bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptability in Swimming Pattern: How Propulsive Action Is Modified as a Function of Speed and Skill
Authors: Schnitzler Christophe , Seifert Ludovic , Button Chris
Published: April 2021

The objectives of this study were to identify how spatiotemporal, kinetic, and kinematic parameters could (i) characterize swimmers' adaptability to different swimming speeds and (ii) discriminate expertise level among swimmers. Twenty male participants, grouped into (a) low-, (b) medium-, and (c) high-expertise levels, swam at four different swim paces of 70, 80, 90% (for 20 s), and 100% (for 10 s) of their maximal speed in a swimming flume. We hypothesized that (i) to swim faster, swimmers increase both propulsion time and the overall force impulse during a swimming cycle; (ii) in the frequency domain, expert swimmers are able to maintain the relative contribution of the main harmonics to the overall force spectrum. We used three underwater video cameras to derive stroking parameters [stroke rate (SR), stroke length (SL), stroke index (SI)]. Force sensors placed on the hands were used to compute kinetic parameters, in conjunction with video data. Parametric statistics examined speed and expertise effects. Results showed that swimmers shared similarities across expertise levels to increase swim speed: SR, the percentage of time devoted to propulsion within a cycle, and the index of coordination (IdC) increased significantly. In contrast, the force impulse (I+) generated by the hand during propulsion remained constant. Only the high-expertise group showed modification in the spectral content of its force distribution at high SR. Examination of stroking parameters showed that only high-expertise swimmers exhibited higher values of both SL and SI and that the low- and high-expertise groups exhibited similar IdC and even higher magnitude inI+. In conclusion, all swimmers exhibit adaptable behavior to change swim pace when required. However, high-skilled swimming is characterized by broader functional adaptation in force parameters.
Knockdown of GPSM1 Inhibits the Proliferation and Promotes the Apoptosis of B-Cell Acute Lymphoblastic Leukemia Cells by Suppressing the ADCY6-RAPGEF3-JNK Signaling Pathway
Authors: Zhang Ye , Zhou Bo , Sun Jingjing , He Qun , Zhao Yujie
Published: April 2021

B-cell acute lymphoblastic leukemia (B-ALL) is the common type of blood cancer. Although the remission rate has increased, the current treatment options for B-ALL are usually related to adverse reactions and recurrence, so it is necessary to find other treatment options. G protein signaling modulator 1 (GPSM1) is one of several factors that affect the basic activity of the G protein signaling system, but its role in B-ALL has not yet been clarified. In this study, we analyzed the expression of GPSM1 in the Oncomine database and found that the GPSM1 levels were higher in B-ALL cells than in peripheral blood mononuclear cells (PBMCs). Analyses of the Gene Expression Profiling Interactive Analysis (GEPIA) demonstrated that patients with high GPSM1 levels had shorter survival times than those with low levels. Additionally, gene set enrichment analysis (GSEA) suggested that GPSM1 was positively correlated with proliferation, G protein-coupled receptor (GPCR) ligand binding, Gαs signaling and calcium signaling pathways. In further experiments, GPSM1 was found to be highly expressed in Acute lymphoblastic leukemia (ALL) cell lines, and downregulation of GPSM1 inhibited proliferation and promoted cell cycle arrest and apoptosis in BALL-1 and Reh cells. Moreover, knockdown of GPSM1 suppressed ADCY6 and RAPGEF3 expression in BALL-1 and Reh cells. Furthermore, we reported that GPSM1 regulated JNK expression via ADCY6-RAPGEF3. The present study demonstrates that GPSM1 promotes tumor growth in BALL-1 and Reh cells by modulating ADCY6-RAPGEF3-JNK signaling.
Aircraft Fleet Health Monitoring with Anomaly Detection Techniques
Authors: Basora Luis , Bry Paloma , Olive Xavier , Freeman Floris
Published: April 2021

Predictive maintenance has received considerable attention in the aviation industry where costs, system availability and reliability are major concerns. In spite of recent advances, effective health monitoring and prognostics for the scheduling of condition-based maintenance operations is still very challenging. The increasing availability of maintenance and operational data along with recent progress made in machine learning has boosted the development of data-driven prognostics and health management (PHM) models. In this paper, we describe the data workflow in place at an airline for the maintenance of an aircraft system and highlight the difficulties related to a proper labelling of the health status of such systems, resulting in a poor suitability of supervised learning techniques. We focus on investigating the feasibility and the potential of semi-supervised anomaly detection methods for the health monitoring of a real aircraft system. Proposed methods are evaluated on large volumes of real sensor data from a cooling unit system on a modern wide body aircraft from a major European airline. For the sake of confidentiality, data has been anonymized and only few technical and operational details about the system had been made available. We trained several deep neural network autoencoder architectures on nominal data and used the anomaly scores to calculate a health indicator. Results suggest that high anomaly scores are correlated with identified failures in the maintenance logs. Also, some situations see an increase in the anomaly score for several flights prior to the system’s failure, which paves a natural way for early fault identification.
Efficacy of Irrigation Interval after Anthesis on Grain Quality, Alkali Digestion, and Gel Consistency of Rice
Authors: Rayee Ramin , Xuan Tran Dang , Khanh Tran Dang , Tran Hoang-Dung , Kifayatullah Kifayatullah
Published: April 2021

