bluuebunny/crossref_metadata_2025 huggingface dataset:
The Mediating Effects of Nursing Professional Commitment on the Relationship between Social Support, Resilience, and Intention to Stay among Newly Graduated Male Nurses: A Cross-Sectional Questionnaire Survey
Authors: Yu Hsingyi , Huang Chunhsia , Chin Yenfan , Shen Yungchao , Chiang Yuehtao , Chang Chiwen , Lou Jiunnhorng
Published: July 2021

The current shortage of nurses is an important global issue. Most male nurses leave nursing within four years of starting their nursing career. It is crucial to understand the influencing factors on newly graduated male nurses staying in nursing. Previous studies on intentions to stay as nurses were seldom based on theory and failed to consider the differences between genders. Based on the Job Demands-Resources (JD-R) model, this study tested the model that social support, resilience, and nursing professional commitment influence the intention to stay and the mediating effect of nursing professional commitment in the above relationship. This cross-sectional study adopted purposive and snowball sampling methods. Data were collected using online questionnaire, and 272 newly graduated male nurses completed it. The hypothetical model had a good fit with the data. Nursing professional commitment had a complete mediating effect between social support and intention to stay and between resilience and intention to stay. Nursing professional commitment was highly positively correlated to intention to stay. It is suggested that future research and practice should enhance male nurses’ professional commitment to increase their intention to stay. The findings can serve as reference for developing newly graduated male nurse retention programs.
Health Promotion through Movement Behaviors and Its Relationship with Quality of Life in Spanish High School Adolescents: A Predictive Study
Authors: Vaquero-Solís Mikel , Tapia-Serrano Miguel Angel , Hortigüela-Alcalá David , Jacob-Sierra Manuel , Sánchez-Miguel Pedro Antonio
Published: July 2021

A growing number of studies have highlighted the health benefits of high physical activity, low screen time, and optimal sleep duration among school-age children and adolescents. Objective: The present study proposes to examine the individual and combined association between movement behaviors (physical activity, screen time, and sleep time) and quality of life in boys and girls. Method: A total of 319 Spanish primary and secondary school students participated in the study. Physical activity, screen time, sleep duration, and quality of life were evaluated. Results: Descriptive, correlation, and regression analyses were carried out in order to improve knowledge about health-related behaviors for all participants. The results found significant positive associations between physical activities and sleep time with quality of life. Finally, the regression models showed that physical activity scores predict quality of life, especially in children. It is concluded that movement behaviors are important in association with quality of life. Likewise, the impact of physical activity on the quality of life is highlighted as the main behavior in the prediction of the quality of life for a population of school adolescents.
Ultrasound Imaging as a Visual Biofeedback Tool in Rehabilitation: An Updated Systematic Review
Authors: Valera-Calero Juan Antonio , Fernández-de-las-Peñas César , Varol Umut , Ortega-Santiago Ricardo , Gallego-Sendarrubias Gracia María , Arias-Buría José Luis
Published: July 2021

Rehabilitative ultrasound imaging (RUSI) is used by physical therapists as a feedback tool for measuring changes in muscle morphology during therapeutic interventions such as motor control exercises (MCE). However, a structured overview of its efficacy is lacking. We aimed to systematically review the efficacy of RUSI for improving MCE programs compared with no feedback and other feedback methods. MEDLINE, PubMed, SCOPUS and Web of Science databases were searched for studies evaluating efficacy data of RUSI to improve muscular morphology, quality, and/or function of skeletal muscles and MCE success. Eleven studies analyzing RUSI feedback during MCE were included. Most studies showed acceptable methodological quality. Seven studies assessed abdominal wall muscles, one assessed pelvic floor muscles, one serratus anterior muscle, and two lumbar multifidi. Eight studies involved healthy subjects and three studies clinical populations. Eight studies assessed muscle thickness and pressure differences during MCE, two assessed the number of trials needed to successfully perform MCE, three assessed the retain success, seven assessed the muscle activity with electromyography and one assessed clinical severity outcomes. Visual RUSI feedback seems to be more effective than tactile and/or verbal biofeedback for improving MCE performance and retention success, but no differences with pressure unit biofeedback were found.
Breast Cancer Characteristics in the Population of Survivors Participating in the World Trade Center Environmental Health Center Program 2002–2019
Authors: Arslan Alan A. , Zhang Yian , Durmus Nedim , Pehlivan Sultan , Addessi Adrienne , Schnabel Freya , Shao Yongzhao , Reibman Joan
Published: July 2021

The destruction of World Trade Center on 11 September 2001 exposed local community members to a complex mixture of known carcinogens and potentially carcinogenic substances. To date, breast cancer has not been characterized in detail in the WTC-exposed civilian populations. The cancer characteristics of breast cancer patients were derived from the newly developed Pan-Cancer Database at the WTC Environmental Health Center (WTC EHC). We used the Surveillance, Epidemiology, and End Results (SEER) Program breast cancer data as a reference source. Between May 2002 and 31 December 2019, 2840 persons were diagnosed with any type of cancer at the WTC EHC, including 601 patients with a primary breast cancer diagnosis (592 women and 9 men). There was a higher proportion of grade 3 (poorly differentiated) tumors (34%) among the WTC EHC female breast cancers compared to that of the SEER-18 data (25%). Compared to that of the SEER data, female breast cancers in the WTC EHC had a lower proportion of luminal A (88% and 65%, respectively), higher proportion of luminal B (13% and 15%, respectively), and HER-2-enriched (5.5% and 7%, respectively) subtypes. These findings suggest considerable differences in the breast cancer characteristics and distribution of breast cancer intrinsic subtypes in the WTC-exposed civilian population compared to that of the general population. This is important because of the known effect of molecular subtypes on breast cancer prognosis.
Development of a Codebook of Online Anti-Vaccination Rhetoric to Manage COVID-19 Vaccine Misinformation
Authors: Hughes Brian , Miller-Idriss Cynthia , Piltch-Loeb Rachael , Goldberg Beth , White Kesa , Criezis Meili , Savoia Elena
Published: July 2021

