bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved osteogenesis of human adipose-derived stromal cells on hydroxyapatite-mineralized graphene film
Authors: Park Seong Chae , Yang Woo Sub , Ahn Ji Yeon , Park Jong Bo , Lee Jong-Hwan , Jung Youngjin , Kim Hwa Rang , Kim Ji Yoon , Lim Jeong Mook , Hong Byung Hee 
Published: February 2021

Abstract
This study investigated whether hydroxyapatite (HAp)-mineralized graphene (GR) film could support osteogenic differentiation of human adipose-derived, stromal cell (hASCs) in vitro. GR was produced by a chemical vapor deposition (CVD) method and the physical and chemical characteristics of the GR film, which was functionalized with HAp mineralization following ultraviolet-ozone (GR_UVO) treatment, were subsequently validated. Results of scanning electron microscopy, x-ray photoelectron spectroscopy and Raman spectroscopy showed GR_UVO for 5 min yielded applicable GR coverage (97.98 ± 0.85%), conversion of chemical composition ratio (29.78% C–O, 18.34% C=O and 8.49% O–C=O) and degree of oxidation, (I
2D/I
G ratios 2.22) with maximal density of HAp-GR layer. In vitro-cell proliferation, viability and adhesion of hASCs after being cultured on HAp-mineralized, GR-coated glass (HAp/GR) with the optimized GR_UVO treatment (5 min) demonstrated a significant increment of proliferation (1.56 ± 0.1 vs 1–1.13 ± 0.1, p< 0.05) without changing in viability (94.83 ± 1% to 95.3 ± 1.6%, p= 0.9651) compared with the control (intact glass). There were no differences in F-actin and vinculin on day 1 (p= 0.1422 and 0.5025, respectively) and on day 4 (p= 0.3787 and 0.9208) of culture. Osteogenic differentiation of hASCs was significantly improved on the HAp/GR with increasing of osteogenesis-related genes (Runx2 and Osteocalcin). The hASCs culture with the HAp/GR glass promoted phospho-SMAD1/5/9 and SMAD4 expression with increased patterns of BMP/Smad signal-related genes, regardless of differentiation induction or not. These results demonstrated that HAp-mineralized GR film prepared by CVD method and optimal ultraviolet treatment promoted osteogenic differentiation of hASCs, which BMP/Smad signaling was involved.
Intramolecular interactions in a target specific anti-tumor nanodrug: a theoretical study
Authors: Dwivedi Manoj Kumar 
Published: February 2021

Abstract
Through this authoritative report, an application of fragment molecular orbital (FMO) method on a functionalized carbon nanotube (CNT) has been proposed. A targeted anti-tumor nanodrug, based on CNT that converges towards cancerous cells, has been innovated in this regard. The anticancer drug cisplatin and the target selector arginine-aspartate-glycine acid (RGD) have been attached via poly ethylene glycol (PEG) on CNT. This nanodrug has been divided into 12 fragments including CNT as one of them. General atomic molecular electronic structure system (GAMESS), an ab initio package, has been used for calculations. The contributions of various fragments have been discussed in terms of inter-fragment interactions. Results indicate that the CNT shares the important role in stabilizing the different parts of its derivatives. In addition, this report proves CNT as a fragment for FMO method.
Polishing and planarization of single crystal diamonds: state-of-the-art and perspectives
Authors: Luo Hu , Ajmal Khan Muhammad , Liu Wang , Yamamura Kazuya , Deng Hui 
Published: February 2021

Abstract
Diamond is a promising material for the modern industry. It is widely used in different applications, such as cutting tools, optical windows, heat dissipation, and semiconductors. However, these application areas require exceptionally flattened and polished diamond surfaces. Unfortunately, due to the extreme hardness and chemical inertness of diamond, the polishing of diamond is challenging. Since the 1920s, various conventional and modern mechanical, chemical, and thermal polishing techniques have been proposed and developed for finishing diamond surfaces. Therefore, to impart proper guidance on selecting a good polishing technique for production practice, this paper presents an in-depth and informative literature survey of the current research and engineering developments regarding diamond polishing. At first, a brief review of the general developments and basic material removal principles is discussed. This review concludes with a detailed analysis of each techniques’ polishing performance and critical challenges, and a discussion of the new insights and future applications of diamond polishing.
The Modified Skate Flap: A New Technique for Nipple-Areola Complex Reconstruction in Implant-Based Breast Reconstruction
Authors: Pu Lee L Q , Song Ping 
Published: February 2021

