bluuebunny/crossref_metadata_2025 huggingface dataset:
Trehalose Restrains the Fibril Load towards α-Lactalbumin Aggregation and Halts Fibrillation in a Concentration-Dependent Manner
Authors: Bashir Sania , Ahanger Ishfaq Ahmad , Shamsi Anas , Alajmi Mohamed F. , Hussain Afzal , Choudhry Hani , Ahmad Faizan , Hassan Md. Imtaiyaz , Islam Asimul
Published: March 2021

Protein aggregation and misfolding are some of the most challenging obstacles, customarily studied for their association with amyloid pathologies. The mechanism of amyloid fibrillation development is a dynamic phenomenon involving various factors such as the intrinsic properties of protein and the physical and chemical environmental conditions. The purpose of this study was to see the thermal aggregation profile of alpha-lactalbumin (α-LA) and to delineate the effect of trehalose on its aggregation profile. α-LA was subjected to thermal aggregation at high concentrations. UV-Vis spectroscopy, a turbidity assay, intrinsic fluorescence, Rayleigh scattering and a thioflavin T (ThT) assay explained the steady outcomes that 1 M trehalose repressed α-LA aggregation in the most effective way followed by 0.75 M and 0.5 M and to a significantly lesser degree by 0.25 M. Multi spectroscopic obser Sania Bashir ations were further entrenched by microscopy. Transmission electron microscopy confirmed that in the presence of its higher concentration, trehalose hinders fibril development in α-LA. In vitro studies were further validated by in silico studies. Molecular docking analysis indicated that trehalose occupied the binding pocket cavity of α-LA and offered several significant interactions, including H-bonds with important residues. This study provides a platform for trehalose in the therapeutic management of protein aggregation-related diseases.
Colposcopic Impression Has a Key Role in the Estimation of the Risk of HSIL/CIN3
Authors: del Pino Marta , Angeles Martina Aida , Martí Cristina , Henere Carla , Munmany Meritxell , Marimon Lorena , Saco Adela , Rakislova Natalia , Ordi Jaume , Torné Aureli
Published: March 2021

Recently published guidelines stratify the risk of high-grade squamous intraepithelial lesion/grade 3 cervical intraepithelial neoplasia (HSIL/CIN3) based on hrHPV detection and Pap smear results. However, colposcopic impression could also provide valuable information for risk estimation. We aimed to analyze the value of adding colposcopic impression to screening tests for the diagnosis of HSIL/CIN3 in 302 women referred for colposcopy due to an abnormal Pap smear. All women underwent hrHPV detection and genotyping (HPV 16/18 vs. non-16/18 hrHPV), Pap smear, and colposcopy with at least one biopsy. HSIL Pap smear, HPV 16/18, and grade 2 colposcopy findings increased the risk of HSIL/CIN3 in the univariate analysis but only colposcopy retained significance in the multivariate model. At least 30% of the women with grade 2 colposcopy findings had HSIL/CIN3, independent of the screening test results. Among women with an HSIL Pap smear and grade 2 colposcopy findings, 53.3% had HSIL/CIN3 independently of the hrHPV genotype. Contrarily, the prevalence of HSIL/CIN3 in women with <HSIL Pap smear, non-HPV 16/18 infection, and normal colposcopy or with grade 1 findings was 2.9% and 8.1%, respectively. In conclusion, colposcopy impression provides essential information to identify women at risk of HSIL/CIN3.
Co–Ce Oxides Supported on SBA-15 for VOCs Oxidation
Authors: Blin Jean-Luc , Michelin Laure , Lebeau Bénédicte , Naydenov Anton , Velinova Ralitsa , Kolev Hristo , Gaudin Pierrick , Vidal Loïc , Dotzeva Anna , Tenchev Krasimir , Todorova Silviya
Published: March 2021

Reported here are new data on the structural and catalytic properties of a series of mono-component cobalt and bi-component Co–Ce catalysts supported on SBA-15 (Santa Barbara Amorphous-15)). The catalysts performance has been evaluated by tests on combustion of methane, propane, and n-hexane. It was established that the preparation of the Co–Ce catalysts by the ‘two-solvent’ technique does not significantly change the mesoporous structure, however, its pores are clogging with the Co and Ce guest species. Cobalt and cerium are uniformly distributed and preferentially fill up the channels of SBA-15, but oxide agglomerates located on the surface are observed as well. The highest activity of the mono-component cobalt sample is explained by its higher reducibility as a result of lower interaction of the cobalt oxide with the SBA-15. The fine dispersion of cobalt and cerium oxide and their strong interaction in the channels of the SBA-15 molecular sieve, leads to the formation of difficult-to-reduce oxide phases and, consequently, to lower catalytic activity compared to monocomponent cobalt oxide catalyst. The synthesised mesoporous structure can prevent the agglomeration of the oxide particles, thus leading to the successful development of a new and stable catalyst for decreasing greenhouse gas emissions.
Genetic Deletion of Polo-Like Kinase 2 Induces a Pro-Fibrotic Pulmonary Phenotype
Authors: Kant Theresa A. , Newe Manja , Winter Luise , Hoffmann Maximilian , Kämmerer Susanne , Klapproth Erik , Künzel Karolina , Kühnel Mark P. , Neubert Lavinia , El-Armouche Ali , Künzel Stephan R.
Published: March 2021

