bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing Nursing Homes Quality Indicators’ between-Provider Variability and Reliability: A Cross-Sectional Study Using ICCs and Rankability
Authors: Favez Lauriane , Zúñiga Franziska , Sharma Narayan , Blatter Catherine , Simon Michael
Published: December 2020

Nursing home quality indicators are often used to publicly report the quality of nursing home care. In Switzerland, six national nursing home quality indicators covering four clinical domains (polypharmacy, pain, use of physical restraints and weight loss) were recently developed. To allow for meaningful comparisons, these indicators must reliably show differences in quality of care levels between nursing homes. This study’s objectives were to assess nursing home quality indicators’ between-provider variability and reliability using intraclass correlations and rankability. This approach has not yet been used in long-term care contexts but presents methodological advantages. This cross-sectional multicenter study uses data of 11,412 residents from a convenience sample of 152 Swiss nursing homes. After calculating intraclass correlation 1 (ICC1) and rankability, we describe between-provider variability for each quality indicator using empirical Bayes estimate-based caterpillar plots. To assess reliability, we used intraclass correlation 2 (ICC2). Overall, ICC1 values were high, ranging from 0.068 (95% confidence interval (CI) 0.047–0.086) for polypharmacy to 0.396 (95% CI 0.297–0.474) for physical restraints, with quality indicator caterpillar plots showing sufficient between-provider variability. However, testing for rankability produced mixed results, with low figures for two indicators (0.144 for polypharmacy; 0.471 for self-reported pain) and moderate to high figures for the four others (from 0.692 for observed pain to 0.976 for physical restraints). High ICC2 figures, ranging from 0.896 (95% CI 0.852–0.917) (self-reported pain) to 0.990 (95% CI 0.985–0.993) (physical restraints), indicated good reliability for all six quality indicators. Intraclass correlations and rankability can be used to assess nursing home quality indicators’ between-provider variability and reliability. The six selected quality indicators reliably distinguish care differences between nursing homes and can be recommended for use, although the variability of two—polypharmacy and self-reported pain—is substantially chance-driven, limiting their utility.
Modulatory Effect of Myokines on Reactive Oxygen Species in Ischemia/Reperfusion
Authors: Szabó Márton Richárd , Pipicz Márton , Csont Tamás , Csonka Csaba
Published: December 2020

There is a growing body of evidence showing the importance of physical activity against acute ischemic events in various organs. Ischemia/reperfusion injury (I/R) is characterized by tissue damage as a result of restriction and subsequent restoration of blood supply to an organ. Oxidative stress due to increased reactive oxygen species formation and/or insufficient antioxidant defense is considered to play an important role in I/R. Physical activity not only decreases the general risk factors for ischemia but also confers direct anti-ischemic protection via myokine production. Myokines are skeletal muscle-derived cytokines, representing multifunctional communication channels between the contracting skeletal muscle and other organs through an endocrine manner. In this review, we discuss the most prominent members of the myokines (i.e., brain-derived neurotrophic factor (BDNF), cathepsin B, decorin, fibroblast growth factors-2 and -21, follistatin, follistatin-like, insulin-like growth factor-1; interleukin-6, interleukin-7, interleukin-15, irisin, leukemia inhibitory factor, meteorin-like, myonectin, musclin, myostatin, and osteoglycin) with a particular interest in their potential influence on reactive oxygen and nitrogen species formation or antioxidant capacity. A better understanding of the mechanism of action of myokines and particularly their participation in the regulation of oxidative stress may widen their possible therapeutic use and, thereby, may support the fight against I/R.
Transferrin-Bound Doxorubicin Enhances Apoptosis and DNA Damage through the Generation of Pro-Inflammatory Responses in Human Leukemia Cells
Authors: Jedrzejczyk Monika , Wisniewska Katarzyna , Kania Katarzyna Dominika , Marczak Agnieszka , Szwed Marzena
Published: December 2020

Doxorubicin (DOX) is an effective antineoplastic drug against many solid tumors and hematological malignancies. However, the clinical use of DOX is limited, because of its unspecific mode of action. Since leukemia cells overexpress transferrin (Tf) receptors on their surface, we proposed doxorubicin–transferrin (DOX–Tf) conjugate as a new vehicle to increase drug concentration directly in cancer cells. The data obtained after experiments performed on K562 and CCRF-CEM human leukemia cell lines clearly indicate severe cytotoxic and genotoxic properties of the conjugate drug. On the other hand, normal peripheral blood mononuclear cells (PBMCs) were more resistant to DOX–Tf than to DOX. In comparison to free drug, we observed that Tf-bound DOX induced apoptosis in a TRAIL-dependent manner and caused DNA damage typical of programmed cell death. These fatal hallmarks of cell death were confirmed upon morphological observation of cells incubated with DOX or DOX–Tf. Studies of expression of TNF-α, IL-4, and IL-6 at the mRNA and protein levels revealed that the pro-inflammatory response plays an important role in the toxicity of the conjugate. Altogether, the results demonstrated here describe a mechanism of the antitumor activity of the DOX–Tf conjugate.
Brassica Bioactives Could Ameliorate the Chronic Inflammatory Condition of Endometriosis
Authors: García-Ibañez Paula , Yepes-Molina Lucía , Ruiz-Alcaraz Antonio J. , Martínez-Esparza María , Moreno Diego A. , Carvajal Micaela , García-Peñarrubia Pilar
Published: December 2020

