bluuebunny/crossref_metadata_2025 huggingface dataset:
Cluster Analysis of Urban Acoustic Environments on Barcelona Sensor Network Data
Authors: Pita Antonio , Rodriguez Francisco J. , Navarro Juan M.
Published: August 2021

As cities grow in size and number of inhabitants, continuous monitoring of the environmental impact of sound sources becomes essential for the assessment of the urban acoustic environments. This requires the use of management systems that should be fed with large amounts of data captured by acoustic sensors, mostly remote nodes that belong to a wireless acoustic sensor network. These systems help city managers to conduct data-driven analysis and propose action plans in different areas of the city, for instance, to reduce citizens’ exposure to noise. In this paper, unsupervised learning techniques are applied to discover different behavior patterns, both time and space, of sound pressure levels captured by acoustic sensors and to cluster them allowing the identification of various urban acoustic environments. In this approach, the categorization of urban acoustic environments is based on a clustering algorithm using yearly acoustic indexes, such as Lday, Levening, Lnight and standard deviation of Lden. Data collected over three years by a network of acoustic sensors deployed in the city of Barcelona, Spain, are used to train several clustering methods. Comparison between methods concludes that the k-means algorithm has the best performance for these data. After an analysis of several solutions, an optimal clustering of four groups of nodes is chosen. Geographical analysis of the clusters shows insights about the relation between nodes and areas of the city, detecting clusters that are close to urban roads, residential areas and leisure areas mostly. Moreover, temporal analysis of the clusters gives information about their stability. Using one-year size of the sliding window, changes in the membership of nodes in the clusters regarding tendency of the acoustic environments are discovered. In contrast, using one-month windowing, changes due to seasonality and special events, such as COVID-19 lockdown, are recognized. Finally, the sensor clusters obtained by the algorithm are compared with the areas defined in the strategic noise map, previously created by the Barcelona city council. The developed k-means model identified most of the locations found on the overcoming map and also discovered a new area.
Conservative and Surgical Treatment of Talar Fractures: A Systematic Review and Meta-Analysis on Clinical Outcomes and Complications
Authors: Saravi Babak , Lang Gernot , Ruff Robert , Schmal Hagen , Südkamp Norbert , Ülkümen Sara , Zwingmann Jörn
Published: August 2021

The integrity of the talus is crucial for the physiologic function of the feet. The present study sought to summarize the available evidence on clinical outcomes and complications following conservative and surgical treatment of talar fractures. We systematically searched Medline via OVID to find relevant studies with a follow-up of at least six months. Hereafter, the success and complication rates were extracted and analyzed in a random effects proportion meta-analysis. Complications were defined as avascular bone necrosis (AVN) and posttraumatic osteoarthritis (OA). Additionally, a subgroup analysis was performed for fracture localization (talar neck fractures (TN) and combined talar body/neck fractures (TN/TB)) and severity of the fracture. The quality of the included studies was assessed utilizing the Coleman Methodology Score (CMS). A total of 29 retrospective studies, including 987 fractures with a mean follow-up of 49.9 months, were examined. Success rates were 62%, 60%, and 50% for pooled fractures, TN, and TN/TB, respectively. The overall complication rate for AVN was 25%. The rate was higher for TN (43%) than TN/TB (25%). Talar fractures revealed a 43% posttraumatic osteoarthritis (OA) rate in our meta-analysis. Success rates showed an association with fracture severity, and were generally low in complex multi-fragmentary fractures. The mean CMS was 34.3 (range: 19–47), indicating a moderate methodological quality of the studies. The present systematic review on clinical outcomes of patients undergoing conservative or surgical treatment for talar fractures reveals a lack of reliable prospective evidence. Talar fractures are associated with relatively poor postoperative outcomes, high rates of AVN, and posttraumatic osteoarthritis. Poor outcomes revealed a positive association with fracture severity. Prospective studies investigating predictors for treatment success and/or failure are urgently needed to improve the overall quality of life and function of patients undergoing surgical treatment due to talar fractures.
Factors Associated with School Nurses’ Triage Competency in South Korea
Authors: Yoon Jaehee , Son Heesook
Published: August 2021

This study examined the factors associated with triage competency among school nurses in South Korea. Using a convenience sampling method, 386 school nurses employed in elementary, middle, or high schools completed a cross-sectional survey that included a modified version of the Triage Competency Scale for emergency room nurses. Information regarding experience working in schools and hospitals, education level, school types, age, emergency nursing care certifications, school locations, and serious emergency experience at school was collected. Analyses were performed using SPSS version 25.0, independent t-tests, analyses of variance, Spearman’s correlation, and ordinal logistic regression. Triage competency was higher for school nurses who were employed in metropolitan regions (odds ratio [OR] = 1.63, p = 0.017) and had serious emergency experience (OR = 1.76, p = 0.008). As the participants’ experience at schools or hospitals increased by one year, their triage competency score increased by 2% (OR = 1.02, p = 0.037) and 14% (OR = 1.14, p < 0.001), respectively. These findings could be used to develop policies and educational programs that promote school nurses’ triage competency. Further, they suggest the importance of establishing an organizational support system to develop guidelines and a feedback system to improve school nurses’ triage competency.
Exposomes to Exosomes: Exosomes as Tools to Study Epigenetic Adaptive Mechanisms in High-Altitude Humans
Authors: Padmasekar Manju , Savai Rajkumar , Seeger Werner , Pullamsetti Soni Savai
Published: August 2021

