Miracle-dz/UniFAR-FTUs huggingface dataset:
Marking RNA: m6A writers, readers, and functions in Arabidopsis

Abstract N6-methyladenosine (m6A) emerges as an important modification in eukaryotic mRNAs. m6A has first been reported in 1974, and its functional significance in mammalian gene regulation and importance for proper development have been well established. An arsenal of writer, eraser, and reader proteins accomplish deposition, removal, and interpretation of the m6A mark, resulting in dynamic function. This led to the concept of an epitranscriptome, the compendium of RNA species with chemical modification of the nucleobases in the cell, in analogy to the epigenome. While m6A has long been known to also exist in plant mRNAs, proteins involved in m6A metabolism have only recently been detected by mutant analysis, homology search, and mRNA interactome capture in the reference plant Arabidopsis thaliana. Dysregulation of the m6A modification causes severe developmental abnormalities of leaves and roots and altered timing of reproductive development. Furthermore, m6A modification affects viral infection. Here, we discuss recent progress in identifying m6A sites transcriptome-wide, in identifying the molecular players involved in writing, removing, and reading the mark, and in assigning functions to this RNA modification in A. thaliana. We highlight similarities and differences to m6A modification in mammals and provide an outlook on important questions that remain to be addressed.
Genetic admixture accelerates invasion via provisioning rapid adaptive evolution

Genetic admixture, the intraspecific hybridization among divergent introduced sources, can immediately facilitate colonization via hybrid vigor and profoundly enhance invasion via contributing novel genetic variation to adaption. As hybrid vigor is short‐lived, provisioning adaptation is anticipated to be the dominant and long‐term profit of genetic admixture, but the evidence for this is rare. We employed the 30 years' geographic‐scale invasion of the salt marsh grass, Spartina alterniflora, as an evolutionary experiment and evaluated the consequences of genetic admixture by combining the reciprocal transplant experiment with quantitative and population genetic surveys. Consistent with the documentation, we found that the invasive populations in China had multiple origins from the southern Atlantic coast and the Gulf of Mexico in the US. Interbreeding among these multiple sources generated a “hybrid swarm” that spread throughout the coast of China. In the northern and mid‐latitude China, natural selection greatly enhanced fecundity, plant height and shoot regeneration compared to the native populations. Furthermore, genetic admixture appeared to have broken the negative correlation between plant height and shoot regeneration, which was genetically‐based in the native range, and have facilitated the evolution of super competitive genotypes in the invasive range. In contrast to the evolved northern and mid‐latitude populations, the southern invasive populations showed slight increase of plant height and shoot regeneration compared to the native populations, possibly reflecting the heterotic effect of the intraspecific hybridization. Therefore, our study suggests a critical role of genetic admixture in accelerating the geographic invasion via provisioning rapid adaptive evolution.
The association between statin use and survival of esophageal cancer patients

Abstract Whether statin use has any impact on survival of esophageal cancer patients remains controversial. Therefore, we conducted a meta-analysis focusing on current topic for the first time. We systematically searched the following databases for relevant studies comparing survival between statin users and non-users among esophageal cancer patients up to March 16, 2019: Pubmed, Embase, and Web of Science. We extracted data of hazard ratio (HR) with 95%confidence interval (CI) of all-cause and cancer-specific mortality for analysis. We used the STATA 12.0 software to perform this meta-analysis. We finally included a total of 4 cohort studies involving a total of 20,435 esophageal cancer patients (5319 statin users and 15116 non-users). Our meta-analysis found that statin use after diagnosis of esophageal cancer was significantly correlated to decreased all-cause (random effects: HR = 0.81, 95%CI: 0.75–0.89, P < .001; I2 = 68.1%) and cancer-specific mortality (fixed effects: HR = 0.84, 95%CI: 0.78–0.89, P < .001; I2 = 46.6%) in esophageal cancer patients. When stratified by pathological subtypes, the protective effect of statin use after diagnosis of esophageal cancer was observed in both esophageal adenocarcinoma patients and esophageal squamous cell carcinoma patients. Moreover, statin use before diagnosis of esophageal cancer was also confirmed to have favorable survival benefit for esophageal cancer patients. Statin use was significantly correlated to lower mortality risk of esophageal cancer patients regardless of the time when statins were taken and pathological subtypes of esophageal cancer. Statins may serve as promising adjunctive anticancer agents for treating esophageal cancer.
ApoA-I-Mediated Lipoprotein Remodeling Monitored with a Fluorescent Phospholipid

