bluuebunny/crossref_metadata_2025 huggingface dataset:
Space Weather Effects on the Earth’s Upper Atmosphere: Short Report on Ionospheric Storm Effects at Middle Latitudes
Authors: Tsagouri Ioanna
Published: February 2022

During geomagnetic storm events, the highly variable solar wind energy input in the magnetosphere significantly alters the structure of the Earth’s upper atmosphere through the interaction of the ionospheric plasma with atmospheric neutrals. A key element of the ionospheric storm-time response is considered to be the large-scale increases and decreases in the peak electron density that are observed globally to formulate the so-called positive and negative ionospheric storms, respectively. Mainly due to their significant impact on the reliable performance of technological systems, ionospheric storms have been extensively studied in recent decades, and cumulated knowledge and experience have been assigned to their understanding. Nevertheless, ionospheric storms constitute an important link in the complex chain of solar-terrestrial relations. In this respect, any new challenge introduced in the field by a better understanding of the geospace environment, new modeling and monitoring capabilities and/or new technologies and requirements also introduces new challenges for the interpretation of ionospheric storms. This paper attempts a brief survey of present knowledge on the fundamental aspects of large-scale ionospheric storm time response at middle latitudes. Further attention is paid to the results obtained regarding the critical role that solar wind conditions which trigger disturbances may play on the morphology and the occurrence of ionospheric storm effects.
Spatial Distribution of Primary and Secondary PM2.5 Concentrations Emitted by Vehicles in the Guanzhong Plain, China
Authors: Lu Pan , Deng Shunxi , Li Guanghua , Li Jianghao , Xu Ke , Lu Zhenzhen
Published: February 2022

With the rapid increase of the vehicle population in the Guanzhong Plain (GZP), the fine particulate matter (PM2.5) emitted by vehicles has an impact on regional air quality and public health. The spatial distribution of primary and secondary PM2.5 concentrations from vehicles in GZP in January and July 2017 was simulated in this study by using the Weather Research and Forecasting (WRF) model and the California Puff (CALPUFF) air quality model. The contributions of vehicle-related emission sources to total PM2.5 concentrations were also calculated. The results show that although the emissions of primary PM2.5, NOx, and SO2 in July were greater than those in January, the hourly average concentrations of primary and secondary PM2.5 in January were significantly higher than those in July. The highest concentrations of primary and total PM2.5 were mostly located in the urban areas of Xi’an and Xianyang in the central region of GZP. The contributions of exhaust emissions, secondary nitrates, brake wear, tire wear, and secondary sulfate to the total PM2.5 concentrations in GZP were 50.37%, 34.76%, 10.79%, 4.06%, and 0.04% in January and 71.91%, 11.14%, 11.89%, 5.03%, and 0.03% in July, respectively. These results will help us to further control PM2.5 pollution caused by vehicles.
A New Method for the Assessment of the Oxidative Potential of Both Water-Soluble and Insoluble PM
Authors: Frezzini Maria Agostina , Di Iulio Gianluca , Tiraboschi Caterina , Canepari Silvia , Massimi Lorenzo
Published: February 2022

Water-soluble and insoluble fractions of airborne particulate matter (PM) exhibit different toxicological potentials and peculiar mechanisms of action in biological systems. However, most of the research on the oxidative potential (OP) of PM is focused exclusively on its water-soluble fraction, since experimental criticisms were encountered for detaching the whole PM (soluble and insoluble species) from field filters. However, to estimate the actual potential effects of PM on human health, it is essential to assess the OP of both its water-soluble and insoluble fractions. In this study, to estimate the total OP (TOP), an efficient method for the detachment of intact PM10 from field filters by using an electrical toothbrush was applied to 20 PM10 filters in order to obtain PM10 water suspensions to be used for the DCFH, AA and DTT oxidative potential assays (OPDCFH, OPAA and OPDTT). The contribution of the insoluble PM10 to the TOP was evaluated by comparing the TOP values to those obtained by applying the three OP assays to the water-soluble fraction of 20 equivalent PM10 filters. The OP of the insoluble fraction (IOP) was calculated as the difference between the TOP and the WSOP. Moreover, each PM10 sample was analyzed for the water-soluble and insoluble fractions of 10 elements (Al, Cr, Cs, Cu, Fe, Li, Ni, Rb, Sb, Sn) identified as primary elemental tracers of the main emission sources in the study area. A principal component analysis (PCA) was performed on the data obtained to identify the predominant sources for the determination of TOP, WSOP, and IOP. Results showed that water-soluble PM10 released by traffic, steel plant, and biomass burning is mainly responsible for the generation of the TOP as well as of the WSOP. This evidence gave strength to the reliability of the results from OP assays performed only on the water-soluble fraction of PM. Lastly, the IOPDCFH and IOPDTT were found to be principally determined by insoluble PM10 from mineral dust.
Intra-Seasonal and Intra-Annual Variation of the Latent Heat Flux Transfer Coefficient for a Freshwater Lake
Authors: Lükő Gabriella , Torma Péter , Weidinger Tamás
Published: February 2022

