bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic Policy Uncertainty, Environmental Regulation, and Green Innovation—An Empirical Study Based on Chinese High-Tech Enterprises
Authors: Zhu Yue , Sun Ziyuan , Zhang Shiyu , Wang Xiaolin
Published: September 2021

As the continuous changes in environmental regulations have a non-negligible impact on the innovation activities of micro subjects, and economic policy uncertainty has become one of the important influencing factors to be considered in the development of enterprises. Therefore, based on the panel data of Chinese high-tech enterprises from 2012–2017, this paper explores the impact of heterogeneous environmental regulations on firms’ green innovation from the perspective of economic policy uncertainty as a moderating variable. The empirical results show that, first, market-incentivized environmental regulation instruments have an inverted U-shaped relationship with innovation output, while voluntary environmental regulation produces a significant positive impact. Second, the U-shaped relationship between market-based environmental regulation and innovation output becomes more pronounced when economic policy uncertainty is high. However, it plays a negative moderating role in regulating the relationship between voluntary-based environmental regulation and innovation output. This paper not only illustrates the process of technological innovation by revealing the intrinsic mechanism of environmental regulation on firm innovation, but also provides insights for government in environmental governance from the perspective of economic policy uncertainty as well.
Comparison of Suicide Attempts and Suicide Deaths by Jumping from a High Place in Korean Children and Adolescents
Authors: Song Jungeun , Hong Sung-Hee , Kim Joonbeom , Chang Seyeun , Yook Ki-Hwan , Hong Hyun Ju
Published: September 2021

Jumping from a high place is the most common method of suicide among Korean children and adolescents. The aim of this study was to examine the personal, family, and school life of Korean children and adolescents who chose jumping from a high place, among suicide attempts and suicide deaths, based on teachers’ reports. Data on suicide attempts and suicide deaths by jumping from a high place in children and adolescents were collected through the Ministry of Education in South Korea from 2016 to 2018. We compared sociodemographic variables, suicide-related variables, emotional and behavioral status, school life related variables, and variables related to family problems among suicide deaths (n = 262), actual suicide attempts (n = 50), and interrupted or aborted suicide attempts (n = 210). There were differences in educational stage (p < 0.001), place of suicide (p < 0.001), presence of suicide note (p < 0.05) and previous suicide attempt (p < 0.001) among the three groups. The total difficulty score on the Strength Difficulty Questionnaire of interrupted or aborted suicide attempts was higher than that of the other two groups. Our study suggests that the suicide death group tend to present fewer personal and family pathologies and better school adjustment than the suicide attempt group.
Walking Ability Outcome Measures in Individuals with Spinal Cord Injury: A Systematic Review
Authors: Sinovas-Alonso Isabel , Gil-Agudo Ángel , Cano-de-la-Cuerda Roberto , del-Ama Antonio J.
Published: September 2021

Walking function recovery in spinal cord injury (SCI) is tackled through several therapeutic approaches in which precise evaluation is essential. A systematic review was performed to provide an updated qualitative review of walking ability outcome measures in SCI and to analyze their psychometric properties. PubMed, Cochrane, and PEDro databases were consulted until 1 April 2020. Seventeen articles written in English were included. Five of them studied the walking index for SCI, four studied the 10 meter walk test, and two studied the six-minute walk test, the timed Up and go test, and the Berg balance scale. The rest of the articles studied the following metrics: gait profile score, spinal cord injury functional ambulation profile, five times sit-to-stand test, spinal cord injury functional ambulation inventory, spinal cord independence measure (indoors and outdoors mobility items), locomotor stages in spinal cord injury, community balance and mobility scale, and activity-based balance level evaluation scale. The choice of a single or a set of metrics should be determined by the clinician. Based on the results obtained in this review, a combination of outcome measures is proposed to assess walking ability. Future work is required to integrate a more realistic environment for walking assessment.
The Consequences of Disdainful Hook-Ups for Later Egalitarian Relationships of Girls
Authors: López de Aguileta Ane , Melgar Patricia , Torras-Gómez Elisabeth , Gutiérrez-Fernández Nerea
Published: September 2021

Introduction: There is extensive research about the consequences that toxic relationships with dominant masculinities have on different areas of women’s lives, including how they can influence future relationships they establish. Some of these women reproduce toxic relationships with dominant masculinities in their following relationships, and some women start to establish sexual-affective relationships with non-dominant masculinity models. However, less is known about the specific consequences in non-dominant masculinities who establish relationships with women who have not overcome the false memory of excitement regarding their toxic relationships. Methodology: In order to shed light on the consequences for non-dominant masculinities, eight communicative interviews were conducted with four women and four men. Results: The main findings indicate that those female participants who have kept an exciting memory of toxic relationships, when in an equal relationship, have attitudes of disdain towards non-dominant masculinities. They may ridicule them, not value their personal or intellectual abilities, talk down to them, and even negatively value their sexual aptitudes. Discussion: The application of the previous literature to our results leads to establishing the work on memories of relationships that have led to socialization in violent relationships as a preventive approach. Conclusion: The previously mentioned attitudes could generate health problems for non-dominant masculinities engaged in these relationships.
Recent Advances in Phenolic Metabolites and Skin Cancer
Authors: Pop Teodora Daria , Diaconeasa Zorita
Published: September 2021

