bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of COVID-19 pandemic on workflows and infection prevention strategies of endoscopy units in Hungary - a cross-sectional survey
Authors: Bor Renáta , Szántó Kata Judit , Fábián Anna , Farkas Klaudia , Szűcs Mónika , Rutka Mariann , Tóth Tibor , Bálint Anita , Milassin Ágnes , Dubravcsik Zsolt , Szepes Zoltán , Molnár Tamás
Published: November 2020

Background
Health care professionals in endoscopic labs have an elevated risk for COVID-19 infection, therefore, we aimed to determine the effect of current pandemic on the workflow and infection prevention and control strategies of endoscopy units in real-life setting.
Methods
All members of Hungarian Society of Gastroenterology were invited between 7 and 17 April 2020 to participate in this cross-section survey study and to complete an online, anonymous questionnaire.
Results
Total of 120 endoscopists from 83 institutes were enrolled of which 35.83% worked in regions with high cumulative incidence of COVID-19. Only 33.33% of them had undergone training about infection prevention in their workplace. 95.83% of endoscopists regularly used risk stratification of patients for infection prior endoscopy. While indications of examinations in low risk patients varied widely, in high-risk or positive patients endoscopy was limited to gastrointestinal bleeding (95.00%), removal of foreign body from esophagus (87.50%), management of obstructive jaundice (72.50%) and biliary pancreatitis (67.50%). Appropriate amount of personal protective equipment was available in 60.85% of endoscopy units. In high-risk or positive patients, surgical mask, filtering facepiece mask, protective eyewear and two pairs of gloves were applied in 30.83%, 76.67%, 90.00% and 87.50% of cases, respectively. Personal protective equipment fully complied with European guideline only in 67.50% of cases.
Conclusions
Survey found large variability in indications of endoscopy and relative weak compliance to national and international practical recommendations in terms of protective equipment. This could be improved by adequate training about infection prevention.
Comparative evaluation of the effect of different growth media on in vitro sensitivity to azithromycin in multi-drug resistant Pseudomonas aeruginosa isolated from cystic fibrosis patients
Authors: Sörensen Michael , Khakimov Bakhodur , Nurjadi Dennis , Boutin Sébastien , Yi Buqing , Dalpke Alexander H. , Eigenbrod Tatjana
Published: November 2020

Long-term treatment with azithromycin is a therapeutic option in Cystic Fibrosis (CF) patients chronically infected with P. aeruginosa. It was recently shown that azithromycin has direct antimicrobial activity when P. aeruginosa isolates are tested in Roswell Park Memorial Institute medium supplemented with fetal calf serum (RPMI 1640/FCS) by broth microdilution. We now investigated whether (i) azithromycin might also be active against multidrug resistant (MDR) P. aeruginosa isolated from CF patients and (ii) how in vitro sensitivity assays perform in synthetic cystic fibrosis sputum medium (SCFM), a medium that mimics the particular CF airway environment. In 17 (59%) out of 29 MDR P. aeruginosa CF isolates MICs for azithromycin ranged between 0.25 and 8 µg/ml and 12 isolates (41%) showed a MIC ≥512 µg/ml when measured in RPMI/FCS. In contrast, MICs were ≥256 µg/ml for all P. aeruginosa MDR isolates when tested in either SCFM or in conventional cation-adjusted Mueller Hinton Broth. High MIC values observed in CF adapted medium SCFM for both PAO1 and MDR P. aeruginosa CF isolates, as opposed to findings in RPMI, argue against routine azithromycin MIC testing of CF isolates.
Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome
Authors: pandolfi laura , Tommaso Fossali , Vanessa Frangipane , Sara Bozzini , Monica Morosini , Maura D’Amato , Sara Lettieri , Mario Urtis , Alessandro Di Toro , Laura Saracino , Elena Percivalle , Stefano Tomaselli , Lorenzo Cavagna , Emanuela Cova , Francesco Mojoli , Paola Bergomi , Davide Ottolina , Daniele Lilleri , Guido Corsico Angelo , Eloisa Arbustini , Riccardo Colombo , Federica Meloni
Published: November 2020

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic proportions. Given that the main target of SARS-CoV-2 are lungs leading to severe pneumonia with hyperactivation of the inflammatory cascade, we conducted a prospective study to assess alveolar inflammatory status in patients with moderate to severe COVID-19. Methods: Diagnostic bronchoalveolar lavage (BAL) was performed in 33 adult patients with SARS-CoV-2 infection by real-time PCR on nasopharyngeal swab admitted to the Intensive care unit (ICU) (n=28) and to the Intermediate Medicine Ward (IMW) (n=5). We analyze the differential cell count, ultrastructure of cells and Interleukin(IL)6, 8 and 10 levels.Results: ICU patients showed a marked increase in neutrophils (1.24 x 105 ml-1 , 0.85-2.07), lower lymphocyte (0.97 x 105 ml-1, 0.024-0.34) and macrophages fractions (0.43 x 105 ml-1, 0.34-1.62) compared to IMW patients (0.095 x 105 ml-1, 0.05-0.73; 0.47 x 105 ml-1, 0.28-1.01 and 2.14 x 105 ml-1, 1.17-3.01, respectively) (p<0.01). Study of ICU patients BAL by electron transmission microscopy showed viral particles inside mononuclear cells confirmed by immunostaining with anti-viral capsid and spike antibodies. IL6 and IL8 were significantly higher in ICU patients than in IMW (IL6 p<0.01, IL8 p<0.0001), and also in patients who did not survive (IL6 p < 0.05, IL8 p = 0.05 vs. survivors). IL10 did not show a significant variation between groups. Dividing patients by treatment received, lower BAL concentrations of IL6 were found in patients treated with steroids as compared to those treated with tocilizumab (p<0.1) or antivirals (p<0.05). Conclusions: Alveolitis, associated with COVID-19, is mainly sustained by innate effectors which showed features of extensive activation. The burden of pro-inflammatory cytokines IL6 and IL8 in the broncho-alveolar environment is associated with clinical outcome.
Assessment and treatment of recurrent urinary tract infections in women: qualitative study of patient expectations in secondary care
Authors: Pat Jorik , Aart Tamar van der , Steffens Martijn , Witte Lambertus , Blanker Marco
Published: November 2020

