bluuebunny/crossref_metadata_2025 huggingface dataset:
Chitosan Oligosaccharide Supplementation Affects Immunity Markers in Ewes and Lambs during Gestation and Lactation
Authors: Jahan Marefa , Wilson Cara , McGrath Shawn , Francis Nidhish , Wynn Peter C. , Du Yuguang , Allworth Bruce , Wang Bing
Published: September 2022

Chitosan oligosaccharide (COS) is derived through deacetylation of chitin from crustacean shells. Previous studies reported the benefits of COS to gut microbiota, immunity and health of host species. In this study, 120 pregnant composite ewes were subdivided into treatment and control groups in duplicate. COS was supplemented via a loose lick to provide an estimated intake of COS @100–600 mg/d/ewe for five weeks pre-lambing until lamb marking. Body weight was recorded pre-treatment for ewes, and at lamb marking and weaning for both ewes and lambs. Serum immunity markers immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA), secretory immunoglobulin A (sIgA), interleukin (IL)-2, IL10 and faecal sIgA were determined for ewes and lambs at lamb marking and weaning by enzyme-linked immunosorbent assay (ELISA). We found that COS can be incorporated in sheep feed without compromising palatability. Maternal COS supplementation did not influence the body weight of ewes or lambs. It did, however, significantly increase the concentrations of serum IL2 in ewes at marking and weaning (p < 0.001). In lambs, COS also significantly increased the IL2 concentration at making (p = 0.018) and weaning (p = 0.029) and serum IgM at marking (p < 0.001). No significant effect was observed in the concentration of any other immune marker or cytokine in either ewes or lambs. In conclusion, maternal COS supplementation significantly modulated some immunity markers in both ewes and lambs. The short duration of maternal COS supplementation and optimal seasonal conditions during the trial may explain the lack of significant body weight in ewes and lambs from the COS supplementation.
Optimizing the Ultrasound Image Quality of Carotid Artery Stenosis Patients via Taguchi’s Dynamic Analysis and an Indigenous Water Phantom
Authors: Hsiao Kai-Yu , Lin Chih-Sheng , Li Wan-Ming , Huang Shih-Hsun , Cho Yu-Ting , Peng Bing-Ru , Pan Lung-Kwang , Pan Lung-Fa
Published: September 2022

This study optimized the ultrasound image of carotid artery stenosis using Taguchi dynamic analysis and an indigenous water phantom. Eighteen combinations of seven essential factors of the ultrasound scan facility were organized according to Taguchi’s L18 orthogonal array. The seven factors were assigned as follows: (1) angle of probe; (2) signal gain; (3) resolution vs. speed; (4) dynamic range; (5) XRES; (6) zoom; (7) time gain compensation. An indigenous water phantom was customized to satisfy the quantified need in Taguchi’s analysis. Unlike the conventional dynamic Taguchi analysis, an innovative quantified index, the figure of merit (FOM), was proposed to integrate four specific quality characteristics, namely (i) average difference between the practical scan and theoretically preset area (78.5, 50.2 and 12.6 mm2) of stenosis, (ii) standard deviation of the average, (iii) practical scan’s sensitivity β to various stenosis diameters (10, 8, and 4 mm), and (iv) correlation coefficient r2 of the linear regressed sensitivity curve. The highest value (FOM = 0.413) was furnished by the optimal combination of factors on 18 groups under study, yielding high r2 and low β or standard deviation values and the best quality of ultrasound images for the further clinical diagnosis. The comparison between FOM and the conventional signal-to-noise (S/N) ratio in Taguchi’s analysis revealed that FOM compiled more quality characteristics that were superior by nature to fulfill the practical need in clinical diagnosis. The alternative choice in ultrasound scan optimization can be based on stenosis diameter variation from a different perspective to be explored in the follow-up study.
Digital High: The Art of Visual Seduction?
Authors: Zholkovsky Alexander
Published: September 2022

The paper focuses on the structure of an advertising image for a 2010s computer company in the neo-capitalist Moscow, Russia. The analysis looks back to the pioneering studies of advertising as a commercial “applied art” by Sergei Eisenstein, Leo Spitzer and Roland Barthes. The picture’s plot and composition are shown to be a consistent and sophisticated near-artistic design that uses textual puns, poetic topoi and visual stereotypes (in particular, sex appeal) for the promotion of the advertised merchandise (a smartphone). The psychological naturalization of the design is clarified with references to the insights of Sigmund Freud, Heinz Kohut and Gerard Genette into the dynamics of narcissism. In a widening circle, the contextualization of the design involves: the literary topos of using birds in love poetry (made famous by its treatment in the lyrics of the Roman poet Catullus) and in painterly variations on the theme; the narcissist discourse of a modern Russian poet (Eduard Limonov); and the grand pictorial tradition of portraying a nude (Venus) before the mirror (relevant classical canvases are considered briefly).
Effect of Densification on Biomass Combustion and Particulate Matter Emission Characteristics
Authors: Yang Wei , Lv Leida , Han Yong , Li Yu , Liu Huihui , Zhu Youjian , Zhang Wennan , Yang Haiping
Published: September 2022

