bluuebunny/crossref_metadata_2025 huggingface dataset:
Analytical and Numerical Reliability Analysis of Certain Pratt Steel Truss
Authors: Kamiński Marcin , Błoński Rafał
Published: March 2022

The main aim of this paper was to propose a new reliability index for steel structure assessment and to check it using the example of a popular Pratt truss girder. Structural analysis was completed in the finite element method system Autodesk ROBOT, and probabilistic analysis was implemented in the computer algebra software MAPLE. The stochastic finite element method (SFEM) was contrasted here with the Monte Carlo simulation and the girder span was selected as the input structural uncertainty source. Both methods were based on the same structural polynomial response functions determined for extreme deformation, for extreme stresses and also for the structural joint exhibiting the largest effort. These polynomials were statistically optimized during the additional least squares method experiments. The first four basic probabilistic characteristics of the structural responses, the first-order reliability method (FORM) index, and as the new proposition for this index were computed and presented. This new index formula follows the relative probabilistic entropy model proposed by Bhattacharyya. The computer analysis results presented here show a very strong coincidence of both probabilistic numerical techniques and confirms the applicability of the new reliability index for the input coefficient of variation not larger than 0.15. These studies should be continued for other engineering systems’ reliability and, particularly, for large-scale and multiscale computer simulations. The results presented in this paper may serve in different applied sciences, from biology through to econometrics, experimental physics and, of course, various branches of engineering.
Robust Process Parameter Design Methodology: A New Estimation Approach by Using Feed-Forward Neural Network Structures and Machine Learning Algorithms
Authors: Le Tuan-Ho , Dai Li , Jang Hyeonae , Shin Sangmun
Published: March 2022

In robust design (RD) modeling, the response surface methodology (RSM) based on the least-squares method (LSM) is a useful statistical tool for estimating functional relationships between input factors and their associated output responses. Neural network (NN)-based models provide an alternative means of executing input-output functions without the assumptions necessary with LSM-based RSM. However, current NN-based estimation methods do not always provide suitable response functions. Thus, there is room for improvement in the realm of RD modeling. In this study, a new NN-based RD modeling procedure is proposed to obtain the process mean and standard deviation response functions. Second, RD modeling methods based on the feed-forward back-propagation neural network (FFNN), cascade-forward back-propagation neural network (CFNN), and radial basis function network (RBFN) are proposed. Third, two simulation studies are conducted using a given true function to verify the proposed three methods. Fourth, a case study is examined to illustrate the potential of the proposed approach. In conclusion, a comparative analysis of the three feed-forward NN structure-based modeling methods and conventional LSM-based RSM proposed in this study showed that the proposed methods were significantly lower in the expected quality loss (EQL) and various variability indicators.
A Brief Review of Machine Learning-Based Bioactive Compound Research
Authors: Park Jihye , Beck Bo Ram , Kim Hoo Hyun , Lee Sangbum , Kang Keunsoo
Published: March 2022

Bioactive compounds are often used as initial substances for many therapeutic agents. In recent years, both theoretical and practical innovations in hardware-assisted and fast-evolving machine learning (ML) have made it possible to identify desired bioactive compounds in chemical spaces, such as those in natural products (NPs). This review introduces how machine learning approaches can be used for the identification and evaluation of bioactive compounds. It also provides an overview of recent research trends in machine learning-based prediction and the evaluation of bioactive compounds by listing real-world examples along with various input data. In addition, several ML-based approaches to identify specific bioactive compounds for cardiovascular and metabolic diseases are described. Overall, these approaches are important for the discovery of novel bioactive compounds and provide new insights into the machine learning basis for various traditional applications of bioactive compound-related research.
Catalytic Degradation of Anionic Organic Dye on Greenly Synthesized CuO/ZnO Nanocomposites
Authors: Da’na Enshirah , Taha Amel , Hessien Manal
Published: March 2022

CuO/ZnO nanocomposites were greenly prepared and tested for the catalytic degradation of methyl orange. The XRD analysis confirmed the existence of CuO and ZnO with crystallite sizes within the range of 15–30 nm. TEM and SEM images showed different morphological properties. The TGA analysis revealed a good thermal stability of the nanocomposite, with a total loss of less than 18% at a temperature of 700 °C. The nanocomposites were tested for the catalytic degradation of methyl orange under mild conditions with a catalyst mass/wastewater volume of 10 g/3 L, an initial dye concentration of 40 ppm, a pH of 4.5, and a degradation time of 3 h. The best efficiency of 49.1% was achieved by CuO nanoparticles (C), followed by 47.6%, which was obtained by 1C1Z. The degradation efficiency of ZnO (Z) was 16.4%, and it was increased by increasing the CuO precursor in the synthesis mixture, while adding ZnO to the CuO, resulting in a decrease in its catalytic performance.
Air Pollutants over Industrial and Non-Industrial Areas: Historical Concentration Estimates
Authors: Michalik Jiri , Machaczka Ondrej , Jirik Vitezslav , Heryan Tomas , Janout Vladimir
Published: March 2022