In the case of lakes, evaporation is one of the most significant losses of water and energy. Based on high-frequency eddy-covariance (EC) measurements between May and September of 2019, the offshore heat and water vapor exchanges are evaluated for the large (~600 km2) but shallow (~3.2 m deep) Lake Balaton (Transdanubian region, Hungary). The role of local driving forces of evaporation in different time scales (from 20 min to one month) is explored, such as water surface and air temperatures, humidity, atmospheric stability, net radiation, and energy budget components. EC-derived water vapor roughness lengths and transfer coefficients (Cq) show an apparent intra-seasonal variation. Different energy balance-based evaporation estimation methods (such as the Priestley-Taylor and the Penman-Monteith) confirm this observation. Furthermore, this has suggested the existence of an intra-annual variation in these parameters. This hypothesis is verified using ten years of water balance measurements, from which, as a first step, evaporation rates and, second, transfer coefficients are derived on a monthly scale. Cq is highly reduced in winter months (~1 × 10−3) compared to summer months (~2.5 × 10−3) and strongly correlated with net radiation. The application of time-varying Cq significantly increases the accuracy of evaporation estimation when the Monin-Obukhov similarity theory-based aerodynamic method is applied. The determination coefficient increases to 0.84 compared to 0.52 when a constant Cq is employed.
Possible Relationships between the Interdecadal Anomalies of Heavy Rainfall under Northeastern China Cold Vortexes and the Sea Surface Temperature (SST)
Authors: Zhu Dan , Zhi Xiefei , Sein Zin Mie Mie , Ji Yan , Tian Xiao , Pan Mengting
Published: February 2022

As an important component of the East Asian monsoon system, the northeast cold vortex (NECV) exerts a significant impact on weather and climate, especially in Northeast China. This study investigated the interdecadal spatiotemporal variability of heavy rainfall under the cold vortex of Northeast China (NECVHR) and its relationship with sea surface temperature (SST) during 1961–2019 over Northeast China. To investigate the dominant factors affecting variability in the heavy rainfall between May and September, an empirical orthogonal function (EOF) analysis was performed. To detect the trends and changes, a Mann-Kendall (MK) test was used. The sliding t-test was used to identify the change points and the significance. Pearson correlation analysis was used to analyze the relationship between SST and NECVHR, and the t-test was used to verify the significance. The results showed that the total amount of cold vortex heavy rainfall during May–September ranged from 153 to 12,509 mm for 1961–2019. An abrupt interdecadal change was seen after 2014 in Northeast China. The EOF analyses revealed that the first, second, and third EOFs explain 76%, 12.1%, and 5.5% of the total variance, respectively. The EOF followed the heavy rainfall pattern, with increases in the south (southeast) and decreases in the north (northwest) over Northeast China. Heavy rainfall over Northeast China positively correlated with the Atlantic multidecadal oscillation (AMO) index. The heavier rainfall under cold vortex (MCVHR) years revealed that the equipotential height was obviously located over the Sea of Japan, west of Northeast China and the Qinghai Tibet plateau. The cyclonic circulation over the East China Sea and north (northeasterly) wind prevails over Northeast China during less heavy rainfall under cold vortex (LCVHR) years. A high anticyclonic circulation over the Qinghai Tibet plateau resulted in stronger cold advection over Northeast China. The anticyclonic circulations over the East China Sea and the Sea of Japan (east), and the western (southwesterly) winds prevail over Northeast China, with a relatively shallow cold trough over the Qinghai Tibet plateau. The findings in this paper provided a better understanding of the interdecadal variability of NECVHR over Northeast China. The findings can be helpful for several stakeholders regarding agricultural production, water resource management, and natural habitat conversation in Northeast China.
Optimization of Marine Two-Stroke Diesel Engine Based on Air Intake Composition and Temperature Control
Authors: He Xianzhong , Tan Qinming , Wu Yuehong , Wei Cunfeng
Published: February 2022

The influence of gas intake temperature, composition and the volume concentration of each gas component on diesel engine combustion, emission and the output power was studied by building a calculation model of the B&W 6S35ME-B9 marine two-stroke low-speed diesel engine, followed by a comprehensive optimization exploration. The results showed that under 295 K and 18.5% O2 of intake gas, the engine’s NOx emission is only 4.5 g/kWh and reduced to 58% from the normal air gas intake condition. Moreover, their power output is very similar. In addition, the effect of CO2 or H2O added into the intake of the diesel engine on the performance of the diesel engine can be compensated by reducing the intake temperature. At the intake temperature of 295 K, the engine’s NOx emission with 20.58% O2, 77.42% N2 and 2% H2O is 8.62 g/kWh, and 9.06 g/kWh under 20.79% O2, 78.21% N2 and 2% CO2. It is lower than 11.77 g/kWh, which is under normal intake conditions (315 K, 21%O2 and 79%N2). The power output is also similar to the normal intake condition. Therefore, the comprehensive optimization of gas intake temperature, composition and concentration can effectively optimize the diesel engine’s performance in terms of combustion, emission and power output. The research results have an important reference value for the optimization of diesel engine performance.
The Transcription Factor FgAtrR Regulates Asexual and Sexual Development, Virulence, and DON Production and Contributes to Intrinsic Resistance to Azole Fungicides in Fusarium graminearum
Authors: Zhao Yanxiang , Sun Huilin , Li Jingwen , Ju Chao , Huang Jinguang
Published: February 2022