Abstract
Nipple-areola complex (NAC) reconstruction is an important part of breast reconstruction. Although several techniques for NAC reconstruction have been described in the literature, the long-term outcomes after NAC reconstruction remain less satisfactory, especially following implant-based breast reconstruction. The authors reported their newly developed technique for NAC reconstruction in implant-based breast reconstruction. The authors describe their modified skate flap, by preserving more dermal tissues from the skate flap, for NAC reconstruction, following implant-based breast reconstruction. Additional derma-fat grafts, harvested from the full-thickness skin graft site, are also added to the reconstructed nipple to ensure long-term shape, size, and projection of the reconstructed nipple. A total of 30 patients underwent such a NAC reconstruction after successful implant-based breast reconstruction by the senior author. The minimum follow-up time was 1 year. No significant surgical complications have been observed in their series of 30 patients, and only a minor office procedure was performed subsequently in 6 patients (4 unilateral and 2 bilateral) to improve the shape of the reconstructed nipple. During a minimum of a 1-year follow-up period, outcomes with the authors’ technique in 30 patients are satisfactory; good size, shape, and projection of the reconstructed nipple are maintained. The long-term outcome of NAC reconstruction after implant-based breast reconstruction can be optimized with their modified skate flap by using all available flap tissue and with the addition of derma-fat grafts. The authors’ technique can be used safely for NAC reconstruction after implant-based breast reconstruction with good outcome and high patient satisfaction.
Development of a novel mouse model of diet-induced nonalcoholic steatohepatitis–related progressive bridging fibrosis
Authors: Ichimura-Shimizu Mayuko , Omagari Katsuhisa , Yamashita Michiko , Tsuneyama Koichi 
Published: February 2021

ABSTRACT
Nonalcoholic steatohepatitis (NASH) progresses to liver fibrosis and cirrhosis. Existing mouse models of NASH rarely develop diet-induced severe fibrosis. We aimed to establish a dietary model of NASH with rapid progression to fibrosis. Six-week-old male Tsumura-Suzuki obese diabetes (TSOD) mice (a model of spontaneous metabolic syndrome) and corresponding control Tsumura-Suzuki nonobese (TSNO) mice were fed a novel diet high in fat, cholesterol, and cholate (iHFC). Histologic steatohepatitis, including steatosis, inflammation, and fibrosis, were observed in both TSNO and TSOD iHFC diet–fed mice at 20 weeks of age. As compared with TSOD mice, TSNO mice developed much more severe fibrosis and reached stage 3 of bridging fibrosis within 14 weeks under the iHFC diet feeding. Perivenular/perisinusoidal pattern of fibrosis in TSNO mice resembled human NASH. Our model of NASH with advanced fibrosis by simple diet offers many advantages useful in studying the mechanism of liver fibrosis and preclinical drug testing.
Downregulation of the broad-specificity amino acid permease Agp1 mediated by the ubiquitin ligase Rsp5 and the arrestin-like protein Bul1 in yeast
Authors: Tanahashi Ryoya , Matsushita Tomonori , Nishimura Akira , Takagi Hiroshi 
Published: February 2021