Endometriosis is a chronic, inflammatory, hormone-dependent disease characterized by histological lesions produced by the presence of endometrial tissue outside the uterine cavity. Despite the fact that an estimated 176 million women are affected worldwide by this gynecological disorder, risk factors that cause endometriosis have not been properly defined and current treatments are not efficient. Although the interaction between diet and human health has been the focus of many studies, little information about the correlation of foods and their bioactive derivates with endometriosis is available. In this framework, Brassica crops have emerged as potential candidates for ameliorating the chronic inflammatory condition of endometriosis, due to their abundant content of health-promoting compounds such as glucosinolates and their hydrolysis products, isothiocyanates. Several inflammation-related signaling pathways have been included among the known targets of isothiocyanates, but those involving aquaporin water channels have an important role in endometriosis. Therefore, the aim of this review is to highlight the promising effects of the phytochemicals present in Brassica spp. as major candidates for inclusion in a dietary approach aiming to improve the inflammatory condition of women affected with endometriosis. This review points out the potential roles of glucosinolates and isothiocyanates from Brassicas as anti-inflammatory compounds, which might contribute to a reduction in endometriosis symptoms. In view of these promising results, further investigation of the effect of glucosinolates on chronic inflammatory diseases, either as diet coadjuvants or as therapeutic molecules, should be performed. In addition, we highlight the involvement of aquaporins in the maintenance of immune homeostasis. In brief, glucosinolates and the modulation of cellular water by aquaporins could shed light on new approaches to improve the quality of life for women with endometriosis.
Editorial of Special Issue “Genetics and Molecular Pathogenesis of Non-Ischemic Cardiomyopathies”
Authors: Lombardi Raffaella , Chen Suet Nee
Published: December 2020

This editorial aims to summarize the eight scientific papers published in the Special Issue “Genetics and Molecular Pathogenesis of Non-ischemic Cardiomyopathies” [...]
Small Noncoding RNA Signatures for Determining the Developmental Potential of an Embryo at the Morula Stage
Authors: Timofeeva Angelika , Drapkina Yulia , Fedorov Ivan , Chagovets Vitaliy , Makarova Nataliya , Shamina Maria , Kalinina Elena , Sukhikh Gennady
Published: December 2020

As part of the optimization of assisted reproductive technology programs, the aim of the study was to identify key small noncoding RNA (sncRNA) molecules that participate in maternal-to-zygotic transition and determine development potential and competence to form a healthy fetus. Small RNA deep sequencing followed by quantitative real-time RT-PCR was used to profile sncRNAs in 50 samples of spent culture medium from morula with different development potentials (no potential (degradation/developmental arrest), low potential (poor-quality blastocyst), and high potential (good/excellent quality blastocyst capable of implanting and leading to live birth)) obtained from 27 subfertile couples who underwent in vitro fertilization. We have shown that the quality of embryos at the morula stage is determined by secretion/uptake rates of certain sets of piRNAs and miRNAs, namely hsa_piR_011291, hsa_piR_019122, hsa_piR_001311, hsa_piR_015026, hsa_piR_015462, hsa_piR_016735, hsa_piR_019675, hsa_piR_020381, hsa_piR_020485, hsa_piR_004880, hsa_piR_000807, hsa-let-7b-5p, and hsa-let-7i-5p. Predicted gene targets of these sncRNAs included those globally decreased at the 8-cell–morula–blastocyst stage and critical to early embryo development. We show new original data on sncRNA profiling in spent culture medium from morula with different development potential. Our findings provide a view of a more complex network that controls human embryogenesis at the pre-implantation stage. Further research is required using reporter analysis to experimentally confirm interactions between identified sncRNA/gene target pairs.
Emergence of Nanotechnology to Fight HIV Sexual Transmission: The Trip of G2-S16 Polyanionic Carbosilane Dendrimer to Possible Pre-Clinical Trials
Authors: Relaño-Rodríguez Ignacio , Muñoz-Fernández Maria Ángeles
Published: December 2020

Development of new, safe, and effective microbicides to prevent human immunodeficiency virus HIV sexual transmission is needed. Unfortunately, most microbicides proved ineffective to prevent the risk of HIV-infection in clinical trials. We are working with G2-S16 polyanionic carbosilane dendrimer (PCD) as a new possible vaginal topical microbicide, based on its short reaction times, wide availability, high reproducibility, and quantitative yields of reaction. G2-S16 PCD exerts anti-HIV activity at an early stage of viral replication, by blocking gp120/CD4/CCR5 interaction, and providing a barrier against infection for long periods of time. G2-S16 PCD was stable at different pH values, as well as in the presence of seminal fluids. It maintained the anti-HIV activity against R5/X4 HIV over time, did not generate any type of drug resistance, and retained the anti-HIV effect when exposed to semen-enhanced viral infection. Importantly, G2-S16 PCD did not modify vaginal microbiota neither in vitro or in vivo. Histopathological examination did not show vaginal irritation, inflammation, lesions, or damage in the vaginal mucosa, after administration of G2-S16 PCD at different concentrations and times in female mice and rabbit animal models. Based on these promising data, G2-S16 PCD could become a good, safe, and readily available candidate to use as a topical vaginal microbicide against HIV.
Facile and Safe Synthesis of Novel Self-Pored Amine-Functionalized Polystyrene with Nanoscale Bicontinuous Morphology
Authors: Gui Qilin , Ouyang Qi , Xu Chunrong , Ding Hongxue , Shi Shuxian , Chen Xiaonong
Published: December 2020

