bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental-Numerical Investigation of a Steel Pipe Repaired with a Composite Sleeve
Authors: Ansari Sadrabadi Saeid , Dadashi Amin , Yuan Sichen , Giannella Venanzio , Citarella Roberto
Published: July 2022

Pressure vessels are subjected to deterioration and damage, which can significantly reduce their strength and loading capabilities. Among several procedures nowadays available to repair damaged steel pipelines, composite-repairing systems have become popular over the past few years to restore the loading capacity of damaged pipelines. This study reports a numerical-experimental investigation performed for a composite-repaired pipeline made of API 5L X60 steel. An experimental burst test was carried out on a 4 m long pipe section, closed by two lateral caps, and tested up to failure by means of high-pressure water. In parallel, the test was numerically replicated through a FEM model of the composite-repaired steel tank, allowing for a cross-comparison of results. It was found that the composite repairing system has almost eliminated both the noteworthy thickness reduction of 80% and the related stress concentrations in the pipe body. These outcomes allow for a better understanding of these repairing procedures in order to drive their subsequent optimization.
Comparison of Human Intestinal Parasite Ova Segmentation Using Machine Learning and Deep Learning Techniques
Authors: Lim Chee Chin , Khairudin Norhanis Ayunie Ahmad , Loke Siew Wen , Nasir Aimi Salihah Abdul , Chong Yen Fook , Mohamed Zeehaida
Published: July 2022

Helminthiasis disease is one of the most serious health problems in the world and frequently occurs in children, especially in unhygienic conditions. The manual diagnosis method is time consuming and challenging, especially when there are a large number of samples. An automated system is acknowledged as a quick and easy technique to assess helminth sample images by offering direct visibility on the computer monitor without the requirement for examination under a microscope. Thus, this paper aims to compare the human intestinal parasite ova segmentation performance between machine learning segmentation and deep learning segmentation. Four types of helminth ova are tested, which are Ascaris Lumbricoides Ova (ALO), Enterobious Vermicularis Ova (EVO), Hookworm Ova (HWO), and Trichuris Trichiura Ova (TTO). In this paper, fuzzy c-Mean (FCM) segmentation technique is used in machine learning segmentation, while convolutional neural network (CNN) segmentation technique is used for deep learning. The performance of segmentation algorithms based on FCM and CNN segmentation techniques is investigated and compared to select the best segmentation procedure for helminth ova detection. The results reveal that the accuracy obtained for each helminth species is in the range of 97% to 100% for both techniques. However, IoU analysis showed that CNN based on ResNet technique performed better than FCM for ALO, EVO, and TTO with values of 75.80%, 55.48%, and 77.06%, respectively. Therefore, segmentation through deep learning is more suitable for segmenting the human intestinal parasite ova.
A Long-Range Internet of Things-Based Advanced Vehicle Pollution Monitoring System with Node Authentication and Blockchain
Authors: Rana Arti , Rawat Arvind Singh , Afifi Ashraf , Singh Rajesh , Rashid Mamoon , Gehlot Anita , Akram Shaik Vaseem , Alshamrani Sultan S.
Published: July 2022

According to United Nations (UN) 2030 agenda, the pollution detection system needs to be improved for the establishment of fresh air to obtain healthy life of living things. There are many reasons for the pollution and one of the reasons for pollution is from the emissions of the vehicles. Currently digital technologies such as the Internet of Things and Long-Range are showing significant impact on establishment of smart infrastructure for achieving the sustainability. Based on this motivation, this study implemented a sensor node and gateway-based Internet of Things architecture to monitor the air quality index value from any location through Long-Range communication, and Internet connectivity. To realize the proposed system, a customization of hardware is carried out and implemented the customized hardware i.e., sensor node and gateway in real-time. The sensor node is powered with node mapping to minimize the data redundancy. In this study, the evaluation metrics such as bit rate, receiver sensitivity, and time on air are evaluated by spreading factor (SF), code rate (CR), bandwidth, number of packets, payload size, preamble, and noise figure. The real-time sensor values are logged on the cloud server through sensor node and gateway. The sensor values recorded in the cloud server is compared with optimal values and concluded that the PM10, PM2.5 are high in the air and remaining values of NO2, O3, CO are optimal in the air. Along with this an architecture is proposed for interfacing the hardware with blockchain network through cloud server and API for node authentication.
Early Earthquake Detection Using Batch Normalization Graph Convolutional Neural Network (BNGCNN)
Authors: Bilal Muhammad Atif , Ji Yanju , Wang Yongzhi , Akhter Muhammad Pervez , Yaqub Muhammad
Published: July 2022

Earthquake is a major hazard to humans, buildings, and infrastructure. Early warning systems should detect an earthquake and issue a warning with earthquake information such as location, magnitude, and depth. Earthquake detection from raw waveform data using deep learning models such as graph neural networks (GNN) is becoming an important research area. The multilayered structure of the GNN with a number of epochs takes more training time. It is also hard to train the model with saturating nonlinearities. The batch normalization technique is applied to each mini-batch to reduce epochs in training and obtain a steady distribution of activation values. It improves model training and prediction accuracy. This study proposes a deep learning model batch normalization graph convolutional neural network (BNGCNN) for early earthquake detection. It consists of two main components: CNN and GNN. Input to the CNN model is multi-station and three-component waveform data with magnitude ≥3.0 were collected from January 2000 to January 2015 for Southern California. The extracted features of CNN are appended with location information and input to GNN model for earthquake detection. After hyperparameter tuning of the BNGCNN, when testing and evaluating the model on the Southern California dataset, our method shows promising results to the baseline model GNN by obtaining a low error rate to predict the magnitude, depth, and location of an earthquake.
A Comparative Study and Analysis of Layered-Beam and Single-Beam Metamaterial Structures: Transmissibility Bandgap Development
Authors: Anigbogu Winner , Bardaweel Hamzeh
Published: July 2022

