bluuebunny/crossref_metadata_2025 huggingface dataset:
Ecophysiological Parameters of Medicinal Plant Filipendula vulgaris in Diverse Habitat Conditions
Authors: Barabasz-Krasny Beata , Możdżeń Katarzyna , Tatoj Agnieszka , Rożek Katarzyna , Zandi Peiman , Schnug Ewald , Stachurska-Swakoń Alina
Published: August 2022

This study attempts to determine which of the habitats occupied by Filipendula vulgaris creates better conditions for its growth and development. Selected physiological parameters—PSII activity, chlorophyll content, electrolyte leakage, hydrogen peroxide content as well as biomass, the occurrence of mycorrhiza, and soil characteristics—were investigated. Grassland soils had a higher content of macronutrients and a lower concentration of heavy metals. The degree of colonization of F. vulgaris by AMF (Arum type) oscillated around high values in both types of stands. Plants growing on xerothermic grasslands achieved much better fluorescence parameters than those collected from meadows. Similar results were obtained from the analysis of chlorophyll content. The destabilization degree of cell membranes was significantly higher in plants collected in meadows than in grasslands. Biomass analysis showed higher values of these parameters in grassland plants. In the case of the parameters of fluorescence emission, plants growing on grasslands achieved significantly lower values than plants collected from meadows. The analyses carried out showed that better conditions for growth and physiological activity of F. vulgaris are probably associated with grasslands on a calcareous substrate.
Use of Lichens to Evaluate the Impact of Post-Earthquake Reconstruction Activities on Air Quality: A Case Study from the City of L’Aquila
Authors: Di Biase Letizia , Di Lisio Paolo , Pace Loretta , Arrizza Lorenzo , Fattorini Simone
Published: August 2022

Lichens are widely used as bioindicators of air quality because of their ability to absorb chemical pollutants. We used the Lichen Diversity Value (LDV) index to assess the effects of the urban reconstruction activities in the city of L’Aquila ten years after the 2009 earthquake on air quality. Sampling was conducted from the city centre (still mostly under reconstruction and closed to traffic) to suburban areas (where reconstruction is minimal). We tested if the LDV index varied with distance from the city centre because of the presence of air pollutants produced by reconstruction works. We also used Energy-Dispersive X-ray Spectroscopy (EDS) to detect the main pollutants accumulated in the sampled lichens. The LDV increased from the city centre towards suburban areas. EDS revealed high concentrations of pollutants related to demolition and reconstruction activities, such as aluminium and silicon (used in the manufacture of concrete), in the more central areas. These results suggest that the LDV index can be a useful tool to monitor air quality, even on a small scale, and in urban environments subject to building demolition and reconstruction. Moreover, EDS could represent a good preliminary analytical technique to identify the air pollutants associated with all of these activities.
New PCL/PEC Blends: In Vitro Cell Response of Preosteoblasts and Human Mesenchymal Stem Cells
Authors: Pablos Jesus L. , Cicuéndez Mónica , Hernández-Rivas María , Catalina Fernando , Vallet-Regí María , Corrales Teresa
Published: August 2022

In this study, new blends of PCL/PEC have been prepared in an easy manner by casting with the objective of obtaining new biomaterials to apply to tissue engineering and bone regeneration. The PCL/PEC blends obtained, together with neat polymer blends, were characterized by infrared spectroscopy (FTIR), atomic force microscopy (AFM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). This full characterization is the key to disentangle the miscibility, which means good compatibility, of the polymer blends used in this work. The addition of increasing amounts of PEC, has shown in the new biomaterials obtained, a remarkable improvement in relation with the mechanical properties (manageable materials) and above all, in terms of an increase in their hydrophilic character with respect to the PCL neat polymer. The improvement of all these properties is reflected in their biological properties. With these thoughts in mind, the blends obtained were tested through the assessment of several biological parameters such as cell viability, proliferation, and differentiation of both the MC3T3-E1 osteoblastic cell line and hMSCs to evaluate their cell response to different polymer membranes aimed at bone tissue regeneration. “In vitro” biocompatibility methods have been chosen rather than in vivo studies due to their lower cost, faster procedure time, and minimum ethical concerns, and because it was the first time that the biological effects of these blends were studied. The results show that the PCL/PEC blends obtained, with tunable properties in terms of hydrophilic character and hydrolytic degradation, may be regarded as good candidates to perform “in vivo” tests and check their real-life applicability for bone regeneration. The polymer acronym (the weight percentage in the sub index) is PCLx/PECy as noted in table one with the summary of compositions.
Can PPAR γ Keep Cadmium in Check?
Authors: Robinson Caila , Lockey Richard F. , Kolliputi Narasaiah
Published: August 2022

Cd, a naturally occurring endocrine toxin found in tobacco leaves, originates in the environment and enters the body through inhalation, targeting the lungs and kidneys. A study published by Larsen-Carey et al. revealed that cadmium mediates the persistence of classically activated lung macrophages to exacerbate lung injury. The research discovered a novel role for PPAR γ as an effective regulator for the alternative activation of macrophages in response to Cd and Cd-induced lung injury.
Assessing the NLRP3 Inflammasome Activating Potential of a Large Panel of Micro- and Nanoplastics in THP-1 Cells
Authors: Busch Mathias , Bredeck Gerrit , Waag Friedrich , Rahimi Khosrow , Ramachandran Haribaskar , Bessel Tobias , Barcikowski Stephan , Herrmann Andreas , Rossi Andrea , Schins Roel P. F.
Published: August 2022

