bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypoxia-Autophagy Axis Induces VEGFA by Peritoneal Mesothelial Cells to Promote Gastric Cancer Peritoneal Metastasis Through an Integrin α5-Fibronectin Pathway
Authors: Wang Xiaoxun , Che Xiaofang , Yu Yang , Cheng Yu , Bai Ming , Yang Zichang , Guo Qiqiang , Xie Xiaochen , Li Danni , Guo Min , Hou Kezuo , Guo Wendong , Qu Xiujuan , Cao Liu
Published: August 2020

Background: Peritoneal metastasis (PM) is an important pathological process in the progression of gastric cancer (GC). The metastatic potential of tumor and stromal cells is governed by hypoxia, which is a key molecular feature of the tumor microenvironment. Mesothelial cells also participate in this complex and dynamic process. However, the molecular mechanisms underlying the hypoxia-driven mesothelial-tumor interactions that promote peritoneal metastasis of GC remain unclear.Methods: We determined the hypoxic microenvironment in PM of nude mice by immunohistochemical analysis and screened VEGFA by human growth factor array kit. The crosstalk mediated by VEGFA between peritoneal mesothelial cells (PMCs) and GC cells was determined in GC cells incubated with conditioned medium prepared from hypoxia-treated PMCs. The association between VEGFR1 and integrin α5 and fibronectin in GC cells was enriched using Gene Set Enrichment Analysis and KEGG pathway enrichment analysis. In vitro and xenograft mouse models were used to evaluate the impact of VEGFA/VEGFR1 on gastric cancer peritoneal metastasis. Confocal microscopy and immunoprecipitation were performed to determine the effect of hypoxia-induced autophagy.Results: Here we report that in the PMCs of the hypoxic microenvironment, SIRT1 is degraded via the autophagic lysosomal pathway, leading to increased acetylation of HIF-1α and secretion of VEGFA. Under hypoxic conditions, VEGFA derived from PMCs acts on VEGFR1 of GC cells, resulting in p-ERK/p-JNK pathway activation, increased integrin α5 and fibronectin expression, and promotion of PM.Conclusions: Our findings have elucidated the mechanisms by which PMCs promote PM in GC in hypoxic environments. This study also provides a theoretical basis for considering autophagic pathways or VEGFA as potential therapeutic targets to treat PM in GC.
Circular RNA MCTP2 Inhibits Cisplatin Resistance in Gastric Cancer by miR-99a-5p-Mediated Induction of MTMR3 Expression
Authors: Sun Guangli , Li Zheng , He Zhongyuan , Wang Weizhi , Wang Sen , Zhang Xing , Cao Jiacheng , Xu Penghui , Wang Haixiao , Huang Xiaoxu , Xia Yiwen , Lv Jialun , Xuan Zhe , Jiang Tianlu , Fang Lang , Yang Jing , Zhang Diancai , Xu Hao , Xu Zekuan
Published: August 2020

Background: Cisplatin (CDDP) is the first-line chemotherapy for gastric cancer (GC). Poor prognosis of GC patients is partially due to development of CDDP resistance. Circular RNAs (circRNAs) are a subclass of non-coding RNAs that function as microRNA (miRNA) sponges. The role of circRNAs in CDDP resistance in GC has not been evaluated. Methods: RNA-sequencing was used to identify the differentially expressed circRNAs between the CDDP-resistant and CDDP-sensitive GC cells. qRT-PCR was used to detect the expression of circMCTP2 in GC tissues. The effects of circMCTP2 on CDDP resistance were investigated in vitro and in vivo. Pull-down assays and Luciferase reporter assays were performed to confirm the interaction among circMCTP2, miR-99a-5p, and myotubularin related protein 3 (MTMR3). The protein expression levels of MTMR3 were detected by western blotting. Autophagy was evaluated by confocal microscopy and transmission electron microscopy (TEM).Results: CircMCTP2 was found to be downregulated in the CDDP-resistant GC cells and tissues as compared to that of the CDDP-sensitive ones. A high level of circMCTP2 was found to be a favorable factor for the prognosis of patients with GC. CircMCTP2 inhibited cell proliferation and autophagy while promoting apoptosis of CDDP-resistant GC cells in response to CDDP treatment. CircMCTP2 upregulated MTMR3 by sponging miR-99a-5p, and knockdown of MTMR3 could reverse the effects of circMCTP2 on CDDP resistance and autophagy of GC cells. Conclusions: CircMCTP2 sensitizes GC to CDDP through the upregulation of MTMR3 by sponging miR-99a-5p. Overexpression of CircMCTP2 could be a new therapeutic strategy for counteracting CDDP resistance in GC.
Determinant of Practice of Birth Preparedness and Complication Readiness Plan Among Pregnant Women at Debretabor, North west Ethiopia: A Community Based Cross Sectional Study.
Authors: Negash Berhan Tsegaye
Published: August 2020

