bluuebunny/crossref_metadata_2025 huggingface dataset:
A Large-scale Static-dynamic Model Test System for Stability Study of Tunnel under Static-dynamic Load
Authors: Li Shucai , Zhang Bing , Wang Hanpeng , Wang Wei , Xu Fei , Li Qingchuan
Published: April 2021

In order to study the stability of tunnels under static-dynamic load, a new large-scale static-dynamic model test system was developed. The system is composed of a static loading unit, a dynamic loading unit, a data acquisition unit and a test bench, which are specially designed to overcome the technical problems of large-scale static-dynamic model test, such as dynamic loading and control, high-rate strain measurement and easy operation. The system uses a model of 3600 × 3600 × 2500 mm in size to study a larger load disturbance area than static tests. It can accurately apply three-dimensional gradient static stress and dynamic load with adjustable amplitude (or magnitude), frequency and waveform to simulate the true geo-stress field and disturbance field, and accurately and rapidly collect displacement, stress, strain, velocity, acceleration and other important parameters of the model. In addition, it is convenient to adjust the scale of the model, remove and retain the test model. The system was used to carry out a static load model test and a static-dynamic load model test with a tunnel as a prototype, and its reliability and accuracy were verified.
Sand Supplementation to Eutrophic Sediments Improves the Growth and Survival of Seagrass Thalassia Hemprichii: Implication for Seagrass Restoration and Management
Authors: Jiang Zhijian , Liu Songlin , Cui Lijun , He Jialu , Fang Yang , Premarathne Chanaka , Li Linglan , Wu Yunchao , Huang Xiaoping , Kumar Manoj
Published: April 2021

Aims Sediment composition is highly crucial for seagrass growth and survival. Eutrophication has been suggested a major cause of seagrass decline globally. We investigated the effects of beach sand supplementation to natural sediments under eutrophic condition on the growth and survival of tropical dominant seagrass Thalassia hemprichii. Methods We cultured seagrass T. hemprichii under the controlled laboratory conditions in three sediment types by combining different ratio of in-situ eutrophic sediment and coarse beach sand. We examined the effect of beach sand mixing to natural eutrophic sediments on the growth of seagrass using photobiology, metabolomics and isotope labeling approaches. Results Seagrass grown in eutrophic sediments mixed with sand exhibited significantly higher photosynthetic activity with high relative maximum electron transport rate and minimum saturating irradiance. Simultaneously, considerably greater belowground amino acid and flavonoid concentrations were observed to counteract anoxic stress in eutrophic sediment without mixing sand. This led to more positive belowground stable sulfur isotope in the eutrophic sediment with lower Eh. Conclusions These results indicated coarse beach sand indirectly enhanced photosynthesis and growth for T. hemprichii by reducing sulfide intrusion with lower concentrations of amino acid and flavonoid. This could possibly explain why T. hemprichii often grow better in the coarse sand substrate. Therefore, it is imperative to consider adding sand soil in the sediments to improve the growth condition for seagrass and restoring the seagrass shoots during transplantation in eutrophicated ecosystem.
Healthcare Professionals’ Views on the Most Important Outcomes for Non- Infectious Uveitis of the Posterior Segment: A Qualitative Study
Authors: Tallouzi Mohammad O. , Moore David J. , Bucknall Nicholas , Murray Philip. I , Calvert Melanie J. , Denniston Alastair K. , Mathers Jonathan M.
Published: April 2021

BackgroundUveitis refers to a range of conditions that result in intraocular inflammation. Non-infectious Intermediate, posterior and panuveitis are the most serious forms of uveitis grouped as Non-Infectious Uveitis affecting the Posterior Segment (NIU-PS). To evaluate new and existing treatments trialists and clinicians aim to report certain measurements known as outcomes. The aim of this study was to understand the perspectives of healthcare professionals on what outcomes they thought important for adult patients with NIU-PS and their carers.MethodsTwelve semi-structured telephone interviews were undertaken to understand the perspectives of healthcare professionals - ophthalmologists (n=5), nurse practitioners (n=3) and health policy-makers/commissioners (n=4) on outcomes for NIU-PS. Interviews were audio recorded, transcribed and thematically analysed and a domain framework developed with focus group data from patients and carers applied to the data. Findings were compared with the views of patients and carers and outcomes abstracted from a previously published systematic review.ResultsEleven core domains were identified as important to healthcare professionals, which is broadly comparable to those previously identified by patients and carers: (1) visual function, (2) symptoms, (3) functional ability, (4) impact on relationships, (5) financial impact, (6) psychological morbidity and emotional well-being (7) psychosocial adjustment to uveitis, (8) doctor / patient / interprofessional relationships and access to health care, (9) treatment burden, (10) treatment side effects, (11) disease control. Healthcare professionals placed more emphasis on some items and identified additional outcomes, particularly in the disease control domain.ConclusionAlthough healthcare professionals recognise all of the same domains as patients/carers these findings are not yet implemented in practice or clinical research. These findings provide the basis to reflect on the nature of those outcomes at present used in uveitis clinical practice and clinical trials with those utilised in the development process of a core outcome set for NIU-PS.
Comprehensive Comparison Between Geriatric and Nongeriatric Patients With Trauma
Authors: Lin Pei-Chen , Wu Nan-Chun , Su Hsiu-Chen , Hsu Chien-Chin , Chen Kuo-Tai
Published: April 2021

