bluuebunny/crossref_metadata_2025 huggingface dataset:
Circ_0030998 Promotes Tumor Proliferation and Angiogenesis by Sponging miR-567 to Regulate VEGFA in Colorectal Cancer
Authors: Jin Longyang , Han Chao , Zhai Tianyu , Zhang Xiaoyu , Chen Chun , Lian Lei
Published: October 2020

BackgroundColorectal cancer (CRC) is one of the most common malignancies worldwide. Accumulating studies have demonstrated that circular RNAs (circRNAs), a novel class of noncoding RNAs, are involved in pathological processes, especially in the development of cancers. But the roles of circRNAs in CRC are largely unknown.MethodsThe microarray data GSE138589 was analyzed and qRT-PCR was performed to screen out the circRNA with the highest upregulated level in CRC. QRT-PCR was used to determine the expression of genes in different tissues or cells. RNA-FISH was conducted to identify the subcellular localization of Circ_0030998. In vitro and in vivo assays were performed to determine the effect of Circ_0030998 on the CRC cells proliferation and angiogenesis. The relationships of Circ_0030998, miR-567 and VEGFA were predicted and validated using bioinformatic tools, RIP and luciferase assays.ResultsWe identified a novel circRNA, Circ_0030998, was upregulated in CRC tissues and cells, and its upregulation was related with poor prognosis in CRC patients. Circ_0030998 promoted CRC cells proliferation and angiogenesis. RNA-FISH showed that Circ_0030998 was mainly localized in the cytoplasm of CRC cells. Mechanistic studies demonstrated that Circ_0030998 acted as a miR-567 sponge to relieve its inhibitory effect on VEGFA. Rescue assays validated that Circ_0030998 functioned in CRC cells proliferation and angiogenesis relying on VEGFA.ConclusionsThe present study clarified the Circ_0030998/miR-567/VEGFA regulation axis and indicated that Circ_0030998 could be a potential therapeutic target for CRC.
A Novel Immune Classification Reveals Distinct Immune Escape Mechanism and Genomic Alterations: Implications for Immunotherapy in Hepatocellular Carcinoma
Authors: Liu Zaoqu , Zhang Yuyuan , Shi Chengcheng , Zhou Xueliang , Xu Kaihao , Jiao Dechao , Sun Zhenqiang , han xinwei
Published: October 2020

BackgroundThe tumor immunological microenvironment (TIME) has a prominent impact on prognosis and immunotherapy. However, the heterogeneous TIME and the mechanisms by which TIME affects immunotherapy have not been elucidated in hepatocellular carcinoma (HCC).MethodsA total of 2195 eligible HCC patients from TCGA and GEO database were collected. We comprehensively explored the different heterogeneous TIME phenotypes and its clinical significance. The potential immune escape mechanisms and what genomic alterations may drive the formation of different phenotypes were further investigated.ResultsWe identified three phenotypes in HCC: TIME-1, the “immune-deficiency” phenotype, with immune cell depletion and proliferation; TIME-2, the “immune-suppressed” phenotype, with being in immunosuppressive states; TIME-3, the “immune-activated phenotype”, with abundant leukocytes infiltration and immune activation. The prognosis and sensitivity to both sorafenib and immunotherapy differed among the three phenotypes. We also underlined the potential immune escape mechanisms: lack of leukocytes and defective tumor antigen presentation capacity in TIME-1, increased immunosuppressive cells in TIME-2, and rich in immunoinhibitory molecules in TIME-3. The different phenotypes also demonstrated specific genomic events: TIME-1 characterized by TP53, CDKN2A, CTNNB1, AXIN1 and FOXD4 alterations; TIME-2 characterized by significant alteration patterns in the PI3K pathway; TIME-3 characterized by ARID1A mutation. Besides, the TIME index (TI) was proposed to quantify TIME infiltration pattern, and it was a superior prognostic and immunotherapy predictor. ConclusionsWe identified three TIME phenotypes with different clinical outcomes, immune escape mechanisms and genomic alterations in HCC, which could present strategies for improving the efficacy of immunotherapy. TI as a novel prognostic and immunotherapeutic signature that could guide personalized immunotherapy and clinical management of HCC.
Keywords Reflecting Sepsis Presentation and Mode of Emergency Department Arrival: A Retrospective Cross-sectional Study
Authors: Wallgren Ulrika Margareta , Larsson Eric , Su Anna , Short Jennifer , Järnbert-Pettersson Hans , Kurland Lisa
Published: October 2020