We describe simple, sensitive and robust methods to monitor lipoprotein remodeling and cholesterol and apolipoprotein exchange, using fluorescent Lissamine Rhodamine B head-group tagged phosphatidylethanolamine (*PE) as a lipoprotein reference marker. Fluorescent Bodipy cholesterol (*Chol) and *PE directly incorporated into whole plasma lipoproteins in proportion to lipoprotein cholesterol and phospholipid mass, respectively. *Chol, but not *PE, passively exchanged between isolated plasma lipoproteins. Fluorescent apoA-I (*apoA-I) specifically bound to high-density lipoprotein (HDL) and remodeled *PE- and *Chol-labeled synthetic lipoprotein-X multilamellar vesicles (MLV) into a pre-β HDL-like particle containing *PE, *Chol, and *apoA-I. Fluorescent MLV-derived *PE specifically incorporated into plasma HDL, whereas MLV-derived *Chol incorporation into plasma lipoproteins was similar to direct *Chol incorporation, consistent with apoA-I-mediated remodeling of fluorescent MLV to HDL with concomitant exchange of *Chol between lipoproteins. Based on these findings, we developed a model system to study lipid transfer by depositing fluorescent *PE and *Chol-labeled on calcium silicate hydrate crystals, forming dense lipid-coated donor particles that are readily separated from acceptor lipoprotein particles by low-speed centrifugation. Transfer of *PE from donor particles to mouse plasma lipoproteins was shown to be HDL-specific and apoA-I-dependent. Transfer of donor particle *PE and *Chol to HDL in whole human plasma was highly correlated. Taken together, these studies suggest that cell-free *PE efflux monitors apoA-I functionality.
An Integrative Review Examining Student-to-Student Incivility and Effective Strategies to Address Incivility in Nursing Education

Supplemental digital content is available in the text. Background Incivility is a low-intensity, discourteous behavior intended to disrupt or harm positive interaction. If allowed, student-to-student incivility can undermine the educational environment. Purpose The purpose of the integrative review was to examine factors influencing incivility among nursing students and teaching strategies used to reduce incivility in nursing education. Methods Qualitative and quantitative studies were reviewed. The Johns Hopkins Research Evidence Appraisal tool was used to narrow down the selection of articles. Content analysis was used to evaluate the qualitative research. Results Five major points of interest were identified: workload and high expectations contributed to incivility, degrees of incivility, effects of incivility, coping mechanisms among individuals, and effective teaching strategies addressing incivility. Conclusion Continued research on innovative teaching strategies that raise awareness of civility while reducing incivility is warranted.
Boosting Drug Discovery for Parkinson’s: Enhancement of the Delivery of a Monoamine Oxidase-B Inhibitor by Brain-Targeted PEGylated Polycaprolactone-Based Nanoparticles

The current pharmacological treatments for Parkinson’s disease only offer symptomatic relief to the patients and are based on the administration of levodopa and catechol-O-methyltransferase or monoamine oxidase-B inhibitors (IMAO-B). Since the majority of drug candidates fail in pre- and clinical trials, due largely to bioavailability pitfalls, the use of polymeric nanoparticles (NPs) as drug delivery systems has been reported as an interesting tool to increase the stealth capacity of drugs or help drug candidates to surpass biological barriers, among other benefits. Thus, a novel potent, selective, and reversible IMAO-B (chromone C27, IC50 = 670 ± 130 pM) was encapsulated in poly(caprolactone) (PCL) NPs by a nanoprecipitation process. The resulting C27-loaded PEGylated PCL NPs (~213 nm) showed high stability and no cytotoxic effects in neuronal (SH-SY5Y), epithelial (Caco-2), and endothelial (hCMEC/D3) cells. An accumulation of PEGylated PCL NPs in the cytoplasm of SH-SY5Y and hCMEC/D3 cells was also observed, and their permeation across Caco-2 and hCMEC/D3 cell monolayers, used as in vitro models of the human intestine and blood-brain barrier, respectively, was demonstrated. PEGylated PCL NPs delivered C27 at concentrations higher than the MAO-B IC50 value, which provides evidence of their relevance to solving the drug discovery pitfalls.
Patient Education and Continuing Medical Education to Promote Shared Decision-Making. A Systematic Literature Review

