bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal assessment of the health-related quality of life among older people with diabetes: results of a nationwide study in New Zealand
Authors: Shamshirgaran Seyed Morteza , Stephens Christine , Alpass Fiona , Aminisani Nayyereh
Published: February 2020

Background: The current work examined experiences of Health Related Quality of Life (HRQOL) among older adults with a diagnosis of Diabetes Mellitus (DM) over time compared to those without a diagnoses DM. Methods: The sample was drawn from six biennial waves of the New Zealand Health, Work and Retirement survey, a prospective population-based cohort study of older adults 55-70 years at baseline. Data on sociodemographic factors, health behaviours, chronic disease diagnoses and physical and mental HRQOL (SF-12v2) were obtained using six biennial surveys administered 2006-2016. Generalised Estimating Equation models, adjusted for time-constant and -varying factors, were employed to compare HRQOL and its determinants over time for older adults with and without a diagnosis of DM. Results: DM was negatively associated with physical HRQOL [β (95% CI) −7.43 (−8.41, −6.44)] with older adults affected by DM reporting scores 7.4 points lower than those without DM. Similarly, the mean Mental HRQOL score was lower among those affected by DM [β = −4.97 (−5.93, −4.01)] however, scores increased over time for both groups ( p <0.001). Greater age, more chronic conditions, sight and sleep problems, obesity, lower annual income, and fewer years of education were predictors of poorer HRQOL among older adults. Conclusions: Older adults affected by diabetes experienced poorer physical and mental HRQOL compared to those not affected when controlling for a range of sociodemographic and health related indices. A management aim must be to minimise the gap between two groups, particularly as people age.
Dissociated responses at initial computed tomography evaluation is a good prognostic factor in non-small cell lung cancer patients treated with anti-program cell death-1/ligand 1 inhibitors
Authors: Tozuka Takehiro , Kitazono Satoru , Sakamoto Hiroaki , Yoshida Hiroshi , Amino Yoshiaki , Uematsu Shinya , Yoshizawa Takahiro , Hasegawa Tsukasa , Uchibori Ken , Yanagitani Noriko , Horiike Atsushi , Horai Takeshi , Seike Masahiro , Gemma Akihiko , Nishio Makoto
Published: February 2020

Background: Dissociated responses (DR) are phenomena in which some tumors shrink, whereas others progress during treatment of patients with cancer. The purpose of the present study was to evaluate the frequency and prognosis of DR in non-small cell lung cancer (NSCLC) patients treated with anti-program cell death-1/ligand 1 (anti-PD-1/L1) inhibitors.

Methods: This retrospective study included NSCLC patients who received anti-PD-1/L1 inhibitor as second- or later-line treatment. We excluded patients without radiological evaluation.

In patients who showed progressive disease (PD) according to the RECIST 1.1 at the initial CT evaluation, we evaluated all measurable lesions in each organ to identify DR independently of RECIST 1.1. We defined DR as a disease with some shrinking lesions as well as growing or emerging new lesions. Cases not classified as DR were defined as ‘true PD’. Overall survival was compared between patients with DR and those with true PD using Cox proportional hazards models.

Results: The present study included 62 NSCLC patients aged 27–82 years (median: 65 years). DR and true PD were observed in 11 and 51 patients, respectively. The frequency of DR in NSCLC patients who showed PD to anti-PD-1/L1 was 17.7%. Median overall survival was significantly longer in patients with DR versus true PD (14.0 vs. 6.6 months, respectively; hazard ratio for death: 0.40; 95% confidence interval: 0.17–0.94).

Conclusions: Patients with DR exhibited a relatively favorable prognosis.
Australian Aedes aegypti mosquitoes are susceptible to infection with a highly divergent and sylvatic strain of dengue virus type 2 but are unlikely to transmit it
Authors: Pickering Paul , Hugo Leon , Devine Gregor J , Aaskov John G , Liu wenjun
Published: February 2020

Background: Humans are the primary hosts of dengue viruses (DENV). However, sylvatic cycles of transmission can occur among non-human primates and human encroachment into forested regions can be a source of emergence of new strains such as the highly divergent and sylvatic strain of DENV2, QML22, recovered from a dengue fever patient returning to Australia from Borneo. The objective of the present study was to evaluate the vector competence of Australian Aedes aegypti (A. aegypti) mosquitoes for this virus.

Methods: Four day old mosquitoes from two strains of A. aegypti from Queensland, Australia, were feed a meal of sheep blood containing 10 8 50% cell culture infectious dose per ml (CCID 50 /ml) of either QML22 or an epidemic strain of DENV serotype 2 (QML16) isolated from a dengue fever patient in Australia in 2015. Mosquitoes were maintained at 28°C, 75% relative humidity and sampled at 7, 10 and 14 days post-infection (DPI). Live virions in mosquito bodies (abdomen/thorax), legs and wings and saliva expectorates from individual mosquitoes were quantified using a Cell Culture Enzyme-linked Immunosorbant Assay (CCELISA) to determine infection, dissemination and transmission rates.

Findings: The infection and dissemination rates of the sylvatic DENV2 strain, QML22, were significantly lower than that for QML16. While the titres of virus in the bodies of mosquitoes infected with either of these viruses were similar, titres in legs and wings were significantly lower in mosquitoes infected with QML22 at most time points although they reached similar levels by 14 DPI. QML16 was detected in 16% (n = 25) and 28% (n = 25) of saliva expectorates at 10 and 14 DPI, respectively. In contrast, no virus was detected in the saliva expectorates of QML22 infected mosquitoes.