Background. To develop a questionnaire to facilitate the inventorying of women’s expectations for the assessment and treatment of recurrent urinary tract infection (UTI) in secondary care.Methods. Semi-structured interviews were conducted among women with recurrent UTI referred to our urology department. The interviews were conducted by one interviewer, recorded, transcribed verbatim, and analyzed thematically by two researchers. We first developed 35 questions to identify potential themes, and we then tested them among women with and without recurrent UTI. Changes were made according to the feedback received.Results. Six interviews were conducted before saturation was reached. Thematic analysis identified three themes: patient pathway, personal knowledge, and social implications. All respondents had received multiple antibiotic courses but no prophylactic antibiotic therapy, and although all were aware of some preventive measures, they wanted more information about their disease. However, some women were afraid to access information for fear of what they might learn. Recurrent UTI also significantly affected the daily lives all respondents. Some women expressed fears over frequent antibiotic use, and others felt that there must be something wrong with their body to have so many UTIs. Women expected the urologist to provide an explanation and to start adequate therapy for their recurrent UTI. We created a 32-item questionnaire based on these themesConclusion. This study not only developed a questionnaire for use when assessing patient expectations of recurrent UTI management in secondary care but also provided novel insights into the thoughts, opinions, and expectations of women who are referred.
Contribution of Autologous Omentum Transposition to the Regeneration of Renal Injuries in the Rat Model
Authors: Bilgic Tayfun , Ince Umit , Narter Fehmi
Published: November 2020

Aim: After renal trauma, surgical treatment is vital, but sometimes there may be loss of function due to fibrosis. We aimed to evaluate the repair effect of transpositioned autologous omentum on injured renal tissue in a rat model. Methods: A total of 30 female Wistar Albino rats were included and they were randomly separated into a sham group and four study groups. Iatrogenic renal injuries were repaired using a surgical technique (primary repair 1 and 2 groups) or transpositioned autologous omentum (omentum repair 1 and 2 groups). In all groups, blood samples were taken preoperatively and on the 7 th postoperative day in all groups and also on the 18 th postoperative day in the control and two study groups. All rats were sacrificed on the 7 th or 18 th day postoperatively and their right kidneys were taken for histopathological evaluation.Results: There was a trend toward decrease in urea and creatinine levels in all the groups. There was no significant correlation between urea and creatinine levels and histological finding scores. The omentum repair group had significantly lower inflammation and granulation scores compared with the primary repair and sham groups. There was a significant and positive correlation between inflammation and granulation and fibrosis scores. There was a significant and negative correlation between healing completion score and either inflammation and granulation scores. There were also positive correlations between histological findings in the kidney specimen and surrounding tissues. Conclusion: The use of the autologous omentum tissue for repair of kidney injury had attenuation effects on inflammation and granulation compared with primary repair. These results imply that use of omentum tissue to facilitate healing of kidney injury may theoretically lead to a more effective healing process and reduced fibrosis and tissue and function loss. These potentially beneficial effects of autologous omentum tissue should be investigated in further well-designed experimental and clinical studies.
An empirical analysis of dealing with patients who are lost to follow-up when developing prognostic models using a cohort design
Authors: Reps Jenna M , Rijnbeek Peter , Cuthbert Alana , Ryan Patrick B , Pratt Nicole , Schuemie Martijn J
Published: November 2020