The chloromethyl-functionalized polystyrene is the most commonly used ammonium cation precursor for making anion exchange resins (AER) and membranes (AEM). However, the chloromethylation of polystyrene or styrene involves highly toxic and carcinogenic raw materials (e.g., chloromethyl ether) and the resultant ammonium cation structural motif is not stable enough in alkaline media. Herein, we present a novel self-pored amine-functionalized polystyrene, which may provide a safe, convenient, and green process to make polystyrene-based AER and AEM. It is realized by hydrolysis of the copolymer obtained via random copolymerization of N-vinylformamide (NVF) with styrene (St). The composition and structure of the NVF-St copolymer could be controlled by monomeric ratio, and the copolymers with high NVF content could form bicontinuous morphology at sub-100 nm levels. Such bicontinuous morphology allows the copolymers to be swollen in water and self-pored by freeze-drying, yielding a large specific surface area. Thus, the copolymer exhibits high adsorption capacity (226 mg/g for bisphenol A). Further, the amine-functionalized polystyrene has all-carbon backbone and hydrophilic/hydrophobic microphase separation morphology. It can be quaternized to produce ammonium cations and would be an excellent precursor for making AEM and AER with good alkaline stability and smooth ion transport channels. Therefore, the present strategy may open a new pathway to develop porous alkaline stable AER and AEM without using metal catalysts, organic pore-forming agents, and carcinogenic raw materials.
Alpha Ketoglutarate Exerts In Vitro Anti-Osteosarcoma Effects through Inhibition of Cell Proliferation, Induction of Apoptosis via the JNK and Caspase 9-Dependent Mechanism, and Suppression of TGF-β and VEGF Production and Metastatic Potential of Cells
Authors: Kaławaj Katarzyna , Sławińska-Brych Adrianna , Mizerska-Kowalska Magdalena , Żurek Aleksandra , Bojarska-Junak Agnieszka , Kandefer-Szerszeń Martyna , Zdzisińska Barbara
Published: December 2020

Osteosarcoma (OS) is the most common type of primary bone tumor. Currently, there are limited treatment options for metastatic OS. Alpha-ketoglutarate (AKG), i.e., a multifunctional intermediate of the Krebs cycle, is one of the central metabolic regulators of tumor fate and plays an important role in cancerogenesis and tumor progression. There is growing evidence suggesting that AKG may represent a novel adjuvant therapeutic opportunity in anti-cancer therapy. The present study was intended to check whether supplementation of Saos-2 and HOS osteosarcoma cell lines (harboring a TP53 mutation) with exogenous AKG exerted an anti-cancer effect. The results revealed that AKG inhibited the proliferation of both OS cell lines in a concentration-dependent manner. As evidenced by flow cytometry, AKG blocked cell cycle progression at the G1 stage in both cell lines, which was accompanied by a decreased level of cyclin D1 in HOS and increased expression of p21Waf1/Cip1 protein in Saos-2 cells (evaluated with the ELISA method). Moreover, AKG induced apoptotic cell death and caspase-3 activation in both OS cell lines (determined by cytometric analysis). Both the immunoblotting and cytometric analysis revealed that the AKG-induced apoptosis proceeded predominantly through activation of an intrinsic caspase 9-dependent apoptotic pathway and an increased Bax/Bcl-2 ratio. The apoptotic process in the AKG-treated cells was mediated via c-Jun N-terminal protein kinase (JNK) activation, as the specific inhibitor of this kinase partially rescued the cells from apoptotic death. In addition, the AKG treatment led to reduced activation of extracellular signal-regulated kinase (ERK1/2) and significant inhibition of cell migration and invasion in vitro concomitantly with decreased production of pro-metastatic transforming growth factor β (TGF-β) and pro-angiogenic vascular endothelial growth factor (VEGF) in both OS cell lines suggesting the anti-metastatic potential of this compound. In conclusion, we showed the anti-osteosarcoma potential of AKG and provided a rationale for a further study of the possible application of AKG in OS therapy.
The Role of the Adipokines in the Most Common Gestational Complications
Authors: Gutaj Paweł , Sibiak Rafał , Jankowski Maurycy , Awdi Karina , Bryl Rut , Mozdziak Paul , Kempisty Bartosz , Wender-Ozegowska Ewa
Published: December 2020

Adipocytokines are hormonally active molecules that are believed to play a key role in the regulation of crucial biological processes in the human body. Numerous experimental studies established significant alterations in the adipokine secretion patterns throughout pregnancy. The exact etiology of various gestational complications, such as gestational diabetes, preeclampsia, and fetal growth abnormalities, needs to be fully elucidated. The discovery of adipokines raised questions about their potential contribution to the molecular pathophysiology of those diseases. Multiple studies analyzed their local mRNA expression and circulating protein levels. However, most studies report conflicting results. Several adipokines such as leptin, resistin, irisin, apelin, chemerin, and omentin were proposed as potential novel early markers of heterogeneous gestational complications. The inclusion of the adipokines in the standard predictive multifactorial models could improve their prognostic values. Nonetheless, their independent diagnostic value is mostly insufficient to be implemented into standard clinical practice. Routine assessments of adipokine levels during pregnancy are not recommended in the management of both normal and complicated pregnancies. Based on the animal models (e.g., apelin and its receptors in the rodent preeclampsia models), future implementation of adipokines and their receptors as new therapeutic targets appears promising but requires further validation in humans.
Toll-Like Receptor 2 at the Crossroad between Cancer Cells, the Immune System, and the Microbiota
Authors: Di Lorenzo Antonino , Bolli Elisabetta , Tarone Lidia , Cavallo Federica , Conti Laura
Published: December 2020

