bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization, in-silico, and in-vitro study of a new steroid derivative from Ophiocoma dentata as a potential treatment for COVID-19
Authors: Abd El Hafez Mohamed S. M. , AbdEl-Wahab Miral G. , Seadawy Mohamed G. , El-Hosseny Mostafa F. , Beskales Osama , Saber Ali Abdel-Hamid Ali , El Demellawy Maha A. , Ghareeb Doaa A. 
Published: April 2022

AbstractThe medicinal potential of marine invertebrates' bioactive components that may act as anti-COVID-19 demonstrated promising results. Ophiocoma dentata, which is common in the Red Sea, is one such source. Therefore, this study aimed to isolate a new compound from the brittle star, Ophiocoma dentata, and evaluate its efficacy as anti-COVID-19 in-silico and in-vitro. Standard procedures were followed in order to assess the isolated compound’s preliminary toxicity and anti-inflammatory properties. Computer virtual screening technology through molecular docking and ADMET studies was conducted as well as a new steroid derivative was isolated for the first time, named 5α-cholesta-4(27), 24-dien-3β, 23 β-diol. Investigation of the Anti-Covid-19 activity of the isolated compound using a Plaque reduction assay revealed 95% inhibition at a concentration of 5 ng/µl (12.48 µM). Moreover, this compound showed an IC50 of 11,350 ± 1500 ng/ml against the normal fibroblast cells, indicating its safety. Interestingly, this compound exhibited anti-inflammatory activity with an IC50 of 51.92 ± 0.03 μg/ml compared to a reference drug’s IC50 of 53.64 ± 0.01 μg/ml, indicating that this compound is a potent anti-inflammatory. In silico data have proved that the isolated compound is a promising viral inhibitor against SARS-CoV2 and is thus recommended as a future nature preventive and curative antiviral drug.
Dihydromyricetin improves social isolation-induced cognitive impairments and astrocytic changes in mice
Authors: Watanabe Saki , Omran Alzahra Al , Shao Amy S. , Xue Chen , Zhang Zeyu , Zhang Jifeng , Davies Daryl L. , Shao Xuesi M. , Watanabe Junji , Liang Jing 
Published: April 2022

AbstractSocial isolation induces stress, anxiety, and mild cognitive impairment that could progress towards irreversible brain damage. A probable player in the mechanism of social isolation-induced anxiety is astrocytes, specialized glial cells that support proper brain function. Using a social isolation mouse model, we observed worsened cognitive and memory abilities with reductions of Object Recognition Index (ORI) in novel object recognition test and Recognition Index (RI) in novel context recognition test. Social isolation also increased astrocyte density, reduced astrocyte size with shorter branches, and reduced morphological complexity in the hippocampus. Dihydromyricetin, a flavonoid that we previously demonstrated to have anxiolytic properties, improved memory/cognition and restored astrocyte plasticity in these mice. Our study indicates astrocytic involvement in social isolation-induced cognitive impairment as well as anxiety and suggest dihydromyricetin as an early-stage intervention against anxiety, cognitive impairment, and potential permanent brain damage.
Executive failure hypothesis explains the trait-level association between motivation and mind wandering
Authors: Kawagoe Toshikazu 
Published: April 2022

AbstractMind wandering (MW) is commonly observable in daily life. Early studies established an association between motivation and MW at the trait level using a questionnaire survey. Considering that the mechanism of state-level association between them is known, this study was conducted to replicate the trait-level association and determine its possible mechanisms. Two independent samples were analysed using several questionnaires, which included motivation and MW. General one- and multi-dimensional scales were administered for both variables. Besides the successful replication of the significant association between motivation and MW at the trait level, we found that people with low levels of executive function experience high rates of spontaneous MW. This finding indicates that the underlying mechanism of trait-level association is the executive failure hypothesis, which postulates that a failure of executive control during task-related objectives evokes MW. Further, the motivation–MW relationship exhibits a different psychological basis at the state and trait levels.
Investigation of the support constraint effect and failure instability law of tunnels constructed using the New Austrian tunneling method
Authors: Chen Dongxu , Wang Laigui , Sun Chuang , Jia Chengzhi , Zheng Luxin 
Published: April 2022