Purpose:The incidence of geriatric trauma is increasing due to the growing elderly population. Healthcare providers require a global perspective to differentiate critical factors that might alter patients’ prognosis.Methods: We retrospectively reviewed all adult patients admitted to a trauma center during a 4-year period. We identified 655 adult trauma patients aged from 18 to 64 (nongeriatric group) and 273 trauma patients ≥65 years (geriatric group). Clinical data were collected and compared between the two groups. Results:The geriatric group had a higher incidence of trauma and higher Injury Severity Scores than did the nongeriatric group. Fewer geriatric patients underwent surgical treatment (all patients: geriatric vs. nongeriatric: 65.9% vs. 70.7%; patients with severe trauma: geriatric vs. nongeriatric: 27.6% vs. 44.5%). Regarding prognosis, the geriatric group exhibited higher mortality rate and less need for long-term care (geriatric vs. nongeriatric: mortality: 5.5% vs. 1.8%; long-term care: 2.2% vs. 5.0%). Conclusion:We observed that geriatric patients had higher trauma incidence and higher trauma mortality rate. Aging is a definite predictor of poor outcomes for trauma patients. Limited physiological reserves and preference for less aggressive treatment might be the main reasons for poor outcomes in elderly individuals.
High-Fidelity Control of Spin Ensemble Dynamics via Artificial Intelligence: From Quantum Computing to Imaging
Authors: Manu V.S. , Pavuluri KowsalyaDevi , Mullen Michael , Garwood Michael , Veglia Gianluigi
Published: April 2021

High-fidelity control of spin ensemble dynamics is essential to many fields, spanning from quantum computing to optical, coherent, and nuclear magnetic resonance (NMR) spectroscopy and imaging (MRI). However, attaining robust and high-fidelity quantum spin operations remains an unmet challenge. Using a combination of an evolutionary algorithm and artificial intelligence, we designed time-optimal, radio frequency (RF) pulses with tunable spatial or temporal field inhomogeneity compensation and fidelity for unitary operations up to 0.9999. As a benchmark, we constructed a spin entanglement operator and a programmable quantum state creator for a weakly-coupled two-spin-1/2 system. We achieved high-fidelity transformations under multiple inhomogeneity sources. The newly designed RF pulses are more robust and less prone to imperfection than the commonly used shapes for basic liquid-state NMR experiments and reduce RF artifacts in MRI. This new strategy will enable the design of efficient quantum computing opera-tors as well as new spectroscopic and imaging techniques.
Spike-Directed Vaccination Elicits Robust Spike-Specific T cell Responses Including to Mutant Strains
Authors: Stanojevic Maja , Geiger Ashley , Ostermeier Brita , Sohai Danielle , Lazarski Christopher , Lang Haili , Jensen-Wachspress Mariah , Webber Kathleen , Burbelo Peter , Cohen Jeffrey , Keller Michael , Bollard Catherine , Cruz Conrad Russell
Published: April 2021

While most studies describing COVID-19 vaccine responses have focused on antibodies, there is increasing evidence that T cells play a critical role. Here we evaluated T cell responses in seronegative donors before and after vaccination to define responses to SARS-CoV-2 reference strain, as well as to mutations in the variant strains B.1.1.7 and B.1.351. We observed enhanced T cell responses to reference and variant Spike strains post vaccination.
Pharmacokinetics and Diuretic Effect of Furosemide after Single Intravenous, Oral Tablet, and Newly Developed Oral Disintegrating Film Administration in Healthy Beagle Dogs
Authors: Koh Suk-kyu , Jeong Jong-Woo , Choi Seo-In , Kim Rae-Man , Koo Tae-Sung , Cho Kwang-Hyung , Seo Kyoung-Won
Published: April 2021

Background: Furosemide, a diuretic that acts on the loop of Henle, is commonly used to treat congestive heart failure in veterinary medicine. Some owners have difficulty in administering oral tablet medication to animal patients, which leads to noncompliance, especially during long-term administration. The oral disintegrating film (ODF) has the advantages of easy administration via a non-invasive route, rapid dissolution, and low suffocating risk. The objective of this study was to research the pharmacokinetic and pharmacodynamics (PK/PD) profiles of furosemide after intravenous (IV), orally uncoated tablet (OUT), and newly developed ODF administration in healthy beagle dogs. In this study, a furosemide-loaded ODF (FS-ODF) formulation was developed and five beagle dogs were administered a single dose (2 mg/kg) of furosemide via each route using a cross-over design.Results: The most suitable film-forming agent was sodium alginate; thus, this was used to develop an ODF for easy drug administration. No significant differences were detected in the PK profiles between OUT and FS-ODF. The maximum plasma concentration of furosemide was higher and the elimination half-life and time at maximum concentration were slightly lower after FS-ODF administration than after OUT administration. In the blood profiles, the concentration of total protein was significantly increased compared to the baseline (0 h), whereas no significant difference was detected in the concentration of creatinine and hematocrit compared to the baseline. FS-ODF resulted in a similar hourly urinary output to OUT during the initial 2 h after administration. The urine specific gravity was significantly decreased compared to the baseline in each group. The peak times of urine electrolyte (sodium and chloride) excretion per hour were 1 h (IV), 2 h (OUT), and 2 h (FS-ODF). Conclusions: These results suggest that the PK/PD of furosemide after administration of newly developed FS-ODF are similar to those of OUT in healthy dogs. Therefore, the ODF formulation has the benefits of ease and convenience, which would be helpful to owners of companion animals, such as small dogs (<10 kg) or cats, for the management of congestive heart failure.
Impact of Rainfall Spatiotemporal Variability and Model Structures on Flood Simulation in Semi-Arid Regions
Authors: Liu Yuhuan , Li Zhijia , Liu Zhiyu , Luo Yun
Published: April 2021