Fusarium graminearum is the predominant causal agent of cereal Fusarium head blight disease (FHB) worldwide. The application of chemical fungicides such as azole antifungals is still the primary method for FHB control. However, to date, our knowledge of transcriptional regulation in the azole resistance of F. graminearum is quite limited. In this study, we identified and functionally characterized a Zn(II)2-Cys6 transcription factor FgAtrR in F. graminearum. We constructed a FgAtrR deletion mutant and found that deletion of FgAtrR resulted in faster radial growth with serious pigmentation defects, significantly reduced conidial production, and an inability to form perithecia. The pathogenicity of the ΔFgAtrR mutant on wheat spikes and corn silks was severely impaired with reduced deoxynivalenol production, while the tolerance to prochloraz and propiconazole of the deletion mutant was also significantly decreased. RNA-seq indicated that many metabolic pathways were affected by the deletion of FgAtrR. Importantly, FgAtrR could regulate the expression of the FgCYP51A and ABC transporters, which are the main contributors to azole resistance. These results demonstrated that FgAtrR played essential roles in asexual and sexual development, DON production, and pathogenicity, and contributed to intrinsic resistance to azole fungicides in F. graminearum. This study will help us improve the understanding of the azole resistance mechanism in F. graminearum.
Dismemberment and Body Encasement—Case Report and an Empiric Study
Authors: Matzen Jana , Ondruschka Benjamin , Fitzek Antonia , Püschel Klaus , Jopp-van Well Eilin
Published: February 2022

The mutilation and encasement of corpses are rare in daily forensic work, but when they occur, close cooperation between different disciplines, such as legal medicine and forensic anthropology, is necessary to obtain the most valuable results. One forensic examination method is the radiological evaluation of victims or body parts by postmortem CT (pmCT) and X-ray images. In relation to a case described in this paper, an empirical study was conducted to figure out the value of radiological imaging and the ability to visualize and temporally classify changes in a corpse encased in concrete. For this purpose, the head and paw of a pig were encased in concrete and scanned regularly over a period of one year. Body parts such as the head and paw are clearly visible on X-ray images. Although decay-related changes are shown, a specific minimum time interval cannot yet be found, as these changes occur continuously in lesser amounts.
Network Approaches to Study Endogenous RNA Competition and Its Impact on Tissue-Specific microRNA Functions
Authors: Marques Tânia Monteiro , Gama-Carvalho Margarida
Published: February 2022

microRNAs are small non-coding RNAs that play a key role in regulating gene expression. These molecules exert their function through sequence complementarity with microRNA responsive elements and are typically located in the 3′ untranslated region of mRNAs, negatively regulating expression. Even though the relevant role of miRNA-dependent regulation is broadly recognized, the principles governing their ability to lead to specific functional outcomes in distinct cell types are still not well understood. In recent years, an intriguing hypothesis proposed that miRNA-responsive elements act as communication links between different RNA species, making the investigation of microRNA function even more complex than previously thought. The competing endogenous RNA hypothesis suggests the presence of a new level of regulation, whereby a specific RNA transcript can indirectly influence the abundance of other transcripts by limiting the availability of a common miRNA, acting as a “molecular sponge”. Since this idea has been proposed, several studies have tried to pinpoint the interaction networks that have been established between different RNA species and whether they contribute to normal cell function and disease. The focus of this review is to highlight recent developments and achievements made towards the process of characterizing competing endogenous RNA networks and their role in cellular function.
Biomarkers in Patients with Left Ventricular Assist Device: An Insight on Current Evidence
Authors: Sciaccaluga Carlotta , Ghionzoli Nicolò , Mandoli Giulia Elena , D’Ascenzi Flavio , Focardi Marta , Valente Serafina , Cameli Matteo
Published: February 2022

Left ventricular assist devices (LVADs) have been representing a cornerstone therapy for patients with end-stage heart failure during the last decades. However, their use induces several pathophysiological modifications which are partially responsible for the complications that typically characterize these patients, such as right ventricular failure, thromboembolic events, as well as bleedings. During the last years, biomarkers involved in the pathways of neurohormonal activation, myocardial injury, adverse remodeling, oxidative stress and systemic inflammation have raised attention. The search and analysis of potential biomarkers in LVAD patients could lead to the identification of a subset of patients with an increased risk of developing these adverse events. This could then promote a closer follow-up as well as therapeutic modifications. Furthermore, it might highlight some new therapeutic pharmacological targets that could lead to improved long-term survival. The aim of this review is to provide current evidence on the role of different biomarkers in patients with LVAD, in particular highlighting their possible implications in clinical practice.
Carnation-like Morphology of BiVO4-7 Enables Sensitive Photoelectrochemical Determination of Cr(VI) in the Food and Environment
Authors: Wu Wenqin , Tan Zhao , Chen Xiao , Chen Xiaomei , Cheng Ling , Wu Huimin , Li Peiwu , Zhang Zhaowei
Published: February 2022

Hexavalent chromium, namely, Cr(VI), is a significant threat to ecological and food safety. Current detection methods are not sensitive to Cr(VI). A photoelectrochemical (PEC) sensor based on bismuth vanadate (BiVO4) was developed for sensitive detection of Cr(VI). First, BiVO4-X (X: the pH of the reaction precursor solution) was synthesized using a facile surfactant-free hydrothermal method. The BiVO4-X morphology was well controlled according to pH values, showing rock-like (X = 1), wrinkled bark-like (X = 4), carnation-like (X = 7), and the collapsed sheet-like morphologies (X = 9, 12). BiVO4-7 exhibited excellent photoelectric performance due to a proper band structure under visible light and a large specific surface area. Then, BiVO4-7 was used to construct a PEC sensor to detect Cr(VI), which was demonstrated to have a low detection limit (10 nM) and wide detection range (2–210 μM). The BiVO4-7 PEC sensor had a stable output signal, as well as excellent reproducibility, repeatability, and selectivity. We used the BiVO4-7 PEC sensor to detect Cr(VI) in real environmental and food samples, resulting in a satisfactory recovery of 90.3–103.0%, as determined by comparison with results obtained using a spectrophotometric method. The BiVO4-7 PEC sensor is promising for practical application to heavy metal detection in the food and environment.
Disrupted Resting State Attentional Network Connectivity in Adolescent and Young Adult Cannabis Users following Two-Weeks of Monitored Abstinence
Authors: Harris Julia C. , Wallace Alexander L. , Thomas Alicia M. , Wirtz Hailey G. , Kaiver Christine M. , Lisdahl Krista M.
Published: February 2022

