bluuebunny/crossref_metadata_2025 huggingface dataset:
Biodiversity of Sago (Metroxylon spp.) and Its Understory in Maluku, Indonesia
Authors: Senewe Rein Estefanus , Pesireron Marietje , Darsa Yusuf , Leiwakabessy Christoffol , Yusron Muchamad
Published: January 2021

Sago (Metroxylon spp.) is an important crop in Maluku. This study aims to identify the biodiversity of sago palm and understorey vegetation around sago clumps in Maluku. The research was carried out in six sago area from September 2015 to October 2016. The Sago Plant identification was carried out through the growth phase of sago, i.e. seedlings, saplings, weaning, trunks, and ripening. Vegetation observation was done in radius 100 m2 surrounding sago clumps. The result shows that Metroxylon rumphii Mart type. (Tuni sago), M. sagus Rottb. (Molat sago) and M. Silvester Mart. (Ihur Sago) dominates sago palms area in Seram and Ambon Islands, Maluku. There are significant morphological differences between the types of sago, especially in stem height, midrib width, leaf midrib colour, number of thorns, and flower stalk length, as well as the difference of carbohydrate content. Understorey vegetation of each observation sites diverse consist of 15 families and 20 species. The families that dominate the vegetation under the sago palms are Araceae, Thelypteridaceae, and Athyriaceae. The types of plants from Araceae are taro types and broadleaf, while those from the Thelypteridaceae and Athyriaceae families are types of ferns.
EP4 as a Therapeutic Target to Impede Breast Cancer-associated Angiogenesis and Lymphangiogenesis
Authors: De Paz Linares Gullermo Antonio , Opperman Reid M , Majumder Mousumi , Lala Peeyush K.
Published: January 2021

Formation of new blood (angiogenesis) and lymphatic (lymphangiogenesis) vessels are major events associated with most epithelial malignancies, including breast cancer. Angiogenesis is essential for cancer cell survival. Lymphangiogenesis is critical in maintaining tumoral interstitial fluid balance and importing tumor-facilitatory immune cells. Both vascular routes also serve as conduits for cancer metastasis. Intratumoral hypoxia promotes both events by stimulating multiple angiogenic/lymphangiogenic growth factors. Studies on tumor-associated lymphangiogenesis and its exploitation for therapy have received less attention from the research community than those on angiogenesis. Inflammation is a key mediator of both processes, hijacked by many cancers by aberrant expression of the inflammation-associated enzyme cyclo-oxygenase (COX)-2. In this review, we focus on breast cancer and show that COX-2 is a major promoter of both events, primarily resulting from the activation of Prostaglandin (PG) E receptor EP4 on tumor cells, tumor-infiltrating immune cells, and endothelial cells; and induction of oncogenic microRNAs. COX-2/EP4 pathway also promotes additional events in breast cancer progression, such as cancer cell migration, invasion, and stimulation of stem–like cells. Based on a combination of studies using multiple breast cancer models, we show that EP4 antagonists hold a major promise in breast cancer therapy in combination with other modalities including immune check-point inhibitors
Free Convection Heat Transfer from Two Equal Triangular Cylinders Confined in Triangular Enclosure
Authors: Laidoudi Houssem
Published: January 2021

This paper studied the natural convection heat transfer from two equal-sized cylinders of triangular cross-section confined in triangular enclosure. The inner cylinders have hot surfaces and the outer enclosure has a cold surfaces. The annular space between inner cylinders and the outer one was filled with incompressible Newtonian fluid. The work examined the behavior of fluid flow in the process of transferring heat energy. The work was achieved numerically using the commercial code ANSYS-CFX. The adopted initial conditions were selected for these ranges: Prantl number (Pr = 1 to 103), Rayleigh number (Ra = 103 to 105). It was found that the increment of Ra number increases the rate of heat transfer. However, the effect of Pr number on heat transfer is almost negligible.
Students’ Views Towards SARS-CoV-2 Mass Asymptomatic Testing, Social Distancing and Self-Isolation in a University Setting during the COVID-19 Pandemic: A Qualitative Study
Authors: Blake Holly , Knight Holly , Jia Ru , Corner Jessica , Morling Joanne R , Denning Chris , Ball Jonathan K , Bolton Kirsty , Figeuredo Grazziela , Morris David , Tighe Patrick , Villalon Armando , Ayling Kieran , Vedhara Kavita
Published: January 2021

