bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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&nbsp;
Authors: Abreu Carla , Reis Rui L , Marques Alexandra P 
Published: August 2020

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.