bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preparation and Characterization of Paclitaxel Palmitate Albumin Nanoparticles With High Loading Efficacy: an in Vitro and in Vivo Anti-tumor Study in Mouse Models
Authors: Chen Hang , Huang Sifan , Wang Heyi , Chen Xinmei , Zhang Haiyan , Xu Youfa , Fan Wei , Pan Yun , Wen Qiuyan , Lin Zhizhe , Wang Xuena , Gu Yongwei , Ding Baoyue , Chen Jianming , Wu Xin 
Published: December 2020

Abstract
Background: Combination of the prodrug technique with an albumin nanodrug-loaded system is a novel promising approach for cancer treatment. However, the long-lasting and far-reaching challenge for the treatment of cancers lies in how to construct the albumin nanometer drug delivery system with lead compounds and their derivatives. Results: In this study, we reported the preparation of injectable albumin nanoparticles (NPs) with a high and quantitative drug loading system based on the NabTM technology of paclitaxel palmitate (PTX-PA). Our experimental study on drug tissue distribution in vivo demonstrated that the paclitaxel palmitate albumin NPs (Nab-PTX-PA) remained in the tumor for a longer time post injection. Compared with saline and Abraxane® (nanoparticle albumin-bound (nab)-paclitaxel), intravenous injection of Nab-PTX-PA not only reduced the toxicity of the drug in normal organs and increased the body weight of the animals but maintained sustained release of paclitaxel (PTX) in the tumor, thereby displaying an excellent antitumor activity. Blood routine analysis showed that Nab-PTX-PA had fewer adverse effects or less toxicity to the normal organsand more importantly it inhibited tumor cell proliferation more effectively as compared with commercial Abraxane®.Conclusions: This carrier strategy for small molecule drugs is based on naturally evolved interactions between LCFAs(Long Chain Fatty Acids) and HSA(human serum albumin), demonstrated here for PTX. Nab-PTX-PA shows higher maximum tolerated doses and increased efficacy in vivo in breast cancer models, as compared to Abraxane for FDA-approved clinical formulations. This novel injectable Nab-PTX-PA platform has great potential as an effective drug delivery system in the treatment of breast cancer.
Study on the Therapeutic Effects of Traditional Chinese Medicine on Insulin Resistance in Obese Mice by Modulating Intestinal Function
Authors: Ma Lirong , Bai Yongquan , Wang Wenwen , Shi Rui , Wang Furong , Liu Jun , Liu Chaoyang , Deng Hui , Xu Qing , Wenli Zhang , Guo Chen , Lu Zifan 
Published: December 2020

Abstract

Background: Obesity, in particular with the excessive visceral fat distribution which accompanied by several alterations at hormonal, inflammatory and endothelial level, was great to the detriment to human health. Although there were many treatments for obesity, most of them fail to had a radical effect or were accompanied with several side effects. Traditional Chinese medicine (TCM) for regulating the intestinal flora, lipids, and inflammation were considered to be effective. Based on previous research, Artemisia capillaris, Astragalus propinquus, Phellodendron amurense, Salvia miltiorrhiza, Poria cocos, and Anemarrhena asphodeloides were eventually selected to form an innovative herbal formula.Methods: The anti-inflammatory and lipid-lowering effects of the TCM were evaluated in an obese mouse models fed with a high-fat diet, and the effects of the TCM on the intestinal flora were further investigated.Results: The weights and insulin resistant of mice, as well as the inflammation, decreased after treatment. At the same time, the lipid metabolism increased after the mice were gavage with the TCM formula for 2 weeks. The intestinal motility of mice in the drug administration group was enhanced, and the intestinal flora was partially restored.Conclusion: In summary, our innovative Chinese herbal formula could significantly reduce the weight of obese mice, reduce the intestinal inflammation, improve intestinal motility, and improve the lipid metabolism in mice. Furthermore, the innovative formular could effectively prevent relevant metastasis diseases induced by obesity in mice.
Neutral Theory: Applicability and Neutrality of Using Generic Health-related Quality of Life Tools in Diseases or Conditions Where Specific Tools Are Available
Authors: Jandhyala Ravi 
Published: December 2020