Due to the ubiquity of environmental micro- and nanoplastics (MNPs), inhalation and ingestion by humans is very likely, but human health effects remain largely unknown. The NLRP3 inflammasome is a key player of the innate immune system and is involved in responses towards foreign particulate matter and the development of chronic intestinal and respiratory inflammatory diseases. We established NLRP3-proficient and -deficient THP-1 cells as an alternative in vitro screening tool to assess the potential of MNPs to activate the NLRP3 inflammasome. By investigating cytokine release (IL-1β and IL-8) and cytotoxicity after treatment with engineered nanomaterials, this in vitro approach was compared to earlier published ex vivo murine bone marrow-derived macrophages and in vivo data. This approach showed a strong correlation with previously published data, verifying that THP-1 cells are a suitable model to investigate NLRP3 inflammasome activation. We then investigated the proinflammatory potential of eight MNPs of different size, shape, and chemical composition. Only amine-modified polystyrene (PS-NH2) acted as a direct NLRP3 activator. However, polyethylene terephthalate (PET), polyacrylonitrile (PAN), and nylon (PA6) induced a significant increase in IL-8 release in NLRP3−/− cells. Our results suggest that most MNPs are not direct activators of the NLRP3 inflammasome, but specific MNP types might still possess pro-inflammatory potential via other pathways.
Correlation between the Skin Permeation Profile of the Synthetic Sesquiterpene Compounds, Beta-Caryophyllene and Caryophyllene Oxide, and the Antiedematogenic Activity by Topical Application of Nanoemulgels
Authors: Weimer Patrícia , Kreutz Tainá , Limberger Renata P. , Rossi Rochele C. , de Lima Ádley A. N. , Veiga Valdir F. , de Araújo Bibiana Verlindo , Koester Letícia S.
Published: August 2022

Sesquiterpene compounds are applied as permeation promoters in topical formulations. However, studies exploring their impact on nanostructured systems, changes in permeation profile, and consequently, its biological activity are restricted. This study aimed to investigate the correlation between the skin permeation of the major sesquiterpenes, beta-caryophyllene, and caryophyllene oxide from the oleoresin of Copaifera multijuga, after delivery into topical nanoemulgels, and the in vivo antiedematogenic activity. First, ten nanoemulgels were prepared and characterized, and their in vitro permeation profile and in vivo anti-inflammatory activity were evaluated. In equivalent concentrations, β-caryophyllene permeation was greater from oleoresin nanoemulgels, resulting in greater in vivo antiedematogenic activity. However, an inverse relationship was observed for caryophyllene oxide, which showed its favored permeation and better in vivo anti-inflammatory effect carried as an isolated compound in the nanoemulgels. These results suggest that the presence of similar compounds may interfere with the permeation profile when comparing the profiles of the compounds alone or when presented in oleoresin. Furthermore, the correlation results between the permeation profile and in vivo antiedematogenic activity corroborate the establishment of beta-caryophyllene as an essential compound for this pharmacological activity of C. multijuga oleoresin.
Exploratory Evaluation of EGFR-Targeted Anti-Tumor Drugs for Lung Cancer Based on Lung-on-a-Chip
Authors: Tan Jianfeng , Sun Xindi , Zhang Jianhua , Li Huili , Kuang Jun , Xu Lulu , Gao Xinghua , Zhou Chengbin
Published: August 2022

In this study, we used three-dimensional (3D) printing to prepare a template of a microfluidic chip from which a polydimethylsiloxane (PDMS)lung chip was successfully constructed. The upper and lower channels of the chip are separated by a microporous membrane. The upper channel is seeded with lung cancer cells, and the lower channel is seeded with vascular endothelial cells and continuously perfused with cell culture medium. This lung chip can simulate the microenvironment of lung tissue and realize the coculture of two kinds of cells at different levels. We used a two-dimensional (2D) well plate and a 3D lung chip to evaluate the effects of different EGFR-targeting drugs (gefitinib, afatinib, and osimertinib) on tumor cells. The 3D lung chip was superior to the 2D well plate at evaluating the effect of drugs on the NCI-H650, and the results were more consistent with existing clinical data. For primary tumor cells, 3D lung chips have more advantages because they simulate conditions that are more similar to the physiological cell microenvironment. The evaluation of EGFR-targeted drugs on lung chips is of great significance for personalized diagnosis and treatment and pharmacodynamic evaluation.
A Rapid and Sensitive Microfluidics-Based Tool for Seroprevalence Immunity Assessment of COVID-19 and Vaccination-Induced Humoral Antibody Response at the Point of Care
Authors: Rajsri Kritika Srinivasan , McRae Michael P. , Simmons Glennon W. , Christodoulides Nicolaos J. , Matz Hanover , Dooley Helen , Koide Akiko , Koide Shohei , McDevitt John T.
Published: August 2022