Background: Researchers developing prediction models are faced with numerous design choices that may impact model performance. One key decision is how to include patients who are lost to follow-up. In this paper we perform a large-scale empirical evaluation investigating the impact of this decision. In addition, we aim to provide guidelines for how to deal with loss to follow-up.Methods: We generate a partially synthetic dataset with complete follow-up and simulate loss to follow-up based either on random selection or on selection based on comorbidity. In addition to our synthetic data study we investigate 21 real-world data prediction problems. We compare four simple strategies for developing models when using a cohort design that encounters loss to follow-up. Three strategies employ a binary classifier with data that: i) include all patients (including those lost to follow-up), ii) exclude all patients lost to follow-up or iii) only exclude patients lost to follow-up who do not have the outcome before being lost to follow-up. The fourth strategy uses a survival model with data that include all patients. We empirically evaluate the discrimination and calibration performance.Results: The partially synthetic data study results show that excluding patients who are lost to follow-up can introduce bias when loss to follow-up is common and does not occur at random. However, when loss to follow-up was completely at random, the choice of addressing it had negligible impact on the model performance. Our empirical real-world data results showed that the four design choices investigated to deal with loss to follow-up resulted in comparable performance when the time-at-risk was 1-year, but demonstrated differential bias when we looked into 3-year time-at-risk. Removing patients who are lost to follow-up before experiencing the outcome but keeping patients who are lost to follow-up after the outcome can bias a model and should be avoided.Conclusion: Based on this study we therefore recommend i) developing models using data that includes patients that are lost to follow-up and ii) evaluate the discrimination and calibration of models twice: on a test set including patients lost to follow-up and a test set excluding patients lost to follow-up.
Death in hospital following ICU discharge: insights from the LUNG SAFE study
Authors: Madotto Fabiana , McNicholas Bairbre , Rezoagli Emanuele , Pham Tài , Laffey John , Bellani Giacomo
Published: November 2020

Background: To determine the frequency of, and factors associated with, death in hospital following ICU discharge to the ward.Methods: The Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study was an international, multicenter, prospective cohort study of patients with severe respiratory failure, conducted across 459 ICUs from 50 countries globally. This study aimed to understand the frequency and factors associated with death in hospital in patients who survived their ICU stay. We examined outcomes in the subpopulation discharged with no limitations of life sustaining treatments (‘treatment limitations’), and the subpopulations with treatment limitations.Results: 2,186 (94%) patients with no treatment limitations discharged from ICU survived, while 142 (6%) died in hospital. 118 (61%) of patients with treatment limitations survived while 77 (39%) patients died in hospital. Patients without treatment limitations that died in hospital after ICU discharge were older, more likely to have COPD, immunocompromise or chronic renal failure, less likely to have trauma as a risk factor for ARDS. Patients that died post ICU discharge were less likely to receive neuromuscular blockade, or to receive any adjunctive measure, and had a higher pre- ICU discharge non-pulmonary SOFA score. A similar pattern was seen in patients with treatment limitations that died in hospital following ICU discharge.Conclusions: A significant proportion of patients die in hospital following discharge from ICU, with higher mortality in patients with limitations of life-sustaining treatments in place. Non-survivors had higher systemic illness severity scores at ICU discharge than survivors. (Word count 251)Trial Registration: ClinicalTrials.gov NCT02010073
Low-dosage Ozonation in Gas-phase Biofilter Promotes Community Diversity and Robustness.
Authors: Yeung Marvin , Saingam Prakit , Xu Yang , Xi Jinying
Published: November 2020

Background: The ozonation of biofilters is known to alleviate clogging and pressure drop issues while maintaining removal performances in biofiltration systems treating gaseous volatile organic compounds (VOCs). The effects of ozone on the biofilter microbiome in terms of biodiversity, community structure, metabolic abilities, and dominant taxa correlated with performance remain largely unknown. Methods: This study investigated two biofilters treating high-concentration toluene operating in parallel, with one acting as control and the other exposed to low-dosage (200 mg/m3) ozonation. The microbial community diversity, metabolic rates of different carbon sources, functional predictions, and microbial co-occurrence networks of both communities were examined. Results: Consistently higher biodiversity of over 30% was observed in the microbiome after ozonation, with increased overall metabolic abilities for amino acids and carboxylic acids. The relative abundance of species with reported stress-tolerant and biofilm-forming abilities significantly increased, with a consortium of changes in predicted biological pathways, including shifts in degradation pathways of intermediate compounds, while the correlation of top ASVs and genus with performance indicators showed diversifications in microbiota responsible for toluene degradation. A co-occurrence network of the community showed a decrease in average path distance and average betweenness with ozonation. Conclusion: Major degrading species highly correlated with performance shifted after ozonation. An increase in microbial biodiversity coupled with improvements in metabolizing performances of multiple carbon sources including organic acids could explain the consistent performance commonly seen in the ozonation of biofilters despite the decrease in biomass, while avoiding acid buildup in long term operation. The increased presence of stress-tolerant microbes in the microbiome coupled with the decentralization of the co-occurrence network suggested that ozonation could not only ameliorate clogging issues but also provide a microbiome more robust to loading shock seen in full-scale biofilters.
Endothelial progenitor cells promote osteogenic differentiation in co-cultured with mesenchymal stem cells via the MAPK-dependent pathway
Authors: xu chu , liu haijie , he yuanjia , li yuanqing , he xiaoning
Published: November 2020

