bluuebunny/crossref_metadata_2025 huggingface dataset:
Regorafenib-Attenuated, Bleomycin-Induced Pulmonary Fibrosis by Inhibiting the TGF-β1 Signaling Pathway
Authors: Li Xiaohe , Ma Ling , Huang Kai , Wei Yuli , Long Shida , Liu Qinyi , Zhang Deqiang , Wu Shuyang , Wang Wenrui , Yang Guang , Zhou Honggang , Yang Cheng
Published: February 2021

Idiopathic pulmonary fibrosis (IPF) is a fatal and age-related pulmonary disease. Nintedanib is a receptor tyrosine kinase inhibitor, and one of the only two listed drugs against IPF. Regorafenib is a novel, orally active, multi-kinase inhibitor that has similar targets to nintedanib and is applied to treat colorectal cancer and gastrointestinal stromal tumors in patients. In this study, we first identified that regorafenib could alleviate bleomycin-induced pulmonary fibrosis in mice. The in vivo experiments indicated that regorafenib suppresses collagen accumulation and myofibroblast activation. Further in vitro mechanism studies showed that regorafenib inhibits the activation and migration of myofibroblasts and extracellular matrix production, mainly through suppressing the transforming growth factor (TGF)-β1/Smad and non-Smad signaling pathways. In vitro studies have also indicated that regorafenib could augment autophagy in myofibroblasts by suppressing TGF-β1/mTOR (mechanistic target of rapamycin) signaling, and could promote apoptosis in myofibroblasts. In conclusion, regorafenib attenuates bleomycin-induced pulmonary fibrosis by suppressing the TGF-β1 signaling pathway.
Transcriptome Analysis of Subcutaneous Adipose Tissue from Severely Obese Patients Highlights Deregulation Profiles in Coding and Non-Coding Oncogenes
Authors: Rey Federica , Messa Letizia , Pandini Cecilia , Launi Rossella , Barzaghini Bianca , Micheletto Giancarlo , Raimondi Manuela Teresa , Bertoli Simona , Cereda Cristina , Zuccotti Gian Vincenzo , Cancello Raffaella , Carelli Stephana
Published: February 2021

Obesity is a major risk factor for a large number of secondary diseases, including cancer. Specific insights into the role of gender differences and secondary comorbidities, such as type 2 diabetes (T2D) and cancer risk, are yet to be fully identified. The aim of this study is thus to find a correlation between the transcriptional deregulation present in the subcutaneous adipose tissue of obese patients and the oncogenic signature present in multiple cancers, in the presence of T2D, and considering gender differences. The subcutaneous adipose tissue (SAT) of five healthy, normal-weight women, five obese women, five obese women with T2D and five obese men were subjected to RNA-sequencing, leading to the identification of deregulated coding and non-coding RNAs, classified for their oncogenic score. A panel of DE RNAs was validated via Real-Time PCR and oncogene expression levels correlated the oncogenes with anthropometrical parameters, highlighting significant trends. For each analyzed condition, we identified the deregulated pathways associated with cancer, the prediction of possible prognosis for different cancer types and the lncRNAs involved in oncogenic networks and tissues. Our results provided a comprehensive characterization of oncogenesis correlation in SAT, providing specific insights into the possible molecular targets implicated in this process. Indeed, the identification of deregulated oncogenes also in SAT highlights hypothetical targets implicated in the increased oncogenic risk in highly obese subjects. These results could shed light on new molecular targets to be specifically modulated in obesity and highlight which cancers should receive the most attention in terms of better prevention in obesity-affected patients.
Inhibition of Potassium Channels Affects the Ability of Pig Spermatozoa to Elicit Capacitation and Trigger the Acrosome Exocytosis Induced by Progesterone
Authors: Noto Federico , Recuero Sandra , Valencia Julián , Saporito Beatrice , Robbe Domenico , Bonet Sergi , Carluccio Augusto , Yeste Marc
Published: February 2021

During capacitation, sperm undergo a myriad of changes, including remodeling of plasma membrane, modification of sperm motility and kinematic parameters, membrane hyperpolarization, increase in intracellular calcium levels, and tyrosine phosphorylation of certain sperm proteins. While potassium channels have been reported to be crucial for capacitation of mouse and human sperm, their role in pigs has not been investigated. With this purpose, sperm samples from 15 boars were incubated in capacitation medium for 300 min with quinine, a general blocker of potassium channels (including voltage-gated potassium channels, calcium-activated potassium channels, and tandem pore domain potassium channels), and paxilline (PAX), a specific inhibitor of calcium-activated potassium channels. In all samples, acrosome exocytosis was induced after 240 min of incubation with progesterone. Plasma membrane and acrosome integrity, membrane lipid disorder, intracellular calcium levels, mitochondrial membrane potential, and total and progressive sperm motility were evaluated after 0, 120, and 240 min of incubation, and after 5, 30, and 60 min of progesterone addition. Although blocking potassium channels with quinine and PAX prevented sperm to elicit in vitro capacitation by impairing motility and mitochondrial function, as well as reducing intracellular calcium levels, the extent of that inhibition was larger with quinine than with PAX. Therefore, while our data support that calcium-activated potassium channels are essential for sperm capacitation in pigs, they also suggest that other potassium channels, such as the voltage-gated, tandem pore domain, and mitochondrial ATP-regulated ones, are involved in that process. Thus, further research is needed to elucidate the specific functions of these channels and the mechanisms underlying its regulation during sperm capacitation.
Activation of Apoptosis in a βB1-CTGF Transgenic Mouse Model
Authors: Weiss Maximilian , Reinehr Sabrina , Mueller-Buehl Ana M. , Doerner Johanna D. , Fuchshofer Rudolf , Stute Gesa , Dick H. Burkhard , Joachim Stephanie C.
Published: February 2021

