bluuebunny/crossref_metadata_2025 huggingface dataset:
Transversal Competences in Engineering Degrees: Integrating Content and Foreign Language Teaching
Authors: Oksana Polyakova , Galstyan-Sargsyan Ruzana , López-Jiménez P. Amparo , Pérez-Sánchez Modesto
Published: October 2020

There has been a constant advance of the labour markets and permanent reorientation towards digital Industry 4.0. Yet, the environments for learning remain unchallenged when it comes to the provision of new professionals across the globe. Therefore, this has created a gap in transversal competences, which has compelled students of higher learning institutions to pursue them. The majority of higher learning institutions have emphasised transversal skills among learners and developed curriculums to accomplish these demands. The primary focus of the study was to attain integration and fusion of transversal skills into the development of specialised curriculum training for foreign language proficiency. The study applied mixed methodology techniques, which combined qualitative and quantitative methods in the study. To guarantee cohesion of the study, four research and monitoring techniques such as course dossiers, needs analysis, task-based activities and adapted competences scales were used. The outcome of the research shows findings provided by the piloting stage of the teaching experience and emphasises the need for student-based skill training.
Cross-Coupling Inductance Parameter Estimation for More Accurate Performance Evaluation of Wound-Field Flux Modulation Machines
Authors: Mabhula Mkhululi , Akuru Udochukwu B. , Kamper Maarten J.
Published: October 2020

In this paper, a proposed numerical frozen permeability modeling procedure is fully derived to accurately estimate the parameters of two variants of wound-field flux modulation machines (WF-FMMs) namely: wound-field flux switching machine (WF-FSM) and DC-excited vernier reluctance machine (DC-VRM). During the procedure, the contribution of saturation to the variation of the machine parameters is investigated. The parameter variation effects on the machine performance is also investigated. It is shown that analysis of WF-FMMs is better understood by using the proposed procedure which computes accurately the machine parameters.
Channel-Hopping-Based Jamming Mitigation in Wireless LAN Considering Throughput and Fairness
Authors: Djuraev Sirojiddin , Nam Seung Yeob
Published: October 2020

Because of the popularity of wireless technology, jamming attack is one of the most critical issues in wireless networks. Wireless jamming attack is one type of denial-of-service attacks where attackers send malicious messages or signal on a legitimate channel by causing intentional interference in the network. In order to avoid jamming attacks, various jamming defense schemes have been proposed. One of the popular methods is a channel-hopping scheme. However, the main challenge of this method is generating a common channel number between the users and the access point without leaking that information to the jammer. We propose a new channel-hopping scheme where the access point shares a separate key with each user to isolate the damage on the network when a key has been compromised, while maintaining high throughput and fairness. We evaluate the proposed scheme through experiment on a test bed.
A Privacy-Preserving Routing Protocol Using Mix Networks in Opportunistic Networks
Authors: Chen Depeng , Borrego Carlos , Navarro-Arribas Guillermo
Published: October 2020

This paper focuses on the problem of providing anonymous communications in opportunistic networks. To that end, we propose an approach using Mix networks that enables a relatively simple solution. Opportunistic networks present some constraints that make the deployment of typical network anonymity solutions difficult or infeasible. We show, utilizing simulations on the basis of real mobility traces, that the proposed solution is feasible for some scenarios by introducing a tolerable penalty in terms of message delay and delivery. To investigate the impact of routing strategies, we offer two different methods to select Mix nodes. From the experiment results, we show the trade-off between network performance and security.
Developing an Innovative Medical Training Simulation Device for Peripheral Venous Access: A User-Centered Design Approach
Authors: Miranda Constanza , Altermatt Fernando , Villagrán Ignacio , Goñi Julián
Published: October 2020

Nurses and other health students may lack the proper time for training procedural tasks, such as peripheral venous access. There is a need to develop these abilities in novices so that errors can be avoided when treating real patients. Nonetheless, from an experiential point of view, the simulation devices offered in the market do not always make sense for educators and trainees. This could make the adoption of new technology difficult. The purpose of this case study is to describe the development of an innovative simulation device and to propose concrete tactics for the involvement of the educators and trainees. We used a participative design based approach, with an ethnographic basis, where incremental cycles of user testing, development and iteration were involved. The study showcases methods from the field of design and anthropology that can be used to develop future simulation devices that resonate with students and educators to achieve a long term learning experience. Results could shed a light on new ways for the involvement of educators and students to create devices that resonate with them, making learning significant and effective.
Leg Muscle Activity and Perception of Effort before and after Four Short Sessions of Submaximal Eccentric Cycling
Authors: Clos Pierre , Lepers Romuald
Published: October 2020

