bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal Reopening Pathways With COVID-19 Vaccine Rollout and Emerging Variants of Concern
Authors: Xiao Yanyu , Chen Shengyuan , Zhu Yi , McCarthy Zachary , Bragazzi Nicola Luigi , Asgary Ali , Wu Jianhong
Published: September 2021

We developed a stochastic optimization technology based on a COVID-19 transmission dynamics model to determine optimal pathways from lockdown toward reopening with different scales and speeds of mass vaccine rollout in order to maximize social economical activities while not overwhelming the health system capacity in general, hospitalization beds, and intensive care units in particular. We used the Province of Ontario, Canada as a case study to demonstrate the methodology and the optimal decision trees; but our method and algorithm are generic and can be adapted to other settings. Our model framework and optimization strategies take into account the likely range of social contacts during different phases of a gradual reopening process and consider the uncertainties of these contact rates due to variations of individual behaviors and compliance. The results show that, without a mass vaccination rollout, there would be multiple optimal pathways should this strategy be adopted right after the Province's lockdown and stay-at-home order; however, once reopening has started earlier than the timing determined in the optimal pathway, an optimal pathway with similar constraints no longer exists, and sub-optimal pathways with increased demand for intensive care units can be found, but the choice is limited and the pathway is narrow. We also simulated the situation when the reopening starts after the mass vaccination has been rolled out, and we concluded that optimal pathways toward near pre-pandemic activity level is feasible given an accelerated vaccination rollout plan, with the final activity level being determined by the vaccine coverage and the transmissibility of the dominating strain.
The Singleton Fallacy: Why Current Critiques of Language Models Miss the Point
Authors: Sahlgren Magnus , Carlsson Fredrik
Published: September 2021

This paper discusses the current critique against neural network-based Natural Language Understanding solutions known as language models. We argue that much of the current debate revolves around an argumentation error that we refer to as the singleton fallacy: the assumption that a concept (in this case, language, meaning, and understanding) refers to a single and uniform phenomenon, which in the current debate is assumed to be unobtainable by (current) language models. By contrast, we argue that positing some form of (mental) “unobtanium” as definiens for understanding inevitably leads to a dualistic position, and that such a position is precisely the original motivation for developing distributional methods in computational linguistics. As such, we argue that language models present a theoretically (and practically) sound approach that is our current best bet for computers to achieve language understanding. This understanding must however be understood as a computational means to an end.
Design of a Wearable Haptic Device for Hand Palm Cutaneous Feedback
Authors: Dragusanu Mihai , Villani Alberto , Prattichizzo Domenico , Malvezzi Monica
Published: September 2021

This study describes the main design and prototyping steps of a novel haptic device for cutaneous stimulus of a hand palm. This part of the hand is fundamental in several grasping and manipulation tasks, but is still less exploited in haptics applications than other parts of the hand, as for instance the fingertips. The proposed device has a parallel tendon-based mechanical structure and is actuated by three motors positioned on the hand’s back. The device is able to apply both normal and tangential forces and to render the contact with surfaces with different slopes. The end-effector can be easily changed to simulate the contact with different surface curvatures. The design is inspired by a smaller device previously developed for the fingertips; however, in the device presented in this study, there are significant differences due to the wider size, the different form-factor, and the structure of hand palm. The hand palm represents the support for the fingers and is connected to the arm through the wrist. The device has to be developed taking into account fingers’ and wrist’s motions, and this requirement constrains the number of actuators and the features of the transmission system. The larger size of the palm and the higher forces challenge the device from a structural point of view. Since tendons can apply only tensile forces, a spring-based support has been developed to keep the end-effector separated from the palm when the device is not actuated or when the force to be rendered is null. The study presents the main design guidelines and the main features of the proposed device. A prototype has been realized for the preliminary tests, and an application scenario with a VR environment is introduced.
Comparative Effects of E-Cigarette Aerosol on Periodontium of Periodontitis Patients
Authors: Xu Fangxi , Aboseria Eman , Janal Malvin N. , Pushalkar Smruti , Bederoff Maria V. , Vasconcelos Rebeca , Sapru Sakshi , Paul Bidisha , Queiroz Erica , Makwana Shreya , Solarewicz Julia , Guo Yuqi , Aguallo Deanna , Gomez Claudia , Shelly Donna , Aphinyanaphongs Yindalon , Gordon Terry , Corby Patricia M. , Kamer Angela R. , Li Xin , Saxena Deepak
Published: September 2021

Introduction: Tobacco use is one of the main causes of periodontitis. E-cigarette are gaining in popularity, and studies are needed to better understand the impact of e-cigarettes on oral health.

Objective: To perform a longitudinal study to evaluate the adverse effects of e-cigarettes on periodontal health.

Methods: Naïve E-cigarette users, cigarette smokers, and non-smokers were recruited using newspaper and social media. Age, gender, and ethnicity, were recorded. Participants were scheduled for two visits 6 months apart. At each visit, we collected data on the frequency and magnitude of e-cigarette and cigarette use, and alcohol consumption. Carbon monoxide (CO) levels, cotinine levels, salivary flow rate, periodontal probing depth (PD), bleeding on probing (BoP), and clinical attachment loss (CAL) were also determined at both baseline and follow-up visits and compared between groups with two-way repeated measures ANOVA. Periodontal diagnosis and other categorical variables were compared between groups with the chi-square statistic and logistic regression.