The management of amylose and protein contents and cooking quality are the main challenges in rice macronutrients and quality improvement. This experiment was conducted to examine the rice grain quality, alkali digestion, and gel consistency responses to irrigation interval after anthesis. Three rice varieties (K1, K3, and K4) were subjected to different irrigation intervals (1, 2, and 3 d) after anthesis. The findings of this study showed that the protein content was markedly increased from 6.53–6.63% to 9.93–10.16%, whilst the amylose content was decreased significantly from 22.00–22.43% to 16.33–17.56% under stressed treatments at irrigation intervals, whilst the quantity of fatty acids was not affected. The 3-d irrigation interval recorded the highest protein content but the lowest amylose value. In addition, this treatment shows lower gelatinization temperature, but it is negatively associated with hard gel consistency under irrigation interval. This study highlights that the water management following a 3-d irrigation interval from anthesis is a useful and simple treatment to improve rice nutrients and grain cooking quality.
The Effect of Brassinosteroids on Rootting of Stem Cuttings in Two Barberry (Berberis thunbergii L.) Cultivars
Authors: Pacholczak Andrzej , Zajączkowska Małgorzata , Nowakowska Karolina
Published: April 2021

Brassinosteroids are a group of over seventy steroid compounds whose discovery in lower and higher plant organisms created new possibilities of plant growth control. The aim of the work was to evaluate the effect of two brassinosteroids: brassinolide (BL) and 24-epibrassinolide (24epiBL) as compared to the auxin rooting enhancer indole-3-butyric acid (IBA), on the rooting of stem cuttings in two Thunberg’s barberry cultivars ‘Maria’ and ‘Red Rocket’. The cuttings were sprayed with water solutions of growth regulators: IBA (200 mg·L−1), 0.05% BL or 24epiBL, as well as with a combination of each of brassinosteroids with the auxin while the control cuttings were sprayed with water. In both cultivars brassinosteroids positively affected a degree of rooting and root length. Their application resulted in elevated contents of chlorophyll, total soluble sugars, free amino acids, hydrogen peroxide and catalase activity. Brassinosteroids were more effective when combined with the auxin than when used singly.
Alfalfa Forage Production and Nutritive Value, Fermentation Characteristics and Hygienic Quality of Ensilage, and Soil Properties after Broiler Litter Amendment
Authors: Netthisinghe Annesly , Woosley Paul , Rowland Naomi , Willian Todd , Gilfillen Becky , Sistani Karamat
Published: April 2021

Recycling broiler litter (BL) nutrients is an important strategy for sustainable forage production. However, BL can contain Clostridia bacteria that can contaminate forages at harvest, resulting in poor ensilage quality and botulism-related animal health risks. A better understanding of the effects of BL amendment on alfalfa (Medicago sativa L.) production and ensiling is beneficial for promoting manure-based alfalfa production. This 2-year study examined the effects of high-level BL (HBL) at 112 kg N ha−1 and low-level (LBL) at 56 kg N ha−1 on alfalfa forage production, fermentation characteristics, and Clostridium botulinum concentrations in silage and haylage produced from 350 g dry matter (DM) kg−1 forage and 500 g DM kg−1 forage respectively, and soil characteristics compared to a control treatment (CT). Results showed that the application of BL did not affect forage production (12.8–13.1 MG ha−1) and nutritive value. The alfalfa produced high forage yield with superior ensilabilty in the second year. The BL application increased soil NH4-N, Ca, Fe, and B, but did not affect fermentation characteristics or Clostridium botulinum concentrations in ensilage. Silage had superior fermentation quality, and Clostridium botulinum concentration was found to be higher than in haylage. Broiler litter fertilization for alfalfa is environmentally safe and has forge production, ensilage fermentation quality, and botulism risks similar to CT.
Influence of Rhizopheric H2O2 on Growth, Mineral Absorption, Root Anatomy and Nematode Infection of Ficus deltoidea
Authors: Ralmi Nurul Hafiza Al Abadiyah , Khandaker Mohammad Moneruzzaman , Mohd Khamsah Suryati , Majrashi Ali , Fallatah Ahmed M. , Badaluddin Noor Afiza , Yusoff Nornasuha , Mahmud Khairil , Saifuddin Mohamed , Osman Normaniza , Mohd Nor Zanariah
Published: April 2021

