bluuebunny/crossref_metadata_2025 huggingface dataset:
Shear bond strength analysis and marginal gap evaluation of restoration–tooth interface of aesthetic restorations after simulated Co-60 gamma irradiation
Authors: Tikku Aseem P. , Bhatt Madan L. B. , Painuly Narendra K. , Bharti Ramesh , Bains Rhythm , Misra Sakshma
Published: September 2021

Background:

Radiotherapy to the head and neck region may cause considerable radiotherapy-induced changes in the surrounding tissues. These changes are oral mucositis, hyposalivation, dental caries, osteoradionecrosis, trismus and overall impact on patients’ quality of life. Tooth-coloured synthetic materials, unlike metallic restoration, did not influence radiation dose distribution. However, their exposure to a gamma radiation therapeutic dose during treatment might cause structural and compositional changes that alter their mechanical and physical properties.

Aim:

This study intends to evaluate the effect of Co 60 gamma rays on shear bond strength and marginal adaptation of already restored tooth surfaces, to help in material selection before the onset of radiotherapy.

Materials and methods:

Hundred freshly extracted human permanent mandibular molar teeth collected and stored in a 0·2% thymol solution for disinfection and were randomly divided into two groups of 50 each, to be tested for the shear bond strength of restoration to dentin and the marginal gap at tooth–restoration interface, respectively.

Results:

ANOVA showed a significant effect of both radiotherapy (F = 40·33, p < 0·001) and restorations (134·00, p < 0·001) on the marginal gap at the interface. In the without radiotherapy group, the mean marginal gap was least in Group Z250, and in with radiation, Bulk Fill has the least mean marginal gap. The mean shear bond strength was comparatively higher for all restorations without radiation than with radiation (p < 0·001).

Findings:

Gamma radiation affects the physical or mechanical properties of tooth structure and the tooth restorative interface. Composites seem to be good restorative material when placed before the onset of radiotherapy in head and neck cancer patients.
Knowledge-Based Stable Roommates Problem: A Real-World Application
Authors: FIDAN MÜGE , ERDEM ESRA
Published: September 2021

The Stable Roommates problem with Ties and Incomplete lists (SRTI) is a matching problem characterized by the preferences of agents over other agents as roommates, where the preferences may have ties or be incomplete. SRTI asks for a matching that is stable and, sometimes, optimizes a domain-independent fairness criterion (e.g. Egalitarian). However, in real-world applications (e.g. assigning students as roommates at a dormitory), we usually consider a variety of domain-specific criteria depending on preferences over the habits and desires of the agents. With this motivation, we introduce a knowledge-based method to SRTI considering domain-specific knowledge and investigate its real-world application for assigning students as roommates at a university dormitory.
Saturation of Global Terrestrial Carbon Sink Under a High Warming Scenario
Authors: Shi Hao , Tian Hanqin , Pan Naiqing , Reyer Christopher P. O. , Ciais Philippe , Chang Jinfeng , Forrest Matthew , Frieler Katja , Fu Bojie , Gädeke Anne , Hickler Thomas , Ito Akihiko , Ostberg Sebastian , Pan Shufen , Stevanović Miodrag , Yang Jia
Published: September 2021

The terrestrial carbon sink provides a critical negative feedback to climate warming, yet large uncertainty exists on its long‐term dynamics. Here we combined terrestrial biosphere models (TBMs) and climate projections, together with climate‐specific land use change, to investigate both the trend and interannual variability (IAV) of the terrestrial carbon sink from 1986 to 2099 under two representative concentration pathways RCP2.6 and RCP6.0. The results reveal a saturation of the terrestrial carbon sink by the end of this century under RCP6.0 due to warming and declined CO2 effects. Compared to 1986–2005 (0.96 ± 0.44 Pg C yr−1), during 2080–2099 the terrestrial carbon sink would decrease to 0.60 ± 0.71 Pg C yr−1 but increase to 3.36 ± 0.77 Pg C yr−1, respectively, under RCP2.6 and RCP6.0. The carbon sink caused by CO2, land use change and climate change during 2080–2099 is −0.08 ± 0.11 Pg C yr−1, 0.44 ± 0.05 Pg C yr−1, and 0.24 ± 0.70 Pg C yr−1 under RCP2.6, and 4.61 ± 0.17 Pg C yr−1, 0.22 ± 0.07 Pg C yr−1, and ‐1.47 ± 0.72 Pg C yr−1 under RCP6.0. In addition, the carbon sink IAV shows stronger variance under RCP6.0 than RCP2.6. Under RCP2.6, temperature shows higher correlation with the carbon sink IAV than precipitation in most time, which however is the opposite under RCP6.0. These results suggest that the role of terrestrial carbon sink in curbing climate warming would be weakened in a no‐mitigation world in future, and active mitigation efforts are required as assumed under RCP2.6.
Responses of the Ionosphere and Neutral Winds in the Mesosphere and Lower Thermosphere in the Asian‐Australian Sector to the 2019 Southern Hemisphere Sudden Stratospheric Warming
Authors: Li Na , Lei Jiuhou , Huang Fuqing , Yi Wen , Chen Jinsong , Xue Xianghui , Gu Shengyang , Luan Xiaoli , Zhong Jiahao , Liu Feifan , Dou Xiankang , Qin Yusong , Owolabi Charles
Published: September 2021

