bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered gut microbiota correlate with different immune response to HAART in HIV-infected individual
Authors: Sun Jia , Wei Li , Jiang Haiyin , Hu Caiqin , Yang Jiezuan , Huang Ying , Ruan Bing , Zhu Biao , Xie Yirui
Published: July 2020

Background: Although gut microbiota dysbiosis has recently been reported in HIV infected individuals, the relationship between the gut microbiota and immune activation in patients with different immune response to highly active antiretroviral therapy (HAART) is still not well understood. Gut microbiota and immune activation were studied in 36 non-HIV-infected subjects (Health Control) and 58 HIV-infected individuals which included 28 immunological responders (IR) and 30 immunological non-responders (INR) (≥500 and <200 CD4+ T-cell counts/µl after 2 years of HIV-1 viral suppression respectively) without comorbidities. Results: Metagenome sequencing revealed that the diversity and composition of gut microbiota could not be recovered completely as normal gut environment in HIV-infected individuals although with immunological response after long-term effective ART. At the genus level, predominant genera Fusobacterium, Ruminococcus_gnavus and Megamonas were more abundant, whereas Faecalibacterium, Alistipes, Bifidobacterium, Eubacteriumrectale, and Roseburia were depleted in IR and INR group than health control. Ruminococcaceae and Alistipes were positively correlated to nadir and current CD4+ T-cell, but negatively correlated to CD8+CD57+ T-cell. Inflammation markers and translocation biomarkers (LPS) levels were positively correlated to the abundance of genus Ruminococcus and Fusobacterium, but were negatively correlated to genus Faecalibacterium. Escherichia-Shigella and Blautia were enriched significantly in IR than INR group. Escherichia-Shigella were negatively correlated to CD4/CD8 ratio, but positively correlated to CD8+CD57+ T-cell. Conclusions: Altogether, the gut microbiota is one of the factors contributing to different immune response to HAART. Fusobacterium, Alistipes, Ruminococcaceae, Faecalibacterium and Escherichia-Shigella maybe the major genus contributed to different immune response in immunodiscordant and immunoconcordant patients on long-term suppressive ART.
Plasma levels of lipocalin 2 is increased in neovascular age-related macular degeneration patients, particularly those with macular fibrosis
Authors: Chen Mei , Yang Nan , Lechner Judith , Toch Levente , Hogg Ruth , Silverstri Giuliana , Chakravarthy Usha , Xu Heping
Published: July 2020

Background: Previously, we and others have reported high populations of circulating neutrophils in patients with neovascular age-related macular degeneration (nAMD). Neutrophil gelatinase-associated lipocalin (NGAL, also known as lipocalin-2, LCN2), an important innate immune mediator, is known to be critically involved in sterile inflammation-mediated organ failure, fibrosis, cancer progression and retinal degeneration. This study investigated the plasma levels of LCN2, matrix metalloproteinase 9 (MMP9) and LCN2/MMP9 complex in different types of nAMD and examined whether the levels were related to patients’ responsiveness to anti-VEGF therapy. Results: One hundred and seventy-four nAMD patients, including 108 with choroidal neovascularisation (CNV), 32 with retinal angiomatous proliferation (RAP), 23 with polypoidal choroidal vasculopathy (PCV) and 11 unclassified patients, and 43 controls were recruited to this case-control study. Fifty-eight nAMD patients had macular fibrosis and 110 patients did not. Out of the 174 nAMD patients, 80 patients responded completely, 90 responded partially, and 4 did not respond to the anti-VEGF therapy. The plasma levels of LCN2 in nAMD patients (181.46 ± 73.62 ng/ml) was significantly higher than that in healthy controls (152.24 ± 49.55 ng/ml, P = 0.047). However, the difference disappeared after adjusting for age. A positive correlation between plasma level of LCN2 and age was observed in nAMD patients (r=0.29, P=0.0002) but not in healthy controls. The plasma level of LCN2 was also positively correlated with circulating neutrophils in nAMD patients (r=0.34, p=0.0007) but not in healthy controls (r=0.057, p=0.77). No correlation was observed between age and circulating neutrophils. Further analysis of nAMD subtypes uncovered a significantly higher level of LCN2 in patients with macular fibrosis even after adjusting for age. No relationship was observed between plasma levels of LCN2 and patients’ responsiveness to anti-VEGF therapy. The plasma levels of MMP9 and LCN2/MMP9 complex were comparable between nAMD and controls. Conclusions: Our results suggest that higher plasma levels of LCN2 in nAMD are related to ageing and increased population of circulating neutrophils. Our results also suggest that higher levels of LCN2 may increase the risk of macular fibrosis in nAMD.
Trend and treatment outcomes of latent tuberculosis infection among migrant persons in Japan: analysis of Japan Tuberculosis Surveillance data
Authors: Kawatsu Lisa , Uchimura Kazuhiro , Ohkado Akihiro
Published: July 2020