Background: The role of bone tissue engineering is to regenerate tissue using biomaterials and stem cell based approaches. Combination of two or more cell types is one of the strategies to promote bone formation. Endothelial progenitor cells (EPCs) may enhance the osteogenic properties of mesenchymal stem cells (MSCs) and promote bone healing, this study aimed to investigate the possible mechanisms of EPCs on promoting osteogenic differentiation of MSCs.Methods: MSCs and EPCs were isolated and co-cultured in Transwell chambers, the effects of EPCs on the regulation of MSC biological properties was investigated. Real-time PCR array and western blotting were performed to explore possible signaling pathways involved in osteogenesis. The expression of osteogenesis markers and calcium nodule formation was quantified by qRT-PCR, western blotting and Alizarin Red staining. Results: Results showed that MSCs exhibited greater alkaline phosphatase (ALP) activity and increased calcium mineral deposition significantly when co-cultured with EPCs. The mitogen-activated protein kinase (MAPK) signaling pathway was involved in this process. p38 gene expression and p38 protein phosphorylation levels showed significant up-regulation in co-cultured MSCs. Silencing expression of p38 in co-cultured MSCs reduced osteogenic gene expression, protein synthesis, ALP activity and calcium nodule formation. Conclusions: These data suggest paracrine signaling from EPCs influence the biological function and promote MSCs osteogenic differentiation. Activation of the p38MAPK pathway may be the key to enhancing MSCs osteogenic differentiation via indirect interactions with EPCs.
Exposure to negative socio-emotional events induces sustained alteration of resting-state brain networks in the elderly
Authors: Lugo Sebastian Baez , Deza-Araujo Yacila , Collette Fabienne , Vuilleumier Patrik , Klimecki Olga , group and The Medit-Ageing Research
Published: November 2020

Socio-emotional functions seem well-preserved in the elderly. However, the long-lasting effects that the exposure to others’ distress may provoke in the brain remain unknown in this population. To evaluate how the aging brain reacts during and after emotionally challenging social events, we designed a new "task-rest" paradigm in which elderly participants (N=127) underwent functional magnetic resonance imaging (fMRI) while exposed to socio-emotional videos. We unveil neural markers of "emotional inertia" in brain activity and connectivity following negative scenes. Exposure to others' suffering induced differential activations that lingered over time into the subsequent resting-state in regions of the default mode network (DMN). Moreover, emotional elicitation potentiated subsequent resting-state connectivity between posterior DMN and amygdala, which in turn was related to anxiety, rumination, and negative thoughts. These findings uncover brain mechanisms underlying emotional resilience and empathy in the elderly and may help understand how poor social stress regulation promotes neurodegenerative diseases.
Generation of functional liver tissue by establishing hepatobiliary connections ex vivo
Authors: Tanimizu Naoki , Ichinohe Norihisa , Sasaki Yasushi , Itoh Tohru , Sudo Ryo , Yamaguchi Tomoko , Katsuda Takashi , Tokino Takashi , Ochiya Takahiro , Miyajima Atsushi , Mitaka Toshihiro
Published: November 2020

In the liver, the bile canaliculi of hepatocytes are connected to intrahepatic bile ducts lined with cholangiocytes, which remove cytotoxic bile from the liver tissue. We have developed a hepatobiliary organoid using mouse hepatocyte progenitors and cholangiocytes. Hepatocyte metabolites were secreted into the bile canaliculi, and then transported into the biliary structure. Hepatocytes in the organoid acquired and maintained metabolic functions including albumin secretion and cytochrome P450 activities, over the long term. In this study, we established functional liver tissue incorporating a bile drainage system ex vivo. This hepatobiliary organoid enabled us to reproduce the transport of hepatocyte metabolites in liver tissue, and to investigate the way in which the two types of epithelial cells establish functional connections.
Thermal plasticity in coral reef symbionts is mediated by oxidation of membrane lipids
Authors: Botana Marina , Chaves-Filho Adriano , Inague Alex , Guth Arthur , Saldanha-Corrêa Flavia , Muller Marius , Sumida Paulo , Miyamoto Sayuri , Kellermann Matthias , Valentine Raymond , Yoshinaga Marcos
Published: November 2020

The oxidation of polyunsaturated fatty acids (PUFA) is a common stress response across biomes with potential to trigger impairment of cell growth and reproduction. The oxidative stress theory of coral bleaching induced by global warming has been widely accepted to explain coral reef decline, but its underlying physiological mechanism remains under debate. Here we used lipidomic and population density data to examine cell cultures of three coral reef symbionts after a heat shock (sudden rise of 12 °C for 4 hours). Heat tolerance in S. microadriaticum and C. goreaui was characterized by preservation of thylakoid-derived glycolipids. Conversely, heat sensitivity in B. minutum was linked to elevated concentrations of oxidized PUFA esterified to glycolipids, suggesting that culture growth had ceased due to severe oxidative damage. Our findings provide a basis to further understand the role played by oxidative stress in coral bleaching and reveal novel biomarkers for the monitoring of symbiont-coral health.
A Note on COVID-19 Diagnosis Number Prediction Model in China
Authors: Li Yi , Yin Xianhong , Wang Yi , Liang Meng , Liu Xiaoyu , Hao Meng
Published: November 2020