Background: Nearly all of maternal deaths in the world occurred in sub-Saharan African countries. As Ethiopian demographic health survey report, there were 412 maternal deaths per 100,000 live births in 2016. Delays in decision to seek and receive care are the main causes of these deaths. Birth preparedness and complication readiness plan has been globally endorsed pivotal strategy to decrease these delays. Therefore, this study was aimed to assess the level of practice and factors associated with practice of birth preparedness plan among pregnant women. Methods: Community based cross-sectional study was done among 356 pregnant women selected by simple random sampling technique from July 1-30/2017 in Debretabor town. We selected samples by simple random sampling technique. Data were collected using interview administered questionnaire. Then, we coded, cleaned and entered data through Epidata version 3.1. Finally, exported and analyzed by SPSS. Logistic regression analysis was done to identify association between explanatory variables and practice of birth preparedness and complication plan. An adjusted odds ratio with 95% confidence interval and p-value less than 0.05 was computed to determine the level of significance in multi-variable logistic regression model.Results: Prevalence of birth preparedness and complication readiness plan was 73.9% in this study. primary education status (AOR=3.2,95%CI,1.3-7.8) and secondary educational status (AOR=4.1,95%CI,1.6-10.3), Primigravida (AOR=4.7,95%CI,1.9-11.3), partner involvement in birth preparedness and complication readiness plan (AOR=3.4,95%CI,1.9-6.1), initiating antenatal care in first trimester and media exposure (AOR=1.9,95%CI,1.0-3.3) were significantly associated factors with birth preparedness and complication readiness plan in this study. Conclusions: Level of practice of birth preparedness and complication readiness plan was high in the current study. Higher education status, early ante-natal care initiation, partner involvement in birth preparedness and exposure to media were the factors associated with practice of birth preparedness and complication readiness. Therefore, emphasize on continues education through media, design educational curriculum which should include birth preparedness plan, increase partner participation in birth preparedness and complication readiness plan. Furthermore, early initiation of antenatal care is mandatory.
Status of Disrespectful and Abusive Maternity Care Among Women who Delivered in Hospitals of Sidama zone, South Ethiopia, in 2019.
Authors: Negash Berhan Tsegaye , Yoseph Amanuel
Published: August 2020

Background: Disrespectful and abusive maternity care is occurred at various degree at health institutions across many countries including Ethiopia. Consequently, maternal mortality remains high in Ethiopia. Despite its importance, information is scarce about disrespect and abusive care. Hence, this study aimed to assesses magnitude and factors associated with disrespectful and abusive maternity care during child birth in public health facilities of Sidama zone, South Ethiopia. Methods: Facility based cross-sectional study was conducted in sidama zone public health institutions from February 1-30, 2019. We have applied purposive sampling method for selection of health institutions. In addition, study participants were selected by systematic random sampling technique. Data were collected using checklist and exist interview administered questionnaire. Then, we coded, cleaned and entered data through Epidata version 3.1. Finally, exported and analyzed by SPSS. Logistic regression analysis was done to identify association between explanatory variables and disrespectful and abusive care. An adjusted odds ratio with 95% confidence interval and p-value less than 0.05 was computed to determine the level of significance.Result: From a total of 577 study participants, only 548 study participants have participated in this study making a response rate of 95%. Magnitude of disrespect and abuse maternity care was 46.9% [95%CI: 42.8-51]. Marital status of single (AOR= 2.6, 95% CI=1.8-6.67), four and more births (AOR=4.67,95%CI:1.6-12.8), instrumental delivery (AOR=2.63,95% CI,1.0-6.6), and care provision by female birth attendants (AOR=1.7,95%CI,1.1-2.7) were factors positively associated with disrespect and abusive maternity care during childbirth. Conclusion: Magnitude of disrespect and abusive maternity care is high in this study. Instrumental delivery, female health care provider and four and above deliveries and single marital status were factors associated with disrespect and abuse care. Therefore, government facilities should national health strategies and policies should focus on respectful maternity care. It is also recommended to give intensive training on respectful maternity care especially in public hospitals by involving more female health care provider. Promotion of family planning service can be used as alternative method of reduction of reduction of disrespect and abusive maternal care indirectly.
Relationship Between Obstetric Complications in Women Undergoing IVF with PCOS: A Retrospective Cohort Study
Authors: Muharam R , Danang Prasetyo Yohanes , Maidarti Mila , Harzif Achmad Kemal , Pratama Gita , Wiweko Budi , Hestiantoro Andon
Published: August 2020

Background: Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine and metabolic disorder. One of its complications is infertility. In Vitro Fertilization (IVF) is one of the alternatives to the problem. However, there are no study describing the differences in obstetric complications of PCOS patients undergoing IVF compared to other patients. This study aims to determine the relationship of obstruction complications in women undergoing IVF programs with PCOS.Methods: This was a retrospective cohort study conducted at Cipto Mangunkusumo National General Hospital on 2013-2019. The study subjects were all women aged over 18 years who underwent IVF programs without other gynecological abnormalities besides PCOS. The outcomes in this study were obstetric complications in the form of abortion. Analysis is done by using cox-regression to get the value of Hazard Ratio (HR) after controlling for confounding factors.Results: This study included 355 women, of whom 72 had PCOS (20.3%). Complications found in subjects with PCOS were preterm found in (2.78%), abortion (9.72%) and ectopic pregnancy (1.39%). No association was found between PCOS and abortion in women undergoing IVF programs (p-value > 0.05). Interaction between PCOS and cleavage ratio <6 had higher probability of having abortion in women undergoing IVF program obtained. (RR: 7.32, 95% CI: 2.10-25.45, P-value: 0.002).Conclusion: PCOS does not affect the occurrence of abortion in women undergoing IVF program.
The effect of autoantibody against M2-muscarinic acetylcholine receptor in peripartum cardiomyopathy patients on digoxin additional to standard treatment
Authors: Ma Guiling , Chen Long , Yue Yin , Liu Xiyan , Wang Yidan , Shi Cheng , Song Fei , Shi Wei , Luo Yingshi , Li Tuanye , Zhang Lin
Published: August 2020

