bluuebunny/crossref_metadata_2025 huggingface dataset:
Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) Inhibits Steroidogenesis in Adrenocortical Cell by Macrophage-derived Exosomes in Lipopolysaccharide-induced Septic Shock
Authors: Ye Hui , Li Pinhao , Zhai Qian , Fang Ping , Yang Shiyue , Sun Yaqi , Wu Shuijing , Huang Ruoqiong , Chen Qixing , Fang Xiangming
Published: August 2020

Background: Endogenously produced glucocorticoids exhibit immunomodulating properties and are of pivotal importance for sepsis outcome. Uncontrolled activation of the immune-adrenal crosstalk increases the risk of sepsis-related death. Triggering receptor expressed on myeloid cells-2 (TREM2) is richly expressed on macrophages and has been demonstrated to improve outcome of sepsis by enhancing elimination of pathogens. However, the role and mode of action of macrophage TREM2 on adrenocortical steroidogenesis remains unclear in septic shock.Methods: The acute septic shock model was established by intraperitoneally challenging wild-type (WT) and TREM2 knock-out (Trem2-/-) mice with lipopolysaccharide (30 mg/kg). The mice were assessed for TREM2 expression and local inflammation in adrenal gland and synthesis of corticotropin releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) in vivo. Bone marrow-derived macrophages or macrophage-derived exosomes were isolated from WT and Trem2-/- mice and co-cultured with adrenocortical cells. The expression of steroidogenic enzymes and corticosterone production were assessed.Results: Genetic deficiency of TREM2 caused significantly higher corticosterone levels (326.6 ± 73.0 ng/ml in Trem2-/- mice vs. 151.1 ± 58.9 ng/ml in WT mice; p < 0.001) at the early stage of LPS-induced septic shock. While TREM2 deficiency neither increased CRH and ACTH, nor exacerbated the inflammation in adrenocortical tissue during septic shock. Ex vivo study revealed that Trem2-/- macrophages significantly promoted the expression of steroidogenic enzymes and increased production of corticosterone (27.73 ± 1.78 ng/ml in Trem2-/- mice vs. 22.96 ± 1.94 ng/ml in W T mice; p < 0.01). Furthermore, Trem2-/- macrophage-derived exosomes were able to mimic Trem2-/- macrophages in enhancing adrenocortical steroidogenesis. Conclusions: At the early stage of lipopolysaccharide-induced septic shock, macrophage TREM2 inhibited the steroid synthesis and corticosterone production in adrenocortical cells, which may be partially associated with macrophage-derived exosomes.
Prevalence and associated factors of substance use among regular students in Debre Tabor University, Amhara region, Ethiopia in 2019
Authors: bezie minale Bezie , Belay Habtamu Gebrehana
Published: August 2020

Background: Substance abuse is inappropriate use of drugs or psychoactive substances in which the user consumes the substance with amount or methods which are harmful to them or others. Prevalence and associated factors of substance use among regular students in Debre Tabor University, Ethiopia 2019G.C Methods: Institutional based cross-sectional study was conducted using structured pretest and self-administered questionnaires. Systematic random sampling technique was used to collect data within sample size of 308. Result. The overall prevalence of substance use from the respondents was (62.6%). Specifically chat (11.8%), Cigarette (9%), Shisha (2.5%), Alcohol use (65.2%), and the remaining 11.8% use more than two substances This result shows that, (AOR=17.141, 95% CI=2.5-115.2770) using substance by peer friends was higher than who had no peer friends .Male students were 0.6 times more likely use substance than Females students [AOR =0.663 95%CI(0.415-1.061]. Conclusion: In this study area, prevalence of substance use among regular students was relatively high than other studies Friendly use of substances, academically fourth year students and department of accounting students were significantly associated. Key words: Substance use, prevalence, associated factors, Khat, Alcohol and Tobacco
Long noncoding RNA MEG3 blocks telomerase activity in human liver cancer stem cells epigenetically
Authors: Jiang Xiaoxue , Wang Liyan , Xie Sijie , Chen Yingjie , Song Shuting , Lu Yanan , Lu Dongdong
Published: August 2020

Background: MEG3 is abnormally down-regulated in most tumors and inhibits tumorigenesis.Methods: Gene infection, Western blotting and tumorigenesis test in vitro and in vivo were performed to analyze the signaling pathway. Results: MEG3 increased the loading of P300 and RNA polymerase II onto the promoter regions of P53. Notably, MEG3 increased the methylation of histone H3 at lysine 27 through increasing the interplay between PRC2 and histone H3. Furthermore, MEG3 inhibited the expression of TERT by increasing the H3K27me3 and decreasing the loading of RNA pol Ⅱ in TERT promoter regions. Moreover, MEG3 inhibit the activity of telomerase by reducing the binding of TERT to TERC competitively. In addition, MEG3 also increased the TERRA through reducing DNA methyltransferase DNMT3b binding to the promoter regions of TERRA competitively. Therefore, the interaction between TERC and TERT was competitively attenuated by increasing the interaction between TERRA and TERT, which inhibited the activity of telomerase in hLCSCs.In particular, MEG3 shortened the length of telomere by blocking the formation of complex maintaining telomere length(POT1-Exo1-TRF2-SNM1B) and decreasing the binding of the complex to telomere competitively, which was caused by increasing the interplay between P53 and HULC in hLCSCs.Strikingly, MEG3 inhibited the growth in vitro and in vivo of hLCSCs by reducing the activity of telomerase and attenuating telomeric repeat binding factor 2(TRF2).Conclusions: our results demonstrated MEG3 inhibits the occurrence of human liver cancer and these findings provide an important insight into the prevention and treatment of human liver cancer.
The Clinical Sustainability Assessment Tool: Measuring Organizational Capacity to Promote Sustainability in Healthcare
Authors: Malone Sara , Prewitt Kim , Hackett Rachel , Lin John C. , McKay Virginia , Walsh-Bailey Callie , Luke Douglas
Published: August 2020