Results: We screened 159 subjects and recruited 119 subjects. One-hundred-one subjects (31 cigarette smokers, 32 e-cigarette smokers, and 38 non-smokers) completed every assessment in both visits. The retention and compliance rate of subjects was 84.9%. The use of social media and craigslist was significant in recruiting e-cigarette subjects. Ethnicity and race differed between groups, as did average age in the male subjects. Carbon monoxide and salivary cotinine levels were highest among cigarette smokers. Bleeding on probing and average PDs similarly increased over time in all three groups, but CAL uniquely increased in e-cigarette smokers. Rates of severe periodontal disease were higher in cigarette smokers and e-cigarette users than non-smokers, but interpretation is confounded by the older age of the cigarette smokers.

Conclusion: Among the recruited participants, CAL after 6 months was significantly worse only in the e-cigarette smokers. This study design and protocol will assist in future larger studies on e-cigarette and oral health.
Qualitative Behavioral Assessment in Juvenile Farmed Atlantic Salmon (Salmo salar): Potential for On-Farm Welfare Assessment
Authors: Jarvis Susan , Ellis Maureen A. , Turnbull James F. , Rey Planellas Sonia , Wemelsfelder Francoise
Published: September 2021

There is a growing scientific and legislative consensus that fish are sentient, and therefore have the capacity to experience pain and suffering. The assessment of the welfare of farmed fish is challenging due to the aquatic environment and the number of animals housed together. However, with increasing global production and intensification of aquaculture comes greater impetus for developing effective tools which are suitable for the aquatic environment to assess the emotional experience and welfare of farmed fish. This study therefore aimed to investigate the use of Qualitative Behavioral Assessment (QBA), originally developed for terrestrial farmed animals, in farmed salmon and evaluate its potential for use as a welfare monitoring tool. QBA is a “whole animal” approach based on the description and quantification of the expressive qualities of an animal's dynamic style of behaving, using descriptors such as relaxed, agitated, lethargic, or confident. A list of 20 qualitative descriptors was generated by fish farmers after viewing video-footage showing behavior expressions representative of the full repertoire of salmon in this context. A separate, non-experienced group of 10 observers subsequently watched 25 video clips of farmed salmon, and scored the 20 descriptors for each clip using a Visual Analog Scale (VAS). To assess intra-observer reliability each observer viewed the same 25 video clips twice, in two sessions 10 days apart, with the second clip set presented in a different order. The observers were unaware that the two sets of video clips were identical. Data were analyzed using Principal Component (PC) Analysis (correlation matrix, no rotation), revealing four dimensions that together explained 79% of the variation between video clips, with PC1 (Tense/anxious/skittish—Calm/mellow/relaxed) explaining the greatest percentage of variation (56%). PC1 was the only dimension to show acceptable inter- and intra-observer reliability, and mean PC1 scores correlated significantly to durations of slow and erratic physical movements measured for the same 25 video clips. Further refinements to the methodology may be necessary, but this study is the first to provide evidence for the potential of Qualitative Behavioral Assessment to serve as a time-efficient welfare assessment tool for juvenile salmon under farmed conditions.
Estimation of Distances in 3D by Orthodontists Using Digital Models
Authors: Makaremi Masrour , N’Kaoua Bernard
Published: September 2021

In the field of orthodontics, digital dental arch models are increasingly replacing plaster models in orthodontic diagnostics. This change in interface from physical plaster models to digital image-based models raises the question of how orthodontists interpret intra- and inter-arch relationships from an image on a screen. In particular, the issue of the accuracy of the distances estimated on numerical models is crucial since the estimation of distances is the basis of the therapeutic decision-making process. Studies have shown that distances were well estimated on plaster models, but no study has verified this point on numerical models. This is the question that our study addresses. The experimental protocol consisted of collecting estimates of measurements made by orthodontists using digital models. The reliability of these measurements was then assessed by comparing them to the actual physical distances. We asked 31 orthodontists (19 women and 12 men; an average age of 37 years) to generate 3D model-based measurements of seven different elements: mandibular congestion, the maxillary intermolar distance, Spee’s curve, 16/26 symmetry, the right canine class, overbite, and overjet. These values were then compared to the actual measurements calculated using Insignia® software (ORMCO Corporation: Brea, CA, USA), using single sample t-tests. This test makes it possible to compare a distance estimated by the participants with a reference value, which corresponds here to the real distance. The results indicate that, overall, the distance estimates made on the 3D models differ significantly from the actual distances measured using the Insignia® software. This was particularly so for mandibular crowding (test value = 0; t (30) = 10.74; p ≤ 0.01), test value = 1; t (30) = 6.23; p ≤ 0.01). Although no study has focused on distance estimation on numerical models in the field of orthodontics, our results agree with the conclusions of studies showing that distances are not estimated in the same way in real environments and virtual environments. Additional studies will make it possible to identify more clearly the parameters (individual factors, equipment, etc.), which make it possible to improve the estimation of distances in the practice of orthodontics. In any case, these studies are necessary to improve the training of future practitioners in the use of virtual models for decision-making and to support them in the digital transition.
Integrated High-Accuracy Correction Technology of Radio-Wave Refraction for Deep-Space (High-Orbit) Targets
Authors: Liu Kun , Yuan Zhigang , Zhou Chen , Zhu Qinglin , Wang Haining , Sheng Dongsheng , Dong Xiang
Published: September 2021