The effect of biomass densification on combustion characteristics and particulate matter (PM) emission was studied in this work by means of thermogravimetric, combustion kinetic, and PM analyses with respect to the size distribution and elementary composition. Cornstalk as a typical agricultural biomass residue and camphorwood as a woody biomass were used in the experiment for comparison. It can be concluded that the biomass densification increases the ignition, burnout, and composite combustion indexes, leading to a better performance of biomass combustion. The main reaction mechanism of cornstalk pellets can be well-expressed with the chemical reaction series model, whereas the diffusion mechanism and chemical reaction series models can be applied to the combustion of camphorwood pellets. The biomass densification has little effect on the composition of PM but significantly changes the yield of PM. The influence of biomass densification on PM emission is related to the biomass properties. The densification significantly reduces the PM emission for cornstalk but significantly increases the yield of particles of aerodynamic cutoff diameters less than 1μm (PM1) for camphorwood.
Feasibility of Using Isokinetic Sampling Techniques to Extract a Representative Sample from Processes in the United Kingdom
Authors: Nicklin Daniel , Gohari Darabkhani Hamidreza
Published: September 2022

The requirement to monitor and control particulate emissions from industrial processes using continuous emission monitoring systems (CEMS) has significantly increased over recent years. Under current legislation, CEMS equipment requires calibration against the standard reference method (SRM) using isokinetic sampling and gravimetric analysis under controlled conditions as detailed through BS EN 13284-1 “Stationary source emissions–Determination of low range mass concentration of dust. Manual gravimetric method”. This process includes pumping a known volume of gas through a filter, which is weighed before and after sampling, and the total mass of dust per m3 can then be calculated to output results in mg/m3. As tougher legislation is introduced and stringent emission limit values (ELVs) are imposed on emissions processes in the United Kingdom (UK), the calibration of CEMS is increasingly more difficult due to the reliability of the SRM at low concentrations. The accuracy of results from the SRM and therefore CEMS equipment must be questioned when the uncertainty of measurement is higher than process ELVs. This research analyses data taken from an industrial survey and 21 UK processes where the standard reference method, in accordance with the procedure in BS EN 13284-1 has been used for particulate measurement. Investigating the reliability of isokinetic sampling when used as a method to extract a representative sample from a stack process when used in conjunction with innovative, alternative methods of sample analysis. In processes with particulate emissions <5 mg/m3, 80.7% of the total sample was collected in the rinse, and for processes >5 mg/m3, 56.4% of the sample was collected in the rinse. The data does not suggest any correlation between any of the measured parameters and the percentage of particulate in the rinse, including the stack velocity, isokinetic percentage, sample volume, and total mass concentration.
Evaluation of Microclimate Benefits Due to Cool Pavements and Green Infrastructures on Urban Heat Islands
Authors: Del Serrone Giulia , Peluso Paolo , Moretti Laura
Published: September 2022

Ongoing climate change is manifesting in the expansion of the urban heat island (UHI) effect. This paper evaluates the microclimate benefits of cool pavements and green infrastructures in a historical square in Rome, Italy. The ENVI-Met software enabled us to conduct a microclimatic analysis of the examined square in July 2021, through a comparison of the thermal performances of the current asphalt and sampietrini pavement (AS) with three alternatives. The proposed options are to change the existing layout to include: light concrete slabs and green furniture consisting of 5 m high trees (LC+G1), a perimeter hedge with 5 m high trees (LC+G2), and a perimeter hedge with 15 m high trees (LC+G3). The effects of the road pavements as passive countermeasures to the UHI effect are investigated in terms of air temperature (AT), mean radiant temperature (MRT), and predicted mean vote (PMV). The results show that the existing asphalt pavement is the worst option, while the cool pavement integrated with vegetation is greatly beneficial to human thermal comfort. Compared to the current layout, LC+G3 is the best scenario, because it implies an AT reduction higher than 3 °C, a MRT reduction equal to 50%, and a maximum PMV value equal to 2.2.
CO2 and CH4 Emission Factors from Light-Duty Vehicles by Fuel Types in Thailand
Authors: Sirithian Duanpen , Thanatrakolsri Pantitcha , Pongpan Surangrat
Published: September 2022

Correct emission factors are necessary for evaluating vehicle emissions and making proper decisions to manage air pollution in the transportation sector. In this study, using a chassis dynamometer at the Automotive Emission Laboratory, CO2 and CH4 emission factors of light-duty vehicles (LDVs) were developed by fuel types and driving speeds. The Bangkok driving cycle was used for the vehicle’s running and controlling under the standard procedure. Results present that the highest average CO2 and CH4 emission factors were emitted from LDG vehicles, at 232.25 g/km and 9.50 mg/km, respectively. The average CO2 emission factor of the LDD vehicles was higher than that of the LDG vehicles, at 182.53 g/km and 171.01 g/km, respectively. Nevertheless, the average CH4 emission factors of the LDD vehicles were lower than those of the LDG vehicles, at 2.21 mg/km and 3.02 mg/km, respectively. The result reveals that the lower driving speed emitted higher CO2 emission factors for LDVs. It reflects the higher fuel consumption rate (L/100 km) and the lower fuel economy rate (km/L). Moreover, the portion of CO2 emissions emitted from LDVs was 99.96% of total GHG emissions. The CO2 and CH4 emission factors developed through this study will be used to support the greenhouse gas reduction policies, especially concerning the CO2 and CH4 emitted from vehicles. Furthermore, it can be used as a database that encourages Thailand’s green transportation management system.
Validation and Comparison of Climate Reanalysis Data in the East Asian Monsoon Region
Authors: Kim Minseok , Lee Eungul
Published: September 2022

