bluuebunny/crossref_metadata_2025_split huggingface dataset:
Smoc1 and Smoc2 regulate bone formation as novel downstream molecules of Runx2
Authors: Takahata Yoshifumi , Hagino Hiromasa , Kimura Ayaka , Urushizaki Mitsuki , Kobayashi Sachi , Wakamori Kanta , Fujiwara Chika , Nakamura Eriko , Yu Kayon , Kiyonari Hiroshi , Bando Kana , Murakami Tomohiko , Komori Toshihisa , Hata Kenji , Nishimura Riko 
Published: April 2021

Abstract
Runx2 is an essential transcription factor for bone formation. Although osteocalcin, osteopontin, and bone sialoprotein are well-known Runx2-regulated bone-specific genes, the skeletal phenotypes of knockout (KO) mice for these genes are marginal compared with those of Runx2 KO mice. These inconsistencies suggest that unknown Runx2-regulated genes play important roles in bone formation. To address this, we attempted to identify the Runx2 targets by performing RNA-sequencing and found Smoc1 and Smoc2 upregulation by Runx2. Smoc1 or Smoc2 knockdown inhibited osteoblastogenesis. Smoc1 KO mice displayed no fibula formation, while Smoc2 KO mice had mild craniofacial phenotypes. Surprisingly, Smoc1 and Smoc2 double KO (DKO) mice manifested no skull, shortened tibiae, and no fibulae. Endochondral bone formation was also impaired at the late stage in the DKO mice. Collectively, these results suggest that Smoc1 and Smoc2 function as novel targets for Runx2, and play important roles in intramembranous and endochondral bone formation.
Novel variants in Krueppel Like Factor 1 that cause Persistence of Fetal Hemoglobin in In(Lu) individuals
Authors: Eernstman Jesse , Veldhuisen Barbera , Ligthart Peter , Lindern Marieke von , Schoot Ellen van der , Akker Emile van den 
Published: April 2021

Abstract
Beta-hemoglobinopathies become prominent after birth due to a switch from γ-globin to the mutated β-globin. Haploinsufficiency for the erythroid specific indispensable transcription factor Krueppel-like factor 1 (KLF1) is associated with high persistence of fetal hemoglobin (HPFH). The In(Lu) phenotype, characterized by low to undetectable Lutheran blood group expression is caused by mutations within KLF1 gene. These KLF1 variants often lead to KLF1 haploinsufficiency. We screened a donor cohort of 55 Lutheran weak or negative donors for KLF1 variants. To discriminate between weak and negative Lutheran expression, a flow cytometry (FCM) assay was developed to detect Lu polymorphisms. The Lu(a-b-) (negative) donor group, showing a significant decreased CD44 (Indian blood group) expression, also showed increased HbF and HbA2 levels, with outliers expressing >5% HbF. KLF1 exons and promoter sequencing revealed variants in 80% of the Lutheran negative donors. Thirteen different variants plus one high frequency SNP (c.304T>C) were identified of which 6 were novel. In primary erythroblasts, knockdown of endogenous KLF1 resulted in decreased CD44, Lu and increased HbF expression, while KLF1 over-expressing cells were comparable to wild type (WT). In line with the pleiotropic effects of KLF1 during erythropoiesis, distinct KLF1 mutants expressed in erythroblasts display different abilities to rescue CD44 and Lu expression and/or to affect fetal (HbF) or adult (HbA) hemoglobin expression.
Selenium and the risk of cardiovascular disease and all-cause mortality: a meta-analysis of prospective observational studies and randomized controlled trials
Authors: Sun Hualei , Long Shao Rong , Chen Gaiyun , Wang Yajuan , Liang Rui , Li Wenjie 
Published: April 2021