Pulmonary fibrosis is the chronic-progressive replacement of healthy lung tissue by extracellular matrix, leading to the destruction of the alveolar architecture and ultimately death. Due to limited pathophysiological knowledge, causal therapies are still missing and consequently the prognosis is poor. Thus, there is an urgent clinical need for models to derive effective therapies. Polo-like kinase 2 (PLK2) is an emerging regulator of fibroblast function and fibrosis. We found a significant downregulation of PLK2 in four different entities of human pulmonary fibrosis. Therefore, we characterized the pulmonary phenotype of PLK2 knockout (KO) mice. Isolated pulmonary PLK2 KO fibroblasts displayed a pronounced myofibroblast phenotype reflected by increased expression of αSMA, reduced proliferation rates and enhanced ERK1/2 and SMAD2/3 phosphorylation. In PLK2 KO, the expression of the fibrotic cytokines osteopontin and IL18 was elevated compared to controls. Histological analysis of PLK2 KO lungs revealed early stage remodeling in terms of alveolar wall thickening, increased alveolar collagen deposition and myofibroblast foci. Our results prompt further investigation of PLK2 function in pulmonary fibrosis and suggest that the PLK2 KO model displays a genetic predisposition towards pulmonary fibrosis, which could be leveraged in future research on this topic.
The G-Protein-Coupled Estrogen Receptor (GPER) Regulates Trimethylation of Histone H3 at Lysine 4 and Represses Migration and Proliferation of Ovarian Cancer Cells In Vitro
Authors: Han Nan , Heublein Sabine , Jeschke Udo , Kuhn Christina , Hester Anna , Czogalla Bastian , Mahner Sven , Rottmann Miriam , Mayr Doris , Schmoeckel Elisa , Trillsch Fabian
Published: March 2021

Histone H3 lysine 4 trimethylation (H3K4me3) is one of the most recognized epigenetic regulators of transcriptional activity representing, an epigenetic modification of Histone H3. Previous reports have suggested that the broad H3K4me3 domain can be considered as an epigenetic signature for tumor-suppressor genes in human cells. G-protein-coupled estrogen receptor (GPER), a new membrane-bound estrogen receptor, acts as an inhibitor on cell growth via epigenetic regulation in breast and ovarian cancer cells. This study was conducted to evaluate the relationship of GPER and H3K4me3 in ovarian cancer tissue samples as well as in two different cell lines (Caov3 and Caov4). Silencing of GPER by a specific siRNA and two selective regulators with agonistic (G1) and antagonistic (G15) activity were applied for consecutive in vitro studies to investigate their impacts on tumor cell growth and the changes in phosphorylated ERK1/2 (p-ERK1/2) and H3K4me3. We found a positive correlation between GPER and H3K4me3 expression in ovarian cancer patients. Patients overexpressing GPER as well as H3K4me3 had significantly improved overall survival. Increased H3K4me3 and p-ERK1/2 levels and attenuated cell proliferation and migration were observed in Caov3 and Caov4 cells via activation of GPER by G1. Conversely, antagonizing GPER activity by G15 resulted in opposite effects in the Caov4 cell line. In conclusion, interaction of GPER and H3K4me3 appears to be of prognostic significance for ovarian cancer patients. The results of the in vitro analyses confirm the biological rationale for their interplay and identify GPER agonists, such as G1, as a potential therapeutic approach for future investigations.
Intensity of Radiative Recombination in the Germanium/Silicon Nanosystem with Germanium Quantum Dots
Authors: Pokutnyi Sergey I. , Jacak Lucjan
Published: March 2021

It is shown that in a germanium/silicon nanosystem with germanium quantum dots, the hole leaving the germanium quantum dot causes the appearance of the hole energy level in the bandgap energy in a silicon matrix. The dependences of the energies of the ground state of a hole and an electron are obtained as well as spatially indirect excitons on the radius of the germanium quantum dot and on the depth of the potential well for holes in the germanium quantum dot. It is found that as a result of a direct electron transition in real space between the electron level that is located in the conduction band of the silicon matrix and the hole level located in the bandgap of the silicon matrix, the radiative recombination intensity in the germanium/silicon nanosystem with germanium quantum dots increases significantly.
Regional Heterogeneity of Preferences and Intergovernmental Transfers
Authors: Ponce Rodríguez Raúl Alberto , Ponce Rodríguez Benito Alan
Published: March 2021

We develop a model with optimal shares of intergovernmental transfers, and we apply a simulation analysis of our model for the case of Mexico. The main outcomes of this paper are as follows: First, we provide optimal shares of intergovernmental funds to be allocated in each state considering the regional distribution of the benefits of local public spending in Mexico. Second, our analysis shows that the regional heterogeneity of preferences across regions should be an important determinant of federal funds allocated to state governments. Third, the current system of finance relies on a tax revenue sharing accord that emphasizes nationwide tax collection issues as the main determinants of intergovernmental transfers and local spending. Our analysis provides a contrast between how fiscal policy is conducted, and feasible choices of policy reform. Fourth, our analysis of simulation identifies winners and losers from policy reform, and so our analysis contributes to a better understanding of the advantages and shortcomings of the current policy of intergovernmental transfers, providing feasible ways to improve the outcomes of subnational government spending.
Digital Technologies—And Teacher Wellbeing?
Authors: Passey Don
Published: March 2021

