bluuebunny/crossref_metadata_2025 huggingface dataset:
Recombinant AMA1 Virus-like Particle Antigen for Serodiagnosis of Toxoplasma gondii Infection
Authors: Kim Min-Ju , Chu Ki-Back , Mao Jie , Kang Hae-Ji , Eom Gi-Deok , Yoon Keon-Woong , Lee Su-Hwa , Moon Eun-Kyung , Lee Young-Ha , Quan Fu-Shi
Published: November 2022

Toxoplasmosis diagnosis predominantly relies on serology testing via enzyme-linked immunosorbent assay (ELISA), but these results are highly variable. Consequently, various antigens are being evaluated to improve the sensitivity and specificity of toxoplasmosis serological diagnosis. Here, we generated Toxoplasma gondii virus-like particles displaying AMA1 of T. gondii and evaluated their diagnostic potential. We found that AMA1 VLPs were highly sensitive and reacted with the sera acquired from mice infected with either T. gondii ME49 or RH strains. The overall IgG and IgM antibody responses elicited by AMA1 VLPs were substantially higher than those induced by the conventionally used T. gondii lysate antigen (TLA). Importantly, AMA1 VLPs were capable of detecting parasitic infection with T. gondii RH and ME49 as early as 1 week post-infection, even when mice were exposed to low infectious doses (5 × 103 and 10 cysts, respectively). AMA1 VLPs also did not cross-react with the immune sera acquired from Plasmodium berghei-infected mice. Compared to TLA, stronger antibody responses were induced by AMA1 VLPs when tested using T. gondii-infected human sera. The sensitivities and specificities of the two antigens were substantially different, with AMA1 VLPs demonstrating over 90% sensitivity and specificity, whereas these values were in the 70% range for the TLA. These results indicated that AMA1 VLPs can detect infections of both T. gondii ME49 and RH at an early stage of infection caused by very low infection doses in mice, and these could be used for serological diagnosis of human toxoplasmosis.
Asymmetric Airfoil Morphing via Deep Reinforcement Learning
Authors: Lu Kelin , Fu Qien , Cao Rui , Peng Jicheng , Wang Qianshuai
Published: November 2022

Morphing aircraft are capable of modifying their geometry configurations according to different flight conditions to improve their performance, such as by increasing the lift-to-drag ratio or reducing their fuel consumption. In this article, we focus on the airfoil morphing of wings and propose a novel morphing control method for an asymmetric deformable airfoil based on deep reinforcement learning approaches. Firstly, we develop an asymmetric airfoil shaped using piece-wise Bézier curves and modeled by shape memory alloys. Resistive heating is adopted to actuate the shape memory alloys and realize the airfoil morphing. With regard to the hysteresis characteristics exhibited in the phase transformation of shape memory alloys, we construct a second-order Markov decision process for the morphing procedure to formulate a reinforcement learning environment with hysteresis properties explicitly considered. Subsequently, we learn the morphing policy based on deep reinforcement learning techniques where the accurate information of the system model is unavailable. Lastly, we conduct simulations to demonstrate the benefits brought by our learning implementations and validate the morphing performance of the proposed method. The simulation results show that the proposed method provides an average 29.8% performance improvement over traditional methods.
Preparation of Novel Nanoformulation to Enhance Efficacy in the Treatment of Cardiovascular Disease
Authors: Jayakodi Santhoshkumar , Kim Hyunjin , Menon Soumya , Shanmugam Venkat Kumar , Choi Inho , Sekhar Medidi Raja , Bhaskar Rakesh , Han Sung Soo
Published: November 2022

Despite many efforts over the last few decades, cardiac-based drug delivery systems are experiencing major problems, such as the effective delivery of the precise amount of a drug. In the current study, an effort has been made to prepare a nano-herbformulation (NHF) to overcome the major problem of conventional intervention. Copper oxide-based NHF was prepared using plant extract of Alternanthera sessilis and characterized using physicochemical techniques such as Transmission electron microscopy (TEM), X-ray powder diffraction (XRD), Dynamic light scattering (DLS), UV-Vis spectroscopy, and Fourier-transform infrared spectroscopy (FTIR). TEM analysis revealed that spherical NHF obtained of size 20–50 nm. In addition, XRD and FTIR confirmed the presence of phytochemicals with biological properties over the surface of copper oxide-based NHF. It was demonstrated that dose-dependent antiapoptotic activity was shown against DOX-induced cardiomyocytes, where ROS levels were significantly reduced to 0.29% from 37.99%. The results of the flow cytometry analysis using PI and Annexin staining further confirmed the antiapoptotic activity of NHF against DOX-induced cardiomyocytes by ROS scavenging. Thus, NHF might be used for cardiovascular disease treatment.
Electrochemically Exfoliated Graphene Quantum Dots Based Biosensor for CD44 Breast Cancer Biomarker
Authors: Kumar Neeraj , Yadav Shalu , Sadique Mohd Abubakar , Khan Raju
Published: November 2022

