bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative FT-IR Prospecting for Cellulose in Stems of Some Fiber Plants: Flax, Velvet Leaf, Hemp and Jute
Authors: Vârban Rodica , Crișan Ioana , Vârban Dan , Ona Andreea , Olar Loredana , Stoie Andrei , Ștefan Răzvan
Published: September 2021

Plant fibers are sustainable sources of materials for many industries, and can be obtained from a variety of plants. Cellulose is the main constituent of plant-based fibers, and its properties give the characteristics of the fibers obtained. Detailed characterization of cellulosic fibers is often performed after lengthy extraction procedures, while fast screening might bring the benefit of quick qualitative assessment of unprocessed stems. The aim of this research was to define some marker spectral regions that could serve for fast, preliminary qualitative characterization of unprocessed stems from some textile plants through a practical and minimally invasive method without lengthy extraction procedures. This could serve as a screening method for sorting raw materials by providing an accurate overall fingerprint of chemical composition. For this purpose, we conducted comparative Fourier Transform Infrared Spectroscopy (FT-IR) prospecting for quality markers in stems of flax (Linum usitatissimum L.), velvet leaf (Abutilon theophrasti Medik.), hemp (Cannabis sativa L.) and jute (Corchorus olitorius L.). Analysis confirmed the presence of major components in the stems of the studied plants. Fingerprint regions for cellulose signals were attributed to bands at 1420–1428 cm−1 assigned to the crystalline region and 896–898 cm−1 assigned to the amorphous region of cellulose. The optimization of characterization methods for raw materials is important and can find immediate practical applications.
Cancelable Multimodal Biometrics Based on Chaotic Maps
Authors: Ghouzali Sanaa , Nafea Ohoud , Wadood Abdul , Hussain Muhammad
Published: September 2021

Biometric authentication systems raise certain concerns with regard to security, violation of privacy, and storage issues of biometric templates. This paper proposes a protection approach of biometric templates storage in a multimodal biometric system while ensuring both the cancelability of biometric templates and the efficiency of the authentication process. We propose applying a chaotic maps-based transform on the biometric features to address the cancelability issue. We used Logistic map and Torus Automorphism to generate cancelable biometric features of the face and fingerprint minutia points, respectively. Both transformed features would be concatenated and saved in the database of the system instead of the original features. In the authentication stage, the similarity scores of both transformed face and fingerprint templates are computed and fused using the weighted sum rule. The results of the experimentation, conducted using images from the ORL face and FVC2002 DB1 fingerprint databases, demonstrated the higher performance of the proposed approach achieving a genuine accept rate equal to 100%. Moreover, the obtained results confirmed the soundness of the proposed cancelable technique to satisfy the biometric systems’ requirements (i.e., security, revocability, and diversity).
Confidence Learning for Semi-Supervised Acoustic Event Detection
Authors: Liu Yuzhuo , Chen Hangting , Wang Jian , Wang Pei , Zhang Pengyuan
Published: September 2021

In recent years, the involvement of synthetic strongly labeled data, weakly labeled data, and unlabeled data has drawn much research attention in semi-supervised acoustic event detection (SAED). The classic self-training method carries out predictions for unlabeled data and then selects predictions with high probabilities as pseudo-labels for retraining. Such models have shown its effectiveness in SAED. However, probabilities are poorly calibrated confidence estimates, and samples with low probabilities are ignored. Hence, we introduce a confidence-based semi-supervised Acoustic event detection (C-SAED) framework. The C-SAED method learns confidence deliberately and retrains all data distinctly by applying confidence as weights. Additionally, we apply a power pooling function whose coefficient can be trained automatically and use weakly labeled data more efficiently. The experimental results demonstrate that the generated confidence is proportional to the accuracy of the predictions. Our C-SAED framework achieves a relative error rate reduction of 34% in contrast to the baseline model.
Influence of Root Canal Fillings on Alveolar Bone Crest Level—An Observational Cross Sectional CBCT Analysis
Authors: Lubrich Marco , Donnermeyer David , Schäfer Edgar , Bürklein Sebastian
Published: September 2021

The aim of this study was to compare the alveolar bone crest (ABC) level of root canal filled (RCF) teeth without apical periodontitis with corresponding non-filled teeth in the same individual using three-dimensionally cone-beam computed tomography (CBCT) data. Two hundred and thirty-five matching pairs of RCF teeth and corresponding teeth without RCF were selected from a pool of 580 random CBCT-images (voxel size 160–200 µm). Teeth with apical periodontitis, perio-endodontic lesions or surgical endodontic treatment were excluded. The distance between the cemento–enamel-junction (CEJ) and the ABC was assessed centrally mesial, distal, palatal/lingual and buccal at each tooth (∑1880 measuring points) in a standardized manner. Topographic, gender, and age-related relationships were also noted. Data were analyzed using the Kruskal–Wallis-test. The ABC-level between RCF teeth (2.64 ± 1.25 mm) and teeth without RCF (2.61 ± 1.16 mm) did not differ significantly (p > 0.05). No differences concerning localization (maxilla/mandible, tooth type) and gender (p > 0.05) occurred. Overall, ABC-level in the maxilla (2.74 ± 1.48 mm) was significantly lower (p < 0.001) compared to mandibular teeth (2.50 ± 1.41 mm). Patients > 41 years had significantly lower ABC-levels than younger patients (p < 0.05). Men showed a reduced bone level compared to women (p < 0.05). In conclusion, RCF teeth are identical to their non-RCF counterparts, at least in terms of crestal bone level, regardless of the location or type of tooth and the gender of the patient. Thus, root canal treatment is an essential pillar for long-term tooth preservation.
High-Rate Precipitation Occurrence Modulated by Solar Wind High-Speed Streams
Authors: Prikryl Paul , Rušin Vojto , Prikryl Emil A.
Published: September 2021