Background: Current sepsis screening tools rely predominantly on vital signs. Since patients with serious infections frequently present with normal vital signs there is a need for other variables to be included to detect sepsis. As a first step, it is essential to understand the clinical presentation of septic patients. The aim was to compare the prevalence of keywords reflecting the clinical presentation of sepsis and mode of arrival, among septic patients presenting to the emergency department. Methods: Retrospective cross-sectional study of 479 adult septic patients. Keywords reflecting sepsis presentation upon emergency department arrival were quantified and analyzed based on mode of arrival, i.e. by emergency medical services or by other means. We adjusted for multiple comparisons by applying Bonferroni-adjusted significance levels for all comparisons. Adjustments for age, gender and sepsis severity were performed by stratification. All patients were admitted to the emergency department of Södersjukhuset, Stockholm, and discharged with an ICD-10 code compatible with sepsis between January 1stand December 31st, 2013. Results: “Abnormal breathing” (51.8% vs 20.5%, p-value <0.001), “abnormal circulation” (38.4% vs 21.3%, p-value <0.001), “acute altered mental status” (31.1% vs 13.1%, p-value <0.001) and “decreased mobility” (26.1% vs 10.7%, p-value <0.001) were more common among patients arriving by emergency medical services, while “pain” (71.3% vs 40.1%, p-value <0.001) and “risk factors for sepsis” (50.8% vs 30.8%, p-value <0.001) were more common among patients arriving by other means.Conclusions: The distribution of most keywords related to sepsis presentation was similar irrespective of mode of arrival, however, some differences were present. This information may be useful in clinical decision tools or sepsis screening tools.
Major Challenges and Barriers in Clinical Decision-making as Perceived by Emergency Medical Services Personnel: A Qualitative Content Analysis
Authors: bijani Mostafa , Abedi Saeed , Karimi Shahnaz , Tehranineshat Banafsheh
Published: October 2020

Background: Having to work in unpredictable and critical conditions, emergency care services (EMS) personnel experience complicated situations at the scene of accidents which, inevitably, influence their clinical decisions. There is a lack of research into the challenges which these professionals encounter. Accordingly, the present study aims to explore the major challenges and barriers which affect clinical decision-making from the perspective of EMS personnel. Methods: The present study is a qualitative work with a content analysis approach. Selected via purposeful sampling, the subjects were 25 members of the EMC personnel in Iran who met the inclusion criteria. The study lasted from December 2019 to July 2020. Sampling was maintained to the point of data saturation. Data were collected using semi-structured, in-depth, individual interviews. The collected data were analyzed via qualitative content analysis. Results: 4 main categories—professional capabilities, occupational and environmental factors, inefficient organizational management, and ethical issues—and 23 subcategories were extracted from the findings of the study. Conclusion: The results of the present study show that personal and occupational factors, organizational management, and ethical issues are the most significant sources of challenge which affect the clinical decision-making and, consequently, the performance of EMC personnel at the scene of accidents. Thus, it is essential that pre-hospital emergency care managers improve the quality of EMC personnel’s clinical decision-making skills and the reliability of care provided by them by creating the right professional and organizational settings, free of occupational distress.
Impact of Probiotic B. Infantis EVC001 Feeding in Premature Infants on the Gut Microbiome, Nosocomially Acquired Antibiotic Resistance, and Enteric Inflammation
Authors: Nguyen Marielle , Holdbrooks Heaven , Mishra Prasanthi , Abrantes Maria , Eskew Sherri , Garma MariaJamiela , Oca Cyr-Geraurd , McGuckin Carrie , Hein Cynthia , Mitchell Ryan , Kazi Sufyan , Chew Stephanie , Casaburi Giorgio , Brown Heather , Frese Steve , Henrick Bethany Michele
Published: October 2020

BackgroundPreterm birth is a major determinant of neonatal survival and morbidity, but the gut microbiome and associated enteric inflammation are also key factors in neonatal development and the risk of associated morbidities. We prospectively and longitudinally followed two cohorts of preterm infants, one of which was fed Bifidobacterium longum subsp. infantis (B. infantis) EVC001 daily, and the other was not fed a probiotic. Hospital feeding protocol assigned all infants born at less than 1500g and/or 34 weeks corrected gestational age to the probiotic feeding protocol, whereas infants born at > 1500g and/or 34 weeks corrected gestational age were not fed a probiotic. Fecal samples collected opportunistically (approximately 2 samples per week) throughout the hospital stay were analyzed from 292 samples collected from 77 infants. Fecal samples were subjected to shotgun metagenomic sequencing and quantification of enteric inflammation markers. We also collected de-identified metadata from patient medical records.ResultsThe gut microbiome of preterm infants was typified by a high abundance of Enterobacteriaceae and/or Staphylococcaceae and multivariate modeling identified the probiotic intervention, rather than degree of prematurity, day of life, or other clinical interventions as the primary source of change in the gut microbiome. Among infants fed B. infantis EVC001, a high abundance of total Bifidobacteriaceae developed rapidly, the majority of which was B. infantis confirmed via subspecies-specific qPCR. Associated with this higher abundance of Bifidobacteriaceae, we found increased functional capacity for utilization of human milk oligosaccharides (HMOs), as well as reduced abundance of antibiotic resistance genes (ARGs) and the taxa that harbored them. Importantly, we found that infants fed B. infantis EVC001 experienced diminished enteric inflammation, even when other clinical variables were accounted for using multivariate modeling.ConclusionThese results provide an important observational background for probiotic use in a NICU setting, and describe the clinical, physiological, and microbiome-associated improvements in preterm infants associated with B. infantis EVC001 feeding.
Identifying the Dynamic Pattern and Influencing Factors of Influenza in Northwest China from 2013 to 2020, Based on Dynamic Regression Model and Wavelet Analysis
Authors: Wang Ruonan , Du Jiancai , Li Jiangping , Zhang Yajuan , Wen Jing , Zhao Yu
Published: October 2020