The concept of teacher wellbeing, the importance of considering teacher wellbeing, concerns for developing digital wellbeing and concerns for using digital technologies to support teaching practices have all been previously studied. The idea that uses of digital technologies can support teacher wellbeing (or not) and ways that uses might do this have not been studied to the same extent. Indeed, it can be argued that this topic requires a complete and focused area of study in its own right. This methodologically focused paper takes an initial step in this direction, exploring existing research and backgrounds to wellbeing, teacher wellbeing, digital wellbeing and uses of digital technologies to support teachers’ practices. The paper reviews conceptions of digital technologies supporting teacher wellbeing and offers a newly developed outline conceptual model and framework for this research field. The framework is tested, identifying influencing factors from evidence presented in a number of existing relevant case studies where digital technologies have been used to support teacher practices. The efficacy of the proposed framework is assessed, and the paper concludes by offering a proposed research instrument and strategy to advance knowledge in this area.
Project-Based Learning and Evaluation in an Online Digital Design Course
Authors: Skliarova Iouliia
Published: March 2021

This paper reports an experience of an abrupt shift from traditional teaching to distance learning within a course on digital system design using programmable logic platforms. The course organization and evaluation model had to be modified on the fly due to the COVID-19 pandemic. The adopted teaching and assessment methodology puts a strong focus on the laboratory component, assigning a very significant weight to project-based evaluation. As the access to laboratory equipment was cut, all the previously accumulated experience had to be modified and adapted to new circumstances. The paper discusses teaching methods employed within the course and analyzes in detail a project-based evaluation accentuated on modeling of a simplified processor. The advantages and drawbacks of the reported teaching methods are appointed. Possible design extensions are also suggested, which permit assigning the same core project to different students. We believe that the proposed project is a valuable instructional tool, in particular, for remote learning/assessment.
A Wireless Covert Channel Based on Dirty Constellation with Phase Drift
Authors: Grzesiak Krystian , Piotrowski Zbigniew , Kelner Jan M.
Published: March 2021

Modern telecommunications systems require the use of various transmission techniques, which are either open or hidden. The open transmission system uses various security techniques against its unauthorized reception, and cryptographic solutions ensure the highest security. In the case of hidden transmissions, steganographic techniques are used, which are based on the so-called covert channels. In this case, the transparency and stealth of the transmission ensure its security against being picked up by an unauthorized user. These covert channels can be implemented in multimedia content, network protocols, or physical layer transmissions. This paper focuses on wireless covert channels. We present a novel method of steganographic transmission which is based on phase drift in phase-shift keying or quadrature amplitude modulation (QAM) and is included in the so-called dirty constellation techniques. The proposed approach is based on the drift correction modulation method, which was previously used in the watermarking of audio-signals. The developed solution is characterized by a variable bit rate, which can be adapted to the used modulation type and transmission conditions occurring in radio channels. In the paper, we present the method of generating and receiving hidden information, simulation research, and practical implementation of the proposed solution using the software-defined radio platform for selected QAM.
Cyber Attacks and Faults Discrimination in Intelligent Electronic Device-Based Energy Management Systems
Authors: Amin B. M. Ruhul , Hossain M. J. , Anwar Adnan , Zaman Shafquat
Published: March 2021

Intelligent electronic devices (IEDs) along with advanced information and communication technology (ICT)-based networks are emerging in the legacy power grid to obtain real-time system states and provide the energy management system (EMS) with wide-area monitoring and advanced control capabilities. Cyber attackers can inject malicious data into the EMS to mislead the state estimation process and disrupt operations or initiate blackouts. A machine learning algorithm (MLA)-based approach is presented in this paper to detect false data injection attacks (FDIAs) in an IED-based EMS. In addition, stealthy construction of FDIAs and their impact on the detection rate of MLAs are analyzed. Furthermore, the impacts of natural disturbances such as faults on the system are considered, and the research work is extended to distinguish between cyber attacks and faults by using state-of-the-art MLAs. In this paper, state-of-the-art MLAs such as Random Forest, OneR, Naive Bayes, SVM, and AdaBoost are used as detection classifiers, and performance parameters such as detection rate, false positive rate, precision, recall, and f-measure are analyzed for different case scenarios on the IEEE benchmark 14-bus system. The experimental results are validated using real-time load flow data from the New York Independent System Operator (NYISO).
When Data Fly: An Open Data Trading System in Vehicular Ad Hoc Networks
Authors: Lücking Markus , Kretzer Felix , Kannengießer Niclas , Beigl Michael , Sunyaev Ali , Stork Wilhelm
Published: March 2021

Communication between vehicles and their environment (i.e., vehicle-to-everything or V2X communication) in vehicular ad hoc networks (VANETs) has become of particular importance for smart cities. However, economic challenges, such as the cost incurred by data sharing (e.g., due to power consumption), hinder the integration of data sharing in open systems into smart city applications, such as dynamic environmental zones. Moving from open data sharing to open data trading can address the economic challenges and incentivize vehicle drivers to share their data. In this context, integrating distributed ledger technology (DLT) into open systems for data trading is promising for reducing the transaction cost of payments in data trading, avoiding dependencies on third parties, and guaranteeing openness. However, because the integration of DLT conflicts with the short available communication time between fast moving objects in VANETs, it remains unclear how open data trading in VANETs using DLT should be designed to be viable. In this work, we present a system design for data trading in VANETs using DLT. We measure the required communication time for data trading between a vehicle and a roadside unit in a real scenario and estimate the associated cost. Our results show that the proposed system design is technically feasible and economically viable.
The VIT Transform Approach to Discrete-Time Signals and Linear Time-Varying Systems
Authors: Kamen Edward W.
Published: March 2021

