bluuebunny/crossref_metadata_2025 huggingface dataset:
Rationale and Design of GnG-Trial: A Randomized Phase-III Study to Compare Two Schedules of Gemtuzumab Ozogamicin as Adjunct to Intensive Induction Therapy and to Compare Double-Blinded Intensive Postremission Therapy with or Without Glasdegib in Older Patients with Newly Diagnosed AML
Authors: Jaramillo Sonia , Krisam Johannes , Cornet Lucian Le , Kratzmann Markus , Baumann Lukas , Sauer Tim , Crysandt Martina , Rank Andreas , Behringer Dirk , Teichmann Lino , Görner Martin , Trappe Ralf Ulrich , Röllig Christoph , Krause Stefan , Hanoun Maher , Hopfer Olaf , Held Gerhard , Buske Sebastian , Fransecky Lars , Kayser Sabine , Schliemann Christoph , Schaefer-Eckart Kerstin , Al-Fareh Yousef , Schubert Jörg , Geer Thomas , Kaufmann Martin , Brecht Arne , Niemann Dirk , Kieser Meinhard , Bornhäuser Martin , Platzbecker Uwe , Serve Hubert , Baldus Claudia D. , Müller-Tidow Carsten , Schlenk Richard F.
Published: May 2021

BackgroundOverall survival remains poor in older patients with acute myeloid leukemia (AML) with less than 10% being alive after five years. In recent studies, a significant improvement in event-free, relapse-free and overall survival was shown by adding gemtuzumab ozogamicin (GO), a humanized antibody-drug conjugate directed against CD33, to intensive induction therapy once or in a sequential dosing schedule. Glasdegib, the small-molecule inhibitor of smoothened (SMO), also showed improved overall survival in patients not eligible for intensive chemotherapy when combined with low-dose cytarabine compared to low-dose cytarabine alone. These findings warrant further investigations in the phase III GnG trial.Methods/DesignThis is a randomized phase III trial with measurable residual disease (MRD) after induction therapy and event-free survival (EFS) as primary endpoints. The two research questions are addressed in a 2 by 2 factorial design. Patients age 60 years and older are upfront randomized 1:1 in one of the two induction arms: GO administered to intensive induction therapy on days 1,4 and 7 versus GO administered once on day 1 (GO-147 versus GO-1), and double-blinded 1:1 in one of the subsequent treatment arms glasdegib vs. placebo as adjunct to consolidation therapy and as single-agent maintenance therapy for six months. Chemotherapy backbone for induction therapy consists of standard 7+3 schedule with cytarabine 200mg/m² continuously days 1 to 7, daunorubicin 60mg/m² days 1, 2 and 3 and high-dose cytarabine (1g/m², bi-daily, days 1,2,3) for consolidation therapy. Addressing two primary endpoints, MRD-negativity after induction therapy and event-free survival (EFS), 252 evaluable patients are needed to reject each of the two null hypotheses at a two-sided significance level of 2.5% with a power of at least 85%. ETHICS AND DISSEMINATION: Ethical approval and approvals from the local and federal competent authorities were granted. Trial results will be reported via peer-reviewed journals and presented at conferences and scientific meetings.TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04093505; EudraCT Number: 2019-003913-32.TRIAL REGISTRATION DATE: October 30, 2018
In Silico Structural Modeling of Wildtype and Mutant PRODH Proteins Involved in Psychiatric Disorder.
Authors: Muzammal Muhammad , Abbasi Sumra Wajid , Abbasi Ansar Ahmad , Khan Muzammil Ahmad
Published: May 2021

Proline dehydrogenase is an important mitochondrial enzyme that is encoded by the PRODH gene. Biologically, a mutation in this gene affects the activity of proline dehydrogenase enzyme that is normally involved in conversion of proline to glutamate. However, its reduced or null activity leads to excess quantity of proline in the body, which results in different psychiatric phenotypes along with intellectual disability. In the present study, we performed in silico analysis on all reported mutations of PRODH. The 3D models of normal and mutant PRODH were predicted using I-TASSER. The predicted structures were visualized and superimposed using chimera 1.13.1. The CASTp was used to identify active sites in modelled proteins. Protein-protein docking was done with Cluspro, while protein-substrate docking was done with Auto Dock 1.5.6 and-MGL tools and the results were visualized using LigPlus+ v.2.2 and Discovery studio 2020 respectively. Alignment of 3D models (mutant with wildtype) revealed that Arg185Gln (73.83 % ) and Gln19Ter (6.25% ) had the highest and lowest similarity indices, respectively. Enzyme pocket prediction identified three largest sites, with the second largest active site pocket containing substrate proline binding residues Leu527, Tyr548, and Arg563. Moreover, docking of mutant and wildtype PRODH with its close interactor “ALDH4A1” showed differences with respect to number, position, and nature of interacting amino acids residues. We observed that the nature of amino acid substitution and the number of bonds affect the binding of proline molecule with proline dehydrogenase enzyme, and therefore, affect its biological activity.
Genome survey sequencing and identification of genomic SSR markers for Batocera horsfieldi (Coleoptera: Cerambycidae)
Authors: Peng Xin , Yang Zhende , Xu Lei , Wang Hantang , Guo Chunhui , Hu Ping
Published: May 2021

