bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of Small Horizontal Axis Wind Turbines Based on Aerodynamic, Steady-State, and Dynamic Analyses
Authors: Deghoum Khalil , Gherbi Mohammed Taher , Sultan Hakim S. , Jameel Al-Tamimi Adnan N. , Abed Azher M. , Abdullah Oday Ibraheem , Mechakra Hamza , Boukhari Ali
Published: February 2023

In this article, the model of a 5 kW small wind turbine blade is developed and improved. Emphasis has been placed on improving the blade’s efficiency and aerodynamics and selecting the most optimal material for the wind blade. The QBlade software was used to enhance the chord and twist. Also, a new finite element model was developed using the ANSYS software to analyze the structure and modal problems of the wind blade. The results presented the wind blade’s von Mises stresses and deformations using three different materials (Carbon/epoxy, E-Glass/epoxy, and braided composite). The modal analysis results presented the natural frequencies and mode shapes for each material. It was found, based on the results, that the maximum deflections of E-glass, braided composite and carbon fiber were 46.46 mm, 33.54 mm, and 18.29 mm, respectively.
Is There a Formaldehyde Deficit in Emissions Inventories for Southeast Michigan?
Authors: Olaguer Eduardo P. , Hu Yongtao , Kilmer Susan , Adelman Zachariah E. , Vasilakos Petros , Odman M. Talat , Vaerten Marissa , McDonald Tracey , Gregory David , Lomerson Bryan , Russell Armistead G.
Published: February 2023

Formaldehyde is a key Volatile Organic Compound (VOC) and ozone precursor that plays a vital role in the urban atmospheric radical budget on par with water vapor, ozone, and nitrous acid. In addition to modulating radical and ozone production, ambient formaldehyde has both carcinogenic and non-carcinogenic inhalation health effects. This study concludes that ambient formaldehyde in the Southeast Michigan (SEMI) ozone nonattainment area may be underestimated up to a factor of two or more by regional air quality models. The addition of plausible amounts of primary formaldehyde to the U.S. National Emissions Inventory based on estimated formaldehyde-to-CO emission ratios partially alleviates this modeling deficit and indicates the presence of formaldehyde concentrations above 5 ppb at a previously unsuspected location northeast of Detroit. Standard 24-h formaldehyde samples obtained during the Michigan-Ontario Ozone Source Experiment (MOOSE) verified the presence of high ambient formaldehyde concentrations at this location. Moreover, the addition of plausible amounts of primary formaldehyde to VOC emissions inventories may add more than 1 ppb of ozone to ambient air in the SEMI nonattainment area, where ozone design values exceeded the U.S. National Ambient Air Quality Standard (NAAQS) by 1–2 ppb for the 2018–2020 design value period.
Spatial Analysis of SO2, PM10, CO, NO2, and O3 Pollutants: The Case of Konya Province, Turkey
Authors: Bugdayci Ilkay , Ugurlu Oguz , Kunt Fatma
Published: February 2023

Geographical information systems are frequently used in analyses of air quality based on location and time. They are also used in the creation of pollution distribution maps to determine the parameters related to air pollutants. In this study, a spatial analysis of SO2, PM10, CO, NO2 and O3 pollutants, which cause air pollution within the borders of the municipal urban areas of Konya province, was carried out for the years 2019–2020. In this context, air pollution maps were produced using the IDW interpolation method with data obtained from the National Air Quality Monitoring Network stations, which belong to the Ministry of Environment and Urbanization, in the Konya region. The results obtained were examined with maps and graphics based on the limit values found in the Air Quality Assessment and Management Regulation published by the Ministry of Environment and Urbanization. In this context, the periods of lockdown experienced during the COVID-19 pandemic were also evaluated in terms of air pollution. From the evaluation made on the values taken from the air quality stations, it can be observed that the air pollution did not violate the national limit value much in 2019 and 2020.
Particle Size Matters: Distribution, Source, and Seasonality Characteristics of Airborne and Pathogenic Bacteria in Wastewater Treatment Plants
Authors: Wan Jianan , Zhang Zhiruo , Huo Yang , Wang Xianze , Wang Yifan , Wu Jinghui , Huo Mingxin
Published: February 2023

Wastewater treatment plants (WWTPs) are a crucial source of bioaerosols, which account for both environmental and health hazards. Although various culture-based studies on bioaerosols have been reported, little knowledge remains about distribution and potential risks for more omnipresent non-culturable bacterial aerosols. Here, in summer, an eight-stage Andersen air sampler was applied to capture particles of various sizes from the atmospheric environment of eight treatment units from two WWTPs in northeastern China. Particles of various sizes in aeration tank (AT) were sampled in autumn and winter. The abundance and community composition of the bacterial aerosols were investigated using 16S rRNA gene sequencing. In order to explore the importance of particle size on community composition of bacterial aerosols, this study investigated the particle size distribution of bacterial aerosols in different treatment units. The results indicated that the sludge dewatering room was the major source of bacterial aerosols in both WWTPs, with the abundance of stage VII (0.65–1.1 μm) demonstrating a 4-fold to 9-fold increase when compared to any other treatment unit. The highest relative abundance of bacterial aerosols was in autumn, while the lowest was found in winter. However, most particles detected in autumn were larger than 4.7 µm in diameter, while submicron particles (less than 1.1 µm, over 40%) were detected primarily in winter. The most 15 dominant bacterial aerosol genera in were observed at submicron level, and about half of the genera (6 and 8) were detected as human pathogens, suggesting their easier penetration to human respiratory tracts. This study demonstrates that size distribution characteristics should be crucial information for the comprehensive assessment of the potential health risks of bacterial aerosols from WWTPs.
Deep Sequence Learning for Prediction of Daily NO2 Concentration in Coastal Cities of Northern China
Authors: Jia Xingbin , Gong Xiang , Liu Xiaohuan , Zhao Xianzhi , Meng He , Dong Quanyue , Liu Guangliang , Gao Huiwang
Published: February 2023