We aimed to explore university students’ perceptions and experiences of SARS-CoV-2 mass asymptomatic testing, social distancing and self-isolation during the COVID-19 pandemic. This qualitative study comprised of four rapid online focus groups conducted at a higher education institution in England during high alert (tier 2) national COVID-19 restrictions. Data were analysed thematically. Participants were purposively sampled university students (n = 25) representing a range of gender, age, living circumstances (on/off campus) and SARS-CoV-2 testing/self-isolation experiences. Six themes with 16 sub-themes emerged from the analysis of the qualitative data: ‘Term-time Experiences’, ‘Risk Perception and Worry’, ‘Engagement in Protective Behaviours’, ‘Openness to Testing’, ‘Barriers to Testing’ and ‘General Wellbeing’. Students described feeling safe on campus, believed most of their peers are adherent to protective behaviours and were positive towards asymptomatic testing in university settings. University communications about COVID-19 testing and social behaviours need to be timely and presented in a more inclusive way to reach groups of students who currently feel marginalised. Barriers to engagement with SARS-CoV-2 testing, social distancing and self-isolation were primarily associated with fear of the mental health impacts of self-isolation, including worry about how they will cope, high anxiety, low mood, guilt relating to impact on others and loneliness. Loneliness in students could be mitigated through increased intra-university communications and a focus on establishment of low COVID-risk social activities to help students build and enhance their social support networks. These findings are particularly pertinent in the context of mass asymptomatic testing programmes being implemented in educational settings and high numbers of students being required to self-isolate. Universities need to determine the support needs of students during self-isolation and prepare for the long-term impacts of the pandemic on student mental health and welfare support services.
Analysis of Transient Voltage Problem Caused by Electric Arc Furnace
Authors: Yang Liu , Tan Qinyue , Xiong Di
Published: January 2021

Three-phase AC electric arc furnace (EAF) is a typical non-linear load, causing many power quality problems. Most of the researches on the voltage problems of EAF mainly focus on the voltage fluctuation, and less on the transient voltage problems caused by EAF short circuit and open circuit. In this paper, the relationship between voltage and current of EAF is obtained by combining hyperbolic function and exponential function, then the white noise and chaotic circuit are added to establish the EAF model which is suitable for the study of voltage fluctuation and transient voltage. This paper analyzes the causes of the transient voltage problem of the EAF, calculates the short-circuit current, reactive impact and the influence on voltage at the point of common coupling (PCC) in the three-phase short-circuit of the EAF, and compares the calculation results with the simulation results to prove the accuracy of this model. The results show that the reactive impact of three-phase short circuit is about twice as much as that of normal operation of EAF, resulting in about 30% voltage sag at the PCC, which is very unfavorable to the power grid. This paper provides reference for transient power quality evaluation and dynamic reactive power compensation of EAF.
Experiências de participação no sertão alagoano: a criança com voz e vez no cotidiano da educação infantil
Authors: Souza Isaura Lays Sá Fernandes de , Libardi Suzana Santos
Published: January 2021

A presente pesquisa objetivou compreender se/como ocorre a participação de crianças no cotidiano da Educação Infantil, a partir de estudo de caso numa pré-escola localizada no Sertão de Alagoas. Foram realizadas observação participante e algumas atividades pedagógicas com crianças no ambiente educativo. Uma turma do Jardim I foi envolvida na pesquisa, com 24 crianças na faixa de quatro a cinco anos de idade. As análises dos relatórios de campo refletem o fenômeno da participação de crianças no contexto estudado. Apresentamos as formas pelas quais as crianças agem criativamente e tomam posse do local e da dinâmica em que estão inseridas. São relatadas cenas do cotidiano infantil que nos permitiram pensar analiticamente sobre participação. Observamos que a ação das crianças depende muito do olhar do adulto, pois ele é quem ocupa o papel de prevê-la no processo de ensino e aprendizagem e/ou de, ocasionalmente, não a reconhecer.
Virtuality in university teaching-learning versus COVID-19
Authors: Morales José Néstor Sánchez , León Edith Eloísa Huerta , Rivera-Lozada Oriana , Coronado Miriam Liliana Flores , Lira Luis Alberto Núñez
Published: January 2021

The research aimed to analyze the use of virtual resources in teaching-learning in times of pandemic at the Daniel Alcides Carrion National University. The methodology used was of qualitative approach through field work to explain the behaviors assumed in the processes of learning management by students and teachers. The information was collected through various techniques such as observation of virtual classes, documentary analysis, and focus groups with students, unstructured interviews and, in depth, with experts in the subject that allowed us to conduct the discussion and triangulation. The results allowed us to affirm that students recognize the importance of technology and the use of ICTs for their professional training; in addition, students and teachers have been demonstrating high levels of value, responsibility and commitment to their learning.
Outbreaks of Mumps Genotype G Viruses in the Netherlands Between October 2019 and March 2020: Clusters Associated With Multiple Introductions 
Authors: Shah Anita , Bodewes Rogier , Reijnen Linda , Boelsums Timo , Weller Claudia , Fanoy Ewout , Veldhuijzen Irene
Published: January 2021

