bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Detection of Steroid-Induced Femoral Head Necrosis using 99mTc-Cys-Annexin V-based Apoptosis Imaging in a Rabbit Model
Authors: Wang Xiaolong , Li Jianbo , Man Da , Liu Rui , Zhao Jianmin 
Published: November 2020

Abstract
BackgroundAt present, the early diagnosis of femoral head necrosis mainly relies on Magnetic resonance imaging (MRI), and most early patients are difficult to make an accurate diagnosis. Therefore, to investigate the early diagnostic value of 99mTc-Cys-Annexin V Single-photon emission computed tomography (SPECT) imaging were compared with MRI in rabbit models of steroid-induced femoral head necrosis.MethodsThe animal model of steroid-induced femoral head necrosis (SIFHN) was established in 5-month-old healthy New Zealand white rabbits by injecting horse serum into ear vein and methylprednisolone into gluteal muscle, the purpose of modeling is to simulate the actual clinical situation of SIFNH. 99mTc-Cys-Annexin V SPECT imaging and MRI were performed at 2nd week, 4th week, and 6th week after modeling. After that, histopathology was used to verify the success of modeling. Apoptosis was detected by transmission electron microscopy (TEM) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL). ResultsAt 2 weeks after the injection of hormone, 99mTc-Cys-Annexin V SPECT image showed abnormal radioactive uptake in the bilateral femoral head. And over time, the radioactivity concentration was more obvious, and the ratio of T/NT (target tissue/non-target tissues, which is the ratio of femoral head and the ipsilateral femoral shaft) was gradually increased. In the 99mTc-Cys-Annexin V SPECT imaging at each time point, T/NT ratio of the model group was significantly higher than that of the control group (P < 0.01); at 4 weeks after the injection of hormone, MRI showed an abnormal signal of osteonecrosis. At 2, 4, and 6 weeks after hormone injection, apoptosis was observed by TUNEL and TEM. Conclusions99mTc-Cys-Annexin V SPECT imaging can diagnose steroid-induced femoral head necrosis earlier than MRI, and has potential application value for non-invasively detecting early and even ultra-early stage of femoral head necrosis.
A novel circular RNA circ-LRIG3 facilitates the malignant progression of hepatocellular carcinoma by modulating the EZH2/STAT3 signaling
Authors: Sun Suofeng , Gao Jing , Zhou Shen , Li Yuan , Wang Yu , Jin Li , Li Jian , Liu Bowei , Zhang Bingyong , Han Shuangyin , Ding Hui , Li Xiuling 
Published: November 2020

Abstract
Background: Circular RNA (circRNA) is emerging as an important player in human diseases, especially cancer. In our previous study, we identified a series of deregulated circRNAs in hepatocellular carcinoma (HCC) by performing circRNA microarray expression profile. Here, we aimed to explore the role of circ-LRIG3 (hsa_circ_0027345) in HCC.Methods: qRT-PCR and western blot were used to asses gene and protein expression, respectively. CCK-8, EdU and Transwell assays were used to detect cell proliferation, migration and invasion. GSEA software was applied to analyze the pathway related to circ-LRIG3. Co-IP, RIP and ChIP assays were used to identify the positive feedback axis of circ-LRIG3/EZH2/STAT3. Animal study was carried to test the role of circ-LRIG3 in vivo.Results: Circ-LRIG3 was notably upregulated in HCC and promoted HCC cell proliferation, migration, invasion and reduced apoptosis. Circ-LRIG3 formed a ternary complex with EZH2 and STAT3, facilitating EZH2-induced STAT3 methylation and subsequent phosphorylation, resulting in the activation of STAT3 signaling. In turn, activated STAT3 could directly bind to circ-LRIG3 promoter to increase circ-LRIG3 transcription activity, thus forming a positive feedback loop. The animal models showed that exogenous expression of circ-LRIG3 enhanced tumorigenicity and metastasis in vivo, whereas these effects were blocked after treatment with C188-9, a specific STAT3 small-molecule inhibitor. Clinically, high circ-LRIG3 was closely linked with aggressive clinicopathological features and was identified as an independent risk prognostic factor of overall survival. Importantly, plasma circ-LRIG3 was found to be a highly sensitive and specific non-invasive diagnostic indicator for HCC. Conclusions: Our study reveals the carcinogenic role of circ-LRIG3 in HCC, which may provide a new therapeutic target for HCC patients.
Mingjing Granule, a Traditional Chinese Medicine in the treatment of neovascular age-related macular degeneration: study protocol for a randomized controlled trial
Authors: Li Yamin , Liang Lina , Snellingen Torkel , Xu Kai , Gao Yun , Zhang Fengmei , Guo Chengwei , Zuo Tao , Liang Fengming , Yao Xiaoping , Yang Xueyan 
Published: November 2020