Background
Screening for latent tuberculosis infection (LTBI) among migrant population has become a critical issue for many low TB burden countries. Evidence regarding effectiveness of LTBI programs are limited, however, partly because of paucity of national data on treatment outcomes for LTBI. In Japan, notification of LTBI is mandatory, and its treatment outcome is reported as part of Japan’s national TB surveillance system. We thus conducted a detailed analysis of LTBI among foreign-born persons, to update the epidemiological trend of newly notified LTBI between 2007 and 2018, and, to examine the treatment regimen and outcome of those notified in 2016 and 2017, focusing specifically on the potential risk factors for lost to follow-up.
Methods
We analyzed the data of newly notified LTBI patients to examine the overall trend of notification and by age groups and modes of detection between 2007 and 2018, and the cohort data for treatment regimen and outcomes of foreign-born persons notified with LTBI in 2016 and 2017. Potential reasons for lost to follow-up were explored, and logistic regression analysis was conducted to identify risk factors. Comparisons were made with the Japan-born patients where appropriate.
Results
Both the number and proportion of LTBI among foreign-born persons have been constantly increasing, reaching 963 cases in 2018. Analysis of cohort data indicated that the proportion of those on shorter regimen was higher among the foreign- than Japan-born patients (5.5% vs. 1.8%, p < 0.001). The proportion of those who have been lost to follow-up and transferred outside of Japan combined was higher among the foreign- than Japan-born patients (12.0% vs, 8.2%, p < 0.001). Risk factors for lost to follow-up were being employed on a temporal basis, and job status unknown (adjusted odds ratios 3.11 and 4.09, 95% confidence intervals 1.34–7.26 and 1.60-10.48, respectively).
Conclusions
Migrant population face greater risk of interrupting LTBI treatment, and interventions to improve adherence are a critical component of programmatic management of LTBI. Further studies are needed to explore the cultural and socioeconomic situation in which foreign-born persons undergo LTBI treatment in Japan.
Evaluation of hepatic fibrosis in HIV/HCV Co-infected individuals in Yaoundé, Cameroon: Usefulness of APRI score in resource-constrained settings
Authors: Dobseu Rodolphe Steven , Nanfack Aubin Joseph , Kowo Mathurin , Ambada Georgia , Kamgaing Rachel Simo , Chenwi Collins , Fainguem Nadine , Ka’e Aude , Ngangoum Eric , Sosso Samuel Martin , Tchiegang Clergé , Ndjolo Alexis
Published: July 2020

Background
HIV infection exacerbates the prognosis of HCV infection, with a faster progression of hepatitis. Hepatic fibrosis is the major disruption of the hepatic tissue architecture characterized by anarchic deposition and excess of the extracellular matrix. The objective of this study was to evaluate hepatic fibrosis in HIV/HCV co-infected individuals as compared to HCV mono-infected.
Methods
A total of 97 participants (mean age 60.2 ± 14.3 years and 0.76 male/female sex ratio) was enrolled in a study conducted in Yaoundé, Cameroon from November 2018 to January 2019. Liver fibrosis was assessed by the APRI score (Aspartate Aminotransferase or AST/Platelet Ratio Index) which identifies the stage of fibrosis classified by the Metavir system (F0 to F4). CD4 counts and plasmatic HIV viral load of HIV/HCV co-infected individuals were determined and the correlation between hepatic fibrosis and immuno-virological status established. Statistical analysis was done using Microsoft Excel 2016 and EpiInfo7 software.
Results
A high proportion (63.6%) of HIV/HCV co-infected participants had an abnormal AST level: 73.6 ± 45.8 IU/L as compared to 58.5 ± 39.3 IU/L (59.3%) among HCV mono-infected participants. The frequency of thrombocytopenia was 63.6% with a mean platelet count of 137 ± 50 × 103 IU/L in HIV/HCV co-infected participants as compared to 176 ± 67 × 103 IU/L in HCV mono-infected participants (38.4%). The progression of hepatic fibrosis in participants with clinically significant fibrosis: F2, F3 and F4 was higher among HIV/HCV co-infected and the mean APRI score was 1.7 ± 1.4 versus 1 ± 0.8 among HCV mono-infected (26.7%). All participants (100%) with detectable HIV viral load had clinically significant fibrosis compared to 33.4% in those with undetectable HIV viral load (p = 0.55). Only 42.9% participants with CD4 > 500 cells/µL had clinically significant fibrosis (p = 0.72) while 100% participants with CD4 < 200 cells/µL had clinically significant fibrosis (p = 0.58).
Conclusions
A high level of AST combined with thrombocytopenia (APRI score > 1.5) is an indicator of hepatic fibrosis in HIV/HCV co-infected individuals. Because of its non-invasive and less costly nature, the APRI score can be a suitable biomarker to monitor hepatic fibrosis in HIV/HCV co-infected individuals in resource constrained settings.
Obesity is a Risk Factor for Epidural Lipomatosis: A Meta-analysis
Authors: Zhang Bi , Yuan Haifeng , Hu Lihong , Saad Muhammad
Published: July 2020

Background: Many studies have investigated the relationship between spinal epidural lipomatosis and obesity, no meta-analysis of studies have provided definitive evidence. To summarize the evidence of associations between obesity factors and spinal epidural lipomatosis (SEL) and to evaluate the strength and validity of these associations. Methods: Electronic databases such as Wiley Online Library, PubMed, Embase, Cochrane Library were searched and manual retrieval of references, the time limit was from the establishment of the database to May 2020. The included literature was case-control studies that reported body mass index (BMI) and SEL correlation, and excluded any primary and secondary tumors or other compression diseases in the spinal canal. Methodological quality evaluations of the included studies were assessed using the bias risk assessment tool recommended by the Cochrane Guidelines. The RevMan 5.3 software was used for meta-analysis. Results: Finally, ten studies were included for systematic review, all of which were observational studies with mixed bias risk. These studies involved 1,541 patients, with an average age of 54.9 to 73.6 years, and 60.2 percent of the participants were male. The sample sizes for the included studies ranged from 28 to 398. The results of meta-analysis showed that high BMI was one of the factors affecting SEL. All reviews had a high risk of bias, and the most common source of bias was that there was no strict unified case diagnosis standard between researches, and some studies (four items) did not clearly describe the confounders that they controlled. Conclusions: We suggest that physicians should consider obesity as a factor leading to SEL, and to control body mass index actively should be considered as the preferred treatment strategy before surgical intervention is conducted.
Transcriptomes Analysis Reveals Novel Insight Into the Molecular Mechanisms of Somatic Embryogenesis in Hevea Brasiliensis
Authors: Wang Ying , Li Hui-Liang , Zhou Yong-Kai , Guo Dong , Zhu Jia-Hong , Peng Shiqing
Published: July 2020