Only a few researchers have addressed the issue of lifetime exposure related to air pollutant concentration. This study aims to develop a methodology to obtain the most reliable estimates of historical concentrations of air pollutants, which would be further applied to the long-term exposure evaluation. In particular, PM10, PM2.5, NO2, SO2, benzene, and B(a)P concentrations have been obtained. Data of monitored concentrations, model calculations, and subsequent implementation of several corrections based on previous work on temporal and spatial correlations of these substances in the air have been deployed. This work makes an original contribution to the field of meteorology and epidemiology because of this innovative technique to estimate the most reliable historical concentrations of air pollutants. The novelty of our work lies in the additional implications of this study because historical concentration data serve as input data for the construction of epidemiological associations. The approach is based primarily on the availability of monitoring results of air pollutants.
Ship-Borne Observations of Atmospheric CH4 and δ13C Isotope Signature in Methane over Arctic Seas in Summer and Autumn 2021
Authors: Pankratova Natalia , Skorokhod Andrey , Belikov Igor , Belousov Valery , Muravya Valeria , Flint Mikhail
Published: March 2022

Determining the sources of methane emissions in the Arctic remains a complex problem, due to their heterogeneity and diversity. Information on the amount of emissions has significant uncertainties and may differ by an order of magnitude in various literature sources. Measurements made in the immediate vicinity of emission sources help to clarify emissions and reduce these uncertainties. This paper analyzes the data of three expeditions, carried out in the western Arctic seas during Arctic spring, summer, and early autumn in 2021, which obtained continuous data on the concentration of methane and its isotope signature δ13C. CH4 concentrations and δ13C displayed temporal and spatial variations ranging from 1.952 to 2.694 ppm and from −54.7‰ to −40.9‰, respectively. A clear correlation was revealed between the surface methane concentration and the direction of air flow during the measurement period. At the same time, even with advection from areas with a significant anthropogenic burden or from locations of natural gas mining and transportation, we cannot identify particular source of emissions; there is a dilution or mixing of gas from different sources. Our results indicate footprints of methane sources from wetlands, freshwater sources, shelf sediments, and even hydrates.
Spatiotemporal Influences of LULC Changes on Land Surface Temperature in Rapid Urbanization Area by Using Landsat-TM and TIRS Images
Authors: Kaiser Eduardo Andre , Rolim Silvia Beatriz Alves , Grondona Atilio Efrain Bica , Hackmann Cristiano Lima , de Marsillac Linn Rodrigo , Käfer Pâmela Suélen , da Rocha Nájila Souza , Diaz Lucas Ribeiro
Published: March 2022

The inverse correlation between NDVI and LST is widely known for its long time series. However, when more specific statistical tests were performed, subtle differences in the correlation behavior over time are more clearly observed. In this work, regression analyses were performed between NDVI and LST at intervals of approximately 10 years, quantifying this relationship for an area of transition from vegetation to urban occupation from 1985 to 2018. The removal of vegetation cover (reduction of 51% to 7% in grassland and 14.4% to 0.6% in forest) to occupy impermeable surfaces ( increase of 31% to 91% in urban areas) caused an average LST increase of 4.18 °C when compared to the first and last decades of the historical series. Temporal analysis allowed us to verify the increase in temperature in the four seasons. The largest difference was 6.36 °C between the first and last decade of autumn, 4.40 °C in spring, 4.09 °C in summer, and 2.41 °C in winter. The results also show that LST has a negative correlation with NDVI, especially in urban areas, with an increase in this correlation during the period (1989: R = −0.55; 1999: R = −0.58; 2008: R = −0.59; 2018: R = −0.76). Our study results will help policymakers understand the dynamics of temperature increases by adding scientifically relevant information on the sustainable organization of the urban environment.
Optimal Consumption, Investment, and Housing Choice: A Dynamic Programming Approach
Authors: Li Qi , Ahn Seryoong
Published: March 2022

We investigate a portfolio selection problem involving an agent’s realistic housing service choice, where the agent not only has to choose the size of house to live in, but also has to select between renting and purchasing a house. Adopting a dynamic programming approach, we derive a closed-form solution to obtain the optimal policies for the consumption, investment, housing service, and purchasing time for a house. We also present various numerical demonstrations showing the impacts of parameters in the financial and housing markets and the agent’s preference, which visually show the economic implications of our model. Our model makes a significant contribution because it is a pioneering model for the optimal time to purchase a house, which has not been investigated in depth in existing mathematical portfolio optimization models.
The VIP/VPAC1R Pathway Regulates Energy and Glucose Homeostasis by Modulating GLP-1, Glucagon, Leptin and PYY Levels in Mice
Authors: Sanford Daniel , Luong Leon , Vu John P. , Oh Suwan , Gabalski Arielle , Lewis Michael , Pisegna Joseph R. , Germano Patrizia
Published: March 2022

Vasoactive Intestinal Peptide binds with high affinity to VPAC1R and VPAC2R, thus regulating key physiologic functions. Previously, we documented in VIP−/− mice a leaner body phenotype and altered metabolic hormones. Past reports described in VPAC2−/− mice impaired circadian rhythm, reduced food intake, and altered metabolism. To better define the effects of VPAC1R on body phenotype, energy/glucose homeostasis, and metabolism, we conducted a 12-week study in a VPAC1R null model. Our results reveal that VPAC1−/− mice experienced significant metabolic alterations during the dark cycle with greater numbers of feeding bouts (p = 0.009), lower Total Energy Expenditure (p = 0.025), VO2 (p = 0.029), and VCO2 (p = 0.016); as well as during the light cycle with lower Total Energy Expenditure (p = 0.04), VO2 (p = 0.044), and VCO2 (p = 0.029). Furthermore, VPAC1−/− mice had significantly higher levels of GLP-1 and PYY during fasting, and higher levels of GLP-1, glucagon leptin and PYY during postprandial conditions. In addition, VPAC1−/− mice had lower levels of glucose at 60′ and 120′, as assessed by insulin tolerance test. In conclusion, this study supports a key role for VPAC1R in the regulation of body glucose/energy homeostasis and metabolism.
Heterozygosity of the Complex Corfu δ0β+ Thalassemic Allele (HBD Deletion and HBB:c.92+5G>A) Revisited
Authors: Kattamis Christos , Skafida Myrto , Delaporta Polyxeni , Vrettou Christina , Traeger-Synodinos Joanne , Sofocleous Christalena , Kattamis Antonis
Published: March 2022

