bluuebunny/crossref_metadata_2025_split huggingface dataset:
Path analysis of skin cancer preventive behavior among the rural women based on protection motivation theory
Authors: Roozbahani Nasrin , Kaviani Abdol-Hossain , Khorsandi Mahboobeh 
Published: June 2020

Abstract
Background
Determining the effective factors on the adoption of preventive behaviors capable of reducing the risk of skin cancer is an important step in designing interventions to promote these behaviors. Based on the protection motivation theory, the present study is aimed to conduct a path analysis of skin cancer preventive behaviors in rural women to explore these factors.

Methods
In this cross-sectional study, 243 rural women were randomly selected from the west of Iran to receive a valid and reliable questionnaire assessing constructs from the protection motivation theory, as well as demographic information. Fully completed questionnaires were returned by 230 women and the data were analyzed by SPSS 22 and LISREL8.8.

Results
Concerning skin cancer preventive behaviors, 27.8% of women wore sun-blocking clothing when working under the sun, 21.7% used sunscreen cream, 5.7% wore a cap, and 4.8% used gloves and sunglasses. Protection motivation theory and per capita income explained 51% of motivation variance and 25% of the variance of skin cancer preventive behaviors. The response efficacy construct was the strongest predictor of the motivation of protection (ß = − 0.44, p < 0/001). Per-capita income (ß = − 0.34, p < 0/001) and motivation (ß = − 0.33, p < 0/001) were the strongest predictors of these behaviors.

Conclusions
This study showed that protection motivation theory is efficient in predicting skin cancer preventive behaviors and the interventions can be designed and implemented by this theory. Proper planning is also necessary for promoting these behaviors among people with low per-capita income.
Altitude impact on the chemical profile and biological activities of Satureja thymbra L. essential oil
Authors: Khalil Noha , El-Jalel Lamya , Yousif Miriam , Gonaid Mariam 
Published: June 2020

Abstract
Background
Several agricultural or environmental factors affect plants’ chemical and pharmacological properties.

Methods
In this study, the essential oil of Libyan Satureja thymbra was isolated from plants collected during two successive years at two different altitudes; Wasita (WEO) and Safsaf (SEO), 156 and 661 m above sea level, respectively.

Results
GC/MS allowed the identification of 21 and 23 compounds, respectively. Thymol prevailed in WEO (26.69%), while carvacrol prevailed in SEO (14.30%). Antimicrobial activity was tested by agar-well diffusion method, and MIC/MLC values were determined by broth dilution method. Values of MIC/MLC were 0.125/0.25 μg/ml for SEO against S. aureus, P. mirabilis and K. pneumonia and for WEO against B. subtilus. It was observed that plants growing at lower altitude in Wasita locality had better antifungal activity, while those growing at higher altitude at Safsaf locality had better antibacterial activity. Both essential oils had a better anthelmintic activity than the standard piperazine citrate against a tested earthworm. However, SEO oil had a significantly higher anthelmintic activity than WEO. Cytotoxicity of the oils tested using SRB assay on human breast cancer (MCF-7) and colon cancer cell lines (HCT-116) showed better activity for SEO, especially against HCT-116 with IC50 2.45 ± 0.21 μg/ml.

Conclusions
Thus, altitude is an important factor that should be considered as it affected the yield, composition and biology of the plant extracts.
Embedding international medical student electives within a 30-year partnership: the Ghana-Michigan collaboration
Authors: Lawrence Emma R. , Moyer Cheryl , Ashton Carrie , Ibine Bolade A. R. , Abedini Nauzley C. , Spraggins Yaera , Kolars Joseph C. , Johnson Timothy R. B. 
Published: June 2020

