bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring Clinical Efficacy Through the Lens of Audit Data in Different Adult Eating Disorder Treatment Programmes
Authors: Li Zhuo , Dandil Yasemin , Toloza Cindy , Carr Anna , Oyeleye Oyenike , Kinnaird Emma , Tchanturia Kate
Published: December 2020

Background:Audit data is important in creating a clear picture of clinical reality in clinical services, and evaluating treatment outcomes. This paper explored the data from an audit of a large national eating disorder (ED) service and evaluated the outcome of inpatient and day treatment programmes for patients with anorexia nervosa (AN) with and without autistic traits.

Methods:Four hundred and seventy-six patients receiving treatment for AN at inpatient (IP), day-care (DC) and step-up (SU) programmes were assessed at admission and at discharge on the following measures: autistic traits, body-mass-index (BMI), ED symptoms, depression and anxiety symptoms, work and social functioning, and motivation for change. Outcomes were analyzed first at a within-group level based on change in mean scores and then at an individual level based on the clinical significance of improvement in eating disorder symptoms. Outcomes were compared between patients with high autistic traits (HAT) and low autistic traits (LAT) in each programme.

Results:The findings suggest that 45.5% of DC and 35.1% of IP patients showed clinically significant changes in ED symptoms following treatment. Co-occurring high autistic traits positively predicted improvement in ED symptoms in IP setting, but was a negative predictor in DC. In IP, more HAT inpatients no longer met the BMI cut-off for AN compared to LAT peers. In terms of general psychopathology, patients with AN and HAT exhibited more severe depression symptoms, anxiety symptoms and social functioning impairment than their LAT peers, and these symptoms stayed clinically severe after treatment.

Conclusions:Patients with AN and hight autistic traits are more likely than their peers with low autistic traits to show weight restoration and improvement in ED systems after inpatient treatment. This reverses in DC, with high autistic trait patients less likely to improve after treatment compared to low autistic trait patients. Our results suggest that inpatient treatment with individualized and structured routine care may be an effective model of treatment for patients with AN and high autistic traits.
Analysis of Hemorrhagic Fever With Renal Syndrome Using Wavelet Tools in Mainland China, 2004–2019
Authors: Zou Lu-Xi , Sun Ling
Published: December 2020

Introduction : Hemorrhagic fever with renal syndrome (HFRS) is a life-threatening public health problem in China, accounting for ~90% of HFRS cases reported globally. Accurate analysis and prediction of the HFRS epidemic could help to establish effective preventive measures.

Materials and Methods : In this study, the geographical information system (GIS) explored the spatiotemporal features of HFRS, the wavelet power spectrum (WPS) unfolded the cyclical fluctuation of HFRS, and the wavelet neural network (WNN) model predicted the trends of HFRS outbreaks in mainland China.

Results : A total of 209,209 HFRS cases were reported in mainland China from 2004 to 2019, with the annual incidence ranged from 0 to 13.05 per 100,0000 persons at the province level. The WPS proved that the periodicity of HFRS could be half a year, 1 year, and roughly 7-year at different time intervals. The WNN structure of 12-6-1 was set up as the fittest forecasting model for the HFRS epidemic.

Conclusions : This study provided several potential support tools for the control and risk-management of HFRS in China.
Ten Epidemiological Parameters of COVID-19: Use of Rapid Literature Review to Inform Predictive Models During the Pandemic
Authors: Gallo Luciana Guerra , Oliveira Ana Flávia de Morais , Abrahão Amanda Amaral , Sandoval Leticia Assad Maia , Martins Yure Rodrigues Araújo , Almirón Maria , dos Santos Fabiana Sherine Ganem , Araújo Wildo Navegantes , de Oliveira Maria Regina Fernandes , Peixoto Henry Maia
Published: December 2020

Objective: To describe the methods used in a rapid review of the literature and to present the main epidemiological parameters that describe the transmission of SARS-Cov-2 and the illness caused by this virus, coronavirus disease 2019 (COVID-19).

Methods: This is a methodological protocol that enabled a rapid review of COVID-19 epidemiological parameters.

Findings: The protocol consisted of the following steps: definition of scope; eligibility criteria; information sources; search strategies; selection of studies; and data extraction. Four reviewers and three supervisors conducted this review in 40 days. Of the 1,266 studies found, 65 were included, mostly observational and descriptive in content, indicating relative homogeneity as to the quality of the evidence. The variation in the basic reproduction number, between 0.48 and 14.8; and the median of the hospitalization period, between 7.5 and 20.5 days stand out as key findings.