The radio-wave refraction error caused by the troposphere and ionosphere badly affects accuracy in terms of the navigation, positioning, measurement, and control of a target; it is the main source of errors in high-accuracy measurement and control systems. The high-accuracy technology needed for radio-wave refraction error correction (mainly in the troposphere and ionosphere) has been the focus of research for a long time. At present, the correction methods used for radio-wave refraction errors have a low accuracy. For an S-band radio-wave signal, the accuracy of refraction error correction can generally only reach m-level (elevation angle of 15° and above), and thus has difficulty meeting the requirements of dm-level accuracy refraction error correction for deep-space and high-orbit targets. To improve the accuracy of radio-wave refraction error correction for deep-space and high-orbit targets, a novel correction method for tropospheric and ionospheric range error due to refraction is proposed in this study, on the basis of the measured data from a water vapor radiometer and dual-frequency Global Navigation Satellite System (GNSS). The comprehensive calibration test is conducted in combination with the Chinese Area Positioning System (CAPS) in Kunming. Results show that this method can effectively correct the range error due to refraction that is caused by the troposphere and ionosphere. For an S-band radio-wave signal, the accuracy of refraction error correction can reach dm-level accuracy (elevation angle of 15° and above), which is 50% higher than that achieved with traditional methods. This work provides an effective support system for major projects, such as lunar exploration and Mars exploration.
Daily River Water Temperature Prediction: A Comparison between Neural Network and Stochastic Techniques
Authors: Graf Renata , Aghelpour Pouya
Published: September 2021

The temperature of river water (TRW) is an important factor in river ecosystem predictions. This study aims to compare two different types of numerical model for predicting daily TRW in the Warta River basin in Poland. The implemented models were of the stochastic type—Autoregressive (AR), Moving Average (MA), Autoregressive Moving Average (ARMA) and Autoregressive Integrated Moving Average (ARIMA)—and the artificial intelligence (AI) type—Adaptive Neuro Fuzzy Inference System (ANFIS), Radial Basis Function (RBF) and Group Method of Data Handling (GMDH). The ANFIS and RBF models had the most fitted outputs and the AR, ARMA and ARIMA patterns were the most accurate ones. The results showed that both of the model types can significantly present suitable predictions. The stochastic models have somewhat less error with respect to both the highest and lowest TRW deciles than the AIs and were found to be better for prediction studies, with the GMDH complex model in some cases reaching Root Mean Square Error (RMSE) = 0.619 °C and Nash-Sutcliff coefficient (NS) = 0.992, while the AR(2) simple linear model with just two inputs was partially able to achieve better results (RMSE = 0.606 °C and NS = 0.994). Due to these promising outcomes, it is suggested that this work be extended to other catchment areas to extend and generalize the results.
Investigation of Anaerobic Digestion of the Aqueous Phase from Hydrothermal Carbonization of Mixed Municipal Solid Waste
Authors: Adams Kameron J. , Stuart Ben , Kumar Sandeep
Published: September 2021

In 2017, the United States Environmental Protection Agency (EPA) reported that Americans generated over 268 million tons of municipal solid waste (MSW). The majority (52%) of this waste ends up in landfills, which are the third largest source of anthropogenic methane emissions. Improvements in terms of waste management and energy production could be solved by integrating MSW processing with hydrothermal carbonization (HTC) and anaerobic digestion (AD) for converting organic carbon of MSW to fuels. The objectives of this study were to (a) investigate HTC experiments at varying temperatures and residence times (b) evaluate aqueous phase and solids properties, and (c) perform AD bench scale bottle test on the aqueous phase. A mixture of different feedstock representing MSW was used. HTC at 280 °C and 10 min yielded the highest total organic carbon (TOC) of 8.16 g/L with biogas yields of 222 mL biogas/g TOC. Results showed that AD of the aqueous phase from a mixed MSW feedstock is feasible. The integrated approach shows organic carbon recovery of 58% (hydrochar and biogas). This study is the first of its kind to investigate varying temperature and times for a heterogeneous feedstock (mixed MSW), and specifically evaluating HTC MSW aqueous phase anaerobic biodegradability.
Assessment of the Seismic Behavior of a Precast Reinforced Concrete Industrial Building with the Presence of Horizontal Cladding Panels
Authors: Ostetto Liana , Sousa Romain , Rodrigues Hugo , Fernandes Paulo
Published: September 2021

The latest earthquakes in Europe exposed some critical problems in the connections of cladding panels in industrial precast reinforced concrete (PRC) structures. These connections did not perform as desired, causing the panels to fall, leading to significant nonstructural damage that resulted in the loss of human life and significant socio-economic impacts due to the interruption of business. Furthermore, in addition to the behavior of the cladding system itself, it is still not clear to what extent it can influence the overall seismic performance of the main structure. Making use of a simplified macroelement, the present study assesses the seismic performance of commonly employed cladding-to-structure connections, as well as the interaction of cladding panels with industrial PRC buildings. The analyses were carried out considering a PRC building representative of a Portuguese industrial park, studied with and without cladding panels. The seismic behavior of the structure was assessed considering both nonlinear static and dynamic procedures.
Resistin Induces LIN28A-Mediated Let-7a Repression in Breast Cancer Cells Leading to IL-6 and STAT3 Upregulation
Authors: Deshmukh Sachin Kumar , Srivastava Sanjeev Kumar , Zubair Haseeb , Khan Mohammad Aslam , Singh Ajay Pratap , Singh Seema
Published: September 2021