In this study, the neutral winds from meteor radars and the total electron content (TEC) from Beidou Geostationary (GEO) satellites were utilized to study the responses of the mesosphere and lower thermosphere and the ionosphere in the Asian‐Australian sector to the recent Sudden Stratospheric Warming (SSW) occurred in the Antarctic polar region during September 2019. It was demonstrated that the ionospheric TEC increased significantly, especially around the equatorial ionization anomaly (EIA) region during this SSW. A pronounced semidiurnal signature in the deviation TEC was observed near the EIA crest region, which was more significant in the southern hemisphere. Meanwhile, the enhancement period of the amplitudes of solar and lunar semidiurnal tides in winds in the mesosphere was coincided with that in TEC. The solar semidiurnal amplitudes increased from about 18 to 35 m/s in the zonal wind and from 15 to 25 m/s in the meridional wind at Mengcheng (33.4°N, 116.5°E, MLAT 27.4°N), and from about 15–38 m/s in the zonal wind at Kunming (25.6°N, 103.6°E, MLAT 19.3°N). The lunar semidiurnal amplitudes increased from 2 to 6 m/s in the zonal wind and from about 3–9 m/s in the meridional wind at Mengcheng, and from about 3–7 m/s in the meridional wind at Kunming, respectively. These indicated that the semidiurnal signature in TEC during the 2019 southern hemisphere SSW could be associated with the SSW induced by the atmospheric semidiurnal tide variations in the mesosphere.
Radiative and Aerodynamic Contribution to Evaporation: Eddy‐Covariance Comparison Between a Plain and a Plateau Lake
Authors: Cui Yifan , Zhang Xueqin , Liu Yuanbo
Published: September 2021

Water surface‐atmosphere interactions play an important role in the climate system on regional and even global scale. Yet, it remains unclear whether radiative or aerodynamic forces contribute more to water surface evaporation, which may lead to different strategies in model parameterization. This study compared the eddy covariance observations taken at two contrasting lakes in China: Poyang Lake (subtropical, plain, and warm) in 2018 and Yamzhog Yum Co (alpine, plateau, and cold) in 2016. Both lakes of similar latitude have similar solar radiation, and Yamzhog Yum Co has a lower atmospheric pressure and air density and a larger temperature difference between water surface and air. Poyang Lake had a total evaporation of 741 mm from 6 May to 31 December 2018, relatively higher than that of Yamzhog Yum Co (677 mm) for the same season in 2016. Evaporation peaked in August for Poyang Lake but in October for Yamzhog Yum Co. The Penman equation disclosed that radiative forces contributed more than aerodynamic forces in both lakes. Evaporation was found to be most sensitive to air temperature in Poyang Lake but to surface net radiation in Yamzhog Yum Co, attributable to their sensitivity differences in iso‐radiative and isothermal conditions. Higher elevation reduced the aerodynamic contribution with lower air temperature and atmospheric pressure in Yamzhog Yum Co. The findings should be useful for understanding different behaviors of lake evaporation under common mechanisms.
The Role of Free‐Tropospheric Moisture Convergence for Summertime Heavy Rainfall in Western Japan
Authors: Tsuji Hiroki , Takayabu Yukari N. , Shibuya Ryosuke , Kamahori Hirotaka , Yokoyama Chie
Published: September 2021

The role of vertically integrated water vapor flux convergence (IVFC) in heavy rainfall events in western Japan is investigated by dividing the atmosphere into a boundary layer and free troposphere using the Japan Meteorological Agency's mesoscale gridded analysis product and reanalysis product. Rainfall events are defined by peaks of area‐averaged precipitation. The results show an increase in the free‐tropospheric IVFC more than 15 h before rainfall events, contributing to atmosphere moistening. This preceding moistening is favorable for mesoscale convective systems (MCSs) with slantwise ascending deep inflow layers (layer lifting) that produce large precipitation amounts. Appearance frequency of the moist absolutely unstable layer (MAUL) increases around the precipitation peak times, which is especially notable for larger peaks. These results indicate that the free‐tropospheric IVFC contributes to heavy rainfall in western Japan by providing environments favorable for producing and maintaining MAUL, enhancing the organization of MCSs.
Quasiperiodic Emissions and Related Particle Precipitation Bursts Observed by the DEMETER Spacecraft
Authors: Němec F. , Hajoš M. , Parrot M. , Santolík O.
Published: September 2021

Electromagnetic waves observed in the inner magnetosphere at frequencies between about 0.5 and 4 kHz sometimes exhibit a quasiperiodic (QP) time modulation of the wave intensity with modulation periods from tens of seconds up to a few minutes. Such waves are typically termed “QP emissions” and their origin is still not fully understood. We use a large set of more than 2,000 of these events identified in the low‐altitude DEMETER spacecraft data to check for energetic electron flux variations matching the individual QP wave elements. Altogether, seven such events are identified and their detailed analysis is performed. Energetic electron fluxes are found to be modulated primarily at energies lower than about 250 keV. While the waves may propagate unducted across L‐shells, the energetic particles follow magnetic field lines from the interaction region down to the observation point. This is used to estimate the locations of anticipated generation regions to L‐shells between about 4 and 6, and the respective source radial dimensions to about 0.6–1.2 Earth radii. The frequencies of the events are confined below half of the equatorial electron gyrofrequency in the determined source regions. Finally, it is shown that individual QP elements exhibit a fine inner structure corresponding to the wave bouncing between the hemispheres.
Effect of Poroelastic Coupling and Fracture Dynamics on Solute Transport and Geomechanical Stability
Authors: Tran Minh , Jha Birendra
Published: September 2021