Conclusion: We identified and synthesized 10 epidemiological parameters that may support predictive models and other rapid reviews to inform modeling of this and other future public health emergencies.
The Effect of Non-Personalised Tips on the Continued Use of Self-Monitoring mHealth Applications
Authors: Unnikrishnan Vishnu , Schleicher Miro , Shah Yash , Jamaludeen Noor , Pryss Ruediger , Schobel Johannes , Kraft Robin , Schlee Winfried , Spiliopoulou Myra
Published: December 2020

Chronic tinnitus, the perception of a phantom sound in the absence of corresponding stimulus, is a condition known to affect patients’ quality of life. Recent advances in mHealth have enabled patients to maintain a ‘disease journal’ of ecologically-valid momentary assessments, improving patients’ own awareness of their disease while also providing clinicians valuable data for research. In this study, we investigate the effect of non-personalised tips on patients’ perception of tinnitus, and on their continued use of the application. The data collected from the study involved three groups of patients that used the app for 16 weeks. Groups A & Y were exposed to feedback from the start of the study, while group B only received tips for the second half of the study. Groups A and Y were run by different supervisors and also differed in the number of hospital visits during the study. Users of Group A and B underwent assessment at baseline, mid-study, post-study and follow-up, while users of group Y were only assessed at baseline and post-study. It is seen that the users in group B use the app for longer, and also more often during the day. The answers of the users to the Ecological Momentary Assessments are seen to form clusters where the degree to which the tinnitus distress depends on tinnitus loudness varies. Additionally, cluster-level models were able to predict new unseen data with better accuracy than a single global model. This strengthens the argument that the discovered clusters really do reflect underlying patterns in disease expression.
Changes in Psychological Anxiety and Physiological Stress Hormones in Korea National Shooters
Authors: Park Sang-Hyuk , Park In-Hye , Lim Seung-Taek , Lee Eunjae
Published: December 2020

Psychological anxiety and physiological stress hormone management is closely related to an athlete’s performance, especially in shooting competitions. Thus, we aimed to investigate the changes in saliva stress hormones according to anxiety scores of Korean elite shooters immediately before a shooting competition. Seventy-two Korean national shooting athletes (Rifle = 62, Pistol = 8, Shotgun = 2) were recruited for the present study. The physiological stress hormones were assessed based on cortisol and immunoglobulin A level in saliva. The psychological stress was assessed based on Beck Anxiety Inventory (BAI) questionnaire. Cortisol concentration and cortisol secretion rate were significant higher in severe anxiety group. Secretory immunoglobulin A (SIgA) concentration and SIgA secretion rate did not significant different in among the groups. A positive correlation was found between BAI score and cortisol concentration. These findings provide preliminary evidence indicating that psychological anxiety affects physiological stress and therefore may have a negative effect on athletes’ performance. Thus, research is needed to develop a strategy to reduce physiological stress in these athletes.
Towards Interactive Search: Investigating Visual Search in a Novel Real-World Paradigm
Authors: Sauter Marian , Stefani Maximilian , Mack Wolfgang
Published: December 2020

An overwhelming majority of studies on visual search and selective attention were conducted using computer screens. There are arguably shortcomings in transferring knowledge from computer-based studies to real-world search behavior as findings are based on viewing static pictures on computer screens. This does not go well with the dynamic and interactive nature of vision in the real world. It is crucial to take visual search research to the real world in order to study everyday visual search processes. The aim of the present study was to develop an interactive search paradigm that can serve as a “bridge” between classical computerized search and everyday interactive search. We based our search paradigm on simple LEGO® bricks arranged on tabletop trays to ensure comparability with classical computerized visual search studies while providing room for easily increasing the complexity of the search environment. We found that targets were grasped slower when there were more distractors (Experiment 1) and there were sizable differences between various search conditions (Experiment 2), largely in line with classical visual search research and revealing similarities to research in natural scenes. Therefore, our paradigm can be seen as a valuable asset complementing visual search research in an environment between computerized search and everyday search.
Examining Procrastination among University Students through the Lens of the Self-Regulated Learning Model
Authors: Limone Pierpaolo , Sinatra Maria , Ceglie Flavio , Monacis Lucia
Published: December 2020

Generally considered as a prevalent occurrence in academic settings, procrastination was analyzed in association with constructs such as self-efficacy, self-esteem, anxiety, stress, and fear of failure. This study investigated the role played by self-regulated learning strategies in predicting procrastination among university students. To this purpose, the relationships of procrastination with cognitive and metacognitive learning strategies and time management were explored in the entire sample, as well as in male and female groups. Gender differences were taken into account due to the mixed results that emerged in previous studies. This cross-sectional study involved 450 university students (M = 230; F = 220; Mage = 21.08, DS = 3.25) who completed a self-reported questionnaire including a sociodemographic section, the Tuckman Procrastination Scale, the Time Management Scale, and the Metacognitive Self-Regulation and Critical Thinking Scales. Descriptive and inferential analyses were applied to the data. The main findings indicated that temporal and metacognitive components play an important role in students’ academic achievement and that, compared to females, males procrastinate more due to poor time management skills and metacognitive strategies. Practical implications were suggested to help students to overcome their dilatory behavior.
Robotic Liver Resection Versus Percutaneous Ablation for Early HCC: Short- and Long-Term Results
Authors: Magistri Paolo , Catellani Barbara , Frassoni Samuele , Guidetti Cristiano , Olivieri Tiziana , Assirati Giacomo , Caporali Cristian , Pecchi Annarita , Serra Valentina , Ballarin Roberto , Guerrini Gian Piero , Bagnardi Vincenzo , Di Sandro Stefano , Di Benedetto Fabrizio
Published: December 2020

