bluuebunny/crossref_metadata_2025 huggingface dataset:
Discussion On The Mechanism of Que In The Treatment of Breast Neoplasms And Immune Prevention And Treatment
Authors: Qiu Dan , Yan Xianxin , Xiao Xinqin , Zhang Guijuan , Wang Yanqiu , Cao Jingyu , Ma Ruirui , Hong Shouyi , Ma Min
Published: August 2021

Background: The precancerous disease of breast cancer is an inevitable stage in the emergence and development of breast neoplasms. Breast cancer (BC) is a common malignant tumor in female worldwide. A large number of literatures have proved that, as antitumor drugs, flavonoid compounds can promote proliferation and immune regulation of T cell. Many researchers believe that Quercetin (Que) has great potential in the field of anti-breast cancer. Besides that, γδ T cells are a class of non-traditional T cells, which have long attracted attention due to their potential in immunotherapy. Above all, JAK/STAT1 signaling pathway is closely related to the immunity.MethodsIn the experiment designed in this paper, we first used Que, one of the flavonoids, to screen the target gene. Then, MCF-10A, MCF-10AT, MCF-7 and MDA-MB231 BC cells were co-cultured with Que for 24h and 48h, apoptosis was found in some the cells. We then cultured Que with γδ T cells and found that Que can promote the proliferation of Vδ2 T cell subsets of γδ T cells, thus enhancing the killing effect of γδ T cells. Western blot was use to showed the change of JAK/STAT1 signaling pathway related proteins after the Que was co-cultured with MCF-10AT and MCF-7 for 48h.ResultsNetwork pharmacology has shown that Que related pathways include the JAK/STAT1 signaling pathway and are associated with precancerous breast cancers. Que induced apoptosis of MCF-10AT, MCF-7 and MDA-MB-231 in a time and concentration-dependent manner. Most importantly, Que can promote the differentiation of γδ T cells into the Vδ2 T cell subpopulation, this means that Que and γδ T cells may play a synergistic role in killing tumor cells and cellular immune regulation. In addition, our results showed that Que can increase in protein levels of IFNγ-R, p-JAK2 and p-STAT1, while the concomitant decrease protein levels of PD-L1.ConclusionsIn conclusion, Que plays a synergistic role in killing BC cells and promoting apoptosis by regulating the expression of IFNγ-R, p-JAK2, p-STAT1, and PD-L1 in the JAK/STAT1 signaling pathway and promoting the regulation of γδ T cells. Que may be a potential drug for the prevention of precancerous breast cancer and adjuvant treatment of BC.
A study of antimicrobial activities of aqueous and ethanolic extract of bee pollen against
Authors: Jilo Kasim Roba
Published: August 2021

Background

Ethiopia is one of the plant species-rich countries in the world and the center of origin of many medicinal plants. Studying antimicrobial activities of pollen is vivacious to investigate plant resources for medicinal values and the study was conducted to evaluate antimicrobial properties of bee pollen against mentioned bacteria.
Methods

Completely Randomized Design was used for laboratory work. After adjusting turbidity, consistent growth of bacterial culture was made using a sterilized cotton swab. 20 grams of bee pollen was added to 200 ml of distilled water as well as ethanol and finally, the extract was filtered by Whatman filter by paper, dried and weighted and stock solutions were made as follows,3.6 gm. was added to 12 ml of distilled water to prepare stock solutions as follows 3.6:12 = 0.3 x \({10}^{6}\) = 3 x \({10}^{5}\) ppm stock solution and antimicrobial activities of pollen were tested against mentioned bacteria. Data were imported to R software version 3.44. Multilevel analysis was used to see the interaction between bacteria species and each concentration of pollen and Anova was used to see the significance of these concentrations on bacteria species. A p-value of < 0.05 was considered statistically significant.
Results

Results indicated that bacteria were more inhibited at 72 hours than 48 and 24 hours and the results showed an ethanolic extract of bee pollen had antimicrobial activities against both Gram-negative and Gram-positive bacteria mentioned above. Time has significant effects on tested bacteria (p = 0.000) and treatments have significant effects on tested organisms (p = 0.000). The ethanolic extract inhibited the growth of more Gram-negative bacteria: Escherichia coli and Shigella boydii. Bacillus subtilis was mostly inhibited by aqueous extract of bee pollen than others.
Conclusions

Ethanolic extract of pollen had antibacterial activities against all tested bacterial strains even though it is concentration and time-based. The ethanolic extract inhibited more Gram-negative bacteria relatively while aqueous extract inhibited more Gram-positive relatively. Negative controls (sterilized water) didn’t show any antimicrobial properties, while positive control (Chloramphenicol) had antimicrobial activities. Further isolation and characterization of bioactive compounds from pollen are useful to develop a novel botanical formulation for further applications from the pollen of medicinal plants.
Levels, Variations and Sources of 90sr and 137cs in Environmental and Food Samples Around Qinshan Nuclear Power Plant, China in 2012-2019
Authors: Cao Yiyao , Zhao Zhixin , Lou Xiaoming , Yu Shunfei , Zhang Meibian , Xuan Zhiqiang , Lai Zhongjun , Gao Xiangjing , Zhao Yaoxian , Ren Hong , Zhang Dongxia , Wang Peng
Published: August 2021