Toll-like receptor 2 (TLR2) expressed on myeloid cells mediates the recognition of harmful molecules belonging to invading pathogens or host damaged tissues, leading to inflammation. For this ability to activate immune responses, TLR2 has been considered a player in anti-cancer immunity. Therefore, TLR2 agonists have been used as adjuvants for anti-cancer immunotherapies. However, TLR2 is also expressed on neoplastic cells from different malignancies and promotes their proliferation through activation of the myeloid differentiation primary response protein 88 (MyD88)/nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) pathway. Furthermore, its activation on regulatory immune cells may contribute to the generation of an immunosuppressive microenvironment and of the pre-metastatic niche, promoting cancer progression. Thus, TLR2 represents a double-edge sword, whose role in cancer needs to be carefully understood for the setup of effective therapies. In this review, we discuss the divergent effects induced by TLR2 activation in different immune cell populations, cancer cells, and cancer stem cells. Moreover, we analyze the stimuli that lead to its activation in the tumor microenvironment, addressing the role of danger, pathogen, and microbiota-associated molecular patterns and their modulation during cancer treatments. This information will contribute to the scientific debate on the use of TLR2 agonists or antagonists in cancer treatment and pave the way for new therapeutic avenues.
Whole-Genome Sequencing-Based Characterization of Listeria monocytogenes from Fish and Fish Production Environments in Poland
Authors: Wieczorek Kinga , Bomba Arkadiusz , Osek Jacek
Published: December 2020

Listeria monocytogenes, an important foodborne pathogen, may be present in different kinds of food and in food processing environments where it can persist for a long time. In this study, 28 L. monocytogenes isolates from fish and fish manufactures were characterized by whole genome sequencing (WGS). Core genome multilocus sequence typing (cgMLST) analysis was applied to compare the present isolates with publicly available genomes of L. monocytogenes strains recovered worldwide from food and from humans with listeriosis. All but one (96.4%) of the examined isolates belonged to molecular serogroup IIa, and one isolate (3.6%) was classified to serogroup IVb. The isolates of group IIa were mainly of MLST sequence types ST121 (13 strains) and ST8 (four strains) whereas the isolate of serogroup IVb was classified to ST1. Strains of serogroup IIa were further subtyped into eight different sublineages with the most numerous being SL121 (13; 48.1% strains) which belonged to six cgMLST types. The majority of strains, irrespective of the genotypic subtype, had the same antimicrobial resistance profile. The cluster analysis identified several molecular clones typical for L. monocytogenes isolated from similar sources in other countries; however, novel molecular cgMLST types not present in the Listeria database were also identified.
SPInDel Analysis of the Non-Coding Regions of cpDNA as a More Useful Tool for the Identification of Rye (Poaceae: Secale) Species
Authors: Skuza Lidia , Filip Ewa , Szućko Izabela , Bocianowski Jan
Published: December 2020

Secale is a small but very diverse genus from the tribe Triticeae (family Poaceae), which includes annual, perennial, self-pollinating and open-pollinating, cultivated, weedy and wild species of various phenotypes. Despite its high economic importance, classification of this genus, comprising 3–8 species, is inconsistent. This has resulted in significantly reduced progress in the breeding of rye which could be enriched with functional traits derived from wild rye species. Our previous research has suggested the utility of non-coding sequences of chloroplast and mitochondrial DNA in studies on closely related species of the genus Secale. Here we applied the SPInDel (Species Identification by Insertions/Deletions) approach, which targets hypervariable genomic regions containing multiple insertions/deletions (indels) and exhibiting extensive length variability. We analysed a total of 140 and 210 non-coding sequences from cpDNA and mtDNA, respectively. The resulting data highlight regions which may represent useful molecular markers with respect to closely related species of the genus Secale, however, we found the chloroplast genome to be more informative. These molecular markers include non-coding regions of chloroplast DNA: atpB-rbcL and trnT-trnL and non-coding regions of mitochondrial DNA: nad1B-nad1C and rrn5/rrn18. Our results demonstrate the utility of the SPInDel concept for the characterisation of Secale species.
Perspective in Alternative Splicing Coupled to Nonsense-Mediated mRNA Decay
Authors: García-Moreno Juan F. , Romão Luísa
Published: December 2020