Background: The correct approach for early hepatocellular carcinoma (HCC) is debatable, since multiple options are currently available. Percutaneous ablation (PA) is associated in some series to reduced morbidity compared to liver resection (LR); therefore, minimally invasive surgery may play a significant role in this setting. Methods: All consecutive patients treated by robotic liver resection (RLR) or PA between January 2014 and October 2019 for a newly diagnosed single HCC, less than 3 cm in size (very early/early stages according to the Barcelona Clinic Liver Cancer (BCLC)) on chronic liver disease or liver cirrhosis, were enrolled in this retrospective study. The aim of this study was to compare short- and long-term outcomes to define the best approach in this specific cohort. Results: 60 patients fulfilled the inclusion criteria: 24 RLR and 36 PA. The two populations were homogeneous in terms of baseline characteristics. There were no statistically significant differences regarding the incidence of postoperative morbidity (RLR 38% vs. PA 19%, p = 0.15). The cumulative incidence of recurrence (CIR) was significantly higher in patients who underwent PA, with the one, two, and three years of CIR being 42%, 69%, and 73% in the PA group and 17%, 27%, and 27% in the RLR group, respectively. Conclusions: RLR provides a significantly higher potential of cure and tumor-related free survival in cases of newly diagnosed single HCCs smaller than 3 cm. Therefore, it can be considered as a first-line approach for the treatment of patients with those characteristics in high-volume centers with extensive experience in the field of hepatobiliary surgery and minimally invasive approaches.
Differential Effects of Cancer-Associated Mutations Enriched in Helix H3 of PPARγ
Authors: Jang Dong Man , Jang Jun Young , Kim Hyun-Jung , Han Byung Woo
Published: December 2020

Peroxisome proliferator-activated receptor gamma (PPARγ) has recently been revealed to regulate tumor microenvironments. In particular, genetic alterations of PPARγ found in various cancers have been reported to play important roles in tumorigenesis by affecting PPARγ transactivation. In this study, we found that helix H3 of the PPARγ ligand-binding domain (LBD) has a number of sites that are mutated in cancers. To uncover underlying molecular mechanisms between helix H3 mutations and tumorigenesis, we performed structure‒function studies on the PPARγ LBDs containing helix H3 mutations found in cancers. Interestingly, PPARγ Q286E found in bladder cancer induces a constitutively active conformation of PPARγ LBD and thus abnormal activation of PPARγ/RXRα pathway, which suggests tumorigenic roles of PPARγ in bladder cancer. In contrast, other helix H3 mutations found in various cancers impair ligand binding essential for transcriptional activity of PPARγ. These data indicate that cancer-associated mutations clustered in helix H3 of PPARγ LBD exhibit differential effects in PPARγ-mediated tumorigenesis and provide a basis for the development of new biomarkers targeting tumor microenvironments.
Beyond the Influence of IDH Mutations: Exploring Epigenetic Vulnerabilities in Chondrosarcoma
Authors: Venneker Sanne , Kruisselbrink Alwine B. , Baranski Zuzanna , Palubeckaite Ieva , Briaire-de Bruijn Inge H. , Oosting Jan , French Pim J. , Danen Erik H. J. , Bovée Judith V. M. G.
Published: December 2020

Mutations in the isocitrate dehydrogenase (IDH1 or IDH2) genes are common in enchondromas and chondrosarcomas, and lead to elevated levels of the oncometabolite D-2-hydroxyglutarate causing widespread changes in the epigenetic landscape of these tumors. With the use of a DNA methylation array, we explored whether the methylome is altered upon progression from IDH mutant enchondroma towards high-grade chondrosarcoma. High-grade tumors show an overall increase in the number of highly methylated genes, indicating that remodeling of the methylome is associated with tumor progression. Therefore, an epigenetics compound screen was performed in five chondrosarcoma cell lines to therapeutically explore these underlying epigenetic vulnerabilities. Chondrosarcomas demonstrated high sensitivity to histone deacetylase (HDAC) inhibition in both 2D and 3D in vitro models, independent of the IDH mutation status or the chondrosarcoma subtype. siRNA knockdown and RNA expression data showed that chondrosarcomas rely on the expression of multiple HDACs, especially class I subtypes. Furthermore, class I HDAC inhibition sensitized chondrosarcoma to glutaminolysis and Bcl-2 family member inhibitors, suggesting that HDACs define the metabolic state and apoptotic threshold in chondrosarcoma. Taken together, HDAC inhibition may represent a promising targeted therapeutic strategy for chondrosarcoma patients, either as monotherapy or as part of combination treatment regimens.
Gamma Delta T Cells (γδ T Cells) in Health and Disease: In Memory of Professor Wendy Havran
Authors: Kabelitz Dieter
Published: December 2020

Gamma delta (γδ) T cells are a small subset of CD3-positive T cells in the peripheral blood but occur at increased frequency in mucosal tissues [...]
The Relevance of Aquaporins for the Physiology, Pathology, and Aging of the Female Reproductive System in Mammals
Authors: Kordowitzki Paweł , Kranc Wiesława , Bryl Rut , Kempisty Bartosz , Skowronska Agnieszka , Skowronski Mariusz T.
Published: December 2020