AbstractThe application of a reasonable numerical calculation method is the key to accurately analyzing tunnel rock-support interactions. In this paper, we address the support constraint effect of tunnels and analyze the influence of related factors based on the confinement convergence method. Rupturable support models are developed using FLAC3D to intuitively show the numerical calculation results of tunnels. The results imply that the virtual supporting force generated by the support constraint effect should be considered in two-dimensional rock tunnel model calculations, and that the supporting force of the support should be increased by 2–3% of the maximum supporting force. Boundary effects should be considered in the three-dimensional tunnel model calculations, in which the influence range of the model boundary effect is nearly 1.5 times the tunnel span. A comparison of the field monitoring data and numerical calculations of the Baoshan tunnel project shows that the numerical results that consider the support constraint effect are in better agreement with the actual project situation. The rupturable support models can also reflect the stress and failure evolution law of supports, and provide support for the accurate evaluation of tunnel engineering stability.
Quantifying and categorising national extinction-risk footprints
Authors: Irwin Amanda , Geschke Arne , Brooks Thomas M. , Siikamaki Juha , Mair Louise , Strassburg Bernardo B. N. 
Published: April 2022

AbstractBiodiversity, essential to delivering the ecosystem services that support humanity, is under threat. Projections show that loss of biodiversity, specifically increases in species extinction, is likely to continue without significant intervention. Human activity is the principal driver of this loss, generating direct threats such as habitat loss and indirect threats such as climate change. Often, these threats are induced by consumption of products and services in locations far-removed from the affected species, creating a geographical displacement between cause and effect. Here we quantify and categorise extinction-risk footprints for 188 countries. Seventy-six countries are net importers of extinction-risk footprint, 16 countries are net exporters of extinction-risk footprint, and in 96 countries domestic consumption is the largest contributor to the extinction-risk footprint. These profiles provide insight into the underlying sources of consumption which contribute to species extinction risk, a valuable input to the formulation of interventions aimed at transforming humanity’s interactions with biodiversity.
Syngeneically transplanted insulin producing cells differentiated from adipose derived stem cells undergo delayed damage by autoimmune responses in NOD mice
Authors: Tokuda Kazunori , Ikemoto Tetsuya , Yamashita Shoko , Miyazaki Katsuki , Okikawa Shohei , Yamada Shinichiro , Saito Yu , Morine Yuji , Shimada Mitsuo 
Published: April 2022

AbstractInsulin-producing cells (IPCs) generated by our established protocol have reached the non-clinical ‘proof of concept’ stage. Our strategy for their clinical application is the autotransplantation of IPCs into patients with type 1 diabetes mellitus (T1DM). In this context, the autoimmunity that characterized T1DM is important, rather than allorejection. We aimed to determine how these IPCs respond to T1DM autoimmunity. IPCs were generated from the subcutaneous fat tissue of non-obese diabetic (NOD) mice using our protocol. IPCs derived from NOD mice were transplanted under the kidney capsules of NOD mice at the onset of diabetes and the subsequent changes in blood glucose concentration were characterized. Blood glucose decreased within 30 days of transplantation, but increased again after 40–60 days in three of four recipient NOD mice. In tissue samples, the numbers of CD4+and CD8+T cells were significantly higher 60 days after transplantation than 30 days after transplantation. In conclusion, IPCs significantly ameliorate the diabetes of mice in the short term, but are damaged by autoimmunity in the longer term, as evidenced by local T cells accumulation. This study provides new insights into potential stem cell therapies for T1DM.
Occupant safety effectiveness of proactive safety seat in autonomous emergency braking
Authors: Kang Myeongkwan , Kim Hyungjoo , Cho Youngkuen , Kim Seonglae , Lim Dohyung 
Published: April 2022