Vaccine hesitancy (delay in obtaining a vaccine, despite availability) represents a significant hurdle to managing the COVID-19 pandemic. Vaccine hesitancy is in part related to the prevalence of anti-vaccine misinformation and disinformation, which are spread through social media and user-generated content platforms. This study uses qualitative coding methodology to identify salient narratives and rhetorical styles common to anti-vaccine and COVID-denialist media. It organizes these narratives and rhetorics according to theme, imagined antagonist, and frequency. Most frequent were narratives centered on “corrupt elites” and rhetorics appealing to the vulnerability of children. The identification of these narratives and rhetorics may assist in developing effective public health messaging campaigns, since narrative and emotion have demonstrated persuasive effectiveness in other public health communication settings.
Recent Advances in Kinase Drug Discovery Part I: The Editors’ Take
Authors: Tucker Julie A. , Martin Mathew P.
Published: July 2021

This special issue on Advances in Kinase Drug Discovery provides a selection of research articles and topical reviews covering all aspects of drug discovery targeting the phosphotransferase enzyme family [...]
The Functional Diversity of Nitric Oxide Synthase Isoforms in Human Nose and Paranasal Sinuses: Contrasting Pathophysiological Aspects in Nasal Allergy and Chronic Rhinosinusitis
Authors: Kawasumi Tomohiro , Takeno Sachio , Ishikawa Chie , Takahara Daisuke , Taruya Takayuki , Takemoto Kota , Hamamoto Takao , Ishino Takashi , Ueda Tsutomu
Published: July 2021

The human paranasal sinuses are the major source of intrinsic nitric oxide (NO) production in the human airway. NO plays several roles in the maintenance of physiological homeostasis and the regulation of airway inflammation through the expression of three NO synthase (NOS) isoforms. Measuring NO levels can contribute to the diagnosis and assessment of allergic rhinitis (AR) and chronic rhinosinusitis (CRS). In symptomatic AR patients, pro-inflammatory cytokines upregulate the expression of inducible NOS (iNOS) in the inferior turbinate. Excessive amounts of NO cause oxidative damage to cellular components, leading to the deposition of cytotoxic substances. CRS phenotype and endotype classifications have provided insights into modern treatment strategies. Analyses of the production of sinus NO and its metabolites revealed pathobiological diversity that can be exploited for useful biomarkers. Measuring nasal NO based on different NOS activities is a potent tool for specific interventions targeting molecular pathways underlying CRS endotype-specific inflammation. We provide a comprehensive review of the functional diversity of NOS isoforms in the human sinonasal system in relation to these two major nasal disorders’ pathologies. The regulatory mechanisms of NOS expression associated with the substrate bioavailability indicate the involvement of both type 1 and type 2 immune responses.
Mitochondrial Bioenergetics in Different Pathophysiological Conditions
Authors: Valenti Daniela , Atlante Anna
Published: July 2021

Mitochondria are complex intracellular organelles involved in many aspects of cellular life, with a primary role in bioenergy production via oxidative phosphorylation (OXPHOS) [...]
N-3-Hydroxy Dodecanoyl-DL-homoserine Lactone (OH-dDHL) Triggers Apoptosis of Bone Marrow-Derived Macrophages through the ER- and Mitochondria-Mediated Pathways
Authors: Woo Kyungho , Kim Dong Ho , Oh Man Hwan , Park Ho Sung , Choi Chul Hee
Published: July 2021

Quorum sensing of Acinetobacter nosocomialis for cell-to-cell communication produces N-3-hydroxy dodecanoyl-DL-homoserine lactone (OH-dDHL) by an AnoR/I two-component system. However, OH-dDHL-driven apoptotic mechanisms in hosts have not been clearly defined. Here, we investigated the induction of apoptosis signaling pathways in bone marrow-derived macrophages treated with synthetic OH-dDHL. Moreover, the quorum-sensing system for virulence regulation was evaluated in vivo using wild-type and anoI-deletion mutant strains. OH-dDHL decreased the viability of macrophage and epithelial cells in dose- and time-dependent manners. OH-dDHL induced Ca2+ efflux and caspase-12 activation by ER stress transmembrane protein (IRE1 and ATF6a p50) aggregation and induced mitochondrial dysfunction through reactive oxygen species (ROS) production, which caused cytochrome c to leak. Pretreatment with a pan-caspase inhibitor reduced caspase-3, -8, and -9, which were activated by OH-dDHL. Pro-inflammatory cytokine and paraoxonase-2 (PON2) gene expression were increased by OH-dDHL. We showed that the anoI-deletion mutant strains have less intracellular invasion compared to the wild-type strain, and their virulence, such as colonization and dissemination, was decreased in vivo. Consequently, these findings revealed that OH-dDHL, as a virulence factor, contributes to bacterial infection and survival as well as the modification of host responses in the early stages of infection.
Wild-Type and Mutant FUS Expression Reduce Proliferation and Neuronal Differentiation Properties of Neural Stem Progenitor Cells
Authors: Stronati Eleonora , Biagioni Stefano , Fiore Mario , Giorgi Mauro , Poiana Giancarlo , Toselli Camilla , Cacci Emanuele
Published: July 2021