Humans on earth inhabit a wide range of environmental conditions and some environments are more challenging for human survival than others. However, many living beings, including humans, have developed adaptive mechanisms to live in such inhospitable, harsh environments. Among different difficult environments, high-altitude living is especially demanding because of diminished partial pressure of oxygen and resulting chronic hypobaric hypoxia. This results in poor blood oxygenation and reduces aerobic oxidative respiration in the mitochondria, leading to increased reactive oxygen species generation and activation of hypoxia-inducible gene expression. Genetic mechanisms in the adaptation to high altitude is well-studied, but there are only limited studies regarding the role of epigenetic mechanisms. The purpose of this review is to understand the epigenetic mechanisms behind high-altitude adaptive and maladaptive phenotypes. Hypobaric hypoxia is a form of cellular hypoxia, which is similar to the one suffered by critically-ill hypoxemia patients. Thus, understanding the adaptive epigenetic signals operating in in high-altitude adjusted indigenous populations may help in therapeutically modulating signaling pathways in hypoxemia patients by copying the most successful epigenotype. In addition, we have summarized the current information about exosomes in hypoxia research and prospects to use them as diagnostic tools to study the epigenome of high-altitude adapted healthy or maladapted individuals.
Moderate Exercise Combined with Enriched Environment Enhances Learning and Memory through BDNF/TrkB Signaling Pathway in Rats
Authors: Xu Liyuan , Zhu Linna , Zhu Lina , Chen Dandan , Cai Kelong , Liu Zhimei , Chen Aiguo
Published: August 2021

This study aimed to investigate the effects and potential mechanisms of exercise combined with an enriched environment on learning and memory in rats. Forty healthy male Wistar rats (7 weeks old) were randomly assigned into 4 groups (N = 10 in each group): control (C) group, treadmill exercise (TE) group, enriched environment (EE) group and the TE + EE group. The Morris water maze (MWM) test was used to evaluate the learning and memory ability in all rats after eight weeks of exposure in the different conditions. Moreover, we employed enzyme-linked immunosorbent assay (ELISA) to determine the expression of brain-derived neurotrophic factor (BDNF) and receptor tyrosine kinase B (TrkB) in the rats. The data showed that the escape latency and the number of platform crossings were significantly better in the TE + EE group compared to the TE, EE or C groups (p < 0.05). In addition, there was upregulation of BDNF and TrkB in rats in the TE + EE group compared to those in the TE, EE or C groups (p < 0.05). Taken together, the data robustly demonstrate that the combination of TE + EE enhances learning and memory ability and upregulates the expression of both BDNF and TrkB in rats. Thus, the BDNF/TrkB signaling pathway might be modulating the effect of exercise and enriched environment in improving learning and memory ability in rats.
Active Aging in ASEAN Countries: Influences from Age-Friendly Environments, Lifestyles, and Socio-Demographic Factors
Authors: Tiraphat Sariyamon , Kasemsup Vijj , Buntup Doungjai , Munisamy Murallitharan , Nguyen Thang Huu , Hpone Myint Aung
Published: August 2021

Active aging is a challenging issue to promote older population health; still, there is little clarity on research investigating the determinants of active aging in developing countries. Therefore, this research aimed to examine the factors associated with the active aging of the older populations in ASEAN’s low and middle-income countries by focusing on Malaysia, Myanmar, Vietnam, and Thailand. The study is a cross-sectional quantitative research study using multi-stage cluster sampling to randomize the sample. The sample consists of 2031 older people aged 55 years and over, including 510 Thai, 537 Malaysian, 487 Myanmar, and 497 Vietnamese. We collected a quantitative questionnaire of age-friendly environmental scale and active aging scale based on the World Health Organization (WHO) concept. The predictors of active aging include age-friendly environments, lifestyles, and socioeconomic factors; the data are analyzed by using multiple logistic regression. After adjusting for other factors, we found that older people living in a community with higher levels of age-friendly environments are 5.52 times more active than those in lower levels of age-friendly environments. Moreover, the older population with healthy lifestyles such as good dietary intake and high physical activity will be 4.93 times more active than those with unhealthy lifestyles. Additionally, older adults with partners, higher education, and aged between 55 and 64 years will be 1.70, 2.61, and 1.63 times more active than those with separate/divorce/widow, primary education, and age at 75 years or higher, respectively. Our results contribute considerable evidence for ASEAN policy-making to promote active aging in this region.
Smartphone Addiction and Sleep Quality on Academic Performance of University Students: An Exploratory Research
Authors: Rathakrishnan Balan , Bikar Singh Soon Singh , Kamaluddin Mohammad Rahim , Yahaya Azizi , Mohd Nasir Mohd Azrin , Ibrahim Fauziah , Ab Rahman Zaizul
Published: August 2021