Background
Somatic embryogenesis (SE) is a promising technology for plant vegetative propagation, which has an important role in tree breeding. Though rubber tree (Hevea brasiliensis Muell. Arg.) SE has been founded, few late SE-related genes had been identified and the molecular regulation mechanisms of late SE still not well understood.
Results
In this study, the transcriptomes of embryogenic calluses (EC), primary embryo (PE), cotyledonary embryo (CE), abnormal embryo (AE), mature cotyledonary embryo (MCE) and withered abnormal embryo (WAE) were analyzed. A total of 887,852,416 clean reads were generated, more than 85.92% of the clean reads were mapped to the rubber tree genome. The de novo assembly generated 36937 unigenes. The differentially expressed genes (DEGs) were identified in the pairwise comparisons of CE vs. AE and MCE vs. WAE, respectively. The specific common DEGs mainly involved in phytohormones signaling pathway, biosynthesis of phenylpropanoid and starch and sucrose metabolism. Among them, hormone signal transduction related genes were significantly enriched, especially the auxin signaling factors (AUX-like1, GH3.1, SAUR32-like, IAA9-like, IAA14-like, IAA27-like, IAA28-like and ARF5-like). The transcript factors including WRKY40, WRKY70, MYBS3-like, MYB1R1-like, AIL6 and bHLH93-like were characterized as molecular markers for rubber tree late SE. CML13, CML36, CAM-7, SERK1 and LEAD-29-like were related to rubber tree late SE. In addition, histone modification had crucial roles during rubber tree late SE.
Conclusions
This study provides important information to elucidate the molecular regulation during rubber tree late SE.
Dusp6 Depletion Enhances Gut Barrier Integrity and Microbiota Eubiosis Against Dextran Sulfate Sodium-Induced Colitis in Mice
Authors: Chang Cherng-Shyang , Liao Yi-Chu , Huang Chih-Ting , Lin Chiao-Mei , Cheung Chantal Hoi Yin , Ruan Jhen-Wei , Yu Wen-Hsuan , Tsai Yi-Ting , Juan Hsueh-Fen , Huang Hsuan-Cheng , Chan Hong-Lin , Liao Yu-Chieh , Su Yu-Wen , Tan Tse-Hua , KAO CHENG-YUAN
Published: July 2020

Background: Leaky gut and microbiota dysbiosis have been linked to many chronic inflammatory diseases. Strengthening the gut epithelial barrier is a novel but overlooked strategy for management of gut microbiota-associated illnesses. Results: Using the dextran sulfate sodium (DSS)-induced gut barrier injury-based colitis model, we found that DSS-induced weight loss, rectal bleeding, and colonic epithelium damage were ameliorated in dual-specificity phosphatase 6 (Dusp6)-deficient mice. These protective effects could be attributed to the enhanced colon barrier integrity conferred by Dusp6-deficiency. Consistently, DUSP6 mutation in Caco-2 cells elevated transepithelial electrical resistance, enhanced tight-junctions, and increased expression of microvilli-associated genes. DUSP6-deficient Caco-2 cells also showed increased mitochondrial oxygen consumption accompanied by altered glucose metabolism and decreased glycolysis. Remarkably, our microbiome analysis found that Dusp6-deficient mice harbored fewer pathobionts and facultative anaerobes and more obligate anaerobes than wild-type mice after DSS treatment. Our cohousing and fecal microbiota transplantation experiments demonstrated that the gut/fecal microbiota derived from Dusp6-deficient mice also conferred protection against colitis.Conclusion: We have thus identified Dusp6 deficiency as beneficial in enhancing gut barrier integrity, elevating epithelial phosphoxidation, and maintaining the gut microbiota eubiosis necessary to protect against colitis.
Epidemiological and clinical characteristics of COVID-19 pneumonia in Zhejiang province, China: a description of early stage
Authors: Gong Caixia , Ma Cheng , Li Shumin , Yang Yunmei , Zhang Qin
Published: July 2020