Abstract
BackgroundThis meta-analysis of prospective observational studies and randomized controlled trials (RCTs) was carried out to explore the association between selenium and the risk of cardiovascular disease (CVD) and all-cause mortality.Methods and Study DesignWe searched the PubMed, EMBASE and Web of Science database for eligible studies which included the relationship between selenium and the outcomes of interest. 25 prospective observational studies and 9 RCTs were included in our meta-analysis.ResultsThe observational studies showed that there was a significant inverse association between serum selenium and the risk of CVD (RR: 0.78; 95% CI: 0.68–0.89), coronary heart disease (CHD) (RR: 0.75; 95% CI: 0.58–0.95) and all-cause mortality (RR: 0.77; 95% CI: 0.71–0.84). We also found a significant inverse association between selenium supplements and the risk of total CVD (RR: 0.78; 95% CI: 0.62–0.98) and all-cause mortality (RR: 0.81; 95% CI: 0.65-1.00) in RCTs studies.ConclusionsOur meta-analysis found a significant inverse association between selenium and CVD, CHD, and all-cause mortality in prospective observational studies and RCTs, which indicate the selenium has protective effect in cardiovascular disease and all-cause mortality.
In-situ Conservation of Traditional Vegetable Diversity in Wa Homegardens in Southwestern Yunnan, China
Authors: Shao Hua , Hill Rosemary , Xue Dayuan , Yang Jingbiao 
Published: April 2021

Abstract
Background: Homegardens are recognized as in-situ conservation sources of germplasm diversity to overcome homogenous germplasm problems in the industrial agriculture system; it is crucial to understand how smallholders manage their homegardens to maintain traditional genetic resources. Wa is a long-dwelling ethnic group living mainly in southwest Yunnan, China. Traditional vegetables in homegardens management are still central to farmers’ livelihoods in Wa villages. We surveyed traditional vegetables in Wa homegardens and analyzed the factors conserving traditional vegetables in the homegardens management. Methods: The methods used in this work included semi-structured interviews, questionnaires, and field surveys. A total of 60 households through purposive sampling in three townships, 6 villages were surveyed. We documented ethnobotanical information on local name, edible methods, edible parts of traditional vegetables maintained in Wa homegardens. Plant species cultivated in Wa homegardens were identified according to Flora of China.Results: Fifty-five traditional vegetable varieties and 36 hybrid vegetable varieties in the homegardens were recorded. Among all the villages, 23 ± 6 (average ± S.D.) traditional vegetable varieties per homegarden and 9 ± 3 (average ± S.D.) introduced vegetable varieties per homegarden were recorded. 78% of households choose to store the local seeds themselves, with a further 9% of households’ seed supplies coming from neighbors and relatives, other 13% of households choose to purchase local seeds in the markets. In 83% of families, the female head holds the main responsibility for decision making for traditional vegetables planted in homegardens; in 10% of families were male head household to take responsibility for decision-making, and a small percentage which is 2% is determined by the elderly. 5% of families will make decisions jointly between both male and female household heads.Conclusions: This study demonstrated that rich traditional germplasm diversity is harbored in the Wa homegardens because of Wa communities’ unique culture and traditional knowledge, which is practiced daily using homegrown food plants. Local vegetable seed saving and sharing systems can help maintain the germplasm diversity in the Wa community’s homegardens. Wa homegardens can be a practical solution to protect the traditional germplasm diversity and maintain a lifestyle with traditional culture.
A Novel Tooth Tip Relief Method for Reducing Micro-Pitting of Spur Gears
Authors: Xu Xiangyang , Liang Yinghua , Zuo Shumiao , Dong Peng , Liu Yanfang , Wang Shuhan , Wang Zhuo 
Published: April 2021

Abstract
Micro-pitting is a common fatigue failure mode of spur gears. To reduce it, this paper proposes a novel tooth tip relief method. Gear meshing simulation is firstly performed considering the actual contact path, showing that there are four Hertz contact stress peaks in the transition areas of the tooth flank. Equations are then developed for the novel tooth tip relief method: one focuses on the smooth transition between the involute profile and the tip relief region, the other on the smooth transition between the tip relief region and the tooth tip. The results of curvature radius and Hertz contact stress show that the proposed novel method can effectively reduce the Hertz contact stress peaks, which indicates this tip relief method could benefit for reducing the micro-pitting. Finally, both wear simulations and bench tests are conducted, verifying the effectiveness of the proposed method for reducing the micro-pitting of spur gears.
Palmitoylethanolamide for Sleep Disturbance. A Double-blind, Randomised, Placebo-controlled Interventional Study
Authors: Rao Amanda , Ebelt Phillippa , Mallard Alistair , Briskey David 
Published: April 2021

