bluuebunny/crossref_metadata_2025 huggingface dataset:
Micro-EDM Drilling/Milling as a Potential Technique for Fabrication of Bespoke Artificial Defects on Bearing Raceways
Authors: Ye Long , Saxena Krishna Kumar , Qian Jun , Reynaerts Dominiek
Published: March 2022

The fabrication of bespoke artificial defects on bearing raceways helps in mimicking incipient faults during real application or for directly validating the diagnostic technology depending on their shapes and sizes. This is particularly useful when run-to-failure experiments are time-consuming and even difficult in some cases. However, there has been limited systematic research on the design and fabrication of artificial defects on bearing raceways, particularly for the purpose of accelerated testing. In this work, micro-EDM is put forward as a potential technique for the fabrication of artificial defects using drilling/milling mode. A methodology is developed, not only to achieve the full control of the dimension and distribution of defects on a bearing element, but also to qualitatively and quantitatively perform the efficient characterization of the defect surface. A linear regression model with the inclusion of two-way interactions based on an analysis of variance (ANOVA) is presented to optimally select the process parameters. The verification experiments show that this mathematical model obtains a good fit for approximately 80% of the observed data. Through a combination of optical microscopy and confocal microscopy, the morphology and topography of the artificial defects was measured and compared. To conclude, micro-EDM evidences its great potential in terms of machining efficiency, e.g., with an MRR of 0.060 mm3/min, TWR of 0.032 mm3/min and dimensional controllability, e.g., the standard deviation of pitting diameter and depth being 0.5 µm and 0.8 µm, respectively, to achieve a desirable feature shape for bearing defects.
Circulation of SARS-CoV-2 Variants among Children from November 2020 to January 2022 in Trieste (Italy)
Authors: Dolci Maria , Signorini Lucia , Cason Carolina , Campisciano Giuseppina , Kunderfranco Paolo , Pariani Elena , Galli Cristina , Petix Vincenzo , Ferrante Pasquale , Delbue Serena , Comar Manola
Published: March 2022

Introduction: The ongoing coronavirus disease 19 (COVID-19) outbreak involves the pediatric population, but to date, few reports have investigated the circulation of variants among children. Material and Methods: In this retrospective study, non-hospitalized pediatric patients with SARS-CoV-2-positive nasopharyngeal swabs (NPS) were enrolled at the Institute for Maternal and Child Health-IRCCS Burlo Garofolo, Trieste (Italy), from November 2020 to January 2022. SARS-CoV-2 variants were identified by in vitro viral isolation, amplification, automatic sequencing of the receptor binding domain (RBD) of the SARS-CoV-2 spike coding gene, and subsequent next-generation sequencing. The growth curves of the isolated strains were defined in vitro by infecting Vero-E6 cells and quantifying the viral load in the supernatants up to 72 h post-infection by qRT–PCR. The neutralization activity of sera obtained from a COVID-19 vaccinated subject, recovered (2020) patient, vaccinated and recovered (2021) patient, and seronegative subject was assessed by microneutralization assay against the different variants. Results: In total, 32 SARS-CoV-2-positive children, 16 (50%) females, with a median age of 1.4 years (range: 1 day–13 years), were enrolled. The D614G amino acid substitution was detected in all isolated and amplified viral strains. Of the 32 isolates, 4 (12.5%) carried a nonsynonymous nucleotide mutation leading to the N439K (3/4), lineage B.1.258 (∆H69/∆V70), and S477N (1/4) substitution. In 7/32 (21.8%) isolates, amino acid substitutions allowed the identification of a delta variant, lineage B.1.617.2-AY.43, and in 1/32 (3.1%), the Omicron strain (B.1.1.529.BA1) was identified. The growth curves of the B.1, B.1.258 (∆H69/∆V70), B.1.617.2-AY.43, and B.1.1.529.BA1 variants did not show any significant differences. A reduction in the serum neutralizing activity against B.1.258 (∆H69/∆V70) only in a vaccinated subject (1.7-fold difference), against B.1.617.2-AY.43 in a vaccinated subject and in recovered patients (12.7 and ≥2.5-fold differences, respectively), and against B.1.1.529.BA1 variant (57.6- and 1.4-fold differences in vaccinated and in vaccinated and recovered patients) were observed compared to the B.1 variant. Conclusions: SARS-CoV-2 variants carrying the B.1.258 (∆H69/∆V70) and S477N substitutions were reported here in a pediatric population for the first time. Although the growth rates of the isolated strains (B.1.258, B.1.617.2-AY.43, B.1.1.529.BA1) did not differ from the B.1 variant, neutralizing activity of the sera from vaccinated subjects significantly decreased against these variants. Attention should be devoted to the pediatric population to prevent the spread of new SARS-CoV-2 variants in an unvaccinated and predominantly naive population.
Expanding the Universe of Hemoplasmas: Multi-Locus Sequencing Reveals Putative Novel Hemoplasmas in Lowland Tapirs (Tapirus terrestris), the Largest Land Mammals in Brazil
Authors: Mongruel Anna Claudia Baumel , Medici Emília Patrícia , Canena Ariel da Costa , Calchi Ana Cláudia , Machado Rosangela Zacarias , André Marcos Rogério
Published: March 2022

