bluuebunny/crossref_metadata_2025 huggingface dataset:
Expectations and Assumptions: Examining the Influence of Staff Culture on a Novel School-Based Intervention to Enable Risky Play for Children with Disabilities
Authors: Grady-Dominguez Patricia , Ragen Jo , Sterman Julia , Spencer Grace , Tranter Paul , Villeneuve Michelle , Bundy Anita
Published: January 2021

Risky play is challenging, exciting play with the possibility of physical, social, or emotional harm. Through risky play, children learn, develop, and experience wellbeing. Children with disabilities have fewer opportunities than their typically developing peers to engage in this beneficial type of play. Our team designed a novel, school-based intervention to address this disparity; however, our intervention yielded unexpected quantitative results. In the present study, we qualitatively examined divergent results at two of the five schools that participated in the intervention. Specifically, we aimed to explore how staff culture (i.e., shared beliefs, values, and practices) influenced the intervention. To explore this relationship, we employed a retrospective, qualitative, multiple case study. We used thematic analysis of evaluative interviews with staff members to elucidate the cultures at each school. Then, we used cross-case analysis to understand the relationships between aspects of staff culture and the intervention’s implementation and results. We found that staff cultures around play, risk, disability influenced the way, and the extent to which, staff were willing to let go and allowed children to engage in risky play. Adults’ beliefs about the purpose of play and recess, as well as their expectations for children with disabilities, particularly influenced the intervention. Furthermore, when the assumptions of the intervention and the staff culture did not align, the intervention could not succeed. The results of this study highlight the importance of (1) evaluating each schools’ unique staff culture before implementing play-focused interventions and (2) tailoring interventions to meet the needs of individual schools.
Young Swimmers’ Middle-Distance Performance Variation within a Training Season
Authors: Ferreira Sara , Carvalho Diogo Duarte , Cardoso Ricardo , Rios Manoel , Soares Susana , Toubekis Argyris , Fernandes Ricardo J.
Published: January 2021

The current study aimed to longitudinally evaluate anthropometric, physiological, and biomechanical variables related to middle-distance performance during a 45-week swimming training season. Thirty-four swimmers (age: 12.07 ± 1.14 years) performed a maximum of 400 m front crawl at the beginning (T1) and finish of the first macrocycle (T2, 15 weeks) and the finish of the second (T3, 18 weeks) and third macrocycles (T4, 12 weeks). Time-related variables, stroke rate (SR), stroke length (SL), and stroke index (SI) were recorded during the test, and blood lactate ([La]) and glucose ([Glu]) concentrations were measured post-exercise. The time of the 400 m effort decreased after each macrocycle (T2 vs. T1, 7.8 ± 5.6%; T3 vs. T2, 3.7 ± 3.1%; T4 vs. T3, 3.8 ± 3.4%; p < 0.01). Four hundred meter speed changes between T1 and T2 were positively related to variations in [La], [Glu], SL, and SI (r = 0.36–0.60, p < 0.05). Changes between T2 and T3 were related to SI only (r = 0.5, p < 0.05), and modifications between T3 and T4 were associated with SL and SI variations (r = 0.34 and 0.65, p < 0.05). These results indicate that a well-structured year plan including three macrocycles leads to a significant age-group swimming performance improvement, mostly connected with an increase in technical proficiency.
Thermal and Current Flow Effects of a Capacitive–Resistive Electric Transfer Application Protocol on Chronic Elbow Tendinopathy. A Cadaveric Study
Authors: López-de-Celis Carlos , Rodríguez-Sanz Jacobo , Hidalgo-García César , Cedeño-Bermúdez Simón A. , Zegarra-Chávez Daniel , Fanlo-Mazas Pablo , Pérez-Bellmunt Albert
Published: January 2021

Lateral elbow tendinopathy, or “tennis elbow,” is a pathology that affects around 1.3% of the general population. Capacitive–resistive electric transfer therapy aims to provoke temperature and current flow changes in superficial and deep tissues. The aim of this in vitro study was to analyze the thermal behavior and transmission of electric current on the superficial and deep tissues of the elbow during the application of different modalities of a capacitive–resistive electric transfer treatment protocol for chronic elbow tendinopathy. A cross-sectional study was designed; five fresh cryopreserved cadavers (10 elbows) were included in this study. A 30 min intervention was performed based on a protocol commonly used in clinics for the treatment of chronic lateral elbow tendinopathy by diathermy using the “T-Plus.” Common extensor tendon, radiohumeral capsule, and superficial temperatures were registered after each application for the duration of the 30 min treatment protocol. During all applications, we observed a current flow of over 0.03 A. The protocol showed a statistically significant increase in superficial temperature by 24% (5.02°) (p < 0.005), the common extensor tendon by 19.7% (4.36°) (p < 0.007), and the radiohumeral joint capsule by 17.5% (3.41°) (p < 0.005) at the end of the 30 min protocol compared with the baseline temperature. The different applications of the protocol showed specific effects on the temperature and current flow in the common extensor tendon and radiohumeral capsule. All applications of the protocol produced a current flow that is associated with the generation of cell proliferation. These results strengthen the hypothesis of cell proliferation and thermal changes in deep and distal structures. More studies are needed to confirm these results.
Effectiveness of Complementary Therapies in Cancer Patients: A Systematic Review
Authors: Guerra-Martín María Dolores , Tejedor-Bueno María Sandra , Correa-Casado Matías
Published: January 2021