Nervous system development involves proliferation and cell specification of progenitor cells into neurons and glial cells. Unveiling how this complex process is orchestrated under physiological conditions and deciphering the molecular and cellular changes leading to neurological diseases is mandatory. To date, great efforts have been aimed at identifying gene mutations associated with many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Mutations in the RNA/DNA binding protein Fused in Sarcoma/Translocated in Liposarcoma (FUS/TLS) have been associated with motor neuron degeneration in rodents and humans. Furthermore, increased levels of the wild-type protein can promote neuronal cell death. Despite the well-established causal link between FUS mutations and ALS, its role in neural cells remains elusive. In order to shed new light on FUS functions we studied its role in the control of neural stem progenitor cell (NSPC) properties. Here, we report that human wild-type Fused in Sarcoma (WT FUS), exogenously expressed in mouse embryonic spinal cord-derived NSPCs, was localized in the nucleus, caused cell cycle arrest in G1 phase by affecting cell cycle regulator expression, and strongly reduced neuronal differentiation. Furthermore, the expression of the human mutant form of FUS (P525L-FUS), associated with early-onset ALS, drives the cells preferentially towards a glial lineage, strongly reducing the number of developing neurons. These results provide insight into the involvement of FUS in NSPC proliferation and differentiation into neurons and glia.
Ruthenium(II) and Platinum(II) Complexes with Biologically Active Aminoflavone Ligands Exhibit In Vitro Anticancer Activity
Authors: Fabijańska Małgorzata , Kasprzak Maria M. , Ochocki Justyn
Published: July 2021

Continuing our studies on the mechanisms underlying the cytotoxicity of potential drugs, we have described several aspects of the in vitro anticancer activity of ruthenium(II) and platinum(II) complexes with bioactive, synthetic aminoflavone ligands. We examined the mechanism of proapoptotic activity of cis-dichlorobis(3-imino-2-methoxyflavanone)ruthenium(II), cis-dichlorobis(3-imino-2-ethoxyflavanone)ruthenium(II), and trans-dichlorobis(3-aminoflavone)platinum(II). Cisplatin was used as a reference compound. The cytotoxicity was investigated by MTT assay. The mechanism of proapoptotic activity of the tested compounds was investigated by evaluation of caspase-8 activity, cytometric analysis of annexin-V positive cells, and mitochondrial potential loss measurement. The results showed that ruthenium compounds break partially or completely the cisplatin resistance by activating the caspase 8-dependent apoptosis pathway and loss of mitochondrial membrane potential. Platinum compounds also have a cytostatic effect, but their action requires more exposure time. Potential mechanisms underlying drug resistance in the two pairs of cancer cell lines were investigated: total glutathione content, P-glycoprotein activity, and differences in the activity of DNA repair induced by nucleotide excision. Results showed that cisplatin-resistant cells have elevated glutathione levels relative to sensitive cells. Moreover, they indicated the mechanisms enabling cells to avoid apoptosis caused by DNA damage. Pg-P activity has no effect on the development of cisplatin resistance in the cell lines described.
Somatotroph Tumors and the Epigenetic Status of the GNAS Locus
Authors: Romanet Pauline , Galluso Justine , Kamenicky Peter , Hage Mirella , Theodoropoulou Marily , Roche Catherine , Graillon Thomas , Etchevers Heather C. , De Murat Daniel , Mougel Grégory , Figarella-Branger Dominique , Dufour Henry , Cuny Thomas , Assié Guillaume , Barlier Anne
Published: July 2021

Forty percent of somatotroph tumors harbor recurrent activating GNAS mutations, historically called the gsp oncogene. In gsp-negative somatotroph tumors, GNAS expression itself is highly variable; those with GNAS overexpression most resemble phenotypically those carrying the gsp oncogene. GNAS is monoallelically expressed in the normal pituitary due to methylation-based imprinting. We hypothesize that changes in GNAS imprinting of gsp-negative tumors affect GNAS expression levels and tumorigenesis. We characterized the GNAS locus in two independent somatotroph tumor cohorts: one of 23 tumors previously published (PMID: 31883967) and classified by pan-genomic analysis, and a second with 82 tumors. Multi-omics analysis of the first cohort identified a significant difference between gsp-negative and gsp-positive tumors in the methylation index at the known differentially methylated region (DMR) of the GNAS A/B transcript promoter, which was confirmed in the larger series of 82 tumors. GNAS allelic expression was analyzed using a polymorphic Fok1 cleavage site in 32 heterozygous gsp-negative tumors. GNAS expression was significantly reduced in the 14 tumors with relaxed GNAS imprinting and biallelic expression, compared to 18 tumors with monoallelic expression. Tumors with relaxed GNAS imprinting showed significantly lower SSTR2 and AIP expression levels. Altered A/B DMR methylation was found exclusively in gsp-negative somatotroph tumors. 43% of gsp-negative tumors showed GNAS imprinting relaxation, which correlated with lower GNAS, SSTR2 and AIP expression, indicating lower sensitivity to somatostatin analogues and potentially aggressive behavior.
Current Options and Future Directions for NAFLD and NASH Treatment
Authors: Zhang Chunye , Yang Ming
Published: July 2021

