bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of Stop Plan for Skip-Stop Operation on Suburban Railway Line
Authors: Xu Jun , Liang Qinghuai , Huang Xiaoyu , Wang Le
Published: October 2021

A combination of express and local trains (E/L mode) is generally used to operate a suburban rail service, it can meet the rapid and direct service needs of long-distance travelers as well the needs of short-distance travelers. Generally, a stop plan is the core of the E/L mode. A stop plan optimization model in E/L mode, which aims to minimize the total passenger travel time and the number of operating trains during the peak period with the safe headway and departure frequency constraints, is proposed in this study. Meanwhile, an algorithm based on a genetic algorithm is designed to solve the proposed model. A case study of the Jiangjin Line, a suburban railway in Chongqing, China, is carried out. The results show the efficiency and feasibility of the proposed method. The calculation results also show that the total passenger travel time under E/L mode with the overtaking condition is significantly reduced compared with the all-stops (AS) mode and E/L mode without overtaking condition. The superiority of the E/L mode can be enhanced by reducing the dwell time at stations and adopting the overtaking condition.
Exploratory Analysis of Fundamental Spiritual Support Factors to a Positive Attitude in Patients with COVID-19 Using Natural-Language Processing Algorithms
Authors: Sánchez-Garcés Jorge , López-Gonzales Javier Linkolk , Palacio-Farfán Miguel , Coronel-Sacón Víctor , Ferney-Teheran Yonny , Peñuela-Pineda Jahisber , Avila-George Himer
Published: October 2021

The SARS-CoV-2 virus that causes COVID-19 affects the respiratory tract and is highly infectious. Those patients who knew that the disease could cause death or that their healing process is quite painful because of the symptoms and conditions developed extreme stress, anxiety, and depression, which aggravated the effects of the disease. Therefore, it is vital to conduct research to analyze these effects and generate self-help and support mechanisms during the disease process. This paper presents exploratory analysis related to stress, coping attitudes, emotional responses, and sources of support that were vital in patients affected by COVID-19; the focus of this study is the consideration of the spiritual factor, which may influence religious resilience that allows for a positive attitude and tenacity. To carry out this research, interviews were conducted with patients who had suffered from COVID-19 disease, and the collected information was processed using text-mining techniques using a two-phase methodology. The first phase is based on the Colaizzi method. Interview responses were coded through the search for patterns in the key phrases, and these codes were grouped, forming semantic relationships. In the second phase, natural-language processing algorithms (WordCloud, WordEmbedding, sentiment analysis of opinions) were used, summarizing the interviews in relevant factors of the patient’s experience during the disease. Spiritual resilience stood out the most of all key phrases of the code group tables. Likewise, words such as security, confidence, tranquility, and peace indicated that the patients took a positive attitude towards the symptoms and complications of the disease. Therefore, it is important to be the resilience to face a crisis process, and one of the factors that generated such resilience in COVID-19 patients was religious faith, which was expressed in the interviews using the factors of security, trust, promises of healing, tranquility, and the impossibility of discouragement. All this contributed to the positive attitude of the interviewees during the process of recovery from the disease.
“Pro Honore et Libertate Ecclesiae Invicta Fortitude Sustinuit”—The Oratory of St Thomas Becket in the Cathedral of Anagni
Authors: Quattrocchi Claudia
Published: October 2021

On the 9th of October, 1170 Pope Alexander III resided in Anagni, which had been the ancient residence of the court of the Popes for at least two centuries. He wrote to two influential local archbishops for help in pacifying King Henry II and Archbishop Thomas Becket, who had been in dispute for six years. Sensing Becket’s looming tragic fate, Alexander III began slowly to encircle the archbishop with rhetoric of the new martyr of Libertas Ecclesiae. When he had to flee from Rome besieged by factions led by Frederick I, the pope found refuge in Segni, where he canonised Thomas Becket on 21 February 1173. However, it was in faithful Anagni that he settled on and off from March 1173 through the following years (November 1176; December 1177–March 1178; September 1179). It was here that he decided to elaborate a powerful speech in images. In an oratory in the crypt of the grandiose cathedral, Alexander III had the last painful moments of the Archbishop’s death painted in a program imitating that of St. Peter’s in the Vatican. Becket thus became the new imitator of Christ, the new Peter, the new martyr on the altar of the Church of Rome.
Soft Sensors for State of Charge, State of Energy, and Power Loss in Formula Student Electric Vehicle
Authors: Purohit Kanishkavikram , Srivastava Shivangi , Nookala Varun , Joshi Vivek , Shah Pritesh , Sekhar Ravi , Panchal Satyam , Fowler Michael , Fraser Roydon , Tran Manh-Kien , Shum Chris
Published: October 2021