Conclusions: Australia urban/peri-urban A. aegypti species are susceptible to infection by the sylvatic and highly divergent DENV2 virus QML22. Our results indicate that replication of QML22 is attenuated relative to the contemporary strain QML16. Alternatively a salivary gland infection or escape barrier acts to prevent infection of saliva, potentially preventing onward transmission of this highly divergent virus in Australia.
Breast milk Vitamin B12 Concentration and Incidence of Diarrhea and Respiratory Infections among Infants in Urban Tanzania: a prospective cohort study
Authors: Lweno Omar Ndano , Sudfeld Christopher R , Hertzmark Ellen , Manji Karim P , Darling Anne Marie , Fawzi Wafaie W
Published: February 2020

Objective: A recent trial of vitamin B12 supplementation among Indian children 6-30 months found no effect on the incidence of diarrhea and respiratory infections. These results differ with studies in adults that showed improvement of the immune response following treatment with vitamin B12. We sought to determine how the adequacy of vitamin B12 concentrations in breast milk could act as immune modulator and protect against the incidence of diarrhea and respiratory infections of children up to 18 months in urban Tanzania. Results: A prospective cohort study was undertaken to determine the association of breast milk vitamin B12 concentration with the incidence of acute respiratory infection and diarrhea among infants in urban Tanzania. A random sample of 491 women enrolled in a trial of multivitamins provided milk for B12 analysis at or around 6 weeks postpartum. Of 491 women, 345 had breast milk vitamin B12 inadequacy (<310 pmol/L). Using generalized estimating equations, we found no overall association of milk vitamin B12 concentration with incident diarrhea and acute respiratory infections in infants. Studies measuring longitudinal changes of breast milk B12 concentration over time are needed to clarify the role of breast milk vitamin B12 in childhood infections.
The Relationship between Household Chaos and Child, Parent, and Family Outcomes: A Systematic Scoping Review
Authors: Marsh Samantha , Dobson Rosie , Maddison Ralph
Published: February 2020

Background: Household chaos, represented by the level of disorganisation or environmental confusion in the home, has been associated with a range of adverse child and family outcomes. This review aims to (1) identify how household chaos is measured, (2) chart study details of household chaos literature, and (3) map the existing literature with respect to the relationship between household chaos and child, parent, and family outcomes. We expect that this review will highlight the need to consider the importance of household chaos in child well-being research, particularly in those families where children may be more vulnerable to the adverse effects of household chaos.Methods: We searched five electronic databases (last updated September 1st 2018) in addition to Google Scholar, and identified publications via a 3-stage screening process, which was conducted by two researchers. Published studies were included if they investigated the association between household chaos and child, parent, or family outcomes. Research that investigated household chaos as a mediator or moderator, or that investigated how the relationship between household chaos and the outcome of interest was mediated or moderated, were also included. Results: 112 studies in 111 publications were included. The majority were conducted in the United States (n=71), and used either cross-sectional (n=60) or longitudinal (n=49) study designs. Outcomes of interest were categorised into seven categories: (1) cognitive and academic (n=16), (2) socio-emotional and behavioural (n=60), (3) communication (n=6), (4) parenting, family, and household functioning (n=21), (5) parent outcomes (n=6), (6) hormone (n=8), and (7) physical health and health behaviours (n=19). There was consistent evidence for significant correlations between household chaos and adverse outcomes across all seven categories in diverse populations with respect to age, disease status, and socio-economic status (SES).Conclusion: There is consistent evidence for associations between household chaos and a number of adverse child, parent, and family-level outcomes. Household chaos may also help describe variations in outcomes between low SES and child development.
“…we were like tourists in the theatre, the interns assisted almost all procedures…” Task sharing and the training of Assistant Medical Officers in Tanzania.
Authors: Sirili Nathanael , Anaeli Amani , Mselle Lilian , Massawe Siriel
Published: February 2020

Background: Tanzania is among the countries that adopted task sharing as a strategy of addressing health workforce shortage. Although the strategy has existed for over five decades, concerns are upon the quality of the training of the mid-level cadres amidst the growing number of medical universities. This study sought to explore the challenges facing the training of the Assistant Medical Offices, AMOs (a mid-level cadre) in Tanzania.Methods: An exploratory qualitative case study was carried out in four regions to include one rural district in each of the selected regions and two AMOs Training Colleges in Tanzania. A semi-structured interview guide was used to interview 29 Key informants from the district hospitals, district management, regional management, AMOs training college and one retired AMO. In addition, four focus group discussions were conducted with 35 AMO trainees.Results: Training of AMOs in Tanzania faces many challenges. The challenges include; use of outdated and static curriculum, inadequate tutors (lack of teaching skills and experience of teaching adults), Inadequate teaching infrastructure in existence of many other trainees to include interns, and limited or lack of scholarships and sponsorship for the AMO trainees. Conclusions: The challenges facing AMO training not only affect the quality of the graduates but also affect the realization of task sharing strategy that requires that task sharing should not compromise the quality of services produced by the task-shared cadre. It is high time for revising the AMOs curricula and train the tutor through continued medical education programmes to reflect the dynamics of medical education. The government in collaboration with other stakeholders should work together to address the challenges on teaching infrastructure and scholarships to this cadre that has continued to be the backbone of the primary health care in Tanzania. Keywords; Assistant medical Officers, Task sharing, Task shifting, Medical education, Tanzania, Primary health care
Primary syphilis: a histological and immunohistochemical evaluation
Authors: Leng Ling , Gong Hui Zi , Wang Tao , Zheng He Yi , Li Jun
Published: February 2020