Understanding East Asian monsoon (EAM) has been a crucial issue due to its socio-economic effects on one-fifth of the world’s population and its interactions with the global climate system. However, the reliabilities of climate reanalysis data are still uncertain at varying temporal and spatial scales. In this study, we examined the correlations and differences for climate reanalyses with weather observations and suggested the best climate reanalysis for the EAM region. The three reanalyses of ERA5, JRA55, and NCEP2 along with a gridded observation (CRU) were evaluated using the correlation coefficients (Pearson, Spearman, and Kendall), difference statistics (RMSE and bias), and Taylor diagrams, comparing their annual and seasonal temperatures and precipitations with those from the total of 537 weather stations across China, North Korea, South Korea, and Japan. We found that ERA5 showed the best performance in reproducing temporal variations in temperature with the highest correlations in annual, summer, and autumn, and the smallest RMSEs and biases for all seasons and annually. For precipitation, among the three reanalysis datasets, ERA5 had the highest correlations, annually and in four seasons, with the smallest RMSEs, annually and in spring, summer and autumn, and the smallest biases, annually and in summer and autumn. Regarding spatial variations, ERA5 was also the most suitable reanalysis data in representing the annual and seasonal climatological averages.
Recent Advances in CRISPR/Cas-Based Biosensors for Protein Detection
Authors: Wang Jing , Yang Xifang , Wang Xueliang , Wang Wanhe
Published: September 2022

CRISPR is an acquired immune system found in prokaryotes that can accurately recognize and cleave foreign nucleic acids, and has been widely explored for gene editing and biosensing. In the past, CRISPR/Cas-based biosensors were mainly applied to detect nucleic acids in the field of biosensing, and their applications for the detection of other types of analytes were usually overlooked such as small molecules and disease-related proteins. The recent work shows that CRISPR/Cas biosensors not only provide a new tool for protein analysis, but also improve the sensitivity and specificity of protein detections. However, it lacks the latest review to summarize CRISPR/Cas-based biosensors for protein detection and elucidate their mechanisms of action, hindering the development of superior biosensors for proteins. In this review, we summarized CRISPR/Cas-based biosensors for protein detection based on their mechanism of action in three aspects: antibody-assisted CRISPR/Cas-based protein detection, aptamer-assisted CRISPR/Cas-based protein detection, and miscellaneous CRISPR/Cas-based methods for protein detection, respectively. Moreover, the prospects and challenges for CRISPR/Cas-based biosensors for protein detection are also discussed.
Utilization of Function Generation Synthesis on Biomimetics: A Case Study on Moray Eel Double Jaw Design
Authors: Koçak Mertcan , Yazıcı Mustafa Volkan , Akdal Efecan , Can Fatih Cemal , Gezgin Erkin
Published: September 2022

Throughout history, humans have observed living or non-living things in nature and then imitated them in relation to these observations. This is due to the fact that the energy found in nature is generally consumed at an optimal level in order for it to endure. Biomimetic inspiration in many designs and applications is widely displayed, including within the field of engineering. In this paper, we were inspired by the double set of jaws found in the moray eel, which gives this fish a huge advantage while hunting, with a mobile pharyngeal jaw that works together with its oral jaw in order to overcome ineffective suction capabilities. A procedure that mimics the hunting motion of the moray eel was utilized by considering the overall movement as a single degree of freedom with multiple outputs on account of the repeating motion that is required during hunting. This procedure includes structural and dimensioning synthesis, wherein the latter was utilized with analytic kinematic synthesis for each linkage transfer. The flexibilities in parameters were taken into account with a novel multiple iterative kinematic synthesis algorithm that resulted in various mechanisms with the same purpose. Among the excessive number of resultant mechanisms, the optimization was carried out by considering the highest torque transmission ratio at critical timings that were specified as bio-constraints. In the end, the kinematic movement validation was utilized.
Development of Motor Imagery in School-Aged Children with Autism Spectrum Disorder: A Longitudinal Study
Authors: Johansson Anna-Maria , Rudolfsson Thomas , Bäckström Anna , Rönnqvist Louise , von Hofsten Claes , Rosander Kerstin , Domellöf Erik
Published: September 2022

Autism spectrum disorder (ASD) is a diagnosis based on social communication deficits and prevalence of repetitive stereotyped behaviors, but sensorimotor disturbances are commonly exhibited. This longitudinal study aimed at exploring the development of the ability to form mental motor representations (motor imagery; MI) in 14 children with ASD and 17 typically developing (TD) children at 7, 8 and 9 years of age. MI was investigated using a hand laterality paradigm from which response times (RT) and error rates were extracted and compared with performance on a visually based mental rotation task (VI). A criterion task was used to ensure that the children could perform the task. The results showed wide performance variability in the ASD group with more failures than TD in the MI criterion task, especially at 7 years. For all age levels and both the MI and VI tasks, the error rates were significantly higher and RTs longer for the ASD group compared with TD. Signs of MI strategies were however noted in the ASD group as biomechanically constrained orientations had longer RTs than less constrained orientations, a RT pattern that differed from the VI task. The presence of MI in the ASD group was most evident at 9 years, but the error rates remained high at all ages, both in the MI and VI task. In comparison, the TD group showed stable MI strategies at all ages. These findings indicate that MI ability is delayed and/or impaired in children with ASD which may be related to difficulties performing required mental rotations.
Underlying Music Mechanisms Influencing the Neurology of Pain: An Integrative Model
Authors: Loewy Joanne
Published: September 2022