The coupling between solute transport and rock's geomechanical processes, for example, flow‐induced fracture activation, has emerged as an important hydrogeological challenge due to its role in applications such as underground waste disposal, carbon sequestration, contaminant remediation, enhanced oil recovery, and tracer‐based reservoir surveillance. Despite recent advances in modeling flow and geomechanics coupling, a holistic approach to capturing the synergy between fluid flow, solute transport, induced stresses, and fracture mechanics is lacking. This study investigates the rich interplay between these processes within a novel computational framework that is proposed to solve the coupled flow, transport, geomechanics, and fracture mechanics problem. The Embedded Discrete Fracture Modeling (EDFM) method is used to model the flow and transport processes in fractured porous media while an improved Bandis model is employed to capture the fracture mechanical response to flow‐induced stress perturbations. The role of transport‐geomechanics coupling in modulating the spreading and miscibility of a solute slug during viscously unstable flows is examined. We investigate how flow‐transport coupling, parameterized through the solute viscosity contrast and the fracture permeability, influences the stress state and fracture stability in the domain. A case study, inspired by a huff‐n‐puff tracer flowback study, is conducted to investigate the applicability of the proposed framework in the field. A sensitivity analysis is performed to evaluate the dependence of global transport characteristics, permeability evolution, and fracture stability on parameters dictating the strength of coupling between geomechanics, flow, and transport.
An unusual nicotinamide derivative, 4-pyridone-3-carboxamide ribonucleoside (4PYR), is a novel endothelial toxin and oncometabolite
Authors: Mierzejewska Paulina , Kunc Michal , Zabielska-Kaczorowska Magdalena Agnieszka , Kutryb-Zajac Barbara , Pelikant-Malecka Iwona , Braczko Alicja , Jablonska Patrycja , Romaszko Pawel , Koszalka Patrycja , Szade Jolanta , Smolenski Ryszard Tomasz , Slominska Ewa Maria
Published: September 2021

Our recent studies identified a novel pathway of nicotinamide metabolism that involves 4-pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR) and demonstrated its endothelial cytotoxic effect. This study tested the effects of 4PYR and its metabolites in experimental models of breast cancer. Mice were divided into groups: 4T1 (injected with mammary 4T1 cancer cells), 4T1 + 4PYR (4PYR-treated 4T1 mice), and control, maintained for 2 or 21 days. Lung metastasis and endothelial function were analyzed together with blood nucleotides (including 4PYR), plasma amino acids, nicotinamide metabolites, and vascular ectoenzymes of nucleotide catabolism. 4PYR metabolism was also evaluated in cultured 4T1, MDA-MB-231, MCF-7, and T47D cells. An increase in blood 4PYR in 4T1 mice was observed at 2 days. 4PYR and its metabolites were noticed after 21 days in 4T1 only. Higher blood 4PYR was linked with more lung metastases in 4T1 + 4PYR vs. 4T1. Decreased L-arginine, higher asymmetric dimethyl-L-arginine, and higher vascular ecto-adenosine deaminase were observed in 4T1 + 4PYR vs. 4T1 and control. Vascular relaxation caused by flow-dependent endothelial activation in 4PYR-treated mice was significantly lower than in control. The permeability of 4PYR-treated endothelial cells was increased. Decreased nicotinamide but enhanced nicotinamide metabolites were noticed in 4T1 vs. control. Reduced N-methylnicotinamide and a further increase in Met2PY were observed in 4T1 + 4PYR vs. 4T1 and control. In cultured breast cancer cells, estrogen and progesterone receptor antagonists inhibited the production of 4PYR metabolites. 4PYR formation is accelerated in cancer and induces metabolic disturbances that may affect cancer progression and, especially, metastasis, probably through impaired endothelial homeostasis. 4PYR may be considered a new oncometabolite.
Frontal-posterior functional imbalance and aberrant function developmental patterns in schizophrenia
Authors: Sun Dandan , Guo Huiling , Womer Fay Y. , Yang Jingyu , Tang Jingwei , Liu Juan , Zhu Yue , Duan Jia , Peng Zhengwu , Wang Huaning , Tan Qingrong , Zhu Qiwen , Wei Yange , Xu Ke , Zhang Yanbo , Tang Yanqing , Zhang Xizhe , Xu Fuqiang , Wang Jie , Wang Fei
Published: September 2021

Schizophrenia (SZ) is a neurodevelopmental disorder. There remain significant gaps in understanding the neural trajectory across development in SZ. A major research focus is to clarify the developmental functional changes of SZ and to identify the specific timing, the specific brain regions, and the underlying mechanisms of brain alterations during SZ development. Regional homogeneity (ReHo) characterizing brain function was collected and analyzed on humans with SZ (hSZ) and healthy controls (HC) cross-sectionally, and methylazoxymethanol acetate (MAM) rats, a neurodevelopmental model of SZ, and vehicle rats longitudinally from adolescence to adulthood. Metabolomic and proteomic profiling in adult MAM rats and vehicle rats was examined and bioanalyzed. Compared to HC or adult vehicle rats, similar ReHo alterations were observed in hSZ and adult MAM rats, characterized by increased frontal (medial prefrontal and orbitofrontal cortices) and decreased posterior (visual and associated cortices) ReHo. Longitudinal analysis of MAM rats showed aberrant ReHo patterns as decreased posterior ReHo in adolescence and increased frontal and decreased posterior ReHo in adulthood. Accordingly, it was suggested that the visual cortex was a critical locus and adolescence was a sensitive window in SZ development. In addition, metabolic and proteomic alterations in adult MAM rats suggested that central carbon metabolism disturbance and mitochondrial dysfunction were the potential mechanisms underlying the ReHo alterations. This study proposed frontal-posterior functional imbalance and aberrant function developmental patterns in SZ, suggesting that the adolescent visual cortex was a critical locus and a sensitive window in SZ development. These findings from linking data between hSZ and MAM rats may have a significant translational contribution to the development of effective therapies in SZ.
Histone acetyltransferase 1 promotes gemcitabine resistance by regulating the PVT1/EZH2 complex in pancreatic cancer
Authors: Sun Yan , Ren Dianyun , Zhou Yingke , Shen Jian , Wu Heshui , Jin Xin
Published: September 2021