As of 8 August 2022, SARS-CoV-2, the causative agent of COVID-19, has infected over 585 million people and resulted in more than 6.42 million deaths worldwide. While approved SARS-CoV-2 spike (S) protein-based vaccines induce robust seroconversion in most individuals, dramatically reducing disease severity and the risk of hospitalization, poorer responses are observed in aged, immunocompromised individuals and patients with certain pre-existing health conditions. Further, it is difficult to predict the protection conferred through vaccination or previous infection against new viral variants of concern (VoC) as they emerge. In this context, a rapid quantitative point-of-care (POC) serological assay able to quantify circulating anti-SARS-CoV-2 antibodies would allow clinicians to make informed decisions on the timing of booster shots, permit researchers to measure the level of cross-reactive antibody against new VoC in a previously immunized and/or infected individual, and help assess appropriate convalescent plasma donors, among other applications. Utilizing a lab-on-a-chip ecosystem, we present proof of concept, optimization, and validation of a POC strategy to quantitate COVID-19 humoral protection. This platform covers the entire diagnostic timeline of the disease, seroconversion, and vaccination response spanning multiple doses of immunization in a single POC test. Our results demonstrate that this platform is rapid (~15 min) and quantitative for SARS-CoV-2-specific IgG detection.
Electrochemical Biosensor for SARS-CoV-2 cDNA Detection Using AuPs-Modified 3D-Printed Graphene Electrodes
Authors: Silva Luiz R. G. , Stefano Jéssica S. , Orzari Luiz O. , Brazaca Laís C. , Carrilho Emanuel , Marcolino-Junior Luiz H. , Bergamini Marcio F. , Munoz Rodrigo A. A. , Janegitz Bruno C.
Published: August 2022

A low-cost and disposable graphene polylactic (G-PLA) 3D-printed electrode modified with gold particles (AuPs) was explored to detect the cDNA of SARS-CoV-2 and creatinine, a potential biomarker for COVID-19. For that, a simple, non-enzymatic electrochemical sensor, based on a Au-modified G-PLA platform was applied. The AuPs deposited on the electrode were involved in a complexation reaction with creatinine, resulting in a decrease in the analytical response, and thus providing a fast and simple electroanalytical device. Physicochemical characterizations were performed by SEM, EIS, FTIR, and cyclic voltammetry. Square wave voltammetry was employed for the creatinine detection, and the sensor presented a linear response with a detection limit of 0.016 mmol L−1. Finally, a biosensor for the detection of SARS-CoV-2 was developed based on the immobilization of a capture sequence of the viral cDNA upon the Au-modified 3D-printed electrode. The concentration, immobilization time, and hybridization time were evaluated in presence of the DNA target, resulting in a biosensor with rapid and low-cost analysis, capable of sensing the cDNA of the virus with a good limit of detection (0.30 µmol L−1), and high sensitivity (0.583 µA µmol−1 L). Reproducible results were obtained (RSD = 1.14%, n = 3), attesting to the potentiality of 3D-printed platforms for the production of biosensors.
Targeting CNS Neural Mechanisms of Gait in Stroke Neurorehabilitation
Authors: McCabe Jessica P. , Pundik Svetlana , Daly Janis J.
Published: August 2022

The central nervous system (CNS) control of human gait is complex, including descending cortical control, affective ascending neural pathways, interhemispheric communication, whole brain networks of functional connectivity, and neural interactions between the brain and spinal cord. Many important studies were conducted in the past, which administered gait training using externally targeted methods such as treadmill, weight support, over-ground gait coordination training, functional electrical stimulation, bracing, and walking aids. Though the phenomenon of CNS activity-dependent plasticity has served as a basis for more recently developed gait training methods, neurorehabilitation gait training has yet to be precisely focused and quantified according to the CNS source of gait control. Therefore, we offer the following hypotheses to the field: Hypothesis 1. Gait neurorehabilitation after stroke will move forward in important ways if research studies include brain structural and functional characteristics as measures of response to treatment. Hypothesis 2. Individuals with persistent gait dyscoordination after stroke will achieve greater recovery in response to interventions that incorporate the current and emerging knowledge of CNS function by directly engaging CNS plasticity and pairing it with peripherally directed, plasticity-based motor learning interventions. These hypotheses are justified by the increase in the study of neural control of motor function, with emerging research beginning to elucidate neural factors that drive recovery. Some are developing new measures of brain function. A number of groups have developed and are sharing sophisticated, curated databases containing brain images and brain signal data, as well as other types of measures and signal processing methods for data analysis. It will be to the great advantage of stroke survivors if the results of the current state-of-the-art and emerging neural function research can be applied to the development of new gait training interventions.
The Significance of NLRP Inflammasome in Neuropsychiatric Disorders
Authors: Shen Yao , Qian Liyin , Luo Hu , Li Xiaofang , Ruan Yuer , Fan Runyue , Si Zizhen , Chen Yunpeng , Li Longhui , Liu Yu
Published: August 2022

The NLRP inflammasome is a multi-protein complex which mainly consists of the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain. Its activation is linked to microglial-mediated neuroinflammation and partial neuronal degeneration. Many neuropsychiatric illnesses have increased inflammatory responses as both a primary cause and a defining feature. The NLRP inflammasome inhibition delays the progression and alleviates the deteriorating effects of neuroinflammation on several neuropsychiatric disorders. Evidence on the central effects of the NLRP inflammasome potentially provides the scientific base of a promising drug target for the treatment of neuropsychiatric disorders. This review elucidates the classification, composition, and functions of the NLRP inflammasomes. It also explores the underlying mechanisms of NLRP inflammasome activation and its divergent role in neuropsychiatric disorders, including Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, depression, drug use disorders, and anxiety. Furthermore, we explore the treatment potential of the NLRP inflammasome inhibitors against these disorders.
Doing Experimental Psychological Research from Remote: How Alerting Differently Impacts Online vs. Lab Setting
Authors: Del Popolo Cristaldi Fiorella , Granziol Umberto , Bariletti Irene , Mento Giovanni
Published: August 2022