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, with a broad spectrum ranging from simple steatosis to advanced stage of nonalcoholic steatohepatitis (NASH). Although there are many undergoing clinical trials for NAFLD treatment, there is no currently approved treatment. NAFLD accounts as a major causing factor for the development of hepatocellular carcinoma (HCC), and its incidence rises accompanying the prevalence of obesity and diabetes. Reprogramming of antidiabetic and anti-obesity medicine is a major treatment option for NAFLD and NASH. Liver inflammation and cellular death, with or without fibrosis account for the progression of NAFLD to NASH. Therefore, molecules and signaling pathways involved in hepatic inflammation, fibrosis, and cell death are critically important targets for the therapy of NAFLD and NASH. In addition, the avoidance of aberrant infiltration of inflammatory cytokines by treating with CCR antagonists also provides a therapeutic option. Currently, there is an increasing number of pre-clinical and clinical trials undergoing to evaluate the effects of antidiabetic and anti-obesity drugs, antibiotics, pan-caspase inhibitors, CCR2/5 antagonists, and others on NAFLD, NASH, and liver fibrosis. Non-invasive serum diagnostic markers are developed for fulfilling the need of diagnostic testing in a large amount of NAFLD cases. Overall, a better understanding of the underlying mechanism of the pathogenesis of NAFLD is helpful to choose an optimized treatment.
Early Microvascular Dysfunction: Is the Vasa Vasorum a “Missing Link” in Insulin Resistance and Atherosclerosis
Authors: Owusu Jeanette , Barrett Eugene
Published: July 2021

The arterial vasa vasorum is a specialized microvasculature that provides critical perfusion required for the health of the arterial wall, and is increasingly recognized to play a central role in atherogenesis. Cardio-metabolic disease (CMD) (including hypertension, metabolic syndrome, obesity, diabetes, and pre-diabetes) is associated with insulin resistance, and characteristically injures the microvasculature in multiple tissues, (e.g., the eye, kidney, muscle, and heart). CMD also increases the risk for atherosclerotic vascular disease. Despite this, the impact of CMD on vasa vasorum structure and function has been little studied. Here we review emerging information on the early impact of CMD on the microvasculature in multiple tissues and consider the potential impact on atherosclerosis development and progression, if vasa vasorum is similarly affected.
Application of a New Engineered Strain of Yarrowia lipolytica for Effective Production of Calcium Ketoglutarate Dietary Supplements
Authors: Tomaszewska-Hetman Ludwika , Rywińska Anita , Lazar Zbigniew , Juszczyk Piotr , Rakicka-Pustułka Magdalena , Janek Tomasz , Kuźmińska-Bajor Marta , Rymowicz Waldemar
Published: July 2021

The present study aimed to develop a technology for the production of dietary supplements based on yeast biomass and α-ketoglutaric acid (KGA), produced by a new transformant of Yarrowia lipolytica with improved KGA biosynthesis ability, as well to verify the usefulness of the obtained products for food and feed purposes. Transformants of Y. lipolytica were constructed to overexpress genes encoding glycerol kinase, methylcitrate synthase and mitochondrial organic acid transporter. The strains were compared in terms of growth ability in glycerol- and oil-based media as well as their suitability for KGA biosynthesis in mixed glycerol–oil medium. The impact of different C:N:P ratios on KGA production by selected strain was also evaluated. Application of the strain that overexpressed all three genes in the culture with a C:N:P ratio of 87:5:1 allowed us to obtain 53.1 g/L of KGA with productivity of 0.35 g/Lh and yield of 0.53 g/g. Finally, the possibility of obtaining three different products with desired nutritional and health-beneficial characteristics was demonstrated: (1) calcium α-ketoglutarate (CaKGA) with purity of 89.9% obtained by precipitation of KGA with CaCO3, (2) yeast biomass with very good nutritional properties, (3) fixed biomass-CaKGA preparation containing 87.2 μg/g of kynurenic acid, which increases the health-promoting value of the product.
Problems of Pathogenesis and Pathogenetic Therapy of COVID-19 from the Perspective of the General Theory of Pathological Systems (General Pathological Processes)
Authors: Gusev Evgenii , Sarapultsev Alexey , Hu Desheng , Chereshnev Valeriy
Published: July 2021

