bluuebunny/crossref_metadata_2025 huggingface dataset:
Fetuin-a expression profile in mouse and human adipose tissue
Authors: Khadir Abdelkrim , Kavalakatt Sina , Madhu Dhanya , Tiss Ali
Published: March 2020

Fetuin-A (Fet-A) was one of the first hepatokines to be reportedly linked to metabolic diseases. Fet-A was also suggested to be an adipokine, but its expression in the adipose tissue remains debatable. Here we compared the expression of Fet-A between human and mice adipose tissue biopsies as well as among human subcutaneous tissue and visceral adipose tissue primary cells, and mouse 3 T3-L1 cells at various stages of differentiation. Fet-A was expressed in mice biopsies and cells but not in human biopsies and cells, except in visceral adipose tissue primary cells following differentiation. Although the marginal expression of Fet-A in human visceral adipose tissue, a major contribution of Fet-A expression in human adipose tissue to systemic Fet-A levels is discounted, but it could indicate specific local Fet-A action in the visceral adipose tissue.
Correction to: The burden of chronic diseases across Europe: what policies and programs to address diabetes? A SWOT analysis
Authors: Giusti Angela , Maggini Marina , Colaceci Sofia
Published: March 2020

It was highlighted that in the original article [1] Fig. 2 was incorrect and the link for the Additional File was missing. This Correction article provides the correct Fig. 2 and the Additional File with its link. The original file has been updated.
Accelerated immunosenescence in rheumatoid arthritis: impact on clinical progression
Authors: Bauer Moisés E.
Published: March 2020

Patients with rheumatoid arthritis (RA) develop features of accelerated ageing, including immunosenescence. These changes include decreased thymic functionality, expansion of late-differentiated effector T cells, increased telomeric attrition, and excessive production of cytokines (senescence-associated secretory phenotype). The progression of RA has been associated with the early development of age-related co-morbidities, including osteoporosis, cardiovascular complications, and cognitive impairment. Here I review data supporting the hypothesis that immune-senescence contributes to the aggravation of both articular and extra-articular manifestations. Of note, poor cognitive functions in RA were associated with senescent CD28- T cells, inflammaging, and autoantibodies against brain antigens. The pathways of immune-to-brain communication are discussed and provide the rationale for the cognitive impairment reported in RA.
Extraovarian Brenner tumor in the uterus: a case report and review of literature
Authors: Hu Rui-Yue , Deng Yan-Juan , Zhu Hao-Hao , Zhou Jing , Hu Ming , Liang Xiao-Qing , Xiao Qiu-Jin , Zhou Lv , Peng Xiao-Yu , Zhang Xing-Wei , Ji Ning , Deng Huan
Published: March 2020

Background

Extraovarian Brenner tumors (EOBTs) are extremely rare and can be observed incidentally in both female and male patients, raising concerns regarding the origin of Brenner tumors.

Case presentation

A 53-year-old postmenopausal woman presented with a nodular lesion in the left side of the corpus uteri, which was found at a routine health check. Macroscopically, the lesion appeared as a solid nodule with a yellowish-gray cut surface, approximately 6 cm in greatest diameter. Microscopically, the lesion consisted of well-defined epithelial nests and spindled stromal cells. Parenchymal cells expressed CK7, GATA3, CK5/6, 34βE12, and p63. A single layer of cavity-lined cells with umbrella-like shape showed apical Uroplakin III positivity. Stromal cells were positive for SMA, ER, and PR. The final diagnosis was EOBT and the patient was followed for 2 months with no recurrence.

Conclusions

We report here the third case of EOBTs in the uterus. The combination of morphologic and immunohistochemical results supported the involvement of urothelial metaplasia in the development of EOBTs. The similarities between EOBTs and Walthard nests made Müllerian epithelium an attractive candidate as the cellular origin. Changes of tissue structure or sex hormones imbalance may lead to the translocation of Müllerian remnants to distant organs, explaining the pathogenesis of EOBTs.
A multiplex guide RNA expression system and its efficacy for plant genome engineering
Authors: Oh Youngbin , Lee Bora , Kim Hyeonjin , Kim Sang-Gyu
Published: March 2020

Background

TheStreptococcus pyogenesCRISPR system is composed of a Cas9 endonuclease (SpCas9) and a single-stranded guide RNA (gRNA) harboring a target-specific sequence. Theoretically,SpCas9 proteins could cleave as many targeted loci as gRNAs bind in a genome.

Results

We introduce a PCR-free multiple gRNA cloning system for editing plant genomes. This method consists of two steps: (1) cloning the annealed products of two single-stranded oligonucleotide fragments harboring a complimentary target-binding sequence on each strand between tRNA and gRNA scaffold sequences in a pGRNA vector; and (2) assembling tRNA-gRNA units from several pGRNA vectors with a plant binary vector containing aSpCas9 expression cassette using the Golden Gate assembly method. We validated the editing efficiency and patterns of the multiplex gRNA expression system in wild tobacco (Nicotiana attenuata) protoplasts and in transformed plants by performing targeted deep sequencing. Two proximal cleavages bySpCas9-gRNA largely increased the editing efficiency and induced large deletions between two cleavage sites.