Due to pandemic-imposed restrictions on lab-based research, we have recently witnessed a flourishing of online studies in experimental psychology, based on the collection of fine behavioral measures such as reaction times (RTs) and accuracy. However, it remains unclear whether participants’ alerting levels may have a different impact on behavioral performance in the online vs. lab setting. In this work we administered online and in-lab the dynamic temporal prediction (DTP) task, which requires an implicit modulation of participants’ alerting by alternating experimental conditions implying either slower or faster response rates. We then compared data distribution, RTs, accuracy, and time-on-task effects across the adult lifespan between the settings. We replicated online and across the whole age range considered (19–69 y) all the task-specific effects already found in-lab (both in terms of RTs and accuracy) beyond the overall RTs delay typical of the online setting. Moreover, we found an interaction between the setting and task-specific features so that participants showed slower RTs only in experimental conditions implying a less urgent response rate, while no RTs delay and a slight accuracy increase emerged in faster conditions. Thus, the online setting has been shown to be methodologically sound in eliciting comparable effects to those found in-lab. Moreover, behavioral performance seems to be more sensitive to task-induced alerting shifts in the online as compared to the lab setting, leading to either a heightened or reduced efficiency depending on a faster or slower response rate of experimental conditions, respectively.
Towards an Inclusive Walking Community—A Multi-Criteria Digital Evaluation Approach to Facilitate Accessible Journeys
Authors: Huang Xiaoran , White Marcus , Langenheim Nano
Published: August 2022

Half the world’s population now lives in cities, and this figure is expected to reach 70% by 2050. To ensure future cities offer equity for multiple age groups, it is important to plan for spatially inclusive features such as pedestrian accessibility. This feature is strongly related to many emerging global challenges regarding health, an ageing population, and an inclusive society, and should be carefully considered when designing future cities to meet the mobility requirements of different groups of people, reduce reliance on cars, and encourage greater participation by all residents. Independent travel to public open spaces, particularly green spaces, is widely considered a key factor that affects human health and well-being and is considered a primary motivation for walking. At the same time, unfavourable steepness and restrictive access points to open spaces can limit accessibility and restrict the activities of older adults or people with mobility impairments. This paper introduces a novel open access proximity modelling web application, PedestrianCatch, that simulates pedestrian catchments for user-specified destinations utilising a crowd-source road network and open topographic data. Based on this tool, we offer a multi-criteria evaluation approach that considers travel speed, time, urban topography, and visualisation modes to accommodate various simulation needs for different urban scenarios. Two case studies are conducted to demonstrate the technical feasibility and flexibility using the proposed evaluation approach, and explain how new renewal strategies can be tested when designing a more inclusive neighbourhood. This evaluation tool is immediately relevant to urban designers, health planners, and disability communities, and will be increasingly relevant to the wider community as populations age, while the corresponding analysis approach has a huge potential to contribute to the pre-design and design process for developing more walkable and accessible communities for all.
Case Study of Solid Waste Based Soft Soil Solidifying Materials Applied in Deep Mixing Pile
Authors: Shu Benan , Gong Haoliang , Chen Shaoming , Ren Yanfei , Li Yongling , Yang Tengyu , Zeng Guodong , Zhou Min , Barbieri Diego Maria , Li Yuanyuan
Published: August 2022

The research on solid waste based soft soil solidifying materials has received extensive attention in recent years. However, the properties of deep mixing piles are significantly affected by the construction technology. In view of this, this work carried out the systematic study on the influence of materials, the mixing tool and process optimization on the integrity and mechanical properties of deep mixing piles. Factors considered include the shape of the blade (strip and meniscus), the types of solidifying materials (PO 42.5 cement, self-developed soft soil solidifying agent), the content (50 kg/m, 65 kg/m, 80 kg/m and 100 kg/m) and how many times the materials needed to be mixed (two, four and six times). The solidification mechanism was analyzed. The results showed that the utilization of a meniscus blade contributed to the excellent integrity of the deep mixing pile, as well as solved the problems of oozing slurry and wrapped blade during construction. Mixing the materials four times is the most suitable for the construction of deep mixing piles in organic clay. The solidifying agent deep mixing pile showed satisfactory early and late strength. Microscopic analysis showed that more calcium silicate hydrate and ettringite formed in the solidifying agent solidified soil. Organic clay particles were better cemented and pores were fully filled, so that the solidified soil showed an integral and dense structure. The microscopically integral and dense structure contributed to the excellent integrity and mechanical properties of the solidifying agent deep mixing pile.
Research on the Application of Multi-Source Data Analysis for Bridge Safety Monitoring in the Reconstruction and Demolition Process
Authors: Fu Meizhen , Liang Yuxiong , Feng Qingsong , Wu Bitao , Tang Guoxi
Published: August 2022