Environmental radioactivity monitoring in the surroundings of nuclear facilities is important to provide baseline data for effective detection in case of any radioactive release in the region. In this work, we report for the first time the long-term monitoring data of 137Cs and 90Sr in environmental and food samples around Qinshan Nuclear Power Plant (QNPP) in 2012-2019. The distribution levels, temporal variations and source terms of 137Cs and 90Sr in the investigated samples were discussed. The annual effective dose (AED) for the local population from the ingestion of foods was also evaluated. Peak values of 90Sr and 137Cs concentrations and 137Cs/90Sr radioactivity ratio were observed in total atmospheric deposition in 2016 and some water and food samples in the following years. This seems to be associated to an additional radioactive input, mostly likely from the operational release of a local facility. This demonstrates that 90Sr and 137Cs, especially the 137Cs/90Sr activity ratio, are sensitive indicators for detecting potential radioactive releases. Nevertheless, overall 90Sr and 137Cs activity concentrations measured during 2012-2019 in this work were at the background levels with average AED far below the internationally permissible limit and recommendation.
Unique Cerebrospinal Fluid Profiles of Patients With Human Immunodeficiency Virus- Associated Cryptococcal Meningitis With a Ventriculoperitoneal Shunt : A Retrospective Cohort Study
Authors: Tao Ran , Xu Lijun , Guo Yongzheng , Xu Xiaoke , Zheng Jiesheng , Zhu Biao
Published: August 2021

Background: The long-term complications of ventriculoperitoneal shunting in patients with human immunodeficiency virus-associated cryptococcal meningitis remain unclear. We conducted a case-control study investigating the long-term effects of ventriculoperitoneal shunting in patients with human immunodeficiency virus-associated cryptococcal meningitis. Methods: Between January 2011 and December 2019, 112 patients with human immunodeficiency virus-associated cryptococcal meningitis from our hospital were enrolled in this retrospective cohort study. Of those, 30 (26.8%) patients underwent ventriculoperitoneal shunting (VPS group); the remaining (n = 82; 73.2%) were included in the non-VPS group. Survival was estimated using the Kaplan–Meier method. Univariate and multivariate Cox regression analyses were performed to identify factors associated with ventriculoperitoneal shunting. Results: The VPS group (n=21) had lower cerebrospinal fluid glucose (2.51±0.81 vs. 3.16±0.48 mmol/L; P=0.002) and higher cerebrospinal fluid protein levels (1.37 [0.83–1.49] vs. 0.49 [0.49–0.49] g/L; P=0.011) than did the non-VPS group (n=21). Intracranial pressure decreased from 400 (375–450) to 164 (145–172) mmH2O in the VPS group (log-rank, P<0.001). The 24-week cumulative survival rates in the VPS and non-VPS groups were 100.0% and 79.8%, respectively (P=0.035). The misdiagnosis rates of tuberculous meningitis were 28.6% and 0.0%, respectively (P=0.008). Conclusions: Ventriculoperitoneal shunting decreased the intracranial pressure and 24-week mortality in patients with human immunodeficiency virus-associated cryptococcal meningitis, but significantly increased cerebrospinal fluid protein levels, leading to a higher misdiagnosis rate of tuberculous meningitis. Physicians should be aware of these changes in the cerebrospinal fluid profiles of patients with human immunodeficiency virus-associated cryptococcal meningitis with a ventriculoperitoneal shunt.
Robust Design of a Multirotor Aerial Vehicle
Authors: Dutta Abhishek
Published: August 2021

This paper introduces the methodology of systematic robust design of a multirotor vehicle as an example of how to carry out the robust design of a physical system. Robustness in aerial vehicles is highly desirable as it guarantees a desired level of performance even under environmental uncertainties. Thus far, robustness has been considered in terms of active control in the space of multirotor vehicles, but exploration of the design space itself is lacking. In this work, a conceptual design followed by a robust design is performed to come up with the specifications that lead to least uncertain performance of the multirotor vehicle with respect to stochastic wind disturbances.
Effect of Ultrasonic Compound Cutting on the Microstructure and Properties of Formed Chip
Authors: Sun Haimeng , Jiao Feng , Niu Ying , Wang Zhuangfei
Published: August 2021

Sever plastic deformation (SPD) with high strain rate can increase the material dislocation density, reduce the grain size and improve the mechanical properties. In this paper, ultrasonic compound cutting (UCC) was proposed to improve the efficiency of preparing ultra-fine grained (UFG) pure copper by sever plastic deformation methods. The motion characteristics and strain rate model of UCC were analyzed, and it was concluded that ultrasonic vibration can increase the strain rate in the primary shear zone. According to the 3D FEM equivalent model of UCC, the UCC and traditional compound cutting (TCC) were compared and analyzed from the perspective of strain rate. The simulation results show that ultrasonic vibration can significantly increase the strain rate of chip. The microstructure and mechanical properties of pure copper chip were studied by using a self-developed machining device. The experiment results show that the grain refinement, dislocation density and micro-hardness of pure copper chip were significantly improved in UCC. When the ultrasonic amplitude is 3 µm, the UCC chip grains are about 2.66 µm and the hardness reaches 124 HV, which is about 8% higher than the hardness of TCC chip. The findings of this research provide an important reference for machining UFG pure copper with enhanced mechanical properties.
The Protective Role of Protocol Biopsy for Allograft Kidney Maintenance in Kidney Transplantation
Authors: Lee Okjoo , Lee Kyo Won , Park Jae Berm , Lee Jung Eun , Hwang Na Young , Kim Kyunga
Published: August 2021