Background. Numerous neuropsychological studies have shown that cannabis use during adolescence and young adulthood led to deficits in sustained and selective attention. However, few studies have examined functional connectivity in attentional networks among young cannabis users, nor have characterized relationships with cannabis use patterns following abstinence. Methods. Differences in resting state functional connectivity (RSFC) within the dorsal (DAN) and ventral (VAN) attention networks were examined in 36 adolescent and young adult cannabis users and 39 non-substance using controls following two weeks of monitored abstinence. Observed connectivity differences were then correlated with past-year and lifetime cannabis use, length of abstinence, age of regular use onset, and Cannabis Use Disorder symptoms (CUD). Results. After controlling for alcohol and nicotine use, cannabis users had lower RSFC within the DAN network, specifically between right inferior parietal sulcus and right anterior insula, as well as white matter, relative to controls. This region was associated with more severe cannabis use measures, including increased lifetime cannabis use, shorter length of abstinence, and more severe CUD symptoms. Conclusions. Findings demonstrate that regular cannabis use by adolescents and young adults is associated with subtle differences in resting state connectivity within the DAN, even after two weeks of monitored abstinence. Notably, more severe cannabis use markers (greater lifetime use, CUD symptoms, and shorter abstinence) were linked with this reduced connectivity. Thus, findings support public policy aimed at reducing and delaying cannabis use and treatments to assist with sustained abstinence. Future longitudinal studies are needed to investigate causation.
Focused Ultrasound Stimulation as a Neuromodulatory Tool for Parkinson’s Disease: A Scoping Review
Authors: Lee Keng Siang , Clennell Benjamin , Steward Tom G. J. , Gialeli Andriana , Cordero-Llana Oscar , Whitcomb Daniel J.
Published: February 2022

Non-invasive focused ultrasound stimulation (FUS) is a non-ionising neuromodulatory technique that employs acoustic energy to acutely and reversibly modulate brain activity of deep-brain structures. It is currently being investigated as a potential novel treatment for Parkinson’s disease (PD). This scoping review was carried out to map available evidence pertaining to the provision of FUS as a PD neuromodulatory tool. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews, a search was applied to Ovid MEDLINE, Embase, Web of Science and Cochrane Central Register of Controlled Trials on 13 January 2022, with no limits applied. In total, 11 studies were included: 8 were from China and 1 each from Belgium, South Korea and Taiwan. All 11 studies were preclinical (6 in vivo, 2 in vitro, 2 mix of in vivo and in vitro and 1 in silico). The preclinical evidence indicates that FUS is safe and has beneficial neuromodulatory effects on motor behaviour in PD. FUS appears to have a therapeutic role in influencing the disease processes of PD, and therefore holds great promise as an attractive and powerful neuromodulatory tool for PD. Though these initial studies are encouraging, further study to understand the underlying cellular and molecular mechanisms is required before FUS can be routinely used in PD.
Molecular Mechanisms and Clinical Challenges of Glioma Invasion
Authors: Oishi Tomoya , Koizumi Shinichiro , Kurozumi Kazuhiko
Published: February 2022

Glioma is the most common primary brain tumor, and its prognosis is poor. Glioma cells are highly invasive to the brain parenchyma. It is difficult to achieve complete resection due to the nature of the brain tissue, and tumors that invade the parenchyma often recur. The invasiveness of tumor cells has been studied from various aspects, and the related molecular mechanisms are gradually becoming clear. Cell adhesion factors and extracellular matrix factors have a strong influence on glioma invasion. The molecular mechanisms that enhance the invasiveness of glioma stem cells, which have been investigated in recent years, have also been clarified. In addition, it has been discussed from both basic and clinical perspectives that current therapies can alter the invasiveness of tumors, and there is a need to develop therapeutic approaches to glioma invasion in the future. In this review, we will summarize the factors that influence the invasiveness of glioma based on the environment of tumor cells and tissues, and describe the impact of the treatment of glioma on invasion in terms of molecular biology, and the novel therapies for invasion that are currently being developed.
COVID-19 Vaccination and Mental Disorders, What Has Been Accomplished and Future Direction
Authors: Pandolfo Gianluca , Genovese Giovanni , Iannuzzo Fiammetta , Bruno Antonio , Pioggia Giovanni , Gangemi Sebastiano
Published: February 2022

The consequences of the pandemic on mental health are among the most important side effects of COVID-19. Wide concerns have emerged both regarding vaccine hesitation in the general population, and the vaccine’s implementation plan. The aim of this study is to evaluate how the scientific community has investigated the relationship between the COVID-19 vaccine and mental disorders. Contrary to expectations, having a full-blown psychiatric pathology seems to positively affect the attitude towards the vaccine, except for PTSD. The intense fear that accompanied the current world emergency has made this pandemic unique; we discuss how it might be one of the factors involved in this result. Further experimental investigations are needed to estimate how personality traits, hyperarousal, and negative emotions influence vaccine compliance both in the general population and in people living with mental disorders.
A Review of Mathematical Models of Building Physics and Energy Technologies for Environmentally Friendly Integrated Energy Management Systems
Authors: Zhang Yajie , Vand Behrang , Baldi Simone
Published: February 2022