The COVID-19 pandemic examines not only the state of actual health care but also the state of fundamental medicine in various countries. Pro-inflammatory processes extend far beyond the classical concepts of inflammation. They manifest themselves in a variety of ways, beginning with extreme physiology, then allostasis at low-grade inflammation, and finally the shockogenic phenomenon of “inflammatory systemic microcirculation”. The pathogenetic core of critical situations, including COVID-19, is this phenomenon. Microcirculatory abnormalities, on the other hand, lie at the heart of a specific type of general pathological process known as systemic inflammation (SI). Systemic inflammatory response, cytokine release, cytokine storm, and thrombo-inflammatory syndrome are all terms that refer to different aspects of SI. As a result, the metabolic syndrome model does not adequately reflect the pathophysiology of persistent low-grade systemic inflammation (ChSLGI). Diseases associated with ChSLGI, on the other hand, are risk factors for a severe COVID-19 course. The review examines the role of hypoxia, metabolic dysfunction, scavenger receptors, and pattern-recognition receptors, as well as the processes of the hemophagocytic syndrome, in the systemic alteration and development of SI in COVID-19.
CFTR Lifecycle Map—A Systems Medicine Model of CFTR Maturation to Predict Possible Active Compound Combinations
Authors: Vinhoven Liza , Stanke Frauke , Hafkemeyer Sylvia , Nietert Manuel Manfred
Published: July 2021

Different causative therapeutics for CF patients have been developed. There are still no mutation-specific therapeutics for some patients, especially those with rare CFTR mutations. For this purpose, high-throughput screens have been performed which result in various candidate compounds, with mostly unclear modes of action. In order to elucidate the mechanism of action for promising candidate substances and to be able to predict possible synergistic effects of substance combinations, we used a systems biology approach to create a model of the CFTR maturation pathway in cells in a standardized, human- and machine-readable format. It is composed of a core map, manually curated from small-scale experiments in human cells, and a coarse map including interactors identified in large-scale efforts. The manually curated core map includes 170 different molecular entities and 156 reactions from 221 publications. The coarse map encompasses 1384 unique proteins from four publications. The overlap between the two data sources amounts to 46 proteins. The CFTR Lifecycle Map can be used to support the identification of potential targets inside the cell and elucidate the mode of action for candidate substances. It thereby provides a backbone to structure available data as well as a tool to develop hypotheses regarding novel therapeutics.
Integration of Transcriptome and Metabolome Reveals the Genes and Metabolites Involved in Bifidobacterium bifidum Biofilm Formation
Authors: Liu Zongmin , Li Lingzhi , Fang Zhifeng , Lee Yuankun , Zhao Jianxin , Zhang Hao , Chen Wei , Li Haitao , Lu Wenwei
Published: July 2021

Bifidobacterium bifidum strains, an important component of probiotic foods, can form biofilms on abiotic surfaces, leading to increased self-resistance. However, little is known about the molecular mechanism of B. bifidum biofilm formation. A time series transcriptome sequencing and untargeted metabolomics analysis of both B. bifidum biofilm and planktonic cells was performed to identify key genes and metabolites involved in biofilm formation. Two hundred thirty-five nonredundant differentially expressed genes (DEGs) (including vanY, pstS, degP, groS, infC, groL, yajC, tadB and sigA) and 219 nonredundant differentially expressed metabolites (including L-threonine, L-cystine, L-tyrosine, ascorbic acid, niacinamide, butyric acid and sphinganine) were identified. Thirteen pathways were identified during the integration of both transcriptomics and metabolomics data, including ABC transporters; quorum sensing; two-component system; oxidative phosphorylation; cysteine and methionine metabolism; glutathione metabolism; glycine, serine and threonine metabolism; and valine, leucine and isoleucine biosynthesis. The DEGs that relate to the integration pathways included asd, atpB, degP, folC, ilvE, metC, pheA, pstS, pyrE, serB, ulaE, yajC and zwf. The differentially accumulated metabolites included L-cystine, L-serine, L-threonine, L-tyrosine, methylmalonate, monodehydroascorbate, nicotinamide, orthophosphate, spermine and tocopherol. These results indicate that quorum sensing, two-component system and amino acid metabolism are essential during B. bifidum biofilm formation.
Development of a Set of Microsatellite Markers to Investigate Sexually Antagonistic Selection in the Invasive Ant Nylanderia fulva
Authors: Eyer Pierre-Andre , Moran Megan N. , Blumenfeld Alexander J. , Vargo Edward L.
Published: July 2021

Sexually antagonistic selection (SAS) occurs when distinct alleles are differentially selected in each sex. In the invasive tawny crazy ant, Nylanderia fulva, a genomic region is under SAS, while the rest of the genome is randomly selected in males and females. In this study, we designed a suite of 15 microsatellite markers to study the origin and evolution of SAS in N. fulva. These SAS markers were polymorphic, with allelic frequencies that are highly different between males and females. All haploid males carry only a subset of the alleles present in the population, while females are reliably heterozygous, with one allele from the male gene pool and a different allele inherited from their mother. In addition, we identified six polymorphic markers not associated with SAS and six markers yielding consistent, yet monomorphic, amplification in the introduced range of this species. Reaction condition optimizations allowed all retained markers to be co-amplified in four PCR mixes. The SAS markers may be used to test for the strength and the extent of the genomic regions under SAS in both the native and introduced ranges of N. fulva, while the set of non-SAS loci may be used to assess the invasion route of this species. Overall, the application of these microsatellite markers will yield insights into the origin and evolution of SAS within and among species of the genus Nylanderia.
Defensive Traits during White Spruce (Picea glauca) Leaf Ontogeny
Authors: Lirette Antoine-Olivier , Despland Emma
Published: July 2021