AbstractBackgroundGlobal health experiences are an increasingly popular component of medical student curricula. There is little research on the impact of international medical electives embedded within long-standing, sustainable partnerships. Our research explores the University of Michigan medical student elective experience in Ghana within the context of the Ghana-Michigan collaborative.MethodsStudy participants are University of Michigan medical students who completed an international elective in Ghana between March 2006 and June 2017. Post-elective reports were completed by students, including a description of the experience, highlights, disappointments, and the impact of the experience on interest in future international work and future practice of medicine. A retrospective thematic analysis of reports was carried out using NVivo 12 (QSR International, Melbourne, Australia).ResultsA total of 57 reports were analyzed. Benefits of the elective experience included building cross-cultural relationships, exposure to different healthcare environments, hands-on clinical and surgical experience, and exposure to different patient populations. Ninety-five percent of students planned to engage in additional international work in the future. Students felt that the long-standing bidirectional exchange allowed them to build cross-cultural relationships and be incorporated as a trusted part of the local clinical team. The partnership modeled collaboration, and many students found inspiration for the direction of their own careers.ConclusionsEmbedding clinical rotations within a well-established, sustained partnerships provides valuable experiences for trainees by modeling reciprocity, program management by local physicians, and cultural humility—all of which can help prepare learners to ethically engage in balanced, long-term partnerships in the future.
A phase IIb, randomised, parallel-group study: the efficacy, safety and tolerability of once-daily umeclidinium in patients with asthma receiving inhaled corticosteroids
Authors: Kerwin Edward , Pascoe Steven , Bailes Zelie , Nathan Robert , Bernstein David , Dahl Ronald , von Maltzahn Robyn , Robbins Kevin , Fowler Andrew , Lee Laurie 
Published: June 2020

Abstract
Background
Patients with asthma uncontrolled on inhaled corticosteroids may benefit from umeclidinium (UMEC), a long-acting muscarinic antagonist.

Methods
This Phase IIb, double-blind study included patients with reversible, uncontrolled/partially-controlled asthma for ≥6 months, receiving ≥100 mcg/day fluticasone propionate (or equivalent) for ≥12 weeks. Following a 2-week run-in on open-label fluticasone furoate (FF) 100 mcg, patients were randomised (1:1:1) to receive UMEC 31.25 mcg, UMEC 62.5 mcg or placebo on top of FF 100 mcg once-daily for 24 weeks. As-needed salbutamol was provided. Primary and secondary endpoints were change from baseline in clinic trough forced expiratory volume in 1 s (FEV1) and clinic FEV1 3 h post-dose, respectively, at Week 24. Other endpoints included change from baseline in home daily spirometry (trough FEV1, evening FEV1, morning [pre-dose] and evening peak expiratory flow) over 24 weeks. Safety was assessed throughout the study.

Results
The intent-to-treat population comprised 421 patients (UMEC 31.25 mcg: n =139, UMEC 62.5 mcg: n =139, placebo: n =143). UMEC 31.25 mcg and 62.5 mcg demonstrated significantly greater improvements from baseline in clinic trough FEV1 at Week 24 (difference [95% CI]: 0.176 L [0.092, 0.260; p<0.001] and 0.184 L [0.101, 0.268; p<0.001], respectively), clinic FEV1 3 h post-dose at Week 24 (0.190 L [0.100, 0.279; p<0.001] and 0.198 L [0.109, 0.287; p<0.001], respectively) and mean change from baseline in daily home spirometry over 24 weeks versus placebo. No new safety signals were identified.

Conclusions
UMEC is a highly effective bronchodilator that leads to improved lung function when administered as a single bronchodilator on top of FF in subjects with fully reversible, uncontrolled/partially-controlled moderate asthma. These data support a favourable benefit/risk profile for UMEC (31.25 mcg and 62.5 mcg).

Trial registration
GSK study ID: 205832; Clinicaltrials.gov ID: NCT03012061.
Identification of a competing endogenous RNA network associated with prognosis of pancreatic adenocarcinoma
Authors: Weng Wanqing , Zhang Zhongjing , Huang Weiguo , Xu Xiangxiang , Wu Boda , Ye Tingbo , Shan Yunfeng , Shi Keqing , Lin Zhuo 
Published: June 2020

Abstract
Background
Emerging evidence suggests that competing endogenous RNAs plays a crucial role in the development and progress of pancreatic adenocarcinoma (PAAD). The objective was to identify a new lncRNA-miRNA-mRNA network as prognostic markers, and develop and validate a multi-mRNAs-based classifier for predicting overall survival (OS) in PAAD.

Methods
Data on pancreatic RNA expression and clinical information of 445 PAAD patients and 328 normal subjects were downloaded from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Genotype-Tissue Expression (GTEx). The weighted correlation network analysis (WGCNA) was used to analyze long non-coding RNA (lncRNA) and mRNA, clustering genes with similar expression patterns. MiRcode was used to predict the sponge microRNAs (miRNAs) corresponding to lncRNAs. The downstream targeted mRNAs of miRNAs were identified by starBase, miRDB, miRTarBase and Targetscan. A multi-mRNAs-based classifier was develop using least absolute shrinkage and selection operator method (LASSO) COX regression model, which was tested in an independent validation cohort.