The poor prognosis of pancreatic cancer is primarily due to the development of resistance to therapies, including gemcitabine. The long noncoding RNA PVT1 (lncRNA PVT1) has been shown to interact with enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), promoting gemcitabine resistance in pancreatic cancer. In this study, we found histone acetyltransferase 1 (HAT1) enhanced the tolerance of pancreatic cancer cells to gemcitabine and HAT1-mediated resistance mechanisms were regulated by PVT1 and EZH2. Our results showed that the aberrant HAT1 expression promoted gemcitabine resistance, while silencing HAT1 restored gemcitabine sensitivity. Moreover, HAT1 depletion caused a notable increase of gemcitabine sensitivity in gemcitabine-resistant pancreatic cancer cell lines. Further research found that HAT1 increased PVT1 expression to induce gemcitabine resistance, which enhanced the binding of bromodomain containing 4 (BRD4) to the PVT1 promoter, thereby promoting PVT1 transcription. Besides, HAT1 prevented EZH2 degradation by interfering with ubiquitin protein ligase E3 component n-recognin 4 (UBR4) binding to the N-terminal domain of EZH2, thus maintaining EZH2 protein stability to elevate the level of EZH2 protein, which also promoted HAT1-mediated gemcitabine resistance. These results suggested that HAT1 induced gemcitabine resistance of pancreatic cancer cells through regulating PVT1/EZH2 complex. Given this, Chitosan (CS)-tripolyphosphate (TPP)-siHAT1 nanoparticles were developed to block HAT1 expression and improve the antitumor effect of gemcitabine. The results showed that CS-TPP-siHAT1 nanoparticles augmented the antitumor effects of gemcitabine in vitro and in vivo. In conclusion, HAT1-targeted therapy can improve observably gemcitabine sensitivity of pancreatic cancer cells. HAT1 is a promising therapeutic target for pancreatic cancer.
Fear-of-intimacy-mediated zinc transport controls fat body cell dissociation through modulating Mmp activity in Drosophila
Authors: Wei Tian , Ji Xiaowen , Yu Qunhui , Li Guangying , Wu Lei , Gao Yan , Xiao Guiran
Published: September 2021

Matrix metalloproteinases (Mmps) are pivotal extracellular proteinases that have been implicated in tumour invasion and metastasis. Drosophila fat body is important for energy storage and utilization, as well as biosynthetic and metabolic activities. The fat body undergoes remodelling during metamorphosis which is characterized by the dissociation of the fat body into individual cells. Mmps play important roles in the regulation of fat body cell dissociation. Here we show that a zinc transporter fear-of-intimacy (foi) is necessary for the cell dissociation of fat body in Drosophila. The progression of fat body cell dissociation was delayed by fat body-specific foi knockdown while it was accelerated by foi overexpression (OE). In essence, these phenotypes are closely associated with intracellular zinc homeostasis, which can be modulated by dietary zinc intervention or genetic modulation of other zinc transporters. Further study indicated that Mmp1 and Mmp2 levels could be transcriptionally regulated by zinc in vivo. Consistently, the retarded fat body cell dissociation caused by Mmp1 or Mmp2 RNAi could be regulated by modulating the expression of foi. Further, by using Drosophila models of malignant tumour RafGOFscrib−/− and RasV12lgl−/−, we showed that the tumour growth, invasion and migration could be markedly inhibited by foi knockdown. These findings demonstrate a close connection between zinc levels and cell dissociation in vivo, and also suggest that manipulation of zinc levels may provide a novel therapeutic strategy for cancer.
CHPF promotes gastric cancer tumorigenesis through the activation of E2F1
Authors: Lin Xiaolin , Han Ting , Xia Qing , Cui Jiujie , Zhuo Meng , Liang Yiyi , Su Wenyu , Wang Lisha , Wang Liwei , Liu Zebing , Xiao Xiuying
Published: September 2021

Chondroitin polymerizing factor (CHPF) is an important glycosyltransferase involved in the biosynthesis of chondroitin sulfate. However, the relationship between CHPF and gastric cancer has not been fully investigated. CHPF expression in gastric cancer tissues was detected by immunohistochemistry and correlated with gastric cancer patient prognosis. Cultured gastric cancer cells and human gastric epithelial cell line GES1 were used to investigate the effects of shCHPF and shE2F1 on the development and progression of gastric cancer by MTT, western blotting, flow cytometry analysis of cell apoptosis, colony formation, transwell and gastric cancer xenograft mouse models, in vitro and in vivo. In gastric cancer tissues, CHPF was found to be significantly upregulated, and its expression correlated with tumor infiltration and advanced tumor stage and shorter patient survival in gastric cancer. CHPF may promote gastric cancer development by regulating cell proliferation, colony formation, cell apoptosis and cell migration, while knockdown induced the opposite effects. Moreover, the results from in vivo experiments demonstrated that tumor growth was suppressed by CHPF knockdown. Additionally, E2F1 was identified as a potential downstream target of CHPF in the regulation of gastric cancer, and its knockdown decreased the CHPF-induced promotion of gastric cancer. Mechanistic study revealed that CHPF may regulate E2F1 through affecting UBE2T-mediated E2F1 ubiquitination. This study showed, for the first time, that CHPF is a potential prognostic indicator and tumor promoter in gastric cancer whose function is likely carried out through the regulation of E2F1.
Negative regulation of TGFβ-induced apoptosis by RAC1B enhances intestinal tumourigenesis
Authors: Gudiño Victoria , Cammareri Patrizia , Billard Caroline V. , Myant Kevin B.
Published: September 2021

