bluuebunny/crossref_metadata_2025 huggingface dataset:
Gas Detection and Identification Using Multimodal Artificial Intelligence Based Sensor Fusion
Authors: Narkhede Parag , Walambe Rahee , Mandaokar Shruti , Chandel Pulkit , Kotecha Ketan , Ghinea George
Published: January 2021

With the rapid industrialization and technological advancements, innovative engineering technologies which are cost effective, faster and easier to implement are essential. One such area of concern is the rising number of accidents happening due to gas leaks at coal mines, chemical industries, home appliances etc. In this paper we propose a novel approach to detect and identify the gaseous emissions using the multimodal AI fusion techniques. Most of the gases and their fumes are colorless, odorless, and tasteless, thereby challenging our normal human senses. Sensing based on a single sensor may not be accurate, and sensor fusion is essential for robust and reliable detection in several real-world applications. We manually collected 6400 gas samples (1600 samples per class for four classes) using two specific sensors: the 7-semiconductor gas sensors array, and a thermal camera. The early fusion method of multimodal AI, is applied The network architecture consists of a feature extraction module for individual modality, which is then fused using a merged layer followed by a dense layer, which provides a single output for identifying the gas. We obtained the testing accuracy of 96% (for fused model) as opposed to individual model accuracies of 82% (based on Gas Sensor data using LSTM) and 93% (based on thermal images data using CNN model). Results demonstrate that the fusion of multiple sensors and modalities outperforms the outcome of a single sensor.
Systems Engineering Methodology for Designing Digital Public–Private Partnership Platforms
Authors: Glukhikh Igor Nikolaevich , Tolstolesova Liudmila Anatolevna , Arzikulov Otabek Anzor ugli
Published: January 2021

The modern approach to realization of large, expensive projects with long payback periods in various sectors of infrastructure often involves combining the financial resources of public authorities and the private sector through a public–private partnership (PPP) mechanism. The PPP mechanism has a high potential for attracting investments and facilitating other conditions necessary for the project. At the same time, the project participants need a third-party coordination platform that is objective and able to organize their dialog on equal terms. The authors of this article, for these purposes, consider the capabilities of digital platforms (DP). Digital platforms are able to unite many project participants in a single information field and provide them with the necessary services. Given the potential multitude of participants in such a system, there arises the question of meeting their basic needs to create mutually beneficial conditions during the implementation of projects. Thus, there is a need for flexible DPs. Flexibility can be achieved by using systems engineering (SE) approaches during the design of the DP. The practice of interaction with stakeholders in the framework of systems engineering allows the determination of the basic needs and areas of activity of the participants. The results of this practice will form the basis for the functional and physical design of the future DPs.
Characteristics of Locally Occurring High PM2.5 Concentration Episodes in a Small City in South Korea
Authors: Choi Su-Yeon , Park Sung-Won , Byun Jin-Yeo , Han Young-Ji
Published: January 2021

In this study, the ionic and carbonaceous compounds in PM2.5 were analysed in the small residential city of Chuncheon, Korea. To identify the local sources that substantially influence PM2.5 concentrations, the samples were divided into two groups: samples with PM2.5 concentrations higher than those in the upwind metropolitan area (Seoul) and samples with lower PM2.5 concentrations. During the sampling period (December 2016–August 2018), the average PM2.5 was 23.2 μg m−3, which exceeds the annual national ambient air quality standard (15 μg m−3). When the PM2.5 concentrations were higher in Chuncheon than in Seoul, the organic carbon (OC) and elemental carbon (EC) concentrations increased the most among all the PM2.5 components measured in this study. This is attributable to secondary formation and biomass burning, because secondary OC was enhanced and water soluble OC was strongly correlated with K+, EC, and OC. A principal component analysis identified four factors contributing to PM2.5: fossil-fuel combustion, secondary inorganic and organic reactions in biomass burning plumes, crustal dust, and secondary NH4+ formation.
Parametrizations of Liquid and Ice Clouds’ Optical Properties in Operational Numerical Weather Prediction Models
Authors: Muskatel Harel. B. , Blahak Ulrich , Khain Pavel , Levi Yoav , Fu Qiang
Published: January 2021

Parametrization of radiation transfer through clouds is an important factor in the ability of Numerical Weather Prediction models to correctly describe the weather evolution. Here we present a practical parameterization of both liquid droplets and ice optical properties in the longwave and shortwave radiation. An advanced spectral averaging method is used to calculate the extinction coefficient, single scattering albedo, forward scattered fraction and asymmetry factor (βext, ϖ, f, g), taking into account the nonlinear effects of light attenuation in the spectral averaging. An ensemble of particle size distributions was used for the ice optical properties calculations, which enables the effective size range to be extended up to 570 μm and thus be applicable for larger hydrometeor categories such as snow, graupel, and rain. The new parameterization was applied both in the COSMO limited-area model and in ICON global model and was evaluated by using the COSMO model to simulate stratiform ice and water clouds. Numerical weather prediction models usually determine the asymmetry factor as a function of effective size. For the first time in an operational numerical weather prediction (NWP) model, the asymmetry factor is parametrized as a function of aspect ratio. The method is generalized and is available on-line to be readily applied to any optical properties dataset and spectral intervals of a wide range of radiation transfer models and applications.
Recent Advances in Studying Air Quality and Health Effects of Shipping Emissions
Authors: Contini Daniele , Merico Eva
Published: January 2021