Many studies have reported that protocol biopsy (PB) may help preserve kidney function in kidney transplant recipients. Early detection and treatment of subclinical rejection may reduce the incidence of chronic allograft nephropathy and graft failure. However, no consensus has been reached regarding PB effectiveness, timing, and policy. This study aimed to evaluate the protective role of routine PB performed 2 weeks and 1 year after kidney transplantation. We reviewed 854 kidney transplant recipients at the Samsung Medical Center between July 2007 and August 2017, with PBs planned at 2 weeks and 1 year after transplantation. We compared the trends in graft function, chronic kidney disease progression, new-onset chronic kidney disease, infection, and patient and graft survival between the 504 patients who underwent PB and 350 who did not undergo PB. The PB group was again divided into two groups: the single PB group (n = 207) and the double PB group (n = 297). In the PB group, the donors and recipients were significantly older and there was a greater presence of recipient diabetes mellitus and donor hypertension, donor-specific antigen, and a higher proportion of ABO-incompatible kidney transplantations. The PB group was significantly different from the no-PB group in terms of the trends in graft function (estimated glomerular filtration rate). The Kaplan-Meier curve showed that PB did not significantly improve graft survival or overall patient survival. However, in the multivariate Cox analysis, the double PB group had advantages in graft survival, chronic kidney disease progression, and new-onset chronic kidney disease. PB can play a protective role in the maintenance of kidney grafts in kidney transplant recipients.
Overlapped Gate-Source/Drain H-shaped TFET: Proposal, Design and Linearity Analysis
Authors: Upadhyay Utkarsh , Raman Ashish , RANJAN RAVI , Kumar Naveen
Published: August 2021

In this paper, the proposed design of H-shaped TFET has been discussed. This design is providing a high Ion/Ioff ratio with better Ion. HfO2 is used for better tunneling current. With this device, Different parameters such as unit parameter, analogue parameter, and linearity parameter have been studied and investigated the output of the H-TFET. As unit parameters, the electric field, electric potential, energy band diagram, and non-local band-to-band tunneling rate (BTBT) have all been observed. Second and third-order harmonics distortion (HD2, HD3), third-order current intercept point (IIP3), third-order intermodulation distortions (IMD3), and second and third-order voltage intercept point (VIP2, VIP3) are evaluated as linearity parameters that characterize the device's distortions and linearity. We obtained Ion\({\text{=1.6×}10}^{-4}\) A/µm, Ioff=2.1\({\text{×}10}^{-19}\) A/µm, Ion /Ioff=7.6\({\text{×}10}^{14}\),threshold voltage Vt=0.3449 V. © 2017 Elsevier Inc. All rights reserved.
Impact of treatment with anti-parasitic (Ivermectin) during prepartum period on mastitis and postpartum reproductive efficiency measurements in Egyptian Baladi cows
Authors: Damarany Ahmed Ismail
Published: August 2021

The current investigation was designed to determine the effect of treatment with anti-parasites (Ivermectin) on mastitis and postpartum reproductive efficiency measurements in Egyptian Baladi cows. Twenty-four of the cows included in this study were split into two groups. The first group (n = 12 cows) was injected two months prepartum with two doses (15 days inter-treatment) of IVOMEC® Plus solution subcutaneously behind the shoulder, 1ml/50kg live body weight as prescribed by the manufacturer, whilst the other group (n = 12 cows) was used as a control group. The present results revealed that the incident rate of mastitis in treated cows’ group was significantly (P < 0.05) lower (16.7%) than control cows’ group (41.7%). The conception rate in treated cows’ group was significantly (P < 0.05) higher (66.7%) compared with (33.3%) in control group. The time from calving to conception in treated cows was significantly (P < 0.05) lower 86.5 ± 11.4 days compared to 123.3 ± 13.2 days in the control group. The occurrence rate of anestrous cases was significantly (P < 0.05) lower (8.3%) in treated cows than (control group) (25%). In conclusion, the current study indicates there is an association between treated cows with anti-parasites (Ivermectin) two months prepartum and incidence rate of mastitis addition an improvement in the reproductive performance in treated cows relative to untreated cows. Therefore, the current study recommends the herdsmen treats their cows with anti-parasites (Ivermectin) during the prepartum period for less mastitis incidence rate and better reproductive efficiency.
Novel Method for Evaluating Spatial Resolution of Magnetic Resonance Images
Authors: takeuchi tomokazu , Hayashi Norio , Asai Yuta , Kayaoka Yuka , Yoshida Kiichi
Published: August 2021

Purpose Recently, several methods for evaluating the spatial resolution of magnetic resonance imaging (MRI) have been reported. However, these methods are not simple and can only be used for specific devices. The International Electrotechnical Commission (IEC) 62464-1 recommends a method that uses a periodic array pattern to evaluate the spatial resolution of an MRI device. In this study, we develop a new method (the ladder method) and evaluate its measurement accuracy by adapting the IEC method to evaluate the spatial resolution. Methods First, the adaptation of the IEC method is analyzed by simulating the ladder method using a phantom with a periodic pattern, which is constructed using acrylic plates and a nickel sulfate aqueous solution. Subsequently, the ladder method is evaluated in terms of spatial resolution by dividing the standard deviation (SD) by the average signal in the region of interest (ROI) on the ladder phantom image. To evaluate the precision of the ladder method, it is compared with the modulation transfer function (MTF) using a magnitude image with the partial volume effect of the edge image. Results The simulation result shows that the evaluation of the spatial resolution using the ladder method is viable, in which a coefficient of correlation of 0.90 or higher is obtained for all evaluations using the ladder and MTF methods. ConclusionsThe ladder method can be assessed using only the signal mean value and SD in the ROI on the target image. Therefore, the ladder method is a promising method as a substitute for the MTF.
A Protective Tidal Volume Adapted To Lung Compliance and The PEEP Level With Lowest Transpulmonary Driving Pressure May Be Determined By a Rapid PEEP-Step Procedure
Authors: Grivans Christina , Stenqvist Ola
Published: August 2021