Conclusions

This multiplex gRNA expression system enables high-throughput production of a single binary vector and increases the efficiency of plant genome editing.
Indications, feasibility, safety, and efficacy of CyberKnife radiotherapy for the treatment of olfactory groove meningiomas: a single institutional retrospective series
Authors: Liu Jianmin , Rojas Rafael , Lam Fred C. , Mirza Farhan A. , Mahadevan Anand , Kasper Ekkehard M.
Published: March 2020

Purpose

To assess the safety and efficacy of CyberKnife® radiotherapy (CKRT) for the treatment of olfactory groove meningiomas (OGMs).

Methods

A retrospective review was performed of 13 patients with OGM treated with CKRT from September 2005 to May 2018 at our institution. Nine patients were treated primarily with CKRT, 3 for residual disease following resection, and 1 for disease recurrence.

Results

Five patients were treated with stereotactic radiosurgery (SRS), 6 with hypofractionated stereotactic radiotherapy (HSRT), and 2 with fractionated stereotactic radiotherapy (FSRT). The median tumor volume was 8.12 cm3. The median prescribed dose was 14.8 Gy for SRS, 27.3 Gy for HSRT, and 50.2 Gy for FSRT. The median maximal dose delivered was 32.27 Gy. Median post treatment follow-up was 48 months. Twelve of 13 patients yielded a 100% regional control rate with a median tumor volume reduction of 31.7%. Six of the 12 patients had reduced tumor volumes while the other 6 had no changes. The thirteenth patient had significant radiation-induced edema requiring surgical decompression. Twelve patients were alive and neurologically stable at the time of the review. One patient died from pneumonia unrelated to his CKRT treatment.

Conclusions

CKRT appears to be safe and effective for the treatment of OGMs.
A roadmap to using historical controls in clinical trials – by Drug Information Association Adaptive Design Scientific Working Group (DIA-ADSWG)
Authors: Ghadessi Mercedeh , Tang Rui , Zhou Joey , Liu Rong , Wang Chenkun , Toyoizumi Kiichiro , Mei Chaoqun , Zhang Lixia , Deng C. Q. , Beckman Robert A.
Published: March 2020

Historical controls (HCs) can be used for model parameter estimation at the study design phase, adaptation within a study, or supplementation or replacement of a control arm. Currently on the latter, there is no practical roadmap from design to analysis of a clinical trial to address selection and inclusion of HCs, while maintaining scientific validity. This paper provides a comprehensive roadmap for planning, conducting, analyzing and reporting of studies using HCs, mainly when a randomized clinical trial is not possible. We review recent applications of HC in clinical trials, in which either predominantly a large treatment effect overcame concerns about bias, or the trial targeted a life-threatening disease with no treatment options. In contrast, we address how the evidentiary standard of a trial can be strengthened with optimized study designs and analysis strategies, emphasizing rare and pediatric indications. We highlight the importance of simulation and sensitivity analyses for estimating the range of uncertainties in the estimation of treatment effect when traditional randomization is not possible. Overall, the paper provides a roadmap for using HCs.
Development and validation of the prognostic value of ferritin in adult patients with Hemophagocytic Lymphohistiocytosis
Authors: Zhou Jun , Zhou Jing , Shen Dan-Ting , Goyal Hemant , Wu Zhi-Qi , Xu Hua-Guo
Published: March 2020

Background

Hemophagocytic Lymphohistiocytosis (HLH) is a rare clinical syndrome with high mortality rate. The diagnosis of HLH draws on a constellation of clinical and laboratory abnormalities including extremely high serum ferritin levels. However, no biomarker has been firmly established as a clinically useful prognostic tool in HLH patients. We aimed to perform a retrospective analysis of two independent cohorts to explore the prognostic value of discharge serum ferritin for newly diagnosed adult HLH patients who recently started treatment. The prognostic value of serum ferritin levels at discharge (will be called as post-treatment ferritin level) was initially evaluated in a “test cohort” of 161 previously untreated consecutive adult HLH patients. It was then validated in a second cohort of 68 consecutive previously untreated patients (validation cohort).

Results

Multivariate analysis revealed that significantly high post-treatment serum ferritin levels (>1050 μg/L) were associated with a higher risk of death and poor overall survival in the test cohort (hazard ratio (HR): 3.176, 95% confidence interval (CI) 1.468–6.869, P = 0.003), and the validation cohort (HR: 13.412, 95%CI 1.716–104.816, P = 0.013). At 6-month follow-up period in the test cohort, patients with a > 81% decrease in the serum ferritin level had a significantly higher probability of survival when compared with the patients with ≥14% increase in the serum ferritin level (94% vs. 31%, P < 0.001). Similar findings were observed on the analysis of the decrease in the serum ferritin level in the validation cohort.

Conclusions

These results suggest that the serum ferritin level can be used as an independent prognostic marker in the adult HLH patients.
Health, wellbeing and lived experiences of adults with SMA: a scoping systematic review
Authors: Wan Hamish W. Y. , Carey Kate A. , D’Silva Arlene , Vucic Steve , Kiernan Matthew C. , Kasparian Nadine A. , Farrar Michelle A.
Published: March 2020

Background

Spinal muscular atrophy (SMA) is a neurodegenerative disease that has a substantial and multifaceted burden on affected adults. While advances in supportive care and therapies are rapidly reshaping the therapeutic environment, these efforts have largely centered on pediatric populations. Understanding the natural history, care pathways, and patient-reported outcomes associated with SMA in adulthood is critical to advancing health policy, practice and research across the disease spectrum. The aim of this study was to systematically review research investigating the healthcare, well-being and lived experiences of adults with SMA.

