bluuebunny/crossref_metadata_2025 huggingface dataset:
Preservation and Restoration of an Old Wooden Icon with Complex Carved Ornaments, in a Conservation State of Precollapse
Authors: Nica Liliana , Vasilache Viorica , Drob Ana , Pruteanu Silvea , Sandu Ion
Published: May 2022

Wooden icons used in liturgical activities suffer a series of evolutionary deteriorations and degradations over time, due to improper storage and use conditions. The deterioration of the physical state of the structural-functional elements and degradation of the chemical nature of the components often lead old easel paintings to precarious preservation (almost close to pre-collapse), impossible to use or display as an artifact. In this study was included an old oil-painted icon on a carved linden wood support with fine gilded ornaments, which frames a central icon (“Coronation of Virgin Mary”) and a complex Menaion icon system with iconographic scenes. It was made by an anonymous author and dates back to the late 18th and early 19th centuries. As the icon has a special beauty and an ornamental and iconographic complexity, having a great heritage value, it required the elaboration of an optimal preservation–restoration protocol for the museum exhibition. Initially, the nature of the pictorial materials was determined, and their preservation state was evaluated using the OM, SEM-EDX, micro-FTIR methods, and CIE L*a*b* colorimetry and visible and UV reflectography were used in the evaluation of the wash test and in compatibility studies. Based on the data obtained, the optimal materials and procedures for structural reintegration were selected (including support fillings and filling of gaps), then chromatic reintegration and gilding, followed by final revarnishing, with or without patination additives.
An Experimental and Theoretical Comparison of 3D Models for Ultrasonic Non-Destructive Testing of Cracks: Part I, Embedded Cracks
Authors: Darmon Michel , Toullelan Gwenael , Dorval Vincent
Published: May 2022

Ultrasonic Non-Destructive Testing (NDT) methods are broadly used for detection and characterization/imaging of cracks. Simulation is of great interest for designing such NDT methods. To model the ultrasonic 3D response of a crack, ultrasonic high frequency asymptotic (semi-analytical) models (such as the Physical Theory of Diffraction—PTD) are known to provide accurate predictions for most classical NDT configurations, and 3D numerical models have also emerged more recently. The aim of this paper is to carry out for the first time an experimental and theoretical comparison of 3D models for ultrasonic NDT of embedded cracks in 3D configurations. Semi-analytical models and a hybrid 3D FEM strategy—combining high-order spectral Finite Elements Method (FEM) for flaw scattering and an asymptotic ray model for beam propagation—have been compared. Both numerical validations and comparisons between simulation and experiments prove the effectiveness of PTD in numerous configurations but validate and demonstrate the improvement provided by the 3D hybrid code, notably for small flaws compared to the wavelength and for shear waves.
Characterization of New Probiotic Isolates from Fermented Ajwa Dates of Madinah and Their Anti-Inflammatory Potential
Authors: Malki Abdullah Al , Yoon So-Hyun , Firoz Ahmad , Ali Hani Mohammed , Park Yong-Ha , Hor Yan-Yan , Rather Irfan A.
Published: May 2022

A total of 20 Lactobacillus strains isolated from fermented dates were tested for their probiotic potential by comparing their pH stability, resistance to low pH, and ability to tolerate bile salts. Out of 20 strains, 3 strains named as Lactobacillus pentosus KAU001, Lactiplantibacillus pentosus KAU002, and Lactiplantibacillus plantarum KAU003 had a high tolerance of acids and bile salts and the capability to adhere to the intestinal wall. In addition, the three isolates were tested for their anti-oxidation, anti-glucosidase inhibition, cholesterol-lowering, and anti-inflammation properties. Among them, strain KAU001 and KAU002 inhibited α-glucosidase, lowered cholesterol level, inhibited nitric oxide production, and showed a higher anti-oxidative ability that was significantly better than strain KAU003. Both strains also significantly inhibited the release of inflammatory mediators such as TNF-α, IL-6 and IL-10 induced by LPS on RAW 264.7 macrophages (p < 0.001). The results indicated that KAU001 and KAU002 have the highest probiotic potential, potentially modulating metabolic health and reducing pro-inflammatory cytokines in response to allergic reactions.
Histological Change in Cucumber Tissue and Cellulase Activity of Plectosphaerella melonis Strain 502
Authors: Patyka Volodymyr , Tsekhmister Hanna , Kopylov Yevhenii , Kyslynska Anna , Kalinichenko Antonina , Sporek Monika , Stebila Jan
Published: May 2022

In the last ten years, many countries around the world recorded a new disease of the Cucurbitaceae, the agent of which was P. melonis. The ability of P. melonis 502 to form intracellular mycelium in the epidermal and parenchymal tissues of roots was shown. Leading tissues (xylem and phloem) did not colonize, which indicates the impossibility of plant vessel clogging and shows the fungus’s biochemical effects on plants, which causes the process of pathogenesis. P. melonis 502 is able to develop in a wide range of pH values, while the pH-optimum is 8.5. P. melonis 502 is able to adjust the pH of the medium to the optimal value—8.5. We also showed that cellulase enzyme synthesis depends on pH. We studied the exo-, endo- and β-glucasidase activity of P. melonis 502 and found that the highest activity of cellulase enzymes was on a medium whose pH was 8.5. In the process, the total cellulolytic activity was 0.326 U mL−1, exoglucanase activity—0.539 U mL−1, endoglucanase activity—0.950 U mL−1 and β-glucosidase activity—0.795 U mL−1.
Neutrophil Gelatinase-Associated Lipocalin (NGAL) in Peritoneal Dialytic Effluent: Preliminary Results on the Comparison between Two Different Methods in Patients with and without Peritonitis
Authors: Virzì Grazia Maria , Milan Manani Sabrina , Marcello Matteo , Costa Elisa , Marturano Davide , Tantillo Ilaria , Lerco Silvia , Corradi Valentina , De Cal Massimo , Martino Francesca K. , Giuliani Anna , Carta Mariarosa , Giavarina Davide , Ronco Claudio , Zanella Monica
Published: May 2022