This study was conducted to examine the relationship between smartphone addiction, sleep quality, and academic performance. The study presented quantitative research on 323 students in a public university in Sabah to explore the relationship between smartphone addiction, sleep quality, and academic performance. A simple random sampling was used in the study. The Smartphone Addiction Scale Short Version (SAS-SV) and the Pittsburgh Sleep Quality Index (PSQI) were used in this study. SPSS was used as a tool of analysis for descriptive and inferential analysis. Pearson correlation was involved to test the hypothesis of the study. The result indicated that the greater the smartphone addiction, the lower the academic performance of university students. The finding also proved that students with poor sleep quality might exhibit low academic performance. Smartphone addiction was found to be associated with sleep quality where overusing smartphones was related to poor sleep quality in university students. On this basis, the problem of smartphone addiction and sleep quality should be tackled in order to improve the academic performance of university students and their overall health.
Prevalence and Risk Factors of Sarcopenia among Older Adults Aged ≥65 Years Admitted to Daycare Centers of Taiwan: Using AWGS 2019 Guidelines
Authors: Chang Cheng-Fen , Yeh Yu-Lyu , Chang Huang-Yu , Tsai Sheng-Hua , Wang Jiun-Yi
Published: August 2021

Sarcopenia is a geriatric syndrome which is likely to cause disability, body unbalance, and mortality and thus can lead to heavy healthcare expenditure and caregiver burden. Although some studies have addressed the prevalence of sarcopenia for older adults, there are limited studies conducted in daycare centers. The present study aimed to (i) estimate the prevalence of sarcopenia and (ii) explore associated factors of sarcopenia and standing balance among older adults admitted to daycare centers in Taiwan. The cross-sectional study collected data on demographics, health status, handgrip strength, gait speed (GS), skeletal muscle mass, Taiwan-Mini Nutritional Assessment Short-Form (TW-MNA-SF), and Short Physical Performance Battery from daycare centers in northern Taiwan. The definition of sarcopenia followed the Asian Working Group for Sarcopenia 2019 guidelines. Among 173 participants ≥65 year-old, 50.9% had confirmed sarcopenia, 47.4% possible sarcopenia, and 1.7% normal. Results showed that calf circumference, TW-MNA-SF, dementia, and body mass index (BMI) were associated with sarcopenia. Moreover, BMI, GS, and sarcopenia were associated factors of standing balance. The study estimated a high prevalence of sarcopenia in daycare centers and identified some significant factors of sarcopenia and standing balance. Early nutritional and physiotherapy interventions could benefit older adults to prevent sarcopenia or unbalance.
Impacts of Male Intimate Partner Violence on Women: A Life Course Perspective
Authors: Hing Nerilee , O’Mullan Catherine , Mainey Lydia , Nuske Elaine , Breen Helen , Taylor Annabel
Published: August 2021

The nature and extent of the impacts of intimate partner violence (IPV) on victims are well documented, particularly male partner violence against women. However, less is known about how these impacts might change over time, including their legacy after women leave an abusive relationship and the lasting effects in their later lives. The purpose of this study was to examine women’s experiences of IPV at different stages over their life courses. Interviews with a cohort of 18 older women who had left an abusive relationship were analysed using thematic narrative analysis and the findings were presented according to trajectories, transitions, and turning points over their life courses. When in the relationship, the women experienced direct impacts on their physical, mental, social, and financial wellbeing. During separation, many experienced continued abuse and housing, legal, and financial stress. Life after separation was marked by loneliness, trauma, financial insecurity, and damaged relationships. Some women reached a turning point in their recovery through helping others. Understanding these impacts can inform interventions during each stage. Crisis support is critical when women are in an abusive relationship and during the dangerous phase of separation. Interventions can also assist women’s longer-term wellbeing and help them recover through post-traumatic growth.
Case Fatality as an Indicator for the Human Toxicity of Pesticides—A Systematic Scoping Review on the Availability and Variability of Severity Indicators of Pesticide Poisoning
Authors: Moebus Susanne , Boedeker Wolfgang
Published: August 2021

Objective: To investigate if case fatality and other indicators of the severity of human pesticide poisonings can be used to prioritize pesticides of public health concern. To study the heterogeneity of data across countries, cause of poisonings, and treatment facilities. Methods: We searched literature databases as well as the internet for studies on case-fatality and severity scores of pesticide poisoning. Studies published between 1990 and 2014 providing information on active ingredients in pesticides or chemical groups of active ingredients were included. The variability of case-fatality-ratios was analyzed by computing the coefficient of variation as the ratio of the standard deviation to the mean. Findings: A total of 149 papers were identified of which 67 could be included after assessment. Case-fatality-ratio (CFR) on 66 active ingredients and additionally on 13 groups of active ingredients were reported from 20 countries. The overall median CFR for group of pesticides was 9%, for single pesticides 8%. Of those 12 active ingredients with a CFR above 20% more than half are WHO-classified as “moderately hazardous” or “unlikely to present acute hazard”. Two of seven pesticides considered “unlikely to present hazard in normal use” showed a CFR above 20%. The cross-study variability of reported case fatality was rather low. Studies most often utilized the Glasgow Coma Score for grading the severity of poisoning. Conclusion: Although human pesticide poisoning is a serious public health problem, an unexpectedly small number of publications report on the clinical outcomes within our study period. However, CFRs of acute human pesticide poisoning are available for several groups of pesticides as well as for active ingredients showing moderate cross-study variability. Our results underline that CFR is an indicator of the human toxicity of pesticides and can be utilized to prioritize highly hazardous pesticides especially since there is limited correspondence between the animal-test-based hazard classification and the human CFR of the respective pesticide. The reporting of available poisoning data should be improved, human case-fatality data are a reasonable tool to be included systematically in the periodic statutory review of pesticides and their regulation.
Exploring Intraindividual Profiles for Home Buildings Based on Architectural Compositional Elements and Psychological Health Factors: A Transdisciplinary Approach
Authors: Lara-Moreno Raquel , Lara Ester , Godoy-Izquierdo Débora
Published: August 2021