Alternative splicing (AS) of precursor mRNA (pre-mRNA) is a cellular post-transcriptional process that generates protein isoform diversity. Nonsense-mediated RNA decay (NMD) is an mRNA surveillance pathway that recognizes and selectively degrades transcripts containing premature translation-termination codons (PTCs), thereby preventing the production of truncated proteins. Nevertheless, NMD also fine-tunes the gene expression of physiological mRNAs encoding full-length proteins. Interestingly, around one third of all AS events results in PTC-containing transcripts that undergo NMD. Numerous studies have reported a coordinated action between AS and NMD, in order to regulate the expression of several genes, especially those coding for RNA-binding proteins (RBPs). This coupling of AS to NMD (AS-NMD) is considered a gene expression tool that controls the ratio of productive to unproductive mRNA isoforms, ultimately degrading PTC-containing non-functional mRNAs. In this review, we focus on the mechanisms underlying AS-NMD, and how this regulatory process is able to control the homeostatic expression of numerous RBPs, including splicing factors, through auto- and cross-regulatory feedback loops. Furthermore, we discuss the importance of AS-NMD in the regulation of biological processes, such as cell differentiation. Finally, we analyze interesting recent data on the relevance of AS-NMD to human health, covering its potential roles in cancer and other disorders.
Hiding the Source Code of Stored Database Programs
Authors: Yesin Vitalii , Karpinski Mikolaj , Yesina Maryna , Vilihura Vladyslav , Warwas Kornel
Published: December 2020

The objective of the article is to reveal an approach to hiding the code of stored programs stored in the database. The essence of this approach is the complex use of the method of random permutation of code symbols related to a specific stored program, located in several rows of some attribute of the database system table, as well as the substitution method. Moreover, with the possible substitute of each character obtained after the permutation with another one randomly selected from the Unicode standard, a legitimate user with the appropriate privileges gets access to the source code of the stored program due to the ability to quickly perform the inverse to masking transformation and overwrite the program code into the database. All other users and attackers without knowledge of certain information can only read the codes of stored programs masked with format preserving. The proposed solution is more efficient than the existing methods of hiding the code of stored programs provided by the developers of some modern database management systems (DBMS), since an attacker will need much greater computational and time consumption to disclose the source code of stored programs.
Pulmonary Manifestations of Plasma Cell Type Idiopathic Multicentric Castleman Disease: A Clinicopathological Study in Comparison with IgG4-Related Disease
Authors: Nishimura Midori Filiz , Igawa Takuro , Gion Yuka , Tomita Sakura , Inoue Dai , Izumozaki Akira , Ubara Yoshifumi , Nishimura Yoshito , Yoshino Tadashi , Sato Yasuharu
Published: December 2020

Plasma cell type idiopathic multicentric Castleman disease (PC-iMCD) occasionally manifests as parenchymal lung disease. This study aimed to elucidate the detailed clinicopathological features of lung lesions in PC-iMCD and compare the findings with those in immunoglobulin (Ig) G4-related disease (IgG4-RD), the most difficult differential diagnosis of PC-iMCD. We analyzed the clinicopathological findings and immunohistochemical expression patterns of interleukin-6 (IL-6) and Igs in lung specimens from 16 patients with PC-iMCD and 7 patients with IgG4-RD. Histologically, pulmonary PC-iMCD could not be differentiated from IgG4-RD based on lesion distribution patterns, the number of lymphoid follicles and obliterative vasculitis, or fibrosis types. The eosinophil count was higher in the IgG4-RD group than in the PC-iMCD group (p = 0.004). The IgG4/IgG-positive cell ratio was significantly higher in the IgG4-RD group (p < 0.001). The IgA-positive cell count and IL-6 expression intensity were higher in the PC-iMCD group than in the IgG4-RD group (p < 0.001). Based on these findings, we proposed a new diagnostic approach to differentiate lung lesions of PC-iMCD and IgG4-RD. Our approach can be utilized to stratify patients with suspected lung-dominant PC-iMCD to identify candidates for strong immunosuppressive treatment, including IL-6 blockade, at an early stage.
FSH-R Human Early Male Genital Tract, Testicular Tumors and Sperm: Its Involvement in Testicular Disorders
Authors: Panza Salvatore , Giordano Francesca , De Rose Daniela , Panno Maria Luisa , De Amicis Francesca , Santoro Marta , Malivindi Rocco , Rago Vittoria , Aquila Saveria
Published: December 2020

The follicle-stimulating hormone receptor (FSH-R) expression was always considered human gonad-specific. The receptor has also been newly detected in extragonadal tissues. In this finding, we evaluated FSH-R expression in the human male early genital tract, in testicular tumors, and in sperm from healthy and varicocele patients. In sperm, we also studied the mechanism of FSH-R action. Immunohystochemistry and Western blot analysis showed FSH-R presence in the first pathways of the human genital tract, in embryonal carcinoma, and in sperm, but it was absent in seminoma and in lower varicocele. In sperm, FSH/FSH-R activity is mediated by G proteins activating the PKA pathway, as we observed by using the H89. It emerged that increasing FSH treatments induced motility, survival, capacitation, and acrosome reaction in both sperm samples. The different FSH-R expression in tumor testicular tissues may be discriminate by tumor histological type. In spermatozoa, FSH-R indicates a direct action of FSH in these cells, which could be beneficial during semen preparation for in vitro fertilization procedures. For instance, FSH positive effects could be relevant in idiopathic infertility and in the clinic surgery of varicocele. In conclusion, FSH-R expression may be considered a molecular marker of testicular disorders.
Sex-Specific Differences in Extracellular Vesicle Protein Cargo in Synovial Fluid of Patients with Osteoarthritis
Authors: Kolhe Ravindra , Owens Virgenal , Sharma Ashok , Lee Tae Jin , Zhi Wenbo , Ghilzai Umar , Mondal Ashis K. , Liu Yutao , Isales Carlos M. , Hamrick Mark W. , Hunter Monte , Fulzele Sadanand
Published: December 2020