RAC1B is a tumour-related alternative splice isoform of the small GTPase RAC1, found overexpressed in a large number of tumour types. Building evidence suggests it promotes tumour progression but compelling in vivo evidence, demonstrating a role in driving tumour invasion, is currently lacking. In the present study, we have overexpressed RAC1B in a colorectal cancer mouse model with potential invasive properties. Interestingly, RAC1B overexpression did not trigger tumour invasion, rather it led to an acceleration of tumour initiation and reduced mouse survival. By modelling early stages of adenoma initiation we observed a reduced apoptotic rate in RAC1B overexpressing tumours, suggesting protection from apoptosis as a mediator of this phenotype. RAC1B overexpressing tumours displayed attenuated TGFβ signalling and functional analysis in ex vivo organoid cultures demonstrated that RAC1B negatively modulates TGFβ signalling and confers resistance to TGFβ-driven cell death. This work defines a novel mechanism by which early adenoma cells can overcome the cytostatic and cytotoxic effects of TGFβ signalling and characterises a new oncogenic function of RAC1B in vivo.
An international comparison of age and sex dependency of COVID-19 deaths in 2020: a descriptive analysis
Authors: Bauer Peter , Brugger Jonas , König Franz , Posch Martin
Published: September 2021

The number of reported coronavirus disease (COVID-19) deaths per 100,000 persons observed so far in 2020 is described in 15 European countries and the USA as dependent on age groups and sex. It is compared with the corresponding historic all-cause mortality per year depending on age and sex observed in these countries. Some common features exist although substantial differences in age and sex dependency of COVID-19 mortality were noted between countries. An exponential increase with age is a good model to describe and analyze both COVID-19 and all-cause mortality above 40 years old, where almost all COVID-19 deaths occur. Moreover, age dependency is stronger for COVID-19 mortality than for all-cause mortality, and males have an excess risk compared with women, which is less pronounced in the higher age groups. Additionally, concerning calendar time, differences in the age and sex dependency between countries were noted with the common tendency that male excess risk for COVID-19 mortality was smaller in the second half of the year.
Weekly Paclitaxel given concurrently with Durvalumab has a favorable safety profile in triple-negative metastatic breast cancer
Authors: Ghebeh Hazem , Al-Sayed Adher , Eiada Riham , Cabangon Leilani , Ajarim Dahish , Suleman Kausar , Tulbah Asma , Al-Tweigeri Taher
Published: September 2021

Therapeutic anti-PD-L1 antibodies are safe as a monotherapy, albeit with minimal efficacy in triple-negative breast cancer (TNBC). This trial aimed to test the safety and efficacy of Durvalumab and Paclitaxel in metastatic TNBC. In this open-label, one-arm trial, five cycles of weekly paclitaxel were delivered intravenously (IV) concurrent with Durvalumab that was given IV every 2 weeks. The combination was preceded by one cycle of paclitaxel alone, for immunological priming, followed by Durvalumab solo until disease progression or unacceptable toxicity. Between 2017 and 2019, 14 patients received at least one cycle of the combination therapy. The therapy was safe with no-dose limiting toxicity, except one case of skin lesions. Adverse events (AEs) were reported in 71% of patients, and there was no death due to the combination therapy. Regardless of grade, the most common AEs were headache and peripheral neuropathy, as each happened in four patients (29%), followed by fatigue and skin rash in three patients (21%) each. Grade 3/4 AEs were experienced by three patients (21%), with the most common being headache and anemia, which happened in two patients (14%). The confirmed objective response rate (ORR) was observed in five patients with a median duration of 10.0 months. Median Progression-free survival (PFS) and overall survival (OS) were 5 and 20.7 months, respectively. The combination of Durvalumab and Paclitaxel is safe, leaving room for additional agents. This is the first report on the combination of Durvalumab and Paclitaxel in the treatment of TNBC (NCT02628132).
Cone beam CT optimisation for detection of vertical root fracture with metal in the field of view or the exomass
Authors: Candemil Amanda P. , Salmon Benjamin , Vasconcelos Karla F. , Oenning Anne C. , Jacobs Reinhilde , Freitas Deborah Q. , Haiter-Neto Francisco , Mangione Francesca , Oliveira Matheus L.
Published: September 2021

Dose optimisation has been revisited in the literature due to the frequent use of cone beam computed tomography (CBCT). Although the reduction of the field-of-view (FOV) size has shown to be an effective strategy, this indirectly increases the negative effect from the exomass. The aim of this study was to evaluate the diagnostic accuracy of an optimised CBCT protocol in the detection of simulated vertical root fracture (VRF) in the presence of metal in the exomass and/or inside the FOV. Twenty teeth were endodontically instrumented and VRF was induced in half of them. All teeth were individually placed in a human mandible covered with a soft tissue equivalent material, metallic materials were placed at different dispositions in the exomass and/or endomass, and CBCT scans were obtained at two dose protocols: standard and optimised. Five radiologists evaluated the images and indicated the presence of VRF using a 5-point scale. Area under the ROC curve (AUC), sensitivity, and specificity were calculated and compared using ANOVA (α = 0.05). Overall, AUC, sensitivity, and specificity did not differ significantly (p > 0.05) between the dose protocols. In conclusion, optimised dose protocols should be considered in the detection of simulated VRF irrespective of the occurrence of artefacts from metallic materials in the exomass and/or inside the FOV.
Comparative transcriptome analysis revealed omnivorous adaptation of the small intestine of Melinae
Authors: Wang Lidong , Yang Xiufeng , Zhou Shengyang , Lyu Tianshu , Shi Lupeng , Dong Yuehuan , Zhang Honghai
Published: September 2021