The lowland tapir (Tapirus terrestris) is the largest land mammal in Brazil and classified as a vulnerable species, according to the assessment of the risk of extinction. The present study aimed at investigating the occurrence and genetic diversity of hemoplasmas in free-ranging T. terrestris from the Brazilian Pantanal and Cerrado biomes. Blood samples were collected from 94 living and eight road-killed tapirs, totalizing 125 samples Conventional PCR targeting four different genes (16S rRNA, 23S rRNA, RNAse P, and dnaK) were performed, and the obtained sequences were submitted for phylogenetic, genotype diversity, and distance analyses. The association between hemoplasma positivity and possible risk variables (age, gender, and origin) was assessed. Out of 122 analyzed samples, 41 (41/122; 33.61% CI: 25.84–42.38%) were positive in the 16S rRNA-based PCR assay for hemoplasmas. Positivity for hemoplasmas did not differ between tapirs’ gender and age. Tapirs from Pantanal were 5.64 times more likely to present positive results for hemoplasmas when compared to tapirs sampled in Cerrado. BLASTn, phylogenetic, genotype diversity, and distance analyses performed herein showed that the sampled lowland tapirs might be infected by two genetically distinct hemoplasmas, namely ‘Candidatus Mycoplasma haematoterrestris’ and ‘Candidatus Mycoplasma haematotapirus’. While the former was positioned into “Mycoplasma haemofelis group” and closely related to ‘Candidatus Mycoplasma haematoparvum, the latter was positioned into “Mycoplasma suis group” and closely related to ‘Candidatus Mycoplasma haematobos’. The impact of both putative novel species on tapir health status should be investigated.
Microbiota, IgA and Multiple Sclerosis
Authors: Boussamet Léo , Rajoka Muhammad Shahid Riaz , Berthelot Laureline
Published: March 2022

Multiple sclerosis (MS) is a neuroinflammatory disease characterized by immune cell infiltration in the central nervous system and destruction of myelin sheaths. Alterations of gut bacteria abundances are present in MS patients. In mouse models of neuroinflammation, depletion of microbiota results in amelioration of symptoms, and gavage with MS patient microbiota exacerbates the disease and inflammation via Th17 cells. On the other hand, depletion of B cells using anti-CD20 is an efficient therapy in MS, and growing evidence shows an important deleterious role of B cells in MS pathology. However, the failure of TACI-Ig treatment in MS highlighted the potential regulatory role of plasma cells. The mechanism was recently demonstrated involving IgA+ plasma cells, specific for gut microbiota and producing IL-10. IgA-coated bacteria in MS patient gut exhibit also modifications. We will focus our review on IgA interactions with gut microbiota and IgA+ B cells in MS. These recent data emphasize new pathways of neuroinflammation regulation in MS.
Characterization of Bifidobacterium asteroides Isolates
Authors: Pino Alessandra , Benkaddour Bachir , Inturri Rosanna , Amico Pietro , Vaccaro Susanna C. , Russo Nunziatina , Vaccalluzzo Amanda , Agolino Gianluigi , Caggia Cinzia , Miloud Hadadji , Randazzo Cinzia L.
Published: March 2022

Bifidobacteria have long been recognized as bacteria with probiotic and therapeutic features. The aim of this work is to characterize the Bifidobacterium asteroides BA15 and BA17 strains, isolated from honeybee gut, to evaluate its safety for human use. An in-depth assessment was carried out on safety properties (antibiotic resistance profiling, β-hemolytic, DNase and gelatinase activities and virulence factor presence) and other properties (antimicrobial activity, auto-aggregation, co-aggregation and hydrophobicity). Based on phenotypic and genotypic characterization, both strains satisfied all the safety requirements. More specifically, genome analysis showed the absence of genes encoding for glycopeptide (vanA, vanB, vanC-1, vanC-2, vanD, vanE, vanG), resistance to tetracycline (tetM, tetL and tetO) and virulence genes (asa1, gelE, cylA, esp, hyl).
Interplay between Arabidopsis thaliana Genotype, Plant Growth and Rhizosphere Colonization by Phytobeneficial Phenazine-Producing Pseudomonas chlororaphis
Authors: Zboralski Antoine , Saadia Hara , Novinscak Amy , Filion Martin
Published: March 2022

Rhizosphere colonization by phytobeneficial Pseudomonas spp. is pivotal in triggering their positive effects on plant health. Many Pseudomonas spp. Determinants, involved in rhizosphere colonization, have already been deciphered. However, few studies have explored the role played by specific plant genes in rhizosphere colonization by these bacteria. Using isogenic Arabidopsis thaliana mutants, we studied the effect of 20 distinct plant genes on rhizosphere colonization by two phenazine-producing P. chlororaphis strains of biocontrol interest, differing in their colonization abilities: DTR133, a strong rhizosphere colonizer and ToZa7, which displays lower rhizocompetence. The investigated plant mutations were related to root exudation, immunity, and root system architecture. Mutations in smb and shv3, both involved in root architecture, were shown to positively affect rhizosphere colonization by ToZa7, but not DTR133. While these strains were not promoting plant growth in wild-type plants, increased plant biomass was measured in inoculated plants lacking fez, wrky70, cbp60g, pft1 and rlp30, genes mostly involved in plant immunity. These results point to an interplay between plant genotype, plant growth and rhizosphere colonization by phytobeneficial Pseudomonas spp. Some of the studied genes could become targets for plant breeding programs to improve plant-beneficial Pseudomonas rhizocompetence and biocontrol efficiency in the field.
A Farm-to-Fork Quantitative Microbial Exposure Assessment of β-Lactam-Resistant Escherichia coli among U.S. Beef Consumers
Authors: Zhang Yangjunna , Schmidt John W. , Arthur Terrance M. , Wheeler Tommy L. , Zhang Qi , Wang Bing
Published: March 2022

