bluuebunny/crossref_metadata_2025 huggingface dataset:
Nuclear Respiratory Factor 1 Associated with Prognosis and Immune Infiltration in Hepatocellular Carcinoma
Authors: Wang Dan , Huang Linlin , Zhang Xiaojing , Sun Pingping , Lu Yapeng , Zhu Li
Published: August 2020

Background: Recent studies have shown that functional mitochondria are essential for cancer cells. Nuclear respiratory factor 1 (NRF1) is a transcription factor that activates mitochondrial biogenesis and the expression of the respiratory chain, but little is known about its prognostic value and tumor-infiltrating lymphocytes association. Here, we evaluated the association among expression of NRF1, clinicopathological characteristics, survival and immune infiltration in hepatocellular carcinoma (HCC).Methods: We used the Tumor Immune Estimation Resource (TIMER) to analyze the difference of NRF1 mRNA expression in human cancers. Clinical-pathological information and follow-up data were collected from HCC (n = 171) and chronic hepatitis (n = 113) patients. NRF1 expression were scored based on the percentage and intensity of immunohistochemical staining in pathological slides. Correlations between clinical features and the expression of NRF1 were evaluated by Chi-square test, Kaplan-Meier curves, logrank tests and multivariate Cox regression analysis. The correlations between NRF1 expression and gene marker sets of tumor infiltrating lymphocytes (TILs) were analyzed by TIMER and Gene Expression Profiling Interactive Analysis (GEPIA) databases. Results: NRF1 mRNA expression was significantly higher in HCC than in normal tissue. Compared with chronic hepatitis, more frequency of NRF1 high expression are found in HCC (31.58 % vs 13.27 %, P < 0.001, P < 0.001). In addition, the NRF1 expression was significantly associated with hepatic cirrhosis (P = 0.021) and vascular invasion (P = 0.025). NRF1 expression was also a significant independent predictor of survival in HCC (P = 0.003; HRadj = 0.20; 95% CI = 0.09 – 0.44). NRF1 showed positively correlated with TILs, including B cell (r = 0.384, P = 1.68e-13), CD8+ T cells (r = 0.246, P = 3.99e-06), CD4+ T cells (r = 0.535, P = 6.90e-27), macrophage (r = 0.506, P = 1.52e-23), neutrophils (r = 0.465, P = 6.08e-20) and dendritic cell (r = 0.404, P = 8.61e-15). The marker genes of TILs correlated significantly with NRF1 expression.Conclusions: NRF1 expression was a useful independent prognostic factor and correlated with tumor immune infiltration in HCC.
A Novel Prognostic Nomogram for 2-Year Survival in HER2-Positive Breast Cancer Patients
Authors: Chen Mengdi , Wu Jiayi , Liu Deyue , Chen Weilin , Lin Caijin , Andriani Lisa , Ding Shuning , Shen Kunwei , Zhu Li
Published: August 2020

Background: Targeted therapies have largely improved prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Yet, disease can still progress rapidly for some patients in the first two years after diagnosis. Our study aimed to establish a nomogram model to predict 2-year breast cancer-specific survival (BCSS) in early HER2-positive breast cancer patients. Methods: A total of 32,481 HER2-positive patients derived from Surveillance, Epidemiology, and End Results (SEER) database were included in the construction of nomogram. Concordance index (C-index) and calibration curve were used to evaluate the discrimination ability and predictive accuracy. We also tested the model in 804 patients from Shanghai Jiao Tong University Breast Cancer Data Base (SJTU-BCDB). Results: Age, estrogen receptor (ER) status, progesterone receptor (PR) status, histologic type, T stage and N stage were selected to construct the nomogram according to multivariable analysis. The 2-year BCSS rate was 95% and 60% for patients at low risk (<8 points) and high risk (>13 scores) respectively. The C-index of model derived from SEER database is 0.81 (95%CI 0.79-0.83). Sensitivity analysis was performed in patients undergoing breast surgeries with the C-index of 0.81 (95%CI 0.79-0.83). Validation in 804 patients from SJTU-BCDB showed respective C-index of 0.77 (95%CI, 0.62-0.92) in total population, 0.67 (95%CI 0.44-0.90) in patients receiving anti-HER2 therapy and 0.90 (95%CI 0.81-0.90) in those without targeted therapy. Conclusions: The novel nomogram can predict 2-year survival outcome in HER2-positive patients independent of receiving anti-HER2 therapy or not and help clinicians to adjust therapeutic strategies for those patients with higher risk.
Treatment of Patient With Angina Pectoris by the Mineral Pulse Light Stimulus on PC6 Acupoints - A Case Report
Authors: cha yongchol , choe hyok , oh songjin , cha zinhwa
Published: August 2020

Background; Angina pectoris is a clinical syndrome of precordial discomfort or pressure due to transient myocardial ischemia without infarction. Treatment may include antiplatelet drugs, nitrates, beta-blockers, calcium channel blockers, ACE inhibitors, statins, and coronary angioplasty or coronary artery bypass graft surgery.Objectives; The purpose of this study is to perform clinical trial on an angina pectoris patient by mineral pulse light stimulus on PC6 acupoints without any drugs use.Methods; Angina pectoris patient was stimulated by mineral pulse light stimulator (MPLS). Stimulus acupoints; PC6. The selected acupoints were stimulated by MPLS for 50~60 minutes once a day. The same method was performed on the patient for 15days without any drugs use (nitroglycerin, isosorbide, atenolol, diltiazem, etc.).Results; A heart attack after treatment decreased gradually, a heart attack disappeared after 3 days, and the recurrence was no for 3 years until now.Conclusions; Angina pectoris patient was recovered to normal by mineral pulse light stimulus on PC6 acupoints without any drugs use.
MiR-378 Has the Capacity to Serve as a Diagnostic Biomarker for Prostate Cancer Patient
Authors: Cao Shuangqing , Zheng Lei
Published: August 2020