Background From October 2019–March 2020, several clusters of mumps cases were identified in the Netherlands. Our objective was to describe cluster-associated mumps virus transmission using epidemiological and molecular information in order to help future mumps prevention efforts. Methods An epidemiological cluster includes ≥2 mumps cases with at least an epidemiological-link to a laboratory-confirmed mumps case. A molecular group includes ≥2 mumps cases with identical mumps virus sequences. Cases with symptom onset date between 1 October 2019–31 March 2020 reported through the National Notifiable Diseases Surveillance System were included. We described epidemiological and clinical characteristics of mumps cases. Sequence data was obtained from selected regions of mumps virus genomes (2270 nucleotides). Correlations between epidemiological and molecular information were investigated. Results In total, 102 mumps cases were notified (90% laboratory-confirmed, 10% epidemiologically-linked). Fourteen epidemiological clusters were identified containing 46 (range 2–12) cases. Complete sequence data was obtained from 50 mumps genotype G viruses. Twelve molecular groups were identified containing 43 (range 2–13) cases, dispersed geographically and timewise. Combined information redefined 7 epidemiological clusters into 2 distinct molecular groups. The first lasting for 14 weeks, the other for 6. Additionally, one molecular group was detected, linked by geography and time but without an epidemiological-link. Conclusions Combined epidemiological and molecular information indicated ongoing mumps virus transmission from multiple introductions for extended time periods. Sequence analysis provided valuable insights into epidemiological clustering. If combined information is available real-time, this would improve outbreak detection, generate further insight into mumps transmission, and guide necessary control measures.
SIMBA: Using Kolb’s Learning Theory in Simulation-Based Learning to Improve Participants' Confidence
Authors: Davitadze Meri , Ooi Emma , Ng Cai Ying , Zhou Dengyi , Thomas Lucretia , Hanania Thia , Blaggan Parisha , Evans Nia , Chen Wentin , Melson Eka , Arlt Wiebke , Kempegowda Punith
Published: January 2021

BackgroundSimulation via Instant Messaging- Birmingham Advance (SIMBA) delivers simulation-based learning (SBL) through WhatsApp and Zoom based on Kolb’s experiential learning theory. This study aimed to implement Kolb’s theory in practice during SIMBA adrenal session. MethodsKolb’s 4-stage cycle: concrete experience—simulation, reflective observation—discussion following simulation, abstract conceptualisation and assimilation of new information—Q&A and MCQs, and active experimentation—reflect on the acquired knowledge. Participants’ self-reported confidence levels pre- and post-SIMBA were analysed using Wilcoxon Signed Rank test. Key takeaway and feedback were assessed quantitatively and qualitatively in a thematic analysis. ResultsParticipants’ self-reported confidence improved significantly post-SIMBA in their approach to Cushing’s syndrome (p<0.0001) and adrenocortical carcinoma (p<0.0001). 93.9% (n=31/33) and 84.8% (n=28/33) strongly agreed/agreed the topics were applicable to their clinical practice and accommodated their personal learning style, respectively. 81.8% (n=27/33) reported increase in knowledge on patient management, and 75.8% (n=25/33) anticipated implementing learning points in their practice. ConclusionsSIMBA effectively adopts Kolb’s theory to provide best possible experience to learners, highlighting the advantages of utilising social media platforms for SBL in medical education. The ability to conduct SIMBA sessions at a low cost with high fidelity internationally paves way to engage more healthcare professionals worldwide.
Denosumab Versus Romosozumab for Postmenopausal Treatment
Authors: Kobayakawa Tomonori , Miyazaki Akiko , Saito Makoto , Suzuki Takako , Nakamura Yukio , Takahashi Jun
Published: January 2021

INTRODUCTION Denosumab and romosozumab, the recently approved new drug, are effective and widely known molecular-targeted drugs for postmenopausal osteoporosis treatment. However, no studies have directly compared their therapeutic effects or safety in postmenopausal osteoporosis. We believe the data evaluating the efficacy of each drug might be strong ground for further osteoporosis treatment. METHODS This retrospective observational registry study compared the efficacy of 12-month denosumab or romosozumab treatment in postmenopausal osteoporosis patients. The primary outcome was the change in bone mineral density (BMD) at the lumbar spine. Secondary outcomes included BMD changes at the total hip and femoral neck, changes in bone turnover markers, and adverse events. Propensity score matching was employed to assemble patient groups with similar baseline characteristics. RESULTS Sixty-nine patients each received either denosumab or romosozumab for 12 months. The mean 12-month percentage change from baseline in lumbar spine BMD was 7.2% in the denosumab group and 12.5% in the romosozumab group, indicating a significant difference between the groups. The percentage changes in BMD at both the total hip and femoral neck were also significantly higher at 12 months in the romosozumab group than in the denosumab group. In denosumab patients, bone formation and bone resorption markers were significantly decreased at 6 and 12 months from baseline. In the romosozumab group, the bone formation marker was significantly increased at 6 months and then returned to baseline, while the bone resorption marker was significantly decreased at both time points. Adverse events were few and predominantly minor in both groups. CONCLUSION Romosozumab showed a higher potential for improving BMD than denosumab in this clinical study of postmenopausal osteoporosis patient treatment.
What Protects Us Against the COVID-19 Threat? Cultural Tightness Matters
Authors: Dong Dan , Chen Zhipeng , Zong Min , Zhang Peng , Gu Wen , Feng Yi , Qiao Zhihong
Published: January 2021