Background: A protective ventilation strategy should be based on lung mechanics and transpulmonary pressure, as this is the pressure that directly “hits” the lung. Esophageal pressure has been used for this purpose but has not gained widespread clinical acceptance. Instead, respiratory system mechanics and airway driving pressure have been used as surrogate measures. We have shown that the lung pressure/volume (P/V) curve coincides with the line connecting the end-expiratory airway P/V points of a PEEP trial. Consequently, transpulmonary pressure increases as much as PEEP and lung compliance (CL) can be determined as ΔEELV/ΔPEEP and transpulmonary driving pressure (ΔPTP) as tidal volume divided by ΔEELV/ΔPEEP.Methods: In ten patients with acute respiratory failure, ΔEELV was measured during each 4 cmH2O PEEP-step from 0 to 16 cmH2O and CL for each PEEP interval calculated as ΔEELV/ΔPEEP giving a lung P/V curve for the whole PEEP trial. Similarily, a lung P/V curve was obtained also for the PEEP levels 8, 12, and 16 cmH2O only.Results: A two-step PEEP procedure starting from a clinical PEEP level of 8 cmH2O gave almost identical lung P/V curves as the four PEEP-step procedure. The lung P/V curves showed a marked individual variation with an over-all CL (CLoa ) 50-137 ml/cmH2O. ΔPTP of a tidal volume of 6-7 ml/kg ideal body weight divided by CLoa ranged from 8.6-2.8 cmH2O, while ΔPTP of tidal volume adapted to CLoa ranged from 3.3 in the patient with lowest to 4.3 cmH 2 O in the patient with highest CLoa . The ratio of airway driving pressure to transpulmonary driving pressure (ΔPTP/ΔPAW) varied between patients and changed with PEEP, reducing the value of ΔPAW as surrogate for ΔPTP in individual patients.Conclusion: Only a two PEEP-step procedure is required for obtaining a lung P/V curve from baseline clinical PEEP to end-inspiration at the highest PEEP level, i.e. without esophageal pressure measurements. The best-fit equation for the curve can be used to determine a tidal volume related to lung compliance instead of ideal body weight and the PEEP level where transpulmonary driving pressure is lowest and possibly least injurious for any given tidal volume.
Predictors of Heart Failure Symptoms in Hereditary Hemorrhagic Telangiectasia Patients With Hepatic Arteriovenous Malformations
Authors: Cusumano Lucas Russell , Tesoriero Joseph A , Wilsen Craig B , Sayre James , Quirk Matthew , McWilliams Justin P
Published: August 2021

BackgroundHepatic arteriovenous malformations (AVMs) in hereditary hemorrhagic telangiectasia (HHT) patients are most commonly hepatic artery to hepatic venous shunts which can result in high-output heart failure. This condition can be debilitating and is a leading cause of liver transplantation in HHT patients. However, it is not known what characteristics can discriminate between asymptomatic patients and those who will develop heart failure symptoms.Results176 patients with HHT were evaluated with computed tomography angiography (CTA) between April 2004 and February 2019 at our HHT Center of Excellence. 63/176 (35.8%) patients were found to have hepatic AVMs on CTA. 18 of these patients were excluded because of the presence of another condition which could confound evaluation of heart failure symptoms. In the remaining 45 patients included in our cohort, 25/45 (55.6%) patients were classified as asymptomatic and 20/45 (44.4%) were classified as symptomatic, and these groups were compared. In symptomatic patients, mean common hepatic artery (CHA) diameter was significantly higher (11.1 versus 8.4 mm) and mean hemoglobin levels were significantly lower (10.7 vs 12.6 g/dL). A stepwise multiple logistic regression analysis demonstrated that both CHA diameter and hemoglobin level were independent predictors of heart failure symptoms with ORs of 2.554 (95% CI 1.372-4.754) and 0.489 (95% CI 0.299-0.799), respectively. The receiver operator characteristic (ROC) curve of our analysis demonstrated an AUC of 0.906 (95% CI 0.816–0.996), sensitivity 80.0% (95% CI 55.7-93.4%), and specificity 75.0% (95% CI 52.9-89.4%).ConclusionsCTA is an effective and easily reproducible method to evaluate hepatic involvement of HHT. Utilizing CTA, clinical, and laboratory data we determined CHA diameter and hemoglobin level were independent predictors of heart failure symptoms.
Acute Diplopia of Non-neurological/restrictive Etiology: a Retrospective Comparative Study.
Authors: Savino Gustavo , Scampoli Alessandra , Piccinni Fabrizio , Mattei Roberta , Salerni Annabella , Crincoli Emanuele
Published: August 2021