An innovative electrochemical biosensor based on graphene quantum dots (GQDs) is developed for a simple, rapid, and highly sensitive primary diagnosis of the breast cancer biomarker cluster of differentiation-44 (CD44) antigen. Herein, electrochemical exfoliation of waste dry batteries provides facile, eco-friendly, and cost-effective synthesis of GQDs. Transmission electron microscopy (TEM) analysis reveals that GQDs exhibit spherical shapes with an average diameter of 4.75 nm. Further, electrochemical analysis through cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) reveals that the electrochemical properties of GQDs are suitable for biosensing applications. Subsequently, GQDs have a large electroactive surface area that has been utilized for the immobilization of CD44 antibodies to fabricate the electrochemical biosensor. The electroanalytical performance of GQDs for CD44 biosensing capabilities is studied by differential pulse voltammetry (DPV). The developed electrochemical biosensor has high sensitivity with the lowest detection limit (LOD) of 2.11 fg/mL in the linear range of 0.1 pg/mL to 100.0 ng/mL in phosphate buffer saline (PBS). Further, the linear response of the electrochemical biosensor for CD44 antigen concentration is in the range of 1.0 pg/mL to 100.0 ng/mL with a LOD of 2.71 fg/mL in spiked serum samples. The outcomes suggest that the synthesized GQDs demonstrate promising attributes to be utilized as a viable nanomaterial in biosensing applications.
The Effect of an α-7 Nicotinic Allosteric Modulator PNU120596 and NMDA Receptor Antagonist Memantine on Depressive-like Behavior Induced by LPS in Mice: The Involvement of Brain Microglia
Authors: Alzarea Sami , Abbas Muzaffar , Ronan Patrick J. , Lutfy Kabirullah , Rahman Shafiqur
Published: November 2022

Nicotinic acetylcholine receptors (nAChRs), particularly the α7 nAChR, play a critical role in neuroinflammation and microglial activation associated with major depressive disorder (MDD). Microglial quinolinic acid (QUIN), which is synthesized by 3-hydroxyanthranilic acid dioxygenase (HAAO), is an N-methyl-D-aspartate (NMDA) receptor agonist and has been implicated in the development of MDD-related symptoms. In the present study, we assessed the effects of PNU120596, an α7 nAChR positive allosteric modulator (PAM), on HAAO expression and QUIN formation in the hippocampus and prefrontal cortex. We also investigated the effects of memantine, an NMDA receptor antagonist, alone and in combination with PNU120596 on cognitive deficit and depressive-like behaviors induced by lipopolysaccharide (LPS) in mice using the Y-maze and forced swim test, respectively. LPS (1 mg/kg, i.p.) elevated HAAO expression and QUIN formation in the hippocampus and prefrontal cortex, which were reduced with pretreatment with PNU120596 (4 mg/kg, i.p.). Furthermore, memantine (1 or 3 mg/kg, i.p.) prevented the cognitive deficit and depressive-like behaviors induced by LPS in mice. Together, these results suggest that the antidepressant-like effects of PNU120596 are mediated by attenuation of LPS-induced QUIN formation. Therefore, α7 nAChR PAM could be a potential therapeutic candidate for MDD associated with neurotoxic glutamatergic transmission.
Well Played! Promoting Phonemic Awareness Training Using EdTech—GraphoGame Brazil—During the COVID-19 Pandemic
Authors: Marques de Souza Juliana G. , Weissheimer Janaina , Buchweitz Augusto
Published: November 2022

Early literacy skills such as alphabet knowledge and phonemic awareness are made up the foundation for learning to read. These skills are more effectively taught with explicit instruction starting inpreschool and then continuing during early elementary school years. The COVID19 pandemic school closures severely impacted early literacy development worldwide. Brazil had one of the longest school closure periods, which resulted in several children having no access to any educational activities. Education Technology (EdTech) tools can leverage access to pedagogical materials and remediate the consequences of school closure. We investigated the impact of using an early literacy EdTech, GraphoGame Brazil, to foster learning of early literacy skills during the height of COVID19 school closures, in Brazil. We carried out a quasi-experimental, pretest and posttest study with elementary school students who were taking online classes. Participants were pseudo randomly assigned to (1) an experimental group, who played GraphoGame Brazil, and to (2) an active control group, who played an EdTech that focuses on early numeracy skills. The results show a significant positive training effect on word reading accuracy associated with the use of GraphoGame for the children in the experimental group, relative to the control group. We also found statistically significant negative effect in lowercase naming for the control group. We address the consequences of COVID19 school closures, the promise of EdTech and its limitations, and discuss the issue of fostering successful early literacy instruction in countries that have struggled with teaching children to read even before the pandemic.
Effects of Anti-Parkinsonian Drugs on Verbal Fluency in Patients with Parkinson’s Disease: A Network Meta-Analysis
Authors: Zhu Yuxia , Li Sichen , Lai Hongyu , Mo Lijuan , Tan Changhong , Liu Xi , Deng Fen , Chen Lifen
Published: November 2022

Verbal fluency impairment is common in patients with Parkinson’s disease (PD), but the effect of drugs on verbal fluency in PD patients has not been comprehensively evaluated. We conducted a network meta-analysis based on four online databases to compare the effect of drugs on verbal fluency in PD patients. This study was performed and reported according to PRISMA-NMA guidelines. In total, 6 out of 3707 articles (three RCTS and three cross-sectional studies) covering eight drug regimens were included (five for letter fluency, five for semantic fluency). In terms of letter fluency, the ranking of the overall efficacy of included drug regimens was: levodopa, levodopa combined with pramipexole, rotigotine, cabergoline, pramipexole, pergolide, but no drug regimen presented a significant advantage over the others. In terms of semantic fluency, the ranking of the overall efficacy of included drug regimens was: rotigotine, levodopa, cabergoline, pergolide, pramipexole, among which, levodopa alone (SMD = 0.93, 95%CI: 0.28–1.59) and rotigotine alone (SMD = 1.18, 95%CI: 0.28–2.09) were statistically superior to pramipexole, while no significant difference was identified between all the other drug regimens. Levodopa and rotigotine seem to be more appropriate choices for PD patients with verbal fluency impairment. Further study is needed to illustrate the efficacy of drugs on verbal fluency in PD patients.
Bayesian Optimization of Machine Learning Classification of Resting-State EEG Microstates in Schizophrenia: A Proof-of-Concept Preliminary Study Based on Secondary Analysis
Authors: Keihani Ahmadreza , Sajadi Seyed Saman , Hasani Mahsa , Ferrarelli Fabio
Published: November 2022