Hydrogen peroxide (H2O2) is a broad-range chemical catalyst that is receiving rapidly increasing attention recently due to its role as a signaling molecule in various plant physiological and biochemical processes. A study was carried out to investigate the effects of H2O2 on the plant physiology, root growth, mineral nutrient accumulation, root anatomy, and nematode control of Ficus deltoidea, a slow growing shade tolerant and nematode susceptible medicinal plant. H2O2 at 0 (control), 15, 30, 60, and 90 mM was injected into the root zone of plants weekly. The results showed that the treatment of H2O2 enhanced the accumulation of pigments, photosynthetic characteristics, and quantum yield (Fv/Fm) of F. deltoidea. H2O2 at a 90 mM treatment significantly increased seedling height, leaf number, syconium number, biomass yield, relative water content, leaf dry matter, leaf moisture, and live line fuel moisture of the plant by 1.35-, 3.02-, 3.60-, 5.13-, 1.21-, 1.12-, 1.79- and 1.06-fold, respectively, over the control plant. In addition, root growth, which includes root crown diameter, root length, root volume, root tips, number of roots and root biomass, also exhibited the highest values with an application of 90 mM of H2O2. Heavy metals arsenic (As+) and antimony (Sb+) content in the leaves decreased by 4.08-and 1.63-fold, respectively, in the 60 mM H2O2 treated plant when compared to the control plant. In addition, 90 mM H2O2 was the best treatment for magnesium (Mg2+), calcium (Ca2+), and sodium (Na+) mineral accumulation in the syconium of F. deltoidea. Treatments with 60 mM H2O2 increased magnesium (Mg2+), calcium (Ca2+), and potassium (K+) content in leaves by 14%, 19%, and 15%, respectively, over the control plant. In the study of controlling root-knot nematode, both control and 15 mM treatments produced many root galls, whereas, 60 mM H2O2 treatment produced fewer tiny root galls and 90 mM of H2O2 showed no root gall formation. H2O2 treatments reduced root gall size, root/shoot ratio, and increased the shoot biomass of plants. The treated root developed an epidermal suberin, root periderm, resin duct, cortex, druses, and a well-developed vascular system compared to the control plants. Furthermore, no nematodes were observed in the roots of treated plants with 30–90 mM H2O2. The study concluded that injections of 60–90 mM H2O2 to the root zone weekly improved plant physiology, increased mineral accumulation, root growth and development, reduced root gall formation, improved root cellular structure, and controlled root-knot nematode of F. deltoidea plants.
Genetic Mapping of Grain Shape Associated QTL Utilizing Recombinant Inbred Sister Lines in High Yielding Rice (Oryza sativa L.)
Authors: Kang Yiwei , Zhang Miao , Zhang Yue , Wu Weixun , Xue Pao , Zhan Xiaodeng , Cao Liyong , Cheng Shihua , Zhang Yingxin
Published: April 2021

Grain shape is a key factor for yield and quality in rice. To investigate the genetic basis of grain shape in the high-yielding hybrid rice variety Nei2You No.6, a set of recombinant inbred sister lines (RISLs) were used to map quantitative trait loci (QTLs) determining grain length (GL), grain width (GW), and length-width ratio (LWR) in four environments. A total of 91 medium/minor-effect QTL were detected using a high-density genetic map consisting of 3203 Bin markers composed of single nucleotide polymorphisms, among which 64 QTL formed 15 clusters. Twelve of 15 clusters co-localized with QTL previously reported for grain shape/weight. Three new QTL were detected: qGL-7a, qGL-8, and qGL-11a. A QTL cluster, qLWR-12c/qGW-12, was detected across all four environments with phenotypic variation explained (PVE) ranging from 3.67% to 11.93%, which was subsequently validated in paired lines of F17 progeny and tightly linked marker assay in F10 generation. Subsequently, 17 candidate genes for qLWR-12c/qGW-12 were detected in the 431 Kb interval utilizing bulk segregant analysis (BSA). Among these, OsR498G1222170400, OsR498G1222171900, OsR498G1222185100, OsR498G1222173400, and OsR498G1222170500 were the best candidates, which lays the foundation for further cloning and will facilitate high-yield breeding in rice.
Antibiotics: Conventional Therapy and Natural Compounds with Antibacterial Activity—A Pharmaco-Toxicological Screening
Authors: Pancu Daniel Florin , Scurtu Alexandra , Macasoi Ioana Gabriela , Marti Daniela , Mioc Marius , Soica Codruta , Coricovac Dorina , Horhat Delia , Poenaru Marioara , Dehelean Cristina
Published: April 2021

Antibiotics are considered as a cornerstone of modern medicine and their discovery offers the resolution to the infectious diseases problem. However, the excessive use of antibiotics worldwide has generated a critical public health issue and the bacterial resistance correlated with antibiotics inefficiency is still unsolved. Finding novel therapeutic approaches to overcome bacterial resistance is imperative, and natural compounds with antibacterial effects could be considered a promising option. The role played by antibiotics in tumorigenesis and their interrelation with the microbiota are still debatable and are far from being elucidated. Thus, the present manuscript offers a global perspective on antibiotics in terms of evolution from a historical perspective with an emphasis on the main classes of antibiotics and their adverse effects. It also highlights the connection between antibiotics and microbiota, focusing on the dual role played by antibiotics in tumorigenesis. In addition, using the natural compounds with antibacterial properties as potential alternatives for the classical antibiotic therapy is discussed.
Analytical Approximations for Sub Wavelength Sound Absorption by Porous Layers with Labyrinthine Slit Perforations
Authors: Attenborough Keith
Published: April 2021

Analytical approximations for the acoustical properties of a rigid-porous matrix perforated by labyrinthine slits are developed using classical theories for sound propagation in tortuous slits and for sound absorption by double porosity materials. Predictions of enhanced low-frequency absorption result from a combination of pressure diffusion and labyrinth tortuosity if there is a high permeability contrast between the matrix and the labyrinthine slit. Additional insight into the predicted influence of the properties of the porous matrix is gained by considering the matrix porosity to be provided by inclined micro-slits. Extra tortuosity can be introduced by alternating the width of the labyrinthine slit. An alternating-width vertical-wall labyrinth perforation is predicted to lead to low-frequency absorption peaks in a relatively low-flow-resistivity and low-porosity matrix. Example predictions, even when using underestimates of labyrinth tortuosity, demonstrate the potential of labyrinthine slit perforations for achieving narrowband deep sub wavelength absorption peaks from thin hard-backed porous layers.
A Geometrical Structure-Based New Approach for City Logistics System Planning with Cargo Bikes and Its Application for the Shopping Malls of Budapest
Authors: Sárdi Dávid Lajos , Bóna Krisztián
Published: April 2021