Background: This study aimed to examine the expression of serum miR-378 in prostate cancer (PCa) patients and healthy individuals and to identify the value of miR-378 in PCa diagnosis.Methods: The expression of serum miR-378 between groups was compared by t-test. The association between miR-378 expression and clinical characteristics of PCa patients was assessed using Chi-square test. The diagnostic value of serum miR-378 in PCa was estimated by the receiver operating characteristic (ROC) analysis.Results: The expression level of serum miR-378 in PCa patients was significantly lower than that in healthy individuals (P<0.0001). MiR-378 expression was affected by positive AR (P=0.004), large Gleason score (P=0.013) and advanced TNM stage (P=0.020), however, it had no relationship with age, serum PSA, NED rate and urine retention (all, P>0.05). The ROC curve showed that the optimal cutoff value was 1.845, giving the sensitivity and specificity of 75.21% and 89.77%, respectively. Besides, the area under the ROC curve (AUC) was 0.894, indicating serum miR-378 was of great diagnostic value in screening PCa patients from healthy controls (P<0.0001, 95%CI =0.852-0.936).Conclusions: Taken together, the increased expression of serum miR-378 might act as a potential biomarker for PCa diagnosis.
25-gauge vitrectomy with gas tamponade for rhegmatogenous retinal detachment: experienced vs. inexperienced surgeons
Authors: Pencak Martin , Veith Miroslav , Stranak Zbynek , Dite Jakub , Vranova Jana , Studeny Pavel
Published: August 2020

Background: To compare the results and complication rates of a 25-gauge pars plana vitrectomy (25 g PPV) with gas tamponade for rhegmatogenous retinal detachment (RRD) between experienced and inexperienced surgeons.Methods: This is a retrospective comparative consecutive case series study of patients with uncomplicated RRD treated with 25 g PPV with gas tamponade. Patients were divided into 2 groups: In Group 1 (ESG) the procedure was performed by an experienced vitreoretinal surgeon and in Group 2 (ISG) the procedure was performed by 2 inexperienced surgeons. Anatomical and functional results and complication rates were compared between the two groups.Results: 216 eyes were included in the study. In the ESG (106 eyes), the single operation success rate was 94.3%, and the final success rate was 100%. The mean best-corrected visual acuity (BCVA) improved from 0.38 decimal to 0.73 decimal. In the ISG (110 eyes), the single operation success rate was 93.6%, and the final success rate was 100.0%. The mean BCVA improved from 0.33 decimal to 0.74 decimal. The differences between groups were not statistically significant. There was no difference in complication rates between groups.Conclusions: A 25 g PPV with gas tamponade for uncomplicated RRD renders excellent functional and anatomical results even when performed by an inexperienced surgeon. The complication rate was comparable between experienced and inexperienced surgeons.
Private Diabetes Care Delivery in Iran, is it Cost-Effective?
Authors: davari majid , bayazidi yahya , Kebriaeezadeh Abbas , shahtaheri rahil , Hezaveh Alireza Mahdavi , Sadeghi Abolfazl , Lami Ahmed Hayder Mohsin aL
Published: August 2020

BackgroundThe quality of health care provided to diabetic patients has a significant impact on long-term costs and health outcomes. This study aims to determine the long-term cost-effectiveness analysis between private and public Diabetic Centers in Iran.MethodsUsing the localized UKPDS model, we performed a cost-effectiveness analysis to forecast 20 years quality-adjusted life expectancy (QALE) gains and direct medical costs(management of complications and Treatment Costs) in under-treatment patients referred to private and public Diabetic Centers in Iran. Costs and utility decrements derived from 1978 patients with type 2 diabetes from 7 private and eight Public diabetes centers in 5 provinces. We used statistical techniques (internal loops (Monte-Carlo trials) and bootstraps) to examine the robustness of the results.ResultsIn a 20-year time horizon, the private sector will be more effective and more costly(5.17 vs 4.95 QALE and 15385 vs 8092 ). The incremental cost-effectiveness ratio (ICER) was $33,148.02 per QALE gained that was higher than our country threshold.Conclusion Although the pattern and quality of care in private-sector diabetes centers resulted in a slight increase in the life expectancy of T2DM patients, it is associated with unfavorable costs too.
Dermal Papilla Cells and Melanocytes Response to Physiological Oxygen Levels Depends on Their Interactions 
Authors: Abreu Carla , Reis Rui L , Marques Alexandra P
Published: August 2020