Extreme weather events, such as heavy rainfall causing floods and flash floods continue to present difficult challenges in forecasting. Using gridded daily precipitation datasets in conjunction with solar wind data it is shown that high-rate precipitation occurrence is modulated by solar wind high-speed streams. Superposed epoch analysis shows a statistical increase in the occurrence of high-rate precipitation following arrivals of high-speed streams from coronal holes, including their recurrence with the solar rotation period of 27 days. These results are consistent with the observed tendency of heavy rainfall leading to floods and flash floods in Japan, Australia, and continental United States to follow arrivals of high-speed streams. A possible role of the solar wind–magnetosphere–ionosphere–atmosphere coupling in weather as mediated by globally propagating aurorally excited atmospheric gravity waves triggering conditional moist instabilities leading to convection in the troposphere that has been proposed in previous publications is highlighted.
Simulation of the Dynamic and Thermodynamic Structure and Microphysical Evolution of a Squall Line in South China
Authors: Li Jingyuan , Su Yang , Ping Fan , Tang Jiahui
Published: September 2021

A squall line that occurred in south China on 31 March 2014 was simulated with the Weather Research and Forecasting model. The microphysical processes had an important influence on the dynamic and thermodynamic structure of the squall line. The process of water vapor condensation (PCC+) provided heat for the ascending movement inside the squall line. The forward movement of the heating area of PCC+ was an important reason for the squall line’s tilting. The convergence of the outflow of the cold pool and the warm and wet air constantly triggered new convection cells in the front of the cold pool, which made the squall line propagate forwards. The cooling process of graupel melting into rain corresponded closely with the rear inflow jet. During the mature period of the squall line, the effect of cooling strengthened the rear inflow jet. This promoted low-layer inflow and a convective ascending motion, thus further promoting the development of the squall line system. During the decay period, the strong backflow center of the stratospheric region cut off the forward inflow of the middle and low layer towards the high layer, and cooperated with the cold pool to cut off the warm and wet air transport of the low layer, making the system decline gradually.
The Impact of the El Niño Southern Oscillation on the Number of Visitors to Natural Attractions: The Moderating Effect of Disposable Personal Income, per Capita GDP and Population
Authors: Xiong Li , Gong Ke , Tang Qingyun , Dong Yuanxiang , Xu Wei
Published: September 2021

Analyzing the impact of El Nilo Southern Oscillation (ENSO) on the number of tourists is essential in realizing the sustainable development of natural scenic spots. From the current research results, research on the effects of ENSO on tourism focuses on the impact of the formation of the natural environment. However, there is a lack of ENSO-related research on the number of people arriving at natural attractions. This paper considers the adjustment effects of personal disposable income, per capita GDP, and population size and constructs a new framework of ENSO’s influence on tourism. This paper builds a system GMM (Gaussian Mixture Model) and analyzes the impact of ENSO on tourist flow by using Google Trend data (big data technology) to obtain annual passenger flow data of 48 natural scenic spots in the United States (mainly national parks and national forests). The empirical results show that the increase in ENSO has led to a significant decrease in visitors to natural attractions in the United States. Moreover, the increase in personal disposable income, per capita GDP, and population size can weaken the relationship between ENSO and the number of tourists. This research expands and enriches the theoretical perspective of ENSO and outdoor tourism.
Anti-Malarial and Anti-Lipid Peroxidation Activities of Deferiprone-Resveratrol Hybrid in Plasmodium berghei-Infected Mice
Authors: Chuljerm Hataichanok , Maneekesorn Supawadee , Somsak Voravuth , Ma Yongmin , Srichairatanakool Somdet , Koonyosying Pimpisid
Published: September 2021

Iron is essential for all organisms including fast-dividing malarial parasites. Inversely, iron chelators can inhibit parasite growth through the inhibition of DNA synthesis and can ameliorate oxidative cell damage. Deferiprone (DFP)-resveratrol (RVT) hybrid (DFP-RVT) is a lipophilic anti-oxidative, iron-chelating agent that has displayed potent neuroprotective and anti-plasmodium activities in vitro. The goal of this work was to investigate the inhibitory effects of DFP-RVT on parasite growth and oxidative stress levels during malaria infections. Mice were intraperitoneally infected with P. berghei and orally administered with DFP, DFP-RVT and pyrimethamine for 4 d. The percentage of parasitemia was determined using Giemsa’s staining/microscopic examination. Amounts of the lipid-peroxidation product, thiobarbituric acid-reactive substance (TBARS), were determined in both plasma and liver tissue. In our findings, DFP-RVT exhibited a greater potent inhibitory effect and revealed an improvement in anemia and liver damage in infected mice than DFP. To this point, the anti-malarial activity was found to be associated with anti-RBC hemolysis and the liver weight index. In addition, plasma and liver TBARS levels in the DFP-RVT-treated mice were lower than those in DFP-treated mice. Thus, DFP-RVT could exert anti-plasmodium, anti-hemolysis and anti-lipid peroxidation activities to a better degree than DFP in P. berghei-infected mice.
Clinical Relevance of the Microbiome in Odontogenic Abscesses
Authors: Böttger Sebastian , Zechel-Gran Silke , Schmermund Daniel , Streckbein Philipp , Wilbrand Jan-Falco , Knitschke Michael , Pons-Kühnemann Jörn , Hain Torsten , Weigel Markus , Imirzalioglu Can , Howaldt Hans-Peter , Domann Eugen , Attia Sameh
Published: September 2021