Neutrophil gelatinase-associated lipocalin (NGAL) is a lipocalin involved in the immune response and is significantly high in the peritoneal dialytic effluent (PDE) of peritoneal dialysis (PD) patients with inflammation of the peritoneum membrane (peritonitis). The focus of this study was to match two different techniques for peritoneal NGAL evaluation: NGAL point-of-care test-POCT (NGAL Dipstick—NGALds) versus the laboratory-based NGAL assay and with the white cell count in PDE. In this study, we included 30 PD patients: 17 with peritonitis and 13 without. Peritoneal NGAL was tested by a turbidimetric immunoassay and by NGALds. We noticed a good positive linear correlation between the POCT results and the laboratory-based test and between the peritoneal NGALds and white cell count in PDE (both, p < 0.01). NGALds values resulted in being elevated in patients with peritonitis (300 ng/mL, IQR 300–600) in comparison to patients without (100 ng/mL, IQR 50–150) (p < 0.01). Furthermore, the NGALds test was performed in a median time of 20 mins (IQR 18–21) in comparison with the median time of 65 mins (IQR 55–69) necessary for the laboratory-based test (p < 0.01). The results of the NGALds were coherent with the laboratory-based NGAL and with the white cell count in PDE; furthermore, it was a user-friendly method with real-time findings. NGALds could be an extra tool for the diagnosis of peritonitis, helpful at the bedside of the patient, shortening the length of diagnosis, and if the laboratory-based NGAL test is not accessible.
Performance of Steel-Bolt-Connected Industrialized Building System Frame Subjected to Hydrodynamic Force
Authors: Auwalu Abubakar Sharif , Noor Norhazilan Md , Ahmad Shah Mohamad Shazwan , Umar Sarehati , Amran Mugahed , Adamu Musa , Vatin Nikolai Ivanovich , Fediuk Roman
Published: May 2022

People need durable shelters for living safely due to devastation caused by flooding in some areas, and it is not easy to mitigate the frequency and intensity of the flooding. Therefore, in this research, an industrialized building system (IBS) has been proposed as one of the best solutions. However, most of the existing IBSs were not designed and tested for resisting a sudden horizontal impact. Furthermore, the joints of some IBSs would likely be vulnerable to failure when subjected to a horizontal impact. There is a need to develop a bolt-connected IBS that is able to withstand a horizontal impact load. Thus, this study aimed to investigate the performance of steel-bolt-connected IBS frames subjected to the sudden impact of hydrodynamic force. Autodesk computational fluid dynamic (CFD) simulation was used for optimizing the laboratory experiment. A 1:5-scale IBS frame was designed and tested for the dam-break test using 1 m, 2 m, and 3 m reservoir water levels. The results showed that the bolt connections were very effective and robust in the IBS frame. They also restricted damages from spreading to other structural components due to energy dissipation. The main findings of this study are crucial to improving the current IBS method of construction.
Current Advances and Future Aspects of Sweetener Synergy: Properties, Evaluation Methods and Molecular Mechanisms
Authors: Wang Congrui , Liu Yi , Zhao Xiangzhong , Liu Bo
Published: May 2022

Sweetener synergy is the phenomenon in which certain combinations of sweeteners work more effectively than the theoretical sum of the effects of each components. It provides benefits in reducing sweetener dosages and improving their sweetness. Many mixtures of sweeteners with synergistic effects have been reported up to now. Both artificial high-intensity sweeteners and natural sweeteners are popularly used in sweetener mixtures for synergism, although the former seem to display more potential to exhibit synergy than the latter. Furthermore, several evaluation methods to investigate sweetener synergy have been applied, which could lead to discrepancies in results. Moreover, structurally dissimilar sweeteners could cooperatively bind at the different sites in the sweet taste receptor T1R2/T1R3 to activate the receptor, and their hydration characters/packing characteristics in solvents could affect their interaction with the receptor, providing the preliminary explanations for the molecular basis of sweetener synergy. In this article, we firstly present a systematic review, analysis and comment on the properties, evaluation methods and molecular mechanisms of sweetener synergy. Secondly, challenges of sweetener synergy in both theory and practice and possible strategies to overcome these limitations are comprehensively discussed. Finally, future perspectives for this important performance in human sweet taste perception are proposed.
Investigation into the Explicit Solutions of the Integrable (2+1)—Dimensional Maccari System via the Variational Approach
Authors: Wang Kang-Jia , Si Jing
Published: May 2022

In this paper, the integrable (2+1)-dimensional Maccari system (MS), which can model many complex phenomena in hydrodynamics, plasma physics and nonlinear optics, is investigated by the variational approach (VA). This proposed approach that based on the variational theory and Ritz-like method can construct the explicit solutions via the stationary conditions only taking two steps. Finally, the dynamic behaviors of the solutions are exhibited by choosing the appropriate parameters through the 3-D and density plots. It can be seen that the proposed method is concise and straightforward, and can be adopted to study the travelling wave theory in physics.
COVID-19 Tweets Classification Based on a Hybrid Word Embedding Method
Authors: Didi Yosra , Walha Ahlam , Wali Ali
Published: May 2022