Background: The specialized dermal papilla (DP) cells and the tyrosinase-active melanocytes are central players in hair growth and pigmentation, respectively. In the hair follicle (HF), oxygen levels average about 5%O2 (physoxia) and are intimately coupled with the production of reactive oxygen species (ROS), which contribute to hair growth. Considering that oxygen and ROS might have a major role in the maintenance of the HF cellular functions, we studied the effect of physoxia over human DP cells and melanocytes (hMel) and investigated if these cells interaction altered this response.Results: Physoxia decreased DP cells senescence and improved their secretome and phenotype, representing a reliable in vitro culture environment. Further, hMel proliferation, migration and tyrosinase activity were also enhanced, demonstrating physoxia capacity to sustain biologically relevant features. Physoxia affected DP cells alkaline phosphatase (ALP) activity, but their signalling did not influence hMel proliferation or tyrosinase activity when indirectly co-cultured. Additionally, ROS production in co-cultured cells was higher than in the respective monocultures, but lower in response to physoxia than in normoxia (21%O2). Considering the results, we further assessed a potential link between DP cells ALP activity and ROS levels, but DP cells treatment with H2O2 showed that these are not directly correlated. Moreover, and given their proximity within the HF, hMel were directly cultured with DP spheroids, rendering 3D-aggregates that recreated these cells native microarchitecture and phenotype. Further, both hMel tyrosinase activity and DP cells ALP activity, their main functional indicators, as well as ROS production were higher in the 3D-aggregates cultured under physoxia than in normoxia. Conclusions: Overall, we provide evidence that the response to physoxia differs according to hMel-DP cells interactions, and that the microenvironment recreated when they are in direct contact favours their follicular functions, including hair growth and pigmentation promoting capacity.
The EGFR-HSF1 Axis Accelerates the Tumorigenesis of Pancreatic Cancer
Authors: Qian Weikun , Chen Ke , Qin Tao , Xiao Ying , Jie Li , Yue Yangyang , Zhou Cancan , Ma Jiguang , Duan Wanxing , Lei Jianjun , Han Liang , Shen Xin , Wu Zheng , Ma Qingyong , Wang Zheng
Published: August 2020

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant diseases because of its non-symptomatic tumorigenesis. We previous found heat shock factor 1 (HSF1) was critical for PDAC progression and the aim of this study was to clarified the mechanisms on early activation of HSF1 and its role in the pancreatic cancer tumorigenesis. Methods: The expression and location of HSF1 on human or mice pancreatic tissues were examined by immunohistochemically staining. We mainly used pancreatic acinar cell 3-dimensional (3D) culture and a spontaneous pancreatic precancerous lesion mouse model called LSL-KrasG12D/+; Pdx1-Cre (KC) (and pancreatitis models derived from KC mice) to explore the pro-tumorigenesis mechanisms of the HSF1 in vitro and in vivo. Bioinformatics and molecular experiments were used to explore the underlying mechanisms between HSF1 and EGFR. Results: In this study, we found that pharmacological inhibition of HSF1 slowed pancreatic cancer initiation and suppressed the pancreatitis-induced formation of pancreatic precancerous lesion. Next, bioinformatics analysis revealed the closely linked between HSF1 and epidermal growth factor receptor (EGFR) pathway and we also confirmed their parallel activation in pancreatic precancerous lesions. Besides, the pharmacological inhibition of EGFR suppressed the initiation of pancreatic cancer and the activation of HSF1 in vivo. Indeed, we demonstrated that the EGFR activation that mediated pancreatic cancer tumorigenesis was partly HSF1-dependent in vitro.Conclusion: Hence, we concluded that the EGFR-HSF1 axis promoted the initiation of pancreatic cancer.
Spatial Distribution and Trend Analysis of Current Status of COVID-19 in Nepal and Global Future Preventive Perspectives
Authors: Pant Ramesh Raj , Bahadur Buddha Bahadur , Bishwakarma Kiran , Paudel Sudip , Pandey Nashib , Adhikari Samir Kumar , Ranabhat Kamal
Published: August 2020

Background: Coronavirus disease (COVID-19) is a recently discovered severe and contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has received worldwide attention. The risk of COVID-19 is serious for the infected persons of chronic diseases as well as vulnerable populations including elder group. Still, the present scenario of scarcity of effective treatment options and limited recovery rate of ongoing treatment are prevailed in Nepal. This study aims to analyze the spatial distribution and trends of COVID-19 with the help of geographic information system (GIS) software and outlook future preventive perspectives.Methods: In this research work, we used GIS tool ArcGIS 10.4.1 to map the distribution patterns of population of COVID-19 cases. Federal, provincial and district level daily cases data of COVID-19 confirmed, cured and death from 23rd January to 13th July 2020 were obtained from the Ministry of Health and Population (MoHP), Government of Nepal. In addition, we reviewed several peer-reviewed research papers to summarize the global scenarios and preventive perspectives on COVID-19.Results: In context to Nepal SARS-CoV-2 has spread throughout the country infecting 16,945 persons in all 77 districts, as of 13th July, 2020. Confirmed, cured and death cases experienced an upward trend up to 1st July, 2020 followed by downward trend as of 13th July, 2020. Over 70% of total confirmed cases of reported COVID-19 patients were from the lowland-plain area. Spatial clustering suggested that provinces 2 and 5 were at potentially increased risk of COVID-19, and Province 1 and Bagmati province could be grouped as future "hot spots". In addition, we proposed four strategies namely, identification of the key medical and social elements, discovery and development of treatment options for a future pandemic, investing in ethno-medicine research and epidemic preparedness of health care system to decrease the efficacy of calamities of future pandemics.Conclusion: Our study demonstrates one of the best ways to protect; control and sluggish transmission of SARS-CoV-2 could be achieved by monitoring active ties using GIS spatial analysis. And, the severity of future pandemic could be minimized by integrative action on the abovementioned four different preventive master plans.
miR-361-3p Regulates Liver Tumor-initiating Cells Expansion and Chemo-resistance
Authors: Qu Shuping , Zhang Xiaobing , Fan Hengwei , Wu Yue , Zhai Jian , Wu Dong
Published: August 2020