With the increase of bridge-required demolition/dismantling for reconstruction or modification, the early warning of construction emergencies is greatly needed for monitoring the structural safety of bridges under construction. In this paper, based on the multi-source data of nearby construction and demolition construction of a large-span RC arch bridge in China, the Analytic Hierarchy Process (AHP) method is adopted to analyze the multi-source data and set the early warning threshold for bridge safety in construction. According to the analytical results, a reasonable evaluation of AHP factors can improve the accuracy and timeliness of safety early warning in the structural safety monitoring of bridges during the construction process. The weight of the monitoring data in AHP should be assigned according to its reliability, stability, and importance. Bridge safety assessment of nearby construction having harmful vibration should prioritize dynamic bridge monitoring by cooperating with multi-source data, including stress, and deformation monitoring of the bridge is necessary. The assessment results proved that multi-source data, including but not limited to structural stress and deformation monitoring data, vibration data, theoretical prediction data, environment data such as temperature data, and construction/maintenance history data, are necessary for safety monitoring and early warning of construction with specifications related to bridge construction. The early warnings triggered by the evaluation results successfully ensure the safety status of the bridge during nearby construction and demolition construction, which shows the proposed method can provide a guideline for comprehensively evaluating and early warning of the status of bridge construction.
Influences of the Plot Area and Floor Area Ratio of Residential Quarters on the Housing Vacancy Rate: A Case Study of the Guangzhou Metropolitan Area in China
Authors: Yue Xiaoli , Wang Yang , Zhang Hong’ou
Published: August 2022

Factors affecting the housing vacancy rate (HVR) vary, but few studies have considered the relationships between the HVR and plot area (PA) and floor area ratio (FAR). This study thus considered 212 residential quarters in the Guangzhou metropolitan area as the research object, and we constructed a regression model of the factors impacting housing vacancies. The model includes two explanatory variables, PA and FAR, and the remaining six impact factors as control variables. In this study, the influences of PA and FAR on the HVR was analyzed by combining the traditional ordinary least squares (OLS) and two spatial regression models: the spatial lag model (SLM) and spatial error model (SEM). The results indicate that (1) the HVR in the Guangzhou metropolitan area shows spatial difference characteristics of the low central area and high edge, and there is spatial autocorrelation. (2) The PA of the residential quarters gradually increases from the central to the edge area, but the spatial pattern of FAR is the opposite. (3) The SLM results indicate that the PA and FAR of the residential quarters have significant positive correlations with HVR; that is, the larger the PA and FAR, the larger the HVR of the residential quarters, which is in accordance with the expected direction of the theory; furthermore, basic education convenience, road density, and waterfront accessibility have significant negative effects on HVR. This conclusion provides a reference for government departments to formulate reasonable and effective housing policies aimed at the current housing vacancy problem and should help alleviate urban housing vacancies.
Architectural Characteristics and Seismic Vulnerability Assessment of a Historical Masonry Minaret under Different Seismic Risks and Probabilities of Exceedance
Authors: Işık Ercan , Avcil Fatih , Harirchian Ehsan , Arkan Enes , Bilgin Hüseyin , Özmen Hayri Baytan
Published: August 2022

Masonry structures began to be built with the existence of human beings and are an inspiration for today’s structures. Monumental historical buildings built according to people’s religious beliefs have special importance among such structures. Despite being exposed to many natural disasters over time, such structures that have survived till today are an indispensable part of the historical heritage. Within the scope of this study, structural analyses were carried out for the historical Ulu Mosque’s minaret in Bitlis (Turkey), located in the Van Lake basin, using both on-site measurements and finite element methods. Detailed historical and architectural features were given for the minaret and the mosque. In addition to four different earthquake ground motion levels of 2%, 10%, 50% and 68%, structural analyses were deployed separately for seven different geographical locations in the same seismic risk area. Moreover, time history analyses were conducted using the acceleration records of the Van earthquake that occurred in the region. The minaret performance levels were determined by using the displacement values obtained. The study examined the different probabilities of exceedance and the changes in the regions with the same seismic risk. As a result of each structural analysis, base shear forces, displacement, period and maximum stress values were obtained for the minaret. The displacement, base shear force, and stress values increased as the exceedance probability decreased. While the same seismic and structural analysis results were obtained for the selected settlements in the same earthquake zone in this study, remarkable differences were observed for these settlements using the geographical-location-specific design spectrum.
Numerical Study on Evacuation Evaluation and Strategy of Theater with Rotating Auditorium
Authors: Xiong Kang , Weng Miaocheng , Liu Fang , Lu Yuhan
Published: August 2022

In recent years, more and more theaters with rotating mechanisms have been built and used, such as theaters with rotating auditoriums. The rotation mechanism in this type of building may lead to the uncertainty of evacuation distances and routes, which undoubtedly poses a higher challenge to performance-based fire protection design. Taking the revolving auditorium theater as an example, this paper proposes a systematic method to solve the problem of randomness in evacuation scenarios. The numerical simulations based on FDS and Pathfinder were carried out, and two improved evacuation strategies for theaters with rotating auditorium were proposed. The results show that the blockage of evacuation exits is an important factor affecting the success of evacuation and the evacuation time. In addition, the establishment of emergency evacuation stairs and rotating auditoriums can effectively reduce the evacuation time.
Green Building Construction: A Systematic Review of BIM Utilization
Authors: Cao Yu , Kamaruzzaman Syahrul , Aziz Nur
Published: August 2022