Methods

In accordance with the Preferred Reported Items for Systematic Reviews and Meta-Analysis guidelines, seven electronic databases were systematically searched until January 2020 for studies examining clinical (physical health, natural history, treatment) and patient-reported (symptoms, physical function, mental health, quality of life, lived experiences) outcomes in adults with SMA. Study risk of bias and the level of evidence were assessed using validated tools.

Results

Ninety-five articles met eligibility criteria with clinical and methodological diversity observed across studies. A heterogeneous clinical spectrum with variability in natural history was evident in adults, yet slow declines in motor function were reported when observational periods extended beyond 2 years. There remains no high quality evidence of an efficacious drug treatment for adults. Limitations in mobility and daily activities associated with deteriorating physical health were commonly reported, alongside emotional difficulties, fatigue and a perceived lack of societal support, however there was no evidence regarding effective interventions.

Conclusions

This systematic review identifies the many uncertainties regarding best clinical practice, treatment response, and long-term outcomes for adults with SMA. This comprehensive identification of the current gaps in knowledge is essential to guide future clinical research, best practice care, and advance health policy with the ultimate aim of reducing the burden associated with adult SMA.
Reversal of ABCB1-related multidrug resistance by ERK5-IN-1
Authors: Wang Fang , Li Delan , Zheng ZongHeng , Kin Wah To Kenneth , Chen Zhen , Zhong Mengjun , Su Xiaodong , Chen Likun , Fu Liwu
Published: March 2020

Background

Inhibition of ABC transporters is considered the most effective way to circumvent multidrug resistance (MDR). In the present study, we evaluated the MDR modulatory potential of ERK5-IN-1, a potent extracelluar signal regulated kinase 5 (ERK5) inhibitor.

Methods

The cytotoxicity and MDR reversal effect of ERK5-IN-1 were assessed by MTT assay. The KBv200-inoculated nude mice xenograft model was used for the in vivo study. Doxorubicin efflux and accumulation were measured by flow cytometry. The modulation of ABCB1 activity was measured by colorimetric ATPase assay and [125I]-iodoarylazidoprazosin (IAAP) photolabeling assay. Effect of ERK5-IN-1 on expression of ABCB1 and its downstream markers was measured by PCR and/or Western blot. Cell surface expression and subcellular localization of ABCB1 were tested by flow cytometry and immunofluorescence.

Results

Our results showed that ERK5-IN-1 significantly increased the sensitivity of vincristine, paclitaxel and doxorubicin in KBv200, MCF7/adr and HEK293/ABCB1 cells, respectively. This effect was not found in respective drug sensitive parental cell lines. Moreover, in vivo combination studies showed that ERK5-IN-1 effectively enhanced the antitumor activity of paclitaxel in KBv200 xenografts without causing addition toxicity. Mechanistically, ERK5-IN-1 increased intracellular accumulation of doxorubicin dose dependently by directly inhibiting the efflux function of ABCB1. ERK5-IN-1 stimulated the ABCB1 ATPase activity and inhibited the incorporation of [125I]-iodoarylazidoprazosin (IAAP) into ABCB1 in a concentration-dependent manner. In addition, ERK5-IN-1 treatment neither altered the expression level of ABCB1 nor blocked the phosphorylation of downstream Akt or Erk1/2. No significant reversal effect was observed on ABCG2-, ABCC1-, MRP7- and LRP-mediated drug resistance.

Conclusions

Collectively, these results indicated that ERK5-IN-1 efficiently reversed ABCB1-mediated MDR by competitively inhibiting the ABCB1 drug efflux function. The use of ERK5-IN-1 to restore sensitivity to chemotherapy or to prevent resistance could be a potential treatment strategy for cancer patients.
Assisted mechanical ventilation promotes recovery of diaphragmatic thickness in critically ill patients: a prospective observational study
Authors: Grassi Alice , Ferlicca Daniela , Lupieri Ermes , Calcinati Serena , Francesconi Silvia , Sala Vittoria , Ormas Valentina , Chiodaroli Elena , Abbruzzese Chiara , Curto Francesco , Sanna Andrea , Zambon Massimo , Fumagalli Roberto , Foti Giuseppe , Bellani Giacomo
Published: March 2020

Background

Diaphragm atrophy and dysfunction are consequences of mechanical ventilation and are determinants of clinical outcomes. We hypothesize that partial preservation of diaphragm function, such as during assisted modes of ventilation, will restore diaphragm thickness. We also aim to correlate the changes in diaphragm thickness and function to outcomes and clinical factors.

Methods

This is a prospective, multicentre, observational study. Patients mechanically ventilated for more than 48 h in controlled mode and eventually switched to assisted ventilation were enrolled. Diaphragm ultrasound and clinical data collection were performed every 48 h until discharge or death. A threshold of 10% was used to define thinning during controlled and recovery of thickness during assisted ventilation. Patients were also classified based on the level of diaphragm activity during assisted ventilation. We evaluated the association between changes in diaphragm thickness and activity and clinical outcomes and data, such as ventilation parameters.