ABSTRACT
Most of plasma membrane transporters are downregulated by ubiquitination-dependent endocytosis to avoid the excess uptake of their substrates. In Saccharomyces cerevisiae, ubiquitination of transporters is mediated by the HECT-type ubiquitin ligase Rsp5. We report here a mechanism underlying the substrate-induced endocytosis of the broad-specificity amino acid permease Agp1. First, we found that Agp1 underwent ubiquitination and endocytosis in response to the addition of excess asparagine, which is a substrate of Agp1. Moreover, the substrate-induced internalization of Agp1 was dependent on the ubiquitination activity of Rsp5. Since Rsp5 requires α-arrestin family proteins as adaptors to bind with substrates, we next developed a method of genetic screening to identify adaptor proteins for Agp1 endocytosis. This screening and biochemical analysis revealed that Bul1, but not its paralogue Bul2, was essential for the substrate-induced endocytosis of Agp1. Our results support that the substrate-induced endocytosis of Agp1 requires Rsp5 and Bul1.
DeepDTAF: a deep learning method to predict protein–ligand binding affinity
Authors: Wang Kaili , Zhou Renyi , Li Yaohang , Li Min 
Published: February 2021

AbstractBiomolecular recognition between ligand and protein plays an essential role in drug discovery and development. However, it is extremely time and resource consuming to determine the protein–ligand binding affinity by experiments. At present, many computational methods have been proposed to predict binding affinity, most of which usually require protein 3D structures that are not often available. Therefore, new methods that can fully take advantage of sequence-level features are greatly needed to predict protein–ligand binding affinity and accelerate the drug discovery process. We developed a novel deep learning approach, named DeepDTAF, to predict the protein–ligand binding affinity. DeepDTAF was constructed by integrating local and global contextual features. More specifically, the protein-binding pocket, which possesses some special properties for directly binding the ligand, was firstly used as the local input feature for protein–ligand binding affinity prediction. Furthermore, dilated convolution was used to capture multiscale long-range interactions. We compared DeepDTAF with the recent state-of-art methods and analyzed the effectiveness of different parts of our model, the significant accuracy improvement showed that DeepDTAF was a reliable tool for affinity prediction. The resource codes and data are available at https: //github.com/KailiWang1/DeepDTAF.
Bridging heterogeneous mutation data to enhance disease gene discovery
Authors: Zhou Kaiyin , Wang Yuxing , Bretonnel Cohen Kevin , Kim Jin-Dong , Ma Xiaohang , Shen Zhixue , Meng Xiangyu , Xia Jingbo 
Published: February 2021

Abstract
Bridging heterogeneous mutation data fills in the gap between various data categories and propels discovery of disease-related genes. It is known that genome-wide association study (GWAS) infers significant mutation associations that link genotype and phenotype. However, due to the differences of size and quality between GWAS studies, not all de facto vital variations are able to pass the multiple testing. In the meantime, mutation events widely reported in literature unveil typical functional biological process, including mutation types like gain of function and loss of function. To bring together the heterogeneous mutation data, we propose a ‘Gene–Disease Association prediction by Mutation Data Bridging (GDAMDB)’ pipeline with a statistic generative model. The model learns the distribution parameters of mutation associations and mutation types and recovers false-negative GWAS mutations that fail to pass significant test but represent supportive evidences of functional biological process in literature. Eventually, we applied GDAMDB in Alzheimer’s disease (AD) and predicted 79 AD-associated genes. Besides, 12 of them from the original GWAS, 60 of them are supported to be AD-related by other GWAS or literature report, and rest of them are newly predicted genes. Our model is capable of enhancing the GWAS-based gene association discovery by well combining text mining results. The positive result indicates that bridging the heterogeneous mutation data is contributory for the novel disease-related gene discovery.
PICS2: next-generation fine mapping via probabilistic identification of causal SNPs
Authors: Taylor Kimberly E , Ansel K Mark , Marson Alexander , Criswell Lindsey A , Farh Kyle Kai-How 
Published: February 2021

Abstract

Summary
The Probabilistic Identification of Causal SNPs (PICS) algorithm and web application was developed as a fine-mapping tool to determine the likelihood that each single nucleotide polymorphism (SNP) in LD with a reported index SNP is a true causal polymorphism. PICS is notable for its ability to identify candidate causal SNPs within a locus using only the index SNP, which are widely available from published GWAS, whereas other methods require full summary statistics or full genotype data. However, the original PICS web application operates on a single SNP at a time, with slow performance, severely limiting its usability. We have developed a next-generation PICS tool, PICS2, which enables performance of PICS analyses of large batches of index SNPs with much faster performance. Additional updates and extensions include use of LD reference data generated from 1000 Genomes phase 3; annotation of variant consequences; annotation of GTEx eQTL genes and downloadable PICS SNPs from GTEx eQTLs; the option of generating PICS probabilities from experimental summary statistics; and generation of PICS SNPs from all SNPs of the GWAS catalog, automatically updated weekly. These free and easy-to-use resources will enable efficient determination of candidate loci for biological studies to investigate the true causal variants underlying disease processes.