Background: Increasing evidence shows that liver tumor-initiating cells (T-ICs) closely associated with the progression, metastasis, recurrence and chemo-resistance of hepatocellular carcinoma (HCC). However, the underlying mechanism for the propagation of liver T-ICs remains unclear. The purpose of our study was to explore the role of miR-361-3p in the expansion of liver T-ICs and the potential molecular mechanism.Results: Flow cytometry analysis was performed to isolate CD24+, CD133+ or EpCAM+ cells from primary HCC cells or HCC cell lines. Real-time PCR was used to detect the expression of miR-361-3p in liver T-ICs. The impact of miR-361-3p on liver T-ICS expansion was investigated both in vivo and in vitro. The correlation between miR-361-3p expression and TACE (transcatheter arterial chemoembolization) or sorafenib benefits in HCC was evaluated in patient cohorts. miR-361-3p expression is upregulated in liver T-ICs. Knockdown of miR-361-3p impairs the self-renewal and tumorigenicity liver T-ICs. Conversely, forced miR-361-3p expression enhances the self-renewal and tumorigenicity liver T-ICs. Mechanistically, miR-361-3p directly targets SOX1 via binding its 3’-UTR in liver T-ICs. Moreover, miR-361-3p knockdown hepatoma cells are more sensitive to cisplatin or sorafenib treatment. Clinical cohort analysis demonstrates that miR-361-3p low HCC patients are benefited from TACE or sorafenib treatment. Conclusions: Our findings revealed the crucial role of the miR-361-3p in liver T-IC expansion and TACE or sorafenib response, rendering miR-361-3p an optimal target for the prevention and intervention in HCC.
Are Danish vocational schools ready to implement ‘smoke-free school hours’? A qualitative study informed by the theory of organizational readiness for change
Authors: Hjort Anneke Vang , Schreuders Michael , Rasmussen Kathrine Højlund , Klinker Charlotte Demant
Published: August 2020

Background
Vocational education and training is a lower level of education and the smoking prevalence among Danish vocational students is high. The school tobacco policy regarding smoke-free school hours stipulates that students and staff are not allowed to smoke during school hours—inside or outside school premises—and it might be an effective intervention for reducing smoking in vocational schools. For school tobacco policies to be effective, they must be appropriately implemented. A primary predictor for successful implementation is organizational readiness for change. This study seeks to identify and understand the barriers to and facilitators for developing organizational readiness to implement smoke-free school hours in Danish vocational schools.
Methods
Semi-structured interviews and focus groups were carried out with managers and teachers (n = 22 participants) from six vocational schools. The interview guides were informed by ‘A theory of organizational readiness for change’ developed by Weiner, which was also used as a framework to analyze the data.
Results
We identified 13 facilitators and barriers. Nine factors acted as facilitators, including the following: believing that health promotion is a school role and duty; believing that society and workplaces are becoming more smoke-free, and believing that smoke-free school hours is a beneficial strategy to achieve fewer educational interruptions. Additional facilitators include establishing clear rules for sanctioning and enforcement; developing a joint understanding about smoke-free school hours; developing skills to deal with student responses to smoke-free school hours; establishing social alternatives to smoking; offering smoking cessation help and mandating smoke-free school hours by law. Four organizational norms, practices or discourses acted as barriers: Believing that smoke-free school hours violate personal freedom; believing that students have more important problems than smoking; believing that it is difficult to administer the level of enforcement; and believing that the enforcement of smoke-free school hours negatively influences student-teacher relations.
Discussion
Our results suggest that developing organizational readiness before adopting a comprehensive tobacco policy such as smoke-free school hours is important for successful implementation. Further research should investigate how to strengthen the facilitators for and counter the barriers to developing readiness for implementing smoke-free school hours.
Osmotic stress activated protein kinase 5 (SAPK5) positively regulates immune response and blast resistance in rice
Authors: Zhu Xiaobo , Long Xiaoyu , Ma WeiWei , Shi Hui , Yi Hong , Xu Li , Mao Wei , Yin Junjie , He Min , Li Weitao , Song Li , Wang Long , Liu Jiali , Qing Hai , Bi Yu , Li Mingwu , Hu Kun , Qi Tuo , Hou QingQing , Chen Xuewei , Wang Jing
Published: August 2020

Background

The sucrose non-fermenting 1 (SNF1) related protein kinase 2 (SnRK2) family proteins are plant-specific Ser/Thr protein kinases that are mainly involved in response to abiotic stress. However, their regulation roles on immune response and disease resistance in crops are largely unknown.
Results

In this study, we report the characterization of a rice SnRK2 family member, osmotic stress activated protein kinases 5 (SAPK5), on plant immune response. The SAPK5 protein is localized in cytoplasm and possesses kinase activity. The kinase activity of SAPK5 is promoted upon treatment with chitin, a conserved pathogen-associated molecular pattern (PAMP). Knockout of SAPK5 compromises rice immune response and resistance against the fungal pathogen Magnaporthe oryzae.
Conclusions

Our study demonstrates that SAPK5 positively regulates immune response and disease resistance in rice and provides new insights into the regulatory roles of SnRK2 proteins on plant immunity.
Picornavirus 3C proteins inhibit RIG-I-mediated innate immune responses by reducing TRIM25 expression
Authors: Xiao Huimin , Li Jingliang , Yang Xu , Li Zhaolong , Rui Yajuan , Liu Bin , Zhang Wenyan
Published: August 2020