The proliferation of electric vehicle (EV) technology is an important step towards a more sustainable future. In the current work, two-layer feed-forward artificial neural-network-based machine learning is applied to design soft sensors to estimate the state of charge (SOC), state of energy (SOE), and power loss (PL) of a formula student electric vehicle (FSEV) battery-pack system. The proposed soft sensors were designed to predict the SOC, SOE, and PL of the EV battery pack on the basis of the input current profile. The input current profile was derived on the basis of the designed vehicle parameters, and formula Bharat track features and guidelines. All developed soft sensors were tested for mean squared error (MSE) and R-squared metrics of the dataset partitions; equations relating the derived and predicted outputs; error histograms of the training, validation, and testing datasets; training state indicators such as gradient, mu, and validation fails; validation performance over successive epochs; and predicted versus derived plots over one lap time. Moreover, the prediction accuracy of the proposed soft sensors was compared against linear or nonlinear regression models and parametric structure models used for system identification such as autoregressive with exogenous variables (ARX), autoregressive moving average with exogenous variables (ARMAX), output error (OE) and Box Jenkins (BJ). The testing dataset accuracy of the proposed FSEV SOC, SOE, PL soft sensors was 99.96%, 99.96%, and 99.99%, respectively. The proposed soft sensors attained higher prediction accuracy than that of the modelling structures mentioned above. FSEV results also indicated that the SOC and SOE dropped from 97% to 93.5% and 93.8%, respectively, during the running time of 118 s (one lap time). Thus, two-layer feed-forward neural-network-based soft sensors can be applied for the effective monitoring and prediction of SOC, SOE, and PL during the operation of EVs.
The Effects of the Width of an Isolated Valley on Near-Surface Turbulence
Authors: Freitas Sylvio , Harms Frank , Leitl Bernd
Published: October 2021

With the aim of ascertaining the effects of the widths (A) of valleys on near-surface turbulence, flows over an isolated symmetric three-dimensional valley of constant depth (H) and slopes are characterized in a large-boundary-layer wind tunnel. Starting at A = 4H, valley widths were systematically varied to A = 12H with constant increments of 2H. High-resolution laser-Doppler velocimetry measurements were made at several equivalent locations above each of the resulting valley geometries and compared with data from undisturbed flows over flat terrain. Flow separation caused by the first ridges generated inner-valley recirculation bubbles with lengths dependent on the valley widths. Secondary recirculation zones were also observed downstream from the crests of the second ridges. Results show that the width modifications exert the strongest effects on turbulence within the valleys and the vicinities of the second ridges. Above these locations, maximal magnitudes of turbulence are generally found for the larger width geometries. Furthermore, lateral turbulence overpowers the longitudinal counterparts nearest to the surface, with maximal gains occurring for the smaller widths. Our data indicate that valley widths are impactful on near-surface flows and should be considered together with other more established geometric parameters of influence.
Health Risks to the Russian Population from Temperature Extremes at the Beginning of the XXI Century
Authors: Grigorieva Elena A. , Revich Boris A.
Published: October 2021

Climate change and climate-sensitive disasters caused by climatic hazards have a significant and increasing direct and indirect impact on human health. Due to its vast area, complex geographical environment and various climatic conditions, Russia is one of the countries that suffers significantly from frequent climate hazards. This paper provides information about temperature extremes in Russia in the beginning of the 21st century, and their impact on human health. A literature search was conducted using the electronic databases Web of Science, Science Direct, Scopus, and e-Library, focusing on peer-reviewed journal articles published in English and in Russian from 2000 to 2021. The results are summarized in 16 studies, which are divided into location-based groups, including Moscow, Saint Petersburg and other large cities located in various climatic zones: in the Arctic, in Siberia and in the southern regions, in ultra-continental and monsoon climate. Heat waves in cities with a temperate continental climate lead to a significant increase in all-cause mortality than cold waves, compared with cities in other climatic zones. At the same time, in northern cities, in contrast to the southern regions and central Siberia, the influence of cold waves is more pronounced on mortality than heat waves. To adequately protect the population from the effects of temperature waves and to carry out preventive measures, it is necessary to know specific threshold values of air temperature in each city.
Indoor Air Quality in Healthcare and Care Facilities: Chemical Pollutants and Microbiological Contaminants
Authors: Baudet Alexandre , Baurès Estelle , Guegan Hélène , Blanchard Olivier , Guillaso Monique , Le Cann Pierre , Gangneux Jean-Pierre , Florentin Arnaud
Published: October 2021

The indoor air quality of healthcare and care facilities is poorly studied. The aim of this study was to qualitatively and quantitatively describe the chemical pollution and the microbiological contaminations of the indoor environment of these facilities. Methods: A wide range of chemical compounds (39 volatile and 13 semi-volatile organic compounds, carbon dioxide, fine particulate matter) and microorganisms (fungi and bacteria) were studied. Sampling campaigns were conducted in two French cities in summer 2018 and winter 2019 in six private healthcare facilities (general practitioner’s offices, dental offices, pharmacies) and four care facilities (nursing homes). Results: The highest median concentrations of chemical compounds (μg/m3) were measured for alcohols (ethanol: 378.9 and isopropanol: 23.6), ketones (acetone: 18.8), aldehydes (formaldehyde: 11.4 and acetaldehyde: 6.5) and terpenes (limonene: 4.3). The median concentration of PM2.5 was 9.0 µg/m3. The main bacteria of these indoor environments were Staphylococcus, Micrococcus and Bacillus genera, with median bacterial concentrations in the indoor air of 14 cfu/m3. The two major fungal genera were Cladosporium and Penicillium, with median fungal concentrations of 7 cfu/m3. Conclusions: Indoor air in healthcare and care facilities contains a complex mixture of many pollutants found in higher concentrations compared to the indoor air in French hospitals in a previous study.
Spatiotemporal Change of Air-Quality Patterns in Hubei Province—A Pre- to Post-COVID-19 Analysis Using Path Analysis and Regression
Authors: Aamir Muhammad , Li Zeyun , Bazai Sibghatullah , Wagan Raja Asif , Bhatti Uzair Aslam , Nizamani Mir Muhammad , Akram Shakeel
Published: October 2021