The increase of global commerce and tourism makes the shipping sector an important contributor of atmospheric particles and gaseous pollutants. These have impacts on both health and climate, especially in populated coastal areas. Maritime activities could be an important driver for economic and social development, however, they are also an environmental pressure. Several policies were implemented in the last decades, at local/regional or international levels, mainly focused on reducing the content of sulphur in marine fuels. The last international IMO-2020 regulation was enforced on 1 January 2020. This work reviews some recent studies on this topic delineating current knowledge of the impacts of maritime emissions on air quality and health and the future projections relative to the benefits of the implementation of the new IMO-2020 regulation. In addition, future perspectives for further mitigation strategies are discussed.
Multi-Oxygenated Organic Compounds in Fine Particulate Matter Collected in the Western Mediterranean Area
Authors: Borrás Esther , Tortajada-Genaro Luis Antonio , Sanz Francisco , Muñoz Amalia
Published: January 2021

The chemical characterization of aerosols, especially fine organic fraction, is a relevant atmospheric challenge because their composition highly depends on localization. Herein, we studied the concentration of multi-oxygenated organic compounds in the western Mediterranean area, focusing on sources and the effect of air patterns. The organic aerosol fraction ranged 3–22% of the total organic mass in particulate matter (PM)2.5. Seventy multi-oxygenated organic pollutants were identified by gas chromatography–mass spectrometry, including n-alkanones, n-alcohols, anhydrosugars, monocarboxylic acids, dicarboxylic acids, and keto-derivatives. The highest concentrations were found for carboxylic acids, such as linoleic acid, tetradecanoic acid and, palmitic acid. Biomarkers for vegetation sources, such as levoglucosan and some fatty acids were detected at most locations. In addition, carboxylic acids from anthropogenic sources—mainly traffic and cooking—have been identified. The results indicate that the organic PM fraction in this region is formed mainly from biogenic pollutants, emitted directly by vegetation, and from the degradation products of anthropogenic and biogenic volatile organic pollutants. Moreover, the chemical profile suggested that this area is interesting for aerosol studies because several processes such as local costal breezes, industrial emissions, and desert intrusions affect fine PM composition.
Evaluation of Different Storm Parameters as the Proxies for Gridded Total Lightning Flash Rates: A Convection-Allowing Model Study
Authors: Qian Xinyao , Wang Haoliang
Published: January 2021

Lightning simulation is important for a variety of applications, including lightning forecast, atmospheric chemical simulation, and lightning data assimilation. In this study, the potential of five storm parameters (graupel volume, precipitation ice mass, radar echo volume, maximum updraft, and updraft volume) to be used as the proxy for the diagnosis of gridded total lightning flash rates has been investigated in a convection-allowing model. A mesoscale convective system occurred in the Guangdong province of China was selected as the test case. Radar data assimilation was used to improve the simulation accuracy of the convective clouds, hence providing strong instantaneous correlations between observed and simulated storm signatures. The areal coverage and magnitude of the simulated lightning flash rates were evaluated by comparing to those of the total lightning observations. Subjective and the Fractions Skill Score (FSS) evaluations suggest that all the five proxies tested in this study are useful to indicate general tendencies for the occurrence, region, and time of lightning at convection-allowing scale (FSS statistics for the threshold of 1 flash per 9 km2 per hour were around 0.7 for each scheme). The FSS values were decreasing as the lightning flash rate thresholds used for FSS computation increased for all the lightning diagnostic schemes with different proxies. For thresholds from 1 to 3 and 16 to 20 flashes per 9 km2 per hour, the graupel contents related schemes achieved higher FSS values compared to the other three schemes. For thresholds from 5 to 15 flashes per 9 km2 per hour, the updraft volume related scheme yielded the largest FSS. When the thresholds of lightning flash rates were greater than 13 flashes per 9 km2 per hour, the FSS values were below 0.5 for all the lightning diagnostic schemes with different proxies.
A Comparison of Meteor Radar Observation over China Region with Horizontal Wind Model (HWM14)
Authors: Tang Qiong , Zhou Yufeng , Du Zhitao , Zhou Chen , Qiao Jiandong , Liu Yi , Chen Guanyi
Published: January 2021

This paper compares the wind fields measured by the meteor radar at Mohe, Beijing, Wuhan, and Sanya stations and horizontal wind model (HWM14) predictions. HWM14 appears to successfully reproduce the height-time distribution of the monthly mean zonal winds, although large discrepancies occur in wind speed between the model and measurement, especially in the summer and winter months. For meridional wind, the consistency between model prediction and radar observation is worse than that of zonal wind. The consistency between radar measurements and model prediction at Sanya station is worse than other sites located at higher latitudes. Harmonic analysis reveals large discrepancies in diurnal, semidiurnal, and terdiurnal tides extracted from meteor radar observations and HWM14 predictions.
Effect of Adaptive, Rotary, and Manual Root Canal Instrumentation in Primary Molars: A Triple-Armed, Randomized Controlled Clinical Trial
Authors: Pawar Bhaggyashri A. , Pawar Ajinkya M. , Bhardwaj Anuj , Wahjuningrum Dian Agustin , Rahardjo Amelia Kristanti , Luke Alexander Maniangat , Metzger Zvi , Kfir Anda
Published: January 2021