Resting-state electroencephalography (EEG) microstates reflect sub-second, quasi-stable states of brain activity. Several studies have reported alterations of microstate features in patients with schizophrenia (SZ). Based on these findings, it has been suggested that microstates may represent neurophysiological biomarkers for the classification of SZ. To explore this possibility, machine learning approaches can be employed. Bayesian optimization is a machine learning approach that selects the best-fitted machine learning model with tuned hyperparameters from existing models to improve the classification. In this proof-of-concept preliminary study based on secondary analysis, 20 microstate features were extracted from 14 SZ patients and 14 healthy controls’ EEG signals. These parameters were then ranked as predictors based on their importance, and an optimized machine learning approach was applied to evaluate the performance of the classification. SZ patients had altered microstate features compared to healthy controls. Furthermore, Bayesian optimization outperformed conventional multivariate analyses and showed the highest accuracy (90.93%), AUC (0.90), sensitivity (91.37%), and specificity (90.48%), with reliable results using just six microstate predictors. Altogether, in this proof-of-concept study, we showed that machine learning with Bayesian optimization can be utilized to characterize EEG microstate alterations and contribute to the classification of SZ patients.
Development of Non-Proprietary Ultra-High Performance Concrete Mixtures
Authors: Hasan Tawsif Mohammad , Gilbert Levi , Allena Srinivas , Owusu-Danquah Josiah , Torres Anthony
Published: November 2022

The development of non-proprietary Ultra-High Performance Concrete (UHPC) is one way to reduce the initial cost of construction. However, workability is a major issue for which such mixtures are not practical in field conditions. Ultra-high performance cannot be achieved in field conditions if the concrete is not placed, finished, and compacted properly during placement. In this research, six UHPC mixtures were developed (three with steel fibers and three without fibers) using materials which are readily available on the local marketplace with water-to-cementitious materials ratios ranging between 0.17 to 0.30. The workability was determined using standard ASTM flow table apparatus, and specimens were prepared to determine compressive strength, splitting tensile strength, and permeable porosity. Flow table test exhibited flow values greater than 250 mm. Such high workability of the mixtures was achieved by optimizing the silica fume content and water reducing admixture dosage. These mixtures exhibited compressive strengths greater than 120 MPa and splitting tensile strengths greater than 5.10 MPa in both ambient and elevated curing temperatures. Results indicated that UHPC can be produced with a water-to-cementitious materials ratio as high as 0.30. Steel fibers helped to increase splitting tensile strength due to fiber-matrix interactions. Very low permeable porosity (1.7–16.7%) was observed which indicates superior durability due to the significant reduction of ingress of deleterious ions.
Energy Retrofitting Assessment of Public Building Envelopes in China’s Hot Summer and Cold Winter Climate Region
Authors: Liu Changchun , Ma Wenting , Hao Jianli , Luo Daiwei , Zuo Jian , Zhang Cheng
Published: November 2022

The retrofitting of existing public buildings to save energy and reduce carbon emissions is a priority for China’s building sector. Accordingly, the Chinese government requires all public buildings to be energy retrofitted based on the Design Standard for Energy Efficiency of Public Buildings GB50189-2015. However, few studies have been conducted to assess the energy efficiency of this design standard in the hot summer and cold winter (HSCW) climate region of China. The aim of this study was therefore to provide sensitivity analysis for the thermal properties of the envelope of a typical public building energy retrofit in China’s HSCW climate region. The results show that the thermal performance of the existing envelope of the sample building was very poor, with heating and cooling energy consumption 18.94% higher than the GB90189-2015 baseline model. It was found that better optimized parameters could reduce the heating and cooling energy load by 28.26% compared with the parameters of the sample building. The findings from this study provide valuable references for local governments and practitioners eager to improve the energy efficiency of existing public buildings in China’s HSCW region.
Flexural Behaviour of Built-Up Beams Made of Optimised Sections
Authors: Kanthasamy Elilarasi , Hussain Janaid , Thirunavukkarasu Kajaharan , Poologanathan Keerthan , Roy Krishanu , Beulah Gnana Ananthi G. , Suntharalingam Thadshajini
Published: November 2022