According to the World Health Organization, cancer is the second leading cause of death in the world. In Spain, about a quarter of a million cases were diagnosed in 2017, and 81% of the Spanish population has used, at least once, some kind of complementary therapy. Said therapies are increasingly being used by cancer patients. The purpose of the study is to analyse the effectiveness of complementary therapies among cancer patients. A systematic peer review was conducted following the PRISMA-ScR guide in four databases (PubMed, CINAHL, Scopus and WOS). The inclusion criteria were Randomised Clinical Trials, published between 2013 and 2018, with a value of 3 or more on the Jadad Scale. The protocol was registered in PROSPERO (CRD42019127593). The study sample amounted to 1845 patients (64.55% women), the most common being breast cancer patients (794), followed by lung cancer patients (341). Fifteen complementary therapies were identified. We found two studies for each of the following: electroacupuncture, phytotherapy, hypnotherapy, guided imagery and progressive muscle relaxation. From the remaining ones, we identified a study on each therapy. The findings reveal some effective complementary therapies: auriculotherapy and acupuncture, laser moxibustion, hypnosis, Ayurveda, electroacupuncture, progressive muscle relaxation and guided imagery, yoga, phytotherapy, music therapy and traditional Chinese medicine. On the other hand, electroacupuncture, laser moxibustion and traditional Chinese medicine presented adverse effects, and kinesiology did not show effectiveness.
Treatment of Stage 2 Medication-Induced Osteonecrosis of the Jaw: A Case Series
Authors: Pardo-Zamora Guillermo , Martínez Yanet , Moreno Jose Antonio , Ortiz-Ruíz Antonio J.
Published: January 2021

Medication-induced jaw osteonecrosis (MRONJ) is a rare and serious disease with a negative impact on patients’ quality of life, whose exact cause remains unclear and which may have a multifactorial origin. Although there are different therapeutic protocols, there is still no consensus. This case series evaluated three patients diagnosed with staged 2 MRONJ treated at the University of Murcia dental clinic according to the protocols described by the Spanish Society of Oral and Maxillofacial Surgery and the American Association of Oral and Maxillofacial Surgeons. Within 12 months of the application of therapeutic protocols, the lesions were completely healed in all cases. Radiography showed slow but progressive healing with normal bone structure. Conservative treatment with antibiotics, chlorhexidine rinses and minimally invasive surgical intervention with necrotic bone resection is effective in treating stage 2 of MRONJ. In cases of refractory osteonecrosis, the application of platelet and leukocyte-rich fibrin (PRF-L) in the surgical approach improves the outcome in soft tissue healing and bone regeneration but further research is needed to confirm its effectiveness.
Reliability and Validity of the Malay Mindful Eating Questionnaire (MEQ-M) among Overweight and Obese Adults
Authors: Abdul Basir Siti Munirah , Abdul Manaf Zahara , Ahmad Mahadir , Abdul Kadir Nor Ba’yah , Ismail Wan Nur Khairunnisa , Mat Ludin Arimi Fitri , Shahar Suzana
Published: January 2021

The Mindful Eating Questionnaire is a reliable tool for the assessment of mindful eating behavior among the general population. This study aimed to determine the reliability and validity of The Malay Mindful Eating Questionnaire (MEQ-M) in a sample of overweight and obese adults. This is a cross-sectional survey which involved 144 overweight and obese adults in a selected public university. After linguistic validation of the Malay version of the MEQ, exploratory factor analysis (EFA) with varimax rotation was performed on the scale constructs. The psychometric properties of the MEQ were assessed through Cronbach’s alpha and intraclass correlation coefficient (ICC) analysis. The EFA of the MEQ produced a seven-dimensional model (58.8% of overall variances). The concurrent validity analysis between total MEQ scores and total Mindfulness Attention Awareness Scale (MAAS) scores indicated a weak non-significant correlation (p = 0.679). The internal consistency reliability of the MEQ was reasonable (Cronbach’s α = 0.64). The agreement stability of the MEQ over eight weeks was poor (ICC = 0.10). In conclusion, the psychometric properties of the Malay-translated MEQ are acceptable through construct validity and internal consistency reliability tests. This instrument may be used for assessing mindful eating habits in the Malaysian population, especially among overweight and obese adults.
Effects on Strength, Power and Speed Execution Using Exercise Balls, Semi-Sphere Balance Balls and Suspension Training Devices: A Systematic Review
Authors: Marquina Moisés , Lorenzo-Calvo Jorge , Rivilla-García Jesús , García-Aliaga Abraham , Refoyo Román Ignacio
Published: January 2021

Research in instability has focused on the analysis of muscle activation. The aim of this systematic review was to analyse the effects of unstable devices on speed, strength and muscle power measurements administered in the form of controlled trials to healthy individuals in adulthood. A computerized systematic literature search was performed through electronic databases. According to the criteria for preparing systematic reviews PRISMA, nine studies met the inclusion criteria. The quality of the selected studies was evaluated using STROBE. The average score was 14.3 points, and the highest scores were located in ‘Introduction’ (100%) and ‘Discussion’ (80%). There is great heterogeneity in terms of performance variables. However, instability seems to affect these variables negatively. The strength variable was affected to a greater degree, but with intensities near to the 1RM, no differences are observed. As for power, a greater number of repetitions seems to benefit the production of this variable in instability in the upper limb. Instability, in comparison to a stable condition, decreases the parameters of strength, power, and muscular speed in adults. The differences shown are quite significant in most situations although slight decreases can be seen in certain situations.
Improving the Field’s Understanding of Suicide Protective Factors and Translational Suicide Prevention Initiatives
Authors: Cramer Robert J. , Tucker Raymond
Published: January 2021