Changes during leaf ontogeny affect palatability to herbivores, such that many insects, including the eastern spruce budworm (Choristoneura fumiferana (Clem.)), are specialist feeders on growing conifer leaves and buds. Developmental constraints imply lower toughness in developing foliage, and optimal defense theory predicts higher investment in chemical defense in these vulnerable yet valuable developing leaves. We summarize the literature on the time course of defensive compounds in developing white spruce (Picea glauca (Moench) Voss) needles and report original research findings on the ontogeny of white spruce needle toughness. Our results show the predicted pattern of buds decreasing in toughness followed by leaves increasing in toughness during expansion, accompanied by opposite trends in water content. Toughness of mature foliage decreased slightly during the growing season, with no significant relationship with water content. Toughness of sun-grown leaves was slightly higher than that of shade-grown leaves. However, the literature review did not support the expected pattern of higher defensive compounds in expanding leaves than in mature leaves, suggesting that white spruce might instead exhibit a fast-growth low-defense strategy.
A Cost-Effective IoT Model for a Smart Sewerage Management System Using Sensors
Authors: Rony Jahid Hasan , Karim Nazmul , Rouf MD. Abdur , Islam Md. Monirul , Uddin Jia , Begum Momotaz
Published: July 2021

The sewerage system is a primary element of a city and is responsible for the congestion of both rain and gray water from homes and industries. It is essential to have a monitoring system and a plan to perform prior expansion in the sewerage management system, to avoid massive disruption. However, there is no monitoring system in several overpopulated cities in the world, and the expansion process faces myriad difficulties and takes much time. This paper presents a model for an intelligent sewerage management system that provides real-time monitoring without any major changes to the previous system, using water sensors, a Global System for Mobile Communications (GSM) module, and a micro-controller. The condition of the sewerage acts as an input through the sensors; then, the microcontroller stores the value in the cloud and performs waste collection depending on the current situation. Meanwhile, after processing, the information reaches the monitoring system. Various trial installations of the proposed system have shown that it enables real-time monitoring to observe live conditions and helps to prevent sewerage blockage caused by solid waste. Considering a deficient cost model, this system can intensify the performance of poorly managed sewerage systems.
Current Concepts of Pediatric Acute Kidney Injury—Are We Ready to Translate Them into Everyday Practice?
Authors: Musiał Kinga
Published: July 2021

Pediatric acute kidney injury (AKI) is a major cause of morbidity and mortality in children undergoing interventional procedures. The review summarizes current classifications of AKI and acute kidney disease (AKD), as well as systematizes the knowledge on pathophysiology of kidney injury, with a special focus on renal functional reserve and tubuloglomerular feedback. The aim of this review is also to show the state-of-the-art in methods assessing risk and prognosis by discussing the potential role of risk stratification strategies, taking into account both glomerular function and clinical settings conditioned by fluid overload, urine output, or drug nephrotoxicity. The last task is to suggest careful assessment of eGFR as a surrogate marker of renal functional reserve and implementation of point-of-care testing, available in the case of biomarkers like NGAL and [IGFBP-7] × [TIMP-2] product, into everyday practice in patients at risk of AKI due to planned invasive procedures or treatment.
Sex, Lies, and Coronary Artery Disease
Authors: Martínez-Sellés Helena , Martínez-Sellés David , Martínez-Sellés Manuel
Published: July 2021

Epidemiological and clinical data have shown clear differences in several aspects of cardiovascular disease, particularly in the case of coronary artery disease (CAD), between men and women, including risk factors, response to therapy, quality of care, and natural history.[...]
Association between Inflammatory Conditions and Alzheimer’s Disease Age of Onset in Down Syndrome
Authors: Lai Florence , Mercaldo Nathaniel , Wang Cassandra M. , Hersch Giovi G. , Rosas Herminia Diana
Published: July 2021

Adults with Down syndrome (DS) have an exceptionally high prevalence of Alzheimer disease (AD), with an earlier age of onset compared with the neurotypical population. In addition to beta amyloid, immunological processes involved in neuroinflammation and in peripheral inflammatory/autoimmune conditions are thought to play important roles in the pathophysiology of AD. Individuals with DS also have a high prevalence of autoimmune/inflammatory conditions which may contribute to an increased risk of early AD onset, but this has not been studied. Given the wide range in the age of AD onset in those with DS, we sought to evaluate the relationship between the presence of inflammatory conditions and the age of AD onset. We performed a retrospective study on 339 adults with DS, 125 who were cognitively stable (CS) and 214 with a diagnosis of AD. Data were available for six autoimmune conditions (alopecia, celiac disease, hypothyroidism, psoriasis, diabetes and vitamin B12 deficiency) and for one inflammatory condition, gout. Gout was associated with a significant delay in the age of AD onset by more than 2.5 years. Our data suggests that inflammatory conditions may play a role in the age of AD onset in DS. Further studies are warranted.
Drug Policies Skyline during COVID-19 Pandemic
Authors: Vita Serena , Forliano Dora , De Luca Aldo , Beccacece Alessia , Marchioni Luisa , Nicastri Emanuele ,   on behalf of the COVID-19 INMI Study Group
Published: July 2021

The COVID-19 pandemic has produced an extraordinary care setting where physicians played, and continue to play, a critical role in containing viral spread and treating affected patients. Frontline workers have been receiving day-to-day new information about therapeutic advances. The purpose of the study is to analyse COVID-19 drug consumption trends in both acute and intensive care settings comparing Defined Daily Doses and the release of scientific clinical data from January to December 2020.
Fixed-Dose Combination of NSAIDs and Spasmolytic Agents in the Treatment of Different Types of Pain—A Practical Review
Authors: Janczura Magdalena , Kobus-Moryson Małgorzata , Sip Szymon , Żarowski Marcin , Wareńczak Agnieszka , Cielecka-Piontek Judyta
Published: July 2021