Abstract
Background: Sleep is essential for wellbeing, yet sleep disturbance is a common problem linked to a wide range of health conditions. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide proposed to promote better sleep via potential interaction with the endocannabinoid system.Methods: This double-blind, randomized study on 103 adults compared the efficacy and tolerability of 8 weeks of daily supplemented PEA formulation (350 mg Levagen+TM) to a placebo. Sleep quality and quantity were measured using wrist actigraphy, a sleep diary and questionnaires. Results: At week 8, PEA supplementation reduced sleep onset latency, time to feel completely awake and improved cognition on waking. After 8 weeks, both groups improved their sleep quality and quantity scores similarly. There was no difference between groups at baseline or week 8 for sleep quantity or quality as measured from actigraphy or sleep diaries. Conclusion: These findings support PEA as a potential sleeping aid capable of reducing sleep onset time and improving cognition on waking. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12618001339246. Registered 9th August 2018, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375493&isReview=true
Polyaniline as a Hippocampus-inspired Biomimetic Device for Electrochemical Monitoring of Phosphorylated Tau induced Neurodegenerative Processes
Authors: Hsu Chien-Chih , Wang Yu-Rong , Tripathi Adarsh , Wang Yu-Lin , Chen Jung-Chih 
Published: April 2021

Abstract
Tau protein plays an important role in Alzheimer’s Disease (AD), especially its hyper-phosphorylated state, which is involved in aggregating and triggering entangled nerve fibers, eventually leading to neuronal death. This study investigates whether this hyper-phosphorylated tau can be dephosphorylated by electrochemical techniques. Aiming at the phosphorylation sites only found in AD brain, we utilized human tau (pS214) peptide as the target for this study. With the help of electrochemical quartz crystal microbalance (EQCM) system, we utilized electrochemical methods to trigger interaction between potential charge and tau protein and monitor the whole reaction on the electrode by QCM. The polyaniline membrane was then used as a hippocampus-inspired biomimetic device to observe charge-protein interactions where positive potential attaches phosphorylated tau and negative potential detaches the phosphoryl group. We successfully found out that 0.5 V can induce complete attachment to phosphorylated tau and − 0.3 V can achieve dephosphorylation of tau peptide. Furthermore, to demonstrate dephosphorylation of tau peptide, we performed mass spectrometry to examine the reaction product and prove our hypothesis. To sum up, this device could be a potential novel treatment for tau-related neurodegenerative diseases.
A Comparative Analysis on Risk Communication between International and Chinese Literature from the Perspective of Knowledge Domains Visualization
Authors: Dong Huiling , Wu Qunhong , Pang Yue , Wu Bingyi 
Published: April 2021

Abstract
Background At the end of 2019, the outbreak of coronavirus disease (COVID-19) severely damaged and endangered people’s lives. Risk communication plays an important role in the response to COVID-19 successfully. Therefore, a comprehensive analysis of risk communication research is necessary, which can understand current research hotspots and reveal new trends.Methods In this study, international articles come from Web of science database (3983), Chinese articles come from the China National Knowledge Infrastructure database (1134), Bibliometric and mapping knowledge domain analysis were used for cooperation network, co-word co-occurrence network and burst detection analysis.Results The first article in this field was published by western scholars earlier, while the first Chinese article in 2002. Research institutions mainly come from universities. The United States play a key role in this field. Chinese scholars had a closer cooperation network, but there was less cooperation among domestic institutions. Risk perception, public trust, risk management, and risk information dissemination had always been the research hot-spots in this academic direction. Trust, sentiment research, and public risk events were essential directions for future. There are 25 burst words for international articles, while 11 burst words for Chinese articles from 2000–2020.Conclusions In summary, both domestic and international researchers are concerned about risk communication, risk perception, trust, and risk information. International scholars begin to take cares with ecological and technological risks research, radiating many areas of social risk. Compared with international research on risk communication more systematic and comprehensive, Chinese scholars takes SARS as the research background and reviewing foreign knowledge as the research starting point. With purpose of practical and applied research based on a public emergency, the risk-communication research lacks continuity in Chinese academy in the past years.
Organic N-type Electrets for Field-effect Transistors, Photo Memories and Artificial Synapses
Authors: Li Dongfan , Qin Zongze , Lu Wanlong , Ren Yurong , Zhu Yuanwei , Wang Hong , Li Shengtao , Bu Laju , Lu Guanghao 
Published: April 2021