This clinical trial focused on collating the instrumentation time and quality of root canal obturation in primary molars treated with three instrumentation techniques: adaptive, rotary, and manual. A triple-armed, randomized controlled clinical trial was performed on 75 primary molars requiring pulpectomy treatment, divided into three groups (n = 25 per group). The teeth in Group 1 were instrumented with an adaptive technique (XP-endo Shaper, FKG Dentaire, La Chaux-de-Fonds, Switzerland), Group 2 with pediatric rotary files (Kedo-S; D1 and E1), and Group 3 with a manual technique (hand K-files). The apical size of the final instrumentation was maintained at #30 for all groups. Instrumentation time and the grade of the root canal obturation were evaluated. Instrumentation duration was recorded, employing a digital stopwatch from the insertion of the first file until the completion of final irrigation. Obturation quality was assessed using radiographs. The criteria taken as a reference for obturation were: optimal (1 mm short of the apex), underfilled (2 mm short of the apex), or overfilled (beyond the apex). The use of an adaptive technique was associated with the lowest instrumentation time (p < 0.0001) when used for instrumenting primary molars and with the highest root canal filling quality of the three groups. The application of the new concept of adaptive instrumentation for pulpectomy of primary molars was a favorable technique, considering the significant reduction in instrumentation time and better obturation.
Efficacy and Safety of Mesenchymal Stem/Stromal Cell Therapy for Inflammatory Bowel Diseases: An Up-to-Date Systematic Review
Authors: Ko Jeffrey Zheng-Hsien , Johnson Sheeva , Dave Maneesh
Published: January 2021

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gut that can lead to severe gastrointestinal symptoms, malnutrition, and complications such as fistulas and cancer. Mesenchymal stem/stromal cells (MSCs) are being investigated as a novel therapy for IBD and have been demonstrated to be safe and effective for perianal fistulizing Crohn’s disease (PFCD). This systematic review aims to present the most recent studies on the safety and efficacy of MSC therapy in IBD. A detailed search strategy of clinical trials on MSCs and IBD was performed on PubMed, with 32 studies selected for inclusion in this review. The newest studies on local MSC injection for PFCD continue to support long-term efficacy while maintaining a favorable safety profile. The evidence for systemic MSC infusion in luminal IBD remains mixed due to marked methodological heterogeneity and unclear safety profiles. Although further studies are needed to better establish the role of this novel treatment modality, MSCs are proving to be a very exciting addition to the limited therapies available for IBD.
Orchestration of Neutrophil Extracellular Traps (Nets), a Unique Innate Immune Function during Chronic Obstructive Pulmonary Disease (COPD) Development
Authors: Trivedi Anjali , Khan Meraj A. , Bade Geetanjali , Talwar Anjana
Published: January 2021

Morbidity, mortality and economic burden caused by chronic obstructive pulmonary disease (COPD) is a significant global concern. Surprisingly, COPD is already the third leading cause of death worldwide, something that WHO had not predicted to occur until 2030. It is characterized by persistent respiratory symptoms and airway limitation due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles of gases. Neutrophil is one of the key infiltrated innate immune cells in the lung during the pathogenesis of COPD. Neutrophils during pathogenic attack or injury decide to undergo for a suicidal death by releasing decondensed chromatin entangled with antimicrobial peptides to trap and ensnare pathogens. Casting neutrophil extracellular traps (NETs) has been widely demonstrated to be an effective mechanism against invading microorganisms thus controlling overwhelming infections. However, aberrant and massive NETs formation has been reported in several pulmonary diseases, including chronic obstructive pulmonary disease. Moreover, NETs can directly induce epithelial and endothelial cell death resulting in impairing pulmonary function and accelerating the progression of the disease. Therefore, understanding the regulatory mechanism of NET formation is the need of the hour in order to use NETs for beneficial purpose and controlling their involvement in disease exacerbation. For example, DNA neutralization of NET proteins using protease inhibitors and disintegration with recombinant human DNase would be helpful in controlling excess NETs. Targeting CXC chemokine receptor 2 (CXCR2) would also reduce neutrophilic inflammation, mucus production and neutrophil-proteinase mediated tissue destruction in lung. In this review, we discuss the interplay of NETs in the development and pathophysiology of COPD and how these NETs associated therapies could be leveraged to disrupt NETopathic inflammation as observed in COPD, for better management of the disease.
Detection of Hypoxanthine from Inosine and Unusual Hydrolysis of Immunosuppressive Drug Azathioprine through the Formation of a Diruthenium(III) System
Authors: Orts-Arroyo Marta , Castro Isabel , Martínez-Lillo José
Published: January 2021

Hypoxanthine (hpx) is an important molecule for both biochemistry research and biomedical applications. It is involved in several biological processes associated to energy and purine metabolism and has been proposed as a biomarker for a variety of disease states. Consequently, the discovery and development of systems suitable for the detection of hypoxanthine is pretty appealing in this research field. Thus, we have obtained a stable diruthenium (III) compound in its dehydrated and hydrated forms with formula [{Ru(µ-Cl)(µ-hpx)}2Cl4] (1a) and [{Ru(µ-Cl)(µ-hpx)}2Cl4]·2H2O (1b), respectively. This purine-based diruthenium(III) system was prepared from two very different starting materials, namely, inosine and azathioprine, the latter being an immunosuppressive drug. Remarkably, it was observed that an unusual azathioprine hydrolysis occurs in the presence of ruthenium, thus generating hypoxanthine instead of the expected 6-mercaptopurine antimetabolite, so that the hpx molecule is linked to two ruthenium(III) ions. 1a and 1b were characterized through IR, SEM, powder and single-crystal X-ray Diffraction and Cyclic Voltammetry (CV). The electrochemical studies allowed us to detect the hpx molecule when coordinated to ruthenium in the reported compound. The grade of sensitivity, repeatability and stability reached by this diruthenium system make it potentially useful and could provide a first step to develop new sensor devices suitable to detect hypoxanthine.
Astrocyte-Derived TGFβ1 Facilitates Blood–Brain Barrier Function via Non-Canonical Hedgehog Signaling in Brain Microvascular Endothelial Cells
Authors: Fu Jiyang , Li Liang , Huo Dong , Zhi Shuli , Yang Ruicheng , Yang Bo , Xu Bojie , Zhang Tao , Dai Menghong , Tan Chen , Chen Huanchun , Wang Xiangru
Published: January 2021