Background: Influenza remains a serious global public health problem and a substantial economic burden. The dynamic pattern of influenza differs considerably among geographic and climatological areas, however, the factors underlying these differences are still uncertain. The aim of this paper is to characterize the dynamic pattern of influenza and its potential influencing factors in Northwest China. Methods: Influenza cases in Ningxia China from Nov. 2013 to Jun. 2020 were served as influenza proxy. Firstly, the baseline seasonal ARIMA model of influenza cases and seasonal pattern were analyzed. Then, the dynamic regression model was used to identifying the potential influencing factors of influenza. In addition, the wavelet analysis was further used to explore the coherence between influenza cases and these significant influencing factors.Results: The high risk periods of influenza in Ningxia presented a winter cycle outbreaks pattern and the fastigium came in January. The seasonal ARIMA(0,0,1)(1,1,0)12 was the optimal baseline forecast model. The dynamic regression models and wavelet analysis indicated that PM2.5 and public awareness are significantly positively associated with influenza, as well as minimum temperature is negatively associated. Conclusion: Meteorological (minimum temperature), pollution (PM2.5) and social (public awareness) factors may significantly associated with influenza in Northwest China. Decreasing PM2.5 concentration or increasing the public awareness prior to the fastigium of influenza may be the serviceable methods to reduce the disease risk of influenza, which have an important implication for policy-makers to choose an optimal time for influenza prevention campaign.
Evaluation of gene mutations in resistant strains of Mycobacterium tuberculosis isolated from pulmonary tuberculosis patients in Mazandaran and Golestan provinces of Iran - a 2-year study
Authors: Alikhani Ahmad , Amini Elnaz , Arabi Mohsen , Goli Hamid Reza
Published: October 2020

Background: Due to the significant prevalence of tuberculosis (TB) in Mazandaran and Golestan provinces in northern Iran, we aimed to investigate the gene mutations in resistant Mycobacterium tuberculosis isolated from pulmonary TB patients in these provinces of Iran. Methods: In this cross-sectional study, sputum of patients with suspected tuberculosis were evaluated in the central TB laboratory of Golestan in a period of two years from 2017 to 2019. After growing the isolates on Lowenstein-Jensen medium, the antibiotic-resistant cases identified using the resistance ratio method. Then, the DNAs of the resistant isolates were extracted manually by the CTAB-Proteinase K method and investigated for gene mutations using PCR test and sequencing.Results: The mean age of 26 patients was 52 years, while smoking, addiction, and diabetes were more common risk factors. However, 4 isolates (15.38%) were resistant to antibiotics, while one (3.84%) of them was resistant to rifampin, and two isolates (7.69%) were resistant against isoniazid, whereas one other isolate (3.84%) exhibited a multidrug-resistant (MDR) phenotype. The MDR isolate had a mutation in codon 315 of the KatG gene resulting in the conversion of serine to threonine, and a mutation in the codon 450 of the rpoB gene, causing the alteration of serine to leucine. In the rifampin-resistant isolate, a mutation occurred at the same site converting serine to leucine. Conclusions: The low prevalence of antibiotic resistance in clinical isolates of Mycobacterium tuberculosis in this study indicates the appropriate treatment of the patients in this area, however, the prevalence of resistance to isoniazid was higher than rifampin. The more important point was that the single MDR isolate was identified in Mazandaran province.
Prevalence of UL97 gene mutations in cytomegalovirus reactivation in the colon associated with or without ulcerative colitis
Authors: Tamura Satoshi , Osawa Satoshi , Ishida Natsuki , Miyazu Takahiro , Suzuki Satoshi , Tani Shinya , Yamade Mihoko , Iwaizumi Moriya , Hamaya Yasushi , Kosugi Isao , Furuta Takahisa , Miyajima Hiroaki , Sugimoto Ken
Published: October 2020

Background: Cytomegalovirus (CMV) reactivation in the colon is common in patients with severe ulcerative colitis (UC) and in immunocompromised patients, and may be associated with poor prognosis. Ganciclovir (GCV) resistance conferring CMV UL97 gene mutations have been reported in recent years. However, the prevalence of UL97 gene mutations in GCV-naive CMV colitis remains to date unknown. The present study aimed to investigate the prevalence of CMV UL97 gene mutations in Japanese patients with colonic CMV infection associated with or without UC.Methods: Twenty-two GCV-naive patients with colonic CMV infection, 15 with UC and 7 with other diseases, were enrolled. Frozen biopsy samples or formalin-fixed paraffin-embedded samples were used for nested polymerase chain reaction (PCR) amplification of the UL97 gene. Sanger DNA sequencing of the PCR products was performed.Results: UL97 mutations were frequently detected in codons T75A (95.5%), Q126L (86.4%), and D605E (86.4%), and less frequently (<10%) in L228P, D263G, A53S, R137C, A140V, G188S, A674T, and T675A. However, no known GCV resistance mutations were found. There was no significant difference between the ratio of mutations in patients with and without UC.Conclusions: We did not detect UL97 gene mutations associated with GCV resistance in GCV-naive patients with or without UC. In contrast, T75A, Q126L, and D605E mutations may be used as genetic markers for CMV in East Asian countries.
Surface Functionalization of Thermoset Composite for Infrared Hybrid Welding
Authors: PERRIN Henri , Mertz Grégory , Senoussaoui Noha-Lys , Borghini Loïc , Klein Sébastien , Vaudemont Régis
Published: October 2020