AbstractThe proactive safety seat (PSS) is a recently developed active safety system for securing occupant safety in out-of-seat position (OOSP), which was applied in the Hyundai Genesis G80 in 2020. However, there has not been sufficient quantifiable verification supporting the effectiveness of the PSS. The present study was performed to determine the effectiveness of the PSS for occupant safety in OOSP and to identify areas for additional improvement. Six test conditions were considered to determine the effectiveness of the PSS for augmentation of occupant safety in OOSP. Ten healthy men participated in the tests. Compared with the no PSS condition, maximum head excursion and neck rotation were significantly decreased in the PSS condition by 0.6–0.8-fold and 0.6–0.7-fold, respectively (P < 0.05). The PSS condition in which the seat pan was moved forward to the mid position showed a greater effect in reducing the characteristic motions related to submarining, compared with the condition in which the seat pan was moved rearward to the mid position (P < 0.05). These results suggested that PSS augments occupant safety in OOSP. This study provides valuable insights in ameliorating risks to the occupant in unintended seat positions before braking and/or collision.
Characterization and molecular docking study of cathepsin L inhibitory peptides (SnuCalCpIs) from Calotropis procera R. Br
Authors: Kwon Chang Woo , Yeo Subin , Chang Pahn-Shick 
Published: April 2022

AbstractPropeptides, released from the autocatalytic activation of its zymogen, are potential inhibitors against proteases involved in cancer cell invasion and migration. Our research team previously obtained novel propeptides (SnuCalCpIs) from transcriptome analysis of the medicinal plant Calotropis procera R. Br. and reported them as promising candidates for cancer therapeutics due to their cathepsin L inhibition activity. In the present study, inhibitory activity among SnuCalCpIs was compared with inhibition efficiency and verified by in silico molecular docking analysis. Only SnuCalCpI03 and SnuCalCpI15, expressed in Escherichia coli, showed inhibitory activity against cathepsin L as competitive inhibitors, and the half-maximal inhibitory concentrations (IC50) values of 2.1 nM and 1.6 nM, respectively. They were stable below 70 °C, maintaining more than 90% inhibitory activity over a wide range of pH (2.0–10.0), except at the isoelectric point (pI). The template-based docking simulation models showed that SnuCalCpI02, SnuCalCpI12, and SnuCalCpI16 could not interact with the substrate-binding cleft of cathepsin L even though they possessed the same conserved domain. In contrast, SnuCalCpI03 and SnuCalCpI15 interacted with cathepsin L along the propeptide binding loop and substrate-binding cleft, resulting in obstruction of substrate access to the active site.
Ultrafast laser ablation simulator using deep neural networks
Authors: Tani Shuntaro , Kobayashi Yohei 
Published: April 2022

AbstractLaser-based material removal, or ablation, using ultrafast pulses enables precision micro-scale processing of almost any material for a wide range of applications and is likely to play a pivotal role in providing mass customization capabilities in future manufacturing. However, optimization of the processing parameters can currently take several weeks because of the absence of an appropriate simulator. The difficulties in realizing such a simulator lie in the multi-scale nature of the relevant processes and the high nonlinearity and irreversibility of these processes, which can differ substantially depending on the target material. Here we show that an ultrafast laser ablation simulator can be realized using deep neural networks. The simulator can calculate the three-dimensional structure after irradiation by multiple laser pulses at arbitrary positions and with arbitrary pulse energies, and we applied the simulator to a variety of materials, including dielectrics, semiconductors, and an organic polymer. The simulator successfully predicted their depth profiles after irradiation by a number of pulses, even though the neural networks were trained using single-shot datasets. Our results indicate that deep neural networks trained with single-shot experiments are able to address physics with irreversibility and chaoticity that cannot be accessed using conventional repetitive experiments.
In vitro production of desired sex ovine embryos modulating polarity of oocytes for sex-specific sperm binding during fertilization
Authors: G. Ramesh Kumar , Mishra Ashish , Dhali Arindam , Reddy Ippala Janardhan , Dey Debpriyo Kumar , Pal Dintaran , Bhatta Raghavendra 
Published: April 2022