Integrated quantitative descriptions of the transmission of β-lactam-resistant Escherichia coli (BR-EC) from commercial beef products to consumers are not available. Here, a quantitative microbial exposure assessment model was established to simulate the fate of BR-EC in a farm-to-fork continuum and provide an estimate of BR-EC exposure among beef consumers in the U.S. The model compared the per-serving exposures from the consumption of intact beef cuts, non-intact beef cuts, and ground beef. Additionally, scenario analysis was performed to evaluate the relative contribution of antibiotic use during beef cattle production to the level of human exposure to BR-EC. The model predicted mean numbers of BR-EC of 1.7 × 10−4, 8.7 × 10−4, and 6.9 × 10−1 CFU/serving for intact beef cuts, non-intact beef cuts, and ground beef, respectively, at the time of consumption. Sensitivity analyses using the baseline model suggested that factors related to sectors along the supply chain, i.e., feedlots, processing plants, retailers, and consumers, were all important for controlling human exposure to BR-EC. Interventions at the processing and post-processing stages are expected to be most effective. Simulation results showed that a decrease in antibiotic use among beef cattle might be associated with a reduction in exposure to BR-EC from beef consumption. However, the absolute reduction was moderate, indicating that the effectiveness of restricting antibiotic use as a standalone strategy for mitigating human exposure to BR-EC through beef consumption is still uncertain. Good cooking and hygiene practices at home and advanced safety management practices in the beef processing and post-processing continuum are more powerful approaches for reducing human exposure to antibiotic-resistant bacteria in beef products.
Typing of the Gut Microbiota Community in Japanese Subjects
Authors: Takagi Tomohisa , Inoue Ryo , Oshima Akira , Sakazume Hiroshi , Ogawa Kenta , Tominaga Tomo , Mihara Yoichi , Sugaya Takeshi , Mizushima Katsura , Uchiyama Kazuhiko , Itoh Yoshito , Naito Yuji
Published: March 2022

Gut microbiota are involved in both host health and disease and can be stratified based on bacteriological composition. However, gut microbiota clustering data are limited for Asians. In this study, fecal microbiota of 1803 Japanese subjects, including 283 healthy individuals, were analyzed by 16S rRNA sequencing and clustered using two models. The association of various diseases with each community type was also assessed. Five and fifteen communities were identified using partitioning around medoids (PAM) and the Dirichlet multinominal mixtures model, respectively. Bacteria exhibiting characteristically high abundance among the PAM-identified types were of the family Ruminococcaceae (Type A) and genera Bacteroides, Blautia, and Faecalibacterium (Type B); Bacteroides, Fusobacterium, and Proteus (Type C); and Bifidobacterium (Type D), and Prevotella (Type E). The most noteworthy community found in the Japanese subjects was the Bifidobacterium-rich community. The odds ratio based on type E, which had the largest population of healthy subjects, revealed that other types (especially types A, C, and D) were highly associated with various diseases, including inflammatory bowel disease, functional gastrointestinal disorder, and lifestyle-related diseases. Gut microbiota community typing reproducibly identified organisms that may represent enterotypes peculiar to Japanese individuals and that are partly different from those of indivuals from Western countries.
Study on Fracture and Seepage Evolution Law of Stope Covered by Thin Bedrock under Mining Influence
Authors: Li Zhaolin , Wang Lianguo , Ding Ke , Ren Bo , Wang Shuai , Jiang Chongyang , Pan Zhiyuan
Published: March 2022

Aiming to better understand the fracture evolution characteristics of thin bedrock affected by mining, a program was developed to establish a numerical calculation model for the fracture evolution of the overlying rock in the stope under the coupled seepage-stress condition. The fracturing law of mining overburden during the advancing process of the coal seam working face has been deeply studied. The dynamic change process of the development height of the overburden fissure zone is analyzed. The results show that with the advance of the working surface, shear and tension compound rupture occurs in the overlying rock layer bottom-up. The rupture penetrates into the sand-water layer and forms a stable rupture zone, which terminates at the bottom of the clay layer in the vertical direction and no longer develops upward. The equivalent stress concentration area is obviously separated at the bottom of the clay layer. Additionally, there is no obvious damage to the clay layer, indicating that the integrity of the clay layer has been protected. This pattern is consistent with the field monitoring results. Under the dual action of mining stress and pore water pressure, the bedrock aquifer ruptured in a wide range, and gradually caused water to flow to the goaf. The low pore pressure zone runs through the entire bedrock layer and ends at the bottom of the clay layer; also, the effective velocity of pore fluid shows a consistent pattern. The on-site water inflow monitoring results found that the main source of water inflow was the sandstone aquifer in the bedrock section, and the shallow groundwater and surface water did not enter the working face in large quantities with coal mining. This shows that the clay layer has a good water barrier effect, effectively blocking the inflow of shallow groundwater or surface water into the working face. It also shows that the “soft–hard” roof layer combination feature greatly buffers the impact of mining on the water isolation layer and has a good water separation effect.
Preliminary Mineralogical Characterization of Branching Selenite Gypsum: New Insights for the Paleoenvironmental Reconstruction and Mechanical Characterization
Authors: Caselle Chiara , Pastero Linda , Cavagna Simona , Bonetto Sabrina
Published: March 2022