Recently, layered-beam metamaterial structures have been gaining popularity in a variety of engineering applications including energy harvesting and vibration isolation. While both single-beam metamaterial structures and layered-beam metamaterial structures are capable of generating bandgaps, it is important to understand the limitations of each type of metamaterial structure in order to make informed design decisions. In this article, a comparative study of bandgap development in single-beam metamaterial structures and layered-beam metamaterial structures is presented. The results show that for the single-beam metamaterial structure, with equally spaced local resonator designs, only one significant bandgap is developed at approximately 300–415 Hz. This bandgap occurs near the resonant frequency of the local resonators, i.e., 309 Hz. The results also show that when the spacing and the design of the local resonators are desired to remain fixed, layering the horizontal beams offers a significant pathway for both lowering the bandgap and developing additional bandgaps. The double-layered beam-type metamaterial structure studied in this work generates two bandgaps at approximately 238–275 Hz and 298–410 Hz. When the goal is to keep the number of local resonators per beam constant, increasing the length of the unit cells offers an alternative technique for lowering the bandgaps.
Unusual Clinical Experience in BRAF Exon 15 p.K601E-Mutated Lung Cancer: A Case Report and Brief Review of the Literature
Authors: De Felice Marco , Pisapia Pasquale , Pepe Francesco , De Luca Caterina , Iaccarino Antonino , Malapelle Umberto , Troncone Giancarlo , Ianniello Giovanni Pietro
Published: July 2022

Molecular profiling has revolutionized the treatment of metastatic NSCLC. Uncommon mutations have been reported primarily in EGFR and BRAF genes and are frequently associated with atypical clinical presentations. Here, we present a rare case of a patient affected by BRAF exon 15 p.K601E-mutated lung cancer with synchronous peritoneal carcinomatosis. First line treatment with chemo-immunotherapy combinations provided a PFS of 8–9 months, whereas a second line treatment with BRAF and MEK inhibitors elicited a dissociated response. The latter clinical outcome suggests that these inhibitors have only partial activity against this rare mutation.
Dynamics Analysis of Rotating Cantilever Beams with Free End Mass
Authors: Du Xiaokang , Zhang Jing , Guo Xian , Li Liang , Zhang Dingguo
Published: July 2022

An improved modeling method for the dynamics analysis of rotating cantilever beams with free end mass is introduced. The proposed improved modeling method is based on the nonlinear Green strain theory in this study. By using the Hamilton principle and the Galerkin method, the discrete dynamic equations of the axial and chordwise motions are obtained. Meanwhile, the equations for free vibrations analysis of the rotating cantilever beam with free end mass are derived by introducing the equilibrium axial deformation into both axial and chordwise motions. Numerical simulations are performed to validate the proposed model, and the results are compared and discussed with the other modeling methods. The comparison shows that even a small free end mass has an important influence on the dynamic characteristics of the rotating beam. Furthermore, the influences of various parameters on the vibration frequencies and axial deformations of the rotating cantilever beams are analyzed, such as the angular speed, the free end mass to beam mass ratio, and the center body radius to beam length ratio. Under the same conditions, the influence of the free end mass on the variation in the first- and high-order frequencies with the increasing angular speed are different.
UHT Milk Characterization by Electrical Impedance Spectroscopy
Authors: Scandurra Graziella , Cardillo Emanuele , Ciofi Carmine , Ferro Luigi
Published: July 2022

Ultra-High Temperature (UHT) pasteurized milk is the most diffused variety of milk in Europe. In this paper, a method is presented, employing Electrical Impedance Spectroscopy to characterize the different commercial milks commonly available in grocery stores and supermarkets. The curves of the measured admittance allow for the classification of the type of milk (whole, semi-skimmed, fat-free) and to distinguish lactose-free milk. An electrical circuit model has been derived and different values of circuit parameters add interesting information on the classification of the samples. Furthermore, the characterization allows for the identification of the degradation of the milk before it is visible to the eye, thus highlighting the difference between storage in the fridge and at room temperature, and identifying expired milk.
Special Issue on Optical Sensors and Gauges Based on Plasmonic Resonance
Authors: Pérez-Ocón Francisco
Published: July 2022

A surface plasmon is a plasmon that propagates through a surface; i [...]
Evaluating the Usefulness of the Modified Swimming Anaerobic Sprint Test (SAST) Based on the Relationship with the 100- and 200-m Freestyle
Authors: Wądrzyk Łukasz , Staszkiewicz Robert , Strzała Marek
Published: July 2022