In March 2020, the World Health Organisation declared that COVID-19 was a new pandemic. This deadly virus spread and affected many countries in the world. During the outbreak, social media platforms such as Twitter contributed valuable and massive amounts of data to better assess health-related decision making. Therefore, we propose that users’ sentiments could be analysed with the application of effective supervised machine learning approaches to predict disease prevalence and provide early warnings. The collected tweets were prepared for preprocessing and categorised into: negative, positive, and neutral. In the second phase, different features were extracted from the posts by applying several widely used techniques, such as TF-IDF, Word2Vec, Glove, and FastText to capture features’ datasets. The novelty of this study is based on hybrid features extraction, where we combined syntactic features (TF-IDF) with semantic features (FastText and Glove) to represent posts accurately, which helps in improving the classification process. Experimental results show that FastText combined with TF-IDF performed better with SVM than the other models. SVM outperformed the other models by 88.72%, as well as for XGBoost, with an 85.29% accuracy score. This study shows that the hybrid methods proved their capability of extracting features from the tweets and increasing the performance of classification.
De Novo Transcriptome of the Flagellate Isochrysis galbana Identifies Genes Involved in the Metabolism of Antiproliferative Metabolites
Authors: Riccio Gennaro , Martinez Kevin A. , Ianora Adrianna , Lauritano Chiara
Published: May 2022

Haptophytes are important primary producers in the oceans, and among the phylum Haptophyta, the flagellate Isochrysis galbana has been found to be rich in high-value compounds, such as lipids, carotenoids and highly branched polysaccharides. In the present work, I. galbana was cultured and collected at both stationary and exponential growth phases. A transcriptomic approach was used to analyze the possible activation of metabolic pathways responsible for bioactive compound synthesis at the gene level. Differential expression analysis of samples collected at the exponential versus stationary growth phase allowed the identification of genes involved in the glycerophospholipid metabolic process, the sterol biosynthetic process, ADP-ribose diphosphatase activity and others. I. galbana raw extracts and fractions were tested on specific human cancer cells for possible antiproliferative activity. The most active fractions, without affecting normal cells, were fractions enriched in nucleosides (fraction B) and triglycerides (fraction E) for algae collected in the exponential growth phase and fraction E for stationary phase samples. Overall, transcriptomic and bioactivity data confirmed the activation of metabolic pathways involved in the synthesis of bioactive compounds giving new insights on possible Isochrysis applications in the anticancer sector.
Immunometabolic Markers in a Small Patient Cohort Undergoing Immunotherapy
Authors: Hofbauer Joshua , Hauck Andreas , Matos Carina , Babl Nathalie , Decking Sonja-Maria , Rechenmacher Michael , Schulz Christian , Regotta Sabine , Mickler Marion , Haferkamp Sebastian , Siska Peter J. , Herr Wolfgang , Renner Kathrin , Kreutz Marina , Schnell Annette
Published: May 2022

Although the discovery of immune checkpoints was hailed as a major breakthrough in cancer therapy, generating a sufficient response to immunotherapy is still limited. Thus, the objective of this exploratory, hypothesis-generating study was to identify potentially novel peripheral biomarkers and discuss the possible predictive relevance of combining scarcely investigated metabolic and hormonal markers with immune subsets. Sixteen markers that differed significantly between responders and non-responders were identified. In a further step, the correlation with progression-free survival (PFS) and false discovery correction (Benjamini and Hochberg) revealed potential predictive roles for the immune subset absolute lymphocyte count (rs = 0.51; p = 0.0224 *), absolute basophil count (rs = 0.43; p = 0.04 *), PD-1+ monocytes (rs = −0.49; p = 0.04 *), hemoglobin (rs = 0.44; p = 0.04 *), metabolic markers LDL (rs = 0.53; p = 0.0224 *), free androgen index (rs = 0.57; p = 0.0224 *) and CRP (rs = −0.46; p = 0.0352 *). The absolute lymphocyte count, LDL and free androgen index were the most significant individual markers, and combining the immune subsets with the metabolic markers into a biomarker ratio enhanced correlation with PFS (rs = −0.74; p ≤ 0.0001 ****). In summary, in addition to well-established markers, we identified PD-1+ monocytes and the free androgen index as potentially novel peripheral markers in the context of immunotherapy. Furthermore, the combination of immune subsets with metabolic and hormonal markers may have the potential to enhance the power of future predictive scores and should, therefore, be investigated further in larger trials.
Oxygen Therapy during Exercise in Patients with Interstitial Lung Diseases
Authors: Viani Magda , Ventura Vittoria , Bianchi Francesco , d’Alessandro Miriana , Bergantini Laura , Sestini Piersante , Bargagli Elena
Published: May 2022

Introduction: ILDs are a varied group of diffuse parenchymal lung diseases associated with high morbidity and mortality. Current treatments can only slow their progression but not cure the disease. Other treatments such as oxygen therapy can also be used as support. We know very little about the effects of oxygen therapy on patients with ILDs. The aim of this study was to collect data from the literature in order to determine whether oxygen therapy can actually decrease the mortality rate or whether it is only suitable for supportive therapy for patients with ILDs. Methods: We reviewed the literature since 2010 on oxygen therapy during exercise in patients with ILDs. Studies that used cardio-pulmonary tests were excluded. We only reviewed those that used the 6 min walking test (6MWT) or the free walking test. We located 11 relevant articles. Results: All the articles except a Japanese study showed an augmentation in oxyhaemoglobin saturation during exercise when oxygen was supplied. A 2018 study called AmbOx provided important data on the effects of oxygen therapy during daily activities, showing significant improvements in quality of life. Conclusions: This review showed that the literature on the benefits of oxygen therapy in patients with ILDs does not provide sufficient evidence to draft specific guidelines. It was not possible to conclude whether oxygen therapy has an effect on mortality or can only play a supportive role.
Targeted Inhibition of O-Linked β-N-Acetylglucosamine Transferase as a Promising Therapeutic Strategy to Restore Chemosensitivity and Attenuate Aggressive Tumor Traits in Chemoresistant Urothelial Carcinoma of the Bladder
Authors: Lee Hye , Kang Mi , Kwon Young-Ju , Abdi Nansa Sama , Jung Eui , Kim Sung , Lee Sang-Jin , Jeong Kyung-Chae , Kim Youngwook , Cheong Heesun , Seo Ho
Published: May 2022