PurposeTo describe and compare the clinical features and management of different types of acute diplopia of non-neurological/restrictive etiology.MethodsRetrospective comparative study carried out reviewing medical records of forty-eight patients referred to one tertiary referral center between January 2016 and June 2020.Thirty-two were classified as Acute Acquired Comitant Esotropia (AACE), 3 cases as type I (group A), 12 cases as type II (group B) and 17 cases as type III (group C). Four cases were classified as Decompensated MonoFixation Syndrome (DMFS) (group D), 6 cases as High Myopia-Comitant Esotropia (HMCE) (group E) and 6 cases as Sagging Eye Syndrome (SES) (group F). Patients with diplopia of neurological or restrictive etiology were excluded.All patients underwent a complete orthoptic and ophthalmologic assessment with a postoperative follow-up of 11.4 ± 4.1 months (ranging from 5 to 20 months).ResultsType 3 AACE (Group C) was the most frequent cause of diplopia among the groups (35.4%). High Myopia-Comitant Esotropia (Group E) and Sagging Eye Syndrome (Group F) were significantly older at onset and baseline examination (both P= .001). Constant acute onset was significantly more represented in Group C (P= .026) while all patients in Group F showed an intermittent onset. Near angle of deviation was significantly lower in Group E and Group F compared to Group C (P= .030). A significantly higher near divergence fusion amplitude was detected in Group C (P= .017). Compensation (angle of deviation increasing) at Prism Adaptation Test (PAT) was observed in 75% of total study population, without significant differences among group. Fifty-four % of the total sample underwent surgery as first or secondary treatment choice with good functional results regardless of pathogenesis.ConclusionDemographic characteristics and clinical features (refraction, type of diplopia at onset, angle deviation, fusion amplitudes, response to prismatic correction) can differentiate different types of acute or subacute onset diplopia of not neurological/restrictive etiology.
Theoretical design of high-nitrogen energetic molecules: Performance prediction of pentazole-based derivatives
Authors: Wang Hao-Ran , Zhang Chong , Sun Cheng-Guo , Hu Bing-Cheng , Ju Xue-Hai
Published: August 2021

High nitrogen energetic compounds have always been a hot spot in energetic materials. In this work, we provide a new approach for the design of promising energetic molecules containing pentazole. Attractive energetic compounds include 5-amino-3-nitro-1H-1,2,4-triazole (ANTA) and 5-nitro-1,2,4-triazol-3-one(NTO) are used to effectively combine with pentazole to form a series of pentazole derivatives. Then, the NH2, NO2 or NF2 groups were introduced into the system to further adjust the property. Herein, the structures and densities of designed compounds as well as the heats of formation, detonation properties and impact sensitivities were predicted based on density functional theory (DFT). The results show that all ten designed molecules have excellent densities (1.81 g/cm3 to 1.97 g/cm3) and high heats of formation (621.66 kJ/mol to 1374.63 kJ/mol). Furthermore, detonation performances of compounds A3 (P = 41.16 GPa and D = 9.45 km/s) and A4 (P = 43.90 GPa and D = 9.69 km/s) are superior to 1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX), and lower impact sensitivity than HMX. It exhibited that they could be taken as promising candidates of high-energy density materials. This work provides a worthy way to explore the energetic compounds with excellent performance based on pentazole.
The Rexinoid V-125 Reduces Tumor Growth in Preclinical Models of Breast and Lung Cancer
Authors: Reich Lyndsey A. , Moerland Jessica A. , Leal Ana , Zhang Di , Carapellucci Sarah , Lockwood Beth , Jurutka Peter W. , Marshall Pamela A. , Wagner Carl E. , Liby Karen T.
Published: August 2021

Rexinoids are ligands which activate retinoid X receptors (RXRs), regulating transcription of genes involved in cancer-relevant processes. Rexinoids have anti-neoplastic activity in multiple preclinical studies. Bexarotene, used to treat cutaneous T cell lymphoma, is the only FDA-approved rexinoid. Bexarotene has also been evaluated in clinical trials for lung and metastatic breast cancer, wherein subsets of patients responded despite advanced disease. By modifying structures of known rexinoids, we can improve potency and toxicity. We previously screened a series of novel rexinoids and selected V-125 as the lead based on performance in optimized in vitro assays. To validate our screening paradigm, we tested V-125 in clinically relevant mouse models of breast and lung cancer. V-125 significantly (p < 0.001) increased time to tumor development in the MMTV-Neu breast cancer model. Treatment of established mammary tumors with V-125 significantly (p < 0.05) increased overall survival. In the A/J lung cancer model, V-125 significantly (p < 0.01) decreased number, size, and burden of lung tumors. Although bexarotene elevated triglycerides and cholesterol in these models, V-125 demonstrated an improved safety profile. These studies provide evidence that our screening paradigm predicts novel rexinoid efficacy and suggest that V-125 could be developed into a new cancer therapeutic.
The Surrogate Decision Making Participation Experience of Severe Acute Pancreatitis Patient In ICU: A Phenomenological Research In China
Authors: Fang Ting , Wang Shasha , Zhuang Yiyu , Zhang Xiuwei
Published: August 2021

Background Patients with severe acute pancreatitis mental state，tissues and organs function severely affected, patients themselves unable to effective participation in decision making, they have to rely on their family members to participate in clinical decision making, when the patient was admitted in ICU. However, it is unclear what factors influence the surrogate involved in decision making during anxiety, depression, post-traumatic stress disorder and other adverse psychological reactions.To describe the experiences of ICU patient’s family members with severe acute pancreatitis during decision making process.Methods Husserl’s phenomenology was applied in this study. This study was conducted in a critical care unit of a China tertiary hospital. They used Semi-structured face-to-face interviews with 12 surrogates of people with severe acute pancreatitis patient to explore the influencing factors of decision participation. This study followed the Colaizzi’s phenomenological method guided.Results/Finding Our sample consisted of 12 participants. Data analysis revealed four main themes: (i) ICU family surrogate cognitive self-role, (ii) ICU family surrogate consider of uncertainty, (iii) ICU family surrogate Communication and consulting, (iv) Decision-making attitude of ICU surrogate.Conclusion A framework of 4 themes of decisional involvement of family members of patients with severe acute pancreatitis in the ICU was constructed, and the interrelationship of the 4 themes was revealed. Psychological and somatic experience of the family as an outward expression of participation in decision-making, self-ability cognition is the internal cause of decision-making participation, consulting experience and considering uncertain factors are the external cause of decision-making participation. It is very important for ICU professionals to consider family members' decision-making participation. The suggestion that the family members of ICU patients participate in the intervention plan was initially formed ICU professionals should respect the values of patients' family members, to improve the disease awareness of the patient's family, to improve the support of the medical care system, and to improve Communication and emotional support skills for health care workers.
Comparative Analysis Of Orthologous Mast Cell Chymases Active Sites Using Bioinformatics Tools
Authors: Kiran Jawairia
Published: August 2021