The present study proposes a characterization of textural and mineralogical features of branching selenite gypsum lithofacies from the Monferrato area (NW Italy). This facies is considered to have appeared during the sequence of the primary lower gypsum of the Messinian Salinity Crisis starting from the sixth stratigraphical cycle, providing a useful tool for stratigraphic correlation throughout the Mediterranean. It is often associated with thick and continuous beds that are exploited by open-pit and underground quarries. We provide the results of a characterization of the non-gypsum minerals that represent approximately 10% in weight of the rock. Mineralogical data were collected with energy-dispersive X-ray spectroscopy (EDS) and X-ray powder diffraction (XRPD) techniques. In addition, a detailed characterization of clay families was performed through dedicated XRPD analyses. Results highlight the presence of detrital minerals (quartz, feldspars and clay minerals), calcite, dolomite and epsomite. Clay analysis registered the existence of five different families (illite, chlorite, smectite and two mixed layers). These mineralogical data suggest that the origin of this lithofacies is connected to both depositional processes and in situ precipitation processes under different conditions of saturation of the brine (respectively undersaturated and supersaturated in sulfates). The mineralogical and textural heterogeneity also represents an important element in controlling the mechanical response of the material and the consequent stability of quarry sites.
Influence of Urbanization on Groundwater Chemistry at Lanzhou Valley Basin in China
Authors: Lü Xiaoli , Han Zhantao , Li Haijun , Zheng Yuejun , Liu Jingtao
Published: March 2022

With the rapid development of the economy, urbanization and industrialization gradually become an important driving force of groundwater chemical evolution. In this study, Lanzhou City, which is one of the biggest industrial cities in northwest China, was selected to investigate the impacts of city development on groundwater quality. Several hydrochemical methods together with principal component analysis (PCA) were used for the hydrochemistry evolution characteristics and sensitive factors of groundwater chemistry in different urban functional areas of Lanzhou City. The results show that 96% of the groundwater in the study area cannot meet the groundwater quality standards of China. The main factors affecting the quality are SO42−, TDS, total hardness, Mg2+ and Na+. Urbanization and industrialization lead to further deterioration of the already naturally high TDS groundwater. NO3−, Cl− and NH4+ are the characteristic factors of human input sources for commercial residential areas; total Fe and NO3− are the characteristic factors of new urban areas in the urban-rural junction; and SO42−, NO3−, Cl−, Total Fe, Mn2+, F−, I−, Pb2+, Cr6+ and As3+ are the characteristic factors of industrial areas. Domestic sewage infiltration and manure infiltration are the main driving factors of groundwater quality deterioration in commercial residential areas. Nitrate fertilizer infiltration and sewage irrigation are the main factors leading to the increase in nitrate nitrogen in groundwater in the new urban area. Industrial wastewater leakage and organic pollution that promote the dissolution of minerals in the aquifer (the dissolution of fluorine-containing minerals and reductive dissolution of iron manganese oxides) are the main driving factors for the deterioration of groundwater quality in the petrochemical industrial area.
Towards Predicting the Sequential Appearance of Zeolitic Imidazolate Frameworks Synthesized by Mechanochemistry
Authors: Cherif Mohamed , Zhang Gaixia , Gao Yang , Sun Shuhui , Vidal François
Published: March 2022

We use computational materials methods to study the sequential appearance of zinc-based zeolitic imidazolate frameworks (ZIFs) generated in the mechanochemical conversion process. We consider nine ZIF topologies, namely RHO, ANA, QTZ, SOD, KAT, DIA, NEB, CAG and GIS, combined with the two ligands 2-methylimidazolate and 2-ethylimidazolate. Of the 18 combinations obtained, only six (three for each ligand) were actually observed during the mechanosynthesis process. Energy and porosity calculations based on density functional theory, in combination with the Ostwald rule of stages, were found to be insufficient to distinguish the experimentally observed ZIFs. We then show, using classical molecular dynamics, that only ZIFs withstanding quasi-hydrostatic pressure P ≥ 0.3 GPa without being destroyed were observed in the laboratory. This finding, along with the requirement that successive ZIFs be generated with decreasing porosity and/or energy, provides heuristic rules for predicting the sequences of mechanically generated ZIFs for the two ligands considered.
Interactive Analysis, Exploration, and Visualization of RNA-Seq Data with SeqCVIBE
Authors: Bothos Efthimios , Hatzis Pantelis , Moulos Panagiotis
Published: March 2022

The rise of modern gene expression profiling techniques, such as RNA-Seq, has generated a wealth of high-quality datasets spanning all fields of current biological research. The large data sets and the continually expanding applications for which they can be mined, such as the investigation of alternative splicing and others, have created novel challenges for data management, exploration, analysis, and visualization. Although a large variety of RNA-Seq data analysis software packages has emerged, both open-source and commercial, most fail to simultaneously address the above challenges, while they lack obvious functionalities, such as estimating RNA abundance over non-annotated genomic regions of interest in real time. We have developed SeqCVIBE, an R Shiny web application for the interactive exploration, analysis, visualization, and genome browsing of large RNA-Seq datasets. SeqCVIBE allows for multiple on-the-fly visualizations and calculations, such as differential expression analysis, averaging genomic signals over specific regions of the genome, and calculating RNA abundances over custom, potentially non-annotated regions, such as novel long non-coding RNAs. In addition, SeqCVIBE comprises a database for pre-analyzed data, where users can navigate and explore results, as well as perform a variety of basic on-the-fly analyses and export the outcomes. Finally, we demonstrate the value of SeqCVIBE in the elucidation of the interplay of a novel lincRNA, WiNTRLINC1, and Wnt signaling in colon cancer.
Antipsychotic Polypharmacy-Related Cardiovascular Morbidity and Mortality: A Comprehensive Review
Authors: Edinoff Amber N. , Ellis Emily D. , Nussdorf Laura M. , Hill Taylor W. , Cornett Elyse M. , Kaye Adam M. , Kaye Alan D.
Published: March 2022