The spatiotemporal heterogeneity in precipitation and underlying surfaces and hybrid runoff generation mechanism make hydrological modelling and forecasting in semi-arid regions becoming a challenge work. Therefore, to provide a reference for the development of hydrological models in such regions, two nested hydrological experimental watersheds in semi-arid regions were selected for attribution analysis. Based on the concept of large-sample hydrology, Large-scale numerical simulation experiments were performed by constructing different spatial and temporal scale rainfall schemes and combining three hydrological models with different runoff generation mechanisms. Finally, the influences of the time step, station density, and model structure on the flood simulations in semi-arid regions were evaluated. The spatial interpolation technique was used simultaneously to describe the high-dimensional complicated nonlinear relationships between the influencing factors and simulation results. The results show the following: ① the flood simulation accuracy was more sensitive to the time step than the spatial station density of the rainfall schemes and was highly dependent on the time step of the original observation data; and ② compared with the accuracy of the rainfall schemes, the model structure plays a dominant role in flood simulation accuracy. Thus, the hybrid model has significant potential for flood forecasting in semi-arid regions by combining different runoff generation mechanisms. ③ The spatial interpolation technique based on the k-nearest neighbour algorithm can construct a high-dimensional distribution of the influencing factors, yield high model simulation accuracy, and describe the complicated relationships among the time step, station density, model structure, and simulations.
Postoperative Concurrent Chemoradiotherapy Plus Apatinib for First-line Treatment of Patients with Malignant Glioma: From One Single Research Institute
Authors: FU Zhichao , Li Xiaoyan , YING Wenmin , CAI lvjuan , LI Guo , LUO Huachun , WANG Xinpeng , WU Mengjing , FENG Jing
Published: April 2021

Objective: To explore the effectiveness and safety of apatinib in patients with malignant glioma. Methods: This is a retrospective case-control study in a single center. Patients with new postoperative pathological diagnosis of malignant glioma (WHO Ⅲ~Ⅳ) were selected. Enrolled patients received concurrent chemoradiotherapy (60Gy/30f/6w; TMZ75mg/m2,po,d1-d42)combined with or without apatinib (250mg, po, d1-d42,qd), then maintain 6 cycles(28 days a cycle)of TMZ chemotherapy(200mg/m2, d1-d5) .The primary endpoints were progression free survival (PFS) and the grade of peritumoral brain edema (PTBE) evaluated by edema index(EI). The secondary endpoint was overall survival(OS). Hazard ratios of PFS and OS were compared between trials in a Cox proportional hazards model.Results: 48 patients (24 in apatinib group and 24 in control group) were enrolled in this study. The results elucidated that the mPFS of the apatinib group was longer than control group, but the difference was not statistically significant(9.63 vs. 7.33 months; P=0.073).As for mOS, the results of two groups were almost similar.(15.47 vs. 14.70 months, P=0.612). Cox multivariate regression model revealed that Apatinib was not a prognostic factor for PFS and OS (P>0.05). Multivariate analysis showed that tumor grade was an important risk factor for PFS and OS.The grade of PTBE was improved in 15 of 23 patients (65.2%) in apatinib group versus 6 of 24 (25%) in control group. There was no grade 3 or 4 adverse events and serious adverse events.Conclusion: Apatinib group can improve mPFS by 2.3 months in patients with malignant glioma,but there was no statistical significance (P>0.05).The results also indicated that apatinib conferred a significant beneficial effect on PTBE improvement. All occurred adverse reactions were moderate and controllable.
Growth and Survival of Satellite Glial Cells in Different Culture Supplementations
Authors: Wei Na , Liu Ya-Ping , Wang Rui-Rui , Wang Xiao-Liang , Yang Yan , He Ting , Wang Huan , Yu Yao-Qing
Published: April 2021

Background: In dorsal root ganglion (DRG), satellite glial cells (SGCs) tightly surrounded neurons and modulated microenvironment and sensory transmission. However, the biological properties of primary SGCs in culture were not fully understood. In the present study, we provided a method to harvest abundant and high-purity SGCs from neonatal rats. Three supplementations containing Dulbecco’s Modified Eagle Medium (DMEM)/F12, DMEM high glucose (HG) and Neurobasal-A (NB) were used to evaluate SGCs growth and survival in culture. Results: CCK-8 proliferation assay showed the increased proliferation in DMEM/F12 and DMEM/HG, but not in NB medium. NB medium caused cell death indicated by Bax, AnnexinV and PI staining. Glutamine was the major nutrition source for SGCs in culture and its exogenous application improved the poor proliferation and severe cell death in NB medium. SGCs markers GS and GFAP were similar in three supplementations and intensively expressed in culture. Differently, GS but not GFAP was remarkable in the intact DRG under normal condition. Conclusions: These results suggested that SGCs growth in culture depended on time and culture supplementation and DMEM/F12 medium was recommended to get high-purity SGCs. Glutamine was the major nutrition and the key molecule to maintain cell growth and survival in culture. Our study shed a new light on understanding the biological property and modulation of glial cells in the peripheral sensory ganglia.
Impact of geomorphometric parameters on landslide occurrence and distribution in Yamuna River Basin, North-Western Himalaya, India
Authors: Shankar Ravi , Satyam Gyan Prakash , Singh Prakash Kumar , Paswan Ranjeet Kumar
Published: April 2021