World Health Organization data show that approximately 800,000 persons die by suicide each year [...]
Are the Parameters of Novel Two-Point Force-Velocity Model Generalizable in Leg Muscles?
Authors: Đurić Saša , Grbić Vladimir , Živković Milena , Majstorović Nikola , Sember Vedrana
Published: January 2021

The two-point force-velocity model allows the assessment of the muscle mechanical capacities in fast, almost fatigue-free conditions. The aim of this study was to investigate the concurrent validity of the two-point parameters with directly measured force and power and to examine the generalization of the two-point parameters across the different functional movement tests of leg muscles. Twelve physically active participants were tested performing three functional lower limb maximal tests under two different magnitudes of loads: countermovement jumps, maximal cycling sprint, and maximal force under isokinetic conditions of the knee extensors. The results showed that all values from the two-point model were higher than the values from the standard tests (p < 0.05). We also found strong correlations between the same variables from different tests (r ≥ 0.84; p < 0.01), except for force in maximal cycling sprint, where it was low and negligible (r = −0.24). The results regarding our second aim showed that the correlation coefficients between the same two-point parameters of different lower limb tests ranged from moderate to strong (r −0.47 to 0.72). In particular, the relationships were stronger between power variables than between force variables and somewhat stronger between standard tests and two-point parameters. We can conclude that mechanical capacities of the leg muscles can be partially generalized between different functional tests.
The Effect of the Built Environment on Older Men′s and Women′s Leisure-Time Physical Activity in the Mid-Scale City of Jinhua, China
Authors: Yu Jiabin , Yang Chen , Zhang Shen , Zhai Diankai , Wang Aiwen , Li Jianshe
Published: January 2021

Physical activity has been suggested to be beneficial in preventing disease and improving body function in older people. Older people’s leisure-time physical activity (LTPA) is affected by various factors, especially environmental factors. However, the differences in the association between older people’s LTPA and the built environment in different sex groups remain unclear. Perceived built environment scores and older people’s LTPA were collected for 240 older people in Jinhua using the Neighborhood Environment Walkability Scale and International Physical Activity Questionnaire, respectively. A linear regression method was used to analyze the associations between older people’s LTPA and the built environment in men, women, and all participants. The results showed that land use mix diversity was associated with LTPA in older people for both sexes. In men, LTPA was also associated with access to services. However, in women, LTPA was associated with residential density, street connectivity, and crime safety. The relationship varied when demographic variables were incorporated into the regression analysis. Those results indicated that a shorter perceived distance from home to destination would motivate older people to engage more in LTPA. Older people’s LTPA was affected by various built environment factors according to different sex groups. Women’s LTPA was generally more sensitive to the built environment. More studies are needed to confirm the association between LTPA in older people and the built environment in men and women in mid- or small-sized Chinese cities in the future.
How Do Pharmaceutical Companies Overcome a Corporate Productivity Crisis? Business Diversification into Medical Devices for Growth Potential
Authors: Euh Yoonje , Lee Daeho
Published: January 2021

The purpose of this study was to analyze the performance of pharmaceutical companies’ business diversification into medical devices in terms of their technical efficiency (TE) as compared to that of traditional pharmaceutical companies. For a total of 174 externally audited pharmaceutical companies engaged in the drug product business between 2008 and 2019, pharmaceutical companies were classified into two groups according to medical device business diversification. The TE of pharmaceutical companies that diversify the medical device business was lower than that of traditional pharmaceutical companies. However, in terms of the meta-technology ratio (MTR) calculated using meta-frontier analysis, pharmaceutical companies diversified into medical devices showed higher MTR than the traditional pharmaceutical company group. The results imply that the corporate performance growth potential of traditional pharmaceutical companies is lower than that of pharmaceutical companies that have diversified into the medical device business.
Analysis of Single Nucleotide Variants (SNVs) Induced by Exposure to PM10 in Lung Epithelial Cells Using Whole Genome Sequencing
Authors: Park Se Jin , Ku Gwan Woo , Lee Su Yel , Kang Daeun , Hwang Wan Jin , Jeong In Beom , Kwon Sun Jung , Kang Jaeku , Son Ji Woong
Published: January 2021

There are many epidemiological studies asserting that fine dust causes lung cancer, but the biological mechanism is not clear. This study was conducted to investigate the effect of PM10 (particulate matter less than 10 μm) on single nucleotide variants through whole genome sequencing in lung epithelial cancer cell lines (HCC-827, NCI-H358) that have been exposed to PM10. The two cell lines were exposed to PM10 for 15 days. We performed experimental and next generation sequencing analyses on experimental group that had been exposed to PM10 as well as an unexposed control group. After exposure to PM10, 3005 single nucleotide variants were newly identified in the NCI-H358 group, and 4402 mutations were identified in the HCC-827 group. We analyzed these single nucleotide variants with the Mutalisk program. We observed kataegis in chromosome 1 in NCI-H358 and chromosome 7 in HCC-827. In mutational signatures analysis, the COSMIC mutational signature 5 was highest in both HCC-827 and NCI-H358 groups, and each cosine similarity was 0.964 in HCC-827 and 0.979 in the NCI-H358 group. The etiology of COSMIC mutational signature 5 is unknown at present. Well-designed studies are needed to determine whether environmental factors, such as PM10, cause COSMIC mutational signature 5.
Health Advertising during the Lockdown: A Comparative Analysis of Commercial TV in Spain
Authors: Blanco-Herrero David , Gallardo-Camacho Jorge , Arcila-Calderón Carlos
Published: January 2021