The white-striped longhorn beetle Batocera horsfieldi (Coleoptera: Cerambycidae) is a polyphagous wood-boring pest that causes substantial damage to the lumber, fruit and nut industry. Here, next-generation sequencing was used to generate a whole genome survey dataset to provide fundamental information of its genome and develop genome-wide microsatellite markers for it. The genome size of B. horsfieldi was estimated as approximate 520 Mb by using K-mer analyses, and its heterozygosity ratio and repeat sequence ratio were 0.26% and 51.03%, respectively. The assembled genome was 528.56Mb with GC content of 35.40%. A total of 121750 microsatellite motifs were identified. The most frequent repeat motif was mononucleotide with a frequency of 85.84%, followed by 8.08% of dinonucleotide, 5.04% of trinonucleotide, 0.73% of tetranonucleotide, 0.20% of pentanonucleotide and 0.12% of hexanonucleotide motifs. The AT/AT, TA/TAand GA/TC repeats were the most abundant motifs of dinucleotide motifs, and AAT/ATT, TAA/TTA and ATA/TAT were the most abundant motifs of trinucleotide motifs, respectively. ninety six pairs of SSR primers were randomly selected for PCR amplification and agarose gel electrophoresis detection, among which 56 pairs of primers can be effectively amplified to obtain the target fragment. In summary, various candidate microsatellite markers were identified and characterized in this study using genome survey analysis.
The Biomechanical Role of the Fibula in Lower Limbs: A Fracture Mechanics Analysis
Authors: Shao Bin , Xing Jianqiang , Liu Dong , Wang Dawei , Zhao Bei , Wang Tingguang , Mu Weidong
Published: May 2021

BackgroundFibular grafting is widely used in the treatment of various bone nonunions and defects because of its good therapeutic effects. Furthermore, partial fibular resection has been used as a treatment for fibular tumors, injuries, and other conditions. The fibula plays important roles in the biomechanics of the lower limbs. Some experts have used cadaver specimens to study these aspects. In this study, the biomechanical effects of the fibula in lower limbs were researched through mechanics analysis.MethodsWe randomly collected knee joint computed tomography (CT) scans from eight adults, including three left knees and five right knees. The DICOM formatted CT scan images were imported into Mimics software. The tibia and fibula were extracted with the CT-bone function in Mimics software, and 3D models of the tibia and fibula were obtained. Each model was imported into 3-MATIC and LS-DYNA software to smooth the surface, perform meshing, define material properties, and set the failure parameters, interface properties, vertical loads and boundary conditions. The tibial fractures in both models were calculated to evaluate the biomechanical role of the fibula in the lower leg.ResultsThe validity of the model was verified, and the fibular load condition was similar to those previously reported. In the model with fibular support, the fracture load of the tibia was 78.27±3.36 KN, the initial fracture time was 0.69±0.01 s, and the complete fracture time was 0.75±0.01 s. The fibula carried approximately 7% of the load on the lower leg. In the fibular defect model, the fracture load of the tibia was 72.71±3.25 KN, the initial fracture time was 0.54±0.02 s, and the complete fracture time was 0.62±0.01 s.Conclusions﻿The fibula play an essential biomechanical role in lower limb load-bearing and therefore is worthy of clinical attention. We believe that LS-DYNA can be used as an effective tool for the study of fracture mechanics.
Association Between IL-18 Gene Polymorphism and Hashimoto Thyroiditis
Authors: Karakaya Dilek , Genc Gunes Cakmak , Celik Sevim Karakas , Aktas Tugba , Bayraktaroglu Taner , Dursun Ahmet
Published: May 2021

BackgroundHashimoto’s thyroiditis (HT) is the most frequent organ-specific autoimmune disease (AIT), which is called lymphocytic thyroiditis in which T helper-1 lymphocytes mediate the disease. IL-18 is expressed in thyroid follicular cells (TFCs) during HT. The findings of studies aimed at investigating the relationship between IL-18 and HT are highly contradictory. In this study, we aimed to investigate the association between IL-18 gene polymorphism and HT.Methods and ResultsThe study was included 97 patients diagnosed with HT and 86 volunteers in the healthy control group. The IL18-607C/A (rs1946518) ve -137G/C (rs187238) genotypes were determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. No significant difference in the mean ages and gender was observed between the groups (p = 0.763 and p = 0.658, respectively). -137 IL18 CG genotype is higher in HT than controls. The risk of the IL-18 CG genotype for HT patients was more than 2.237 times higher (OR; 2.237 %95 Cl: 1.195–4.187, p = 0.039) compared to that of the G/G genotype. Also, -607 AC genotype is higher in the control group than in the HT group (in individuals with the IL18 CG genotype).Conclusions﻿According to our results, the CG genotype might be a risk factor for HT. Conversely, there is a possibility that the AC genotype also plays a protective role against the condition. However, further studies will contribute to the emergence of new solutions by revealing the molecular and cellular mechanisms of HT.
Bmal1- and Per2-Mediated Regulation of the Osteogenic Differentiation and Proliferation of Mouse BMSCs by Modulating the Wnt/β-catenin Pathway
Authors: Zheng Jiawen , Zhang Lanxin , Tan Zhen , Wang Yuhong , Zhao Qing , Zhang Chenxiaoxue , Wei Xiaoyu , Yang Yuqing
Published: May 2021