Background：Enterovirus (EV) 3C proteins suppress type I interferon (IFN) responses mediated by retinoid acid-inducible gene I (RIG-I). An E3 ubiquitin ligase, tripartite motif protein 25 (TRIM25)-mediated RIG-I ubiquitination is essential for RIG-I antiviral activity. However, whether the effect of EV 3C on RIG-I is associated with TRIM25 remains unknown.Methods：In this study，luciferase reporter assays was used to detected the activity of IFN-β. Western Blot was used to detected the expression of proteins. Real-time PCR are used to detect that the mRNAs expression. And the co-immunoprecipitation assay was used to detect the interaction between TRIM25 and 3C protein.Results：Here, we demonstrated that 3C proteins of EV71 and CVB3 reduced the expression of RIG-I and TRIM25 through protease cleavage activities. Overexpression of TRIM25 restored RIG-I expression and IFN production reduced by 3C proteins. Further investigation confirmed that the two amino acids in TRIM25 required for RIG-I ubiquitination and structural conformation of TRIM25 were essential for RIG-I recovery. Moreover, we observed that TRIM25 could rescue RIG-I expression reduced by CVA6and EVD68 but not CVA16 3C.Conclusions：Our findings provide an insightful interpretation of 3C protein-mediated host innate immune suppression and support TRIM25 as an attractive target against EV infection.
Prognostic factors for radiation responses in patients with cervical cancer: A nested case-control study
Authors: Ramli Irwan , Susworo Susworo , Nuranna Laila , Mansyur Muchtaruddin , Harahap Alida Roswita , Soetopo Setiawan , Siregar Nuryati Chairani , Wanandi Septelia Inawati
Published: August 2020

Background: The radiation response of cervical cancer is believed to be enhanced by the levels of melatonin because of its roles in the circadian cycle and cancer growth. However, several other factors can affect the radiation response, such as haemoglobin (Hb) levels and tumour size. This study examined the role of circadian rhythms and melatonin levels as prognostic factors for predicting the radiation response in patients with cervical cancer.Methods: In this nested case-control study, good and poor radiation responses were assessed in patients treated with radiotherapy. Data on tumour size and other biological parameters were collected and analysed with the binary logistic regression using SPSS for Windows version 20.Results: Among the 56 examined patients, most subjects had good radiation responses. Other common features of the patients were as follows: <50 years old, initial weight >50 kg, no pain before radiation, low erythrocyte sedimentation rates, normal IVP, moderate or well differentiation on pathology and non-keratinised histopathology. The combination of the time of day of radiation as a surrogate of the circadian cycle (morning vs afternoon), the initial Hb level and the clinical tumour size significantly predicted the radiation response in multivariate analysis.Conclusion: The circadian cycle, tumour size and Hb levels may affect the radiation response in patients with cervical cancer. Further research is needed to identify more suitable prognostic factors using different radiotherapy techniques.
Water Intake Restriction Induces Primary Cilia Shortening and Concentrated Urine Formation via Hdac6 Activation in Mice
Authors: Kong Min Jung , Han Sang Jun , Seu Sung Young , Kim Jee In , Han Ki-Hwan , Park Kwon Moo
Published: August 2020

Background: The primary cilium, a microtubule-based cellular organelle, acts as a mechano-sensor for monitoring the fluid flow in cells. In kidneys, the primary cilia protrude into the tubular lumen from the tubular cells and therefore, directly contact pro-urine flow and components. However, it remains to be defined how the cilia are associated with kidney function and diseases. Here, we investigated whether water access restriction affects the cilia length in the renal tubular cells, whether cilia length changes are associated with kidney functions, and how cilia lengths are regulated. Methods: C57BL/6 mice were provided free access to water (control), but water supply was stopped for some mice for 24 to 48 h (water restriction). Among each group, some mice were administered with tubastatin A (10 mg/kg BW), a specific inhibitor of histone deacetylase 6 (HDAC6), daily from 2 days before water restriction. Cultured tubular epithelial cells were treated with either 10 or 20 mM NaCl or 20 mM mannitol with or without tubastatin A. Primary cilia were determined by immunofluorescence staining using acetylated-α-tubulin antibody or scanning electron microscope. Results: Water restriction shortened the primary cilia of kidney tubular epithelial cells along with increasing urine osmolality. Water restriction increased the activity of HDAC6 with increased the deacetylation of α-tubulin, a substrate of HDAC6 and a major comprising protein of microtubule of primary cilia. HDAC6 inhibitor blocked water restriction-induced primary cilia shortening along with the inhibition of α-tubulin deacetylation. In addition, HDAC6 inhibitor blocked the increase in water restriction-induced urine osmolality. Increases of NaCl or mannitol concentration in the medium for Madin-Darby canine kidney tubule cell culture shortened the cilia length and increased HDAC6 activity and α-tubulin deacetylation. HDAC6 inhibitor blocked those NaCl and mannitol-induced effects. Conclusions: Our data have demonstrated that water restriction shortened the primary cilia of kidney tubular cells via HDAC6 activation and α-tubulin deacetylation along with increasing urine osmolality, suggesting that the alteration of primary cilia length is an adaptive response to the water intake to maintain body water balance and that the primary cilia length regulation may be a therapeutic strategy of kidney diseases related to the body water and electrolyte imbalances.
Exploring General Practitioners’ Perceptions About the Primary Care Gatekeeper Role in Indonesia
Authors: Mulyanto Joko , Wibowo Yudhi , Kringos Dionne S.
Published: August 2020