Background: Syphilitic chancre could be misdiagnosed as other skin diseases and a biopsy is sometimes done before serological testing, which makes it essential to find possible primary syphilis patients through histopathology and immunohistochemistry (IHC).Method: We sought to determine the histopathological and IHC characteristics in primary syphilis. Eleven biopsy specimens were collected from 9 patients diagnosed with primary syphilis. Specimens were analyzed for T. pallidum using antibody to T. pallidum. We also compared IHC results with the histological characteristics.Results: In our study, plasma cells infiltration was the most common pattern [90.9% (10/11)] in primary syphilis. Necrotic keratinocytes could be observed in 54.5% (6/11) of primary syphilis. T. pallidum was discovered in 9 of 10 (90.0%) primary syphilis by IHC. T. pallidum is mainly detected in the medium to superficial dermis and the lower epidermis regions. In the dermis area, T. pallidum was discovered mainly around the perivascular regions. Conclusion: Although serological tests remain the gold standard for the confirming diagnosis of syphilis infection, Histopathological and IHC could be helpful in the diagnosis of some syphilitic patients when serologic testing is not capable of detecting T. pallidum antibodies in serum. Using IHC technique allows us to precisely find out the location of the microorganism in the syphilitic skin lesions.
Proteomic analysis demonstrated transcription factor YRR1 gene deletion in Saccharomyces cerevisiae enhances its resistance to vanillin through the upregulation of transcriptional activator Haa1, coactivator Mbf1, and proteasome assembly chaperone Tma17 expression
Authors: Cao Wenyan , Wang Xinning , Zhao Weiquan , Shen Yu , Qin Wensheng , Li Zailu , Bao Xiaoming
Published: February 2020

Background: Vanillin is one of the major phenolic inhibitors in Saccharomyces cerevisiae for cellulosic ethanol production. Deleting transcription factor gene YRR1 improves vanillin resistance by promoting some translation-related processes that were confirmed at the transcription level in our previous studies. However, the known genes regulated by Yrr1 are not related to translation process. Therefore, in this work, we investigated the effects of proteomic changes on vanillin stress and YRR1 deletion to provide different perspectives from transcriptome analysis for comprehending the mechanisms of YRR1 deletion in yeast protective response to vanillin.Results: In wild-type cells, vanillin reduced the numbers of ribosomal proteins quantities and thereby inhibited cells’ translation. YRR1 deletion changed the quantities of 121 proteins which have no overlaps with transcriptomic changes. Of 112 proteins were up-regulated; 48 of 112 up-regulated proteins are involved in stress response, translational and basal transcriptional regulation. Fermentation data showed that the overexpression of HAA1, MBF1, and TMA17, which encode transcriptional activator, coactivator, and proteasome assembly chaperone, respectively, enhanced resistance to vanillin in S. cerevisiae. Conclusions: These results showed how YRR1 deletion increase vanillin resistance at protein level. This may advance our understanding of molecular mechanisms for YRR1 deletion to protect yeast from vanillin stress and offer novel targets of genetic engineering for designing inhibitor-resistant ethanologenic yeast strains.
Coding transcriptome analyses reveal altered functions underlying immunotolerance of PEG-fused rat sciatic nerve allografts
Authors: Smith Tyler A. , Ghergherehchi Cameron L. , Tucker Haley O. , Bittner George
Published: February 2020

Background Current methods to repair ablation-type peripheral nerve injuries (PNIs) using peripheral nerve allografts (PNAs) often result in poor functional recovery due to immunological rejection as well as slow and inaccurate outgrowth of regenerating axonal sprouts. In contrast, ablation-type PNIs repaired by PNAs using a multistep protocol, in which one step uses the membrane fusogen polyethylene glycol (PEG), permanently restore sciatic-mediated behaviors within weeks. Axons and cells within the PNA remain viable, even though outbred host and donor tissues are neither immunosuppressed nor tissue matched. PEG-fused PNAs exhibit significantly reduced T cell and macrophage infiltration, apoptosis, and expression of major histocompatibility complex I/II. In this study, we analyzed the coding transcriptome of PEG-fused PNAs to examine possible mechanisms underlying immunosuppression. Methods Ablation-type sciatic PNIs in adult Sprague Dawley rats were repaired using PNAs and a PEG-fusion protocol combined with neurorrhaphy. Electrophysiological and behavioral tests confirmed successful PEG-fusion of PNAs. RNA sequencing analyzed differential expression profiles of protein-coding genes between PEG-fused PNAs and Negative Control PNAs (not treated with PEG) at 14d PO, along with Unoperated Control nerves. Sequencing results were validated by Quantitative Reverse Transcription PCR (RT-qPCR). Results PEG-fused PNAs display significant downregulation of many gene transcripts associated with innate and adaptive allorejection responses. Schwann cell-associated transcripts are often upregulated, and cellular processes such as extracellular matrix remodeling, cell and tissue development are particularly enriched. Transcripts encoding several potentially immunosuppressive proteins (e.g. Thrombospondins 1 and 2) are also upregulated in PEG-fused PNAs. Conclusions This study is the first to characterize the coding transcriptome of PEG-fused PNAs, and identifies possible links between alterations of the extracellular matrix and suppression of the allorejection response. The results establish a molecular-basis to begin to understand mechanisms underlying PEG-mediated immunosuppression.
Analysis of primary oral and oropharyngeal squamous cell carcinoma in Beijing inhabitants, China—a 10-year continuous study of a single center
Authors: Bai Xuexiao , Zhang Jie , Wei Li
Published: February 2020