Nowadays, cargo bikes are seeing an ever-greater role in city logistics with an increasing number of deliveries, and it is essential to examine their future role in green and smart cities. In our work, we examine the application of cargo bikes in the city logistics system of the urban concentrated sets of delivery locations, focusing first on shopping malls, with the investigation of the geometrical structure of the logistics network. In the examined concept, the use of cargo bikes will be combined with electric trucks to make possible green deliveries of urban concentrated sets of delivery locations. In this paper, we present the experiences of the existing systems and the related research, the simulation model of the examined new concept with cargo bikes and its results, the graph theory-based geometric model of the examined city logistics system with graph theory-based notation, and the application of the new approach for Budapest. The main output of this research is the geometrical model of the urban concentrated sets of delivery locations and its application. Based on this geometrical model, it will be possible to decide about the suitability of the examined cargo bike-based city logistics concepts for given cities.
Semi-Minimal-Pruned Hedge (SMPH) as a Climate Change Adaptation Strategy: Impact of Different Yield Regulation Approaches on Vegetative and Generative Development, Maturity Progress and Grape Quality in Riesling
Authors: Schäfer Jan , Friedel Matthias , Molitor Daniel , Stoll Manfred
Published: April 2021

The training system Semi-Minimal-Pruned Hedge (SMPH) blends features of traditional Vertical Shoot Positioning-type (VSP) trellising systems with the concept of minimal pruning. While saving labor, this training system results in relatively high crop load and a poor leaf area to fruit weight-ratio (LFR), and thus, needs to be able to ripen grapes in a cool to moderate climate. For these reasons the impact of yield regulation strategies, including (i) shoot thinning (Darwin-Rotor), (ii) biotechnological thinning (Gibberellic acid), and (iii) bunch thinning (harvest machine) were trialed in a three year study at Geisenheim, Germany between 2017 and 2019 using Riesling (Vitis vinifera L.). The average yield per vine in SMPH (5.34 ± 1.10 kg) was 61.1% higher with a narrower LFR (14.01 cm2 g−1), compared with VSP (3.32 ± 1.02 kg, LFR: 16.99 cm2 g−1). The yield was successfully reduced and LFR simultaneously increased with shoot thinning (−33.1%, LFR: 19.04 cm2 g−1), biotechnological thinning (−18.3%, LFR: 16.69 cm2 g−1) and bunch thinning (−37.3%, LFR: 21.49 cm2 g−1). Ripening was delayed in SMPH. On average, two maturity thresholds (14.1 °Brix and 18.2 °Brix) were achieved 129 GDD (seven days according to the recorded daily mean temperatures, respectively) and 269 GDD (16 days) later in non-thinned SMPH, compared to VSP. All thinning treatments accelerated maturity progress ranging from 27 GDD (two days) to 58 GDD (three days) for 14.1 °Brix and 59 GDD (three days) to 105 GDD (six days) for 18.2 °Brix. Apart from immediate benefits on the economic efficiency, the adaption of the leaf area to fruit weight ratio using SMPH holds high potential to, (i) produce grapes targeting specific wine profiles and/or (ii) reducing the velocity of ripening under conditions of climatic change.
High Intensity Training Increases Muscle Area Occupied by Type II Muscle Fibers of the Multifidus Muscle in Persons with Non-Specific Chronic Low Back Pain: A Pilot Trial
Authors: Agten Anouk , Verbrugghe Jonas , Stevens Sjoerd , Eijnde Bert O. , Timmermans Annick , Vandenabeele Frank
Published: April 2021

Low back pain is a prevalent musculoskeletal disorder with high disability. Although exercise therapy is an important part of the multidisciplinary treatment of non-specific chronic low back pain (NSCLBP), the impact of exercise therapy on muscle morphology of the paraspinal muscles is largely unknown. The main aim of this study is to evaluate the effects of a high intensity training (HIT) program on muscle fiber characteristics of the multifidus (MF) and the erector spinae (ES) musculature in persons with NSCLBP and to compare these results with the effects of a moderate intensity training (MIT) program, which is used as a control group. In total, 38 participants with NSCLBP were randomly assigned to a HIT or MIT intervention group. Participants performed a 12-week training program. At baseline and after the training program, biopsy samples from the lumbar MF and ES were obtained. Muscle fiber characteristics were analyzed by immunofluorescence. For the ES, no significant changes were found in muscle fiber CSA and distribution of muscle fiber types in response to a training program at moderate or at high intensity. For the MF, a significant higher muscle area occupied by type II muscle fibers, referred to as the relative cross-sectional area (RCSA), was found in the HIT group. Based on muscle fiber characteristics in biopsy samples, a HIT program of 12 weeks seems to result in a more glycolytic profile in the MF.
Multiple Brain Abscesses of Odontogenic Origin. May Oral Microbiota Affect Their Development? A Review of the Current Literature
Authors: Montemurro Nicola , Perrini Paolo , Marani Walter , Chaurasia Bipin , Corsalini Massimo , Scarano Antonio , Rapone Biagio
Published: April 2021