Pain is often debilitating, and is associated with many pathologies, as either a cause or consequence. Pharmacological interventions, such as opioids, to manage pain may lead to potential problems, such as addiction. When pain is controlled and managed, it can prevent negative associated outcomes affiliated with disease. Music is a low-cost option that shows promise in the management of painful circumstances. Music therapy has provided potent options for pain relief across a variety of ages and populations. As a nonpharmacological alternative or complement lacking side effects, music interventions are growing in clinical application and research protocols. This article considers the neurological implications of varying kinds of pain to provide working considerations that preempt the use of music and music-therapy applications in treating pain.
Construction 4.0 Application: Industry 4.0, Internet of Things and Lean Construction Tools’ Application in Quality Management System of Residential Building Projects
Authors: Lekan Amusan , Clinton Aigbavboa , Stella Essien , Moses Emetere , Biodun Obaju
Published: September 2022

The advent of Construction 4.0 has played a major role in construction industry development through the improvement of quality performance. One of the parameters that have contributed immensely to the management of construction quality in the industrial revolution era is Industry 4.0, the Internet of Things (IoT), and Lean thinking concepts. Lean construction is characterized by a set of clear objectives in project delivery involving the concurrent design of products and processes. The study aims to carry out an exploratory study of the application of Construction 4.0 and Industrial 4.0 in quality management of building works and the development of Lean-based quality management models: The study engaged a survey design approach, and a random sampling technique was used to select the study samples. A structured questionnaire designed on a Likert scale 1–5 was used to collate data on the quality aspect of a construction project, and the data were used in model creation. The parameters that emerged are cast as the quality management model. The resultant factors were categorized into three (3) quality categories, which are the Zero level Defect range, Medium Quality, and High-Level Quality Range. The three (3) quality factors were recommended for adoption for quality management of residential building projects.
Bis(chloroacetamidino)-Derived Heteroarene-Fused Anthraquinones Bind to and Cause Proteasomal Degradation of tNOX, Leading to c-Flip Downregulation and Apoptosis in Oral Cancer Cells
Authors: Chang Jeng Shiun , Chen Chien-Yu , Tikhomirov Alexander S. , Islam Atikul , Liang Ru-Hao , Weng Chia-Wei , Wu Wei-Hou , Shchekotikhin Andrey E. , Chueh Pin Ju
Published: September 2022

Anthraquinone-based intercalating compounds, namely doxorubicin and mitoxantrone, have been used clinically based on their capacity to bind DNA and induce DNA damage. However, their applications have been limited by side effects and drug resistance. New-generation anthraquinone derivatives fused with different heterocycles have been chemically synthesized and screened for higher anticancer potency. Among the compounds reported in our previous study, 4,11-bis(2-(2-chloroacetamidine)ethylamino)anthra[2,3-b]thiophene-5,10-dione dihydrochloride (designated 2c) was found to be apoptotic, but the direct cellular target responsible for the cytotoxicity remained unknown. Here, we report the synthesis and anticancer properties of two other derivatives, 4,11-bis(2-(2-chloroacetamidine)ethylamino)naphtho[2,3-f]indole-5,10-dione dihydrochloride (2a) and 4,11-bis(2-(2-chloroacetamidine)ethylamino)-2-methylanthra[2,3-b]furan-5,10-dione dihydrochloride (2b). We sought to identify and validate the protein target(s) of these derivatives in oral cancer cells, using molecular docking simulations and cellular thermal shift assays (CETSA). Our CETSA results illustrate that these derivatives targeted the tumor-associated NADH oxidase (tNOX, ENOX2), and their direct binding downregulated tNOX in p53-functional SAS and p53-mutated HSC-3 cells. Interestingly, the compounds targeted and downregulated tNOX to reduce SIRT1 deacetylase activity and increase Ku70 acetylation, which triggers c-Flip ubiquitination and induces apoptosis in oral cancer cells. Together, our data highlight the potential value of these heteroarene-fused anthraquinones in managing cancer by targeting tNOX and augmenting apoptosis.
Prognostic Ability of Tumor Budding Outperforms Poorly Differentiated Clusters in Gastric Cancer
Authors: Szalai Luca , Jakab Ákos , Kocsmár Ildikó , Szirtes Ildikó , Kenessey István , Szijártó Attila , Schaff Zsuzsa , Kiss András , Lotz Gábor , Kocsmár Éva
Published: September 2022

The prognostic value of histological phenomena tumor budding (TB) and poorly differentiated clusters (PDCs) have been less studied in gastric cancer (GAC) and the data provided so far are controversial. In our study, 290 surgically resected GAC cases were evaluated for TB according to the criteria of International Tumor Budding Consensus Conference (ITBCC) and PDC, and both parameters were scored on a three-grade scale as described for colorectal cancer previously (0: Grade0, 1–4: Grade1, 5–9: Grade2 and ≥10: Grade3) and classified as low (Grade0–2) and high (Grade3) TB/PDC. High TB/PDC was associated with diffuse-type morphology, higher pT status, incomplete surgical resection, poor tumor differentiation and perineural and lymphovascular invasion. Multivariable survival analyses have shown an independent prognostic role of high TB with poorer overall survival in the total cohort (p = 0.014) and in intestinal-type adenocarcinomas (p = 0.005). Multivariable model revealed high TB as an independent predictor for lymph node metastasis in both the total cohort (p = 0.019) and in the intestinal type adenocarcinomas (p = 0.038). In contrast to tumor budding, no significant association was found between PDC and the occurrence of lymph node metastasis and tumor stage and even survival. In conclusion, tumor budding is an independent prognostic factor of survival in gastric cancer, especially in intestinal-type adenocarcinomas.
Nuclear Beclin 1 Destabilizes Retinoblastoma Protein to Promote Cell Cycle Progression and Colorectal Cancer Growth
Authors: Pan Yang , Zhao Zhiqiang , Li Juan , Li Jinsong , Luo Yue , Li Weiyuxin , You Wanbang , Zhang Yujun , Li Zhonghan , Yang Jian , Xiao Zhi-Xiong Jim , Wang Yang
Published: September 2022