BackgroundThe outbreak of the 2019 novel coronavirus since December, 2019, has now causing nearly 75 thousand confirmed cases in China (until paper preparing). This epidemic has posed significant threats to international health and the economy. Zhejiang province, which once had the 2nd most accumulative cases among all provinces, has now dropped to top No.5 (until paper preparing). It had a high discharge rates (43.86%) from hospital and the lowest death rate among all top 5 epidemic provinces, this drew our attention to the epidemiological, clinical characteristics and local government engagement of this region.MethodsIn this study, we included all confirmed cases of COVID-19 pneumonia in Zhejiang province from Jan 21 to Feb 11, 2020. All data come from cases issued by Zhejiang provincial health commission.ResultsUntil Feb 11, 2020, 1143 cases were confirmed in Zhejiang province. We analysed the cases growth information in Zhejiang province and age, gender, severe cases percent, the source of the patients, the time of disease onset to confirm and the clinical symptoms of the patients. We also compared the clinical symptoms of elders and the young.ConclusionsThe patients in Zhejiang province had no age and gender preference, and the average time of disease onset to confirm was 5.9 days. The clinical symptoms were mainly fever, cough and weakness, similarly with before reported. The difference between elders and younger are not significant. Until paper preparing, Zhejiang province has very high discharge rate and low death rate, low cases increase rate in China.
Transprofessional Clinical Practice Improves Medical Students’ Attitudes Towards Team Collaboration
Authors: Ganjitsuda Kazunori , Tagawa Masami , Saiki Takuya , Kikukawa Makoto , Takamura Akiteru , Okazaki Hitoaki , Matsuyama Yasushi , Moriya Rika , Chiba Hiroki , Takagi Yasushi , Setoyama Hitoshi , Tomihara Kazuya
Published: July 2020

Background Collaborative work between multiple health professions provides high quality health services and results in optimum outcomes, and interprofessional education is known as an effective strategy for improving attitudes towards interprofessional work. However, it has been repeatedly reported that physicians have poor attitudes towards collaboration with other health professionals, and how medical trainees develop their collaborative attitude during undergraduate education has not been examined in detail. The aim of this study was to investigate how medical trainees’ collaborative attitude changes and whether educational intervention modifies this process.Methods This was a cross-sectional study targeting first- (just after admission), fourth- (pre-clinical) and sixth- (prior to graduation) year medical students in seven medical schools in Japan, second-year residents in four medical school hospitals, and doctors in one university. A survey using the Japanese version of the Jefferson Scale of Attitudes Toward Interprofessional Collaboration was conducted from 2016 to 2017. The average score of each group, institution and gender, and the relationship between scores and length of teamwork courses and clinical clerkship were analyzed.Results A total of 2504 (response rate 83.0%) responses were received. The average scores of first-, fourth- and sixth-year medical students, residents, and doctors were 110.1, 105.8, 105.6, 102.4, and 107.0, respectively. A three-way analysis of variance of students’ scores showed that learning year, institution, gender, and the interaction between institution and learning year were significant variables. Scores of female students were significantly higher than those of male students.The length of interprofessional education courses in preclinical years was significantly correlated with scores among fourth-year students, but not sixth-year medical students. The length of clinical clerkship was significantly correlated with scores among sixth-year medical students.Conclusion Collaborative attitude towards teamwork was low among advanced year medical students and residents. Clinical practice with multiple professions in long-term clinical clerkship, which was classified as transprofessional education, might be the most effective intervention for improving attitudes towards collaboration among medical students.
Investigation of the benefit of PVC in high resolution PET as a post and within reconstruction method for FDG brain data
Authors: Raptis Evangelos , Parkes Laura , Anton-Rodriguez Jose , Carter Stephen , Herholz Karl , Matthews Julian
Published: July 2020

Purpose: The combination of positron emission tomography (PET) with magnetic resonance imaging (MRI) may enable novel research in the field of dementia. MR data is commonly used in the analysis of PET data for dementia due to its anatomical information and good soft tissue contrast. PET image reconstruction is currently performed independently of MRI data and the images typically suffer from low resolution, poor signal-to-noise ratio and count dependent bias, due to random error in acquired data and the reconstruction process which is ill conditioned. The aim of this research is to investigate the benefit of using anatomical information from MR data within PET image reconstruction, applied to dementia research. Methods: Real PET and MRI patient data of 5 FDG scans of a healthy elderly volunteers, were used in order to create realistic ground truth images of the distribution of matter and activity for these individuals. These ground truth images underwent a Monte-Carlo simulation using SimSET, in order to generate simulated raw data of the high research resolution tomograph (HRRT) PET scanner. The simulations were validated by comparing the reconstructed images to real HRRT data and focusing on image resolution. A comparison of partial volume correction (PVC) of PET data applied within image reconstruction with the conventional approach of applying it post-reconstruction was conducted with typical count levels in order to evaluate the hypothesis that there would be benefit of applying PVC within image reconstruction. Results: Results showed a little improvement in the recovered activity values is seen when using Lucy-Richardson deconvolution both post and within the image reconstruction. Similarly the use of RM modelling showed little benefit. Differences were observed when using Rousset PVC, with larger differences observed when interleaved with reconstruction. Generally the used of Rousset PVC within reconstruction resulted in a decrease in the bias (average error) for large cortical regions, but an increase in bias was observed for small regions and there were apparent region specific and patient specific variations in the observed bias. Conclusions: The benefit of applying PVC as a reconstruction based method showed to be minimal. A region specific bias was observed for most of the reconstruction methods, either applied within or post image reconstruction. Further work is needed to evaluate the benefit of applying PVC methods for high resolution scanners.
Bt cotton seed purity in Burkina Faso: Status and lessons learnt
Authors: Bourgou Larbouga , Kargougou Ester , Sawadogo Mahamadou , Fok Michel
Published: July 2020