In the last few years, the role of oral microbiota in the setting of oral diseases such as caries, periodontal disease, oral cancer and systemic infections, including rheumatoid arthritis, cardiovascular disease and brain abscess (BA), has attracted the attention of physicians and researchers. Approximately 5–7% of all BAs have an odontogenic origin, representing an important pathological systemic condition with a high morbidity and mortality. A systematic search of two databases (Pubmed and Ovid EMBASE) was performed for studies published up to 5 January 2021, reporting multiple BAs attributed to an odontogenic origin. According to PRISMA guidelines, we included a total of 16 papers reporting multiple BAs due to odontogenic infections. The aim of this review is to investigate the treatment modality and the clinical outcome of patients with multiple BAs due to odontogenic infections, as well as to identify the most common pathogens involved in this pathological status and their role, in the oral microbiota, in the onset of oral infections. A multidisciplinary approach is essential in the management of multiple BAs. Further studies are required to understand better the role of microbiota in the development of multiple BAs.
Multi-Purpose Dataset of Webpages and Its Content Blocks: Design and Structure Validation
Authors: Griazev Kiril , Ramanauskaitė Simona
Published: April 2021

The need for automated data extraction is continuously growing due to the constant addition of information to the worldwide web. Researchers are developing new data extraction methods to achieve increased performance compared to existing methods. Comparing algorithms to evaluate their performance is vital when developing new solutions. Different algorithms require different datasets to test their performance due to the various data extraction approaches. Currently, most datasets tend to focus on a specific data extraction approach. Thus, they generally lack the data that may be useful for other extraction methods. That leads to difficulties when comparing the performance of algorithms that are vastly different in their approach. We propose a dataset of web page content blocks that includes various data points to counter this. We also validate its design and structure by performing block labeling experiments. Web developers of varying experience levels labeled multiple websites presented to them. Their labeling results were stored in the newly proposed dataset structure. The experiment proved the need for proposed data points and validated dataset structure suitability for multi-purpose dataset design.
New Insights into Cellular Functions of Nuclear Actin
Authors: Kloc Malgorzata , Chanana Priyanka , Vaughn Nicole , Uosef Ahmed , Kubiak Jacek Z. , Ghobrial Rafik M.
Published: April 2021

Actin is one of the most abundant proteins in eukaryotic cells. There are different pools of nuclear actin often undetectable by conventional staining and commercial antibodies used to identify cytoplasmic actin. With the development of more sophisticated imaging and analytical techniques, it became clear that nuclear actin plays a crucial role in shaping the chromatin, genomic, and epigenetic landscape, transcriptional regulation, and DNA repair. This multifaceted role of nuclear actin is not only important for the function of the individual cell but also for the establishment of cell fate, and tissue and organ differentiation during development. Moreover, the changes in the nuclear, chromatin, and genomic architecture are preamble to various diseases. Here, we discuss some of the newly described functions of nuclear actin.
3D Imaging and Quantitative Characterization of Mouse Capillary Coronary Network Architecture
Authors: Nicolas Nabil , Roux Etienne
Published: April 2021

Characterization of the cardiac capillary network structure is of critical importance to understand the normal coronary functional properties and coronary microvascular diseases. The aim of our study was to establish an accessible methodology for 3D imaging and 3D processing to quantitatively characterize the capillary coronary network architecture in mice. Experiments were done on C57BL/6J mice. 3D imaging was performed by light sheet microscopy and confocal microscopy on iDISCO+ optical cleared hearts after labelling of the capillary endothelium by lectin injection. 3D images were processed with the open source software ImageJ. Non-visual image segmentation was based of the frequency distribution of the voxel greyscale values, followed by skeletonization and distance mapping. Capillary networks in left and right ventricles and septum were characterized by the volume network density, the fractal dimension, the number of segments and nodes and their ratio, the total network length, and the average length, diameter, and tortuosity of the segments. Scale-dependent parameter values can be impacted by the resolution limit of the 3D imaging technique. The proposed standardized methodology for 3D image processing is easily accessible for a biologist in terms of investment and difficulty level, and allows the quantification of the 3D capillary architecture and its statistical comparison in different conditions.
Exosomal microRNAs: Pleiotropic Impacts on Breast Cancer Metastasis and Their Clinical Perspectives
Authors: Tang Li-Bo , Ma Shu-Xin , Chen Zhuo-Hui , Huang Qi-Yuan , Wu Long-Yuan , Wang Yi , Zhao Rui-Chen , Xiong Li-Xia
Published: April 2021