Autophagy is elevated in colorectal cancer (CRC) and is generally associated with poor prognosis. However, the role of autophagy core-protein Beclin 1 remains controversial in CRC development. Here, we show that the expression of nuclear Beclin 1 protein is upregulated in CRC with a negative correlation to retinoblastoma (RB) protein expression. Silencing of BECN1 upregulates RB resulting in cell cycle G1 arrest and growth inhibition of CRC cells independent of p53. Furthermore, ablation of BECN1 inhibits xenograft tumor growth through elevated RB expression and reduced autophagy, while simultaneous silencing of RB1 restores tumor growth but has little effect on autophagy. Mechanistically, knockdown of BECN1 promotes the complex formation of MDM2 and MDMX, resulting in MDM2-dependent MDMX instability and RB stabilization. Our results demonstrate that nuclear Beclin 1 can promote cell cycle progression through modulation of the MDM2/X-RB pathway and suggest that Beclin 1 promotes CRC development by facilitating both cell cycle progression and autophagy.
Plasma-Based microRNA Expression Analysis in Advanced Stage NSCLC Patients Treated with Nivolumab
Authors: Monastirioti Alexia , Papadaki Chara , Kalapanida Despoina , Rounis Konstantinos , Michaelidou Kleita , Papadaki Maria A. , Mavroudis Dimitrios , Agelaki Sofia
Published: September 2022

Since circulating microRNAs (miRNAs) are involved in the modulation of the immune response, they are tested as liquid biopsy-based biomarkers in patients with NSCLC treated with immunotherapy. We analyzed the expression levels and examined the clinical significance of immunoregulatory miRNAs involved in immune checkpoint regulation (miR-34a, miR-200b, miR-200c), T-cell activity (miR-155), and the function of myeloid-derived suppressive cells (MDSCs) (miR-223) or regulatory T lymphocytes (Tregs) (miR-146a), in patients with advanced NSCLC (N = 69) treated with anti-PD-1 (Nivolumab) immunotherapy as 2nd or 3rd line of treatment therapy. Plasma levels of circulating miRNAs were analyzed by RT-qPCR before the initiation of immunotherapy. Expression of miR-34a, miR-146a, mir-200c, and miR-223 was found to be associated with response to immunotherapy. High miR-200c expression emerged as an independent prognostic factor for inferior overall survival in all patients with NSCLC (OS, HR: 2.243, 95% CI: 1.208–4.163; p = 0.010) and in patients with non-Squamous (non-SqCC) subtype (N = 38) (HR: 2.809, 95% CI: 1.116–7.074; p = 0.028). Low miR-34a expression independently predicted for shorter OS (HR: 3.189, 95% CI: 1.193–8.527; p = 0.021) in the non-SqCC subgroup. Our findings suggest that alterations in circulating miR-200c and miR-34a expression levels are associated with the response and outcome in patients with advanced NSCLC treated with anti-PD1 immunotherapy.
Multiple Myeloma in Patients over 80: A Real World Retrospective Study of First Line Conservative Approach with Bortezomib Dexamethasone Doublet Therapy and Mini-Review of Literature
Authors: Huynh Laurence , Birsen Rudy , Mora Lucie , Couderc Anne-Laure , Mitha Nathalie , Farcet Anaïs , Chebib Amale , Chaibi Pascal
Published: September 2022

Data on octogenarian patients with MM are scarce, and optimal management remains controversial. We report a retrospective cohort of unselected octogenarian patients with NDMM treated with bortezomib dexamethasone (Vd). Seventy-four patients were treated with an initial doublet therapy (Vd regimen, 2–3 cycles, induction). A dose escalation with an adjunction of melphalan or cyclophosphamide was proposed for patients who had an insufficient response after induction and who could tolerate it. In responders, the treatment was continued until progression or a plateau response for 6 months (consolidation). The overall response rate was 73%. After a median follow-up of 31.4 months, median progression-free survival (PFS) and overall survival (OS) were 13.2 and 26.9 months, respectively. PFS and OS of patients with ECOG PS < 3 (25.4 and 54.9 months, respectively) were better in comparison to PFS and OS of patients with ECOG PS ≥ 3 (9.3 and 11.3 months, respectively). Thirteen patients (17.6%) died during induction. Twelve patients (16.2%) died during consolidation. In conclusion, a conservative therapeutic strategy based on Vd resulted in a good response rate. However, the survival remains poor in the population of patients with an ECOG PS ≥ 3, mainly because of early mortality not related to progressive disease.
IL-2K35C-moFA, a Long-Acting Engineered Cytokine with Decreased Interleukin 2 Receptor α Binding, Improved the Cellular Selectivity Profile and Antitumor Efficacy in a Mouse Tumor Model
Authors: Wang Xiaoze , Chen Gang , Nie Lei , Wu Zhenhua , Wang Xinzeng , Pan Chenxiao , Chen Xuchen , Zhao Xiaobei , Zhu Jie , He Qiaojun , Wang Haibin
Published: September 2022