Abstract
Background:Health-related quality of life (HRQoL) tools are limited by the indicators included in the construct and variation in interpretation by different researchers. Neutral Theory describes the ideal construct that includes all relevant indicators and, therefore, complete accuracy, or Neutrality. Neutral Theory can thereby provide the framework to develop or test constructs. To assess the application of Neutral Theory, the Neutrality of generic tools (SF-36 and EQ-5D) at measuring HRQoL was compared to disease/condition-specific tools, with the latter considered surrogates for the Neutral construct. Methods:Full descriptions of all disease/condition-specific HRQoL tools published on PubMed (to 01-Jul-19) were sourced. For each tool, the number of items with and without a direct match within the SF-36 and EQ-5D was recorded and the sensitivity/specificity calculated. Results:The SF-36 and EQ-5D did not achieve a sensitivity/specificity both >50% against any of the 163 disease/condition-specific tools identified. At 20% prevalence of poor HRQoL, the false positive rate (FPR) was >75% for all but two tools against the SF-36 and six tools against the EQ-5D. Increasing poor HRQoL to 80%, 47 tools for the SF-36 and 48 tools for the EQ-5D had a FPR <50%. For rare disease tools (<1/2,000 population; n=17), sensitivity/specificity ranged from 0-40%/5-31% for the SF-36 and 0-22%/29-100% for the EQ-5D. For non-rare (n=75) and symptom-specific tools (n=71) sensitivity/specificity was: 0-100%/0-100% (SF-36) and 0-50%/0-100% (EQ-5D); and 0-60%/0-19% (SF-36) and 0-25%/0-100% (EQ-5D), respectively. No concordance was recorded for 18% (2/11) of results from studies of rare disease tools versus the SF-36 (no data vs EQ-5D). For non-rare, disease-specific tools, results were discordant for 30% (25/84) and 35% (23/65) of studies against the SF-36 and EQ-5D, respectively. For symptom-specific tools, corresponding results were 36% (24/66) and 16% (5/31).Conclusions:Generic HRQoL tools appear poorly correlated with disease/condition-specific tools, which indicates that adoption of Neutral Theory in the development and assessment of HRQoL tools could improve their relevance, accuracy, and utility in economic evaluations of health interventions.
Inter-Vendor Performance of Deep Learning in Segmenting Acute Ischemic Lesions on Diffusion-Weighted Imaging: A Multicenter Study
Authors: Alis Deniz , Yergin Mert , Alis Ceren , Topel Cagdas , Asmakutlu Ozan , Bagcilar Omer , Senli Yeseren , Ustundag Ahmet , Salt Vefa , Dogan Sebahat , Velioglu Murat , Selcuk Hakan , Kara Batuhan , Oksuz Ilkay , Kizilkilic Osman , Karaarslan Ercan 
Published: December 2020

Abstract
There is little evidence on the applicability of deep learning (DL) in segmentation of acute ischemic lesions on diffusion-weighted imaging (DWI) between magnetic resonance imaging (MRI) scanners of different manufacturers. We retrospectively included DWI data of patients with acute ischemic lesions from six centers. Dataset A (n=2986) and B (n=3951) included data from Siemens and GE MRI scanners, respectively. The datasets were split into the training (80%), validation (10%), and internal test (10%) sets and six neuroradiologist created ground-truth masks. Models A and B were the proposed neural networks trained on datasets A and B and also fine-tuned across the datasets using their validation data. Another radiologist performed the segmentation on the test sets for comparisons. The median Dice scores of models A and B were 0.858 and 0.857 for the internal tests, which were non-inferior to the radiologist’s performance, but demonstrated lower performance than the radiologist on the external tests. Fine-tuned models A and B achieved median Dice scores of 0.832 and 0.846, which were non-inferior to the radiologist's performance on the external tests. The present work shows that inter-vendor operability of deep learning for the segmentation of ischemic lesions on DWI might be enhanced via transfer learning; thereby, their clinical applicability and generalizability could be improved.
High Cytoplasmic and Membranous Versus Nuclear Talin-1 Expression Associated With Malignancy Potential and Determine Survival and Metastasis of Clear Cell Renal Cell Carcinoma
Authors: Zanjani Leili Saeednejad , Vafaei Somayeh , Abolhasani Maryam , Fattahi Fahimeh , Madjd Zahra 
Published: December 2020