Women are at a significantly higher risk of developing osteoarthritis (OA) compared to males. The pathogenesis of osteoarthritis (OA) in women is poorly understood. Extracellular vesicles (EVs) have been shown to play an essential role in numerous signaling processes during the pathogenesis of age-related diseases via paracrine signaling. Molecular profiling of the synovial fluid-derived EVs cargo in women may help in the discovery of novel biomarkers and therapeutics for the treatment of OA in women. Previously, we reported that synovial fluid-derived EV miRNA cargo differs in a sex-specific manner. This study aims to characterize synovial fluid-derived EV protein cargo in OA patients. Our data showed sex-specific EVs protein content in OA. We found haptoglobin, orosomucoid, and ceruloplasmin significantly up-regulated, whereas apolipoprotein down-regulated in female OA EVs. In males, we discovered β-2-glycoprotein, and complement component 5 proteins significantly up-regulated and Spt-Ada-Gcn5 acetyltransferase (SAGA)-associated factor 29 down-regulated in male OA EVs. Database for Annotation, Visualization, and Integrated Discovery (DAVID) and QuickGO analysis revealed OA-specific protein involvement in several biological, molecular, and cellular pathways, specifically in inflammatory processes. In conclusion, synovial fluid EV protein content is altered in a sex-specific manner with OA, explaining the increased prevalence and severity of OA in women.
The Medium Is the Message: How Do Canadian University Students Want Digital Medication Information?
Authors: Monkman Helen , Kushniruk Andre , Borycki Elizabeth , Sheets Debra , Barnett Jeff , Nøhr Christian
Published: December 2020

(1) Background: To facilitate optimal prescription medication benefits and safety, it is important that people are informed about their prescription medications. As we shift towards using the digital medium to communicate medication information, it is important to address the needs and preferences of different user groups so that they are more likely to read and use this information. In this study, we examined what digital medication information (DMI) format Canadian University students want and why. (2) Methods: This study was a qualitative investigation of young (aged 18–35) Canadian University students’ (N = 36) preferences and rationale supporting these preferences with respect to three potential formats for providing DMI: email, a mobile application (app), and online. Reported advantages and disadvantages of each of the three DMI formats were identified and categorized into unique themes. (3) Results: Findings from this study suggest that Canadian University Students most want to receive DMI by email, followed by a mobile app, and finally they were least receptive to online DMI. Participants provided diverse themes of reasons supporting their preferences. (4) Conclusions: Different user groups may have different needs with respect to receiving DMI. The themes from this study suggest that using a formative evaluation framework for assessing different DMI formats may be useful in future research. Email may be the best way to share DMI with younger, generally healthy, Canadian University students who are on few medications. Further research is required to explore whether other mediums for DMI are more appropriate for users with other characteristics (e.g., older and less educated) and contexts (e.g., polypharmacy and complex conditions). Given the flexibility of digital information, DMI could plausibly be provided in multiple formats and could allow users to choose the option they like best and would be most likely to use.
Influence of Artificial Turf Surface Stiffness on Athlete Performance
Authors: Wannop John , Kowalchuk Shaylyn , Esposito Michael , Stefanyshyn Darren
Published: December 2020

Properties of conventional playing surfaces have been investigated for many years and the stiffness of the surface has potential to influence athletic performance. However, despite the proliferation of different infilled artificial turfs with varying properties, the effect of surface stiffness of these types of surfaces on athlete performance remains unknown. Therefore, the purpose of this project was to determine the influence of surface stiffness of artificial turf systems on athlete performance. Seventeen male athletes performed four movements (running, 5-10-5 agility, vertical jumping and sprinting) on five surfaces of varying stiffness: Softest (−50%), Softer (−34%), Soft (−16%), Control, Stiff (+17%). Performance metrics (running economy, jump height, sprint/agility time) and kinematic data were recorded during each movement and participants performed a subjective evaluation of the surface. When compared to the Control surface, performance was significantly improved during running (Softer, Soft), the agility drill (Softest) and vertical jumping (Soft). Subjectively, participants could not discern between any of the softer surfaces in terms of surface cushioning, however, the stiffer surface was rated as harder and less comfortable. Overall, changes in surface stiffness altered athletic performance and, to a lesser extent, subjective assessments of performance, with changes in performance being surface and movement specific.
Repair Kinetics of DNA Double Strand Breaks Induced by Simulated Space Radiation
Authors: Oizumi Takashi , Ohno Rieko , Yamabe Souichiro , Funayama Tomoo , Nakamura Asako J.
Published: December 2020

Radiation is unavoidable in space. Energetic particles in space radiation are reported to induce cluster DNA damage that is difficult to repair. In this study, normal human fibroblasts were irradiated with components of space radiation such as proton, helium, or carbon ion beams. Immunostaining for γ-H2AX and 53BP1 was performed over time to evaluate the kinetics of DNA damage repair. Our data clearly show that the repair kinetics of DNA double strand breaks (DSBs) induced by carbon ion irradiation, which has a high linear energy transfer (LET), are significantly slower than those of proton and helium ion irradiation. Mixed irradiation with carbon ions, followed by helium ions, did not have an additive effect on the DSB repair kinetics. Interestingly, the mean γ-H2AX focus size was shown to increase with LET, suggesting that the delay in repair kinetics was due to damage that is more complex. Further, the 53BP1 focus size also increased in an LET-dependent manner. Repair of DSBs, characterized by large 53BP1 foci, was a slow process within the biphasic kinetics of DSB repair, suggesting non-homologous end joining with error-prone end resection. Our data suggest that the biological effects of space radiation may be significantly influenced by the dose as well as the type of radiation exposure.
Time Course and Magnitude of Tolerance to the Ergogenic Effect of Caffeine on the Second Ventilatory Threshold
Authors: Ruiz-Moreno Carlos , Lara Beatriz , Gutiérrez-Hellín Jorge , González-García Jaime , Del Coso Juan
Published: December 2020