BackgroundSince the commercial release of Bt cotton the issue of seed purity in producers' fields has been little addressed and in an unbalanced way when it was. It is well documented that the loss of purity in conventional seeds has endangered the continuation of organic cotton production. However, studies are rare on the purity of Bt-cotton seeds despite its implications on the effectiveness and sustainability of their use.This paper compensates for the mentioned lack of literature by analyzing data collected in 2015 in Burkina Faso, namely results of ELISA tests on samples of seeds from 646 fields grown with conventional or Bt varieties. ResultsAccording to the conservative criteria retained to declare the presence of Bt gene (more than 10% and 90% of controlled seeds for conventional and Bt variety, respectively), seed purity was very questionable for both types of varieties. For the conventional variety, the presence of Bt gene was observed on 63.6 and 59.3% of samples for Cry1Ac and Cry2Ab, respectively. Only 29.3% of samples corresponded to pure conventional seeds while 52.2% were double Bt seeds. Conversely, for the Bt variety, the presence of Bt gene was observed on 59.6 and 53.6% of samples for Cry1Ac and Cry2Ab, respectively. Actually BG2 seeds with both Bt genes were found in 40.4% of samples against 27.2% of samples of actually conventional seeds while the remaining of 32.4% of samples corresponded to single Bt gene seeds.Two factors affected the severe lack of seed purity. As regard to conventional seeds, it clearly resulted from a phenomenon of contamination, indicative of a failure in adjusting the seed production scheme to the use of Bt-cotton. With regard to the Bt variety, the lack of purity of the original seeds provided to Burkina Faso accounted and should even be the major factor.The observed lack of seed purity is a threat to the initiative of organic cotton production, albeit a very minor production mode in the country. It also calls upon the effectiveness and furthermore the sustainability of Bt cotton to control target pests. ConclusionOur results show the extent of purity loss when no especial attention is paid to the preservation of seed purity. Pure conventional seeds could totally vanish while Bt seeds become a combination of seeds of various types encompassing or not the expected Bt genes.Any country willing to embark the use of Bt cotton, or to resume this use like Burkina Faso, must previously adjust its seed production scheme and enforce its operation. This is a condition to preserve pure seeds both to enable the launch or the continuation of identity-cotton production and to ensure a sustainable effectiveness of Bt-cotton. The mentioned condition implies that seed purity must be checked and the related information shared.
Serotyping of sub-Saharan Africa Salmonella Strains Isolated from Different Sources Using Multiplex PCR and Capillary Electrophoresis Analysis and whole Genome Sequencing
Authors: Kagambèga Assèta , Hiott Lari M. , Boyle David S. , McMillan Elizabeth A. , Haukka Kaisa , Sharma Poonam , Gupta Sushim K. , Ramadan Hazem , Cho Sohyun , Humayoun Shaheen B. , Woodley Tiffanie A. , Barro Nicolas , Jackson Charlene R. , Frye Jonathan G.
Published: July 2020

BackgroundSalmonella enterica remains a leading cause of food-borne diseases worldwide. Serotype information is important in food safety and public health activities to reduce the burden of salmonellosis. In the current study, two methods were used to determine serotypes of 225 clinical, environmental, food and veterinary isolates of Salmonella from Burkina Faso. First, Salmonella Multiplex Assay for Rapid Typing (SMART) Polymerase Chain Reaction (PCR) was used to determine the serovars of the S. enterica isolates. Second, serovar prediction based on whole genome sequencing (WGS) data was performed using SeqSero 2.0.ResultsAmong the 225 Salmonella isolates, serotypes for 48 (21.33%) isolates were identified based on comparison to a panel of representative SMART codes previously determined for the 50 most common serovars in the United States. One hundred and seventy-six new SMART codes were developed for common and uncommon serotypes. Serotypes for a total of 205 (91.1%) isolates were identified using SeqSero 2.0 for serovar prediction based on WGS data.ConclusionWe determined that SeqSero 2.0 was more comprehensive for identifying Salmonella serotypes from Burkina Faso than SMART PCR.
Echo Simulation of dual polarization Doppler Weather Radar based on physical Model
Authors: JieLa Qutie , Wang Haijiang , Hu Shipeng , Zhu Jiahui , Gao Mengqing
Published: July 2020

Using the scattering characteristics of particles to simulate the radar echo can supply the test signals close to the real precipitation echo for the weather radar, and save the time and cost of the research and development and maintenance of the weather radar. In this paper, the precipitation echo of weather radar is simulated based on the theoretical basis that the raindrops in the falling process satisfy the oblate spheroidal particles in the atmosphere. The Marshal-Palmer distribution is applied to describe the raindrop spectrum distribution of precipitation particles. It is assumed that the raindrop particles of different sizes have the random distribution in the radar resolution volume, and then the spatial distribution of precipitation particles in the resolution volume is modeled. The echo signals of horizontal and vertical polarization channels of dual polarization weather radar are obtained by vector superposition of backscattering echoes of each particle. The experimental results show that this method can describe the microphysical characteristics of precipitation particles more completely and can be used to test the signal processing module of dual polarization Doppler weather radar.
Drug Repurposing of β-blocker Propranolol in Osteosarcoma: Preclinical Antitumor Efficacy Alone or in Combination with Chemotherapy.
Authors: Solernó Luisina M. , Sobol Natasha T. , Capobianco Carla S. , Vásquez Liliana , Ripoll Giselle V. , Alonso Daniel F. , Garona Juan
Published: July 2020