Based on the transactional and salutogenic perspectives, we explored individual profiles that integrate psychosocial factors and compositional elements of the built home environment. Adults with different socio-demographic characteristics completed several self-report measures on psychological factors (personality traits, self-efficacy, mental health, and happiness) and architectural elements constituting the ideal home environment. Adopting an individual-centered perspective, three distinct intra-individual psycho-architectural (person-environment) profiles were found with different compositional preferences and psychosocial characteristics in terms of functioning, health, and well-being: endopathic (characterized by higher levels of psychosocial resources and well-being indicating a highly adapted and successful profile, and architectural preferences corresponding to their identities and experiences—expression through spaces), assimilative (characterized by average levels in all regulatory parameters indicating moderately adaptive individuals, and architectural preferences of spaces created in interactive processes—introjection of spaces), and additive individuals (characterized by a comparatively dysfunctional, poorer psychosocial profile, and architectural preferences in line with provoking a restorative effect—change with spaces). An awareness of the psychosocial features of the users for whom the homes are built can help in designing spaces to inhabit that are adapted to them for an enhancement of their overall well-being. Therefore, a better understanding of the interconnections between psychology and architecture will help in designing healthy spaces.
Reviewing the Significance of Blood–Brain Barrier Disruption in Multiple Sclerosis Pathology and Treatment
Authors: Balasa Rodica , Barcutean Laura , Mosora Oana , Manu Doina
Published: August 2021

The disruption of blood–brain barrier (BBB) for multiple sclerosis (MS) pathogenesis has a double effect: early on during the onset of the immune attack and later for the CNS self-sustained ‘inside-out’ demyelination and neurodegeneration processes. This review presents the characteristics of BBB malfunction in MS but mostly highlights current developments regarding the impairment of the neurovascular unit (NVU) and the metabolic and mitochondrial dysfunctions of the BBB’s endothelial cells. The hypoxic hypothesis is largely studied and agreed upon recently in the pathologic processes in MS. Hypoxia in MS might be produced per se by the NVU malfunction or secondary to mitochondria dysfunction. We present three different but related terms that denominate the ongoing neurodegenerative process in progressive forms of MS that are indirectly related to BBB disruption: progression independent of relapses, no evidence of disease activity and smoldering demyelination or silent progression. Dimethyl fumarate (DMF), modulators of S1P receptor, cladribine and laquinimode are DMTs that are able to cross the BBB and exhibit beneficial direct effects in the CNS with very different mechanisms of action, providing hope that a combined therapy might be effective in treating MS. Detailed mechanisms of action of these DMTs are described and also illustrated in dedicated images. With increasing knowledge about the involvement of BBB in MS pathology, BBB might become a therapeutic target in MS not only to make it impenetrable against activated immune cells but also to allow molecules that have a neuroprotective effect in reaching the cell target inside the CNS.
Conjugation with Phospholipids as a Modification Increasing Anticancer Activity of Phenolic Acids in Metastatic Melanoma—In Vitro and In Silico Studies
Authors: Palko-Łabuz Anna , Gliszczyńska Anna , Skonieczna Magdalena , Poła Andrzej , Wesołowska Olga , Środa-Pomianek Kamila
Published: August 2021

Phenolic acids possess many beneficial biological activities, including antioxidant and anti-inflammatory properties. Unfortunately, their low bioavailability restricts their potential medical uses, as it limits the concentration of phenolic acids achievable in the organism. The conjugation with phospholipids constitutes one of the most effective strategies to enhance compounds bioavailability in biological systems. In the present study, the conjugates of anisic (ANISA) and veratric acid (VA) with phosphatidylcholine (PC) were investigated. Since both ANISA and VA are inhibitors of tyrosinase, a melanocyte enzyme, the expression of which increases during tumorigenesis, anticancer potential of the conjugates was tested in several metastatic melanoma cell lines. The conjugates proved to be antiproliferative, apoptosis-inducing and cell-cycle-affecting agents, selective for cancerous cells and not affecting normal fibroblasts. The conjugates substituted by ANISA and VA, respectively, at both the sn-1 and sn-2 positions of PC, appeared the most promising, since they were effective against the vast majority of metastatic melanoma cell lines. Additionally, the conjugation of phenolic acids to PC increased their antioxidant activity. Molecular modeling was employed for the first time to estimate the features of the investigated conjugates relevant to their anticancer properties and membrane permeation. Again, the conjugates substituted by phenolic acid at both the sn-1 and sn-2 positions of PC seemed to be presumably most bioavailable.
Efficient Neuroprotective Rescue of Sacsin-Related Disease Phenotypes in Zebrafish
Authors: Naef Valentina , Marchese Maria , Ogi Asahi , Fichi Gianluca , Galatolo Daniele , Licitra Rosario , Doccini Stefano , Verri Tiziano , Argenton Francesco , Morani Federica , Santorelli Filippo M.
Published: August 2021