AbstractThe present study aimed to modulate the oxidative status-mediated polarity of the oocytes for sex-specific sperm fertilization to generate desired sex embryos. In vitro embryos were produced at different oxidative status, varying O2 concentrations, and without/with l-carnitine in maturation and culture media. The majority of the embryos produced at high oxidative stress were males whereas; low oxidative status favoured female embryos production. Low O2 doubled the proportion of female embryos (10.59 vs 21.95%); however, l-carnitine supplementation in media increased approximately seven-folds of the female embryos (12.26 vs. 77.62%) production. Oocytes matured at high oxidative status were in the repolarized state favouring positively charged Y sperm fertilization to produce significantly more male embryos. Low oxidative status favoured negatively charged X sperm fertilization to the oocytes in the depolarized state to produce more female embryos. Intracellular ROS was significantly low in female embryos than in males; however, female embryos were more stressful than males. The study concluded that the oxidative status-mediated alteration in pH of the medium to modulate the intracellular positive ions is the main critical factor to influence the sex of embryos through sex-specific sperms fertilization to the oocytes as per their polarity.
Randomized controlled trial of early endoscopy for upper gastrointestinal bleeding in acute coronary syndrome patients
Authors: Chung Chen-Shuan , Chen Chieh-Chang , Chen Kuan-Chih , Fang Yu-Jen , Hsu Wen-Feng , Chen Yen-Nien , Tseng Wei-Chuang , Lin Cheng-Kuan , Lee Tzong-Hsi , Wang Hsiu-Po , Wu Yen-Wen 
Published: April 2022

AbstractAcute upper gastrointestinal bleeding (UGIB) in acute coronary syndrome (ACS) patients are not uncommon, particularly under dual antiplatelet therapy (DAPT). The efficiency and safety of early endoscopy (EE) for UGIB in these patients needs to be elucidated. This multicenter randomized controlled trial randomized recent ACS patients presenting acute UGIB to non-EE and EE groups. All eligible patients received intravenous proton pump inhibitor therapy. Those in EE group underwent therapeutic endoscopy within 24 h after bleeding. The data regarding efficacy and safety of EE were analyzed. It was early terminated because the UGIB rate was lower than expected and interim analysis was done. In total, 43 patients were randomized to non-EE (21 patients) and EE (22 patients) groups. The failure rate of control hemorrhage (intention-to-treat [ITT] 4.55% vs. 23.81%, p < 0.001; per-protocol [PP] 0% vs. 4.55%, p = 0.058) and 3-day rebleeding rate (ITT 4.55% vs. 28.57%, p = 0.033; PP 0% vs. 21.05%, p = 0.027) were lower in EE than non-EE group. The mortality, minor and major complication rates were not different between two groups. Male patients were at higher risk of minor and major complications after EE with OR (95% CI) of 3.50 (1.15–10.63) and 4.25 (1.43–12.63), respectively. In multivariate analysis, EE was associated with lower needs for blood transfusion (HR 0.13, 95% CI 0.02–0.98). Among patients who discontinued DAPT during acute UGIB, a higher risk (OR 5.25, 95% CI 1.21–22.74) of coronary artery stent re-thrombosis within 6 months was noticed. EE for acute UGIB in recent ACS patients has higher rate of bleeding control, lower 3-day rebleeding rate and lower needs for blood transfusion, but more complications in male patients. Further enrollment is mandatory to avoid bias from small sample size (ClinicalTrial.gov Number NCT02618980, registration date 02/12/2015).
Systematic evaluating and modeling of SARS-CoV-2 UVC disinfection
Authors: Freeman Sebastian , Kibler Karen , Lipsky Zachary , Jin Sha , German Guy K. , Ye Kaiming 
Published: April 2022

AbstractThe ongoing COVID-19 global pandemic has necessitated evaluating various disinfection technologies for reducing viral transmission in public settings. Ultraviolet (UV) radiation can inactivate pathogens and viruses but more insight is needed into the performance of different UV wavelengths and their applications. We observed greater than a 3-log reduction of SARS-CoV-2 infectivity with a dose of 12.5 mJ/cm2of 254 nm UV light when the viruses were suspended in PBS, while a dose of 25 mJ/cm2was necessary to achieve a similar reduction when they were in an EMEM culture medium containing 2%(v/v) FBS, highlighting the critical effect of media in which the virus is suspended, given that SARS-CoV-2 is always aerosolized when airborne or deposited on a surface. It was found that SARS-CoV-2 susceptibility (a measure of the effectiveness of the UV light) in a buffer such as PBS was 4.4-fold greater than that in a cell culture medium. Furthermore, we discovered the attenuation of UVC disinfection by amino acids, vitamins, and niacinamide, highlighting the importance of determining UVC dosages under a condition close to aerosols that wrap the viruses. We developed a disinfection model to determine the effect of the environment on UVC effectiveness with three different wavelengths, 222 nm, 254 nm, and 265 nm. An inverse correlation between the liquid absorbance and the viral susceptibility was observed. We found that 222 nm light was most effective at reducing viral infectivity in low absorbing liquids such as PBS, whereas 265 nm light was most effective in high absorbing liquids such as cell culture medium. Viral susceptibility was further decreased in N95 masks with 222 nm light being the most effective. The safety of 222 nm was also studied. We detected changes to the mechanical properties of the stratum corneum of human skins when the 222 nm accumulative exposure exceeded 50 J/cm2.The findings highlight the need to evaluate each UV for a given application, as well as limiting the dose to the lowest dose necessary to avoid unnecessary exposure to the public.
Pre-treatment serum albumin and mutational burden as biomarkers of response to immune checkpoint blockade
Authors: Yoo Seong-Keun , Chowell Diego , Valero Cristina , Morris Luc G. T. , Chan Timothy A. 
Published: April 2022