Downregulation of the Let-7 family of microRNAs (miRNAs) has been reported in several cancers, including breast malignancy; however, underlying mechanisms are not completely understood. Resistin is an important component of the tumor microenvironment, having a functional impact on the tumor cell phenotypes. Here, we examined the role of resistin in the regulation of Let-7 miRNAs and studied its downstream consequences. We found that resistin treatment led to the reduced expression of Let-7 family miRNAs in breast cancer (BC) cells, with the highest downregulation reported for Let-7a. Furthermore, resistin induced the expression of LIN28A, and its silencing abrogated resistin-mediated Let-7a suppression. Let-7a restoration or LIN28A silencing abolished the resistin-induced growth, clonogenicity, and sphere-forming ability of BC cells. Restoration of Let-7a also suppressed the resistin-induced expression of genes associated with growth, survival, and stemness. Pathway analysis suggested STAT3 as a putative central node associated with Let-7a-mediated gene regulation. In silico analysis identified STAT3 and its upstream modifier, IL-6, as putative Let-7a gene targets, which were later confirmed by 3′UTR-reporter assays. Together, our findings demonstrate a novel resistin/LIN28A/Let-7a/IL-6/STAT3 signaling axis supporting the growth and stemness of BC cells.
Potential of Bioactive Food Components against Gastric Cancer: Insights into Molecular Mechanism and Therapeutic Targets
Authors: Kang Seog Young , Hwang Dongwon , Shin Soyoung , Park Jinju , Kim Myoungchan , Rahman MD. Hasanur , Rahman Md. Ataur , Ko Seong-Gyu , Kim Bonglee
Published: September 2021

Gastric cancer, also known as stomach cancer, is a cancer that develops from the lining of the stomach. Accumulated evidence and epidemiological studies have indicated that bioactive food components from natural products play an important role in gastric cancer prevention and treatment, although its mechanism of action has not yet been elucidated. Particularly, experimental studies have shown that natural bioactive food products display a protective effect against gastric cancer via numerous molecular mechanisms, such as suppression of cell metastasis, anti-angiogenesis, inhibition of cell proliferation, induction of apoptosis, and modulation of autophagy. Chemotherapy remains the standard treatment for advanced gastric cancer along with surgery, radiation therapy, hormone therapy, as well as immunotherapy, and its adverse side effects including neutropenia, stomatitis, mucositis, diarrhea, nausea, and emesis are well documented. However, administration of naturally occurring bioactive phytochemical food components could increase the efficacy of gastric chemotherapy and other chemotherapeutic resistance. Additionally, several studies have suggested that bioactive food components with structural stability, potential bioavailability, and powerful bioactivity are important to develop novel treatment strategies for gastric cancer management, which may minimize the adverse effects. Therefore, the purpose of this review is to summarize the potential therapeutic effects of natural bioactive food products on the prevention and treatment of gastric cancer with intensive molecular mechanisms of action, bioavailability, and safety efficacy.
Deep-Learning Assessed Muscular Hypodensity Independently Predicts Mortality in DLBCL Patients Younger Than 60 Years
Authors: Jullien Maxime , Tessoulin Benoit , Ghesquières Hervé , Oberic Lucie , Morschhauser Franck , Tilly Hervé , Ribrag Vincent , Lamy Thierry , Thieblemont Catherine , Villemagne Bruno , Gressin Rémy , Bouabdallah Kamal , Haioun Corinne , Damaj Gandhi , Fornecker Luc-Matthieu , Schiano De Colella Jean-Marc , Feugier Pierre , Hermine Olivier , Cartron Guillaume , Bonnet Christophe , André Marc , Bailly Clément , Casasnovas René-Olivier , Le Gouill Steven
Published: September 2021

Background. Muscle depletion (MD) assessed by computed tomography (CT) has been shown to be a predictive marker in solid tumors, but has not been assessed in non-Hodgkin’s lymphomas. Despite software improvements, MD measurement remains highly time-consuming and cannot be used in clinical practice. Methods. This study reports the development of a Deep-Learning automatic segmentation algorithm (DLASA) to measure MD, and investigate its predictive value in a cohort of 656 diffuse large B cell lymphoma (DLBCL) patients included in the GAINED phase III prospective trial (NCT01659099). Results. After training on a series of 190 patients, the DLASA achieved a Dice coefficient of 0.97 ± 0.03. In the cohort, the median skeletal muscle index was 50.2 cm2/m2 and median muscle attenuation (MA) was 36.1 Hounsfield units (HU). No impact of sarcopenia was found on either progression free survival (PFS) or overall survival (OS). Muscular hypodensity, defined as MA below the tenth percentile according to sex, was associated with a lower OS and PFS, respectively (HR = 2.80 (95% CI 1.58–4.95), p < 0.001, and HR = 2.22 (95% CI 1.43–3.45), p < 0.001). Muscular hypodensity appears to be an independent risk factor for mortality in DLBCL and because of DLASA can be estimated in routine practice.
Erlotinib Promotes Ligand-Induced EGFR Degradation in 3D but Not 2D Cultures of Pancreatic Ductal Adenocarcinoma Cells
Authors: Betriu Nausika , Andreeva Anna , Semino Carlos E.
Published: September 2021