Aquaporins constitute a group of water channel proteins located in numerous cell types. These are pore-forming transmembrane proteins, which mediate the specific passage of water molecules through membranes. It is well-known that water homeostasis plays a crucial role in different reproductive processes, e.g., oocyte transport, hormonal secretion, completion of successful fertilization, blastocyst formation, pregnancy, and birth. Further, aquaporins are involved in the process of spermatogenesis, and they have been reported to be involved during the storage of spermatozoa. It is noteworthy that aquaporins are relevant for the physiological function of specific parts in the female reproductive system, which will be presented in detail in the first section of this review. Moreover, they are relevant in different pathologies in the female reproductive system. The contribution of aquaporins in selected reproductive disorders and aging will be summarized in the second section of this review, followed by a section dedicated to aquaporin-related proteins. Since the relevance of aquaporins for the male reproductive system has been reviewed several times in the recent past, this review aims to provide an update on the distribution and impact of aquaporins only in the female reproductive system. Therefore, this paper seeks to determine the physiological and patho-physiological relevance of aquaporins on female reproduction, and female reproductive aging.
Surface Characterization and Tribological Behavior of Graphene-Reinforced Cellulose Composites Prepared by Large-Area Spray Coating on Flexible Substrate
Authors: Shi Shih-Chen , Wang Chih-Chia , Cheng Yung-Chen , Lin Yue-Feng
Published: December 2020

A large-area spray coating process is introduced to efficiently apply a graphene/Cu/cellulose composite on a flexible glass substrate. The dispersion characteristics of nano-additives are measured and the Tyndall effect observed. The characteristics of the composite coating such as the film thickness, surface roughness, water contact angle, and lubricating characteristics are measured. The tribological properties of the composite coating are measured using a ball-on-disk. The wear width of the abrasive parts, as well as the wear and friction coefficient of the grinding balls, are investigated. Adding graphene/Cu helps to improve the anti-wear ability of cellulose. The transfer layer was observed using the Raman spectroscopy and mapping technology. Finally, the lubricating mechanism is discussed, and the wear mechanism is proposed. Nanoparticles existed in the wear track as the third-body particles and improved the load capacity of the composites. The wear mechanism of the composites is discussed in terms of the worn surfaces and the analysis of the transfer film with the third-body approach.
Special Issue: Surface Engineering of Light Alloys
Authors: Ferraris Sara
Published: December 2020

Light alloys (mainly aluminum, magnesium and titanium alloys) are of great interest in applications where lightweight has an high impact, such as automotive, aerospace and biomedical fields [...]
Investigation of Catalyst Development from Mg2NiH4 Hydride and Its Application for the CO2 Methanation Reaction
Authors: Lelis Martynas , Varnagiris Sarunas , Urbonavicius Marius , Zakarauskas Kestutis
Published: December 2020

In current study various aspects of catalyst development for the Sabatier type methanation reaction were investigated. It was demonstrated that starting from 330–380 °C Mg2NiH4 hydride heating under CO2 and H2 gas flow initiates hydride decomposition, disproportionation and oxidation. These reactions empower catalytic properties of the material and promotes CO2 methanation reaction. Detailed structural, colorimetric and thermogravimetric analysis revealed that in order to have fast and full-scale development of the catalyst (formation of MgO decorated by nanocrystalline Ni) initial hydride has to be heated above 500 °C. Another considerable finding of the study was confirmation that potentially both high grade and low grade starting Mg2Ni alloy can be equally suitable for the hydride synthesis and its usage for the promotion of methanation reactions.
Almost Fully Secured Lattice-Based Group Signatures with Verifier-Local Revocation
Authors: Perera Maharage Nisansala Sevwandi , Koshiba Takeshi
Published: December 2020

An efficient member revocation mechanism is a desirable feature when group signature schemes are applied in practical scenarios. Revocation methods, such as verifier-local revocation (VLR), provide an efficient member revocation in applications of group signatures. However, VLR-group signatures rely on a weaker security notion. On the other hand, group signature schemes for static groups gain stronger security with the full-anonymity security notion. Even though an outsider sees the secret signing keys of all group members in the full-anonymity, the signer is still anonymous. Achieving the full-anonymity for VLR group signature schemes is challenging due to the structure of secret signing keys. The secret signing keys of those schemes consist of tokens, which are used to manage revocation. The reveal of tokens may destroy the anonymity of the signers. We obtain stronger security for the lattice-based VLR group signature schemes by providing a new key generation method, which outputs revocation tokens without deriving from the members’ secret signing keys. We propose a new group signature scheme from lattices with VLR, which achieves stronger security than the previous related works. To avoid signature forgeries, we suggest a new zero-knowledge proof system that requires signers to validate themselves. Moreover, we output an efficient tracing mechanism.
A Portable Environmental Data-Monitoring System for Air Hazard Evaluation in Deep Underground Mines
Authors: Ziętek Bartłomiej , Banasiewicz Aleksandra , Zimroz Radosław , Szrek Jarosław , Gola Sebastian
Published: December 2020