Nitrogen dioxide (NO2) is an important precursor of atmospheric aerosol. Forecasting urban NO2 concentration is vital for effective control of air pollution. This paper proposes a hybrid deep learning model for predicting daily average NO2 concentrations on the next day, based on atmospheric pollutants, meteorological data, and historical data during 2014 to 2020 in five coastal cities of Shandong peninsula, northern China. A random Forest (RF) algorithm was used to select input variables to reduce data dimensionality trained by the sequence to sequence (Seq2Seq) the model and describe how the Seq2Seq model understands each predictor variable. The hybrid model combining an RF with Seq2Seq network (RF-S2S) was evaluated and achieved a Pearson’s correlation coefficient of 0.93, a Nash–Sutcliffe coefficient (NS) of 0.79, a Root Mean Square Error (RMSE) of 5.85 µg/m3, a Mean Absolute Error (MAE) of 4.50 µg/m3, and a Mean Absolute Percentage Error (MAPE) of 20.86%. Feature selection by an RF model improves the performance of the Seq2Seq model, reducing errors by 19.7% (RMSE), 20.3% (MAE), and 29.3% (MAPE), respectively. Carbon monoxide (CO) and PM10 are two common, important features influencing the prediction of NO2 concentrations in coastal areas of northern China. The results of RF-S2S models can capture general trends and disruptions more accurately than can long-short term memory (LSTM) models with and without feature selection. The decreasing tendency of NO2 from 2014 to 2020 illustrated by the empirical mode decomposition (EMD) method is one important obstacle to improving the RF-S2S prediction accuracy. An EMD-based RF-S2S model could help to perform the short-term forecast of NO2 concentrations efficiently.
Characterization by Gene Expression Analysis of Two Groups of Dopaminergic Cells Isolated from the Mouse Olfactory Bulb
Authors: Casciano Fabio , Bianchi Nicoletta , Borin Mirta , Vellani Vittorio , Secchiero Paola , Bergamini Carlo M. , Capsoni Simona , Pignatelli Angela
Published: February 2023

The olfactory bulb (OB) is one of two regions of the mammalian brain which undergo continuous neuronal replacement during adulthood. A significant fraction of the cells added in adulthood to the bulbar circuitry is constituted by dopaminergic (DA) neurons. We took advantage of a peculiar property of dopaminergic neurons in transgenic mice expressing eGFP under the tyrosine hydroxylase (TH) promoter: while DA neurons located in the glomerular layer (GL) display full electrophysiological maturation, eGFP+ cells in the mitral layer (ML) show characteristics of immature cells. In addition, they also display a lower fluorescence intensity, possibly reflecting different degrees of maturation. To investigate whether this difference in maturation might be confirmed at the gene expression level, we used a fluorescence-activated cell sorting technique on enzymatically dissociated cells of the OB. The cells were divided into two groups based on their level of fluorescence, possibly corresponding to immature ML cells and fully mature DA neurons from the GL. Semiquantitative real-time PCR was performed to detect the level of expression of genes linked to the degree of maturation of DA neurons. We showed that indeed the cells expressing low eGFP fluorescence are immature neurons. Our method can be further used to explore the differences between these two groups of DA neurons.
The Role of Autophagy in the Female Reproduction System: For Beginners to Experts in This Field
Authors: Nakashima Akitoshi , Furuta Atsushi , Yamada Kiyotaka , Yoshida-Kawaguchi Mihoko , Yamaki-Ushijima Akemi , Yasuda Ippei , Ito Masami , Yamashita Satoshi , Tsuda Sayaka , Yoneda Satoshi , Cheng Shibin , Sharma Surendra , Shima Tomoko
Published: February 2023

Autophagy is a fundamental process involved in regulating cellular homeostasis. Autophagy has been classically discovered as a cellular process that degrades cytoplasmic components non-selectively to produce energy. Over the past few decades, this process has been shown to work in energy production, as well as in the reduction of excessive proteins, damaged organelles, and membrane trafficking. It contributes to many human diseases, such as neurodegenerative diseases, carcinogenesis, diabetes mellitus, development, longevity, and reproduction. In this review, we provide important information for interpreting results related to autophagic experiments and present the role of autophagy in this field.
Circulating Tumor Cell Detection by Liquid Biopsy during Early-Stage Endometrial Cancer Surgery: A Pilot Study
Authors: Francini Sarah , Duraes Martha , Rathat Gauthier , Macioce Valérie , Mollevi Caroline , Pages Laurence , Ferrer Catherine , Cayrefourcq Laure , Alix-Panabières Catherine
Published: February 2023