In December 2019, pneumonia infected with the novel coronavirus burst in Wuhan, China. We aimed to use a mathematical model to predict number of diagnosed patients in future to ease anxiety on the emergent situation. Our model was based on the epidemic situation in China, which could provide referential significance for disease prediction in other countries, and provide clues for prevention and intervention of relevant health authorities. In this retrospective, all diagnosis number from Jan 21 to Feb 10, 2020 reported from China was included and downloaded from WHO website. We develop a simple but accurate formula to predict the next day diagnosis number: N_i/N_(i-1) =〖(N_(i-1)/N_(i-2) )〗^α，where Ni is the total diagnosed patient till the ith day, and α was estimated as 0.904 at Feb 10. Based on this model, it is predicted that the rate of disease infection will decrease exponentially. The total number of infected people is limited; thus, the disease will have limited impact. However, new diagnosis will last to end of March. Through the establishment of our model, we can better predict the trend of the epidemic in China.
Study on the Pharmacological Mechanism of Phthalazinone Derivatives as Potential Drugs for Alzheimer’s Disease Treatment by Network Pharmacology Analysis and Molecular Docking
Authors: Ye Huimin , Li Zhong
Published: November 2020

Objective: To screen the bioactivity of phthalazinone derivatives for AD treatment and investigate the potential pharmacological mechanism, the network pharmacology analysis and molecular docking were adopted in this study.Methods: Those phthalazinone derivatives with certain structures and physical properties were screened out by Pubchem database in this study. Besides, to explore the potential activity of these phthalazinone derivatives as drugs for AD treatment, network pharmacology study was employed, including targets prediction, gene enrichment analysis and network analysis. Network analysis of AD approved drugs and molecular docking studies were also adopted to further investigate drug-likeness of phthalazinone derivatives for AD treatment.Results: Five compounds and 57 common targets were recognized and adopted to the construction of compounds-targets network. 15 approved drugs with clear indication for AD were figured out, with 57 associated targets that originated from Homo sapiens. The KEGG enrichment analysis showed that phthalazinone derivatives and approved drugs shared the same essential pathway (neuroactive ligand-receptor interaction) and other important pathways with associated targets. The result of molecular docking indicated that these phthalazinone derivatives could interact with essential targets stably.Conclusion: In silico analysis suggested that these derivatives are probable to be effective for the treatment of AD by interacting with the essential targets and initiating ATP binding, signal transduction, finally regulating neuroactive ligand-receptor interaction pathway、calcium signaling pathway , and so on.
Risk of Arterial Stiffness According to Metabolically Healthy Obese Phenotype: A Combined Cross-Sectional and Longitudinal Study in Kailuan Cohort
Authors: Wang Anxin , Wang Yu , Zuo Yingting , Tian Xue , Chen Shuohua , Ma Yihan , Han Xu , Wu Shouling , Zhao Xingquan
Published: November 2020

BackgroundTo investigate the risk of incident arterial stiffness according to metabolically healthy obese (MHO) phenotype in Chinese population.Materials and methodsThe Kailuan study is an ongoing prospective cohort study, 37,180 participants with at least one-time measurement of branchial-ankle pulse wave velocity (baPWV) were included in the cross-sectional analysis, and 16,236 participants with repeated measurement of baPWV during the follow-ups were included in the longitudinal study from March 1, 2010, to January 31, 2020. Cross-classification of body mass index (BMI) categories and metabolic health status created six groups. Linear and logistic regression analyses were used to assess the association between BMI-metabolic status phenotypes and baPWV in mono-factor and multi-factor models. ResultsThe results of cross-sectional and longitudinal investigation were basically the same, as the abnormality of baPWV increased with BMI categories in metabolically healthy participants, while the increasing tendency disappeared in metabolically unhealthy participants. A 1.6-fold, 2.8-fold increased risk for the new occurrence of arterial stiffness were documented in MHO and metabolically unhealthy obese participants compared to metabolically healthy normal weight controls in the fully adjusted model. Further stratified analysis shown that metabolic health status was an interaction factor between BMI and arterial stiffness in either study population (P<0.0001 for cross-sectional study and P=0.0003 for longitudinal study).ConclusionsMetabolic health status and BMI categories contribute to the progression of arterial stiffness, while BMI is positively associated with arterial stiffness only in metabolically healthy participants. Moreover, MHO is an intermediate stage between metabolically healthy and unhealthy status.Trial registration: ChiCTR-TNRC-11001489. Registered 24 August 2011 - Retrospectively registered, http://www.chictr.org.cn/showprojen.aspx?proj=8050
The SGLT-2 Inhibitor Empagliflozin Improves Myocardial Strain, Reduces Cardiac Fibrosis and Pro-Inflammatory Cytokines in Non-Diabetic Mice Treated With Doxorubicin
Authors: Quagliariello Vincenzo , Laurentiis Michelino De , Rea Domenica , Barbieri Antonio , Monti Maria Gaia , Caronna Antonietta , Bonelli Annamaria , Botti Gerardo , Maurea Nicola
Published: November 2020