To reveal the pathomechanisms of glaucoma, a common cause of blindness, suitable animal models are needed. As previously shown, retinal ganglion cell and optic nerve degeneration occur in βB1-CTGF mice. Here, we aimed to determine possible apoptotic mechanisms and degeneration of different retinal cells. Hence, retinae were processed for immunohistology (n = 5–9/group) and quantitative real-time PCR analysis (n = 5–7/group) in 5- and 10-week-old βB1-CTGF and wildtype controls. We noted significantly more cleaved caspase 3+ cells in βB1-CTGF retinae at 5 (p = 0.005) and 10 weeks (p = 0.02), and a significant upregulation of Casp3 and Bax/Bcl2 mRNA levels (p < 0.05). Furthermore, more terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL+) cells were detected in transgenic mice at 5 (p = 0.03) and 10 weeks (p = 0.02). Neurofilament H staining (p = 0.01) as well as Nefh (p = 0.02) and Tubb3 (p = 0.009) mRNA levels were significantly decreased at 10 weeks. GABAergic synapse intensity was lower at 5 weeks, while no alterations were noted at 10 weeks. The glutamatergic synapse intensity was decreased at 5 (p = 0.007) and 10 weeks (p = 0.01). No changes were observed for bipolar cells, photoreceptors, and macroglia. We conclude that apoptotic processes and synapse loss precede neuronal death in this model. This slow progression rate makes the βB1-CTGF mice a suitable model to study primary open-angle glaucoma.
Upstream Statin Therapy and Long-Term Recurrence of Atrial Fibrillation after Cardioversion: A Propensity-Matched Analysis
Authors: Fiedler Lukas , Hallsson Lára , Tscharre Maximilian , Oebel Sabrina , Pfeffer Michael , Schönbauer Robert , Tokarska Lyudmyla , Stix Laura , Haiden Anton , Kraus Johannes , Blessberger Hermann , Siebert Uwe , Roithinger Franz Xaver
Published: February 2021

The relationship of statin therapy with recurrence of atrial fibrillation (AF) after cardioversion (CV) has been evaluated by several investigations, which provided conflicting results and particularly long-term data is scarce. We sought to examine whether upstream statin therapy is associated with long-term recurrence of AF after CV. This was a single-center registry study including consecutive AF patients (n = 454) undergoing CV. Cox regression models were performed to estimate AF recurrence comparing patients with and without statins. In addition, we performed a propensity score matched analysis with a 1:1 ratio. Statins were prescribed to 183 (40.3%) patients. After a median follow-up period of 373 (207–805) days, recurrence of AF was present in 150 (33.0%) patients. Patients receiving statins had a significantly lower rate of AF recurrence (log-rank p < 0.001). In univariate analysis, statin therapy was associated with a significantly reduced rate of AF recurrence (HR 0.333 (95% CI 0.225–0.493), p = 0.001), which remained significant after adjustment (HR 0.238 (95% CI 0.151–0.375), p < 0.001). After propensity score matching treatment with statins resulted in an absolute risk reduction of 27.5% for recurrent AF (21 (18.1%) vs. 53 (45.7%); p < 0.001). Statin therapy was associated with a reduced risk of long-term AF recurrence after successful cardioversion.
A Review of the Major Prosthetic Factors Influencing the Prognosis of Implant Prosthodontics
Authors: Montero Javier
Published: February 2021

Background: The treatment plan of prosthetic restorations supported by dental implants requires comprehensive scientific knowledge to deliver prostheses with good prognosis, even before the implant insertion. This review aims to analyze the main prosthetic determinants of the prognosis of implant-supported prostheses. Methods: A comprehensive review of the literature was conducted with a PICO (Patient Intervention Comparison Outcomes) question: “For partially or complete edentulous subjects treated with implant-supported prostheses, which prosthetic factors could affect clinical outcomes?”. A literature search was performed electronically in PubMed (MEDLINE), Scopus and Cochrane Library with the following equation [PROGNOS * OR RISK] FACTOR IMPLANT DENTAL, and by hand search in relevant journals and throughout the selected papers. Results: This revision was carried out based on 50 papers focused on several prosthodontics-related risk factors that were grouped as follows: implant-connection, loading protocol, transmucosal abutments, prosthetic fit, provisionalization, type of retention, impression technique, fabrication technique, and occlusion. More than a half of the studies were systematic reviews (30%), meta-analysis (16%), or prospective evaluations of prosthesis with various kinds of events (18%). However, narrative reviews of literature (14%) and in vitro/animal studies (16%) were also found. Conclusions: The current literature provides insufficient evidence for most of the investigated topics. However, based on the accumulated data, it seems reasonable to defend that the best treatment approach is the use of morse taper implants with transmucosal abutments, recorded by means of rigidly splinted copings through the pick-up technique, and screwed by milled prosthesis occlusally adjusted to minimize functional overloading.
Delivering Personalized Care at a Distance: How Telemedicine Can Foster Getting to Know the Patient as a Person
Authors: Record Janet , Ziegelstein Roy , Christmas Colleen , Rand Cynthia , Hanyok Laura
Published: February 2021