Human interleukin 2 (IL-2) has shown impressive results as a therapeutic agent for cancer. However, IL-2-based cancer therapy is limited by strong Treg amplification owing to its high binding affinity to IL-2 receptor α (IL-2Rα) and its short half-life owing to its small molecular size. In this study, we solved these problems using a covalent modification strategy of the IL-2 variant, i.e., substituting cysteine (C) for lysine (K) at position 35, using octadecanedicarboxylic acid through maleimide chemistry, creating IL-2K35C-moFA. IL-2K35C-moFA was equipotent to human IL-2 wild type (IL-2WT) in activating tumor-killing CD8+ memory effector T cells (CD8+ T) and NK cells bearing the intermediate affinity IL-2 receptors, and less potent than IL-2WT on CTLL-2 cells bearing the high-affinity IL-2 receptors. Moreover, it was shown to support the preferential activation of IL-2 receptor β (IL-2Rβ) over IL-2Rα because of the mutation and fatty acid conjugation. In a B16F10 murine tumor model, IL-2K35C-moFA showed efficacy as a single dose and provided durable immunity for 1 week. Our results support the further evaluation of IL-2K35C-moFA as a novel cancer immunotherapy.
Multiparametric Sonographic Imaging of Thyroid Lesions: Chances of B-Mode, Elastography and CEUS in Relation to Preoperative Histopathology
Authors: Brandenstein Moritz , Wiesinger Isabel , Künzel Julian , Hornung Matthias , Stroszczynski Christian , Jung Ernst-Michael
Published: September 2022

Background: The aim was to improve preoperative diagnostics of solid non-cystic thyroid lesions by using new high-performance multiparametric ultrasound examination techniques. Methods: Multiparametric ultrasound consists of B-mode, shear-wave elastography and contrast enhanced ultrasound (CEUS) including Time-Intensity-Curve (TIC) analysis. A bolus of 1–2.4 mL Sulfur Hexafluorid microbubbles was injected for CEUS. Postoperative histopathology was the diagnostic gold standard. Results: 116 patients were included in this study. 102 benign thyroid nodules were diagnosed as well as 20 carcinomas. Suspicious B-mode findings like microcalcifications, a blurry edge and no homogeneous sonomorphological structure were detected in 60, 75 and 80% of all carcinomas but only in 13.7, 36.3 and 46.1% of all benign lesions. The average shear-wave elastography measurements of malignant lesions (4.6 m/s or 69.8 kPa centrally and 4.2 m/s or 60.1 kPa marginally) exceed the values of benign nodules. Suspicious CEUS findings like a not-homogeneous wash-in and a wash-out were detected almost twice as often in carcinomas. Conclusion: Multiparametric ultrasound offers new possibilities for the preoperative distinction between benign and malignant thyroid nodules. A score based system of B-mode, shear-wave and CEUS malignancy criteria shows promising results in the detection of thyroid carcinomas. It reaches a sensitivity of 95% and specificity of 75.49%.
Asymmetric Synthesis of Both Enantiomers of Dimethyl 2-Methylsuccinate by the Ene-Reductase-Catalyzed Reduction at High Substrate Concentration
Authors: Li Jiacheng , Li Jianjiong , Cui Yunfeng , Wang Min , Feng Jinhui , Yao Peiyuan , Wu Qiaqing , Zhu Dunming
Published: September 2022

Chiral dimethyl 2-methylsuccinate (1) is a very important building block for the manufacturing of many active pharmaceutical ingredients and fine chemicals. The asymmetric reduction of C=C double bond of dimethyl citraconate (2), dimethyl mesaconate (3) or dimethyl itaconate (4) by ene-reductases (ERs) represents an attractive straightforward approach, but lack of high-performance ERs, especially (S)-selective ones, has limited implementing this method to prepare the optically pure dimethyl 2-methylsuccinate. Herein, three ERs (Bac-OYE1 from Bacillus sp., SeER from Saccharomyces eubayanus and AfER from Aspergillus flavus) with high substrate tolerance and stereoselectivity towards 2, 3 and 4 have been identified. Up to 500 mM of 3 was converted to (S)-dimethyl 2-methylsuccinate ((S)-1) by SeER in high yields (80%) and enantioselectivity (98% ee), and 700 mM of 2 and 400 mM of 4 were converted to (R)-1 by Bac-OYE1 and AfER, respectively, in high yields (86% and 77%) with excellent enantioselectivity (99% ee). The reductions of diethyl citraconate (5), diethyl mesaconate (6) and diethyl itaconate (7) were also tested with the three ERs. Although up to 500 mM of 5 was completely converted to (R)-diethyl 2-methylsuccinate ((R)-8) by Bac-OYE1 with excellent enantioselectivity (99% ee), the alcohol moiety of the esters had a great effect on the activity and enantioselectivity of ERs. This work provides an efficient methodology for the enantiocomplementary production of optically pure dimethyl 2-methylsuccinate from dimethyl itaconate and its isomers at high titer.
On a Response Surface Analysis: Hydrodeoxygenation of Phenol over a CoMoS-Based Active Phase
Authors: Pinzón-Ramos Itzayana , Castillo-Araiza Carlos O. , Tavizón-Pozos Jesús Andrés , de los Reyes José Antonio
Published: September 2022