BackgroundBmal1 and Per2 are the core components of the circadian clock genes(CCGs). Bmal1-/- mice exhibit premature aging, as indicated by hypotrichosis and osteoporosis, with a loss of proliferation ability. The same occurs in Per2-/- mice, albeit to a less severe degree. However, whether the effects of Bmal1 and Per2 on proliferation and osteogenic differentiation are synergistic or antagonistic remains unclear. Thus, our study aimed to explore the effects and specific mechanism.Materials and methodsLentiviral and adenoviral vectors were constructed to silence or overexpress Bmal1 or Per2 and MTT, flow cytometry, RT-qPCR, WB, immunohistochemistry, alizarin red staining and ChIP-Seq analyses were applied to identify the possible mechanism. ResultsThe successful knockdown and overexpression of Bmal1/Per2 were detected by fluorescence microcopy. Flow cytometry found out that Bmal1 or Per2 knockdown resulted in G1-phase cell cycle arrest. RT-qPCR showed the different expression levels of Wnt-3a, c-myc1 and axin2 in the Wnt/β-catenin signaling pathway as well as the gene expression change of Rorα and Rev-erbα. Meanwhile, Related proteins such as β-catenin, TCF-1, and P-GSK-3β were detected. ALP activity and the amount of mineral nodules were compared. ChIP-Seq results showed the possible mechanism.Conclusions﻿Bmal1 and Per2, as primary canonical clock genes, showed synergistic effects on the proliferation and differentiation of BMSCs. They would inhibit the Wnt/β-catenin signaling pathway by downregulating Rorα expression or upregulating Rev-erbα expression, both of which were also key elements of CCGs. And this may be the mechanism by which they negatively regulate the osteogenic differentiation of BMSCs.
A Questionnaire Based on A Sub-Regional Hierarchical Level Showed the Following: Application of Medical Accident Insurance is Suitable in Shanghai, China
Authors: Wan Li-Tao , Chen Gang
Published: May 2021

Background: The application of medical accident insurance could not only cover parts of patients’ property loss caused by non-medical negligence, but also reduce the risks of medical staff during medical services. However, the compensation mechanism for medical accidents is unsound in china. Methods: In order to figure out the awareness and acceptance of the medical accident insurance in Shanghai medical institutions, medical staff and patients, a questionnaire survey was conducted. The feedback, which in total came from 22 medical institutions, 1,689 medical staff and 1,342 patients, was statistically analyzed by chi-square test.Results：Only 22.72% of the 22 hospitals in this questionnaire survey purchased medical accident insurance. As a result, medical accident insurance only accounts for 3.13% of medical compensation, which was far lower than the negotiated compensation ratio (61.25%) and the medical liability insurance compensation ratio (14.38%). This may be due to the low awareness of medical accident insurance, and our survey also proves this phenomenon. In this survey, we find that only a small proportion (22.73%) of medical institutions purchase medical accident insurance. What is more unexpected is that the vast majorities of patients (50.00%) and medical workers (64.00%) have only heard of it and are not aware of it. Although nearly half of the patients (45.16%) and medical workers (58.26%) are willing to buy medical accident insurance, there were still some patients and medical workers who were uncertain (32.80% and 38.82%, respectively) or unwilling to buy it (8.94% and 16.02%, respectively). The reason is nothing more than that no benefits will occur while the cost is high. Among those willing to buy, the majority of the patients (58.19%) and medical workers (54.39%) only accept the amount of insurance less than RMB 200 yuan. Conclusions: The acceptability and cognition of medical accident insurance in medical workers and patients are still at a low level in Shanghai. In addition, preliminary data from medical institutions purchasing medical accident insurance shows that the insurance can effectively reduce medical disputes and ease economic burden. To sum up, medical accident insurance has good application prospect and space in Shanghai, China.
Exploring Socioeconomic Inequities in Access to Palliative and End-of-life Care in the Uk: A Mixed Methods Narrative Synthesis
Authors: French Maddy , Keegan Thomas , Anestis Eleftherios , Preston Nancy
Published: May 2021

Background: Efforts to understand and tackle socioeconomic inequities in access to palliative and end-of-life care require comprehensive understanding about the extent of and reasons for inequities. Most research on this topic examines differences in receipt of care. There is a need for theoretically driven research that considers both receipt of care and the wider factors influencing the relationship between socioeconomic position and access to palliative and end-of-life care. Methods: A mixed-methods narrative synthesis on socioeconomic position and access to palliative and end-of-life care in the UK. Study searches were conducted in databases AMED, Medline, Embase, CINAHL, SocIndex, and Academic Literature Search along with grey literature sources in July 2020. The candidacy model of access, which describes access as a seven-stage negotiation between patients and providers, guided study searches and provided a theoretical lens through which data were synthesised.Results: Searches retrieved 5303 studies (after de-duplication), 29 of which were included. The synthesis generated four overarching themes, within which concepts of candidacy were evident: identifying needs; taking action; local conditions; and receiving care.Conclusion: Socioeconomic position does not have a consistent association with receipt of palliative and end-of-life care in the UK. The use of the candidacy model of access helped to identify key gaps in the UK evidence, including those concerning the relationship between socioeconomic position, organisational context, and assessing need for palliative care.
Breastfeeding and Humanitarian Emergencies: the Experiences of Pregnant and Lactating Women During the Earthquake in Abruzzo, Italy
Authors: Giusti Angela , Marchetti Francesca , Zambri Francesca , Pro Elide , Brillo Eleonora , Colaceci Sofia
Published: May 2021