Results

Sixty-two patients ventilated in controlled mode and then switched to the assisted mode of ventilation were enrolled. Diaphragm thickness significantly decreased during controlled ventilation (1.84 ± 0.44 to 1.49 ± 0.37 mm, p < 0.001) and was partially restored during assisted ventilation (1.49 ± 0.37 to 1.75 ± 0.43 mm, p < 0.001). A diaphragm thinning of more than 10% was associated with longer duration of controlled ventilation (10 [5, 15] versus 5 [4, 8.5] days, p = 0.004) and higher PEEP levels (12.6 ± 4 versus 10.4 ± 4 cmH2O, p = 0.034). An increase in diaphragm thickness of more than 10% during assisted ventilation was not associated with any clinical outcome but with lower respiratory rate (16.7 ± 3.2 versus 19.2 ± 4 bpm, p = 0.019) and Rapid Shallow Breathing Index (37 ± 11 versus 44 ± 13, p = 0.029) and with higher Pressure Muscle Index (2 [0.5, 3] versus 0.4 [0, 1.9], p = 0.024). Change in diaphragm thickness was not related to diaphragm function expressed as diaphragm thickening fraction.

Conclusion

Mode of ventilation affects diaphragm thickness, and preservation of diaphragmatic contraction, as during assisted modes, can partially reverse the muscle atrophy process. Avoiding a strenuous inspiratory work, as measured by Rapid Shallow Breathing Index and Pressure Muscle Index, may help diaphragm thickness restoration.
Improved recording of work relatedness during patient consultations in occupational primary health care: a cluster randomized controlled trial using routine data
Authors: Atkins Salla , Reho Tiia , Talola Nina , Sumanen Markku , Viljamaa Mervi , Uitti Jukka
Published: March 2020

Background

Prolonging working careers is a key policy goal in ageing populations in Europe, but reaching this goal is complex. Occupational health services are in the best position to contribute towards prolonging working careers through preventing illnesses that cause work disability and early retirement. However, impacting on the trajectory between illness and work disability requires continuity of care and follow up, enabled through identifying patients at risk. We aimed to determine whether a combined educational and electronic reminder system in occupational health care could improve the recording and follow up of primary care visits made by patients at risk of work disability, and whether the system could impact on sickness absence rates.

Methods

This study is a pragmatic, cluster-randomized controlled trial using medical record data. Twenty-two Pihlajalinna Työterveys units were randomized into an intervention group receiving education and electronic reminders or a group receiving usual care through minimization methods. Patient consultation data were extracted from routine Pihlajalinna Työterveys patient registers from 2015 to 2017. In addition, process indicators were collected from the electronic system. Data were cleaned and analysed on an intention-to-treat basis using analysis of covariance.

Results

There was no significant difference between intervention and control units in terms of sickness absences of different duration. Process indicators suggested that there was a change in physicians’ practice of recording patients’ risk of work disability and work-relatedness of visits following the educational intervention.

Conclusion

Education with an electronic reminder can change physicians’ practice, but long-term follow up is needed to determine whether this impacts on patients’ sickness absences.

Trial registration

ISRCTN Registry: ISRCTN45728263. Registered on 12 April 2016.
Correction to: 3D vs. 4 K Display System - Influence of “State-of-the-art”-Display Technique On Surgical Performance (IDOSP-Study) in minimally invasive surgery: protocol for a randomized cross-over trial
Authors: Wahba Roger , Datta Rabi Raj , Hedergott Andrea , Bußhoff Jana , Bruns Thomas , Kleinert Robert , Dieplinger Georg , Fuchs Hans , Gietzelt Caroline , Möller Desdemona , Hellmich Martin , Bruns Christiane J. , Stippel Dirk L.
Published: March 2020

After publication of our article [1] the authors have notified us that one of the names has been incorrectly spelled.
Why do patients take part in research? An overview of systematic reviews of psychosocial barriers and facilitators
Authors: Sheridan Rebecca , Martin-Kerry Jacqueline , Hudson Joanna , Parker Adwoa , Bower Peter , Knapp Peter
Published: March 2020

Background

Understanding why people take part in health research is critical to improve research efficiency and generalisability. The aim of this overview of systematic reviews was to identify psychosocial determinants of research participation and map them to psychological theory and empirical recruitment research, to identify effective strategies to increase research participation.

Methods

Qualitative and quantitative systematic reviews were systematically identified. No date or language limits were applied. Two reviewers independently selected reviews. Methodological quality was rated using AMSTAR, and poor-quality reviews (scoring 0–3) were excluded. Barriers and facilitators were coded to psychological theory (Theoretical Domains Framework) and empirical recruitment research (recruitment interventions that had been subjected to randomised controlled trial evaluation).

Results

We included 26 systematic reviews (429 unique primary studies), covering a wide range of patient populations and health settings. We identified five groups of facilitators, of which three were dominant (potential for personal benefit, altruism, trust) and appear to be relevant across research setting and design. We identified nine groups of barriers, which were more dependent on the particular study (context, population, design). Two determinants (participant information, social influences) were found to be both barriers and facilitators. Barriers and facilitators could be coded to the Motivation and Opportunity components of the Theoretical Domains Framework; only one was coded to a Capability component. There was some overlap between psychosocial determinants and empirical recruitment research, but some barriers and facilitators had not been tested at all.