Abstract
BackgroundNeovascular age-related macular degeneration (nAMD) is the most common cause of irreversible vision loss and blindness among the elderly people aged 50 and over. Although anti-vascular endothelial growth factor(anti-VEGF) therapies have resulted in improving patient outcomes, there are limitations associated with these treatments. In China, Traditional Chinese medicine(TCM) has been used to treat eye diseases for more than 2000 years. Previous studies have shown that TCM may be beneficial for nAMD patients. However, explicit evidence has not been obtained. The purpose of the present trial is to examine the efficacy and safety of the Mingjing Granule, a compound Chinese herbal medicine, for nAMD patients. Methods/DesignThis is a double-blind, placebo-controlled, randomized trial of Mingjing Granule as an add-on to intravitreous ranibizumab for nAMD. 180 nAMD patients from six hospitals in China will be enrolled according to the inclusion and exclusion criteria, and randomly allocated into two groups, 90 in each. All participants will receive a 24-week treatment and then be followed-up for another 24 weeks. The primary outcome is the mean change of best-corrected visual acuity at week 24 and 48 as compared to the baseline. The secondary outcomes include mean change in central retinal thickness, area of retinal hemorrhage and exudation, and TCM syndrome score, mean number of intravitreal ranibizumab injection and total cost of the treatment. Indexes of safety include blood regular test, urine regular test, liver function test, renal function test and electrocardiogram from baseline to week 24 and 48. Qualitative control and some standard operating processes will be formed throughout the trial. Any ocular or systemic adverse events will be treated suitably and related data will be recorded accurately and completely in the case report form.DiscussionBased on previous empirical and animal laboratory studies, this study will address the question of whether Mingjing Granule could contribute to improving efficacy, safety and efficiency with need for fewer intravitreal injections of anti-VEGF, improving compliance and visual outcomes in the management of persons with nAMD.Trial registrationChinese Clinical Trial Registry (http://www.chictr.org.cn), ChiCTR2000035990. Registered on 21 August 2020.
Minimizing the cost of a curved corner trapezoidal canal section
Authors: Fattouh Ehab M. , Saad Neveen Y. 
Published: November 2020

Abstract
Designing a curved corner trapezoidal channel section with a minimal cost, which is the study's objective function, encompasses minimizing the channel lining and excavation costs. The discharge, as the prime constraint, and the permissible velocities, as subsidiary constraints, were considered to solve the problem. Mathematical optimization was used to obtain the optimum canal dimensions. The results were represented in chart form to facilitate easy design of the optimal channel dimensions with minimum cost. To demonstrate the practicability of the proposed method, a design example has been included. A comparison between the parameters and the cost of the proposed section with the conventional trapezoidal section revealed that the proposed section is more economic, and more suitable from a maintenance point of view. At last, sensitivity analysis was derived to show the effect of changing the canal dimensions on the cost.
An Overview of the Compounds Tested In Vivo for Leishmania spp. of the Last 5 Years
Authors: de Barros Dias Mabilly Cox Holanda , Freitas Luiz Alberto Barros , dos Santos Ignes Regina , de Almeida Vanessa Silva , do Amaral e Melo Roberta Taylane , de Melo Silva Vanessa Gouveia , de Fátima Maia de Santana Beatriz , da Conceição Juliana Maria , Lima Leite Ana Cristina 
Published: November 2020

Background:
Leishmaniasis, a still important public health problem, exhibits environmental risk factors such as
massive migrations, urbanization, and deforestation. WHO research for Leishmaniasis has been mainly focused on the development
of new tools, such as diagnostic tests, drugs, and vaccines. During the drug development strategy, only a few
compounds seem promising and call for further study after the in vitro and in vivo preclinical tests.

Objective:
In this review, our group aimed to highlight the utmost research done during 2014 to 2019 in the fields of natural
and synthetic compounds, as well as repurposed drugs and new formulations tested in vivo for Leishmania spp.