Schizophrenia is a psychotic disorder that exists at the more extreme end of a spectrum of diseases, and significantly affects daily functioning. Cardiovascular adverse effects of antipsychotic medications are well known, and include changes in blood pressure and arrhythmias. Sudden cardiac death is the leading cause of death worldwide, and antipsychotic medications are associated with numerous cardiac side effects. A possible link exists between antipsychotic medications and sudden cardiac death. Common prescribing patterns that may influence cardiovascular events include the use of multiple antipsychotics and/or additional drugs commonly prescribed to patients on antipsychotics. The results of this review reflect an association between antipsychotic drugs and increased risk of ventricular arrhythmias and sudden cardiac death by iatrogenic prolongation of the QTc interval. QTc prolongation and sudden cardiac death exist in patients taking antipsychotic monotherapy. The risk increases for the concomitant use of specific drugs that prolong the QTc interval, such as opioids, antibiotics, and illicit drugs. However, evidence suggests that QTc intervals may not adequately predict sudden cardiac death. In considering the findings of this narrative review, we conclude that it is unclear whether there is a precise association between antipsychotic polypharmacy and sudden cardiac death with QTc interval changes. The present narrative review warrants further research on this important potential association.
Effects of Drainage Water Management in a Corn–Soy Rotation on Soil N2O and CH4 Fluxes
Authors: Hagedorn Jacob G. , Davidson Eric A. , Fisher Thomas R. , Fox Rebecca J. , Zhu Qiurui , Gustafson Anne B. , Koontz Erika , Castro Mark S. , Lewis James
Published: March 2022

Drainage water management (DWM), also known as controlled drainage, is a best management practice (BMP) deployed on drainage ditches with demonstrated success at reducing dissolved nitrogen export from agricultural fields. By slowing discharge from agricultural ditches, subsequent anaerobic soil conditions provide an environment for nitrate to be reduced via denitrification. Despite this success, incomplete denitrification might increase nitrous oxide (N2O) emissions and more reducing conditions might increase methanogenesis, resulting in increased methane (CH4) emissions. These two gases, N2O and CH4, are potent greenhouse gases (GHG) and N2O also depletes stratospheric ozone. This potential pollution swapping of nitrate reduction for GHG production could negatively impact the desirability of this BMP. We conducted three years of static chamber measurements of GHG emissions from the soil surface in farm plots with and without DWM in a corn–soybean rotation on the Delmarva Peninsula. We found that DWM raised the water table at the drainage ditch edge, but had no statistically significant effect on water-filled pore space in the field soil surface. Nor did we find a significant effect of DWM on GHG emissions. These findings are encouraging and suggest that, at least for this farm site, DWM can be used to remove nitrate without a significant tradeoff of increased GHG emissions.
Nanoforming Hyaluronan-Based Thermoresponsive Hydrogels: Optimized and Tunable Functionality in Osteoarthritis Management
Authors: Porcello Alexandre , Gonzalez-Fernandez Paula , Jordan Olivier , Allémann Eric
Published: March 2022

Hyaluronic acid (HA) constitutes a versatile chemical framework for the development of osteoarthritis pain treatment by means of injection in the joints, so-called viscosupplementation. Without appropriate physico-chemical tuning, such preparations are inherently hindered by prompt in vivo degradation, mediated by hyaluronidases and oxidative stress. To prolong hydrogel residence time and confer optimized product functionality, novel thermoresponsive nanoforming HA derivatives were proposed and characterized. Combined use of sulfo-dibenzocyclooctyne-PEG4-amine linkers and poly(N-isopropylacrylamide) in green chemistry process enabled the synthesis of HA-based polymers, with in situ obtention of appropriate viscoelastic properties. Spontaneous and reversible thermoformation of nanoparticles above 30 °C was experimentally confirmed. Lead formulations were compared to a commercially available HA-based product and shown significantly better in vitro resistance to enzymatic and oxidative degradation, required half the injection force with optimal viscoelastic hydrogel properties in equine synovial fluids. Results highlighted the vast potential of appropriately engineered HA-based systems as next-generation long-acting viscosupplementation products for osteoarthritic patients.
Absorption of Direct Oral Anticoagulants in Cancer Patients after Gastrectomy
Authors: Puhr Hannah C. , Ilhan-Mutlu Aysegül , Preusser Matthias , Quehenberger Peter , Kyrle Paul A. , Eichinger Sabine , Eischer Lisbeth
Published: March 2022