The promise of precision medicine is based on the use of new technologies to better characterize patients by defining individuals in the areas of genomics, proteomics, metabolomics and other aspects of biologic variability. Wise application of modern technology can similarly transform health visits with patients, allowing for better characterization of the patient’s individual life circumstances than possible in a traditional office visit. The use of, and experience with, telemedicine have increased significantly during the COVID-19 pandemic. Patients and clinicians report high satisfaction with telemedicine, and the quality of communication and patient-centeredness experienced in this setting are both rated highly. In this article, we explore the benefits offered by telemedicine in facilitating personalized care with particular focus on telemedicine delivered by video platforms. We propose strategies and skills specific to the effective implementation of personalized telemedicine, drawing on literature in patient-centered communication and home visits. While traditional in-person office visits continue to offer important opportunities such as thorough physical examination and the potential for enhanced non-verbal communication, telemedicine offers many important advantages that can facilitate the process of getting to know the patient as a person.
Lyophilized Emulsions in the Form of 3D Porous Matrices as a Novel Material for Topical Application
Authors: Prus-Walendziak Weronika , Kozlowska Justyna
Published: February 2021

Researchers are constantly searching for innovations that can be applied to the cosmetic industry. Production of porous materials stored in a lyophilized form and swollen directly before use may be beneficial considering their facilitated packaging, transport and storage. In this study, we propose porous materials based on sodium alginate, gelatin, glycerol and lipids (cottonseed oil and beeswax) obtained by freeze-drying and cross-linking. Material composition with the most promising properties was modified by the addition of PLA microparticles with Calendula officinalis flower extract. The structure and properties of obtained porous materials were analyzed. ATR-FTIR, mechanical properties, residual moisture content, porosity and density were assessed, as well as swelling properties and degradation after their cross-linking. The loading capacity and in vitro release of Calendula officinalis flower extract were performed for samples with incorporated PLA microparticles containing plant extract. The modification of the composition and fabrication method of materials significantly influenced their physicochemical properties. The selected plant extract was successfully incorporated into polymeric microparticles that were subsequently added into developed materials. Prepared materials may be considered during designing new cosmetic formulations.
Investigation of Multiparameter Laser Stripping of AlTiN and DLC C Coatings
Authors: Primus Tomáš , Hlavinka Josef , Zeman Pavel , Brajer Jan , Šorm Martin , Čermák Adam , Kožmín Pavel , Holešovský František
Published: February 2021

The lifetime and properties of cutting tools and forming moulds can be prolonged and enhanced by the deposition of hard, thin coatings. After a certain period of usage, the coating will deteriorate. Any remaining coating must be removed prior to successful recoating. Laser stripping is a fast and environmentally friendly coating removal method. In this paper, we present laser removal of two types of coatings deposited on a 1.2379 tool steel substrate, namely, an AlTiN coating with high hardness and a DLC C coating with a small coefficient of friction (COF). A powerful nanosecond laser was employed to remove the coating from the substrate with high efficiency, along with suitable residual surface roughness. Measurements were taken of surface roughness, removed depth, and working time on a stripped area of 1 cm2. The samples were evaluated under a microscope, with a 3D profilometer, and by EDS chemical analysis. Successful removal of the coating was confirmed by optical analysis, but detailed chemical characterisation showed that about 30% of the coating element may remain on the surface. Moreover, a working time of less than 7.5 s per cm2 was obtained in this study. In addition, it was shown that the application of a second low energy, high frequency laser beam pass leads to remelting of the peaks of the material and reduced surface roughness.
Hybrid Assembly Path Planning for Complex Products by Reusing a Priori Data
Authors: Yi Guodong , Zhou Chuanyuan , Cao Yanpeng , Hu Hangjian
Published: February 2021

Assembly path planning (APP) for complex products is challenging due to the large number of parts and intricate coupling requirements. A hybrid assembly path planning method is proposed herein that reuses a priori paths to improve the efficiency and success ratio. The assembly path is initially segmented to improve its reusability. Subsequently, the planned assembly paths are employed as a priori paths to establish an a priori tree, which is expanded according to the bounding sphere of the part to create the a priori space for path searching. Three rapidly exploring random tree (RRT)-based algorithms are studied for path planning based on a priori path reuse. The RRT* algorithm establishes the new path exploration tree in the early planning stage when there is no a priori path to reuse. The static RRT* (S-RRT*) and dynamic RRT* (D-RRT*) algorithms form the connection between the exploration tree and the a priori tree with a pair of connection points after the extension of the exploration tree to a priori space. The difference between the two algorithms is that the S-RRT* algorithm directly reuses an a priori path and obtains a new path through static backtracking from the endpoint to the starting point. However, the D-RRT* algorithm further extends the exploration tree via the dynamic window approach to avoid collision between an a priori path and obstacles. The algorithm subsequently obtains a new path through dynamic and non-continuous backtracking from the endpoint to the starting point. A hybrid process combining the RRT*, S-RRT*, and D-RRT* algorithms is designed to plan the assembly path for complex products in several cases. The performances of these algorithms are compared, and simulations indicate that the S-RRT* and D-RRT* algorithms are significantly superior to the RRT* algorithm in terms of the efficiency and success ratio of APP. Therefore, hybrid path planning combining the three algorithms is helpful to improving the assembly path planning of complex products.
From Boolean Valued Analysis to Quantum Set Theory: Mathematical Worldview of Gaisi Takeuti
Authors: Ozawa Masanao
Published: February 2021