Landscape evolution is a dynamic process controlled by several geomorphic parameters along with geology, tectonics and climatic condition of the area. The Himalayan mountain belt is highly geodynamic with immature topography which offer one of the best places to study the impact of geomorphotectonic characteristics on the occurrence and distribution of landslides along with tectonically modified geomorphic features. The morphotectonic study of the drainage basin is extensively utilized to analyze the landscape evolution in the study area along with impact of neotectonic activity in landscape evolution. The study shows that the Yamuna River, originating from the mighty Himalayas, flows downslope by adjusting its course due to ongoing tectonic activities, underlying structures, and climatic factors. Active tectonics play important role in modifying the landscape and impacting the occurrence and distribution of landslides. The characteristics of rainfall induced landslides have been studied in relation to morphotectonic parameters. The analysis shows that the probability density of landslides was highest in the range of 25o-30o and that landslide size increased up to 20o-25o slope angle, decreasing on further increase in slope angle. The study also shows that slope angle merely controls number of landslides rather than size of the landslides. Landslides were mostly restricted to South facing slopes. About 91% of the landslide occur in the drainage density range of 1.2 to 2.1 km/km2 while landslides show very low occurrence in either lower (< 1.2) or higher (> 2.1) drainage density. The present analysis can be very helpful in landslide risk reduction and landslide hazard zonation and probably to plan critical locations for installation of early warning signals.
Whole Exome Sequencing in Patients With Ossification of the Spinal Ligaments
Authors: Zhai Jiliang , Li Jiahao , Zhao Yu , Wei Xing
Published: April 2021

Background
The clinical presentations of ossification of spinal ligament (OSL) are majorly myelopathy and/or radiculopathy, with serious neurological pathology resulting in paralysis of extremities and disturbances of motility (motor function) lowering the quality of life. Currently, studies find that missense single nucleotide polymorphisms (SNPs) play a vital role in the susceptibility for complex diseases.
Methods
In the present study, we used whole exome sequencing (WES) method to explore variants in exomes and found out novel potential responsible genes for OSL. Genomic DNA was extracted from ligamentum flavum collected from 5 OSL patients and 5 control patients. Whole-exome sequencing was then performed, while variation forecasts and conservation examination were subsequently assessed.
Results
8 common SNP variants were exhibited in all 5 subjects of OSL, presented in the genes of GRHL2, CUL3, WHAMM, IL17RD, POM121L12, SLC26A8 and PTPN23. After screened with numbers of samples and additional screenings with deleterious Polyphen2_HDIV_score, Polyphen2_HVAR_score and SIFT, 4 common SNP variants were displayed in 4 subjects of OSL, presented in the genes of KRT84, KIF1B, NRAP and CETN1. 7 common SNP variants were existed in 3 subjects of OSL, presented in the genes of CCT3, ANLN, ESRRB, SRBD1, ODF3L1, BRAT1 and RBP3.
Conclusion
We found out novel potential variants in several genes, especially WHAMM, KIF1B and ESRRB, which represented potentially pathogenic mutations in patients with OSL.
The spatiotemporal evolution of cities from the ancient state period to the kingdom period in the Central Plains region, China
Authors: Yan Lijie , Yang Ruixia , Lu Peng , Teng Fei , Wang Xia , Zhang Li , Chen Panpan , Li Xiang , Guo Lanbo , Zhao Dong
Published: April 2021

The Central Plains region in China has been an important area for human settlement since ancient times. As the only continuous civilization over thousands of years in the world, the Central Plains Civilization is the origin of the Chinese nation. The number, size, and distribution of cities have changed greatly from the ancient state period (i.e. the Yangshao and Longshan periods) to the kingdom period (i.e. the Xia and Shang Dynasties), which reflects the evolution of settlement and social organization. In this study, GIS technology was used to establish the city spatial database for the periods that witnessed the transition from ancient states to the kingdom, including the Yangshao period, the Longshan period, and the Xia and Shang Dynasties. Moreover, the nearest neighbor distance analysis and the gravity center analysis were implemented to explore the possible factors that were considered in the city site selection, including altitude and distances to nearest rivers. Furthermore, efforts were made to investigate the spatiotemporal evolution of the shape, size, agglomeration, and varying gravity center of cities as well as the spatiotemporal evolution of moats. The results show that: (1) Most city sites were distributed in areas with altitudes of < 500 m above sea level and distances of less than 3 km away from rivers during all three periods. (2) From the Yangshao period to the Xia and Shang Dynasties, the shape of the city gradually changed from circular to square, and the type of moats changed from trenches in the Yangshao period to city walls in the Longshan period and no walls in Xia and Shang Dynasties. (3) The size and grade of the 18 cities in the Yangshao period shared high similarity, with an average area of 20 hectares. In comparison, the sizes of 24 cities in the Longshan period increased significantly, with an average of 39 hectares. During the Xia and Shang Dynasties, there were 22 cities with an average size of 340 hectares, and the grade of sizes became obvious, marking the entrance into the centralized kingdom period. (4) Cities were scattered in the decentralized pattern during the ancient state periods (i.e. Yangshao and Longshan periods), whereas they became agglomerative in the kingdom period (i.e. Xia and Shang Dynasties). This reflects the evolution of the spatial scopes and social organizational forms. (5) From ancient states to the kingdom, the city center moved around Songshan Mountain from the northwest to the southeast and again to the northeast.
Effects of Linear and Non-periodized Combined Training on Health-related Quality of Life of Adults With Obesity: a Randomized Clinical Trial
Authors: Tozetto Willen Remon , Leonel Larissa dos Santos , Turnes Tiago , Duca Giovani Firpo Del
Published: April 2021