Conclusions

Identifying effective recruitment strategies could increase the efficiency and generalisability of primary research. We identified a number of barriers and facilitators that could be addressed by researchers. There is a need for more research to identify effective recruitment strategies that draw on the psychosocial facilitators and barriers identified in this overview.
Camelina sativa meal hydrolysate as sustainable biomass for the production of carotenoids by Rhodosporidium toruloides
Authors: Bertacchi Stefano , Bettiga Maurizio , Porro Danilo , Branduardi Paola
Published: March 2020

Background

As the circular economy advocates a near total waste reduction, the industry has shown an increased interest toward the exploitation of various residual biomasses. The origin and availability of biomass used as feedstock strongly affect the sustainability of biorefineries, where it is converted in energy and chemicals. Here, we explored the valorization ofCamelinameal, the leftover residue fromCamelina sativaoil extraction. In fact, in addition toCamelinameal use as animal feed, there is an increasing interest in further valorizing its macromolecular content or its nutritional value.

Results

Camelinameal hydrolysates were used as nutrient and energy sources for the fermentation of the carotenoid-producing yeastRhodosporidium toruloidesin shake flasks. Total acid hydrolysis revealed that carbohydrates accounted for a maximum of 31 ± 1.0% ofCamelinameal. However, because acid hydrolysis is not optimal for subsequent microbial fermentation, an enzymatic hydrolysis protocol was assessed, yielding a maximum sugar recovery of 53.3%. Separate hydrolysis and fermentation (SHF), simultaneous saccharification and fermentation (SSF), and SSF preceded by presaccharification ofCamelinameal hydrolysate produced 5 ± 0.7, 16 ± 1.9, and 13 ± 2.6 mg/L of carotenoids, respectively. Importantly, the presence of water-insoluble solids, which normally inhibit microbial growth, correlated with a higher titer of carotenoids, suggesting that the latter could act as scavengers.

Conclusions

This study paves the way for the exploitation ofCamelinameal as feedstock in biorefinery processes. The process under development provides an example of how different final products can be obtained from this side stream, such as pure carotenoids and carotenoid-enrichedCamelinameal, can potentially increase the initial value of the source material. The obtained data will help assess the feasibility of usingCamelinameal to generate high value-added products.
Correction to: Identification and molecular characterization of Wolbachia strains in natural populations of Aedes albopictus in China
Authors: Hu Yaping , Xi Zhiyong , Liu Xiaobo , Wang Jun , Guo Yuhong , Ren Dongsheng , Wu Haixia , Wang Xiaohua , Chen Bin , Liu Qiyong
Published: March 2020

Following publication of the original article [1], the corresponding author flagged that the article had published with two errors.
Fault localization by analyzing failure propagation with samples in cloud computing environment
Authors: Wang Tiantian , Wang Kechao , Su Xiaohong
Published: March 2020

With the development of information technology such as cloud computing, IoT, etc, software becomes the infrastructure. On the one hand, it is critical to ensure the reliability of software, on the other, sample code can be mined from open source software to provide reference for automatic debugging. Most of existing automated debugging researches are based on the assumption that defect programs are nearly correct, therefore they can successfully pass some test cases and fail to execute others. However, this assumption sometimes does not hold. In view of the fact that a programs may fail for all the given test cases in the test suite, but there are a large number of examples available for reference, a sample based fault localization method is studied. A fault localization method by analyzing the context of failure propagation is proposed, which locates suspicious statements by identifying the execution status and structural semantics differences between the defective program and sample program. Through the interactive analysis of value sequences and structure semantics, the influence of code variations and failure propagation is reduced. The experimental results have shown that the method can effectively locate suspicious statements and provide assistance for defect repair when there are enough sample programs.
Challenges and opportunities for China entering global research and development for emerging infectious diseases: a case study from Ebola experience
Authors: Li Chao , Chen Jing-Yi , Huang Yang-Mu
Published: March 2020

Background

China has emerged as a powerful platform for global pharmaceutical research and development (R&D) amid the 2014 Ebola outbreak. The research and development impact of developing countries on prevention and control of infectious disease outbreaks has long been underestimated, particularly for emerging economies like China. Here, we studied its research and development progress and government support in response to Ebola outbreak by timeline, input, and output at each research and development stage. This study will contribute to a deeper understanding of the research and development gaps and challenges faced by China, as well as providing evidence-based suggestions on how to accelerate the drug development process to meet urgent needs during future outbreaks.

Methods

Data were obtained from the National Nature Science Foundation of China database, PubMed database, Patent Search System of the State Intellectual Property Office of China, National Medical Products Administration, national policy reports and literature between Jan 1st, 2006 and Dec 31st, 2017. An overview of research funding, research output, pharmaceutical product patent, and product licensed was described and analyzed by Microsoft Excel. A descriptive analysis with a visualization of plotting charts and graphs was conducted by reporting the mean ± standard deviation.