During the lockdown declared in Spain to fight the spread of COVID-19 from 14 March to 3 May 2020, a context in which health information has gained relevance, the agenda-setting theory was used to study the proportion of health advertisements broadcasted during this period on Spanish television. Previous and posterior phases were compared, and the period was compared with the same period in 2019. A total of 191,738 advertisements were downloaded using the Instar Analytics application and analyzed using inferential statistics to observe the presence of health advertisements during the four study periods. It was observed that during the lockdown, there were more health advertisements than after, as well as during the same period in 2019, although health advertisements had the strongest presence during the pre-lockdown phase. The presence of most types of health advertisements also changed during the four phases of the study. We conclude that, although many differences can be explained by the time of the year—due to the presence of allergies or colds, for instance—the lockdown and the pandemic affected health advertising. However, the effects were mostly visible after the lockdown, when advertisers and broadcasters had had time to adapt to the unexpected circumstances.
Reactive Oxygen Species Accumulation Strongly Allied with Genetic Male Sterility Convertible to Cytoplasmic Male Sterility in Kenaf
Authors: Liu Yiding , Zhou Bujin , Khan Aziz , Zheng Jie , Dawar Farman Ullah , Akhtar Kashif , Zhou Ruiyang
Published: January 2021

Male sterility (MS) plays a key role in the hybrid breed production of plants. Researchers have focused on the association between genetic male sterility (GMS) and cytoplasmic male sterility (CMS) in kenaf. In this study, P9BS (a natural GMS mutant of the kenaf line P9B) and male plants of P9B were used as parents in multiple backcross generations to produce P9SA, a CMS line with stable sterility, to explore the molecular mechanisms of the association between GMS and CMS. The anthers of the maintainer (P9B), GMS (P9BS), and CMS (P9SA) lines were compared through phenotypic, cell morphological, physiological, biochemical observations, and transcriptome analysis. Premature degradation of the tapetum was observed at the mononuclear stage in P9BS and P9SA, which also had lower activity of reactive oxygen species (ROS) scavenging enzymes compared with P9B. Many coexpressed differentially expressed genes were related to ROS balance, including ATP synthase, electron chain transfer, and ROS scavenging processes were upregulated in P9B. CMS plants had a higher ROS accumulation than GMS plants. The MDA content in P9SA was 3.2 times that of P9BS, and therefore, a higher degree of abortion occurred in P9SA, which may indicate that the conversion between CMS and GMS is related to intracellular ROS accumulation. Our study adds new insights into the natural transformation of GMS and CMS in plants in general and kenaf in particular.
Replication-Coupled Chromatin Remodeling: An Overview of Disassembly and Assembly of Chromatin during Replication
Authors: Duc Céline , Thiriet Christophe
Published: January 2021

The doubling of genomic DNA during the S-phase of the cell cycle involves the global remodeling of chromatin at replication forks. The present review focuses on the eviction of nucleosomes in front of the replication forks to facilitate the passage of replication machinery and the mechanism of replication-coupled chromatin assembly behind the replication forks. The recycling of parental histones as well as the nuclear import and the assembly of newly synthesized histones are also discussed with regard to the epigenetic inheritance.
Strategies for Bone Regeneration: From Graft to Tissue Engineering
Authors: Battafarano Giulia , Rossi Michela , De Martino Viviana , Marampon Francesco , Borro Luca , Secinaro Aurelio , Del Fattore Andrea
Published: January 2021

Bone is a regenerative organ characterized by self-renewal ability. Indeed, it is a very dynamic tissue subjected to continuous remodeling in order to preserve its structure and function. However, in clinical practice, impaired bone healing can be observed in patients and medical intervention is needed to regenerate the tissue via the use of natural bone grafts or synthetic bone grafts. The main elements required for tissue engineering include cells, growth factors and a scaffold material to support them. Three different materials (metals, ceramics, and polymers) can be used to create a scaffold suitable for bone regeneration. Several cell types have been investigated in combination with biomaterials. In this review, we describe the options available for bone regeneration, focusing on tissue engineering strategies based on the use of different biomaterials combined with cells and growth factors.
Regulation of the CoA Biosynthetic Complex Assembly in Mammalian Cells
Authors: Baković Jovana , López Martínez David , Nikolaou Savvas , Yu Bess Yi Kun , Tossounian Maria-Armineh , Tsuchiya Yugo , Thrasivoulou Christopher , Filonenko Valeriy , Gout Ivan
Published: January 2021