The recurrence of non-metastatic endometrial carcinoma (EC) (6 to 21%) might be due to disseminated tumor cells. This feasibility study investigated whether circulating tumor cells (CTCs) were detectable in blood samples from the peripheral and ovarian veins of 10 patients undergoing laparoscopic resection of stage I-II EC between July 2019 and September 2021. CTCs were detected using the CellSearch® system (i) preoperatively (T0) in peripheral blood, (ii) after ovary suspensory ligament pediculation in ovarian vein blood (T1), and (iii) before colpotomy in peripheral blood (T2). CTCs were detected only in ovarian vein samples in 8/10 patients. The CTC median number did not differ with patient age (37 (min-max: 0–91) in <70-year-old vs. 11 (0–65) in ≥70 year-old women, p = 0.59), tumor grade (15 (0–72) for grade 1 vs. 15 (0–91) for grade 2, p = 0.97), FIGO stage (72 (27–91) vs. 2 (0–65) vs. 3 (0–6]) for stage IA, B, and II, respectively; p = 0.08), and tumor size (40 (2–72) for size < 30 mm vs. 4 (0–91) for size ≥ 30 mm, p = 0.39). Estrogen receptor-positive CTCs and CTC clusters were identified. The prognostic and therapeutic values of CTCs released during EC surgery need to be determined.
GABAB Receptor Activation Affects Eye Growth in Chickens with Visually Induced Refractive Errors
Authors: Liu Hong , Schaeffel Frank , Yang Zhikuan , Feldkaemper Marita Pauline
Published: February 2023

This study aims to explore the role of GABAB receptors in the development of deprivation myopia (DM), lens-induced myopia (LIM) and lens-induced hyperopia (LIH). Chicks were intravitreally injected with 25 µg baclofen (GABABR agonist) in one eye and saline into the fellow eye. Choroidal thickness (ChT) was measured via OCT before and 2, 4, 6, 8, 24 h after injection. ChT decreased strongly at 6 and 8 h after baclofen injection and returned back to baseline level after 24 h. Moreover, chicks were monocularly treated with translucent diffusers, −7D or +7D lenses and randomly assigned to baclofen or saline treatment. DM chicks were injected daily into both eyes, while LIM and LIH chicks were monocularly injected into the lens-wearing eyes, for 4 days. Refractive error, axial length and ChT were measured before and after treatment. Dopamine and its metabolites were analyzed via HPLC. Baclofen significantly reduced the myopic shift and eye growth in DM and LIM eyes. However, it did not change ChT compared to respective saline-injected eyes. On the other hand, baclofen inhibited the hyperopic shift and choroidal thickening in LIH eyes. All the baclofen-injected eyes showed significantly lower vitreal DOPAC content. Since GABA is an inhibitory ubiquitous neurotransmitter, interfering with its signaling affects spatial retinal processing and therefore refractive error development with both diffusers and lenses.
Comparative Analysis of G-Layers in Bast Fiber and Xylem Cell Walls in Flax Using Raman Spectroscopy
Authors: Blervacq Anne-Sophie , Moreau Myriam , Duputié Anne , Hawkins Simon
Published: February 2023

In a response to gravitropic stress, G-layers (gelatinous layers) were deposited in xylem cell walls of tilted flax plants. G-layers were produced in both tension wood (upper side) as expected but were also observed in opposite wood (lower side). Raman spectral profiles were acquired for xylem G-layers from the tension and opposite side as well as from the G-layer of bast fibers grown under non-tilted conditions. Statistical analysis by principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA) clearly distinguished bast fiber G-layers from xylem G-layers. Discriminating bands were observed for cellulose (380–1150–1376 cm–1), hemicelluloses (517–1094–1126–1452 cm–1) and aromatics (1270–1599–1658 cm–1). PCA did not allow separation of G-layers from tension/opposite-wood sides. In contrast, the two types of xylem G-layers could be incompletely discriminated through PLS-DA. Overall, the results suggested that while the architecture (polymer spatial distribution) of bast fibers G-layers and xylem G-layers are similar, they should be considered as belonging to a different cell wall layer category based upon ontogenetical and chemical composition parameters.
Tyrosine Kinase Inhibitors Target B Lymphocytes
Authors: Upfold Nikki Lyn Esnardo , Petakh Pavlo , Kamyshnyi Aleksandr , Oksenych Valentyn
Published: February 2023

Autoimmune disorders and some types of blood cancer originate when B lymphocytes malfunction. In particular, when B cells produce antibodies recognizing the body’s proteins, it leads to various autoimmune disorders. Additionally, when B cells of various developmental stages transform into cancer cells, it results in blood cancers, including multiple myeloma, lymphoma, and leukemia. Thus, new methods of targeting B cells are required for various patient groups. Here, we used protein kinase inhibitors alectinib, brigatinib, ceritinib, crizotinib, entrectinib, and lorlatinib previously approved as drugs treating anaplastic lymphoma kinase (ALK)-positive lung cancer cells. We hypothesized that the same inhibitors will efficiently target leukocyte tyrosine kinase (LTK)-positive, actively protein-secreting mature B lymphocytes, including plasma cells. We isolated CD19-positive human B cells from the blood of healthy donors and used two alternative methods to stimulate cell maturation toward plasma cells. Using cell proliferation and flow cytometry assays, we found that ceritinib and entrectinib eliminate plasma cells from B cell populations. Alectinib, brigatinib, and crizotinib also inhibited B cell proliferation, while lorlatinib had no or limited effect on B cells. More generally, we concluded that several drugs previously developed to treat ALK-positive malignant cells can be also used to treat LTK-positive B cells.
Genome-Wide Analysis of microRNA Expression Profile in Roots and Leaves of Three Wheat Cultivars under Water and Drought Conditions
Authors: Gómez-Martín Cristina , Zhou Hui , Medina José María , Aparicio-Puerta Ernesto , Shi Bujun , Hackenberg Michael
Published: February 2023