Background In the current healthcare delivery system funded by National Health Insurance (NHI) in Indonesia, the gatekeeper role of primary care services is critical to ensuring equal healthcare access for the population. To be effective, gatekeeping relies on the performance of general practitioners (GPs). However, the perceptions held by Indonesian GPs about their gatekeeper role are not yet well documented. This study describes the self-perceived knowledge, attitudes and performance of Indonesian GPs with respect to the gatekeeper role and explores associated factors. Methods We conducted a cross-sectional study of all primary care facilities (N = 75) contracted by the regional NHI office in the Banyumas district. The 73 participating GPs completed a written questionnaire that assessed their knowledge, attitudes and performance in relation to the gatekeeper role. Personal and facility characteristics were analysed in a generalised linear model as possible associating factors.ResultsGPs scored relatively high in the domains of knowledge and performance but scored lower in their attitudes towards the gatekeeper role of primary care. In the full-adjusted model, no factors were significantly associated with the knowledge score. Work experience as GPs, private or civil service employment status and rural or urban location of the primary care facility were linked to attitude scores. Full- or part-time employment and type of facility were factors associated with the performance score. Conclusion GPs in Indonesia are knowledgeable and report that they adequately perform their function as gatekeepers in primary care. However, their attitudes towards the gatekeeper function are less positive. Attitudes and performance with respect to the primary care gatekeeper role are likely influenced more by contextual factors such as location and type of facility than by personal factors. Efforts to address contextual issues could include improvements in practice standards for privately practising physicians and public information campaigns about gatekeeping regulations. Such efforts will be crucial to improving the gatekeeper role of primary care in Indonesia and assuring efficient access to high-quality care for all.
Highly Efficient Biosynthesis of Indole-3-acetic acid by Enterobacter xiangfangensis BHW6
Authors: Zhang Bi-Xian , Wang Ying-Ying , Hu Xiaomei
Published: August 2020

Background: Indole-3-acetic acid (IAA) plays an important role in the growth and development of plants. Various bacteria in the rhizosphere are capable to produce IAA that acts as a signaling molecule for the communication between plants and microbes to promote the plant growth. Due to the low IAA content and various interfering analogs, it is difficult to detect and isolate IAA from microbial secondary metabolites. Results: A predominant strain with a remarkable capability to secrete IAA was identified as Enterobacter xiangfangensis BHW6 based on 16S rRNA gene sequence, the determination of average nucleotide identity (ANI) and digital DDH (dDDH). The maximum IAA content (134-1129 μg/mL) was found with the addition of 0.2-15 g/L of L-tryptophan at pH 5 for 6 days, which was 4-40 fold higher than that in the absence of L-tryptophan. The highest yield of IAA was obtained at the stationary phase of bacterial growth. An acidic culture medium was preferred for the IAA biosynthesis of the strain. The strain was tolerant and stable to produce IAA in the presence 2.5%-5% (w/v) of NaCl. IAA was then isolated through column chromatography with a mobile phase of hexane/ethyl acetate (1/2, v/v) and characterized by 1H Nuclear Magnetic Resonance (1H NMR). Conclusions: A remarkable IAA production was obtained from E. xiangfangensis BHW6 that was tryptophan–dependent. According to genomic analysis, the ipdC gene coding for the key enzyme (indole-3-pyruvate decarboxylase) was identified indicating that IAA biosynthesis was mainly through the indole-3-pyruvia acid (IPyA) pathway, which was further confirmed by intermediate assay. E. xiangfangensis BHW6 with an important economic value has great prospect in agricultural and industrial application.
Choosing the best embryogenesis medium in carrot by data mining technology
Authors: Ziarani Masoumeh Fallah , Tohidfar Masoud , Mirjalili Mohammah Hosein , Gavlighi Hassan Ahmadi , Hesami Mohsen
Published: August 2020

Plant cell, tissue and organ culture (PCTOC) is extensively used to propagate faster and more plants, to produce virus-free plants, and secondary metabolites production as well. This requires the optimization of PCTOC conditions for each plant and final aim. Optimizing the micropropagation is time-consuming and costly, because it is different from the plant and even for each variety. In addition requires the optimization of the concentration and type of hormone and the type of explants for each variety in the stages of callogenesis, embryogenesis, shooting and rooting. Hence, today researchers have used Data Mining with using an artificial neural network (ANN) to predict the best conditions for tissue culture and saved time and money considerably. In this research, radial basis function (RBF) model was used to predict the best conditions for carrot tissue culture and the results showed that the highest and the least sensitivity were related to variety and percentage of Agar in liter, respectively. The results prediction of the RBF model showed that the percentage of embryogenesis was 62.5%, but the percentage of embryogenesis in laboratory obtain 75%. The results showed that the RBF model is a good model to predict the results.
Sum of High-Risk Gene Mutation (SHGM): A Novel Attempt to Assist Differential Diagnosis for Adrenocortical Carcinoma with Benign Adenoma, Based Detection of Mutations of Nine Target Genes.
Authors: Zheng Guo-Yang , Zhang Xue-Bin , Li Han-Zhong , Zhang Yu-Shi , Deng Jian-Hua , Wu Xing-Cheng
Published: August 2020