Skin cancer represents any tumor development from the cutaneous structures within the epidermis, dermis or subcutaneous tissue, and is considered to be the most prevalent type of cancer. Compared to other types of cancer, skin cancer is proven to have a positive growth rate of prevalence and mortality. There are available various treatments, including chemotherapy, immunotherapy, radiotherapy and targeted therapy, but because of the multidrug resistance development, a low success has been registered. By this, the importance of studying naturally occurring compounds that are both safe and effective in the chemoprevention of skin cancer is emphasized. This review focuses on melanoma because it is the deadliest form of skin cancer, with a significantly increasing incidence in the last decades. As chemopreventive agents, we present polyphenols and their antioxidant activity, anti-inflammatory effect, their ability to balance the cell cycle and to induce apoptosis and their various other effects on skin melanoma. Besides chemoprevention, studies suggest that polyphenols can have treating abilities in some conditions. The limitations of using polyphenols are also pointed out, which are related to their poor bioavailability and stability, but as the technology is well developed, it is possible to augment the efficacy of polyphenols in the case of melanoma.
Fusarium oxysporum f. sp. niveum Molecular Diagnostics Past, Present and Future
Authors: Hudson Owen , Fulton James C. , Dong Alexi K. , Dufault Nicholas S. , Ali Md Emran
Published: September 2021

Watermelon is an important commercial crop in the Southeastern United States and around the world. However, production is significantly limited by biotic factors including fusarium wilt caused by the hemibiotrophic fungus Fusarium oxysporum forma specialis niveum (Fon). Unfortunately, this disease has increased significantly in its presence over the last several decades as races have emerged which can overcome the available commercial resistance. Management strategies include rotation, improved crop resistance, and chemical control, but early and accurate diagnostics are required for appropriate management. Accurate diagnostics require molecular and genomic strategies due to the near identical genomic sequences of the various races. Bioassays exist for evaluating both the pathogenicity and virulence of an isolate but are limited by the time and resources required. Molecular strategies are still imperfect but greatly reduce the time to complete the diagnosis. This article presents the current state of the research surrounding races, both how races have been detected and diagnosed in the past and future prospects for improving the system of differentiation. Additionally, the available Fon genomes were analyzed using a strategy previously described in separate formae speciales avirulence gene association studies in Fusarium oxysporum races.
A Computational Workflow for the Identification of Novel Fragments Acting as Inhibitors of the Activity of Protein Kinase CK1δ
Authors: Bolcato Giovanni , Cescon Eleonora , Pavan Matteo , Bissaro Maicol , Bassani Davide , Federico Stephanie , Spalluto Giampiero , Sturlese Mattia , Moro Stefano
Published: September 2021

Fragment-Based Drug Discovery (FBDD) has become, in recent years, a consolidated approach in the drug discovery process, leading to several drug candidates under investigation in clinical trials and some approved drugs. Among these successful applications of the FBDD approach, kinases represent a class of targets where this strategy has demonstrated its real potential with the approved kinase inhibitor Vemurafenib. In the Kinase family, protein kinase CK1 isoform δ (CK1δ) has become a promising target in the treatment of different neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. In the present work, we set up and applied a computational workflow for the identification of putative fragment binders in large virtual databases. To validate the method, the selected compounds were tested in vitro to assess the CK1δ inhibition.
Mesoporous Aerogel Microparticles Injected into the Abdominal Cavity of Mice Accumulate in Parathymic Lymph Nodes
Authors: Király Gábor , Egu John Chinonso , Hargitai Zoltán , Kovács Ilona , Fábián István , Kalmár József , Szemán-Nagy Gábor
Published: September 2021

Mesoporous aerogel microparticles are promising drug delivery systems. However, their in vivo biodistribution pathways and health effects are unknown. Suspensions of fluorescein-labeled silica–gelatin hybrid aerogel microparticles were injected into the peritoneum (abdominal cavity) of healthy mice in concentrations of 52 and 104 mg kg−1 in a 3-week-long acute toxicity experiment. No physiological dysfunctions were detected, and all mice were healthy. An autopsy revealed that the aerogel microparticles were not present at the site of injection in the abdominal cavity at the end of the experiment. The histological study of the liver, spleen, kidneys, thymus and lymphatic tissues showed no signs of toxicity. The localization of the aerogel microparticles in the organs was studied by fluorescence microscopy. Aerogel microparticles were not detected in any of the abdominal organs, but they were clearly visible in the cortical part of the parathymic lymph nodes, where they accumulated. The accumulation of aerogel microparticles in parathymic lymph nodes in combination with their absence in the reticuloendothelial system organs, such as the liver or spleen, suggests that the microparticles entered the lymphatic circulation. This biodistribution pathway could be exploited to design passive targeting drug delivery systems for flooding metastatic pathways of abdominal cancers that spread via the lymphatic circulation.
Ablation of KDM2A Inhibits Preadipocyte Proliferation and Promotes Adipogenic Differentiation
Authors: Hua Yonglin , Yue Yongqi , Zhao Dan , Ma Yan , Xiong Yan , Xiong Xianrong , Li Jian
Published: September 2021