Backgroud The aim of the study was to evaluate whether Beijing inhabitants with oral and oropharyngeal squamous cell carcinoma(OSCC) differ from previous reports with regard to clinicopathological characteristics and prognosis, and study the influence of prognostic factors. Methods Consecutive cases of primary oral and oropharyngeal squamous cell carcinoma in Beijing patients admitted between 2004 and 2013 were analyzed retrospectively. Clinical data included age, sex, location, site, TNM stage, history of drinking and smoking, differentiation and follow up information. Results A total of 603 cases were included in this study. The male: female ratio was 1.1:1. The frequency of sites decreased in the order tongue, gingiva, buccal mucosa, oral floor, oropharynx, lip and palate. Differences in location, age and stage between males and females were statistically significant (P < 0.05). Whereas 65.3% of male patients smoked or drank, only 6.3% of female patients did so. The overall 5-year survival rate was 64%. Female patients have a worse prognosis than male. For patients who received surgery, tumor size, lymph node involvement were independent prognostic factors. Smoking and drinking were not prognostic factors. Conclusion Our study indicates that the clinical characteristics OSCC patients in Beijing is similar to some developed countries, both regarding male/female ratio, diagnostic age, prognosis, which is different from previous reports in other districts of China. Lymph node involvement was the most important prognostic factor, followed by tumor size, pathological grade.
SPP1 targeted by miR-4262 in gastric cancer functions as an enhancer of cell growth and correlates with dismal prognosis
Authors: Wang Junqing , Hao Fengjie , Yang Yuchen , Fei Xiaochun , Chen Xunhua
Published: February 2020

Background Advanced gastric cancer (GC) induces diamal prognosis and high mortality. Discovery of new biomarkers or differentially expressed genes (DEGs) is serving for early diagnosis, prevention and therapautic treatmen in GC. In this study, by combining with biostatistics analysis, we aimed to verify the aberrant high expression and enhancing effects of SPP1 on GC, and to explore the probable relative post-transcriptional regulation. Methods Three datasets (GSE13911, GSE19826 and GSE27342) from NCBI GEO database were explored. SPP1 was screened out and detected in 105 real GC patients through immunohistochemistry analysis and RT-qPCR assay. The patients’ clinicopathologic features were collected and analyzed. The expression of SPP1 was examinated in three GC cell lines (MKN-45, AGS and SNU-16) . MKN-45 cell model with SPP1 depletd was constrcted through shRNA transfection. CCK8 assay, cell cycle detection and apoptosis rate calculation were conducted to evaluate the ability of cell growth. MiR-4262 was filtered out as a potential up-streaming regulator of SPP1 mRNA through bioinformatic prediction, and the dual-luciferase reporter assay was used for validation. Rescue experiment was introduced to confirm the post-transcriptional regulation. Results Thirteen DEGs increased in GC were selected, among which SPP1 was screened out for its significant over-expression in GC. SPP1 expression profile was validated in both the 105 real GC patients’ samples and three GC cell liens. High SPP1 expression was found significantly associated with the patients’ clinicopathologic features related to unideal prognosis, including tumor size, lymph node metastasis, local invasion grade and TNM stage. Depletion of SPP1 remarkably suppressed the GC cell growth. Whilst, microRNA-4262 was validated directly binding to the 3’-UTR of SPP1 mRNA in GC cells, degenerating the expression of SPP1. Conclusions SPP1 probably functions as an oncogenic gene in GC, and provides us a new biomarker in GC hopeful to promote GC prevention, diagnose and therapeutic treatment.
WITHDRAWN: Identification of a novel lncRNA‑miRNA‑mRNA competing endogenous RNA network associated with prognosis of breast cancer
Authors: Wan Xiaohui , Hao Shuhong , Hu Chunmei , Qu Rongfeng
Published: February 2020

Background: Breast cancer is one of the most common malignant tumors. Recently, the effects of competing endogenous RNA (ceRNA) on molecular biological mechanism of cancer has aroused great interext. However, research on the pathogenesis and biomarkers of breast cancer is still limited. Thus, this study is aimed to identify the competing endogenous RNA (ceRNA) network related to prognosis of patients with breast cancer. Methods: The RNA SEQ data and corresponding clinical information were downloaded from the Cancer Genome Atlas (TCGA) database, and the difference analysis was performed after data quality control. The similarity between two groups of genes with traits in the network was analyzed by weighted correlation network analysis (WGCNA) . Next, the interaction among lncRNA, miRNA, and mRNA was predicted using miRcode, TargetScan, miRDB, and miRTarBase database, and the lncRNA-miRNA-mRNA ceRNA network was constructed. Finally, the survival model of target mRNA was established by Cox regression analysis. Results: In total 5056 differentially expressed lncRNAs, 712 differentially expressed miRNAs, and 9878 differentially expressed mRNAs were identified. WGCNA predicted that 823 lncRNAs and 1813 mRNAs were closely related to the breast cancer. The lncRNA-miRNA-mRNA ceRNA network involved in breast cancer was constructed with 27 lncRNA, 14 miRNAs and 4 mRNAs. The AUC of four survival models of target mRNA (ZC3H12B + HRH1 + TMEM132C + PAG1) was 0.609, which suggested the sensitivity and specificity of prognosis prediction of breast cancer. Conclusion: This study provides insight into the ceRNA network involved in breast cancer biology, which significantly associated with gene regulation and prognosis of breast cancer.
Use of miR-34a, miR-126, and miR-125a-5p expression level as diagnostic factor and therapeutic target for α-L-guluronic acid and β-D-mannuronic acid in Type-I diabetic rat models
Authors: sharifzade Mohammad , emami Mohammad reza , Esmaeili-Bandboni Aghil , Javanbakht Mohammad Hassan , Mirshafiey Abbas
Published: February 2020