Background Few validated assessment tools are available to support sustainable implementation, an increasingly recognized need among clinicians. We describe the development of the Clinical Sustainability Assessment Tool, or CSAT, designed to assess factors that contribute to sustainable practices in clinical settings. Methods Fifty participants from clinical and research fields were recruited to brainstorm factors that lead to sustained clinical practices. Once repeated factors were removed, participants sorted remaining factors based on similarity. Using concept mapping analyses, we grouped these factors into meaningful domains and developed an initial tool. We then recruited 126 practicing clinicians to pilot and evaluate the tool. Individuals were recruited from clinical settings across pediatric (53%) and adult (47%) medical and surgical subspecialties, and averaged 11 years in their position. The data were analyzed using confirmatory factor analysis (CFA) to test hypothesized subscale structure in the instrument. We used root mean square error of approximation (RMSEA) and the standardized root mean square residual (SRMR) to assess fit and thus the ability of CSAT to measure the identified domains.Results The concept mapping resulted in seven domains and 47 items. The pilot and CFA resulted in 35 items, five per domain. The RMSEA of 0.084 and the SRMR of 0.075 indicated good fit. The final domains were: engaged staff and leadership, engaged stakeholders, organizational readiness, workflow integration, implementation and training, monitoring and evaluation, and outcomes and effectiveness. Conclusions The CSAT is a new reliable assessment tool which allows for greater practical and scientific understanding of contextual factors that enable sustainable clinical practices over time. The full CSAT instrument is available at https://sustaintool.org.
Is the Perceived Neighborhood Built Environment Associated With Domain-Specific Physical Activity in Latin American Adults? An Eight-Country Observational Study
Authors: Ferrari Gerson , Werneck André O. , Silva Danilo Rodrigues , Kovalskys Irina , Gómez Georgina , Rigotti Attilio , Sanabria Lilia Yadira Cortés , García Martha Cecilia Yépez , Pareja Rossina G. , Herrera-Cuenca Marianella , Zimberg Ioná Zalcman , Guajardo Viviana , Pratt Michael , Cristi-Montero Carlos , Rodríguez-Rodríguez Fernando , Marques Adilson , Cerin Ester , Dyck Delfien Van , Pires Carlos André Miranda , Fisberg Mauro
Published: August 2020

Background: Characteristics of the neighborhood built environment are associated with physical activity (PA). However, few studies with representative samples have examined environmental correlates of domain-specific PA in Latin America. We examined the associations of the perceived neighborhood built environment with domain-specific PA in a large sample of adults from eight Latin American countries. Methods: This study examined data from 8185 adults (aged 18–65 years) from eight Latin American countries. The Neighbourhood Environment Walkability Survey - Abbreviated (NEWS-A) scale was used to assess perceptions of land use mix–diversity, land use mix-access, street connectivity, walking/cycling facilities, aesthetics, safety from traffic, and safety from crime. Perceived proximity from home to public open spaces (metropolitan parks, playgrounds, public squares) and to shopping centers was also assessed. Transport-related and leisure-time PA were assessed using the long form of the International Physical Activity Questionnaire. Both logistic and linear regression models were estimated on pooled data. Results: Perceptions of higher land use mix-access (OR: 1.40; 95% CI: 1.22,1.61), the existence of many alternative routes in the neighbourhood (1.12; 1.04,1.20), slow speed of traffic (1.19; 1.03,1.35) and few drivers exceeding the speed limits (1.09; 1.03,1.15) were associated with greater odds of reporting at least 10 min/week of transport-related PA. Perceptions of higher levels of land use mix-diversity, better aesthetics and greater safety from crime, the presence of crosswalks and pedestrian signals, and greater proximity of shopping centers were associated with more min/week of transport-related PA. Perceptions of higher land use mix-diversity (1.12; 1.05,1.20), higher land use mix-access (1.27; 1.13,1.43), more walking/cycling facilities (1.18; 1.09,1.28), and better aesthetics (1.10; 1.02,1.18) were associated with greater odds of engaging in at least 10 min/week of leisure-time PA versus none. Perceptions of higher land use mix-diversity were associated with more min/week of leisure PA. Conclusions: Different perceived neighborhood built environment characteristics were associated with domain-specific PA among adults from Latin America countries. Interventions designed to modify perceptions of the neighbourhood built environment might influence initiation or maintenance of domain-specific PA.Trial registration: ClinicalTrials.Gov NCT02226627. Retrospectively registered on August 27, 2014.
Interleukin (IL)-33 is dispensable for Schistosoma mansoni worm maturation, egg excretion, and the maintenance of egg-induced pathology in intestines of mice
Authors: Mukendi Jean Pierre Kambala , Nakamura Risa , Uematsu Satoshi , Hamano Shinjiro
Published: August 2020