Epigenetic signals and chromatin-modifying proteins play critical roles in adipogenesis, which determines the risk of obesity and which has recently attracted increasing interest. Histone demethylase 2A (KDM2A) is an important component of histone demethylase; however, its direct effect on fat deposition remains unclear. Here, a KDM2A loss of function was performed using two unbiased methods, small interfering RNA (siRNA) and Cre-Loxp recombinase systems, to reveal its function in adipogenesis. The results show that the knockdown of KDM2A by siRNAs inhibited the proliferation capacity of 3T3-L1 preadipocytes. Furthermore, the promotion of preadipocyte differentiation was observed in siRNA-treated cells, manifested by the increasing content of lipid droplets and the expression level of adipogenic-related genes. Consistently, the genetic deletion of KDM2A by Adipoq-Cre in primary adipocytes exhibited similar phenotypes to those of 3T3-L1 preadipocytes. Interestingly, the knockdown of KDM2A upregulates the expression level of Transportin 1(TNPO1), which in turn may induce the nuclear translocation of PPARγ and the accumulation of lipid droplets. In conclusion, the ablation of KDM2A inhibits preadipocyte proliferation and promotes its adipogenic differentiation. This work provides direct evidence of the exact role of KDM2A in fat deposition and provides theoretical support for obesity therapy that targets KDM2A.
Extracellular Vesicle MicroRNA That Are Involved in β-Thalassemia Complications
Authors: Levin Carina , Koren Ariel , Rebibo-Sabbah Annie , Levin Maya , Koifman Na’ama , Brenner Benjamin , Aharon Anat
Published: September 2021

Beta thalassemia major (βT) is a hereditary anemia characterized by transfusion-dependency, lifelong requirement of chelation, and organ dysfunction. MicroRNA (miRNA) can be packed into extracellular vesicles (EVs) that carry them to target cells. We explored EV-miRNA in βT and their pathophysiologic role. Circulating EVs were isolated from 35 βT-patients and 15 controls. EV miRNA was evaluated by nano-string technology and real-time quantitative polymerase chain reaction (RT-qPCR). We explored effects of EVs on cell culture proliferation, apoptosis, and signal transduction. Higher amounts of small EV (exosomes) were found in patients than in controls. The expression of 21 miRNA was > two-fold higher, and of 17 miRNA < three-fold lower in βT-EVs than control-EVs. RT-qPCR confirmed differential expression of six miRNAs in βT, particularly miR-144-3p, a regulator of erythropoiesis. Exposure of endothelial, liver Huh7, and pancreatic 1.1B4 cells to βT-EVs significantly reduced cell viability and increased cell apoptosis. βT-EV-induced endothelial cell apoptosis involved the MAPK/JNK signal-transduction pathway. In contrast, splenectomized βT-EVs induced proliferation of bone marrow mesenchymal stem cells (BM-MSC). In summary, the miR-144-3p was strongly increased; βT-EVs induced apoptosis and decreased endothelial, pancreatic, and liver cell survival while supporting BM-MSC proliferation. These mechanisms may contribute to βT organ dysfunction and complications.
Two Paralogous Gb3/CD77 Synthases in Birds Show Different Preferences for Their Glycoprotein and Glycosphingolipid Substrates
Authors: Bereznicka Anna , Mikolajczyk Krzysztof , Szymczak-Kulus Katarzyna , Kapczynska Katarzyna , Majorczyk Edyta , Modlinska Anna , Piasecki Tomasz , Kaczmarek Radoslaw , Czerwinski Marcin
Published: September 2021

Most glycosyltransferases show remarkable gross and fine substrate specificity, which is reflected in the old one enzyme-one linkage paradigm. While human Gb3/CD77 synthase is a glycosyltransferase that synthesizes the Galα1→4Gal moiety mainly on glycosphingolipids, its pigeon homolog prefers glycoproteins as acceptors. In this study, we characterized two Gb3/CD77 synthase paralogs found in pigeons (Columba livia). We evaluated their specificities in transfected human teratocarcinoma 2102Ep cells by flow cytofluorometry, Western blotting, high-performance thin-layer chromatography, mass spectrometry and metabolic labelling with 14C-galactose. We found that the previously described pigeon Gb3/CD77 synthase (called P) can use predominately glycoproteins as acceptors, while its paralog (called M), which we serendipitously discovered while conducting this study, efficiently synthesizes Galα1→4Gal caps on both glycoproteins and glycosphingolipids. These two paralogs may underlie the difference in expression profiles of Galα1→4Gal-terminated glycoconjugates between neoavians and mammals.
Hydroxygenkwanin Increases the Sensitivity of Liver Cancer Cells to Chemotherapy by Inhibiting DNA Damage Response in Mouse Xenograft Models
Authors: Chen Chin-Chuan , Chen Chi-Yuan , Cheng Shu-Fang , Shieh Tzong-Ming , Leu Yann-Lii , Chuang Wen-Yu , Liu Kuang-Ting , Ueng Shir-Hwa , Shih Yin-Hwa , Chou Li-Fang , Wang Tong-Hong
Published: September 2021

Molecules involved in DNA damage response (DDR) are often overexpressed in cancer cells, resulting in poor responses to chemotherapy and radiotherapy. Although treatment efficacy can be improved with the concomitant use of DNA repair inhibitors, the accompanying side effects can compromise the quality of life of patients. Therefore, in this study, we identified a natural compound that could inhibit DDR, using the single-strand annealing yeast-cell analysis system, and explored its mechanisms of action and potential as a chemotherapy adjuvant in hepatocellular carcinoma (HCC) cell lines using comet assay, flow cytometry, Western blotting, immunofluorescence staining, and functional analyses. We developed a mouse model to verify the in vitro findings. We found that hydroxygenkwanin (HGK) inhibited the expression of RAD51 and progression of homologous recombination, thereby suppressing the ability of the HCC cell lines to repair DNA damage and enhancing their sensitivity to doxorubicin. HGK inhibited the phosphorylation of DNA damage checkpoint proteins, leading to apoptosis in the HCC cell lines. In the mouse xenograft model, HGK enhanced the sensitivity of liver cancer cells to doxorubicin without any physiological toxicity. Thus, HGK can inhibit DDR in liver cancer cells and mouse models, making it suitable for use as a chemotherapy adjuvant.
Protocadherin 19 Clustering Epilepsy and Neurosteroids: Opportunities for Intervention
Authors: de Nys Rebekah , Kumar Raman , Gecz Jozef
Published: September 2021