As a major threat factor for female health, breast cancer (BC) has garnered a lot of attention for its malignancy and diverse molecules participating in its carcinogenesis process. Among these complex carcinogenesis processes, cell proliferation, epithelial-to-mesenchymal transition (EMT), mesenchymal-to-epithelial transition (MET), and angiogenesis are the major causes for the occurrence of metastasis and chemoresistance which account for cancer malignancy. MicroRNAs packaged and secreted in exosomes are termed “exosomal microRNAs (miRNAs)”. Nowadays, more researches have uncovered the roles of exosomal miRNAs played in BC metastasis. In this review, we recapitulated the dual actions of exosomal miRNAs exerted in the aggressiveness of BC by influencing migration, invasion, and distant metastasis. Next, we presented how exosomal miRNAs modify angiogenesis and stemness maintenance. Clinically, several exosomal miRNAs can govern the transformation between drug sensitivity and chemoresistance. Since the balance of the number and type of exosomal miRNAs is disturbed in pathological conditions, they are able to serve as instructive biomarkers for BC diagnosis and prognosis. More efforts are needed to connect the theoretical studies and clinical traits together. This review provides an outline of the pleiotropic impacts of exosomal miRNAs on BC metastasis and their clinical implications, paving the way for future personalized drugs.
Viscoelastic Response of Neurofilaments: An Atomistic Simulation Approach
Authors: Khan Md Ishak , Hasan Fuad , Mahmud Khandakar Abu Hasan Al , Adnan Ashfaq
Published: April 2021

Existent literature has limitations regarding the mechanical behavior of axonal cytoskeletal components in a high strain rate scenario, which is mainly due to limitations regarding the structure of some components such as tau protein and neurofilaments (NF). This study performs molecular dynamics (MD) simulations on NFs to extract their strain rate-dependent behavior. It is found that they are highly stretchable and show multiple stages of unfolding. Furthermore, NFs show high tensile stiffness. Also, viscoelastic modeling shows that they correspond to simplified viscoelastic models. This study effectively enhances the existent axonal models focusing on axonal injury.
Colon Fibroblasts and Inflammation: Sparring Partners in Colorectal Cancer Initiation?
Authors: Onfroy-Roy Lauriane , Hamel Dimitri , Malaquin Laurent , Ferrand Audrey
Published: April 2021

Colorectal cancer (CRC) is the third most common cause of cancer-related death. Significant improvements in CRC treatment have been made for the last 20 years, on one hand thanks to a better detection, allowing surgical resection of the incriminated area, and on the other hand, thanks to a better knowledge of CRC’s development allowing the improvement of drug strategies. Despite this crucial progress, CRC remains a public health issue. The current model for CRC initiation and progression is based on accumulation of sequential known genetic mutations in the colon epithelial cells’ genome leading to a loss of control over proliferation and survival. However, increasing evidence reveals that CRC initiation is more complex. Indeed, chronic inflammatory contexts, such as inflammatory bowel diseases, have been shown to increase the risk for CRC development in mice and humans. In this manuscript, we review whether colon fibroblasts can go from the main regulators of the ISC homeostasis, regulating not only the renewal process but also the epithelial cells’ differentiation occurring along the colon crypt, to the main player in the initiation of the colorectal cancer process due to chronic inflammation.
The “COVID-19 Pandemic Gap” and Its Influence on Oncologic Outcomes of Bladder Cancer
Authors: Tulchiner Gennadi , Staudacher Nina , Fritz Josef , Radmayr Christian , Culig Zoran , Horninger Wolfgang , Pichler Renate
Published: April 2021

Coronavirus-19 (COVID-19)-induced effects on deferred diagnosis and treatment of bladder cancer (BC) patients are currently not clarified. The aim of this study was to evaluate outcomes of the COVID-19 pandemic by considering its effects on tumor stage and grade, and to create feasible clinical triage decisions. A retrospective single-center analysis of all patients who underwent diagnostic and surgical procedures due to BC, during January 2019 and December 2020, was performed. Due to COVID-19 lockdowns, significantly fewer (diagnostic and therapeutic) endoscopic procedures were performed in the first 6 months of 2020 compared to 2019 (p = 0.002). In patients with a primary diagnosis of BC, a significant increase of high-grade tumors (p < 0.001), as well as advanced tumor stages (p = 0.014), were noticed during 2020 in comparison to 2019. On the contrary, patients with recurrent BC undergoing risk-adapted surveillance, depending on previous tumor histology, showed no adverse outcomes regarding tumor stage and grade when comparing the pre COVID-19 era with 2020. Thus, more awareness in clinical urologic practice is mandatory to avoid adverse consequences, with increased rates of advanced and aggressive tumors in patients with primary BC. In recurrent BC, an individual risk stratification in order to avoid worse outcomes during the COVID-19 pandemic seems to be justified.
A Novel Two-Lipid Signature Is a Strong and Independent Prognostic Factor in Ovarian Cancer
Authors: Salminen Liina , Braicu Elena Ioana , Lääperi Mitja , Jylhä Antti , Oksa Sinikka , Hietanen Sakari , Sehouli Jalid , Kulbe Hagen , Bois Andreas du , Mahner Sven , Harter Philipp , Carpén Olli , Huhtinen Kaisa , Hynninen Johanna , Hilvo Mika
Published: April 2021