Background: Schistosomes are trematode worms that dwell in their definitive host’s blood vessels, where females lay eggs that need to be eliminated in the environment with host excreta to maintain their life cycle. Both worms and eggs require type 2 immunity for their maturation and excretion, respectively. However, immune molecules that orchestrate such immunity remain unclear. IL-33 is one of the epithelium-derived cytokines that induce type 2 immunity in tissues. This study aimed at determining its role in the maturation, reproduction, and excretion of S. mansoni eggs, and in the maintenance of egg-induced pathology in the intestines of mice.Methods: Using S. mansoni-infected IL-33-deficient (IL-33-/-) and wild-type (WT) mice, worm morphology, reproduction, and egg excretion were studied at different time points of infection. IL-5 and IL-13 production in spleens and mesenteric lymph nodes were measured. Tissue histology was performed on the terminal ilea of non- and infected mice.Results: Morphology-wise, worms from IL-33-/- and WT mice at the fourth and sixth weeks of infection did not differ. The worms' reproduction, expressed as eggs per worm pair, as well as the excretion of eggs, expressed as the number of eggs in intestinal tissues, did not differ between IL-33-/- and WT mice. In the sixth week of infection, IL-33-/- mice presented impaired type 2 immunity in intestines, characterized by decreased production of IL-5 and IL-13 in mesenteric lymph nodes and fewer inflammatory infiltrates with fewer eosinophils in the ilea. Besides, there was no difference between IL-33-/- and WT mice in the levels of IL-25 and TSLP in intestinal tissues.Conclusions: Despite its ability to initiate type 2 immunity in tissues, IL-33 alone seems dispensable for S. mansoni maturation, reproduction, and egg excretion. The transient impairment of type 2 immunity observed in the intestines, but not spleens, highlights the importance of IL-33 over IL-25 and TSLP in initiating, but not maintaining, locally induced type 2 immunity in intestinal tissues in schistosome infection. Further studies are needed to decipher the role of each of them in schistosomiasis and clarify the possible interactions that might exist between them.
Efficacy of Widely Used Hand Disinfectants Against Human Echovirus Type 11 in China
Authors: Zhang Lei , Ji Xunmin , Peng Tuohua , He Chiming , Zheng Xiaoling , Zhou Ying , Xiao Wei , Wang Yajing , Zhang Xianchang , Zhang Jikai , Zhong Yuwen
Published: August 2020

Background: In the summer of 2019 an outbreak of Nosocomial infections in a newborn nursery occurred in a Shunde hospital near Foshan, resulting in five babies deaths. Echovirus-11 was proven to be the responsible agent. Echovirus-11 infections are a significant health threat in the hospitals and occasionally cause severe neurological complications and even death in children. Although good hand hygiene is important for controlling infection, relevant data regarding the efficacy of widely used hand disinfectants against Echovirus-11 are still lacking. Aim: To investigate the virucidal activity of widely used hand disinfectants against Echovirus-11. Methods: The 13 widely used hand disinfectants from Guangdong hospitals were tested for virucidal activity against Echovirus-11 with the identification test of residual disinfectants removal and the suspension test with a 60 s exposure time based on Technical Standard For Disinfection (2002). Findings: Both Disinfectant A and Disinfectant C achieved a mean log10 reduction factor in Echovirus-11 titre of ≥ 5.00, respectively, within 60 s. Disinfectant B, Disinfectant D, Disinfectant H and Disinfectant M had an effect on Echovirus-11 in a mean log10 reduction factor of ≥ 4.00.By contrast, Disinfectant E, Disinfectant F, Disinfectant G, Disinfectant I, Disinfectant J, Disinfectant K and Disinfectant L didn't improved the mean log10 reduction factor in Echovirus-11 titre with producing a factor of ＜4 after a 60 s exposure time.Conclusions: 46.2% (6/13 products) of widely used hand disinfectants have effectiveness against Echovirus-11. In general, it is risky to rely too much on hand disinfectants. In case of epidemic season or definite enterovirus contamination, washing hands with soap and water is recommended for reducing viral contamination of enterovirus 11 in clinical practice, rather than hand hygiene with alcohol-based hand disinfectants alone.
Milk Production and Constituents of Beef Cows with Different Breed Compositions
Authors: Azambuja Rodrigo C. C. , Rodrigues Pedro F. , Menezes Leonardo M. , Costa Rodrigo F. , Teixeira Bruno B. M. , Mendonça Fabio S. , Suñé Renata W. , Silveira Isabella D. B. , Cardoso Fernando F.
Published: August 2020

Background: There are two classes of factors that affect cow milk production and, as a consequence, the performance of calves: environmental and genetic factors. Considering the importance of milk production of beef cattle, it is essential to measure the milk production of such cows. However, such estimation presents some difficulties, especially when cows are raised exclusively in a grazing regime. This study aimed to evaluate the milk production and the nutritional composition of beef cows from eight different breed compositions (Angus: ANAN, Hereford: HHHH, Nellore: NENE, Hereford-Angus: HHAN, Angus-Hereford: ANHH, Nellore-Angus: NEAN, Angus-Nellore: ANNE, and Caracu-Angus: CRAN) raised under continuous natural pasture grazing, besides evaluating the calves' adjusted weight at 210 days until weaning.Results: NEAN cows were the most productive but did not differ from ANNE, ANHH, and CRAN, with estimated average yields of 6.2, 5.97, 5.93 and 5.86 kg/day, respectively, throughout the lactation period. NENE cows presented the lowest yields, with a daily average of 4.61 kg, although this value did not differ significantly from those of HHHH, ANAN and HHAN cows, which had means of 4.67, 4.79 and 4.84 kg/day, respectively. Calves of CRAN, NEAN, and ANNE cows were heavier than calves of ANAN, HHAN, HHHH, and NENE cows at weaning, not differing from ANHH cows, which in turn also had heavier calves than HHHH cows. NEAN, ANNE, HHHH and NENE cows had higher concentrations of total solids in milk than ANAN and ANHH.Conclusions: In conclusion, as expected, the crossbreeding of genetically more distant breed increases the milk production of beef cows. Therefore, for cow-calf operations in a subtropical climate, crossbreeding between Angus and Nellore or Caracu can be used as a genetic tool to increase cow maternal ability, through greater milk production and nutrient content, and consequently yielding heavier calves at weaning.
Risk-of-falling related outcomes improved in community-dwelling older adults after a 6-week sideways walking intervention: a feasibility and pilot study
Authors: Skiadopoulos Andreas , Stergiou Nick
Published: August 2020