A transform approach based on a variable initial time (VIT) formulation is developed for discrete-time signals and linear time-varying discrete-time systems or digital filters. The VIT transform is a formal power series in z−1, which converts functions given by linear time-varying difference equations into left polynomial fractions with variable coefficients, and with initial conditions incorporated into the framework. It is shown that the transform satisfies a number of properties that are analogous to those of the ordinary z-transform, and that it is possible to do scaling of z−i by time functions, which results in left-fraction forms for the transform of a large class of functions including sinusoids with general time-varying amplitudes and frequencies. Using the extended right Euclidean algorithm in a skew polynomial ring with time-varying coefficients, it is shown that a sum of left polynomial fractions can be written as a single fraction, which results in linear time-varying recursions for the inverse transform of the combined fraction. The extraction of a first-order term from a given polynomial fraction is carried out in terms of the evaluation of zi at time functions. In the application to linear time-varying systems, it is proved that the VIT transform of the system output is equal to the product of the VIT transform of the input and the VIT transform of the unit-pulse response function. For systems given by a time-varying moving average or an autoregressive model, the transform framework is used to determine the steady-state output response resulting from various signal inputs such as the step and cosine functions.
Antioxidative, Antifungal and Additive Activity of the Antimicrobial Peptides Leg1 and Leg2 from Chickpea
Authors: Heymich Marie-Louise , Nißl Laura , Hahn Dominik , Noll Matthias , Pischetsrieder Monika
Published: March 2021

The fight against food waste benefits from novel agents inhibiting spoilage. The present study investigated the preservative potential of the antimicrobial peptides Leg1 (RIKTVTSFDLPALRFLKL) and Leg2 (RIKTVTSFDLPALRWLKL) recently identified in chickpea legumin hydrolysates. Checkerboard assays revealed strong additive antimicrobial effects of Leg1/Leg2 with sodium benzoate against Escherichia coli and Bacillus subtilis with fractional inhibitory concentrations of 0.625 and 0.75. Additionally, Leg1/Leg2 displayed antifungal activity with minimum inhibitory concentrations of 500/250 µM against Saccharomyces cerevisiae and 250/125 µM against Zygosaccharomyces bailii. In contrast, no cytotoxic effects were observed against human Caco-2 cells at concentrations below 2000 µM (Leg1) and 1000 µM (Leg2). Particularly Leg2 showed antioxidative activity by radical scavenging and reducing mechanisms (maximally 91.5/86.3% compared to 91.2/94.7% for the control ascorbic acid). The present results demonstrate that Leg1/Leg2 have the potential to be applied as preservatives protecting food and other products against bacterial, fungal and oxidative spoilage.
Whey Protein Derived Mouthdrying Found to Relate Directly to Retention Post Consumption but Not to Induced Differences in Salivary Flow Rate
Authors: Norton Victoria , Lignou Stella , Methven Lisa
Published: March 2021

Whey protein is fortified into beverages to provide functional benefits, however, these beverages are considered mouthdrying. To date whey protein derived mouthdrying has not been quantified using a ‘physical measure’ in parallel with rated perception. Saliva flow could also relate to whey protein derived mouthdrying, however this has not been previously tested as an intervention. Accordingly, volunteers (n = 40) tested mouthdrying in different whey beverages and the sensory profile was evaluated by a trained sensory panel (n = 10). Volunteers also rated mouthdrying combined with collection of saliva samples post beverage consumption to measure retention to the oral cavity. To modulate saliva flow rate, volunteers both chewed on parafilm (to increase saliva flow) and used cotton wool (to remove saliva) before tasting beverages and rating mouthdrying. Both the volunteers and sensory panel rated whey protein beverages (WPB) as significantly more mouthdrying than the control beverage (whey permeate). The significantly higher rating of mouthdrying from the volunteers coincided with significantly higher protein concentration in saliva samples post WPB consumption, supporting mucoadhesion as the mechanism. Modulating saliva flow did not lead to any difference in rated mouthdrying and future work would be beneficial to evaluate further the influence of natural variation in salivary flow rate.
Arthrospira platensis Extract: A Non-Invasive Strategy to Obtain Adjunct Attenuated Cultures
Authors: Bancalari Elena , Martelli Francesco , Bottari Benedetta , Neviani Erasmo , Gatti Monica
Published: March 2021

This study aims at proposing the use of Arthrospira platensis, commonly known as Spirulina, extract as a non-invasive method to attenuate the growth rate of non-starter adjunct cultures, thus preventing the over-acidification that may occur during cheese manufacturing. A preliminary screening using four different concentrations (0.20%, 0.30%, 0.50%, and 0.70%) of A. platensis extract and four starter and three non-starter lactic acid bacteria strains was performed by impedometric analysis. This allowed us to select one starter and one non-starter strain to be used in the in vitro simulation of a co-culture in milk with the best antimicrobial concentration (0.3%). The growth dynamics of the two selected strains, starter Lactococcus lactis 1426 and non-sarter Lacticaseibacillus rhamnosus 1473, co-cultured for 120 h was monitored by three different approaches: (i) plate counting on M17, for the enumeration of lactococci, and MRS for lactobacilli; (ii) fluorescence microscopic counting of viable and non-viable coccoid Lactococcus lactis 1426 and rod-shaped Lacticaseibacillus rhamnosus 1473 cells; (iii) the overall estimation of co-culture growth behavior by impedometric parameters Lag, Rate, and yEnd. All the data obtained from the in vitro simulation were in agreement, revealing that a slowdown of non-starter growth occurred, while the starter strain was not affected, or slightly stimulated, from the antimicrobial presence. In particular, the growth of Lb. rhamnosus 1473 was delayed without adversely compromise the cells’ integrity, connected with metabolic functions, showing a great potential for use in cheese production.
Volume-of-Interest Aware Deep Neural Networks for Rapid Chest CT-Based COVID-19 Patient Risk Assessment
Authors: Chatzitofis Anargyros , Cancian Pierandrea , Gkitsas Vasileios , Carlucci Alessandro , Stalidis Panagiotis , Albanis Georgios , Karakottas Antonis , Semertzidis Theodoros , Daras Petros , Giannitto Caterina , Casiraghi Elena , Sposta Federica Mrakic , Vatteroni Giulia , Ammirabile Angela , Lofino Ludovica , Ragucci Pasquala , Laino Maria Elena , Voza Antonio , Desai Antonio , Cecconi Maurizio , Balzarini Luca , Chiti Arturo , Zarpalas Dimitrios , Savevski Victor
Published: March 2021