Background: Osteosarcoma is still associated with poor response to therapy and alarmingly elevated mortality rates, especially in developing countries, highlighting the urgent need of novel therapeutic strategies. Given that β-adrenergic receptor (β-AR) signaling regulates many cellular processes involved in the initiation and progression of cancer, multiple efforts have been made to repurpose non-selective β-blocker propranolol in oncology. Considering the unsatisfied clinical needs of osteosarcoma, we evaluated the in vitro and in vivo antitumoral activity of propranolol as a monotherapy or in combination with metronomic chemotherapy, in β-AR-expressing human osteosarcoma cells. Methods: In vitro anti-osteosarcoma effects of propranolol were assessed on high-density cell growth, chemotaxis, colony-forming ability and three-dimensional spheroids. Cell cycle phase distribution and apoptosis were evaluated using flow cytometry analysis, and quantification of hypodiploid cell population and TUNEL labelling, respectively. Propranolol addition to chemotherapy was evaluated in vitro and in human osteosarcoma xenografts generated in athymic mice.Results: Propranolol significantly impaired MG-63 and U-2 OS cellular growth in a concentration range of 10-100 µM (IC50 ≈ 45µM) and was capable of blocking in vitro protumoral effects triggered by catecholamines. Cytostatic activity of propranolol was associated to reduced mitosis and G0/G1 cell cycle, but not to apoptosis induction. Moreover, β-blocker drastically reduced colony formation, spheroid progression and migration of osteosarcoma cells. Synergistic effects were observed in vitro after combining propranolol with chemotherapeutic agents methotrexate or cisplatin. In vivo, treatment with propranolol (10 mg/kg i.p.), alone and especially in addition to non-interrupted low-dose cisplatin (2 mg/kg i.p.), markedly abrogated xenograft progression, reducing tumor growth rates by 25 or 70%, respectively. After histological analysis, propranolol and cisplatin combined therapy resulted in low tumor mitotic index and increased tumor necrosis. Conclusions: Considering its robust antitumoral effects, β-AR antagonization using β-blocker propranolol seems to be an achievable and cost-effective therapeutic approach to modulate osteosarcoma aggressiveness, in addition to chemotherapy. Propranolol could be proposed as a co-adjuvant agent for the management of osteosarcoma, especially in low- and middle-income countries where access to treatment resources are limited. Further preclinical and clinical studies of propranolol repurposing in osteosarcoma are warranted.
Siglec10 as an Immunosuppressive and Tumorgenesis Signature for Prediction of Survival Prognosis in Gliomas
Authors: Feng Yanyan , Zhang Yuxiang , Wang Ting , Feng Yuyin , Wang Hesong , Yuan Kai
Published: July 2020

Background Glioma is a type of tumor occurring in central nervous system. Specific factors mutations and molecular abnormalities are used to conduct glioma classification and clinical decision in recent decade. Siglec10 is a member of sialic acid binding immunoglobulin superfamily. Methods We analyzed the siglec10 expression in glioma patients with immunohistochemical (IHC) staining method and evaluated the survival prognosis. Bioinformatic datasets including TCGA and CGGA were used to validate the IHC results. Functional enrichment analysis including GO, KEGG, and GSEA were conducted to study the related mechanism of siglec10, either. Results High siglec10 expression had shorter survival prognosis than low siglec10 expression in patients especially with malignant gliomas. Bioinformatic datasets including TCGA and CGGA validated the IHC results and discovered the expression of siglec10 was higher in malignant subtype than benign subtype of gliomas. So, siglec10 contributes to the poor prognosis of gliomas. Furthermore, the related mechanisms of siglec10 in gliomas were investigated by functional enrichment analysis including GSEA, GO, and KEGG analysis. Siglec10 was correlated with inflammatory mediators, inflammatory cells, and inflammatory pathways in gliomas. Conclusions Siglec10 might take part in the immune response in tumor microenvironment to induce the progression and metastasis of glioma. This study showed siglec10 was a biomarker in glioma and it might be the potential target of glioma immunotherapy in the future.
Ultrasound Image Patterns Right After Birth Can Predict Healthy Neonates – A Nested Case-Control Study
Authors: Xi Guannan , Dai Jiale , Wang Xuefeng , Luo Fei , Lu Chengqiu , Yang Yun , Wang Jimei
Published: July 2020

Background Lungultarsound(LUS) is widely used to diagnose neonatal lung diseases, yet image patterns on intrauterine to extrauterine stage(right after birth), of which impairment is well related to lung disease, remains unclear. Objectives To identify these image patterns that can distinguish healthy infants from infants with lung disease.Methods This is a nested case-control study in a top-ranking obstetrics hospital in China, between 1 January 2020 to 1 April 2020. Infants transferred to the NICU after birth who had LUS obtained at 0.5, 1, 2, 4, 6 hours time intervals were enrolled. Confirmed by 3-day follow-up, case and control groups contains 22 patients and 473 healthy infants. Their GA ranges from 33.5 to 41.0 weeks. A newly designed protocol was used to capture the LUS image. The image patterns and their variations were shown and categorized as high and low-risk groups. The predictive value for healthy infants and patients were calculated. Results Low-risk patterns, accompanied with no high-risk ones, typically appeared in healthy infants (specificity=86.4%, PPV=99.0%), whereas four high-risk patterns could be seen in both healthy infants and patients (specificity=62.4%, PPV=9.6%). High-risk patterns were more likely to be pathological signs when appearing at the oxter and lower back and to be physiological signs when appearing at the prothorax. Conclusions LUS is valid to differentiate healthy infants from potential patients shortly after birth. Infants with low-risk patterns only are highly likely to be healthy, whereas infants with high-risk patterns have a risk for respiratory issues but need prolonged monitoring to confirm.
Evaluation of a Genetic Risk Score for Severity of COVID-19 Using Human Chromosomal-scale Length Variation
Authors: Toh Chris , Brody James
Published: July 2020