Gaisi Takeuti introduced Boolean valued analysis around 1974 to provide systematic applications of the Boolean valued models of set theory to analysis. Later, his methods were further developed by his followers, leading to solving several open problems in analysis and algebra. Using the methods of Boolean valued analysis, he further stepped forward to construct set theory that is based on quantum logic, as the first step to construct "quantum mathematics", a mathematics based on quantum logic. While it is known that the distributive law does not apply to quantum logic, and the equality axiom turns out not to hold in quantum set theory, he showed that the real numbers in quantum set theory are in one-to-one correspondence with the self-adjoint operators on a Hilbert space, or equivalently the physical quantities of the corresponding quantum system. As quantum logic is intrinsic and empirical, the results of the quantum set theory can be experimentally verified by quantum mechanics. In this paper, we analyze Takeuti’s mathematical world view underlying his program from two perspectives: set theoretical foundations of modern mathematics and extending the notion of sets to multi-valued logic. We outlook the present status of his program, and envisage the further development of the program, by which we would be able to take a huge step forward toward unraveling the mysteries of quantum mechanics that have persisted for many years.
Oil Bioremediation in the Marine Environment of Antarctica: A Review and Bibliometric Keyword Cluster Analysis
Authors: Zakaria Nur Nadhirah , Convey Peter , Gomez-Fuentes Claudio , Zulkharnain Azham , Sabri Suriana , Shaharuddin Noor Azmi , Ahmad Siti Aqlima
Published: February 2021

Bioremediation of hydrocarbons has received much attention in recent decades, particularly relating to fuel and other oils. While of great relevance globally, there has recently been increasing interest in hydrocarbon bioremediation in the marine environments of Antarctica. To provide an objective assessment of the research interest in this field we used VOSviewer software to analyze publication data obtained from the ScienceDirect database covering the period 1970 to the present, but with a primary focus on the years 2000–2020. A bibliometric analysis of the database allowed identification of the co-occurrence of keywords. There was an increasing trend over time for publications relating to oil bioremediation in maritime Antarctica, including both studies on marine bioremediation and of the metabolic pathways of hydrocarbon degradation. Studies of marine anaerobic degradation remain under-represented compared to those of aerobic degradation. Emerging keywords in recent years included bioprospecting, metagenomic, bioindicator, and giving insight into changing research foci, such as increasing attention to microbial diversity. The study of microbial genomes using metagenomic approaches or whole genome studies is increasing rapidly and is likely to drive emerging fields in future, including rapid expansion of bioprospecting in diverse fields of biotechnology.
Determination of Biogenic Amines in Different Parts of Lycium barbarum L. by HPLC with Precolumn Dansylation
Authors: Ai Yun , Sun Yan Ni , Liu Li , Yao Fang Yuan , Zhang Yan , Guo Feng Yi , Zhao Wen Jie , Liu Jian Li , Zhang Ning
Published: February 2021

The aim of this work was to characterize biogenic amines (BAs) in different parts of Lycium barbarum L. using HPLC with dansyl chloride derivatization, and jointly, to provide referential data for further exploration and utilization of Lycium barbarum L. The linear correlation coefficients for all BAs were above 0.9989. The limits of detection and quantification were 0.015–0.075 and 0.05–0.25 μg/mL, respectively. The relative standard deviations for the intra-day and inter-day precision were 0.66–2.69% and 0.91–4.38%. The described method has good repeatability and intermediate precision for the quantitative determination of BAs in different parts of Lycium barbarum L. Satisfactory recovery for all amines was obtained (79.3–110.3%). The result showed that there were four kinds of BAs. The highest putrescine content (20.9 ± 3.2 mg/kg) was found in the flower. The highest histamine content (102.7 ± 5.8 mg/kg) was detected in the bark, and the highest spermidine (13.3 ± 1.6 mg/kg) and spermine (23.7 ± 2.0 mg/kg) contents were detected in the young leaves. The high histamine (HIS) content in the bark may be one of the reasons why all of the parts of Lycium barbarum L., except the bark, are used for medicine or food in China. Meanwhile, the issue of the high concentration of HIS should be considered when exploiting or utilizing the bark of Lycium barbarum L.
DNA Manipulation and Single-Molecule Imaging
Authors: Takahashi Shunsuke , Oshige Masahiko , Katsura Shinji
Published: February 2021

DNA replication, repair, and recombination in the cell play a significant role in the regulation of the inheritance, maintenance, and transfer of genetic information. To elucidate the biomolecular mechanism in the cell, some molecular models of DNA replication, repair, and recombination have been proposed. These biological studies have been conducted using bulk assays, such as gel electrophoresis. Because in bulk assays, several millions of biomolecules are subjected to analysis, the results of the biological analysis only reveal the average behavior of a large number of biomolecules. Therefore, revealing the elementary biological processes of a protein acting on DNA (e.g., the binding of protein to DNA, DNA synthesis, the pause of DNA synthesis, and the release of protein from DNA) is difficult. Single-molecule imaging allows the analysis of the dynamic behaviors of individual biomolecules that are hidden during bulk experiments. Thus, the methods for single-molecule imaging have provided new insights into almost all of the aspects of the elementary processes of DNA replication, repair, and recombination. However, in an aqueous solution, DNA molecules are in a randomly coiled state. Thus, the manipulation of the physical form of the single DNA molecules is important. In this review, we provide an overview of the unique studies on DNA manipulation and single-molecule imaging to analyze the dynamic interaction between DNA and protein.
The Cream of the Crop of the Medicinal Chemistry Section of Molecules—2019
Authors: Muñoz-Torrero Diego
Published: February 2021