Mitigation measures and control strategies relating to the novel coronavirus disease 2019 (COVID-19) have been widely applied in many countries to reduce the transmission of this pandemic disease. China was the first country to implement a strong lockdown policy to control COVID-19 when countries worldwide were struggling to manage COVID-19 cases. However, lockdown causes numerous changes to air-quality patterns due to the low amount of traffic and the decreased human mobility it results in. To study the impact of the strict control measures of the new COVID-19 epidemic on the air quality of Hubei in early 2020, the air-quality monitoring data of Hubei’s four cities, namely Huangshi, Yichang, Jingzhou, and Wuhan, from 2019 to 2021, specifically 1 January to 30 August, was examined to analyze the characteristics of the temporal and spatial distribution. All air-quality pollutants decreased during the active-COVID-19 period, with a maximum decrease of 26% observed in PM10, followed by 23% of PM2.5, and a minimum decrease of 5% observed in O3. Changes in air pollutants from 2017 to 2021 were also compared, and a decrease in all pollutants through to 2020 was found. The air-quality index (AQI) recorded an increase of 2% post-COVID-19, which shows that air quality will worsen in future, but it decreased by 22% during the active-COVID-19 period. A path analysis model was developed to further understand the relationship between the AQI and air-quality patterns. This path analysis shows a strong correlation between the AQI and PM10 and PM2.5, however its correlation with other air pollutants is weak. Regression analysis shows a similar pattern of there being a strong relationship between AQI and PM10 (r2 = 0.97) and PM2.5 (r2 = 0.93). Although the COVID-19 pandemic had numerous negative effects on human health and the global economy, it is likely that the reduction in air pollution and the significant improvement in ambient air quality due to lockdowns provided substantial short-term health benefits. The government must implement policies to control the environmental issues which are causing poor air quality in post-COVID-19.
Impact of Agricultural Drought on Sunflower Production across Hungary
Authors: Harsányi Endre , Bashir Bashar , Alsilibe Firas , Alsafadi Karam , Alsalman Abdullah , Széles Adrienn , Rahman Muhammad Habib ur , Bácskai István , Juhász Csaba , Ratonyi Tamás , Mohammed Safwan
Published: October 2021

In the last few decades, agricultural drought (Ag.D) has seriously affected crop production and food security worldwide. In Hungary, little research has been carried out to assess the impacts of climate change, particularly regarding droughts and crop production, and especially on regional scales. Thus, the main aim of this study was to evaluate the impact of agricultural drought on sunflower production across Hungary. Drought data for the Standardized Precipitation Index (SPI) and the Standardized Precipitation Evapotranspiration Index (SPEI) were collected from the CARBATCLIM database (1961–2010), whereas sunflower production was collected from the Hungarian national statistical center (KSH) on regional and national scales. To address the impact of Ag.D on sunflower production, the sequence of standardized yield residuals (SSYR) and yield losses YlossAD was applied. Additionally, sunflower resilience to Ag.D (SRAg.D) was assessed on a regional scale. The results showed that Ag.D is more severe in the western regions of Hungary, with a significantly positive trend. Interestingly, drought events were more frequent between 1990 and 2010. Moreover, the lowest SSYR values were reported as −3.20 in the Hajdu-Bihar region (2010). In this sense, during the sunflower growing cycle, the relationship between SSYR and Ag.D revealed that the highest correlations were recorded in the central and western regions of Hungary. However, 75% of the regions showed that the plantation of sunflower is not resilient to drought where SRAg.Dx < 1. To cope with climate change in Hungary, an urgent mitigation plan should be implemented.
Effects of Neuro-Cognitive Load on Learning Transfer Using a Virtual Reality-Based Driving System
Authors: Abdurrahman Usman Alhaji , Yeh Shih-Ching , Wong Yunying , Wei Liang
Published: October 2021

Understanding the ways different people perceive and apply acquired knowledge, especially when driving, is an important area of study. This study introduced a novel virtual reality (VR)-based driving system to determine the effects of neuro-cognitive load on learning transfer. In the experiment, easy and difficult routes were introduced to the participants, and the VR system is capable of recording eye-gaze, pupil dilation, heart rate, as well as driving performance data. So, the main purpose here is to apply multimodal data fusion, several machine learning algorithms, and strategic analytic methods to measure neurocognitive load for user classification. A total of ninety-eight (98) university students participated in the experiment, in which forty-nine (49) were male participants and forty-nine (49) were female participants. The results showed that data fusion methods achieved higher accuracy compared to other classification methods. These findings highlight the importance of physiological monitoring to measure mental workload during the process of learning transfer.
Effects of Low Stocking Densities on Zootechnical Parameters and Physiological Responses of Rainbow Trout (Oncorhynchus mykiss) Juveniles
Authors: Roy Jérôme , Terrier Frederic , Marchand Michael , Herman Alexandre , Heraud Cécile , Surget Anne , Lanuque Anthony , Sandres Franck , Marandel Lucie
Published: October 2021