The epithelial growth factor receptor (EGFR) is a tyrosine kinase receptor that participates in many biological processes such as cell proliferation. In addition, EGFR is overexpressed in many epithelial cancers and therefore is a target for cancer therapy. Moreover, EGFR responds to lots of stimuli by internalizing into endosomes from where it can be recycled to the membrane or further sorted into lysosomes where it undergoes degradation. Two-dimensional cell cultures have been classically used to study EGFR trafficking mechanisms in cancer cells. However, it has been widely demonstrated that in 2D cultures cells are exposed to a non-physiological environment as compared to 3D cultures that provide the normal cellular conformation, matrix dimensionality and stiffness, as well as molecular gradients. Therefore, the microenvironment of solid tumors is better recreated in 3D culture models, and this is why they are becoming a more physiological alternative to study cancer physiology. Here, we develop a new model of EGFR internalization and degradation upon erlotinib treatment in pancreatic ductal adenocarcinoma (PDAC) cells cultured in a 3D self-assembling peptide scaffold. In this work, we show that treatment with the tyrosine kinase inhibitor erlotinib promotes EGFR degradation in 3D cultures of PDAC cell lines but not in 2D cultures. We also show that this receptor degradation does not occur in normal fibroblast cells, regardless of culture dimensionality. In conclusion, we demonstrate not only that erlotinib has a distinct effect on tumor and normal cells but also that pancreatic ductal adenocarcinoma cells respond differently to drug treatment when cultured in a 3D microenvironment. This study highlights the importance of culture systems that can more accurately mimic the in vivo tumor physiology.
The Role of p53 in Progression of Cutaneous Squamous Cell Carcinoma
Authors: Piipponen Minna , Riihilä Pilvi , Nissinen Liisa , Kähäri Veli-Matti
Published: September 2021

Skin cancers are the most common types of cancer worldwide, and their incidence is increasing. Melanoma, basal cell carcinoma (BCC), and cutaneous squamous cell carcinoma (cSCC) are the three major types of skin cancer. Melanoma originates from melanocytes, whereas BCC and cSCC originate from epidermal keratinocytes and are therefore called keratinocyte carcinomas. Chronic exposure to ultraviolet radiation (UVR) is a common risk factor for skin cancers, but they differ with respect to oncogenic mutational profiles and alterations in cellular signaling pathways. cSCC is the most common metastatic skin cancer, and it is associated with poor prognosis in the advanced stage. An important early event in cSCC development is mutation of the TP53 gene and inactivation of the tumor suppressor function of the tumor protein 53 gene (TP53) in epidermal keratinocytes, which then leads to accumulation of additional oncogenic mutations. Additional genomic and proteomic alterations are required for the progression of premalignant lesion, actinic keratosis, to invasive and metastatic cSCC. Recently, the role of p53 in the invasion of cSCC has also been elucidated. In this review, the role of p53 in the progression of cSCC and as potential new therapeutic target for cSCC will be discussed.
Accuracy and Reliability of Internet Resources for Information on Monoclonal Gammopathy of Undetermined Significance—What Information Is out There for Our Patients?
Authors: Kreutzer Emma Pauline , Sauer Sandra , Kriegsmann Mark , Staemmler Henrike , Egerer Gerlinde , Kriegsmann Katharina
Published: September 2021

Background: Online information gathering can increase patients’ engagement in decision-making. The quality of online resources available for monoclonal gammopathy of undetermined significance (MGUS) was evaluated. Methods: 900 websites from Google, Bing, Yahoo, and 150 YouTube videos were assessed. Results: The websites did not differ regarding their search rank or between the search engines. The median time since last update was 24 months. The 86 unique websites showed a medium to poor general quality (JAMA score 3/4, only 8.1% websites with a valid HON certificate). The patient- (user-) focused quality was poor (sum DISCERN score 27/80 points). The reading level was difficult (11th US school grade). The content level was very low (13/50 points). 12.8% of websites contained misleading/wrong facts. Websites provided by scientific/governmental organizations had a higher content level. For the 61 unique videos, the median time since upload was 34 months. The videos showed a medium general quality (HON Foundation score). The patient- (user-) focused quality was poor (sum DISCERN score 24 points). The content level was very low (6 points). Conclusion: MGUS-relevant online sources showed a low quality that was provided on a high reading level. Incorporation of quality indices and regular review of online content is warranted.
Applications of CRISPR-Cas9 Technology to Genome Editing in Glioblastoma Multiforme
Authors: Al-Sammarraie Nadia , Ray Swapan K.
Published: September 2021