Background: To evaluate the effects of autoantibodies against the M2-muscarinic receptor (anti-M2-R) on digoxin additional to standard treatment in peripartum cardiomyopathy (PPCM) patients.Methods: 86 PPCM patients were separated into anti-M2-R negative or positive group according to the anti-M2-R reactivity. All the patients received digoxin additional to standard treatment regimen. Echocardiography was performed at baseline and after 5 years treatment. Serum digoxin concentration (SDC) were performed every 3 to 6 months. All-cause mortality, cardiovascular mortality and re-hospitalization for heart failure were compared after 5 years of follow-up.Results: There were 82 patients completed the final data analysis, including 38 in the anti-M2-R (+) group and 44 in the anti-M2-R (-) group. The heart rate of the positive group was higher than that of the negative group at baseline (102.3 ± 6.3 vs. 95.9 ± 6.8, p < 0.001). The initial SDC of patients in the positive group was higher than that of patients in the negative group with the same dose of digoxin (1.21 ± 0.41 vs. 0.73 ± 0.16 ng/mL, p < 0.001). Patients in the anti-M2-R (-) group had better tolerance to metoprolol and digoxin (p < 0.05). All the PPCM patients showed prominent improvement in cardiac function, especially in the anti-M2-R (-) group. Re-hospitalization for heart failure was decreased in the negative group, but not of all-cause or cardiovascular mortality. Conclusions: Patients negative for anti-M2-R showed better tolerance to metoprolol and digoxin. Anti-M2-R maybe a predictor for vagus nerve overactivation and is associated with poor response to digoxin treatment in PPCM patients.
Ginsenoside Rg1 alleviates Aβ deposition and neuronal damage by inhibiting NLRP1 inflammasome activation in APP/PS1 mice
Authors: Zhang Han , Su Yong , Sun Zhenghao , Chen Ming , Han Yuli , Li Yan , Dong Xianan , Ding Shixin , Fang Zhirui , Li Weiping , Li Weizu
Published: August 2020

Background: Oxidative stress and neuroinflammation play important roles in the whole pathogenesis of Alzheimer's disease (AD). NADPH oxidase 2 (NOX2) is an important enzyme that is responsible for ROS generation in many neurodegenerative diseases. The nucleotide-binding oligomerization domain (NOD)-like receptor protein 1 (NLRP1) inflammasome is responsible for the formation of pro-inflammatory molecules in neurons. However, it is still unclear whether inhibition of NOX2 and NLRP1 inflammasome decreases amyloid-beta (Aβ) generation and deposition in APP/PS1 mice. Ginsenoside Rg1 (Rg1) is an active component in ginseng, and maybe a potential agent for neurodegenerative diseases. In this study, we investigated the effects and mechanisms of Rg1 treatment on cognitive performance, neuronal damage, Aβ deposition and NOX2-NLRP1 inflammasome activation in APP/PS1 mice.Methods: WT and APP/PS1 mice were used in the experiment from 6 months (M) old to 9M old, and 6M APP/PS1 mice were used as pre-treatment controls. The open field test (OFT) and Morris water maze (MWM) were used to detect behavioral change and cognitive function. The H&E and Nissl staining were used to assess neuronal damage. We further examined PSD95 expression, Aβ generation and deposition, Tau and p-Tau expression, NOX2-mediated ROS generation and NLRP1 inflammasome activation by using immunofluorescence, western blot analysis, and real time q-PCR.Results: Rg1 treatment for 12 weeks alleviated learning and memory impairments and neuronal damage, decreased p-Tau level, APP expression and Aβ deposition in APP/PS1 mice. Meanwhile, Rg1 treatment significantly decreased the levels of ROS and IL-1β, and reduced the expressions of NOX2 and NLRP1 inflammasome in the brain cortex and hippocampus in APP/PS1 mice. Furthermore, apocynin (a NOX inhibitor) and NLRP1-siRNA treatment also alleviated cognitive impairments, neuronal damage and Aβ deposition, and reduced the expression of NLRP1 inflammasome in brain cortex and hippocampus in APP/PS1 mice.Conclusions: Rg1 treatment could alleviate learning and memory impairment, neuronal damage, and reduce Aβ generation and deposition by inhibiting NLRP1 inflammasome activation in APP/PS1 mice.
Awareness of cognitive decline trajectories in asymptomatic individuals at risk for AD
Authors: Cacciamani Federica , Sambati Luisa , Houot Marion , Habert Marie-Odile , Dubois Bruno , Epelbaum Stephane
Published: August 2020

BackgroundLack of awareness of cognitive decline (ACD) is common in late-stage Alzheimer's disease (AD). Recent studies showed that ACD can also be reduced in the early stages.MethodsWe performed a Latent Class Analysis to identify longitudinal changes of ACD over 3 years in 314 elderly memory-complainers and its association to amyloid burden and brain metabolism. We also analysed the impact of ACD at baseline on the cognitive scores’ evolution.Results76.8% of subjects constantly had an accurate ACD (reference class). 18.95% showed a persistent heightened ACD (“worried-well” individuals). 4.25% constantly showed low ACD. They had higher amyloid burden than the reference class, and were mostly men. We found no overall effect of baseline ACD on cognitive scores’ evolution.ConclusionsACD begins to decrease during the preclinical phase in a certain group of individuals, who are of great interest because more at risk of being affected by AD.Trial registrationThe present study was conducted as part of the INSIGHT-PreAD study. The identification number of INSIGHT-PreAD study (ID-RCB) is 2012-A01731-42
Crosstalk of multi-omics reveals specific characteristics in active ulcerative colitis patients with depression and anxiety
Authors: Yuan Xiaomin , Chen Biqing , Duan Zhenglan , Xia Ziqian , Ding Yang , Chen Tuo , Liu Huize , Wang Baosheng , Yang Bolin , Wang Xiaoyong , Liu Shijia , Zhou Jin-Yong , Liu Yajun , Shen Zhaofeng , Xiao Jun , Shang Hongtao , Liu Weiwei , Shi Guoping , Zhu Lei , Chen Yugen
Published: August 2020