The MDPI journal Molecules is organized into 25 sections that cover many different areas of the broad field of chemistry [...]
Synergistic Roles of Curcumin in Sensitising the Cisplatin Effect on a Cancer Stem Cell-Like Population Derived from Non-Small Cell Lung Cancer Cell Lines
Authors: Abdul Satar Nazilah , Ismail Mohd Nazri , Yahaya Badrul Hisham
Published: February 2021

Cancer stem cells (CSCs) represent a small subpopulation within a tumour. These cells possess stem cell-like properties but also initiate resistance to cytotoxic agents, which contributes to cancer relapse. Natural compounds such as curcumin that contain high amounts of polyphenols can have a chemosensitivity effect that sensitises CSCs to cytotoxic agents such as cisplatin. This study was designed to investigate the efficacy of curcumin as a chemo-sensitiser in CSCs subpopulation of non-small cell lung cancer (NSCLC) using the lung cancer adenocarcinoma human alveolar basal epithelial cells A549 and H2170. The ability of curcumin to sensitise lung CSCs to cisplatin was determined by evaluating stemness characteristics, including proliferation activity, colony formation, and spheroid formation of cells treated with curcumin alone, cisplatin alone, or the combination of both at 24, 48, and 72 h. The mRNA level of genes involved in stemness was analysed using quantitative real-time polymerase chain reaction. Liquid chromatography-mass spectrometry was used to evaluate the effect of curcumin on the CSC niche. A combined treatment of A549 subpopulations with curcumin reduced cellular proliferation activity at all time points. Curcumin significantly (p < 0.001) suppressed colonies formation by 50% and shrank the spheroids in CSC subpopulations, indicating inhibition of their self-renewal capability. This effect also was manifested by the down-regulation of SOX2, NANOG, and KLF4. Curcumin also regulated the niche of CSCs by inhibiting chemoresistance proteins, aldehyde dehydrogenase, metastasis, angiogenesis, and proliferation of cancer-related proteins. These results show the potential of using curcumin as a therapeutic approach for targeting CSC subpopulations in non-small cell lung cancer.
Efficacy of Docosahexaenoic Acid for the Prevention of Necrotizing Enterocolitis in Preterm Infants: A Randomized Clinical Trial
Authors: Bernabe-García Mariela , Calder Philip , Villegas-Silva Raúl , Rodríguez-Cruz Maricela , Chávez-Sánchez Luis , Cruz-Reynoso Leonardo , Mateos-Sánchez Leovigildo , Lara-Flores Gabriel , Aguilera-Joaquín Augusto , Sánchez-García Luisa
Published: February 2021

Necrotizing enterocolitis (NEC) is an inflammatory bowel disease and a leading cause of morbidity and mortality in preterm infants. In this study, a randomized double-blind parallel-group (1:1) trial was carried out in two neonatal intensive care units of two tertiary hospitals. Two hundred and twenty-five preterm newborns with an expected functional gastrointestinal tract were recruited and received an enteral dose of 75 mg of docosahexaenoic acid (DHA)/kg body weight or high-oleic sunflower oil daily for 14 days from the first enteral feed after birth. Confirmed NEC was evaluated with Bell’s scale from stage ≥ IIa. Two hundred and fourteen randomized infants were analyzed in terms of the intent-to-treat (DHA-group: n = 105; control-group: n = 109); data for two hundred infants were analysed per protocol. Confirmed NEC was lower in infants from the DHA-group compared with the control-group (0/100 vs. 7/100; p = 0.007), with RR = 0.93 (95% CI 0.881 to 0.981), risk difference = −7%, (95% CI −12.00 to −1.99), and number needed-to-treat = 15 (95% CI 8.3 to 50). Intent-to-treat analysis showed a lower level of treatment failure in the DHA-group compared with the control-group (6/105 (6%) vs. 16/109 (15%); p = 0.03, RR = 0.905, (95% CI 0.826 to 0.991)). The results after multivariate-regression analysis remained significant. Adverse events (apart from the incidence of NEC) were not different between groups. A daily dose of DHA for 14 days starting with the first enteral feed may prevent NEC in preterm infants.
Regional Intestinal Drug Absorption: Biopharmaceutics and Drug Formulation
Authors: Dahan Arik , González-Álvarez Isabel
Published: February 2021

The gastrointestinal tract (GIT) can be broadly divided into several regions: the stomach, the small intestine (which is subdivided to duodenum, jejunum, and ileum), and the colon. The conditions and environment in each of these segments, and even within the segment, are dependent on many factors, e.g., the surrounding pH, fluid composition, transporters expression, metabolic enzymes activity, tight junction resistance, different morphology along the GIT, variable intestinal mucosal cell differentiation, changes in drug concentration (in cases of carrier-mediated transport), thickness and types of mucus, and resident microflora. Each of these variables, alone or in combination with others, can fundamentally alter the solubility/dissolution, the intestinal permeability, and the overall absorption of various drugs. This is the underlying mechanistic basis of regional-dependent intestinal drug absorption, which has led to many attempts to deliver drugs to specific regions throughout the GIT, aiming to optimize drug absorption, bioavailability, pharmacokinetics, and/or pharmacodynamics. In this Editorial we provide an overview of the Special Issue "Regional Intestinal Drug Absorption: Biopharmaceutics and Drug Formulation". The objective of this Special Issue is to highlight the current progress and to provide an overview of the latest developments in the field of regional-dependent intestinal drug absorption and delivery, as well as pointing out the unmet needs of the field.
Comparison of Huggins Coefficients and Osmotic Second Virial Coefficients of Buffered Solutions of Monoclonal Antibodies
Authors: Pathak Jai , Nugent Sean , Bender Michael , Roberts Christopher , Curtis Robin , Douglas Jack
Published: February 2021