Background: The only previous studies that formulated a theoretical model of epidemics for psychological response relative to cultural perspectives have focused on the role of individualism–collectivism and have omitted analysis of tightness–looseness. This study explored the role of cultural tightness in relation to psychological disorders during the outbreak of the COVID-19 pandemic.Methods: We recruited 1827 Chinese adolescents (Mage = 17.78 ± 1.94 years, 55.5% female) to participate a cross-sectional survey. Participants completed a series of questionnaires, including the scales of cultural tightness, risk perception of COVID-19 pandemic, perceived protection efficacy, anxiety and depression. A latent moderated structural equations model was used to analyse the mediating and moderating effects of risk perception regarding COVID-19, cultural tightness and perceived protection efficacy on psychological disorders. Results: The results showed that greater risk perception of COVID-19 predicted greater psychological disorders, however cultural tightness moderated this positive relationship. The increase in psychological disorders with risk perception regarding COVID-19 was less pronounced among people who lived in tighter cultural areas. In addition, this moderating effect of cultural tightness was further mediated by perceived protection efficacy; that is, tight culture protects against psychological disorders by enhancing perceived protection efficacy. Conclusion: This study enriched the theoretical framework of cultural tightness and indicated its importance in the field of mental health and health policies. It also emphasized the importance of tight culture as a protective factor against psychological disorders in case of COVID-19 outbreaks, providing valuable practical insight into psychological prevention for COVID-19 outbreaks.
Protected Area Networks Do Not Represent Unseen Diversity
Authors: Delso Angel , Muñoz Jesús , Fajardo Javier
Published: January 2021

Most existing protected area networks are usually biased to protect charismatic species or showy landscapes. We hypothesized that conservation networks designed including unseen diversity –groups usually species-rich but consisting of inconspicuous taxa, or affected by knowledge gaps– would be more efficient than networks ignoring those groups. To test this hypothesis, we created species distribution models for 3,006 species of arthropods and determined which were represented in three networks of different size and biogeographic origin. We assessed the efficiency of each network using spatial prioritization to measure its completeness –increment needed to achieve conservation targets– and specificity –how much overlap the priority areas based on unseen diversity with existing networks. We find that representativeness of unseen diversity in existing protected areas –extrinsic representativeness– was low, as ~40% of unseen diversity species were unprotected. We also find that existing networks should be expanded by an additional ~26-46% of their current area to complete targets, and that specificity can be as low as 8.8%, meaning that existing networks are not efficient to conserve unseen diversity. We conclude that information on unseen diversity must be included in systematic conservation planning approaches to design more efficient and ecologically representative protected areas.
Disparity of Central-Peripheral Refraction Inheritance in Twins
Authors: Pusti Dibyendu , Benito Antonio , Madrid-Valero Juan J , Ordonana Juan R , Artal Pablo
Published: January 2021

The large incidence of myopia during the last decades is becoming a worldwide public health problem. Increasing myopia during childhood has been related to changing lifestyle and linked to larger eye growth, although the mechanism to explain how visual exposures affect ocular development is still unclear. The gene-environment interaction in myopia was investigated in a sample of 100 pairs of young twins with large prevalence of myopia. A classical twin’s study model was performed on objective refraction measured with an open-view peripheral wave-front sensor across a wide range of horizontal retinal eccentricities. In this sample, variance of refractive errors at the area surrounding the line of sight was mainly related to variance in shared-environmental exposures. From there, while moving towards the retinal periphery, the environmental influence over peripheral refractive error variance decreased gradually towards a genetically-driven model. In conclusion, environmental exposures, responsible of the increase in myopia incidence, seems to be affecting mainly the central area of the retinal in young myopes.
Managing Overlap of Primary Studies Results Across Systematic Reviews: Practical Considerations for Authors of Overviews of Reviews
Authors: Lunny Carole , Pieper Dawid , Thabet Pierre , Kanji Salmaan
Published: January 2021

Background: In overviews, inclusion of the same primary study in multiple systematic review gives undue weight to this study. Using a study result multiple times in the same analysis overstates its sample size and number of events, falsely leading to greater precision in the analysis. This paper aims to: (a) describe types of overlapping data that arise from the same primary studies reported across multiple reviews, (b) describe methods to identify and explain overlap of primary study data, and (c) present six case studies illustrating different approaches to manage overlap. Methods: We first updated the search in PubMed for methods from the MOoR framework relating to overlap of primary studies. One author screened the studies titles and abstracts, and any full-text articles retrieved, extracted methods data relating to overlap of primary studies and mapped it to the overlap methods from the MOoR framework. We also describe six case studies as examples of overviews that use specific methods across the steps in the conduct of an overview. For each case study, we discuss potential implications in terms of methodological limitations, efficiency, usability, and resource use.Results: Eight studies were mapped to the methods identified by the MOoR framework to address overlap. Several overlap methods mapped across four steps in the conduct of an overview – the eligibility criteria step, the data extraction step, the assessment of risk of bias step, and the synthesis step. Our overview case studies used multiple methods to reduce overlap at different steps in the conduct of an overview.Conclusions: Our study underlines that there is currently no standard methodological approach to deal with overlap in primary studies across reviews. The level of complexity when dealing with overlap can vary depending on the yield, trends and patterns of the included literature and the scope of the overview question. Choosing a method might be dependent on the number of included reviews and their primary studies. Gaps in in evaluation of methods to address overlap were found and further investigation in this area is needed.
An Exploration of Black, Asian and Minority Ethnic Women’s Perceptions of Public Health Messages to Reduce Stillbirth in the UK: a Qualitative Study.
Authors: Stacey Tomasina , Haith-Cooper Melanie , Almas Nisa , Kenyon Charlotte
Published: January 2021