BackgroundEmpagliflozin (EMPA), a selective inhibitor of the sodium glucose co-transporter 2, reduced the risk of hospitalization for heart failure and cardiovascular death in type 2 diabetic patients in the EMPA‐REG OUTCOME trial. Other clinical trials evaluated beneficial effects of empagliflozin in non-diabetic patients. We aimed to evaluate the effects of empagliflozin on myocardial strain of non-diabetic mice treated with doxorubicin evaluating changes in cardiac cytokine profile, fibrosis and apoptosis. Methods Preliminary cellular studies were performed on HL-1 human cardiomyocytes exposed to doxorubicin alone or combined to empagliflozin. Reactive oxygen species, intracellular calcium homeostasis, expression of leukotrienes, NF-kB and interleukin-1β, 8 and 6 were analysed. C57Bl/6 mice were untreated (Sham, n=6) or treated for 10 days with doxorubicin (DOXO, n=6), empagliflozin (EMPA, n=6) or doxorubicin and empagliflozin (DOXO-EMPA, n=6). Radial and longitudinal strain were analysed through transthoracic echocardiography (Vevo 2100). Cardiac fibrosis and apoptosis were studied through Picrosirius red and TdT-mediated dUTP nick-end labelling (TUNEL) assay, respectively; interleukins were quantified in tissues through ELISA.ResultsA significant increase in intracellular calcium and pro-inflammatory markers associated to pro-oxidant mediators were seen after cell exposure to doxorubicin; co-incubation with empagliflozin reduced significantly the magnitude of the effects. Oral administration of empagliflozin in mice prevented the reduction of radial and longitudinal strain during treatment with doxorubicin, reduced significantly both cardiac fibrosis and apoptosis. A reduced expression of pro-inflammatory cytokines, NLRP3 and NF-kB in heart, liver and kidney was also seen in DOXO-EMPA group (p<0.001).ConclusionEmpagliflozin reduced fibrosis, apoptosis and inflammation in doxorubicin-treated mice, enhancing significantly the myocardial strain. These findings provides the proof of concept for translational studies designed to reduce adverse cardiovascular outcomes in non-diabetic cancer patients treated with doxorubicin.
The Impact of Serum 25-hydroxyvitamin D, Calcium, and Parathyroid Hormone Levels on the Risk of Coronary Artery Disease in Patients With Diabetes: A Mendelian Randomization Study
Authors: Chen Songzan , Yang Fangkun , Xu Tian , Wang Yao , Zhang Kaijie , Fu Guosheng , Zhang Wenbin
Published: November 2020

BackgroundTo investigate the causal association between serum 25-hydroxyvitamin D (25OHD), calcium (Ca), and parathyroid hormone (PTH) levels and the risk of coronary artery disease (CAD) in patients with diabetes using a Mendelian randomization approach.MethodsGenetic signatures associated with serum 25OHD, Ca, and PTH levels were extracted from recently published genome-wide association study (GWAS), including 79,366, 39,400, 29,155 individuals, respectively. Genetic association estimates for CAD in patients with diabetes were obtained from a GWAS of 15,666 individuals with diabetes (3,968 CAD cases, 11,696 controls). The inverse-variance-weighted method was employed for the primary analysis, and other robust methods were applied for sensitivity analyses.ResultsSix, seven and five single nucleotide polymorphisms were identified as instrumental variables for serum 25OHD, Ca and PTH levels, respectively. There was no significant association between genetically predicted serum 25OHD levels and the risk of CAD in patients with diabetes (odds ratio (OR) = 1.04, 95% confidence interval (CI): 0.58 - 1.87, P = 0.888). Similarly, genetically predicted serum Ca (OR = 1.83, 95% CI: 0.62 – 5.35, P = 0.273) and PTH levels (OR = 1.27, 95% CI: 0.67 – 2.44, P = 0.464) were not significantly associated with the risk of CAD in patients with diabetes. These findings were robust in sensitivity analyses.Conclusions/interpretationThis study found no evidence to support the causal association between serum 25OHD, Ca and PTH levels and the risk of CAD in patients with diabetes.
Research on Saponin Active Ingredient of Stir-Fried Dolichos Lablab L. Kernel for Treatment of Type-2 Diabetes Based on UHPLC-Q-Exactive Orbitrap MS and Network Pharmacology
Authors: Jun Han , Fang Liangzi , Zheng Qinfang
Published: November 2020

BackgroundAlthough the clinical effect of stir-fried Dolichos lablab L. kernel has been approved in modern traditional Chinese medicine, existing associated studies mainly focus on its clinical studies and chemical ingredients. However, there are few studies on pharmacodynamics material basis and molecular mechanism of stirfried Dolichos lablab L. kernel in treatment of type-2 diabetes(T2DM), thus restricting the further development and utilization of stir-fried Dolichos lablab L. kernel.MethodsA qualitative analysis on saponin chemical ingredients of stir-fried Dolichos lablab L. kernel was performed using UHPLC-Q-Exactive Orbitrap MS. A total of 10 saponin ingredients were selected. Moreover, target screening, biological process and metabolism pathway analysis were accomplished by network pharmacology. Four key proteins(EGFR, IGF1, MAPK1 and PIK3R1) of type-2 diabetes were selected for molecular docking verification with saponin ingredients. Specifically, molecular dynamics simulation of ingredients which have strong bindings with proteins was conducted. ResultsIn this study, 16 saponin ingredients were identified from stir-fried Dolichos lablab L. kernel. There were 91 intersection targets and the KEGG pathway enrichment involved 20 relevant pathways. According to the molecular docking verification, saponin ingredients of stir-fried Dolichos lablab L. kernel can form stable binding with key protein targets. The molecular dynamics simulation further verifies stability and reasonability of the docking results. ConclusionsThis study provides references to identification of efficient ingredients of stir-fried Dolichos lablab L. kernel, screening of quality markers and explanation of relevant action mechanism by combining UHPLC-Q-Exactive Orbitrap MS and network pharmacology.
Scanning Various Nanomaterials and Variable Camouflages to Evaluate the Biocompatibility in Multi-organs of Embryos
Authors: Zheng Bin , Guo Mingming , Pang Meijun , Ming Dong
Published: November 2020