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a multisystem hereditary ataxia associated with mutations in SACS, which encodes sacsin, a protein of still only partially understood function. Although mouse models of ARSACS mimic largely the disease progression seen in humans, their use in the validation of effective therapies has not yet been proposed. Recently, the teleost Danio rerio has attracted increasing attention as a vertebrate model that allows rapid and economical screening, of candidate molecules, and thus combines the advantages of whole-organism phenotypic assays and in vitro high-throughput screening assays. Through CRISPR/Cas9-based mutagenesis, we generated and characterized a zebrafish sacs-null mutant line that replicates the main features of ARSACS. The sacs-null fish showed motor impairment, hindbrain atrophy, mitochondrial dysfunction, and reactive oxygen species accumulation. As proof of principle for using these mutant fish in high-throughput screening studies, we showed that both acetyl-DL-leucine and tauroursodeoxycholic acid improved locomotor and biochemical phenotypes in sacs−/− larvae treated with these neuroprotective agents, by mediating significant rescue of the molecular functions altered by sacsin loss. Taken together, the evidence here reported shows the zebrafish to be a valuable model organism for the identification of novel molecular mechanisms and for efficient and rapid in vivo optimization and screening of potential therapeutic compounds. These findings may pave the way for new interventions targeting the earliest phases of Purkinje cell degeneration in ARSACS.
Systematic Genome-Wide Study and Expression Analysis of SWEET Gene Family: Sugar Transporter Family Contributes to Biotic and Abiotic Stimuli in Watermelon
Authors: Xuan Changqing , Lan Guangpu , Si Fengfei , Zeng Zhilong , Wang Chunxia , Yadav Vivek , Wei Chunhua , Zhang Xian
Published: August 2021

The SWEET (Sugars Will Eventually be Exported Transporter) proteins are a novel family of sugar transporters that play key roles in sugar efflux, signal transduction, plant growth and development, plant–pathogen interactions, and stress tolerance. In this study, 22 ClaSWEET genes were identified in Citrullus lanatus (Thunb.) through homology searches and classified into four groups by phylogenetic analysis. The genes with similar structures, conserved domains, and motifs were clustered into the same groups. Further analysis of the gene promoter regions uncovered various growth, development, and biotic and abiotic stress responsive cis-regulatory elements. Tissue-specific analysis showed most of the genes were highly expressed in male flowers and the roots of cultivated varieties and wild cultivars. In addition, qRT-PCR results further imply that ClaSWEET proteins might be involved in resistance to Fusarium oxysporum infection. Moreover, a significantly higher expression level of these genes under various abiotic stresses suggests its multifaceted role in mediating plant responses to drought, salt, and low-temperature stress. The genome-wide characterization and phylogenetic analysis of ClaSWEET genes, together with the expression patterns in different tissues and stimuli, lays a solid foundation for future research into their molecular function in watermelon developmental processes and responses to biotic and abiotic stresses.
The Clinical Impact of the EPH/Ephrin System in Cancer: Unwinding the Thread
Authors: Pergaris Alexandros , Danas Eugene , Goutas Dimitrios , Sykaras Alexandros G. , Soranidis Angelos , Theocharis Stamatios
Published: August 2021

Erythropoietin-producing human hepatocellular receptors (EPHs) compose the largest known subfamily of receptor tyrosine kinases (RTKs). They bind and interact with the EPH family receptor interacting proteins (ephrins). EPHs/ephrins are implicated in a variety of physiological processes, as well as in cancer pathogenesis. With neoplastic disease remaining a leading cause of death world-wide, the development of novel biomarkers aiding in the field of diagnosis, prognosis, and disease monitoring is of utmost importance. A multitude of studies have proven the association between the expression of members of the EPH/ephrin system and various clinicopathological parameters, including disease stage, tumor histologic grade, and patients’ overall survival. Besides their utilization in timely disease detection and assessment of outcome, EPHs/ephrins could also represent possible novel therapeutic targets. The aim of the current review of the literature was to present the existing data regarding the association between EPH/ephrin system expression and the clinical characteristics of malignant tumors.
Neurotoxic Effects of Neonicotinoids on Mammals: What Is There beyond the Activation of Nicotinic Acetylcholine Receptors?—A Systematic Review
Authors: Costas-Ferreira Carmen , Faro Lilian R. F.
Published: August 2021

Neonicotinoids are a class of insecticides that exert their effect through a specific action on neuronal nicotinic acetylcholine receptors (nAChRs). The success of these insecticides is due to this mechanism of action, since they act as potent agonists of insect nAChRs, presenting low affinity for vertebrate nAChRs, which reduces potential toxic risk and increases safety for non-target species. However, although neonicotinoids are considered safe, their presence in the environment could increase the risk of exposure and toxicity. On the other hand, although neonicotinoids have low affinity for mammalian nAChRs, the large quantity, variety, and ubiquity of these receptors, combined with its diversity of functions, raises the question of what effects these insecticides can produce in non-target species. In the present systematic review, we investigate the available evidence on the biochemical and behavioral effects of neonicotinoids on the mammalian nervous system. In general, exposure to neonicotinoids at an early age alters the correct neuronal development, with decreases in neurogenesis and alterations in migration, and induces neuroinflammation. In adulthood, neonicotinoids induce neurobehavioral toxicity, these effects being associated with their modulating action on nAChRs, with consequent neurochemical alterations. These alterations include decreased expression of nAChRs, modifications in acetylcholinesterase activity, and significant changes in the function of the nigrostriatal dopaminergic system. All these effects can lead to the activation of a series of intracellular signaling pathways that generate oxidative stress, neuroinflammation and, finally, neuronal death. Neonicotinoid-induced changes in nAChR function could be responsible for most of the effects observed in the different studies.
Dual Activation of Phosphodiesterase 3 and 4 Regulates Basal Cardiac Pacemaker Function and Beyond
Authors: Vinogradova Tatiana M. , Lakatta Edward G.
Published: August 2021