Pre-exercise caffeine ingestion has been shown to increase the workload at ventilatory threshold, suggesting an ergogenic effect of this stimulant on submaximal aerobic exercise. However, the time course of tolerance to the effect of caffeine on ventilatory threshold is unknown. This study aimed to determine the evolution of tolerance to the ergogenic effect of caffeine on the ventilatory threshold. Methods: Eleven participants (age 32.3 ± 4.9 yrs, height 171 ± 8 cm, body mass 66.6 ± 13.6 kg, VO2max = 48.0 ± 3.8 mL/kg/min) took part in a longitudinal, double-blind, placebo-controlled, randomized, crossover experimental design. Each participant took part in two identical treatments: in one treatment, participants ingested a capsule containing 3 mg of caffeine per kg of body mass per day (mg/kg/day) for twenty consecutive days; in the other treatment, participants ingested a capsule filled with a placebo for the same duration and frequency. During these treatments, participants performed a maximal ramp test on a cycle ergometer three times per week and the second ventilatory threshold (VT2) was assessed by using the ventilatory equivalents for oxygen and carbon dioxide. Results: A two-way ANOVA with repeated measures (substance × time) revealed statistically significant main effects of caffeine (p < 0.01) and time (p = 0.04) on the wattage obtained at VT2, although there was no interaction (p = 0.09). In comparison to the placebo, caffeine increased the workload at VT2 on days 1, 4, 6 and 15 of ingestion (p < 0.05). The size of the ergogenic effect of caffeine over the placebo on the workload at VT2 was progressively reduced with the duration of the treatment. In addition, there were main effects of caffeine (p = 0.03) and time (p = 0.16) on VO2 obtained at VT2, with no interaction (p = 0.49). Specifically, caffeine increased oxygen uptake at VT2 on days 1 and 4 (p < 0.05), with no other caffeine–placebo differences afterwards. For heart rate obtained at VT2, there was a main effect of substance (p < 0.01), while the overall effect of time (p = 0.13) and the interaction (p = 0.22) did not reach statistical significance. Heart rate at VT2 was higher with caffeine than with the placebo on days 1 and 4 (p < 0.05). The size of the effect of caffeine on VO2 and heart at VT2 tended to decline over time. Conclusion: Pre-exercise intake of 3 mg/kg/day of caffeine for twenty days enhanced the wattage obtained at VT2 during cycling ramp tests for ~15 days of ingestion, while there was a progressive attenuation of the size of the ergogenic effect of caffeine on this performance variable. Therefore, habituation to caffeine through daily ingestion may reduce the ergogenic effect of this stimulant on aerobic exercise of submaximal intensity.
Utilization of Iron Tailings Sand as an Environmentally Friendly Alternative to Natural River Sand in High-Strength Concrete: Shrinkage Characterization and Mitigation Strategies
Authors: Zhang Zhiqiang , Zhang Zhilu , Yin Shaoning , Yu Linwen
Published: December 2020

The increasing annual emissions of iron ore tailings have proved a great threat to the natural environment, and the shortage of natural river sand, as well as the pursuit of sustainable development materials, provides motivation to reuse iron ore tailings as a fine aggregate in concrete. Due to the significantly different properties of iron tailings sand compared with natural river sand—such as the higher density, higher content of limestone particles smaller than 75 μm and its rough and angular shape—concretes prepared with iron tailings sand show remarkably higher shrinkage. This study presents the shrinkage characterization and shrinkage-reducing efficiency of three different methods on iron tailings, sand concrete and river sand concrete. The internal humidity was also monitored to reveal the shrinkage-reducing mechanism. The obtained results indicated that the autogenous and total shrinkage of iron tailings sand concrete were 9.8% and 13.3% higher than the river sand concrete at the age of 90 d, respectively. The shrinkage reducing agent (SRA) was the most effective shrinkage reducing method for river sand concrete, while for iron tailings sand concrete, super absorbent polymer (SAP) and controlled permeable formwork liner (CPFL) it worked best on autogenous shrinkage and drying shrinkage, respectively. Furthermore, the shrinkage mitigation strategies worked earlier for the drying shrinkage behavior of iron tailings sand concrete, while no such condition could be found for autogenous shrinkage.
Fabrication of Porous Anodic Alumina (PAA) by High-Temperature Pulse-Anodization: Tuning the Optical Characteristics of PAA-Based DBR in the NIR-MIR Region
Authors: Białek Ewelina , Włodarski Maksymilian , Norek Małgorzata
Published: December 2020