Background: Stillbirth is a global public health priority. Within the United Kingdom, perinatal mortality disproportionately impacts Black, Asian and Minority Ethic (BAME) women, these communities have double the rates of stillbirth than white women. Although the explanation for this remains unclear, it is thought to be multidimensional and includes access to key public health information. Improving perinatal mortality is reliant upon raising awareness of stillbirth and its associated risk factors. The aim of this study was to explore BAME women’s awareness of stillbirth, perceptions of how it can be prevented through maternal behaviour change and how key public health messages could be more accessible to BAME women. Method: Two semi-structured focus groups and 13 one to one interviews were completed with a purposive sample of 30 participants from 18 countries and across 4 NHS Trusts. Participants provided a detailed account of their recollection of stillbirth advice and risk factors both before and during pregnancy. They also suggested approaches to more effectively communicate key messages to BAME women. Results: The results indicate limited awareness of stillbirth and potentially modifiable risk factors. They highlight the importance of the way in which resources to communicate key messages are developed and how they are communicated. The study supports the need for a range of resources which should be developed and shared within communities and as well as by trusted health professionals. Conclusion: Our study found that the term “stillbirth” does not routinely exist in many women’s narrative of perinatal health. This introduces additional complexity for health professionals when discussing stillbirth prevention with women from culturally and linguistically diverse backgrounds. Through co-development messages can be more accessible, acceptable and communicated effectively. It was clear that there was no ‘one size fits all’ and that a multi-pronged approach is required.
Towards a Personalized Organized Screening in Breast Cancer : Practical Determination of Thresholds of Risk in Women at Average-Risk
Authors: Bonnet Emmanuel , Daures Jean Pierre , Landais Paul
Published: January 2021

In France, more than 10 million women at ”average” risk of breast cancer (BC), are included in the organized BC screening. Existing predictive models of BC risk are not adapted to the French population. Thus, we set up a new score in the French Hérault region and looked for a graded level of risk in women at "average" risk. We recruited a retrospective cohort of women, aged 50 to 60, who underwent the organized BC screening, and included 2241 non-cancer women and 527 who developed a BC during a 12-year follow-up period (2006-2018). The risk factors identified were high breast density (ACR BI-RADS grading)(B vs A: HR 1.41, 95%CI [1.05; 1.9], p=0.023; C vs A: HR=1.65 [1.2; 2.27], p=0.02 ; D vs A: HR=2.11 [1.25;3.58],p=0.006), a history of maternal breast cancer (HR=1.61 [1.24; 2.09], p < 0.001), and socioeconomic difficulties (HR 1.23 [1.09; 1.55], p=0.003). While early menopause (HR=0.36 [0.13; 0.99], p=0.003) and an age at menarche after 12 years (HR=0.77 [0.63; 0.95], p=0.047) were protective factors. We identified 3 groups at risk: lower, average, and higher, respectively. A low threshold was characterized at 1.9% of risk and a high threshold at 4.5%. Mean risks in the 3 groups of risk were 1.37%, 2.68%, and 5.84%, respectively. Thus, 12% of women presented a level of risk different from the average risk group, corresponding to 600,000 women involved in the French organized BC screening, enabling to propose a new strategy for performing an organized and personalized national BC screening.
PNO1 regulates autophagy and apoptosis of hepatocellular carcinoma via the MAPK signaling pathway
Authors: Han Zhiqiang , Liu Dongming , Chen Lu , He Yuchao , Tian Xiangdong , Qi Lisha , Chen Liwei , Luo Yi , Chen Ziye , Hu Xiaomeng , Li Guangtao , Zhan Linlin , Wang Yu , Li Qiang , Chen Peng , Liu Zhiyong , Guo Hua
Published: January 2021

Background

Some studies have reported that the activated ribosomes are positively associated with malignant tumors, especially in hepatocellular carcinoma (HCC). The RNA-binding protein PNO1, as a critical ribosome has been rarely reported in human tumors. Thus, the roles of PNO1 in HCC should be explored.
Methods

We collected 150 formalin-fixed and paraffin-embedded (FFPE) samples and 8 fresh samples to explore the expression and prognosis of PNO1 in HCC by immunohistochemistry, Western Blotting and RT-PCR. Public databases (TCGA and GEO) were used to verify the expression and prognosis. The functions of PNO1 in HCC was verified by in vitro and in vivo experiments. The underlying molecular mechanisms of PNO1 were examined by RNA-seq analysis and a series of functional experiments.
Results

PNO1 expression was considerably higher in HCC tissues and the higher expression of PNO1 was associated with poor prognosis of HCC patients. In vitro experiments indicated that PNO1 overexpression promoted proliferation and depressed apoptosis of HCC cells. In addition, high expression of PNO1 increased autophagy of HCC cells. Consistent results were also observed in vivo experiments. The results of the RNA-seq analysis indicted that PNO1 as an oncogene promoted HCC progression through the MAPK signaling pathway. The results were also verified by in vivo experiments.
Conclusions

PNO1 was overexpressed in HCC, promoted autophagy and inhibited apoptosis of HCC cells via the MAPK signaling pathway.
Exploration of the Mechanism and Active Targets of Chinese Herbal Formula, JTTZ, for the Treatment of Type 2 Diabetes with Obesity and Hyperlipidemia Based on Network Pharmacology
Authors: Zhang Haiyu , An Xuedong , Jin De , Tian Jiaxing , Liu Wenke , Zhao Shenghui , Wang Xinmiao , Hu Yeying , Lian Fengmei , Tong Xiaolin
Published: January 2021