Wheat is one of the most important food sources on Earth. MicroRNAs (miRNAs) play important roles in wheat productivity. To identify wheat miRNAs as well as their expression profiles under drought condition, we constructed and sequenced small RNA (sRNA) libraries from the leaves and roots of three wheat cultivars (Kukri, RAC875 and Excalibur) under water and drought conditions. A total of 636 known miRNAs and 294 novel miRNAs were identified, of which 34 miRNAs were tissue- or cultivar-specific. Among these, 314 were significantly regulated under drought conditions. miRNAs that were drought-regulated in all cultivars displayed notably higher expression than those that responded in a cultivar-specific manner. Cultivar-specific drought response miRNAs were mainly detected in roots and showed significantly different drought regulations between cultivars. By using wheat degradome library, 6619 target genes were identified. Many target genes were strongly enriched for protein domains, such as MEKHLA, that play roles in drought response. Targeting analysis showed that drought-downregulated miRNAs targeted more genes than drought-upregulated miRNAs. Furthermore, such genes had more important functions. Additionally, the genes targeted by drought-downregulated miRNAs had multiple interactions with each other, while the genes targeted by drought-upregulated miRNAs had no interactions. Our data provide valuable information on wheat miRNA expression profiles and potential functions in different tissues, cultivars and drought conditions.
Evidence for Natural Products as Alternative Wound-Healing Therapies
Authors: Moses Rachael L. , Prescott Thomas A. K. , Mas-Claret Eduard , Steadman Robert , Moseley Ryan , Sloan Alastair J.
Published: February 2023

Chronic, non-healing wounds represent a significant area of unmet medical need and are a growing problem for healthcare systems around the world. They affect the quality of life for patients and are an economic burden, being difficult and time consuming to treat. They are an escalating problem across the developed world due to the increasing incidence of diabetes and the higher prevalence of ageing populations. Effective treatment options are currently lacking, and in some cases chronic wounds can persist for years. Some traditional medicines are believed to contain bioactive small molecules that induce the healing of chronic wounds by reducing excessive inflammation, thereby allowing re-epithelisation to occur. Furthermore, many small molecules found in plants are known to have antibacterial properties and, although they lack the therapeutic selectivity of antibiotics, they are certainly capable of acting as topical antiseptics when applied to infected wounds. As these molecules act through mechanisms of action distinct from those of clinically used antibiotics, they are often active against antibiotic resistant bacteria. Although there are numerous studies highlighting the effects of naturally occurring small molecules in wound-healing assays in vitro, only evidence from well conducted clinical trials can allow these molecules or the remedies that contain them to progress to the clinic. With this in mind, we review wound-healing natural remedies that have entered clinical trials over a twenty-year period to the present. We examine the bioactive small molecules likely to be in involved and, where possible, their mechanisms of action.
Residues of Legume AG41 Peptide Crucial to Its Bio-Insecticidal Activity
Authors: Diya Fatima , Jouvensal Laurence , Rahioui Isabelle , Loth Karine , Sivignon Catherine , Karaki Lamis , Kfoury Linda , Rizk Francine , Da Silva Pedro
Published: February 2023

Currently, crop protection relies heavily on chemical treatments, which ultimately leads to environmental contamination and pest resistance. Societal and public policy considerations urge the need for new eco-friendly solutions. In this perspective, biopesticides are effective alternatives to chemical insecticides for the control of various insect pests. Legumes contain numerous insecticidal proteins aimed at protecting their high nitrogen content from animal/insect predation. Investigating one such protein family at genome scale, we discovered a unique diversity of the albumin 1 family in the (model) barrel medic genome. Only some members retained very high insecticidal activity. We uncovered that AG41 peptide from the alfalfa roots displays an outstanding insecticidal activity against several pests such as aphids and weevils. Here we report the 3D structure and activity of AG41 peptide. Significant insights into the structural/functional relationships explained AG41 high insecticidal activity. Such observations pave the way for the development of bio-insecticides, with AG41 peptide as the lead compound.
Vagus Nerve Visualization Using Fused Images of 3D-CT Angiography and MRI as Preoperative Evaluation for Vagus Nerve Stimulation
Authors: Nakae Shunsuke , Kumon Masanobu , Katagata Akio , Murayama Kazuhiro , Hirose Yuichi
Published: February 2023

Vagus nerve stimulation (VNS) is an effective surgical option for intractable epilepsy. Although the surgical procedure is not so complicated, vagus nerve detection is sometimes difficult due to its anatomical variations, which may lead to surgical manipulation-associated complications. Thus, this study aimed to visualize the vagus nerve location preoperatively by fused images of three-dimensional computed tomography angiography (3D-CTA) and magnetic resonance imaging (MRI). This technique was applied to two cases. The neck 3D-CTA and MRI were performed, and the fused images were generated using the software. The vagus nerve and its anatomical relationship with the internal jugular vein (IJV) and common carotid artery were clearly visualized. The authors predicted that the vagus nerve was detected by laterally pulling the IJV according to the images. Intraoperatively, the vagus nerve was located as the authors predicted. The time of the surgery until the vagus nerve detection was <60 min in both cases. This novel radiological technique for visualizing the vagus nerve is effective to quickly detect the vagus nerve, which has anatomical variations, during the VNS.
Early Identification and Intervention in Pediatric Obsessive-Compulsive Disorder
Authors: Liu Xingyu , Fan Qing
Published: February 2023

Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by persistent thoughts with subsequent repetitive behaviors. Interventions that are effective for adult OCD cannot simply be generalized to pediatric OCD, since OCD in children and adolescents usually has a different clinical presentation, etiology and course from adult OCD. Delayed and inadequate treatment is associated with a worse prognosis, making the need for early identification and intervention in pediatric OCD very urgent. In this paper, we reflected on the current constraints that make early interventions for pediatric OCD unpromoted and reviewed the approaches with potential application for early identification and early intervention in pediatric OCD, categorized by three-level prevention stages corresponding to a clinical staging model. Since the etiology of pediatric OCD is still unclear, primary prevention is most lacking, and early interventions for pediatric OCD are currently focused on the secondary prevention stage, which aims to prevent the conversion of obsessive-compulsive symptoms into full-blown OCD; tertiary prevention mostly focuses on the alleviation of mild to moderate OCD, while interventions for co-morbidities are still in their infancy. We closed by considering the important research questions on this topic.
Differential Treatment Responses in Pakistani Schizophrenia Samples: Correlation with Sociodemographic Parameters, Drug Addiction, Attitude to the Treatment and Antipsychotic Agents
Authors: Habiba Umme , Malik Aafia , Raja Ghazala Kaukab , Memon Muhammad Raza , Nizami Asad Tameezud din , Ishaq Rafaqat , Ilyas Muhammad , Valadi Hadi , Nawaz Muhammad , Shaiq Pakeeza Arzoo
Published: February 2023

Schizophrenia patients demonstrate variations in response to different therapies that are currently being used for the treatment of disorders, such as augmentation therapy (ECT or mood stabilizer) and combination therapy (with antipsychotics). These therapies are also used to treat schizophrenia patients in Pakistan; however, patients show poor overall response. Therefore, this study was conducted to investigate the association between the patients’ response to treatment and the use of antipsychotic agents, with variability in overall response, within different groups of patients. Methods: We conducted a retrospective study that included schizophrenia subjects (N = 200) belonging to different age groups, ethnicities, and regions from different outpatient and inpatient departments in psychiatric institutes located in different cities of Pakistan. These patients were assessed for their response to treatment therapies and categorized into four groups (non-responders (N-R), slow response (S-R), patients with relapse, and completely recovered patients (C-R)) according to their responses. Results: The final analysis included 200 subjects, of which 73.5% were males. Mean age was 34 ± 10 years. Percentage of N-R was 5%, S-R was 42%, patients with relapse were 24%, and C-R was 1.5%. The generalized linear regression model shows a significant association between medication response and age (p = 0.0231), age of onset (p = 0.0086), gender (p = 0.005), and marital status (p = 0.00169). Variability within the medication responses was a result of the treatment regime followed. Antipsychotic agents were significantly associated with the treatment response (p = 0.00258, F = 4.981) of the patients. Significant variation was also observed in the treatment response (p = 0.00128) of the patients that were given augmentation therapy as well as combination therapy. Conclusion: The data suggests proper monitoring of patients’ behavior in response to treatment therapies to implement tailored interventions. Despite several genetic studies supporting the heritability of schizophrenia, an insignificant association between characteristic features and family history might have been due to the limited sample size, suggesting collaborative work with massive sample sizes.
Lexico-Semantic Influence on Syntactic Processing: An Eye-Tracking Study with Spanish Relative Clauses
Authors: Álvarez-García Esther , Igoa González José Manuel
Published: February 2023

This paper investigates the interaction between lexicosemantic and syntactic information in sentence processing by examining the online comprehension of Spanish relative clauses (RCs) of both restrictive and non-restrictive types. A corpus study shows that, in Spanish, a RC may be introduced by different function words (called relativizers), which differ in lexical frequency, as well as semantic features. Based on these facts, an eye-tracking experiment was conducted with the aim of analyzing whether lexicosemantic information could influence sentence processing at the early stages. The results report an early influence of lexicosemantic information not only when activating a relativizer but also when integrating it within the syntactic structure. Additionally, the semantic role played by each RC type seems to constrain sentence processing at different regions. Our results favor an interactive view of language processing, according to which language comprehension is guided from the early stages by different kinds of linguistic information rather than syntactic information alone.
Effect of a Microalgae Facade on Design Behaviors: A Pilot Study with Architecture Students
Authors: Warren Kathryn , Milovanovic Julie , Kim Kyoung Hee
Published: February 2023

The influence of nature on occupant well-being and performance has been proved in office, hospital, and educational settings. There is evidence that plants and green colors affect creative and psychological responses. The microalgae facade in the study integrated spirulina, blue-green microalgae, which were cultivated using natural daylight and room air. While a good body of research explores nature’s impact on people, research on microalgae systems has not been linked to creative performance. This pilot study, therefore, focused on how the microalgae facade influences occupant mood and creativity. Forty architecture students were randomly assigned to the control and experimental rooms. The control group was surveyed in a room with a traditional window, whereas the experimental group was surveyed in a room with a biochromic window. Research design for the two conditions remained the same under IEQ-controlled environments except for the inclusion of the microalgae facade. Forty architecture students completed two creativity tasks—alternative use test (AUT) and remote association test (RAT)—and brainstorming for sustainable design in control and experimental settings. Our preliminary findings indicate that the microalgae facade did not affect divergent ideas and convergent thinking during tasks, but participants in the microalgae façade developed more design solutions that included greenery than students in the control space. This research is a preliminary investigation into the human impact of a microalgae façade and represents a new focus for scientific research. More work is needed to better grasp to what extent implementing a microalgae façade will impact human behavior in space.
Stochastic Dynamic Response and Long-Term Settlement Performance of Superstructure–Underground Tunnel–Soil Systems Subjected to Subway-Traffic Excitation
Authors: Wang Lin , Yang Shifei , Hu Hongqiang
Published: February 2023