Background: Emergencies have a great impact on infant and young child feeding. Although the evidence, the recommended feeding practices are often not implemented in the emergency response, undermining infant and maternal health. The aim of this study was to explore the experiences of pregnant and lactating women during the earthquake emergency that occurred in L’Aquila on April 6, 2009.Methods: The study design was qualitative descriptive. Data were collected by individual semi-structured interviews, investigating the mother’s experiences of pregnancy, childbirth, breastfeeding, infant formula or complementary feeding during the emergency and the post emergency phase. Data analysis was categorical and was performed by using N-Vivo software.Results: Six women who were pregnant at the time of the earthquake were interviewed in January 2010. In addition to the essential needs of pregnant and lactating women, such as those related to the emergency shelters conditions, the main findings emerged from this study were: the reconfiguration of relationships and the central role of partners and family support; the need of spaces for sharing experiences and practices with other mothers; the lack of breastfeeding support after the hospital discharge; the inappropriate donations and distribution of Breast Milk Substitutes.Conclusions: During and after L’Aquila earthquake, several aspects of infant and young child feeding did not comply with standard practices and recommendations. The response system appeared not always able to address the specific needs of pregnant and lactating women. It is urgent to develop management plans, policies and procedures and provide communication, sensitization, and training on infant and young child feeding at all levels and sectors of the emergency response.
Chronic Co-morbidity and Self-management Skills Among Adult HIV Patients in Ethopia
Authors: Woldie Yadessa Tegene , Bilal Selamawit Mengesha , Tanis Rianne , Spaargaren Babette , Toma Alemayehu , Spigt Mark
Published: May 2021

Background: HIV requires life-long adherence to treatment and diet, also to avoid chronic co-morbidity. Self-management is widely recognized as an essential part of care for people with chronic disease. We aimed to quantify the prevalence of co-morbidity among adult HIV patients and their self-management skills.Methods: An institutional based cross sectional study was conducted from May to June 2019. We selected a total of 520 adult HIV patients, attending antiretroviral therapy clinics in three Hospitals in Southern Ethiopia. Data were collected at routine care consultations by nine trained nurses using a pre-tested structured questionnaire. Result: The mean age of the study participants was 38.7±9 years. Prevalence of diabetes and Hypertension was 1.5% and 9.4%, respectively. Being older, overweight, and obese was significantly associated with chronic comorbidity. The total score of HIV Self-management was 42±3.92 out of 60. The least mean score (1.69±0.9) was seen in the social support domain of HIV self-management.Conclusion: The prevalence of diabetes and hypertension was relatively low in our population. Self-management skills seem to be low, but many aspects of self-management are poorly understood in Ethiopia (low-income) setting.
The Gut Microbiota Mediates the Inhibition of Seizure-induced Respiratory Arrest in DBA/1 Mice fed a High Tryptophan Diet
Authors: Yue Qiang , Cai Mingfei , Xiao Bo , Zhan Qiong , Zeng Chang
Published: May 2021

Background: Central 5-hydroxytryptamine (5-HT) defects are responsible for the occurrence of audiogenic seizure-induced respiratory arrest (S-IRA) in DBA/1 mice, an animal model of sudden unexpected death in epilepsy (SUDEP). We aimed to explore the effect of a high tryptophan diet (HTD) on SUDEP and its possible mechanism involving 5-HT metabolism via gut microbiota.Methods: Primed animals were randomly assigned to the normal diet (ND) group or HTD group. Before and after diet interventions, 1) S-IRA rates were evaluated, 2) the concentrations of upstream-to-downstream 5-HT metabolites in the plasma and brain were detected by ultra-high-pressure liquid chromatography, and 3) the fecal flora biodiversity and species composition were analysed by 16S rDNA microbiota profiling. Second, antibiotics or probiotics combined with the HTD and S-IRA rates were reassessed.Results: The S-IRA rate in DBA/1 mice was significantly reduced in the HTD group compared with that in control. The HTD obviously increased the levels of tryptophan in the telencephalon and 5-HT and 5-hydroxyindoleacetic acid levels in both the telencephalon and midbrain. The HTD significantly increased the species richness and diversity of gut microbiota. Moreover, there was a significant difference in the gut microbiota composition between the HTD and ND groups. However, antibiotics or probiotics had no synergistic or antagonistic effects on S-IRA reduction mediated by the HTD.Conclusions: An HTD is efficient in lowering S-IRA rates in DBA/1 mice, possibly via modulation of 5-HT metabolism and gut microbiota. Our findings shed light on dietary prevention of SUDEP.
How Do Soil Resources Affect Herbivory in Tropical Plants Along Environmental Gradients? A Test Using Contrasting Congeneric Species
Authors: Pinto Victor Diniz , Badia Clara Cruz Vidart , Soares Glória Ramos , Sousa Hildeberto Caldas , Cornelissen Tatiana , Ribeiro Sérvio Pontes
Published: May 2021

Plants adapted to different habitats exhibit differences in functional traits and these characteristics are influenced by soil properties. We tested the hypothesis that soil resource availability influences the functional traits of plants, affecting therefore herbivory levels. We examined three Byrsonima plant species with different life forms that occurred across a distinct edaphic habitat along the Doce River Basin, South-eastern Brazil. We characterize habitats according to soil nutrient concentration and measured functional characteristics of crown architecture, leaf nutrients, sclerophylly, leaf area and leaf density. In addition, we evaluated how these variables influenced herbivory levels of congeneric plants. Our data have shown that species along a gradient of soil nutrients have functional characteristics influenced by habitat, which in turn affected herbivory levels. By comparing species from different life forms but within the same genus along a stress-gradient of continuous habitats, we described a corresponding gradient of plant functional traits and tissue consumption by herbivorous insects.
Comparative Genomic Characterization of Multidrug-resistant Citrobacter Spp. Strains in Fennec Fox Imported to China
Authors: Qin Jie , Xu Hao , Zhao Yishu , Wang Aifang , Chi Xiaohui , Wen Peipei , Li Shuang , Wu Lingjiao , Bi Sheng
Published: May 2021