Results

China has successfully completed the research and development of the Ebola Ad5-EBOV vaccine within 26 months, while the preparation and implementation of clinical trials took relative long time. The National Nature Science Foundation of China funded CNY 44.05 million (USD 6.27 million) for Ebola-related researches and committed strongly to the phase of basic research (87.8%). A proliferation of literature arose between 2014 and 2015, with a 1.7-fold increase in drug research and a 2.5-fold increase in diagnostic research within 1 year. Three years on from the Ebola outbreak, six Ebola-related products in China were approved by the National Medical Products Administration.

Conclusions

China has started to emphasize the importance of medical product innovation as one of the solutions for tackling emerging infectious diseases. Continuing research on the development of regulatory and market incentives, as well as a multilateral collaboration mechanism that unifies cross-channel supports, would advance the process for China to enter global R&D market more effectively.
Current landscape and influence of big data on finance
Authors: Hasan Md. Morshadul , Popp József , Oláh Judit
Published: March 2020

Big data is one of the most recent business and technical issues in the age of technology. Hundreds of millions of events occur every day. The financial field is deeply involved in the calculation of big data events. As a result, hundreds of millions of financial transactions occur in the financial world each day. Therefore, financial practitioners and analysts consider it an emerging issue of the data management and analytics of different financial products and services. Also, big data has significant impacts on financial products and services. Therefore, identifying the financial issues where big data has a significant influence is also an important issue to explore with the influences. Based on these concepts, the objective of this paper was to show the current landscape of finance dealing with big data, and also to show how big data influences different financial sectors, more specifically, its impact on financial markets, financial institutions, and the relationship with internet finance, financial management, internet credit service companies, fraud detection, risk analysis, financial application management, and so on. The connection between big data and financial-related components will be revealed in an exploratory literature review of secondary data sources. Since big data in the financial field is an extremely new concept, future research directions will be pointed out at the end of this study.
Bayesian hierarchical analyses for entrepreneurial intention of students
Authors: Ayalew Mesfin Mulu
Published: March 2020

In recent years, entrepreneurship has become an important issue due to national economic development and the contribution of society. Data with a hierarchical structure received more attention and occur frequently in social science, public health and epidemiological researches. In such research, binary outcomes are common. Multilevel logistic regression models allow one to account for the clustering of subjects within clusters of higher-level units when estimating the effect of subject and cluster characteristics on subject outcomes. Traditional logistic regression is inappropriate when data are hierarchically structured. Therefore, this study presents multi-level Bayesian logistic analysis for entrepreneurial intention of students using classical and Bayesian approach. The descriptive result revealed that about 57.4% of the students had an entrepreneurial intention while 42.6% do not have an intention. The results also showed that entrepreneurial education/training and entrepreneurial attitudes significantly predicts students’ entrepreneurial intention at 5% level of significance. The model results indicate that the effects of the selected variable on entrepreneurial intention vary across university. By failing to take into account the clustering within university (level 2), Bayesian multilevel effects are not taken into consideration in modeling, the β coefficients in multilevel logistic model using classical approach are distorted somewhat in both directions either in over or under direction. This study also evaluates and compares the behavior of maximum likelihood and Bayesian estimators to investigate the relationship between covariates and the response. Both point and interval estimation performances were investigated. The results revealed that lower standard errors of the estimated coefficients in the Bayesian logistic regression approach as compared to classical approach. Moreover, the results revealed that the length of the Bayesian credible interval is smaller than the length of the maximum likelihood confidence interval for all factors. In order to identify the most plausible method between Bayesian method and maximum likelihood estimation of the data, AIC, BIC and DIC are adopted in this paper. The result of the study depicts that the Bayesian method performs better and more efficient than maximum likelihood estimation. The study recommends that the government as well as the universities should design programs that facilitate entrepreneurship to change the mindset, attitude, and intention of those students who do not have knowhow about entrepreneurship as a future career.
Occurrence characteristics of electromagnetic ion cyclotron waves at sub-auroral Antarctic station Maitri during solar cycle 24
Authors: Upadhyay Aditi , Kakad Bharati , Kakad Amar , Omura Yoshiharu , Sinha Ashwini Kumar
Published: March 2020

We present a statistical study of electromagnetic ion cyclotron (EMIC) waves observed at Antarctic station (geographic $$70.7{^\circ }\,\hbox {S}$$70.7∘S, $$11.8{^\circ }\,\hbox {E}$$11.8∘E, $$L=5$$L=5) on quiet and disturbed days during 2011–2017. The data span a fairly good period of both ascending and descending phases of the solar cycle 24, which has witnessed extremely low activity. We noted EMIC wave occurrence by examining wave power in different frequency ranges in the spectrogram. EMIC wave occurrence during ascending and descending phases of solar cycle 24, its local time, seasonal dependence and durations have been examined. There are total 2367 days for which data are available. Overall, EMIC waves are observed for 3166.5 h ($$\approx 5.57\%$$≈5.57% of total duration) which has contributions from 1263 days. We find a significantly higher EMIC wave occurrence during the descending phase ($$\approx$$≈ 6.83%) as compared to the ascending phase ($$\approx$$≈ 4.08%) of the solar cycle, which implies nearly a twofold increase in EMIC wave occurrence. This feature is attributed to the higher solar wind dynamic pressure during descending phase of solar activity. There is no evident difference in the percentage occurrence of EMIC waves on magnetically disturbed and quiet days. On ground, EMIC waves show marginally higher occurrence during winter as compared to summer. This seasonal tendency is attributed to lower electron densities and conductivities in the ionosphere, which can affect the propagation of EMIC waves through ionospheric ducts. In local time, the probability distribution function of EMIC wave occurrence shows enhancement during 11.7–20.7 LT (i.e., afternoon–dusk sector). Daily durations of EMIC waves are in the range of 5–1015 min and it is noted that the longer duration (240–1015 min) events are prevalent on quiet days and are mostly seen during the descending phase of solar cycle.
Free viewpoint image generation system using fisheye cameras and a laser rangefinder for indoor robot teleoperation
Authors: Komatsu Ren , Fujii Hiromitsu , Tamura Yusuke , Yamashita Atsushi , Asama Hajime
Published: March 2020