Results
A lncRNA-miRNA-mRNA co-expression network which consisted of 60 lncRNAs, 3 miRNAs and 3 mRNAs associated with the prognosis of patients with PAAD was established. In addition, we constructed a 14-mRNAs-based classifier based on a training cohort composed of 178 PAAD patients, of which the area under receiver operating characteristic (AUC) in predicting 1-year, 3-year, and 5-year OS was 0.719, 0.806 and 0.794, respectively. The classifier also shown good prediction function in independent verification cohorts, with the AUC of 0.604, 0.639 and 0.607, respectively.

Conclusions
A novel competitive endogenous RNA (ceRNA) network associated with progression of PAAD could be used as a reference for future molecular biology research.
LncRNA ST8SIA6-AS1 promotes hepatocellular carcinoma cell proliferation and resistance to apoptosis by targeting miR-4656/HDAC11 axis
Authors: Fei Qiang , Song Feihong , Jiang Xinwei , Hong Han , Xu Xiaoyong , Jin Zhengkang , Zhu Xiang , Dai Binghua , Yang Jiamei , Sui Chengjun , Xu Minhui 
Published: June 2020

Abstract
Background
Dysregulation of long non-coding RNAs (lncRNAs) results in development of human diseases including hepatocellular carcinoma (HCC). Although several HCC related lncRNAs have been reported, the biological functions of many lncRNAs during the development of HCC remains unknown.

Methods
The expression of ST8SIA6-AS1 was studied by realtime PCR (RT-qPCR) and bioinformatic analysis. The biological functions of ST8SIA6-AS1 was examined by CCK-8 assay and flow cytometry analysis. The target of ST8SIA6-AS1 was analyzed by bioinformatic analysis and validated by dual luciferase reporter assay, western blotting and RT-qPCR.

Results
In this study we demonstrated that ST8SIA6-AS1 was an upregulated lncRNA in hepatocellular carcinoma. SiRNA-mediated knockdown of ST8SIA6-AS1 repressed cell proliferation and induced cell apoptosis in HCC cells. Bioinformatic analysis and RT-qPCR further showed that ST8SIA6-AS1 mainly located in cytoplasm. Dual luciferase reporter assay further revealed that ST8SIA6-AS1 interacted with miR-4656 in HCC cells. In addition, HDAC11 was identified as a target gene in HCC cells and ST8SIA6-AS1 could upregulate HDAC11 via sponging miR-4656. Transfection of recombinant HDAC11 partially rescued the inhibition of cell proliferation and increase of cell apoptosis inducing by knockdown of ST8SIA6-AS1.

Conclusion
In conclusion, our findings suggested that ST8SIA6-AS1 was a novel upregulated lncRNA in HCC and could facilitate cell proliferation and resistance to cell apoptosis via sponging miR-4656 and elevation of HDAC11, which might be a promising biomarker for patients with HCC.
Farnesal-loaded pH-sensitive polymeric micelles provided effective prevention and treatment on dental caries
Authors: Yi Youping , Wang Lujun , Chen Lin , Lin Yan , Luo Zhongling , Chen Zhenyu , Li Ting , Wu Jianming , Zhong Zhirong 
Published: June 2020

Abstract
Background
Farnesol is a sesquiterpene from propolis and citrus fruit that shows promising anti-bacterial activity for caries treatment and prevention, but its hydrophobicity limits the clinical application. We aimed to develop the novel polymeric micelles (PMs) containing a kind of derivative of farnesol and a ligand of pyrophosphate (PPi) that mediated PMs to adhere tightly with the tooth enamel.

Results
Farnesal (Far) was derived from farnesol and successfully linked to PEG via an acid-labile hydrazone bond to form PEG-hyd-Far, which was then conjugated to PPi and loaded into PMs to form the aimed novel drug delivery system, PPi-Far-PMs. The in vitro test about the binding of PPi-Far-PMs to hydroxyapatite showed that PPi-Far-PMs could bind rapidly to hydroxyapatite and quickly release Far under the acidic conditions. Results from the mechanical testing and the micro-computed tomography indicated that PPi-Far-PMs could restore the microarchitecture of teeth with caries. Moreover, PPi-Far-PMs diminished the incidence and severity of smooth and sulcal surface caries in rats that were infected with Streptococcus mutans while being fed with a high-sucrose diet. The anti-caries efficacy of free Far can be improved significantly by PPi-Far-PMs through the effective binding of it with tooth enamel via PPi.