Abstract
Background: Talin-1 as a cytoskeleton protein participates in cell migration and has an essential role in cell adhesion, proliferation, tumorigenesis, invasion, and metastasis in various types of malignancies.Methods: Bioinformatics analysis has been performed by a using protein-protein interaction network, analyses among PRIDE databases, and indicated that Talin-1 protein as a potential prognostic focal adhesion factor in renal cell carcinoma (RCC). We, therefore, examined the protein expression levels and prognostic significance of Talin-1 with clinical follow-up in a total of 269 formalin-fixed paraffin-embedded tissue specimens from three important subtypes of RCC undergone radical nephrectomy and 30 adjacent normal tissues in three levels including, membrane, cytoplasm, and nucleus using immunohistochemistry on tissue microarrays. Then, we used a combined analysis with B7-H3 to confirm that Talin-1 may be related to metastasis.Results: The results showed that the expression of Talin-1 is significantly upregulated in most RCCs compared to adjacent normal tissues in protein levels. Further, there was a statistically significant difference between the membranous and cytoplasmic expression of Talin-1 and different subtypes of RCC (P < 0.001, P = 0.003, respectively). High membranous and cytoplasmic expression of Talin-1 was significantly associated with advanced nucleolar grade (P < 0.001, all), microvascular invasion (P = 0.007, P = 0.004), histological tumor necrosis (P = 0.020, P = 0.018), and invasion to Gerota’s fascia (P = 0.025, P = 0.050) in clear cell RCC (ccRCC). In addition, high membranous and cytoplasmic expression of Talin-1 was associated with significantly poorer disease-specific survival (DSS) (P = 0.043, P = 0.024, respectively) and progression-free survival (PFS) (P = 0.046, only in cytoplasmic expression). The co-expression of cytoplasmic Talin-1High /B7-H3High was observed to be associated with more aggressive tumor behavior and metastasis. Moreover, increased cytoplasmic expression of Talin-1High/B7-H3High compared to the other phenotypes was associated with poor prognosis and progression of the disease in patients with distant metastasis. Conclusion: Collectively, these observations indicate that Talin-1 is an important molecule involved in the spread and progression of ccRCC when expressed particularly in the cytoplasm and may serve as a novel prognostic biomarker in ccRCC if follow up time more prolonged.
Circular RNA circASPM Promotes the Progression of Glioblastoma by Acting as a Competing Endogenous RNA to Regulate miR-130b–3p/E2F1 Axis
Authors: Hou Dianqi , Wang Zhenlin , Li Haimeng , Liu Juan , Liu Yaohua , Jiang Yang , Lou Meiqing 
Published: December 2020

Abstract
background: Glioblastoma Multiform (GBM) is the primary malignancy with the highest incidence and worst prognosis in the adult CNS. Circular RNAs (circRNAs) are a novel and widely diverse class of endogenous non-coding RNAs that can promote or inhibit gliomagenesis. Our study aimed to explore the role of circASPM in GBM and its molecular mechanism.Methods: Levels of circASPM, miR-130b-3p and E2F1 were determined by quantitative real-time PCR (qRT-PCR) or western blotting assay. MTS, Edu, neurospheres formation and extreme limiting dilution assays were used to detect the tumorigenesis and proliferation of GSCs in vitro. The interactions between miR-130b-3p and circASPM or E2F1 was demonstrated via qPCR, western blotting, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft experiments was used to analyze tumor growth in vivo.Results: CircASPM was overexpressed in GBM and could promote the tumorigenesis and proliferation of GSCs both in vitro and in vivo. Mechanistically, circASPM up-regulated the expression of E2F1 in GSCs via miR-130b-3p sponging. We furtherly demonstrated that circAPSM could promote the GSCs proliferation via E2F1 up-regulating. Therefore, our study identified a novel circRNA and its possible mechanism in the development and tumorigenesis of GBM.Conclusions: CircASPM can promote GBM progression via regulating miR-130b-3p/E2F1 axis, suggesting that circAPSM could provide an effective biomarker for GBM diagnosis and prognostic evaluation and possibly being used for molecular targeted therapy.
Acidified Pepsin Promotes Laryngeal Precancerosis by Upregulating H+/K+-ATPase and Activating Mitophagy in Laryngeal Epithelial Cells
Authors: Cheng Ke-Jia , Xu Qiong , Li Zhi-Mei , Zhou Shui-Hong , Bao Yang-Yang , Chen Zhe , Fan Jun 
Published: December 2020