The modular construction industry often seeks cost-effective, high-performing, and longer-span members in buildings to ensure efficiency and quality. Accordingly, the idea of built-up sections was brought into gain numerous benefits including higher structural capacity, improved torsional rigidity, and increased stiffness. While limited research studies have been carried out to study the structural performances of built-up sections, few innovative section profiles have been developed in the industry considering the structural benefits, including improved stiffness. Hence, the application of newly developed built-up sections could enhance the employment of built-up sections in the industry. On that note, this research is focused on the flexural behaviour of optimised section profiles named the LCB-benchmark (Lipped Channel Beam), the optimised-LCB, folded-flange and the super-sigma sections. In addition, different materials, namely cold-formed carbon steel (CFS), cold-formed (CF) aluminium and CF stainless steel, were considered for built-up sections, in order to provide recommendations based on their flexural performances. Numerical analysis was carried out on single sections as well as on built-up sections to the developed parametric plan after the successful validation of experimental studies. The results were compared for single and built-up sections. Finally, based on the comparisons, the folded-flange built-up section is recommended for all three materials as it displayed the highest bending capacity, and the capacity enhancement compared to the corresponding single section was a minimum of 131%.
Crack Identification for Bridge Structures Using an Unmanned Aerial Vehicle (UAV) Incorporating Image Geometric Correction
Authors: Li Jiapo , Li Xiaoda , Liu Kai , Yao Zhiyong
Published: November 2022

Crack assessment of bridge structures is essential for maintaining safe transportation infrastructure. Traditional crack detection by manual visual observation has drawbacks, as it is expensive, time-consuming, and limited by the height and volume of bridges. Recently, unmanned aerial vehicles (UAVs) with image processing have been used to address these limitations. However, cameras on UAVs will generally not be perpendicular to the crack surface during actual measurements; therefore, deviation in the perspective angle can lead to inaccuracies in crack identification. In this work, we propose a robust and straightforward crack detection method based on geometric correction and calibration algorithms to address these issues. Four parallel laser emitters were installed on the UAV camera for crack image acquisition, and the laser-obtained images were geometrically adjusted using the four-point linear correction algorithm. After crack image processing, the object-to-image resolution was analyzed, and the crack information was extracted. Compared to the lens imaging concept method, the method based on the four-point lasers showed greater precision for crack width identification, with a measurement accuracy of over 95%. This indicated that the proposed crack identification system showed great potential for actual crack detection of bridges.
Predicting Crack Width in CFRP-Strengthened RC One-Way Slabs Using Hybrid Grey Wolf Optimizer Neural Network Model
Authors: Razavi Tosee Seyed , Faridmehr Iman , Nehdi Moncef , Plevris Vagelis , Valerievich Kiyanets
Published: November 2022

This study deploys a hybrid Grey Wolf Optimizer Neural Network Model for predicting the crack width in reinforced concrete slabs strengthened with carbon fiber-reinforced polymers (CFRP). Reinforced concrete (RC) one-way slabs (1800 × 400 × 120 mm in size) were strengthened with CFRP with various lengths (1800, 1100, and 700 mm) and subjected to four-point bending. The experimental results were compared to corresponding values for conventional RC slabs. The observed crack width results were recorded, and subsequently examined against the expression recommended by Eurocode 2. To estimate the crack width of CFRP-reinforced slabs, ANN combined with the Grey Wolf Optimizer algorithm was employed whereby the applied load, CFRP width/length, X/Y crack positions, and stress in steel reinforcement and concrete were defined as the input parameters. Experimental results showed that the larger the length and width of the carbon fiber, the smaller the maximum crack width in the tensile area of the slab at the final load step. On average, the crack width in slabs retrofitted with CFRP laminates increased by around 80% compared to a slab without CFRP. The results confirm that the equation provided by Eurocode 2 provides an unconservative estimation of crack widths for RC slabs strengthened with CFRP laminates. On the other hand, the results also confirm that the proposed informational model could be used as a reliable tool for estimating the crack width in RC slabs. The findings provide valuable insight into the design approaches for RC slabs and rehabilitation strategies for existing deficient RC slabs using CFRP.
Experimental and Numerical Investigation of Internal Explosion in an Earth-Covered Magazine
Authors: Xu Guangan , Qiu Yanyu , Xing Huadao , Li Xiaodong , Gong Cheng
Published: November 2022

Earth-covered magazine has some characteristics that are safer than the above-ground magazine and are more economical than underground magazine. To investigate the pressure distribution and the structural failure under the internal explosion, the scaled tests of the earth-covered magazine were conducted under a 0.5 kg TNT explosive charge. The overpressure in the 0°, 90°, and 180° directions outside the structure and the debris distribution were obtained. The numerical simulations were constructed in LS-DYNA software to analyze the test results. The results show that the external overpressure has a directional characteristic that the maximum and minimum overpressure appear in 0° and 180° directions, respectively. In the double logarithmic coordinate system, the overpressure peaks in three directions are linearly related to the scaled distance. Most of the fragments in the 0° direction hit the ground within the front range of ±60°, and the further fragments (40 m or more) were confined to a limited sector within the front range of ±30°. The internal explosion numerical simulation shows that the concrete cracks first appeared at the roof and the ground, and then the damage occurred at the intersection of the walls, and then the damage occurred at each surface. The maximum debris velocity of the side and rear walls is lower than that of the front wall due to the limitation of the soil. The motion equations of the debris combined with numerical simulation can be adopted to predict the projection distance of fragments.
Compressive Properties of Self-Compacting Concrete after Cooling from High Temperatures
Authors: Zhu Junru , Zhang Chuntao , Yu Wei
Published: November 2022