The construction of specialized physiological tests for swimmers is often based on those previously used in versions on land. So far, no attempt has been made to adapt the RAST test to conditions of an aquatic environment. The aim of the study was to evaluate the relationship between the results from the 6 × 25 m front crawl test (Swimming Anaerobic Sprint Test—SAST) and 100- and 200-m freestyle performance. In a group of 22 swimmers (9 girls, 13 boys, mean age 17.2 years, body mass 67.6 kg, body height 1.76 m), the SAST was performed (10-s interval between repetition). To determine speed (v), stroke rate (SR), stroke length (SL), and stroke index (SI), the test and races were recorded with the use of cameras. The analysis included times from the competition and fatigue indices (the decrease in SI during the SAST). Analysis of variance was performed, and a correlation matrix was created considering variables from the SAST and competition. The indices describing the 200-m event differed from those recorded for the SAST and 100 m freestyle race. The SAST results (v, SL, SI) were strongly correlated with the 100- and 200-m performances. Fatigue indices have not been shown to correlate with competition performance. The SAST may be useful in the context of predicting results for the 100- and, to a limited extent, 200-m freestyle races.
Special Issue on Big Data for eHealth Applications
Authors: Silvestri Stefano , Gargiulo Francesco
Published: July 2022

In the last few years, the rapid growth in available digitised medical data has opened new challenges for the scientific research community in the healthcare informatics field [...]
Integrated Switched Reluctance Starter/Generator for Aerospace Applications: Particle Swarm Optimization for Constant Current and Constant Voltage Control Designs
Authors: Sedky Mohamed M. , Abdel-Azim Wessam E. , Abdel-Khalik Ayman S. , Massoud Ahmed M.
Published: July 2022

Extensive efforts have been made to develop reliable and efficient onboard generation systems for electric aircraft. Due to the inherited robustness, Switched Reluctance Machines (SRMs) have attracted attention as a promising candidate for an integrated starter/generator in aerospace applications. This paper presents two modes of operation: Constant Current (CC) and Constant Voltage (CV). A Particle Swarm Optimization (PSO)-based tuning approach is employed to optimize the controller of a Switched Reluctance Generator (SRG). The presented controller is evaluated using a three-phase 6/4 SRG. The Control-Hardware-in-the-loop (CHiL) has been used to elucidate the viability of the explored control concept practically.
Embroidering the Life of Thomas Becket during the Middle Ages: Cult and Devotion in Liturgical Vestments
Authors: Le Luel Nathalie
Published: July 2022

From the early studies of Tancred Borenius (1885–1948) to the present, the iconography of the archbishop Thomas Becket has drawn attention among scholars. Numerous studies have been published on the representation of Becket’s martyrdom in mural painting, sculpture, and reliquary caskets. Despite this attention, many questions concerning the selection of episodes embroidered in liturgical vestments and textiles, as well as the commissioning of these objects, remain unresolved. How devotion to Becket spread globally in the Western world has not yet been satisfactorily determined, and there may have been a number of different factors and transmitters. Thus, medieval embroidery could also have been a driving force behind the development and the dissemination of Becket’s cult—notably in the ecclesiastical and, more specifically, episcopal milieu across the Latin Church. This type of production quickly reached ecclesiastical patrons, who were interested in the opportunity of wearing a headpiece or vestments (copes and chasubles) that would serve as reminders of the Archbishop of Canterbury. This was the perfect opportunity for a papal curia that, since Alexander III, had tasked itself with promoting Thomas Becket’s legacy, integrating the saint within Christian martyrial history and within a history of a militant Church.
Numerical Modeling of the Radio Wave Over-the-Horizon Propagation in the Troposphere
Authors: Xu Min , Olaimat Melad , Tang Tao , Ramahi Omar M. , Aldhaeebi Maged , Jin Zhu , Zhu Ming
Published: July 2022

Using atmospheric data, which include pressure, temperature, relative humidity and water vapor pressure, the actual refractive index of a specific segment of the atmosphere has been modeled. Based on the refractive index, a numerical method is presented to quickly estimate the propagation path of the radio wave in the troposphere. Utilizing the terrain and the surface medium model of the propagation area and the parabolic equation (PE) method, an image of the electric field distribution of radio waves in the troposphere is obtained. A comparison of propagation paths between the numerical method and the PE model is presented. Additionally, the effects of the antenna’s elevation angle have been studied. Physical measurements provide a reference for the accuracy of the simulation results obtained using the method presented in this work.
Snails as Temporal Biomonitors of the Occurrence and Distribution of Pesticides in an Apple Orchard
Authors: Al-Alam Josephine , Millet Maurice , Khoury Dani , Rodrigues Anaïs , Harb Moustapha , Akoury Elias , Tokajian Sima , Wazne Mahmoud
Published: July 2022

The intensive use of pesticides in agricultural areas and the resulting effects have created a need to develop monitoring programs for their active assessment at low cost. This research entails a biomonitoring study of the pesticides in an apple orchard, using juvenile Cornu aspersum (O. F. Müller, 1774) snails exposed in field microcosms. The snails were deployed at three different locations in the orchard area and were used to assess the temporal biomonitoring of 100 different semi-volatile and non-volatile pesticides. The study was performed over an 18-week period and targeted the center, the border, and the outside of the orchard. Results showed that greater levels of pesticides were detected at the center of the orchard as compared to the other sites. The type and level of the applied pesticide influenced its environmental dissipation, as significantly greater levels of semi-volatile pesticides were accumulated by the caged snails in comparison to non-volatile pesticides. The presence of semi-volatile pesticides in the snails outside the orchard revealed the usefulness of these species in the biomonitoring of off-site pesticide emissions. The findings of this study showed that C. aspersum can serve as a reliable and effective model organism for the active biomonitoring of pesticide emissions in agricultural sites.
Modeling Ground Ozone Concentration Changes after Variations in Precursor Emissions and Assessing Their Benefits in the Kanto Region of Japan
Authors: Vazquez Santiago Jairo , Inoue Kazuya , Tonokura Kenichi
Published: July 2022