Background: Health-related quality of life (HRQoL) is impaired by obesity and can be improved by combined training, even the effects of training periodization on HRQoL are not clear. The study aimed to compare combined training with the non-periodized and the linear periodization on HRQoL of obese adults.Methods: This is a blinded, controlled clinical trial involving adults with obesity (BMI ≥ 30 kg/m²), randomized into control (CG), non-periodized (NG) and linear periodization (PG) group. Three times a week for 16 weeks, NG and PG performed combined training for 60 minutes. The NG performed aerobic exercises between 50-59% of the reserve heart rate (HRres) and strength at 10-12 maximum repetitions (MR). The PG started with 40-49% of HRres and 12-14 MRs and progressively increased the intensity (50-59% and 10-12 MRs; 60-69% and 8-10 MRs) with total volume equalized with NG. HRQoL was investigated through the SF-36 questionnaire, according to its components and domains. In statistics, Generalized Estimation Equations and mean differences (∆) were used.Results: Of the 69 participants (23 in each group), 36 completed the intervention (CG=13, NG=9 and PG=14). A significant difference was observed in time of physical function, with superiority in training groups (CG:∆=1.2 vs NG and PG, respectively: ∆=10.0). The mental component and mental health domain showed a significant difference for NG (∆=30.2 and ∆=23.1, respectively).Conclusion: The combined training was able to bring benefits to the physical functioning of adults with obesity and, specifically, the non-periodized training improved mental health indicators effectively.Name of the registry: Effects of different types of Aerobic Exercise and Weight Training protocols combined on adult health indicators with Obesity.Trial registration number: RBR-3c7rt3Date of registration: 07/02/2018URL of trial registry record: https://ensaiosclinicos.gov.br/rg/RBR-3c7rt3
Downregulation of the long non-coding RNA MEG3 promotes osteogenic differentiation of BMSCs and bone repairing by activating Wnt/β-catenin signaling pathway
Authors: Liu Juan , Qi Xin , Miao Hong-Sheng , Xue Zi-Chao , Zhao San-Hu , Gao Guo-Yi , Lou Mei-Qing , Yi Cheng-Qing
Published: April 2021

Background: Previous studies have demonstrated long non-coding RNA maternally expressed gene 3 (MEG3) emerged as a key regulator in development and tumorigenesis. However, whether MEG3 participate in osteogenic differentiation and bone regeneration remains unclear. This study aims to investigate the function and mechanism of MEG3 in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and explores the use of MEG3 in skull defects bone repairing. Methods: Endogenous expression of MEG3 during BMSCs osteogenic differentiation were detected by qPCR. MEG3 was knockdown in BMSCs by lentivirus. The proliferation, osteogenic-related genes and proteins expression were assessed by the CCK-8, PCR, alizarin red and alkaline phosphatase staining in MEG3 knockdown BMSCs. Western blot was used to detected β-catenin expression in MEG3 knockdown BMSCs. DKK1 was used to block wnt/β-catenin pathway, the osteogenic-related genes and proteins expression were assessed by PCR, alizarin red and alkaline phosphatase staining in MEG3 knockdown BMSCs. MEG3 knockdown BMSCs scaffold with PHMG were implanted in a critical-sized skull defects of rat model, micro-CT, hematoxylin and eosin staining, and immunohistochemistry were performed to evaluate the bone repairing. Results: MEG3 was increased during osteogenic differentiation of BMSCs. Downregulation of MEG3 could promote osteogenic differentiation of BMSCs in vitro. Notably, a further mechanism study revealed MEG3 knockdown could activate Wnt/β-catenin signaling pathway in BMSCs. Wnt/β-catenin inhibition would impair MEG3-induced osteogenic differentiation of BMSCs. By using PHMG scaffold with MEG3 knockdown BMSCs, we found that downregulation of MEG3 in BMSCs could accelerated bone repairing in a critical-sized skull defects rat model. Conclusions: Our study reveals the important role of MEG3 during osteogenic differentiation and bone regeneration. Thus, MEG3 engineered BMSCs may be effective potential therapeutic targets for skull defects.
Sex differences in heritable and environmental risk of abdominal obesity: family-based study and case-control study of rural adults in China
Authors: Yu Songcheng , Feng Yinhua , Qu Chenling , Li Xing , Huo Wenqian , Mao Zhenxing , Chen Changying , Wang Chongjian , Li Wenjie
Published: April 2021

Background: Abdominal obesity (AO) has shown a dramatic increase trend in the past decades. But there were few studies on sex differences in the risk of AO, especially the heritable risk. This study aimed to investigate the sex differences of AO risk in China rural areas.Methods: A family-based study coupled with the Henan Rural Cohort was carried out, including 1,533 people and 39,259 people, respectively. Questionnaires were applied in including included demographics, dietary intake and physical activity. Combined family-based study with the Henan Rural Cohort, sex differences in heritable risk of AO was analyzed among rural people. Chi-square test was applied to study the heritable risk of AO. Environmental factors for AO were assessed in couple case-control study. Logistic regression analysis was carried out to assess the association of lifestyles with AO.Results: Women had higher risk to develop AO than men in Henan Rural Cohort (OR: 3.070, 95% CI: 2.943, 3.203, P<0.001). The female first-degree relatives were more susceptible to AO than those in the Henan Rural Cohort (OR: 1.854, 95% CI: 1.318, 2.608, P<0.001). Moreover, female offspring had higher risk to develop AO than male offspring when their mothers suffered from AO (OR: 1.797, 95% CI: 1.111, 2.907, P=0.016), and this risk increased if their grandmothers suffered from AO (OR: 6.750, 95% CI: 1.667, 27.336, P=0.007). In addition, low physical activity increased the risk to develop AO for women when compared with their husbands (OR: 2.253, 95% CI: 1.283, 3.957, P=0.005). Conclusion: This study indicated females are heritably susceptible to AO than men, especially for those who have maternal family history and reinforce the benefits of increasing physical activity for protecting females from suffering from AO. Proactive action based on maternal family history is a cost-effective strategy for the prevention of AO, although larger family-based studies are required to verify the conclusion.
Thermal and Crystallization Behavior of B2O3 – SiO2 – Bi2O3 – TiO2 – Y2O3 Glasses
Authors: shaaban Kh. S.
Published: April 2021