Conclusions
This novel drug-delivery system may be useful for the treatment and prevention of dental caries as well as the targeting therapy of anti-bacterial drugs in the oral disease.
Three-dimensional culture and clinical drug responses of a highly metastatic human ovarian cancer HO-8910PM cells in nanofibrous microenvironments of three hydrogel biomaterials
Authors: Song Hong , Cai Guo-hui , Liang Jian , Ao Di-shu , Wang Huan , Yang Ze-hong 
Published: June 2020

Abstract
Background
Ovarian cancer is a highly aggressive malignant disease in gynecologic cancer. It is an urgent task to develop three-dimensional (3D) cell models in vitro and dissect the cell progression-related drug resistance mechanisms in vivo. In the present study, RADA16-I peptide has the reticulated nanofiber scaffold networks in hydrogel, which is utilized to develop robust 3D cell culture of a high metastatic human ovarian cancer HO-8910PM cell line accompanied with the counterparts of Matrigel and collagen I.

Results
Consequently, HO-8910PM cells were successfully cultivated in three types of hydrogel biomaterials, such as RADA16-I hydrogel, Matrigel, and collagen I, according to 3D cell culture protocols. Designer RADA16-I peptide had well-defined nanofiber networks architecture in hydrogel, which provided nanofiber cell microenvironments analogous to Matrigel and collagen I. 3D-cultured HO-8910PM cells in RADA16-I hydrogel, Matrigel, and collagen I showed viable cell proliferation, proper cell growth, and diverse cell shapes in morphology at the desired time points. For a long 3D cell culture period, HO-8910PM cells showed distinct cell aggregate growth patterns in RADA16-I hydrogel, Matrigel, and collagen I, such as cell aggregates, cell colonies, cell clusters, cell strips, and multicellular tumor spheroids (MCTS). The cell distribution and alignment were described vigorously. Moreover, the molecular expression of integrin β1, E-cadherin and N-cadherin were quantitatively analyzed in 3D-cultured MCTS of HO-8910PM cells by immunohistochemistry and western blotting assays. The chemosensitivity assay for clinical drug responses in 3D context indicated that HO-8910PM cells in three types of hydrogels showed significantly higher chemoresistance to cisplatin and paclitaxel compared to 2D flat cell culture, including IC50 values and inhibition rates.

Conclusion
Based on these results, RADA16-I hydrogel is a highly competent, high-profile, and proactive nanofiber scaffold to maintain viable cell proliferation and high cell vitality in 3D cell models, which may be particularly utilized to develop useful clinical drug screening platform in vitro.
Excitability, synaptic balance, and addiction: The homeostatic dynamics of ionotropic glutamatergic receptors in VTA after cocaine exposure
Authors: Moulin Thiago C. , Schiöth Helgi B. 
Published: June 2020

AbstractGlutamatergic AMPA and NMDA receptors in the ventral tegmental area (VTA) are central for cocaine first exposure and posterior craving maintenance. However, the exact rules that coordinate the synaptic dynamics of these receptors in dopaminergic VTA neurons and behavioral outcomes are poorly understood. Additionally, synaptic homeostatic plasticity is present in response to chronic excitability changes in neuronal circuits, adjusting the strength of synapses to stabilize the firing rate. Despite having correspondent mechanisms, little is known about the relationship between continuous cocaine exposure and homeostatic synaptic changes in the VTA neurons. Here, we assess the role of homeostatic mechanisms in the neurobiology of cocaine addiction by providing a brief overview of the parallels between cocaine-induced synaptic potentiation and long-term synaptic adaptations, focusing on the regulation of GluA1- and GluN1- containing receptors.
Toll-like receptor 9 and the inflammatory response to surgical trauma and cardiopulmonary bypass
Authors: Naase Hatam , Harling Leanne , Kidher Emaddin , Sepehripour Amir , Nguyen Bao , Kapelouzou Alkistis , Cokkinos Dennis , Stavridis George , Angelini Gianni , Evans Paul C. , Athanasiou Thanos 
Published: June 2020

Abstract
Objectives
Cardiac surgery can lead to post-operative end-organ complications secondary to activation of systemic inflammatory response. We hypothesize that surgical trauma or cardiopulmonary bypass (CPB) may initiate systemic inflammatory response via release of mitochondrial DNA (mtDNA) signaling Toll-like receptor 9 (TLR9) and interleukin-6 production (IL-6).