Abstract
Background: Although laryngopharyngeal reflux (LPR) has been implicated in various upper aerodigestive tract and laryngeal diseases, the underlying mechanisms remain elusive. In this study, we investigated the role of gastric acidified pepsin in laryngeal precancerosis. Results: Acidified pepsin (pH=3) enhanced the growth and survival of mouse laryngeal epithelial cells in vitro and promoted laryngeal mucosal thickening and laryngeal epithelial cell growth in vivo. Furthermore, acidified pepsin promoted autophagy/mitophagy induction, accompanied by a significant decrease in mitochondrial membrane potential (MMP). Inhibition of autophagy by chloroquine abolished the ability of acidified pepsin to promote mitophagy and cell growth in laryngeal epithelial cells. Additionally, chloroquine promoted cell apoptosis and further reduced MMP in laryngeal epithelial cells treated with acidified pepsin. The expression levels of pepsin and H+/K+-ATPase α and β subunits in 31 human laryngeal mucosa specimens were 51.6%, 48.4%, and 48.4%, respectively. Importantly, the pepsin level was correlated with the H+/K+-ATPase β subunit level. H+/K+-ATPase upregulation in laryngeal epithelial cells in response to acidified pepsin was essential for the mitophagy-promoting effect of acidified pepsin. H+/K+-ATPase knockout or inhibition further reduced MMP in the presence of acidified pepsin. Conclusions: Our findings suggest that in an acidic environment, pepsin promotes laryngeal epithelial cell growth and survival by upregulating H+/K+-ATPase and activating mitophagy, potentially leading to laryngeal precancerosis.
Effects of Empagliflozin in Different Phases of Diabetes Mellitus-Related Cardiomyopathy
Authors: Oka Satoshi , Kai Takahiko , Hoshino Katsuomi , Watanabe Kazunori , Nakamura Jun , Abe Makoto , Watanabe Akinori 
Published: December 2020

Abstract
Background: In diabetes mellitus-related cardiomyopathy (DMCMP), hyperglycemia causes endothelial dysfunction, fibrosis, and myocardial injury, which result in left ventricular (LV) dysfunction. Treatment with sodium–glucose co-transporter 2 inhibitor (SGLT2i) reduces the risk of exacerbation of heart failure (HF). The beneficial effects of SGLT2i on HF depend not only on indirect actions such as osmotic diuresis but also direct actions on the myocardium leading to improvements in LV function. However, it remains unclear whether SGLT2i treatment is equally effective in any phase of DMCMP. The aim of this observational study was to compare the efficacy of SGLT2i treatment on LV dysfunction between early and advanced DMCMP.Methods: Thirty-five symptomatic non-ischemic HF patients with LV ejection fraction (EF) greater than 40% and type 2 diabetes mellitus (T2DM) treated with administration of empagliflozin (10 mg/day) were enrolled. According to the myocardial extracellular volume fraction (ECV), a reliable marker of cardiac fibrosis quantified by cardiac magnetic resonance, the patients were divided into the early DMCMP group (n = 16, ECV ≤ 30%) and advanced DMCMP group (n = 19, ECV > 30%) and followed-up prospectively. Echocardiography was performed at baseline and after 12 months. LV systolic function assessed as LV global longitudinal strain (GLS) and diastolic function assessed as the ratio of early diastolic mitral inflow velocity to early diastolic mitral annular velocity (E/e’) were compared.Results: ECV was strongly correlated with T2DM duration (r2 = 0.65, p < 0.001). At baseline, both groups had similar backgrounds (LVGLS: 7.9 ± 2.4% vs. 6.7 ± 3.0%, p = 0.207, and E/e’: 13.2 ± 6.1 vs. 12.6 ± 3.8, p = 0.694). After 12 months, the early DMCMP group showed greater improvement in LVGLS (ΔLVGLS: 4.6 ± 1.5% vs. 1.6 ± 3.3%, p = 0.003) and E/e’ (ΔE/e’: -3.4 ± 5.5 vs. -0.1 ± 3.5, p = 0.043) than in the advanced DMCMP group.Conclusions: The positive effects of empagliflozin on LV dysfunction were more remarkable in DMCMP with mild cardiac fibrosis than with advanced fibrosis. Early intervention of SGLT2i for DMCMP is preferable.
Uncertainty Management Associated With Project Scheduling in Mine Construction: A Coal Mining Case Study
Authors: Renaud Matt , Kumral Mustafa 
Published: December 2020