The present study investigated the effect of low stocking density on growth, survival, feed parameters and physiological responses (blood metabolites, welfare indicators, immune biomarkers, and transcriptomic responses of stress and immune-related genes) on juvenile rainbow trout (Oncorhynchus mykiss) reared under a recirculating aquaculture system during 12 weeks. Fish (average weight 29.64 g) were reared in triplicate under four initial densities: nine fish per tank (D9, 3.76 ± 0.06 kg/m3), 18 fish per tank (D18, 7.66 ± 0.18 kg/m3), 27 fish per tank (D27, 9.67 ± 0.01 kg/m3) and 36 fish per tank (D36, 12.94 ± 0.14 kg/m3). Results showed that lower stocking density D9 significantly altered survival with several fish dying during the experiment and an alteration of growth and feed efficiency for the remaining fish. In parallel, the study revealed that low stocking density induced a chronic stress altering the physiological responses of trout by dysregulation of the inflammatory, immune system, and indolamine/catecholamine brain levels. In conclusion, regarding all the variables observed, low stocking density (D9) alters survival, growth and feed efficiency of rainbow trout with alteration of their physiological responses. Selecting appropriate fish density relating to rearing conditions proved to be an essential concern to improve welfare in an aquaculture context.
DIPEND: An Open-Source Pipeline to Generate Ensembles of Disordered Segments Using Neighbor-Dependent Backbone Preferences
Authors: Harmat Zita , Dudola Dániel , Gáspári Zoltán
Published: October 2021

Ensemble-based structural modeling of flexible protein segments such as intrinsically disordered regions is a complex task often solved by selection of conformers from an initial pool based on their conformity to experimental data. However, the properties of the conformational pool are crucial, as the sampling of the conformational space should be sufficient and, in the optimal case, relatively uniform. In other words, the ideal sampling is both efficient and exhaustive. To achieve this, specialized tools are usually necessary, which might not be maintained in the long term, available on all platforms or flexible enough to be tweaked to individual needs. Here, we present an open-source and extendable pipeline to generate initial protein structure pools for use with selection-based tools to obtain ensemble models of flexible protein segments. Our method is implemented in Python and uses ChimeraX, Scwrl4, Gromacs and neighbor-dependent backbone distributions compiled and published previously by the Dunbrack lab. All these tools and data are publicly available and maintained. Our basic premise is that by using residue-specific, neighbor-dependent Ramachandran distributions, we can enhance the efficient exploration of the relevant region of the conformational space. We have also provided a straightforward way to bias the sampling towards specific conformations for selected residues by combining different conformational distributions. This allows the consideration of a priori known conformational preferences such as in the case of preformed structural elements. The open-source and modular nature of the pipeline allows easy adaptation for specific problems. We tested the pipeline on an intrinsically disordered segment of the protein Cd3ϵ and also a single-alpha helical (SAH) region by generating conformational pools and selecting ensembles matching experimental data using the CoNSEnsX+ server.
A Scoping Review of the Role of Metalloproteinases in the Pathogenesis of Autoimmune Pemphigus and Pemphigoid
Authors: Cirillo Nicola , Prime Stephen S.
Published: October 2021

Pemphigus and pemphigoid diseases are potentially life-threatening autoimmune blistering disorders that are characterized by intraepithelial and subepithelial blister formation, respectively. In both disease groups, skin and/or mucosal blistering develop as a result of a disruption of intercellular adhesion (pemphigus) and cell-extracellular matrix (ECM) adhesion (pemphigoid). Given that metalloproteinases can target cell adhesion molecules, the purpose of the present study was to investigate the role of these enzymes in the pathogenesis of these bullous dermatoses. Studies examining MMPs (matrix metalloproteinases) and the ADAM (a disintegrin and metalloproteinase) family of proteases in pemphigus and pemphigoid were selected from articles published in the repository of the National Library of Medicine (MEDLINE/PubMed) and bioRxiv. Multiple phases of screening were conducted, and relevant data were extracted and tabulated, with 29 articles included in the final qualitative analysis. The majority of the literature investigated the role of specific components of the MMP family primarily in bullous pemphigoid (BP) whereas studies that focused on pemphigus were rarer. The most commonly studied metalloproteinase was MMP-9 followed by MMP-2; other MMPs included MMP-1, MMP-3, MMP-8, MMP-12 and MMP-13. Molecules related to MMPs were also included, namely, ADAM5, 8, 10, 15, 17, together with TIMP-1 and TIMP-3. The results demonstrated that ADAM10 and MMP-9 activity is necessary for blister formation in experimental models of pemphigus vulgaris (PV) and BP, respectively. The data linking MMPs to the pathogenesis of experimental BP were relatively strong but the evidence for involvement of metalloproteinases in PV was more tentative. These molecules represent potential candidates for the development of mechanism-based treatments of these blistering diseases.
Mitochondrial Dysfunction, Protein Misfolding and Neuroinflammation in Parkinson’s Disease: Roads to Biomarker Discovery
Authors: Picca Anna , Guerra Flora , Calvani Riccardo , Romano Roberta , Coelho-Júnior Hélio José , Bucci Cecilia , Marzetti Emanuele
Published: October 2021