Introduction.The course of COVID-19 varies from asymptomatic to severe in patients. The basis for this range in symptoms is unknown. One possibility is that genetic variation is partly responsible for the highly variable response. We evaluated how well a genetic risk score based on chromosomal-scale length variation and machine learning classification algorithms could predict severity of response to SARS-CoV-2 infection. Methods.We compared 981 patients from the UK Biobank dataset who had a severe reaction to SARS-CoV-2 infection before 27 April 2020 to a similar number of age matched patients drawn for the general UK Biobank population. For each patient, we built a profile of 88 numbers characterizing the chromosomal-scale length variability of their germ line DNA. Each number represented one quarter of the 22 autosomes. We used the machine learning algorithm XGBoost to build a classifier that could predict whether a person would have a severe reaction to COVID-19 based only on their 88-number classification.Results. We found that the XGBoost classifier could differentiate between the two classes at a significant level (I as measured against a randomized control and (n as measured against the expected value of a random guessing algorithm (AUC=0.5). However, we found that the AUC of the classifier was only 0.51, too low for a clinically useful test.Conclusion.Genetics play a role in the severity of COVID-19, but we cannot yet develop a useful genetic test to predict severity.
Genetic Aetiology of Primary Adrenal Insufficiency in Chinese Children
Authors: Chang Zhuo , Lu Wei , Zhao Zhu-Hui , Xi Li , Li Xiao-Jing , Ye Rong , Ni Jin-Wen , Pei Zhou , Zhang Miao-Ying , Cheng Ruo-Qian , Zheng Zhang-Qian , Sun Cheng-Jun , Wu Jing , Luo Feihong
Published: July 2020

Background
Primary adrenal insufficiency (PAI) is a life-threatening condition, and a definitive aetiological diagnosis is essential for management and prognostication. We conducted this study to investigate the genetic aetiologies of PAI in South China and explore their clinical features.
Results
Among the 70 children, 84.29% (59/70) were diagnosed with congenital adrenal hyperplasia (CAH), and a diagnosis of 21-hydroxylase deficiency (21-OHD) was subsequently genetically confirmed in 91.53% of the cases. Salt wasting (SW), simple virilization (SV), and non-classic (NC) CAH accounted for 66.10% (39/59), 30.51% (18/59), and 3.39% (2/59) of the cases, respectively. Interestingly, 17-hydroxyprogesterone (17-OHP) and testosterone levels in females were significantly higher than those in males among both SW and SV CAH patients. Additionally, 15.71% (11/70) of the patients were diagnosed with PAI, 72.73% (8/11) of whom had positive genetic findings. Among all the cases, two novel variants in CYP21A2, c.833dupT (p. 279GfsX17) and c.651 + 2T > G, were harboured by CAH patients. A microdeletion (Xp21.2-21.3) and five novel variants, including 2 in the NR0B1 gene (p. 108S > X, p.L411Vfs*6, c.1231_1234delCTCA, p.L411Vfs*6), 2 in the AAAS gene (c.399 + 1G > A, p.V103Afs*8, c.250delT, p.W84Gfs*10) and 1 in the NNT gene (p.I758Mfs*10), were detected. The novel variant c.399 + 1G > A in the AAAS gene was further confirmed to lead to exon 4 deletion in mRNA transcription and produce a truncated ALADIN protein.
Conclusions
We found ethnic differences in the CYP21A2 gene variant spectrum among different study populations. Female 21-OHD patients tended to have higher 17-OHP and testosterone levels, which warrants caution in relation to the virilization effect both physically and psychologically. Novel gene variants detected in the CYP21A2, NR0B1, AAAS and NNT genes expanded the genetic spectrum of paediatric PAI; however, further improvement of genetic testing tools beyond our protocol is still needed to uncover the complete aetiology of PAI in children.
Emerging of Commensal Escherichia Coli Carrying Resistance Genes Against Carbapenems, a Threat to Public Health
Authors: Mahmoodi Fahimeh , Rezatofighi Seyedeh Elham , Akhoond Mohammad Reza
Published: July 2020

Background: The emergence of metallo-beta-lactamase (MBL)-producing isolates is alarming since they carry mobile genetic elements with great ability to spread; therefore, early detection of these isolates, particularly their reservoir, is crucial to prevent their inter- and intra-care setting dissemination and establish suitable antimicrobial therapies. The current study was designed to evaluate the frequency of antimicrobial resistance (AMR), MBL producers and identification of MBL resistance genes in Escherichia coli strains isolated from fecal samples of the healthy children under three years old.Methods: A total of 412 fecal E. coli isolates were collected from October 2017 to December 2018 and assessed for the pattern of AMR, the production of extended spectrum beta lactamase (ESBL) and MBL by phenotypic methods. Carbapenem-resistant isolates were investigated for the presence of MBL and carbapenemase genes, plasmid profiling, and the ability of conjugation.Results: In sum, AMR, multi-drug resistance (MDR) and ESBL production were observed in more than 54.9%, 36.2% and 11.7% of commensal E. coli isolates, respectively. Out of six isolates resistant to imipenem and meropenem, four isolates were phenotypically detected as MBL producers. Two and one E. coli strains carried the blaNDM-1 and blaVIM-2 genes, respectively and were able to transmit imipenem resistance through conjugation. Conclusion: Our findings showed that children not exposed to antibiotics can be colonized by E. coli isolates resistant to the commonly used antimicrobial compounds and can be a good indicator for the occurrence and prevalence of AMR in the community. These bacteria can act as a potential reservoir of AMR genes including MBL genes of pathogenic bacteria and lead to the dissemination of resistance mechanisms to other bacteria.
Hypofractionated Intensity-Modulated Radiotherapy with Concurrent Chemotherapy for Elderly Patients with Locally Advanced Pancreatic Carcinoma
Authors: Iwai Takahiro , Yoshimura Michio , Ashida Ryo , Goto Yoko , Kishi Takahiro , Itasaka Satoshi , Shibuya Keiko , Kanai Masashi , Masui Toshihiko , Fukuda Akihisa , Isoda Hiroyoshi , Hiraoka Masahiro , Mizowaki Takashi
Published: July 2020