Glasses with the chemical composition of 52B2O3 – 12SiO2- 26Bi2O3 – (10 - x ) TiO2 - xY2O3, : (0 ≤ x ≥ 10 )prepared using the melt-quench method. The goal of this study is to investigate the structural, thermal, and crystallization characteristics of these samples. XRD analysis has explored the nature of the glass system. Molar volume obtained reduced while the density denotes increased in the present system. FTIR analysis revealed that as Y2O3 replaced by TiO2, because of an increasing trend in bridging oxygens (BOs), structural units and interconnection of modifier oxide tetrahedral increment, while non-bridging oxygens (NBOs) reduce. These glasses' thermal stability investigated using DTA. As the concentration of Y2O3 increased, so the thermal parameter values. The glass-ceramic denoted prepared under controlled heat and investigated using XRD & SEM. Ultrasonic velocities and elastic moduli of glass-ceramic samples increase as internal energy increases. The significance of Y2O3 modifier in the glass system signifies proved. Y2O3 is a powerful nucleating agent that can cause crystallization, assisting in the formation of glass-ceramic phases.
Awake Prone Positioning in Patients with Hypoxemic Respiratory Failure Due to COVID-19: The PROFLO Multicenter Randomized Clinical Trial
Authors: Rosen Jacob , Oelreich Erik von , Fors Diddi , Fagerlund Malin Jonsson , Taxbro Knut , Skorup Paul , Eby Ludvig , Jalde Francesca Campoccia , Johansson Niclas , Bergström Gustav , Frykholm Peter
Published: April 2021

Background: The effect of awake prone positioning on intubation rates is not established. The aim of this trial was to investigate if a protocol for awake prone positioning reduces the rate of endotracheal intubation compared with standard care among patients with moderate to severe hypoxemic respiratory failure due to COVID-19. Methods: We conducted a multicenter randomized controlled trial. Adult patients with confirmed COVID-19, high-flow nasal oxygen or noninvasive ventilation for respiratory support and a PaO2/FiO2 ratio ≤ 20 kPa were randomly assigned to a protocol targeting 16 hours prone positioning per day or standard care. The primary endpoint was intubation within 30 days. Secondary endpoints included duration of awake prone positioning, 30-day mortality, ventilator free days, hospital and intensive care unit length of stay, use of noninvasive ventilation, organ support and adverse events. The trial was terminated early due to futility. Results: Of 141 patients assessed for eligibility, 75 were randomized of whom 39 were allocated to the control group and 36 to the prone group. Within 30 days after enrollment, 13 patients (33%) were intubated in the control group versus 12 patients (33%) in the prone group (HR 1.01 (95% CI 0.46-2.21), P=0.99). Median prone duration was 3.4 hours [IQR 1.8-8.4] in the control group compared with 9.0 hours per day [IQR 4.4-10.6] in the prone group (P=0.014). Nine patients (23%) in the control group had pressure sores compared with two patients (6%) in the prone group (difference -18% (95% CI -2% to -33%); P=0.032). There were no other differences in secondary outcomes between groups.Conclusions: A protocol for awake prone positioning increased duration of prone positioning, but did not reduce the rate of intubation in patients with hypoxemic respiratory failure due to COVID-19 compared to standard care.Trial registration: ISRCTN54918435. Registered 15 June 2020 (https://doi.org/10.1186/ISRCTN54917435)
Genetic Diversity and Genomic Selection in Eucalyptus Benthamii
Authors: DE SOUZA BRUNO MARCHETTI , de Abreu Lucas Moura , Pappas Marília de Castro Rodrigues , Azevedo Vânia Cristina Rennó , Santos Paulo Eduardo Telles dos , de Souza Valderês Aparecida , Santos Rodrigo Furtado dos , de Aguiar Ananda Virgínia
Published: April 2021

The study investigates the genetic diversity and the ability of genomic-wide selection to predict breeding genomic values of an E. benthamii trial. All individuals (115) of the breeding population were genotyped with 13 microsatellites loci. The diameter at breast height and total height were measured. The data analysis was carried using the softwares: Structure, Popgene, GDA, SPAGeDi1.5 and R. Predictive ability, heritability and standard errors markers were estimated using the RRblup method. The average number of alleles per locus was nine, and the polymorphism level for each locus varied from 3 to 17. The average expected heterozygosity (He=0.655) was very similar to observed heterozygosity and the estimated inbreeding (F = 0.02) was very low. These results corroborate that this population is in Hardy-Weinberg equilibrium for the most loci. The trial genetic diversity is considered high, once the trial sampling demonstrated similar values to the natural populations. The group coancestry (0.085) demonstrate that the trees, in general, related at the half-sib level in this population. By using the Evanno’s method it is inferred that the individuals came from two original populations. The genetic distance calculated among the two groups was low ( =0.21). The heritability estimated from genomic selection for phenotypic traits was very low; however, the heritability estimated using the kinship coefficients was higher. The marker-based heritability using kinship coefficients probably is the more accurate than the one estimated using genomic selection, showing that the population samples can be used to establish breeding populations, hybrids and enriching the species germplasm bank.
Frequency microcomb distillation for optical superchannel transmission
Authors: Prayoonyong Chawaphon , Boes Andreas , xu xingyuan , Tan Mengxi , Chu Sai , Little Brent , Morandotti Roberto , Mitchell Arnan , Corcoran Bill , Moss David
Published: April 2021