Fusion assembly is a highly promising technique to join thermoplas- tic to thermoset composites, enabling the use of both the most affordable com- posite material and process for each sub structure.Yet, some major challenges need to be pull through such as the functionalizing of the thermoset compos- ite surface by co-curing an appropriate thermoplastic interlayer or realizing a fast and robust welding process that fulfils all quality and mechanical require- ments. In the present paper, we investigated the potential of Polyetherether- ketone (PEEK) and its amorphous (PEEK A) and semi-cristalline (PEEK SC) states as interlayer materials, co-cured onto the thermoset composite. A surface preparation by atmospheric plasma process demonstrated that both PEEK state materials can be used as interlayer with auspicious resulting ad- hesion properties. The influence of the plasma treatment on surface properties and morphology is also experimentally characterized. An infrared (IR) welding process, barely studied in the literature, is studied to assemble hybrid struc- tural composite. In order to avoid the expected thermal degradation of the thermoset matrix, a dissimilar infrared heating input power is proposed. More- over, to decrease the possible thermal degradation of the thermoset composites during the fusion bonding, a dissimilar infrared welding process have been ex- plored. Single lap shear test and failure mode analysis have been performed to highlight the promising performance of PEI as well as PEEK interlayer based hybrid joint.
WITHDRAWN: Effects of Satureja Edmondi Briq on Ameliorate Reproductive Parameters in Pentylenetetrazol-Induced Epilepsy Models in Rats
Authors: bohlouli somayeh , mahmoodi gelavij
Published: October 2020

BackgroundEpilepsy is one of the common neurological brain defects that causes unpredictable, recurrent seizures. It has adverse effects on the reproductive functions.Oxidative stress contributes to the evolution of epilepsy, including reduction of sperm count and motility,increase of abnormal sperm morphology, and low testosterone.Antioxidants are beneficial to spermatogenesis and sperm parameters. Satureja edmondiBriq is known as a powerful antioxidant that can reduce the effects of oxidative stress. The aim of this study was to evaluate the effects of Satureja edmondion reproductive potential in pentylenetetrazol (PTZ)-induced epileptic male rats.MethodsIn this experimental study, 48 Wistar male rats with an average age of 10 weeks and weightof 240- 260g were used. Animals were randomized into normal and kindled groups that were treated with different doses of S.edmondi essential oil. Treatment of animals lasted 4 weeks. In the end, testosterone, follicle-stimulating hormone, luteinizing hormone, and sperm parameters were measured according to the World Health Organization (WHO) standards.ResultsThis study showed that all sperm parameters,including sperm count, sperm viability, and progressive sperm motility were increased and testosterone, follicle-stimulating hormone and luteinizing hormone (FSH,LH) changes in the epileptic and normal groups were changed with an increase in the dose of S.edmondi essential oil. ConclutionsThe changes were significant in some parameters. S.edmondi as a good source of antioxidants can improve sperm parameters and reproductive potential in PTZ-induced epileptic male rats.
A 10-Year Follow-Up on the Practice of Luteal Phase Support Using Worldwide Web-Based Surveys
Authors: Shoham Gon , Leong Milton , Weissman Ariel
Published: October 2020

BackgroundIt has been demonstrated that luteal phase support (LPS) is crucial in filling the gap between the disappearance of exogenously administered hCG for ovulation triggering and the initiation of secretion of endogenous hCG from the implanting conceptus. LPS has a pivotal role of in establishing and maintaining in vitro fertilization (IVF) pregnancies. Over the last decade, a plethora of studies bringing new information on many aspects of LPS have been published. Due to lack of consent between researchers and a dearth of robust evidence-based guidelines, we wanted to make the leap from the bench to the bedside, what are the common LPS practices in fresh IVF cycles compared to current evidence and guidelines? How has expert opinion changed over 10 years in light of recent literature?MethodsOver a decade (2009 - 2019), we conducted 4 web-based surveys on a large IVF-specialist website on common LPS practices and controversies. The self-report, multiple-choice surveys quantified results by annual IVF cycles.ResultsOn average, 303 IVF units responded to each survey, representing, on average, 231,000 annual IVF cycles. Most respondents in 2019 initiated LPS on the day of, or the day after egg collection (48.7% and 36.3%, respectively). In 2018, 72% of respondents administered LPS for 8-10 gestational weeks, while in 2019, 65% continued LPS until 10-12 weeks. Vaginal progesterone is the predominant delivery route; its utilization rose from 64% of cycles in 2009 to 74.1% in 2019. Oral P use has remained negligible; a slight increase to 2.9% in 2019 likely reflects dydrogesterone’s introduction into practice. E2 and GnRH agonists are rarely used for LPS, as is hCG alone, limited by its associated risk of ovarian hyperstimulation syndrome (OHSS). ConclusionsOur Assisted reproductive technology (ART)-community survey series gave us insights into physician views on using progesterone for LPS. Despite extensive research and numerous publications, evidence quality and recommendation levels are surprisingly low for most topics. Clinical guidelines use mostly low-quality evidence. There is no single accepted LPS protocol. Our study highlights the gaps between science and practice and the need for further LPS research, with an emphasis on treatment individualization.
Protective effect of high n-3/n-6 PUFA ratio on acute hypoxic-ischemic brain damage in mfat-1 transgenic mice and possible inflammation-related targets identified by transcriptome analysis
Authors: geng xue , Wang Meng , Leng Yunjun , Li Lin , Yang Haiyuan , Dai Yifan , Wang Ying
Published: October 2020