Parkinson’s Disease (PD) is a highly prevalent neurodegenerative disease among older adults. PD neuropathology is marked by the progressive loss of the dopaminergic neurons of the substantia nigra pars compacta and the widespread accumulation of misfolded intracellular α-synuclein (α-syn). Genetic mutations and post-translational modifications, such as α-syn phosphorylation, have been identified among the multiple factors supporting α-syn accrual during PD. A decline in the clearance capacity of the ubiquitin-proteasome and the autophagy-lysosomal systems, together with mitochondrial dysfunction, have been indicated as major pathophysiological mechanisms of PD neurodegeneration. The accrual of misfolded α-syn aggregates into soluble oligomers, and the generation of insoluble fibrils composing the core of intraneuronal Lewy bodies and Lewy neurites observed during PD neurodegeneration, are ignited by the overproduction of reactive oxygen species (ROS). The ROS activate the α-syn aggregation cascade and, together with the Lewy bodies, promote neurodegeneration. However, the molecular pathways underlying the dynamic evolution of PD remain undeciphered. These gaps in knowledge, together with the clinical heterogeneity of PD, have hampered the identification of the biomarkers that may be used to assist in diagnosis, treatment monitoring, and prognostication. Herein, we illustrate the main pathways involved in PD pathogenesis and discuss their possible exploitation for biomarker discovery.
Impact of Vitamin D Supplementation on Bone Mineral Density and All-Cause Mortality in Heart Transplant Patients
Authors: Abulmeaty Mahmoud M. A. , Almutawa Deema A. , Selimovic Nedim , Almuammar May , Al-Khureif Abdulaziz A. , Hashem Mohamed I. , Hassan Heba M. , Moety Doaa A. Abdel
Published: October 2021

Vitamin D (VD) deficiency is frequently reported in heart transplant (HT) recipients and routinely supplemented. However, the efficacy of VD supplementation on bone mineral density (BMD) and its association with all-cause mortality is underinvestigated. The VD levels and BMD were studied for two years, and the association of VD and BMD with all-cause mortality risk was investigated. Ninety-six HT patients (38.18 ± 12.10 years old; 74% men) were followed up during VD, Ca, and Mg supplementation. Anthropometric measurements, BMD by Dual-energy X-ray absorptiometry (DEXA) scan, VD concentrations, and related biochemical parameters were analyzed before, 1 year, and 2 years after HT. Despite significant improvement of VD3 and 25-hydroxy VD (25OHVD) levels especially in the men, BMD parameters were insignificantly changed. After 2 years, the all-cause mortality rate was 15.6%. High pretransplant levels of 25OHVD failed to improve the survival probability. Cox’s regression showed a 32.7% increased hazard ratio for each unit increase in body mass index (95% CI: 1.015–1.733, p = 0.038), in the VD-deficient group rather than in the VD-sufficient one. In conclusion, VD supplementation improves the biochemical status, especially in VD-deficient HT. However, its impact on the BMD and mortality was not as usually expected. Further investigation of the disturbed VD metabolism in HT is warranted.
Chip-Based Sensing of the Intercellular Transfer of Cell Surface Proteins: Regulation by the Metabolic State
Authors: Müller Günter A. , Tschöp Matthias H. , Müller Timo D.
Published: October 2021

Glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) are anchored at the surface of mammalian blood and tissue cells through a carboxy-terminal GPI glycolipid. Eventually, they are released into incubation medium in vitro and blood in vivo and subsequently inserted into neighboring cells, potentially leading to inappropriate surface expression or lysis. To obtain first insight into the potential (patho)physiological relevance of intercellular GPI-AP transfer and its biochemical characterization, a cell-free chip- and microfluidic channel-based sensing system was introduced. For this, rat or human adipocyte or erythrocyte plasma membranes (PM) were covalently captured by the TiO2 chip surface operating as the acceptor PM. To measure transfer between PM, donor erythrocyte or adipocyte PM were injected into the channels of a flow chamber, incubated, and washed out, and the type and amount of proteins which had been transferred to acceptor PM evaluated with specific antibodies. Antibody binding was detected as phase shift of horizontal surface acoustic waves propagating over the chip surface. Time- and temperature-dependent transfer, which did not rely on fusion of donor and acceptor PM, was detected for GPI-APs, but not typical transmembrane proteins. Transfer of GPI-APs was found to be prevented by α-toxin, which binds to the glycan core of GPI anchors, and serum proteins in concentration-dependent fashion. Blockade of transfer, which was restored by synthetic phosphoinositolglycans mimicking the glycan core of GPI anchors, led to accumulation in the chip channels of full-length GPI-APs in association with phospholipids and cholesterol in non-membrane structures. Strikingly, efficacy of transfer between adipocytes and erythrocytes was determined by the metabolic state (genotype and feeding state) of the rats, which were used as source for the PM and sera, with upregulation in obese and diabetic rats and counterbalance by serum proteins. The novel chip-based sensing system for GPI-AP transfer may be useful for the prediction and stratification of metabolic diseases as well as elucidation of the putative role of intercellular transfer of cell surface proteins, such as GPI-APs, in (patho)physiological mechanisms.
Differential Capability of Clinically Employed Dermal Regeneration Scaffolds to Support Vascularization for Tissue Bioengineering
Authors: Agostinis Chiara , Spazzapan Mariagiulia , Vuerich Roman , Balduit Andrea , Stocco Chiara , Mangogna Alessandro , Ricci Giuseppe , Papa Giovanni , Zacchigna Serena , Bulla Roberta
Published: October 2021