Background:Ulcerative colitis (UC) patients have a high incidence of mental disorders. The microbiota-gut-brain axis dysfunction is considered as one important pathogenesis of mental diseases. At present, little is known about how gut microbiota interact with the host in UC patients with depression and anxiety.Results: This prospective observational study enrolled 240 Chinese patients in two cohorts: the discovery cohort, including 69 active UC patients, 49 non-inflammatory bowel disease (IBD) depression and anxiety patients, and 62 healthy people, and the replication cohort of 60 active UC patients. About half of active UC patients showed symptoms of depression or anxiety. Through 16s rRNA sequencing, it was found that these UC patients accompanied with depression and anxiety had lower fecal microbial abundance with more Sellimonas , Eubacterium ventriosum group , Enterococcus , and Peptoclostridium , but less Prevotella_9 , Erysipelotrichaceae UCG_003 , Collinsella , and Dorea , compared with non-depressed/ anxious UC patients. Serum metabolome and proteome analysed using liquid chromatography/ mass spectrometry showed significantly increased glycochenodeoxycholate, stearoyllysophosphatidylcholine, and glyceryl stearates, while decreased 2'-deoxy-D-ribose and a set of immunoglobulin protein in the serum of UC patients with depression and anxiety. Through integration of multiple statistical analyses and multi-omics correlation analyses, we revealed a highly connected and comprehensive network, centring on Prevotella_9 and 1-stearoyl-sn-glycerol, composed of these bacteria, metabolites and proteins associated with UC-specific depression and anxiety.Conclusion: This study has identified a highly connected multi-omics network, composed of a set of gut microbiota, serum metabolites and proteins, specifically related to depression and anxiety in active UC. This network might influence host's mental state through mediating the effect of gut inflammation on synapse pruning in the central nervous system.
Genetic Characterization Among Carbapenem-resistant Escherichia coli Strains Using Enterobacterial Repetitive Intergenic Consensus Polymerase Chain Reaction (ERIC-PCR) Fingerprinting in South Africa
Authors: Ebomah Kingsley Ehi , Okoh Anthony Ifeanyi
Published: August 2020

Background Carbapenems belong to beta-lactam class of antibiotics usually considered as the last line of defense because they can be effective against severe infections caused by prevalent multidrug-resistant (MDR) pathogens. However, carbapenems can be deactivated by bacteria that produce carbapenemase (beta-lactamase). This study was conducted to screen for carbapenem-resistance genes (CRGs) harbored by pathogenic strains of Escherichia coli recovered from different environmental samples. We also assessed the genetic relatedness among selected E. coli pathotypes using enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR).Method: Molecular identification and characterization of the presumptive isolates were performed using PCR and isolates that exhibited antimicrobial resistance (AMR) phenotypically were further screened for some relevant CRGs (blaNDM−1, blaKPC and blaOXA−48−like). Furthermore, ERIC-PCR was used to determine the similarity and diversity of 31 E. coli strains which were randomly selected from the different sources analyzed in this study.Result Our findings revealed a total of 238 presumptive E. coli isolates, out of which 192 were confirmed positive for uidA gene. Further screening revealed 77 (40%) isolates belong to six key E. coli pathotypes and 70 of them exhibited phenotypic AMR. Additionally, twenty-nine (41%) of the 70 MDR pathogenic E. coli strains harbored CRGs; with 24 strains harboring blaNDM−1, 8 harboring blaKPC and 2 harboring blaOXA−48−like genes.Conclusion Findings also suggest that the selected E. coli pathotypes belonged to different genomic clusters, while the cluster analysis showed a possible genetic diversity among aquatic and farm isolates. Proper treatment of final effluents before discharge as well as the development of more effective strategies to control and manage the use of antimicrobial agents were strongly recommended.
Mesenchymal Stem Cells Secreted-Prostaglandin E2 Ameliorates Acute Liver Failure via Attenuation Cell Death and Regulation of Macrophage Polarization
Authors: Liu Yang , Wang Jinglin , Ding Haoran , Ren Haozhen , Shi Xiaolei
Published: August 2020