The Corfu δ0β+ thalassemic allele is a unique thalassemic allele consisting of the simultaneous presence in cis of a deletion of the δ-globin (Hemoglobin Subunit Delta, HBD) and a single nucleotide variant in the β-globin gene (Hemoglobin Subunit Beta, HBB). The allele has, so far, been described in individuals of Greek origin. The objectives of the study are to ascertain the prevalence of the Corfu δ0β+ allele in comparison to other β-thalassemia variants encountered in Greece using our in-house data repository of 2558 β-thalassemia heterozygotes, and to evaluate the hematological phenotype of Corfu δ0β+ heterozygotes in comparison to heterozygotes with the most common β+- and deletion α0- thalassemia variants in Greece. The results of the study showed a relative incidence of heterozygotes with Corfu δ0β+ at 1.56% of all β-thalassemic alleles, and a distinct hematological phenotype of the heterozygotes characterized by microcytic, hypochromic anemia with normal levels of HbA2 (Hemoglobin A2) and elevated HbF (Hemoglobin F) levels. The application of a specific methodology for the identification of the Corfu δ0β+ allele is important for precise prenatal and antenatal diagnosis programs in Greece.
Pathobiology of Second-Generation Antihistamines Related to Sleep in Urticaria Patients
Authors: Mann Caroline , Wegner Joanna , Weeß Hans-Günter , Staubach Petra
Published: March 2022

Background: Standard treatment options for urticaria are second-generation antihistamines; however, their effect on sleep is uncertain. This study measures the influence of different antihistamines on the biologic sleep pattern of urticaria patients and the relevance of sleep in urticaria patients. Methods: Ten patients with chronic spontaneous urticaria (CSU) and uncontrolled symptoms under a single dose of second-generation antihistamines were included. Two nights were monitored: the first night after 5 days on single dosage and the second night after 5 days on fourfold dosage. Patient-rated questionnaires were used and sleep was monitored using polygraphy. Results: The patients’ rated daytime sleepiness decreased (p = 0.0319), as did their insomnia severity (p = 0.0349). The urticaria control (UCT) improved (p = 0.0007), as did the quality of life (p < 0.0001). There was no significant change of nightly pruritus (p = 0.1173), but there was an improvement of daytime pruritus (p = 0.0120). A significant increase in rapid eye movement (REM) sleep was seen (p = 0.0002) (from a mean of 3.9% to 14.3%). The deep sleep state (N3) also improved (8.7% to 12.3%) (p = 0.1172). Conclusion: This study has demonstrated an improvement of the sleep pattern in CSU patients under up-dosed second-generation antihistamines, without increased daytime sleepiness, alongside an improvement of urticaria symptoms and quality of life.
Long-Term Outcomes of Dose-Escalated Hypofractionated Radiotherapy in Localized Prostate Cancer
Authors: Lazo Antonio , de la Torre-Luque Alejandro , Arregui Gregorio , Rivas Daniel , Serradilla Ana , Gómez Joaquin , Jurado Francisca , Núñez María Isabel , López Escarlata
Published: March 2022

This retrospective study aimed to provide some clinical outcomes regarding effectiveness, toxicity, and quality of life in PCa patients treated with dose-escalated moderately hypofractionated radiation therapy (HFRT). Patients received HFRT to a total dose of 66 Gy in 22 fractions (3 Gy/fraction) delivered via volume modulated arc therapy (VMAT) in 2011–2016. Treatment effectiveness was measured by the biochemical failure-free survival rate. Toxicity was assessed according to the criteria of the Radiation Therapy Oncology Group (RTOG) and quality of life according to the criteria of the European Organization for Research and Treatment of Cancer (EORTC). In this regard, quality of life (QoL) was measured longitudinally, at a median of 2 and 5 years after RT. Enrolled patients had low-risk (40.2%), intermediate-risk (47.5%), and high-risk (12.3%) PCa. Median follow-up was 75 months. The biochemical failure-free survival rate was 94.2%. The incidence of acute grade 2 or higher gastrointestinal (GI) and genitourinary (GU) toxicity was 9.84% and 28.69%, respectively. The incidence rate of late grade 2 or higher GI and GU toxicity was 1.64% and 4.10%, respectively. Expanded Prostate Cancer Index Composite (EPIC) scores showed that the majority of patients maintained their QoL. HFRT to 66 Gy with VMAT was associated with adequate biochemical control, low toxicity and good reported GU and GI quality of life.
Continuous Low-Intensity Ultrasound Preserves Chondrogenesis of Mesenchymal Stromal Cells in the Presence of Cytokines by Inhibiting NFκB Activation
Authors: Bhogoju Sarayu , Khan Shahid , Subramanian Anuradha
Published: March 2022