Background: To investigate the antimicrobial profiles and genomic characteristics of MDR-Citrobacter spp. strains isolated from Fennec fox imported from Sudan to China.Methods: Citrobacter spp. strains were isolated from stool samples. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) was used for identification. Antimicrobial susceptibility testing was performed using the broth microdilution method. Whole-genome sequencing was performed on an Illumina Novaseq-6000 platform. Acquired antimicrobial resistance genes and plasmid replicons were detected using ResFinder 4.1 and PlasmidFinder 1.3, respectively. Comparative genomic analysis of 277 Citrobacter genomes was also investigated.Results: Isolate FF141 was identified as Citrobacter cronae, isolate FF371, isolate FF414, and isolate FF423 were identified as Citrobacter braakii. Of these, three C. braakii isolates were further confirmed to be ESBL-producer. All isolates are all MDR with resistance to multiple antimicrobials. Plasmids of incompatibility (Inc) group pKPC-CAV1321. Comparative genomics analysis of Citrobacter isolates generated a large core-genome. Genetic diversity was observed in our bacterial collection, which clustered into five main clades. Human, environmental and animal Citrobacter isolates were distributed into five clusters.Conclusions: To our knowledge, this is the first investigation of MDR-Citrobacter from Fennec Fox. Our phenotypic and genomic data further underscore the threat of increased ESBL prevalence in wildlife and emphasize that increased effort should be committed to monitoring the potentially rapid dissemination of ESBL-producers with one health perspective.
Association Between Tfeb Gene Polymorphism, Gene–environment Interaction, and Fatty Liver Disease: a Case–control Study in China
Authors: Mo Chunbao , Mai Tingyu , Cai Jiansheng , He Haoyu , Lu Huaxiang , Tang Xu , Chen Quanhui , Xu Xia , Nong Chuntao , Liu Shuzhen , Tan Dechan , Liu Qiumei , Xu Min , Li You , Zhang Zhiyong , Qin Jian
Published: May 2021

Background: Fatty liver disease (FLD) is a serious public health problem that is rapidly increasing. Evidences indicated that the transcription factor EB (TFEB) gene may be involved in the pathophysiology of FLD; however, whether TEFB polymorphism is association with FLD remains unclear.Objectives: To explore the association among TFEB polymorphism, gene–environment interaction, and FLD and provide epidemiological evidence for clarifying the genetic factors of FLD.Methods: This study is a case–control study. Sequenom MassARRAY was applied in genotyping. Logical regression was used to analyze the association between TFEB polymorphism and FLD, and the gene–environment interaction in FLD was evaluated by multiplication and additive interaction models.Results: (1) The alleles and genotypes of each single nucleotide polymorphism of TFEB in the case and control groups were evenly distributed; no statistically substantial difference was observed. (2) Logistic regression analysis indicated that TFEB polymorphism is not remarkably associated with FLD. (3) In the multiplicative interaction model, rs1015149, rs1062966, and rs11754668 had remarkable interaction with smoking amount. Rs1062966 and rs11754668 also had a considerable interaction with body mass index and alcohol intake, respectively. However, no remarkable additive interaction was observed.Conclusion: TFEB polymorphism is not directly associated with FLD susceptibility, but the risk can be changed through gene–environment interaction.
Spectral Imaging With Dual-layer Spectral Detector Computed Tomography for Acute Coronary Syndrome
Authors: Mochizuki Junji , Nakaura Takeshi , Yoshida Naofumi , Nagayama Yasunori , Kidoh Masafumi , Uetani Hiroyuki , Funama Yoshinori , Hata Yoshiki , Azuma Minako , Hirai Toshinori
Published: May 2021

Purpose: To evaluate the feasibility of spectral imaging with dual-layer spectral detector computed tomography (CT) for the diagnosis of acute coronary syndrome.Methods: We identified 33 consecutive patients who underwent cardiac CT using dual-layer spectral detector CT and were diagnosed with acute ischemic syndrome by an invasive coronary angiography. We reconstructed 120 kVp images and generated virtual monochromatic images (VMIs; 40–200 keV in 10 keV increments), iodine concentration maps, and effective atomic number (Z) maps. We calculated the contrast and contrast-to-noise noise ratio (CNR) between myocardial normal and hypo-perfusion and chose the VMIs with the best CNR for quantitative analysis. We compared the image noise, contrast, and CNR of 120 kVp images and the best VMIs, CT value, iodine concentration, and effective Z between myocardial normal and hypo-perfusion with the paired t-test.Results: As the X-ray energy decreased, venous attenuation, contrast, and CNR gradually increased. The 40 keV image yielded the best CNR. There was no significant difference in image noise between the 120 kVp and 40 keV images. The contrast and CNR between myocardial normal and hypo-perfusion were significantly higher in 40 keV images than those in 120 kVp images. The iodine concentration and the effective Z were significantly higher in normal myocardium than those in hypo-perfused myocardium.Conclusion: Spectral imaging with dual-layer spectral detector CT is a feasible technique to detect the hypo-perfused area of acute ischemic syndrome.
Akt1 is required to maintain lipid droplets for release of HCV infectious virions
Authors: Lee Wei-Ping , Lan Keng-Li , Liao Shi-Xian , Huang Yi-Hsiang , Hou Ming-Chih , Lan Keng-Hsin
Published: May 2021