The loss of skin integrity has always represented a major challenge for clinicians dealing with dermal defects, such as ulcers (diabetic, vascular and chronic), postoncologic resections (i.e., radical vulvectomy) or dermatologic disorders. The introduction in recent decades of acellular dermal matrices (ADMs) supporting the repair and restoration of skin functionality represented a significant step toward achieving clean wound repair before performing skin grafts. Hard-to-heal ulcers generally depend on local ischemia and nonadequate vascularization. In this context, one possible innovative approach could be the prevascularization of matrices with vessel-forming cells (inosculation). This paper presents a comparative analysis of the most widely used dermal templates, i.e., Integra® Bilayer Matrix Wound Dressing, PELNAC®, PriMatrix® Dermal Repair Scaffold, Endoform® Natural Dermal Template, and Myriad Matrix®, testing their ability to be colonized by human adult dermal microvascular endothelial cells (ADMECs) and to induce and support angiogenesis in vitro and in vivo. By in vitro studies, we demonstrated that Integra® and PELNAC® possess superior pro-adhesive and pro-angiogenetic properties. Animal models allowed us to demonstrate the ability of preseeded ADMECs on Integra® to promote the engraftment, integration and vascularization of ADMs at the site of application.
Expression Profiles and Prognostic Value of FABPs in Colorectal Adenocarcinomas
Authors: Prayugo Fidelia Berenice , Kao Tzu-Jen , Anuraga Gangga , Ta Hoang Dang Khoa , Chuang Jian-Ying , Lin Li-Chia , Wu Yung-Fu , Wang Chih-Yang , Lee Kuen-Haur
Published: October 2021

Colorectal cancer (CRC) is one of the world’s leading causes of cancer-related deaths; thus, it is important to detect it as early as possible. Obesity is thought to be linked to a large rise in the CRC incidence as a result of bad dietary choices, such as a high intake of animal fats. Fatty acid-binding proteins (FABPs) are a set of molecules that coordinate intracellular lipid responses and are highly associated with metabolism and inflammatory pathways. There are nine types of FABP genes that have been found in mammals, which are FABP1–7, FABP9, and FABP12. Each FABP gene has its own roles in different organs of the body; hence, each one has different expression levels in different cancers. The roles of FABP family genes in the development of CRC are still poorly understood. We used a bioinformatics approach to examine FABP family gene expression profiles using the Oncomine, GEPIA, PrognoScan, STRING, cBioPortal, MetaCore, and TIMER platforms. Results showed that the FABP6 messenger (m)RNA level is overexpressed in CRC cells compared to normal cells. The overexpression of FABP6 was found to be related to poor prognosis in CRC patients’ overall survival. The immunohistochemical results in the Human Protein Atlas showed that FABP1 and FABP6 exhibited strong staining in CRC tissues. An enrichment analysis showed that high expression of FABP6 was significantly correlated with the role of microRNAs in cell proliferation in the development of CRC through the insulin-like growth factor (IGF) signaling pathway. FABP6 functions as an intracellular bile-acid transporter in the ileal epithelium. We looked at FABP6 expression in CRC since bile acids are important in the carcinogenesis of CRC. In conclusion, high FABP6 expression is expected to be a potential biomarker for detecting CRC at the early stage.
Portable and Label-Free Quantitative Loop-Mediated Isothermal Amplification (LF-qLamp) for Reliable COVID-19 Diagnostics in Three Minutes of Reaction Time: Arduino-Based Detection System Assisted by a pH Microelectrode
Authors: Alvarez Mario Moisés , Bravo-González Sergio , González-González Everardo , Trujillo-de Santiago Grissel
Published: October 2021

Loop-mediated isothermal amplification (LAMP) has been recently studied as an alternative method for cost-effective diagnostics in the context of the current COVID-19 pandemic. Recent reports document that LAMP-based diagnostic methods have a comparable sensitivity and specificity to that of RT-qPCR. We report the use of a portable Arduino-based LAMP-based amplification system assisted by pH microelectrodes for the accurate and reliable diagnosis of SARS-CoV-2 during the first 3 min of the amplification reaction. We show that this simple system enables a straightforward discrimination between samples containing or not containing artificial SARS-CoV-2 genetic material in the range of 10 to 10,000 copies per 50 µL of reaction mix. We also spiked saliva samples with SARS-CoV-2 synthetic material and corroborated that the LAMP reaction can be successfully monitored in real time using microelectrodes in saliva samples as well. These results may have profound implications for the design of real-time and portable quantitative systems for the reliable detection of viral pathogens including SARS-CoV-2.
Obstructive Apnea and Hypopnea Length in Normal Children and Adolescents
Authors: DelRosso Lourdes M. , Panek David , Redding Greg , Mogavero Maria Paola , Ruth Chris , Sheldon Nicole , Blazier Holly , Strong Candace , Samson Maria , Fickenscher Amy , Ferri Raffaele
Published: October 2021

