the effects of lead intoxication, as judged by the indicators of the cardiovascular system.
A Systematic Review of Atypical Endometriosis-Associated Biomarkers
Authors: Bartiromo Ludovica , Schimberni Matteo , Villanacci Roberta , Mangili Giorgia , Ferrari Stefano , Ottolina Jessica , Salmeri Noemi , Dolci Carolina , Tandoi Iacopo , Candiani Massimo
Published: April 2022

Ovarian endometriosis may increase the risk of malignancy. Several studies have suggested atypical endometriosis as the direct precursor of endometriosis-associated ovarian cancer. We performed an advanced, systematic search of the online medical databases PubMed and Medline. The search revealed n = 40 studies eligible for inclusion in this systematic review. Of these, n = 39 were finally included. The results from included studies are characterized by high heterogeneity, but some consistency has been found for altered expression in phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway, ARID1a, estrogen and progesterone receptors, transcriptional, nuclear, and growth factors in atypical endometriosis. Although many targets have been proposed as biomarkers for the presence of atypical endometriosis, none of them has such strong evidence to justify their systematic use in clinical practice, and they all need expensive molecular analyses. Further well-designed studies are needed to validate the evidence on available biomarkers and to investigate novel serum markers for atypical endometriosis.
Non-Coding RNAs in Tuberculosis Epidemiology: Platforms and Approaches for Investigating the Genome’s Dark Matter
Authors: Almatroudi Ahmad
Published: April 2022

A growing amount of information about the different types, functions, and roles played by non-coding RNAs (ncRNAs) is becoming available, as more and more research is done. ncRNAs have been identified as potential therapeutic targets in the treatment of tuberculosis (TB), because they may be essential regulators of the gene network. ncRNA profiling and sequencing has recently revealed significant dysregulation in tuberculosis, primarily due to aberrant processes of ncRNA synthesis, including amplification, deletion, improper epigenetic regulation, or abnormal transcription. Despite the fact that ncRNAs may have a role in TB characteristics, the detailed mechanisms behind these occurrences are still unknown. The dark matter of the genome can only be explored through the development of cutting-edge bioinformatics and molecular technologies. In this review, ncRNAs’ synthesis and functions are discussed in detail, with an emphasis on the potential role of ncRNAs in tuberculosis. We also focus on current platforms, experimental strategies, and computational analyses to explore ncRNAs in TB. Finally, a viewpoint is presented on the key challenges and novel techniques for the future and for a wide-ranging therapeutic application of ncRNAs.
Compartment-Specific Proximity Ligation Expands the Toolbox to Assess the Interactome of the Long Non-Coding RNA NEAT1
Authors: Mamontova Victoria , Trifault Barbara , Burger Kaspar
Published: April 2022

The nuclear paraspeckle assembly transcript 1 (NEAT1) locus encodes two long non-coding (lnc)RNA isoforms that are upregulated in many tumours and dynamically expressed in response to stress. NEAT1 transcripts form ribonucleoprotein complexes with numerous RNA-binding proteins (RBPs) to assemble paraspeckles and modulate the localisation and activity of gene regulatory enzymes as well as a subset of messenger (m)RNA transcripts. The investigation of the dynamic composition of NEAT1-associated proteins and mRNAs is critical to understand the function of NEAT1. Interestingly, a growing number of biochemical and genetic tools to assess NEAT1 interactomes has been reported. Here, we discuss the Hybridisation Proximity (HyPro) labeling technique in the context of NEAT1. HyPro labeling is a recently developed method to detect spatially ordered interactions of RNA-containing nuclear compartments in cultured human cells. After introducing NEAT1 and paraspeckles, we describe the advantages of the HyPro technology in the context of other methods to study RNA interactomes, and review the key findings in mapping NEAT1-associated RNA transcripts and protein binding partners. We further discuss the limitations and potential improvements of HyPro labeling, and conclude by delineating its applicability in paraspeckles-related cancer research.
1,5-Disubstituted Acylated 2-Amino-4,5-dihydroimidazoles as a New Class of Retinoic Acid Receptor–Related Orphan Receptor (ROR) Inhibitors
Authors: Ortiz Maria A. , Piedrafita F. Javier , Nefzi Adel
Published: April 2022