Type 2 diabetes mellitus (T2DM) affects microRNAs (miRNAs) expression that are known as Post-transcriptional repressors of gene expression in plants and animals. This research aimed to investigate the expression levels of miR-34a, miR-126, miR-125a-5p, and miR-29b for diabetes diagnosis, and the effect of α-L-guluronic acid and β-D-mannuronic acid supplementation on the expression pattern of these miRNAs in diabetic rats. Total miRNAs were extracted and evaluated by qRT-PCR method. body weight, fasting insulin levels, food intake and Vitamin D level in four group after 4-week intervention also measured. The analyzes showed significant increase in expression levels of miR-126 and miR-125a-5p, in diabetic control groups (p=0.001). Also, miR-29b was undetectable in the sera of experimental rats. After treatment with β-D-mannuronic acid, the expression level of miR-34a was upregulated in diabetic rats (p=0.026), but α-L-guluronic acid was not significantly effective. Also, expression levels of miR-126 (p=0.026) and miR-125a-5p (p=0.041) were downregulated significantly in diabetic rats, after treatment with β-D-mannuronic acid and, α-L-guluronic acid respectively. these results suggest that use of miR 126 ,125a-5p and miR 34a for diagnosing diabetes is sensible, also we can consider β-D-mannuronic acid as new therapeutic agent for correct disturbance in miRNA profile of diabetic rats.
The epidemic characteristics, guidelines and policies: A compared analysis of literature between COVID-19 and SARS
Authors: Li Jing , Yang Jiayi , Wen Kaili , Lu Rong , Du Xiaoliang
Published: February 2020

Background: COVID-19 broke out in Wuhan, and rapidly spread to other province of China and other countries. To understand epidemic characteristics, guidelines and policiesof COVID-19 compared to SARS, and further explore the gap of health system facing with major outbreaks for improvement in China. Methods: A systematic review was performed using China academic literature (CNKI), Wan Fang, PubMed, medRxiv, bioRxiv,offical website of World Health Organization, National Health Commission of the People’s Republic of China, the Hubei Province Health Commission, and Wuhan City Health Commission for literature of epidemiological and clinical characteristics, guidelines an policies of COVID-19 and SARS from 2003 to 2020. Two dataset were obtained from the National Health Commission's open data information, and daily SARS epidemic section authorized by the State Council`s Information Office.Results: The 113 related studies finally entered final analysis, among which 63 were Chinese articles. Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) and 2019 novel coronavirus (SARS-CoV-2) caused outbreak in 2002 and 2019 in China called SARS and 2019 coronavirus disease (COVID-19). Both belong to Beta Coronavirus (β-CoV). Their original cluster confirmed cases had contact history to wild animals, and clinical symptoms are similar. However, COVID-19 has a high human-to-human transmission capability, and more rapidly spread from Hubei province (97.9% cases) across China and over the world. R0 was estimated around 2.2 (1.4-3.8), and incubation period of COVID-19 is 1-14 days. Transmission routes predominantly have respiratory droplets, close contact and even air transmission by aerosols. A fatality rate was 2.70% (2004/74185) with the highest of 14.8% at over 80 years old, and cases mainly were males in the middle and elder ages. For prevention and control, strategies and policies consecutively were issued. Compared to those of SARS, responsiveness for COVID-19 is more prompt. Policy priorities tend to multi-sectors of cooperation, strong action to cut off source of infection (sealed Wuhan city),strengthening community prevention and mental health. Conclusions: The major gap facing with epidemic outbreak exists in the weak health system especially public health system, although we already made a great progress and improvement in our preventive awareness. Therefore, we forcefully appeal to a strong public health system by government for continuous investment and improvement. An advanced public health system stands by us in times of peace, and while fights for us during epidemic outbreak period.
Evolution of CT Manifestations of 105 novel coronavirus pneumonia patients in Wuhan, China
Authors: Guan Hanxiong , Zhou Shuchang , Zhu Tingting , Xia Liming , Wang Yujin , Pan Yueying
Published: February 2020

Objectives: The purpose of this study was to observe the chest HRCT manifestation evolution of the 105 patients with pneumonia caused by SARS-CoV-2.Methods: 105 confirmed patients were enrolled from January 11, 2020 to February 9, 2020. Chest HRCT were performed. The number of affected lung lobes, lesion shape, density, range, and dynamic changes of various lesions in each CT examination of each patient were recorded to comprehensively evaluate whether it is improved. Results: CT images of 105 confirmed patients were collected. The patients underwent 2-7 chest CT examinations. M/F ratio: 49/56. The age range was 23-72 y, and the mean age was 48.6±13.1 y. The patients' chest CT examinations were divided into 5 groups according to the re-examination interval, group A (25 cases): ≤3 days, group B (70 cases): 4-7 days, group C (75 cases): 8-14 days, group D (29 cases): 15-21 days, group E (4 cases):> 21 days. There was significant difference in the improvement and progress rates between group B and C. Furthermore, the changes of ground glass nodules (GGO), consolidation and cord lesions in each group were recorded.Conclusions: The chest CT manifestations of the patients changed rapidly, and the re-examination of 7-14 days was of great significance in evaluating the prognosis of patients while minimizing the radiation dose.
Probucol enhances the therapeutic efficiency of mesenchymal stem cells in the treatment of erectile dysfunction in diabetic rats by prolonging their survival time via Nrf2 pathway
Authors: Wang Haoran , Zhang Keqin , Ruan Zheng , Sun Dingqi , Zhang Hui , Lin Guiting , Hu Liangliang , Zhao Shengtian , Fu Qiang
Published: February 2020