Optical frequency combs potentially can provide a compact and efficient light source for multi-Terabit-per-second optical superchannels. However, as the bandwidth of these multi-wavelength light sources is increased, it can result in low per-line power. Optical amplifiers can be used to overcome power limitations, but the accompanying spontaneous optical noise can degrade performance in optical systems. To overcome this, we demonstrate wideband noise reduction for comb lines using a high-Q microring resonator whose resonances align with the comb lines. When applying the proposed distillation to a superchannel system at 18 Gbaud, with 64-QAM sub-channels in a > 10 Tb/s optical superchannel, we find that noise-corrupted comb lines can reduce the optical signal-to-noise ratio required for the comb by ~ 9 dB when used as optical carriers at the transmitter side, and by ~ 12 dB when used as a local oscillator at the receiver side. By filtering with a MRR, we eliminate this degradation in OSNR.
Doxycycline promotes proteasome fitness in the central nervous system
Authors: Jenkins Edmund Charles , O’Connell Matthew J. , Manfredi Giovanni , Germain Doris
Published: April 2021

Several studies reported that mitochondrial stress induces cytosolic proteostasis in yeast and C.elegans. Notably, inhibition of mitochondrial translation with doxcycyline decreases the toxicity of b-amyloid aggregates, in a C. elegans. However, how mitochondrial stress activates cytosolic proteostasis remains unclear. Further whether doxycycline has this effect in mammals and in disease relevant tissues also remain unclear. We show here that doxycycline treatment in mice drastically reduces the accumulation of proteins destined for degradation by the proteasome in a CNS region-specific manner. This effect is associated with the activation of the ERa axis of the mitochondrial unfolded protein response (UPR mt), in both males and females. However, sexually dimorphic mechanisms of proteasome activation were observed. Doxycycline also activates the proteasome in fission yeast, where ERa is not expressed. Rather, the ancient ERa-coactivator Mms19 regulates this response in yeast. Our results suggest that the UPR mt initiates a conserved mitochondria-to-cytosol stress signal, resulting in proteasome activation, and that this signal has adapted during evolution, in a sex and tissue specific-manner. Therefore, while our results support the use of doxycycline in the prevention of proteopathic diseases, they also indicate that sex is an important variable to consider in the design of future clinical trials using doxycycline.
Comprehensive in silico structural-functional analysis of Enterobacter GH19 class I chitinase (chiRAM) gene: cloning and heterologous expression
Authors: Abady Shahinaz M. , Ghanem Khaled M. , Ghanem Nevine B. , Embaby Amira M.
Published: April 2021

I. Background. Present study aims to clone and express the gene-encoding chitinase / GH19 family from Enterobacter sp. in E.coli with in silico sequence analyses.. II. Methods and results. The putative open reading frame of GH19 chitinase from Enterobacter sp. strain EGY1 was cloned and expressed into pGEM-T and pET-28a + vectors, respectively using a degenerate primer. The isolated nucleotide sequence (1821 bp, Genbank accession no.: MK533791.2) was translated to chiRAM protein (606 amino acids, UniProt accession no.: A0A4D6J2L9). chiRAM in silico protein sequence analysis revealed GH19 class I chitinase: N-terminus signal peptide (Met1-Ala23), catalytic domain (Val83-Glu347 & catalytic triad Glu149, Glu171, Ser218), proline-rich hinge (Pro414 -Pro450), (polycystic kidney disease protein motif (Gly 465-Ser 533), C-terminus chitin-binding domain (Ala553- Glu593), and class I conserved motifs (NYNY and AQETGG). Three dimensional model was constructed by LOMETS MODELLER, PDB template: 2dkvA (Oryza sativa L. japonica class I chitinase). Recombinant chiRAM was overexpressed as inclusion bodies (IBs) (~ 72kDa; SDS-PAGE) in 1.0 mM IPTG induced E.coli BL21 (DE3) Rosetta at room temperature, 18 hrs post induction. Optimized expression yielded active chiRAM with 1.974 U/mL ± 0.0002, on shrimp colloidal chitin (SCC), in induced E.coli BL21 (DE3) Rosetta cells growing in SB medium. LC-MS/MS identified the 72 kDa band in the soluble fraction with 52.3% coverage sequence exclusive to Enterobacter cloacae chitinase/GH19 (WP_063869339.1). III. Conclusions. Despite the successful cloning and expression of chiRAM of Enterobacter sp. in E.coli with an appreciable chitinase activity, prospective studies would focus on minimizing IBs to facilitate chiRAM purification and characterization.
Risk Literacy Promotes Representative Understanding: Numerate People are Less Biased, More Knowledgeable, and More Concerned about Climate Change
Authors: Cho Jinhyo , Cokely Edward , Ramasubramanian Madhuri , Allan Jinan , Feltz Adam , Garcia-Retamero Rocio
Published: April 2021

The authors have requested that this preprint be removed from Research Square.
A Novel Model of Acquired Hydrocephalus for Evaluation of Neurosurgical Treatments
Authors: Mcallister James (Pat) , Talcott Michael , Isaacs Albert M. , Castaneyra-Ruiz Leandro , Zwick Sarah H. , Hartman Alexis L. , Garcia-Bonilla Maria , Dilger Ryan N. , Fleming Stephen A. , Golden Rebecca K. , Morales Diego M. , Harris Carolyn A. , Limbrick David D.
Published: April 2021