Background: It is important to understand how elderly patients with locally advanced pancreatic carcinoma (LAPC) should be treated, since the number of elderly patients with cancer has been increasing recently. However, the optimal treatment for elderly patients with LAPC is unclear. The purpose of this study was to evaluate the efficacy and safety of hypofractionated intensity-modulated radiotherapy (IMRT) with concurrent gemcitabine for elderly patients with LAPC. Methods: We retrospectively analyzed data of LAPC patients aged ≥75 years treated with hypofractionated IMRT (48 Gy in 15 fractions), with concurrent weekly gemcitabine at our institution from February 2013 to December 2018. Overall survival (OS), progression free survival (PFS), locoregional progression free survival (LRPFS), distant metastasis free survival (DMFS) and the pattern of recurrence and toxicity were analyzed.Results: Fifteen patients were administered this treatment during the period. The median age was 78 years (range, 75-86 years), and the Eastern Cooperative Oncology Group (ECOG) performance status (PS) of all patients was 0-1. The median survival time (MST) and median PFS were 20.4 (95% confidence interval (CI) 10.3-36.8) and 13.5 (95% CI 6.4-20.3) months, respectively, and the one-year OS and PFS rates were 80.0% (95% CI 50-93.1%) and 66.7% (95% CI, 37.5-84.6%), respectively. The median LRPFS and median DMFS were 15.6 (95% CI 6.4-36.8) and 14.9 (95% CI 7.0-20.5) months, respectively, and the one-year LRPFS and DMFS rates were 73.3% (95% CI, 43.6-89.1%) and 66.7% (95% CI 37.5-84.6%), respectively. Non-hematologic grade 3 toxicity was observed in three cases of which only one was induced by radiotherapy, and grade 4-5 non-hematologic acute or late toxicities were not observed.Conclusions: The OS and PFS of elderly patients with LAPC treated using hypofractionated IMRT using gemcitabine concurrently were favorable without the occurrence of severe toxicity. This treatment strategy is feasible and promising for the elderly LAPC patients with good PS.Trial registrationRetrospectively registered.
Expression and prognostic value of E2F family members in gastric cancer
Authors: Li Hui , Zhao Shufen , Shen Liwei , Wang Peige , Liu Shihai , Ma Yingji , Liang Zhiwei , Wang Gongjun , Lv Jing , Qiu Wensheng
Published: July 2020

Background

E2F is a family of transcription factor proteins involved in multiple processes, including cell cycle regulation, cell differentiation, the DNA damage response and cell death. Studies have shown that E2Fs have prognostic significance in many cancers, but the expression patterns and prognostic values of E2Fs in gastric cancer have not been systematically elucidated.
Methods

In this study, we used the ONCOMINE database and UALCAN online analysis to compare the transcriptional levels and expression of eight E2F family members between gastric cancer and normal samples. UALCAN was also used to analyze the relationship between the expression of 8 E2F members and clinicopathological parameters. A protein-protein interaction (PPI) network was constructed using the STRING database. The functions and pathways of the E2F family and 50 frequently changed genes closely associated with the family members were analyzed using Database for Annotation, Visualization, and Integrated Discovery (DAVID) software. The prognostic value of the E2Fs was determined by Kaplan-Meier Plotter and Cox regression. Western blot and qPCR were used to analyze the expression of E2F2 in gastric cancer. CCK8 and EdU analyses were conducted to assess cell proliferation, and wound-healing and Transwell assays were used to analyze cell migration and invasion.
Results

The expression patterns of 8 E2F members were significantly related to the clinical cancer stage and tumor grade of gastric cancer patients. A high mutation rate (51%) for E2Fs was observed in patients with gastric cancer. In addition, high mRNA expression of E2F1/2/3/4/5 was a prognostic factor for poor overall survival (OS) in gastric cancer patients, while high expression of E2F6/7/8 was associated with better OS. Cox regression analysis found that E2F2 can be used as an independent prognostic factor for gastric cancer, and compared with normal cells, the expression of E2F2 in gastric cancer cells was significantly increased. In addition, we found that E2F2 silencing inhibits the proliferation, invasion and metastasis of gastric cancer cells.
Conclusions

Our study evaluated the expression and prognosis of the E2F family in gastric cancer and discussed the role of E2F2 in gastric cancer in detail. We found that members of the E2F family show differences in expression between cancer and normal tissues and may be closely related to the prognosis of gastric cancer. Among them, E2F2 can serve as an independent prognostic factor for gastric cancer and promote the proliferation, invasion and metastasis of gastric cancer cells. These data indicate that E2F2 could be a potential biomarker for gastric cancer.