Background
There has been no research on applying gene detection to differential diagnosis of adrenocortical carcinoma (ACC). We attempted to explore a novel auxiliary method for differential diagnosis between ACC with benign adrenocortical adenoma (ACA), based on mutations of target genes in tissues.
Methods
Nine genes were chosen as target genes, including TP53, CTNNB1, ARMC5, PRKAR1A, ZNRF3, RB1, APC, MEN1 and RPL22. Exons capture and sequencing of target genes were performed in 98 cases of tissue samples by using FastTarget technology, including 41 ACC tissues, 32 ACA tissues and 25 normal adrenal gland tissues. Significant mutations were detected and identified, and the clinical information was collected, for further comparative analysis and application to assist differential diagnosis of ACC.
Results
We identified 132 significant gene mutations and 227 significant mutation sites in 37 ACC tissues, much more than ACA and normal adrenal gland tissues. Mutation rates of 6 genes in ACC tissues were obviously higher than ACA tissues, including ZNRF3, ARMC5, TP53, APC, RB1, and PRKAR1A, which were regarded as high-risk genes. The sum of mutated high-risk genes detected in each sample was denominated sum of high-risk gene mutation (SHGM), and the rates of SHGM > 0 and SHGM > 1 in ACC tissues were 73.0% and 62.2% respectively, which were both obviously higher than those in ACA tissues, with significant statistic differences. Especially for the 8 cases of ACC with diameter < 5 cm, SHGM > 0 and SHGM > 1 were found in 6 samples (75%) and 4 samples (50%), respectively. However, no relevance was found between SHGM and clinical characteristics of ACC.
Conclusions
We identified 6 high-risk genes in ACC tissues, of which the mutation rates in ACC tissues were significantly higher than those in ACA or normal adrenal gland tissues. The sum of mutated high-risk genes detected in ACC tissues was denominated SHGM, which was potential to assist the differential diagnosis of ACC with ACA, especially for the small-size ACC.
Combination of Circulating Cell-Free DNA and Metabolic Tumor Burden to Distinguish Non-Small Cell Lung Cancer from Tuberculosis
Authors: Zheng Wen-qiang , Zhang Puhong , Quan Bin , Gao Guang-jian , Chen Qing , Dai Yun-hai , Zhai Jian
Published: August 2020

Background: Non-small cell lung (NSCLC) holds high mortality owing to the difficulty to early detection from other lung mass, such as tuberculosis. This study evaluates the clinical value of the combination of circulating cell-free DNA (cfDNA) quantification and metabolic tumor burden to distinguish NSCLC from tuberculosis. Methods: A total of 149 NSCLC patients, 151 tuberculosis patients and 150 healthy controls were included. Quantifying serum cfDNA fragments from ALU (115 bp) gene by RT-PCR. Metabolic tumor burden (SUV-Maxa) values were detected by preoperative the 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT). A549 cell, NCI–H460 cell, NSCLC and tuberculosis mice model were used to elucidate the specific mechanism. Results: Serum cfDNA levels and SUV-Maxa were higher in NSCLC patients than those in healthy controls and those in tuberculosis. Meanwhile, mice models showed the similar discovery. In addition, obvious correlations of cfDNA and metabolic tumor burden were only existed in NSCLC patients and mice model, rather than tuberculosis and control. Moreover, the combination of cfDNA and metabolic tumor burden displayed better effect to distinguish NSCLC from tuberculosis than alone use. Mechanistically, upregulated Glucose transporter 1 (GLU1) increased necroptosis-induce cfDNA rise by FasL/caspase 8/caspase 3 pathway and promoted metabolic tumor burden in NSCLC. Conclusions: The combination of cfDNA and metabolic tumor burden displayed better effect to distinguish NSCLC from tuberculosis, owing to upregulated GLU1 increased cfDNA levels by FasL/caspase 8/caspase 3 pathways and promoted metabolic tumor burden in NSCLC.
Transcriptomic and Metabolomic Profiling Reveal the p53-Dependent Benzeneacetic Acid Attenuation of Silica-Induced Epithelial–Mesenchymal Transition in Human Bronchial Epithelial Cells
Authors: Zhou Meiling , Ju Zhao , Jin Jing , Pan Huiji , Ding Ping , Huang Ruixue
Published: August 2020

Background: Silica exposure underlies the development of silicosis, one of the most serious occupational hazards worldwide. We aimed to explore the interaction of the silica-induced epithelial–mesenchymal transition (EMT)-related transcripts with the cellular metabolism regulated by p53.Methods: We knocked out p53 using CRISPR/Cas9 in the human bronchial epithelial (HBE) cell line. The transcriptomic and metabolomic analyses and integrative omics were conducted using microarrays, GC-MS, and MetaboAnalyst, respectively. Results: Fifty-two mRNAs showed significantly altered expression in the HBE p53-KO cells post-silica exposure. A total of 42 metabolites were putatively involved in p53-dependent silica-mediated HBE cell dysfunction. Through integrated data analysis, we obtained five significant p53-dependent metabolic pathways including phenylalanine, glyoxylate, dicarboxylate, and linoleic acid metabolism, and the citrate cycle. Through metabolite screening, we further identified that benzeneacetic acid, a key regulation metabolite in the phenylalanine metabolic pathway, attenuated the silica-induced EMT in HBE cells ina p53-dependent manner. Interestingly, despite the extensive p53-related published literature, the clinical translation of these studies remains unsubstantial. Conclusions: Our study offers new insights into the molecular mechanisms by which epithelial cells respond to silica exposure and provide fresh perspective and direction for future clinical biomarker research and potential clinically sustainable and translatable role of p53.
LncRNA CBR3-AS1 Regulates of Breast Cancer Drug Sensitivity as a Competing Endogenous RNA Through the JNK1/MEK4‑Mediated MAPK Signal Pathway
Authors: Zhang Ming , Wang Yan , Jiang Longyang , Song Xinyue , Zheng Ang , Gao Hua , Wei Minjie , Zhao Lin
Published: August 2020