The sinoatrial (SA) node is the physiological pacemaker of the heart, and resting heart rate in humans is a well-known risk factor for cardiovascular disease and mortality. Consequently, the mechanisms of initiating and regulating the normal spontaneous SA node beating rate are of vital importance. Spontaneous firing of the SA node is generated within sinoatrial nodal cells (SANC), which is regulated by the coupled-clock pacemaker system. Normal spontaneous beating of SANC is driven by a high level of cAMP-mediated PKA-dependent protein phosphorylation, which rely on the balance between high basal cAMP production by adenylyl cyclases and high basal cAMP degradation by cyclic nucleotide phosphodiesterases (PDEs). This diverse class of enzymes includes 11 families and PDE3 and PDE4 families dominate in both the SA node and cardiac myocardium, degrading cAMP and, consequently, regulating basal cardiac pacemaker function and excitation-contraction coupling. In this review, we will demonstrate similarities between expression, distribution, and colocalization of various PDE subtypes in SANC and cardiac myocytes of different species, including humans, focusing on PDE3 and PDE4. Here, we will describe specific targets of the coupled-clock pacemaker system modulated by dual PDE3 + PDE4 activation and provide evidence that concurrent activation of PDE3 + PDE4, operating in a synergistic manner, regulates the basal cardiac pacemaker function and provides control over normal spontaneous beating of SANCs through (PDE3 + PDE4)-dependent modulation of local subsarcolemmal Ca2+ releases (LCRs).
Harnessing the Potential of CRISPR/Cas in Atherosclerosis: Disease Modeling and Therapeutic Applications
Authors: Siew Wei Sheng , Tang Yin Quan , Kong Chee Kei , Goh Bey-Hing , Zacchigna Serena , Dua Kamal , Chellappan Dinesh Kumar , Duangjai Acharaporn , Saokaew Surasak , Phisalprapa Pochamana , Yap Wei Hsum
Published: August 2021

Atherosclerosis represents one of the major causes of death globally. The high mortality rates and limitations of current therapeutic modalities have urged researchers to explore potential alternative therapies. The clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) system is commonly deployed for investigating the genetic aspects of Atherosclerosis. Besides, advances in CRISPR/Cas system has led to extensive options for researchers to study the pathogenesis of this disease. The recent discovery of Cas9 variants, such as dCas9, Cas9n, and xCas9 have been established for various applications, including single base editing, regulation of gene expression, live-cell imaging, epigenetic modification, and genome landscaping. Meanwhile, other Cas proteins, such as Cas12 and Cas13, are gaining popularity for their applications in nucleic acid detection and single-base DNA/RNA modifications. To date, many studies have utilized the CRISPR/Cas9 system to generate disease models of atherosclerosis and identify potential molecular targets that are associated with atherosclerosis. These studies provided proof-of-concept evidence which have established the feasibility of implementing the CRISPR/Cas system in correcting disease-causing alleles. The CRISPR/Cas system holds great potential to be developed as a targeted treatment for patients who are suffering from atherosclerosis. This review highlights the advances in CRISPR/Cas systems and their applications in establishing pathogenetic and therapeutic role of specific genes in atherosclerosis.
Anti-Inflammatory and Anti-Allergic Effects of Saponarin and Its Impact on Signaling Pathways of RAW 264.7, RBL-2H3, and HaCaT Cells
Authors: Min Seon-Young , Park Che-Hwon , Yu Hye-Won , Park Young-Jin
Published: August 2021

Saponarin{5-hydroxy-2-(4-hydroxyphenyl)-6-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]-7-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one}, a flavone found in young green barley leaves, is known to possess antioxidant, antidiabetic, and hepatoprotective effects. In the present study, the anti-inflammatory, anti-allergic, and skin-protective effects of saponarin were investigated to evaluate its usefulness as a functional ingredient in cosmetics. In lipopolysaccharide-induced RAW264.7 (murine macrophage) cells, saponarin (80 μM) significantly inhibited cytokine expression, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, inducible nitric oxide synthase, and cyclooxygenase (COX)-2. Saponarin (80 μM) also inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) and p38 involved in the mitogen-activated protein kinase signaling pathway in RAW264.7 cells. Saponarin (40 μM) significantly inhibited β-hexosaminidase degranulation as well as the phosphorylation of signaling effectors (Syk, phospholipase Cγ1, ERK, JNK, and p38) and the expression of inflammatory mediators (tumor necrosis factor [TNF]-α, IL-4, IL-5, IL-6, IL-13, COX-2, and FcεRIα/γ) in DNP-IgE- and DNP-BSA-stimulated RBL-2H3 (rat basophilic leukemia) cells. In addition, saponarin (100 μM) significantly inhibited the expression of macrophage-derived chemokine, thymus and activation-regulated chemokine, IL-33, thymic stromal lymphopoietin, and the phosphorylation of signaling molecules (ERK, p38 and signal transducer and activator of transcription 1 [STAT1]) in TNF-α- and interferon (IFN)-γ-stimulated HaCaT (human immortalized keratinocyte) cells. Saponarin (100 μM) also significantly induced the expression of hyaluronan synthase-3, aquaporin 3, and cathelicidin antimicrobial peptide (LL-37) in HaCaT cells, which play an important role as skin barriers. Saponarin remarkably inhibited the essential factors involved in the inflammatory and allergic responses of RAW264.7, RBL-2H3, and HaCaT cells, and induced the expression of factors that function as physical and chemical skin barriers in HaCaT cells. Therefore, saponarin could potentially be used to prevent and relieve immune-related skin diseases, including atopic dermatitis.
A Multi-Scale Model of Disease Transfer in Honey Bee Colonies
Authors: Betti Matthew , Shaw Karalyne
Published: August 2021