Acquisition of acquired chemoresistance during treatment cycles in urothelial carcinoma of the bladder (UCB) is the major cause of death through enhancing the risk of cancer progression and metastasis. Elevated glucose flux through the abnormal upregulation of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) controls key signaling and metabolic pathways regulating diverse cancer cell phenotypes. This study showed that OGT expression levels in two human UCB cell models with acquired resistance to gemcitabine and paclitaxel were significantly upregulated compared with those in parental cells. Reducing hyper-O-GlcNAcylation by OGT knockdown (KD) markedly facilitated chemosensitivity to the corresponding chemotherapeutics in both cells, and combination treatment with OGT-KD showed more severe growth defects in chemoresistant sublines. We subsequently verified the suppressive effects of OGT-KD monotherapy on cell migration/invasion in vitro and xenograft tumor growth in vivo in chemoresistant UCB cells. Transcriptome analysis of these cells revealed 97 upregulated genes, which were enriched in multiple oncogenic pathways. Our final choice of suspected OGT glycosylation substrate was VCAN, S1PR3, PDGFRB, and PRKCG, the knockdown of which induced cell growth defects. These findings demonstrate the vital role of dysregulated OGT activity and hyper-O-GlcNAcylation in modulating treatment failure and tumor aggression in chemoresistant UCB.
Analyzing Human Periodontal Soft Tissue Inflammation and Drug Responses In Vitro Using Epithelium-Capillary Interface On-a-Chip
Authors: Jin Laidi , Kou Ni , An Fan , Gao Zehang , Tian Tian , Hui Jianan , Chen Chen , Ma Guowu , Mao Hongju , Liu Huiying
Published: May 2022

The gingival epithelium–capillary interface is a unique feature of periodontal soft tissue, preserving periodontal tissue homeostasis and preventing microorganism and toxic substances from entering the subepithelial tissue. However, the function of the interface is disturbed in periodontitis, and mechanisms of the breakdown of the interface are incompletely understood. To address these limitations, we developed a microfluidic epithelium–capillary barrier with a thin culture membrane (10 μm) that closely mimics the in vivo gingival epithelial barrier with an immune micro-environment. To test the validity of the fabricated gingival epithelial barrier model, epithelium–capillary interface-on-a-chip was cultured with human gingival epithelial cells (HGECs) and human vascular endothelial cells (HUVEC). Their key properties were tested using optical microscope, transepithelial/transendothelial electrical resistance (TEER), and permeability assays. The clear expression of VE-cadherin revealed the tight junctions in endothelial cells. Live/dead assays indicated a high cell viability, and the astrocytic morphology of HGE cells was confirmed by F-actin immunostaining. By the third day of cell culture, TEER levels typically exceeded in co-cultures. The resultant permeability coefficients showed a significant difference between 70 kDa and 40 kDa FITC-dextran. The expression of protein intercellular cell adhesion molecule (ICAM-1) and human beta defensin-2 (HBD2) decreased when exposed to TNF-α and LPS, but recovered with the NF-κB inhibitor treatment- Pyrrolidinedithiocarbamic acid (PDTC), indicating the stability of the fabricated chip. These results demonstrate that the developed epithelium-capillary interface system is a valid model for studying periodontal soft tissue function and drug delivery.
Investigation and Comparison of Specific Antibodies’ Affinity Interaction with SARS-CoV-2 Wild-Type, B.1.1.7, and B.1.351 Spike Protein by Total Internal Reflection Ellipsometry
Authors: Plikusiene Ieva , Maciulis Vincentas , Juciute Silvija , Maciuleviciene Ruta , Balevicius Saulius , Ramanavicius Arunas , Ramanaviciene Almira
Published: May 2022

SARS-CoV-2 vaccines provide strong protection against COVID-19. However, the emergence of SARS-CoV-2 variants has raised concerns about the efficacy of vaccines. In this study, we investigated the interactions of specific polyclonal human antibodies (pAb-SCoV2-S) produced after vaccination with the Vaxzevria vaccine with the spike proteins of three SARS-CoV-2 variants of concern: wild-type, B.1.1.7, and B.1.351. Highly sensitive, label-free, and real-time monitoring of these interactions was accomplished using the total internal reflection ellipsometry method. Thermodynamic parameters such as association and dissociation rate constants, the stable immune complex formation rate constant (kr), the equilibrium association and dissociation (KD) constants and steric factors (Ps) were calculated using a two-step irreversible binding mathematical model. The results obtained show that the KD values for the specific antibody interactions with all three types of spike protein are in the same nanomolar range. The KD values for B.1.1.7 and B.1.351 suggest that the antibody produced after vaccination can successfully protect the population from the alpha (B.1.1.7) and beta (B.1.351) SARS-CoV-2 mutations. The steric factors (Ps) obtained for all three types of spike proteins showed a 100-fold lower requirement for the formation of an immune complex when compared with nucleocapsid protein.
Motor Imagery Classification via Kernel-Based Domain Adaptation on an SPD Manifold
Authors: Jiang Qin , Zhang Yi , Zheng Kai
Published: May 2022