Epithelial ovarian cancer (EOC) generally responds well to oncological treatments, but the eventual development of a refractory disease is a major clinical problem. Presently, there are no prognostic blood-based biomarkers for the stratification of EOC patients at the time of diagnosis. We set out to assess and validate the prognostic utility of a novel two-lipid signature, as the lipidome is known to be markedly aberrant in EOC patients. The study consisted of 499 women with histologically confirmed EOC that were prospectively recruited at the university hospitals in Turku (Finland) and Charité (Berlin, Germany). Lipidomic screening by tandem liquid chromatography–mass spectrometry (LC-MS/MS) was performed for all baseline serum samples of these patients, and additionally for 20 patients of the Turku cohort at various timepoints. A two-lipid signature, based on the ratio of the ceramide Cer(d18:1/18:0) and phosphatidylcholine PC(O-38:4), showed consistent prognostic performance in all investigated study cohorts. In the Turku cohort, the unadjusted hazard ratios (HRs) per standard deviation (SD) (95% confidence interval) were 1.79 (1.40, 2.29) for overall and 1.40 (1.14, 1.71) for progression-free survival. In a Charité cohort incorporating only stage III completely resected patients, the corresponding HRs were 1.59 (1.08, 2.35) and 1.53 (1.02, 2.30). In linear-mixed models predicting progression of the disease, the two-lipid signature showed higher performance (beta per SD increase 1.99 (1.38, 2.97)) than cancer antigen 125 (CA-125, 1.78 (1.13, 2.87)). The two-lipid signature was able to identify EOC patients with an especially poor prognosis at the time of diagnosis, and also showed promise for the detection of disease relapse.
Systematic Analysis of the Transcriptome Profiles and Co-Expression Networks of Tumour Endothelial Cells Identifies Several Tumour-Associated Modules and Potential Therapeutic Targets in Hepatocellular Carcinoma
Authors: Mohr Thomas , Katz Sonja , Paulitschke Verena , Aizarani Nadim , Tolios Alexander
Published: April 2021

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most common cause of cancer-related death, with tumour associated liver endothelial cells being thought to be major drivers in HCC progression. This study aims to compare the gene expression profiles of tumour endothelial cells from the liver with endothelial cells from non-tumour liver tissue, to identify perturbed biologic functions, co-expression modules, and potentially drugable hub genes that could give rise to novel therapeutic targets and strategies. Gene Set Variation Analysis (GSVA) showed that cell growth-related pathways were upregulated, whereas apoptosis induction, immune and inflammatory-related pathways were downregulated in tumour endothelial cells. Weighted Gene Co-expression Network Analysis (WGCNA) identified several modules strongly associated to tumour endothelial cells or angiogenic activated endothelial cells with high endoglin (ENG) expression. In tumour cells, upregulated modules were associated with cell growth, cell proliferation, and DNA-replication, whereas downregulated modules were involved in immune functions, particularly complement activation. In ENG+ cells, upregulated modules were associated with cell adhesion and endothelial functions. One downregulated module was associated with immune system-related functions. Querying the STRING database revealed known functional-interaction networks underlying the modules. Several possible hub genes were identified, of which some (for example FEN1, BIRC5, NEK2, CDKN3, and TTK) are potentially druggable as determined by querying the Drug Gene Interaction database. In summary, our study provides a detailed picture of the transcriptomic differences between tumour and non-tumour endothelium in the liver on a co-expression network level, indicates several potential therapeutic targets and presents an analysis workflow that can be easily adapted to other projects.
Catalytic Concepts for Methane Combustion
Authors: Wohlrab Sebastian , Kondratenko Evgenii V.
Published: April 2021

The release of methane from vehicles or/and stationary industrial sources must be reduced in order to control the emission of this greenhouse gas into the atmosphere [...]
The β-Fructofuranosidase from Rhodotorula dairenensis: Molecular Cloning, Heterologous Expression, and Evaluation of Its Transferase Activity
Authors: Gimeno-Pérez María , Merdzo Zoran , Castillo-Rosa Eva , Hijas Carlos Martín de , Fernández-Lobato María
Published: April 2021

The β-fructofuranosidase from the yeast Rhodotorula dairenensis (RdINV) produces a mixture of potential prebiotic fructooligosaccharides (FOS) of the levan-, inulin- and neo-FOS series by transfructosylation of sucrose. In this work, the gene responsible for this activity was characterized and its functionality proved in Pichia pastoris. The amino acid sequence of the new protein contained most of the characteristic elements of β-fructofuranosidases included in the family 32 of the glycosyl hydrolases (GH32). The heterologous yeast produced a protein of about 170 kDa, where N-linked and O-linked carbohydrates constituted about 15% and 38% of the total protein mass, respectively. Biochemical and kinetic properties of the heterologous protein were similar to the native enzyme, including its ability to produce prebiotic sugars. The maximum concentration of FOS obtained was 82.2 g/L, of which 6-kestose represented about 59% (w/w) of the total products synthesized. The potential of RdINV to fructosylate 19 hydroxylated compounds was also explored, of which eight sugars and four alditols were modified. The flexibility to recognize diverse fructosyl acceptors makes this protein valuable to produce novel glycosyl-compounds with potential applications in food and pharmaceutical industries.
Phosphorylation of Kindlins and the Control of Integrin Function
Authors: Bialkowska Katarzyna , Qin Jun , Plow Edward F.
Published: April 2021