Background: This study tested muscle activity (EMG) and perception of effort in eccentric (ECC) and concentric (CON) cycling before and after four sessions of both. Methods: Twelve volunteers naïve to ECC cycling attended the laboratory six times. On day 1, they performed a CON cycling peak power output (PPO) test. They then carried-out four sessions comprising two sets of 1 to 1.5-min cycling bouts at 5 intensities (30, 45, 60, 75, and 90% PPO) in ECC and CON cycling. On day 2 and day 6 (two weeks apart), EMG root mean square of the vastus lateralis (VL), rectus femoris (RF), biceps femoris (BF), and soleus (SOL) muscles, was averaged from 15 to 30 s within each 1-min bout and perception of effort was asked after 45 s. Results: Before the four cycling sessions, while VL EMG was lower in ECC than CON cycling, most variables were not different. Afterwards, ECC cycling exhibited lower RF EMG at 75 and 90% PPO (all p < 0.02), lower VL and BF EMG at all exercise intensities (all p < 0.02), and inferior SOL EMG (all p < 0.04) except at 45% PPO (p = 0.07). Perception of effort was lower in ECC cycling at all exercise intensities (all p < 0.03) but 60% PPO (p = 0.11). Conclusions: After four short sessions of ECC cycling, the activity of four leg muscles and perception of effort became lower in ECC than in CON cycling at most of five power outputs, while they were similar before.
Secondary Prevention of Depressive Prodrome in Adolescents: Before and after Attending a Jogging Program on Campus
Authors: Yen Ke Tien , Cherng Shen
Published: October 2020

The adolescent depressive prodrome has been conceptualized as an early integrated sign of depressive symptoms, which may develop to a first episode of depression or return to normal for the adolescents. In this study, depressive prodrome presented the early self-rated depressive symptoms for the sample participants. By referring to the Kutcher Adolescent Depression Scale and the psychometric characteristics of the Adolescent Depression Scale (ADR), we proposed a self-rated questionnaire to assess the severity of the depressive symptoms in adolescents before and after attending the jogging program on a high school campus in Taiwan. With the parental co-signature and self-signed informed consent form, 284 high school students under the average age of 15 years, participated in this study in March 2019. Through the software of IBMSPSS 25, we used a binary logistic model, principal component analysis (PCA), multiple-dimensional analysis, and receiver operating characteristic curve (ROC) to analyze the severity of the depressive prodrome via the threshold severity score (SC) and false positive rate (FPR). Findings revealed that attending the 15-week jogging program (3 times a week, 45 min each) on campus can change the severity status and reduce the prevalence of moderate-severe depressive prodrome by 26%. The two-dimensional approach identified three symptoms, which were the crying spell, loss of pleasure doing daily activities, and feeling the decline in memory. They kept being invariant symptoms during the course of depressive prodrome assessment for sample participants. In this study, the campus jogging program appeared to be able to affect the FPR of the measure of depressive prodrome. Compared with the subthreshold depression, the depressive prodrome emphasized the assessment from the view of the secondary prevention by representing the change from a person’s premorbid functioning up until the first onset of depression or returning to normal. However, the subthreshold depression is a form of minor depression according to DSM-5 criteria varying on the number of symptoms and duration required, highly prevalent in the concern of primary care.
Monitoring of Water Quality, Antibiotic Residues, and Antibiotic-Resistant Escherichia coli in the Kshipra River in India over a 3-Year Period
Authors: Hanna Nada , Purohit Manju , Diwan Vishal , Chandran Salesh P. , Riggi Emilia , Parashar Vivek , Tamhankar Ashok J. , Lundborg Cecilia Stålsby
Published: October 2020

The emergence of antibiotic resistance is a major global and environmental health issue, yet the presence of antibiotic residues and resistance in the water and sediment of a river subjected to excessive anthropogenic activities and their relationship with water quality of the river are not well studied. The objectives of the present study were a) to investigate the occurrence of antibiotic residues and antibiotic-resistant Escherichia coli (E. coli) in the water and sediment of the Kshipra river in India at seven selected sites during different seasons of the years 2014, 2015, and 2016 and b) to investigate the association between antibiotic residues and antibiotic-resistant E. coli in water and sediment and measured water quality parameters of the river. Antibiotic residues and resistant E. coli were present in the water and sediment and were associated with the measured water quality parameters. Sulfamethoxazole was the most frequently detected antibiotic in water at the highest concentration of 4.66 µg/L and was positively correlated with the water quality parameters. Significant (p < 0.05) seasonal and spatial variations of antibiotic-resistant E. coli in water and sediment were found. The resistance of E. coli to antibiotics (e.g., sulfamethiazole, norfloxacin, ciprofloxacine, cefotaxime, co-trimoxazole, ceftazidime, meropenem, ampicillin, amikacin, metronidazole, tetracycline, and tigecycline) had varying associations with the measured water and sediment quality parameters. Based on the results of this study, it is suggested that regular monitoring and surveillance of water quality, including antibiotic residues and antibiotic resistance, of all rivers should be taken up as a key priority, in national and Global Action Plans as these can have implications for the buildup of antibiotic resistance.
Diode versus CO2 Laser Therapy in the Treatment of High Labial Frenulum Attachment: A Pilot Randomized, Double-Blinded Clinical Trial
Authors: Sfasciotti Gian Luca , Zara Francesca , Vozza Iole , Carocci Veronica , Ierardo Gaetano , Polimeni Antonella
Published: October 2020