AbstractThe effects of cytokine and protein stabilizing carriers, such as serum albumin, on tumor response to immune checkpoint blockade (ICB) is not well understood. By examining 1714 patients across 16 cancer types, we found that high pretreatment serum albumin level predicts favorable tumor radiographic response following ICB treatment in a dose-dependent fashion. Serum albumin is a candidate biomarker that can be combined with tumor mutational burden (TMB) for additional predictive capacity, and the tumor response rate to ICB was ~49% in the albumin-high/TMB-high group.
Glutathione S-transferase Mu 2 inhibits hepatic steatosis via ASK1 suppression
Authors: Jin Yi , Tan Yanjie , Zhao Pengxiang , Guo Yu , Chen Shilin , Wu Jian , Ren Zhuqing 
Published: April 2022

AbstractHepatic steatosis is the main characteristic of some liver metabolism diseases. However, unclear molecular mechanism of hepatic steatosis impedes the therapy of this hepatic steatosis. Glutathione-S-transferase mu 2 (GSTM2), as a member of phase II drug metabolizing enzymes (DMEs), regulates cellular antioxidant and detoxificant.GSTM2was highly up-regulated in hepatic steatosis tissues and high-fat diet (HFD) fed mice. Loss-of-functionGSTM2mouse model demonstrated thatGSTM2protected mice from excess fat accumulation. Mechanistically,GSTM2interacted with ASK1 and suppressed its phosphorylation and the activation of subsequent downstream p38-JNK signalling. Moreover,GSTM2overexpression in the liver effectively ameliorated hepatic lipid accumulation. Therefore, we identifiedGSTM2as an important negative regulator in progression of hepatic steatosis via both its detoxification/antioxidant and inhibition of ASK1-p38/JNK signalling. This study showed potential therapeutic function of the DME in progression of hepatic steatosis.
RhopH2 and RhopH3 export enables assembly of the RhopH complex on P. falciparum-infected erythrocyte membranes
Authors: Pasternak Michał , Verhoef Julie M. J. , Wong Wilson , Triglia Tony , Mlodzianoski Michael J. , Geoghegan Niall , Evelyn Cindy , Wardak Ahmad Z. , Rogers Kelly , Cowman Alan F. 
Published: April 2022

AbstractRhopH complexes consists of Clag3, RhopH2 and RhopH3 and are essential for growth of Plasmodium falciparum inside infected erythrocytes. Proteins are released from rhoptry organelles during merozoite invasion and trafficked to the surface of infected erythrocytes and enable uptake of nutrients. RhopH3, unlike other RhopH proteins, is required for parasite invasion, suggesting some cellular processes RhopH proteins function as single players rather than a complex. We show the RhopH complex has not formed during merozoite invasion. Clag3 is directly released into the host cell cytoplasm, whilst RhopH2 and RhopH3 are released into the nascent parasitophorous vacuole. Export of RhopH2 and RhopH3 from the parasitophorous vacuole into the infected erythrocyte cytoplasm enables assembly of Clag3/RhopH2/RhopH3 complexes and incorporation into the host cell membrane concomitant with activation of nutrient uptake. This suggests compartmentalisation prevents premature channel assembly before intact complex is assembled at the host cell membrane.