Since December 2019, the world has been devastated by the Coronavirus Disease 2019 (COVID-19) pandemic. Emergency Departments have been experiencing situations of urgency where clinical experts, without long experience and mature means in the fight against COVID-19, have to rapidly decide the most proper patient treatment. In this context, we introduce an artificially intelligent tool for effective and efficient Computed Tomography (CT)-based risk assessment to improve treatment and patient care. In this paper, we introduce a data-driven approach built on top of volume-of-interest aware deep neural networks for automatic COVID-19 patient risk assessment (discharged, hospitalized, intensive care unit) based on lung infection quantization through segmentation and, subsequently, CT classification. We tackle the high and varying dimensionality of the CT input by detecting and analyzing only a sub-volume of the CT, the Volume-of-Interest (VoI). Differently from recent strategies that consider infected CT slices without requiring any spatial coherency between them, or use the whole lung volume by applying abrupt and lossy volume down-sampling, we assess only the “most infected volume” composed of slices at its original spatial resolution. To achieve the above, we create, present and publish a new labeled and annotated CT dataset with 626 CT samples from COVID-19 patients. The comparison against such strategies proves the effectiveness of our VoI-based approach. We achieve remarkable performance on patient risk assessment evaluated on balanced data by reaching 88.88%, 89.77%, 94.73% and 88.88% accuracy, sensitivity, specificity and F1-score, respectively.
Factors Affecting the Initial Engagement of Older Adults in the Use of Interactive Technology
Authors: Lee Lina , Maher Mary Lou
Published: March 2021

Smart environments and the use of interactive technology has the potential to improve the quality of life for the senior community as well as to support the connections among the senior community and the world outside their community. In addition to the increasing number of studies in the field of aging and technologies, research is needed to understand the practical issues of user focus, adoption, and engagement for older adults to accept interactive technologies in their lives. In this study, we use two commercial technological interventions (uDraw and GrandPad) to understand technology-related perceptions and behaviors of older adults. We present five case studies that emerge from empirical observations of initial engagement with technology through research methods such as focus group discussions, in-depth interviews, observations, and diary studies. The contributions of this study are identification of the key factors that influence the initial engagement with interactive technology for older adults.
Associations between Hip Fracture Operation Waiting Time and Complications in Asian Geriatric Patients: A Taiwan Medical Center Study
Authors: Shen Ching-Yi , Hsiao Chien-Han , Tsai Weide , Chang Wen-Han , Chen Tse-Hao
Published: March 2021

Early surgical intervention in hip fractures is associated with lower complications. This study aimed to determine the appropriate operation time among Asian geriatric patients. The data of 1118 elderly patients with hip fracture at Mackay Memorial Hospital from 1 January 2011, to 31 July 2019, were retrospectively examined. Association between operation waiting time and the occurrence of complications was calculated using a cubic spline model. Significantly increased incidence of pneumonia, myocardial infarction, and heart failure was observed in 30 and 90 days when the patient’s surgical waiting time exceeded 36 h. The incidence rates of pneumonia across the early and delayed groups within 30 and 90 days were 4.4% vs. 7.9%, and 6.2% vs. 10.7%, those of myocardial infarction were 3.0% vs. 7.2%, and 5.7% vs. 9.3%, and those of heart failure were 15.2% vs. 26.8%, and 16.2% vs. 28.5%. Deep vein thrombosis and pulmonary embolism were not associated with surgical delay. The overall 30-day mortality rate was 5.4%, and no significant difference was observed when the surgical waiting time exceeded 36 h. In summary, operation waiting time exceeding 36-h was associated with increased rates of pneumonia, myocardial infarction, and heart failure in Asian geriatric patients undergoing hip fracture surgery.
A Contributor-Focused Intrinsic Quality Assessment of OpenStreetMap in Mozambique Using Unsupervised Machine Learning
Authors: Madubedube Aphiwe , Coetzee Serena , Rautenbach Victoria
Published: March 2021