Odontogenic abscesses are usually caused by bacteria of the oral microbiome. However, the diagnostic culture of these bacteria is often prone to errors and sometimes fails completely due to the fastidiousness of the relevant bacterial species. The question arises whether additional pathogen diagnostics using molecular methods provide additional benefits for diagnostics and therapy. Experimental 16S rRNA gene analysis with next-generation sequencing (NGS) and bioinformatics was used to identify the microbiome of the pus in patients with severe odontogenic infections and was compared to the result of standard diagnostic culture. The pus microbiome was determined in 48 hospitalized patients with a severe odontogenic abscess in addition to standard cultural pathogen detection. Cultural detection was possible in 41 (85.42%) of 48 patients, while a pus-microbiome could be determined in all cases. The microbiomes showed polymicrobial infections in 46 (95.83%) cases, while the picture of a mono-infection occurred only twice (4.17%). In most cases, a predominantly anaerobic spectrum with an abundance of bacteria was found in the pus-microbiome, while culture detected mainly Streptococcus, Staphylococcus, and Prevotella spp. The determination of the microbiome of odontogenic abscesses clearly shows a higher number of bacteria and a significantly higher proportion of anaerobes than classical cultural methods. The 16S rRNA gene analysis detects considerably more bacteria than conventional cultural methods, even in culture-negative samples. Molecular methods should be implemented as standards in medical microbiology diagnostics, particularly for the detection of polymicrobial infections with a predominance of anaerobic bacteria.
Gaseous Elemental Mercury Exchange Fluxes over Air-Soil Interfaces in the Degraded Grasslands of Northeastern China
Authors: Zhang Gang , Zhou Xuhang , Li Xu , Wang Lei , Li Xiangyun , Luo Zheng , Zhang Yangjie , Yang Zhiyun , Hu Rongfang , Tang Zhanhui , Wang Deli , Wang Zhaojun
Published: September 2021

Mercury (Hg) is a global pollutant that may potentially have serious impacts on human health and ecologies. The gaseous elemental mercury (GEM) exchanges between terrestrial surfaces and the atmosphere play important roles in the global Hg cycle. This study investigated GEM exchange fluxes over two land cover types (including Artemisia anethifolia coverage and removal and bare soil) using a dynamic flux chamber attached to the LumexR RA915+ Hg analyzer during the growing season from May to September of 2018, in which the interactive effects of plant coverage and meteorological conditions were highlighted. The daily mean ambient levels of GEM and the total mercury concentrations of the soil (TSM) were determined to be 12.4 ± 3.6 to 16.4 ± 5.6 ng·m−3 and 32.8 to 36.2 ng·g−1, respectively, for all the measurements from May to September. The GEM exchange fluxes (ng·m−2·h−1) during the five-month period for the three treatments included the net emissions from the soil to the atmosphere (mean 5.4 to 7.1; range of −27.0 to 47.3), which varied diurnally, with releases occurring during the daytime hours and depositions occurring during the nighttime hours. Significant differences were observed in the fluxes between the vegetation coverage and removal during the growing months (p < 0.05). In addition, it was determined that the Hg fluxes were positively correlated with the solar radiation and air/soil temperature levels and negatively correlated with the air relative humidity and soil moisture under all the conditions (p < 0.05). Overall, the results obtained in this study demonstrated that the grassland soil served as both a source and a sink for atmospheric Hg, depending on the season and meteorological factors. Furthermore, the plants played an important inhibiting role in the Hg exchanges between the soil and the atmosphere.
Isolation and Identification of Long Non-Coding RNAs in Exosomes Derived from the Serum of Colorectal Carcinoma Patients
Authors: Ng Chin Tat , Azwar Shamin , Yip Wai Kien , Zahari Sham Siti Yazmin , Faisal Jabar Mohd , Sahak Norren Haneezah , Mohtarrudin Norhafizah , Seow Heng Fong
Published: September 2021