Inter-colony disease transfer poses a serious hurdle to successfully managing healthy honeybee colonies. In this study, we build a multi-scale model of two interacting honey bee colonies. The model considers the effects of forager and drone drift, guarding behaviour, and resource robbing of dying colonies on the spread of disease between colonies. Our results show that when drifting is high, disease can spread rapidly between colonies, that guarding behaviour needs to be particularly efficient to be effective, and that for dense apiaries drifting is of greater concern than robbing. We show that while disease can put an individual colony at greater risk, drifting can help less the burden of disease in a colony. We posit some evolutionary questions that come from this study that can be addressed with this model.
The Global Limb Anatomic Staging System (GLASS) for CLTI: Improving Inter-Observer Agreement
Authors: Wijnand Joep G. J. , Zarkowsky Devin , Wu Bian , van Haelst Steven T. W. , Vonken Evert-Jan P. A. , Sorrentino Thomas A. , Pallister Zachary , Chung Jayer , Mills Joseph L. , Teraa Martin , Verhaar Marianne C. , de Borst Gert J. , Conte Michael S.
Published: August 2021

Objective: The 2020 Global Vascular Guidelines aim at improving decision making in Chronic Limb-Threatening Ischemia (CLTI) by providing a framework for evidence-based revascularization. Herein, the Global Limb Anatomic Staging System (GLASS) serves to estimate the chance of success and patency of arterial pathway revascularization based on the extent and distribution of the atherosclerotic lesions. We report the preliminary feasibility results and observer variability of the GLASS. GLASS is a part of the new global guideline and posed as a promising additional tool for EBR strategies to predict the success of lower extremity arterial revascularization. This study reports on the consistency of GLASS scoring to maximize inter-observer agreement and facilitate its application. Methods: GLASS separately scores the femoropopliteal (FP) and infrapopliteal (IP) segment based on stenosis severity, lesion length and the extent of calcification within the target artery pathway (TAP). In our stepwise approach, we used two angiographic datasets. Each following step was based on the lessons learned from the previous step. The primary outcome was inter-observer agreement measured as Cohen’s Kappa, scored by two (step 1 + 2) and four (step 3) blinded and experienced observers, respectively. Steps 1 (n = 139) and 2 (n = 50) were executed within a dataset of a Dutch interventional RCT in CLTI. Step 3 (n = 100) was performed in randomly selected all-comer CLTI patients from two vascular centers in the United States. Results: In step 1, kappa values were 0.346 (FP) and 0.180 (IP). In step 2, applied in the same dataset, the use of other experienced observers and a provided TAP, resulted in similar low kappa values 0.406 (FP) and 0.089 (IP). Subsequently, in step 3, the formation of an altered stepwise approach using component scoring, such as separate scoring of calcification and adding a ruler to the images resulted in kappa values increasing to 0.796 (FP) and 0.730 (IP). Conclusion: This retrospective GLASS validation study revealed low inter-observer agreement for unconditioned scoring. A stepwise component scoring provides acceptable agreement and a solid base for further prospective validation studies to investigate how GLASS relates to treatment outcomes.
Role of miRNAs in Normal Endometrium and in Endometrial Disorders: Comprehensive Review
Authors: Kolanska Kamila , Bendifallah Sofiane , Canlorbe Geoffroy , Mekinian Arsène , Touboul Cyril , Aractingi Selim , Chabbert-Buffet Nathalie , Daraï Emile
Published: August 2021

The molecular responses to hormonal stimuli in the endometrium are modulated at the transcriptional and post-transcriptional stages. Any imbalance in cellular and molecular endometrial homeostasis may lead to gynecological disorders. MicroRNAs (miRNAs) are involved in a wide variety of physiological mechanisms and their expression patterns in the endometrium are currently attracting a lot of interest. miRNA regulation could be hormone dependent. Conversely, miRNAs could regulate the action of sexual hormones. Modifications to miRNA expression in pathological situations could either be a cause or a result of the existing pathology. The complexity of miRNA actions and the diversity of signaling pathways controlled by numerous miRNAs require rigorous analysis and findings need to be interpreted with caution. Alteration of miRNA expression in women with endometriosis has been reported. Thus, a potential diagnostic test supported by a specific miRNA signature could contribute to early diagnosis and a change in the therapeutic paradigm. Similarly, specific miRNA profile signatures are expected for RIF and endometrial cancer, with direct implications for associated therapies for RIF and adjuvant therapies for endometrial cancer. Advances in targeted therapies based on the regulation of miRNA expression are under evaluation.
The Assessment of Muscle Mass and Function in Patients with Long-Standing Rheumatoid Arthritis
Authors: Yun Hye-Won , Kim Chun-Ja , Kim Ji-Won , Kim Hyoun-Ah , Suh Chang-Hee , Jung Ju-Yang
Published: August 2021