The Huggins coefficient kH is a well-known metric for quantifying the increase in solution viscosity arising from intermolecular interactions in relatively dilute macromolecular solutions, and there has been much interest in this solution property in connection with developing improved antibody therapeutics. While numerous kH measurements have been reported for select monoclonal antibodies (mAbs) solutions, there has been limited study of kH in terms of the fundamental molecular interactions that determine this property. In this paper, we compare measurements of the osmotic second virial coefficient B22, a common metric of intermolecular and interparticle interaction strength, to measurements of kH for model antibody solutions. This comparison is motivated by the seminal work of Russel for hard sphere particles having a short-range “sticky” interparticle interaction, and we also compare our data with known results for uncharged flexible polymers having variable excluded volume interactions because proteins are polypeptide chains. Our observations indicate that neither the adhesive hard sphere model, a common colloidal model of globular proteins, nor the familiar uncharged flexible polymer model, an excellent model of intrinsically disordered proteins, describes the dependence of kH of these antibodies on B22. Clearly, an improved understanding of protein and ion solvation by water as well as dipole–dipole and charge–dipole effects is required to understand the significance of kH from the standpoint of fundamental protein–protein interactions. Despite shortcomings in our theoretical understanding of kH for antibody solutions, this quantity provides a useful practical measure of the strength of interprotein interactions at elevated protein concentrations that is of direct significance for the development of antibody formulations that minimize the solution viscosity.
Effects and Risk Assessment of the Polycyclic Musk Compounds Galaxolide® and Tonalide® on Marine Microalgae, Invertebrates, and Fish
Authors: Ehiguese Friday , González-Delgado M. , Garrido-Perez Carmen , Araújo Cristiano , Martin-Diaz M.
Published: February 2021

The current research investigated the potential environmental risk of the polycyclic musk compounds, Galaxolide® (HHCB) and Tonalide® (AHTN), in the marine environments. These substances are lipophilic, bioaccumulated, and potentially biomagnified in aquatic organisms. To understand the toxicity of HHCB and AHTN, acute toxicity tests were performed by exposing marine microalgae (Phaeodactylum tricornutum, Tretraselmis chuii, and Isochrysis galbana), crustaceans (Artemia franciscana), echinoderms (Paracentrotus lividus), bivalves (Mytilus galloprovincialis), fish (Sparus aurata), and a candidate freshwater microalga (Raphidocelis subcapitata) to environmentally relevant concentrations (0.005–5 µg/L) following standardized protocols (US EPA, Environment Canada and OECD). P. tricornutum and I. galbana were sensitive to both substances and for P. tricornutum exposed to HHCB and AHTN, the IC10 values (the inhibition concentration at which 10% microalgae growth inhibition was observed) were 0.127 and 0.002 µg/L, respectively, while IC10 values calculated for I. galbana were 5.22 µg/L (a little higher than the highest concentration) and 0.328 µg/L, for HHCB and AHTN, respectively. Significant (p < 0.01) concentration dependent responses were measured in P. lividus and M. galloprovincialis larvae developments, as well as S. aurata mortality tested with HHCB. The effect of HHCB on P. lividus larvae development was the most sensitive endpoint recorded, producing an EC50 value (the effect concentration at which 50% effect was observed) of 4.063 µg/L. Considering the risk quotients both substances seem to represent high environmental risk to P. tricornutum and M. galloprovincialis in marine environments.
Multi-Channel Singular Spectrum Analysis on Geocenter Motion and Its Precise Prediction
Authors: Jin Xin , Liu Xin , Guo Jinyun , Shen Yi
Published: February 2021

Geocenter is the center of the mass of the Earth system including the solid Earth, ocean, and atmosphere. The time-varying characteristics of geocenter motion (GCM) reflect the redistribution of the Earth’s mass and the interaction between solid Earth and mass loading. Multi-channel singular spectrum analysis (MSSA) was introduced to analyze the GCM products determined from satellite laser ranging data released by the Center for Space Research through January 1993 to February 2017 for extracting the periods and the long-term trend of GCM. The results show that the GCM has obvious seasonal characteristics of the annual, semiannual, quasi-0.6-year, and quasi-1.5-year in the X, Y, and Z directions, the annual characteristics make great domination, and its amplitudes are 1.7, 2.8, and 4.4 mm, respectively. It also shows long-period terms of 6.09 years as well as the non-linear trends of 0.05, 0.04, and –0.10 mm/yr in the three directions, respectively. To obtain real-time GCM parameters, the MSSA method combining a linear model (LM) and autoregressive moving average model (ARMA) was applied to predict GCM for 2 years into the future. The precision of predictions made using the proposed model was evaluated by the root mean squared error (RMSE). The results show that the proposed method can effectively predict GCM parameters, and the prediction precision in the three directions is 1.53, 1.08, and 3.46 mm, respectively.
Mitigation Effects of Bentonite and Yeast Cell Wall Binders on AFB1, DON, and OTA Induced Changes in Laying Hen Performance, Egg Quality, and Health
Authors: Zhao Ling , Feng Yue , Wei Jing-Tao , Zhu Meng-Xiang , Zhang Lei , Zhang Jia-Cai , Karrow Niel Alexander , Han Yan-Ming , Wu Yuan-Yuan , Guo Yu-Ming , Sun Lv-Hui
Published: February 2021