As the main digestive organ, the small intestine plays a vital role in the digestion of animals. At present, most of the research on animal feeding habits focuses on carnivores and herbivores. However, the mechanism of feeding and digestion in omnivores remains unclear. This study aims to reveal the molecular basis of the omnivorous adaptive evolution of Melinae by comparing the transcriptome of the small intestines of Asian Badgers (Meles leucurus) and Northern Hog Badgers (Arctonyx albogularis). We obtained high-quality small intestinal transcriptome data from these two species. Key genes and signalling pathways were analysed through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and other databases. Research has mainly found that orthologous genes related to six enzymes have undergone adaptive evolution. In addition, the study also found three digestion-related pathways (cGMP-PKG, cAMP, and Hippo). They are related to the digestion and absorption of nutrients, the secretion of intestinal fluids, and the transport of food through the small intestine, which may help omnivorous animals adapt to an omnivorous diet. Our study provides insight into the adaptation of Melinae to omnivores and affords a valuable transcriptome resource for future research.
Prevalence of peripheral neuropathy defined by monofilament insensitivity in middle-aged and older adults in two US cohorts
Authors: Hicks Caitlin W. , Wang Dan , Windham B. Gwen , Matsushita Kunihiro , Selvin Elizabeth
Published: September 2021

Peripheral neuropathy is associated with substantial morbidity, but risk factors other than diabetes are largely uncharacterized. The aim of this study was to describe the prevalence and risk factors for peripheral neuropathy in adults with and without diabetes from two different population-based studies in the US. We performed a cross-sectional analysis of 5200 black and white participants from NHANES (1999–2004, age 40–85 years) and 3362 black and white participants from the ARIC Study (2016–2017, age 70–89 years) who underwent monofilament testing for peripheral neuropathy using a shared protocol. We used logistic regression to quantify age, sex, and race-adjusted risk factor associations for peripheral neuropathy among middle-aged (40–69 years) and older (≥ 70 years) adults. The age, sex, and race-adjusted prevalence of peripheral neuropathy (decreased sensation on monofilament testing) was 10.4% for middle-aged adults in NHANES, 26.8% for older adults in NHANES, and 39.2% for older adults in ARIC. Diabetes was an important risk factor, but more strongly associated with peripheral neuropathy in middle-aged (OR ~ 5 for long-standing diabetes) compared to older adults (ORs ~ 1.5–2). Male sex (ORs ~ 2), black race (ORs ~ 1.3–1.5), and greater height (ORs ~ 1.5–3) were robust risk factors for peripheral neuropathy. Other risk factors included body mass index, education, and peripheral artery disease. The burden of peripheral neuropathy defined by abnormal monofilament testing among older adults is substantial, even among adults without diabetes. Studies are needed to understand the etiology and prognosis of peripheral neuropathy in the absence of diabetes.
Coal–rock damage characteristics caused by blasting within a reverse fault and its resultant effects on coal and gas outburst
Authors: Gao Kui , Huang Ping , Liu Zegong , Liu Jian , Shu ChiMin , Qiao Guodong
Published: September 2021

In view of the coal and gas outburst accidents occur frequently caused by blasting in geological structural belt, in order to study the mechanical characteristics of coal rock in tectonic belt disturbance by blasting and blasting vibration effect influenced on the stability of surrounding rock, coal–rock damage and failure characteristics within a reverse fault caused by a blasting stress wave were investigated using numerical analyses and experiments. According to the experimental results, the causes of coal and gas outburst dynamic disasters within a reverse fault during blasting are analyzed. The outcomes indicated that the crushing circle created by the crack propagation near the blasting hole severely damaged the fault plane and floor rocks adjacent to the footwall of the reverse fault. Fractures also extended to the upper and lower coal seams of the reverse fault; this caused the surface of the coal seam to fall off and severe internal damage. According to theoretical analysis, the reflection of the blasting stress wave propagating to the reverse fault intensified the damage to coal and rock. Elastic strain energy accumulation within the reverse fault structural zone was accompanied by high-stress concentration. The reverse fault tectonic region was destroyed by blasting vibration. It increased gas pressure and caused a weak surface, which provided a channel for gas flow and a dynamic basis for the occurrence of coal and gas outburst. The research results have important theoretical value to reveal the mechanism of coal and gas outburst in tectonic belt induced by blasting.
Selectivity of weak intermolecular forces and precursor state of elementary oxidation reactions, a new insight on Ne* + N2 chemiionization
Authors: Falcinelli Stefano , Vecchiocattivi Franco , Pirani Fernando
Published: September 2021

This paper reports on the collision dynamics of N2 with metastable Ne* promoting chemiionizations, prototype of barrier-less oxidation reactions of great interest for fundamental and applied research. Extending guidelines presented in previous papers for the atom–atom case, an innovative treatment of the reaction stereodynamics involving molecules in a quantum state-to-state resolution conditions is proposed that emphasizes the role of structure and stability of the precursor that is here the reaction transition state. A critical test of such treatment, carried out exploiting a new formulation both of real and imaginary parts of the optical potential driving the reaction dynamics, is represented by the detailed-combined description of all relevant findings, provided by high resolution molecular beam scattering experiments carried out in our and other laboratories. The present analysis casts light on basic electronic rearrangements of such prototype oxidation reaction which are expected to be of fundamental interest for many other reactions involving open shell atoms and free radicals.
Usability of abattoir-acquired pig eyes for refractive excimer laser research
Authors: Topka Marius , Zhang Yao , Bock Antonia , Riedel Peter , Lörner Johannes , Hammer Alexander , Maier Eva , Paulsen Friedrich , Hammer Christian M.
Published: September 2021