BackgroundAging increases fall risk and alters gait mechanics and control. Our previous work has identified sideways walking as a potential training regimen to decrease fall risk by improving frontal plane control in older adults’ gait. The purposes of this pilot study were to test the feasibility of sideways walking as an exercise intervention and to explore its preliminary effects on risk-of-falling related outcomes.MethodsWe conducted a 6-week single-arm intervention pilot study. Participants were community-dwelling older adults ≥ 65 years old with walking ability. Key exclusion criteria were neuromusculoskeletal and cardiovascular disorders that affect gait. Individualized sideways walking intervention carried out under close supervision in a 200 m indoor walking track (3 days∙week− 1). Recruitment and retention capability, safety, and fidelity of intervention delivery were recorded. We also collected (open-label) walking speed, gait variability, self-reported and performance-based functional measures to assess participants’ risk-of-falling at baseline and post-intervention: immediate, and 6 weeks after the completion of the intervention.ResultsOver a 7-month period, 42 individuals expressed interest, 21 assessed for eligibility (21/42), and 15 consented to participate (15/21). Most of the potential participants were reluctant to commit to a 6-week intervention. Desired recruitment rate was achieved after revising the recruitment strategy. One participant dropped out (1/15). Remaining participants demonstrated excellent adherence to the protocol. Participants improved on most outcomes and the effects remained at follow-up. No serious adverse events were recorded during the intervention.ConclusionOur 6-week sideways walking training was feasible to deliver and demonstrated strong potential as an exercise intervention to improve risk-of-falling outcomes in community-dwelling older adults. In a future trial, alternative clinical tools should be considered to minimize the presence of ceiling/floor effects. A future large trial is needed to confirm sideways walking as a fall prevention intervention.Trial registrationClinicalTrials.gov identifier: NCT04505527. Retrospectively registered 10 August 2020.Trial fundingCenter for Research in Human Movement Variability, National Institutes for Health, University of Nebraska Collaboration Initiative.
Mortality calculator as a possible prognostic predictor of overall survival after gastrectomy in elderly patients with gastric cancer
Authors: Akaike Hidenori , Kawaguchi Yoshihiko , Maruyama Suguru , Shoda Katsutoshi , Satio Ryo , Furuya Shinji , Hosomura Naohiro , Amemiya Hidetake , Kawaida Hiromichi , Sudoh Makoto , Inoue Shingo , Kohno Hiroshi , Ichikawa Daisuke
Published: August 2020

Background: The number of elderly patients with gastric cancer has been increasing. Most elderly patients have associated reduced physiologic functions, that can sometimes become an obstacle to safe surgical treatment. The National Clinical Database Risk Calculator, which based on a large Japanese surgical database, provides mortality and morbidity as the surgical-related risks. The purpose of this study was to investigate the clinical significance of the risk for operative mortality (NRC-mortality), as calculated by the National Clinical Database Risk Calculator, during long-term follow-up after gastrectomy for elderly patients with gastric cancer.Methods: We enrolled 73 patients aged ≥80 years and underwent gastrectomy at our institution. Their surgical risk was evaluated based on the NRC-mortality. Several clinicopathologic factors, including NRC-mortality, were selected, and analyzed as the possible prognostic factors for elderly patients who have undergone gastrectomy for gastric cancer. Statistical analysis was performed using the log-rank test and Cox proportional hazard model.Results: NRC-mortality ranged from 0.5% to 10.6%, and the median value was 1.7%. Dividing the patients according to mortality, the overall survival was significantly worse in the high mortality group (≥1.7%, n = 38) than in the low mortality group (<1.7%, n = 35), whereas disease-specific survival was not different between the two groups. In the Cox proportional hazard model, multivariate analysis revealed NRC-mortality, performance status, and surgical procedure as the independent prognostic factors for overall survival. For disease-specific survival, the independent prognostic factors were performance status and pathological stage but not NRC-mortality.Conclusion: The NRC-mortality might be clinically useful for predicting both surgical mortality and overall survival after gastrectomy in elderly patients with gastric cancer.
Expressing a Cytosolic Pyruvate Dehydrogenase Complex to Increase Free Fatty Acid Production in Saccharomyces Cerevisiae
Authors: Zhang Yiming , Su Mo , Qin Ning , Nielsen Jens , Liu Zihe
Published: August 2020