Muscular dysfunction in rheumatoid arthritis (RA) can affect the quality of life and comorbidities. We enrolled 320 patients with RA, and evaluated their muscle mass, grip strength, and physical performance. Seven (2.2%) and 21 RA patients (6.6%) had sarcopenia, as defined by the European and Asian Working Group for Sarcopenia (EWGS and AWGS), respectively; 54 patients (16.9%) were determined to have low muscle mass with normal muscle function, as defined by the EWGS; 38 patients (11.9%) reported sarcopenia by SARC-F questionnaire. Male sex (odds ratio (OR) 140.65), low body mass index (BMI) (OR 0.41), and use of tumor necrosis factor (TNF) inhibitors (OR 4.84) were associated with a low muscle mass as defined by the EWGS, while male sex, old age, and low BMI were associated with sarcopenia as defined by the AWGS. Old age (OR 1.11), high BMI (OR 1.13), and a high Disease Activity Score 28 (OR 1.95) were associated with sarcopenia as reported on the SARC-F. Male, low BMI, and use of TNF inhibitors were associated with a low muscle mass, while male sex, old age, and low BMI were associated with sarcopenia in patients with long-standing RA.
The Relationship between Stress and Masticatory Muscle Activity in Female Students
Authors: Zieliński Grzegorz , Ginszt Michał , Zawadka Magdalena , Rutkowska Katarzyna , Podstawka Zuzanna , Szkutnik Jacek , Majcher Piotr , Gawda Piotr
Published: August 2021

The aim of the study was to analyze the relationship between stress measured by the perceived stress scale (PSS-10) questionnaire and masticatory muscle activity. Experimental design assumed the study of healthy young women without temporomandibular disorders, dividing them into three groups depending on the result of the stress level and then comparing these groups in terms of bioelectrical activity of the masticatory muscles. After the exclusion criteria were applied, 63 female students (mean age: 22.3 ± 2.4 years) from Medical University of Lublin were included in the study. The subjects were then divided into 3 groups: with low (n = 18), medium (n = 18) and high stress level (n = 27), according to PSS-10 results. Resting and functional activity of temporalis anterior (TA) and masseter (MM) muscles were measured by electromyograph BioEMG III. There were statistically significant effects of group on the absolute value of asymmetry index (AsI) of TA and MM during maximum voluntary clenching on dental cotton rollers (both p = 0.02). Post hoc analysis shows that there were statistically significant differences between medium and high stress groups in AsI TA (p = 0.01) and between low and high stress groups in AsI MM (p = 0.02). Perceived stress measured by PSS-10 questionnaire seems to be associated with changes in muscular asymmetry in functional clenching activity.
Decoding the Myeloid-Derived Suppressor Cells in Lymphoid Malignancies
Authors: Papafragkos Iosif , Markaki Efrosyni , Kalpadakis Christina , Verginis Panayotis
Published: August 2021

Myeloid-derived suppressor cells (MDSCs) are immature myeloid precursors which emerged as a potent regulator of the immune system, exerting suppressive properties in diverse disease settings. In regards to cancer, MDSCs have an established role in solid tumors; however, their contribution to immune regulation during hematologic malignancies and particularly in lymphomas remains ill-defined. Herein focused on lymphoma, we discuss the literature on MDSC cells in all histologic types, and we also refer to lessons learned by animal models of lymphoma. Furthermore, we elaborate on future directions and unmet needs and challenges in the MDSC field related to lymphoma malignancies which may shed light on the complex nature of the immune system in malignancies.
Special Issue: “The Latest Clinical Advances in Thrombocytopenia”
Authors: ten Cate Hugo , Lämmle Bernhard
Published: August 2021

Platelets are critical elements in the blood stream, supporting hemostasis as well as performing even more complex tasks within networks of biological (immunity) and pathophysiological processes, such as cancer and ischemia/reperfusion injury [...]
Aberrantly Glycosylated IgA1 in IgA Nephropathy: What We Know and What We Don’t Know
Authors: Ohyama Yukako , Renfrow Matthew B. , Novak Jan , Takahashi Kazuo
Published: August 2021

IgA nephropathy (IgAN), the most common primary glomerular disease worldwide, is characterized by glomerular deposition of IgA1-containing immune complexes. The IgA1 hinge region (HR) has up to six clustered O-glycans consisting of Ser/Thr-linked N-acetylgalactosamine usually with β1,3-linked galactose and variable sialylation. Circulating levels of IgA1 with abnormally O-glycosylated HR, termed galactose-deficient IgA1 (Gd-IgA1), are increased in patients with IgAN. Current evidence suggests that IgAN is induced by multiple sequential pathogenic steps, and production of aberrantly glycosylated IgA1 is considered the initial step. Thus, the mechanisms of biosynthesis of aberrantly glycosylated IgA1 and the involvement of aberrant glycoforms of IgA1 in disease development have been studied. Furthermore, Gd-IgA1 represents an attractive biomarker for IgAN, and its clinical significance is still being evaluated. To elucidate the pathogenesis of IgAN, it is important to deconvolute the biosynthetic origins of Gd-IgA1 and characterize the pathogenic IgA1 HR O-glycoform(s), including the glycan structures and their sites of attachment. These efforts will likely lead to development of new biomarkers. Here, we review the IgA1 HR O-glycosylation in general and the role of aberrantly glycosylated IgA1 in the pathogenesis of IgAN in particular.