Mast cells, neutrophils, basophils, natural killer cells, and cytotoxic T cells are among the hematopoietic cell lines originating from immune cells. The importance of mammalian mast cells in innate immunity has piqued the scientific community's interest. cytoplasmic granules of mast cells. Histamine, proteoglycans, proteins, and cytokines are examples of compounds (mediators) that produce mast cell cytoplasmic granules. When external stimuli are received, these granules are released, causing degranulation. Mast cells generate a lot of proteases including chymase, tryptase, and type A carboxypeptidase, among other things. The structure of chymase cma1 was unknown in mice, but it shares 74 percent of its human sequence with chymase CMA1, which was used as a reference. The human CMA1 structure was used to establish and interpret the mouse cma1 structure. Significant residues from the active site, such as catalytic triads and binding residues, were examined. The position of a catalytic triad in human CMA1 chymase and mouse cma1 chymase has been discovered to be similar. Val 175 and Val 197, respectively, replaced two Ala 192 and Gly 214 residues in active site binding residues in target, according to active site residue analysis. We may deduce from this substitution that the cleavage specificity of mouse cma1 chymase varies from that of human CMA1 chymase.
Fabrication of chitosan-coated mixed spinel ferrite integrated with graphene oxide (GO) for magnetic extraction of viral RNA for potential detection of SARS-CoV-2
Authors: Singh Vijay , Batoo Khalid Mujasam , Singh Mahavir
Published: August 2021

Genetic variants of the COVID-19 causative virus have been arising and circulating globally. In many countries especially in developing ones with a huge population, vaccination has become one of the major challenges. SARS-CoV-2 variants’ fast transmission rate has upsurge the COVID cases, leading to more stress on health systems. In the current COVID-19 scenario, there is the requirement of more adequate diagnostic approaches to check the COVID-19 spread. Out of many diagnostic approaches, a magnetic nanoparticle-based reverse transcription-polymerase chain reaction could be nontrivial. The use of magnetic nanoparticles to separate nucleic acid of SARS-CoV-2 from the patient samples and applied for detection is an easy and more effective way for COVID-19 patient detection. Herein, the magnetic nanoparticles are synthesized using the sol-gel autocombustion methods and then, successfully coated with biopolymer (chitosan) using ultra-sonication. Chitosan-coated nanoparticles are successfully integrated into the graphene oxide sheets to introduce carboxyl groups. Crystallite size calculation, morphological and magnetic studies of synthesized magnetic nanoparticles, and multifunctional magnetic nanoparticles are done using XRD, SEM, TEM, and VSM respectively. Besides the potentiality of the fabricated nanocomposites in RNA extraction protocol is also discussed with schematic representation.
Role of the Kuroshio Current on the Diurnal Variation of the Early-Summer Meiyu-Baiu Rainband
Authors: Park Hyung-Ju , Kim Kwang-Yul
Published: August 2021

Mechanism of the strong diurnal cycle of precipitation over the Kuroshio Current (KC) during mid-June is investigated, when the climatological location of the Meiyu-Baiu front overlaps the KC. Heating from the KC intensifies in the morning when the temperature difference between the sea surface and the surface air (TDF) maximizes. The diurnal cycle of precipitation, on the other hand, peaks in the afternoon, consistent with previous studies. It is revealed that convective precipitation (CP) due to convective instability is in phase with TDF, whereas large-scale precipitation (LSP) caused by the cross-frontal circulation matures later. Intensified convective instability via enhanced heating from the KC in the morning hours (03–12 LST) increases the mean amount of CP as well as the probability of stronger CP. Surface wind convergence is also strengthened during the morning hours and helps sustain the convection. The diurnal cycle of LSP, which peaks in the afternoon hours (12–15 LST), covaries with the intensity of the Meiyu-Baiu front and the assocaited cross-frontal circulation. The wind convergence and deformation anomalies associated with the intensified thermal heating over the KC during the morning hours intensifies the frontogenesis function, which leads to the maximization of the frontal intensity in the afternoon. The direct contribution of diabatic heating to the frontogenesis is relatively weak.
Resistin Forms A Network With Inflammatory Cytokines And Endothelial Damage Markers And Provides Prognostic And Therapeutic Information For COVID-19
Authors: Ebihara Takeshi , Matsumoto Hisatake , Matsubara Tsunehiro , Togami Yuki , Nakao Shunichiro , Matsuura Hiroshi , Kojima Takashi , Sugihara Fuminori , Okuzaki Daisuke , Hirata Haruhiko , Yamamura Hitoshi , Ogura Hiroshi
Published: August 2021