Background: Over recent years, the use of decision aids to promote shared decision-making have been examined. Studies on patient education and on continuing medical education for physicians are less common. This review analyzes intervention and evaluation studies on patient education and continuing medical education which aim to enhance shared decision-making. The following study parameters are of interest: Study designs, objectives, numbers of participants in the education courses, interventions, primary results, and quality of the studies. Methods: We systematically searched for suitable studies in two databases (Pubmed and the Cochrane Database of Systematic Reviews) from the beginning of April through to mid-June 2016. Results: 16 studies from a total of 462 hits were included: Three studies on patient education and 13 studies on continuing medical education for physicians. Overall, the study parameters were heterogeneous. Major differences were found between the courses; how the courses were conducted, their length, and participants. Conclusions: The differences found in the studies made it difficult to compare the interventions and the results. There is a need for studies that systematically evaluate and further develop interventions in this area to promote shared decision-making.
Barriers and facilitators to employment in borderline personality disorder: A qualitative study among patients, mental health practitioners and insurance physicians

Background Borderline personality disorder (BPD) is associated with unemployment and impaired functioning. However, a comprehensive understanding of barriers and facilitators to employment from a multidisciplinary perspective is currently lacking. Therefore, the aim of this qualitative study was to explore barriers and facilitators in gaining and maintaining employment in BPD from the perspectives of patients, mental health practitioners (MHPs) and insurance physicians (IPs). Methods Fifteen semi-structured interviews were conducted in patients with BPD and two focus groups were carried out among MHPs (n = 7) and IPs (n = 6) following a thematic content analysis approach. Results All participants described barriers and facilitators relating to three overall themes: characteristics of BPD, stigma, and support to employment. Barriers to employment mainly related to characteristics of BPD, such as low self-image, difficulty posing personal boundaries, difficulty regulating emotions, and lack of structure. MHPs and IPs additionally mentioned externalization and overestimation of competencies on the part of patients. Enhancing emotion regulation and self-reflection by successful treatment was suggested as a facilitator to enhance employment. Increasing collaboration between mental health and vocational rehabilitation services, and increasing knowledge about BPD, were suggested to increase sustainable employment and decrease stigma. Conclusions The present findings revealed that both facilitators and barriers are important in gaining and maintaining employment in BPD in which diminishing symptoms, examining stigma and increasing support to employment are key. As a next step, supported employment strategies that follow patient preferences and integrate employment and mental health services, should be studied in the context of BPD.
Device Engineering for All-Inorganic Perovskite Light-Emitting Diodes

Recently, all-inorganic perovskite light-emitting diodes (PeLEDs) have attracted both academic and industrial interest thanks to their outstanding properties, such as high efficiency, bright luminance, excellent color purity, low cost and potentially good operational stability. Apart from the design and treatment of all-inorganic emitters, the device engineering is another significant factor to guarantee the high performance. In this review, we have summarized the state-of-the-art concepts for device engineering in all-inorganic PeLEDs, where the charge injection, transport, balance and leakage play a critical role in the performance. First, we have described the fundamental concepts of all-inorganic PeLEDs. Then, we have introduced the enhancement of device engineering in all-inorganic PeLEDs. Particularly, we have comprehensively highlighted the emergence of all-inorganic PeLEDs, strategies to improve the hole injection, approaches to enhance the electron injection, schemes to increase the charge balance and methods to decrease the charge leakage. Finally, we have clarified the issues and ways to further enhance the performance of all-inorganic PeLEDs.
A qualitative transcriptional signature for the early diagnosis of colorectal cancer