Ozone (O3) is a pollutant of concern in urban areas because of its effects on health, crops, ecosystems, and materials. Despite efforts to meet the Japanese air quality standard for O3 in the Kanto region, the attainment percentage is close to zero. Considering that O3 formation is sensitive to emissions of volatile organic compounds (VOC) and nitrogen oxides (NOx), this study evaluated a range of reductions in the emissions of both precursors using a regional air quality model (ADMER-PRO) and estimated their benefits measured as the economic change due to O3 concentration differences between scenarios. The simulation period was set during the 2016 O3 season. The results showed that O3 concentrations could be reduced using two approaches: significant reduction in VOC levels combined with minor NOx level changes or significant NOx emission reduction. Significant reduction in NOx levels was the most effective strategy for a generalized decrease in the O3 levels in the Kanto region, and the benefit analysis revealed that the most significant economic impacts could be achieved by adopting the latter approach.
CRISPRi-Mediated Down-Regulation of the Cinnamate-4-Hydroxylase (C4H) Gene Enhances the Flavonoid Biosynthesis in Nicotiana tabacum
Authors: Karlson Chou Khai Soong , Mohd Noor Siti Nurfadhlina , Khalid Norzulaani , Tan Boon Chin
Published: July 2022

Flavonoids are an important class of natural compounds present in plants. However, despite various known biological activities and therapeutic potential, the low abundance of flavonoids in nature limits their development for industrial applications. In this study, we aimed to enhance flavonoid production by silencing cinnamate-4-hydroxylase (C4H), an enzyme involved in the branch point of the flavonoid biosynthetic pathway, using the clustered regularly interspaced short palindromic repeats interference (CRISPRi) approach. We designed three sgRNAs targeting the promoter region of NtC4H and cloned them into a CRISPRi construct. After being introduced into Nicotiana tabacum cell suspension culture, the transformed cells were sampled for qPCR and liquid chromatography-mass spectrometry analyses. Sixteen of 21 cell lines showed PCR-positive, confirming the presence of the CRISPRi transgene. The NtC4H transcript in the transgenic cells was 0.44-fold lower than in the wild-type. In contrast, the flavonoid-related genes in the other branching pathways, such as Nt4CL and NtCHS, in the C4H-silenced cells showed higher expression than wild-type. The upregulation of these genes increased their respective products, including pinostrobin, naringenin, and chlorogenic acid. This study provides valuable insight into the future development of CRISPRi-based metabolic engineering to suppress target genes in plants.
Expression of Tumor Suppressor SFRP1 Predicts Biological Behaviors and Prognosis: A Potential Target for Oral Squamous Cell Carcinoma
Authors: Chen Chun , Zhang Yifei , Liu Yupeng , Hang Lei , Yang Jun
Published: July 2022

Background: Genomic instability is implicated in the initiation and progression of oral squamous cell carcinoma (OSCC). Tumor suppressor Secreted Frizzled-Related Protein 1 (SFRP1) may participate in the aberrant evolution of OSCC, the intrinsic molecular mechanisms of which may provide effective therapeutic targets. Methods: A bioinformatics analysis was carried out on a publicly available database using R language to map the prognostic value, immune infiltration and enrichment of SFRP1 expression. Subsequently, in vitro experiments were conducted to unveil the biological function of SFRP1. Results: SFRP1 was found to be ubiquitously lowly expressed in OSCC using a Wilcoxon rank-sum test. Univariate analysis confirmed that those patients characterized by a low SFRP1 expression were significantly associated with advanced T-stage, clinical stage and poor mortality (p < 0.05). Furthermore, SFRP1 displayed a positive performance in tumor immune infiltration, especially in mast cells. Functional annotations indicated that highly expressed SFRP1 was associated with membrane potential and passive transmembrane transporter activity and it was mainly enriched in calcium pathway and neuroactive ligand–receptor interaction. In vitro, the overexpression of SFRP1 inhibited its proliferation, migration, and invasion and resulted in G0+G1 phase arrest within Cal27 cells (p < 0.05). Conclusions: The bioinformation data suggest that SFRP1 expression provides an insight into the risk and prognostic stratification in OSCC. SFRP1 was validated as a potential biomarker with anticarcinogenic behaviors for use in targeted therapy.
Green, Efficient Detection and Removal of Hg2+ by Water-Soluble Fluorescent Pillar[5]arene Supramolecular Self-Assembly
Authors: Jiang Xiaomei , Wang Lingyun , Ran Xueguang , Tang Hao , Cao Derong
Published: July 2022