Self-compacting concrete (SCC) has been widely used in building structures. However, previous research focused only on the mechanical properties and working properties of SCC at room temperature. Thus, there is limited research on the change of compressive strength of SCC after a fire. This paper aims to investigate the compressive properties of SCC after being cooled from high temperatures. The SCC specimens were firstly heated to a target temperature of 100–700 °C and were then cooled to ambient temperatures by water or in air. The heating and cooling damage to the SCC specimens was assessed by the mass loss and the ultrasonic pulse velocity (UPV) separately. Afterward, the axial compression tests were carried out to investigate the compressive properties of the fire-affected SCC specimens under uniaxial compression. The residual mass, UPV, stress–strain curves, post-fire failure characteristics, and compressive strengths of the SCC specimens were discussed in detail. The mass loss of the SCC specimens showed an obvious increase with the rising temperatures, while the UPV exhibited a converse pattern. The mass loss of the SCC specimens after being naturally cooled increased more significantly, while the two cooling methods used in this experiment had little effect on the UPV. When the SCC specimens were cooled from 100 °C, the compressive strength of the SCC specimens cooled in air or water dropped by 32.54% and 35.15%, respectively. However, while the heating temperature rose to 700 °C, the compressive strengths of the SCC specimens cooled in air or water dropped sharply by 72.98% and 86.51%, respectively. Finally, an improved mathematical model for SCC after cooling from high temperatures was proposed based on Jones and Nelson’s equation. This improved material model matched the experimental results well, which demonstrates that the proposed constitutive model can provide better predictions for the SCC structures after a fire.
Knowledge Transfer Characteristics of Construction Workers Based on Social Network Analysis
Authors: Cao Xinying , Qin Peicheng , Zhang Ping
Published: November 2022

Effects of traditional training methods are not obvious when transferring competent knowledge to construction workers to allow them to deal with new technology and intelligent equipment. The purpose of this study was to explore knowledge transfer paths and transfer characteristics within worker groups and to provide a theoretical basis for formulating new measures to improve knowledge and skills in worker groups. Firstly, we analyzed and verified the group characteristics of workers. Then, the social network analysis (SNA) method was used to study the knowledge transfer characteristics of worker groups, and the following conclusions were drawn: (1) construction workers have obvious group closure and regional concentration, which have significant impacts on knowledge transfer; (2) team leaders are the core and authority of knowledge transfer within entire networks, so improving the knowledge and skills of team leaders has a significant impact on promoting the overall knowledge and skills of workers; (3) it is very difficult for expatriate technical instructors with high levels of education but no blood or geographical relationships with other workers to establish knowledge authority among workers; and (4) due to the large gaps in knowledge and skills among workers, one-way flows of knowledge occur easily within groups.
Conducting Polymer Metallic Emerald: Magnetic Measurements of Nanocarbons/Polyaniline and Preparation of Plastic Composites
Authors: Koshikawa Yusuke , Miyashita Ryo , Yonehara Takuya , Komaba Kyoka , Kumai Reiji , Goto Hiromasa
Published: November 2022

Synthesis of polyaniline in the presence of fullerene nanotubes (nanocarbons) in water was carried out with oxidative polymerization. The surface of the sample showed metallic emerald green color in bulk like the brilliance of encrusted gemstones. The composite showed unique magnetic behavior, such as microwave power-dependent magnetic resonance as magnetic spin behavior and macroscopic paramagnetism with a maximum χ value at room temperature evaluated with superconductor interference device. Surface structure of the composite was observed with optical microscopy, circular polarized differential interference contrast optical microscopy, scanning electron microscopy, and electron probe micro analyzer. Polymer blends consisting of polyaniline, nano-carbons, and hydroxypropylcellulose or acryl resin with both conducting polymer and carbon characters were prepared, which can be applied for electrical conducting plastics. The combination of conducting polymer and nano-carbon materials can produce new electro-magneto-active soft materials by forming a composite. This paper reports evaluation of magnetic properties as a new point of nanocarbon and conducting polymer composite.
An Indeterminate for Malignancy FNA Report Does Not Increase the Surgical Risk of Incidental Thyroid Carcinoma
Authors: Seminati Davide , Mane Eltjona , Ceola Stefano , Casati Gabriele , Putignano Pietro , Garancini Mattia , Gatti Andrea , Leni Davide , Pincelli Angela Ida , Fusco Nicola , L’Imperio Vincenzo , Pagni Fabio
Published: November 2022

Incidental thyroid carcinomas (ITCs) are a fairly frequent finding in daily routine practice, with papillary thyroid microcarcinoma being the most frequent entity. In our work, we isolated incidental cases arising in thyroids removed for other cytologically indeterminate and histologically benign nodules. We retrospectively retrieved cases with available thyroid Fine Needle Aspiration (FNA, 3270 cases), selecting those with an indeterminate cytological diagnosis (Bethesda classes III–IV, 652 cases). Subsequently, we restricted the analysis to surgically treated patients (163 cases) finding an incidental thyroid carcinoma in 22 of them. We found a 13.5% ITC rate, with ITCs representing 46.8% of all cancer histologically diagnosed in this indeterminate setting. Patients received a cytological diagnosis of Bethesda class III and IV in 41% and 59% of cases, respectively. All ITC cases turned out to be papillary thyroid microcarcinomas; 36% of cases were multifocal, with foci bilaterally detected in 50% of cases. We found an overall ITC rate concordant with the literature and with our previous findings. The assignment of an indeterminate category to FNA did not increase the risk of ITCs in our cohort. Rather, a strong statistical significance (p < 0.01) was found comparing the larger size of nodules that underwent FNA and the smaller size of their corresponding ITC nodule.
The Vessels That Encapsulate Tumor Clusters (VETC) Pattern Is a Poor Prognosis Factor in Patients with Hepatocellular Carcinoma: An Analysis of Microvessel Density
Authors: Huang Chun-Wei , Lin Sey-En , Huang Song-Fong , Yu Ming-Chin , Tang Jui-Hsiang , Tsai Chi-Neu , Hsu Heng-Yuan
Published: November 2022