Background Intracavernous injection of mesenchymal stem cells (MSCs) is a promising method for Diabetic mellitus-induced erectile dysfunction (DMED), but short survival time of MSCs in cavernous is fatal defect for therapy. This study investigated therapeutic efficiency and potential mechanism of Probucol combined with MSCs. Methods In vivo study, total forty-eight 10-week-old male Sprague-Dawley (SD) rats were used in this study. Twelve rats received intraperitoneal injection of PBS as Sham Group; the rest received intraperitoneal injection of 60mg/kg streptozotocin to establish DM models. DM rats were randomly divided into three groups: received intracavernosal (IC) injection of either PBS (DM Group), MSCs (M Group), and administrated Probucol after intracavernosal injection of MSCs (P+M Group). Erectile function was assessed by electrical stimulation of the cavernous nerves with real-time intracavernous pressure measurement. After euthanasia, penile tissue was investigated for histologic examination and Western blotting. In vitro experiment, H 2 O 2 was used to create oxidative stress environment to detect changes in cell viability. CCK8 was used to measure cell viability of MSCs treated with or without Probucol. Intracellular ROS changes were detected by flow cytometry. Autophagy and apoptosis were detected by Western blotting and confocal microscopy. Results Recovery of erectile function was observed in the P+M Group. The combination therapy decreased fibrosis and increased endothelial function compared with MSCs therapy alone. Western blotting results confirmed the increased expression of Nrf2 and HO-1 in cavernous body. Vitro experiment indicated H 2 O 2 -induced high oxidative stress reduced cell viability, which was gradually reversed with increased concentration of Probucol. H 2 O 2 reduced Nrf2 expression, which was reversed by Probucol's intervention. Furthmore, the expression of Bax, Caspase3 and Cleaved-Caspase3 decreased, and the expression of Bcl-2 increased in a dose-dependent manner because of Probucol's intervention. In addition, Beclin1 and LC3II both increased in a dose-dependent manner. Meanwhile, the expression of P62 decreased. In study of autophagy flux, we found Probucol didn’t block it. Conclusion Probucol enhanced therapeutic efficiency of MSCs in DMED by prolonging their survival time, which mediated through improving the transplanted microenvironment of MSCs, increasing self-antioxidant ability of MSCs, strengthening protective autophagy and inhibiting apoptosis of MSCs via Nrf2 pathway.
Molecular hydrogen induces metabolic reprogramming to promote differentiation of glioma stem cells
Authors: Ma Sheng-nan , Xie Fei , Zhang Yan , Yao Ting-ting , Liu Meng-yu , Zhang Xiao-kang , Zhao Peng-xiang , Ma Xuemei
Published: February 2020

Background: Our previous study showed that molecular hydrogen could effectively suppress glioblastoma multiforme (GBM) tumor growth via induction of glioblastoma stem cells (GSCs) differentiation. Metabolic reprogramming has been demonstrated to delicately regulate the stemness of cancer stem cells. In the present study, we explored whether metabolic reprogramming is involved in the hydrogen-induced GSCs differentiation. Methods: Immunofluorescence staining was conducted to determine the expression of cell surface markers. Glucose uptake and lactate secretion was determined by spectrophotometric method. Untargeted metabolomics analyses were conducted to investigate the metabolic alteration in GSCs after hydrogen treatment. 13 C-labeled metabolic flux analysis was performed to explore the regulatory effects of molecular hydrogen on the glucose metabolism of GSCs. Results: Immunofluorescence staining showed the up-regulated expression of oligodendroglial markers in hydrogen-treated GSCs. Both glucose uptake and lactate production in GSCs were significantly inhibited by hydrogen treatment. Untargeted metabolomics analyses showed hydrogen-induced promotion of de novo synthesis of nucleotides in GSCs. Metabolic flux analysis showed decreased glucose metabolism in GSCs induced by hydrogen. Conversely, the content of glycerol 3-phosphate, glutamate and glutamine were increased by hydrogen treatment. Conclusions: Results from this study demonstrated that molecular hydrogen could inhibit glucose metabolism and promote de novo synthesis of nucleotides in GSCs, suggesting the involvement of metabolic reprogramming in the hydrogen-induced GSCs differentiation. Our study also provides important new clues to seek the target of molecular hydrogen.
Identification and genetic analysis of qCL1.2, a novel allele of the “green revolution” gene SD1 from wild rice (Oryza rufipogon) that enhances plant height
Authors: Zhang Lizhen , Huang Jingfen , Wang Yanyan , Xu Rui , Yang Ziyi , Zhao Zigang , Liu Shijia , Tian Yunlu , Zheng Xiaoming , Li Fei , Wang Junrui , Song Yue , Li Jiaqi , Cui Yongxia , Zhang Lifang , Cheng Yunlian , Lan Jinhao , Qiao Weihua , Yang Qingwen
Published: February 2020