Background: The labial frenula are triangular plicas departing from the alveolar mucosa and attaching themselves at different heights of the gingiva. Sometimes a high attachment can determine a gingival recession. The most suitable surgical resolution is the use of laser devices. The aim of this study was to compare the labial frenulectomy through the use of Diode and CO2 laser techniques in pediatric patients with a high labial frenulum attachment, clarifying at the same time the preventive role of the surgical treatment to avoid further recession. Methods: A pilot randomized, double-blinded clinical trial was conducted to compare both the surgical advantages and the preventive treatment of laser technology using two different wavelengths within a population of pediatric patients with a high labial frenulum attachment. Different parameters intra and post-surgery were taken into account (Bleeding, Wound Healing, Gingival Recession, Periodontal pocket and Numerical Scale Value for pain) to compare Diode versus CO2 laser therapy. Results: Although both the laser devices provide a good performance in the post-operative period, the Diode laser shows better results (p < 0.001) in three of the five parameters evaluated. Conclusions: From the results it was found that the Diode Laser device is more suitable compared to the CO2 device.
Assessment of the Consultation Rate with General Practitioners in the Initial Phase of the COVID-19 Pandemic
Authors: Ochal Michał , Romaszko Małgorzata , Glińska-Lewczuk Katarzyna , Gromadziński Leszek , Romaszko Jerzy
Published: October 2020

Background: The COVID-19 pandemic affected the functioning of healthcare systems (HSs) in a way that was difficult to foresee earlier. It quickened the introduction of e-medicine, and changed the manner and number of services provided in the open medical setting. Aim: To assess variations in the consultation rate of patients in primary healthcare centers (PHCs) in consecutive months of the pandemic. Method: Data collected from two PHCs located in Olsztyn (Poland) were analyzed retrospectively. Collectively, these two centers provide care for approximately 20,000 inhabitants and perform approximately 100,000 medical services annually. The analysis was based on data covering the period April–July of the years 2010–2020, consisting in total of 337,510 medical services records. Results: A large, statistically significant decrease in the consultation rate (consultation rate understood as the number of individuals seeking consultation in relation to the number of people under care in a given time period) was revealed in each age group in the initial phase of the pandemic. In consecutive months, the approximated consultation rate achieved mean long-term values. Conclusions. The largest reduction in the consultation rate was revealed in the youngest age group, with the smallest occurring in the oldest. In the group of patients older than 65 years of age, the consultation rate after 3 months of the pandemic was the same as before the outbreak. Variations in the consultation rate were independent of the epidemiological situation. During the study, we observed an increased level of the administrative and paperwork activities carried out by PHC physicians.
Evaluating Mortality Response Associated with Two Different Nordic Heat Warning Systems in Riga, Latvia
Authors: Pfeifer Kerstin , Oudin Åström Daniel , Martinsone Žanna , Kaļužnaja Darja , Oudin Anna
Published: October 2020

Background and objectives: Progressing climate change is accompanied by a worldwide increase in the intensity, frequency, and duration of heat wave events. Research has shown that heat waves are an emerging public health problem, as they have a significant impact on mortality. As studies exploring this relationship are scarce for Latvia, this study aims to investigate the short-term associations between heat waves and all-cause mortality as well as cause-specific mortality, during the summer months (May-September) in Riga. Materials and Methods: An ecological time series study using daily reported mortality and temperature data from Riga between 2009 and 2015 was employed. Heat waves were defined based on the categories of the Latvian and Swedish heat warning system. Using a Quasi-Poisson regression, the relationships between heat waves and all-cause as well as cause-specific mortality were investigated. Results: Heat waves in Riga were associated with a 10% to 20% increase in the risk of all-cause mortality, depending on the applied heat wave definition, compared to days with normal temperature. In addition, heat-related mortality was found to increase significantly in the ≥65 age group between 12% and 22% during heat waves. In terms of cause-specific mortality, a significant increase of approximately 15% to 26% was observed for cardiovascular mortality. No significant associations were found between heat waves and respiratory or external causes of mortality. Conclusion: These results indicate that there are short-term associations between heat waves and all-cause as well as cardiovascular mortality in Riga and that heat waves therefore represent a public health problem in this Baltic city.
A Six-Year Point Prevalence Survey of Healthcare-Associated Infections in an Italian Teaching Acute Care Hospital
Authors: Gentili Andrea , Di Pumpo Marcello , La Milia Daniele Ignazio , Vallone Doriana , Vangi Gino , Corbo Maria Incoronata , Berloco Filippo , Cambieri Andrea , Damiani Gianfranco , Ricciardi Walter , Laurenti Patrizia
Published: October 2020

Healthcare-associated infections (HAI) represent one of the most common cause of infection and an important burden of disease. The aim of this study was to analyze the results of a six-year HAI point prevalence survey carried out yearly in a teaching acute care hospital from 2013 to 2018, following the European Center for Disease Prevention and Control (ECDC) guidelines. Surgical site infections, urinary tract infections, bloodstream infections, pneumonia, meningitis, and Clostridium difficile infections were considered as risk factors. A total of 328 patients with HAI were detected during the 6-year survey, with an average point prevalence of 5.24% (95% CI: 4.70–5.83%). Respiratory tract infections were the most common, followed by surgical site infections, urinary tract infections, primary bloodstream infections, Clostridium difficile infections, and central nervous system infections. A regression model showed length of stay at the moment of HAI detection, urinary catheter, central venous catheter, and antibiotic therapy to be the most important predictors of HAI prevalence, yielding a significant adjusted coefficient of determination (adjusted R2) of 0.2780. This will provide future infection control programs with specific HAI to focus on in order to introduce a proper prophylaxis and to limit exposure whenever possible.
Obstetric Violence in Spain (Part I): Women’s Perception and Interterritorial Differences
Authors: Mena-Tudela Desirée , Iglesias-Casás Susana , González-Chordá Víctor Manuel , Cervera-Gasch Águeda , Andreu-Pejó Laura , Valero-Chilleron María Jesús
Published: October 2020