Steroids yield great influence on neurological development through nuclear hormone receptor (NHR)-mediated gene regulation. We recently reported that cell adhesion molecule protocadherin 19 (encoded by the PCDH19 gene) is involved in the coregulation of steroid receptor activity on gene expression. PCDH19 variants cause early-onset developmental epileptic encephalopathy clustering epilepsy (CE), with altered steroidogenesis and NHR-related gene expression being identified in these individuals. The implication of hormonal pathways in CE pathogenesis has led to the investigation of various steroid-based antiepileptic drugs in the treatment of this disorder, with mixed results so far. Therefore, there are many unmet challenges in assessing the antiseizure targets and efficiency of steroid-based therapeutics for CE. We review and assess the evidence for and against the implication of neurosteroids in the pathogenesis of CE and in view of their possible clinical benefit.
Insights into Comparative Modeling of VHH Domains
Authors: Vattekatte Akhila Melarkode , Cadet Frédéric , Gelly Jean-Christophe , de Brevern Alexandre G.
Published: September 2021

In the particular case of the Camelidae family, immunoglobulin proteins have evolved into a unique and more simplified architecture with only heavy chains. The variable domains of these chains, named VHHs, have a number of Complementary Determining Regions (CDRs) reduced by half, and can function as single domains making them good candidates for molecular tools. 3D structure prediction of these domains is a beneficial and advantageous step to advance their developability as molecular tools. Nonetheless, the conformations of CDRs loops in these domains remain difficult to predict due to their higher conformational diversity. In addition to CDRs loop diversity, our earlier study has established that Framework Regions (FRs) are also not entirely conformationally conserved which establishes a need for more rigorous analyses of these regions that could assist in template selection. In the current study, VHHs models using different template selection strategies for comparative modeling using Modeller have been extensively assessed. This study analyses the conformational changes in both CDRs and FRs using an original strategy of conformational discretization based on a structural alphabet. Conformational sampling in selected cases is precisely reported. Some interesting outcomes of the structural analyses of models also draw attention towards the distinct difficulty in 3D structure prediction of VHH domains.
Copper(II) Prevents the Saccarine-Dialkylcyanamide Coupling by Forming Mononuclear (Saccharinate)(Dialkylcyanamide)copper(II) Complexes
Authors: Toikka Yulia N. , Spiridonova Dar’ya V. , Novikov Alexander S. , Bokach Nadezhda A.
Published: September 2021

The reaction in the system CuII/sacNa(H)/NCNR2 (sacNa(H) = sodium saccharinate (saccharin); R = Me, Et) results in the formation of the complexes [Cu(sac)2(NCNR2)(H2O)2] (R = Me 1, Et 2) instead of the expected products derived from the saccharin–cyanamide coupling. Complexes 1, 2, and hydrate 1·2H2O were characterized by IR, AAS (Cu%), TGA, and also by single-crystal X-ray diffraction for 1 and 1·2H2O. An integrated computational study of model structure 1 in the gas phase demonstrates that the Cu–Ncyanamide and Cu–Nsac coordination bonds exhibited a single bond character, polarized toward the N atom and almost purely electrostatic, with the calculated vertical total energies for the Cu–Ncyanamide and Cu–Nsac of 43.6 and 156.4 kcal/mol, respectively. These data confirmed that the copper(II) completely blocks the nucleophilic centers of ligands via coordination, thus preventing the saccharin–cyanamide coupling.
Solitary Living Brings a Decreased Weight and an Increased Agility to the Domestic Silkworm, Bombyx mori
Authors: Zhu Zhenglin , Tan Yuting , Xiao Siyu , Guan Zhufen , Zhao Wen , Dai Zhijun , Liu Gexin , Zhang Ze
Published: September 2021

The domestic silkworms, Bombyx mori, always live in groups and little is known of the outcomes of solitary living. We bred solitary silkworms and performed a comprehensive investigation of the difference between solitary and group-living silkworms. The results show that solitary silkworms had significantly lower weights than group-living counterparts. Moreover, solitary silkworms had faster movements under food luring or heat stress than the group-living ones, supported by extensive behavior experiments. These findings inferred that an increased agility resulted from solitary living. For an understanding of the molecular mechanism associated with solitary living, we performed integrated mRNA and miRNA (microRNA) sequencing of tissues for solitary and group-living silkworms. We identified 165 differently expressed genes (DEGs) and 6 differently expressed miRNAs between the solitary and group-living silkworms. Functional and pathway analyses indicated that these DEGs are associated with weight loss and agility increase. These findings compose a sketch depicting an association between the phenotypes and genes resulted from solitary living and refresh the understanding of solitary living and loneliness, which has an increased prevalence in our modern society.
Enhanced Medical and Community Face Masks with Antimicrobial Properties: A Systematic Review
Authors: Stokes Katy , Peltrini Roberto , Bracale Umberto , Trombetta Marcella , Pecchia Leandro , Basoli Francesco
Published: September 2021