The vibration impact force from the long-term operation of a subway affects the comfort of the residents living above the superstructure and the long-term settlement deformation of the tunnel foundation. A method for evaluating the dynamic responses of superstructure–tunnel systems is important, especially because of the randomness of vibration impact force. The coupling effect of the randomness of train-vibration excitation and the nonlinearity of the geotechnical properties that are subjected to dynamic action leads to challenges in the evaluation of the performance of superstructure–underground tunnel–soil systems under train vibration. In this study, a stochastic dynamic model of subway vibration-load excitation was established; then, the time histories of samples with rich probability characteristics in the same set system were generated. According to the nonlinear dynamic finite element analysis, several nonlinear dynamic responses of the deterministic superstructure–tunnel soil-foundation system were obtained. Finally, the probabilistic performance evolution of the superstructure–tunnel soil-foundation system was obtained by integrating the first-passage and probability density evolution theories, and the long-term deformation performance of the tunnel foundation was evaluated using time-varying reliability. This study presents a novel probabilistic method and a more objective performance index for the dynamic performance assessment of superstructure–underground tunnel–soil systems that are subjected to subway-traffic excitation.
Quality Indicators Compliance and Survival Outcomes in Breast Cancer according to Age in a Certified Center
Authors: Osório Fernando , Barros António S. , Peleteiro Bárbara , Amendoeira Isabel , Fougo José Luís
Published: February 2023

Age as a breast cancer (BC) prognostic factor remains debatable. Several studies have investigated clinicopathological features at different ages, but few make an age group direct comparison. The European Society of Breast Cancer Specialists quality indicators (EUSOMA-QIs) allow a standardized quality assurance of BC diagnosis, treatment, and follow-up. Our objective was to compare clinicopathological features, compliance to EUSOMA-QIs and BC outcomes in three age groups (≤45 years, 46–69 years, and ≥70 years). Data from 1580 patients with staged 0–IV BC from 2015 to 2019 were analyzed. The minimum standard and desirable target on 19 mandatory and 7 recommended QIs were studied. The 5-year relapse rate, overall survival (OS), and BC-specific survival (BCSS) were also evaluated. No meaningful differences in TNM staging and molecular subtyping classification between age groups were found. On the contrary, disparities in QIs compliance were observed: 73.1% in ≤45 years and 46–69 years women vs. 54% in older patients. No differences in loco-regional or distant progression were observed between age groups. Nevertheless, lower OS was found in older patients due to concurrent non-oncological causes. After survival curves adjustment, we underscored evidence of undertreatment impacting BCSS in ≥70 years women. Despite a unique exception—more invasive G3 tumors in younger patients—no age-specific differences in BC biology impacting outcome were found. Although increased noncompliance in older women, no outcome correlation was observed with QIs noncompliance in any age group. Clinicopathological features and differences in multimodal treatment (not the chronological age) are predictors of lower BCSS.
High Expression of IRS-1, RUNX3 and SMAD4 Are Positive Prognostic Factors in Stage I–III Colon Cancer
Authors: Selven Hallgeir , Busund Lill-Tove Rasmussen , Andersen Sigve , Pedersen Mona Irene , Lombardi Ana Paola Giometti , Kilvaer Thomas Karsten
Published: February 2023

Colon cancer is a common malignancy and a major contributor to human morbidity and mortality. In this study, we explore the expression and prognostic impact of IRS-1, IRS-2, RUNx3, and SMAD4 in colon cancer. Furthermore, we elucidate their correlations with miRs 126, 17-5p, and 20a-5p, which are identified as potential regulators of these proteins. Tumor tissue from 452 patients operated for stage I–III colon cancer was retrospectively collected and assembled into tissue microarrays. Biomarkers’ expressions were examined by immunohistochemistry and analyzed using digital pathology. In univariate analyses, high expression levels of IRS1 in stromal cytoplasm, RUNX3 in tumor (nucleus and cytoplasm) and stroma (nucleus and cytoplasm), and SMAD4 in tumor (nucleus and cytoplasm) and stromal cytoplasm were related to increased disease-specific survival (DSS). In multivariate analyses, high expression of IRS1 in stromal cytoplasm, RUNX3 in tumor nucleus and stromal cytoplasm, and high expression of SMAD4 in tumor and stromal cytoplasm remained independent predictors of improved DSS. Surprisingly, with the exception of weak correlations (0.2 < r < 0.25) between miR-126 and SMAD4, the investigated markers were mostly uncorrelated with the miRs. However, weak to moderate/strong correlations (0.3 < r < 0.6) were observed between CD3 and CD8 positive lymphocyte density and stromal RUNX3 expression. High expression levels of IRS1, RUNX3, and SMAD4 are positive prognostic factors in stage I–III colon cancer. Furthermore, stromal expression of RUNX3 is associated with increased lymphocyte density, suggesting that RUNX3 is an important mediator during recruitment and activation of immune cells in colon cancer.
Extrahepatic Distal Cholangiocarcinoma vs. Pancreatic Ductal Adenocarcinoma: Histology and Molecular Profiling for Differential Diagnosis and Treatment
Authors: Gkountakos Anastasios , Martelli Filippo M. , Silvestris Nicola , Bevere Michele , De Bellis Mario , Alaimo Laura , Sapuppo Elena , Masetto Francesca , Mombello Aldo , Simbolo Michele , Bariani Elena , Milella Michele , Fassan Matteo , Scarpa Aldo , Luchini Claudio
Published: February 2023