Developing a water-soluble supramolecular system for the detection and removal of Hg2+ is extremely needed but remains challenging. Herein, we reported the facile construction of a fluorescent supramolecular system (H⊃G) in 100% water through the self-assembly of carboxylatopillar[5]arene sodium salts (H) and diketopyrrolopyrrole-bridged bis(quaternary ammonium) guest (G) by host–guest interaction. With the addition of Hg2+, the fluorescence of H⊃G could be efficiently quenched. Since Hg2+ showed synergistic interactions (coordination and Hg2+- cavity interactions with G and H, respectively), crosslinked networks of H⊃G@Hg2+ were formed. A sensitive response to Hg2+ with excellent selectivity and a low limit of detection (LOD) of 7.17 × 10−7 M was obtained. Significantly, the quenching fluorescence of H⊃G@Hg2+ can be recovered after a simple treatment with Na2S. The reusability of H⊃G for the detection of Hg2+ ions was retained for four cycles, indicating the H⊃G could be efficiently used in a reversible manner. In addition, the H⊃G could efficiently detect Hg2+ concentration in real samples (tap water and lake water). The developed supramolecular system in 100% water provides great potential in the treatment of Hg2+ detection and removal for environmental sustainability.
Identification and Typing of Strains of Wood-Rotting Basidiomycetes by Protein Profiling Using MALDI-TOF MS
Authors: Horisawa Sakae , Iwamoto Koki
Published: July 2022

The accurate identification and proper typing of basidiomycetes are required in medical, sanitary maintenance, agriculture, and biotechnology fields. A diagnostic method based on information from whole-cell proteins acquired by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was investigated to identify wood-rotting fungi, a group of filamentous fungi. In this study, mass spectra of intracellular peptides obtained from cultured mycelia of 50 strains of 10 wood-rotting fungal species were obtained multiple times and mass spectral patterns (MSPs) consisting of peaks that characterized the fungal species or strain was created to construct an in-house database. The species identification was conducted by comparing the newly obtained raw mass spectra with the MSPs in the database using the MALDI Biotyper. The results showed that the peak patterns of the mass spectra were reproducible and matched at the strain level. A cluster analysis based on the MSPs was also conducted to examine inter-and intraspecific diversity among the tested wood-rotting basidiomycetes. Most of the fungal strains examined in this study could be identified to a species level; however, the strains belonging to Pleurotus could only be identified to a genus level. This was due to an intraspecific variation, so the identification accuracy could be amendable with a more enhanced database.
Body Image Concerns: The Impact of Digital Technologies and Psychopathological Risks in a Normative Sample of Adolescents
Authors: Mesce Martina , Cerniglia Luca , Cimino Silvia
Published: July 2022

Background and Objectives: Previous research on associations between Body Image Concerns (BIC) and technological addictions, such as Internet addiction (IA) and Social Media Addiction (SMA), has focused on female samples, neglecting the impact they may have on males and the risk factor associated with age. The present study analyzed the correlations between BIC, IA, and SMA and between internalizing and externalizing problems. Methods: A sample of 204 participants (118 females; mean age = 15.88 years) were divided into three age groups (early, middle, and late adolescence) and completed a battery of scales including (i) Body Image Concern Inventory, (ii) Bergen Instagram Addiction Scale, (iii) Internet Addiction Test, and (iv) Youth Self Report. Results: Significant associations between BIC and technology addictions (SMA and IA) appeared both in the total sample and in the subgroups related to gender and age; bivariate correlations between internalizing and externalizing problems and variables were significant for the total sample but only in some of the gender- and age-related subgroups. Discussion and Conclusions: This research has shown how associations between BIC and behavioral technology addictions, especially associations with internalizing and externalizing symptoms, may vary by the gender affiliation and developmental stage of the individual.
Impacts of Occupant Behavior on Building Energy Consumption and Energy Savings Analysis of Upgrading ASHRAE 90.1 Energy Efficiency Standards
Authors: He Yaling , Chen Yixing , Chen Zhihua , Deng Zhang , Yuan Yue
Published: July 2022

Commercial prototype building models were developed by the United States Department of Energy (DOE) to analyze the energy savings of the ASHRAE 90.1 standard. However, in the DOE models, occupant behavior inputs were deterministic and the stochasticity of occupant behavior was not fully characterized. This study evaluated the impacts of stochastic occupant behavior on building energy consumption and energy savings analysis from upgrading the ASHRAE 90.1-2016 to 2019 in sixteen climate zones in the United States (U.S.). Three occupant behavior styles (austerity, normal, and wasteful) were defined to represent the different levels of energy consciousness. The DOE medium office prototype models were used as the baseline (normal behavior style). The occupant behavior functional mock-up unit (obFMU) was used to model the stochastic occupant behavior models (austerity and wasteful). The EnergyPlus medium office prototype models were modified to co-simulate with the obFMU models. The results of 16 climate zones were aggregated by the relative construction volume of each climate zone. The results showed that the weighted national annual source energy use intensity (EUI) of the austerity, normal, and wasteful behavior styles were 203.81 kWh/m2, 287.15 kWh/m2, and 388.33 kWh/m2 for ASHRAE 90.1-2016, and 192.43 kWh/m2, 273.48 kWh/m2, and 371.28 kWh/m2 for ASHRAE 90.1-2019, respectively. Compared to the normal behavior style, the austerity behavior style consumed 29% less source energy, while the wasteful behavior style consumed 36% more source energy. From upgrading the ASHRAE 90.1-2016 to 2019, the energy saving percentages based on the austerity, normal, and wasteful behavior styles were 5.59%, 4.78%, and 4.42%, respectively. The stochastic occupant behavior significantly impacted the building energy consumption, and their impacts on the energy savings analysis of upgrading ASHRAE 90.1 were also not negligible.
Risk Identification, Assessment, and Allocation in PPP Projects: A Systematic Review
Authors: Rasheed Nasir , Shahzad Wajiha , Khalfan Malik , Rotimi James
Published: July 2022