BackgroundPrevious studies have indicated that the JTTZ formula exhibits clinical benefit in T2D with obesity and hyperlipidemia such as lowering blood glucose, blood lipids, weight, and ameliorating symptoms as well as regulating islet function. However, their mechanism of action remains unclear. T2D with obesity and hyperlipidemia is associated with a severely poor management duo to difficulty in achieving the clinical goals and lack of effective multi-targeted therapies. In this study, we explored its potential mechanisms and therapeutic targets by network pharmacology. MethodsThe active ingredients and targets of JTTZ were obtained in the TCMSP, TCMID, TCM Database@Taiwan, PubChem and Swiss Target Prediction. And the therapeutic targets were searched from TTD, DrugBank Database and DisGeNET. Then, topology analysis were used as secondary screens to identify key hubs of the network. Finally, the data was integrated by Cytoscape software to construct a common network module. PPI networks were visualized to identify the interaction of the candidate targets. GO and KEGG pathway analysis were implemented. Rerult: 110 active compounds and 166 candidate targets of JTTZ against T2D with obesity and hyperlipidemia were obtained to construct compound-targets network. And, the therapeutic targets AKT2, RELA, NFKB1 and GSK3B were identified. GO and KEGG pathway analysis indicated that the biological processes related to inflammatory response, insulin secretion, steroid and bile acid metabolism, and 13 pathways mainly including adipocytokine signaling pathway, cAMP signaling pathway and cGMP-PKG signaling pathway were enriched. ConclusionOur data established that JTTZ intervenes with adipose tissue dysfunction via regulating to the adipocytokine (leptin and adiponectin), AMPK signaling pathway, cAMP and cGMP-PKG signaling pathway, inhibits systematic inflammatory response by NF-κB and MAPK signaling pathway, and ameliorates insulin resistance through PI3K/AKT2 pathway, all of which could thus offer a promising therapeutic strategy. In addition, AKT2, RELA, NFKB1 and GSK3B were identified to be regarded as potential therapeutic targets as well.
The Role of mGluR4 Receptors Within the Nucleus Accumbens in the Acquisition and Expression of Morphine-induced Conditioned Place Preference in Male Rats
Authors: Ebrahimi Zahra , Kahvandi Nazanin , Komaki Alireza , Karimi Seyed Asaad , Naderishahab Marzieh , Sarihi Abdolrahman
Published: January 2021

Background: Several studies have shown that glutamate neurotransmission in the nucleus accumbens (NAc) is required for the development of morphine-induced conditional place preference (CPP). Also, metabotropic glutamate receptors (mGluRs) into the NAc play important roles in the reward pathways. However, the precise role of mGluR4 in different steps of the morphine-induced CPP is less well known. In the present study we investigated the effect of bilateral intra-accumbal infusion of VU0155041, as a specific mGluR4 agonist on the acquisition and expression of morphine induced CPP in male Wistar rats. Animals were bilaterally implanted with guide cannulae above the NAc. In the first part of the study, the VU0155041 was administered at doses of 10, 30 and 50 μg/0.5 μL saline per side into the NAc during the 3 days of morphine (5 mg/kg) conditioning (acquisition) phase of morphine-induced CPP. In the next part of the study, the rats bilaterally received VU0155041 at the dose of 50 μg/0.5 μL, 5 min before the post-conditioning test to check the effect of VU0155041 on the expression of morphine-induced CPP. Results: The results showed that the intra-accumbal injection of VU0155041 inhibits the acquisition of morphine-induced CPP in a dose dependent manner, but had no effect on expression Our data indicated that intra-NAc administration of VU0155041 dose-dependently blocks the establishment of morphine-induced CPP and reduces the rewarding properties of morphine.These effects may be related to changes in glutamate activity in the NAC and/or learning dependent mechanism of glutamate neurotransmission in reward pathway(s).
Predominant role of gut-vagus-brain neuronal pathway in postoperative nausea and vomiting: evidence from an observational cohort study
Authors: Li Nana , Liu Lu , Sun Menghan , Wang Ruiliang , Jin Wenjie , Liu Cunming , Hu Youli
Published: January 2021

Background

Postoperative nausea and vomiting (PONV) as a clinically most common postoperative complication requires multimodal antiemetic medications targeting at a wide range of neurotransmitter pathways. Lacking of neurobiological mechanism makes this big little problem still unresolved. We hypothesized that gut-vagus-brain reflex generally considered as one of four typical emetic neuronal pathways is the primary mediator of PONV.
Methods

3223 patients who underwent vagotomy (esophagectomy and gastrectomy) and non-vagotomy surgery (hepatectomy, pulmonary lobectomy and colorectomy) from December 2016 to January 2019 were enrolled. Nausea and intensity of vomiting (mild, < 3 times;severe, ≥ 3 times) was recorded within 24 h after the operation.
Results