Background: Acute liver failure (ALF) is an acute inflammatory liver disease with high mortality. Previous preclinical and clinical trials have confirmed that mesenchymal stem cell (MSC) is a promising therapeutic approach, however the effect is not satisfied as the underlying molecular mechanisms of MSC in treating ALF remain unclear.Methods: MSC isolated from 4- to 6-week-old C57BL/6 mice were used to treat ALF. Histological and serological parameters were analyzed to evaluate the efficacy of MSC. We explored the molecular mechanism of MSC in the treatment of ALF by detecting liver inflammatory response and hepatocyte death.Results: In this study, we found that therapeutic potential of MSC on ALF dependent on secretion of prostaglandin E2 (PGE2), a bioactive lipid. MSC-derived PGE2 inhibited TGF-β-activated kinase 1 (TAK1) signaling and NLRP3 inflammasome activation in liver macrophages to decrease the production of inflammatory cytokines. Meanwhile, macrophages in liver could be induced to anti-inflammatory (M2) macrophages by MSC-derived PGE2 via STAT6 and mechanistic target of rapamycin (mTOR) signaling, which then to promote inflammatory resolution and limit liver injury. Finally, administrating of EP4 antagonist significantly ameliorated the therapeutic ability of MSC, which promoted liver inflammation and decreased M2 macrophages.Conclusions: Our results indicate that PGE2 might be a novel important mediator of MSC on treating ALF, which through inhibiting liver inflammatory response and hepatocyte death.
Isolating the Energetic and Mechanical Consequences of Imposed Reductions in Ankle and Knee Flexion during Gait.
Authors: McCain Emily , Libera Theresa , Berno Matthew , Sawicki Gregory , Saul Katherine , Lewek Michael
Published: August 2020

Background: Weakness of ankle and knee musculature following injury or disorder is associated with metabolically expensive gait compensations to enable limb support and advancement. However, neuromechanical coupling between the ankle and knee makes it difficult to discern independent roles of these joint dysfunctions on compensatory mechanics and metabolic penalties.Methods: We sought to determine relative impacts of ankle and knee impairment on compensatory gait strategies and energetic outcomes using an unimpaired cohort (N=15) with imposed unilateral joint range of motion restrictions as a surrogate for gait pathology. Participants walked on a dual-belt instrumented treadmill at 0.8 m s-1 using a 3D printed ankle stay and a knee brace to systematically limit ankle motion (locked-ank), knee motion (locked-knee), and ankle and knee motion (locked-a+k) simultaneously. In addition, participants walked without any ankle or knee bracing (control) and with knee bracing worn but unlocked (unlocked).Results: When ankle motion was restricted (locked-ank, locked-a+k) we observed decreased peak propulsion of the locked limb relative to unlocked. Reduced knee motion (locked-knee, locked-a+k) increased locked limb circumduction relative to the locked-ank condition through ipsilateral hip hiking. Interestingly, locked limb average positive hip power increased in the locked-ank condition but decreased in the locked-a+k and locked-knee conditions, suggesting that locking the knee impeded hip compensation. As expected, reduced ankle motion, either without (locked-ank) or in addition to knee restriction (locked-a+k) yielded significant increase in net metabolic rate when compared with unlocked. Furthermore, the relative increase in metabolic cost was significantly larger with locked-a+k when compared to locked-knee condition.Conclusions: Our methods allowed for the reproduction of asymmetric gait characteristics including reduced locked limb propulsion and increased circumduction. The metabolic consequences bolster the potential energetic benefit of targeting ankle function during rehabilitation.
Intelligent and Hybrid Control Method of a 3-DOF Robot Used for Hip, Knee and Ankle Rehabilitation
Authors: aminiazar wahab , Farahi Rasoul
Published: August 2020

Background: There is an increasing trend in using robots for medical purposes. One specific area is rehabilitation. Rehabilitation is one of the non-drug treatments in community health which means the restoration of the abilities to maximize independence. It is a prolonged work and costly labor. On the other hand, by using the flexible and efficient robots in rehabilitation area, this process will be more useful for handicapped patients.Methods: In this study, a rule-based intelligent control methodology is proposed to mimic the behavior of a healthy limb in a satisfactory way by a 3-DOF planar robot. Inverse kinematic of the planar robot will be solved by neural networks and control parameters will be optimized by genetic algorithm, as rehabilitation progress.Results: The results of simulations are presented by defining a physiotherapy simple mode on desired trajectory. MATLAB/Simulink is used for simulations. The system is capable of learning the action of the physiotherapist for each patient and imitating this behaviour in the absence of a physiotherapist that can be called robotherapy.Conclusions: In this study, a therapeutic exercise planar 2-DOF robot is designed and controlled for lower-limb rehabilitation. The robot manipulator is controlled by combination of hybrid and adaptive controls. Some safety factors and stability constraints are defined and obtained. The robot is stopped when the safety factors are not satisfied. Kinematics of robot is estimated by an MLP neural network and proper control parameters are achieved using GA optimization
A retrospective study of hypofractionated radiotherapy for small cell lung cancer
Authors: Li Man , Ge Chao , Chang Pengyu , Chen Kunzhi , Wang Libo , Dong Lihua
Published: August 2020

Purpose: Hypofractionated radiotherapy (HypoRT) shows the superiority in cancer treatment because of its high biological equivalent dose. This retrospective study aims to evaluate the toxicity and efficacy of HypoRT on small cell lung cancer (SCLC).Methods: Medical records of SCLC patients between July 2018 and October 2019 were collected. All patients treated with chemotherapy plus HypoRT (PTV: 30 Gy/10F, PGTV: 45 Gy/10F) were eligible for analysis. The chemotherapy was performed for a total of 4-6 cycles by using Etoposide plus Cisplatin or Carboplatin in peri-radiotherapy phase. Meanwhile, indexes including in-field recurrence rate (ifRR), in-field relapse-free survival (ifRFS) and overall survival (OS) were calculated. Results: Medical data of 30 patients were eligible for analysis. Male to female ratio was 19: 11. The median age was 64 (range from 46 to 75 years old, 95% CI: 52.5-83.75). The median follow-up time was 15 months (range from 1 to 19 months). In follow-up period, either radiation esophagitis or radiation pneumonitis of grade 3 occurred in 6.7% of the patients (2/30). The incidences of severe hematologic toxicities (grade 3/4) including leukopenia, granulocytopenia, thrombocytopenia and anemia were 33.3%, 66.7%, 26.7% and 16.7%, respectively. The ifRR post-HypoRT was 6.7% (2/30) with a median ifRFS of 15 months (rang from 1 to 19 months, 95% CI: 11.25-18.75) and a median OS of 15 months (range from 1 to 19, 95% CI: 11.25-18.75).Conclusion: HypoRT can be tolerated by most of enrolled patients, and HypoRT exhibits its efficacy in controlling SCLC tumors.
SOCS-6 promotes mitochondrial fission and cardiomyocyte apoptosis and is negatively regulated by QKI mediated miR-19b
Authors: Zhang Peng , Guan Ping , Ye Xiaomiao , Lu Yi , Hang Yanwen , Su Yanling , Hu Wei
Published: August 2020