As a multi-function method, Building Information Modeling (BIM) can assist construction organizations in improving their project’s quality, optimize collaboration efficiency, and reduce construction periods and expenditure. Given the distinguished contributions of BIM utilization, there is a trend that BIM has significant potential to be utilized in the construction phase of green buildings. Compared with traditional buildings, green buildings have more stringent requirements, including environmental protection, saving energy, and residents’ comfort. Although BIM is deemed an effective method to achieve the abovementioned requirements in the construction process of green buildings, there are few systematic reviews that explore the capabilities of BIM in the construction phase of green buildings. This has hindered the utilization of BIM in the construction of green buildings. To bridge this research gap and review the latest BIM capabilities, this study was developed to perform a systematic review of the BIM capabilities in the construction phase of green buildings. In this systematic review, the PRISMA protocol has been used as the primary procedure for article screening and review. The entire systematic review was performed from January 2022 to April 2022. In this process, 165 articles were included, reviewed, and discussed. Web of Science (WoS) and Scopus were adopted as the databases. Through this systematic review, it can be identified that BIM capabilities have significant advantages in project quality improvement, lifecycle data storage and management, collaboration optimization, planning, and schedule management optimization in the construction phase of green buildings. Through the discussion, it can be concluded that BIM utilization can be adopted from the pre-construction phase to the post-construction stage in the green building construction process. Besides these, the barriers to BIM utilization in the green building construction phase are also revealed in the discussion section, including the non-uniform data format, insufficient interactivity, ambiguous ownership, insufficient BIM training, and hesitation toward BIM adoption. Moreover, the challenges and future directions of BIM utilization in green building construction are identified. The findings of this study can facilitate construction personnel to be acquainted with BIM capabilities in the construction of green buildings to promote the utilization and optimization of BIM capabilities in the green building construction process.
Circulating Low Density Neutrophils Are Associated with Resistance to First Line Anti-PD1/PDL1 Immunotherapy in Non-Small Cell Lung Cancer
Authors: Arasanz Hugo , Bocanegra Ana Isabel , Morilla Idoia , Fernández-Irigoyen Joaquín , Martínez-Aguillo Maite , Teijeira Lucía , Garnica Maider , Blanco Ester , Chocarro Luisa , Ausin Karina , Zuazo Miren , Fernández-Hinojal Gonzalo , Echaide Miriam , Fernández-Rubio Leticia , Piñeiro-Hermida Sergio , Ramos Pablo , Mezquita Laura , Escors David , Vera Ruth , Kochan Grazyna
Published: August 2022

Single-agent immunotherapy has been widely accepted as frontline treatment for advanced non-small cell lung cancer (NSCLC) with high tumor PD-L1 expression, but most patients do not respond and the mechanisms of resistance are not well known. Several works have highlighted the immunosuppressive activities of myeloid subpopulations, including low-density neutrophils (LDNs), although the context in which these cells play their role is not well defined. We prospectively monitored LDNs in peripheral blood from patients with NSCLC treated with anti-PD-1 immune checkpoint inhibitors (ICIs) as frontline therapy, in a cohort of patients treated with anti-PD1 immunotherapy combined with chemotherapy (CT+IT), and correlated values with outcomes. We explored the underlying mechanisms through ex vivo experiments. Elevated baseline LDNs predict primary resistance to ICI monotherapy in patients with NSCLC, and are not associated with response to CT+IT. Circulating LDNs mediate resistance in NSCLC receiving ICI as frontline therapy through humoral immunosuppression. A depletion of this population with CT+IT might overcome resistance, suggesting that patients with high PD-L1 tumor expression and high baseline LDNs might benefit from this combination. The activation of the HGF/c-MET pathway in patients with elevated LDNs revealed by quantitative proteomics supports potential drug combinations targeting this pathway.
DNA Damage Regulates the Functions of the RNA Binding Protein Sam68 through ATM-Dependent Phosphorylation
Authors: Stagni Venturina , Orecchia Silvia , Mignini Luca , Beji Sara , Antonioni Ambra , Caggiano Cinzia , Barilà Daniela , Bielli Pamela , Sette Claudio
Published: August 2022

Cancer cells frequently exhibit dysregulation of the DNA damage response (DDR), genomic instability, and altered RNA metabolism. Recent genome-wide studies have strongly suggested an interaction between the pathways involved in the cellular response to DDR and in the regulation of RNA metabolism, but the molecular mechanism(s) involved in this crosstalk are largely unknown. Herein, we found that activation of the DDR kinase ATM promotes its interaction with Sam68, leading to phosphorylation of this multifunctional RNA binding protein (RBP) on three residues: threonine 61, serine 388 and serine 390. Moreover, we demonstrate that ATM-dependent phosphorylation of threonine 61 promotes the function of Sam68 in the DDR pathway and enhances its RNA processing activity. Importantly, ATM-mediated phosphorylation of Sam68 in prostate cancer cells modulates alternative polyadenylation of transcripts that are targets of Sam68, supporting the notion that the ATM–Sam68 axis exerts a multifaceted role in the response to DNA damage. Thus, our work validates Sam68 as an ATM kinase substrate and uncovers an unexpected bidirectional interplay between ATM and Sam68, which couples the DDR pathway to modulation of RNA metabolism in response to genotoxic stress.
PT-112 Induces Mitochondrial Stress and Immunogenic Cell Death, Targeting Tumor Cells with Mitochondrial Deficiencies
Authors: Soler-Agesta Ruth , Marco-Brualla Joaquín , Minjárez-Sáenz Martha , Yim Christina Y. , Martínez-Júlvez Marta , Price Matthew R. , Moreno-Loshuertos Raquel , Ames Tyler D. , Jimeno José , Anel Alberto
Published: August 2022