Hepatitis C virus (HCV) relies on the interplay of viral and host factors to complete its life cycle. It has evolved to benefit from Akt activation at some point in the life cycle through a variety of mechanisms. Our preliminary result showed that Akt-specific inhibitor reduced cell culture-derived HCV (HCVcc) infectivity in a dose-dependent manner. To dissect the mechanism, we adopted a two-part cell culture-derived HCV infection protocol with Akt1 small interfering RNAs (siRNAs) to determine the role of Akt in the HCV life cycle. The result showed that Akt1 was a crucial host factor involved in the late stage of HCV life cycle. Akt1 depletion reduced viral particles released from Huh-7.5.1 cells to culture medium with consequent reduction of viral reinfection in cell culture system, which was restored by ectopic Akt1 expression. To further study the mechanism, we found that Akt1 enhanced lipogenic pathway through transcriptional activation of fatty acid synthase (FAS) by sterol regulatory element binding protein-1 (SREBP1) to maintain sufficient lipid droplet that is an essential organelle for assembly and release of HCV infectious virions.
Endocuff-Assisted Colonoscopy Does Not increase the Sessile Serrated Lesion Detection Rate – A Randomized Controlled Trial
Authors: Ferreira Alexandre Oliveira , Costa-Santos Maria Pia , Palmela Carolina , Glória Luisa , Cravo Marília , Canena Jorge , Dinis-Ribeiro Mario
Published: May 2021

BackgroundColorectal cancer (CRC) is a leading cause of cancer-related death. Colonoscopy has been shown to decrease the incidence of CRC by facilitating the detection and resection of adenomas and serrated lesions. Endocuff vision (EV) has been shown to increase the detection of adenomas. The aim of this study was to compare the detection of sessile serrated lesions during colonoscopy with and without EV.MethodsA total of 257 patients who underwent elective colonoscopy were prospectively enrolled. The patients were randomly allocated to one of two groups according to the use of EV (standard colonoscopy vs. colonoscopy with EV). We compared the rates of detection of serrated lesions (including hyperplastic lesions ≥ 10 mm) and adenomas.ResultsThe number of serrated lesions per colonoscopy was not significantly higher in the EV group (0.233 vs 0.156, mean difference 0.076, p = 0.381). None of the secondary endpoints regarding the detection rate of adenomas (65.9% vs 66.4%; OR 0.977, 95% CI 0.583–1.638; p = 0.931) or sessile serrated lesions (12.4% vs 7.8%; OR 1.671; 95% CI 0.728–3.836; p = 0.226) were superior in the EV group. The differences were not significantly altered after adjusting for either the Boston Bowel Preparation Score (BBPS) or withdrawal time.ConclusionEV did not increase the rate of detection of serrated lesions or adenomas.Trial registrationClinicalTrials.gov Identifier: NCT03856957. Registered 27 February 2019 - Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT03856957
Antimicrobial activity, antioxidant capacity and attempt to identify Flavonoids Analyses of Crocus sativus leaves and petals by ultra-performance LC-DAD-MS.
Authors: mohamed Jadouali si
Published: May 2021

Saffron leaves and petals are the main by-products of saffron processing which is producing in large amounts annually. The aim of this work is to identified polyphenols in leaves and petals from Saffron. Ultra-performance liquid chromatography coupled to diode array detection (UPLC-DAD) and ion trap mass spectrometry with either electrospray ionization (ESI-MS). Crude extracts from leaf and petal of Crocus sativus were screened for their in vitro antioxidant and antimicrobial properties. A significant content of polyphenols, essentially glycosides of kaempferol, quercetin, Isorhamnetin, Malvidin have identified in petals and leaves of Crocus sativus. The leaf extract revealed higher activity (IC50= 190,43 μg ml-1) for DPPH inhibition in comparison with the petals ethanolic extract (IC50= 504.26 μg ml-1). The leaf extracts gave higher antioxidant capacity (1,090 nm) measured with the FRAP assay. Our tested extracts petals displayed a strong antimicrobial activity with MIC (minimum inhibitory concentration) and MBC (minimum bactericidal concentration) values as equal as 6,25 µg/µl against Aspergillus niger and Escherichia coli. The quantitative analysis data obtained thus far have shown that Crocus sativus leaves and petals are a rich source of flavonoids. The results were showed that the by-products of C. sativus can be exploited to create a different conception of C. sativus L. The identified compounds arouse growing interest in their antioxidant and biological activity as a food supplement, in functional foods, beverages, pharmaceutical preparations, and cosmetic formulations. Farmers and local scientists may no longer view C. sativus flowers as waste but as an important resource for health-enhancing products.
Exploring the effectiveness of multimodal language pedagogy during the COVID-19 time
Authors: Yu Zhonggen
Published: May 2021

The authors have requested that this preprint be removed from Research Square.
Pulmonary Thromboembolism at Extreme High Altitude: A Study of 7 Cases
Authors: Wu Jialin , Han Xiaobo , Ke Haiwen , Wang Li , Wang Kun , Zhang Jianli , Tang Jun , Yan Wei , Wang Guangjun , Jiang Peng
Published: May 2021

Backgrounds: The high incidence of venous thromboembolic disease (VTE) in plateau area has aroused widespread concern. Through the collection and analysis of pulmonary thromboembolism (PTE) cases in extreme high altitude, to explore the epidemiological characteristics and possible risk factors of PTE in extreme plateau region.Methods: Seven cases of pulmonary thromboembolism occurring in extreme plateau region were prospectively collected in a high altitude hospital at 3800 m from May to November 2020. All patients were serving at 5000 m above sea level, and diagnosed with PTE by using computed tomography pulmonary angigraphy (CTPA).Results: Seven patients with an average age of 24±3.6 yr, the mean altitude is 5200±200 m at the onset of symptoms. And the time of them stay at high altitude between 8-210 days (99.29±77.31). Cough, expectoration, chest tightness, fever, short of breath, chest pain were the commonest symptom. 6 of 7 patients were initially diagnosed with pulmonary inflammation and 4 with HAPE by CT or X-ray. Most patients had an increase in inflammatory cells and all of them showed a high level of D-dimer in initial hematologic test during the course of the disease. Conclusions: Pulmonary thromboembolism has a high incidence in plateau areas and shows a younger age trend. Prodromal infection and high altitude pulmonary edema (HAPE) were the potential risk factors for its occurrence.
SUSTAINABLE DEVELOPMENT ACTION PROGRAM: REVIEW OF GREEN, BLUE AND
CIRCULAR ECONOMICS CONCEPTS
Authors: Mishenin Ye. , Koblianska I.
Published: May 2021