The decentralization of health systems can have direct repercussions on maternity care. Some inequalities can be noted in outcomes, like neonatal and child mortality in Spain. This study aimed to make the presence of obstetric violence in Spain visible as an interterritorial equity criterion. A descriptive, restrospective and cross-sectional study was conducted between January 2018 and June 2019. The sample comprised 17,541 questionnaires, which represented all Spanish Autonomous Communities. Of our sample, 38.3% perceived having suffered obstetric violence; 44.4% perceived that they had undergone unnecessary and/or painful procedures, of whom 83.4% were not requested to provide informed consent. The mean satisfaction with the attention women received obtained 6.94 points in the general sample and 4.85 points for those women who viewed themselves as victims of obstetric violence. Spain seems to have a serious problem with public health and respecting human rights in obstetric violence. Offering information to women and requesting their informed consent are barely practiced in the healthcare system, so it is necessary to profoundly reflect on obstetric practices with, and request informed consent from, women in Spain.
Experts’ Views on Behaviour Change Techniques for Smoking Cessation in Pregnancy: A Qualitative Study
Authors: Abidi Fizzah B. , Laing Libby , Cooper Sue , Coleman Tim , Campbell Katarzyna A.
Published: October 2020

Smoking during pregnancy is a global health problem which has devastating health implications. Behavioural support is an important part of smoking cessation support for pregnant women. Research has identified barriers and facilitators (B&Fs) and effective behaviour change techniques (BCTs) to aid women’s quit attempts. However, the extent to which and how these BCTs are used in practice is unclear. The research aimed to establish experts’ views on how behavioural support can be optimised and techniques operationalised in clinical practice, by identifying ways to address known B&Fs for smoking cessation in pregnancy. A focus group discussion took place with six experts, which highlighted how BCTs can be used in practice to support women in their quit attempts. A thematic analysis was conducted to elicit overarching themes. Five themes were found: involving the family, empowering women, using incentives to boost motivation, using practical techniques to help women with their quit attempts and managing expectations about nicotine replacement therapy. Empowering women to make their own decisions and encouraging small positive changes in smoking habits, using visual aids (e.g., growth charts) to inform women of the harms of smoking to the baby and treating families holistically were deemed important.
Systematic Review of Behaviour Change Techniques within Interventions to Reduce Environmental Tobacco Smoke Exposure for Children
Authors: Brown Tracey J. , Gentry Sarah , Bauld Linda , Boyle Elaine M. , Clarke Paul , Hardeman Wendy , Holland Richard , Naughton Felix , Orton Sophie , Ussher Michael , Notley Caitlin
Published: October 2020

Children are particularly vulnerable to environmental tobacco smoke (ETS). There is no routine support to reduce ETS in the home. We systematically reviewed trials to reduce ETS in children in order to identify intervention characteristics and behaviour change techniques (BCTs) to inform future interventions. We searched Medline, EMBASE, CINAHL, PsycINFO, ERIC, Cochrane Central Register of Controlled Trials, and Cochrane Tobacco Addiction Group Specialised Register from January 2017 to June 2020 to update an existing systematic review. We included controlled trials to reduce parent/caregiver smoking or ETS in children <12 years that demonstrated a statistically significant benefit, in comparison to less intensive interventions or usual care. We extracted trial characteristics; and BCTs using Behaviour Change Technique Taxonomy v1. We defined “promising” BCTs as those present in at least 25% of effective interventions. Data synthesis was narrative. We included 16 trials, of which eight were at low risk of bias. All trials used counselling in combination with self-help or other supporting materials. We identified 13 “promising” BCTs centred on education, setting goals and planning, or support to reach goals. Interventions to reduce ETS in children should incorporate effective BCTs and consider counselling and self-help as mechanisms of delivery.
Polysulfide and Hydrogen Sulfide Ameliorate Cisplatin-Induced Nephrotoxicity and Renal Inflammation through Persulfidating STAT3 and IKKβ
Authors: Sun Hai-Jian , Leng Bin , Wu Zhi-Yuan , Bian Jin-Song
Published: October 2020