In robot teleoperation, a lack of depth information often results in collisions between the robots and obstacles in its path or surroundings. To address this issue, free viewpoint images can greatly benefit the operators in terms of collision avoidance as the operators are able to view the robot’s surrounding from the images at arbitrary points, giving them a better depth information. In this paper, a novel free viewpoint image generation system is proposed. One approach to generate free viewpoint images is to use multiple cameras and Light Detection and Ranging (LiDAR). Instead of using the expensive LiDAR, this study utilizes a cost-effective laser rangefinder (LRF) and a characteristic of man-made environments. In other words, we install multiple fisheye cameras and an LRF on a robot. Free viewpoint images are generated under the assumption that walls are perpendicular to the floor. Furthermore, an easy calibration for estimating the poses of the multiple fisheye cameras, the LRF, and the robot model is proposed. Experimental results show that the proposed method can generate free viewpoint images using cameras and an LRF. Finally, the proposed method is primarily implemented using OpenGL Shading Language to utilize a graphics processing unit computation to achieve a real-time processing of the multiple high-resolution images. Supplementary videos and our source code are available at our project page (https://matsuren.github.io/fvp).
Impact of date palm pollen (Phoenix dactylifera) treatment on paracetamol-induced hepatorenal toxicity in rats
Authors: Al-Asmari Abdulrahman Khazim , Al-Said Mansour S. , Abbasmanthiri Rajamohamed , Al-Buraidi Ahmed , Ibrahim Khalid Elfaki , Rafatullah Syed
Published: March 2020

Background

Consumption of plant-derived nutraceuticals and crude drugs in Arab traditional medicine is widely believed to confer beneficial effects in liver and kidney diseases. Fruits from the date palmPhoenix dactyliferaL. are a rich source of nutrients and bioactive phytochemicals which possess a myriad of pharmacological effects. Herein, we examined the impact of Date Palm Pollen (DPP) aqueous suspension treatment on paracetamol (APAP) [Acetaminophen (APAP)] triggered hepatorenal damage in rats and further explored the underlying putative mechanism.

Methods

Thirty Wistar rats were assigned to five groups (n = 6/group). Group I was control group; animals in group II were administered APAP 1000 mg/kg body weight (b.w.) intraperitonealy (i.p.); Group III and IV administered APAP plus date palm pollen with doses of 50, 100 mg/kg b.w and group V were administered APAP plus Silymarin (SIL) 10 mg/kg b.w. (i.p) respectively. Various biochemical parameters and histological assessment were evaluated in serum and tissue homogenate.

Results

Pretreatment with DPP aqueous suspensions (50 and 100 mg/kg b.w.) significantly (p < 0.05) thwarted APAP triggered alterations in serum biomarkers of liver damage [aspartate transaminase (AST), alanine aminotransferase (ALT), γ-glutamyl transferase (GGT) and alkaline phosphatase (ALP)], serum albumin as well as bilirubin. DPP treatment further mitigated APAP triggered dyslipidemia associated with hepatic damage by influencing APAP elicited changes in serum levels of cholesterol, triglycerides, HDL, LDL and VLDL. DPP treatment significantly (p < 0.05) ameliorated extrahepatic manifestations of APAP toxicity by influencing alterations in parameters of renal function (creatinine, urea and uric acid) as well serum electrolytes (Sodium, Potassium and Calcium). DPP treatment further influenced APAP-induced histological lesions by curtailing necrosis and inflammatory changes in the hepatic and renal architecture, respectively. Furthermore, DPP treatment modulated APAP-induced redox imbalance in the hepatic and renal tissue by blunting the increase of malondialdehyde (MDA) as well as decrease of nonprotein sulfhydryls (NP-SH) significantly (p < 0.05) when compared with control. The protective effect of DPP was further confirmed histologically.