Background: Recording the calibration data of a brain–computer interface is a laborious process and is an unpleasant experience for the subjects. Domain adaptation is an effective technology to remedy the shortage of target data by leveraging rich labeled data from the sources. However, most prior methods have needed to extract the features of the EEG signal first, which triggers another challenge in BCI classification, due to small sample sets or a lack of labels for the target. Methods: In this paper, we propose a novel domain adaptation framework, referred to as kernel-based Riemannian manifold domain adaptation (KMDA). KMDA circumvents the tedious feature extraction process by analyzing the covariance matrices of electroencephalogram (EEG) signals. Covariance matrices define a symmetric positive definite space (SPD) that can be described by Riemannian metrics. In KMDA, the covariance matrices are aligned in the Riemannian manifold, and then are mapped to a high dimensional space by a log-Euclidean metric Gaussian kernel, where subspace learning is performed by minimizing the conditional distribution distance between the sources and the target while preserving the target discriminative information. We also present an approach to convert the EEG trials into 2D frames (E-frames) to further lower the dimension of covariance descriptors. Results: Experiments on three EEG datasets demonstrated that KMDA outperforms several state-of-the-art domain adaptation methods in classification accuracy, with an average Kappa of 0.56 for BCI competition IV dataset IIa, 0.75 for BCI competition IV dataset IIIa, and an average accuracy of 81.56% for BCI competition III dataset IVa. Additionally, the overall accuracy was further improved by 5.28% with the E-frames. KMDA showed potential in addressing subject dependence and shortening the calibration time of motor imagery-based brain–computer interfaces.
Determinants of HIV Testing during Pregnancy among Pregnant Sudanese Women: A Cross-Sectional Study
Authors: Elsiddig Elsheikh Ibrahim , Crutzen Rik , Adam Ishag , Ibrahim Abdelraheem Salah , Van den Borne Hubertus W.
Published: May 2022

More than 90% of children who are HIV positive were infected via mother-to-child transmission (MTCT). In Sudan, HIV testing rates during pregnancy remain low. This study aimed to understand the key determinants of HIV testing and their association with pregnant women’s intention to undergo HIV test during pregnancy. A cross-sectional survey was conducted among 770 Sudanese pregnant women attending Antenatal care (ANC) visits at maternity hospitals. Based on the flow of antenatal care attendants, the calculated sample size was proportionally allocated to the hospitals. Doctors were most influential regarding pregnant women’s decision to undergo an HIV test during pregnancy (78.8%). Younger women were more likely to be tested. Most participants (68.9%) had high susceptibility with respect to HIV. Nearly half (48.3%) had a positive attitude towards HIV testing. Self-efficacy with regard to HIV testing was high (59.1%). Women with high self-efficacy and perceived susceptibility were more likely to have a greater intention to be tested for HIV. No significant association was found with perceived severity and stigma. Our study shows that the intention to undergo HIV testing among pregnant women is influenced by doctors and associated with self-efficacy and perceived susceptibility, which are important avenues for future intervention efforts.
Disasters, Diagnosis, and Distress: Multiple Perspectives, Populations, and Methodologies
Authors: North Carol S. , Pollio David E. , Pollio Elizabeth Whitney
Published: May 2022

Disaster mental health is a consequential topic in today’s world in which disasters are increasing in both numbers and magnitude and inflicting deep psychological wounds across wide populations [...]
Assembly Solution for Modular Buildings: Development of an Automated Connecting Device for Light-Framed Structures
Authors: Picard Laurence , Blanchet Pierre , Bégin-Drolet André
Published: May 2022

The prefabricated construction industry, also known as off-site construction, has been operating in North America for several years now and differs from traditional construction in its much shorter project timelines, lower costs, and increased build quality. However, the lack of a suitable and efficient assembly solution has been identified by many as a barrier to the use of off-site construction for larger buildings. To maximise the benefits of off-site manufacturing for multistorey buildings, an automated connection solution is presented in this paper. A new plug-in self-locking device was developed according to the following product design phases: on-site observations, definition of the problem and product specifications, solution generation, prototyping, fabrication, and testing. The plug-in self-locking device allows the assembly process to be accelerated by eliminating the fastening steps and a higher completion of modules off-site to be achieved. The design bears the compressive, tensile, and shear loads and contributes to the load path of the building.
Early Assessment of Chemotherapy Response in Advanced Non-Small Cell Lung Cancer with Circulating Tumor DNA
Authors: Yaung Stephanie J. , Woestmann Corinna , Ju Christine , Ma Xiaoju Max , Gattam Sandeep , Zhou Yiyong , Xi Liu , Pal Subrata , Balasubramanyam Aarthi , Tikoo Nalin , Heussel Claus Peter , Thomas Michael , Kriegsmann Mark , Meister Michael , Schneider Marc A. , Herth Felix J. , Wehnl Birgit , Diehn Maximilian , Alizadeh Ash A. , Palma John F. , Muley Thomas
Published: May 2022