Background: Resistin increases in septic subjects and is associated with severity and prognosis. Its role in Coronavirus disease 2019 (COVID-19) is unknown. We investigated relationships between resistin and the severity, prognosis and time to wean off mechanical ventilation (MV) in two cohorts.Methods: Plasma resistin was available for 306 mild-to-critical COVID-19 patients on days 1, 4 and 8 from the Massachusetts General Hospital Emergency Department COVID-19 (MGH) cohort public proteomics data. The relationship between resistin and severity (World Health Organization COVID-19 outcomes) and the prognosis were evaluated. A cohort of 62 critical COVID-19 patients (Osaka cohort) was used to evaluate the relationship between resistin on days 1 (day of ICU admission), 2–3, 6–8 and 11–15 and the prognosis and time to wean off MV. Correlations among resistin, inflammatory cytokines and endothelial damage markers were evaluated.Results: In the MGH cohort, day 1 resistin was associated with severity and predicted the prognosis in an ROC analysis (AUC, 0.739; 95% CI, 0.659–0.819). Twenty-eight-day non-survivors showed significantly greater resistin levels than 28-day survivors on days 1, 4 and 8. In the Osaka cohort, a Cox proportional hazards model (time dependent) showed a significant relationship between resistin and time to wean off MV (crude hazard ratio, 0.702 [95% CI, 0.508–0.969]). Resistin formed a network with inflammatory cytokines and endothelial damage markers.Conclusions: Resistin was associated with severity, prognosis and time to wean off MV in COVID-19 patients. Resistin formed a network with inflammatory cytokines and endothelial damage markers, suggesting its contribution to the pathogenesis of COVID-19.
Automated Labeling of Chest X-ray Images using a Quantitative Explainable Atlas-Based AI Model
Authors: Kim Doyun , Chung Joowon , Choi Jongmun , Succi Marc , Conklin John , Longo Maria Gabriela Figueiro , Ackman Jeanne , Little Brent , Petranovic Milena , Kalra Mannudeep , Lev Michael , Do Synho
Published: August 2021

The inability to accurately, efficiently label large, open-access medical imaging datasets limits the widespread implementation of artificial intelligence models in healthcare. There have been few attempts, however, to automate the annotation of such public databases; one approach, for example, focused on labor-intensive, manual labeling of subsets of these datasets to be used to train new models. In this study, we describe a method for standardized, automated labeling based on similarity to a previously validated, explainable AI model (xAI), using an atlas-based approach, for which the user can specify a quantitative threshold for a desired level of accuracy, the “probability-of-similarity” (pSim) metric. We showed that our xAI model, by calculating the pSim values for each feature based on comparison to its training-set derived reference atlas, could automatically label the external datasets to a user-selected, high level of accuracy, equaling or exceeding that of human experts.
Health-Seeking Behaviour Among COVID-19 Cases In Singapore: Does Single or Multiple Physicians Make A Difference?
Authors: Tay Min Zhi , Ang Li Wei , Wei Wycliffe Enli , Lee Vernon JM , Leo Yee-Sin , Toh Matthias Paul HS
Published: August 2021

Background: COVID-19 is a novel pandemic affecting almost all countries leading to lockdowns worldwide. In Singapore, locally-acquired cases emerged after the first wave of imported cases, and these two groups may have different health-seeking behaviour affecting disease transmission. Objective: We investigated differences in health-seeking behaviour between locally-acquired cases and imported cases, and within the locally-acquired cases, those who saw single versus multiple healthcare providers.Methods: We conducted a retrospective study of 258 patients who were diagnosed with COVID-19 from 23 January to 17 March 2020. Variables related to health-seeking behaviour included number of visits prior to hospitalisation, timing of the first visit, duration from symptom onset to admission, and places where the cases had at least one visit.Results: Locally-acquired cases had longer duration from symptoms onset to hospital admission (median 6 days, range 1-30) than imported cases (median 4 days, range 1-13) (p<0.0005). Singapore residents were more likely to have at least one visit to private clinics and/or government-subsidised public clinics than non-residents (84.0% vs. 58.7%, p<0.0005). Among locally-acquired cases, those who sought care from a single provider had fewer visits before their hospital admissions compared with those who went to multiple care providers (median 2 vs. 3, p=0.001).Conclusion: Our study indicates the need to encourage individuals to seek medical attention early on in their patient journey, particularly from their family physician or the same doctor. This in turn, would facilitate early detection and isolation, hence limiting local transmission and enabling better control of the pandemic.
High-quality mesoporous SiO2 nanospheres via a confined jet impingement continuous microchannel reactor
Authors: Chen Qiang , Chen Kai , Yu Feng , Guo Aixia , Zou Siqing , Zhou Mei , Li Jiangwei , Dan Jianming , Li Yongsheng , Dai Bin , Guo Xuhong
Published: August 2021

High surface area mesoporous silica (SiO2) nanospheres has been considered an ideal material for the catalytic, adsorption and drug delivery. However, synthesis of ultra-high specific surface area mesoporous silica nanoparticles with well-defined sphere structure and small particle size (< 200 nm) is still challenging. Here, a two-stream confined jet impingement continuous microchannel reactor is proposed to produce novel mesoporous silica nanospheres (MSNs) with ultra-high specific surface area (SSA) and abundant worm-like meso-porosity. The as-obtained MSNs with worm-like mesoporous structure were produced with average particle diameter of 142 ~ 207 nm, high SSA of 1347 ~ 1854 m2/g, total pore volume of 0.86 ~ 1.23 cm3/g and pore diameter of 2.6 ~ 3.3nm. Moreover, the shear force field in the microchannel reactor on the mesoscopic structure of MSNs was simulated by mesoscopic kinetics. Additionally, MSNs was used as the silicon source to synthesize lithium silicate (Li4SiO4), which enhanced carbon dioxide (CO2) adsorption of 27.18 wt% at 650 ℃.
Extranodal Extension Is an Independent Predictor of Lung Metastasis in Papillary Thyroid Cancer
Authors: Hei Hu , Gong Wenbo , Zheng Chen , Zhou Bin , Qin Jianwu
Published: August 2021