Conclusions

The present observations point to an hepatorenal protective effects of acute DPP treatment in APAP-intoxicated rats which is underpinned by its robust antioxidant properties.
Phase II/III randomized trial of CID-ATT with radiotherapy compared with CHOP with radiotherapy as first-line treatment for previously untreated early staging extranodal NK/T-cell lymphoma, nasal type (ENKL).
Authors: Lin Tongyu , Huang He , Liang Chao Yong , Guo Chengcheng , Tian Ying , Liu Tingzhi , Li Xue Ying , Zhang Mengping , Hong Huang Ming , Shrestha Dr.Prem Raj
Published: March 2020

8508

Background: Extranodal NK/T cell lymphoma, nasal type (ENKL) is more prevalent in Asia and has worse prognosis than B-NHL. No therapeutic strategy is currently identified for ENKL. This phase II/III study was undertaken to compare CHOP-B/IMVD/DHAP-Alternating Triple Therapy (CID-ATT) and standard CHOP regimen as first-line treatment prospectively. Methods:109 patients (pts) initially diagnosed as ENKL (16-70 ys old) with Ann Abor Stage I to II were randomized to receive CID-ATT or CHOP regimen from Jan 2006 to Jan 2012. CID-ATT alternated among CHOP-B, IMVD, and DHAP, given in alternating sequence for a total of 6 courses (2 circle). Involved field radiation was administered after 6 courses(2 circle) of CID-ATT regimen or 6 cycles of CHOP regimen. All pts received prophylactic granulocyte colony-stimulating factor, interleukin-11and thrombopoietin for each DHAP cycle. Results: 109 pts were evaluable (54CID-ATT; 55 CHOP). With a median follow-up of 40.3months,OS and PFS was significantly prolonged with CID-ATT compared with CHOP (1yOS :80.2% vs 78.6%, 3yOS:68.0% vs 42.3%, 5yOS: 64.2% vs 34.5%,P=0.023; 1yPFS: 74.9% vs 59.6%, 3yPFS:60.5% vs 32.0%, 5yPFS: 60.5% vs 32.0% ; P=0.016). Compared to CHOP group, CID-ATT group has a much higher complete remission rate (CID-ATT:47/54,87.0 % vs CHOP:29/55,52.7%, P<0.001). The survivals for pts who achieved CR after One circle (3 courses) were significantly better than those who were in non-CR group.(5yOS: CR group in ATT:75.3%, non-CR group in ATT:51.5%, CR group in CHOP:39.3%, non-CR group in CHOP:31.0%; P=0.003). No treatment related death was observed, although Grade III/IV neutropenia (30/54,55.6%) and thrombocytopenia (33/54,61.1%) were observed in CID-ATT regimen, especially in DHAP cycle. Conclusions: Our study has demonstrated that the CID-ATT regimen as an optimal first-line therapy achieved promising clinical activity with safe and tolerated toxicity under close monitoring and good supportive care of untreated early staging ENKL pts. CR of induce chemotherapy following radiotherapy is very important for ENKL survival. Clinical trial information: CSWOG0002.
Phase I/II dose-escalation study of daratumumab in patients with relapsed or refractory multiple myeloma.
Authors: Lokhorst Henk M , Plesner Torben , Gimsing Peter , Nahi Hareth , Minnema Monique , Lassen Ulrik Niels , Krejcik Jakub , Laubach Jacob , Lisby Steen , Basse Linda , Richardson Paul Gerard Guy
Published: March 2020

8512^

Background: Daratumumab (DARA) is a human CD38 monoclonal antibody (mAb) with broad-spectrum killing activity. Preliminary safety and efficacy data from this first-in-human dose-escalation study of DARA in pts with relapsed or refractory (RR) multiple myeloma (MM) have previously been published. Here, we present safety and efficacy data from the finalized part 1 and preliminary safety data from the ongoing part 2 of the study. Methods: Pts ≥18 years requiring systemic therapy and considered RR to at least 2 prior lines of therapy and ineligible for ASCT were enrolled. In part 1, a 3+3 dose-escalation design was applied and DARA was administered over a 9-week period as 2 pre- and 7 full doses. The phase II dose was determined to 8mg/kg and these pts receive DARA weekly for 8 weeks followed by dosing every 2nd week for 16 weeks and every 4th week until disease progression, toxicity or for max. 24 months. Results: Data from 32 pts included in part 1 are presented. In part 2, 7/16 pts have been recruited: all available data will be presented at the meeting. In part 1, the median number of prior treatment lines was 6. PK analysis showed plasma peak levels as expected but relatively rapid clearance at low dose levels. At doses ≥4mg/kg, observed PK values approximated model-predicted values. Efficacy evaluation from part 1 was based on IMWG guidelines. In the ≥4mg/kg groups (n=12), 5 PRs and 3 MRs were observed. 7 of these pts had a 50-100% concomitant reduction in bone marrow plasma cells. Median PFS in the ≥4mg/kg dose groups was not reached (median follow-up at data cut-off was 3.8mths (range: 0-9.6mths). No ADA responses were detected. In part 1, the most common adverse events reported were infusion related (IRE) which occurred predominantly during the first full infusion. 44% of subjects across all dose groups had IREs grade 1-3, of which 2 were grade 3. Six related SAEs (1 anemia, 1 thrombocytopenia, 2 bronchospasm, 1 cytokine release, 1 AST increase) were reported. Conclusions: DARA induced a marked reduction in paraprotein and bone marrow plasma cells at doses ≥4mg/kg in heavily pretreated RR MM pts. In addition, high response rates and encouraging PFS data were observed. This is unprecedented for single-agent mAb treatment of MM. Clinical trial information: NCT00574288.