A growing body of evidence suggests a pathogenic role for pro-inflammatory T helper 17 cells (Th17) in several autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, type I diabetes, and psoriasis—diseases for which no curative treatment is currently available. The nuclear retinoic acid receptor–related orphan receptors alpha and gamma (RORα/γ), in particular the truncated isoform RORγt that is specifically expressed in the thymus, play a critical role in the activation of a pro-inflammatory Th17 response, and RORγ inverse agonists have shown promise as negative regulators of Th17 for the treatment of autoimmune diseases. Our study underscores the screening of a large combinatorial library of 1,5-disubstituted acylated 2-amino-4,5-dihydroimidazoles using a demonstrated synthetic and screening approach and the utility of the positional scanning libraries strategy for the rapid identification of a novel class of ROR inhibitors. We identified compound 1295-273 with the highest activity against RORγ (3.3 µM IC50) in this series, and almost a two-fold selectivity towards this receptor isoform, with 5.3 and 5.8 µM IC50 against RORα and RORβ cells, respectively.
Development of a Simulator for Prototyping Reinforcement Learning-Based Autonomous Cars
Authors: Holen Martin , Knausgård Kristian Muri , Goodwin Morten
Published: April 2022

Autonomous driving is a research field that has received attention in recent years, with increasing applications of reinforcement learning (RL) algorithms. It is impractical to train an autonomous vehicle thoroughly in the physical space, i.e., the so-called ’real world’; therefore, simulators are used in almost all training of autonomous driving algorithms. There are numerous autonomous driving simulators, very few of which are specifically targeted at RL. RL-based cars are challenging due to the variety of reward functions available. There is a lack of simulators addressing many central RL research tasks within autonomous driving, such as scene understanding, localization and mapping, planning and driving policies, and control, which have diverse requirements and goals. It is, therefore, challenging to prototype new RL projects with different simulators, especially when there is a need to examine several reward functions at once. This paper introduces a modified simulator based on the Udacity simulator, made for autonomous cars using RL. It creates reward functions, along with sensors to create a baseline implementation for RL-based vehicles. The modified simulator also resets the vehicle when it gets stuck or is in a non-terminating loop, making it more reliable. Overall, the paper seeks to make the prototyping of new systems simple, with the testing of different RL-based systems.
Whole Genome Sequencing in Hypoplastic Left Heart Syndrome
Authors: Theis Jeanne L. , Olson Timothy M.
Published: April 2022

Hypoplastic left heart syndrome (HLHS) is a genetically complex disorder. Whole genome sequencing enables comprehensive scrutiny of single nucleotide variants and small insertions/deletions, within both coding and regulatory regions of the genome, revolutionizing susceptibility-gene discovery research. Because millions of rare variants comprise an individual genome, identification of alleles linked to HLHS necessitates filtering algorithms based on various parameters, such as inheritance, enrichment, omics data, known genotype–phenotype associations, and predictive or experimental modeling. In this brief review, we highlight family and cohort-based strategies used to analyze whole genome sequencing datasets and identify HLHS candidate genes. Key findings include compound and digenic heterozygosity among several prioritized genes and genetic associations between HLHS and bicuspid aortic valve or cardiomyopathy. Together with findings of independent genomic investigations, MYH6 has emerged as a compelling disease gene for HLHS and other left-sided congenital heart diseases.
Lipopolysaccharide Modifies Sodium Current Kinetics through ROS and PKC Signalling in Induced Pluripotent Stem-Derived Cardiomyocytes from Brugada Syndrome Patient
Authors: Liao Zhenxing , Li Yingrui , Fan Xuehui , Yang Zhen , El-Battrawy Ibrahim , Zhou Xiaobo , Akin Ibrahim
Published: April 2022