The blood–brain barrier is a specialized structure in mammals, separating the brain from the bloodstream and maintaining the homeostasis of the central nervous system. The barrier is composed of various types of cells, and the communication between these cells is critical to blood–brain barrier (BBB) function. Here, we demonstrate the astrocyte-derived TGFβ1-mediated intercellular communication between astrocytes and brain microvascular endothelial cells (BMECs). By using an in vitro co-culture model, we observed that the astrocyte-derived TGFβ1 enhanced the tight junction protein ZO-1 expression in BMECs and the endothelial barrier function via a non-canonical hedgehog signaling. Gli2, the core transcriptional factor of the hedgehog pathway, was demonstrated to modulate ZO-1 expression directly. By the dual-luciferase reporter system and chromatin immunoprecipitation, we further identified the exact sites on Smad2/3 that bound to the gli2 promotor and on Gli2 that bound to the zo-1 promotor. Our work highlighted the TGFβ1-mediated intercellular communication of astrocytes with BMECs in BBB, which shall extend current knowledge on the BBB homeostasis physiologically, and more importantly suggests TGFβ1 as a potential effector for future prevention and amelioration of BBB dysfunction.
Oxidative Stress and Neurodevelopmental Outcomes in Rat Offspring with Intrauterine Growth Restriction Induced by Reduced Uterine Perfusion
Authors: Rains Marcelo E. , Muncie Colin B. , Pang Yi , Fan Lir-Wan , Tien Lu-Tai , Ojeda Norma B.
Published: January 2021

Intrauterine growth restriction (IUGR) is a major cause of morbidity and mortality and is worldwide associated with delayed neurodevelopment. The exact mechanism involved in delayed neurodevelopment associated with IUGR is still unclear. Reduced uterine perfusion (RUP) is among the main causes of placental insufficiency leading to IUGR, which is associated with increases in oxidative stress. This study investigated whether oxidative stress is associated with delayed neurodevelopment in IUGR rat pups. Pregnant rats were exposed to RUP surgery on gestational day 14 to generate IUGR rat offspring. We evaluated offspring’s morphometric at birth, and neurodevelopment on postnatal day 21 (PD21) as well as markers of oxidative stress in plasma and brain. Offspring from dams exposed to RUP showed significant (p < 0.05) lower birth weight compared to controls, indicating IUGR. Motor and cognitive deficits, and levels of oxidative stress markers, were significantly (p < 0.05) elevated in IUGR offspring compared to controls. IUGR offspring showed significant (p < 0.05) negative correlations between brain lipid peroxidation and neurocognitive tests (open field and novel object recognition) in comparison with controls. Our findings suggest that neurodevelopmental delay observed in IUGR rat offspring is associated with increased levels of oxidative stress markers.
Etiology of ‘Sinus Headache’—Moving the Focus from Rhinology to Neurology. A Systematic Review
Authors: Straburzyński Marcin , Gryglas-Dworak Anna , Nowaczewska Magdalena , Brożek-Mądry Eliza , Martelletti Paolo
Published: January 2021

‘Sinus headache and/or facial pain’ (SH) is a common complaint encountered by otorhinolaryngologists, neurologists and general practitioners. However, several studies suggested that the majority of those cases may be attributed to primary headaches (i.e., migraine and tension-type headache (TTH). The purpose of this review is to evaluate the etiology of SH. The first part includes cross-sectional studies analyzing the prevalence of respective diagnoses in subjects with SH. The majority of these publications indicate that migraine and TTH are the most prevalent causes of SH, although most of these studies were conducted in a clinical setting. The second part of this review included treatment trials in subjects with SH. The findings from this part of the review show that SH without rhinosinusitis responds well to pharmacotherapy targeted at primary headaches. This observation further supports a neurologic etiology of the majority of SH cases.
Gray Matter Morphometry Correlates with Attentional Efficiency in Young-Adult Multiple Sclerosis
Authors: Govindarajan Sindhuja T. , Pan Ruiqi , Krupp Lauren , Charvet Leigh , Duong Tim Q.
Published: January 2021

Slowed processing on the alerting, orienting and executive control components of attention measured using the Attention Network Test-Interactions (ANT-I) have been widely reported in multiple sclerosis (MS). Despite the assumption that these components correspond to specific neuroanatomical networks in the brain, little is known about gray matter changes that occur in MS and their association with ANT-I performance. We investigated vertex-wise cortical thickness changes and deep gray matter volumetric changes in young MS participants (N = 21, age range: 18–35) with pediatric or young-adult onset and mild disease severity. ANT-I scores and cortical thickness were not significantly different between MS participants and healthy volunteers (N = 19, age range: 18–35), but thalamic volumes were significantly lower in MS. Slowed reaction times on the alerting component in MS correlated significantly with reduced volume of the right pallidum in MS. Slowed reaction times on executive control component correlated significantly with reduced thickness in the frontal, parietal and visual cortical areas and with reduced volume of the left putamen in MS. These findings demonstrate associations between gray matter changes and attentional performance even in the absence of widespread atrophy or slowed attentional processes.
Focused Ultrasound in Neuroscience. State of the Art and Future Perspectives
Authors: Giammalva Giuseppe Roberto , Gagliardo Cesare , Marrone Salvatore , Paolini Federica , Gerardi Rosa Maria , Umana Giuseppe Emmanuele , Yağmurlu Kaan , Chaurasia Bipin , Scalia Gianluca , Midiri Federico , La Grutta Ludovico , Basile Luigi , Gulì Carlo , Messina Domenico , Pino Maria Angela , Graziano Francesca , Tumbiolo Silvana , Iacopino Domenico Gerardo , Maugeri Rosario
Published: January 2021