Public private partnerships (PPPs) have gained widespread adoption as an innovative way of procuring public infrastructure projects over the last two decades. Risk identification, assessment, and allocation have received considerable attention from researchers due to the risk heavy nature of PPP projects. Adoption of PPPs has triggered a sudden increase in research interest in the area in recent years. This study attempts to provide an updated systematic review of literature related to risks in PPPs using a PRISMA flowchart. The results of the study offer some valuable insights into the future and current state of research. The study found that the focus of research on PPPs has shifted from an overall risk identification and assessment approach to individual risk analysis. Moreover, this research trend is on the rise in developing countries, and that quantitative methods for risk management in PPP research and qualitative methods in practice are preferred. In developed economies, due to negative public sentiments, transparency concerns, and arguments of value for money not being achieved, PPPs are becoming less popular. For these reasons a shift to availability-based payment mechanisms such as in Design-Build-Finance-Maintain (DBFM) from traditional revenue-based mechanisms as in Build-Operate-Transfer (BOT) has been observed. These shifts in research trends and practice offer researchers future opportunities to investigate these relatively newer approaches.
Preliminary Discovery of Small Molecule Inhibitors of Epidermal Growth Factor Receptor (EGFR) That Bind to the Extracellular Domain
Authors: Di Liddo Rosa , Verona Marco , Vaccarin Christian , Acquasaliente Laura , Schrenk Sandra , Piccione Monica , Cenzi Carola , De Franco Michele , Dal Prà Matteo , Ribaudo Giovanni , Ferlin Maria Grazia , Conconi Maria Teresa , Chilin Adriana , Gandin Valentina , Marzaro Giovanni
Published: July 2022

The Epidermal Growth Factor Receptor (EGFR) is a transmembrane glycoprotein belonging to the protein kinase superfamily. It is composed of an extracellular domain, a transmembrane anchoring region and a cytoplasmic region endowed with tyrosine kinase activity. Genetic mutations of EGFR kinase cause higher activity thereby stimulating downstream signaling pathways that, in turn, impact transcription and cell cycle progression. Due to the involvement of mutant EGFR in tumors and inflammatory diseases, in the past decade, several EGFR inhibitory strategies have been extensively studied, either targeting the extracellular domain (through monoclonal antibodies) or the intracellular kinase domain (through ATP-mimic small molecules). Monoclonal antibodies impair the binding to growth factor, the receptor dimerization, and its activation, whereas small molecules block the intracellular catalytic activity. Herein, we describe the development of a novel small molecule, called DSF-102, that interacts with the extracellular domain of EGFR. When tested in vitro in KRAS mutant A549 cells, it impairs EGFR activity by exerting (i) dose-dependent toxicity effects; (ii) a negative regulation of ERK, MAPK p38 and AKT; and (iii) a modulation of the intracellular trafficking and lysosomal degradation of EGFR. Interestingly, DSF-102 exerts its EGFR inhibitory activity without showing interaction with the intracellular kinase domain. Taken together, these findings suggest that DSF-102 is a promising hit compound for the development of a novel class of anti-EGFR compounds, i.e., small molecules able to interact with the extracellular domain of EGFR and useful for overcoming the KRAS-driven resistance to TKI treatment.
Analysis of Genomic Alterations Associated with Recurrence in Early Stage HER2-Positive Breast Cancer
Authors: Kim Yong-Seok , Sun Der Sheng , Ahn Juneyoung , Kim Yongseon , Yoon Jung-Sook , Won Hye Sung
Published: July 2022

We aimed to compare gene expression in primary tumors of patients with recurrence and nonrecurrence to gain insight into the biology of high-risk HER2-positive early breast cancer. Patients who underwent curative resection and received adjuvant trastuzumab for HER2-positive early breast cancer were evaluated. Gene expression analyses were performed using NanoString Technologies’ nCounter Breast Cancer 360 Panel. PAM50 intrinsic subtypes and Breast Cancer Signatures including tumor inflammation signature (TIS) were evaluated. Of 247 patients, 28 (11.3%) had recurrence at a median follow-up of 54.2 months. Patients with pathological stage III, tumor size > 5 cm, axillary lymph node metastases, and hormone receptor-negativity were more frequently observed in the recurrent group compared with the nonrecurrent group. In patients with recurrence, seven genes were upregulated significantly, including WNT11, HAPLN1, FGF10, BBOX1, CXADR, NDP, and EREG, and two genes were downregulated, including CXCL9 and GNLY. TIS score was significantly lower in patients with recurrence compared with controls without recurrence. These findings suggest that activation of oncogenic signaling pathways related to cell proliferation, adhesion, cancer stemness, and noninflamed tumor microenvironment are associated with the risk of recurrence in early stage, HER2-positive breast cancer.
Advances in Cutaneous Squamous Cell Carcinoma Management
Authors: Burns Carrick , Kubicki Shelby , Nguyen Quoc-Bao , Aboul-Fettouh Nader , Wilmas Kelly M. , Chen Olivia M. , Doan Hung Quoc , Silapunt Sirunya , Migden Michael R.
Published: July 2022