Air-quality measurements in a deep underground mine are a critical issue. The cost of ventilation, as well as the geometry of the considered mine, make this process very difficult, and local air quality may be a danger to miners. Thus, portable, personal devices are required to inform miners about gas hazards. There are available tools for that purpose; however, they do not allow the storage of data collected during a shift. Moreover, they do not allow the basic analysis of the acquired data cost-effectively. This paper aims to present a system using low-cost gas sensors and microcontrollers, and takes advantage of commonly used smartphones as a computing and visualization resource. Finally, we demonstrate monitoring system results from a test in an underground mine located in Poland.
Influence of Varieties and Organic Fertilizer in the Elaboration of a New Poplar-Straw Pellet and Its Emissions in a Domestic Boiler
Authors: Paniagua Sergio , Prado-Guerra Alba , Neto Ana Isabel , Nunes Teresa , Tarelho Luís , Alves Célia , Calvo Luis Fernando
Published: December 2020

Pollutants resulting from domestic combustion would have harmful effects on public health, causing disturbances in the atmosphere chemistry and the climate. In this work, the emissions from the combustion of pellets made of 80% poplar (organically fertilized) and 20% cereal straw (Triticum aestivum) have been analysed. Poplar wood from I-214 and AF-8 clones was obtained from fertilized and non-fertilized plots (CONTROL). Dairy wastewater treatment (MUD) and dehydrated sewage sludge (BIOSOLIDS) were the fertilizers employed. BIOSOLIDS-I214 pellets had lower quality standards, so its combustion was omitted. A flue gas sample was sampled together with the particles emitted. The I-214 MUD sample had the highest emitted CO value (1505 mg/MJ). Regarding HCl emission factors, there was a homogeneity in the results linked with the Cl content present in the raw material. A higher particle emission was associated with pellets with higher ash content. Particles were composed mainly for elemental carbon (26–80 mg/MJ), except I-214 MUD. I-214 pellets had the indicators of incomplete combustion and, therefore, major contaminants emission and major environmental impact. Thus, both the poplar clone and the organic fertilizer influenced the parameters and emissions analysed. Therefore, special attention must be paid to both characteristics.
Facility Energy Management Application of HBIM for Historical Low-Carbon Communities: Design, Modelling and Operation Control of Geothermal Energy Retrofit in a Real Italian Case Study
Authors: Piselli Cristina , Guastaveglia Alessio , Romanelli Jessica , Cotana Franco , Pisello Anna Laura
Published: December 2020

The highest challenge of energy efficiency of building stock is achieving improved performance in existing buildings and, especially, in heritage buildings which per se are characterized by massive limitations against the implementation of the most sophisticated solutions for energy saving. In Italy, historical buildings represent more than 30% of the building stock and the vast majority require energy retrofit, while ensuring the preservation of the heritage value and acceptable comfort conditions. In this context, historical buildings must be retrofitted and re-functioned by introducing innovative technologies aimed at reducing energy consumption and improving human comfort, health, and safety. To this aim, this study implements the Historic Building Information Modeling (HBIM) approach for the integrated modeling, monitoring, management, and maintenance of a novel geothermal system involving horizontal ground source heat exchangers (GHEXs) coupled to an adsorption heat pump for the energy refurbishment of historical buildings. In detail, a rural building part of a medieval complex in Perugia, Central Italy, is considered as a pilot case study. The analysis stresses the potential of the Facility Management (FM) applications of HBIM to provide a tool for the human-centric operational management control of the building energy performance and indoor comfort when combined with the building monitoring and supervision system. Therefore, this integrated HBIM approach may drive the path towards the user-centric re-functioning of heritage buildings.
The ADAR Family in Amphioxus: RNA Editing and Conserved Orthologous Site Predictions
Authors: Zawisza-Álvarez Michał , Pérez-Calles Claudia , Gattoni Giacomo , Garcia-Fernàndez Jordi , Benito-Gutiérrez Èlia , Herrera-Úbeda Carlos
Published: December 2020

RNA editing is a relatively unexplored process in which transcribed RNA is modified at specific nucleotides before translation, adding another level of regulation of gene expression. Cephalopods use it extensively to increase the regulatory complexity of their nervous systems, and mammals use it too, but less prominently. Nevertheless, little is known about the specifics of RNA editing in most of the other clades and the relevance of RNA editing from an evolutionary perspective remains unknown. Here we analyze a key element of the editing machinery, the ADAR (adenosine deaminase acting on RNA) gene family, in an animal with a key phylogenetic position at the root of chordates: the cephalochordate amphioxus. We show, that as in cephalopods, ADAR genes in amphioxus are predominantly expressed in the nervous system; we identify a number of RNA editing events in amphioxus; and we provide a newly developed method to identify RNA editing events in highly polymorphic genomes using orthology as a guide. Overall, our work lays the foundations for future comparative analysis of RNA-editing events across the metazoan tree.
Rad21 Haploinsufficiency Prevents ALT-Associated Phenotypes in Zebrafish Brain Tumors
Authors: Idilli Aurora Irene , Pazzi Cecilia , dal Pozzolo Francesca , Roccuzzo Michela , Mione Maria Caterina
Published: December 2020