Transcranial MR-guided Focused ultrasound (tcMRgFUS) is a surgical procedure that adopts focused ultrasounds beam towards a specific therapeutic target through the intact skull. The convergence of focused ultrasound beams onto the target produces tissue effects through released energy. Regarding neurosurgical applications, tcMRgFUS has been successfully adopted as a non-invasive procedure for ablative purposes such as thalamotomy, pallidotomy, and subthalamotomy for movement disorders. Several studies confirmed the effectiveness of tcMRgFUS in the treatment of several neurological conditions, ranging from motor disorders to psychiatric disorders. Moreover, using low-frequencies tcMRgFUS systems temporarily disrupts the blood–brain barrier, making this procedure suitable in neuro-oncology and neurodegenerative disease for controlled drug delivery. Nowadays, tcMRgFUS represents one of the most promising and fascinating technologies in neuroscience. Since it is an emerging technology, tcMRgFUS is still the subject of countless disparate studies, even if its effectiveness has been already proven in many experimental and therapeutic fields. Therefore, although many studies have been carried out, many others are still needed to increase the degree of knowledge of the innumerable potentials of tcMRgFUS and thus expand the future fields of application of this technology.
Congenital Disorders of Glycosylation from a Neurological Perspective
Authors: Paprocka Justyna , Jezela-Stanek Aleksandra , Tylki-Szymańska Anna , Grunewald Stephanie
Published: January 2021

Most plasma proteins, cell membrane proteins and other proteins are glycoproteins with sugar chains attached to the polypeptide-glycans. Glycosylation is the main element of the post-translational transformation of most human proteins. Since glycosylation processes are necessary for many different biological processes, patients present a diverse spectrum of phenotypes and severity of symptoms. The most frequently observed neurological symptoms in congenital disorders of glycosylation (CDG) are: epilepsy, intellectual disability, myopathies, neuropathies and stroke-like episodes. Epilepsy is seen in many CDG subtypes and particularly present in the case of mutations in the following genes: ALG13, DOLK, DPAGT1, SLC35A2, ST3GAL3, PIGA, PIGW, ST3GAL5. On brain neuroimaging, atrophic changes of the cerebellum and cerebrum are frequently seen. Brain malformations particularly in the group of dystroglycanopathies are reported. Despite the growing number of CDG patients in the world and often neurological symptoms dominating in the clinical picture, the number of performed screening tests eg transferrin isoforms is systematically decreasing as broadened genetic testing is recently more favored. The aim of the review is the summary of selected neurological symptoms in CDG described in the literature in one paper. It is especially important for pediatric neurologists not experienced in the field of metabolic medicine. It may help to facilitate the diagnosis of this expanding group of disorders. Biochemically, this paper focuses on protein glycosylation abnormalities.
Seismic Upgrading of a Historical Masonry Bell Tower through an Internal Dissipative Steel Structure
Authors: Pavia Arianna , Scozzese Fabrizio , Petrucci Enrica , Zona Alessandro
Published: January 2021

Masonry towers are part of a valuable architectural heritage characterizing the landscape of many historical areas. These towers are vulnerable structures that are prone to earthquake damage. Hence, the design of effective seismic upgrading interventions is an important task for preserving such architectural forms for future generations. In view of that, the objective of this study is to contribute a possible addition to the portfolio of available approaches for seismic upgrading of masonry towers. This goal was pursued by exploring an innovative structural solution that does not alter the external appearance of the tower and its static scheme under gravity loads, yet is able to increase its capacity to withstand seismic actions through added damping. Specifically, the proposed solution consists of a steel structure internal to the masonry tower that incorporates fluid viscous dampers. In order to evaluate its potentialities, a real case study was taken as a testbed structure, historic analysis as well as geometric and architectural surveys were undertaken, an initial design for the upgrading was made, and numerical simulations were performed. The obtained results, although preliminary, highlight the potentialities of the proposed structural solution for the seismic upgrading of masonry towers and might open the way to future developments and applications.
Understanding the Operation of Contextual Compatibility through the Relationships among Heritage Intensity, Context Density, and Regulation Degree
Authors: Choi Jeongyoon , Park Sohyun
Published: January 2021

It is easy to assume that historic environments consist mainly of traditional pre-modern style buildings; however, contemporary architecture is continuously added to historic environments, and its construction is positively encouraged by international heritage organizations such as UNESCO and ICOMOS. The conditions required for introducing contemporary architecture to historic urban environments manifest through the concept of contextual compatibility. This paper examines the meaning and operation of this compatibility in changing urban historical and cultural environments. It offers an empirical interpretation of ‘compatibility’ using three new conceptual parameters: the level of conservation value and importance designated by the heritage conservation system (heritage intensity), the ratio of contemporary architecture in a historic environment (context density), and the range of controlling measures available for conservation (regulation degree). Based on a content analysis of the relevant literature and a case study of 24 sample sites, this paper illuminates how ‘compatibility’ operates in the field, which sometimes contradicts our common assumptions. The notable findings reveal that heritage intensity and context density in the historical environment are not directly proportional to regulation degree. Meanwhile, low context density tends to correspond with highly detailed regulations and emphasise the physical realization of traditional elements.
Signaling Pathway Mediating Myeloma Cell Growth and Survival
Authors: Hideshima Teru , Anderson Kenneth C.
Published: January 2021