(1) Background: Breathing is an essential function that requires both metabolic (or au-tomatic) and voluntary (behavioral) control during wakefulness but during sleep depends on metabolic control via peripheral and central chemoreceptors. Breathing during sleep disordered breathing also depends on the maturity of the neural centers and the strength of the respiratory muscles. We do not know if the response to apnea varies with age. (2) Methods: We measured the obstructive apneas and hypopneas during REM and NREM in polysomnography studies from children referred for snoring. Exclusion criteria: younger than 1 year of age, neuromuscular or syndrome comorbidity, oxygen or positive airway pressure, central apnea, and studies with loss of airflow sensors. (3) Results: Two-hundred-and-sixty-eight sleep studies were included. Mean age was 8.7 years (4.68 SD), range 1–18 years, 160 were male, and 108 were female. The 5th centile of apnea duration during NREM is above 8 s at all ages, with a tendency to increase in the oldest groups up to 10 s. During REM sleep, it shows a gradual increase from 6 s in the youngest children to 10 s in the oldest. (4) Conclusions: Apnea/hypopnea length increases with age in children and adolescents independently from sex or severity of OSA. Using adult criteria in teens seems to be accurate.
An Effortful Approach to Social Affiliation in Schizophrenia: Preliminary Evidence of Increased Theta and Alpha Connectivity during a Live Social Interaction
Authors: Li Lilian Y. , Schiffman Jason , Hu Derek K. , Lopour Beth A. , Martin Elizabeth A.
Published: October 2021

People with schizophrenia often experience a profound lack of motivation for social affiliation—a facet of negative symptoms that detrimentally impairs functioning. However, the mechanisms underlying social affiliative deficits remain poorly understood, particularly under realistic social contexts. Here, we investigated subjective reports and electroencephalography (EEG) functional connectivity in schizophrenia during a live social interaction. Individuals with schizophrenia (n = 16) and healthy controls (n = 29) completed a face-to-face interaction with a confederate while having EEG recorded. Participants were randomly assigned to either a Closeness condition designed to elicit feelings of closeness through self-disclosure or a Small-Talk condition with minimal disclosure. Compared to controls, patients reported lower positive emotional experiences and feelings of closeness across conditions, but they showed comparably greater subjective affiliative responses for the Closeness (vs. Small-Talk) condition. Additionally, patients in the Closeness (vs. Small-Talk) condition displayed a global increase in connectivity in theta and alpha frequency bands that was not observed for controls. Importantly, greater theta and alpha connectivity was associated with greater subjective affiliative responding, greater negative symptoms, and lower disorganized symptoms in patients. Collectively, findings indicate that patients, because of pronounced negative symptoms, utilized a less efficient, top-down mediated strategy to process social affiliation.
Integrating Plus Energy Buildings and Districts with the EU Energy Community Framework: Regulatory Opportunities, Barriers and Technological Solutions
Authors: Tuerk Andreas , Frieden Dorian , Neumann Camilla , Latanis Konstantinos , Tsitsanis Anastasios , Kousouris Spyridon , Llorente Javier , Heimonen Ismo , Reda Francesco , Ala-Juusela Mia , Allaerts Koen , Caerts Chris , Schwarzl Thomas , Ulbrich Martin , Stosch Annette , Ramschak Thomas
Published: October 2021

The aim of this paper is to assess opportunities the Clean Energy Package provides for Plus Energy Buildings (PEBs) and Plus Energy Districts (PEDs) regarding their economic optimization and market integration, possibly leading to new use cases and revenue streams. At the same time, insights into regulatory limitations at the national level in transposing the set of EU Clean Energy Package provisions are shown. The paper illustrates that the concepts of PEBs and PEDs are in principle compatible with the EU energy community concepts, as they relate to technical characteristics while energy communities provide a legal and regulatory framework for the organization and governance of a community, at the same time providing new regulatory space for specific activities and market integration. To realize new use cases, innovative ICT approaches are needed for a range of actors actively involved in creating and operating energy communities as presented in the paper. The paper discusses a range of different options to realize PEBs and PEDs as energy communities based on the H2020 EXCESS project. It concludes, however, that currently the transposition of the Clean Energy Package by the EU Member States is incomplete and limiting and as a consequence, in the short term, the full potential of PEBs and PEDs cannot be exploited.
Low-Carbon Design Path of Building Integrated Photovoltaics: A Comparative Study Based on Green Building Rating Systems
Authors: Liu Ke , Zhu Beili , Chen Jianping
Published: October 2021