Direct oral anticoagulants (DOACs) are safe and effective in cancer patients treated for venous thromboembolism (VTE) or atrial fibrillation (AF). Gastrectomy is the treatment of choice in patients with localized upper gastrointestinal cancer. DOACs are absorbed in the upper gastrointestinal tract, but to what extent is unclear. In a retrospective analysis, hospital data were searched for adult patients who underwent gastrectomy for gastroesophageal or pancreatic cancer, and DOAC therapy for VTE or AF after gastrectomy. DOAC blood levels were determined by chromogenic assays before and after administration, and thromboembolic and bleeding complications were recorded. Eleven patients (median age 76 years) received a factor Xa inhibitor (FXaI; apixaban (3), edoxaban (3), rivaroxaban (4)) or the factor IIa inhibitor dabigatran (1) for VTE (7) or AF (4) after gastrectomy. Eight patients on FXaI had anti-Xa (aXa) trough levels within the expected range (ER). In all of them, aXa levels increased upon DOAC administration. Two patients on 30 mg edoxaban had low aXa trough levels. Administration of 20 mg of rivaroxaban resulted in trough levels in the ER in one of them. None of the FXaI patients had thromboembolism, while two experienced bleeding (arterial puncture site, gastrointestinal). One dabigatran AF patient with trough and peak concentrations below the ER had strokes during 110 mg and 150 mg dabigatran administration. While on apixaban, aXa levels were in the ER, and no clinical complications occurred. DOACs, particularly FXaI, were adequately absorbed in cancer patients after gastrectomy. Our observation of recurrent thromboembolic events in a patient treated with dabigatran warrants cautious use in this specific patient population.
Finite Element Analysis and Modeling in Pharmaceutical Tableting
Authors: Partheniadis Ioannis , Terzi Vasiliki , Nikolakakis Ioannis
Published: March 2022

Finite element analysis (FEA) is a computational method providing numerical solutions and mathematical modeling of complex physical phenomena that evolve during compression tableting of pharmaceutical powders. Since the early 2000s, FEA has been utilized together with various constitutive material models in a quest for a deeper understanding and unraveling of the complex mechanisms that govern powder compression. The objective of the present review paper is to highlight the potential and feasibility of FEA for implementation in pharmaceutical tableting in order to elucidate important aspects of the process, namely: stress and density distributions, temperature evolution, effect of punch shape on tablet formation, effect of friction, and failure of the tablet under stress. The constitutive models and theoretical background governing the above aspects of tablet compression and tablet fracture under diametral loading are also presented. In the last sections, applications of FEA in pharmaceutical tableting are demonstrated by many examples that prove its utilization and point out further potential applications.
Molecular Tuning of IR-786 for Improved Tumor Imaging and Photothermal Therapy
Authors: Lim Wonbong , Byun Jae Yong , Jo Gayoung , Kim Eun Jeong , Park Min Ho , Hyun Hoon
Published: March 2022

A tumor-targeted near-infrared (NIR) fluorophore CA800Cl was developed based on commercially available IR-786 by modulating its physicochemical properties. IR-786, a hydrophobic cationic heptamethine cyanine fluorophore, was previously recognized as a mitochondria-targeting NIR agent with excellent optical properties. Owing to the poor tumor specificity of IR-786 itself, in vivo studies on tumor-targeted imaging have not yet been investigated. A chloro-cyclohexene ring and indolium side groups on the heptamethine chain are key structural features that improve tumor targetability, owing to better biodistribution and clearance. Thus, IR-786 should be designed to be more soluble in aqueous solutions so that it can preferentially accumulate in the tumor based on the structure-inherent targeting strategy. In this study, we developed a bifunctional NIR fluorophore CA800Cl by incorporating carboxylate moieties in the basic structure of IR-786. This improved its tumor targetability and water solubility, thereby enabling the use of CA800Cl for enhanced photothermal cancer therapy.
A New Approach to Supramolecular Structure Determination in Pharmaceutical Preparation of Self-Assembling Peptides: A Case Study of Lanreotide Autogel
Authors: Grimaldi Manuela , Santoro Angelo , Buonocore Michela , Crivaro Claudio , Funicello Nicola , Sublimi Saponetti Matilde , Ripoli Cristina , Rodriquez Manuela , De Pasquale Salvatore , Bobba Fabrizio , Ferrazzano Lucia , Cabri Walter , D’Ursi Anna Maria , Ricci Antonio
Published: March 2022

The supramolecular structure in peptides’ prolonged-released gel formulations is the most critical parameter for the determination of the pharmaceutical profile of the drug. Here, we report our investigation on lanreotide Autogel as a case study. For the first time, we describe the use of the pulsed field gradient (PFG) diffusion-ordered spectroscopy (DOSY) magic-angle spinning NMR to characterize the supramolecular self-assembly and molecular mobility of different samples of lanreotide Autogel formulations prepared according to different formulation protocols. The diffusion coefficient was used to calculate the hydrodynamic radii of supramolecular assemblies and build relative molecular models. DOSY data were integrated with NMR imaging (MRI) measurements and atomic force microscopy (AFM) imaging.
Intuition and Ingenuity: Gödel on Turing’s “Philosophical Error”
Authors: Chen Long
Published: March 2022

Despite his unreserved appreciation of Turing’s analysis for being a “precise and unquestionably adequate definition” of formal system or mechanical computability, Gödel nevertheless published a short note in 1972 claiming to have found a “philosophical error” in Turing’s argument with regard to the finite nature of mental states and memory. A natural question arises: how could Gödel enjoy the generality conferred on his results by Turing’s work, despite the error of its ways? Previous interpretative strategies by Feferman, Shagrir and others have mainly tried to resolve the disparity by distinguishing different types of arguments in Turing and taking Gödel to approve only some of them. By a more integral examination of their ideas, especially Turing’s response to the “mathematical objection” based on Gödel’s incompleteness theorem and Gödel’s own conception of finite yet non-mechanical procedures, and taking some of the main ideas of current developments in machine learning into consideration, I will try to present a new explanation for the apparent disparity, arguing that there is no “error” on Turing’s side and the seemingly conflicting views held by Turing and Gödel should best be seen as complementary, keeping intuition and ingenuity together.
A Comparison between the Lower Critical Solution Temperature Behavior of Polymers and Biomacromolecules
Authors: Xie Yuxin , Li Nan K. , Singh Abhishek , Deshmukh Sanket A. , Yingling Yaroslava G.
Published: March 2022