Cisplatin, a widely used chemotherapy for the treatment of various tumors, is clinically limited due to its extensive nephrotoxicity. Inflammatory response in tubular cells is a driving force for cisplatin-induced nephrotoxicity. The plant-derived agents are widely used to relieve cisplatin-induced renal dysfunction in preclinical studies. Polysulfide and hydrogen sulfide (H2S) are ubiquitously expressed in garlic, and both of them are documented as potential agents for preventing and treating inflammatory disorders. This study was designed to determine whether polysulfide and H2S could attenuate cisplatin nephrotoxicity through suppression of inflammatory factors. In renal proximal tubular cells, we found that sodium tetrasulfide (Na2S4), a polysulfide donor, and sodium hydrosulfide (NaHS) and GYY4137, two H2S donors, ameliorated cisplatin-caused renal toxicity through suppression of the massive production of inflammatory cytokines, including tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2). Mechanistically, the anti-inflammatory actions of Na2S4 and H2S may be mediated by persulfidation of signal transducer and activator of transcription 3 (STAT3) and inhibitor kappa B kinase β (IKKβ), followed by decreased phosphorylation of STAT3 and IKKβ. Moreover, the nuclear translocation of nuclear transcription factor kappa B (NF-κB), and phosphorylation and degradation of nuclear factor kappa B inhibitor protein alpha (IκBα) induced by cisplatin, were also mitigated by both polysulfide and H2S. In mice, after treatment with polysulfide and H2S donors, cisplatin-associated renal dysfunction was strikingly ameliorated, as evidenced by measurement of serum blood urea nitrogen (BUN) and creatinine levels, renal morphology, and the expression of renal inflammatory factors. Our present work suggests that polysulfide and H2S could afford protection against cisplatin nephrotoxicity, possibly via persulfidating STAT3 and IKKβ and inhibiting NF-κB-mediated inflammatory cascade. Our results might shed light on the potential benefits of garlic-derived polysulfide and H2S in chemotherapy-induced renal damage.
Thermodynamic Insights by Microscale Thermophoresis into Translesion DNA Synthesis Catalyzed by DNA Polymerases Across a Lesion of Antitumor Platinum–Acridine Complex
Authors: Hreusova Monika , Novakova Olga , Brabec Viktor
Published: October 2020

Translesion synthesis (TLS) through DNA adducts of antitumor platinum complexes has been an interesting aspect of DNA synthesis in cells treated with these metal-based drugs because of its correlation to drug sensitivity. We utilized model systems employing a DNA lesion derived from a site-specific monofunctional adduct formed by antitumor [PtCl(en)(L)](NO3)2 (complex AMD, en = ethane-1,2-diamine, L = N-[2-(acridin-9-ylamino)ethyl]-N-methylpropionamidine) at a unique G residue. The catalytic efficiency of TLS DNA polymerases, which differ in their processivity and fidelity for the insertion of correct dCTP, with respect to the other incorrect nucleotides, opposite the adduct of AMD, was investigated. For a deeper understanding of the factors that control the bypass of the site-specific adducts of AMD catalyzed by DNA polymerases, we also used microscale thermophoresis (MST) to measure the thermodynamic changes associated with TLS across a single, site-specific adduct formed in DNA by AMD. The relative catalytic efficiency of the investigated DNA polymerases for the insertion of correct dCTP, with respect to the other incorrect nucleotides, opposite the AMD adduct, was reduced. Nevertheless, incorporation of the correct C opposite the G modified by AMD of the template strand was promoted by an increasing thermodynamic stability of the resulting duplex. The reduced relative efficiency of the investigated DNA polymerases may be a consequence of the DNA intercalation of the acridine moiety of AMD and the size of the adduct. The products of the bypass of this monofunctional lesion produced by AMD and DNA polymerases also resulted from the misincorporation of dNTPs opposite the platinated G residues. The MST analysis suggested that thermodynamic factors may contribute to the forces that governed enhanced incorporation of the incorrect dNTPs by DNA polymerases.
rad21 Is Involved in Corneal Stroma Development by Regulating Neural Crest Migration
Authors: Zhang Bi Ning , Liu Yu , Yang Qichen , Leung Pui Ying , Wang Chengdong , Wong Thomas Chi Bun , Tham Clement C. , Chan Sun On , Pang Chi Pui , Chen Li Jia , Dekker Job , Zhao Hui , Chu Wai Kit
Published: October 2020

Previously, we identified RAD21R450C from a peripheral sclerocornea pedigree. Injection of this rad21 variant mRNA into Xenopus laevis embryos disrupted the organization of corneal stroma fibrils. To understand the mechanisms of RAD21-mediated corneal stroma defects, gene expression and chromosome conformation analysis were performed using cells from family members affected by peripheral sclerocornea. Both gene expression and chromosome conformation of cell adhesion genes were affected in cells carrying the heterozygous rad21 variant. Since cell migration is essential in early embryonic development and sclerocornea is a congenital disease, we studied neural crest migration during cornea development in X. laevis embryos. In X. laevis embryos injected with rad21 mutant mRNA, neural crest migration was disrupted, and the number of neural crest-derived periocular mesenchymes decreased significantly in the corneal stroma region. Our data indicate that the RAD21R450C variant contributes to peripheral sclerocornea by modifying chromosome conformation and gene expression, therefore disturbing neural crest cell migration, which suggests RAD21 plays a key role in corneal stroma development.
The Roles of CCN1/CYR61 in Pulmonary Diseases
Authors: Zhu Yin , Almuntashiri Sultan , Han Yohan , Wang Xiaoyun , Somanath Payaningal , Zhang Duo
Published: October 2020

CCN1 (cysteine-rich 61, connective tissue growth factor, and nephroblastoma-1), previously named CYR61 (cysteine-rich angiogenic inducer 61) belongs to the CCN family of matricellular proteins. CCN1 plays critical roles in the regulation of proliferation, differentiation, apoptosis, angiogenesis, and fibrosis. Recent studies have extensively characterized the important physiological and pathological roles of CCN1 in various tissues and organs. In this review, we summarize both basic and clinical aspects of CCN1 in pulmonary diseases, including acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), lung fibrosis, pulmonary arterial hypertension (PAH), lung infection, and lung cancer. We also emphasize the important challenges for future investigations to better understand the CCN1 and its role in physiology and pathology, as well as the questions that need to be addressed for the therapeutic development of CCN1 antagonists in various lung diseases.
Circular RNAs and Their Linear Transcripts as Diagnostic and Prognostic Tissue Biomarkers in Prostate Cancer after Prostatectomy in Combination with Clinicopathological Factors
Authors: Rochow Hannah , Jung Monika , Weickmann Sabine , Ralla Bernhard , Stephan Carsten , Elezkurtaj Sefer , Kilic Ergin , Zhao Zhongwei , Jung Klaus , Fendler Annika , Franz Antonia
Published: October 2020