Face masks help to limit transmission of infectious diseases entering through the nose and mouth. Beyond reprocessing and decontamination, antimicrobial treatments could extend the lifetime of face masks whilst also further reducing the chance of disease transmission. Here, we review the efficacy of treatments pertaining antimicrobial properties to medical face masks, filtering facepiece respirators and non-medical face masks. Searching databases identified 2113 studies after de-duplication. A total of 17 relevant studies were included in the qualitative synthesis. Risk of bias was found to be moderate or low in all cases. Sixteen articles demonstrated success in avoiding proliferation (if not elimination) of viruses and/or bacteria. In terms of methodology, no two articles employed identical approaches to efficacy testing. Our findings highlight that antimicrobial treatment is a promising route to extending the life and improving the safety of face masks. In order to reach significant achievements, shared and precise methodology and reporting is needed.
Is the Training Intensity in Phase Two Cardiovascular Rehabilitation Different in Telehealth versus Outpatient Rehabilitation?
Authors: Batalik Ladislav , Pepera Garyfallia , Papathanasiou Jannis , Rutkowski Sebastian , Líška David , Batalikova Katerina , Hartman Martin , Felšőci Marián , Dosbaba Filip
Published: September 2021

Telehealth cardiac rehabilitation (CR) is a feasible and effective alternative to conventional outpatient CR. Present evidence is limited on the comparison of exercise intensity adherence in telehealth and outpatient CR. The purpose of the study was to evaluate and compare training intensity adherence through 12-week phase II CR in telehealth and outpatient CR. A sample of 56 patients with coronary artery disease (CAD) with a mean age of 56.7 ± 7.1 entering comprehensive secondary prevention phase II was randomized into telehealth CR (n = 28) and control outpatient CR (n = 28) groups. The primary outcome was a comparison of training intensity adherence in both CR models and heart rate (HR) response from individual CR sessions, expressed by the HR reserve percentage. As a result, the parameter HR reserve percentage as the total average of the training intensity during the telehealth intervention and the outpatient CR did not differ statistically (p = 0.63). There was no death case, and all severe adverse cases required medical admission throughout an exercise training session in study subjects in both groups. This research evidence demonstrated that the telehealth CR model is similar in training intensities to the conventional outpatient CR in CAD patients with low to moderate cardiovascular risk.
Diagnostic and Prognostic Potential of MiR-379/656 MicroRNA Cluster in Molecular Subtypes of Breast Cancer
Authors: Lal Megha , Ansari Asgar Hussain , Agrawal Anurag , Mukhopadhyay Arijit
Published: September 2021

Introduction: Breast cancer is the most frequently diagnosed cancer globally and is one of the most important contributors to cancer-related deaths. Earlier diagnosis is known to reduce mortality, and better biomarkers are needed. MiRNA clusters often co-express and target mRNAs in a coordinated fashion, perturbing entire pathways; they thus merit further exploration for diagnostic or prognostic use. MiR-379/656, at chromosome 14q32, is the second largest miRNA cluster in the human genome and implicated in various malignancies including glioblastoma, melanoma, gastrointestinal tumors and ovarian cancer highlighting its potential importance. In this study, we focus on the diagnostic and prognostic potentials of MiR-379/656 in breast cancer and its molecular subtypes. Materials and Methods: We analyzed miRNA and mRNA next generation sequencing data from 903 primary tumors and 90 normal controls (source: The Cancer Genome Atlas). The differential expression profile between tumor and normal was analyzed using DeSEQ2. Penalized logistic regression modelling (lasso regression) was used to assess the predictive potential of MiR-379/656 expression for tumor and normal samples. The association between MiR-379/656 expression and overall patient survival was studied using Cox Proportional-Hazard Model. The target mRNAs (validated) of MiR-379/656 were annotated via pathway enrichment analysis to understand the biological significance of the cluster in breast cancer. Results: The differential expression analysis for 1390 miRNAs (miRnome) revealed 310 upregulated (22.3%) and 176 downregulated (12.66%) miRNAs in breast cancer patients compared with controls. For MiR-379/656, 32 miRNAs (32/42; 76%) were downregulated. The MiR-379/656 cluster was found to be the most differentially expressed cluster in the human genome (p < 10−30). The Basal and Luminal B subtypes showed at least 83% (35/42) of the miRNAs to be downregulated. The binomial model prioritized 15 miRNAs, which distinguished breast cancer patients from controls with 99.15 ± 0.58% sensitivity and 77.78 ± 5.24% specificity. Overall, the Basal and Luminal B showed the most effective predictive power with respect to the 15 prioritized miRNAs at MiR-379/656 cluster. The decreased expression of MiR-379/656 was found to be associated with poorer clinical outcome in Basal and Luminal B subtypes, increasing tumor stage and tumor size/extent, and overall patient survival. Pathway enrichment for the validated targets of MiR-379/656 was significant for cancer-related pathways, especially DNA repair, transcriptional regulation by p53 and cell cycle checkpoints (adjusted p-value < 0.05). Conclusions: Genome informatics analysis of high throughput data for MiR-379/656 cluster has shown that a subset of 15 miRNAs from MiR-379/656 cluster can be used for the diagnostic and prognostic purpose of breast cancer and its subtypes—especially in Basal and Luminal B.
A Historical Analysis of Randomized Controlled Trials in the Management of Pain in Rotator Cuff Tears
Authors: Berton Alessandra , Longo Umile Giuseppe , De Salvatore Sergio , Sciotti Gaia , Santamaria Giulia , Piergentili Ilaria , De Marinis Maria Grazia , Denaro Vincenzo
Published: September 2021