Materials and methods
The role of TLR9 in systemic inflammatory response in cardiac surgery was studied using a murine model of sternotomy and a porcine model of sternotomy and CPB. mtDNA and IL-6 were measured with and without TLR9-antagonist treatment. To study ischemia-reperfusion injury, we utilized an ex-vivo porcine kidney model.

Results
In the rodent model (n = 15), circulating mtDNA increased 19-fold (19.29 ± 3.31, p < 0.001) and plasma IL-6 levels increased 59-fold (59.06 ± 14.98) at 1-min post-sternotomy compared to pre-sternotomy. In the murine model (n = 11), administration of TLR-9 antagonists lowered IL-6 expression post-sternotomy when compared to controls (59.06 ± 14.98 vs. 5.25 ± 1.08) indicating that TLR-9 is a positive regulator of IL-6 after sternotomy. Using porcine models (n = 10), a significant increase in circulating mtDNA was observed after CPB (Fold change 29.9 ± 4.8, p = 0.005) and along with IL-6 following renal ischaemia-reperfusion. Addition of the antioxidant sulforaphane reduced circulating mtDNA when compared to controls (FC 7.36 ± 0.61 vs. 32.0 ± 4.17 at 60 min post-CPB).

Conclusion
CPB, surgical trauma and ischemic perfusion injury trigger the release of circulating mtDNA that activates TLR-9, in turn stimulating a release of IL-6. Therefore, TLR-9 antagonists may attenuate this response and may provide a future therapeutic target whereby the systemic inflammatory response to cardiac surgery may be manipulated to improve clinical outcomes.
DDIEM: drug database for inborn errors of metabolism
Authors: Abdelhakim Marwa , McMurray Eunice , Syed Ali Raza , Kafkas Senay , Kamau Allan Anthony , Schofield Paul N , Hoehndorf Robert 
Published: June 2020

Abstract
Background
Inborn errors of metabolism (IEM) represent a subclass of rare inherited diseases caused by a wide range of defects in metabolic enzymes or their regulation. Of over a thousand characterized IEMs, only about half are understood at the molecular level, and overall the development of treatment and management strategies has proved challenging. An overview of the changing landscape of therapeutic approaches is helpful in assessing strategic patterns in the approach to therapy, but the information is scattered throughout the literature and public data resources.

Results
We gathered data on therapeutic strategies for 300 diseases into the Drug Database for Inborn Errors of Metabolism (DDIEM). Therapeutic approaches, including both successful and ineffective treatments, were manually classified by their mechanisms of action using a new ontology.

Conclusions
We present a manually curated, ontologically formalized knowledgebase of drugs, therapeutic procedures, and mitigated phenotypes. DDIEM is freely available through a web interface and for download at http://ddiem.phenomebrowser.net.
A moonshot approach toward the management of cancer patients in the COVID-19 time: what have we learned and what could the Italian network of cancer centers (Alliance Against Cancer, ACC) do after the pandemic wave?
Authors: Silvestris Nicola , Apolone Giovanni , Botti Gerardo , Ciliberto Gennaro , Costantini Massimo , De Paoli Paolo , Franceschi Silvia , Opocher Giuseppe , Paradiso Angelo , Pronzato Paolo , Sgambato Alessandro , De Maria Ruggero 
Published: June 2020

AbstractIf we focus our attention on seven main features of COVID-19 infection (heterogeneity, fragility, lack of effective treatments and vaccines, “miraculous cures”, psychological suffering, deprivation, and globalization), we may establish parallelism with the challenges faced in the steep road to the understanding and treatment of neoplastic diseases. How the similarities between these two conditions can help us cope with the emergency effort represented by the management of cancer patients in the COVID-19 era, today and in the future? In a manner similar to the Cancer Moonshot initiative in the United States, we can hypothesize a multinational moonshot project towards the management of cancer patients during COVID-19 pandemic. In particular, we believe that the main road to elaborate meaningful scientific evidence is represented by the collection of all the data on COVID-19 and cancer comorbidity that are and will become available in cancer centers, coupled with the design of large clinical studies. To address this goal, it is essential to identify the entity that can produce this scientific evidences and the potentially most successful research strategy to undertake. The largest Italian organization for cancer research, Alliance Against Cancer (Alleanza Contro il Cancro, ACC), is called to play a scientific leadership in addressing these challenges, which requires the coordination of oncology teams at regional, national, and international levels. To fulfill this commitment, ACC will create a liaison with health government agencies in order to develop “dynamic” indications able to fight such an unpredictable pandemic.