This work aims at assessing the hydrodeoxygenation (HDO) of phenol over a promising catalytic material: a CoMoS-based active phase with a Co/(Co + Mo) = 0.2, supported on a promising mixed oxide, Al2O3-TiO2 (Al/Ti = 2). Particularly, to optimize the catalytic and kinetic performance of CoMoS/Al2O3-TiO2, a response surface methodology (RSM) is carried out by following a Box–Behnken experimental design. The response variables are the initial reaction rate and the reaction selectivity, determined via a proper contribution analysis (𝜑) of both the direct hydrodeoxygenation (DDO) and the hydrogenation (HYD). At the same time, the operating conditions used as factors are the reaction temperature (280–360 °C), the total pressure (3–5.5 MPa), and the Mo loading (10–15 wt.%). The activity and selectivity are correlated to the catalysts’ physicochemical properties determined by XRD, UV-Vis DRS, TPR, and Raman Spectroscopy. Regarding the CoMo-based active phase, a Mo loading of 12.5 wt.% leads to the optimal reaction performance, which is associated with the lowest (Co + Mo)oh/(Co + Mo)th ratio. Concerning the operating conditions, a temperature of 360 °C and a total pressure of 5.5 MPa give rise to the optimal initial reaction rates, in which the DDO (𝜑 = 65%) is selectively favored over HYD (𝜑 = 35%).
The Use of Retinal Microvascular Function and Telomere Length in Age and Blood Pressure Prediction in Individuals with Low Cardiovascular Risk
Authors: Shokr Hala , Lush Victoria , Dias Irundika HK , Ekárt Anikó , De Moraes Gustavo , Gherghel Doina
Published: September 2022

Ageing represents a major risk factor for many pathologies that limit human lifespan, including cardiovascular diseases. Biological ageing is a good biomarker to assess early individual risk for CVD. However, finding good measurements of biological ageing is an ongoing quest. This study aims to assess the use retinal microvascular function, separate or in combination with telomere length, as a predictor for age and systemic blood pressure in individuals with low cardiovascular risk. In all, 123 healthy participants with low cardiovascular risk were recruited and divided into three groups: group 1 (less than 30 years old), group 2 (31–50 years old) and group 3 (over 50 years old). Relative telomere length (RTL), parameters of retinal microvascular function, CVD circulatory markers and blood pressure (BP) were measured in all individuals. Symbolic regression- analysis was used to infer chronological age and systemic BP measurements using either RTL or a combination of RTL and parameters for retinal microvascular function. RTL decreased significantly with age (p = 0.010). There were also age-related differences between the study groups in retinal arterial time to maximum dilation (p = 0.005), maximum constriction (p = 0.007) and maximum constriction percentage (p = 0.010). In the youngest participants, the error between predicted versus actual values for the chronological age were smallest in the case of using both retinal vascular functions only (p = 0.039) or the combination of this parameter with RTL (p = 0.0045). Systolic BP was better predicted by RTL also only in younger individuals (p = 0.043). The assessment of retinal arterial vascular function is a better predictor than RTL for non-modifiable variables such as age, and only in younger individuals. In the same age group, RTL is better than microvascular function when inferring modifiable risk factors for CVDs. In older individuals, the accumulation of physiological and structural biological changes makes such predictions unreliable.
Structural Basis of β2 Integrin Inside—Out Activation
Authors: Wen Lai , Lyu Qingkang , Ley Klaus , Goult Benjamin T.
Published: September 2022

β2 integrins are expressed on all leukocytes. Precise regulation of the β2 integrin is critical for leukocyte adhesion and trafficking. In neutrophils, β2 integrins participate in slow rolling. When activated by inside–out signaling, fully activated β2 integrins mediate rapid leukocyte arrest and adhesion. The two activation pathways, starting with selectin ligand engagement and chemokine receptor ligation, respectively, converge on phosphoinositide 3-kinase, talin-1, kindlin-3 and Rap1. Here, we focus on recent structural insights into autoinhibited talin-1 and autoinhibited trimeric kindlin-3. When activated, both talin-1 and kindlin-3 can bind the β2 cytoplasmic tail at separate but adjacent sites. We discuss possible pathways for talin-1 and kindlin-3 activation, recruitment to the plasma membrane, and their role in integrin activation. We propose new models of the final steps of integrin activation involving the complex of talin-1, kindlin-3, integrin and the plasma membrane.
Recent Progress and Future Prospect of CRISPR/Cas-Derived Transcription Activation (CRISPRa) System in Plants
Authors: Ding Xiao , Yu Lu , Chen Luo , Li Yujie , Zhang Jinlun , Sheng Hanyan , Ren Zhengwei , Li Yunlong , Yu Xiaohan , Jin Shuangxia , Cao Jinglin
Published: September 2022

Genome editing technology has become one of the hottest research areas in recent years. Among diverse genome editing tools, the Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated proteins system (CRISPR/Cas system) has exhibited the obvious advantages of specificity, simplicity, and flexibility over any previous genome editing system. In addition, the emergence of Cas9 mutants, such as dCas9 (dead Cas9), which lost its endonuclease activity but maintains DNA recognition activity with the guide RNA, provides powerful genetic manipulation tools. In particular, combining the dCas9 protein and transcriptional activator to achieve specific regulation of gene expression has made important contributions to biotechnology in medical research as well as agriculture. CRISPR/dCas9 activation (CRISPRa) can increase the transcription of endogenous genes. Overexpression of foreign genes by traditional transgenic technology in plant cells is the routine method to verify gene function by elevating genes transcription. One of the main limitations of the overexpression is the vector capacity constraint that makes it difficult to express multiple genes using the typical Ti plasmid vectors from Agrobacterium. The CRISPRa system can overcome these limitations of the traditional gene overexpression method and achieve multiple gene activation by simply designating several guide RNAs in one vector. This review summarizes the latest progress based on the development of CRISPRa systems, including SunTag, dCas9-VPR, dCas9-TV, scRNA, SAM, and CRISPR-Act and their applications in plants. Furthermore, limitations, challenges of current CRISPRa systems and future prospective applications are also discussed.
Airway Management in Pediatric Patients: Cuff-Solved Problem?
Authors: Klabusayová Eva , Klučka Jozef , Kratochvíl Milan , Musilová Tereza , Vafek Václav , Skříšovská Tamara , Djakow Jana , Kosinová Martina , Havránková Pavla , Štourač Petr
Published: September 2022