The outcomes of patients with hepatocellular carcinoma (HCC) are unsatisfactory because of its high recurrence rate. The Vessels that encapsulate tumor clusters (VETC) pattern is a unique vascular structure. In this study, we investigated the clinical–pathological features of HCC patients with the VETC pattern. We retrospectively reviewed patients with HCC who underwent curative hepatectomy at Chang Gung Memorial Hospital between 2007 and 2013. The form of the VETC pattern was established using an anti-CD31 stain. The results were classified into positive (VETC+) and negative (VETC−) patterns. We investigated and compared demographic data between these two groups. Overall, 174 patients were classified into either the VETC+ or VETC− groups. The median followed-up period was 80.5 months. There were significant differences in the number of hepatitis B carriers, the occurrence of vascular invasion, tumor size, TNM staging, microvessel density, and recurrence (all p < 0.05). Regarding the prediction of disease-free survival, after COX regression multivariate analysis, VETC+ remained independently associated with recurrent episodes (p = 0.003). The intra-tumoral microvessel density, demonstrated by CD-31, was the only clinical–pathological feature independently associated with VETC+. Our study demonstrated that the VETC pattern is an independent factor of poor prognosis for DFS. Higher intra-tumoral microvessel density was significantly associated with the VETC pattern. Further studies are needed to validate our findings.
KRAS in NSCLC: State of the Art and Future Perspectives
Authors: Cascetta Priscilla , Marinello Arianna , Lazzari Chiara , Gregorc Vanesa , Planchard David , Bianco Roberto , Normanno Nicola , Morabito Alessandro
Published: November 2022

In NSCLC, KRAS mutations occur in up to 30% of all cases, most frequently at codon 12 and 13. KRAS mutations have been linked to adenocarcinoma histology, positive smoking history, and Caucasian ethnicity, although differences have been described across KRAS mutational variants subtypes. KRAS mutations often concur with other molecular alterations, notably TP53, STK11, and KEAP1, which could play an important role in treatment efficacy and patient outcomes. For many years, KRAS mutations have been considered undruggable mainly due to a high toxicity profile and low specificity of compounds. Sotorasib and adagrasib are novel KRAS inhibitors that recently gained FDA approval for pre-treated KRAS mutant NSCLC patients, and other molecules such as GDC-6036 are currently being investigated with promising results. Despite their approval, the efficacy of these drugs is lower than expected and progression among responders has been reported. Mechanisms of acquired resistance to anti-KRAS molecules typically involves either on target secondary mutations (e.g., G12, G13, Q61H, R68S, H95, Y96C, V8L) or off-target alterations. Ongoing trials are currently evaluating strategies for implementing efficacy and overcoming acquired resistance to these compounds. Finally, the efficacy of immune-checkpoint inhibitors still needs to be completely assessed and responses to anti-PD-1/PD-L1 agents may strongly depend on concomitant mutations.
Targeted Therapies in Advanced and Metastatic Urothelial Carcinoma
Authors: Katims Andrew B. , Reisz Peter A. , Nogueira Lucas , Truong Hong , Lenis Andrew T. , Pietzak Eugene J. , Kim Kwanghee , Coleman Jonathan A.
Published: November 2022

This review describes the current landscape of targeted therapies in urothelial carcinoma. The standard of care for advanced urothelial carcinoma patients remains platinum-based combination chemotherapy followed by immunotherapy. However, median overall survival for these patients is still <1 year and there is an urgent need for alternative therapies. The advent of next-generation sequencing has allowed widespread comprehensive molecular characterization of urothelial tumors and, subsequently, the development of therapies targeting specific molecular pathways implicated in carcinogenesis such as FGFR inhibition, Nectin-4, Trop-2, and HER2 targeting. As these therapies are demonstrated to be effective in the second-line setting, they will be advanced in the treatment paradigm to localized and even non-muscle invasive disease.
Interplay between Tumor Mutational Burden and Mutational Profile and Its Effect on Overall Survival: A Pilot Study of Metastatic Patients Treated with Immune Checkpoint Inhibitors
Authors: Xavier Camila B. , Lopes Carlos Diego H. , Awni Beatriz M. , Campos Eduardo F. , Alves João Pedro B. , Camargo Anamaria A. , Guardia Gabriela D. A. , Galante Pedro A. F. , Jardim Denis L.
Published: November 2022