In the whole PONV incidence, vagotomy surgeries with vagus nerve trunk resection significantly reduced PONV incidence by approximately 4-fold (from 80.6–19.4%). Multivariate logistic regression result revealed that vagotomy was one of underlying factor that significantly involved in PONV (OR = 0.311; 95% CI, 0.246–0.393). Propensity score matching found that 35.3% patients who underwent vagus nerve trunk resection experienced PONV, while PONV was seen in 60.9% patients undergoing surgeries with intact vagus nerve (P < 0.001). Nausea was reported in 5.9%ཞ8.6% vagotomy and 12ཞ17% non-vagotomy patients. Most vomiting were mild, being approximately 3% in vagotomy and 8ཞ13% in non-vagotomy patients. Sever vomiting was much less experienced in patients undergoing vagotomy (ཞ1%) and non-vagotomy (ཞ3%).
Conclusion

Vagus nerve dependent gut-brain signaling mainly contributes to PONV, highlighting the new approach that modulates vagal activation to alleviate anesthetics and surgical stress-induced nausea and vomiting.
Co-Cultivation of Sake Yeast and Kocuria Isolates From the Sake Brewing Process
Authors: Terasaki Momoka , Inoue Airu , Yoshida Saki , Yamada Masato , Toda Hiroshi , Nishida Hiromi
Published: January 2021

Kocuria isolates collected from the sake brewing process have inhabited the Narimasa Sake Brewery in Toyama, Japan. To investigate the effect of these actinobacterial isolates on the growth and metabolism of sake yeast, co-cultivation of sake yeast and Kocuria isolates was performed in a medium containing tryptone, glucose, and yeast extract (TGY), and a solution containing koji (steamed rice covered with Aspergillus oryzae) and glucose. In the TGY medium, the ethanol concentration and the number of living cells of each microorganism were measured. In the koji solution, the concentrations of ethanol and organic acids (citric acid, lactic acid, and succinic acid) were measured. The results showed that in TGY media, the growth of each Kocuria isolate in the co-culture of the two Kocuria isolates was similar to that in each monoculture. However, the growth of both Kocuria isolates was inhibited in the co-cultures of sake yeast and Kocuria isolates. On the other hand, the growth and ethanol productivity of sake yeast did not differ between its monoculture and co-cultures with Kocuria isolates. In the koji solution, although the concentration of succinic acid did not differ between the monocultures of sake yeast and co-cultures with Kocuria isolates, the concentrations of citric acid and lactic acid were different, indicating that Kocuria isolates affected the microbial population and/or sake yeast metabolism, but the effects were not identical between the two isolates. This strongly suggests that bacteria inhabiting a sake brewery influence the flavor of sake products of the brewery.
A Large-scale Karyotype Analysis of Genetic Counselors and Fetuses Among Hakka Population in Southern China
Authors: Zhong Hua , Huang Qingyan , Yu Zhikang , Wu Heming
Published: January 2021

Background: Karyotype analysis has been used in a clinical cytogenetic laboratory. A retrospective analysis of karyotype analysis in Meizhou area to provide valuable reference for clinical genetic counseling. A retrospective analysis of 5-year data of karyotype analysis from 5,289 peripheral blood samples and 2,882 fetuses between January 2015 and March 2020 in Meizhou area.Results: Chromosomal abnormalities were detected in a total of 392 peripheral blood samples, and the abnormality detection rate (ADR) was 7.41% (392/5,289). The ADR for sex chromosome aneuploidies, autosomal aneuploidies, structural abnormalities and chromosome polymorphisms were 1.29% (68/5,289), 0.72% (38/5,289), 1.55% (82/5,289) and 3.86% (204/5,289). Among cases with chromosomal abnormalities, numerical abnormalities, chromosomal structural abnormalities and chromosome polymorphism accounted for 27.04% (106/392), 20.92% (82/392) and 52.04% (204/392), respectively. There were statistically significant differences in the chromosomal abnormalities rate different types of patients. In addition, chromosomal abnormalities were detected in a total of 307 fetus samples, and the ADR was 10.65% (307/2,882). The ADR for sex chromosome aneuploidies, autosomal aneuploidies, triploid/tetraploid, structural abnormalities and chromosome polymorphisms were 1.70% (49/2,882), 5.45% (157/2,882), 0.14% (4/2,882), 1.39% (40/2,882) and 1.94% (56/2,882). Among fetuses with chromosomal abnormalities, numerical abnormalities, chromosomal structural abnormalities and chromosome polymorphism accounted for 68.40% (210/307), 13.03% (40/307) and 18.24% (56/307), respectively. The chromosomal abnormalities rate was higher than that in non-elderly pregnant women. Abnormal chromosome karyotype detection rate is higher in genetic counselors in Meizhou area.Conclusions: Karyotype analysis has great significance for clinical diagnosis, guide the healthy birth, and improve the quality of the population.
Research on E-commerce Enterprise Customer Segmentation Based on Cluster Analysis-Taking Jingdong Century Trading Co., Ltd as an Example
Authors: Liu Yang
Published: January 2021