Monitoring treatment efficacy early during therapy could enable a change in treatment to improve patient outcomes. We report an early assessment of response to treatment in advanced NSCLC using a plasma-only strategy to measure changes in ctDNA levels after one cycle of chemotherapy. Plasma samples were collected from 92 patients with Stage IIIB-IV NSCLC treated with first-line chemo- or chemoradiation therapies in an observational, prospective study. Retrospective ctDNA analysis was performed using next-generation sequencing with a targeted 198-kb panel designed for lung cancer surveillance and monitoring. We assessed whether changes in ctDNA levels after one or two cycles of treatment were associated with clinical outcomes. Subjects with ≤50% decrease in ctDNA level after one cycle of chemotherapy had a lower 6-month progression-free survival rate (33% vs. 58%, HR 2.3, 95% CI 1.2 to 4.2, log-rank p = 0.009) and a lower 12-month overall survival rate (25% vs. 70%, HR 4.3, 95% CI 2.2 to 9.7, log-rank p < 0.001). Subjects with ≤50% decrease in ctDNA level after two cycles of chemotherapy also had shorter survival. Using non-invasive liquid biopsies to measure early changes in ctDNA levels in response to chemotherapy may help identify non-responders before standard-of-care imaging in advanced NSCLC.
Preclinical Head and Neck Squamous Cell Carcinoma Models for Combined Targeted Therapy Approaches
Authors: Schoenwaelder Nina , Krause Mareike , Freitag Thomas , Schneider Björn , Zonnur Sarah , Zimpfer Annette , Becker Anne Sophie , Salewski Inken , Strüder Daniel Fabian , Lemcke Heiko , Grosse-Thie Christina , Junghanss Christian , Maletzki Claudia
Published: May 2022

This study aimed to refine combined targeted approaches on well-characterized, low-passage tumor models. Upon in vivo xenografting in immunodeficient mice, three cell lines from locally advanced or metastatic HNSCC were established. Following quality control and basic characterization, drug response was examined after therapy with 5-FU, Cisplatin, and cyclin-dependent kinase inhibitors (abemaciclib, THZ1). Our cell lines showed different in vitro growth kinetics, morphology, invasive potential, and radiosensitivity. All cell lines were sensitive to 5-FU, Cisplatin, and THZ1. One cell line (HNSCC48 P0 M1) was sensitive to abemaciclib. Here, Cyto-FISH revealed a partial CDKN2a deletion, which resulted from a R58* mutation. Moreover, this cell line demonstrated chromosome 12 polysomy, accompanied by an increase in CDK4-specific copy numbers. In HNSCC16 P1 M1, we likewise identified polysomy-associated CDK4-gains. Although not sensitive to abemaciclib per se, the cell line showed a G1-arrest, an increased number of acidic organelles, and a swollen structure. Notably, intrinsic resistance was conquered by Cisplatin because of cMYC and IDO-1 downregulation. Additionally, this Cisplatin-CDKI combination induced HLA-ABC and PD-L1 upregulation, which may enhance immunogenicity. Performing functional and molecular analysis on patient-individual HNSCC-models, we identified CDK4-gains as a biomarker for abemaciclib response prediction and describe an approach to conquer intrinsic CDKI resistance.
Ce1−xFexVO4 with Improved Activity for Catalytic Reduction of NO with NH3
Authors: Wang Li , Wang Junbo , Cheng Heping , Zhou Xiangxiang , Ma Zhen
Published: May 2022

A series of Ce1−xFexVO4 (x = 0, 0.25, 0.50, 0.75, 1) catalysts prepared by modified hydrothermal synthesis were used for selective catalytic reduction (SCR) of NOx with NH3. Among them, Ce0.5Fe0.5VO4 showed the highest catalytic activity. The catalysts were characterized by X-ray diffraction (XRD), N2 adsorption–desorption, scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), X-ray fluorescence (XRF), X-ray photoelectron spectroscopy (XPS), temperature-programmed reduction using H2 (H2-TPR), and temperature-programmed desorption of NH3 (NH3-TPD). The results indicated the formation of Ce-Fe-V-O solid solutions. The average oxidation states (AOS) of Ce, Fe, V, and O atoms changed obviously with the incorporation of Fe3+ into CeVO4, and the acidity of Ce0.5Fe0.5VO4 differs from that of CeVO4 and FeVO4. The presence of more acid sites and a sharp increase in active oxygen species in Ce0.5Fe0.5VO4 effectively improved the selective catalytic reduction (SCR) activity.
Assessment of a Novel Photocatalytic TiO2-Zirconia Ultrafiltration Membrane and Combination with Solar Photo-Fenton Tertiary Treatment of Urban Wastewater
Authors: Deemter Dennis , Coelho Fabricio Eduardo Bortot , Oller Isabel , Malato Sixto , Amat Ana M.
Published: May 2022

The objective of this study was to assess the combination of a photocatalytic TiO2-coated ZrO2 UF membrane with solar photo-Fenton treatment at circumneutral pH for the filtration and treatment of urban wastewater treatment plant (UWWTP) effluents. Photocatalytic self-cleaning properties were tested with a UWWTP effluent under irradiation in a solar simulator. Then, both the permeates and retentates from the membrane process were treated using the solar photo-Fenton treatment. The UWWTP effluent was spiked with caffeine (CAF), imidacloprid (IMI), thiacloprid (THI), carbamazepine (CBZ) and diclofenac (DCF) at an initial concentration of 100 µg/L each. Retention on the membrane of Pseudomonas Aeruginosa (P. Aeruginosa), a Gram-negative bacterial strain, was tested with and without irradiation. It was demonstrated that filtration of a certain volume of UWWTP effluent in the dark is possible, and the original conditions can then be recovered after illumination. The photocatalytic membrane significantly reduces the turbidity of the UWWTP effluent, significantly increasing the degradation efficiency of the subsequent solar photo-Fenton treatment. The results showed that the membrane allowed consistent retention of P. Aeruginosa at an order of magnitude of 1 × 103–1 × 104 CFU/mL.
Synthetic Routes to Crystalline Complex Metal Alkyl Carbonates and Hydroxycarbonates via Sol–Gel Chemistry—Perspectives for Advanced Materials in Catalysis
Authors: Hanf Schirin , Lizandara-Pueyo Carlos , Emmert Timo Philipp , Jevtovikj Ivana , Gläser Roger , Schunk Stephan Andreas
Published: May 2022