BackgroundAcute hypoxic-ischemic brain damage (HIBD) occurs not only in newborns but also in adults. It is associated with series of cellular and biochemical pathways that lead to neuronal injury. N-3 polyunsaturated fatty acids (PUFAs) have been reported to improve neuron functions via G protein-coupled receptor 120 signal pathway in cells or with exogenous supplementation. Possible protective targets and underlying mechanisms of high proportion of n-3/n-6 PUFAs contained in the brains of mfat-1 transgenic mice on HIBD-induced adult brain damage needed to be further investigated.MethodsThe adult C57BL/6J (WT) and mfat-1 transgenic mice adopted HIBD model. A gas chromatograph was used to determine the composition of PUFAs. Neurological deficit scores test, TTC staining and Nissl staining were employed to evaluate the neuroprotective effects. Cleaved-caspase3 and TUNEL experiment were used to detect apoptosis after injury. Inflammatory factors were detected by ELISA assay. RNA-sequencing analysis was processed and the differential expressed genes were verified by real-time quantitative PCR. Key factors related to inflammation were detected by immunofluorescence and western blot.ResultsThe mfat-1 transgenic mice with high ratio of n-3/n-6 PUFAs in brain tissues were showed to have protective effects on HIBD-induced brain damage by reduced infarct range and greatly improved neurobehavioral defects. Further analysis revealed that the level of neuronal necrosis, apoptosis and inflammation induced by brain injury were relatively low. RNA-seq analysis showed multiple pathways and targets involved in this process. Significant activation of GPR120, reduction of phosphorylation of TAK1 and NF-κB P65 in the downstream of the pro-inflammatory pathway were found in the brains of mfat-1 mice on HIBD. ConclusionsThe study showed that mfat-1 transgenic mice had protective effects on HIBD-induced brain injury by multiple pathways. Activation of GPR120 and reduction of related pro-inflammatory pathway involved in this process, which may improve or prevent dangerous perioperative and postoperative complications, innovate clinical intervention strategy and potentially benefit more patients.
PAK4 Suppresses Motor Neuron Degeneration in hSOD1G93A -Linked ALS Cell and Rat Models
Authors: Cong Chaohua , Liang Weiwei , Zhang Chunting , Wang Ying , Yang Yueqing , Wang Xudong , Wang Shuyu , Huo Di , Wang Hongyong , Wang Di , Feng Honglin
Published: October 2020

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of upper and lower motor neurons. The exact mechanisms underlying motor neuron death in ALS are still not fully understood, but a growing body of evidence indicates that inflammatory could accentuate disease severity and accelerate disease progression. Currently, no neuroprotective strategies have effectively prevented the progression of this disease.Methods: IF, western blotting and RT-PCR were used to analyze the expression of PAK4 in vitro and in vivo models of ALS. We examined PAK4 function in ALS and the underlying mechanism by cell transfection, intraspinally injection of LV-PAK4 in hSOD1G93A mice, flow cytometry, TUNEL staining, IF and western blotting.Results: Here, we observed that the expression and activity of PAK4 significantly decreased in hSOD1G93A-related cell and mouse models of ALS. In hSOD1G93A mice，the expression of PAK4 began to decrease at early-symptom stages of the disease. PAK4 silencing increased degeneration of motor neurons (NSC34 cells) and suppressed the CREB pathway. Overexpression of PAK4 protected motor neurons from hSOD1G93A-induced degeneration by increasing the levels and transcriptional activity of CREB. The neuroprotective effect of PAK4 was markedly inhibited by compound 3i, a specific CREB inhibitor. In hSOD1G93A-linked cell and mice, the CREB pathway, as the downstream target of decreased PAK4, was inhibited, and cell apoptosis increased. We also found that the expression of PAK4 was negatively regulated by miR-9-5p, and the miR-9-5p levels were upregulated in ALS. In vivo experiments revealed that PAK4 overexpression in the spinal neurons of hSOD1G93A mice suppressed motor neuron degeneration, prolonged survival and promoted the CREB pathway. Conclusion: These results indicate that PAK4 plays a protective role for motor neurons by targeting CREB, suggesting it may be a useful therapeutic target in ALS.
Malignant tumor purity reveals the correlation between CD3E and low grade glioma microenvironment
Authors: Liu WangRui , Li Chuanyu , Xu Wenhao , Lian Hao , Qu Yuanyuan , Chen Kui , Huang Huadong , Huang Haineng , Zhong Chunlong
Published: October 2020

Background: Tumor microenvironment (TME) contributes to the initiation and progression of low grade glioma (LGG); however, we are still unclear about the specifics of LGG's TME. Methods: In this article, we selected 161 LGG patients from the Cancer Genome Atlas (TCGA) as data, and calculated the percentage of tumor infiltrating immune cells (TICs) in LGG and the tumor purity of LGG through ESTIMATE and CIBERSORT calculation methods. Immune-related genes were screened out through Cox regression and protein-protein interaction (PPI) network. The data in Gene Expression Omnibus (GEO) was selected to screen out clinically relevant genes. After combining the two, CD3E is selected as the predictor. Finally, we conducted verification at the Affiliated Hospital of YouJiang Medical University for Nationalities (AHYMUN) center. Results: We found that the higher the expression of CD3E, the lower the purity of LGG tumors and the worse the prognosis of patients. Gene Set Enrichment Analysis (GSEA) showed that genes in the high-expressing CD3E group are mainly involved in immune-related activities. This suggests that CD3E may be responsible for regulating LGG's TME and tumor purity.Conclusion: In short, the tumor purity of LGG has a considerable impact on clinical, genomic and biological status. The expression level of CD3E may help doctors evaluate the prognosis of LGG patients and develop personalized immunotherapy plans for patients. Evaluating the ratio of different tumor purity and the new role of CD3E may provide additional insights into the complex role of the LGG microenvironment and clinical treatment.
Impact of gestational diabetes mellitus diagnosed during the third trimester on pregnancy outcomes: A case control study
Authors: Shindo Ryosuke , Aoki Shigeru , Nakanishi Sayuri , Misumi Toshihiro , Miyagi Etsuko
Published: October 2020