Long non-coding RNAs (lncRNAs) are non-coding RNAs consisting of more than 200 nucleotides in length. LncRNAs present in exosomes may play a critical role in the cellular processes involved in cancer pathogenesis and progression including proliferation, invasion, and migration of tumor cells. This paper aims to identify the differential expression of exosomal lncRNAs derived from the sera of non-cancer individuals and patients diagnosed with colorectal carcinoma. These differentially-expressed exosomal serum lncRNAs may provide an insight into the pathogenesis and progression of colorectal cancer (CRC). Serum exosomes and exosomes from SW480-7 cell culture supernatants were isolated and viewed by transmission electron microscope (TEM). The particle size distribution and protein markers of exosomes derived from SW480-7 were further analyzed using the Zetasizer Nano S instrument and western blotting technique. TEM showed that exosomes derived from serum and SW480-7 cells were round vesicles with sizes ranging from 50–200 nm. The exosomes derived from SW480-7 had an average diameter of 274.6 nm and contained the exosomal protein, ALIX/PDCD6IP. In our clinical studies, six lncRNAs, namely GAS5, H19, LINC00152, SNHG16, RMRP, and ZFAS1 were detected in the exosomes from sera of 18 CRC patients. Among these six lncRNAs, the expression level of LINC00152 was found to be significantly lower in CRC patients as compared to non-cancer individuals (p = 0.04) while lncRNA H19 was significantly up-regulated in advanced-stages (stage III and IV) of CRC (p = 0.04) as compared to early-stages (stage I and II). In conclusion, the detection of lower LINC00152 in exosomes of sera from CRC patients versus non-cancer individuals and H19 upregulation in advanced stages suggests that they may play important roles in pathogenesis and progression of CRC.
Bioguided Isolation of Cyclopenin Analogues as Potential SARS-CoV-2 Mpro Inhibitors from Penicillium citrinum TDPEF34
Authors: Thissera Bathini , Sayed Ahmed M. , Hassan Marwa H. A. , Abdelwahab Sayed F. , Amaeze Ngozi , Semler Valeria T. , Alenezi Faizah N. , Yaseen Mohammed , Alhadrami Hani A. , Belbahri Lassaad , Rateb Mostafa E.
Published: September 2021

SARS-CoV-2 virus mutations might increase its virulence, and thus the severity and duration of the ongoing pandemic. Global drug discovery campaigns have successfully developed several vaccines to reduce the number of infections by the virus. However, finding a small molecule pharmaceutical that is effective in inhibiting SARS-CoV-2 remains a challenge. Natural products are the origin of many currently used pharmaceuticals and, for this reason, a library of in-house fungal extracts were screened to assess their potential to inhibit the main viral protease Mpro in vitro. The extract of Penicillium citrinum, TDPEF34, showed potential inhibition and was further analysed to identify potential Mpro inhibitors. Following bio-guided isolation, a series of benzodiazepine alkaloids cyclopenins with good-to-moderate activity against SARS-CoV-2 Mpro were identified. The mode of enzyme inhibition of these compounds was predicted by docking and molecular dynamic simulation. Compounds 1 (isolated as two conformers of S- and R-isomers), 2, and 4 were found to have promising in vitro inhibitory activity towards Mpro, with an IC50 values range of 0.36–0.89 µM comparable to the positive control GC376. The in silico investigation revealed compounds to achieve stable binding with the enzyme active site through multiple H-bonding and hydrophobic interactions. Additionally, the isolated compounds showed very good drug-likeness and ADMET properties. Our findings could be utilized in further in vitro and in vivo investigations to produce anti-SARS-CoV-2 drug candidates. These findings also provide critical structural information that could be used in the future for designing potent Mpro inhibitors.
Endothelial Cell Activation by SARS-CoV-2 Spike S1 Protein: A Crosstalk between Endothelium and Innate Immune Cells
Authors: Rotoli Bianca Maria , Barilli Amelia , Visigalli Rossana , Ferrari Francesca , Dall’Asta Valeria
Published: September 2021

Background. Emerging evidences suggest that in severe COVID-19, multi-organ failure is associated with a hyperinflammatory state (the so-called “cytokine storm”) in combination with the development of a prothrombotic state. The central role of endothelial dysfunction in the pathogenesis of the disease is to date accepted, but the precise mechanisms underlying the associated coagulopathy remain unclear. Whether the alterations in vascular homeostasis directly depend upon the SARS-CoV-2 infection of endothelial cells or, rather, occur secondarily to the activation of the inflammatory response is still a matter of debate. Here, we address the effect of the SARS-CoV-2 spike S1 protein on the activation of human lung microvascular endothelial cells (HLMVEC). In particular, the existence of an endothelium-macrophage crosstalk in the response to the spike protein has been explored. Methods and Results. The effect of the spike protein is addressed in human lung microvascular endothelial cells (HLMVEC), either directly or after incubation with a conditioned medium (CM) of human monocyte-derived macrophages (MDM) previously activated by the spike S1 protein (CM-MDM). Both MDM and HLMVEC are activated in response to the S1 protein, with an increased expression of pro-inflammatory mediators. However, when HLMVEC are exposed to CM-MDM, an enhanced cell activation occurs in terms of the expression of adhesion molecules, pro-coagulant markers, and chemokines. Under this experimental condition, ICAM-1 and VCAM-1, the chemokines CXCL8/IL-8, CCL2/MCP1, and CXCL10/IP-10 as well as the protein tissue factor (TF) are markedly induced. Instead, a decrease of thrombomodulin (THBD) is observed. Conclusion. Our data suggest that pro-inflammatory mediators released by spike-activated macrophages amplify the activation of endothelial cells, likely contributing to the impairment of vascular integrity and to the development of a pro-coagulative endothelium.
Quantitative Approaches to Study Retinal Neurogenesis
Authors: Pérez-Dones Diego , Ledesma-Terrón Mario , Míguez David G.
Published: September 2021

The study of the development of the vertebrate retina can be addressed from several perspectives: from a purely qualitative to a more quantitative approach that takes into account its spatio-temporal features, its three-dimensional structure and also the regulation and properties at the systems level. Here, we review the ongoing transition toward a full four-dimensional characterization of the developing vertebrate retina, focusing on the challenges at the experimental, image acquisition, image processing and quantification. Using the developing zebrafish retina, we illustrate how quantitative data extracted from these type of highly dense, three-dimensional tissues depend strongly on the image quality, image processing and algorithms used to segment and quantify. Therefore, we propose that the scientific community that focuses on developmental systems could strongly benefit from a more detailed disclosure of the tools and pipelines used to process and analyze images from biological samples.
3D Printing of Polysaccharide-Based Self-Healing Hydrogel Reinforced with Alginate for Secondary Cross-Linking
Authors: Roh Hyun-Ho , Kim Hyun-Seung , Kim Chunggoo , Lee Kuen-Yong
Published: September 2021