The multiple myeloma (MM) bone marrow (BM) microenvironment consists of different types of accessory cells. Both soluble factors (i.e., cytokines) secreted from these cells and adhesion of MM cells to these cells play crucial roles in activation of intracellular signaling pathways mediating MM cell growth, survival, migration, and drug resistance. Importantly, there is crosstalk between the signaling pathways, increasing the complexity of signal transduction networks in MM cells in the BM microenvironment, highlighting the requirement for combination treatment strategies to blocking multiple signaling pathways.
Comprehensive Assessment of Copy Number Alterations Uncovers Recurrent AIFM3 and DLK1 Copy Gain in Medullary Thyroid Carcinoma
Authors: Araujo Aline Neves , Camacho Cléber Pinto , Mendes Thais Biude , Lindsey Susan Chow , Moraes Lais , Miyazawa Marta , Delcelo Rosana , Pellegrino Renata , Mazzotti Diego Robles , Maciel Rui Monteiro de Barros , Cerutti Janete Maria
Published: January 2021

Medullary thyroid carcinoma (MTC) is a malignant tumor originating from thyroid C-cells that can occur either in sporadic (70–80%) or hereditary (20–30%) form. In this study we aimed to identify recurrent copy number alterations (CNA) that might be related to the pathogenesis or progression of MTC. We used Affymetrix SNP array 6.0 on MTC and paired-blood samples to identify CNA using PennCNV and Genotyping Console software. The algorithms identified recurrent copy number gains in chromosomes 15q, 10q, 14q and 22q in MTC, whereas 4q cumulated losses. Coding genes were identified within CNA regions. The quantitative PCR analysis performed in an independent series of MTCs (n = 51) confirmed focal recurrent copy number gains encompassing the DLK1 (14q32.2) and AIFM3 (22q11.21) genes. Immunohistochemistry confirmed AIFM3 and DLK1 expression in MTC cases, while no expression was found in normal thyroid tissues and few MTC samples were found with normal copy numbers. The functional relevance of CNA was also assessed by in silico analysis. CNA status correlated with protein expression (DLK1, p = 0.01), tumor size (DLK1, p = 0.04) and AJCC staging (AIFM3p = 0.01 and DLK1p = 0.05). These data provide a novel insight into MTC biology, and suggest a common CNA landscape, regardless of if it is sporadic or hereditary MTC.
Image-Guided Proton Therapy for Elderly Patients with Hepatocellular Carcinoma: High Local Control and Quality of Life Preservation
Authors: Iwata Hiromitsu , Ogino Hiroyuki , Hattori Yukiko , Nakajima Koichiro , Nomura Kento , Hayashi Kensuke , Toshito Toshiyuki , Sasaki Shigeru , Hashimoto Shingo , Mizoe Jun-etsu , Shibamoto Yuta
Published: January 2021

This study retrospectively investigated the efficacy and safety of image-guided proton therapy (IGPT) for elderly (≥80 years old) hepatocellular carcinoma (HCC) patients. Proton therapy was performed using respiratory-gated and image-guided techniques. Seventy-one elderly HCC patients were treated using IGPT. The Child–Pugh score was A5 in 49 patients, A6 in 15, and B7-9 in 7. Forty-seven patients with a peripherally located tumor were administered 66 gray relative biological effectiveness (GyRBE) in 10 fractions, whereas 24 with a centrally located tumor received 72.6 GyRBE in 22 fractions. The median follow-up period of surviving patients was 33 months (range: 9–68). Two-year overall survival (OS) and local control (LC) rates estimated by the Kaplan–Meier method were 76% (95% confidence interval: 66–87%) and 88% (80–97%), respectively. According to the Common Terminology Criteria for Adverse Events version 4.0, no grade 2 or higher radiation-induced liver disease was observed, and only 1 patient developed grade 3 dermatitis. The quality of life score (European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 version 3.0, QLQ-HCC18, and SF-36) did not change after 1 year, except for the three-mental component summary (SF-36, improvement). IGPT is a safe and effective treatment for HCC in elderly patients.
Functional T Cell Reactivity to Melanocyte Antigens Is Lost during the Progression of Malignant Melanoma, but Is Restored by Immunization
Authors: Przybyla Anna , Lehmann Alexander A. , Zhang Ting , Mackiewicz Jacek , Galus Łukasz , Kirchenbaum Greg A. , Mackiewicz Andrzej , Lehmann Paul V.
Published: January 2021

Healthy human subjects develop spontaneous CD8+ T cell responses to melanoma associated antigens (MA) expressed by normal melanocytes, such as Tyrosinase, MAGE-A3, Melan/Mart-1, gp100, and NY-ESO-1. This natural autoimmunity directed against melanocytes might confer protection against the development of malignant melanoma (MM), where MA are present as overexpressed tumor-associated antigens. Consistent with this notion we report here that functional T cell reactivity to MA was found to be significantly diminished to MAGE-A3, Melan-A/Mart-1, and gp100 in untreated MM patients. Three lines of evidence suggest that the MA-reactive T cells present in healthy subjects undergo exhaustion once MM establishes itself. First, only the MA-specific T cell reactivity was affected in the MM patients; that to third party recall antigens was not. Second, in these patients, the residual MA-specific T cells, unlike third party antigen reactive T cells, were functionally impaired, showing a diminished per cell IFN-γ productivity. Third, we show that immunization with MA restored natural CD8+ T cell autoimmunity to MA in 85% of the MM patients. The role of natural T cell autoimmunity to tumor-associated MA is discussed based on discrete levels of T cell activation thresholds.
A 3D View of Colorectal Cancer Models in Predicting Therapeutic Responses and Resistance
Authors: Reidy Eileen , Leonard Niamh A. , Treacy Oliver , Ryan Aideen E.
Published: January 2021