This review presents the most common disease entities in which combinations of NSAIDs and spasmolytic drugs are used to reduce pain. The benefits of fixed-dose combination products (FDCs) are that they improve the response in people with insufficient monotherapy. Using the synergy or additive effect of drugs, it is possible to obtain a significant therapeutic effect and faster action with the use of smaller doses of individual drugs. In addition, one active ingredient may counteract adverse reactions from the other. Another essential aspect of the use of FDCs is the improvement of medical adherence due to the reduction in the pill burden on patients. It is also possible to develop a fixed-dosed combination product de novo to address a new therapeutic claim and be protected by patents so that the manufacturer can obtain exclusive rights to sell a particular FDC or a formulation thereof. The proposed fixed-dose combinations should always be based on valid therapeutic principles and consider the combined safety profile of all active substances included in the medicinal product. This review aims to identify which combinations of NSAIDs and spasmolytics have been developed and tested and which combinations are still under development.
The Types and Proportions of Commensal Microbiota Have a Predictive Value in Coronary Heart Disease
Authors: Chen Lin , Ishigami Tomoaki , Doi Hiroshi , Arakawa Kentaro , Tamura Kouichi
Published: July 2021

Previous clinical studies have suggested that commensal microbiota play an important role in atherosclerotic cardiovascular disease; however, a synthetic analysis of coronary heart disease (CHD) has yet to be performed. Therefore, we aimed to investigate the specific types of commensal microbiota associated with CHD by performing a systematic review of prospective observational studies that have assessed associations between commensal microbiota and CHD. Of the 544 published articles identified in the initial search, 16 publications with data from 16 cohort studies (2210 patients) were included in the analysis. The combined data showed that Bacteroides and Prevotella were commonly identified among nine articles (n = 13) in the fecal samples of patients with CHD, while seven articles commonly identified Firmicutes. Moreover, several types of commensal microbiota were common to atherosclerotic plaque and blood or gut samples in 16 cohort studies. For example, Veillonella, Proteobacteria, and Streptococcus were identified among the plaque and fecal samples, whereas Clostridium was commonly identified among blood and fecal samples of patients with CHD. Collectively, our findings suggest that several types of commensal microbiota are associated with CHD, and their presence may correlate with disease markers of CHD.
Coping with Stress, Executive Functions, and Depressive Symptoms: Focusing on Flexible Responses to Stress
Authors: Kato Tsukasa
Published: July 2021

Coping flexibility is conceptually similar to both inhibition and set-shifting. Though they serve different functions, all three are robustly associated with depression. Coping flexibility is the ability to relinquish a coping strategy regarded as ineffective and to devise and implement an alternative one; the concept is based on stress and coping theory. Inhibition is the ability to suppress responses selectively according to a change in the situation, while set-shifting is the process of switching flexibly between task sets, mental sets, or response rules. Inhibition and set-shifting are both executive functions in cognitive mechanisms. We hypothesized that coping flexibility was associated with a lower risk of depression, even when the effects of inhibition and set-shifting were controlled for. In total, 200 Japanese university students (100 women and 100 men) completed questionnaires that measured coping flexibility and depression and performed the Stroop Color and Word Test and the Wisconsin Card Sorting Test, which measured inhibition and set-shifting. We found that greater coping flexibility was associated with a lower risk of depression, even when the effects of inhibition and set-shifting were controlled for. Our findings suggest that, although coping flexibility is conceptually similar to inhibition and set-shifting, its association with depression differs from theirs.
Hearing Outcomes and Complications of Cochlear Implantation in Elderly Patients over 75 Years of Age
Authors: Kanai Rie , Kanemaru Shin-ichi , Tamura Kaoru , Noda Yoshiko , Umezawa Naomi , Yoshida Misaki , Miwa Toru , Yamaguchi Tomoya , Kita Shinichiro , Kumazawa Akiko , Harada Hiroyuki , Maetani Toshiki
Published: July 2021

Objective: Populations are aging in many countries, and the proportion of elderly people with severe to profound hearing loss is increasing in parallel with the increasing average life span. The objective of this study was to investigate the outcomes of cochlear implant (CI) surgery in elderly patients compared to those in younger patients. Methods: The outcomes of CI surgery were retrospectively investigated for 81 adults (32 men and 49 women) who underwent CI surgery at our hospital. They were divided according to age at the time of implantation into the younger group (<75 years of age; n = 49) or elderly group (≥75 years of age; n = 32). Results: The mean sentence recognition score on the CI-2004 Japanese open-set test battery (±standard deviation) was 82.9% ± 24.1 in the younger group and 81.9% ± 23.2 in the elderly group, with no significant difference between the groups (Mann–Whitney U test). The incidence of major complications that required surgical treatment was not significantly different between the groups (4.1% vs. 6.2%, respectively). Thus, there were no severe complications that could affect general health status in either group. Three patients in each group died for reasons unrelated to CI surgery during follow-up. The proportion of patients who were alive and continued to use the CI five years after surgery was 92.8% and 91.5%, respectively. Conclusion: Our results show good speech recognition and a low incidence of major complications in elderly patients. This comprehensive report on the outcomes of CI surgery in elderly patients will be helpful to the elderly with severe to profound hearing loss when deciding whether to undergo CI surgery.
Predictive Factors for Long-Term Outcomes of Cataract Surgery in Patients Receiving Active Treatment for Neovascular Age-Related Macular Degeneration
Authors: Choi Eun Young , Kim Tae Young , Lee Christopher Seungkyu
Published: July 2021