Metal alkoxides are easily available and versatile precursors for functional materials, such as solid catalysts. However, the poor solubility of metal alkoxides in organic solvents usually hinders their facile application in sol–gel processes and complicates access to complex carbonate or oxidic compounds after hydrolysis of the precursors. In our contribution we have therefore shown three different solubilization strategies for metal alkoxides, namely the derivatization, the hetero-metallization and CO2 insertion. The latter strategy leads to a stoichiometric insertion of CO2 into the metal–oxygen bond of the alkoxide and the subsequent formation of metal alkyl carbonates. These precursors can then be employed advantageously in sol–gel chemistry and, after controlled hydrolysis, result in chemically defined crystalline carbonates and hydroxycarbonates. Cu- and Zn-containing carbonates and hydroxycarbonates were used in an exemplary study for the synthesis of Cu/Zn-based bulk catalysts for methanol synthesis with a final comparable catalytic activity to commercial standard reference catalysts.
Highly Efficient and Selective Carbon-Doped BN Photocatalyst Derived from a Homogeneous Precursor Reconfiguration
Authors: Lu Qiong , An Jing , Duan Yandong , Luo Qingzhi , Shang Yunyun , Liu Qiunan , Tang Yongfu , Huang Jianyu , Tang Chengchun , Yin Rong , Wang Desong
Published: May 2022

The modification of inert boron nitride by carbon doping to make it an efficient photocatalyst has been considered as a promising strategy. Herein, a highly efficient porous BCN (p-BCN) photocatalyst was synthesized via precursor reconfiguration based on the recrystallization of a new homogeneous solution containing melamine diborate and glucose. Two crystal types of the p-BCN were obtained by regulating the recrystallization conditions of the homogeneous solution, which showed high photocatalytic activities and a completely different CO2 reduction selectivity. The CO generation rate and selectivity of the p-BCN-1 were 63.1 μmol·g−1·h−1 and 54.33%; the corresponding values of the p-BCN-2 were 42.6 μmol·g−1·h−1 and 80.86%. The photocatalytic activity of the p-BCN was significantly higher than those of equivalent materials or other noble metals-loaded nanohybrids reported in the literature. It was found that the differences in the interaction sites between the hydroxyl groups in the boric acid and the homolateral hydroxyl groups in the glucose were directly correlated with the structures and properties of the p-BCN photocatalyst. We expect that the developed approach is general and could be extended to incorporate various other raw materials containing hydroxyl groups into the melamine diborate solution and could modulate precursors to obtain porous BN-based materials with excellent performance.
Features of ZED1227: The First-In-Class Tissue Transglutaminase Inhibitor Undergoing Clinical Evaluation for the Treatment of Celiac Disease
Authors: Büchold Christian , Hils Martin , Gerlach Uwe , Weber Johannes , Pelzer Christiane , Heil Andreas , Aeschlimann Daniel , Pasternack Ralf
Published: May 2022

ZED1227 is a small molecule tissue transglutaminase (TG2) inhibitor. The compound selectively binds to the active state of TG2, forming a stable covalent bond with the cysteine in its catalytic center. The molecule was designed for the treatment of celiac disease. Celiac disease is an autoimmune-mediated chronic inflammatory condition of the small intestine affecting about 1–2% of people in Caucasian populations. The autoimmune disease is triggered by dietary gluten. Consumption of staple foods containing wheat, barley, or rye leads to destruction of the small intestinal mucosa in genetically susceptible individuals, and this is accompanied by the generation of characteristic TG2 autoantibodies. TG2 plays a causative role in the pathogenesis of celiac disease. Upon activation by Ca2+, it catalyzes the deamidation of gliadin peptides as well as the crosslinking of gliadin peptides to TG2 itself. These modified biological structures trigger breaking of oral tolerance to gluten, self-tolerance to TG2, and the activation of cytotoxic immune cells in the gut mucosa. Recently, in an exploratory proof-of-concept study, ZED1227 administration clinically validated TG2 as a “druggable” target in celiac disease. Here, we describe the specific features and profiling data of the drug candidate ZED1227. Further, we give an outlook on TG2 inhibition as a therapeutic approach in indications beyond celiac disease.
A Galactooligosaccharide Product Decreases the Rotavirus Infection in Suckling Rats
Authors: Massot-Cladera Malén , Rigo-Adrover María del Mar , Herrero Laura , Franch Àngels , Castell Margarida , Vulevic Jelena , Pérez-Cano Francisco J. , Lagunas María J. Rodríguez
Published: May 2022

The leading cause of gastroenteritis among young children worldwide is the Group A rotaviruses (RV), which produce a wide range of symptoms, from a limited diarrhea to severe dehydration and even death. After an RV infection, immunity is not complete and less severe re-infections usually occur. These infections could be ameliorated by nutritional interventions with bioactive compounds, such as prebiotics. The aim of this research was to study the impact of a particular galactooligosaccharide (B-GOS) on the RV symptomatology and immune response during two consecutive infections. Lewis neonatal rats were inoculated with SA11 (first RV infection) on day 6 of life and with EDIM (second RV infection) on day 17 of life. B-GOS group was administered by oral gavage with a daily dose of B-GOS between days three to nine of life. Clinical and immunological variables were assessed during both infective processes. In the first infection, after the prebiotic intervention with B-GOS, a lower incidence, duration, and overall severity of the diarrhea (p < 0.05) was observed. In addition, it improved another severity indicator, the fecal weight output, during the diarrhea period (p < 0.05). The second RV infection failed in provoking diarrhea in the groups studied. The immune response during first infection with SA11 was not affected by B-GOS administration and had no impact on second infection, but the prebiotic intervention significantly increased IFN-γ and TNF-α intestinal production after the second infection (p < 0.05). In summary, B-GOS supplementation is able to reduce the incidence and severity of the RV-associated diarrhea and to influence the immune response against RV infections.
Depletion of HIF-1α by Inducible Cre/loxP Increases the Sensitivity of Cultured Murine Hepatocytes to Ionizing Radiation in Hypoxia
Authors: Hamidi Akram , Wolf Alexandra , Dueva Rositsa , Kaufmann Melanie , Göpelt Kirsten , Iliakis George , Metzen Eric
Published: May 2022