Although there have been many advances in recent years for the treatment of colorectal cancer (CRC), it still remains the third most common cause of cancer-related deaths worldwide. Many patients with late stage CRC display resistance to multiple different therapeutics. An important aspect in developing effective therapeutics for CRC patients is understanding the interactions that take place in the tumor microenvironment (TME), as it has been shown to contribute to drug resistance in vivo. Much research over the past 100 years has focused on 2D monolayer cultures or in vivo studies, however, the efficacy in translating these to the clinic is very low. More recent studies are turning towards developing an effective 3D model of CRC that is clinically relevant, that can recapitulate the TME in vitro and bridge the gap between 2D cultures and in vivo studies, with the aim of reducing the use of animal models in the future. This review summarises the advantages and limitations of different 3D CRC models. It emphasizes how different 3D models may be optimised to study cellular and extracellular interactions that take place in the TME of CRC in an effort to allow the development of more translatable effective treatment options for patients.
Molecular Heterogeneity of High Grade Colorectal Adenocarcinoma
Authors: Perna Cristian , Navarro Antonia , Ruz-Caracuel Ignacio , Caniego-Casas Tamara , Cristóbal Eva , Leskelä Susanna , Longo Federico , Caminoa Alejandra , Santón Almudena , Ferreiro Reyes , Pizarro David , Palacios-Berraquero María Luisa , Palacios José
Published: January 2021

High grade colorectal carcinomas (HG-CRCs), which comprise 15% of colorectal carcinomas, are underrepresented in reported molecular studies. Clinicopathological, immunohistochemical, and molecular features of 40 HG-CRCs are described. Moreover, glandular and solid areas of 25 tumors were separately analyzed. The expression of MLH1, PMS2, MSH2, MSH6, p53, E-cadherin, CDX2, CK20, CD8, PDL1, PAN-TRK, c-MET, SMARCB1, ARID1A, SMARCA2, and SMARCA4 was analyzed by immunohistochemistry. Promoter MLH1 methylation was analyzed in tumors with MLH1/PMS2 loss. Next-generation sequencing was used to screen 161 genes for hotspot mutations, copy number variations and gene fusions. In this series, 72.5% of HG-CRCs showed mismatch repair deficiency (MMRd). MMR deficient tumor and MMR proficient (MMRp) tumors showed striking molecular differences. Thus, whereas BRAF mutations were only observed in MMRd tumors, mutations in KRAS and TP53 were more frequent in MMR proficient tumors. Moreover, gene fusions (NTRK1 and MET) were detected only in MMRd tumors, whereas gene amplification (MYC, CCND1 and EGFR) predominated in MMRp/TP53-mutated tumors. Loss of expression of proteins involved in chromatin remodeling, such as ARID1A, was observed only in MMRd HG-CRCs, which also showed more frequently PD-L1 expression and a higher number of tumor infiltrating lymphocytes. The separate analysis of glandular and solid areas indicated that the clonal or subclonal nature of the molecular alterations also depended on MMR status. Mutations in genes such as TP53 and KRAS were always clonal in MMRp-CRCs but occurred as subclonal events in MMRd-CRCs. Gene amplification was implicated in the progression of MMRp tumors, but not in MMRd tumors, in which clonal diversity was due to accumulation of mutations in genes of different pathways such as NOTCH, MMR, or PIK3CA. In summary, intertumor and intratumor molecular heterogeneity in HG-CRCs is mainly due to MMR status.
Lidocaine Suppresses Viability and Migration of Human Breast Cancer Cells: TRPM7 as a Target for Some Breast Cancer Cell Lines
Authors: Liu Hengrui , Dilger James P. , Lin Jun
Published: January 2021

Background: The local anesthetic lidocaine suppresses some cancer cell lines but the mechanism is unclear. The melastatin-like transient receptor potential 7 (TRPM7) ion channel is aberrantly expressed in some cancers and may play a role in the disease. Hence, we suggested that lidocaine affects the viability and migration of breast cancer cells by regulating TRPM7. Methods: We measured the effects of lidocaine on TRPM7 function in HEK293 with exogenous TRPM7 expression (HEK-M7) using whole-cell patch-clamp and fura-2AM-based quench assay. We measured the effect of lidocaine on TRPM7 function, cell viability, and migration in TRPM7 expressing human breast cancer cell lines using fura-2AM-based quench, MTT, and wound-healing assays respectively. We compared cell viability and migration of wild type HEK293 cells (WT-HEK) with HEK-M7 and wild type MDA-MB-231 (WT-231) with TRPM7 knockout MDA-MB-231 (KO-231). Results: Lidocaine (1–3 mM) inhibited the viability and migration of all of these breast cancer cell lines. Functional evidence for TRPM7 was confirmed in the MDA-MB-231, AU565, T47D, and MDA-MB-468 cell lines where lidocaine at 0.3–3 mM suppressed the TRPM7 function. Lidocaine preferentially suppressed viability and migration of HEK-M7 over WT-HEK and WT-231 over KO-231. Conclusions: Lidocaine differentially reduced the viability and migration of human breast cancer cell lines tested. TRPM7 is one of the potential targets for the effects of lidocaine on viability and migration in MDA-MB-231, AU565, T47D, and MDA-MB-468.
Preoperative Typing of Thyroid and Parathyroid Tumors with a Combined Molecular Classifier
Authors: Titov Sergei E. , Kozorezova Evgeniya S. , Demenkov Pavel S. , Veryaskina Yulia A. , Kuznetsova Irina V. , Vorobyev Sergey L. , Chernikov Roman A. , Sleptsov Ilya V. , Timofeeva Nataliya I. , Ivanov Mikhail K.
Published: January 2021