Method:
Based on the literature search, we used the databases MEDLINE, PUBMED, CAPES PERIODIC and ELSEVIER
to delineate an interval of the last 5 years of research on each field.

Results:
Among the natural compounds tested, allicin and a fraction of potato tuber extract showed the most promising antileishmanial
activity. Concerning synthetic compounds, quinolines, bornyl ester, thymol, benzoxaborole and nitroimidazole
derivatives exhibited encouraging results. Moreover, repositioned alternatives involved combinations with known drugs and
monotherapy protocols as well. In these years, new formulations were widely assessed as drug delivery systems, such as nanoparticles,
micelles and liposomes in polymer conjugations.

Conclusion:
Drug repurposing and new formulations of already-known drugs are worthwhile approaches to promptly introduce
new treatment schemes to Leishmaniasis. Nevertheless, the interest in new synthetic compounds and new formulations
brings light to new treatment proposals and are notable lines of research.
Novel Derivatives of Nicotinic Acid as Promising Anticancer Agents
Authors: Jain Nisha , Utreja Divya , Kaur Komalpreet , Jain Palak 
Published: November 2020

Background:
Cancer has become the second leading cause of death worldwide. Despite of
the availability of significant number of anticancer agents, cancer is still incurable especially at the
last stages. Remarkable targets for anticancer research and drug discovery are heterocyclic compounds,
and among them, superior effect has been shown by the nitrogen containing compounds than
non-nitrogen containing compounds. Nicotinic acid, a nitrogen containing moiety and its derivatives
have gained an immense importance in the development of anticancer drugs owing to the wide variety
of biological properties displayed by them.

Objective:
The objective of this review is to provide researchers the information about various synthetic
approaches used for the synthesis of anticancer drugs of nicotinic acid from 2001 onwards and
to reveal their application and importance in the treatment of this dreadful disease.

Conclusion:
As indicated by this review, considerable work has been done in terms of synthesis and
investigation of anticancer potential of nicotinamide derivatives. The information provided in this article
may be of great value for the researchers seeking to develop efficient anticancer drugs.
Paclitaxel Priming of TRAIL Expressing Mesenchymal Stromal Cells (MSCs- TRAIL) Increases Antitumor Efficacy of Their Secretome
Authors: Coccè Valentina , Bonomi Arianna , Cavicchini Loredana , Sisto Francesca , Giannì Aldo , Farronato Giampietro , Alessandri Giulio , Petrella Francesco , Sordi Valeria , Parati Eugenio , Bondiolotti Gianpietro , Paino Francesca , Pessina Augusto 
Published: November 2020

Background:
Adipose tissue-derived MSCs engineered with the tumor necrosis factor-
related apoptosis-inducing ligand protein (MSCs-TRAIL) have significant anticancer activity.
MSCs, without any genetic modifications, exposed to high doses of chemotherapeutic agents are
able to uptake the drug and release it in an amount affecting tumor proliferation. The purpose of
this study was to verify the ability of MSCs-TRAIL to uptake and release paclitaxel (PTX) by providing
an increased antitumor efficacy.

Methods:
MSCs and MSCs-TRAIL were tested for their sensitivity to Paclitaxel (PTX) by MTT assay,
and the cells were loaded with PTX according to a standardized procedure. The secretome was
analysed by HPLC for the presence of PTX, microarray assay for soluble TRAIL (s-TRAIL) and
tested for in vitro anticancer activity.

Results:
MSCs-TRAIL were resistant to PTX and able to incorporate and then release the drug.
The secretion of s-TRAIL by PTX loaded MSCs-TRAIL was not inhibited, and the PTX delivery
together with s-TRAIL secretion resulted in increased antitumor efficacy of cell secretome as tested
in vitro on human pancreatic carcinoma (CFPAC-1) and glioblastoma (U87-MG).