Background Ischemia/reperfusion (IR) injury following myocardial infarction can result in debilitating complications and morbidity. Mitochondrial dysfunction and abnormal mitochondrial fission have been implicated in the complications associated with IR injury as cardiomyocytes are abundant in mitochondria. SOCS-6 is known to participate in mitochondrial fragmentation but its exact involvement and the pathways associated are uncertain. Results In the present study, we examine the biological role and regulation of SOCS-6 in mitochondrial dynamics using hypoxia and reoxygenation (H/R) in cardiomyocytes and with a murine model of IR injury. We found that SOCS-6 inhibition by RNA interference attenuated H/R-induced mitochondrial fission and apoptosis in cardiomyocytes. A luciferase assay indicated that SOCS-6 is a direct target of miR-19b. The overexpression of miR-19b decreased mitochondrial fission and apoptosis in vitro . Moreover, the presence of miR-19b reduced the level of SOCS-6 and the injury caused by IR in vivo . There were less apoptotic cells in the myocardium of mice injected with miR-19b. In addition, we found that the RNA-binding protein, QKI, participates in the regulation of miR-19b expression. Conclusions Our results indicate that the inhibition of mitochondrial fission through downregulating SOCS-6 via the QKI/miR-19b/SOCS-6 pathway attenuated the damage sustained by IR. The QKI/miR-19b/SOCS-6 axis plays a vital role in regulation of mitochondrial fission and cardiomyocyte apoptosis and could form the basis of future research in the development of therapies for the management of cardiac diseases.
Patterns Of Insecticide Resistance Among Anopheles Gambiae Mosquitoes In Five Districts In Uganda: 2011-2015
Authors: Okethwangu Denis , Rutazaana Damian , Kyabayinze Daniel , Birungi Doreen , Biribawa Claire , Kwesiga Benon , Alex Ario R. , Opigo Jimmy
Published: August 2020

Background: Malaria ranks among the leading global public health challenges. Resistance to insecticides used in vector control by malaria vectors threatens the effectiveness of this intervention. We analyzed data from routine susceptibility tests conducted in sentinel sites in five Ugandan districts to determine the status and pattern of insecticide resistance among Anopheles gambiae mosquito vectors, and to assess the trend of mortality rates of the vector. Methods: We conducted a cross-sectional study using secondary data from sentinel sites in Apac, Kanungu, Hoima, Tororo, and Wakiso Districts of Uganda. Chemicals from different classes of insecticides were subjected to susceptibility tests, which included both the World Health Organization (WHO) standard test kit and the Centers for Disease Control and Prevention (CDC) bottle bioassay tests. Resistance was defined according to the standard WHO criteria of insecticide resistance. The Fisher’s Exact Test was used to determine the difference in mortality rates across years in the study period.Results: A total of eight chemicals were used in the selected districts over the years of study. Out of the 5 districts, we found that the average mortality rate of the mosquito vector by the carbamates was over 98% in 3 districts. In Tororo and Wakiso Districts, the average was about 90%. Mortality of mosquitoes by pyrethroids used averaged less than 80% in all five districts. The organochlorines averaged less than 50% in four out of five districts. In Apac District, organochlorines averaged a mortality rate of 94%. The organophosphates averaged 100% mortality in all sentinel sites. There was no specific pattern in mortality of Anopheles gambiae by insecticides.Conclusion: There was widespread resistance to pyrethroids and organochlorines, with patchy resistance observed against carbamates. Only organophosphates showed potency in all sentinel sites. This threatens gains made in malaria control, and renews calls for continued insecticide resistance monitoring.
Review And Assessment Of Malaria Epidemic Situation And Re-Transmission Risk In A Central City Of China, 1950-2019
Authors: ZHA Wen-ting , LI Guoqun , FENG Ruihua , LIAO Yu , ZHOU Nan , CHEN Mengxiang , LI Jing , Ren Xiang , SU Yi , YI Shanghui , LV Yuan
Published: August 2020