Background: Adriamycin (ADR) resistance is one of the main obstacles to improve the clinical prognosis of breast cancer (BRCA) patients. Long non-coding RNAs (lncRNAs) can regulate cell behavior, but the role of these RNAs in anti ADR of BRCA remains unclear. Here we aim to investigate the imbalance of a particular long noncoding RNA, lncRNA CBR3 antisense RNA 1 (CBR3-AS1), and its role in ADR resistance.Methods: Microarray analysis of ADR-resistant BRCA cells was performed to identify CBR3-AS1. CCK8 assay and colony formation assay were used to detect the sensitivity of BRCA cells to ADR. Dual-luciferase reporter, RNA pull down, IHC and Western blot were used to verify the relationship between CBR3-AS1, miRNA and target genes. In vivo, the effect of CBR3-AS1 on BRCA resistance was observed by xenograft tumor model. The role of CBR3-AS1 in influencing ADR sensitivity was verified by clinical BRCA specimens, TCGA, CCLE, and GDSC databases.Results: Here, we found that lncRNA CBR3-AS1 was significantly increased in BRCA tissues and was closely correlated with poor prognosis. CBR3-AS1 overexpression promoted ADR resistance in BRCA cells in vitro and in vivo. Mechanistically, we identified that CBR3-AS1 functioned as a competitive endogenous RNA by acting as a molecular sponge of miR-25-3p. MEK4 and JNK1 of MAPK pathway were the direct downstream proteins of CBR3-AS1 / miR-25-3p axis in BRCA cells.Conclusions: In summary, our findings demonstrate that CBR3-AS1 plays a critical role in the chemotherapy resistance of BRCA by mediating the miR-25-3p, MEK4/JNK1 regulatory axis. The potential of CBR3-AS1 as an oncogene and therapeutic biomarker of BRCA was identified.
Drone-Assisted Aerial Surveys of Large Animals in Siberian Winter Forests
Authors: Atuchin Victor , Prosekov Alexander , Vesnina Anna , Kuznetsov Alexander
Published: August 2020

There are two main reasons for monitoring the population of forest animals. First of all, regular surveys reveal the real state of biodiversity. Second, they guarantee a prompt response to any negative environmental factor that affects the animal population and make it possible to eliminate the threat before any permanent damage has been done. The research objective was to study the potential of drone planes equipped with thermal infrared imaging cameras. Drone planes proved effective in covering large areas, while thermal infrared cameras provided accurate statistics in the harsh winter conditions of Siberia. The research featured the population of the European elk (Alces alces), which is gradually deteriorating due to poaching and deforestation. The surveyed territory included the Salair State Nature Reserve in the Kemerovo Region, or Kuzbass (Russia). The authors developed an effective methodology for processing the data obtained from drone-mounted thermal infrared cameras. The research provided reliable results concerning the changes in the elk population on the territory in question. The use of drone planes proved an effective means of ungulate animal survey on large areas of Siberian winter forests.
Cardiac Helical Function
Authors: Trainini Jorge , Lowenstein Jorge , Beraudo Mario , Wernicke Mario , Llabata Vicente Mora , Lowenstein-Haber Diego , Trainini Alejandro , Costa Francesc Carreras
Published: August 2020

Background. The aim of this study was to investigate: a) the starts and ends of the myocardial band; b) the slippage between the band segments, when performing both torsion and ventricular detorsion, implies that there should be an antifriction mechanism that avoids dissipating the energy; c) the electrical activation of the endocardial and epicardial bands and secondarily understand ventricular twist and the mechanism of active suction during the diastolic isovolumic phase. Methods. They were used: a) Ten young-bovine hearts (800-1000 g) and seven human hearts (one embrión, 4 g; one 10 years, 250 g and five adult, 300 g/average); b) five patients with no structural cardiac abnormalities and normal QRS complexes underwent three-dimensional endoepicardial electroanatomic mapping. Results. We have found in all the bovine and human hearts studied a nucleus (fulcrum) underlying the right trigone, whose osseus, chondroid or tendinous histological structure depends on the specimen analyzed. All the hearts studied presented myocardial attachment to the rigid structure of the fulcrum. Hyaluronic acid was found in the cleavage planes between the myocardial bundles.Endo-epicardial mapping demonstrates an electrical activation sequence in the area of the apex loop in agreement with the synchronic contraction of the descending and ascending band segments, consistent with the mechanism of ventricular twist. The late activation of the ascending band segment is consistent with its persistent contraction during the initial period of the isovolumic diastolic phase (the basis of the suction mechanism). Conclusions. The finding of the fulcrum gives support to the spiral myocardial band being the point of fixation that allows the helicoidal torsion. The hyaluronic acid would act as a lubricant and provide great resistance to mechanical pressures. This study explains the ventricular twist and the active suction mechanism during the isovolumic diastolic and early ventricular filling phases.Trial. This work does not correspond to a trial