The objective of this study was to evaluate the efficacy of mycotoxin binders in reducing the adverse effects of co-occurring dietary aflatoxin B1 (AFB1), deoxynivalenol (DON) and ochratoxin A (OTA) on laying hens. Three hundred and sixty 26-week-old Roman laying hens were randomly allocated into four experimental groups with 10 replicates of nine birds each. The four groups received either a basal diet (BD; Control), a BD supplemented with 0.15 mg/kg AFB1 + 1.5 mg/kg DON + 0.12 mg/kg OTA (Toxins), a BD + Toxins with Toxo-HP binder (Toxins + HP), or a BD + Toxins with TOXO XL binder (Toxins + XL) for 12 weeks. Compared to the control, dietary supplementation of mycotoxins decreased (P < 0.10) total feed intake, total egg weight, and egg-laying rate, but increased feed/egg ratio by 2.5–6.1% and mortality during various experimental periods. These alterations induced by mycotoxins were alleviated by supplementation with both TOXO HP and XL binders (P < 0.10). Furthermore, dietary mycotoxins reduced (P < 0.05) eggshell strength by 12.3% and caused an accumulation of 249 μg/kg of DON in eggs at week 12, while dietary supplementation with TOXO HP or XL mitigated DON-induced changes on eggshell strength and prevented accumulation of DON in eggs (P < 0.05). Moreover, dietary mycotoxins increased relative liver weight, but decreased spleen and proventriculus relative weights by 11.6–22.4% (P < 0.05). Mycotoxin exposure also increased alanine aminotransferase activity and reduced immunoglobulin (Ig) A, IgM, and IgG concentrations in serum by 9.2–26.1% (P < 0.05). Additionally, mycotoxin exposure induced histopathological damage and reduced villus height, villus height/crypt depth, and crypt depth in duodenum, jejunum and (or) ileum (P < 0.05). Notably, most of these histological changes were mitigated by supplementation with both TOXO HP and XL (P < 0.05). In conclusion, the present study demonstrated that the mycotoxin binders TOXO HP and XL can help to mitigate the combined effects of AFB1, DON, and OTA on laying hen performance, egg quality, and health.
Theoretical Treatment of Limitations Inherent in Simple 3D Stimuli: Triangles and the P3P Problem
Authors: Minkov Vasiliy , Sawada Tadamasa
Published: February 2021

Understanding the visual stimulus in a psychophysical experiment, theoretically, is critical for controlling the experiment, for interpreting the empirical results of the experiment, and for discussing the mechanisms the visual system used to get these results. This fact encourages visual scientists to use “simple” visual stimuli in their experiments. A triangle is one of the simplest stimuli that has been used by psychophysicists to study 3D perception. It has also been used to compose the polygonal meshes that represent complex 3D surfaces in computer graphics. The relationship between the shape, orientation, and retinal image of a triangle has also been studied as the Perspective-3-Point problem (P3P). In this study, the statistical properties of this relationship between the 2D retinal image of a triangle and its recovered 3D orientation were tested in a simulation experiment whose results showed that a triangle is qualitatively different from more complex shapes that have been used to recover 3D information from their retinal images. This raises an important question, namely, how many, if any, inferences about our visual system can be generalized to our perceptions in everyday life when they are based on psychophysical experiments that used very simple visual stimuli such as triangles.
Electrochemical Treatment of Effluent for the Removal of Contaminants of Emergent Concern and Culturable Microorganisms
Authors: Dionísio Joana , Gonçalves Cristiana , Guedes Paula , Ribeiro Alexandra , Couto Nazaré
Published: February 2021

The present work aims to study the electrochemical (EC) process applied for the removal of contaminants of emergent concern (CECs) from wastewater after secondary treatment and the effect of the process on the total culturable microorganisms. The EC experiments were performed in a cylindrical open reactor with 500 mL of effluent, and a fixed current density of 8 mA/cm² was applied through mixed metal oxide electrodes. The experiments were conducted in different sets. In the first round (Set 1), the effluent sample was spiked with three CECs (200 ppb each): caffeine (CAF), carbamazepine (CBZ), and oxybenzone (OXY). For the best treatment period, 6 h, electrodegradation rates ranged from 41 ± 7% for CAF to 95 ± 6% for OXY, with an 87% removal of total culturable microorganisms. In the second round (Set 2), aiming to assess EC process efficiency in a more complex CEC mixture, the effluent was spiked with six more CECs (200 ppb each): diclofenac (DCF), triclosan (TCS), bisphenol A (BPA), 17β-estradiol (E2), 17α-ethinylestradiol (EE2), and ibuprofen (IBU), giving a total of nine CECs. In this case, the EC process allowed decreasing the CEC content by 19–100% (below the limit of detection), depending on the effluent samples, and the culturable microorganisms by 99.98% after a 6 h treatment. By contributing to CEC degradation and microorganism removal, the EC process proved to be a viable remediation and disinfection technology for secondary effluent from wastewater treatment plants.
Transiciones audiovisuales
Authors: Martínez García María Ángeles , Gómez Aguilar Antonio
Published: February 2021

Realidad Virtual que permite a los alumnos acceder de manera atractiva e interactiva a un contenido básico de la realización audiovisual. El recurso está organizado en dos salas que el alumno puede visitar, con elementos con los que puede interactuar. En la Sala A es una tiene acceso a los contenidos teóricos ejemplificados a través de fragmentos de obras y otros recursos audiovisuales. En la Sala B el alumno puede comprobar, a través de una serie de ejercicios prácticos, si ha comprendido los conceptos desarrollados en la Sala A.