The search for a methodological basis for economic development that meets the principles of sustainable development, and its transformation into real mechanisms of functioning of socio-economic systems, is an urgent problem of our time. Against this background, in less than 20 years, different concepts have been proclaimed as action programs for the economic development of nations: green, blue and circular economiсs. At the same time, the question about the interrelation of concepts of "green", "blue" and "circular" economics remains unresolved. Are these concepts complementary or alternative? Could they be implemented simultaneously? In what way they contribute to the goals of sustainable development? What is the ability of each of these concepts to put into practice progress towards sustainable development at different levels of socio-ecological and economic systems functioning? This study aims to answer these questions through the study, generalization and critical reflection of the research results of world and domestic scientists on the content and methodological principles that form the basis of green, blue and circular economics concepts. The main features, spheres, key accents and relations of these concepts are investigated in the article. The results of the analysis give grounds to conclude that with the change of "colors" of concepts aimed at ensuring the sustainable economic development, there is a transformation of understanding of the relationship between the economy and nature. There is a movement from an anthropocentrism, which, to some extent, formed the basis of a green economy built on the implementation of green technological solutions, to an understanding of the unity and interdependence of resource movements in the natural and economic system within a circular economy. A new vision of the socio-economic system, which operates on the basis of congruence with nature, changes the model based on human dominance. The proposed solutions are becoming more and more concrete – from the general policy guidelines within the Green Economy to specific mechanisms for the transformation of business models and the use of resources in a circular economics. This illustrates the paradigm shift of economic knowledge, its adaptation for sustainable resource management, policy making and support for institutional change and, in fact, gives reason to hope for the implementation of the idea of sustainable development, i.e. the harmonization of socio-economic processes within the natural constraints.
COMPETITIVENESS OF ENTERPRISES: PREREQUISITES FOR ECOLOGIZATION
Authors: Mykhailov A. , Mykhailova L. , Stoyanets N. , Budnik D.
Published: May 2021

An important component of strengthening the competitive position of enterprises is to increase the level of greening of all economic processes. The purpose of the article is to systematize the prerequisites for the formation of environmentally friendly competitive principles. The author identifies the main transformation processes that will contribute to the formation of environmentally oriented competitiveness: development and implementation of green energy, production and promotion of green goods and services, implementation of green processes in business operations. The author substantiates that companies, that contribute to the greening of competitive advantages receive long-term benefits in the form of green brand formation, growth of the company's market capitalization. The article identifies the factors of intensification of green initiatives of enterprises, which are related to the introduction of green energy, environmental innovations, promotion of green consumption, increasing regulatory pressure on enterprises, strengthening competitive differentiation, etc. The author explored the experience of implementing environmental standards as drivers of intensifying the processes of greening competitive strategies. The article identifies and describes the basic components of the system of promoting ecologically oriented competitive advantages of enterprises in the market environment, which are determined by mechanisms for overcoming obstacles to promoting ecologically oriented activities, formation of strategic priorities, long-term transformation processes. The necessity of improvement of methodical approaches on an estimation of a level of greening of competitive advantages of the enterprise is proved. Management decisions about the necessary costs for energy saving / conservation of resources and the introduction of ecological production cause changes in economic indicators of production (cost, efficiency, product quality).Finding a compromise between economic indicators and environmental benefits of clean production will ensure the formation of green competitive advantages of the enterprise.
The investigation of bacterial adhesion of palatine tonsils epithelial cells in patient with infectious mononucleosis
Authors: Nadraga Aleksandr , Lutsyk Aleksandr , Klymenko Khrystyna , Khomyn Olena
Published: May 2021

Aim. To evaluate the features of pharynx tonsils mucous membrane colonization by pathogenic and opportunistic microorganisms by using the pharynx palatine tonsils epithelium electron microscopic examination of the patients with infectious mononucleosis and acute streptococcal tonsillitis.

Materials and methods. Two patients – patient P., 12 years old with a confirmed diagnosis of infectious mononucleosis and patient A., 8 years old with confirmed acute streptococcal tonsillitis. The patients were taken a bacteriological examination of the mucus and epithelium scraping from the surface of the pharyngeal tonsils. Tissue samples were examined in the electron microscopy laboratory of the Lviv National University.

Results and discussion. 36 tonsils epithelial tissue micro preparations of patient A. and 41 micro preparations of patient P. were studied. Streptococcus pyogenes, Str. pneumoniae, Str. viridans, Сandida albicans, as well as non-pathogenic bacteria: Diphtheroides sp., Neisseria sp., Corynebacterium spp. were identified as result of the patient P. bacteriological examination of mucus from the surface of the pharyngeal tonsils. Staph. aureus, Str. viridans, Str. pneumoniae were identified during a bacteriological examination of patient A. Eosinophils with a two-segmented nucleus, specific granularity, phagocytosed spherical bacteria in the cytoplasm were detected during the histological examination of the materials taken from the surface of the patient’s tonsils with acute tonsillitis. Research showed that bacteria were accumulated not only in the structure of extracellular detritus. Numerous bacteria accumulations were also found in the cytoplasm of the epithelial cells in the patient with infectious mononucleosis. The cell's shape looked like a bunch of grapes.