Abstract
Electrets, typically referring to insulator materials with permanently-trapped charges, are widely used for electronic devices, actuators and medical filtering. Here, organic n-type electrets, generated from oxygen-degraded n-type semiconductors, are proposed as photo-induced electrets. The sheet charge densities of such n-type electret films, as high as 7.47 × 1012 cm-2, are used to provide steady built-in electric field to significantly improve the performance of organic field-effect transistors (OFETs). For example, OFETs made of p-type semiconductor 2,7-dioctyl[1]benzothieno[3,2-b][1]benzothiophene (C8-BTBT), in combination with n-type electret N,N′-Dioctyl-3,4,9,10-perylenedicarboximide (C8-PTCDI), show a hole field-effect mobility 13.3 cm2·V−1·s−1, along with a memory window over 100 V, a memory on/off ratio 106 and a stable retention life time over one month in ambient air. Subsequently, the generality of n-type electrets for transistors and photo memories applications are demonstrated. Furthermore, OFETs with organic n-type electrets are employed in artificial synapse, and the recognition rate of brain-inspired neuromorphic computing is 65%.
RLIM: Representation Learning Method for Influence Maximization in social networks
Authors: Chengai Sun , Xiuliang Duan , Liqing Qiu , Qiang Shi , Tengteng Li 
Published: April 2021

Abstract
A core issue in influence propagation is influence maximization, which aims to find a group of nodes under a specific information diffusion model and maximize the final influence of this group of nodes. The limitation of the existing researches is that they excessively depend on the information diffusion model and randomly set the propagation ability (probability). Therefore, most of the algorithms for solving the influence maximization problem are basically difficult to expand in large social networks. Another challenge is that fewer researchers have paid attention to the problem of the large difference between the estimated influence spread and the actual influence spread. A measure to solve the influence maximization problem is applying advanced neural network architecture also represents learning method. Based on this idea, the paper proposes Representation Learning for Influence Maximization (RLIM) algorithm. The premise of this algorithm is to construct the influence cascade of each source node. The key is to adopt neural network architecture to realize the prediction of propagation ability. The purpose is to apply the propagation ability to the influence maximization problem by representation learning. Furthermore, the results of the experiments show that RLIM algorithm has greater diffusion ability than the state-of-the-art algorithms on different online social network data sets, and the diffusion of information is more accurate.
Metformin Resistant MDA-MB-468 Cells Exhibit EMT-like Phenotype and Increased Migration Capacity
Authors: Koker Sahika Cingir , Yalcin Banu , Turacli Irem Dogan 
Published: April 2021

Abstract
Background: Metformin is one of the most prescribed drug for the treatment of type II diabetes. Its anti-proliferative effect is also taken advantage for the treatment of cancer. Despite many of the studies mention the positive effects of metformin in inhibiting the proliferation of cancer cells, there are also studies which questions this idea as well.Methods: In this study, we investigated the most widely studied breast cancer cell lines, ER(+) MCF7 cells, TNBC MDA-MB-231 and MDA-MB468 cells in terms of metastatic behavior under long-term metformin treatment. MCF7, MDA-MB231 and MDA-MB468 cells were gained resistant to metformin starting from 0.2mM to 3.2mM. Results: Compared to MCF7 and MDA-MB231 cell lines, we only observed dramatic changes in MDA-MB468 cells whose morphology has been changed towards mesenchymal like phenotype. Moreoever, migration capacity of these cells were also significanlty increased which were validated at both mRNA and protein levels as well as wound healing assay. In addition EMT like phenotype and increasing migration capacity of metformin resistant MDA-MB468 cells, they exhibited less sensitivity to PI3K inhibitor. Conclusions: All together, our data pointed out that, metformin’s effects should be questioned depending on the subtype of the breast cancer that’s to be treated.
Polyphenol-Rich Muscadine Grape Extract Reduces Triple Negative Breast Cancer Metastasis in Mice with Changes in the Gut Microbiome
Authors: Collard Marianne , Austin Nataleigh N , Brown-Harding Heather , Westwood Brian , Tallant E Ann , Gallagher Patricia E 
Published: April 2021

Abstract
Background

Triple negative breast cancer (TNBC) has a high propensity to metastasize and no treatments are available to slow or prevent metastatic progression. The goal of this study is to determine whether a proprietary high-polyphenol content muscadine grape extract (MGE) inhibits TNBC metastasis.