Coenzyme A (CoA) is an essential cofactor present in all living cells. Under physiological conditions, CoA mainly functions to generate metabolically active CoA thioesters, which are indispensable for cellular metabolism, the regulation of gene expression, and the biosynthesis of neurotransmitters. When cells are exposed to oxidative or metabolic stress, CoA acts as an important cellular antioxidant that protects protein thiols from overoxidation, and this function is mediated by protein CoAlation. CoA and its derivatives are strictly maintained at levels controlled by nutrients, hormones, metabolites, and cellular stresses. Dysregulation of their biosynthesis and homeostasis has deleterious consequences and has been noted in a range of pathological conditions, including cancer, diabetes, Reye’s syndrome, cardiac hypertrophy, and neurodegeneration. The biochemistry of CoA biosynthesis, which involves five enzymatic steps, has been extensively studied. However, the existence of a CoA biosynthetic complex and the mode of its regulation in mammalian cells are unknown. In this study, we report the assembly of all five enzymes that drive CoA biosynthesis, in HEK293/Pank1β and A549 cells, using the in situ proximity ligation assay. Furthermore, we show that the association of CoA biosynthetic enzymes is strongly upregulated in response to serum starvation and oxidative stress, whereas insulin and growth factor signaling downregulate their assembly.
Impact of Digestive Inflammatory Environment and Genipin Crosslinking on Immunomodulatory Capacity of Injectable Musculoskeletal Tissue Scaffold
Authors: Shortridge Colin , Akbari Fakhrabadi Ehsan , Wuescher Leah M. , Worth Randall G. , Liberatore Matthew W. , Yildirim-Ayan Eda
Published: January 2021

The paracrine and autocrine processes of the host response play an integral role in the success of scaffold-based tissue regeneration. Recently, the immunomodulatory scaffolds have received huge attention for modulating inflammation around the host tissue through releasing anti-inflammatory cytokine. However, controlling the inflammation and providing a sustained release of anti-inflammatory cytokine from the scaffold in the digestive inflammatory environment are predicated upon a comprehensive understanding of three fundamental questions. (1) How does the release rate of cytokine from the scaffold change in the digestive inflammatory environment? (2) Can we prevent the premature scaffold degradation and burst release of the loaded cytokine in the digestive inflammatory environment? (3) How does the scaffold degradation prevention technique affect the immunomodulatory capacity of the scaffold? This study investigated the impacts of the digestive inflammatory environment on scaffold degradation and how pre-mature degradation can be prevented using genipin crosslinking and how genipin crosslinking affects the interleukin-4 (IL-4) release from the scaffold and differentiation of naïve macrophages (M0). Our results demonstrated that the digestive inflammatory environment (DIE) attenuates protein retention within the scaffold. Over 14 days, the encapsulated protein released 46% more in DIE than in phosphate buffer saline (PBS), which was improved through genipin crosslinking. We have identified the 0.5 (w/v) genipin concentration as an optimal concentration for improved IL-4 released from the scaffold, cell viability, mechanical strength, and scaffold porosity, and immunomodulation studies. The IL-4 released from the injectable scaffold could differentiate naïve macrophages to an anti-inflammatory (M2) lineage; however, upon genipin crosslinking, the immunomodulatory capacity of the scaffold diminished significantly, and pro-inflammatory markers were expressed dominantly.
Membrane Microvesicles as Potential Vaccine Candidates
Authors: Shkair Layaly , Garanina Ekaterina E. , Stott Robert J. , Foster Toshana L. , Rizvanov Albert A. , Khaiboullina Svetlana F.
Published: January 2021

The prevention and control of infectious diseases is crucial to the maintenance and protection of social and public healthcare. The global impact of SARS-CoV-2 has demonstrated how outbreaks of emerging and re-emerging infections can lead to pandemics of significant public health and socio-economic burden. Vaccination is one of the most effective approaches to protect against infectious diseases, and to date, multiple vaccines have been successfully used to protect against and eradicate both viral and bacterial pathogens. The main criterion of vaccine efficacy is the induction of specific humoral and cellular immune responses, and it is well established that immunogenicity depends on the type of vaccine as well as the route of delivery. In addition, antigen delivery to immune organs and the site of injection can potentiate efficacy of the vaccine. In light of this, microvesicles have been suggested as potential vehicles for antigen delivery as they can carry various immunogenic molecules including proteins, nucleic acids and polysaccharides directly to target cells. In this review, we focus on the mechanisms of microvesicle biogenesis and the role of microvesicles in infectious diseases. Further, we discuss the application of microvesicles as a novel and effective vaccine delivery system.
Magnesium Signaling in Plants
Authors: Kleczkowski Leszek A. , Igamberdiev Abir U.
Published: January 2021

Free magnesium (Mg2+) is a signal of the adenylate (ATP+ADP+AMP) status in the cells. It results from the equilibrium of adenylate kinase (AK), which uses Mg-chelated and Mg-free adenylates as substrates in both directions of its reaction. The AK-mediated primary control of intracellular [Mg2+] is finely interwoven with the operation of membrane-bound adenylate- and Mg2+-translocators, which in a given compartment control the supply of free adenylates and Mg2+ for the AK-mediated equilibration. As a result, [Mg2+] itself varies both between and within the compartments, depending on their energetic status and environmental clues. Other key nucleotide-utilizing/producing enzymes (e.g., nucleoside diphosphate kinase) may also be involved in fine-tuning of the intracellular [Mg2+]. Changes in [Mg2+] regulate activities of myriads of Mg-utilizing/requiring enzymes, affecting metabolism under both normal and stress conditions, and impacting photosynthetic performance, respiration, phloem loading and other processes. In compartments controlled by AK equilibrium (cytosol, chloroplasts, mitochondria, nucleus), the intracellular [Mg2+] can be calculated from total adenylate contents, based on the dependence of the apparent equilibrium constant of AK on [Mg2+]. Magnesium signaling, reflecting cellular adenylate status, is likely widespread in all eukaryotic and prokaryotic organisms, due simply to the omnipresent nature of AK and to its involvement in adenylate equilibration.
Cardiomyocytes Derived from Induced Pluripotent Stem Cells as a Disease Model for Propionic Acidemia
Authors: Alonso-Barroso Esmeralda , Pérez Belén , Desviat Lourdes Ruiz , Richard Eva
Published: January 2021