Background: With characteristics of fast transmission and widespread, malaria was the most deadly parasite disease. In China, 13 ministries and commissions jointly issued the Action Plan For Malaria Eradication, which was aimed to reach malaria elimination by 2020. Scientific analysis of the epidemic situation and assessment of re-transmission risk of malaria in Changsha, an important city of central China, are of certain reference value for China to pass the World Health Organization malaria control assessment in 2020.Method: The epidemic situation and control process of malaria in Changsha from 1950 to 2019 have been illustrated, and an adjusted assessment method was used to analyze the transmission risk index (MRI) of imported malaria in different districts of Changsha in recent years. All data were from Changsha Center for Disease Control and Prevention (CDC).Results: (1) From 1950 to 2019, there were 282,394 incidences and 39 deaths of malaria in Changsha, the incidence rate has been controlled below 10/1,000,000 after 1990; The fatality rate of malaria in Changsha has always been at a low level, but it reached 10.28/1000 after 2010; (2) Before the year 1978, tertian was the major type of malaria in Changsha, which accounted for 92.71%, but the proportion of pernicious malaria gradually increased after 2000, which accounted for 69.3% since 2010. (3) From 1950 to 2009, the percentage of imported malaria cases in Changsha was only 2.93%; In April 2010, the last local case of malaria was reported in Liuyang, Changsha; After 2011, all cases of malaria in Changsha were imported cases, which were mainly from Africa and Southeast Asia. (4) The re-transmission risk of imported malaria in Changsha from high to low were Liuyang City, Yuelu District, Tianxin District, Yuhua District, Ningxiang County, Furong district, Wangcheng District, Changsha County and Kaifu District. Conclusion: After 70 years, implemented three stages of prevention and control measures, Changsha has achieved the goal of malaria elimination. However, with the imported cases increased, the risk of re-transmission of malaria in Changsha still exists, especially in Liuyang and Yuelu district. Malaria control and prevention should still be taken seriously as an important preventive work in case of the secondary spread.
Explorative Analysis of 60 Metagenomes to Unveil the Abundance of Widespread Functions in the Environment and Its Weight on Functional Indices
Authors: Starke Robert , Piché-Choquette Sarah
Published: August 2020

Background

The total bacterial and fungal functional richness was recently predicted to be millions of KEGG level 3 functions but due to limited space and resource availability together with constraining environmental conditions, the local functionality only comprises a subset of the total functionality. However, widespread functions whose abundance and redundancy depends on species richness or sequencing depth could bias functional indices. Here, we used 20 randomly chosen extant metagenomes from low to high species richness each from aerial, aquatic and terrestrial ecosystems to quantify the distribution of widespread KEGG level 3 functions and their buffering effect on diversity, redundancy and richness.
Results

A different number of widespread functions were detected in each ecosystem with 1,201 found in all three. Diversity found to be similar in the three ecosystems and redundancy that was significantly lower in aerial metagenomes showed identical patterns when all functions were used or when the widespread functions were removed. However, functional richness changed from being significantly higher in aquatic than in terrestrial and aerial metagenomes when all functions are used to no significant differences when the widespread functions are removed. The variance in diversity and richness was higher without widespread functions, making it possible to compare highly dense environments that would otherwise result in similar values.
Conclusions

Taken together, we describe the widespread functiome in aerial, aquatic and terrestrial metagenomes, and its buffering effect on functional indices that are driven by widespread functions which is why, moving forward, we recommend to remove widespread functions from the analysis of metagenome functionality.
Aqueous alteration without initial water: Possibility of organic-induced hydration of anhydrous silicates in meteorite parent bodies
Authors: Hirakawa Naoki , Kebukawa Yoko , Furukawa Yoshihiro , Kondo Masashi , Kobayashi Kensei
Published: August 2020

Early evolution of Solar System small bodies proceeded through interactions of mineral and water. Melting of water ice accreted with mineral particles to the parent body results in the formation of secondary minerals, the so-called aqueous alteration. Formation of phyllosilicates from anhydrous silicates is a typical alteration effect recorded in primitive meteorites. In addition to mineral and water, organic matter could have been also a significant component in meteorite parent bodies. However, the role of organic matter in the alteration of silicates is not well understood. Here we show the in-situ formation of hydrated silicates through a mineral–organic interaction without the initial presence of water. Proto-phyllosilicates were experimentally confirmed on the anhydrous mineral (olivine) surface after being heated with molecular cloud organic matter analog at 300 °C for 10 days in this study. It could be due to H 2 O generated through pyrolysis of the organic compounds with hydroxy groups. Our results indicated that formation of phyllosilicates on the olivine surface in contact with organic matter can occur in meteorite parent bodies which formed inside the H 2 O snow line but accreted with organic matter, initially without water. Water formed through decomposition of organic matter could be one candidate for hydrous silicate formation in ordinary chondrites from S-type asteroids inside the H 2 O snow line. Although the origin of water in ordinary chondrites is under debate, water generation from organic matter may also explain the D-rich water in ordinary chondrites because primordial organic matter is known to be D-rich.
An ultra-low magnetic field thermal demagnetizer for high-precision paleomagnetism
Authors: Qin Huafeng , Zhao Xiang , Liu Shuangchi , Paterson Greig A. , Jiang Zhaoxia , Cai Shuhui , Li Jinhua , Liu Qingsong , Zhu Rixiang
Published: August 2020

Thermal demagnetization furnaces are widely used paleomagnetic facilities for progressive removal of naturally acquired magnetic remanence or the imparting of well controlled laboratory magnetization. An ideal thermal demagnetizer should maintain “zero” magnetic field in the sample chamber during thermal treatments. However, magnetic field noises, including the residual magnetic fields of the construction material and the induced fields caused by the alternating current (AC) in the heating element are always present, which often greatly contaminate the paleoamgnetic results at the elevated temperatures or for the magnetically weak samples. Here, we designed a new structure of heating wire named named straight core solenoid to develop a new demagnetization furnace with ultra-low magnetic field noise. Simulation and practical measurement show that the heating current magnetic field can be greatly reduced by using the new technology. Thermal demagnetization experiments demonstrate that the new demagnetizer can yield low noise results even for weakly magnetic samples.
A Simple Self-Adjuvanting Biomimetic Nanovaccine Self-Assembled with the Conjugate of Phospholipids and Nucleotides Can Induce Strong Cancer Immunotherapeutic Effect
Authors: Liu Dan , Liu Jiale , Ma Bing , Deng Bo , Xu Haiyan , Leng Xigang , Kong Deling , Liu Lanxia
Published: August 2020