Proinflammatory joint environment, coupled with impeded chondrogenic differentiation of mesenchymal stromal cells (MSCs), led to inferior cartilage repair outcomes. Nuclear translocation of phosphorylated-NFκB downregulates SOX9 and hinders the chondrogenesis of MSCs. Strategies that minimize the deleterious effects of NFκB, while promoting MSC chondrogenesis, are of interest. This study establishes the ability of continuous low-intensity ultrasound (cLIUS) to preserve MSC chondrogenesis in a proinflammatory environment. MSCs were seeded in alginate:collagen hydrogels and cultured for 21 days in an ultrasound-assisted bioreactor (5.0 MHz, 2.5 Vpp; 4 applications/day) in the presence of IL1β and evaluated by qRT-PCR and immunofluorescence. The differential expression of markers associated with the NFκB pathway was assessed upon a single exposure of cLIUS and assayed by Western blotting, qRT-PCR, and immunofluorescence. Mitochondrial potential was evaluated by tetramethylrhodamine methyl ester (TMRM) assay. The chondroinductive potential of cLIUS was noted by the increased expression of SOX9 and COLII. cLIUS extended its chondroprotective effects by stabilizing the NFκB complex in the cytoplasm via engaging the IκBα feedback mechanism, thus preventing its nuclear translocation. cLIUS acted as a mitochondrial protective agent by restoring the mitochondrial potential and the mitochondrial mRNA expression in a proinflammatory environment. Altogether, our results demonstrated the potential of cLIUS for cartilage repair and regeneration under proinflammatory conditions.
A Review of In Vivo and Clinical Studies Applying Scaffolds and Cell Sheet Technology for Periodontal Ligament Regeneration
Authors: Bousnaki Maria , Beketova Anastasia , Kontonasaki Eleana
Published: March 2022

Different approaches to develop engineered scaffolds for periodontal tissues regeneration have been proposed. In this review, innovations in stem cell technology and scaffolds engineering focused primarily on Periodontal Ligament (PDL) regeneration are discussed and analyzed based on results from pre-clinical in vivo studies and clinical trials. Most of those developments include the use of polymeric materials with different patterning and surface nanotopography and printing of complex and sophisticated multiphasic composite scaffolds with different compartments to accomodate for the different periodontal tissues’ architecture. Despite the increased effort in producing these scaffolds and their undoubtable efficiency to guide and support tissue regeneration, appropriate source of cells is also needed to provide new tissue formation and various biological and mechanochemical cues from the Extraccellular Matrix (ECM) to provide biophysical stimuli for cell growth and differentiation. Cell sheet engineering is a novel promising technique that allows obtaining cells in a sheet format while preserving ECM components. The right combination of those factors has not been discovered yet and efforts are still needed to ameliorate regenerative outcomes towards the functional organisation of the developed tissues.
Calreticulin Regulates β1-Integrin mRNA Stability in PC-3 Prostate Cancer Cells
Authors: Lin Yueh-Chien , Huang Yuan-Li , Wang Ming-Hua , Chen Chih-Yu , Chen Wei-Min , Weng Yi-Cheng , Wu Pei-Yi
Published: March 2022

Prostate cancer (PCa) is the major cause of cancer-related death among aging men worldwide. Recent studies have suggested that calreticulin (CRT), a multifunctional chaperon protein, may play an important role in the regulation of PCa tumorigenesis and progression. However, the underlying mechanisms are still unclear. Integrin is an important regulator of cancer metastasis. Our previous study demonstrated that in J82 bladder cancer cells, CRT affects integrin activity through FUBP-1-FUT-1-dependent fucosylation, rather than directly affecting the expression of β1-integrin itself. However, whether this regulatory mechanism is conserved among different cell types remains to be determined. Herein, we attempted to determine the effects of CRT on β1-integrin in human prostate cancer PC-3 cells. CRT expression was suppressed in PC-3 cells through siRNA treatment, and then the expression levels of FUT-1 and β1-integrin were monitored through RT-PCR. We found that knockdown of CRT expression in PC-3 cells significantly affected the expression of β1-integrin itself. In addition, the lower expression level of β1-integrin was due to affecting the mRNA stability. In contrast, FUT-1 expression level was not affected by knockdown of CRT. These results strongly suggested that CRT regulates cellular behavior differently in different cell types. We further confirmed that CRT directly binds to the 3′UTR of β1-integrin mRNA by EMSA and therefore affects its stability. The suppression of CRT expression also affects PC-3 cell adhesion to type I collagen substrate. In addition, the levels of total and activated β1-integrin expressed on cell surface were both significantly suppressed by CRT knockdown. Furthermore, the intracellular distribution of β1-integrin was also affected by lowering the expression of CRT. This change in distribution is not lysosomal nor proteosomal pathway-dependent. The treatment of fucosydase significantly affected the activation of surface β1-integrin, which is conserved among different cell types. These results suggested that CRT affects the expression of β1-integrin through distinct regulatory mechanisms.
Shared Molecular Targets in Parkinson’s Disease and Arterial Hypertension: A Systematic Review
Authors: Tulbă Delia , Avasilichioaiei Mioara , Dima Natalia , Crăciun Laura , Bălănescu Paul , Buzea Adrian , Băicuș Cristian , Popescu Bogdan Ovidiu
Published: March 2022