Background.Many animal models have been used to study the pathophysiology of hydrocephalus; most of these have been rodent models whose lissencephalic cerebral cortex may not respond to ventriculomegaly in ways similar to gyrencephalic species and whose size is not amenable to evaluation of clinically-relevant neurosurgical treatments. Fewer models of hydrocephalus in gyrencephalic species have been used; thus, we have expanded upon a porcine model of hydrocephalus in juvenile pigs. Methods. Acquired hydrocephalus was induced in 30-35-day old pigs by percutaneous intracisternal injections of kaolin. Intracisternal and intraventricular injections of autologous blood was attempted in 2 cases to induce post-hemorrhagic hydrocephalus. Magnetic resonance imaging (MRI) was employed to evaluate the progression of ventriculomegaly and plan the surgical implantation of ventriculoperitoneal shunts at approximately 1–4 weeks post-kaolin. Behavioral and neurological status was assessed continuously. Results. Bilateral ventriculomegaly occurred post-induction and was characterized by enlargement of all portions of the cerebral ventricles, with prominent CSF flow voids in the third ventricle, foramina of Monro, and cerebral aqueduct. Kaolin deposits formed a solid cast in basal cisterns but the cisterna magna was patent. In 14 untreated hydrocephalic animals, mean total ventricular volumes were 6786 ± 4336 SD mm3 at 17–57 days post-kaolin, which was significantly larger than the baseline values of 2251 ± 194 SD mm3 in sham controls. Consistent with human hydrocephalus, intermittent disruption of the ventricular zone of the lateral ventricles was characterized by loss of multiciliated ependymal cells and the appearance of reactive astrocytes. Past the post-induction recovery period, untreated pigs were asymptomatic in spite of exhibiting mild-moderate ventriculomegaly. Shunted animals developed ataxia and lethargy only when obstruction of the ventricular catheter and/or distal valve occurred. Conclusions. Mechanical induction of acquired hydrocephalus produces a reliable in vivo model that is highly translational, allowing systematic studies of the pathophysiology and clinical treatment of hydrocephalus.
Stress decreases host viral resistance and increases Covid susceptibility in embryonic stem cells.
Authors: Abdulhasan Mohammed , Ruden Ximena , Rappolee Benjamin , Dutta Sudipta , Gurdziel Katherine , Ruden Douglas M , Awonuga Awoniyi O , Korzeniewski Steven , Puscheck Elizabeth E , Rappolee Daniel A
Published: April 2021

Stress-induced changes in viral receptor and susceptibility gene expression were measured in embryonic stem cells (ESC) and differentiated progeny. Rex1 promoter-Red Fluorescence Protein reporter ESC were tested by RNAseq after 72hr exposures to control hyperosmotic sorbitol under stemness culture (NS) to quantify stress forced differentiation (SFD) transcriptomic programs. Control ESC cultured with stemness factor removal produced normal differentiation (ND). Bulk RNAseq transcriptomic analysis showed significant upregulation of two genes involved in Covid-19 cell uptake, Vimentin (VIM) and Transmembrane Serine Protease 2 (TMPRSS2). SFD increased the hepatitis A virus receptor (Havcr1) and the transplacental Herpes simplex 1 (HSV1) virus receptor (Pvrl1) compared with ESC undergoing ND. Several other coronavirus receptors, Glutamyl Aminopep tidase (ENPEP) and Dipeptidyl Peptidase 4 (DPP4) were upregulated significantly in SFD>ND. Although stressed ESC are more susceptible to infection due to increased expression of viral receptors and decreased resistance, the necessary Covid-19 receptor, angiotensin converting enzyme (ACE)2, was not expressed in our experiments. TMPRSS2, ENPEP, and DPP4 mediate Coronavirus uptake, but are also markers of extra-embry onic endoderm (XEN), which arise from ESC undergoing ND or SFD. Mouse and human ESCs differentiated to XEN increase TMPRSS2 and other Covid-19 uptake-mediating gene expression, but only some lines express ACE2. Covid-19 susceptibility appears to be genotype-specific and not ubiquitous. Of the 30 gene ontology (GO) groups for viral susceptibility, 15 underwent significant stress-forced changes. Of these, 4 GO groups mediated negative viral regulation and most genes in these increase in ND and decrease with SFD, thus suggesting that stressed increases ESC viral susceptibility.
Exploring Anxiety and Chain Reaction of Anxiety in COVID-19 Pandemic: A large population Web-based survey in Japan
Authors: Zhuang Jinman , Cai Guoxi , Lu Yixiao , Lin Yulan , Wong Liping Ping , Hu Zhijian , Yamamoto Taro , Morita Kouichi , Aoyagi Kiyoshi , He Fei
Published: April 2021

Background: Anxiety plays an important role in psychology, explore the anxiety and its chain reactions can provide a good insight of the measures to address mental health problem caused by the COVID-19 (Coronavirus Disease 2019) epidemic. Methods: A cross-sectional study using data collected via an online self-reported questionnaire was conduct on Japan during the COVID-19 pandemic. Using State-Trait Anxiety Inventory (STAI-6) to assess the level of anxiety, and explore the relationship of anxiety STAI-6 Score, sources of COVID-19 information, the influences of COVID-19, social anxiety symptoms, discrimination, and evaluation toward the government. Results: 4,127 participants were included to the analysis. The level of anxiety is not equally distributed across the general population with different age, gender, educational level, occupation, income, presence of underlying disease and location (P<0.05). The numbers of sources to get information about COVID-19 have a positive correlation with STAI-6 Score (Spearman’rho=0.176, P<0.001). The influences caused by the pandemic are related to moderate-severe anxiety. Then the high level of anxiety would add to social anxiety (Spearman’rho=0.04, P<0.05) and discrimination behaviors (Spearman’rho=0.11, P<0.01). Generalized additive model shows that high anxiety would lower the responders’ evaluations of the preventive measures took by either national government or local government. Conclusions: Our findings provide a statistical evidence for the chain reaction of anxiety, that anxiety reactions may vary in predictable ways. Further researches can focus on what types of strategic interventions can cut the chain response of anxiety, in order to address the mental health problems in a pandemic.