Availability and implementation
PICS2 is available at https://pics2.ucsf.edu.

Supplementary information
Supplementary data are available at Bioinformatics online.
Reported Individual Costs and Benefits of Sharing Open Data among Canadian Academic Faculty in Ecology and Evolution
Authors: Soeharjono Sandrine , Roche Dominique G 
Published: February 2021

Abstract
Open data facilitate reproducibility and accelerate scientific discovery but are hindered by perceptions that researchers bear costs and gain few benefits from publicly sharing their data, with limited empirical evidence to the contrary. We surveyed 140 faculty members working in ecology and evolution across Canada's top 20 ranked universities and found that more researchers report benefits (47.9%) and neutral outcomes (43.6%) than costs (21.4%) from openly sharing data. The benefits were independent of career stage and gender, but men and early career researchers were more likely to report costs. We outline mechanisms proposed by the study participants to reduce the individual costs and increase the benefits of open data for faculty members.
Simultaneous differential network analysis and classification for matrix-variate data with application to brain connectivity
Authors: Chen Hao , Guo Ying , He Yong , Ji Jiadong , Liu Lei , Shi Yufeng , Wang Yikai , Yu Long , Zhang Xinsheng ,   The Alzheimers Disease Neuroimaging Initiative
Published: February 2021

Summary
Growing evidence has shown that the brain connectivity network experiences alterations for complex diseases such as Alzheimer’s disease (AD). Network comparison, also known as differential network analysis, is thus particularly powerful to reveal the disease pathologies and identify clinical biomarkers for medical diagnoses (classification). Data from neurophysiological measurements are multidimensional and in matrix-form. Naive vectorization method is not sufficient as it ignores the structural information within the matrix. In the article, we adopt the Kronecker product covariance matrices framework to capture both spatial and temporal correlations of the matrix-variate data while the temporal covariance matrix is treated as a nuisance parameter. By recognizing that the strengths of network connections may vary across subjects, we develop an ensemble-learning procedure, which identifies the differential interaction patterns of brain regions between the case group and the control group and conducts medical diagnosis (classification) of the disease simultaneously. Simulation studies are conducted to assess the performance of the proposed method. We apply the proposed procedure to the functional connectivity analysis of an functional magnetic resonance imaging study on AD. The hub nodes and differential interaction patterns identified are consistent with existing experimental studies, and satisfactory out-of-sample classification performance is achieved for medical diagnosis of AD.
Neural Correlates of Successful Memory Encoding in Kindergarten and Early Elementary School Children: Longitudinal Trends and Effects of Schooling
Authors: Nolden Sophie , Brod Garvin , Meyer Ann-Kristin , Fandakova Yana , Shing Yee Lee 
Published: February 2021

Abstract
From age 5 to 7, there are remarkable improvements in children’s cognitive abilities (“5–7 shift”). In many countries, including Germany, formal schooling begins in this age range. It is, thus, unclear to what extent exposure to formal schooling contributes to the “5–7 shift.” In this longitudinal study, we investigated if schooling acts as a catalyst of maturation. We tested 5-year-old children who were born close to the official cutoff date for school entry and who were still attending a play-oriented kindergarten. One year later, the children were tested again. Some of the children had experienced their first year of schooling whereas the others had remained in kindergarten. Using 2 functional magnetic resonance imaging tasks that assessed episodic memory formation (i.e., subsequent memory effect), we found that children relied strongly on the medial temporal lobe (MTL) at both time points but not on the prefrontal cortex (PFC). In contrast, older children and adults typically show subsequent memory effects in both MTL and PFC. Both children groups improved in their memory performance, but there were no longitudinal changes nor group differences in neural activation. We conclude that successful memory formation in this age group relies more heavily on the MTL than in older age groups.
Urine Lipoarabinomannan Testing in Adults With Advanced Human Immunodeficiency Virus in a Trial of Empiric Tuberculosis Therapy
Authors: Matoga Mitch M , Bisson Gregory P , Gupta Amita , Miyahara Sachiko , Sun Xin , Fry Carrie , Manabe Yukari C , Kumwenda Johnstone , Cecilia Kanyama , Nyirenda Mulinda , Ngongondo McNeil , Mbewe Abineli , Lagat David , Wallis Carole , Mugerwa Henry , Hosseinipour Mina C 
Published: February 2021