Glioblastoma multiforme (GBM) is an aggressive malignancy of the brain and spinal cord with a poor life expectancy. The low survivability of GBM patients can be attributed, in part, to its heterogeneity and the presence of multiple genetic alterations causing rapid tumor growth and resistance to conventional therapy. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR associated (Cas) nuclease 9 (CRISPR-Cas9) system is a cost-effective and reliable gene editing technology, which is widely used in cancer research. It leads to novel discoveries of various oncogenes that regulate autophagy, angiogenesis, and invasion and play important role in pathogenesis of various malignancies, including GBM. In this review article, we first describe the principle and methods of delivery of CRISPR-Cas9 genome editing. Second, we summarize the current knowledge and major applications of CRISPR-Cas9 to identifying and modifying the genetic regulators of the hallmark of GBM. Lastly, we elucidate the major limitations of current CRISPR-Cas9 technology in the GBM field and the future perspectives. CRISPR-Cas9 genome editing aids in identifying novel coding and non-coding transcriptional regulators of the hallmarks of GBM particularly in vitro, while work using in vivo systems requires further investigation.
Measurement of Chromosomal Arms and FISH Reveal Complex Genome Architecture and Standardized Karyotype of Model Fish, Genus Carassius
Authors: Knytl Martin , Fornaini Nicola
Published: September 2021

The widely distributed ray-finned fish genus Carassius is very well known due to its unique biological characteristics such as polyploidy, clonality, and/or interspecies hybridization. These biological characteristics have enabled Carassius species to be successfully widespread over relatively short period of evolutionary time. Therefore, this fish model deserves to be the center of attention in the research field. Some studies have already described the Carassius karyotype, but results are inconsistent in the number of morphological categories for individual chromosomes. We investigated three focal species: Carassius auratus, C. carassius and C. gibelio with the aim to describe their standardized diploid karyotypes, and to study their evolutionary relationships using cytogenetic tools. We measured length (q+plength) of each chromosome and calculated centromeric index (i value). We found: (i) The relationship between q+plength and i value showed higher similarity of C. auratus and C. carassius. (ii) The variability of i value within each chromosome expressed by means of the first quartile (Q1) up to the third quartile (Q3) showed higher similarity of C. carassius and C. gibelio. (iii) The fluorescent in situ hybridization (FISH) analysis revealed higher similarity of C. auratus and C. gibelio. (iv) Standardized karyotype formula described using median value (Q2) showed differentiation among all investigated species: C. auratus had 24 metacentric (m), 40 submetacentric (sm), 2 subtelocentric (st), 2 acrocentric (a) and 32 telocentric (T) chromosomes (24m+40sm+2st+2a+32T); C. carassius: 16m+34sm+8st+42T; and C. gibelio: 16m+22sm+10st+2a+50T. (v) We developed R scripts applicable for the description of standardized karyotype for any other species. The diverse results indicated unprecedented complex genomic and chromosomal architecture in the genus Carassius probably influenced by its unique biological characteristics which make the study of evolutionary relationships more difficult than it has been originally postulated.
Spatial Contributions to 1H NMR Chemical Shifts of Free-Base Porphyrinoids
Authors: Fliegl Heike , Dimitrova Maria , Berger Raphael J. F. , Sundholm Dage
Published: September 2021

A recently developed methodology for calculating, analyzing, and visualizing nuclear magnetic shielding densities is used for studying spatial contributions including ring-current contributions to 1H nuclear magnetic resonance (NMR) chemical shifts of aromatic and anti-aromatic free-base porphyrinoids. Our approach allows a visual inspection of the spatial origin of the positive (shielding) and negative (deshielding) contributions to the nuclear magnetic shielding constants. Diatropic and paratropic current-density fluxes yield both shielding and deshielding contributions implying that not merely the tropicity of the current density determines whether the contribution has a shielding or deshielding character. Instead the shielding or deshielding contribution is determined by the direction of the current-density flux with respect to the studied nucleus.
Electronic Currents and Anapolar Response Induced in Molecules by Monochromatic Light
Authors: Summa Francesco Ferdinando , Lazzeretti Paolo
Published: September 2021

It is shown that the electric dipole- and electric quadrupole–anapole polarizabilities, denoted respectively by fαβ′ and gα,βγ′, and the anapole magnetizability aαβ, are intrinsic properties of the electron cloud of molecules responding to optical fields. fαβ′ is a nonvanishing property of chiral and achiral compounds, whereas aαβ is suitable for enantiomer discrimination of chiral species. They can conveniently be evaluated by numerical integration, employing a formulation complementary to that provided by perturbation theory and relying on the preliminary computation of electronic current density tensors all over the molecular domain. The origin dependence of the dynamic anapolar response is rationalized via related computational techniques employing numerical integration, as well as definitions of molecular property tensors, for example, electric dipole and electric quadrupole polarizabilties and magnetizability. A preliminary application of the theory is reported for the Ra enantiomer of the hydrogen peroxide molecule, evaluating tensor components of electric dipole-anapole polarizability and anapole magnetizability as functions of the dihedral angle ϕ≡∠ H-O-O-H in the range 0∘≤ϕ≤180∘.
Yb to Tb Cooperative Upconversion in Supramolecularly Assembled Complexes in a Solution
Authors: Soro Lohona K. , Charpentier Cyrille , Przybilla Frédéric , Mély Yves , Nonat Aline M. , Charbonnière Loïc J.
Published: September 2021