Background: In 2010, the International Association of Diabetes and Pregnancy Study Group (IADPSG) proposed new criteria indicating that gestational diabetes mellitus (GDM) can be diagnosed if the fasting threshold of ≤92 mg/dL, 1-hour threshold of ≤180 mg/dL, or 2-hour threshold of ≤153 mg/dL are exceeded during the 75-g 2-hour oral glucose tolerance test (OGTT) performed at 24–28 weeks of gestation. The World Health Organization (WHO) recommends using the proposed diagnostic threshold values of the IADPSG to diagnose GDM, but it does not limit the timing of the 75-g OGTT. Since 2010 in Japan, GDM has been diagnosed using the same criteria as that proposed by the WHO. Nevertheless, there is no justification for these thresholds during specific time windows.Methods: This was a single-centre retrospective study based on the medical records and delivery registry database of our centre. We included women who underwent a 50-g glucose challenge test (GCT) with results <140 mg/dL at 24–28 weeks of gestation and subsequently underwent a 75-g OGTT after 29 weeks of gestation with abnormal glucose tolerance suspected based on clinical findings. The reference values for the 75-g OGTT followed the IADPSG criteria. Subjects were classified as the normal glucose tolerance (NGT) group and the GDM group. The type of delivery and neonatal outcomes of the two groups were compared. A multivariable analysis was performed to match the backgrounds of both groups.Results: A total of 189 women comprised the NGT group and 49 women comprised the GDM group. Emergency caesarean delivery rates were similar in the GDM and NGT groups (10.6% and 12.2%, respectively; adjusted odds ratio [OR], 1.25; 95% confidence interval [CI], 0.43-3.64; p=0.74), but the elective caesarean delivery rate was higher in the GDM group than in the NGT group (16.3% and 5.3%, respectively, adjusted OR, 3.60; 95% CI, 1.27-10.19; p=0.01). There were no differences in other maternal and neonatal outcomes between groups.Conclusion: Whether diagnosing GDM during the third trimester can improve pregnancy outcomes is unknown. However, pregnant women diagnosed with GDM during the third trimester are more likely to undergo caesarean delivery.
Balancing Scarce Hospital Resources During a Pandemic: A Case-Study of COVID-19 at Addenbrooke’s Hospital (UK)
Authors: Melman George J. , Parlikad Ajith K. , Cameron Ewen A.B.
Published: October 2020

COVID-19 has disrupted healthcare operations and resulted in large-scale cancellations of elective surgery. Hospitals throughout the world made life-altering resource allocation decisions and prioritised the care of COVID-19 patients. Without effective models to evaluate resource allocation strategies encompassing COVID-19 and non-COVID-19 care, hospitals face the risk of making sub-optimal local resource allocation decisions. A discrete-event-simulation model is proposed in this paper to describe COVID-19, elective surgery, and emergency surgery patient flows. COVID-19-specific patient flows and a surgical patient flow network were constructed based on data of 475 COVID-19 patients and 28,831 non-COVID-19 patients in Addenbrooke's hospital in the UK. The model enabled the evaluation of three resource allocation strategies, for two COVID-19 wave scenarios: proactive cancellation of elective surgery, reactive cancellation of elective surgery, and ring-fencing operating theatre capacity. The results suggest that a ring-fencing strategy outperforms the other strategies, regardless of the COVID-19 scenario, in terms of total direct deaths and the number of surgeries performed. However, this does come at the cost of 50% more critical care rejections. In terms of aggregate hospital performance, a reactive cancellation strategy prioritising COVID-19 is no longer favourable if more than 7.3% of elective surgeries can be considered life-saving. Additionally, the model demonstrates the impact of timely hospital preparation and staff availability, on the ability to treat patients during a pandemic. The model can aid hospitals worldwide during pandemics and disasters, to evaluate their resource allocation strategies and identify the effect of redefining the prioritisation of patients.
Reducing the use of empiric antibiotic therapy in patients on admission to the hospital with COVID-19
Authors: Pettit Natasha N. , Nguyen Cynthia T. , Lew Alison , Bhagat Palak B. , Nelson Allison , Olson Gregory , Ridgway Jessica , Pho Mai T. , Pagkas-Bather Jade
Published: October 2020