Conclusions. The electron microscopic examination showed differences in the coccal flora localization: the extracellular localization of bacteria in the patient with acute bacterial tonsillitis and intraepithelial presence of the bacteria in the patient with tonsillitis during infectious mononucleosis were found.
Fatal hemolytic transfusion reaction due to anti-Ku in a Knull patient
Authors: Lin M. , Wang C.L. , Chen F.S. , Ho L.H.
Published: May 2021

A fatal transfusion reaction due to anti-Ku in a Knull (Ko) patient is reported. The patient was transfused with 34 units of incompatible RBCs during 44 days of hospitalization. Apart from the first transfusion, all subsequent transfusions failed to raise the patient’s Hb.No serum antibody was identified until he was transferred to another hospital for dialysis. A compatibility test demonstrated a weak antibody and autocontrol reacting at room temperature by a manual polybrene method. The antibody was considered to be a “cold agglutinin.” A blood sample was sent to a reference laboratory where the patient was found to be Knull and the antibody was identified as anti-Ku.
Immunohematology 2003;19:19–21.
DNA analysis for donor screening of Dombrock blood group antigens
Authors: Storry J.R. , Westhoff C.M. , Charles-Pierre D. , Rios M. , Hue-Roye K. , Vege S. , Nance S. , Reid M.E.
Published: May 2021

Due to the scarcity of reliable antibodies, RBC typing for Doa and Dob is notoriously difficult. Inaccurate typing can place patients at risk for hemolytic transfusion reactions. The molecular basis of the DOA/DOB polymorphism is associated with three nucleotide changes: 378C>T, 624 T>C,and 793 A>G of DO. While the 378 C>T and 624 T>C are silent mutations, the 793A>G polymorphism in codon 265 encodes asparagine for Doa and aspartic acid for Dob. We describe here the use of a PCR-RFLP assay as an alternative to traditional hemagglutination for typing donor blood for Dombrock. Primers were designed to amplify the region of DO containing the 793A>G polymorphism. DNA samples from blood donors were amplified and subjected to RFLP analysis. A total of 613 samples were tested for the Dombrock polymorphism (793 A>G) by PCR-RFLP. PCR-RFLP can be used to screen for Do(a–) or Do(b–) donors. This approach overcomes the scarcity of the reagents required for testing by hemagglutination.
Murine monoclonal antibodies can be used to type RBCs with a positive DAT
Authors: Halverson G.R. , Howard P. , Malyska H. , Tossas E. , Reid M.E.
Published: May 2021

Keywords

RBCs with a positive DAT due to IgG coating require the use of directly agglutinating reagents or treatment with chemicals to remove sufficient IgG to permit typing of the RBCs with antisera that require use of the IAT. In this study we demonstrate that murine IgG MoAbs to human RBC antigens can be used as an alternative if the anti-mouse IgG is neutralized or affinity purified to prevent cross-reaction with cell-bound IgG. We performed DATs on RBC samples coated with IgG in vivo and in vitro, comparing two anti-human IgG reagents (Organon Teknika, Durham, NC, and Ortho-Clinical Diagnostics, Raritan, NJ) with two affinity-purified anti-mouse IgG reagents (The Binding Site, San Diego, CA, and Sigma, St. Louis, MO), and one non-purified anti-mouse IgG reagent. The affinity-purified anti-mouse IgG reagents were nonreactive with the four in vitro sensitized RBC samples and were nonreactive with 8 of 11 in vivo sensitized RBC samples. Non-purified antimouse IgG and both anti-human IgG reagents reacted with every sample. Use of murine MoAbs to antigen type RBCs coated with human IgG is reliable only when the anti-mouse IgG reagents have been affinity purified or neutralized to prevent cross-reactivity. Our results also show the importance of including a saline/RBC control as well as an anti-mouse IgG/RBC control. Murine MoAbs are valuable reagents and we have applied them successfully in typing patients’ RBCs that have a positive DAT.
Loss of enzyme-sensitive antigens due to the presence of leukocytes, neomycin sulfate, and LISS
Authors: Velliquette R.W. , Howard P. , Malyska H. , Reid M.E.
Published: May 2021

Previous studies have shown that RBCs with residual WBCs stored in LISS and neomycin sulfate develop characteristics associated with enzyme-treated RBCs. During a mass screening program to antigen type donor RBCs, we observed that the Fya antigens on a RBC sample from an in-house panel became non-detectable with anti-Fya after incubation overnight in Diluent 2 from Micro Typing Systems, Inc. (MTS, Pompano Beach, FL). In response to this observation, we initiated an investigation to determine the cause. Tests were performed according to the manfacturer’s instructions in MTS neutral gel cards or gel cards containing anti-IgG. We found that a reduction or loss of the Fya, Fyb, and M antigens occurs when RBCs were prepared from samples containing residual WBCs (as a source of enzymes) and subsequently incubated in media containing neomycin sulfate and LISS. We showed that the effect did not occur in the absence of neomycin sulfate. RBC antigens can be altered in LISS if they have first been exposed to neomycin. We recommend restricting the use of RBCs suspended in MTS Diluent 2 to the day of dilution (as indicated in the package insert) if preparing reagent RBCs from sources that were not leukoreduced and were stored in the presence of neomycin.