(1) Background: Parkinson’s disease and arterial hypertension are likely to coexist in the elderly, with possible bidirectional interactions. We aimed to assess the role of antihypertensive agents in PD emergence and/or progression. (2) We performed a systematic search on the PubMed database. Studies enrolling patients with Parkinson’s disease who underwent treatment with drugs pertaining to one of the major antihypertensive drug classes (β-blockers, diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and calcium-channel blockers) prior to or after the diagnosis of parkinsonism were scrutinized. We divided the outcome into two categories: neuroprotective and disease-modifying effect. (3) We included 20 studies in the qualitative synthesis, out of which the majority were observational studies, with only one randomized controlled trial. There are conflicting results regarding the effect of antihypertensive drugs on Parkinson’s disease pathogenesis, mainly because of heterogeneous protocols and population. (4) Conclusions: There is low quality evidence that antihypertensive agents might be potential therapeutic targets in Parkinson’s disease, but this hypothesis needs further testing.
Inorganic Polymeric Materials for Injured Tissue Repair: Biocatalytic Formation and Exploitation
Authors: Schröder Heinz C. , Wang Xiaohong , Neufurth Meik , Wang Shunfeng , Tan Rongwei , Müller Werner E. G.
Published: March 2022

Two biocatalytically produced inorganic biomaterials show great potential for use in regenerative medicine but also other medical applications: bio-silica and bio-polyphosphate (bio-polyP or polyP). Biosilica is synthesized by a group of enzymes called silicateins, which mediate the formation of amorphous hydrated silica from monomeric precursors. The polymeric silicic acid formed by these enzymes, which have been cloned from various siliceous sponge species, then undergoes a maturation process to form a solid biosilica material. The second biomaterial, polyP, has the extraordinary property that it not only has morphogenetic activity similar to biosilica, i.e., can induce cell differentiation through specific gene expression, but also provides metabolic energy through enzymatic cleavage of its high-energy phosphoanhydride bonds. This reaction is catalyzed by alkaline phosphatase, a ubiquitous enzyme that, in combination with adenylate kinase, forms adenosine triphosphate (ATP) from polyP. This article attempts to highlight the biomedical importance of the inorganic polymeric materials biosilica and polyP as well as the enzymes silicatein and alkaline phosphatase, which are involved in their metabolism or mediate their biological activity.
A Hybrid Spiral Microfluidic Platform Coupled with Surface Acoustic Waves for Circulating Tumor Cell Sorting and Separation: A Numerical Study
Authors: Altay Rana , Yapici Murat Kaya , Koşar Ali
Published: March 2022

The separation of circulating tumor cells (CTCs) from blood samples is crucial for the early diagnosis of cancer. During recent years, hybrid microfluidics platforms, consisting of both passive and active components, have been an emerging means for the label-free enrichment of circulating tumor cells due to their advantages such as multi-target cell processing with high efficiency and high sensitivity. In this study, spiral microchannels with different dimensions were coupled with surface acoustic waves (SAWs). Numerical simulations were conducted at different Reynolds numbers to analyze the performance of hybrid devices in the sorting and separation of CTCs from red blood cells (RBCs) and white blood cells (WBCs). Overall, in the first stage, the two-loop spiral microchannel structure allowed for the utilization of inertial forces for passive separation. In the second stage, SAWs were introduced to the device. Thus, five nodal pressure lines corresponding to the lateral position of the five outlets were generated. According to their physical properties, the cells were trapped and lined up on the corresponding nodal lines. The results showed that three different cell types (CTCs, RBCs, and WBCs) were successfully focused and collected from the different outlets of the microchannels by implementing the proposed multi-stage hybrid system.
Assessing Distinct Cognitive Workload Levels Associated with Unambiguous and Ambiguous Pronoun Resolutions in Human–Machine Interactions
Authors: Zhao Mengyuan , Ji Zhangyifan , Zhang Jing , Zhu Yiwen , Ye Chunhua , Wang Guangying , Yin Zhong
Published: March 2022

Pronoun resolution plays an important role in language comprehension. However, little is known about its recruited cognitive mechanisms. Our investigation aims to explore the cognitive mechanisms underlying various types of pronoun resolution in Chinese using an electroencephalograph (EEG). We used three convolutional neural networks (CNNs)—LeNeT-5, GoogleNet, and EffifcientNet—to discover high-level feature abstractions of the EEG spatial topologies. The output of the three models was then fused using different scales by principal component analysis (PCA) to achieve cognitive workload classification. Overall, the workload classification rate by fusing three deep networks can be achieved at 55–63% in a participant-specific manner. We provide evidence that both the behavioral indicator of reaction time and the neural indicator of cognitive workload collected during pronoun resolution vary depending on the type of the pronoun. We observed an increase in reaction time accompanied by a decrease of the theta power while participants were processing ambiguous pronoun resolution compared to unambiguous controls. We propose that ambiguous pronoun resolution involves a more time-consuming yet more flexible cognitive mechanism, consistent with the predictions of the decision-making framework from an influential pragmatic tradition. Our results extend previous research that the cognitive states of resolving ambiguous and unambiguous pronouns are differentiated, indicating that cognitive workload evaluated using the method of machine learning for analysis of EEG signals acts as a complementary indicator for studying pronoun resolution and serves as an important inspiration for human–machine interaction.
Short-Term Intake of Chlorogenic Acids Improves Psychomotor Speed and Motor Speed in Adults: A Randomized Crossover Trial
Authors: Suzukamo Chika , Ochiai Ryuji , Mitsui Yuki , Osaki Noriko , Ono Takahiro
Published: March 2022