Propionic acidemia (PA), one of the most frequent life-threatening organic acidemias, is caused by mutations in either the PCCA or PCCB genes encoding both subunits of the mitochondrial propionyl-CoA carboxylase (PCC) enzyme. Cardiac alterations (hypertrophy, dilated cardiomyopathy, long QT) are one of the major causes of mortality in patients surviving the neonatal period. To overcome limitations of current cellular models of PA, we generated induced pluripotent stem cells (iPSCs) from a PA patient with defects in the PCCA gene, and successfully differentiated them into cardiomyocytes. PCCA iPSC-derived cardiomyocytes exhibited reduced oxygen consumption, an accumulation of residual bodies and lipid droplets, and increased ribosomal biogenesis. Furthermore, we found increased protein levels of HERP, GRP78, GRP75, SIG-1R and MFN2, suggesting endoplasmic reticulum stress and calcium perturbations in these cells. We also analyzed a series of heart-enriched miRNAs previously found deregulated in the heart tissue of a PA murine model and confirmed their altered expression. Our novel results show that PA iPSC-cardiomyocytes represent a promising model for investigating the pathological mechanisms underlying PA cardiomyopathies, also serving as an ex vivo platform for therapeutic evaluation.
Design and Synthesis of Novel Imidazole Derivatives Possessing Triazole Pharmacophore with Potent Anticancer Activity, and In Silico ADMET with GSK-3β Molecular Docking Investigations
Authors: Al-blewi Fawzia , Shaikh Salma Akram , Naqvi Arshi , Aljohani Faizah , Aouad Mohamed Reda , Ihmaid Saleh , Rezki Nadjet
Published: January 2021

A library of novel imidazole-1,2,3-triazole hybrids were designed and synthesized based on the hybrid pharmacophore approach. Therefore, copper(I)catalyzed click reaction of thiopropargylated-imidazole 2 with several organoazides yielded two sets of imidazole-1,2,3-triazole hybrids carrying different un/functionalized alkyl/aryl side chains 4a–k and 6a–e. After full spectroscopic characterization using different spectral techniques (IR, 1H, 13C NMR) and elemental analyses, the resulted adducts were screened for their anticancer activity against four cancer cell lines (Caco-2, HCT-116, HeLa, and MCF-7) by the MTT assay and showed significant activity. In-silico molecular docking study was also investigated on one of the prominent cancer target receptors, i.e., glycogen synthase kinase-3β (GSK-3β), revealing a good binding interaction with our potent compound, 4k and was in agreement with the in vitro cytotoxic results. In addition, the ADMET profile was assessed for these novel derivatives to get an insight on their pharmacokinetic/dynamic attributes. Finally, this research design and synthesis offered click chemistry products with interesting biological motifs mainly 1,2,3 triazoles linked to phenyl imidazole as promising candidates for further investigation as anticancer drugs.
Comparative Study of Interactions between Human cGAS and Inhibitors: Insights from Molecular Dynamics and MM/PBSA Studies
Authors: Wang Xiaowen , Li Wenjin
Published: January 2021

Recent studies have identified cyclic GMP-AMP synthase (cGAS) as an important target for treating autoimmune diseases, and several inhibitors of human cGAS (hcGAS) and their structures in complexation with hcGAS have been reported. However, the mechanisms via which these inhibitors interact with hcGAS are not completely understood. Here, we aimed to assess the performance of molecular mechanics/Poisson–Boltzmann solvent-accessible surface area (MM/PBSA) in evaluating the binding affinity of various hcGAS inhibitors and to elucidate their detailed interactions with hcGAS from an energetic viewpoint. Using molecular dynamics (MD) simulation and MM/PBSA approaches, the estimated free energies were in good agreement with the experimental ones, with a Pearson’s correlation coefficient and Spearman’s rank coefficient of 0.67 and 0.46, respectively. In per-residue energy decomposition analysis, four residues, K362, R376, Y436, and K439 in hcGAS were found to contribute significantly to the binding with inhibitors via hydrogen bonding, salt bridges, and various π interactions, such as π· · ·π stacking, cation· · ·π, hydroxyl· · ·π, and alkyl· · ·π interactions. In addition, we discussed other key interactions between specific residues and ligands, in particular, between H363 and JUJ, F379 and 9BY, and H437 and 8ZM. The sandwiched structures of the inhibitor bound to the guanidinium group of R376 and the phenyl ring of Y436 were also consistent with the experimental data. The results indicated that MM/PBSA in combination with other virtual screening methods, could be a reliable approach to discover new hcGAS inhibitors and thus is valuable for potential treatments of cGAS-dependent inflammatory diseases.
The Role of PKM2 in Metabolic Reprogramming: Insights into the Regulatory Roles of Non-Coding RNAs
Authors: Puckett Dexter L. , Alquraishi Mohammed , Chowanadisai Winyoo , Bettaieb Ahmed
Published: January 2021