Three-dimensional (3D) bioprinting has been attractive for tissue and organ regeneration with the possibility of constructing biologically functional structures useful in many biomedical applications. Autonomous healing of hydrogels composed of oxidized hyaluronate (OHA), glycol chitosan (GC), and adipic acid dihydrazide (ADH) was achieved after damage. Interestingly, the addition of alginate (ALG) to the OHA/GC/ADH self-healing hydrogels was useful for the dual cross-linking system, which enhanced the structural stability of the gels without the loss of their self-healing capability. Various characteristics of OHA/GC/ADH/ALG hydrogels, including viscoelastic properties, cytotoxicity, and 3D printability, were investigated. Additionally, potential applications of 3D bioprinting of OHA/GC/ADH/ALG hydrogels for cartilage regeneration were investigated in vitro. This hydrogel system may have potential for bioprinting of a custom-made scaffold in various tissue engineering applications.
Synergistic Effect of Static Compliance and D-dimers to Predict Outcome of Patients with COVID-19-ARDS: A Prospective Multicenter Study
Authors: Tonetti Tommaso , Grasselli Giacomo , Rucci Paola , Alessandri Francesco , Dell’Olio Alessio , Boscolo Annalisa , Pasin Laura , Sella Nicolò , Mega Chiara , Melotti Rita Maria , Girardis Massimo , Busani Stefano , Bellani Giacomo , Foti Giuseppe , Grieco Domenico Luca , Scaravilli Vittorio , Protti Alessandro , Langer Thomas , Mascia Luciana , Pugliese Francesco , Cecconi Maurizio , Fumagalli Roberto , Nava Stefano , Antonelli Massimo , Slutsky Arthur S. , Navalesi Paolo , Pesenti Antonio , Ranieri Vito Marco
Published: September 2021

The synergic combination of D-dimer (as proxy of thrombotic/vascular injury) and static compliance (as proxy of parenchymal injury) in predicting mortality in COVID-19-ARDS has not been systematically evaluated. The objective is to determine whether the combination of elevated D-dimer and low static compliance can predict mortality in patients with COVID-19-ARDS. A “training sample” (March–June 2020) and a “testing sample” (September 2020–January 2021) of adult patients invasively ventilated for COVID-19-ARDS were collected in nine hospitals. D-dimer and compliance in the first 24 h were recorded. Study outcome was all-cause mortality at 28-days. Cut-offs for D-dimer and compliance were identified by receiver operating characteristic curve analysis. Mutually exclusive groups were selected using classification tree analysis with chi-square automatic interaction detection. Time to death in the resulting groups was estimated with Cox regression adjusted for SOFA, sex, age, PaO2/FiO2 ratio, and sample (training/testing). “Training” and “testing” samples amounted to 347 and 296 patients, respectively. Three groups were identified: D-dimer ≤ 1880 ng/mL (LD); D-dimer > 1880 ng/mL and compliance > 41 mL/cmH2O (LD-HC); D-dimer > 1880 ng/mL and compliance ≤ 41 mL/cmH2O (HD-LC). 28-days mortality progressively increased in the three groups (from 24% to 35% and 57% (training) and from 27% to 39% and 60% (testing), respectively; p < 0.01). Adjusted mortality was significantly higher in HD-LC group compared with LD (HR = 0.479, p < 0.001) and HD-HC (HR = 0.542, p < 0.01); no difference was found between LD and HD-HC. In conclusion, combination of high D-dimer and low static compliance identifies a clinical phenotype with high mortality in COVID-19-ARDS.
A Co-Culture-Based Multiparametric Imaging Technique to Dissect Local H2O2 Signals with Targeted HyPer7
Authors: Secilmis Melike , Altun Hamza Yusuf , Pilic Johannes , Erdogan Yusuf Ceyhun , Cokluk Zeynep , Ata Busra Nur , Sevimli Gulsah , Zaki Asal Ghaffari , Yigit Esra Nur , Öztürk Gürkan , Malli Roland , Eroglu Emrah
Published: September 2021

Multispectral live-cell imaging is an informative approach that permits detecting biological processes simultaneously in the spatial and temporal domain by exploiting spectrally distinct biosensors. However, the combination of fluorescent biosensors with distinct spectral properties such as different sensitivities, and dynamic ranges can undermine accurate co-imaging of the same analyte in different subcellular locales. We advanced a single-color multiparametric imaging method, which allows simultaneous detection of hydrogen peroxide (H2O2) in multiple cell locales (nucleus, cytosol, mitochondria) using the H2O2 biosensor HyPer7. Co-culturing of endothelial cells stably expressing differentially targeted HyPer7 biosensors paved the way for co-imaging compartmentalized H2O2 signals simultaneously in neighboring cells in a single experimental setup. We termed this approach COMPARE IT, which is an acronym for co-culture-based multiparametric imaging technique. Employing this approach, we detected lower H2O2 levels in mitochondria of endothelial cells compared to the cell nucleus and cytosol under basal conditions. Upon administering exogenous H2O2, the cytosolic and nuclear-targeted probes displayed similarly slow and moderate HyPer7 responses, whereas the mitochondria-targeted HyPer7 signal plateaued faster and reached higher amplitudes. Our results indicate striking differences in mitochondrial H2O2 accumulation of endothelial cells. Here, we present the method’s potential as a practicable and informative multiparametric live-cell imaging technique.
Efficacy of Neuro-Psychomotor Approach in Children Affected by Autism Spectrum Disorders: A Multicenter Study in Italian Pediatric Population
Authors: Caliendo Mariarosaria , Di Sessa Anna , D’Alterio Elisa , Frolli Alessandro , Verde Domenico , Iacono Diego , Romano Palmira , Vetri Luigi , Carotenuto Marco
Published: September 2021