Chlorogenic acid (CGA), a polyphenolic compound found in various plants, has been reported to improve cognitive function. However, it remains unclear how long it takes for CGAs to exert their effects. Here, we evaluated the short-term effects of CGAs on cognitive function. We assessed the effects of 2-week CGA intake on cognitive function. The study was carried out as a randomized, double-blind, placebo-controlled, crossover trial. Twenty-six healthy Japanese participants (50–65 years of age) were randomly assigned to either the active beverage (CGAs: 270 mg) or the placebo beverage group daily for 2 weeks. After a 2-week washout period, the participants consumed the other beverages. We assessed cognitive function at baseline and following the first treatment period using the Japanese version of CNS Vital Signs. CGAs significantly improved the scores for psychomotor speed, motor speed, and right and left finger tapping compared to placebo. In addition, processing speed scores improved significantly from baseline only after CGA intake. In conclusion, CGAs were confirmed to improve cognitive function over a short period of two weeks.
Math Fluency during Primary School
Authors: Gliksman Yarden , Berebbi Shir , Henik Avishai
Published: March 2022

Math fluency is the ability to solve arithmetic facts quickly and accurately (i.e., addition and subtraction problems up to 20, and multiplication and division problems from the multiplication table). Curricula in primary school devote a significant period of time for learning and retrieval of arithmetic facts. Recently, a new computerized tool to assess math fluency—the BGU-MF (Ben-Gurion University Math Fluency) test—was developed and found to be a reliable and valid tool for adults. In the current study, we examine the performance of first to sixth-grade children in math fluency using the BGU-MF. The results present the performance of MF during childhood and emphasize that it continues to develop during primary school. Importantly, proficiency of MF differed by operations, and the automaticity of math facts was acquired in different grades. Moreover, we found that the BGU-MF is a reliable and valid tool not only for adults but also for children during primary school. Our study has educational implications for the teaching, practice, and retrieval of arithmetic facts.
Does the Heart Fall Asleep?—Diurnal Variations in Heart Rate Variability in Patients with Disorders of Consciousness
Authors: Angerer Monika , Wilhelm Frank H. , Liedlgruber Michael , Pichler Gerald , Angerer Birgit , Scarpatetti Monika , Blume Christine , Schabus Manuel
Published: March 2022

The current study investigated heart rate (HR) and heart rate variability (HRV) across day and night in patients with disorders of consciousness (DOC). We recorded 24-h electrocardiography in 26 patients with DOC (i.e., unresponsive wakefulness syndrome (UWS; n = 16) and (exit) minimally conscious state ((E)MCS; n = 10)). To examine diurnal variations, HR and HRV indices in the time, frequency, and entropy domains were computed for periods of clear day- (forenoon: 8 a.m.–2 p.m.; afternoon: 2 p.m.–8 p.m.) and nighttime (11 p.m.–5 a.m.). The results indicate that patients’ interbeat intervals (IBIs) were larger during the night than during the day, indicating HR slowing. The patients in UWS showed larger IBIs compared to the patients in (E)MCS, and the patients with non-traumatic brain injury showed lower HRV entropy than the patients with traumatic brain injury. Additionally, higher HRV entropy was associated with higher EEG entropy during the night. Thus, cardiac activity varies with a diurnal pattern in patients with DOC and can differentiate between patients’ diagnoses and etiologies. Moreover, the interaction of heart and brain appears to follow a diurnal rhythm. Thus, HR and HRV seem to mirror the integrity of brain functioning and, consequently, might serve as supplementary measures for improving the validity of assessments in patients with DOC.
Patterns of Attention and Anxiety in Predicting Arithmetic Fluency among School-Aged Children
Authors: Orbach Lars , Fritz Annemarie
Published: March 2022

Although the interaction between anxiety and attention is considered crucial for learning and performance in mathematics, few studies have examined these cognitive and affective predictors in a single framework or explored the role of sustained attention in promoting children’s arithmetic performance, using traditional linear analyses and latent profile analysis (LPA). In this paper, state anxieties (in a math test and in an attention test situation), general anxiety traits, sustained attention (performance-based test and attention deficit/hyperactivity disorder (ADHD) self-ratings) and math achievement of 403 fourth and fifth graders (55.8% girls) were assessed. A negative correlation between state anxiety prior to the math test and arithmetic achievements was identified, even when controlling for other non-math related state anxieties and general anxiety. Sustained attention was a strong predictor of arithmetic achievement and functioned as a moderator in the anxiety-performance link. LPA identified six distinct profiles that revealed a complex relationship with arithmetic fluency. The weakest achievement was found for a specific math anxiety subgroup. The findings highlight the important role of the interaction of anxiety and sustained attention in children’s ability to perform math and enable new conclusions about the specific nature of math anxiety. Implications for future research are discussed.
Feasibility Study and Passive Design of Nearly Zero Energy Building on Rural Houses in Xi’an, China
Authors: Chang Han , Hou Yaolong , Lee Inhee , Liu Tianye , Acharya Tri Dev
Published: March 2022