The purpose of this study was to elucidate, under which conditions abattoir-acquired pig eyes are suitable for refractive excimer laser experiments. Porcine eyes from tunnel-scalded (n = 5) and tank-scalded (n = 10) pigs were compared to unscalded eyes (n = 5) and to eyes scalded in the laboratory (n = 5). The corneal epithelium was removed before an excimer laser was used to perform a − 8.0 D photoablation. Corneal thickness was measured by optical coherence topography before and after photoablation. The ablation depth was determined with a contour measuring station, the morphology of the ablated areas was characterized by scanning electron microscopy and white-light profilometry. The scalded eyes showed an increase in corneal swelling which gained statistical significance in tank-scalded eyes showing a wedge-shaped opaque stromal lesion in the nasal corneal quadrant. A measurable deterioration of photoablation was only found in tank-scalded eyes that exhibited the opaque lesion. Ablated area morphology was smooth and regular in the unscalded and tunnel-scalded eyes. The tank-scalded eyes showed conspicuous wrinkles. While unscalded eyes should always be preferred for excimer laser laboratory experiments, the data suggest that the use of tunnel-scalded eyes may also be acceptable and should be chosen over tank-scalded eyes.
Mechanical properties of bulk Sylgard 184 and its extension with silicone oil
Authors: Moučka R. , Sedlačík M. , Osička J. , Pata V.
Published: September 2021

Due to its simple curing and very good mechanical properties, Sylgard 184 belongs to the most widely and frequently used silicones in many industrial applications such as microfluidics and microengineering. On top of that its mechanical properties are further controllable through the curing temperature, which may vary from ambient temperature up to 200 °C; the lower the curing temperature the lower the mechanical properties (Johnston et al. in J Micromech Microeng 24:7, 2014. 10.1088/0960-1317/24/3/035017). However, certain specialised application may require even a softer binder than the low curing temperature allows for. In this study we show that this softening can be achieved with the addition of silicone oil into the Sylgard 184 system. To this end a series of Sylgard 184 samples with varying silicone oil concentrations were prepared and tested (tensile test, rotational rheometer) in order to determine how curing temperature and silicone oil content affect mechanical properties. Curing reaction of the polymer system was found to observe 2nd order kinetics in all cases, regardless the oil concentration used. The results suggest that within the tested concentration range the silicone oil addition can be used to soften commercial silicone Sylgard 184.
A comparison of head movements tests in force plate and accelerometer based posturography in patients with balance problems due to vestibular dysfunction
Authors: Janc Magdalena , Sliwinska-Kowalska Mariola , Jozefowicz-Korczynska Magdalena , Marciniak Pawel , Rosiak Oskar , Kotas Rafal , Szmytke Zuzanna , Grodecka Joanna , Zamyslowska-Szmytke Ewa
Published: September 2021

This study compares HS posturography on inertial sensors (MediPost) with force platform posturography in patients with unilateral vestibular dysfunction. The study group included 38 patients (age 50.6; SD 11.6) with unilateral vestibular weakness (UV) and 65 healthy volunteers (48.7; SD 11.5). HS tests were performed simultaneously on the force plate and with MediPost sensor attached at L4. Four conditions applied: eyes open/closed, firm/foam. The tests were performed twice, with the head moving at the frequency of 0.3 Hz (HS 0.3) and 0.6 Hz (HS 0.6). Mean sway velocity was significantly lower for MediPost than force plate in 4th condition both in UV and healthy group. For HS 0.3 the differences between devices were marginal; the highest sensitivity (87%) and specificity (95%) were in 4th condition. For HS 0.6 MediPost revealed lower sensitivity than force plate although the surface parameter improved results. MediPost IMU device and force platform posturography revealed a similar ability to differentiate between patients with balance problems in course of vestibular pathology and healthy participants, despite the differences observed between measuring methods. In some tests surface parameter may be more appropriate than sway velocity in improving MediPost sensitivity.
Viral S protein histochemistry reveals few potential SARS-CoV-2 entry sites in human ocular tissues
Authors: Martin Gottfried , Wolf Julian , Lapp Thabo , Agostini Hansjürgen T. , Schlunck Günther , Auw-Hädrich Claudia , Lange Clemens A. K.
Published: September 2021