Background
Saccharomyces cerevisiae is being exploited as a cell factory to produce fatty acids and their derivatives as biofuels. Previous studies found that both precursor supply and fatty acid metabolism deregulation are essential for enhanced fatty acid synthesis. A bacterial pyruvate dehydrogenase (PDH) complex expressed in the yeast cytosol was reported to enable production of cytosolic acetyl-CoA with lower energy cost and no toxic intermediate.
Results
Overexpression of the PDH complex significantly increased cell growth, ethanol consumption and reduced glycerol accumulation. Furthermore, to optimize the redox imbalance in production of fatty acids from glucose, two endogenous NAD+-dependent glycerol-3-phosphate dehydrogenases were deleted, and a heterologous NADP+-dependent glyceraldehyde-3-phosphate dehydrogenase was introduced. The final strain with engineering of precursor and co-factor metabolism could produce 840.5 mg/L free fatty acid in shake flask, which was 83.2% higher than the control strain. Profile analysis of free fatty acid suggested the cytosolic PDH complex mainly resulted in the increases of unsaturated fatty acids (C16:1 and C18:1).
Conclusions
We demonstrated that cytosolic PDH pathway enabled more efficient acetyl-CoA provision with the lower ATP cost, and improved FFA production. Together with engineering of the redox factor rebalance, the cytosolic PDH pathway could achieve high level of FFA production at similar levels of other best acetyl-CoA producing pathways.
Transcriptional response of Bacillus megaterium FDU301 to PEG200-mediated arid stress
Authors: Zhao Lei , Zhou Yanjun , Li Jianbei , Xia Yucheng , Wang Weiyun , Luo Xiuqi , Yin Juan , Zhong Jiang
Published: August 2020

Background
For the microorganisms on the paper surface, the lack of water is one of the most important stress factors. A strain of Bacillus megaterium FDU301 was isolated from plaques on the paper surface using the culture medium with polyethylene glycol 200 (PEG200) to simulate arid condition. Global transcriptomic analysis of B. megaterium FDU301 grown under normal and the simulated arid conditions was performed via RNA-seq technology to identify genes involved in arid stress adaptation.
Results
The transcriptome of B. megaterium FDU301 grown in LB medium under arid (15% PEG200 (w/w)) and normal conditions were compared. A total of 2941 genes were differentially expressed, including 1422 genes up-regulated and 1519 genes down-regulated under arid conditions. Oxidative stress-responsive regulatory genes perR, fur, and tipA were significantly up-regulated, along with DNA protecting protein (dps), catalase (katE). Genes related to Fe2+ uptake (feoB), spore formation stage II (spoIIB, spoIIE, spoIIGA), small acid-soluble spore protein (sspD), and biosynthesis of compatible solute ectoine (ectB, ectA) were also highly expressed to various degrees. Meanwhile, oxidative phosphorylation-related genes (atpB, atpE, atpF, atpH, atpA, atpG, atpD, atpC) and glycolysis-related genes (pgk, tpiA, frmA) were significantly down-regulated.
Conclusion
This is the first report about transcriptomic analysis of a B. megaterium to explore the mechanism of arid resistance. Major changes in transcription were seen in the arid condition simulated by PEG200 (15%), with the most important one being the genes related to oxidative stress. The results showed the complex mechanism for bacteria to adapt to arid stress.
Fusobacterium nucleatum Promotes Gastric Cancer Aggressiveness through Upregulation of Cell Mobility and Interferon Genes
Authors: Hsieh Yung-Yu , Tung Shui-Yi , Pan Hung-Yu , Chang Te-Sheng , Wei Kuo-Liang , Chen Wei-Ming , Deng Yi-Fang , Lu Chung-Kuang , Lai Yu-Hsuan , Wu Cheng-Shyong , Li Chin
Published: August 2020

Background Fusobacterium nucleatum was previously found to become a dominant species in the gastric cancer-associated microbiota of patients from Taiwan. However, the prevalence of Fusobacterium nucleatum infection in gastric cancer has not been examined in a larger patient cohort. In addition, whether Fusobacterium nucleatum elicits a cellular response in gastric cancer remains unknown.Methods A study cohort of resected gastric cancer tissue specimens was examined using nested PCR to detect Fusobacterium nucleatum. In vitro coculture of Fusobacterium nucleatum was carried out to identify the alteration in the expression profile of patient-derived gastric cancer cell line.Results approximately one-third of gastric cancer tissues are positive for Fusobacterium nucleatum. Statistical analysis showed that the risk for Fusobacterium nucleatum infection is increased in late-stage cancer tissue specimens and incurs poorer survival in Helicobacter pylori-positive patients. In vitro coculture experiment shows a drastic interferon response activated only by a high multiplicity of infection, and the response peaks within 24 hours and subsides after 72 hours of incubation. Another set of response genes is the continuous increase of actins and their regulators with prolonged time of incubation, activated by both low and high multiplicity of infection.Conclusions Our data indicates that Fusobacterium nucleatum incites an inflammatory response from the cancer cells and promotes cell mobility, likely
Fine-grained dual-phase high-entropy ceramics derived from boro/carbothermal reduction
Authors: Luo Si-Chun , Guo Wei-Ming , Plucknett Kevin , Lin Hua-Tay
Published: August 2020

In the current work fine-grained dual-phase, high-entropy ceramics (Ti0.2Zr0.2Hf0.2Nb0.2Ta0.2)B2-(Ti0.2Zr0.2Hf0.2Nb0.2Ta0.2)C with different phase ratios are prepared from powders synthesized via a boro/carbothermal reduction approach, by adjusting the content of B4C and C in the precursor powders. Phase compositions, densification, microstructure, and mechanical properties have been investigated. Due to the combination of pinning effect and the boro/carbothermal reduction approach, the average grain sizes (0.5–1.5 µm) of the dual-phase high-entropy ceramics, were much smaller as compared with previously reported values. The dual-phase high-entropy ceramics with 15 mol% boride phase exhibit the highest Vickers hardness (24.21 GPa) and fracture toughness (3.2 MPa•m1/2).
Androgen receptor activity promotes resistance to BRAF-targeted melanoma therapy
Authors: Wargo Jennifer , Vellano Christopher , White Michael , Andrews Miles , Daniele Joseph , Titus Mark , Ologun Gabriel , Cogdill Alex , Morad Golnaz , McQuade Jennifer , Thakur Rohit , Prieto Peter , Lazar Alexander , Khan Md Abdul Wadud , Helmink Beth , Davies Michael , Amaria Rodabe , Kovacs Jeffrey , Woodman Scott , Tawbi Hussein , Patel Sapna , Hwu Patrick , Peoples Michael , Lee Jeffrey , Cooper Zachary , Zhu Haifeng , Gao Guang , Gershenwald Jeffrey , Lucci Anthony , Keung Emily , Ross Merrick , Wani Khalida , Tetzlaff Michael , Haydu Lauren , Mahendra Mikhila , Ma XioYan , Logothetis Christopher , Kulstad Zachary , Johnson Sarah , Hudgens Courtney , Feng Ningping , Federico Lorenzo , Burton Elizabeth , Arur Swathi , Heffernan Timothy , Marszalek Joseph
Published: August 2020