Abstract
Due to the cyclical nature of commodity prices, the profitability of mining projects relies on proper timing. To ensure optimal profits, mines should be brought online at the time, which maximizes the potential value of the asset. In this paper, a coking coal mine construction case is used to demonstrate the effectiveness of scheduling large-scale construction projects with uncertain durations under price cyclicality. Project parameters are obtained stochastically via Monte Carlo sampling, allowing for the influence of uncertainty to be quantified. The critical path method and linear programming are employed to analyze the results and to optimize the construction process, ensuring the maximum value of the mining project. The parameters are repeatedly sampled to obtain distributions of possible project outcomes, allowing for risk and sensitivity quantification. The optimal schedule for construction was determined to be 247 weeks, with a most likely value of $813 million.
Reconstruction of Aesthetic Stomatognathic Function After a High-energy Maxillo-orofacial Fracture: a Case Report
Authors: Kataoka Toshiyuki , Amemiya Kei , Udagawa Gen , Akagi Yuichi , Kagawa Chie , Okamoto Toshihiro 
Published: December 2020

Abstract
Background: High-energy injury patients with head trauma often present with pan-jaw fractures involving loss of teeth and alveolar bone. They experience a significant decrease in their quality of life due to masticatory disorders, dysarthria, and poor aesthetics. In most cases, they are treated separately by a medical team and a prosthodontist. Moreover, removable dentures provide little satisfaction to the patients.Case presentation: A 29-year-old young woman suffered a high-energy trauma from a fall accident. Following surgery for a jaw fracture, she underwent occlusal reconstruction with osseointegrated implants. The same team performed maxillofacial surgery and prosthetic treatments, and the series of treatment plans included bone grafting and periodontal plastic surgery.Conclusions: The treatment proved successful after more than two years with no signs of peri-implantitis. The patient was highly satisfied with the results. Early intervention by an oral and maxillofacial surgeon in such patients is essential for a good prognosis. Surgeons and prosthodontists who belong to the same team could complete the treatment with fewer surgical procedures. Furthermore, implant treatment in a patient with oral and maxillofacial fractures might improve aesthetics and function.
Possible Case of Children Onset Systemic Lupus Erythematosus Triggered by Covid-19
Authors: Bettiol Clémence Odile , Ntagerwa Joseph , Greef Axel De , Tuerlinckx David , Boutsen Yves 
Published: December 2020

Abstract
This case report will present the case of an 11 years old child diagnosed with childhood-onset systemic lupus erythematosus (cSLE) during the coronavirus Covid-19 pandemic. Her initial symptoms were compatible with a Covid-19 infection but repeated PCR on naso-pharyngeal swabs were negative. Two serological assays were carried out but only one showed doubtful IgG results.Considering that viral infection could be responsible for autoimmune disease outbreaks and with increasing evidences of SARS Cov 2 actions on human inflammatory and immune systems; we discuss here a potential cSLE diagnosis triggered by Covid-19 infection.
The Relationship of Anti-Mullerian Hormone in Polycystic Ovary Syndrome Patients With Different Subgroups
Authors: Ran Yu , Li Cong , Yi Qiang , Qiao Hong , Yang Qing , Ye Yanli 
Published: December 2020

Abstract
Purpose To explore the value of anti-Mullerian hormone (AMH) in polycystic ovary syndrome (PCOS) patients for different phenotype and age, and identify the relationship between the hyperandrogenism (HA) and polycystic ovary morphology (PCOM) in Chinese cohort.Methods A total of 2262 women (1631 with PCOS and 631 health controls) were enrolled. The serum AMH and total testosterone (TT) were analyzed, compared the AMH level of each subgroup and evaluated the value of each phenotype and age group of PCOS.Results The level of AMH in PCOS(8.63±4.73ng/ml) was higher than that in health controls(5.57±3.31ng/ml) (P＜0.01).The level of AMH in PCOM subgroup(11.19±6.4ng/ml) was significantly higher than that in HA subgroup(8.58±4.74ng/ml) (P＜0.01), and both higher than that in health controls(P＜0.01). AMH changes highly in PCOS compared with the health control, but as the same value in subgroups of PCOS patients under 30-year-old.Conclusion AMH changed in different subgroups of PCOS, which was the possible reason why AMH was not a diagnostic indicator. However, AMH could differ the subgroup in clinical, AMH was strongly related with PCOM, not hyperandrogenism. AMH changed much as aged, but stable in PCOS patients under 30-year-old.