Methods

4T1 TNBC cells were injected into the mammary fat pad of 6-week-old female Balb/c mice. After 2 weeks, tumors were surgically removed and mice were placed into a control (n=8) or treatment group that received 0.1 mg/mL total phenolics MGE in the drinking water (n=8) for 4 weeks. Immunohistochemistry (Ki67, α-SMA) and hemotoxylin and eosin staining were used to quantify metastases. Gut microbial composition was determined by 16S rRNA sequencing and short chain fatty acids (SCFAs) were detected by gas chromatography. MDA-MB-231, BT-549 and 4T1 TNBC cell motility and cytoskeletal organization was assessed in vitr o by scratch wound migration and confocal microscopy, respectively. Data were evaluated by student’s t -test.

Results

MGE reduced metastatic proliferation in mouse lungs (33.3%) and livers (58.3%) and decreased the number (51.1%) and size (17.4%) of liver metastases, resulting in a 55.7% reduction in metastatic tumor burden ( P < 0.01). Serum IL-6 was reduced 99.6% in MGE-treated mice ( P = 0.06). MGE attenuated migration, altered cytoskeletal organization, and reduced RHAMM expression in TNBC cells ( P < 0.05). The gut microbiota, a mediator of polyphenolic bioactivities, was altered significantly in MGE-treated mice; MGE increased the alpha diversity (7.14%), Firmicutes/Bacteroidetes ratio (2-fold), relative abundance of butyrate-producing genera, and butyrate (3-fold) ( P < 0.05). Butyrate inhibited 4T1 cell proliferation and migration, suggesting butyrate contributes to MGE’s anti-metastatic activities ( P < 0.05).

Conclusion

Our results indicate that MGE may be an effective adjuvant therapy to reduce TNBC metastatic progression.
A Novel Blood-Based Assay for Treatment Monitoring of Tuberculosis
Authors: Zimmer Alexandra Jaye , Schumacher Samuel G , Södersten Erik , Mantsoki Anna , Wyss Romain , Persing David H , Banderby Sara , Meuzelaar Linda Strömqvist , Prieto Jacqueline , Gnanashanmugam Devasena , Khatri Purvesh , Ongarello Stefano , Ruhwald Morten , Denkinger Claudia Maria 
Published: April 2021

Abstract
ObjectivesA novel 3-gene host transcriptional signature (GBP5, DUSP3 and KLF2) that has been validated for TB diagnosis. The signature was recently translated by Cepheid into a prototype cartridge-based test that can be run on the GeneXpert instruments. In this study, we prospectively evaluated the change in the expression of the cartridge-based 3-gene signature with time following treatment initiation among pulmonary TB patients who were microbiologically cured at the end of treatment. ResultsOur results show that the 3-gene signature expression level (TB score) changes significantly over time with respect to baseline levels. The greatest increase in TB score occurred within the first month of treatment (median fold-increase in TB score: 1.08 [IQR 0.54-1.52]) and plateaued after 4 months of treatment (median TB score: 1.97 [IQR: 1.03-2.33]. The rapid and substantial increase of the TB score in the first month of treatment holds promise for the early identification of patients that respond to TB treatment. The plateau in TB score at 4 months may indicate early clearance of disease and could direct treatment to be shortened. These hypotheses need to be further explored with large prospective treatment monitoring and test of cure studies.
The Transcription Factor Complex LMO2/TAL1 Regulates Branching and Endothelial Cell Migration in Sprouting Angiogenesis
Authors: Yamada Yoshihiro , Zhong Yi , Miki Shiho , Taura Akiko , Rabbitts Terence 
Published: April 2021

Abstract
The transcription factor complex, consisting of LMO2, TAL1/LYL1, and GATA2, plays an important role in capillary sprouting by regulating VEGFR2, DLL4, and angiopoietin 2 in tip cells. Overexpression of the basic helix-loophelix transcription factor LYL1 in transgenic mice results in shortened tails. This phenotype is associated with vessel hyperbranching and a relative paucity of straight vessels due to DLL4 downregulation in tip cells by forming aberrant complex consisting of LMO2 and LYL1. Knockdown of LMO2 or TAL1 inhibits capillary sprouting in spheroid-based angiogenesis assays, which is associated with decreased angiopoietin 2 secretion. In the same assay using mixed TAL1- and LYL1-expressing endothelial cells, TAL1 was found to be primarily located in tip cells, while LYL1-expressing cells tended to occupy the stalk position in sprouts by upregulating VEGFR1 than TAL1. Thus, the interaction between LMO2 and TAL1 in tip cells plays a key role in angiogenic switch of sprouting angiogenesis.