Background: Empiric antibiotics for community acquired bacterial pneumonia (CABP) are often prescribed to patients with COVID-19, despite a low reported incidence of co-infections. Stewardship interventions targeted at facilitating appropriate antibiotic prescribing for CABP among COVID-19 patients are needed. We developed a guideline for antibiotic initiation and discontinuation for CABP in COVID-19 patients. The purpose of this study was to assess the impact of this intervention on the duration of empiric CABP antibiotic therapy among patients with COVID-19.Methods: This was a single-center, retrospective, quasi-experimental study of adult patients admitted between 3/1/2020 to 4/25/2020 with COVID-19 pneumonia, who were initiated on empiric CABP antibiotics. Patients were excluded if they were initiated on antibiotics >48hours following admission or if another infection was identified. The primary outcome was the duration of antibiotic therapy (DOT) prior to the guideline (March 1 to March27, 2020) and after guideline implementation (March 28 to April 25, 2020). We also evaluated the clinical outcomes (mortality, readmissions, length of stay) among those initiated on empiric CABP antibiotics.Results: A total of 506 patients with COVID-19 were evaluated, 102 pre-intervention and 404 post-intervention. Prior to the intervention, 74.5% (n=76) of patients with COVID-19 received empiric antibiotics compared to only 42% of patients post-intervention (n=170), p<0.001. The median DOT in the post-intervention group was 1.3 days shorter (p<0.001) than the pre-intervention group, and atypical antibiotic DOT was reduced by 2.8 days (p<0.001). More patients in the post-intervention group were initiated on antibiotics based on criteria consistent with our guideline (68% versus 87%, p=0.001). There were no differences between groups in terms of clinical outcomes.Conclusion: Following the implementation of a guideline outlining recommendations for initiating and discontinuing antibiotics for CABP among COVID-19 inpatients, we observed a reduction in antibiotic prescribing and DOT. The guideline also resulted in a significant increase in the rate of guideline-congruent empiric antibiotic initiation.
Identification of potential biomarkers and inhibitors in SARS-CoV-2 infected macaques
Authors: Gu Hanming , Wang Wei , Yuan Gongsheng
Published: October 2020

The COVID-19 pandemic caused by the infection with SARS-CoV-2 has overwhelmed many health systems globally. Our study is to identify differentially expressed genes (DEGs) and the associated biological pathways of COVID-19 to elucidate the potential pathogenesis and metabolism. The gene expression profile of the GSE155363 dataset was originally produced using the high-throughput Illumina HiSeq 4000 (Macaca mulatta). Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed to discover their functional categories and biochemical pathways. The results suggested that four biological pathways: Fatty acid elongation, Biosynthesis of unsaturated fatty acids, Fatty acid metabolism, and Ribosome were mostly involved in the macaques with COVID-19. Thus, our study provides novel insights into the underlying pathogenesis of COVID-19.
Single Agent and Synergistic Activity of Maritoclax with ABT-263 in Nasopharyngeal Carcinoma (NPC) Cell Lines
Authors: Benedict Lian Shi Xiang , Lo Kwok-Wai , Alan Khoo Soo-Beng , Mohana-Kumaran Nethia
Published: October 2020

The BCL-2 anti-apoptotic proteins are over-expressed in many cancers and hence are attractive therapeutic targets. In this study, we tested the sensitivity of two Nasopharyngeal Carcinoma (NPC) cell lines HK1 and C666-1 to Maritoclax, which is reported to repress anti-apoptotic protein MCL-1 and BH3 mimetic ABT-263, which selectively inhibits anti-apoptotic proteins BCL-2, BCL-XL and BCL-w. We investigated the sensitisation of the NPC cell lines to these drugs using the SYBR Green I assay and 3D NPC spheroids. We report that Maritoclax repressed anti-apoptotic proteins MCL-1, BCL-2, and BCL-XL in a dose- and time-dependent manner and displayed a single agent activity in inhibiting cell proliferation of the NPC cell lines. Moreover, combination of Maritoclax and ABT-263 exhibited synergistic antiproliferative effect in the HK1 cells. Similar results were obtained in the 3D spheroids generated from the HK1 cells. More notably, 3D HK1 spheroids either treated with single agent Maritoclax or combination with ABT-263, over 10 days, did not develop resistance to the treatment rapidly. Collectively, the findings illustrate that Maritoclax as a single agent or combination with BH3 mimetics could be potentially useful as treatment strategies for the management of NPC.
Kibble–Zurek mechanism in the Ising Field Theory
Authors: Hódsági Kristóf , Kormos Márton
Published: October 2020

The Kibble--Zurek mechanism captures universality when a system is driven through a continuous phase transition. Here we study the dynamical aspect of quantum phase transitions in the Ising Field Theory where the quantum critical point can be crossed in different directions in the two-dimensional coupling space leading to different scaling laws. Using the Truncated Conformal Space Approach, we investigate the microscopic details of the Kibble--Zurek mechanism in terms of instantaneous eigenstates in a genuinely interacting field theory. For different protocols, we demonstrate dynamical scaling in the non-adiabatic time window and provide analytic and numerical evidence for specific scaling properties of various quantities. In particular, we argue that the higher cumulants of the excess heat exhibit universal scaling in generic interacting models for a slow enough ramp.
Prospects of Poultry Dung Processing into Biogas when Using the Probiotic Product Amylocin in the Diet of Hens
Authors: Nikulina N.V. , Petrosov D.А.
Published: October 2020