Background: Autism Spectrum Disorder (ASD) is characterized by impairments in social interaction and reciprocal communication. ASD affects about 1% of the general population and is associated with substantial disability and economic loss. A variety of approaches to improve the core deficits and lives of people with ASD have been developed, including behavioral, developmental, educational, and medical interventions. The main objective of this study was to evaluate the efficacy of a neuro-psychomotor approach in children affected by ASD. Methods: The sample consisted of 84 children (66 males, mean age 56.9 ± 15.8 months) affected by ASD assessed between September 2020 to March 2021. The trained therapist was asked to complete the ASD behavior inventory (ASDBI) test at baseline (T0) (September 2020) and after six months (T1) (March 2021) to assess the child’s evolution over the observational period. The study was carried out in southern Italy (Campania Region). Results: ASD children showed a significant improvement for AUTISM composite after 6 months of neuro-psychomotor treatment (T1) compared to baseline (65.4 ± 12.2 vs. 75.8 ± 11.5, p < 0.0001). In particular, significant changes were observed for such domains as the problems of excitability (ECCIT), aggression (AGG), behaviors in social relations (RELSOC), expressive (all p < 0.001), sense/perceptual contact modes (SENS) (p = 0.0007), ritualisms/resistance to changes (RIT) (p = 0.0002), pragmatic/social problems (PPSOC) (p = 0.0009), specific fears (FEARS) (p = 0.01), and learning and memory (AMLR) (p = 0.0007). No differences for the domains Semantic/pragmatic problems (PPSEM) and language (LESP) were found. Conclusions: Our preliminary results suggest the usefulness of the neuro-psychomotor treatment in children with ASD. Although promising, these findings need to be tested further to better understand the long-term effects of this specific type of approach.
Understanding the Modulatory Effects of Cannabidiol on Alzheimer’s Disease
Authors: Xiong Yinyi , Lim Chae-Seok
Published: September 2021

Alzheimer’s disease (AD), the most common neurodegenerative disease, is characterized by progressive cognitive impairment. The deposition of amyloid beta (Aβ) and hyperphosphorylated tau is considered the hallmark of AD pathology. Many therapeutic approaches such as Food and Drug Administration-approved cholinesterase inhibitors and N–methyl–D–aspartate receptor antagonists have been used to intervene in AD pathology. However, current therapies only provide limited symptomatic relief and are ineffective in preventing AD progression. Cannabidiol (CBD), a phytocannabinoid devoid of psychoactive responses, provides neuroprotective effects through both cannabinoid and noncannabinoid receptors. Recent studies using an AD mouse model have suggested that CBD can reverse cognitive deficits along with Aβ-induced neuroinflammatory, oxidative responses, and neuronal death. Furthermore, CBD can reduce the accumulation of Aβ and hyperphosphorylation of tau, suggesting the possibility of delaying AD progression. Particularly, the noncannabinoid receptor, peroxisome proliferator-activated receptor gamma, has been suggested to be involved in multiple functions of CBD. Therefore, understanding the underlying mechanisms of CBD is necessary for intervening in AD pathology in depth and for the translation of preclinical studies into clinical settings. In this review, we summarize recent studies on the effect of CBD in AD and suggest problems to be overcome for the therapeutic use of CBD.
Plantar Pressure and Contact Area Measurement of Foot Abnormalities in Stroke Rehabilitation
Authors: Rusu Ligia , Paun Elvira , Marin Mihnea Ion , Hemanth Jude , Rusu Mihai Robert , Calina Mirela Lucia , Bacanoiu Manuela Violeta , Danoiu Mircea , Danciulescu Daniel
Published: September 2021

Background: Evaluation of plantar pressure in stroke patients is a parameter that could be used for monitoring and comparing how the timing of starting a rehabilitation program effects patient improvement. Methods: We performed the following clinical and functional evaluations: initial moment (T1), intermediate (T2), and final evaluation at one year (T3). At T1 we studied 100 stroke patients in two groups, A and B (each 50 patients). The first group, A, started rehabilitation in the first three months after having a stroke, and group B started after three months from the time of stroke. Due to the impediments observed during rehabilitation, we made biomechanic evaluation for two lots, I and II (each 25 patients). Assessment of the patient was carried out by clinical (neurologic examination), functional (using the Tinetti Functional Gait Assessment Test for classifying the gait), and biomechanical evaluation (maximal plantar pressure (Pmax), contact area (CA), and pressure distribution (COP)). Results: The Tinetti scale for gait had the following scores: for group A, from 1.34 at the initial moment (T1) to 10.64 at final evaluation (T3), and for group B, 3.08 at initial moment (T1) to 9 at final evaluation (T3). Distribution of COP in the left hemiparesis was uneven at T1 but evolved after rehabilitation. The right hemiparesis had uniform COP distribution even at T1, explained by motor dominance on the right side. CA and Pmax for lot I increased more than 100%, meaning that there is a possibility for favorable improvement if the patients start the rehabilitation program in the first three months after stroke. For lot II, increases of the parameters were less than lot I. Discussions: The recovery potential is higher for patients with right hemiparesis. Biomechanic evaluation showed diversity regarding compensatory mechanisms for the paretic and nonparetic lower limb. Conclusions: CA and Pmax are relevant assessments for evaluating the effects on timing of starting a rehabilitation program after a stroke.
Impact of Moderate Individually Tailored Physical Activity in Multiple Sclerosis Patients with Fatigue on Functional, Cognitive, Emotional State, and Postural Stability
Authors: Redlicka Justyna , Zielińska-Nowak Ewa , Lipert Anna , Miller Elżbieta
Published: September 2021