Currently, using biopsy specimens for the early diagnosis of colorectal cancer (CRC) is not entirely reliable due to insufficient sampling amount and inaccurate sampling location. Thus, it is necessary to develop a signature that can accurately identify patients with CRC under these clinical scenarios. Based on the relative expression orderings of genes within individual samples, we developed a qualitative transcriptional signature to discriminate CRC tissues, including CRC adjacent normal tissues from non‐CRC individuals. The signature was validated using multiple microarray and RNA sequencing data from different sources. In the training data, a signature consisting of 7 gene pairs was identified. It was well validated in both biopsy and surgical resection specimens from multiple datasets measured by different platforms. For biopsy specimens, 97.6% of 42 CRC tissues and 94.5% of 163 non‐CRC (normal or inflammatory bowel disease) tissues were correctly classified. For surgically resected specimens, 99.5% of 854 CRC tissues and 96.3% of 81 CRC adjacent normal tissues were correctly identified as CRC. Notably, we additionally measured 33 CRC biopsy specimens by the Affymetrix platform and 13 CRC surgical resection specimens, with different proportions of tumor epithelial cells, ranging from 40% to 100%, by the RNA sequencing platform, and all these samples were correctly identified as CRC. The signature can be used for the early diagnosis of CRC, which is also suitable for minimum biopsy specimens and inaccurately sampled specimens, and thus has potential value for clinical application.
A Korean Sentence and Document Sentiment Classification System Using Sentiment Features

Sentiment classification is a recent subdiscipline of text classification, which is concerned not with the topic but with opinion. In this paper, we present a Korean sentence and document classification system using effective sentiment features. Korean sentiment classification starts from constructing effective sentiment feature sets for positive and negative. The synonym information of a English word thesaurus is used to extract effective sentiment features and then the extracted English sentiment features are translated in Korean features by English-Korean dictionary. A sentence or a document is represented by using the extracted sentiment features and is classified and evaluated by SVM(Support Vector Machine).
Molecular Carcinogenesis

Funding information Alberta Head and Neck Centre for Oncology and Reconstruction (AHNCOR) Foundation; Edmonton Civic Employees Charitable Assistance Fund. Abstract The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has significantly increased in recent decades due to human papillomavirus (HPV)‐mediated oncogenesis. Unfortunately, a growing number of HPV‐positive (+) OPSCC survivors are living with the irreversible side effects of treatment. The novel, well‐tolerated chemotherapeutics with improved side effect profiles are, therefore, in high demand. Metformin is one such drug, widely used as a first‐line oral agent in the treatment of type 2 diabetes mellitus. Curcumin is another well‐tolerated agent quickly gaining attention for its medicinal properties. Both metformin and curcumin have been shown to display anticancer properties. This study aimed to determine the antitumor effects of these agents, individually and combined, in HPV+ and HPV‐negative (−) head and neck squamous cell carcinoma (HNSCC) cell lines. This was achieved by assessing the efficacy of varying drug concentrations on the overall cell viability, proliferation, and expression of common HNSCC biomarkers. The results from protein and RNA expression data are highly variable, as expected, with multiple pathways being affected in cancer. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assays and immunofluorescence microscopy suggest that both agents are capable of slowing proliferation and inducing apoptosis. We conclude that curcumin and metformin display effective antitumor effects in both HPV+ and HPV− HNSCC cell lines. The curcumin effects appear more pronounced in the HPV− cell lines. Metformin appears to be more effective at reducing the overall cell numbers in HPV+ cell lines. Metformin and curcumin combined did not appear to have synergistic effects on the proliferation or apoptosis of the treated cell lines.
Carbon-Nanotube-Based Monolithic CMOS Platform for Electrochemical Detection of Neurotransmitter Glutamate