PT-112 is a novel pyrophosphate–platinum conjugate, with clinical activity reported in advanced pretreated solid tumors. While PT-112 has been shown to induce robust immunogenic cell death (ICD) in vivo but only minimally bind DNA, the molecular mechanism underlying PT-112 target disruption in cancer cells is still under elucidation. The murine L929 in vitro system was used to test whether differential metabolic status alters PT-112’s effects, including cell cytotoxicity. The results showed that tumor cells presenting mutations in mitochondrial DNA (mtDNA) (L929dt and L929dt cybrid cells) and reliant on glycolysis for survival were more sensitive to cell death induced by PT-112 compared to the parental and cybrid cells with an intact oxidative phosphorylation (OXPHOS) pathway (L929 and dtL929 cybrid cells). The type of cell death induced by PT-112 did not follow the classical apoptotic pathway: the general caspase inhibitor Z-VAD-fmk did not inhibit PT-112-induced cell death, alone or in combination with the necroptosis inhibitor necrostatin-1. Interestingly, PT-112 initiated autophagy in all cell lines, though this process was not complete. Autophagy is known to be associated with an integrated stress response in cancer cells and with subsequent ICD. PT-112 also induced a massive accumulation of mitochondrial reactive oxygen species, as well as changes in mitochondrial polarization—only in the sensitive cells harboring mitochondrial dysfunction—along with calreticulin cell-surface exposure consistent with ICD. PT-112 substantially reduced the amount of mitochondrial CoQ10 in L929 cells, while the basal CoQ10 levels were below our detection limits in L929dt cells, suggesting a potential relationship between a low basal level of CoQ10 and PT-112 sensitivity. Finally, the expression of HIF-1α was much higher in cells sensitive to PT-112 compared to cells with an intact OXPHOS pathway, suggesting potential clinical applications.
Integrative, In Silico and Comparative Analysis of Breast Cancer Secretome Highlights Invasive-Ductal-Carcinoma-Grade Progression Biomarkers
Authors: Kastora Stavroula L. , Kounidas Georgios , Speirs Valerie , Masannat Yazan A.
Published: August 2022

Globally, BC is the most frequently diagnosed cancer in women. The aim of this study was to identify novel secreted biomarkers that may indicate progression to high-grade BC malignancies and therefore predict metastatic potential. A total of 33 studies of breast cancer and 78 of other malignancies were screened via a systematic review for eligibility, yielding 26 datasets, 8 breast cancer secretome datasets, and 18 of other cancers that were included in the comparative secretome analysis. Sequential bioinformatic analysis using online resources enabled the identification of enriched GO_terms, overlapping clusters, and pathway reconstruction. This study identified putative predictors of IDC grade progression and their association with breast cancer patient mortality outcomes, namely, HSPG2, ACTG1, and LAMA5 as biomarkers of in silico pathway prediction, offering a putative approach by which the abovementioned proteins may mediate their effects, enabling disease progression. This study also identified ITGB1, FBN1, and THBS1 as putative pan-cancer detection biomarkers. The present study highlights novel, putative secretome biomarkers that may provide insight into the tumor biology and could inform clinical decision making in the context of IDC management in a non-invasive manner.
HSF1 Stimulates Glutamine Transport by Super-Enhancer-Driven lncRNA LINC00857 in Colorectal Cancer
Authors: Shen Qi , Wang Rui , Liu Xinling , Song Ping , Zheng Mingzhu , Ren Xiaomin , Ma Jingang , Lu Zhong , Li Jiaqiu
Published: August 2022

Super enhancers are critical for the gene transcription responsible for cell fate by interacting with transcription factors. However, the relevance of HSF1 to super enhancers in tumors remains obscure. We profiled H3K27ac enrichment by chromatin immunoprecipitation sequencing. HSF1-mediated lncRNAs were identified by lncRNA microarray. The characteristics of LINC00857 were explored by in vitro and in vivo assays. The mechanism was studied via chromatin immunoprecipitation, RNA immunoprecipitation, and HSF1/ANXA11 knockout mice. We found that super enhancers occupied multiple gene loci in colorectal cancer. We screened out an HSF1-mediated super enhancer, lncRNA-LINC00857, which exerts its characteristics in promoting cell growth via regulating glutamine metabolism. Notably, HSF1 could stimulate the super-enhancer activity of LINC00857 by the enrichment of acetyltransferase P300 to its gene loci, contributing to LINC00857 transcription. In turn, nuclear LINC00857 cooperated with HSF1 to promote ANXA11 transcription, which modulated SLC1A5/ASCT2 protein expression by binding competitively to miR-122-5p. The knockout of ANXA11 attenuated colorectal cancer formation in vivo. Collectively, we shed light on a closely cooperative machinery between HSF1 and super enhancers. HSF1 could stimulate acetyltransferase P300-mediated super-enhancer activity to facilitate LINC00857 expression, contributing to SLC1A5-mediated glutamine transport. Targeting the HSF1/LINC00857/ANXA11 axis may provide a valuable therapeutic strategy against colorectal cancer.
Deep Learning Algorithms for Diagnosis of Lung Cancer: A Systematic Review and Meta-Analysis
Authors: Forte Gabriele C. , Altmayer Stephan , Silva Ricardo F. , Stefani Mariana T. , Libermann Lucas L. , Cavion Cesar C. , Youssef Ali , Forghani Reza , King Jeremy , Mohamed Tan-Lucien , Andrade Rubens G. F. , Hochhegger Bruno
Published: August 2022