Pancreatic ductal adenocarcinoma (PDAC) and distal cholangiocarcinoma (dCCA) are very aggressive tumors with a high mortality rate. Pancreas and distal bile ducts share a common embryonic development. Hence, PDAC and dCCA exhibit similar histological features that make a differential diagnosis during routine diagnostic practice challenging. However, there are also significant differences, with potential clinical implications. Even if PDAC and dCCA are generally associated with poor survival, patients with dCCA seem to present a better prognosis. Moreover, although precision oncology-based approaches are still limited in both entities, their most important targets are different and include alterations affecting BRCA1/2 and related genes in PDAC, as well as HER2 amplification in dCCA. Along this line, microsatellite instability represents a potential contact point in terms of tailored treatments, but its prevalence is very low in both tumor types. This review aims at defining the most important similarities and differences in terms of clinicopathological and molecular features between these two entities, also discussing the main theranostic implications derived from this challenging differential diagnosis.
Impact of Novel Treatments in Patients with Melanoma Brain Metastasis: Real-World Data
Authors: Derks Sophie H. A. E. , Jongen Joost L. M. , van der Meer Edgar L. , Ho Li Shen , Slagter Cleo , Joosse Arjen , de Jonge Maja J. A. , Schouten Joost W. , Oomen-de Hoop Esther , van den Bent Martin J. , van der Veldt Astrid A. M.
Published: February 2023

Background: Melanoma brain metastasis (MBM) is associated with poor outcome, but targeted therapies (TTs) and immune checkpoint inhibitors (ICIs) have revolutionized treatment over the past decade. We assessed the impact of these treatments in a real-world setting. Methods: A single-center cohort study was performed at a large, tertiary referral center for melanoma (Erasmus MC, Rotterdam, the Netherlands). Overall survival (OS) was assessed before and after 2015, after which TTs and ICIs were increasingly prescribed. Results: There were 430 patients with MBM included; 152 pre-2015 and 278 post-2015. Median OS improved from 4.4 to 6.9 months (HR 0.67, p < 0.001) after 2015. TTs and ICIs prior to MBM diagnosis were associated with poorer median OS as compared to no prior systemic treatment (TTs: 2.0 vs. 10.9 and ICIs: 4.2 vs. 7.9 months, p < 0.001). ICIs directly after MBM diagnosis were associated with improved median OS as compared to no direct ICIs (21.5 vs. 4.2 months, p < 0.001). Stereotactic radiotherapy (SRT; HR 0.49, p = 0.013) and ICIs (HR 0.32, p < 0.001) were independently associated with improved OS. Conclusion: After 2015, OS significantly improved for patients with MBM, especially with SRT and ICIs. Demonstrating a large survival benefit, ICIs should be considered first after MBM diagnosis, if clinically feasible.
The Influence of Ethnicity on Survival from Malignant Primary Brain Tumours in England: A Population-Based Cohort Study
Authors: Wanis Hiba A. , Møller Henrik , Ashkan Keyoumars , Davies Elizabeth A.
Published: February 2023

Background: In recent years, the completeness of ethnicity data in the English cancer registration data has greatly improved. Using these data, this study aims to estimate the influence of ethnicity on survival from primary malignant brain tumours. Methods: Demographic and clinical data on adult patients diagnosed with malignant primary brain tumour from 2012 to 2017 were obtained (n = 24,319). Univariate and multivariate Cox proportional hazards regression analyses were used to estimate hazard ratios (HR) for the survival of the ethnic groups up to one year following diagnosis. Logistic regressions were then used to estimate odds ratios (OR) for different ethnic groups of (1) being diagnosed with pathologically confirmed glioblastoma, (2) being diagnosed through a hospital stay that included an emergency admission, and (3) receiving optimal treatment. Results: After an adjustment for known prognostic factors and factors potentially affecting access to healthcare, patients with an Indian background (HR 0.84, 95% CI 0.72–0.98), Any Other White (HR 0.83, 95% CI 0.76–0.91), Other Ethnic Group (HR 0.70, 95% CI 0.62–0.79), and Unknown/Not Stated Ethnicity (HR 0.81, 95% CI 0.75–0.88) had better one-year survivals than the White British Group. Individuals with Unknown ethnicity are less likely be diagnosed with glioblastoma (OR 0.70, 95% CI 0.58–0.84) and less likely to be diagnosed through a hospital stay that included an emergency admission (OR 0.61, 95% CI 0.53–0.69). Conclusion: The demonstrated ethnic variations associated with better brain tumour survival suggests the need to identify risk or protective factors that may underlie these differences in patient outcomes.
Population-Based Analysis of National Comprehensive Cancer Network (NCCN) Guideline Adherence for Patients with Anal Squamous Cell Carcinoma in California
Authors: Kumar Priyanka , Del Rosario Michael , Chang Jenny , Ziogas Argyrios , Jafari Mehraneh D. , Bristow Robert E. , Tanjasiri Sora Park , Zell Jason A.
Published: February 2023