As new biomarkers, circular RNAs (circRNAs) have been largely unexplored in prostate cancer (PCa). Using an integrative approach, we aimed to evaluate the potential of circRNAs and their linear transcripts (linRNAs) to act as (i) diagnostic biomarkers for differentiation between normal and tumor tissue and (ii) prognostic biomarkers for the prediction of biochemical recurrence (BCR) after radical prostatectomy. In a first step, eight circRNAs (circATXN10, circCRIM1, circCSNK1G3, circGUCY1A2, circLPP, circNEAT1, circRHOBTB3, and circSTIL) were identified as differentially expressed via a genome-wide circRNA-based microarray analysis of six PCa samples. Additional bioinformatics and literature data were applied for this selection process. In total, 115 malignant PCa and 79 adjacent normal tissue samples were examined using robust RT-qPCR assays specifically established for the circRNAs and their linear counterparts. Their diagnostic and prognostic potential was evaluated using receiver operating characteristic curves, Cox regressions, decision curve analyses, and C-statistic calculations of prognostic indices. The combination of circATXN10 and linSTIL showed a high discriminative ability between malignant and adjacent normal tissue PCa. The combination of linGUCY1A2, linNEAT1, and linSTIL proved to be the best predictive RNA-signature for BCR. The combination of this RNA signature with five established reference models based on only clinicopathological factors resulted in an improved predictive accuracy for BCR in these models. This is an encouraging study for PCa to evaluate circRNAs and their linRNAs in an integrative approach, and the results showed their clinical potential in combination with standard clinicopathological variables.
In the Model Host Caenorhabditis elegans, Sphingosine-1-Phosphate-Mediated Signaling Increases Immunity toward Human Opportunistic Bacteria
Authors: Lee Kiho , Escobar Iliana , Jang Yeeun , Kim Wooseong , Ausubel Frederick M. , Mylonakis Eleftherios
Published: October 2020

Sphingosine-1-phophate (S1P) is a sphingolipid-derived signaling molecule that controls diverse cellular functions including cell growth, homeostasis, and stress responses. In a variety of metazoans, cytosolic S1P is transported into the extracellular space where it activates S1P receptors in a concentration-dependent manner. In the free-living nematode Caenorhabditis elegans, the spin-2 gene, which encodes a S1P transporter, is activated during Gram-positive or Gram-negative bacterial infection of the intestine. However, the role during infection of spin-2 and three additional genes in the C. elegans genome encoding other putative S1P transporters has not been elucidated. Here, we report an evolutionally conserved function for S1P and a non-canonical role for S1P transporters in the C. elegans immune response to bacterial pathogens. We found that mutations in the sphingosine kinase gene (sphk-1) or in the S1P transporter genes spin-2 or spin-3 decreased nematode survival after infection with Pseudomonas aeruginosa or Enterococcus faecalis. In contrast to spin-2 and spin-3, mutating spin-1 leads to an increase in resistance to P. aeruginosa. Consistent with these results, when wild-type C. elegans were supplemented with extracellular S1P, we found an increase in their lifespan when challenged with P. aeruginosa and E. faecalis. In comparison, spin-2 and spin-3 mutations suppressed the ability of S1P to rescue the worms from pathogen-mediated killing, whereas the spin-1 mutation had no effect on the immune-enhancing activity of S1P. S1P demonstrated no antimicrobial activity toward P. aeruginosa and Escherichia coli and only minimal activity against E. faecalis MMH594 (40 µM). These data suggest that spin-2 and spin-3, on the one hand, and spin-1, on the other hand, transport S1P across cellular membranes in opposite directions. Finally, the immune modulatory effect of S1P was diminished in C. eleganssek-1 and pmk-1 mutants, suggesting that the immunomodulatory effects of S1P are mediated by the p38 MAPK signaling pathway.
Impact of Acute and Chronic Stress on Thrombosis in Healthy Individuals and Cardiovascular Disease Patients
Authors: Sandrini Leonardo , Ieraci Alessandro , Amadio Patrizia , Zarà Marta , Barbieri Silvia Stella
Published: October 2020

Psychological stress induces different alterations in the organism in order to maintain homeostasis, including changes in hematopoiesis and hemostasis. In particular, stress-induced hyper activation of the autonomic nervous system and hypothalamic–pituitary–adrenal axis can trigger cellular and molecular alterations in platelets, coagulation factors, endothelial function, redox balance, and sterile inflammatory response. For this reason, mental stress is reported to enhance the risk of cardiovascular disease (CVD). However, contrasting results are often found in the literature considering differences in the response to acute or chronic stress and the health condition of the population analyzed. Since thrombosis is the most common underlying pathology of CVDs, the comprehension of the mechanisms at the basis of the association between stress and this pathology is highly valuable. The aim of this work is to give a comprehensive review of the studies focused on the role of acute and chronic stress in both healthy individuals and CVD patients, focusing on the cellular and molecular mechanisms underlying the relationship between stress and thrombosis.
Vitamin D Binding Protein (VDBP) and Its Gene Polymorphisms—The Risk of Malignant Tumors and Other Diseases
Authors: Rozmus Dominika , Ciesielska Alicja , Płomiński Janusz , Grzybowski Roman , Fiedorowicz Ewa , Kordulewska Natalia , Savelkoul Huub , Kostyra Elżbieta , Cieślińska Anna
Published: October 2020