All-atom molecular dynamics (MD) simulations are employed to compare the lower critical solution temperature (LCST) behaviors of poly(N-isopropylacrylamide) (PNIPAM) and elastin-like polypeptides (ELPs) with the canonical Val-Pro-Gly-Val-Gly ((VPGVG)n) sequence over a range of temperatures from 280 K to 380 K. Our simulations suggest that the structure of proximal water dictates the conformation of both the (VPGVG)n ELPs and PNIPAM chains. Specifically, the LCST transition in ELPs can be attributed to a combination of thermal disruption of the network of the proximal water near both hydrophilic and hydrophobic groups in the backbone and side-chain of (VPGVG)n, resulting in a reduction in solvent accessible surface area (SASA). This is accompanied with an increase in the secondary structure above its LCST. In the case of PNIPAM, the LCST transition is a result of a combination of a reduction in the hydrophobic SASA primarily due to the contributions of isopropyl side-chain and less to the backbone and the formation of intra-chain hydrogen bonds between the amide groups on the side-chain above its LCST.
Identification and Characterization of Two Regiospecific Tricetin UDP-Dependent Glycosyltransferases from Pomegranate (Punica granatum L.)
Authors: Wu Sheng , Chang Lijing , Tian Li
Published: March 2022

Tricetin (5,7,3′,4′,5′-pentahydroxyflavone) is a dietary flavone from flowers of Myrtales plants with demonstrated functions in promoting human health. By contrast, the bioactivity of its glucosylated derivative tricetin 4′-O-glucoside has not been extensively explored. We conducted metabolite profiling analysis of pomegranate (a Myrtales plant) floral tissues and revealed that tricetin and tricetin 4′-O-glucoside accumulate in anthers, but not petals. In addition, the comparative analysis of anther and petal transcriptomes identified 10 UGTs that are more highly expressed in anthers than petals. Of the 10 UGTs, PgUGT76Z1 and PgUGT73AL1 glucosylated specifically at the 4′-O position of tricetin to form tricetin 4′-O-glucoside. The phylogenetic analysis indicated that PgUGT76Z1 and PgUGT73AL1 belong to different plant UGT groups, suggesting a convergent evolution of these tricetin UGTs. Overall, identification and characterization of PgUGT76Z1 and PgUGT73AL1 not only provides evolutionary insights into tricetin glucosylation, but also offers an opportunity to produce tricetin 4′-O-glucoside in large quantities through microbial biotransformation or plant metabolic engineering, thus facilitating the investigation of tricetin 4′-O-glucoside bioactivities.
Research on the Application of Synthetic Polymer Materials in Contemporary Public Art
Authors: Zhang Yajun , Yu Xuelian , Cheng Zhichao
Published: March 2022

Synthetic polymer materials are widely used in contemporary public art creation. This review summarizes the application methods and current situation of synthetic polymer materials in public art, analyzes the reasons behind them and points out the deficiencies in this research field. Finally, the development trend of the interaction between synthetic polymer materials and public art is put forward.
Thermal Storage Performance of Underground Cave Dwellings under Kang Intermittent Heating: A Case Study of Northern China
Authors: Zhu Jiayin , Liu Yingfang , Li Ruixin , Chen Bin , Chen Yu , Lu Jifu
Published: March 2022

The intermittent heating mode of Kang plays an important role in the heat storage and release in cave dwellings. However, research on the effect of Kang heating on the thermal process of traditional buildings is rare. Therefore, based on long-term monitoring of cave dwellings, regular conclusions about the influence of Kang heating on the thermal environment were obtained. Furthermore, an unsteady heat transfer model of the envelope was proposed for the first time. Then, based on this model, the thermal storage performance of cave dwellings during the period of Kang intermittent heating was explored. The results showed that, due to Kang heating, the indoor air temperature of cave dwellings could be increased by an average of 3.1 °C. Furthermore, the inner walls had a large thermal mass and the maximum heat storage in a single day was 487.75 kJ/m2, while the maximum heat release was 419.02 kJ/m2. The heat release at night could reach 87%. In this paper, the law of thermal storage and release characteristics of earthen building envelopes under intermittent heating was firstly obtained. Results can enrich the thermal process theory of earthen buildings and provide a theoretical basis and technical support for building thermal environmental construction.
Modeling the Biosorption Process of Heavy Metal Ions on Soybean-Based Low-Cost Biosorbents Using Artificial Neural Networks
Authors: Fertu Daniela Ionela , Dragoi Elena Niculina , Bulgariu Laura , Curteanu Silvia , Gavrilescu Maria
Published: March 2022