The aim of this analysis was to assess the quality of reporting of randomized controlled trials (RCTs) relating to pain management in rotator cuff (RC) tears. This review evaluated the quality of the studies in the literature regarding this topic through the use of some factors and trends. The online databases used to search all RCTs on the topic of RC surgery were Medline, Scopus, CINAHL, EMBASE, and CENTRAL. This research was completed in September 2020. To assess the quality of reports, the Consolidated Standards of Reporting Trials (CONSORT) and the modified Coleman methodology score (MCMS) were used. From the research, 262 articles emerged. Finally, 79 studies were included in this historical analysis. There were no statistically significant changes in MCMS across trials that included or did not include a CONSORT diagram (p = 0.10). A statistically significant difference in MCMS was discovered between papers produced prior to 2009 and publications produced after 2015 (p = 0.03). There was no association between the number of checklist items for each article and the Coleman score. During the years there has been a significant increase in both quantity and quality of RCTs relating to pain in RC tears.
Machine Learning Prediction of Length of Stay in Adult Spinal Deformity Patients Undergoing Posterior Spine Fusion Surgery
Authors: Zhang Andrew S , Veeramani Ashwin , Quinn Matthew S. , Alsoof Daniel , Kuris Eren O. , Daniels Alan H.
Published: September 2021

(1) Background: Length of stay (LOS) is a commonly reported metric used to assess surgical success, patient outcomes, and economic impact. The focus of this study is to use a variety of machine learning algorithms to reliably predict whether a patient undergoing posterior spinal fusion surgery treatment for Adult Spine Deformity (ASD) will experience a prolonged LOS. (2) Methods: Patients undergoing treatment for ASD with posterior spinal fusion surgery were selected from the American College of Surgeon’s NSQIP dataset. Prolonged LOS was defined as a LOS greater than or equal to 9 days. Data was analyzed with the Logistic Regression, Decision Tree, Random Forest, XGBoost, and Gradient Boosting functions in Python with the Sci-Kit learn package. Prediction accuracy and area under the curve (AUC) were calculated. (3) Results: 1281 posterior patients were analyzed. The five algorithms had prediction accuracies between 68% and 83% for posterior cases (AUC: 0.566–0.821). Multivariable regression indicated that increased Work Relative Value Units (RVU), elevated American Society of Anesthesiologists (ASA) class, and longer operating times were linked to longer LOS. (4) Conclusions: Machine learning algorithms can predict if patients will experience an increased LOS following ASD surgery. Therefore, medical resources can be more appropriately allocated towards patients who are at risk of prolonged LOS.
Aerobic Threshold Identification in a Cardiac Disease Population Based on Correlation Properties of Heart Rate Variability
Authors: Rogers Bruce , Mourot Laurent , Gronwald Thomas
Published: September 2021

An index of heart rate (HR) variability correlation properties, the short-term scaling exponent alpha1 of detrended fluctuation analysis (DFA a1) has shown potential to delineate the first ventilatory threshold (VT1). This study aims to extend this concept to a group of participants with cardiac disease. Sixteen volunteers with stable coronary disease or heart failure performed an incremental cycling ramp to exhaustion PRE and POST a 3-week training intervention. Oxygen uptake (VO2) and HR at VT1 were obtained from a metabolic cart. An ECG was processed for DFA a1 and HR. The HR variability threshold (HRVT) was defined as the VO2, HR or power where DFA a1 reached a value of 0.75. Mean VT1 was reached at 16.82 ± 5.72 mL/kg/min, HR of 91.3 ± 11.9 bpm and power of 67.8 ± 17.9 watts compared to HRVT at 18.02 ± 7.74 mL/kg/min, HR of 94.7 ± 14.2 bpm and power of 73.2 ± 25.0 watts. Linear relationships were seen between modalities, with Pearson’s r of 0.95 (VO2), 0.86 (HR) and 0.87 (power). Bland–Altman assessment showed mean differences of 1.20 mL/kg/min, 3.4 bpm and 5.4 watts. Mean peak VO2 and VT1 did not change after training intervention. However, the correlation between PRE to POST change in VO2 at VT1 with the change in VO2 at HRVT was significant (r = 0.84, p < 0.001). Reaching a DFA a1 of 0.75 was associated with the VT1 in a population with cardiac disease. VT1 change after training intervention followed that of the HRVT, confirming the relationship between these parameters.
Health-Care Professionals Amid the COVID-19 Pandemic: How Emotional Intelligence May Enhance Work Performance Traversing the Mediating Role of Work Engagement
Authors: Sanchez-Gomez Martin , Sadovyy Max , Breso Edgar
Published: September 2021