Pyruvate kinase is a key regulator in glycolysis through the conversion of phosphoenolpyruvate (PEP) into pyruvate. Pyruvate kinase exists in various isoforms that can exhibit diverse biological functions and outcomes. The pyruvate kinase isoenzyme type M2 (PKM2) controls cell progression and survival through the regulation of key signaling pathways. In cancer cells, the dimer form of PKM2 predominates and plays an integral role in cancer metabolism. This predominance of the inactive dimeric form promotes the accumulation of phosphometabolites, allowing cancer cells to engage in high levels of synthetic processing to enhance their proliferative capacity. PKM2 has been recognized for its role in regulating gene expression and transcription factors critical for health and disease. This role enables PKM2 to exert profound regulatory effects that promote cancer cell metabolism, proliferation, and migration. In addition to its role in cancer, PKM2 regulates aspects essential to cellular homeostasis in non-cancer tissues and, in some cases, promotes tissue-specific pathways in health and diseases. In pursuit of understanding the diverse tissue-specific roles of PKM2, investigations targeting tissues such as the kidney, liver, adipose, and pancreas have been conducted. Findings from these studies enhance our understanding of PKM2 functions in various diseases beyond cancer. Therefore, there is substantial interest in PKM2 modulation as a potential therapeutic target for the treatment of multiple conditions. Indeed, a vast plethora of research has focused on identifying therapeutic strategies for targeting PKM2. Recently, targeting PKM2 through its regulatory microRNAs, long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) has gathered increasing interest. Thus, the goal of this review is to highlight recent advancements in PKM2 research, with a focus on PKM2 regulatory microRNAs and lncRNAs and their subsequent physiological significance.
Photodynamic and Cold Atmospheric Plasma Combination Therapy Using Polymeric Nanoparticles for the Synergistic Treatment of Cervical Cancer
Authors: Ha Ji-Hui , Kim Young-Jin
Published: January 2021

Integrating multi-modal therapies into one platform could show great promise in overcoming the drawbacks of conventional single-modal therapy and achieving improved therapeutic efficacy in cancer. In this study, we prepared pheophorbide a (Pheo a)/targeting ligand (epitope analog of oncoprotein E7, EAE7)-conjugated poly(γ-glutamic acid) (γ-PGA)/poly(lactide-co-glycolide)-block-poly(ethylene glycol) methyl ether (MPEG-PLGA)/hyaluronic acid (PPHE) polymeric nanoparticles via self-assembly and encapsulation method for the photodynamic therapy (PDT)/cold atmospheric plasma (CAP) combinatory treatment of human papillomavirus (HPV)-positive cervical cancer, thereby enhancing the therapeutic efficacy. The synthesized PPHE polymeric nanoparticles exhibited a quasi-spherical shape with an average diameter of 80.5 ± 17.6 nm in an aqueous solution. The results from the in vitro PDT efficacy assays demonstrated that PPHE has a superior PDT activity on CaSki cells due to the enhanced targeting ability. In addition, the PDT/CAP combinatory treatment more effectively inhibited the growth of cervical cancer cells by causing elevated intracellular reactive oxygen species generation and apoptotic cell death. Moreover, the three-dimensional cell culture model clearly confirmed the synergistic therapeutic efficacy of the PDT and the CAP combination therapy using PPHE on CaSki cells. Overall, these results indicate that the PDT/CAP combinatory treatment using PPHE is a highly effective new therapeutic modality for cervical cancer.
Expression of Flavodiiron Proteins Flv2-Flv4 in Chloroplasts of Arabidopsis and Tobacco Plants Provides Multiple Stress Tolerance
Authors: Vicino Paula , Carrillo Julieta , Gómez Rodrigo , Shahinnia Fahimeh , Tula Suresh , Melzer Michael , Rutten Twan , Carrillo Néstor , Hajirezaei Mohammad-Reza , Lodeyro Anabella F.
Published: January 2021

With the notable exception of angiosperms, all phototrophs contain different sets of flavodiiron proteins that help to relieve the excess of excitation energy on the photosynthetic electron transport chain during adverse environmental conditions, presumably by reducing oxygen directly to water. Among them, the Flv2-Flv4 dimer is only found in β-cyanobacteria and induced by high light, supporting a role in stress protection. The possibility of a similar protective function in plants was assayed by expressing Synechocystis Flv2-Flv4 in chloroplasts of tobacco and Arabidopsis. Flv-expressing plants exhibited increased tolerance toward high irradiation, salinity, oxidants, and drought. Stress tolerance was reflected by better growth, preservation of photosynthetic activity, and membrane integrity. Metabolic profiling under drought showed enhanced accumulation of soluble sugars and amino acids in transgenic Arabidopsis and a remarkable shift of sucrose into starch, in line with metabolic responses of drought-tolerant genotypes. Our results indicate that the Flv2-Flv4 complex retains its stress protection activities when expressed in chloroplasts of angiosperm species by acting as an additional electron sink. The flv2-flv4 genes constitute a novel biotechnological tool to generate plants with increased tolerance to agronomically relevant stress conditions that represent a significant productivity constraint.
Synthesis and Biological Evaluation of a Novel 18F-Labeled Radiotracer for PET Imaging of the Adenosine A2A Receptor
Authors: Lai Thu Hang , Toussaint Magali , Teodoro Rodrigo , Dukić-Stefanović Sladjana , Kranz Mathias , Deuther-Conrad Winnie , Moldovan Rareş-Petru , Brust Peter
Published: January 2021