Despite the reported low expression of the primary SARS-CoV-2 receptor ACE2 in distinct ocular tissues, some clinical evidence suggests that SARS-CoV-2 can infect the eye. In this study, we explored potential entry sites for SARS-CoV-2 by viral S protein histochemistry on various ocular tissues and compared the staining patterns with RNA and protein expression of TMPRSS2 and ACE2. Potential viral entry sites were investigated by histochemistry using tagged recombinant viral S protein on 52 ocular tissue samples including specimens of the cornea, conjunctiva, lid margin, lacrimal gland tissue, retina, choroid, and RPE. In addition, ACE2 and TMPRSS2 immunohistochemistry were performed on the same ocular tissue, each with distinct antibodies binding to different epitopes. Lung tissue samples were used as positive controls. Finally, bulk RNA sequencing (RNA-Seq) was used to determine the expression of ACE2 and its auxiliary factors in the tissues mentioned above. S protein histochemistry revealed a positive staining in lung tissue but absent staining in the cornea, the conjunctiva, eye lid samples, the lacrimal glands, the retina and the optic nerve which was supported by hardly any immunoreactivity for ACE2 and TMPRSS2 and scarce ACE2 and TMPRSS2 RNA expression. Negligible staining with antibodies targeting ACE2 or TMPRSS2 was seen in the main and accessory lacrimal glands. In contrast, ocular staining (S protein, ACE2, TMPRSS2) was distinctly present in pigmented cells of the RPE and choroid, as well as in the ciliary body and the iris stroma. S protein histochemistry revealed hardly any SARS-CoV-2 entry sites in all ocular tissues examined. Similarly, no significant ACE2 or TMPRSS2 expression was found in extra- and intraocular tissue. While this study suggest a rather low risk of ocular infection with SARS-CoV-2, it should be noted, that potential viral entry sites may increase in response to inflammation or in certain disease states.
Trimetazidine and exercise provide comparable improvements to high fat diet-induced muscle dysfunction through enhancement of mitochondrial quality control
Authors: Zhang Wenliang , You Baiyang , Qi Dake , Qiu Ling , Ripley-Gonzalez Jeffrey W. , Zheng Fan , Fu Siqian , Li Cui , Dun Yaoshan , Liu Suixin
Published: September 2021

Obesity induces skeletal muscle dysfunction. The pathogenesis of which appears to substantially involve mitochondrial dysfunction, arising from impaired quality control. Exercise is a major therapeutic strategy against muscle dysfunction. Trimetazidine, a partial inhibitor of lipid oxidation, has been proposed as a metabolic modulator for several cardiovascular pathologies. However, the effects of Trimetazidine on regulating skeletal muscle function are largely unknown. Our present study used cell culture and obese mice models to test a novel hypothesis that Trimetazidine could improve muscle atrophy with similar results to exercise. In C2C12 cells, high palmitic acid-induced atrophy and mitochondrial dysfunction, which could be reversed by the treatment of Trimetazidine. In our animal models, with high-fat diet-induced obesity associated with skeletal muscle atrophy, Trimetazidine prevented muscle dysfunction, corrected metabolic abnormalities, and improved mitochondrial quality control and mitochondrial functions similarly to exercise. Thus, our study suggests that Trimetazidine successfully mimics exercise to enhance mitochondrial quality control leading to improved high-fat diet-induced muscle dysfunction.
Changes in energy metabolism and respiration in different tracheal narrowing in rats
Authors: Segev Yael , Nujedat Haiat , Arazi Eden , Assadi Mohammad H. , Tarasiuk Ariel
Published: September 2021

Why obstructive sleep apnea (OSA) treatment does not completely restore healthy metabolic physiology is unclear. In rats, the need for respiratory homeostasis maintenance following airway obstruction (AO) is associated with a loss of thermoregulation and abnormal metabolic physiology that persists following successful obstruction removal. Here, we explored the effect of two different types of tracheal narrowing, i.e., AO and mild airway obstruction (mAO), and its removal on respiratory homeostasis and metabolic physiology. We show that after ten weeks, mAO vs. AO consumes sufficient energy that is required to maintain respiratory homeostasis and thermoregulation. Obstruction removal was associated with largely irreversible increased feeding associated with elevated serum ghrelin, hypothalamic growth hormone secretagogue receptor 1a, and a phosphorylated Akt/Akt ratio, despite normalization of breathing and energy requirements. Our study supports the need for lifestyle eating behavior management, in addition to endocrine support, in order to attain healthy metabolic physiology in OSA patients.
Fabrication and characterization of β-carotene emulsions stabilized by soy oleosin and lecithin mixtures with a composition mimicking natural soy oleosomes
Authors: Ding Jian , Dong Yabo , Huang Guo , Zhang Yan , Jiang Lianzhou , Sui Xiaonan
Published: September 2021

Natural soy oleosomes are known to have a remarkable stability, given the advantage of their sophisticated membrane.
Porphyrin bearing phenothiazine pincers as hosts for fullerene binding via concave–convex complementarity: synthesis and complexation study
Authors: Jain Kanika , Duvva Naresh , Roy Tapta Kanchan , Giribabu Lingamallu , Chitta Raghu
Published: September 2021

Free base porphyrin hosts, m-(PTZ)4-H2P and p-(PTZ)4-H2P, tethered with four phenothiazine moieties at the meso-position via a flexible ethoxy phenyl linker were synthesized and used for the selective complexation of fullerenes, C60 and C70.
pH sensing and bioimaging using green synthesized carbon dots from black fungus
Authors: Qin Jing , Gao Xu , Chen Qinqin , Liu Huiling , Liu Shuqi , Hou Juan , Sun Tiedong
Published: September 2021

Carbon dots derived from black fungus were prepared and applied as a pH sensor for real water samples.
Synthesis of cyanooxovanadate and cyanosilylation of ketones
Authors: Kikukawa Yuji , Kawabata Hiroko , Hayashi Yoshihito
Published: September 2021

Two key catalytic vanadium species involved in cyanosilylation of ketones were observed by in situ measurement.
Lithium-ion transport in inorganic active fillers used in PEO-based composite solid electrolyte sheets
Authors: Song Young-Woong , Heo Kookjin , Lee Jongkwan , Hwang Dahee , Kim Min-Young , Kim Su-Jin , Kim Jaekook , Lim Jinsub
Published: September 2021

A lithium ion transport mechanism according to particle size was demonstrated in a PEO-based composite solid electrolyte using inorganic active fillers.