We present a monolithic biosensor platform, based on carbon-nanotube field-effect transistors (CNTFETs), for the detection of the neurotransmitter glutamate. We used an array of 9′216 CNTFET devices with 96 integrated readout and amplification channels that was realized in complementary metal-oxide semiconductor technology (CMOS). The detection principle is based on amperometry, where electrochemically active hydrogen peroxide, a product of the enzymatic reaction of the target analyte and an enzyme that was covalently bonded to the CNTFET, modulated the conductance of the CNTFET-based sensors. We assessed the performance of the CNTs as enzymatic sensors by evaluating the minimal resolvable concentration change of glutamate in aqueous solutions. The minimal resolvable concentration change amounted to 10 µM of glutamate, which was one of the best values reported for CMOS-based systems so far.
Chimpanzee adenoviral vector prime-boost regimen elicits potent immune responses against Ebola virus in mice and rhesus macaques

ABSTRACT In the last few decades, Ebola virus (EBOV) has emerged periodically and infected people in Africa, resulting in an extremely high mortality rate. With no available prophylaxis or cure so far, a highly effective Ebola vaccine is urgently needed. In this study, we developed a novel chimpanzee adenovirus-based prime-boost vaccine by exploiting two recombinant replication-deficient chimpanzee adenoviral vectors, AdC7 and AdC68, which express glycoproteins (GP) of the EBOV strain identified in the 2014 outbreak. Our results indicated that a single immunization using AdC7 or AdC68 could stimulate potent EBOV-specific antibody responses, whereas the AdC7 prime-AdC68 boost regimen induced much stronger and sustained humoral and cellular immune responses in both mice and rhesus monkeys, compared with AdC7 or AdC68 single vaccination or the AdC68 prime-AdC7 boost regimen. This prime-boost vaccine could also protect mice from the simulated infection with EBOV-like particle (EBOVLP) in biosafety level 2 (BSL-2) laboratories, and antibodies from the prime-boost immunized rhesus macaques could passively provide protection against EBOVLP infection. Altogether, our results show that the AdC7 prime-AdC68 boost vaccine is a promising candidate for further development to combat EBOV infections.
Hydrogel-Encapsulated Mesoporous Silica-Coated Gold Nanoshells for Smart Drug Delivery

A “smart” core@shell composite nanoparticle (NP) having dual-response mechanisms (i.e., temperature and light) was synthesized, and its efficacy in the loading and release of small molecules was explored. These core@shell NPs are composed of an optically active gold nanoshell (GNS) core and a mesoporous (m-) silica layer (m-SiO2). The GNS@m-SiO2 nanoparticles are further encapsulated within a thermo-responsive poly(N-isopropylacrylamide-co-acrylic acid) hydrogel (PNIPAM-co-AA). The multi-responsive composite NPs were designed to create thermally and optically modulated drug-delivery vehicles with a m-SiO2 layer providing additional non-collapsible space for drug storage. The influence of the m-SiO2 layer on the efficacy of loading and release of methylene blue, which serves as a model for a small-molecule therapeutic drug, was evaluated. The “smart” core@shell composite NPs having a m-SiO2 layer demonstrated an improved capacity to load and release small molecules compared to the corresponding NPs with no m-SiO2 shell. Additionally, an efficient response by the composite NPs was successfully induced by the thermal energy generated from the gold nanoshell core upon exposure to near infrared (NIR) stimulation.
Nanoparticle Size Effect on Water Vapour Adsorption by Hydroxyapatite

Handling and properties of nanoparticles strongly depend on processes that take place on their surface. Specific surface area and adsorption capacity strongly increase as the nanoparticle size decreases. A crucial factor is adsorption of water from ambient atmosphere. Considering the ever-growing number of hydroxyapatite nanoparticles applications, we decided to investigate how the size of nanoparticles and the changes in relative air humidity affect adsorption of water on their surface. Hydroxyapatite nanoparticles of two sizes: 10 and 40 nm, were tested. It was found that the nanoparticle size has a strong effect on the kinetics and efficiency of water adsorption. For the same value of water activity, the quantity of water adsorbed on the surface of 10 nm nano-hydroxyapatite was five times greater than that adsorbed on the 40 nm. Based on the adsorption isotherm fitting method, it was found that a multilayer physical adsorption mechanism was active. The number of adsorbed water layers at constant humidity strongly depends on particles size and reaches even 23 layers for the 10 nm particles. The amount of water adsorbed on these particles was surprisingly high, comparable to the amount of water absorbed by the commonly used moisture-sorbent silica gel.