Conclusions:
Our result is the first demonstration of the possible merging of two new MSCs therapy
approaches based on genetic manipulation and drug delivery. If confirmed in vivo, this could potentiate
the efficacy of MSCs-TRAIL and strongly contribute to reducing the toxicity due to the systemic
treatment of PTX.
Selective Antitumor Effect of Shikonin Derived DMAKO-20 on Melanoma through CYP1B1
Authors: Cui Junqi , Zhou Xiaobo , Huang Jia , Cui Jiahua , Chen Jun 
Published: November 2020

Background:CYP1B1 is considered as a valuable target for chemotherapy. It catalyzes the bioactivation of naphthoquinone oximes within certain cancer cell lines. However, the expression level of CYP1B1 in melanoma and the functional role regulating the activity of DMAKO-20 as a representative naphthoquinone oxime against skin carcinoma are still unknown.Objective:We sought to examine the expression level of CYP1B1 in melanoma and explore the molecular mechanism behind the anticancer effects of DMAKO-20 in melanoma.Methods:CYP1B1 expression levels in paraffin specimens taken from melanoma patients, and its expression levels in B16/F10 cancer cells were investigated using immunohistochemical staining. The molecular mechanisms behind DMAKO-20 activity against melanoma were investigated by using cytotoxicity, cell scratching, apoptotic, and immunoblotting assays.Results:CYP1B1, the P450 isoform, was expressed at high levels in melanoma tissues and cultured B16/F10 cells but was undetectable in normal tissues or fibroblasts. In cell proliferation assays, the shikonin oxime DMAKO-20 exhibited potent and selective antiproliferative effects against B16/F10 melanoma cells and inhibited migration. Several mechanisms for the anticancer effects of DMAKO-20 have been identified in B16/F10 melanoma cells, including apoptosis, upregulation of mitochondrial apoptotic Bax proteins, and downregulation of anti-apoptotic Bcl-2. The results from these mechanistic investigations indicated that DMAKO-20 underwent CYP1B1-mediated metabolic activation to activate anticancer metabolites within melanoma cells.Conclusion:DMAKO-20 exhibited a selective cytotoxic effect on melanoma cells through CYP1B1-mediated activation. Using DMAKO-20 as a lead compound, further structural optimization may provide new drug entities for the treatments of malignant skin carcinomas.
Transmission Modes of COVID-19: A Systematic Review
Authors: Mehraeen Esmaeil , Salehi Mohammad Amin , Behnezhad Farzane , Moghaddam Hamed Rezakhani , SeyedAlinaghi SeyedAhmad 
Published: November 2020

Background:
The Coronavirus disease 19 (COVID-19) is a highly transmittable viral infection that initiated in
Wuhan, China and has spread around the world. The high prevalence and spread ways of COVID-19 have become an international challenge that requires careful consideration. We aimed to review the current evidence of COVID-19 transmission
modes.

Methods:
This study was a systematic review that was done to identify current evidence on transmission modes of COVID19. We searched selected keywords in six important databases to discover related sources on the main objective of the study.
To identify studies meeting the inclusion criteria, the authors screened the titles and abstracts of retrieved documents. The
appropriate articles were selected and their results were discussed to make the final inclusion.

Results:
We identified five potential transmission modes of COVID-19 including airborne, droplet, contact with contaminated surfaces, oral and fecal secretions. Furthermore, some studies have pointed out other modes of virus transmission,
such as person to person, and direct contact with animals.

Conclusion:
Droplet and contact with contaminated surfaces were the most frequent transmission modes of COVID-19. Fecal excretion, environmental contamination, and fluid pollution might contribute to a viral transmission. The possibility of
fecal transmission of COVID-19 has implications, especially in areas with poor sanitation and the environmental pollution
can be caused by patients with SARS-CoV-2 through respiratory droplets and feces, subsequently, the human environment
will change to a potential medium of virus transmission.
Digital Health Interventions for People With Type 2 Diabetes to Develop Self-Care Expertise, Adapt to Identity Changes, and Influence Other’s Perception: Qualitative Study
Authors: Turnbull Sophie , Lucas Patricia J , Hay Alastair D , Cabral Christie 
Published: November 2020

Background
A diagnosis of type 2 diabetes (T2D) results in widespread changes to a person’s life and can be experienced as an assault on their sense of self. The resources available to an individual influence how the individual adapts to their diabetic identity and subsequently engages in self-care. Digital interventions can be viewed as a resource that people can draw on to adapt to the diagnosis. However, there is an indication that people from disadvantaged groups find digital health technologies more challenging to access and use, which may increase health inequalities.

Objective
This study aims to gain insights into how and why people with T2D use digital self-care technology and how experiences vary between individuals and social groups.

Methods
A purposive sample of people who had used a digital intervention to help them self-care for their T2D were recruited for the study. Semistructured interviews were conducted, and data were analyzed thematically.