Anyone can contribute geographic information to OpenStreetMap (OSM), regardless of their level of experience or skills, which has raised concerns about quality. When reference data is not available to assess the quality of OSM data, intrinsic methods that assess the data and its metadata can be used. In this study, we applied unsupervised machine learning for analysing OSM history data to get a better understanding of who contributed when and how in Mozambique. Even though no absolute statements can be made about the quality of the data, the results provide valuable insight into the quality. Most of the data in Mozambique (93%) was contributed by a small group of active contributors (25%). However, these were less active than the OSM Foundation’s definition of active contributorship and the Humanitarian OpenStreetMap Team (HOT) definition for intermediate mappers. Compared to other contributor classifications, our results revealed a new class: contributors who were new in the area and most likely attracted by HOT mapping events during disaster relief operations in Mozambique in 2019. More studies in different parts of the world would establish whether the patterns observed here are typical for developing countries. Intrinsic methods cannot replace ground truthing or extrinsic methods, but provide alternative ways for gaining insight about quality, and they can also be used to inform efforts to further improve the quality. We provide suggestions for how contributor-focused intrinsic quality assessments could be further refined.
Effect of High-Density Lipoprotein from Healthy Subjects and Chronic Kidney Disease Patients on the CD14 Expression on Polymorphonuclear Leukocytes
Authors: Cohen Gerald
Published: March 2021

In uremic patients, high-density lipoprotein (HDL) loses its anti-inflammatory features and can even become pro-inflammatory due to an altered protein composition. In chronic kidney disease (CKD), impaired functions of polymorphonuclear leukocytes (PMNLs) contribute to inflammation and an increased risk of cardiovascular disease. This study investigated the effect of HDL from CKD and hemodialysis (HD) patients on the CD14 expression on PMNLs. HDL was isolated using a one-step density gradient centrifugation. Isolation of PMNLs was carried out by discontinuous Ficoll-Hypaque density gradient centrifugation. CD14 surface expression was quantified by flow cytometry. The activity of the small GTPase Rac1 was determined by means of an activation pull-down assay. HDL increased the CD14 surface expression on PMNLs. This effect was more pronounced for HDL isolated from uremic patients. The acute phase protein serum amyloid A (SAA) caused higher CD14 expression, while SAA as part of an HDL particle did not. Lipid raft disruption with methyl-β-cyclodextrin led to a reduced CD14 expression in the absence and presence of HDL. HDL from healthy subjects but not from HD patients decreased the activity of Rac1. Considering the known anti-inflammatory effects of HDL, the finding that even HDL from healthy subjects increased the CD14 expression was unexpected. The pathophysiological relevance of this result needs further investigation.
Muscle Proteomic Profile before and after Enzyme Replacement Therapy in Late-Onset Pompe Disease
Authors: Moriggi Manuela , Capitanio Daniele , Torretta Enrica , Barbacini Pietro , Bragato Cinzia , Sartori Patrizia , Moggio Maurizio , Maggi Lorenzo , Mora Marina , Gelfi Cecilia
Published: March 2021

Mutations in the acidic alpha-glucosidase (GAA) coding gene cause Pompe disease. Late-onset Pompe disease (LOPD) is characterized by progressive proximal and axial muscle weakness and atrophy, causing respiratory failure. Enzyme replacement therapy (ERT), based on recombinant human GAA infusions, is the only available treatment; however, the efficacy of ERT is variable. Here we address the question whether proteins at variance in LOPD muscle of patients before and after 1 year of ERT, compared withhealthy age-matched subjects (CTR), reveal a specific signature. Proteins extracted from skeletal muscle of LOPD patients and CTR were analyzed by combining gel based (two-dimensional difference gel electrophoresis) and label-free (liquid chromatography-mass spectrometry) proteomic approaches, and ingenuity pathway analysis. Upstream regulators targeting autophagy and lysosomal tethering were assessed by immunoblotting. 178 proteins were changed in abundance in LOPD patients, 47 of them recovered normal level after ERT. Defects in oxidative metabolism, muscle contractile protein regulation, cytoskeletal rearrangement, and membrane reorganization persisted. Metabolic changes, ER stress and UPR (unfolded protein response) contribute to muscle proteostasis dysregulation with active membrane remodeling (high levels of LC3BII/LC3BI) and accumulation of p62, suggesting imbalance in the autophagic process. Active lysosome biogenesis characterizes both LOPD PRE and POST, unparalleled by molecules involved in lysosome tethering (VAMP8, SNAP29, STX17, and GORASP2) and BNIP3. In conclusion this study reveals a specific signature that suggests ERT prolongation and molecular targets to ameliorate patient’s outcome.
Diagnostic Accuracy in Teleneurological Stroke Consultations
Authors: Kühne Escolà Jordi , Nagel Simon , Verez Sola Christina , Doroszewski Eva , Jaschonek Hannah , Gutschalk Alexander , Gumbinger Christoph , Purrucker Jan C.
Published: March 2021

Background: The accuracy of diagnosing acute cerebrovascular disease via a teleneurology service and the characteristics of misdiagnosed patients are insufficiently known. Methods: A random sample (n = 1500) of all teleneurological consultations conducted between July 2015 and December 2017 was screened. Teleneurological diagnosis and hospital discharge diagnosis were compared. Diagnoses were then grouped into two main categories: cerebrovascular disease (CVD) and noncerebrovascular disease. Test characteristics were calculated. Results: Out of 1078 consultations, 52% (n = 561) had a final diagnosis of CVD. Patients with CVD could be accurately identified via teleneurological consultation (sensitivity 95.2%, 95% CI 93.2–96.8), but we observed a tendency towards false-positive diagnosis (specificity 77.4%, 95% CI 73.6–80.8). Characteristics of patients with a false-negative CVD diagnosis were similar to those of patients with a true-positive diagnosis, but patients with a false-negative CVD diagnosis had ischemic heart disease less frequently. In retrospect, one patient would have been considered a candidate for intravenous thrombolysis (0.2%). Conclusions: Teleneurological consultations are accurate for identifying patients with CVD, and there is a very low rate of missed candidates for thrombolysis. Apart from a lower prevalence of ischemic heart disease, characteristics of “stroke chameleons” were similar to those of correctly identified CVD patients.
Predictive Genetic Variations in the Kynurenine Pathway for Interferon-α-Induced Depression in Patients with Hepatitis C Viral Infection
Authors: Cheng Szu-Wei , Li Jing-Xing , Chen Daniel Tzu-Li , Chien Yu-Chuan , Chang Jane Pei-Chen , Huang Shih-Yi , Galecki Piotr , Su Kuan-Pin
Published: March 2021