Purpose: Solid tumors harboring tumor mutational burden (TMB) ≥10 mutations per megabase (mut/Mb) received agnostic approval for pembrolizumab. This work aims to analyze the somatic mutational profile’s influence on the outcomes of patients with TMB-high tumors treated with immune checkpoint inhibitors (ICIs). Methods: This post-hoc analysis evaluated clinical and molecular features of patients with solid tumors treated with ICIs that could be either monoclonal antibody directed against programmed cell death protein-1 or monoclonal antibody directed against programmed cell death ligand 1 (anti-PD-1/anti-PD-L1), monoclonal antibody directed against cytotoxic T lymphocyte-associated antigen (anti-CTLA-4) or a combined treatment regimen including one anti-PD-1/anti-PD-L1 and one anti-CTLA-4 (ICIs combination). We performed OS analysis for TMB thresholds of ≥10, ≥20, and <10 mut/Mb. We assessed OS according to the mutational profile for a TMB ≥ 10 mut/Mb cutoff. For genes correlated with OS at the univariate assessment, we conducted a Cox multivariate analysis adjusted by median TMB, sex, age, microsatellite instability (MSI), and histology. Results: A total of 1661 patients were investigated; 488 with a TMB ≥10 mut/Mb (29.4%). The median OS was 42 months for TMB ≥10 or 20 mut/Mb, and 15 months for TMB <10 mut/Mb (p < 0.005). Among TMB ≥10 mut/Mb patients, mutations in E2F3 or STK11 correlated with worse OS, and mutations in NTRK3, PTPRD, RNF43, TENT5C, TET1, or ZFHX3 with better OS. These associations were confirmed with univariate and multivariate analyses (p < 0.05). Melanoma histology and TMB above the median endowed patients with better OS (p < 0.05), while MSI status, age, and gender did not have a statistically significant effect on OS. Conclusion: Combining TMB and mutation profiles in key cancer genes can better qualify patients for ICI treatment and predict their OS.
Smoking-Associated Exposure of Human Primary Bronchial Epithelial Cells to Aldehydes: Impact on Molecular Mechanisms Controlling Mitochondrial Content and Function
Authors: Tulen Christy B. M. , Duistermaat Evert , Cremers Johannes W. J. M. , Klerx Walther N. M. , Fokkens Paul H. B. , Weibolt Naömi , Kloosterboer Nico , Dentener Mieke A. , Gremmer Eric R. , Jessen Phyllis J. J. , Koene Evi J. C. , Maas Lou , Opperhuizen Antoon , van Schooten Frederik-Jan , Staal Yvonne C. M. , Remels Alexander H. V.
Published: November 2022

Chronic obstructive pulmonary disease (COPD) is a devastating lung disease primarily caused by exposure to cigarette smoke (CS). During the pyrolysis and combustion of tobacco, reactive aldehydes such as acetaldehyde, acrolein, and formaldehyde are formed, which are known to be involved in respiratory toxicity. Although CS-induced mitochondrial dysfunction has been implicated in the pathophysiology of COPD, the role of aldehydes therein is incompletely understood. To investigate this, we used a physiologically relevant in vitro exposure model of differentiated human primary bronchial epithelial cells (PBEC) exposed to CS (one cigarette) or a mixture of acetaldehyde, acrolein, and formaldehyde (at relevant concentrations of one cigarette) or air, in a continuous flow system using a puff-like exposure protocol. Exposure of PBEC to CS resulted in elevated IL-8 cytokine and mRNA levels, increased abundance of constituents associated with autophagy, decreased protein levels of molecules associated with the mitophagy machinery, and alterations in the abundance of regulators of mitochondrial biogenesis. Furthermore, decreased transcript levels of basal epithelial cell marker KRT5 were reported after CS exposure. Only parts of these changes were replicated in PBEC upon exposure to a combination of acetaldehyde, acrolein, and formaldehyde. More specifically, aldehydes decreased MAP1LC3A mRNA (autophagy) and BNIP3 protein (mitophagy) and increased ESRRA protein (mitochondrial biogenesis). These data suggest that other compounds in addition to aldehydes in CS contribute to CS-induced dysregulation of constituents controlling mitochondrial content and function in airway epithelial cells.
Identification of the Telomere elongation Mutation in Drosophila
Authors: Reddy Hemakumar M. , Randall Thomas A. , Cipressa Francesca , Porrazzo Antonella , Cenci Giovanni , Frydrychova Radmila Capkova , Mason James M.
Published: November 2022

Telomeres in Drosophila melanogaster, which have inspired a large part of Sergio Pimpinelli work, are similar to those of other eukaryotes in terms of their function. Yet, their length maintenance relies on the transposition of the specialized retrotransposons Het-A, TART, and TAHRE, rather than on the activity of the enzyme telomerase as it occurs in most other eukaryotic organisms. The length of the telomeres in Drosophila thus depends on the number of copies of these transposable elements. Our previous work has led to the isolation of a dominant mutation, Tel1, that caused a several-fold elongation of telomeres. In this study, we molecularly identified the Tel1 mutation by a combination of transposon-induced, site-specific recombination and next-generation sequencing. Recombination located Tel1 to a 15 kb region in 92A. Comparison of the DNA sequence in this region with the Drosophila Genetic Reference Panel of wild-type genomic sequences delimited Tel1 to a 3 bp deletion inside intron 8 of Ino80. Furthermore, CRISPR/Cas9-induced deletions surrounding the same region exhibited the Tel1 telomere phenotype, confirming a strict requirement of this intron 8 gene sequence for a proper regulation of Drosophila telomere length.
Mexico: A Landscape of Viroid Origin and Epidemiological Relevance of Endemic Species
Authors: Aviña-Padilla Katia , Zamora-Macorra Erika Janet , Ochoa-Martínez Daniel Leobardo , Alcántar-Aguirre Flor Citlally , Hernández-Rosales Maribel , Calderón-Zamora Loranda , Hammond Rosemarie W.
Published: November 2022