Vitamin D is an important component of the endocrine system that controls calcium homeostasis and bone mineralization. Because of the very short half-life of free serum vitamin D it is stabilized and transported to target tissues by being bound to the vitamin D binding protein (VDBP). The most common polymorphisms: rs4588 and rs7041 in the vitamin D binding protein gene may correlate with differences in vitamin D status in the serum. This review presents data that relate to the presence of genetic variants in the VDBP gene in correlation with certain diseases, mostly concerning cancers (breast, prostate, pancreatic, lung, colorectal, basal cell carcinoma cancer and cutaneous melanoma) or other related diseases (thyroid autoimmunity disorders, obesity, diabetes mellitus, bone metabolism, rheumatoid arthritis, ankylosing spondylitis, asthma, chronic obstructive pulmonary disease, tuberculosis and coronary artery diseases).
Identification of NPB, NPW and Their Receptor in the Rat Heart
Authors: Pandey Shashank , Tuma Zdenek , Peroni Elisa , Monasson Olivier , Papini Anna Maria , Chottova Dvorakova Magdalena
Published: October 2020

Members of neuropeptide B/W signaling system have been predominantly detected and mapped within the CNS. In the rat, this system includes neuropeptide B (NPB), neuropeptide W (NPW) and their specific receptor NPBWR1. This signaling system has a wide spectrum of functions including a role in modulation of inflammatory pain and neuroendocrine functions. Expression of NPB, NPW and NPBWR1 in separate heart compartments, dorsal root ganglia (DRG) and stellate ganglia was proven by RT-qPCR, Western blot (WB) and immunofluorescence. Presence of mRNA for all tested genes was detected within all heart compartments and ganglia. The presence of proteins preproNPB, preproNPW and NPBWR1 was confirmed in all the chambers of heart by WB. Expression of preproNPW and preproNPB was proven in cardiac ganglionic cells obtained by laser capture microdissection. In immunofluorescence analysis, NPB immunoreactivity was detected in nerve fibers, some nerve cell bodies and smooth muscle within heart and both ganglia. NPW immunoreactivity was present in the nerve cell bodies and nerve fibers of heart ganglia. Weak nonhomogenous staining of cardiomyocytes was present within heart ventricles. NPBWR1 immunoreactivity was detected on cardiomyocytes and some nerve fibers. We confirmed the presence of NPB/W signaling system in heart, DRG and stellate ganglia by proteomic and genomic analyses.
A Villin-Driven Fxr Transgene Modulates Enterohepatic Bile Acid Homeostasis and Response to an n-6-Enriched High-Fat Diet
Authors: Wren Spencer N. , Donovan Micah G. , Selmin Ornella I. , Doetschman Tom C. , Romagnolo Donato F.
Published: October 2020

A diet high in n-6 polyunsaturated fatty acids (PUFAs) may contribute to inflammation and tissue damage associated with obesity and pathologies of the colon and liver. One contributing factor may be dysregulation by n-6 fatty acids of enterohepatic bile acid (BA) metabolism. The farnesoid X receptor (FXR) is a nuclear receptor that regulates BA homeostasis in the liver and intestine. This study aims to compare the effects on FXR regulation and BA metabolism of a palm oil-based diet providing 28% energy (28%E) from fat and low n-6 linoleic acid (LA, 2.5%E) (CNTL) with those of a soybean oil-based diet providing 50%E from fat and high (28%E) in LA (n-6HFD). Wild-type (WT) littermates and a transgenic mouse line overexpressing the Fxrα1 isoform under the control of the intestine-specific Villin promoter (Fxrα1TG) were fed the CNTL or n-6HFD starting at weaning through 16 weeks of age. Compared to the CNTL diet, the n-6HFD supports higher weight gain in both WT and FxrαTG littermates; increases the expression of Fxrα1/2, and peroxisome proliferator-activated receptor-γ1 (Pparγ1) in the small intestine, Fxrα1/2 in the colon, and cytochrome P4507A1 (Cyp7a1) and small heterodimer protein (Shp) in the liver; and augments the levels of total BA in the liver, and primary chenodeoxycholic (CDCA), cholic (CA), and β-muricholic (βMCA) acid in the cecum. Intestinal overexpression of the Fxra1TG augments expression of Shp and ileal bile acid-binding protein (Ibabp) in the small intestine and Ibabp in the proximal colon. Conversely, it antagonizes n-6HFD-dependent accumulation of intestinal and hepatic CDCA and CA; hepatic levels of Cyp7a1; and expression of Pparγ in the small intestine. We conclude that intestinal Fxrα1 overexpression represses hepatic de novo BA synthesis and protects against n-6HFD-induced accumulation of human-specific primary bile acids in the cecum.
Acute Systemic Inflammatory Response Alters Transcription Profile of Genes Related to Immune Response and Ca2+ Homeostasis in Hippocampus; Relevance to Neurodegenerative Disorders
Authors: Czapski Grzegorz A. , Zhao Yuhai , Lukiw Walter J. , Strosznajder Joanna B.
Published: October 2020