Abstract

Background
The urine lipoarabinomannan (LAM) antigen test is a tuberculosis (TB) diagnostic test with highest sensitivity in individuals with advanced human immunodeficiency virus (HIV). Its role in TB diagnostic algorithms for HIV-positive outpatients remains unclear.

Methods
The AIDS Clinical Trials Group (ACTG) A5274 trial demonstrated that empiric TB therapy did not improve 24-week survival compared to isoniazid preventive therapy (IPT) in TB screen–negative HIV-positive adults initiating antiretroviral therapy with CD4 counts &lt;50 cells/µL. Retrospective LAM testing was performed on stored urine obtained at baseline. We determined the proportion of LAM-positive participants and conducted modified intent-to-treat analysis excluding LAM-positive participants to determine the effect on 24-week survival, TB incidence, and time to TB using Kaplan-Meier method.

Results
A5274 enrolled 850 participants; 53% were male and the median CD4 count was 18 (interquartile range, 9–32) cells/µL. Of the 850, 566 (67%) had LAM testing (283 per arm); 28 (5%) were positive (21 [7%] and 7 [2%] in the empiric and IPT arms, respectively). Of those LAM-positive, 1 participant in each arm died and 5 of 21 and 0 of 7 in empiric and IPT arms, respectively, developed TB. After excluding these 28 cases, there were 19 and 21 deaths in the empiric and IPT arms, respectively (P = .88). TB incidence remained higher (4.6% vs 2%, P = .04) and time to TB remained faster in the empiric arm (P = .04).

Conclusions
Among outpatients with advanced HIV who screened negative for TB by clinical symptoms, microscopy, and Xpert testing, LAM testing identified an additional 5% of individuals with TB. Positive LAM results did not change mortality or TB incidence.
The Great Debate With IBD Biosimilars
Authors: Limdi Jimmy K , Farraye Francis A 
Published: February 2021

Abstract
The relatively high cost of anti-TNF agents and looming or actual expiry of patents for several biologics have led to the development of “highly similar” versions of the “originator” drugs called “biosimilars.” The approval of biosimilars has been based on “extrapolation,” whereby approval is granted in licensed indications for the reference product without the need for clinical trials. We discuss efficacy and safety data in support of biosimilar use from prospective studies, switching from originator biologic, impact on immunogenicity, pharmaco-economic, and practical considerations for clinicians.
An evolutionary mismatch narrative to improve lifestyle medicine: a patient education hypothesis
Authors: Basile Anthony J , Renner Michael W , Hidaka Brandon H , Sweazea Karen L 
Published: February 2021

Abstract
An evolutionary perspective provides a unifying explanation for the modifiable risk factors and lifestyle-based interventions for the leading causes of morbidity and mortality globally. Non-communicable diseases develop from an evolutionary mismatch between the prior environment and modern patterns of behavior; however, it is unclear whether an evolutionary mismatch narrative could promote positive behavior change in patients. We hypothesize that educating patients about evolutionary mismatch could augment efforts to improve healthful behavior. Specifically, explaining the ‘why’ behind what is being recommended could promote health literacy and adherence. Furthermore, we offer suggestions of how clinicians could educate patients about evolutionary mismatch for key-lifestyle factors, diet and physical activity, as well as several specific modern diseases. We also consider how to sidestep patients’ skepticism of evolutionary theory. Here, we lay the groundwork for research on how educating patients with an evolutionary mismatch narrative could impact health behaviors and improve outcomes.