Treatment with molecularly-targeted therapy has revolutionized cancer care, including BRAF/MEK-targeted melanoma therapy. However responses are heterogenous and frequently not long-lasting. Novel strategies to target resistance are needed. We studied a cohort of patients with resectable metastatic melanoma treated with neoadjuvant BRAF/MEK-targeted therapy (n=52) and noted a strong sexual dimorphism in response to treatment, with female patients demonstrating significantly higher rates of a major pathologic response (MPR) (p=0.0001). RNA sequencing of tumors demonstrated enrichment of androgen-related genes in those failing to achieve MPR. Pre-clinical studies validated these findings, with significantly increased tumor growth in male vs female mice treated with BRAF/MEK inhibitors (BRAF/MEKi) (p=0.0005). Androgen receptor (AR) expression was upregulated in tumors of BRAF/MEKi-treated mice, and modulation of AR signaling via AR-blockade or castration was associated with significantly slower tumor growth (p=0.0001 and p=0.00004, respectively). Together, these results have important implications in the context of treatment with BRAF/MEKi-targeted therapy.
Nanoparticles in 472 Human Cerebrospinal Fluid: Changes in Extracellular Vesicle Concentration and miR-21 Expression as a Biomarker for Leptomeningeal Metastasis
Authors: Lee Kyue-Yim , Im Ji Hye , Lin Weiwei , Gwak Ho-Shin , Kim Jong Heon , Yoo Byong Chul , Kim Tae Hoon , Park Jong Bae , Park Hyeon Jin , Kim Ho-Jin , Kwon Ji-Woong , Shin Sang Hoon , Yoo Heon , Lee Changjin
Published: August 2020

Background
Leptomeningeal metastasis (LM) has a poor prognosis and is difficult to diagnose and predict the response of treatment. In this study, we suggest that the monitoring of changes in the concentration of extracellular vesicles in cerebrospinal fluid could help to diagnose or predict outcomes for LM.
Methods
We measured nanoparticles in 472 human CSF from controls and patients including LM with both Dynamic Light Scattering (DLS) and Nanoparticle Tracking Analysis (NTA) after two-step centrifugations.
Results
NTA revealed nanoparticles distributed at a median 193 nm in size, and 1.74 × 108 /ml in concentration, and those were significantly higher in LM compared to other groups (211 nm vs. 188 nm, p < 0.001 and 2.80 × 108 /ml vs. 1.49 × 108 /ml, p < 0.01, respectively). Changes in NTA-measured nanoparticles (EV from here) concentration after intra-CSF chemotherapy were further examined in non-small cell lung cancer patients with LM (n = 33). Overall survival was longer for patients with increased EV than the others (442 vs. 165 days, p < 0.001). Exosome surface markers (CD9/CD63/CD81) significantly decreased in the EV-decreased group (ratio 0.64, p < 0.0001). MicroRNA-21 expression decreased in this favorable prognostic group, whereas increased in the EV-decreased group (p = 0.003).
Conclusions
The elevated concentration of extracellular vesicles in cerebrospinal fluid in patients with LM can be a diagnostic marker. Moreover, EV changes combined with microRNA-21 might be a biomarker for monitoring intracranial chemotherapy of LM.
A Secondary Analysis of the Childhood Obesity Prevention Literature through a Wider Determinants of Health Lens: Implications for Research Funders, Researchers, Policymakers and Practitioners
Authors: Nobles James David , Summerbell Carolyn , Brown Tamara , Jago Russell , Moore Theresa
Published: August 2020

Background: Over the last 25 years, we have made great advances in our understanding of the complex adaptive systems which drive childhood obesity. Within this, the important role of upstream interventions which focus on the wider determinants of health (WDoH) has been acknowledged. Concurrently, the number of intervention studies aiming to prevent childhood obesity has increased exponentially. One might anticipate that our understanding of theory has been embedded into the development and implementation of interventions in real time. Methods: We tested this hypothesis by conducting secondary analysis of the interventions included in the Cochrane Review on “Interventions for Preventing Obesity in Children”, published since 1993. All 153 randomised controlled trials (RCTs) were independently coded by two authors against the WDoH model using an adaptive framework synthesis approach. We used aspects of the Action Mapping Tool from Public Health England to facilitate our coding and to visualise our findings in contrast to 226 perceived causes of obesity. Results: We found that the proportion of interventions which targeted downstream (e.g. individual and family behaviours) as opposed to upstream (e.g. infrastructure, environmental, policy) determinants has not changed over time (from 1993 to 2015), with most intervention efforts (57.9%) aiming to change individual lifestyle factors via education-based approaches. Almost half of the interventions (45%) targeted two or more levels of the WDoH. Where interventions targeted some of the wider determinants, this was often achieved via upskilling teachers to deliver educational content to children. No notable difference in design or implementation was observed between interventions targeting children of varying ages (0-5 years, 6-12 years, 13-18 years). Conclusions: This study highlights that interventions, evaluated via RCTs, have persisted to focus on downstream, individualistic determinants of obesity over the last 25 years, despite the step change in our understanding of its complex aetiology. We hope that the findings from our analysis will challenge research funders, researchers, policymakers and practitioners to reflect upon, and critique, the evidence-based paradigm in which we operate, and call for a shift in focus of new evidence which takes a WDoH lens.
Lung ultrasound findings in pediatric patients with COVID-19.
Authors: Guitart Carmina , Suárez Ricardo , Girona Mònica , Bobillo-Pérez Sara , Hernández Lluïsa , Balaguer Mònica , Cambra Francisco José , Jordan Iolanda
Published: August 2020