The Energy Management System (EMS) is an efficient technique to monitor, control and enhance the building performance. In the state-of-the-art, building performance analysis is separated into building simulation and control management: this may cause inaccuracies and extra operating time. Thus, a coherent framework to integrate building physics with various energy technologies and energy control management methods is highly required. This framework should be formed by simplified but accurate models of building physics and building energy technologies, and should allow for the selection of proper control strategies according to the control objectives and scenarios. Therefore, this paper reviews the fundamental mathematical modeling and control strategies to create such a framework. The mathematical models of (i) building physics and (ii) popular building energy technologies (renewable energy systems, common heating and cooling energy systems and energy distribution systems) are first presented. Then, it is shown how the collected mathematical models can be linked. Merging with two frequently used EMS strategies, namely rule-based and model predictive controls, is discussed. This work provides an extendable map to model and control buildings and intends to be a foundation for building researchers, designers and engineers.
Analysis of Structural Layouts of Geodesic Dome Structures with Bar Filler Considering Air Transportation
Authors: Kolpakov Andrey , Dolgov Oleg , Korolskiy Vladislav , Popov Semen , Anchutin Vyacheslav , Zykov Vadim
Published: February 2022

The results are presented from a study of three-layer geodesic dome structures with bar fillers under their own weight. An algorithm was developed for selecting the type of structural layout used and the reference parameters chosen in terms of the technological, strength, and weight characteristics. The results of this analysis aim to make it easier for designers to determine the optimal reference parameters in the initial stage of the designing of geodetic hemispherical dome structures, the construction of which is planned to be carried out in remote areas with harsh climatic conditions. Due to the lack of sufficient ground transport infrastructure, cargo delivery to these regions is currently possible only with the help of air transport. The importance of this study rests on the lack of adequate methods for the determination of the reference parameters for geodesic hemispherical dome structures at an early stage of design. In particular, it is common for the issues regarding the transportation of structural elements as well as those that involve ensuring the strength and the technological characteristics of the structure to not be considered simultaneously. This study owes its relevance to the rapid development of the uninhabited territories of the Russian Federation in the context of the global ecological crisis caused by anthropogenic impact on the environment.
Seismic Risk Assessment for Elements of the Electric Network in Romania
Authors: Pavel Florin , Vacareanu Radu
Published: February 2022

This study is focused on the assessment of the seismic risk for elements of the electric network (thermoelectric powerplants and substations) in Romania. Firstly, the main elements of the electric network analyzed in this study are briefly presented. Thermoelectric powerplants account for about 30% of the electricity production capacity and for about 40% of electricity production. The damage to the electric network in Romania caused by the Vrancea 1977 seismic event is presented in this study. The seismic fragility of thermoelectric powerplants as recommended by the SYNER-G project is evaluated in relation to the damage observed after the Vrancea intermediate-depth earthquake of March 1977. The impact of anchoring the components of substations and of powerplants on the seismic risk metrics is also evaluated using fragility parameters from the literature. The analyses show that the impact of anchoring the components on the seismic risk metrics is less important for substations than for thermoelectric powerplants. In addition, it was observed that the level of seismic risk is larger in the case of electric substations as compared to powerplants.
An Effective Fault Detection Method for HVAC Systems Using the LSTM-SVDD Algorithm
Authors: Zhu Hui , Yang Wen , Li Shihong , Pang Aiping
Published: February 2022

Fault detection in heating, ventilation and air-conditioning (HVAC) systems can effectively prevent equipment damage and system energy loss, and enhance the stability and reliability of system operation. However, existing fault detection strategies have not realized high effectiveness, mainly due to the time-delay characteristics of HVAC system faults and the lack of system-fault operation data. Therefore, aiming at the time delay of system faults and the lack of actual system-fault operation data, this paper proposes a fault detection method that combines a system simulation model and an intelligent detection algorithm. The method first uses the Modelica modeling language to build a scalable simulation model of the system to obtain fault data that are not easily accessible in practice. The long short-term memory-support vector data description (LSTM-SVDD) algorithm is then applied to detect faults in real time by dynamically adjusting the fault residuals according to the absolute difference between the predicted and actual values. The experimental results show that the LSTM-SVDD method improves the average detection accuracy by 9.675% and 9.85% over the classical LSTM network and the extreme gradient boosting (XGBoost) method, respectively, under different fault levels.
Proliferative Potential, and Inflammatory Tumor Microenvironment in Meningioma Correlate with Neurological Function at Presentation and Anatomical Location—From Convexity to Skull Base and Spine
Authors: Wach Johannes , Lampmann Tim , Güresir Ági , Vatter Hartmut , Herrlinger Ulrich , Becker Albert , Cases-Cunillera Silvia , Hölzel Michael , Toma Marieta , Güresir Erdem
Published: February 2022