cSCC is increasing in prevalence due to increased lifespans and improvements in survival for conditions that increase the risk of cSCC. The absolute mortality of cSCC exceeds melanoma in the United States and approaches that of melanoma worldwide. This review presents significant changes in the management of cSCC, focusing on improvements in risk stratification, new treatment options, optimization of existing treatments, and prevention strategies. One major breakthrough in cSCC treatment is the advent of immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1), which have ushered in a renaissance in the treatment of patients with locally advanced and metastatic disease. These agents have offered patients with advanced disease decreased therapeutic toxicity compared to traditional chemotherapy agents, a more durable response after discontinuation, and improved survival. cSCC is an active field of research, and this review will highlight some of the novel and more developed clinical trials that are likely to impact cSCC management in the near future.
Regulation of Interleukin-36γ/IL-36R Signaling Axis by PIN1 in Epithelial Cell Transformation and Breast Tumorigenesis
Authors: Poudel Muna , Bhattarai Poshan Yugal , Shrestha Pratikshya , Choi Hong Seok
Published: July 2022

Given the increasing recognition of the relationship between IL-1 cytokines, inflammation, and cancer, the significance of distinct members of the IL-1 cytokine family in the etiology of cancer has been widely researched. In the present study, we investigated the underlying mechanism of the IL-36γ/IL-36R axis during breast cancer progression, which has not yet been elucidated. Initially, we determined the effects of IL-36γ on the proliferation and epithelial cell transformation of JB6 Cl41 mouse epidermal and MCF7 human breast cancer cells using BrdU incorporation and anchorage-independent growth assays. We found that treatment with IL-36γ increased the proliferation and colony formation of JB6 Cl41 and MCF7 cells. Analysis of the mechanism underlying the neoplastic cell transformation revealed that IL-36γ induced IL-36R-mediated phosphorylation of MEK1/2, ERK1/2, JNK1/2, and c-Jun, resulting in increased c-Fos, c-Jun, and AP-1 activities in JB6 Cl41 and MCF7 cells. Furthermore, the IL-36γ-induced tumorigenic capacity of MCF7 cells was considerably enhanced by PIN1, following MEK/ERK and JNK/c-Jun signaling. Interestingly, blocking PIN1 activity using juglone suppressed the IL-36γ-induced increase in the anchorage-independent growth of 4T1 metastatic mouse breast cancer cells. Finally, in a syngeneic mouse model, IL-36γ-induced tumor growth in the breast mammary gland was significantly inhibited following PIN1 knockout.
Differences in Treatment Modalities and Prognosis of Elderly Patients with Ovarian Cancer: A Two-Center Propensity Score-Matched Study
Authors: Zhao Yuxi , Zuo Jing , Li Ning , Zheng Rongshou , Yuan Guangwen , Shen Guihua , Wu Lingying
Published: July 2022

Background: The prognosis of older patients with ovarian cancer is poor. We evaluated the effect of chronological age and different treatment characteristics on the prognosis of older patients with ovarian cancer; Methods: The study retrospectively analyzed patients aged over 60 years who underwent cytoreduction followed by platinum-based adjuvant chemotherapy between January 2011 and December 2019 in two national centers in China. Propensity score matching (PSM, 1:1) was performed to stratify the comorbidity- and treatment-related factors. The Kaplan–Meier method was employed to estimate progression-free survival (PFS) in the original cohort and the cohort after PSM; Results: A total of 324 patients were evaluated. The Age ≥ 70 group often received more neoadjuvant chemotherapy (62.3% vs. 31.2%, p < 0.001), more discontinuation of adjuvant chemotherapy (31.2% vs. 10.8%, p < 0.001), and had more severe chemotherapy-related toxicity (45.6% vs. 34.2%, p = 0.040) than the Age < 70 group. After matching, the PFS of the Age < 70 group was not significantly different from the Age ≥ 70 group (median PFS = 12.4 and 11.9 months, respectively, p = 0.850). Furthermore, the advanced FIGO stage, non-R0 cytoreduction, and discontinuation of adjuvant chemotherapy were all found to be poor prognostic factors. Serum albumin level <40 g/L (HR = 2.441, p = 0.018) and age ≥ 70 years (HR = 2.639, p = 0.008) led to more severe chemotherapy-related toxicity. Additionally, poor renal function (HR = 5.128, p = 0.002) was in association with discontinuation of adjuvant chemotherapy; Conclusions: The chronological age of older patients cannot be seen as a poor prognostic factor. Older patients may benefit most from R0 cytoreduction followed by the completion of chemotherapy. Postoperative poor renal function and serum albumin level <40 g/L may help predict the discontinuation of adjuvant chemotherapy.
Identification of Prognostic Genes in Gliomas Based on Increased Microenvironment Stiffness
Authors: Chen Chaang-Ray , Chang Rong-Shing , Chen Chi-Shuo
Published: July 2022