Background:Nanomaterials are under a wide range of application prospects in human health and disease, such as medical imaging and drug delivery and treatment. With the gradual advent of the nano era, the safety of nanomaterials in biology must be evaluated more widely and deeply. Therefore, superficial safety assessment based on specific cell lines in vitro is difficult to meet the current needs. Multi-organs assessment in vivo will be beneficial in establishing a more comprehensive pathway for the understanding of nanomaterials-induced biotoxicity. Results:In this work, we employed a series of genetically modified zebrafish models for nanomaterials toxicity assessment. The results demonstrated that cadmium selenide (CdSe) quantum dot (QDs) was the most toxic after scanning some popular nanomaterials. Among modified methods of silica coating, core-shell structure development and organic molecular camouflage, the polyethylene glycol camouflage method exhibits a better performance of improving the biocompatibility of CdSe QDs in multiple-organs including hearts, nerves, blood vessels, and immune system. Conclusion:Our work provides an alternative paradigm for more in-depth and sensitive preclinical validation of biocompatibility, especially in neurotoxicity and cardiotoxicity of embryos, and a guidance for reducing the toxicity of biomedical materials.
Realising Sexual and Reproductive Health Rights of Adolescent Girls and Young Women Living in Slums in Uganda: A Qualitative Study
Authors: McGranahan Majel , Bruno-McClung Elizabeth , Nakyeyune Joselyn , Nsibirwa Derrick Aaron , Baguma Christopher , Ogwang Christopher , Serunjoji Francis , Nakalembe Judith , Kayaga Marianna , Sekalala Sharifah , Oyebode Oyinlola
Published: November 2020

BackgroundSexual and reproductive health rights are critical entitlements best supported through human rights-based approaches empowering duty-bearers and rights-holders. Implementing these requires information on the current needs and challenges faced by those seeking to claim their sexual and reproductive health rights. We aimed to identify the underlying factors influencing the realisation of sexual and reproductive health rights for adolescent girls and young women living Ugandan slums by: (1) exploring the role of relevant service providers and stakeholders; and (2) uncovering knowledge and gaps in protecting adolescent girls’ and young women’s sexual and reproductive health rights.Methods Qualitative data were collected through focus groups and interviews focused on current knowledge, behaviours and attitudes towards sexual and reproductive health rights among adolescent girls and young women, service providers and stakeholders. Data were analysed thematically. Results Ten in-depth interviews were conducted with key informants (N=10); two focus groups were held with adolescent girls and young women living in two slums in Uganda (N=21); and three focus groups were held with community leaders, service providers, teachers and parents (N=30). Adolescent girls and young women lacked information regarding their sexual health, services available, and redress mechanisms for rights violations. Formal sources of information were frequently inaccessible. Family members were sometimes the source of rights violations, and informal methods of redressing rights were often sought. Stigma and fear were common features both in healthcare and in the pursuit of formal justice, with duty-bearers habitually breaking confidentiality. Education and training were the predominant suggestions offered for change. Conclusions Adolescent girls and young women continue to face obstacles in achieving their full sexual and reproductive health rights. Targeted interventions for the realisation of adolescent girls’ and young women’s sexual and reproductive health rights can address underlying causes and positively shift attitudes to promote health.
Noble Gases Deliver Cool Dates from Hot Rocks
Authors: Gautheron Cécile , Zeitler Peter K.
Published: November 2020

Heat transfer in the solid Earth drives processes that modify temperatures, leaving behind a clear signature that we can measure using noble gas thermochronology. This allows us to record the thermal histories of rocks and obtain the timing, rate, and magnitude of phenomena such as erosion, deformation, and fluid flow. This is done by measuring the net balance between the accumulation of noble gas atoms from radioactive decay and their loss by temperature-activated diffusion in mineral grains. Together with knowledge about noble gas diffusion in common minerals, we can then use inverse models of this accumulation–diffusion balance to recover thermal histories. This approach is now a mainstream method by which to study geodynamics and Earth evolution.
Lessons from the Ramond sector
Authors: Benjamin Nathan , Lin Ying-Hsuan
Published: November 2020

We revisit the consistency of torus partition functions in (1+1)d fermionic conformal field theories, combining old ingredients of modular invariance/covariance with a modernized understanding of bosonization/fermionization dualities.
Various lessons can be learned by simply examining the oft-ignored Ramond sector.
For several extremal/kinky modular functions in the bootstrap literature, we can either rule out or identify the underlying theory.
We also revisit the N = 1 Maloney-Witten partition function by calculating the spectrum in the Ramond sector, and further extending it to include the modular sum of seed Ramond characters.
Finally, we perform the full N = 1 RNS modular bootstrap and obtain new universal results on the existence of relevant deformations preserving different amounts of supersymmetry.
The role of SMES’ market orientation in developing countries: a general investigation in four countries
Authors: Nikmah Farika , Sudarmiatin  , Wardoyo Cipto , Hermawan Agus , Eko Soetjipto Budi
Published: November 2020