CO2 emissions of buildings have a critical impact on the global climate change, and various green building rating systems (GBRS) have suggested low-carbon requirements to regulate building emissions. Building-integrated photovoltaics (BIPV), as an integrated technology of photovoltaics and buildings, is an important way to reduce building CO2 emissions. At present, the low-carbon design path of BIPV from architecture is still not unified and clear, and there is a lack of BIPV research regarding GBRS or from the perspective of architectural design in China. The objective of this study is to propose a framework of indicators related to carbon emission control in BIPV, guiding the path of BIPV low-carbon design. This study makes comparisons among the Leadership in Energy and Environmental Design (LEED), Building Research Establishment Environmental Assessment Method (BREEAM), and Assessment Standard for Green Buildings (ASGB), mainly in terms of the scope weight, induction, and measure features. The BIPV low-carbon design involves energy, materials, environmental adaptability, management, and innovation, in which energy and materials are the main scopes with weights of 10.98% and 7.46%, respectively. The five scopes included 17 measures. Following the measures, the path of the BIPV low-carbon design was defined with six aspects.
Operational Modal Analysis and Non-Linear Dynamic Simulations of a Prototype Low-Rise Masonry Building
Authors: Capanna Ilaria , Cirella Riccardo , Aloisio Angelo , Di Fabio Franco , Fragiacomo Massimo
Published: October 2021

This paper focuses on the dynamic behaviour of a low-rise masonry building representing the Italian residential heritage through experimental and numerical analyses. The authors discuss an application of combined Operational Modal Analysis and Finite Element Model updating for indirect estimation of the structural parameters. Two ambient vibration tests were carried out to estimate the structure’s dynamic behaviour in operational conditions. The first experimental setup consisted of accelerometers gathered in a row along the first floor to characterize the local dynamic of the floor. Conversely, the second setup had the accelerometers placed at the building’s corners to characterize the global dynamics. The outcomes of the first setup were used to estimate the mechanical parameters of the floor, while the ones form the second were used to characterize the mechanical parameters of the masonry piers. Therefore, two finite element models were implemented: (i) a single beam with an equivalent section of the floor to grasp the local behaviour of the investigated horizontal structure; (ii) an equivalent frame model of the entire building to characterise the global dynamic behaviour. The model updating process was developed in two phases to seize local and global dynamic responses. The updated numerical model formed the basis for a sensitivity analysis using the modelling parameters. The authors chose to delve into the influence of the floor on the dynamic behaviour of low-rise masonry buildings. With this aim, non-linear dynamic analyses were carried out under different mechanical characteristics of floors, expressing the scatter for ordinary masonry buildings. The displacements’ trends along the height of the building evidenced the notable role of the floor’s stiffness in the non-linear dynamic behaviour of the building. Lastly, the authors derived the fragility curves predicting the seismic performance in failure probability under a highly severe damage state.
Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives
Authors: Zhdanovskaya Nadezda , Firrincieli Mariarosaria , Lazzari Sara , Pace Eleonora , Scribani Rossi Pietro , Felli Maria Pia , Talora Claudio , Screpanti Isabella , Palermo Rocco
Published: October 2021

Notch signaling guides cell fate decisions by affecting proliferation, apoptosis, stem cell self-renewal, and differentiation depending on cell and tissue context. Given its multifaceted function during tissue development, both overactivation and loss of Notch signaling have been linked to tumorigenesis in ways that are either oncogenic or oncosuppressive, but always context-dependent. Notch signaling is critical for several mechanisms of chemoresistance including cancer stem cell maintenance, epithelial-mesenchymal transition, tumor-stroma interaction, and malignant neovascularization that makes its targeting an appealing strategy against tumor growth and recurrence. During the last decades, numerous Notch-interfering agents have been developed, and the abundant preclinical evidence has been transformed in orphan drug approval for few rare diseases. However, the majority of Notch-dependent malignancies remain untargeted, even if the application of Notch inhibitors alone or in combination with common chemotherapeutic drugs is being evaluated in clinical trials. The modest clinical success of current Notch-targeting strategies is mostly due to their limited efficacy and severe on-target toxicity in Notch-controlled healthy tissues. Here, we review the available preclinical and clinical evidence on combinatorial treatment between different Notch signaling inhibitors and existent chemotherapeutic drugs, providing a comprehensive picture of molecular mechanisms explaining the potential or lacking success of these combinations.
PPARγ Targets-Derived Diagnostic and Prognostic Index for Papillary Thyroid Cancer
Authors: Kim Jaehyung , Kim Soo Young , Ma Shi-Xun , Kim Seok-Mo , Shin Su-Jin , Lee Yong Sang , Chang Hojin , Chang Hang-Seok , Park Cheong Soo , Lim Su Bin
Published: October 2021

In most cases, papillary thyroid cancer (PTC) is highly curable and associated with an excellent prognosis. Yet, there are several clinicopathological features that lead to a poor prognosis, underscoring the need for a better genomic strategy to refine prognostication and patient management. We hypothesized that PPARγ targets could be potential markers for better diagnosis and prognosis due to the variants found in PPARG in three pairs of monozygotic twins with PTC. Here, we developed a 10-gene personalized prognostic index, designated PPARGi, based on gene expression of 10 PPARγ targets. Through scRNA-seq data analysis of PTC tissues derived from patients, we found that PPARGi genes were predominantly expressed in macrophages and epithelial cells. Machine learning algorithms showed a near-perfect performance of PPARGi in deciding the presence of the disease and in selecting a small subset of patients with poor disease-specific survival in TCGA-THCA and newly developed merged microarray data (MMD) consisting exclusively of thyroid cancers and normal tissues.