In previous studies, we described a method for detecting and typing malignant tumors of the thyroid gland in fine-needle aspiration biopsy samples via analysis of a molecular marker panel (normalized HMGA2 mRNA level; normalized microRNA-146b, -221, and -375 levels; mitochondrial-to-nuclear DNA ratio; and BRAFV600E mutation) in cytological preparations by quantitative PCR. In the present study, we aimed to estimate the specificity of the typing of different thyroid tumors by the proposed method. Fine-needle aspiration cytological preparations from 278 patients were used. The histological diagnosis was known for each sample. The positive and negative predictive values of the method assessed in this study were, respectively, 100% and 98% for papillary thyroid carcinoma (n = 63), 100% and 100% for medullary thyroid carcinoma (n = 19), 43.5% and 98% for follicular carcinoma (n = 15), and 86% and 100% for Hürthle cell carcinoma (n = 6). Thus, we demonstrate that the diagnostic panel, including the analysis of microRNA expression, mRNA expression, the BRAFV600E mutation, and the mitochondrial-to-nuclear DNA ratio, allows the highly accurate identification of papillary thyroid carcinoma, medullary thyroid carcinoma, and Hürthle cell carcinoma but not malignant follicular tumors (positive predictive value was below 50%).
Functional Outcomes after Local Salvage Therapies for Radiation-Recurrent Prostate Cancer Patients: A Systematic Review
Authors: Abufaraj Mohammad , Siyam Abdelmuez , Ali Mustafa Rami , Suarez-Ibarrola Rodrigo , Yang Lin , Foerster Beat , Shariat Shahrokh F.
Published: January 2021

Purpose: To assess the rate and severity of functional outcomes after salvage therapy for radiation recurrent prostate cancer. Methods: This systematic review of the MEDLINE/PubMed database yielded 35 studies, evaluating salvage radical prostatectomy (RP), brachytherapy (BT), high-intensity focal ultrasound (HIFU) and cryotherapy (CT) after failure of primary radiation therapy. Data on pre- and post-salvage rates and severity of functional outcomes (urinary incontinence, erectile dysfunction, and lower urinary tract symptoms) were collected from each study. Results: The rates of severe urinary incontinence ranged from 28–88%, 4.5–42%, 0–6.5%, 2.4–8% post salvage RP, HIFU, CT and BT, respectively. The rates of erectile dysfunction were relatively high reaching as much as 90%, 94.6%, 100%, 62% following RP, HIFU, CT and BT, respectively. Nonetheless, the high pre-salvage rates of ED preclude accurate estimation of the effect of salvage therapy. There was an increase in the median IPSS following salvage HIFU, BT and CT ranging from 2.5–3.4, 3.5–12, and 2, respectively. Extended follow-up showed a return-to-baseline IPSS in a salvage BT study. The reported data suffer from selection, reporting, publication and period of study biases, making inter-study comparisons inappropriate. Conclusions: local salvage therapies for radiation recurrent PCa affect continence, lower urinary tract symptoms and sexual functions. The use of local salvage therapies may be warranted in the setting of local disease control, but each individual decision must be made with the informed patient in a shared decision working process.
Dormant Tumor Cell Vaccination: A Mathematical Model of Immunological Dormancy in Triple-Negative Breast Cancer
Authors: Mehdizadeh Reza , Shariatpanahi Seyed Peyman , Goliaei Bahram , Peyvandi Sanam , Rüegg Curzio
Published: January 2021

Triple-negative breast cancer (TNBC) is a molecular subtype of breast malignancy with a poor clinical prognosis. There is growing evidence that some chemotherapeutic agents induce an adaptive anti-tumor immune response. This reaction has been proposed to maintain the equilibrium phase of the immunoediting process and to control tumor growth by immunological cancer dormancy. We recently reported a model of immunological breast cancer dormancy based on the murine 4T1 TNBC model. Treatment of 4T1 cells in vitro with high-dose chemotherapy activated the type I interferon (type I IFN) signaling pathway, causing a switch from immunosuppressive to cytotoxic T lymphocyte-dependent immune response in vivo, resulting in sustained dormancy. Here, we developed a deterministic mathematical model based on the assumption that two cell subpopulations exist within the treated tumor: one population with high type I IFN signaling and immunogenicity and lower growth rate; the other population with low type I IFN signaling and immunogenicity and higher growth rate. The model reproduced cancer dormancy, elimination, and immune-escape in agreement with our previously reported experimental data. It predicted that the injection of dormant tumor cells with active type I IFN signaling results in complete growth control of the aggressive parental cancer cells injected at a later time point, but also of an already established aggressive tumor. Taken together, our results indicate that a dormant cell population can suppress the growth of an aggressive counterpart by eliciting a cytotoxic T lymphocyte-dependent immune response.