The influence of the probiotic product Amylocin in the diet of laying hens on the biogas production potential of their droppings has been studied. A laboratory batch experiment on litter anaerobic fermentation was carried out. The total and specific biogas and methane yields from poultry droppings in the control and experimental groups were determined. It was found that the use of the probiotic Amylocin in the diet of laying hens reduced the biogas productivity of their dung; the average specific biogas and methane yields from the droppings of hens that received the probiotic was 73.90 and 19.52 ml/g of organic matter, respectively; the corresponding values for hens the diet of which did not contain Amylocin was 120.97 and 46.69 ml/g of organic matter, respectively. At the same time, the litter of the poultry group with the highest productivity was characterized by the lowest yield of biogas and methane (51.56 and 14.05 ml/g organic material, respectively), which may be due to the better conversion of feed nutrients in the poultry body, as well as to the inhibitory effect of probiotic microflora on the methane-forming consortium in the droppings. The methane concentration in the biogas from poultry litter averaged 29.75% in the experimental groups and 38.60% in the control. Only biogas from droppings of poultry that received the lowest dose of the additive contained 46.71% methane and was combustible. The addition of carbon-rich co-substrates can potentially increase the efficiency of converting into biogas of droppings of laying hens fed with Amylocin.

biogas, methane, poultry litter, laying hens, Amylocin, Bacillus subtilis, Bacillus amyloliquefaciens

The work was funded by the Russian Foundation for Basic Research, project no. 18-47-310008 р_а.
Learning Multimodality through Genre-Based Multimodal Texts Analysis: Listening to Students’ Voices
Authors: Abdullah Fuad , Tandiana Soni Tantan , Saputra Yuyus
Published: October 2020

Recently, multimodality has attracted the attention of researchers, notably in the educational milieu. However, only a few studies reported on the way students perceived the use of Genre-Based Multimodal Texts Analysis (GBMTA) for teaching multimodality. After addressing the gap, this study focuses on students’ perceptions on the use of GBMTA in multimodality teaching in higher education. Sixty-nine students were involved in the study. Each of the students produced one journal through three meetings. The journals were then collected for document analysis and thematic analysis (Braun Clarke, 2006). The findings reveal that the students perceived GBMTA as facilitating them in the building of multimodal discourse analysis, challenges and solutions of comprehending multimodal teaching materials, planning better learning strategies in the future, engagement on multimodal learning issues, and multimodal text analysis practices. This study contributes to multimodality teaching or multimodal discourse analysis within genre-based learning.
Polish Way: The Light Cossack Cavalry in the Era of Military Revolution
Authors:   University of Lodz, Bołdyrew Aleksander , Łopatecki Karol ,   University of Bialystok
Published: October 2020

The aim of the article is to show the way of adaptation of the military potential of the Crown to the Tatar threat, which first emerged in 1468. In connection with the particular geopolitical situation we present the dissimilarity of military reforms from those in Western Europe. In order to prevent Tatar raids, a standing frontier army (obrona potoczna or Permanent Defense) was formed. In the 1520s, an innovative strategy was developed which involved creating two defense lines with a very deep reconnaissance, 500 kilometers east of Lviv, already on the territory of the Grand Duchy of Lithuania. The consequence of applying the new model of defense was a new type of armed forces developed approximately two decades later, the cossack cavalry. The article presents a phenomenon of the creation a unified, in terms of weaponry, light cavalry, the process of which took place in the 1540s and 50s. Earlier the troops had consisted of soldiers differently equipped and armored and using various horses. Out of this chaos there emerged more unified units, which was the result of experiences of south-east borderline defense. The article emphasizes it was neither commanders-in-chief nor political and governmental factors that played a key role in the tactical innovation was mid-level commanders (starosts, rotmistrzes). It was their experiments with different types of arms that brought about a revolution in the rearmament and uniformity of the cavalry. The paper indicates that the main originator of the transformations was the starost of Bar and Trembowla Bernard Pretwicz. A clear influence of political decisions and strategic concepts on the final transformations in the warfare tactics should be noted.
Military Traditions of the Don Cossacks in the Late Imperial Period
Authors:   Plekhanov Russian University of Economics, Zul’fugarzade Teimur E. , Peretyatko Artyom Yu. ,   Joint Laboratory of the International Network Center for Fundamental and Applied Research and Volgograd State University
Published: October 2020

The issue of the development of military traditions in the Cossack milieu on the eve of the 20th century is a matter of debate in contemporary Russian historiography. A number of scholars (e. g., A.V.Iarovoi and N.V.Ryzhkova) have argued that the Cossacks’ system of historical military traditions remained viable until 1917. Other researchers (e. g., O.V.Matveev) have claimed that the system of Cossack military traditions had actually experienced a crisis and collapsed by then. This paper seeks to establish the truth. To accomplish this, the authors draws upon a set of newly discovered responses from Russian generals to the report of the Maslakovets Commission. The paper shows that the Cossacks’ historical traditions of military training in the stanitsas were forgotten not by the beginning of the 20th century, but by the 1860s. During this time, declining combat capability of the Don units, with 50% of the young Cossacks entering military service by the beginning of the 20th century “poorly” and “unsatisfactorily” prepared, drew the attention of Alexander II. The War Ministry endeavored to revive the Cossacks’ martial games and military training in the stanitsas. However, according to certain Cossack generals, its actions, at the same time, had violated the historical Cossack traditions of military training, causing, by certain testimonies, their total ruin by the beginning of the 20th century. The main conclusion drawn in this paper is that the image of the Cossack as a “dashing equestrian warrior” going back to official pre-revolutionary historiography is highly idealized.