PurposeLymph node metastasis is common in patients with papillary thyroid cancer (PTC). Some metastatic lymph nodes may present extranodal extension (ENE). The clinical role of ENE in PTC has yet to be clearly identified. We evaluated macroscopic ENE as a potential prognostic indicator of lung metastasis in PTC.Patients and MethodsWe identified 1140 consecutive patients who had PTC initially resected at our cancer center. Clinical data and pathological results were reviewed. Univariate and multivariate logistic regression analyses were used to figure out the association between clinicopathological variables and lung metastasis.ResultsIn this cohort, 51.7% of PTC patients had lymph node metastasis; 10.4% had macroscopic ENE positive nodes; 2.3% had lung metastasis. In patients with lymph node metastasis, the average number of positive nodes was 5.10 ± 4.91. Multivariable analysis of clinicopathological factors revealed that extrathyroidal extension (odds ratio [OR], 3.57; 95% CI, 1.41–9.04), macroscopic ENE (OR, 7.08; 95% CI, 2.54–19.74), and number of positive nodes were significantly associated with lung metastasis. Compared with 0–3 positive nodes, 7–9 positive nodes denoted a moderate risk of lung metastasis (OR, 4.53; 95% CI, 1.03–19.85). And 10 positive nodes or more indicated a high risk of lung metastasis (OR, 9.63; 95% CI, 2.65–35.02).ConclusionMacroscopic ENE could serve as a strong independent prognostic factor of lung metastasis in PTC. More attention should be paid to patients with ENE positive nodes during follow-up.
Ethacrynic Acid Is an Inhibitor of Human Factor XIIIa
Authors: Kar Srabani , Vu Kayla , Mottamal Madhusoodanan , Al-Horani Rami A.
Published: August 2021

Ethacrynic acid (EA) is a loop diuretic that is approved orally and parenterally to manage edema-associated diseases. Nevertheless, it was earlier reported that it is also associated with bleeding upon its parenteral administration. In this report, we investigated the effects of EA on human factor XIIIa (FXIIIa) of the coagulation process using a variety of techniques. FXIIIa is a transglutaminase that works at the end of the coagulation process to form an insoluble, rigid, and cross-linked fibrin rich blood clot. In fact, inhibition of FXIIIa-mediated biological processes has been reported to result in a bleeding diathesis. Inhibition of FXIIIa by EA was investigated given the nucleophilic nature of the thiol-containing active site of the enzyme and the Michael acceptor-based electrophilicity of EA. In a bisubstrate-based fluorescence trans-glutamination assay, EA inhibited FXIIIa with a moderate potency (IC50 ~ 105 µM) and efficacy (∆Y ~ 66%). In SDS-PAGE experiment, EA appears to significantly inhibit the FXIIIa-mediated polymerization of fibrin(ogen) as well as the formation of fibrin(ogen) – α2-antiplasmin complex which indicates that EA affects the physiological functions of FXIIIa. Interestingly, EA did not affect the clotting times of human plasma in the activated partial thromboplastin time (APTT) or prothrombin time (PT) assays at the highest concentration tested of 2.5 mM suggesting the lack of effects on the coagulation serine proteases and potentially the functional selectivity of EA with respect to the clotting process. Molecular modeling studies demonstrated that the Michael acceptor of EA forms a covalent bond with catalytic residue of Cys314 in the active site of FXIIIa. Overall, our studies indicate that EA inhibits the physiological function of human FXIIIa in vitro which may potentially contribute to the bleeding complications that were reported with the association of the parenteral administration of EA.
Eocene-Oligocene terrestrial cryospheric processes: bipolar glaciation and uplifted Tibet
Authors: Xia Guoqing , Wu Chihua , Rodríguez-López Juan Pedro , Mansour Ahmed , Jin Xin , Pei Junling , Yi Haisheng , Li Gaojie , Fan Qiushuang , Shi Zhiqiang
Published: August 2021

There is no agreement regarding the processes that have governed the birth and vanish of ice masses on Earth during Cenozoic, as well as the possible existence of unipolar vs bipolar glaciations which remain controversial. Although it is generally accepted that Cenozoic cryosphere was characterized by a unipolar Antarctic glaciation at the Eocene-Oligocene Transition (~ 34 Ma), recent investigations suggest synchronous cryospheric processes at both hemispheres at this time. Here we present the first worldwide evidence of ice-related structures in Eocene-Oligocene sediments from the mid-latitude Lunpola Basin of central Tibet. The lacustrine deposits contain two intervals dated 37.8–35.6 and 34.0-32.5 Ma, respectively, which preserve seasonal frost events, glendonites and ice-rafted debris. These cryospheric processes were synchronous with two recorded stratigraphic intervals containing ice-rafted debris along offshore Greenland and in the Arctic region. Our results provide robust continental evidence of Eocene-Oligocene bipolar glaciation and a direct evidence for an already uplifted central Tibet during late Eocene. This finding brings into debate the timing and magnitude of inherited elevation of the vast proto-Tibetan Plateau before the continental collision between India and Eurasia.