Studies have suggested a connection between inflammation and arrhythmogenesis of Brugada syndrome (BrS). However, experimental studies regarding the roles of inflammation in the arrhythmogenesis of BrS and its underlying mechanism are still lacking. This study aimed to investigate the influence of inflammation on BrS-phenotype features using human-induced stem cell-derived cardiomyocytes (hiPSC-CMs) from a BrS-patient carrying an SCN10A variant (c.3749G > A). After LPS treatment, the peak sodium current decreased significantly in SCN10A-hiPSC-CMs, but not in healthy donor-hiPSC-CMs. LPS also changed sodium channel gating kinetics, including activation, inactivation, and recovery from inactivation. NAC (N-acetyl-l-cysteine), a blocker of ROS (reactive oxygen species), failed to affect the sodium current, but prevented the LPS-induced reduction of sodium channel currents and changes in gating kinetics, suggesting a contribution of ROS to the LPS effects. Hydrogen peroxide (H2O2), a main form of ROS in cells, mimicked the LPS effects on sodium channel currents and gating kinetics, implying that ROS might mediate LPS-effects on sodium channels. The effects of H2O2 could be attenuated by a PKC blocker chelerythrine, indicating that PKC is a downstream factor of ROS. This study demonstrated that LPS can exacerbate the loss-of-function of sodium channels in BrS cells. Inflammation may play an important role in the pathogenesis of BrS.
Does Wim Hof Method Improve Breathing Economy during Exercise?
Authors: Marko David , Bahenský Petr , Bunc Václav , Grosicki Gregory J. , Vondrasek Joseph D.
Published: April 2022

(1) Background: Breathing economy during endurance sports plays a major role in performance. Poor breathing economy is mainly characterized by excessive breathing frequency (BF) and low tidal volume (VT) due to shallow breathing. The purpose of this study was to evaluate whether a 4 week intervention based on the Wim Hof breathing method (WHBM) would improve breathing economy during exercise in adolescent runners. (2) Methods: 19 adolescent (16.6 ± 1.53 years) middle- and long-distance runners (11 boys and 8 girls) participated in the study. Participants were randomly divided into experimental (n = 11) and control groups (n = 8). The study was set in the transition period between competitive race seasons and both groups had a similar training program in terms of running volume and intensity over the course of the study. The experimental group performed breathing exercises every day (~20 min/day) for 4 weeks. The control group did not perform any kind of breathing exercise. The breathing exercises consisted of three sets of controlled hyperventilation and consecutive maximum breath holds. Before and after the intervention, participants performed incremental cycle ergometer testing sessions consisting of two minute stages at 1, 2, 3, and 4 W·kg−1 with breath-by-breath metabolic analysis. During the testing sessions, BF, VT, and minute ventilation (VE) were assessed and compared. (3) Results: There were no statistically significant differences (p > 0.05) in BF, VT, or VE between experimental and control groups before or after the intervention. A nonsignificant small-to-large effect for an increase in VE and BF in both groups following the 4 week intervention period was observed, possibly due to a reduction in training volume and intensity owing to the down period between competitive seasons. (4) Conclusions: The 4 week intervention of WHBM did not appear to alter parameters of breathing economy during a maximal graded exercise test in adolescent runners.
“No-Reflow” Phenomenon: A Contemporary Review
Authors: Annibali Gianmarco , Scrocca Innocenzo , Aranzulla Tiziana Claudia , Meliga Emanuele , Maiellaro Francesco , Musumeci Giuseppe
Published: April 2022