Since the advent of reforms and opening-up of China, the focus has been on urban development. However, rural development has garnered attention in recent years. This research explores energy performance improvement methods for rural houses in Xi’an, China. It aims to discuss the feasibility of designing a nearly zero-energy building (nZEB), based on typical residential rural housing in Xi’an, through proposing new construction methods and examining the strategies for the refurbishment of an existing house. Initially, a typical rural house was modelled based on data collected from a field survey and historical documents. Subsequently, suitable passive design strategies were explored in the rural house design both in terms of proposing new construction methods and examining the refurbishment strategies of an existing house. After implementation of the passive design, the annual energy demand was reduced from 112 kWh/m2 to 68 kWh/m2 (new construction) and from 112 kWh/m2 to 85 kWh/m2 (refurbished). Even though the passive design significantly reduced the energy demand of the house, it could not achieve the Chinese nZEB standard. Therefore, a photovoltaic (PV) system and a storage battery were incorporated to meet the standard. Eighty per cent of the south roof area of the newly constructed and refurbished house was installed with a PV system and a storage battery with a capacity of 50 kWh and 52 kWh, respectively. After installation of the proposed renewable energy, the annual energy demand from the house was decreased to 35 kWh/m2 (new construction) and 51 kWh/m2 (refurbished), which both achieved the Chinese nZEB standard (equal to or below 55 kWh/m2). The study shows the effectiveness of the methods used to design the nZEB and can be used to instruct the residents to build the nZEB in rural villages like Xi’an in China.
Energy Optimization Design of Limestone Hybrid Concrete in Consideration of Stress Levels and Carbonation Resistance
Authors: Wang Xiao-Yong , Wang Yi-Sheng , Lin Run-Sheng , Cho Hyeong-Kyu , Min Tae-Beom
Published: March 2022

This research describes a genetic algorithm-based process for the optimization design of sustainable concrete with limestone powder. The objective of the optimization design was set as the embodied energy. The restraints of the optimization design consist of strength, workability, and carbonation resistance along with stress. The result of the research is shown as follows: (1) for low-strength concrete, carbonation dominates the mixture design of limestone hybrid concrete. Furthermore, the levels of stress and stress types modify the carbonation and optimization mixtures. The influence of tensile stress on optimization mixtures was much more apparent than compressive stress. (2) For concrete with high strength, strength dominates the mixture design of limestone hybrid concrete. (3) The optimization mixtures with low carbon footprints overlapped with those with low embodied energy. In addition, the new knowledge of the research is shown as follows: (1) find the decisive factor of concrete mixture design, (2) show a material design method considering structural stress, and (3) validate for various aims of optimal material design. In summary, the proposed model can be regarded as a common approach for the design of concrete mixture in consideration of strength, workability, carbonation resistance, and structural stress.
Late Endocrine and Metabolic Sequelae and Long-Term Monitoring of Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma Survivors: A Systematic Review by the Fondazione Italiana Linfomi
Authors: Di Molfetta Sergio , Daniele Antonella , Gerardi Chiara , Allocati Eleonora , Minoia Carla , Loseto Giacomo , Giorgino Francesco , Guarini Attilio , De Sanctis Vitaliana
Published: March 2022

Background: Overall survival after lymphoma has improved in recent years, but the high prevalence of late treatment-related sequelae has been observed as a counterpart. Method: In this systematic review, FIL researchers aimed to: (i) estimate the incidence or prevalence of late endocrine-metabolic sequelae, (ii) evaluate the effects of modern therapeutic approaches on incidence or prevalence of late endocrine-metabolic sequelae, and (iii) determine whether there is evidence of follow-up schemes for their screening/early diagnosis in the subset of long-term classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) survivors treated at adult age. The MEDLINE, Embase and the Cochrane Library databases were searched for relevant articles published up to October, 2020. The study selection process was conducted by three independent reviewers and was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A risk of bias assessment was performed using the Cochrane tool for randomized trials and the Newcastle-Ottawa Scale for observational studies. Results: In the final analysis, eight studies were included, four of which focused on thyroid disease, two on gonadal dysfunction, one on bone disease and one on metabolic syndrome. Hypothyroidism was reported in up to 60% of adult cHL survivors and was frequently recorded even with modern radiotherapy approaches. Menopause occurred in 52–72% of women after chemotherapy. An 86% reduction in vertebral density was reported following R-CHOP-like chemotherapy. Sarcopenia and metabolic syndrome were reported in 37.9% and 60% of patients, respectively. No validated screening protocols were found for the early diagnosis of long-term treatment-related endocrine and metabolic sequelae, thus the authors finally suggest the execution of screening exams according to the risk category which were identified in the epidemiologic studies.
The Thermal Dose of Photothermal Therapy Generates Differential Immunogenicity in Human Neuroblastoma Cells
Authors: Sekhri Palak , Ledezma Debbie K. , Shukla Anshi , Sweeney Elizabeth E. , Fernandes Rohan
Published: March 2022

Photothermal therapy (PTT) is an effective method for tumor eradication and has been successfully combined with immunotherapy. However, besides its cytotoxic effects, little is known about the effect of the PTT thermal dose on the immunogenicity of treated tumor cells. Therefore, we administered a range of thermal doses using Prussian blue nanoparticle-based photothermal therapy (PBNP-PTT) and assessed their effects on tumor cell death and concomitant immunogenicity correlates in two human neuroblastoma cell lines: SH-SY5Y (MYCN-non-amplified) and LAN-1 (MYCN-amplified). PBNP-PTT generated thermal dose-dependent tumor cell killing and immunogenic cell death (ICD) in both tumor lines in vitro. However, the effect of the thermal dose on ICD and the expression of costimulatory molecules, immune checkpoint molecules, major histocompatibility complexes, an NK cell-activating ligand, and a neuroblastoma-associated antigen were significantly more pronounced in SH-SY5Y cells compared with LAN-1 cells, consistent with the high-risk phenotype of LAN-1 cells. In functional co-culture studies in vitro, T cells exhibited significantly higher cytotoxicity toward SH-SY5Y cells relative to LAN-1 cells at equivalent thermal doses. This preliminary report suggests the importance of moving past the traditional focus of using PTT solely for tumor eradication to one that considers the immunogenic effects of PTT thermal dose to facilitate its success in cancer immunotherapy.
Circulating Tumor Cells and the Non-Touch Isolation Technique in Surgery for Non-Small-Cell Lung Cancer
Authors: Adachi Hiroyuki , Ito Hiroyuki , Sawabata Noriyoshi
Published: March 2022