Emerging evidence emphasizes the prognostic importance of meningioma location. The present investigation evaluates whether progression-free survival (PFS), proliferative potential, World Health Organization (WHO) grades, and inflammatory burden differ between anatomical locations (skull base, non-skull base, and spinal) meningiomas. Five-hundred-forty-one patients underwent Simpson grade I or II resection for WHO grade 1 or 2 meningiomas. Univariable analysis revealed that spinal meningioma patients are significantly older, had a worse baseline Karnofsky Performance Status (KPS), higher acute-phase protein levels, lower incidence of WHO grade 2, lower mitotic counts, lower MIB-1 index, and less CD68+ macrophage infiltrates. Multivariable analysis identified WHO grade 2 (OR: 2.1, 95% CI: 1.1–3.7, p = 0.02) and cranial location (OR: 3.0, 95% CI: 1.8–4.9, p = 0.001) as independent predictors of diffuse CD68+ macrophage infiltrates. The mean PFS in cranial meningiomas was 115.9 months (95% CI: 107.5–124.3), compared to 162.2 months (95% CI: 150.5–174.0; log-rank test: p = 0.02) in spinal meningiomas. Multivariable Cox regression analysis revealed cranial location as an independent predictor (HR: 4.7, 95% CI: 1.0–21.3, p = 0.04) of shortened PFS. Increased MIB-1 indices ≥5% were significantly associated with location-specific deficits at presentation, such as decreased vision and seizure burden. Spinal meningiomas have a significantly longer PFS time and differ from the cranial meningiomas regarding MIB-1 index and density of tumor-associated macrophages.
Surgeon–Pathologist Team Approach Dramatically Affects Lymph Nodes Detection and Improves Patients’ Short-Term Outcome
Authors: Ambrosio Maria , Perotti Bruno , Battini Alda , Fattorini Caterina , Cavazzana Andrea , Pasqua Rocco , Palumbo Piergaspare , Gia Liano , Arganini Marco
Published: February 2022

The downstaging of gastric cancer has recently gained particular attention in the field of gastric cancer surgery. The phenomenon is mainly due to an inappropriate sampling of lymph nodes during standard lymphadenectomy. Hence, collection of the maximum number of lymph nodes is a critical factor affecting the outcome of patients. None of the techniques proposed so far have demonstrated a real efficiency in increasing the number of identified lymph nodes. To harvest the maximum number of lymph nodes, we designed a protocol for on-site macroscopic evaluation and sampling of lymph nodes according to the Japanese Gastric Cancer Association protocol. The procedure was carried out by a surgeon/pathologist team in the operating room. We enrolled one hundred patients, 50 of whom belonged to the study group and 50 to a control group. The study group included patients who underwent lymph node dissection following the proposed protocol; the control group encompassed patients undergoing standard procedures for sampling. We compared the number and maximum diameter of lymph nodes collected in both groups, as well as some postoperative variables, the 30-day mortality and the overall survival. In the study group, the mean number of lymph nodes harvested was higher than the control one (p = 0.001). Moreover, by applying the proposed technique, we sampled lymph nodes with a very small diameter, some of which were metastatic. Noticeably, no difference in terms of postoperative course was identified between the two groups, again supporting the feasibility of an extended lymphadenectomy. By comparing the prognosis of patients, a better overall survival (p = 0.03) was detected in the study group; however, to date, no long-term follow-up is available. Interestingly, patients with metastasis in node stations number 8, 9, 11 or with skip metastasis, experienced a worse outcome and died. Based on our preliminary results, the pathologist/surgeon team approach seems to be a reliable option, despite of a slight increase in sfaff workload and technical cost. It allows for the harvesting of a larger number of lymph nodes and improves the outcome of the patients thanks to more precise staging and therapy. Nevertheless, since a higher number of patients are necessary to confirm our findings and assess the impact of this technique on oncological outcome, our study could serve as a proof-of-concept for a larger, multicentric collaboration.
Plasma Gelsolin Confers Chemoresistance in Ovarian Cancer by Resetting the Relative Abundance and Function of Macrophage Subtypes
Authors: Asare-Werehene Meshach , Tsuyoshi Hideaki , Zhang Huilin , Salehi Reza , Chang Chia-Yu , Carmona Euridice , Librach Clifford L. , Mes-Masson Anne-Marie , Chang Chia-Ching , Burger Dylan , Yoshida Yoshio , Tsang Benjamin K.
Published: February 2022

Ovarian cancer (OVCA) is the most lethal gynaecological cancer with a 5-year survival rate less than 50%. Despite new therapeutic strategies, such as immune checkpoint blockers (ICBs), tumor recurrence and drug resistance remain key obstacles in achieving long-term therapeutic success. Therefore, there is an urgent need to understand the cellular mechanisms of immune dysregulation in chemoresistant OVCA in order to harness the host’s immune system to improve survival. The over-expression of plasma gelsolin (pGSN) mRNA is associated with a poorer prognosis in OVCA patients; however, its immuno-modulatory role has not been elucidated. In this study, for the first time, we report pGSN as an inhibitor of M1 macrophage anti-tumor functions in OVCA chemoresistance. Increased epithelial pGSN expression was associated with the loss of chemoresponsiveness and poor survival. While patients with increased M1 macrophage infiltration exhibited better survival due to nitric-oxide-induced ROS accumulation in OVCA cells, cohorts with poor survival had a higher infiltration of M2 macrophages. Interestingly, increased epithelial pGSN expression was significantly associated with the reduced survival benefits of infiltrated M1 macrophages, through apoptosis via increased caspase-3 activation and reduced production of iNOS and TNFα. Additionally, epithelial pGSN expression was an independent prognostic marker in predicting progression-free survival. These findings support our hypothesis that pGSN is a modulator of inflammation and confers chemoresistance in OVCA, in part by resetting the relative abundance and function of macrophage subtypes in the ovarian tumor microenvironment. Our findings raise the possibility that pGSN may be a potential therapeutic target for immune-mediated chemoresistance in OVCA.
Quality of Life in the First Year of Follow-Up in a Randomized Multicenter Trial Assessing the Role of Imaging after Radical Surgery of Stage IIB-C and III Cutaneous Melanoma (TRIM Study)
Authors: Naeser Ylva , Helgadottir Hildur , Hansson Johan , Ingvar Christian , Elander Nils O. , Flygare Petra , Nilsson Cecilia , Jakobsson Frida , Valachis Antonios , Papantoniou Dimitrios , Nordin Danfors Agneta , Johansson Hemming , Sundin Anders , Brandberg Yvonne , Ullenhag Gustav J.
Published: February 2022