The transcription factor hypoxia-inducible factor (HIF) is the main oxygen sensor which regulates adaptation to cellular hypoxia. The aim of this study was to establish cultured murine hepatocyte derived cells (mHDC) as an in vitro model and to analyze the role of HIF-1α in apoptosis induction, DNA damage repair and sensitivity to ionizing radiation (IR). We have crossed C57/BL6 mice that bear loxP sites flanking exon 2 of Hif1a with mice which carry tamoxifen-inducible global Cre expression. From the offspring, we have established transduced hepatocyte cultures which are permanently HIF-1α deficient after tamoxifen treatment. We demonstrated that the cells produce albumin, acetylcholine esterase, and the cytokeratins 8 and 18 which functionally characterizes them as hepatocytes. In moderate hypoxia, HIF-1α deficiency increased IR-induced apoptosis and significantly reduced the surviving fraction of mHDC as compared to HIF-1α expressing cells in colony formation assays. Furthermore, HIF-1α knockout cells displayed increased IR-induced DNA damage as demonstrated by increased generation and persistence of γH2AX foci. HIF-1α deficient cells showed delayed DNA repair after IR in hypoxia in neutral comet assays which may indicate that non-homologous end joining (NHEJ) repair capacity was affected. Overall, our data suggest that HIF-1α inactivation increases radiation sensitivity of mHDC cells.
Metabolomic Profiling in Patients with Heart Failure and Exercise Intolerance: Kynurenine as a Potential Biomarker
Authors: Bekfani Tarek , Bekhite Mohamed , Neugebauer Sophie , Derlien Steffen , Hamadanchi Ali , Nisser Jenny , Hilse Marion S. , Haase Daniela , Kretzschmar Tom , Wu Mei-Fang , Lichtenauer Michael , Kiehntopf Michael , von Haehling Stephan , Schlattmann Peter , Lehmann Gabriele , Franz Marcus , Möbius-Winkler Sven , Schulze Christian
Published: May 2022

Aims: Metabolic and structural perturbations in skeletal muscle have been found in patients with heart failure (HF) both with preserved (HFpEF) and reduced (HFrEF) ejection fraction in association with reduced muscle endurance (RME). We aimed in the current study to create phenotypes for patients with RME and HFpEF compared to RME HFrEF according to their metabolomic profiles and to test the potential of Kynurenine (Kyn) as a marker for RME. Methods: Altogether, 18 HFrEF, 17 HFpEF, and 20 healthy controls (HC) were prospectively included in the current study. The following tests were performed on all participants: isokinetic muscle function tests, echocardiography, spiroergometry, and varied blood tests. Liquid chromatography tandem mass spectrometry was used to quantify metabolites in serum. Results: Except for aromatic and branched amino acids (AA), patients with HF showed reduced AAs compared to HC. Further perturbations were elevated concentrations of Kyn and acylcarnitines (ACs) in HFpEF and HFrEF patients (p < 0.05). While patients with HFpEF and RME presented with reduced concentrations of ACs (long- and medium-chains), those with HFrEF and RME had distorted AAs metabolism (p < 0.05). With an area under the curve (AUC) of 0.83, Kyn shows potential as a marker in HF and RME (specificity 70%, sensitivity 83%). In a multiple regression model consisting of short-chain-ACs, spermine, ornithine, glutamate, and Kyn, the latest was an independent predictor for RME (95% CI: −13.01, −3.30, B: −8.2 per 1 µM increase, p = 0.001). Conclusions: RME in patients with HFpEF vs. HFrEF proved to have different metabolomic profiles suggesting varied pathophysiology. Kyn might be a promising biomarker for patients with HF and RME.
Identification of the Transcriptional Biomarkers Panel Linked to Pathological Remodelling of the Eye Tissues in Various HD Mouse Models
Authors: Mazur-Michałek Iwona , Ruciński Marcin , Sowiński Mateusz , Pietras Paulina , Leśniczak-Staszak Marta , Szaflarski Witold , Isalan Mark , Mielcarek Michal
Published: May 2022

Ocular abnormalities are becoming associated with a spectrum of pathological events in various neurodegenerative diseases. Huntington’s disease (HD) is just such an example of a fatal neurological disorder, where mutated genes (CAG trinucleotide expansions in the Huntingtin gene) have widespread expression, leading to the production of mutant Huntingtin (mHTT) protein. It is well known that mutant HTT protein is prone to form toxic aggregates, which are a typical pathological feature, along with global transcriptome alterations. In this study, we employed well-established quantitative methods such as Affymetrix arrays and quantitative PCR (qPCR) to identify a set of transcriptional biomarkers that will track HD progression in three well-established mouse models: R6/2, R6/1, and HdhQ150. Our array analysis revealed significantly deregulated networks that are related to visual processes and muscle contractions. Furthermore, our targeted quantitative analysis identified a panel of biomarkers with some being dysregulated even at the presymptomatic stage of the disease, e.g., Opn1mw, Opn1sw, and Pfkfb2. Some of the deregulated genes identified in this study have been linked to other genetic ocular disorders such as: GNAT2, a source of achromatopsia, and REEP6, linked to Retinitis pigmentosa. It may thus be a useful platform for preclinical evaluations of therapeutic interventions.