The adenosine A2A receptor (A2AR) has emerged as a potential non-dopaminergic target for the treatment of Parkinson’s disease and, thus, the non-invasive imaging with positron emission tomography (PET) is of utmost importance to monitor the receptor expression and occupancy during an A2AR-tailored therapy. Aiming at the development of a PET radiotracer, we herein report the design of a series of novel fluorinated analogs (TOZ1-TOZ7) based on the structure of the A2AR antagonist tozadenant, and the preclinical evaluation of [18F]TOZ1. Autoradiography proved A2AR-specific in vitro binding of [18F]TOZ1 to striatum of mouse and pig brain. Investigations of the metabolic stability in mice revealed parent fractions of more than 76% and 92% of total activity in plasma and brain samples, respectively. Dynamic PET/magnetic resonance imaging (MRI) studies in mice revealed a brain uptake but no A2AR-specific in vivo binding.
Life History of Oxybelus variegatus Wesmael, 1852 (Hymenoptera: Crabronidae) with a Description of the Mature Larva
Authors: Olszewski Piotr , Bogusch Petr , Szpila Krzysztof
Published: January 2021

The first comprehensive information on the bionomics of the digger wasp Oxybelus variegatus Wesmael, 1852 is presented. Females nested in small aggregations in crevices between paving stones of a frequently used pedestrian pathway in lowland agricultural wasteland. Nests were dug in the ground using mandibles, legs and abdomen. The nest consists of a main burrow with one or, rarely, two cells. The mature larva is described for the first time. The egg stage lasts for about two days before the larva hatches. The female provisioned each cell with an average of 11 paralysed male flies of Delia platura (Meigen, 1826) (Diptera: Anthomyiidae). Numerous females of dipteran kleptoparasites were observed in the nesting area of O. variegatus. However, only a few nests were infested by larvae of Senotainia conica (Fallen, 1810).
Effects of Different Infra-Red Irradiations on the Survival of Granary Weevil Sitophilus granarius: Bioefficacy and Sustainability
Authors: Keszthelyi Sándor , Lukács Helga , Pál-Fám Ferenc
Published: January 2021

Sitophilus granarius (L.) is an important pest of stored grain worldwide. In recent years, sustainable methods against it have received attention as grain stock protective means. Our aim was to obtain information about the efficacy of infrared irradiation (IR) against S. granarius in laboratory conditions. The change in adult-activity and median lethal dose (LD50) triggered by IR in S. granarius was examined. The insecticidal efficacy in the infested grains was also analyzed at 12, 24, 48, and 72h following exposure to IR (250W), and the progeny-production was assessed 45 days upon the treatment. Based on our findings, total mortality ensued in a grain stock of 50 g at 412 s and a for 100 g grain at 256 s. A significant increase in S. granarius mortality could be observed in the higher grain weight regime, which can be accounted for by the higher heat-absorbance of objects with higher weight. The activity of pests immediately after the beginning of IR increased and subsequently became moderated. The observation of activity-peak brought about by irradiation contribute to the optimization of chemical intervention. This treatment could provide an effective and sustainable technique in integrated pest management.
Correction: Dodds, K.J.; DiGirolomo, M.F. Effect of Cleaning Multiple-Funnel Traps on Captures of Bark and Woodboring Beetles in Northeastern United States. Insects 2020, 11, 702
Authors: Dodds Kevin J. , DiGirolomo Marc F.
Published: January 2021

The authors wish to make the following corrections to this paper [...]
Low Latency 5G Distributed Wireless Network Architecture: A Techno-Economic Comparison
Authors: Gedel Ibrahim Alhassan , Nwulu Nnamdi I.
Published: January 2021

The most profound requirements of fifth-generation (5G) technology implementations are the architecture design and the radio base station technology to capably run applications such as device-to-device, machine-to machine and internet of things at a reduced latency. Owing to these requirements, the implementation of 5G technology is very expensive to mobile network operators (MNO). In this study we modified the existing 4G network to form a distributed wireless network architecture (DWNA); the picocell and distributed antenna system were modified to support the enabling technology of 5G technology were a multi-edge computer (MEC), software-defined networking (SDN), massive multiple input multiple output (MIMO), ultra-dense network (UDN), Network Functions Virtualization (NFV) and device-to-device (D2D) communication at a reduced cost of ownership, improved coverage and capacity. We present a mathematical model for operational expenditure, capital expenditure and total cost of ownership (TCO) for the DWNA. A mathematical model for DWNA capacity and throughput was presented. Result shows that it is very economical for MNO to rent the space of the tower infrastructure from tower companies. The sensitivity analysis also shows a significant reduction in TCO for both the modified picocell and modified distributed antenna systems.
Acute Myeloid Leukemia Evolving from Myeloproliferative Neoplasms: Many Sides of a Challenging Disease
Authors: Mannelli Francesco
Published: January 2021

The evolution to blast phase is a frequently unpredictable and almost invariably fatal event in the course of myeloproliferative neoplasms. The molecular mechanisms underlying blast transformation have not been elucidated and the specific genetic and epigenetic events governing leukemogenesis remain unclear. The result of the long-lasting dynamics, passing through progressive genetic steps, is the emergence of one or more clones often characterized by complex genetics, either at conventional karyotyping or at modern high-throughput sequencing analyses, with all clinical and prognostic correlates. The current therapeutic approaches are largely inadequate and incapable of modifying the inherent unfavorable outcome. In this perspective, the application of targeted strategies should aim to prevent the occurrence of leukemic evolution. At transformation, the crucial target of treatment should be the allocation to allogeneic transplant for eligible patients. With this in mind, novel combination treatments may provide useful bridging strategies, beyond potentially improving outcomes for patients who are not candidates for intensive approaches.