Circulating tumor cells (CTCs) are dislodged from the primary tumor into the bloodstream, travel within the bloodstream to distant organs, and finally extravasate and proliferate as epithelial metastatic deposits. The relationship between the existence of CTCs and tumor prognosis has been demonstrated by many researchers. In surgery for malignancies, the surgical manipulation of tumors and tissues around the tumor may lead to the release of CTCs into the bloodstream. The non-touch isolation technique (NTIT) has been advocated to prevent the release of CTCs during surgery. The concept of NTIT is the prevention of intraoperative increment of CTCs from the primary tumor by the early blockade of outflow vessels, and ‘pulmonary vein (PV)-first lobectomy’ during surgery for non-small-cell lung cancer (NSCLC) corresponds to this technique. The concept of PV-first lobectomy is well known among thoracic surgeons, but evidence of its efficacy for preventing the increase of intra- and postoperative CTCs and for improving postoperative prognosis is still uncertain. Our study summarizes evidence regarding the relationship between NTIT and CTCs in NSCLC and suggests the need for further research on CTCs and CTC-detecting modalities.
Ras Pathway Activation and MEKi Resistance Scores Predict the Efficiency of MEKi and SRCi Combination to Induce Apoptosis in Colorectal Cancer
Authors: Davis Thomas Benjamin , Gupta Shilpa , Yang Mingli , Pflieger Lance , Rajan Malini , Wang Heiman , Thota Ramya , Yeatman Timothy J. , Pledger Warren Jackson
Published: March 2022

Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. The RAS pathway is activated in more than 55% of CRC and has been targeted for therapeutic intervention with MEK inhibitors. Unfortunately, many patients have de novo resistance, or can develop resistance to this new class of drugs. We have hypothesized that much of this resistance may pass through SRC as a common signal transduction node, and that inhibition of SRC may suppress MEK inhibition resistance mechanisms. CRC tumors of the Consensus Molecular Subtype (CMS) 4, enriched in stem cells, are difficult to successfully treat and have been suggested to evade traditional chemotherapy agents through resistance mechanisms. Here, we evaluate targeting two pathways simultaneously to produce an effective treatment by overcoming resistance. We show that combining Trametinib (MEKi) with Dasatinib (SRCi) provides enhanced cell death in 8 of the 16 tested CRC cell lines compared to treatment with either agent alone. To be able to select sensitive cells, we simultaneously evaluated a validated 18-gene RAS pathway activation signature score along with a 13-gene MEKi resistance signature score, which we hypothesize predict tumor sensitivity to this dual targeted therapy. We found the cell lines that were sensitive to the dual treatment were predominantly CMS4 and had both a high 18-gene and a high 13-gene score, suggesting these cell lines had potential for de novo MEKi sensitivity but were subject to the rapid development of MEKi resistance. The 13-gene score is highly correlated to a score for SRC activation, suggesting resistance is dependent on SRC. Our data show that gene expression signature scores for RAS pathway activation and for MEKi resistance may be useful in determining which CRC tumors will respond to the novel drug combination of MEKi and SRCi.
DLBCL 1L—What to Expect beyond R-CHOP?
Authors: Stegemann Maike , Denker Sophy , Schmitt Clemens A.
Published: March 2022

The R-CHOP immunochemotherapy protocol has been the first-line (1L) standard of care (SOC) for diffuse large B-cell lymphoma (DLBCL) patients for decades and is curative in approximately two-thirds of patients. Numerous randomized phase III trials, most of them in an “R-CHOP ± X” design, failed to further improve outcomes. This was mainly due to increased toxicity, the large proportion of patients not in need of more than R-CHOP, and the extensive molecular heterogeneity of the disease, raising the bar for “one-size-fits-all” concepts. Recently, an R-CHP regimen extended by the anti-CD79b antibody–drug conjugate (ADC) Polatuzumab Vedotin proved superior to R-CHOP in terms of progression-free survival (PFS) in the POLARIX phase III trial. Moreover, a number of targeted agents, especially the Bruton’s tyrosine kinase (BTK) inhibitor Ibrutinib, seem to have activity in certain patient subsets in 1L and are currently being tested in front-line regimens. Chimeric antigen receptor (CAR) T-cells, achieving remarkable results in ≥3L scenarios, are being exploited in earlier lines of therapy, while T-cell-engaging bispecific antibodies emerge as conceptual competitors of CAR T-cells. Hence, we present here the findings and lessons learnt from phase III 1L trials and piloting phase II studies in relapsed/refractory (R/R) and 1L settings, and survey chemotherapy-free regimens with respect to their efficacy and future potential in 1L. Novel agents and their mode of action will be discussed in light of the molecular landscape of DLBCL and personalized 1L perspectives for the challenging patient population not cured by the SOC.