With the rapid development of many Internet e-commerce companies represented by Alibaba, e.g., Jingdong Mall and Pinduoduo in China, the competition, particularly among them for more customers, has intensified. However, the resources of an enterprise are limited, and it is difficult to serve all customers at the same time. Therefore, it is necessary to effectively classify customers and formulate different marketing strategies based on different customer attributes to serve different types of customers in order to maximize the interests of the enterprise. Based on the research results of the customer segmentation and the cluster analysis by domestic and foreign research scholars, this paper selects the consumption data of the company’s customers based on the actual situation of the Chinese e-commerce company, Jingdong Mall, and uses the K-means clustering algorithm, Kohonen neural network clustering algorithm and the two-step clustering algorithm, as well as the improved K-means clustering algorithm, and other four clustering methods respectively conducted cluster analysis on the company’s customers. Combined with the actual situation of the company, the graphical method and various test methods were used to test the clustering effect. The results show that as compared to the other three algorithms, the two-step clustering algorithm exhibits a better performance in the actual situation and the theoretical test. Then, the customers are divided into five categories, each category is separately analyzed, the characteristics and differences of each category of customers are determined, and different marketing strategies are formulated for the customer groups with different characteristics to provide suggestions for enterprises to differentiate marketing and management in order to achieve the maximum benefits with cost savings.
Evaluating QualiCO: An Ontology to Facilitate Qualitative Methods Sharing to Support Open Science
Authors: Hocker Julian , Bipat Taryn , McDonald David W. , Zachry Mark
Published: January 2021

Qualitative science methods have largely been omitted from discussions of open science. Platforms focused on qualitative science that support open science data and method sharing are rare. Sharing and exchanging coding schemas has great potential for supporting traceability in qualitative research as well as for facilitating the re-use of coding schemas. In this study, we describe and evaluate QualiCO, an ontology for qualitative coding schemas. QualiCO is designed to describe a wide range of qualitative coding schemas. Twenty qualitative researchers used QualiCO to complete two coding tasks. In our findings, we present task performance and interview data that focus participants’ attention on the ontology. Participants used QualiCO to complete the coding tasks, decreasing time on task, while improving accuracy, signifying that QualiCO enabled the reuse of qualitative coding schemas. Our discussion elaborates some issues that participants had and highlights how conceptual and prior practice frames their interpretation of how QualiCo can be used.
Tolerability of Duloxetine in the Elderly and in Young Adults: A Protocol and Preliminary Results of a Systematic Review and Individual Participant Data Meta-Analysis of Randomised Placebo-Controlled Trials.
Authors: Roy Jean-Charles , Rousseau Chloé , Jutel Alexis , Naudet Florian , Robert Gabriel
Published: January 2021

BackgroundDuloxetine is an antidepressant that benefits from a wide range of approval in the elderly population, while its safety for use in the elderly population, compared to younger adults, is not clearly assessed. This protocol outlines a systematic review and individual participant data meta-analysis comparing the tolerability of duloxetine between elderly and younger adults. MethodsOnly randomised controlled clinical trials, comparing duloxetine to placebo, will be included in this meta-analysis. The studies will be selected if participants were adults of less and more than 65 years old, in conditions of use of duloxetine approved by the European Medical Agency (EMA) and the Food and Drug Administration (FDA). The primary outcome will be the rate ratio of serious adverse events under duloxetine compared to placebo, between participants at least 65 years old and younger adults. Second, the number of any adverse events, clinical efficacy and quality of life will be compared between elderly and younger adults under both interventions. The quality of evidence in the tolerability of duloxetine will be assessed using the GRADE system. A two-step random effect meta-analysis will be conducted. Preliminary searches and formal screening of search results against eligibility criteria on have been completed using predefined search term on electronic databases. DiscussionThis study represents the first meta-analysis investigating the safety of duloxetine in the elderly population across all conditions approved by European and American regulatory authorities. The results from this meta-analysis are intended to help prescribers to provide better care for the elderly population.Systematic review registration﻿The protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD42019130488).
CpG Oligodeoxynucleotide Developed For Activating Primate Immune Responses Promotes Anti-Tumoral Effect Combine With Neo-Antigen Based mRNA Cancer Vaccine
Authors: Hu Rongkuan , Li Qin , Ren Jie , Liu Wei , Jiang Guoqin
Published: January 2021

Synthetic phosphorthiolate modified CPG-oligodeoxynucleotides (CPG-ODN) activate innate and adaptive immune responses, which being exploited as a therapeutic approach. Here, we first screened and identified a new CpG-B class ODN (CpG2018B) that effectively stimulates type II interferon both in mouse Plasmacytoid dendritic cells (p-DC) and human PBMC. In addition, CpG2018B promotes cytokine production mainly via toll-like receptor 9 (TLR9) pathways. We further demonstrated that intratumoral (IT) injection of CpG2018B inhibits melanoma growth in syngeneic models and could turn “cold” tumors into “hot” tumors. Then, CpG2018B and mRNA based neo-antigen cancer vaccine were encapsulated into lipid-nanoparticle (LNP) and intratumoral injected into melanoma mice models. Interestingly, vaccination with CpG or mRNA vaccine alone could inhibit tumor growth respectively, while, CpG combine with mRNA vaccine enhanced the anti-tumor effect. At last, we described the long-term safety and tolerability of CpG2018B and mRNA therapy in mice models. In conclusion, we identified a novel CpG-B ODNs to promote immune response and CpG combine with mRNA cancer vaccines are attractive candidate for immune stimulatory sequences (ISS) based therapeutic strategies.