Background: Biomimetic nanoparticles have potential applications in many fields for their favorable properties. Results: Here, we developed a self-adjuvanting biomimetic anti-tumor nanovaccine, which was self-assembled with an amphiphilic conjugate synthetized with phospholipids of 1, 2-Dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and hydrophilic Toll-like receptor (TLR9) agonists CpG ODN. The nanovaccine could not only provide effective initial antigens stimulation and sustained long-term antigen supply with a controlled release, but also induce antigens cross-presentation via MHC-I pathway initiating CD8+ T-cell responses. Moreover, the dense nucleotides shell around the nanovaccine could promote antigens endocytosis via various receptor-mediated pathways into dendritic cells. And CpG ODN interacted with TLR9 triggering the cytokines secretion of TNF-α and IL-10 further boosted the anti-tumor humoral and cellular immune responses, which led to significant tumor suppressive effect and remarkable survival prolongation. Conclusions: So, this nanovaccine self-assembled with phospholipid-nucleotide amphiphiles can serve as a safe, simple and efficient approach for anti-tumor immunotherapy.
Neural progenitor cell-derived nanovesicles promote hair follicle growth via miR-100
Authors: Cao Lei , Tian Tian , Huang Yuanbo , Tao Shiqin , Zhu Xiaohong , Yang Mifang , Gu Jing , Feng Guangdong , Ma Yinni , Xia Rushan , Xu Wenrong , Wang Lei
Published: August 2020

Background: Accumulating evidence shows that mesenchymal stem cell-derived extracellular vesicles (EVs) hold great promise to promote hair growth. However, large-scale production of EVs is still a challenge. Recently, exosome-mimetic nanovesicles (NV) prepared by extruding cells have emerged as an alternative strategy for clinical-scale production. Here, ReNcell VM (ReN) cells, a neural progenitor cell line was serially extruded to produce NV. Results: The ReN cell-derived NV (ReN-NV) were found to promote Dermal papilla cell (DPC) proliferation. In addition, on a mouse model of depilation-induced hair regeneration, ReN-NV were injected subcutaneously, resulting in an acceleration of hair follicle (HF) cycling transition at the site. The underlying mechanism was indicated to be the activation of Wnt/β-catenin signaling pathway. Furthermore, miR-100 was revealed to be abundant in ReN-NV and significantly up-regulated in DPCs receiving ReN-NV treatment. miR-100 inhibition verified its important role in ReN-NV-induced β-catenin signaling activation. Conclusion: These results provide an alternative agent to EVs and suggest a strategy for hair growth therapy.
The Distribution of Work-Related Musculoskeletal Disorders Among Nurses in Sub-Saharan Africa: A Scoping Review Protocol
Authors: Kgakge Kagiso , Hlongwa Mbuzeleni , Ginindza Themba
Published: August 2020

Background

Globally, work related musculoskeletal disorders (WMSD) have emerged as a major occupational public health concern among healthcare workers (HCW), in particular the nurses who are at the forefront of the healthcare delivery system. The 2016 Global Burden of Disease (GBD) data for non-communicable diseases reports that Disability Adjusted Life Year (DALYs) for musculoskeletal conditions increased by 61.6% between 1990 and 2016, with an increase of 19.6% between 2006 and 2016. Furthermore, World Health Organization (WHO, 2018), states that the sustainable development goals (SDGs) and the Decade of Healthy Ageing (DHA) 2020–2030 offer a timely and favorable opportunity for increased global attention and action on musculoskeletal health both at national and global level because the burden of disease profiles are shifting from communicable conditions to predominantly long-term non-communicable diseases, commonly including musculoskeletal conditions. Literature indicates that musculoskeletal disorders (MSD) constitute a notable occupational problem among the nurses with low back pain (LBP) being the most prevalent with consequent occupational injuries. There is an increase in literature regarding the MSD which poses a major threat to the health of nurses, hence there is need to investigate measures that can be used to mitigate the burden of LBP among nurses. Therefore, the scoping review will map the existing evidence on prevalence, incidence, mortality, risk factors and economic costs associated with MSD among nurses in Sub Saharan Africa (SSA).

Methods and analysis

Scoping review will be done to explore, describe and map literature on the prevalence, incidence, mortality, risk factors, and economic costs related to MSD among nurses in SSA. The search will be done using databases such as PubMed, MEDLINE, CINAHL, Google Scholar, nursing academic editions and World Health Organization (WHO) library databases. The search will look for primary studies within peer-reviewed articles as well as gray literature. The list of references from included studies will also be searched. This scoping review will be reported in accordance to the MOOSE and PRISMA-ScR guidelines. The NVivo 12 data analysis software will be used to generate themes, and a thematic content analysis will be used to give the narrative account of the review.

Discussion

At the end, this study anticipates to uncover the relevant literature in SSA in regard to prevalence, incidence, mortality, risk factors and costs related to MSD among nurses, furthermore findings from this study will help in identifying research gaps, informing policy, priority in funding and planning and to guide future research.