Importance: The high incidence of major depressive episodes during interferon-α (IFN-α) therapy is considered the most powerful supportive evidence for the inflammation theory of depression. As the kynurenine pathway plays an important role connecting inflammation and depression, it is plausible to investigate this pathway for predictive genetic markers for IFN-α-induced depression. Methods: In this prospective case-control study, we assessed 291 patients with chronic hepatitis C viral infection taking IFN-α therapy and analyzed the single nucleotide polymorphisms (SNPs) in genes in the kynurenine pathway. Our case group contained patients who developed IFN-α-induced depression during the treatment, and others were defined as the control group. Genomic DNA was extracted from leukocytes in the peripheral blood and analyzed by Affymetrix TWB array. We first tested allelic, dominant, and recessive models on each of our SNPs using Fisher’s exact test. We then conducted 5000 gene-wide max(T) permutations based on the best model of each SNP to provide strong gene-wide family-wise error rate control. Finally, we preformed logistic regression for the significant SNPs acquired in previous procedures, with sex and education level as covariates to build predictive models. Additional haplotype analyses were conducted with Haploview 4.2 to investigate the combining effect of multiple significant SNPs within a gene. Results: With sex and education level as covariates, rs8082252 (p = 0.0015, odds ratio = 2.716), rs8082142 (p = 0.0031, odds ratio = 2.499) in arylformamidase (AFMID), and rs12477181 (p = 0.0004, odds ratio = 0.3478) in kynureninase (KYNU) were significant in logistic regression models with dominant modes of inheritance. Haplotype analyses showed the two significant SNPs in AFMID to be in the same haploblock and highly correlated (r2 = 0.99). There were two significant haplotypes (by the sequence of rs8082252, rs8082142): AT (χ2 = 7.734, p = 0.0054) and GC (χ2 = 6.874, p = 0.0087). Conclusions: This study provided supportive evidence of the involvement of the kynurenine pathway in IFN-α-induced depression. SNPs in this pathway were also predictive of this disease.
Current and Future Land Use Characters of a National Central City in Eco-Fragile Region—A Case Study in Xi’an City Based on FLUS Model
Authors: Feng Dingrao , Bao Wenkai , Fu Meichen , Zhang Min , Sun Yiyu
Published: March 2021

Land use change plays a key role in terrestrial systems and drives the process of ecological pattern change. It is important to investigate the process of land use change, predict land use patterns, and reveal the characteristics of land use dynamics. In this study, we adopted the Markov model and future land use (FLUS) model to predict the future land use conditions in Xi’an city. Furthermore, we investigated the characteristics of land use change from a novel perspective, i.e., via establishment of a complex network model. This model captured the characteristics of the land use system during different periods. The results indicated that urban expansion and cropland loss played an important role in land use pattern change. The future gravity center of urban development moved along the opposite direction to that from 2000 to 2015 in Xi’an city. Although the rate of urban expansion declined in the future, urban expansion remained the primary driver of land use change. The primary urban development directions were east-southeast (ENE), north-northeast (NNE) and west-southwest (WSW) from 1990 to 2000, 2000 to 2015, and 2015 to 2030, respectively. In fact, cropland played a vital role in land use dynamics regarding all land use types, and the stability of the land use system decreased in the future. Our study provides future land use patterns and a novel perspective to better understand land use change.
Pro-Oxidant/Antioxidant Balance during a Prolonged Exposure to Moderate Altitude in Athletes Exhibiting Exercise-Induced Hypoxemia at Sea-Level
Authors: Raberin Antoine , Nader Elie , Lopez Ayerbe Jorge , Alfonsi Gauthier , Mucci Patrick , Rytz Chantal L. , Pialoux Vincent , Durand Fabienne
Published: March 2021

This study examined to what extent athletes exhibiting exercise-induced hypoxemia (EIH) possess an altered redox status at rest, in response to exercise at sea level (SL) and during moderate altitude exposure. EIH was defined as a fall in arterial O2 saturation of at least 4% during exercise. Nine endurance athletes with EIH and ten without (NEIH) performed a maximal incremental test under three conditions: SL, one (H1) and five (H2) days after arrival to 2400 m. Gas exchange and peripheral capillary oxygen saturation (SpO2) were continuously monitored. Blood was sampled before exercise and after exercise cessation. Advanced oxidation protein products (AOPP), catalase, ferric-reducing antioxidant power, glutathione peroxidase, superoxide dismutase (SOD) and nitric oxide metabolites (NOx) were measured in plasma by spectrophotometry. EIH athletes had higher AOPP and NOx concentrations at pre- and post-exercise stages compared to NEIH at SL, H2 but not at H1. Only the EIH group experienced increased SOD activity between pre- and post-exercise exercise at SL and H2 but not at H1. EIH athletes had exacerbated oxidative stress compared to the NEIH athletes at SL and H2. These differences were blunted at H1. Oxidative stress did not alter the EIH groups’ aerobic performance and could lead to higher minute ventilation at H2. These results suggest that higher oxidative stress response EIH athletes could be involved in improved aerobic muscle functionality and a greater ventilatory acclimatization during prolonged hypoxia.
The Cellular Senescence Stress Response in Post-Mitotic Brain Cells: Cell Survival at the Expense of Tissue Degeneration
Authors: Sah Eric , Krishnamurthy Sudarshan , Ahmidouch Mohamed Y. , Gillispie Gregory J. , Milligan Carol , Orr Miranda E.
Published: March 2021