Traditionally, uncuffed tubes were used in pediatric patients under 8 years in pursuit of reducing the risk of postextubation stridor. Although computed tomography and magnetic resonance imaging studies confirmed that the subglottic area remains the narrowest part of pediatric airway, the use of uncuffed tubes failed to reduce the risk of subglottic swelling. Properly used cuffed tubes (correct size and correct cuff management) are currently recommended as the first option in emergency, anesthesiology and intensive care in all pediatric patients. Clinical practice particularly in the intensive care area remains variable. This review aims to analyze the current recommendation for airway management in children in emergency, anesthesiology and intensive care settings.
Sensitivity Analysis for Process Parameters in Mo2FeB2 Ternary Boride Coating by Laser Cladding
Authors: Zhang Hao , Pan Yingjun , Zhang Yang , Lian Guofu , Cao Qiang , Yang Jianghuai
Published: September 2022

The process parameters of laser cladding have a significant influence on the forming quality of the coating. This research investigates the relationship between input process parameters (laser power, scanning speed, pre-placed thickness) and output responses (height, width, dilution rate) of Mo2FeB2 coating through sensitivity analysis. The microstructure and properties of selected coatings were analyzed to discuss the corresponding relations. The results showed that the laser power positively affected the coating width and dilution rate, while negatively affecting the coating height. The scanning speed had a negligible effect on the height and dilution rate. The pre-placed thickness had a positive influence on the height and width; it negatively affected the dilution rate. Based on the sensitivity analysis, the thickness of the pre-placed coating determined the most sensitivity to the height. The sensitivity of the width to laser power was the highest among all parameters. The sensitivity of dilution rate to laser power and pre-placed powder thickness showed a noticeable impact. When the scanning speed was 3 mm/s, the forming quality of coating had a significant sensitivity for a higher or lower laser power (1.5, 2.1 kW) and higher or lower powder thickness (0.8, 1.2 mm). The analysis of microstructure and microhardness of Mo2FeB2 coating indicates that the Mo2FeB2 coating improves substrate properties. The microhardness of the Mo2FeB2 coating was 4–6 times that of the substrate, and the highest microhardness could be obtained by 1.5 kW laser power, 3 mm/s scanning speed, and 1.2 mm powder thickness from the sensitivity analysis results.
Mn-Doped Glass–Ceramic Bioactive (Mn-BG) Thin Film to Selectively Enhance the Bioactivity of Electrospun Fibrous Polymeric Scaffolds
Authors: Curcio Mariangela , Bochicchio Brigida , Pepe Antonietta , Laezza Antonio , De Stefanis Adriana , Rau Julietta V. , Teghil Roberto , De Bonis Angela
Published: September 2022

In recent years, significant progress has been made in the development of new technologies to meet the demand for engineered interfaces with appropriate properties for osteochondral unit repair and regeneration. In this context, we combined two methodologies that have emerged as powerful approaches for tissue engineering application: electrospinning to fabricate a nanofibrous polymeric scaffold and pulsed laser deposition to tune and control the composition and morphology of the scaffold surface. A multi-component scaffold composed of synthetic and natural polymers was proposed to combine the biocompatibility and suitable mechanical properties of poly(D,L-lactic acid) with the hydrophilicity and cellular affinity of gelatin. As part of a biomimetic strategy for the generation of bi-functional scaffolds, we coated the electrospun fibers with a thin film of a bioactive glass–ceramic material supplemented with manganese ions. The physico-chemical properties and composition of the bi-layered scaffold were investigated, and its bioactivity, in terms of induced mineralization, was tested by incubation in a simulated body fluid buffer. The processes of the inorganic film dissolution and the calcium phosphate phases growth were followed by microscopic and spectroscopic techniques, confirming that a combination of bioactive glass–ceramics and nanofibrous scaffolds has promising potential in the regeneration of osteochondral tissue due to its ability to induce mineralization in connective tissues.
The Recent Progress of Two-Dimensional Transition Metal Dichalcogenides and Their Phase Transition
Authors: Chen Hui , Zhang Jiwei , Kan Dongxiao , He Jiabei , Song Mengshan , Pang Jianhua , Wei Songrui , Chen Kaiyun
Published: September 2022

Graphene is attracting much attention in condensed matter physics and material science in the two-dimensional(2D) system due to its special structure, and mechanical and electronic properties. However, the lack of electronic bandgap and uncontrollable phase structure greatly limit its application in semiconductors, such as power conversion devices, optoelectronic devices, transistors, etc. During the past few decades, 2D transition metal dichalcogenides (TMDs) with much more phase structures have attracted intensive research interest in fundamental studies and practical applications for energy storage, as catalysts, and in piezoelectricity, energy harvesting, electronics, optoelectronic, and spintronics. The controllable phase transition also provides another degree of freedom to pave the way for more novel devices. In this review, we introduce the abundant phase structures of 2D-TMDs, including 2H, 1T, 1T’ and charge density waves, and highlight the corresponding attractive properties and applications of each phase. In addition, all the possible methods to trigger the phase transition in TMDs are systematically introduced, including strain engineering, electron doping, alloying, thermal, electric field, and chemical absorption. Finally, the outlook of future opportunities in TMD phase transitions and the corresponding challenges, including both the synthesis and applications, are also addressed.