bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.
Identification of C3GN Presenting in a Proband with Family History of Alport Syndrome
Authors: ding yin , tang xuanli , du yuanyuan , chen hongyu , yu dongrong , zhu bin , yuan bohan 
Published: July 2020

Abstract
BackgroundAlport syndrome and C3GN are all rare kidney diseases and frequently responsible for familial hematuria, proteinuria and/or coexistent renal impairment. With the rapid development of molecular genetic testing, Alport syndrome have been restricted mostly to causal variants in the COL4A5 or COL4A3/COL4A4 genes. And a broad range of genetic contributors in the complement and complement-regulating proteins definitely implicate in the pathogenesis of C3GN.MethodsWe sought a family with persistent microscopic hematuria associated with renal failure. Clinicopathologic and follow-up data were obtained, and molecular genetic testing was used to screen pathogenic variants. ResultsWe describe a three-generation family with Alport syndrome showing a dominant maternally transmitted inheritance. Notably, renal biopsy showed the concurrent histological evidence of C3GN in the proband and further classified as CFHR5-related nephropathy due to a rare heterozygous variation in gene-encoding CFHR5, c.508G>A. The alteration leads to replacement of a highly conserved residue at position 170 of the β-strand subunit of CFHR5 (p.Val170Met). In silico analysis, the variation was predicted to deregulate complement activation by altering the structural property and enhancing C3b binding capacity to compete with CFH, which was in a good agreement with experimental data previously published.ConclusionsThe comorbidity findings between Alport Syndrome and C3GN indicate an underlying overlap, and await further study.
Melatonin alleviated the immune response and improved the salivary gland function in primary Sjögren’s syndrome
Authors: Liu Yi , Weng Xiuhong , Yu Shaoling , Ding Yumei , Cheng Bo 
Published: July 2020

Abstract
Background

Excessive inflammatory reactions participate in primary Sjögren’s syndrome (pSS) progression. In addition, biological clock genes have been detected in the salivary glands, which indicates that clock genes regulate the growth and development of the salivary glands as well as the quality and quantity of saliva secretion. Melatonin is an amine hormone secreted by the pineal gland that has many physiological functions, such as regulating immunity and correcting disorder in the biological clock rhythm. The purpose of this study was to clarify the correlation between pSS and the biological clock rhythm and explore the possibility of applying melatonin to treat pSS.
Methods

Melatonin (10 mg/kg/d or 15 mg/kg/d) or vehicle was administered to NOD/Ltj mice by intraperitoneal injection for 4 weeks. Clock gene expression levels in labial gland biopsy specimens from pSS patients and submandibular gland specimens from mice were measured by Western blotting (WB) and RT-PCR. The salivary flow rate of mice was measured at 12, 14, and 16 weeks. The severity of lymphocyte infiltration in the salivary glands was analysed by haematoxylin and eosin (H&E) staining. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining were used to detect the expression levels of related inflammatory factors in mice. The percentages of Th17, Th2, and Treg cells were analysed by flow cytometry.
Results

There was a distinct expression profile for clock genes in pSS patients compared with controls. Continuous melatonin administration improved salivary gland function in NOD/Ltj mice, with decreased lymphocyte infiltration in the submandibular glands and reduced related inflammatory factor expression in the serum and salivary glands. Melatonin treatment skewed T cells towards the Treg and Th2 subsets while suppressing Th17 responses. Additionally, melatonin administration regulated clock gene expression in NOD/Ltj mice.
Conclusion

pSS pathogenesis and progression are correlated with abnormal circadian gene expression. Melatonin improves the hypofunction of the salivary glands and inhibits the inflammatory development of pSS in NOD/Ltj mice. This study provides a theoretical basis and potential approach for the clinical prevention and treatment of pSS.