Results
A diverse sample of 21 participants were interviewed. Participants used digital interventions to help them to understand and feel more in control of their bodies. Digital interventions were used by participants to project their chosen identity to others. Participants selected technology that allowed them to confirm and enact their preferred positive identities, both by avoiding stigma and by becoming experts in their disease or treatment. Participants preferred using digital interventions that helped them conceal their diabetes, including by buying discrete blood glucose monitors. Some participants used technology to increase their sense of power in their interaction with clinicians, whereas others used technology to demonstrate their goodness.

Conclusions
The technology that people with T2D have access to shapes the way they are able to understand and control their bodies and support preferred social identities.
Health Professional Student Placements and Workforce Location Outcomes: Protocol of an Observational Cohort Study
Authors: Campbell Narelle , Farthing Annie , Witt Susan , Anderson Jessie , Lenthall Sue , Moore Leigh , Rissel Chris 
Published: November 2020

Background
The successful recruitment and retention of health professionals to rural and remote areas of Australia is a health policy priority. Nursing or allied health professional students’ learning placements in the Northern Territory (NT) of Australia, most of which is considered remote, may influence rural or remote work location decisions.

Objective
The aim of this study is to determine where allied health professionals and nurses who have had a student placement in the NT of Australia end up practicing.

Methods
This research is an observational cohort study, with data collection occurring at baseline and then repeated annually over 10 years (ie, 2017-2018 to 2029). The baseline data collection includes a demographic profile of allied health and nursing students and their evaluations of their NT placements using a nationally consistent questionnaire (ie, the Student Satisfaction Survey). The Work Location Survey, which will be administered annually, will track work location and the influences on work location decisions.

Results
This study will generate unique data on the remote and rural work locations of nursing and allied health professional students who had a placement in the NT of Australia. It will be able to determine what are the most important characteristics of those who take up remote and rural employment, even if outside of the NT, and to identify barriers to remote employment.

Conclusions
This study will add knowledge to the literature regarding rates of allied health and nursing professionals working in remote or rural settings following remote or rural learning placements. The results will be of interest to government and remote health workforce planners.

Trial Registration
Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620000797976; https://www.anzctr.org.au/ACTRN12620000797976.aspx

International Registered Report Identifier (IRRID)
PRR1-10.2196/21832
Analysis of the Trends in Publications on Clinical Cancer Research in Mainland China from the Surveillance, Epidemiology, and End Results (SEER) Database: Bibliometric Study
Authors: Lin Min-Qiang , Lian Chen-Lu , Zhou Ping , Lei Jian , Wang Jun , Hua Li , Zhou Juan , Wu San-Gang 
Published: November 2020

Background
The application of China’s big data sector in cancer research is just the beginning. In recent decades, more and more Chinese scholars have used the Surveillance, Epidemiology, and End Results (SEER) database for clinical cancer research. A comprehensive bibliometric study is required to analyze the tendency of Chinese scholars to utilize the SEER database for clinical cancer research and provide a reference for the future of big data analytics.

Objective
Our study aimed to assess the trend of publications on clinical cancer research in mainland China from the SEER database.

Methods
We performed a PubMed search to identify papers published with data from the SEER database in mainland China until August 31, 2020.

Results
A total of 1566 papers utilizing the SEER database that were authored by investigators in mainland China were identified. Over the past years, significant growth in studies based on the SEER database was observed (P<.001). The top 5 research topics were breast cancer (213/1566, 13.6%), followed by colorectal cancer (185/1566, 11.8%), lung cancer (179/1566, 11.4%), gastrointestinal cancer (excluding colorectal cancer; 149/1566, 9.5%), and genital system cancer (93/1566, 5.9%). Approximately 75.2% (1178/1566) of papers were published from the eastern coastal region of China, and Fudan University Shanghai Cancer Center (Shanghai, China) was the most active organization. Overall, 267 journals were analyzed in this study, of which Oncotarget was the most contributing journal (136/267, 50.9%). Of the 1566 papers studied, 585 (37.4%) were published in the second quartile, 489 (31.2%) in the third quartile, 312 (19.9%) in the first quartile, and 80 (5.1%) in the fourth quartile, with 100 (6.4%) having an unknown Journal Citation Reports ranking.

Conclusions
Clinical cancer research based on the SEER database in mainland China underwent constant and rapid growth during recent years. High-quality and comprehensive cancer databases based on Chinese demographic data are urgently needed.