Cohesin is a protein complex consisting of four core subunits responsible for sister chromatid cohesion in mitosis and meiosis, and for 3D genome organization and gene expression through the establishment of long distance interactions regulating transcriptional activity in the interphase. Both roles are important for telomere integrity, but the role of cohesin in telomere maintenance mechanisms in highly replicating cancer cells in vivo is poorly studied. Here we used a zebrafish model of brain tumor, which uses alternative lengthening of telomeres (ALT) as primary telomere maintenance mechanism to test whether haploinsufficiency for Rad21, a member of the cohesin ring, affects ALT development. We found that a reduction in Rad21 levels prevents ALT-associated phenotypes in zebrafish brain tumors and triggers an increase in tert expression. Despite the rescue of ALT phenotypes, tumor cells in rad21+/− fish exhibit an increase in DNA damage foci, probably due to a reduction in double-strand breaks repair efficiency.
Using Personal Genomic Data within Primary Care: A Bioinformatics Approach to Pharmacogenomics
Authors: Overkleeft Rick , Tommel Judith , Evers Andrea W. M. , den Dunnen Johan T. , Roos Marco , Hoefmans Marie-José , Schrader Walter E. , Swen Jesse J. , Numans Mattijs E. , Houwink Elisa J. F.
Published: December 2020

One application of personalized medicine is the tailoring of medication to the individual, so that the medication will have the highest chance of success. In order to individualize medication, one must have a complete inventory of all current pharmaceutical compounds (a detailed formulary) combined with pharmacogenetic datasets, the genetic makeup of the patient, their (medical) family history and other health-related data. For healthcare professionals to make the best use of this information, it must be visualized in a way that makes the most medically relevant data accessible for their decision-making. Similarly, to enable bioinformatics analysis of these data, it must be prepared and provided through an interface for controlled computational analysis. Due to the high degree of personal information gathered for such initiatives, privacy-sensitive implementation choices and ethical standards are paramount. The Personal Genetic Locker project provides an approach to enable the use of personal genomic data in primary care. In this paper, we provide a description of the Personal Genetic Locker project and show its utility through a use case based on open standards, which is illustrated by the 4MedBox system.
A Machine Learning Model Utilizing a Novel SNP Shows Enhanced Prediction of Coronary Artery Disease Severity
Authors: Pattarabanjird Tanyaporn , Cress Corban , Nguyen Anh , Taylor Angela , Bekiranov Stefan , McNamara Coleen
Published: December 2020

Background: Machine learning (ML) has emerged as a powerful approach for predicting outcomes based on patterns and inferences. Improving prediction of severe coronary artery disease (CAD) has the potential for personalizing prevention and treatment strategies and for identifying individuals that may benefit from cardiac catheterization. We developed a novel ML approach combining traditional cardiac risk factors (CRF) with a single nucleotide polymorphism (SNP) in a gene associated with human CAD (ID3 rs11574) to enhance prediction of CAD severity; Methods: ML models incorporating CRF along with ID3 genotype at rs11574 were evaluated. The most predictive model, a deep neural network, was used to classify patients into high (>32) and low level (≤32) Gensini severity score. This model was trained on 325 and validated on 82 patients. Prediction performance of the model was summarized by a confusion matrix and area under the receiver operating characteristics curve (ROC-AUC); and Results: Our neural network predicted severity score with 81% and 87% accuracy for the low and the high groups respectively with an ROC-AUC of 0.84 for 82 patients in the test group. The addition of ID3 rs11574 to CRF significantly enhanced prediction accuracy from 65% to 81% in the low group, and 72% to 84% in the high group. Age, high-density lipoprotein (HDL), and systolic blood pressure were the top 3 contributors in predicting severity score; Conclusions: Our neural network including ID3 rs11574 improved prediction of CAD severity over use of Framingham score, which may potentially be helpful for clinical decision making in patients at increased risk of complications from coronary angiography.
Seminal Plasma Proteomic Biomarkers of Oxidative Stress
Authors: Cannarella Rossella , Crafa Andrea , Barbagallo Federica , Mongioì Laura M. , Condorelli Rosita A. , Aversa Antonio , Calogero Aldo E. , La Vignera Sandro
Published: December 2020

The prevalence of idiopathic male infertility is high, up to 75% of patients with abnormal sperm parameters. Hence, the research of its causes is mandatory. Oxidative stress (OS) can be responsible for male infertility in 30–80% of cases. In recent years, seminal plasma (SP) proteomics has developed as a useful tool to provide biomarkers of specific diseases. This systematic review aims to collect the available evidence on the changes of SP proteome in patients exposed to OS to provide possible SP biomarkers of sperm OS. To accomplish this, the following keyterms “seminal fluid proteome”, “seminal plasma proteome”, “oxidative stress”, and “sperm oxidative stress” were used and 137 records were found. Among these, 17 were finally included. Nine proteins involved with OS were found overexpressed in patients with OS. Twenty-three proteins were found differentially expressed in patients with clinical conditions associated with OS, such as varicocele, male accessory gland infection/inflammation, cigarette smoke, and obesity. These proteins do not seem to overlap among the clinical conditions taken into account. We speculate that specific SP proteins may mediate OS in different clinical conditions. Altogether, these results suggest that proteomics could help to better understand some of the molecular mechanisms involved in the pathogenesis of infertility. However, further studies are needed to identify potential biomarkers of male infertility with valuable clinical significance.
Citrullination-Resistant LL-37 Is a Potent Antimicrobial Agent in the Inflammatory Environment High in Arginine Deiminase Activity
Authors: Bryzek Danuta , Golda Anna , Budziaszek Joanna , Kowalczyk Dominik , Wong Alicia , Bielecka Ewa , Shakamuri Priyanka , Svoboda Pavel , Pohl Jan , Potempa Jan , Koziel Joanna
Published: December 2020