Primary percutaneous angioplasty (pPCI), represents the reperfusion strategy of choice for patients with STEMI according to current international guidelines of the European Society of Cardiology. Coronary no-reflow is characterized by angiographic evidence of slow or no anterograde epicardial flow, resulting in inadequate myocardial perfusion in the absence of evidence of mechanical vessel obstruction. No reflow (NR) is related to a functional and structural alteration of the coronary microcirculation and we can list four main pathophysiological mechanisms: distal atherothrombotic embolization, ischemic damage, reperfusion injury, and individual susceptibility to microvascular damage. This review will provide a contemporary overview of the pathogenesis, diagnosis, and treatment of NR.
Mechanical Characterization and Finite Element Analysis of Hierarchical Sandwich Structures with PLA 3D-Printed Core and Composite Maize Starch Biodegradable Skins
Authors: Zoumaki Maria , Mansour Michel T. , Tsongas Konstantinos , Tzetzis Dimitrios , Mansour Gabriel
Published: April 2022

The objective of this research is the fabrication of biodegradable starch-based sandwich materials. The investigated sandwich structures consist of maize starch-based films as skins and biodegradable 3D-printed polylactic filaments (PLA) as the core. To investigate the tensile properties of the skins, conventional and nanocomposite films were prepared by a solution mixing procedure with maize starch and glycerol as the plasticizer, and they were reinforced with sodium montmorillonite clay, cellulose fibers and fiberglass fabric, with different combinations. Test results indicated a significant improvement in the mechanical and morphological properties of composite films prepared with sodium montmorillonite clay in addition with cellulose fibers and fiberglass fabric, with 20 wt% of glycerol. The morphology of the skins was also examined by scanning electron microscopy (SEM). Three orders of hierarchical honeycombs were designed for the 3D-printed core. To investigate how the skin material and the design of the core affect the mechanical properties of the starch-based sandwich, specimens were tested under a three-point bending regime. The test results have shown that the flexural strength of the biodegradable sandwich structure increased with the use of a second order hierarchy core and starch-based skins improved the strength and stiffness of the neat PLA-based honeycomb core. The bending behavior of the hierarchical honeycombs was also assessed with finite element analysis (FEA) in combination with experimental findings. Flexural properties demonstrated that the use of starch-based films and a PLA honeycomb core is a suitable solution for biodegradable sandwich structures.
Moral Disengagement in Youth Athletes: A Narrative Review
Authors: Gentile Ambra , Milovanovic Ivana , Pišot Saša , Bianco Antonino , Lavanco Gioacchino
Published: April 2022

The sports environment can be considered as a context characterized by interactions typical of social groups, where children have the chance to learn good values. Positive and negative behaviours in sports, also called prosocial and antisocial behaviours, have been studied according to a moral perspective, as has doping behaviour, taking into consideration the concept of moral disengagement. Moral disengagement in children has been associated with maladaptive behaviours later in life, even though it should disappear with growth. Concerning the sports environment, previous reviews on the topic have extensively illustrated the role of moral variables in sport and their relation to antisocial behaviour and doping, positing some research questions that should be investigated in the future. Starting from these questions, the current narrative review aims to update literature about the effects of moral disengagement on youth athletes. Therefore, new studies about the predictors of moral disengagement are introduced, followed by contributions concerning the relationship between moral disengagement and doping and between moral disengagement and antisocial behaviour. Finally, the review summarizes which research questions have been solved in the last decade and which should be researched further on.
Spectral Photon-Counting Computed Tomography: A Review on Technical Principles and Clinical Applications
Authors: Tortora Mario , Gemini Laura , D’Iglio Imma , Ugga Lorenzo , Spadarella Gaia , Cuocolo Renato
Published: April 2022

Photon-counting computed tomography (CT) is a technology that has attracted increasing interest in recent years since, thanks to new-generation detectors, it holds the promise to radically change the clinical use of CT imaging. Photon-counting detectors overcome the major limitations of conventional CT detectors by providing very high spatial resolution without electronic noise, providing a higher contrast-to-noise ratio, and optimizing spectral images. Additionally, photon-counting CT can lead to reduced radiation exposure, reconstruction of higher spatial resolution images, reduction of image artifacts, optimization of the use of contrast agents, and create new opportunities for quantitative imaging. The aim of this review is to briefly explain the technical principles of photon-counting CT and, more extensively, the potential clinical applications of this technology.
Fuzzy Information Discrimination Measures and Their Application to Low Dimensional Embedding Construction in the UMAP Algorithm
Authors: Demidova Liliya A. , Gorchakov Artyom V.
Published: April 2022