Acute systemic inflammatory response (SIR) triggers an alteration in the transcription of brain genes related to neuroinflammation, oxidative stress and cells death. These changes are also characteristic for Alzheimer’s disease (AD) neuropathology. Our aim was to evaluate gene expression patterns in the mouse hippocampus (MH) by using microarray technology 12 and 96 h after SIR evoked by lipopolysaccharide (LPS). The results were compared with microarray analysis of human postmortem hippocampal AD tissues. It was found that 12 h after LPS administration the expression of 231 genes in MH was significantly altered (FC > 2.0); however, after 96 h only the S100a8 gene encoding calgranulin A was activated (FC = 2.9). Gene ontology enrichment analysis demonstrated the alteration of gene expression related mostly to the immune-response including the gene Lcn2 for Lipocalin 2 (FC = 237.8), involved in glia neurotoxicity. The expression of genes coding proteins involved in epigenetic regulation, histone deacetylases (Hdac4,5,8,9,11) and bromo- and extraterminal domain protein Brd3 were downregulated; however, Brd2 was found to be upregulated. Remarkably, the significant increase in expression of Lcn2, S100a8, S100a9 and also Saa3 and Ch25h, was found in AD brains suggesting that early changes of immune-response genes evoked by mild SIR could be crucial in AD pathogenesis.
Fosmanogepix: A Review of the First-in-Class Broad Spectrum Agent for the Treatment of Invasive Fungal Infections
Authors: Shaw Karen Joy , Ibrahim Ashraf S.
Published: October 2020

Fosmanogepix is a first-in-class antifungal currently in Phase 2 clinical trials for the treatment of invasive fungal infections caused by Candida, Aspergillus and rare molds. Fosmanogepix is the N-phosphonooxymethylene prodrug of manogepix, an inhibitor of the fungal enzyme Gwt1. Manogepix demonstrates broad spectrum in vitro activity against yeasts and molds, including difficult to treat pathogens. Because of its novel mechanism of action, manogepix retains potency against many resistant strains including echinocandin-resistant Candida and azole-resistant Aspergillus. Manogepix is also active against pathogens that demonstrate intrinsic resistance to other drug classes, such as Scedosporium, Lomentospora prolificans, and Fusarium with variable activity against Mucorales. Fosmanogepix demonstrates significant in vivo efficacy in mouse and rabbit disseminated infection models due to C. albicans, C. glabrata, C. auris, C. tropicalis, Coccidioides immitis, and F. solani as well as pulmonary infection models of A. fumigatus, A. flavus, S.prolificans, S. apiospermum and Rhizopus arrhizus. Clinical trials demonstrated high oral bioavailability (>90%), enabling switching between fosmanogepix intravenous and oral formulations without compromising blood levels. Favorable drug-drug interaction, tolerability, and wide tissue distribution profiles are observed making fosmanogepix an attractive option for the treatment of invasive fungal infections. This systematic review summarizes the findings of published data on fosmanogepix.
Function and Benefits of Natural Competence in Cyanobacteria: From Ecology to Targeted Manipulation
Authors: Schirmacher Alexandra M. , Hanamghar Sayali S. , Zedler Julie A. Z.
Published: October 2020

Natural competence is the ability of a cell to actively take up and incorporate foreign DNA in its own genome. This trait is widespread and ecologically significant within the prokaryotic kingdom. Here we look at natural competence in cyanobacteria, a group of globally distributed oxygenic photosynthetic bacteria. Many cyanobacterial species appear to have the genetic potential to be naturally competent, however, this ability has only been demonstrated in a few species. Reasons for this might be due to a high variety of largely uncharacterised competence inducers and a lack of understanding the ecological context of natural competence in cyanobacteria. To shed light on these questions, we describe what is known about the molecular mechanisms of natural competence in cyanobacteria and analyse how widespread this trait might be based on available genomic datasets. Potential regulators of natural competence and what benefits or drawbacks may derive from taking up foreign DNA are discussed. Overall, many unknowns about natural competence in cyanobacteria remain to be unravelled. A better understanding of underlying mechanisms and how to manipulate these, can aid the implementation of cyanobacteria as sustainable production chassis.
Multiscale Statistical Analysis of Massive Corrosion Pits Based on Image Recognition of High Resolution and Large Field-of-View Images
Authors: Wang Yafei , Tian Zhiqiang , Hu Songyan
Published: October 2020

In the present study, a new multiscale method is proposed for the statistical analysis of spatial distribution of massive corrosion pits, based on the image recognition of high resolution and large field-of-view (montage) optical images. Pitting corrosion for high strength pipeline steel exposed to sodium chloride solution was observed using an optical microscope. Montage images of the corrosion pits were obtained, with a single image containing a large number of corrosion pits. The diameters and locations of all the pits were determined simultaneously using an image recognition algorithm, followed by statistical analysis of the two-dimensional spatial point pattern. The multiscale spatial distributions of pits were analyzed by dividing the montage image into a number of different windows. The results indicate the clear dependence of distribution features on the spatial scales. The proposed method can provide a better understanding of the pit growth from the perspective of multiscale spatial evolution.