Upon the eruption of COVID-19, frontline health-care workers confronted substantial workload and stress along with braving additional difficulties when performing at work. The main aim of this research was to assess the mediating role of work engagement in the direct impact of emotional intelligence on health-care professionals’ work performance. A cross-sectional study was conducted in several Spanish hospitals during the second half of 2020. A total of 1549 health-care workers (62.1% women; mean age 36.51 years) filled the Wong and Law Emotional Intelligence Scale, the Utrecht Work Engagement Scale and the Individual Work Performance Questionnaire. Our findings demonstrated that work engagement plays a mediating effect between emotional intelligence and work performance, even when accounting for sociodemographic variables. Indeed, among the three constructs of engagement, vigor dimension (a1b1 = 0.09; CI: 0.06; 0.12; p < 0.01) emerges over dedication (a2b2 = 0.083; CI = 0.05, 0.1; p < 0.01) and absorption (a3b3 = 0.047; CI = 0.02, 0.07; p < 0.01) as the most decisive one. Herewith, it is apparent that professionals with a higher self-perception of emotional intelligence report stronger levels of engagement, thereby leading to greater performance overall. The present work evinces the necessity for proactively developing the emotional competencies of the health-care workforce, especially in high-emotional demand contexts.
Glycemic Variability Impacted by SGLT2 Inhibitors and GLP 1 Agonists in Patients with Diabetes Mellitus: A Systematic Review and Meta-Analysis
Authors: Lee Heeyoung , Park Se-eun , Kim Eun-Young
Published: September 2021

To investigate the effect of sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) agonists on glycemic variability (GV), the mean amplitude of glucose excursion (MAGE), mean blood glucose (MBG) levels, and percentage of time maintaining euglycemia were evaluated. Randomized controlled trials evaluating the efficacy of SGLT-2 inhibitors and GLP-1 agonists for treating people with diabetes were selected through searches of PubMed, EMBASE, and other databases. Sixteen studies were finally analyzed. There were no differences in the reductions in MAGE after treatment with SGLT-2 inhibitors or GLP-1 agonists (standardized mean difference (SMD) = −0.59, 95% CI = −0.82 to −0.36 vs. SMD = −0.43, 95% CI = −0.51 to −0.35, respectively), and treatment with SGLT-2 inhibitors was associated with an increased reduction in MBG levels (SMD = −0.56, 95% CI = −0.65 to −0.48, p < 0.00001). Monotherapy and add-on therapy with medications were correlated with MAGE and MBG level reductions. In conclusion, SGLT-2 inhibitors and GLP-1 agonists were associated with a reduction in GV and could be alternatives for treating people with diabetes.
Itch as Major Mediator of Effect of Tofacitinib on Health-Related Quality of Life in Psoriatic Arthritis: A Mediation Analysis
Authors: Taylor Peter C. , Bushmakin Andrew G. , Cappelleri Joseph C. , Young Pamela , Germino Rebecca , Merola Joseph F. , Yosipovitch Gil
Published: September 2021

Patients with psoriatic arthritis (PsA) experience impaired health-related quality of life (HRQoL). Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA, which has been associated with improvements in dermatologic endpoints in patients with PsA. To assess the extent to which tofacitinib affects patient HRQoL via improvements in dermatologic symptoms, including itch, data were pooled from patients with PsA who received tofacitinib in phase III studies (NCT01866668 and NCT01882439). Mediation modeling assessed the indirect effects (via Itch Severity Item [ISI] and Physician’s Global Assessment of Psoriasis [PGA-PsO]) and direct effects (via all other factors) of tofacitinib treatment on dermatology-specific HRQoL (measured by Dermatology Life Quality Index [DLQI]). In the initial model, the treatment effect on DLQI was largely mediated by itch (ISI; p < 0.0001) and PGA-PsO (p < 0.01). The model was re-specified to assess the indirect effects only of itch and PGA-PsO on DLQI. Here, 17.7% of the treatment effect on DLQI was attributable to PGA-PsO (p = 0.0006), and 82.3% to itch (p < 0.0001). Tofacitinib-dependent improvements in DLQI were primarily mediated by itch relief, in addition to improvements in PGA-PsO.
Mechanisms of Exercise Capacity Improvement after Cardiac Rehabilitation Following Myocardial Infarction Assessed with Combined Stress Echocardiography and Cardiopulmonary Exercise Testing
Authors: Smarz Krzysztof , Jaxa-Chamiec Tomasz , Zaborska Beata , Tysarowski Maciej , Budaj Andrzej
Published: September 2021

Cardiac rehabilitation (CR) is indicated in all patients after acute myocardial infarction (AMI) to improve prognosis and exercise capacity (EC). Previous studies reported that up to a third of patients did not improve their EC after CR (non-responders). Our aim was to assess the cardiac and peripheral mechanisms of EC improvement after CR using combined exercise echocardiography and cardiopulmonary exercise testing (CPET-SE). The responders included patients with an improved EC assessed as a rise in peak oxygen uptake (VO2) ≥ 1 mL/kg/min. Peripheral oxygen extraction was calculated as arteriovenous oxygen difference (A-VO2Diff). Out of 41 patients (67% male, mean age 57.5 ± 10 years) after AMI with left ventricular ejection fraction (LVEF) ≥ 40%, 73% improved their EC. In responders, peak VO2 improved by 27% from 17.9 ± 5.2 mL/kg/min to 22.7 ± 5.1 mL/kg/min, p < 0.001, while non-responders had a non-significant 5% decrease in peak VO2. In the responder group, the peak exercise heart rate, early diastolic myocardial velocity at peak exercise, LVEF at rest and at peak exercise, and A-VO2Diff at peak exercise increased, the minute ventilation to carbon dioxide production slope decreased, but the stroke volume and cardiac index were unchanged after CR. Non-responders had no changes in assessed parameters. EC improvement after CR of patients with preserved LVEF after AMI is associated with an increased heart rate response and better peripheral oxygen extraction during exercise.
Proposal for a Novel Abrasive Machining Method for Preparing the Surface of Periarticular Tissue during Orthopedic Surgery on Hip Joints
Authors: Zawadzki Paweł
Published: September 2021