In 1960, Rita Levi-Montalcini and Barbara Booker made an observation that transformed neuroscience: as neurons mature, they become apoptosis resistant. The following year Leonard Hayflick and Paul Moorhead described a stable replicative arrest of cells in vitro, termed “senescence”. For nearly 60 years, the cell biology fields of neuroscience and senescence ran in parallel, each separately defining phenotypes and uncovering molecular mediators to explain the 1960s observations of their founding mothers and fathers, respectively. During this time neuroscientists have consistently observed the remarkable ability of neurons to survive. Despite residing in environments of chronic inflammation and degeneration, as occurs in numerous neurodegenerative diseases, often times the neurons with highest levels of pathology resist death. Similarly, cellular senescence (hereon referred to simply as “senescence”) now is recognized as a complex stress response that culminates with a change in cell fate. Instead of reacting to cellular/DNA damage by proliferation or apoptosis, senescent cells survive in a stable cell cycle arrest. Senescent cells simultaneously contribute to chronic tissue degeneration by secreting deleterious molecules that negatively impact surrounding cells. These fields have finally collided. Neuroscientists have begun applying concepts of senescence to the brain, including post-mitotic cells. This initially presented conceptual challenges to senescence cell biologists. Nonetheless, efforts to understand senescence in the context of brain aging and neurodegenerative disease and injury emerged and are advancing the field. The present review uses pre-defined criteria to evaluate evidence for post-mitotic brain cell senescence. A closer interaction between neuro and senescent cell biologists has potential to advance both disciplines and explain fundamental questions that have plagued their fields for decades.
5-(4-Fluorophenyl)-3-(naphthalen-1-yl)-1-phenyl-1H-pyrazole
Authors: Jasril Jasril , Frimayanti Neni , Nurulita Yuana , Zamri Adel , Ikhtiarudin Ihsan , Guntur Guntur
Published: March 2021

A new fluorinated pyrazole, 5-(4-fluorophenyl)-3-(naphthalen-1-yl)-1-phenyl-1H-pyrazole was successfully synthesized via a two-step reaction. Firstly, the synthesis of pyrazoline was performed via one-pot three-component reaction under microwave irradiation. Secondly, the synthesis of pyrazole was performed via oxidative aromatization of pyrazoline under conventional heating. The structure of the synthesized compound was confirmed by spectroscopic analysis, including FT-IR, HR-MS, 1D and 2D NMR analysis. Then, molecular docking study showed that the binding affinity of the synthesized compound to human estrogen alpha receptor (ERα) was close to 4-OHT as a native ligand.
pH-Sensitive Membranes with Smart Cleaning Capability for Efficient Emulsion Separation and Pollutant Removal
Authors: Zhang Jiaming , Zhang Xiansheng , Wei Wei , Zhang Huiling , Wang Yunfei , Cai Guoqiang , Wu Jindan
Published: March 2021

Since anionic dyes and surfactants abundantly exist in oily wastewater, both the separation of oil/water mixture and removal of low-molecular-weight pollutants are important to realize the advanced purification of water. By grafting poly(2-dimethylaminoethyl methacrylate) (pDMAEMA) onto polyethylene (PP) membrane via ultraviolet (UV)-initiated polymerization, the obtained PP-g-pDMAEMA membrane presented positively in water and negatively in an alkaline buffer (pH 9.0), respectively. Due to the switchable surface charge, the membrane had high emulsion separation efficiency and flux recovery ratio (approximately 100%). Besides, the dye (reactive black 5, RB-5) adsorption capacity reached 140 mg/m2 in water, and approximately 90% RB-5 could be released in pH 9.0. The anionic surfactant (sodium dodecyl benzene sulfonate, SDBS) was also reversely interpreted and released by the membrane via manipulating the ambient pH. The membrane constructed in this study is supposed to realize emulsion separation with smart cleaning capability, as well as the removal of dyes and surfactants, which could be utilized for multifunctional water purification.
Numerical Analysis of the Welding Behaviors in Micro-Copper Bumps
Authors: Hwang Yeong-Maw , Pan Cheng-Tang , Chen Bo-Syun , Jian Sheng-Rui
Published: March 2021

In this study, three-dimensional simulations of the ultrasonic vibration bonding process of micro-copper blocks were conducted using the finite element method. We analyzed the effects of ultrasonic vibration frequency on the stress field, strain field, and temperature field at the copper bump joint surface. The results showed that the bonding process is successfully simulated at room temperature. The stress curve of the bonding process could be divided into three stages: stress rising stage, stress falling stage, and stress stabilization stage. Moreover, it was found that the end of the curve exhibited characteristics of a solid solution phase at higher frequencies. It is hypothesized that the high-density dislocations formed at this stage may result in conveyance channels that facilitate the atomic diffusion at the contact surface. The simulation results indicated that copper micro-bump bonding occurs at an ultrasonic frequency of 50 kHz or higher.