El Recurso puede experimentarse directamente con el navegador en modo 360º tanto en equipos de escritorio como con dispositivos móviles. No obstante, es altamente recomendable una mejor experiencia inmersiva, la cual puede obtenerse ayudándose de unas gafas de Realidad Virtual con las que pueda conectarse mediante Mozilla Firefox (Oculus, HTC Vive, Daydream o Cardboard).

Es un recurso idóneo para explicar de manera amena los diferentes tipos de transiciones que pueden utilizarse en la creación de contenidos audiovisuales. Estos elementos del lenguaje audiovisual tienen múltiples aplicaciones en la realización de obras audiovisuales tanto en el terreno de la ficción como en el de la no ficción.
Regional Plan of Integration of South Moravian and Lower Austrian Border Regions
Authors:   Technical University of Brno, Kyselka Mojmir
Published: February 2021

This transborder regional plan represents the final result of the collaboration of three universities: Faculty of Architecture, Technical University of Bmo – Czech Republic, Institutes of Regional and Landscape Planning TU Vienna – Austria and the Institute of Regional and Environmental Planning, University of Kaiserslautern – Germany. All the participants, students and teachers, architects, urban and regional planners enjoyed the four common workshops – both on the Czech and on the Austrian territory, which was divided till 1989 by the “iron curtain”. They compared the differences of the local culture in architecture, urban and landscape structure, but found the majority of similar ways of life. This was what created the idea of the transborder zone.
Citizen - Building and Place Making in the Design of Cities
Authors:   University of Michigan, Chaffers James
Published: February 2021

In this paper, which draws from my current research on back to-the-city movements in America, I suggest a direct correlation between a predominant emphasis on values of self advancement, individual rights, and mass individual consumption (consumership) and a parallel underdevelopment of values focused on family and civic responsibility (citizenship). I define consumership as a way of thinking and living, broadly guided by three interconnected perspectives: an overarching emphasis on material relationships, a paramount concern for maximum efficiency in human institutions, and a view that our environment is a commodity. I define citizenship as a unique quality of community gained from exercising our human capacity to care, share, and trust beyond our immediate ties of lunship, friendship, and ethnicity; ie., a quality of caring, sharing, and trusting that honors nature’s rhythms and serves as a source of empowerment for individuals seeking to build common opportunities.
Architectural Culture as a Barrier to Urban Regeneration
Authors:   Joint Centre for Urban Design, Bentley Ian , Watson Georgia ,   Oxford Brookes University
Published: February 2021

The importance of involving local residents and workers in the regeneration of run-down urban areas is now enshrined in UK central government policy, through such programmes as Estate Action and City Challenge. However, it is widely accepted that effective community involvement is difficult to achieve in practice; and it is clear that one of the reasons for this difficulty stems from the presence of cultural barriers between architects and local people. The presence and importance of these barriers has been confirmed by various practitioners’ accounts (for example Thompson, 1988) and is consistently clear from the authors’ own consultancy experience in tenant-consultation work with the Oxford Brookes University Urban Regeneration Consultancy (URC) in a variety of situations, over the last six years (Bentley, 1993).
The Urban Canvas: Urbanity and Painting in Maison Curutchet
Authors:   University of Illinois at Urbana-Champaign, Lapunzina Alejandro
Published: February 2021

This paper proposes a reading of the faqade of Maison Curutchet, a significant yet largely unstudied building designed by Le Corbusier in 1949, as a metaphor or a condenser of the architect’s ideas on urban-planning and painting. It also proposes that in this building Le Corbusier proved to be (contrary to what is often asserted) one of the most contextually urban oriented architects of the twentieth century.
Pursuing the Urban Mission: The Inner-City Studio Experience
Authors:   University of Wisconsin-Milwaukee, Greenstreet Bob
Published: February 2021

This paper describes the structure and purpose of the Inner City Studio, an alternative model for urban Schools of architecture which can help enhance their teaching, research and service missions. It ensures a consistent, high quality level of outreach to communities in a way that strengthens the educational experience of the student, as well as reinforcing the role of a school within its urban context.
Elderly Housing and Neighborhood Planning
Authors:   Rensselaer Polytechnic Institute, Tobin John W.
Published: February 2021

As mixed-use neighborhoods integrating dwelling, commercial and civic capacities decline and disappear, so too do the particular advantages of everyday life that they embody. The popular acclaim bestowed on housing developments such as Seaside, Florida is some indication of how truly rare the practice of integrated living is today. For the elderly however, mixed-use neighborhoods may prove to be an essential support structure, one that could affect the rates at which they need to be institutionalized.
Aspects of Preservation of Architecture of the Early Modern Movement
Authors:   The Royal Academy of Fine Arts, Welling Helen G.
Published: February 2021

The following paper contains some of the main points of discussion in a research project about the preservation of architecture of the Modem Movement in preparation at the Royal Academy of Fine Arts, School of Architecture, Copenhagen. It discusses the relativity of historical values within the early Modem Movement. Various aspects on the case of preservation of architecture of the Modem Movement are explained. Different examples of restoration, reconstruction and new interventions are analysed and ordered in a series of methods. The conclusion is that the architecture of this epoch needs a new attitude especially towards the question of authenticity.