Drilling, cutting, and milling are the most common methods used in orthopedic surgery. However, popular machining methods do not obtain the complex shape of the periarticular tissue surfaces, increasing operation time and patient recovery. This paper reports an attempt to research a novel design of a machining process for surgical procedures. A device using abrasion machining based on mechanical erosion was proposed. Machining uses an undefined geometry of the cutting grains to cut tissue in any direction during oscillatory tool movement. This new concept is based on a cylindrical abrasive device made of brown fused alumina and silicon carbide grains deposited with an epoxy resin binder on the surface of a polyamide shaft. The best results in terms of machining efficiency were obtained for grains of the BFA80 type. Cutting experiments with different values in terms of cutting speed, granulation of the abrasive grains, pressure forces, and machining scope showed that the proposed concept, by developing the shape of the device, allows for penetration of the tissue structure. The research shows the possibility of using the proposed method during periarticular tissue machining.
The NADPH Oxidase A of Verticillium dahliae Is Essential for Pathogenicity, Normal Development, and Stress Tolerance, and It Interacts with Yap1 to Regulate Redox Homeostasis
Authors: Vangalis Vasileios , Papaioannou Ioannis A. , Markakis Emmanouil A. , Knop Michael , Typas Milton A.
Published: September 2021

Maintenance of redox homeostasis is vital for aerobic organisms and particularly relevant to plant pathogens. A balance is required between their endogenous ROS production, which is important for their development and pathogenicity, and host-derived oxidative stress. Endogenous ROS in fungi are generated by membrane-bound NADPH oxidase (NOX) complexes and the mitochondrial respiratory chain, while transcription factor Yap1 is a major regulator of the antioxidant response. Here, we investigated the roles of NoxA and Yap1 in fundamental biological processes of the important plant pathogen Verticillium dahliae. Deletion of noxA impaired growth and morphogenesis, compromised formation of hyphopodia, diminished penetration ability and pathogenicity, increased sensitivity against antifungal agents, and dysregulated expression of antioxidant genes. On the other hand, deletion of yap1 resulted in defects in conidial and microsclerotia formation, increased sensitivity against oxidative stress, and down-regulated antioxidant genes. Localized accumulation of ROS was observed before conidial fusion and during the heterokaryon incompatibility reaction upon nonself fusion. The frequency of inviable fusions was not affected by the deletion of Yap1. Analysis of a double knockout mutant revealed an epistatic relationship between noxA and yap1. Our results collectively reveal instrumental roles of NoxA and ROS homeostasis in the biology of V. dahliae.
Current Challenges in Deciphering Sutton Nevi—Literature Review and Personal Experience
Authors: Nedelcu Roxana , Dobre Alexandra , Brinzea Alice , Hulea Ionela , Andrei Razvan , Zurac Sabina , Balaban Mihaela , Antohe Mihaela , Manea Lorena , Calinescu Andreea , Coman Anastasia , Pantelimon Florentina , Dobritoiu Adina , Popescu Catalin , Popescu Raluca , Balasescu Elena , Ion Daniela , Turcu Gabriela
Published: September 2021

Halo nevi, known as leukoderma acquisitum centrifugum, Sutton nevus, leukopigmentary nevus, perinevoid vitiligo, or perinevoid leukoderma, together with vitiligo and melanoma-associated hypopigmentation, belong to the group of dermatoses designated as immunological leukodermas. The etiology and pathogenesis of halo nevi has not been fully elucidated. There are several mechanisms through which a lymphocytic infiltrate can induce tumoral regression. In this review, we aimed to update the knowledge about Sutton nevi starting with the clinical appearance and dermoscopic features, continuing with information regarding conventional microscopy, immunohistochemistry, and the immunological mechanisms responsible for the occurrence of halo nevi. We also included in the article original unpublished results when discussing dermoscopic, pathologic and immunohistochemical results in halo nevi. Sutton nevi are valuable models for studying antitumor reactions that the human body can generate. The slow and effective mechanism against a melanocytic skin tumor can teach us important lessons about both autoimmune diseases and anticancer defenses.
Price Discrimination in the Online Airline Market: An Empirical Study
Authors: Azzolina Stefano , Razza Manuel , Sartiano Kevin , Weitschek Emanuel
Published: September 2021

Big Data technologies have significantly increased the possibility for sellers to adopt personalisation strategies, especially in digital markets. Among such strategies, price discrimination, a practice where the same commodity is sold at different prices, either to the same customer or to different customers, stands out. Particularly, the online airline ticket market has risen the attention of economists in recent studies, both because of its specificity and of the high data availability. This manuscript enters the debate and analyses the airline ticket market in an original way. Indeed, the aim of this work is to empirically understand whether some airline companies discriminate in prices by using the customers’ data that they collect from their websites, and, if so, which is the impact on social welfare. For performing this assessment, a software that is able to automatically collect pricing data is developed and freely released. By executing the software in two time periods, tickets prices of three airlines, three itineraries, and four different user profiles are acquired. A double analysis is performed to check if customers’ information are used to discriminate (intra-user), and if different prices are offered to distinct user profiles (inter-user). Moreover, the analyses consider control data collected from the API of the Global Distribution System Amadeus, the main flight booking platform dedicated to travel agents. Upon inspection, no evidence is found in this study to support the hypothesis that airlines use price discrimination techniques.