Integrins serve as conduits for the transmission of information between cells and their extracellular environment. Signaling across integrins is bidirectional, transducing both inside-out and outside-signaling. Integrin activation, a transition from a low affinity/avidity state to a high affinity/avidity state for cognate ligands, is an outcome of inside-signaling. Such activation is particularly important for the recognition of soluble ligands by blood cells but also influences cell-cell and cell-matrix interactions. Integrin activation depends on a complex series of interactions, which both accelerate and inhibit their interconversion from the low to the high affinity/avidity state. There are three components regarded as being most proximately involved in integrin activation: the integrin cytoplasmic tails, talins and kindlins. The participation of each of these molecules in integrin activation is highly regulated by post-translation modifications. The importance of targeted phosphorylation of integrin cytoplasmic tails and talins in integrin activation is well-established, but much less is known about the role of post-translational modification of kindlins. The kindlins, a three-member family of 4.1-ezrin-radixin-moesin (FERM)-domain proteins in mammals, bind directly to the cytoplasmic tails of integrin beta subunits. This commentary provides a synopsis of the emerging evidence for the role of kindlin phosphorylation in integrin regulation.
Gingival Crevicular Placental Alkaline Phosphatase Is an Early Pregnancy Biomarker for Pre-Eclampsia
Authors: Chaparro Alejandra , Monckeberg Maximiliano , Realini Ornella , Hernández Marcela , Param Fernanda , Albers Daniela , Ramírez Valeria , Kusanovic Juan Pedro , Romero Roberto , Rice Gregory , Illanes Sebastián E.
Published: April 2021

Early and innovative diagnostic strategies are required to predict the risk of developing pre-eclampsia (PE). The purpose of this study was to evaluate the performance of gingival crevicular fluid (GCF) placental alkaline phosphatase (PLAP) concentrations to correctly classify women at risk of PE. A prospectively collected, retrospectively stratified cohort study was conducted, with 412 pregnant women recruited at 11–14 weeks of gestation. Physical, obstetrical, and periodontal data were recorded. GCF and blood samples were collected for PLAP determination by ELISA assay. A multiple logistic regression classification model was developed, and the classification efficiency of the model was established. Within the study cohort, 4.3% of pregnancies developed PE. GCF-PLAP concentration was 3- to 6-fold higher than in plasma samples. GCF-PLAP concentrations and systolic blood pressure were greater in women who developed PE (p = 0.015 and p < 0.001, respectively). The performance of the multiparametric model that combines GCF-PLAP concentration and the levels of systolic blood pressure (at 11–14 weeks gestation) showed an association of systolic blood pressure and GCF-PLAP concentrations with the likelihood of developing PE (OR:1.07; 95% CI 1.01–1.11; p = 0.004 and OR:1.008, 95% CI 1.000–1.015; p = 0.034, respectively). The model had a sensitivity of 83%, a specificity of 72%, and positive and negative predictive values of 12% and 99%, respectively. The area under the receiver operating characteristic (AUC-ROC) curve was 0.77 and correctly classified 72% of PE pregnancies. In conclusion, the multivariate classification model developed may be of utility as an aid in identifying pre-symptomatic women who subsequently develop PE.
A Computationally Efficient Framework for Modelling Energy Consumption of ICE and Electric Vehicles
Authors: Madhusudhanan Anil K. , Na Xiaoxiang , Cebon David
Published: April 2021

This article proposes a novel framework to develop computationally efficient energy consumption models of electric and internal combustion engine vehicles. The number of calculations in a conventional energy consumption model prevents the model’s usage in applications where time is limited. As many fleet operators around the world are in the process of transitioning towards electric vehicles, a computationally efficient energy consumption model will be valuable to analyse the vehicles they trial. A vehicle’s energy consumption depends on the vehicle characteristics, drive cycles and vehicle mass. The proposed modelling framework considers these aspects, is computationally efficient, and can be run using open source software packages. The framework is validated through two use cases: an electric bus and a diesel truck. The model error’s standard deviation is less 5% and its mean is less than 2%. The proposed model’s mean computation time is less than 20 ms, which is two orders of magnitude lower than that of the baseline model. Finally, a case study was performed to illustrate the usefulness of the modelling framework for a fleet operator.
Thermal Modernization Cost and the Potential Ecological Effect—Scenario Analysis for Thermal Modernization in Southern Poland
Authors: Blazy Rafał , Błachut Jakub , Ciepiela Agnieszka , Łabuz Rita , Papież Renata
Published: April 2021

Air pollution is one of the important environmental problems in Poland. The main cause of its occurrence is emissions associated with individual heating of buildings. The reduction of the primary energy demand in a building is influenced by its proper thermal modernization, including in particular insulating. In view of the above, this article presents the results of studies on the possible environmental benefits of thermal modernization of single-family houses for the area of Southern Poland. The analysis was limited to determining the impact of measures to reduce air pollution emissions by insulating the building envelope of single-family houses. The research was conducted for two voivodeships: Śląskie and Małopolskie. Its aim is to identify the financial costs and achievable ecological effects of the thermal modernization of single-family buildings. The geographical selection of the research area was based on the fact that it covers the most polluted region in Poland. This region is characterized by many features that influence poor air quality. Among these features, the most important are: diversified building structure, a diverse topography, and very high population density. To limit multiple variables, we have selected a scenario method that has already been used in similar research. Four scenarios were established to show the relationship between the value of emission reductions and the level of funding for thermal modernization. The analysis allows a comparison of the effectiveness of individual variants and the transposition of their results into the possibilities of action in the region. This research will help to supplement the knowledge of the impact of insulating building envelopes on reducing pollutant emissions by reducing the energy demand of a building. They also identify a possible link between the level of this reduction and the grant amount for thermal modernization. As a result, it was found that a high share of external funding—stimulating the tendency of the inhabitants of the analyzed voivodeships to effective thermal modernization, and thus reducing the buildings’ energy consumption—has a significant impact on the improvement of air quality.