Background: The exploitation of novel alleles from wild rice that were lost during rice cultivation could be very important for rice breeding and evolutionary studies. Plant height (PH) was a target of artificial selection during rice domestication and is still a target of modern breeding. The “green revolution” gene semi-dwarf 1 (SD1) were well documented and used in the past decades, allele from wild rice could provide new insights into the functions and evolution of this gene.Results: We identified a PH-related quantitative trait locus, qCL1.2, from wild rice using a set of chromosome segment substitution lines. qCL1.2 encodes a novel allele of SD1 gene. The wild allele of SD1 is a dominant locus that can significantly promote rice internode length by regulating the expression levels of genes involved in gibberellin biosynthesis and signal transduction. Nucleotide diversity and haplotype network analyses of the SD1 gene were performed using 2,822 rice landraces. Two previously reported functional nucleotide polymorphisms clearly differentiated japonica and indica rice; however, they were not associated with PH selection. Other new functional nucleotide polymorphisms in the coding, but not promoter, regions were involved in PH selection during rice domestication. Our study increases understanding of the rice SD1 gene and provides additional evidence of this gene’s selection during rice domestication.Conclusions: Our findings provide evidence that SD1 gene from wild rice enhances plant height and new functional nucleotide polymorphisms of this gene were artificially selected during cultivated rice differentiation.
The features of polyglutamine regions depend on their evolutionary stability
Authors: Mier Pablo , Andrade-Navarro Miguel A.
Published: February 2020

Background Polyglutamine regions (polyQ) are one of the most studied and prevalent homorepeats in eukaryotes. They have a particular length-dependent codon usage, which relates to a characteristic CAG-slippage mechanism. Pathologically expanded tracts of polyQ are known to form aggregates and are involved in the development of several human neurodegenerative diseases. The non-pathogenic function of polyQ is to mediate protein-protein interactions via a coiled-coil pairing with an interactor. They are usually located in a helical context.Results Here we show how these known features related to polyQ depend on their stability in evolution. We have classified the polyQ regions of 60 proteomes from four distinct taxonomic groups (Insecta, Teleostei, Sauria and Mammalia) in three main categories based on their evolutionary stability. Codon usage, amino acid context, structural conformation and the protein-protein interaction capacity of polyQ from all studied taxa critically depend on the region stability.Conclusions Our results show that apart from the sequence of a polyQ, information about its orthologous sequences is needed to assess its function.
Heme oxygenase-1 deficiency presenting with interstitial lung disease and hemophagocytic flares
Authors: Chau Alice S. , Cole Bonnie L. , Debley Jason S. , Nanda Kabita , Rosen Aaron B.I. , Bamshad Michael J. , Nickerson Deborah A. , Torgerson Troy R. , Allenspach Eric J.
Published: February 2020

Background Heme oxygenase-1 (HMOX1) catalyzes the metabolism of heme into carbon monoxide, ferrous iron, and biliverdin. Through biliverdin reductase, biliverdin becomes bilirubin. HMOX1 -deficiency is an exceedingly rare autosomal recessive disorder with hallmark features of direct antibody negative hemolytic anemia with normal bilirubin, hyperinflammation and features indicating hemophagocytosis lymphohistiocytosis. Clinical findings have included asplenia, nephritis, hepatitis, and evidence of vasculitis. Pulmonary features and evaluation of the immune response have been limited. Results Here, we present the fifth reported case in literature of a young boy who remarkably also presented with chronic respiratory failure due to nonspecific interstitial pneumonia in addition to infection-triggered recurrent hyperinflammatory flares notable for hemolysis without hyperbilirubinemia, immunodeficiency, hepatomegaly with mild transaminitis, asplenia, leukocytosis, thrombocytosis, joint pain and features of macrophage activation with negative autoimmune serologies. Lung biopsy revealed cholesterol granulomas. He was found post-mortem by whole exome sequencing to have a compound heterozygous paternal frame shift a paternal frame shift HMOX1 c.264delCTGG (p.L89Sfs*24) and maternal splice donor HMOX1 (c.636+2 T>A) consistent with HMOX1 deficiency. Western blot analysis confirmed lack of HMOX1 protein upon oxidant stimulation of the patient cells. Conclusions Here, we describe a phenotype expansion for HMOX1-deficiency to include not only asplenia and hepatomegaly, but also interstitial lung disease with cholesterol granulomas and inflammatory flares with hemophagocytosis present in the bone marrow.
The Antiasthma Medication Ciclesonide Suppresses Breast Cancer Stem Cells through Inhibition of the Glucocorticoid Receptor Signaling-dependent YAP Pathway
Authors: Kim Su-Lim , Choi Hack Sun , Kim Ji-Hyang , Lee Dong-Sun
Published: February 2020