Background: the safety and efficacy of cataract surgery in eyes with exudative neovascular age-related macular degeneration (nAMD), receiving active treatment, remain unclear. We evaluated the long-term outcomes and associated predictive factors of cataract surgery in eyes with exudative nAMD. Methods: this retrospective cohort study included 65 eyes (61 patients) treated with anti-vascular endothelial growth factor (VEGF) injections within six months preoperatively. Changes in best-corrected visual acuity (BCVA) and anti-VEGF treatment patterns from before to up to four years after surgery were assessed. Predictive factors were identified in association with one-year surgical outcomes. Results: the BCVA improved at six months (p < 0.001) and was maintained for three years postoperatively. The interval between anti-VEGF injections increased 3.4 times postoperatively (p = 0.001). Risk factors for poor BCVA were low preoperative BCVA (p < 0.001) and prolonged nAMD duration (p = 0.003). Prolonged nAMD duration and short exudation-free period were associated with more frequent postoperative anti-VEGF treatments (p = 0.028 and p = 0.003, respectively). AMD subtypes were not associated with both vision and injection pattern outcomes. Conclusions: patients with cataracts receiving nAMD treatment can safely undergo surgery with favorable long-term visual benefits. The preoperative BCVA, nAMD duration, and exudation-free period are potential predictors of surgery outcomes.
Peri-Surgical Inflammatory Profile Associated with Mini-Invasive or Standard Open Lumbar Interbody Fusion Approaches
Authors: Lombardi Giovanni , Berjano Pedro , Cecchinato Riccardo , Langella Francesco , Perego Silvia , Sansoni Veronica , Tartara Fulvio , Regazzoni Pietro , Lamartina Claudio
Published: July 2021

Background: Different surgical approaches are available for lumbar interbody fusion (LIF) to treat disc degeneration. However, a quantification of their invasiveness is lacking, and the definition of minimally invasive surgery (MIS) has not been biochemically detailed. We aimed at characterizing the inflammatory, hematological, and clinical peri-surgical responses to different LIF techniques. Methods: 68 healthy subjects affected by single-level discopathy (L3 to S1) were addressed to MIS, anterior (ALIF, n = 21) or lateral (LLIF, n = 23), and conventional approaches, transforaminal (TLIF, n = 24), based on the preoperative clinical assessment. Venous blood samples were taken 24 h before the surgery and 24 and 72 h after surgery to assess a wide panel of inflammatory and hematological markers. Results: martial (serum iron and transferrin) and pro-angiogenic profiles (MMP-2, TWEAK) were improved in ALIF and LLIF compared to TLIF, while the acute phase response (C-reactive protein, sCD163) was enhanced in LLIF. Conclusions: MIS procedures (ALIF and LLIF) associated with a reduced incidence of post-operative anemic status, faster recovery, and enhanced pro-angiogenic stimuli compared with TLIF. LLIF associated with an earlier activation of innate immune mechanisms than ALIF and TLIF. The trend of the inflammation markers confirms that the theoretically defined mini-invasive procedures behave as such.
Prognostic Value of Computed Tomographic Coronary Angiography for Long-Term Major Adverse Cardiac Events after Liver Transplantation
Authors: Kim Doo-Hwan , Kim Young-Kug , Ha Tae-Yong , Hwang Shin , Kim Wooil , Koo Hyun-Jung , Yang Dong-Hyun , Kang Joon-Won , Lee Sung-Gyu
Published: July 2021

Computed tomographic coronary angiography (CTCA) has prognostic value for early major adverse cardiac events (MACEs) after liver transplantation. However, the association between CTCA and long-term MACEs in liver transplant (LT) recipients remains unknown. We evaluated the association between CTCA and long-term MACEs within 5 years after living donor liver transplantation (LDLT). A total of 628 LDLT recipients who underwent CTCA were analyzed between 2010 and 2012. MACEs were investigated within 5 years after LDLT. The factors associated with long-term MACEs in transplant recipients were evaluated. Only 48 (7.6%) patients developed MACEs. In the Fine and Gray competing risk regression, a coronary artery calcium score (CACS) of >400 combined with obstructive coronary artery disease (CAD) (subdistribution hazard ratio: 5.01, 95% confidence interval: 2.37–10.58, p < 0.001), age (1.05, 1.01–1.10, p = 0.018), diabetes mellitus (2.43, 1.37–4.29, p = 0.002), dyslipidemia (2.45, 1.23–4.70, p = 0.023), and creatinine (1.19, 1.08–1.30, p < 0.001) were independently associated with long-term MACEs. CACS (>400) combined with obstructive CAD may be associated with MACEs within 5 years after LDLT, suggesting the importance of preoperative noninvasive CTCA in LT recipients. The evaluation of coronary artery stenosis on CTCA combined with CACS may have a prognostic value for long-term MACEs in LT recipients.