The podand-type ligand L, based on a tertiary amine substituted by three pyridyl-6-phosphonic acid functions, forms hydrated complexes with Ln3+ cations. The luminescence properties of the YbL complex were studied in D2O as a function of the pD and temperature. In basic conditions, increases in the luminescence quantum yield and the excited state lifetime of the Yb centered emission associated with the 2F5/2 → 2F7/2 transition were observed and attributed to a change in the hydration number from two water molecules in the first coordination sphere of Yb at acidic pH to a single one in basic conditions. Upon the addition of TbCl3 salts to a solution containing the YbL complex in D2O, heteropolynuclear Yb/Tb species formed, and excitation of the Yb at 980 nm resulted in the observation of the typical visible emission of Tb as a result of a cooperative upconversion (UC) photosensitization process. The UC was further evidenced by the quadratic dependence of the UC emission as a function of the laser power density.
Building Information Modelling in Structural Engineering: A Qualitative Literature Review
Authors: Ciotta Vittoria , Asprone Domenico , Manfredi Gaetano , Cosenza Edoardo
Published: September 2021

Over the past decade, the fields of civil engineering, i.e., structural engineering, have increasingly used the building information modelling (BIM) approach in both professional practice and as the focus of research. However, the field of structural engineering, which can be seen as a sub-discipline of civil engineering, misses, as far as the authors are aware, a real state-of-the-art on the use of BIM in this regard. The aim of this paper, therefore, is to start bridging that gap. In particular, the authors have conducted a traditional literature review on the utilisation of BIM in structural engineering, enabling them to perform a detailed content analysis of publications. The qualitative investigation of the literature that the authors have conducted has highlighted six main BIM uses in structural engineering: (1) structural analyses; (2) production of shop drawings; (3) optimized structural design, early identification of constructability issues, and a comparison of different structural solutions; (4) seismic risk assessments; (5) existing-condition modelling and retrofitting of structures; and (6) structural health monitoring. Each of these is discussed in relation to their reference workflows; use of information models; information exchanges; and main limitations. In the conclusions, the authors identify current gaps in knowledge, as well as likely developments and improvements in the utilization of BIM in structural engineering. The authors also outline the possible significance of this work more broadly.
Effects of Surface Morphology on Erosion–Corrosion and Corrosion Resistance of Highly Hydrophobic Nickel-Tungsten Electrodeposited Film
Authors: Salehikahrizsangi Parinaz , Raeissi Keyvan , Karimzadeh Fathallah , Calabrese Luigi , Proverbio Edoardo
Published: September 2021

Hard nanocrystalline Ni-Co or Ni-W coatings are receiving a growing interest owing to their premium hardness, wear, and corrosion properties for several industrial applications. Furthermore, surface hydrophobicity greatly improves surface corrosion resistance. In this research, the durability of hydrophobic hierarchical NiW electrodeposited film has been evaluated in a high-speed slurry erosion–corrosion (EC) test rig. Two different coatings have been tested: a rough coating obtained in a chloride-based bath (NiWchloride) and a smooth coating obtained in a sulfate-based bath (NiWsulfate). Corrosion behavior over time was evaluated by electrochemical impedance spectroscopy (EIS), while surface hydrophobic performance was determined by the sessile drop method. The morphological features of the coatings were assessed by scanning electron microscopy while roughness modification during the EC tests were identified by means of an atomic force microscopy. During static immersion in the aggressive solution, the impedance modulus of the coatings continuously increased due to an increase in the thickness of corrosion products. During the EC test, the impedance modulus of the smooth NiW coating decreased, losing its barrier property. It was observed that the increase in impedance modulus of the hierarchical structure of the rough NiW coating during EC was far greater than that during static immersion. After 64 min of EC, the NiWchloride was able to resume its hydrophobicity property by storing in air; nevertheless, the NiWsulfate, with a loss of approximately 72% in its initial contact angle, was no longer hydrophobic. The results showed improvements in the lifetime of hydrophobic NiW coatings in erosion–corrosion conditions of the hierarchical nanostructure obtained in a chloride-based electroplating bath.
Clinical Evaluation of Topical Lotion Containing 2-Aza-8-Oxohypoxanthine on Skin Barrier Function against Water Loss
Authors: Aoshima Hisae , Ibuki Rinta , Ito Masayuki , Kawagishi Hirokazu
Published: September 2021

A clinical study was conducted to evaluate the efficacy of 2-aza-8-oxohypoxanthine (AOH) on human skin in a double-blind, placebo-controlled, and split-face comparative trial. To this end, a topical lotion containing 0.1% of AOH and its placebo formulation were applied in 20 Japanese subjects (age: 41–58 years, average: 48.4 ± 4.7 years) to their faces daily for eight weeks. The moisture content in the stratum corneum and the trans-epidermal water loss (TEWL) were measured at the beginning of the study and after eight weeks. The results obtained upon comparing the data of the two measuring points showed that the 0.1% AOH lotion caused a statistically significant larger decrease in TEWL after eight weeks. Moreover, the 0.1% AOH lotion produced a larger increase in the moisture content in the stratum corneum after eight weeks, although there was no statistical difference between the two formulations. These results clearly indicate that AOH is effective as a cosmetic agent with a skin barrier function against water loss.
Study of the Interaction of Sorption and Catalytic Centers in Carboxypeptidase T by X-ray Analysis
Authors: Akparov Valerij , Timofeev Vladimir , Kuranova Inna , Khaliullin Ilias
Published: September 2021