During the pandemic caused by the novel coronavirus (COVID-19), lung ultrasound has been used to diagnose and monitor respiratory condition. The aim of the study was to describe lung ultrasound findings in children with a COVID-19 infection. Patients younger than 18 years old and positive for COVID-19, admitted to pediatric tertiary referral hospital were included. They were divided into two groups depending on the presence of respiratory symptoms. Lung ultrasound results were categorized into three degrees of aeration loss: normal, moderate, and severe; and into three patterns: viral or bacterial pneumonia, and atelectasis.Sixteen patients were recruited. The median age was 11 years old (IQR 2.8-12). Four children (25%) required admission to the intensive care unit. Six patients (37.5%) presented with respiratory symptoms. All of them (100%) showed moderate-to-severe aeration loss on lung ultrasound. A viral pneumonia pattern was observed in four cases (66.6%). Ten patients (62.5%) presented with non-respiratory symptoms, lung ultrasound showed moderate-to-severe aeration loss in nine (90%). Three (30%) were diagnosed of multisystem inflammatory syndrome and lung ultrasounds showed severe aeration loss and bilateral pleural effusion.Conclusions: Children with COVID-19 and respiratory symptoms showed a viral pneumonia pattern with moderate-to-severe aeration loss upon the lung ultrasound assessment.
Baseline assessment of antibiotics prescribing for acute, non-complicated infections in primary care in Germany in the cluster randomized trial ARena
Authors: Poss-Doering Regina , Weber Dorothea , Kamradt Martina , Andres Edith , Kaufmann-Kolle Petra , Szecsenyi Joachim
Published: August 2020

BackgroundAntimicrobial resistance is fueled by inappropriate prescribing and use of antibiotics. Global and national strategies support rational and adequate use of antibiotics to retain treatment options and fight resistances. In Germany, the ARena project (Sustainable reduction of antibiotic-induced antimicrobial resistance) was intended to promote the rational and appropriate use of antibiotics for acute non-complicated infections by addressing physicians, care teams and patients through multiple interacting interventions. This paper presents patterns of antibiotics prescribing for patients with acute non-complicated infections in participating primary care networks prior to the start of the ARena project, explores variation across subgroups of patients and draws comparisons to reference groups which represent standard care. MethodsIn mixed logistic regression models, we explored factors associated with the proportion of patients with acute non-complicated infections consulting primary care practices who received an antibiotic prescription. Secondary outcomes concerned the prescription of different types of antibiotics. Descriptive methods were used to summarize the data referring to primary care networks, reference groups, and subgroups. ResultsAcross all observed cases, antibiotic prescription rates were 31.7% in reference groups and 32.0% in primary care networks. Being the largest group of physicians observed, General practitioners prescribed antibiotics more frequently than other medical specialist groups (otolaryngologists vs. General practitioners OR=0.465 CI=[0.302; 0.719], p<0.001, pediatricians vs. General practitioners: OR=0.369 CI=[0.135; 1.011], p=0.053). Quinolone prescription rates were moderate (8.1% in reference groups and 9.9% in primary care networks). Patients with comorbidities had a higher likelihood of receiving an antibiotic and quinolone prescription and were less likely to receive a recommended substance. Younger patients were less likely to receive antibiotics (OR=0.771 CI=[0.636; 0.933], p=0.008). Female gender was associated with higher rates of antibiotic prescriptions compared to males (OR=1.293 CI=[1.201, 1.392], p<0.001).Conclusion Prior to the ARena project, observed antibiotic prescription rates for acute non-complicated infections were moderate, but there was still room for improvement. The use of recommended substances was low which indicates a need for creating stronger awareness of guideline-conform use of antibiotics.
Unraveling the stability landscape of mutations in the SARS-CoV-2 receptor-binding domain
Authors: Smaoui Mohamed Raef , Yahyaoui Hamdi
Published: August 2020

The interaction between the receptor-binding domain of the SARS-CoV-2 spike glycoprotein and the ACE2 enzyme is believed to be the entry point of the virus into various cells in the body, including the lungs, heart, liver, and kidneys. The current focus of several therapeutic design efforts explore attempts at affecting the binding interaction between the two proteins to limit the activity of the virus and disease progression. In this work, we analyze the stability of the spike protein under all possible single-point mutations in the receptor-binding domain and computationally explore mutations that can affect the binding with the ACE2 enzyme. We unravel the mutation landscape of the receptor region and assess the toxicity potential of single and multi-point mutations, generating insights for future vaccine efforts on potential mutations that might further stabilize the spike protein and increase its infectivity. We developed a tool, called SpikeMutator, to construct full atomic protein structures of the mutant spike proteins and shared a database of 3,800 single-point mutant structures. We analyzed the recent 65,000 reported spike sequences across the globe and observed the emergence of stable multi-point mutant structures. Using the landscape, we searched through 7.5 million possible 2-point mutation combinations and report that the (R355D K424E) mutation produces one of the strongest spike proteins that therapeutic efforts should investigate for the sake of developing an effective vaccine.
When Robots contribute to eradicate the COVID-19 spread in a context of containment
Authors: HOUACINE Naila Aziza , DRIAS Habiba
Published: August 2020