With a median survival time of 15 months, glioblastoma multiforme is one of the most aggressive primary brain cancers. The crucial roles played by the extracellular matrix (ECM) stiffness in glioma progression and treatment resistance have been reported in numerous studies. However, the association between ECM-stiffness-regulated genes and the prognosis of glioma patients remains to be explored. Thus, using bioinformatics analysis, we first identified 180 stiffness-dependent genes from an RNA-Seq dataset, and then evaluated their prognosis in The Cancer Genome Atlas (TCGA) glioma dataset. Our results showed that 11 stiffness-dependent genes common between low- and high-grade gliomas were prognostic. After validation using the Chinese Glioma Genome Atlas (CGGA) database, we further identified four stiffness-dependent prognostic genes: FN1, ITGA5, OSMR, and NGFR. In addition to high-grade glioma, overexpression of the four-gene signature also showed poor prognosis in low-grade glioma patients. Moreover, our analysis confirmed that the expression levels of stiffness-dependent prognostic genes in high-grade glioma were significantly higher than in low-grade glioma, suggesting that these genes were associated with glioma progression. Based on a pathophysiology-inspired approach, our findings illuminate the link between ECM stiffness and the prognosis of glioma patients and suggest a signature of four stiffness-dependent genes as potential therapeutic targets.
Disease Modeling of Pituitary Adenoma Using Human Pluripotent Stem Cells
Authors: Matsumoto Ryusaku , Suga Hidetaka , Arima Hiroshi , Yamamoto Takuya
Published: July 2022

Pituitary adenomas are characterized by abnormal growth in the pituitary gland. Surgical excision is the first-line treatment for functional (hormone-producing) pituitary adenomas, except for prolactin-producing adenomas; however, complete excision is technically challenging, and many patients require long-term medication after the treatment. In addition, the pathophysiology of pituitary adenomas, such as tumorigenesis, has not been fully understood. Pituitary adenoma pathophysiology has mainly been studied using animal models and animal tumor-derived cell lines. Nevertheless, experimental studies on human pituitary adenomas are difficult because of the significant differences among species and the lack of reliable cell lines. Recently, several methods have been established to differentiate pituitary cells from human pluripotent stem cells (hPSCs). The induced pituitary hormone-producing cells retain the physiological properties already lost in tumor-derived cell lines. Moreover, CRISPR/Cas9 systems have expedited the introduction of causative gene mutations in various malignant tumors into hPSCs. Therefore, hPSC-derived pituitary cells have great potential as a novel platform for studying the pathophysiology of human-specific pituitary adenomas and developing novel drugs. This review presents an overview of the recent progresses in hPSC applications for pituitary research, functional pituitary adenoma pathogenesis, and genome-editing techniques for introducing causative mutations. We also discuss future applications of hPSCs for studying pituitary adenomas.
Li–Fraumeni Syndrome: Mutation of TP53 Is a Biomarker of Hereditary Predisposition to Tumor: New Insights and Advances in the Treatment
Authors: Rocca Valentina , Blandino Giovanni , D’Antona Lucia , Iuliano Rodolfo , Di Agostino Silvia
Published: July 2022

Li–Fraumeni syndrome (LFS) is a rare familial tumor predisposition syndrome with autosomal dominant inheritance, involving germline mutations of the TP53 tumor suppressor gene. The most frequent tumors that arise in patients under the age of 45 are osteosarcomas, soft-tissue sarcomas, breast tumors in young women, leukemias/lymphomas, brain tumors, and tumors of the adrenal cortex. To date, no other gene mutations have been associated with LFS. The diagnosis is usually confirmed by genetic testing for the identification of TP53 mutations; therefore, these mutations are considered the biomarkers associated with the tumor spectrum of LFS. Here, we aim to review novel molecular mechanisms involved in the oncogenic functions of mutant p53 in LFS and to discuss recent new diagnostic and therapeutic approaches exploiting TP53 mutations as biomarkers and druggable targets.
Effective Treatment of Patients Experiencing Primary, Acute HIV Infection Decreases Exhausted/Activated CD4+ T Cells and CD8+ T Memory Stem Cells
Authors: Lo Tartaro Domenico , Camiro-Zúñiga Antonio , Nasi Milena , De Biasi Sara , Najera-Avila Marco A. , Jaramillo-Jante Maria Del Rocio , Gibellini Lara , Pinti Marcello , Neroni Anita , Mussini Cristina , Soto-Ramírez Luis E. , Calva Juan J. , Belaunzarán-Zamudio Francisco , Crabtree-Ramirez Brenda , Hernández-Leon Christian , Mosqueda-Gómez Juan L. , Navarro-Álvarez Samuel , Perez-Patrigeon Santiago , Cossarizza Andrea
Published: July 2022

Several studies have identified main changes in T- and B-lymphocyte subsets during chronic HIV infection, but few data exist on how these subsets behave during the initial phase of HIV infection. We enrolled 22 HIV-infected patients during the acute stage of infection before the initiation of antiretroviral therapy (ART). Patients had blood samples drawn previous to ART initiation (T0), and at 2 (T1) and 12 (T2) months after ART initiation. We quantified cellular HIV-DNA content in sorted naïve and effector memory CD4 T cells and identified the main subsets of T- and B-lymphocytes using an 18-parameter flow cytometry panel. We identified correlations between the patients’ clinical and immunological data using PCA. Effective HIV treatment reduces integrated HIV DNA in effector memory T cells after 12 months (T2) of ART. The main changes in CD4+ T cells occurred at T2, with a reduction of activated memory, cytolytic and activated/exhausted stem cell memory T (TSCM) cells. Changes were present among CD8+ T cells since T1, with a reduction of several activated subsets, including activated/exhausted TSCM. At T2 a reduction of plasmablasts and exhausted B cells was also observed. A negative correlation was found between the total CD4+ T-cell count and IgM-negative plasmablasts. In patients initiating ART immediately following acute/early HIV infection, the fine analysis of T- and B-cell subsets has allowed us to identify and follow main modifications due to effective treatment, and to identify significant changes in CD4+ and CD8+ T memory stem cells.