Viroids are single-stranded, circular RNA molecules (234-406 nt) that infect a wide range of crop species and cause economic losses in agriculture worldwide. They are characterized by the existence of a population of sequence variants, attributed to the low fidelity of RNA polymerases involved in their transcription, resulting in high mutation rates. Therefore, these biological entities exist as quasispecies. This feature allows them to replicate within a wide range of host plants, both monocots and dicots. Viroid hosts include economically important crops such as tomato, citrus, and fruit trees such as peach and avocado. Given the high risk of introducing viroids to viroid disease-free countries, these pathogens have been quarantined globally. As discussed herein, Mexico represents a geographical landscape of viroids linked to their origin and comprises considerable biodiversity. The biological features of viroid species endemic to Mexico are highlighted in this communication. In addition, we report the phylogenetic relationships among viroid and viroid strains, their economic impact, geographical distribution, and epidemiological features, including a broad host range and possible long-distance, seed, or insect-mediated transmission. In summary, this review could be helpful for a better understanding of the biology of viroid diseases and future programs on control of movement and spread to avoid economic losses in agricultural industries.
Clinical Applications of Liquid Biopsy in Colorectal Cancer Screening: Current Challenges and Future Perspectives
Authors: Galoș Diana , Gorzo Alecsandra , Balacescu Ovidiu , Sur Daniel
Published: November 2022

Colorectal cancer (CRC) represents the third most prevalent cancer worldwide and a leading cause of mortality among the population of western countries. However, CRC is frequently a preventable malignancy due to various screening tests being available. While failing to obtain real-time data, current screening methods (either endoscopic or stool-based tests) also require disagreeable preparation protocols and tissue sampling through invasive procedures, rendering adherence to CRC screening programs suboptimal. In this context, the necessity for novel, less invasive biomarkers able to identify and assess cancer at an early stage is evident. Liquid biopsy comes as a promising minimally invasive diagnostic tool, able to provide comprehensive information on tumor heterogeneity and dynamics during carcinogenesis. This review focuses on the potential use of circulating tumor cells (CTCs), circulating nucleic acids (CNAs) and extracellular vesicles as emerging liquid biopsy markers with clinical application in the setting of CRC screening. The review also examines the opportunity to implement liquid biopsy analysis during everyday practice and provides highlights on clinical trials researching blood tests designed for early cancer diagnosis. Additionally, the review explores potential applications of liquid biopsies in the era of immunotherapy.
The Solution Combustion Synthesis of ZnO Powder for the Photodegradation of Phenol
Authors: Amosov Aleksandr P. , Novikov Vladislav A. , Kachkin Egor M. , Kryukov Nikita A. , Titov Alexander A. , Sosnin Ilya M. , Merson Dmitry L.
Published: November 2022

Nanoscale and submicron powder of zinc oxide (ZnO) is known as a highly efficient photocatalyst that is promising for solving the problem of wastewater treatment from toxic organic pollutants including phenol and its derivatives. The results of laboratory studies of ZnO preparation by a simple, energy-saving, and highly productive method of solution–combustion synthesis from a mixture of solutions of zinc nitrate and glycine, as well as the use of the ZnO powder synthesized by combustion for the photocatalytic decomposition of phenol, are presented. The modes and characteristics of combustion, phase composition, chemical composition, and structure of the combustion product at different ratios of glycine with zinc nitrate were determined. It is shown that calcination at 650 °C reduces the content of carbon impurity in the combustion product to ~1 wt.% and leads to obtaining ZnO powder in the form of porous agglomerates up to 100 μm in size sintered from crystalline nanoscale and submicron ZnO particles with an average crystallite size of 44 nm. The ZnO powder exhibits high photocatalytic activity, leading to the almost complete degradation of phenol in an aqueous solution under the action of ultraviolet irradiation in less than 4 h.
Forming of Additively Manufactured Ceramics by Magnetic Fields
Authors: Klug Christina , Herzog Simone , Kaletsch Anke , Broeckmann Christoph , Schmitz Thomas H.
Published: November 2022

The application of additive manufacturing using liquid material extrusion is inherently linked to material-related deformations and limitations in the choice of component geometry. This empirical study addresses the question of how the plasticity of a ceramic composite material can be utilized for a new integrated design and manufacturing process. In the exploratory approach, the liquid material is not limited in its soft plastic state, but its malleability is harnessed for a design-oriented approach. For this purpose, soft magnetic particles are added to a liquid clay mass. The developed composite material can be controlled, stabilized, and shaped by magnetic fields directly in the additive manufacturing process using modified equipment. In this study a permanent magnet and an electromagnet were compared while the distance between the printed part and the magnet was controlled by an optical sensor.
Adamantane Three-Dimensional Porous Organic Framework as a Fluorescence Sensor for Rapid Determination of Tetracycline in Aquatic Products
Authors: Lu Zhenyu , Hu Yufei , Li Gongke , Xia Ling
Published: November 2022

A fluorescence adamantane three-dimensional porous organic framework (AdaPOF) was synthesized via a Suzuki coupling reaction. The AdaPOF showed excellent fluorescence performance with a relative high quantum yield and fluorescence stability. Due to its excellent selectivity to tetracycline (TC), a fluorescence sensor based on AdaPOF was constructed for TC determination. The selective sensing mechanism of the AdaPOF towards TC was studied by density functional theory (DFT) calculation experiments. An AdaPOF–based fluorescence method for TC determination was established, with the linear range of 0.1–9.0 μmol/L (R2 = 0.9959) and the limit of detection (S/N = 3) of 43 nmol/L. Moreover, the fluorescence method was used to the determination of TC in aquatic products and the recoveries were ranged from 94.4% to 103.8%. The results obtained by this fluorescence method were consistent with those of the high-performance liquid chromatography (HPLC) method in the TC determination.