In the era of autonomous robots, multi-targets search methods inspired researchers to develop adapted algorithms to robot constraints, and with the rising of Swarm Intelligence (SI) approaches, Swarm Robotics (SRs) became a very popular topic. In this paper, the problem of searching for an exponentially increasing number of targets in a complex and unknown environment is addressed. Our main objective is to propose a Robotic target search strategy based on the EHO (Elephants Herding Optimization) algorithm, namely Robotic-EHO (REHO). The main additions were the collision-free path planning strategy, the velocity limitation, and the extension to the multi-target version in discrete environments. The proposed method has been the subject of many experiments, emulating the search of infected individuals by COVID-19 in a context of containment within complex and unknown random environments, as well as in the real case study of USA. The particularity of these environments is their increasing targets' number and the dynamic Containment Rate (CR) that we propose. The experimental results show that REHO reacts much better in high Containment Rate, early start search mission, and where the robots' speed is higher than the virus spread speed.
Survivin Suppression Strengthens BZML-induced Mitotic Catastrophe to Overcome Multidrug Resistance by Removing Senescent A549/Taxol Cells
Authors: Bai Zhaoshi , Zhou Yiran , Ye Xinyue , Guan Qi , Zhang Weige , Ma Lingman
Published: August 2020

Background: Mitotic catastrophe (MC) of cancer cells induced by BZML, a novel colchicine-binding site inhibitor, exerts a significant advantage in overcoming multidrug resistance (MDR) in NSCLC. However, the long cellular death process resulting from MC is not beneficial for anticancer treatment. Here, we study the mechanisms underlying MC occurrence and development to promote the development of anticancer therapies based on drug-induced MC.Methods: Cellular senescence was confirmed by morphological features, SA-β-Gal and C12FDG staining. Cell cycle analysis and Hoechst 33342 staining were used to detect MC. Relevant signal transduction pathways and protein location were detected by qRT-PCR, westren blot and immunofluorescence. The half-life of proteins was evaluated using the protein synthesis inhibitor cycloheximide. Flow cytometry, MTT assay, crystal violet staining, Hoechst 33342 staining and cell division detection were performed to determine the effects of BZML and/or YM155 on cell fate. Results: We found that BZML induced p53-dependent cellular senescence in A549/Taxol cells, but not in A549, H1299 and MDA-MB-231 cells. Interestingly, BZML-induced senescence was a secondary effect of MC. In addition, the destruction of the protein-degradation system induced by BZML contributed not only to an increase in p53 protein but also to the accumulation of survivin in the nucleus of A549/Taxol cells. However, in A549 cells, the overexpression of survivin had no effect on apoptosis resistance against BZML and failed to promote BZML-induced MC. The inhibition of survivin did not prevent MC occurrence. Unexpectedly, targeting survivin with YM155 accelerated the death of the MC cells by eliminating senescent cells and strengthening the efficiency of BZML in overcoming the MDR of A549/Taxol cells.Conclusions: Our data suggest that nuclear accumulation of survivin can delay cellular death during MC by promoting the survival of senescent BZML-treated A549/Taxol cells. Further, depending on the dose sequence, combination therapy with YM155 to inhibit survivin might be a new strategy for potentiating BZML-induced MC to overcome MDR during cancer treatment.
Associations of Snoring, Daytime Napping and Night Sleep Duration With Hyperuricemia in Rural Chinese Adults: the Henan Rural Cohort Study
Authors: Dong Xiaokang , Liu Xiaotian , Zhang Lulu , Wang Yan , Tu Runqi , Liao Wei , Wang Yikang , Li Ruiying , Hou Jian , Mao Zhenxing , Wang Chongjian , Li Yuqian
Published: August 2020

Background. Evidence on the association of snoring, daytime napping or sleep duration with hyperuricemia (HUA) was limited, especially in the resources-poor areas. This study aimed to investigate the independent and joint effect of snoring frequency, daytime napping and sleep duration with prevalence of HUA in rural Chinese adults. Methods. 29,643 participants aged 18-79 years were included from baseline survey of the Henan Rural Cohort Study. Sleep variables were assessed using the Pittsburgh Sleep Quality Index (PSQI). Multivariate logistic regression and linear regression models with HUA and serum uric acid level as dependent variables were conducted, respectively. Results. Of the 29,643 included adults, 3498 suffered from HUA. Compared to never snoring, the adjusted odds ratio (OR) and 95% confidence interval (CI) of HUA for rare snoring, occasional snoring and habitual snoring were 1.35 (1.17, 1.56), 1.30 (1.14, 1.47) and 1.59 (1.47, 1.73), respectively. Compared with no napping, participants who had daytime napping of 61-90 and >91 min were associated with 29% and 30% increase in prevalence of HUA, respectively. But in night sleep duration groups, no significant associations were observed (all P>0.05). The positive associations between snoring and HUA were attenuated in older, female adults and those with chronic disease conditions. The joint of habitual snoring and longer daytime napping (≥61min) increased 63% prevalence on HUA. Conclusion. Snoring or daytime napping may independently increase the prevalence of HUA and serum uric acid (SUA) level. Moreover, habitual snoring and longer daytime napping might be jointly associated with a higher prevalence of HUA.Clinical Trial Registration The Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). http://www.chictr.org.cn/showproj.aspx?proj=11375