We conducted a systematic review and meta-analysis of the diagnostic performance of current deep learning algorithms for the diagnosis of lung cancer. We searched major databases up to June 2022 to include studies that used artificial intelligence to diagnose lung cancer, using the histopathological analysis of true positive cases as a reference. The quality of the included studies was assessed independently by two authors based on the revised Quality Assessment of Diagnostic Accuracy Studies. Six studies were included in the analysis. The pooled sensitivity and specificity were 0.93 (95% CI 0.85–0.98) and 0.68 (95% CI 0.49–0.84), respectively. Despite the significantly high heterogeneity for sensitivity (I2 = 94%, p < 0.01) and specificity (I2 = 99%, p < 0.01), most of it was attributed to the threshold effect. The pooled SROC curve with a bivariate approach yielded an area under the curve (AUC) of 0.90 (95% CI 0.86 to 0.92). The DOR for the studies was 26.7 (95% CI 19.7–36.2) and heterogeneity was 3% (p = 0.40). In this systematic review and meta-analysis, we found that when using the summary point from the SROC, the pooled sensitivity and specificity of DL algorithms for the diagnosis of lung cancer were 93% and 68%, respectively.
Circulating SOD2 Is a Candidate Response Biomarker for Neoadjuvant Therapy in Breast Cancer
Authors: Juliachs Mercè , Pujals Mireia , Bellio Chiara , Meo-Evoli Nathalie , Duran Juan M. , Zamora Esther , Parés Mireia , Suñol Anna , Méndez Olga , Sánchez-Pla Alex , Canals Francesc , Saura Cristina , Villanueva Josep
Published: August 2022

There is a great need for non-invasive tools that inform of an early molecular response to cancer therapeutic treatment. Here, we tested the hypothesis that proteolytically resistant proteins could be candidate circulating tumor biomarkers for cancer therapy. Proteins resistant to proteolysis are drastically under-sampled by current proteomic workflows. These proteins could be reliable sensors for the response to therapy since they are likely to stay longer in circulation. We selected manganese superoxide dismutase (SOD2), a mitochondrial redox enzyme, from a screening of proteolytic resistant proteins in breast cancer (BC). First, we confirmed the robustness of SOD2 and determined that its proteolytic resistance is mediated by its quaternary protein structure. We also proved that the release of SOD2 upon chemotherapy treatment correlates with cell death in BC cells. Then, after confirming that SOD2 is very stable in human serum, we sought to measure its circulating levels in a cohort of BC patients undergoing neoadjuvant therapy. The results showed that circulating levels of SOD2 increased when patients responded to the treatment according to the tumor shrinkage during neoadjuvant chemotherapy. Therefore, the measurement of SOD2 levels in plasma could improve the non-invasive monitoring of the therapeutic treatment in breast cancer patients. The identification of circulating biomarkers linked to the tumor cell death induced by treatment could be useful for monitoring the action of the large number of cancer drugs currently used in clinics. We envision that our approach could help uncover candidate tumor biomarkers to measure a tumor’s response to cancer therapy in real time by sampling the tumor throughout the course of treatment.
Establishment of a Prediction Model for Overall Survival after Stereotactic Body Radiation Therapy for Primary Non-Small Cell Lung Cancer Using Radiomics Analysis
Authors: Sawayanagi Subaru , Yamashita Hideomi , Nozawa Yuki , Takenaka Ryosuke , Miki Yosuke , Morishima Kosuke , Ueno Hiroyuki , Ohta Takeshi , Katano Atsuto
Published: August 2022

Stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) leads to recurrence in approximately 18% of patients. We aimed to extract the radiomic features, with which we predicted clinical outcomes and to establish predictive models. Patients with primary non-metastatic NSCLC who were treated with SBRT between 2002 and 2022 were retrospectively reviewed. The 358 primary tumors were randomly divided into a training cohort of 250 tumors and a validation cohort of 108 tumors. Clinical features and 744 radiomic features derived from primary tumor delineation on pre-treatment computed tomography were examined as prognostic factors of survival outcomes by univariate and multivariate analyses in the training cohort. Predictive models of survival outcomes were established from the results of the multivariate analysis in the training cohort. The selected radiomic features and prediction models were tested in a validation cohort. We found that one radiomic feature showed a significant difference in overall survival (OS) in the validation cohort (p = 0.044) and one predicting model could estimate OS time (mean: 37.8 months) similar to the real OS time (33.7 months). In this study, we identified one radiomic factor and one prediction model that can be widely used.