Pollution of the environment with heavy metals requires finding solutions to eliminate them from aqueous flows. The current trends aim at exploiting the advantages of the adsorption operation, by using some low-cost sorbents from agricultural waste biomass, and with good retention capacity of some heavy metal ions. In this context, it is important to provide tools that allow the modeling and optimization of the process, in order to transpose the process to a higher operating scale of the biosorption process. This paper capitalizes on the results of previous research on the biosorption of heavy metal ions, namely Pb(II), Cd(II), and Zn(II) on soybean biomass and soybean waste biomass resulting from biofuels extraction process. The data were processed by applying a methodology based on Artificial Neural Networks (ANNs) and evolutionary algorithms (EAs) capable of evolving ANN parameters. EAs are represented in this paper by the Differential Evolution (DE) algorithm, and a simultaneous training and determination of the topology is performed. The resulting hybrid algorithm, hSADE-NN was applied to obtain optimal models for the biosorption process. The expected response of the system addresses biosorption capacity of the biosorbent (q, mg/g), the biosorption efficiency (E, %), as functions of input parameters: pH, biosorbent dose (DS, mg/g), the initial concentration of metal in the solution (c0, mg/L), contact time (tc, h), and temperature (T, °C). Models were developed for the two output variables, for each metal ion, finding a high degree of accuracy. Furthermore, the combinations of input parameters were found which can lead to an optimal output in terms of biosorption capacity and biosorption efficiency.
Calcination Temperature Induced Structural, Optical and Magnetic Transformations in Titanium Ferrite Nanoparticles
Authors: Shukla Abhishek , Singh Subhash C. , Bhardwaj Abhishek , Kotnala Ravindra Kumar , Uttam Kailash Narayan , Guo Chunlei , Gopal Ram
Published: March 2022

Titanium ferrite represents one of the most promising magnetic materials that exhibits optical absorption in both ultraviolet and visible spectral regions with a range of applications in photocatalysis, giant magnetoresistance, sensors, high-frequency modern power supplies, etc. Here in the present work, we report synthesizing titanium ferrite NPs via the co-precipitation method. As obtained ferrite nanopowders were characterized using XRD, UV-Visible absorption, Raman scattering, and variable sample magnetometer techniques. The crystalline size of NPs lies between 35 to 50 nm. The as-obtained nanopowder samples were calcined at 200, 500, 800 °C temperatures, and the resulting change in the optical, structural, and magnetic properties are investigated. The saturation magnetization of 500 °C calcined sample is higher than that calcined at 200 °C, but the magnetization value drastically becomes reduced for powder calcined at 800 °C temperature. The results of the present work can be used to understand the effects of annealing temperature on the structural and magnetic properties of other ferrite nanomaterials.
How Do Chinese Christians Draw Boundaries among Themselves? Reassessing the Question of Chinese Christianities
Authors: Chambon Michel
Published: March 2022

This paper explores how Christians have established six communities in Nanping, Fujian, to discuss the unity and diversity of Chinese Christianity. The research provides a historical and ethnographic account of local churches, revealing the evolution of their modes of being religious and their organizational patterns over time. It argues that the negotiation of inter-ecclesial boundaries depends on specifically Christian features that foster a certain unity within the diversity of the Christian phenomenon. Aware of their different interpretations, all Christian communities still relate to the historical figure of Jesus Christ as their unique God and interact with the Church, a semi-transcendent being standing beyond their own congregation. Therefore, the diversity of churches, practices, and teachings should not be reduced to a juxtaposition of social groups promoting their own values and norms, but requires a multidimensional model of Christianity that encompasses the variety of human and non-human actors and their evolving interconnections.
The Roots of Ambivalence: Makiguchi Tsunesaburō’s Heterodox Discourse and Praxis of “Religion”
Authors: Gebert Andrew
Published: March 2022

In the post-World War II era, Sōka Gakkai has deployed the terminology and concept of “religion” (shūkyō 宗教) in a variety of contexts and to a variety of ends. Do these positions simply reflect a post-war strategic stance? Do they have deeper historical and philosophical roots? A careful reading of key texts by founding president Makiguchi Tsunesaburō 牧口常三郎 (1871–1944) suggests that, from its inception as the Value-Creating Education Society (Sōka Kyōiku Gakkai 創価教育学会) in the 1930s, the movement has occupied an ambiguous space, relative to the conceptualization and practice of “religion”, as these were imported at the start of the Meiji Era (1868–1912), adopted and indigenized to respond to the cultural, social and political exigencies of modernizing Japan. Examples of Makiguchi’s heterodoxy, relative to the established understanding of “religion” and its role, include: the rejection of specific ideas of “religion”, in relation to education and science, as represented in the writings of such intellectuals as Inoue Tetsujirō 井上哲次郎 and Ishiwara Atsushi 石原純; refusal to accept the official definition of Shintō as non-religion; positing an essential continuity between faith/trust among human subjects and faith directed at ideas and objects typically considered “religious”; promoting the idea of worldly benefit, as a result of faith in and practice of “religion”. A careful reading of Makiguchi’s complex, and often heterodox, discourse, relative to the conceptual category of “religion”, can frame a more nuanced interpretation of his ultimate heterodoxy—his rejection of the Ise Shrine amulet, an act for which he was arrested and confined to prison in July 1943. It can also clarify the basis for the Sōka Gakkai’s post-war deployments of the concept of religion, and create a more flexible and expansive interpretative space for considering the organization’s discourse and praxis in the post-war era.
Research on Game-Playing Agents Based on Deep Reinforcement Learning
Authors: Zhao Kai , Song Jia , Luo Yuxie , Liu Yang
Published: March 2022

Path planning is a key technology for the autonomous mobility of intelligent robots. However, there are few studies on how to carry out path planning in real time under the confrontation environment. Therefore, based on the deep deterministic policy gradient (DDPG) algorithm, this paper designs the reward function and adopts the incremental training and reward compensation method to improve the training efficiency and obtain the penetration strategy. The Monte Carlo experiment results show that the algorithm can effectively avoid static obstacles, break through the interception, and finally reach the target area. Moreover, the algorithm is also validated in the Webots simulator.