Multiple sclerosis (MS) is a chronic disease, with fatigue syndrome as one of the main symptoms. The aim of this study was to demonstrate that moderate physical activity (MPA) may have a beneficial effect on postural stability, balance, and clinical parameters. The research group consisted of 137 randomized patients hospitalized at the Department of Neurological Rehabilitation, Medical University of Lodz. Finally, 76 patients were qualified who were divided into two groups—high fatigue (HF) and low fatigue (LF). Participants were assessed twice: before and after a 4-week MPA program using: the Expanded Disability Status Scale (EDSS), the Fatigue Severity Scale (FSS), the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Beck Depression Inventory (BDI), and the Geriatric Depression Scale (GDS), and stabilometric platform tests were performed. Results obtained after the 4-week MPA program showed a positive effect of the MPA with differences between LF and HF groups. The MPA was more effective in MS patients with LF in cognitive functions, functional status, and postural stability but among HF patients in an emotional state, especially in MS patients below 65 years, although in total, both groups benefited from the MPA.
Hospital Admissions for Neurodegenerative Diseases during the First Wave of the COVID-19 Pandemic: A Nationwide Cross-Sectional Study from Germany
Authors: Scherbaum Raphael , Kwon Eun-Hae , Richter Daniel , Bartig Dirk , Gold Ralf , Krogias Christos , Tönges Lars
Published: September 2021

(1) Background: The COVID-19 pandemic impacts healthcare utilization across all care settings and health conditions. The objective of this study was to determine changes in hospital admissions for neurodegenerative diseases (NDD) during the first COVID-19 wave in Germany; (2) Methods: This cross-sectional study used nationwide administrative claims data covering 1468 hospitals. The primary outcome was the year-to-year relative change in case numbers during a four-month study period (16 January–15 May 2020 vs. 2019) during the first pandemic wave. Secondary outcomes included year-to-year relative changes during a four-week peak phase (16 March–15 April) and changes between differential phases of the wave. The analyzed NDD comprised progressive supranuclear palsy (PSP), multiple system atrophy (MSA), Parkinson’s disease, amyotrophic lateral sclerosis (ALS) and Huntington’s disease; (3) Results: Hospital admissions for any reason decreased by 16.7% in 2020 during the study period and by 36.6% during the peak phase, whereas admissions for NDD decreased by 27.6% and 65.0%, respectively. PSP cases decreased during the study period (−34.7%) and the peak phase (−68.1%) and stayed reduced in a late phase with falling COVID-19 numbers. MSA and ALS cases increased strongest after the peak, with ALS cases being comparatively weakly reduced during the study period (−17.3%) and peak phase (−51.7%); (4) Conclusions: Inpatient care utilization for NDD changed differentially during the first wave of the COVID-19 pandemic in Germany and showed a greater reduction than overall and general neurological admissions. Mitigating long-term health deterioration of this vulnerable subgroup is important to reduce morbidity and mortality in the future.
Risk of Thrombo-Embolic Events in Ovarian Cancer: Does Bevacizumab Tilt the Scale? A Systematic Review and Meta-Analysis
Authors: Saerens Michael , De Jaeghere Emiel A. , Kanervo Heini , Vandemaele Nele , Denys Hannelore , Naert Eline
Published: September 2021

Thromboembolic events are the second cause of death in cancer patients. In ovarian cancer, 3–10% of patients present with venous thromboembolism (VTE), but the incidence may rise to 36% along the disease course. Bevacizumab is a monoclonal antibody directed against vascular endothelial-derived growth factor, and in in vitro studies it showed a predisposition to hemostasis perturbation, including thrombosis. However, in vivo and clinical studies have shown conflicting results for its use as a treatment for ovarian cancer, so we conducted a systematic review and meta-analysis on the risk of arterial thromboembolism (ATE) and VTE in ovarian cancer patients treated with bevacizumab. The review comprised 14 trials with 6221 patients: ATE incidence was reported in 5 (4811 patients) where the absolute risk was 2.4% with bevacizumab vs. 1.1% without (RR 2.45; 95% CI 1.27–4.27, p = 0.008). VTE incidence was reported in 9 trials (5121 patients) where the absolute risk was 5.4% with bevacizumab vs. 3.7% without (RR 1.32; 95% CI 1.02–1.79, p = 0.04). Our analysis showed that the risk of arterial and venous thromboembolism increased in patients treated with bevacizumab. Thrombolic events (TEs) are probably underreported, and studies should discriminate between ATE and VTE. Bevacizumab can be considered as an additional risk factor when selecting patients for primary prophylaxis with anticoagulants.
Thrombotic Complications Associated with Immune Checkpoint Inhibitors
Authors: Wang Tzu-Fei , Khorana Alok A. , Carrier Marc
Published: September 2021