SMEs are limited in their business development. This study is built on previous research conducted in four developing countries (Nigeria, South Africa, Turkey and India). It is difficult to access a bank to get a loan, they have no understanding of how to produce quality products or services, and they have no awareness to get used to learning; these are the problems faced by SMEs.The goal of this study is to find out market-oriented strategies to achieve performance in SMEs that are often ignored because they are too expensive. Review papers were used in order to get the stated aim. This study found out that market orientation is not carried out by most SMEs. There are high investment costs for this. Market orientation cannot always guarantee the success of their business. Problem solving was chosen as a strategy in an effort to make market orientation roles more visible, like easy access to finance, awareness of the quality of products and services they produce, and the habit of continuing to learn. The government, along with SME owners and other interested parties, makes some appropriate formulations to strengthen the position of SMEs as a driving force of the economy. It was concluded that SMEs must obtain special policies regarding the ease of financing from banks, availability of training organized by the government to raise knowledge of quality and awareness to always learn, and enabling SMEs to compete with large companies.
Cash flows and financial performance in the industrial sector of Saudi Arabia: With special reference to Insurance and Manufacturing Sectors
Authors: Rahman Abdul , Bahadur Sharma Raj
Published: November 2020

A firm with proper cash flow management can increase its financial performance, while improper management might lead to financial failure. Therefore, it is significant for a firm to manage cash inflows and outflows properly. The current study investigates the effect of cash flow from operations (CFOs) on the financial performance of insurance and manufacturing companies in Saudi Arabia. The data were extracted from companies’ annual reports by considering Return on Assets (ROA) and Return on Equity (ROE) as dependent variables, CFOs as an explanatory variable, firm size (SIZE) and Leverage (LEV) as control variables, and an industry dummy. The results report a positive and significant association between financial performance (ROA and ROE) and operating cash flows (CFOs), and a negative association for SIZE and LEV. Therefore, the study concludes that the firms’ operating cash flows in the insurance and manufacturing sectors in Saudi Arabia affect financial performance.
Formation of the concept of legal regulation of preimplantation genetic
diagnosis in the Russian Federation in the context of ensuring and
protecting reproductive freedom of the individual
Authors: V.V. Komarova , N.A. Altinnik , G.N. Suvorov
Published: November 2020

Objectives. The aim of this study is the formation of a concept of preimplantation genetic diagnosis (PGD)
in the Russian Federation in the context of ensuring and protecting reproductive freedom of the individual.
Material. The regulatory legal acts, the doctrinal sources of the Russian Federation are examined to identify
key problems that impede the formation of the desired concept. Methods used: general philosophical, general
scientific, private scientific, special (structural-legal, formal-legal).
Results. The basic postulates of the concept of legal regulation of PGD in the Russian Federation are
substantiated. As part of the analysis of domestic legislation, key problems are identified that impede the
formation of the desired concept that meets the level of development of medical science and the needs of
consumers of medical services. The conclusion is justified that it is necessary to fix at the legislative level the place
of pre-plantation genetic tests in the assisted reproductive technologies system, thus giving PGD independent
significance outside the context of the problems of infertility treatment. It has been argued that, in addition to
the norms of the basic law on protecting the health of citizens, a separate sub-legislative normative legal act of
the Ministry of Health of the Russian Federation should be developed in the system of legal regulation of PGD in
Russia, forming a set of mandatory requirements for the PGD procedure, depending on diagnostic goals, as well
as determining which methods are preferable depending on the goal and what results the consumer can count on.
Conclusions. It is noted that in the system of norms on genetic research, special attention should be paid
to genetic counseling, establishing mandatory requirements for the content of the consultation - in relation to
PGD, this should include explanations regarding the algorithm and method of the study, the possibilities and
limitations of this type of diagnosis for each a particular case, the features of its application to solve a single
genetic problem.
Da Cidade Inteligente, ao Território Inovador, Rumo à Inteligência Territorial: Aproximações Teóricas e Prospecções sobre o Tema
Authors: Dallabrida Valdir Roque
Published: November 2020

O debate teórico sobre inovação e sua relação com o desenvolvimento, geralmente com foco no espaço urbano, tem resultado em diferentes abordagens sobre cidades inteligentes. As mesmas são passíveis de críticas, como o fato de as prerrogativas não serem replicáveis, a ênfase excessiva ao argumento do desenvolvimento urbano ser impulsionado por negócios privados em aliança com governos e sociedade, ou o fato das experiências carecerem de práticas inclusivas e participativas. Já a abordagem sobre território inovador ou inteligente, permite avançar teoricamente, oportunizando a interação social para a tomada de decisões e a valorização e apropriação territorial do conhecimento. Complementarmente, os enfoques teóricos sobre inteligência territorial, são apresentados como uma inovadora forma de compreender os processos territoriais, produtivos e sociais, de integrar atores e suas perspectivas, visões e iniciativas, com vistas ao desenvolvimento territorial. É sobre estas questões teóricas que se pretende refletir, por meio do acesso às publicações recentes, com o propósito de instigar acedências na direção da efetividade de uma inteligência territorial.