LL-37, the only member of the mammalian cathelicidin in humans, plays an essential role in innate immunity by killing pathogens and regulating the inflammatory response. However, at an inflammatory focus, arginine residues in LL-37 can be converted to citrulline via a reaction catalyzed by peptidyl-arginine deiminases (PAD2 and PAD4), which are expressed in neutrophils and are highly active during the formation of neutrophil extracellular traps (NETs). Citrullination impairs the bactericidal activity of LL-37 and abrogates its immunomodulatory functions. Therefore, we hypothesized that citrullination-resistant LL-37 variants would retain the functionality of the native peptide in the presence of PADs. To test this hypothesis, we synthetized LL-37 in which arginine residues were substituted by homoarginine (hArg-LL-37). Bactericidal activity of hArg-LL-37 was comparable with that of native LL-37, but neither treatment with PAD4 nor exposure to NETs affected the antibacterial and immunomodulatory activities of hArg-LL-37. Importantly, the susceptibilities of LL-37 and hArg-LL-37 to degradation by proteases did not significantly differ. Collectively, we demonstrated that citrullination-resistant hArg-LL-37 is an attractive lead compound for the generation of new agents to treat bacterial infections and other inflammatory diseases associated with enhanced PAD activity. Moreover, our results provide a proof-of-concept for synthesis of therapeutic peptides using homoarginine.
In Silico Food-Drug Interaction: A Case Study of Eluxadoline and Fatty Meal
Authors: Maruca Annalisa , Lupia Antonio , Rocca Roberta , Keszthelyi Daniel , Corsetti Maura , Alcaro Stefano
Published: December 2020

Food-drug interaction is an infrequently considered aspect in clinical practice. Usually, drugs are taken together with meals and what follows may adversely affect pharmacokinetic and pharmacodynamic properties, and hence, the therapeutic effects. In this study, a computational protocol was proposed to explain the different assimilations of two µ-receptors agonists, eluxadoline and loperamide, with a peculiar pharmacokinetic profile. Compared to loperamide, eluxadoline is absorbed less after the intake of a fatty meal, and the LogP values do not explain this event. Firstly, keeping in mind the different pH in the intestinal tract, the protonation states of both compounds were calculated. Then, all structures were subjected to a conformational search by using MonteCarlo and Molecular Dynamics methods, with solvation terms mimicking the water and weak polar solvent (octanol). Both computational results showed that eluxadoline has less conformational freedom in octanol, unlike loperamide, which exhibits constant behavior in both solvents. Therefore, we hypothesize that fatty meal causes the “closure” of the eluxadoline molecule to prevent the exposure of the polar groups and their interaction with water, necessary for the drug absorption. Based on our results, this work could be a reasonable “case study”, useful for future investigation of the drug pharmacokinetic profile.
Extracellular Vesicles in Diagnosing Chronic Coronary Syndromes the Bumpy Road to Clinical Implementation
Authors: Dekker Mirthe , Waissi Farahnaz , Timmerman Nathalie , Silvis Max J. M. , Timmers Leo , de Kleijn Dominique P. V.
Published: December 2020

Coronary artery disease (CAD), comprising both acute coronary syndromes (ACS) and chronic coronary syndromes (CCS), remains one of the most important killers throughout the entire world. ACS is often quickly diagnosed by either deviation on an electrocardiogram or elevated levels of troponin, but CCS appears to be more complicated. The most used noninvasive strategies to diagnose CCS are coronary computed tomography and perfusion imaging. Although both show reasonable accuracy (80–90%), these modalities are becoming more and more subject of debate due to costs, radiation and increasing inappropriate use in low-risk patients. A reliable, blood-based biomarker is not available for CCS but would be of great clinical importance. Extracellular vesicles (EVs) are lipid-bilayer membrane vesicles containing bioactive contents e.g., proteins, lipids and nucleic acids. EVs are often referred to as the “liquid biopsy” since their contents reflect changes in the condition of the cell they originate from. Although EVs are studied extensively for their role as biomarkers in the cardiovascular field during the last decade, they are still not incorporated into clinical practice in this field. This review provides an overview on EV biomarkers in CCS and discusses the clinical and technological aspects important for successful clinical application of EVs.
Functional Identification of Serine Hydroxymethyltransferase as a Key Gene Involved in Lysostaphin Resistance and Virulence Potential of Staphylococcus aureus Strains
Authors: Batool Nayab , Ko Kwan Soo , Chaurasia Akhilesh Kumar , Kim Kyeong Kyu
Published: December 2020