Background Ciclesonide is an inhaled corticosteroid used to treat mild-to-severe asthma. However, whether it has anticancer and anti-cancer stem cell (CSC) effects is unknown. This study focused on studying the effect on breast cancer and breast CSCs by ciclesonide and determining its molecular mechanism. Methods The sensitivity of breast cancer by ciclesonide was determined by cell apoptosis, migration, colony formation, and xenograft. Effect of ciclesonide on CSC formation through GR/YAP pathway was determined by SiRNA of GR and YAP, GR degradation assay, GR antagonist, nuclear localization of GR and YAP, and YAP inhibitor. CSC subpopulation was determined by mammosphere culture, CD44+/CD24-, and aldefluor assay. Results Here, we showed that ciclesonide inhibits breast cancer and CSC growth. Similar glucocorticoids (GC), dexamethasone (DEX) and prednisone, did not suppress CSC formation. Ciclesonide-induced glucocorticoid receptor (GR) degradation was dependent on ubiquitination. We showed via GR small interfering RNA (siRNA) that GR plays a crucial role in CSC formation. We showed via western blot and immunofluorescence assays that ciclesonide reduces the nuclear level of GR. The GR antagonist RU-486 also inhibited CSC formation. Ciclesonide reduced the protein level of the Hippo transducer Yes-associated protein (YAP). GR siRNA induced a decrease in YAP protein expression and inhibited mammosphere formation. The YAP inhibitor verteporfin inhibited CSC formation and transcription of the connective tissue growth factor and cysteine-rich protein 61 genes. The GR/YAP1 pathway regulated breast CSC formation. Conclusions We describe that ciclesonide inhibition CSCs through GR and YAP signaling pathway. These findings suggest that the GR/YAP signaling pathway regulates breast CSC formation and revealed a new approach for targeting GR and YAP to inhibit CSC formation.
Assessing immune infiltration and the tumor microenvironment for the diagnosis and prognosis of sarcoma
Authors: Zhu Naiqiang , Hou Jingyi
Published: February 2020

Background Sarcomas, cancers originating from mesenchymal cells, are comprehensive tumors with poor prognoses, yet their tumorigenic mechanisms are largely unknown. In this study, we aimed to characterize infiltrating immune cells and genes associated with the immunologic response to sarcomas. Method The “CIBERSORT” algorithm was used to calculate the amount of L22 immune cell infiltration in sarcomas. Then, the “ESTIMATE” algorithm was used to assess the “Estimate,” “Immune,” and “Stromal” scores. Weighted gene co-expression network analysis (WGCNA) was utilized to identify the significant module related to the immune therapeutic target. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Gens and Genomes (KEGG) analysis were applied using the “clusterProfiler” package in R for annotation and visualization. Results Macrophages were the most common immune cells infiltrating sarcomas. The number of CD8 T cells was negatively associated with that of M0 and M2 macrophages, and positively associated with M macrophages in sarcomas samples. The clinical parameters (disease type, gender) significantly increased with higher Estimate, Immune, and Stromal scores, and with a better prognosis. The blue module was significantly associated with CD8 T cells. Functional enrichment analysis showed that the blue module was mainly involved in chemokine signaling and the PI3K-Akt signaling pathway. CD48, P2RY10 and RASAL3 were identified and validated at the protein level. Conclusion Based on the immune cell infiltration and immune microenvironment, three key genes were identified, which suggest novel molecular mechanisms of sarcoma metastasis.
Comparison of the factors associated with preference of life-sustaining treatment by caregivers’ and health facility tenants’ families: a cross-sectional study
Authors: Shaku Fumio , Tsutsumi Madoka , Nakamura Asumi , Takagi Hiroshi , Otsuka Takahiro , Maruoka Shuicihro
Published: February 2020

Background: Recently, advance care planning (ACP) in palliative care has been attracting attention in Japan. The Japanese counterpart was established by the Ministry of Health, Labor and Welfare in November 2018. Moreover, discussions on end-of-life treatment are an important part of ACP It is suggested that individual feelings at the end-of-life are different; ACP depends on various situations. Decision making by patients themselves is recommended; however, there are cases where patients with dementia or other disorders cannot make decisions by themselves. Health providers may contact surrogates and consider their background for better ACP. We focused on patents’ families and examined factors related to the preferences of home caregivers’ and old-age health facility tenants’ families on patient ACP, including life-sustaining treatment (LST) at end-of-life.Methods: This cross-sectional study involved home caregivers’ and old-age health facility tenants’ families in Japan. We distributed 925 self-reported questionnaires comprising items such as number of people living together, comprehension of doctor’s explanations, nursing care level and duration, the Patient Health Questionnaire (PHQ)-9 and Short Form (SF)-8, and caregivers’ LST preference.Results: A valid response was obtained from 619 respondents [242 men and 377 women (309 in the home-care group, response rate = 61.1%; 310 in the facility-care group, response rate = 74.0%)]. The mean age of the respondents was 65.29 ± 12.09 years in the home-care group and 63.24 ± 10.39 years in the facility-care group. LST preference was significantly associated with sex, number of people living together, care duration, and comprehension of doctors’ explanations in the home-care group but was not significantly associated in the facility-care group. Furthermore, PHQ-9/SF-8 scores were not significantly associated with LST preference of the groups.Conclusions: Factors associated with decision on ACP differed between home caregivers’ families and health facility tenants’ families. In ACP, healthcare providers should be aware of the nature of each patient’s caregiving situation and living environment when discussing LST preference.
Microscopic theory of fractional excitations in gapless quantum Hall states: semi-quantized quantum Hall states
Authors: turker oguz , Meng Tobias
Published: February 2020

We derive the low-energy theory of semi-quantized quantum Hall
states, a recently observed class of gapless bilayer fractional quantum
Hall states. Our theory shows these states to feature gapless
quasiparticles of fractional charge coupled to an emergent Chern-Simons
gauge field. These gapless quasiparticles can be understood as
composites of electrons and Laughlin-like quasiparticles. We show that
semi-quantized quantum Hall states exhibit perfect interlayer drag, host
non-Fermi liquid physics, and serve as versatile parent states for fully
gapped topological phases hosting anyonic excitations.