In this work, the influence of various electrochemical parameters on the production of porous anodic alumina (PAA)-based DBRs (distributed Bragg reflector) during high-temperature-pulse-anodization was studied. It was observed that lowering the temperature from 30 to 27 °C brings about radical changes in the optical performance of the DBRs. The multilayered PAA fabricated at 27 °C did not show optical characteristics typical for DBR. The DBR performance was further tuned at 30 °C. The current recovery (iamax) after application of subsequent UH pulses started to stabilize upon decreasing high (UH) and low (UL) voltage pulses, which was reflected in a smaller difference between initial and final thickness of alternating dH and dL segments (formed under UH and UL, respectively) and a better DBR performance. Shortening UH pulse duration resulted in a progressive shift of photonic stopbands (PSBs) towards the blue part of the spectrum while keeping intensive and symmetric PSBs in the NIR-MIR range. Despite the obvious improvement of the DBR performance by modulation of electrochemical parameters, the problem regarding full control over the homogeneous formation of dH+dL pairs remains. Solving this problem will certainly lead to the production of affordable and efficient PAA-based photonic crystals with tunable photonic properties in the NIR-MIR region.
1H NMR Spin-Lattice Relaxometry of Cement Pastes with Polycarboxylate Superplasticizers
Authors: Pang Min , Sun Zhenping , Li Qi , Ji Yanliang
Published: December 2020

1H spin-lattice relaxometry (T1, longitudinal) of cement pastes with 0 to 0.18 wt % polycarboxylate superplasticizers (PCEs) at intervals of 0.06 wt % from 10 min to 1210 min was investigated. Results showed that the main peak in T1 relaxometry of cement pastes was shorter and lower along with the hydration times. PCEs delayed and lowered this main peak in T1 relaxometry of cement pastes at 10 min, 605 min and 1210 min, which was highly correlated to its dosages. In contrast, PCEs increased the total signal intensity of T1 of cement pastes at these three times, which still correlated to its dosages. Both changes of the main peak in T1 relaxometry and the total signal intensity of T1 revealed interferences on evaporable water during cement hydration by dispersion mechanisms of PCEs. The time-dependent evolution of weighted average T1 of cement pastes with different PCEs between 10 min and 1210 min was found regular to the four-stage hydration mechanism of tricalcium silicate.
Effect of Natural Aging on the Stress Corrosion Cracking Behavior of A201-T7 Aluminum Alloy
Authors: Chen Mien-Chung , Wen Ming-Che , Chiu Yang-Chun , Pan Tse-An , Tzeng Yu-Chih , Lee Sheng-Long
Published: December 2020

The effect of natural aging on the stress corrosion cracking (SCC) of A201-T7 alloy was investigated by the slow strain rate testing (SSRT), transmission electron microscopy (TEM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), conductivity, and polarization testing. The results indicated that natural aging could significantly improve the resistance of the alloys to SCC. The ductility loss rate of the unaged alloy was 28%, while the rates for the 24 h and 96 h aged alloys were both 5%. The conductivity of the as-quenched alloy was 30.54 (%IACS), and the conductivity of the 24 h and 96 h aged alloys were decreased to 28.85 and 28.65. After T7 tempering, the conductivity of the unaged, 24 h, and 96 h aged alloys were increased to 32.54 (%IACS), 32.52 and 32.45. Besides, the enthalpy change of the 24 h and 96 h aged alloys increased by 36% and 37% compared to the unaged alloy. The clustering of the solute atoms would evidently be enhanced with the increasing time of natural aging. Natural aging after quenching is essential to improve the alloy’s resistance to SCC. It might be due to the prevention of the formation of the precipitation free zone (PFZ) after T7 tempering.
Simulating Stochastic Differential Equations with Conserved Quantities by Improved Explicit Stochastic Runge–Kutta Methods
Authors: Wang Zhenyu , Ma Qiang , Ding Xiaohua
Published: December 2020

Explicit numerical methods have a great advantage in computational cost, but they usually fail to preserve the conserved quantity of original stochastic differential equations (SDEs). In order to overcome this problem, two improved versions of explicit stochastic Runge–Kutta methods are given such that the improved methods can preserve conserved quantity of the original SDEs in Stratonovich sense. In addition, in order to deal with SDEs with multiple conserved quantities, a strategy is represented so that the improved methods can preserve multiple conserved quantities. The mean-square convergence and ability to preserve conserved quantity of the proposed methods are proved. Numerical experiments are implemented to support the theoretical results.
Relating Hydraulic Conductivity Curve to Soil-Water Retention Curve Using a Fractal Model
Authors: Fuentes Carlos , Chávez Carlos , Brambila Fernando
Published: December 2020

In the study of water transference in soil according to Darcy law, the knowledge of hydrodynamic characteristics, formed by the water retention curve θ(ψ), and the hydraulic conductivity curve K(ψ) are of great importance. The first one relates the water volumetric content (θ) with the water-soil pressure (ψ); the second one, the hydraulic conductivity (K) with the water-soil pressure. The objective of this work is to establish relationships between both curves using concepts of probability theory and fractal geometry in order to reduce the number of unknown functions. The introduction of four definitions used at the literature of the pore effective radius that is involve in the general model has permitted to establish four new specials models to predict the relative hydraulic conductivity. Some additional considerations related to the definitions of flow effective area and the tortuosity factor have allow us to deduce four classical models that are extensively used in different studies. In particular, we have given some interpretations of its empirical parameters in the fractal geometry context. The resulting functions for hydrodynamic characteristics can be utilized in many studies of water movement in the soil.