The benefit of imaging in the follow-up setting for high-risk melanoma patients is uncertain, and even less is known about the impact of intensive follow-up on the patient´s quality of life. In 2017, a Swedish prospective randomized multicenter study started, in which high-risk melanoma patients are randomly assigned 1:1 to follow-up by physical examinations +/− whole-body imaging. The first-year examinations are scheduled at 0, 6 and 12 months. The aim of this study was to investigate whether the patients´ health-related quality of life (HRQoL) and levels of anxiety and depression were affected at 1 year by imaging. Anxiety/depression and HRQoL were assessed at 0 and 12 months by the questionnaires Hospital Anxiety and Depression (HAD) scale and EORTC QLQ-C30 version 3. Expected baseline QLQ-C30 values for the patients were calculated using data from the general population. In total, 204 patients were analyzed. Mean differences in subscale scores at 1 year were not statistically significant either for HRQoL or for anxiety/depression. Baseline HRQoL did not differ from expected values in the general Swedish population. In conclusion, the patients in general coped well with the situation, and adding whole-body imaging to physical examinations did not affect the melanoma patients’ HRQoL or levels of anxiety or depression.
Real-World Time on Treatment with First-Line Pembrolizumab Monotherapy for Advanced NSCLC with PD-L1 Expression ≥ 50%: 3-Year Follow-Up Data
Authors: Velcheti Vamsidhar , Hu Xiaohan , Li Yeran , El-Osta Hazem , Pietanza M. Catherine , Burke Thomas
Published: February 2022

Our aim was to evaluate real-world time on treatment (rwToT), overall and by KRAS mutation status, with first-line pembrolizumab monotherapy for advanced non-small cell lung cancer (NSCLC) in real-world oncology practice in the US. rwToT is a readily available, intermediate-range endpoint that is moderately to highly correlated with overall survival in clinical trials and real-world data. Using deidentified electronic medical record data, we studied patients with ECOG performance status (PS) of 0–2 who initiated pembrolizumab (1 November 2016 to 31 March 2020) for advanced NSCLC with programmed death-ligand 1 (PD-L1) expression ≥ 50% and without EGFR/ALK/ROS1 genomic alterations. The data cutoff was 31 March 2021, and the median study follow-up was 34 months. The Kaplan–Meier median rwToT with first-line pembrolizumab monotherapy was 7.4 months (95% CI, 6.3–8.1) for 807 patients with PS 0–1, which was consistent with the median treatment duration in the KEYNOTE-024 trial (7.9 months). The median rwToT for 237 patients with PS 2 was 2.1 months (95% CI, 1.4–2.8). For those with KRAS-mutated and KRAS wild-type nonsquamous NSCLC and PS 0–1, the median rwToT was 7.6 months and 7.0 months, respectively. Our findings suggest long-term benefit of first-line pembrolizumab monotherapy for advanced NSCLC with PD-L1 expression ≥ 50% in real-world settings in the US, particularly for patients with good performance status at the start of therapy, irrespective of KRAS status.
Tumor Cell-Autonomous Pro-Metastatic Activities of PD-L1 in Human Breast Cancer Are Mediated by PD-L1-S283 and Chemokine Axes
Authors: Erlichman Nofar , Baram Tamir , Meshel Tsipi , Morein Dina , Da’adoosh Benny , Ben-Baruch Adit
Published: February 2022

Therapies targeting the PD-L1/PD-1 axis have recently been introduced to triple-negative breast cancer (TNBC) with limited efficacy, suggesting that this axis promotes tumor progression through mechanisms other than immune suppression. Here, we over-expressed WT-PD-L1 in human TNBC cells (express endogenous PD-L1) and in luminal-A breast cancer cells (no endogenous PD-L1 expression) and demonstrated that cell-autonomous PD-L1 activities lead to increased tumor cell growth, invasion and release of pro-metastatic factors (CXCL8, sICAM-1, GM-CSF). These activities were promoted by PD-1 and were inhibited by mutating S283 in PD-L1. Invasion of WT-PD-L1-cells required signaling by chemokine receptors CXCR1/2, CCR2 and CCR5 through autocrine circuits involving CXCL8, CCL2 and CCL5. Studies with T cell-deficient mice demonstrated that cell-autonomous WT-PD-L1 activities in TNBC cells increased tumor growth and metastasis compared to knock-out (KO)-PD-L1-cells, whereas S283A-PD-L1-expressing cells had minimal ability to form tumors and did not metastasize. Overall, our findings reveal autonomous and PD-1-induced tumor-promoting activities of PD-L1 that depend on S283 and on chemokine circuits. These results suggest that TNBC patients whose tumors express PD-L1 could benefit from therapies that prevent immune suppression by targeting PD-1/CTLA-4, alongside with antibodies to PD-L1, which would allow maximal impact by mainly targeting the cancer cells.
The Antianginal Drug Perhexiline Displays Cytotoxicity against Colorectal Cancer Cells In Vitro: A Potential for Drug Repurposing
Authors: Dhakal Bimala , Li Celine Man Ying , Li Runhao , Yeo Kenny , Wright Josephine A. , Gieniec Krystyna A. , Vrbanac Laura , Sammour Tarik , Lawrence Matthew , Thomas Michelle , Lewis Mark , Perry Joanne , Worthley Daniel L. , Woods Susan L. , Drew Paul , Sallustio Benedetta C. , Smith Eric , Horowitz John D. , Maddern Guy J. , Licari Giovanni , Fenix Kevin
Published: February 2022

Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. Perhexiline, a prophylactic anti-anginal drug, has been reported to have anti-tumour effects both in vitro and in vivo. Perhexiline as used clinically is a 50:50 racemic mixture ((R)-P) of (−) and (+) enantiomers. It is not known if the enantiomers differ in terms of their effects on cancer. In this study, we examined the cytotoxic capacity of perhexiline and its enantiomers ((−)-P and (+)-P) on CRC cell lines, grown as monolayers or spheroids, and patient-derived organoids. Treatment of CRC cell lines with (R)-P, (−)-P or (+)-P reduced cell viability, with IC50 values of ~4 µM. Treatment was associated with an increase in annexin V staining and caspase 3/7 activation, indicating apoptosis induction. Caspase 3/7 activation and loss of structural integrity were also observed in CRC cell lines grown as spheroids. Drug treatment at clinically relevant concentrations significantly reduced the viability of patient-derived CRC organoids. Given these in vitro findings, perhexiline, as a racemic mixture or its enantiomers, warrants further investigation as a repurposed drug for use in the management of CRC.
Inflammatory Signaling and DNA Damage Responses after Local Exposure to an Insoluble Radioactive Microparticle
Authors: Matsuya Yusuke , Hamada Nobuyuki , Yachi Yoshie , Satou Yukihiko , Ishikawa Masayori , Date Hiroyuki , Sato Tatsuhiko
Published: February 2022

Cesium-bearing microparticles (Cs-BMPs) can reach the human respiratory system after inhalation, resulting in chronic local internal exposure. We previously investigated the spatial distribution of DNA damage induced in areas around a Cs-BMP; however, the biological impacts have not been fully clarified due to the limited amount of data. Here, we investigated the inflammatory signaling and DNA damage responses after local exposure to a Cs-BMP in vitro. We used two normal human lung cell lines, i.e., lung fibroblast cells (WI-38) and bronchial epithelial cells (HBEC3-KT). After 24 h exposure to a Cs-BMP, inflammation was evaluated by immunofluorescent staining for nuclear factor κB (NF-κB) p65 and cyclooxygenase 2 (COX-2). The number of DNA double-strand breaks (DSBs) was also detected by means of phospholylated histone H2AX (γ-H2AX) focus formation assay. Cs-BMP exposure significantly increased NF-κB p65 and COX-2 expressions, which were related to the number of γ-H2AX foci in the cell nuclei. Compared to the uniform (external) exposure to 137Cs γ-rays, NF-κB tended to be more activated in the cells proximal to the Cs-BMP, while both NF-κB p65 and COX-2 were significantly activated in the distal cells. Experiments with chemical inhibitors for NF-κB p65 and COX-2 suggested the involvement of such inflammatory responses both in the reduced radiosensitivity of the cells proximal to Cs-BMP and the enhanced radiosensitivity of the cells distal from Cs-BMP. The data show that local exposure to Cs-BMP leads to biological effects modified by the NF-κB pathway, suggesting that the radiation risk for Cs-BMP exposure can differ from that estimated based on conventional uniform exposure to normal tissues.
Immunophenotypic Analysis of Hairy Cell Leukemia (HCL) and Hairy Cell Leukemia-like (HCL-like) Disorders
Authors: Maitre Elsa , Cornet Edouard , Salaün Véronique , Kerneves Pauline , Chèze Stéphane , Repesse Yohan , Damaj Gandhi , Troussard Xavier
Published: February 2022

Hairy cell leukemia (HCL) is characterized by abnormal villous lymphoid cells that express CD103, CD123, CD25 and CD11c. HCL-like disorders, including hairy cell leukemia variant (vHCL) and splenic diffuse red pulp lymphoma (SDRPL), have similar morphologic criteria and a distinct phenotypic and genetic profile. We investigated the immunophenotypic features of a large cohort of 82 patients: 68 classical HCL, 5 vHCL/SDRPL and 9 HCL-like NOS. The HCL immunophenotype was heterogeneous: positive CD5 expression in 7/68 (10%), CD10 in 12/68 (18%), CD38 in 24/67 (36%), CD23 in 22/68 (32%) and CD43 in 19/65 (31%) patients. CD26 was expressed in 35/36 (97%) of HCL patients, none of vHCL/SDRPL and one of seven HCL-like NOS (14%). When adding CD26 to the immunologic HCL scoring system (one point for CD103, CD123, CD25, CD11c and CD26), the specificity was improved, increasing from 78.6% to 100%. We used unsupervised analysis of flow cytometry raw data (median fluorescence, percentage of expression) and the mutational profile of BRAF, MAP2K1 and KLF2. The analysis showed good separation between HCL and vHCL/SDRPL. The HCL score is not sufficient, and the use of unsupervised analysis could be promising to achieve a distinction between HCL and HCL-like disorders. However, these preliminary results have to be confirmed in a further study with a higher number of patients.