Dimensionality reduction techniques are often used by researchers in order to make high dimensional data easier to interpret visually, as data visualization is only possible in low dimensional spaces. Recent research in nonlinear dimensionality reduction introduced many effective algorithms, including t-distributed stochastic neighbor embedding (t-SNE), uniform manifold approximation and projection (UMAP), dimensionality reduction technique based on triplet constraints (TriMAP), and pairwise controlled manifold approximation (PaCMAP), aimed to preserve both the local and global structure of high dimensional data while reducing the dimensionality. The UMAP algorithm has found its application in bioinformatics, genetics, genomics, and has been widely used to improve the accuracy of other machine learning algorithms. In this research, we compare the performance of different fuzzy information discrimination measures used as loss functions in the UMAP algorithm while constructing low dimensional embeddings. In order to achieve this, we derive the gradients of the considered losses analytically and employ the Adam algorithm during the loss function optimization process. From the conducted experimental studies we conclude that the use of either the logarithmic fuzzy cross entropy loss without reduced repulsion or the symmetric logarithmic fuzzy cross entropy loss with sufficiently large neighbor count leads to better global structure preservation of the original multidimensional data when compared to the loss function used in the original UMAP algorithm implementation.
Human Tracking in Top-View Fisheye Images: Analysis of Familiar Similarity Measures via HOG and against Various Color Spaces
Authors: Talaoubrid Hicham , Vert Marina , Hayat Khizar , Magnier Baptiste
Published: April 2022

The purpose of this paper is to find the best way to track human subjects in fisheye images by considering the most common similarity measures in the function of various color spaces as well as the HOG. To this end, we have relied on videos taken by a fisheye camera wherein multiple human subjects were recorded walking simultaneously, in random directions. Using an existing deep-learning method for the detection of persons in fisheye images, bounding boxes are extracted each containing information related to a single person. Consequently, each bounding box can be described by color features, usually color histograms; with the HOG relying on object shapes and contours. These descriptors do not inform the same features and they need to be evaluated in the context of tracking in top-view fisheye images. With this in perspective, a distance is computed to compare similarities between the detected bounding boxes of two consecutive frames. To do so, we are proposing a rate function (S) in order to compare and evaluate together the six different color spaces and six distances, and with the HOG. This function links inter-distance (i.e., the distance between the images of the same person throughout the frames of the video) with intra-distance (i.e., the distance between images of different people throughout the frames). It enables ascertaining a given feature descriptor (color or HOG) mapped to a corresponding similarity function and hence deciding the most reliable one to compute the similarity or the difference between two segmented persons. All these comparisons lead to some interesting results, as explained in the later part of the article.
A Comparison of Dense and Sparse Optical Flow Techniques for Low-Resolution Aerial Thermal Imagery
Authors: Nguyen Tran Xuan Bach , Rosser Kent , Chahl Javaan
Published: April 2022

It is necessary to establish the relative performance of established optical flow approaches in airborne scenarios with thermal cameras. This study investigated the performance of a dense optical flow algorithm on 14 bit radiometric images of the ground. While sparse techniques that rely on feature matching techniques perform very well with airborne thermal data in high-contrast thermal conditions, these techniques suffer in low-contrast scenes, where there are fewer detectable and distinct features in the image. On the other hand, some dense optical flow algorithms are highly amenable to parallel processing approaches compared to those that rely on tracking and feature detection. A Long-Wave Infrared (LWIR) micro-sensor and a PX4Flow optical sensor were mounted looking downwards on a drone. We compared the optical flow signals of a representative dense optical flow technique, the Image Interpolation Algorithm (I2A), to the Lucas–Kanade (LK) algorithm in OpenCV and the visible light optical flow results from the PX4Flow in both X and Y displacements. The I2A to LK was found to be generally comparable in performance and better in cold-soaked environments while suffering from the aperture problem in some scenes.