Carboxypeptidase T (CPT; EC 3.4.17.18) from Thermoactinomyces vulgaris is a distant homolog of the highly specific pancreatic carboxypeptidase B; but has a broad substrate specificity; the source of which remains unclear. A previous study of the structural bases of the substrate specificity of CPT using stable sulfamoyl analogs of the transition state of the elimination of leucine; phenylalanine; arginine; and glutamic acid; showed that the binding of the C-terminal residue of the substrate to the primary selectivity pocket of CPT leads to a change in the distance between Zn2+ and the sulfur atom. This value is related to the efficiency of catalysis of the corresponding substrate or the inhibition constant of the corresponding stable analog of the transition state. In this work; we obtained crystallographic and kinetic data of the complex of CPT with N-sulfamoyl-L-valine; confirming the effect of the binding of the ligand’s side group by the primary specificity pocket of CPT on the structure of the catalytic center; which can explain the unusual substrate specificity of CPT.
Long-Term Results of Postoperative Hypofractionated Accelerated Breast and Lymph Node Radiotherapy (HypoAR) with Hypofractionated Boost
Authors: Koukourakis Ioannis M. , Panteliadou Marianthi , Giakzidis Axiotis G. , Nanos Christos , Abatzoglou Ioannis , Giatromanolaki Alexandra , Koukourakis Michael I.
Published: September 2021

We report long-term results (median follow-up 12 years) of hypofractionated accelerated radiotherapy (HypoAR) in patients treated with breast-conserving surgery. In total, 367 women were treated with HypoAR. Axillary and supraclavicular area (ASA) were treated in patients with involved nodes. In total, 290 patients (scheme A) received 3.5 Gy/day ×10 fractions (breast/ASA) followed by two 4 Gy fractions with electrons to the affected breast quadrant within 16 days. In total, 77 patients (Scheme B) received 2.7 Gy/day for 16 consecutive fractions (breast/ASA) within 22 days, while concurrently, the affected breast quadrant received an electron booster dose of 0.8 Gy for the first 13 fractions. Amifostine was offered to 252/367 patients. Early radiation toxicity was minimal. Regarding late toxicities, symptomatic breast edema was noted in 2.2%, asymptomatic breast fibrosis in 1.9%, and arm lymphedema in 3.7% of patients. Amifostine reduced early radiation dermatitis (p = 0.001). In total, 2.2% of patients developed contralateral breast and 1.6% other carcinomas. Locoregional recurrence (LR) occurred in 3.1% of patients (0% for in situ carcinomas). Positive margins after surgery, extracapsular node invasion, and HER2-enriched/triple-negative tumors were linked with significantly worse LR-free survival. The involvement of more than three nodes and luminal type other than A were independent prognostic variables of metastasis and death events. HypoAR delivering a biological dose of 50–52 Gy to the breast/ASA is a safe and effective therapy for patients treated with conservative surgery. The risk of carcinogenesis is low. Positive surgical margins, extracapsular node invasion, and HER2-enriched/triple-negative phenotypes appear as a cluster of features linked with a higher risk for locoregional relapse.
Restricted Geographic Sampling Yields Low Parasitism Rates but Surprisingly Diverse Host Associations in Avian Lice (Insecta: Phthiraptera) from South Texas
Authors: Pistone John P. , Light Jessica E. , Campbell Tyler A. , Catanach Therese A. , Voelker Gary
Published: September 2021

South Texas is a highly variable region encompassing multiple habitat types and harboring a wide diversity of organisms. However, the parasite fauna in this region is poorly known, especially for avian ectoparasites such as lice. To better understand avian louse diversity and host associations in South Texas, we examined a total of 507 birds for chewing lice. Lice were morphologically identified to genus and phylogenetic analysis was performed using one mitochondrial (COI) and two nuclear (18S rRNA and EF-1α) genes. Of the birds examined, 69 (13.5%) were parasitized by lice resulting in a total of 63 host associations across 45 bird species, 29 of which were previously unrecorded. The predominant taxa encountered during this study included two of the most diverse louse genera, Myrsidea and Brueelia. Molecular analyses revealed 21 distinct genetic lineages, 17 of which are associated with novel host associations and may represent new species. This study represents the first extensive examination of avian louse host associations and relationships in Texas and reveals that there is still much to be learned about ectoparasite diversity in the New World.
Localization, Disorder, and Entropy in a Coarse-Grained Model of the Amorphous Solid
Authors: Leishangthem Premkumar , Ahmad Faizyab , Das Shankar
Published: September 2021

We study the role of disorder in producing the metastable states in which the extent of mass localization is intermediate between that of a liquid and a crystal with long-range order. We estimate the corresponding entropy with the coarse-grained description of a many-particle system used in the classical density functional model. We demonstrate that intermediate localization of the particles results in a change of the entropy from what is obtained from a microscopic approach using for sharply localized vibrational modes following a Debye distribution. An additional contribution is included in the density of vibrational states g(ω) to account for this excess entropy. A corresponding peak in g(ω)/ω2 vs. frequency ω matches the characteristic boson peak seen in amorphous solids. In the present work, we also compare the shear modulus for the inhomogeneous solid having localized density profiles with the corresponding elastic response for the uniform liquid in the limit of high frequencies.