Purpose: We analyzed adherence to the National Comprehensive Cancer Network treatment guidelines for anal squamous cell carcinoma in California and the associated impacts on survival. Methods: This was a retrospective study of patients in the California Cancer Registry aged 18 to 79 years with recent diagnoses of anal squamous cell carcinoma. Predefined criteria were used to determine adherence. Adjusted odds ratios and 95% confidence intervals were estimated for those receiving adherent care. Disease-specific survival (DSS) and overall survival (OS) were examined with a Cox proportional hazards model. Results: 4740 patients were analyzed. Female sex was positively associated with adherent care. Medicaid status and low socioeconomic status were negatively associated with adherent care. Non-adherent care was associated with worse OS (Adjusted HR 1.87, 95% CI = 1.66, 2.12, p < 0.0001). DSS was worse in patients receiving non-adherent care (Adjusted HR 1.96, 95% CI = 1.56, 2.46, p < 0.0001). Female sex was associated with improved DSS and OS. Black race, Medicare/Medicaid, and low socioeconomic status were associated with worse OS. Conclusions: Male patients, those with Medicaid insurance, or those with low socioeconomic status are less likely to receive adherent care. Adherent care was associated with improved DSS and OS in anal carcinoma patients.
NSC243928 Treatment Induces Anti-Tumor Immune Response in Mouse Mammary Tumor Models
Authors: Selvanesan Benson Chellakkan , de Mingo Pulido Alvaro , Varghese Sheelu , Rohila Deepak , Hupalo Daniel , Gusev Yuriy , Contente Sara , Wilkerson Matthew D. , Dalgard Clifton L. , Upadhyay Geeta
Published: February 2023

NSC243928 induces cell death in triple-negative breast cancer cells in a LY6K-dependent manner. NSC243928 has been reported as an anti-cancer agent in the NCI small molecule library. The molecular mechanism of NSC243928 as an anti-cancer agent in the treatment of tumor growth in the syngeneic mouse model has not been established. With the success of immunotherapies, novel anti-cancer drugs that may elicit an anti-tumor immune response are of high interest in the development of novel drugs to treat solid cancer. Thus, we focused on studying whether NSC243928 may elicit an anti-tumor immune response in the in vivo mammary tumor models of 4T1 and E0771. We observed that NSC243928 induced immunogenic cell death in 4T1 and E0771 cells. Furthermore, NSC243928 mounted an anti-tumor immune response by increasing immune cells such as patrolling monocytes, NKT cells, B1 cells, and decreasing PMN MDSCs in vivo. Further studies are required to understand the exact mechanism of NSC243928 action in inducing an anti-tumor immune response in vivo, which can be used to determine a molecular signature associated with NSC243928 efficacy. NSC243928 may be a good target for future immuno-oncology drug development for breast cancer.
Predictive and Prognostic Value of Oncogene Mutations and Microsatellite Instability in Locally-Advanced Rectal Cancer Treated with Neoadjuvant Radiation-Based Therapy: A Systematic Review and Meta-Analysis
Authors: De Mattia Elena , Polesel Jerry , Mezzalira Silvia , Palazzari Elisa , Pollesel Sara , Toffoli Giuseppe , Cecchin Erika
Published: February 2023

Markers of pathological complete response (pCR) to preoperative radiation-based therapy in locally advanced rectal cancer (LARC) are strongly needed. This meta-analysis aimed at elucidating the predictive/prognostic role of tumor markers in LARC. We systematically reviewed the impact of RAS, TP53, BRAF, PIK3CA, and SMAD4 mutations and MSI status on response (pCR, downstaging) and prognosis (risk of recurrence, survival) in LARC according to PRISMA guidelines and the PICO model. PubMed, Cochrane Library, and Web of Science Core Collection were systematically searched to identify relevant studies published before October 2022. KRAS mutations were significantly associated with the risk of not achieving pCR after preoperative treatment (summary OR = 1.80, 95% CI: 1.23–2.64). This association was even more significant in patients not receiving cetuximab (summary OR = 2.17, 95% CI: 1.41–3.33) than in patients receiving cetuximab (summary OR = 0.89, 95% CI: 0.39–20.05). MSI status was not associated with pCR (summary OR = 0.80, 95% CI: 0.41–1.57). No effect of KRAS mutation or MSI status on downstaging was detected. Meta-analysis of survival outcomes was not possible due to the large heterogeneity among studies in endpoint assessment. The minimum number of eligible studies to assess the predictive/prognostic role of TP53, BRAF, PIK3CA, and SMAD4 mutations was not reached. KRAS mutation, but not MSI status, proved to be a detrimental marker for response to preoperative radiation-based therapy in LARC. Translating this finding into the clinic could improve the management of LARC patients. More data are needed to clarify the clinical impact of TP53, BRAF, PIK3CA, and SMAD4 mutations.
Circulating Tumor DNA: The Dawn of a New Era in the Optimization of Chemotherapeutic Strategies for Metastatic Colo-Rectal Cancer Focusing on RAS Mutation
Authors: Udagawa Shohei , Ooki Akira , Shinozaki Eiji , Fukuda Koshiro , Yamaguchi Kensei , Osumi Hiroki
Published: February 2023

Genotyping of tumor tissues to assess RAS and BRAF V600E mutations enables us to select optimal molecularly targeted therapies when considering treatment strategies for patients with metastatic colorectal cancer. Tissue-based genetic testing is limited by the difficulty of performing repeated tests, due to the invasive nature of tissue biopsy, and by tumor heterogeneity, which can limit the usefulness of the information it yields. Liquid biopsy, represented by circulating tumor DNA (ctDNA), has attracted attention as a novel method for detecting genetic alterations. Liquid biopsies are more convenient and much less invasive than tissue biopsies and are useful for obtaining comprehensive genomic information on primary and metastatic tumors. Assessing ctDNA can help track genomic evolution and the status of alterations in genes such as RAS, which are sometimes altered following chemotherapy. In this review, we discuss the potential clinical applications of ctDNA, summarize clinical trials focusing on RAS, and present the future prospects of ctDNA analysis that could change daily clinical practice.