Gaining an insight into the mechanism underlying antimicrobial-resistance development in Staphylococcus aureus is crucial for identifying effective antimicrobials. We isolated S. aureus sequence type 72 from a patient in whom the S. aureus infection was highly resistant to various antibiotics and lysostaphin, but no known resistance mechanisms could explain the mechanism of lysostaphin resistance. Genome-sequencing followed by subtractive and functional genomics revealed that serine hydroxymethyltransferase (glyA or shmT gene) plays a key role in lysostaphin resistance. Serine hydroxymethyltransferase (SHMT) is indispensable for the one-carbon metabolism of serine/glycine interconversion and is linked to folate metabolism. Functional studies revealed the involvement of SHMT in lysostaphin resistance, as ΔshmT was susceptible to the lysostaphin, while complementation of the knockout expressing shmT restored resistance against lysostaphin. In addition, the ΔshmT showed reduced virulence under in vitro (mammalian cell lines infection) and in vivo (wax-worm infection) models. The SHMT inhibitor, serine hydroxymethyltransferase inhibitor 1 (SHIN1), protected the 50% of the wax-worm infected with wild type S. aureus. These results suggest SHMT is relevant to the extreme susceptibility to lysostaphin and the host immune system. Thus, the current study established that SHMT plays a key role in lysostaphin resistance development and in determining the virulence potential of multiple drug-resistant S. aureus.
Divide-and-Conquer Matrisome Protein (DC-MaP) Strategy: An MS-Friendly Approach to Proteomic Matrisome Characterization
Authors: Ouni Emna , Ruys Sébastien Pyr dit , Dolmans Marie-Madeleine , Herinckx Gaëtan , Vertommen Didier , Amorim Christiani A.
Published: December 2020

Currently, the extracellular matrix (ECM) is considered a pivotal complex meshwork of macromolecules playing a plethora of biomolecular functions in health and disease beyond its commonly known mechanical role. Only by unraveling its composition can we leverage related tissue engineering and pharmacological efforts. Nevertheless, its unbiased proteomic identification still encounters some limitations mainly due to partial ECM enrichment by precipitation, sequential fractionation using unfriendly-mass spectrometry (MS) detergents, and resuspension with harsh reagents that need to be entirely removed prior to analysis. These methods can be technically challenging and labor-intensive, which affects the reproducibility of ECM identification and induces protein loss. Here, we present a simple new method applicable to tissue fragments of 10 mg and more. The technique has been validated on human ovarian tissue and involves a standardized procedure for sample processing with an MS-compatible detergent and combined centrifugation. This two-step protocol eliminates the need for laborious sample clarification and divides our samples into 2 fractions, soluble and insoluble, successively enriched with matrisome-associated (ECM-interacting) and core matrisome (structural ECM) proteins.
Suppression of Ovarian Cancer Cell Growth by AT-MSC Microvesicles
Authors: Szyposzynska Agnieszka , Bielawska-Pohl Aleksandra , Krawczenko Agnieszka , Doszyn Olga , Paprocka Maria , Klimczak Aleksandra
Published: December 2020

Transport of bioactive cargo of microvesicles (MVs) into target cells can affect their fate and behavior and change their microenvironment. We assessed the effect of MVs derived from human immortalized mesenchymal stem cells of adipose tissue-origin (HATMSC2-MVs) on the biological activity of the ovarian cancer cell lines ES-2 (clear cell carcinoma) and OAW-42 (cystadenocarcinoma). The HATMSC2-MVs were characterized using dynamic light scattering (DLS), transmission electron microscopy, and flow cytometry. The anti-tumor properties of HATMSC2-MVs were assessed using MTT for metabolic activity and flow cytometry for cell survival, cell cycle progression, and phenotype. The secretion profile of ovarian cancer cells was evaluated with a protein antibody array. Both cell lines internalized HATMSC2-MVs, which was associated with a decreased metabolic activity of cancer cells. HATMSC2-MVs exerted a pro-apoptotic and/or necrotic effect on ES-2 and OAW-42 cells and increased the expression of anti-tumor factors in both cell lines compared to control. In conclusion, we confirmed an effective transfer of HATMSC2-MVs into ovarian cancer cells that resulted in the inhibition of cell proliferation via different pathways, apoptosis and/or necrosis, which, with high likelihood, is related to the presence of different anti-tumor factors secreted by the ES-2 and OAW-42 cells.
Smart Roads: An Overview of What Future Mobility Will Look Like
Authors: Trubia Salvatore , Severino Alessandro , Curto Salvatore , Arena Fabio , Pau Giovanni
Published: December 2020

Transport engineering has recently undergone several significant changes and innovations, one of which is the appearance and spread of autonomous vehicles; with this technology becoming more common and ordinary by the day, it is now necessary to implement some systems and contexts to facilitate autonomous vehicle operations. Consequently, a different perspective is now arising when dealing with road infrastructures, aiming to simplify and improve efficiency and maintenance of the existing roads, increase the life cycle of newly built ones, and minimize the economic and financial impact at the same time. Roadway pavements are one of the primary factors affecting vehicle operations; over time, this distinctive aspect has gone through various mechanical and physical changes due to the adoption of new materials or design methods. Consequently, to the spread of autonomous vehicles, scientific research has begun to study and develop systems to make road pavements and platforms not exclusively aimed at bearing loads, but rather at considering them as a means of communication and information exchange, if not even as a source of energy. This new approach introduces the so-called “Smart Roads,” i.e., road infrastructures capable of communicating with vehicles and self-monitoring fundamental perspectives concerning driverless vehicles and the roadway platform life cycle. This paper examines the characteristics of Smart Roads, considering their broad field of application and their potential advantages and drawbacks. This paper also pursues the objective of describing the global vision, the possible future direction of these innovations concerning the automotive and transport industries, and a particular focus on infrastructures and roadways.