Thromboembolism is a common complication in patients with cancer and is associated with significant morbidity and mortality. Anticancer treatment is a known risk factor of cancer-associated thrombosis. Immune checkpoint inhibitors have become a mainstay of treatment in various cancers. Both venous and arterial thrombosis have been increasingly reported as adverse events associated with immune checkpoint inhibitors in recent studies, with a cumulative incidence of venous thrombosis to be 5–8% at 6 months and over 10% at 12 months. Additionally, rates of approximately 1–5% for arterial thrombosis were reported at 12 months. Data also showed an association of thromboembolism with adverse survival. Many pertinent clinical questions in this population deserve further investigation, including the risks of thrombosis associated with immune checkpoint inhibitors as compared to those with traditional systemic therapy, associated risk factors, and the optimal prevention and treatment strategies. In this review, we synthesize data from available literature, provide relevant information for clinicians and potential future directions for research.
Genome Scale Modeling to Study the Metabolic Competition between Cells in the Tumor Microenvironment
Authors: Frades Itziar , Foguet Carles , Cascante Marta , Araúzo-Bravo Marcos J.
Published: September 2021

The tumor’s physiology emerges from the dynamic interplay of numerous cell types, such as cancer cells, immune cells and stromal cells, within the tumor microenvironment. Immune and cancer cells compete for nutrients within the tumor microenvironment, leading to a metabolic battle between these cell populations. Tumor cells can reprogram their metabolism to meet the high demand of building blocks and ATP for proliferation, and to gain an advantage over the action of immune cells. The study of the metabolic reprogramming mechanisms underlying cancer requires the quantification of metabolic fluxes which can be estimated at the genome-scale with constraint-based or kinetic modeling. Constraint-based models use a set of linear constraints to simulate steady-state metabolic fluxes, whereas kinetic models can simulate both the transient behavior and steady-state values of cellular fluxes and concentrations. The integration of cell- or tissue-specific data enables the construction of context-specific models that reflect cell-type- or tissue-specific metabolic properties. While the available modeling frameworks enable limited modeling of the metabolic crosstalk between tumor and immune cells in the tumor stroma, future developments will likely involve new hybrid kinetic/stoichiometric formulations.
3D Cancer Models: Depicting Cellular Crosstalk within the Tumour Microenvironment
Authors: Franchi-Mendes Teresa , Eduardo Rodrigo , Domenici Giacomo , Brito Catarina
Published: September 2021

The tumour microenvironment plays a critical role in tumour progression and drug resistance processes. Non-malignant cell players, such as fibroblasts, endothelial cells, immune cells and others, interact with each other and with the tumour cells, shaping the disease. Though the role of each cell type and cell communication mechanisms have been progressively studied, the complexity of this cellular network and its role in disease mechanism and therapeutic response are still being unveiled. Animal models have been mainly used, as they can represent systemic interactions and conditions, though they face recognized limitations in translational potential due to interspecies differences. In vitro 3D cancer models can surpass these limitations, by incorporating human cells, including patient-derived ones, and allowing a range of experimental designs with precise control of each tumour microenvironment element. We summarize the role of each tumour microenvironment component and review studies proposing 3D co-culture strategies of tumour cells and non-malignant cell components. Moreover, we discuss the potential of these modelling approaches to uncover potential therapeutic targets in the tumour microenvironment and assess therapeutic efficacy, current bottlenecks and perspectives.
Metformin Potentiates the Anticancer Effect of Everolimus on Cervical Cancer In Vitro and In Vivo
Authors: Chen Ya-Hui , Wu Jyun-Xue , Yang Shun-Fa , Chen Mei-Ling , Chen Tze-Ho , Hsiao Yi-Hsuan
Published: September 2021

Cervical cancer is globally the fourth most common cancer in women. Metformin is a widely used drug for the treatment of type II diabetes and has been shown to possess important anticancer properties in cervical cancer. Everolimus is an mTOR inhibitor and is widely used to treat NETs, RCC, TSC, and breast cancers. The present study investigated the anticancer effects of metformin and everolimus in cervical cancer, when used alone or in combination. CaSki and C33A human cervical cancer cells were treated with different concentrations of everolimus alone or in combination with metformin. Cell viability was assessed using a CCK-8 assay. Cell apoptosis, cell-cycle, and mtROS analyses were conducted using flow cytometry. Target protein levels were analyzed by Western blotting. Related mechanisms were confirmed using appropriate inhibitors (z-VAD-fmk and BIRB796). The in vitro results were further confirmed in a xenograft tumor study. Both metformin and everolimus, when used alone, were moderately effective in inhibiting cell proliferation and inducing cell apoptosis of CaSki and C33A cells. When used in combination, these two drugs synergistically inhibited the growth of human cervical cancer cells and xenografts in nude mice, promoted sub-G1- and G0/G1-phase cell-cycle arrest, and enhanced mtROS production. The protein expressions of PI3K (p110α) and p-AKT were significantly downregulated, while P27, P21, p-p38, p-ERK, and p-JNK were upregulated following combined treatment. These results revealed that metformin potentiates the anticancer effect of everolimus on cervical cancer, and combination treatment with metformin and everolimus provides a novel therapeutic strategy for patients with cervical cancer.