Miracle-dz/UniFAR-FTUs huggingface dataset:
ABCB1 polymorphism in clopidogrel-treated Montenegrin patients

Abstract Clopidogrel is an antiplatelet drug that displays significant interindividual variability in treatment response. Its bioavailability depends on the function of P-glycoprotein (P-gp), which is coded by a highly polymorphic ABCB1 gene. Thus, the aim of this study was to investigate the effect of ABCB1 genetic polymorphism on clopidogrel efficacy and safety and to determine the frequency distribution of its most common single nucleotide polymorphisms (SNPs) in 106 Montenegrin cardiology patients. Clopidogrel efficacy and safety were followed up during 1 year after hospitalization, with the lack of efficacy and adverse drug reactions observed in 11 (10.4%) and 8 patients (7.5%), respectively. Genotyping for ABCB1 SNPs rs1128503 (1236C > T), rs2032582 (2677G > A/T), and rs1045642 (3435C > T) was performed by the real-time PCR method, and the variant alleles were detected with the frequencies of 42.9, 44.8, and 52.8%, respectively. No significant association was observed between any of the examined genotypes and clopidogrel efficacy (p = 0.253) or safety (p = 0.424). Due to small sample size, co-treatment with other drugs, and other genetic factors not taken into account, we believe the absence of correlation between ABCB1 genotypes and indicators of clopidogrel efficacy and safety in this study should be apprehended conditionally, and that larger and better-controlled studies are warranted.
Phylogeny of Tipulomorpha - an endless issue

Abstract Phylogeny of the infraorder Tipulomorpha is discussed with emphasis on the family Limoniidae. A negative reaction to the study by Petersen et al. (2010) is presented because they proposed an unusual phylogeny, with hardly acceptable classification. The family Limoniidae is here confirmed as monophyletic, divided into four clades classified as subfamilies (Starý 1992), with recent additional and reasonable changes. A revised phylogenetic arrangement of the family Limoniidae within Tipulomorpha is given.
Geochemistry of the black rock series of lower Cambrian Qiongzhusi Formation, SW Yangtze Block, China: Reconstruction of sedimentary and tectonic environments

Abstract The black rock series in the Qiongzhusi Formation contains important geochemical information about the early Cambrian tectonic and ecological environment of the southwestern Yangtze Block. In this paper, major, trace, and rare earth element data are presented in an attempt to reveal the sediment source during the deposition of the early Cambrian Qiongzhusi Formation and to reconstruct the sedimentary tectonic environment and weathering intensity during that time. The basin primarily received continental clastic material with neutral-acidic igneous rocks from a stable source and with a moderate level of maturity during the depositional period of the Qiongzhusi Formation. Furthermore, the strata were weakly influenced by submarine hydrothermal fluids during diagenesis. The reconstruction of the sedimentary environment and weathering intensity shows that P2O5 enrichment and water body stratification occurred due to the effects of upwelling ocean currents during the depositional period of the Qiongzhusi Formation. The combination of upwelling and bottom-water hydrothermal fluids led to environmental changes in the study area, from dry and hot to moist and warm. Last, the reconstruction of the tectonic environment of the Qiongzhusi Formation indicates that deposition occurred in continental slope and marginal marine environments associated with a continental arc tectonic system. These findings provide an essential basis for the comprehensive reconstruction of the early Cambrian sedimentary environment of the Yangtze Block.
Narrating the Immigrant Experience: Three Adult Educators’ Perspectives

In this collaborative autoethnography, three immigrant adult education scholars examine diverse ways in which their experiences with racialization as immigrants in the United States have informed their scholarship and practice. The three authors originate from different parts of the world and use different theoretical frameworks—critical literary studies; critical theory; and postcolonial and Critical Race Theory, respectively—to complicate the immigrant Self and story. They argue that the use of autoethnography in adult education has the potential to illuminate issues of class, race, gender, and nationality to disrupt the typical immigrant narrative and allow for the advent of new immigrant stories and Subjects. Each narrative is unique; however, they do share the following commonalities: Critique of the postcolonial condition and the colonization of the Subject and culture; complicating the Black–White binary paradigm of race; centering anti-racist praxis; and suggestions for decolonizing the Self and adult education. The authors engage in this anti-racist work in solidarity with the Black Lives Matter movement, in an effort to dismantle systemic inequities and give voice to the subaltern. Patterns arising from their examination of these issues reveal new questions adult educators could consider as we teach, learn with, and from immigrant adult learners, whose cultural-historical contexts remain multi-layered and complex, rather than linear.
The Five Stages of the Macromarketing Field of Study: From Raison D’etre to Field of Significant Promise

This article contributes to the macromarketing field of study by tracing its evolution through five distinct stages. (1) In Era I (1900-1920), macromarketing was the raison d’etre of the marketing discipline. (2) In Era II (1920-1950), macromarketing became the marketing discipline’s central focus. (3) In Era III (1950-1980), marketing management displaced macromarketing as the discipline’s central focus, but macromarketing continued to be an important part of the discipline. (4) In Era IV (1980-2020), macromarketing became one of four, major, institutionalized fields of study in the marketing discipline, with the others being consumer behavior, quantitative/modeling, and marketing management/strategy. (5) In Era V (2020-? ), macromarketing is well-positioned to be not only a major field within the marketing discipline, but also a field of significant promise.
Time‐resolved free carrier lifetime microscopy in bulk GaN

A novel setup for lifetime microscopy measurements was designed and applied for carrier lifetime mapping in a bulk GaN. Photoexcitation by a picosecond UV pump and detection of time‐resolved free carrier absorption (FCA) images on a CCD camera enabled the mapping of carrier lifetime distribution with a spatial resolution of 5 μm. The spatial variation of lifetime in the bulk HVPE‐grown GaN revealed the presence of different‐size crystalline grains, with lifetime peaking up to 70 ns in the centers of the largest grains (∼20 μm in diameter) and dropping to 10 ns in the small ones, while the spatially averaged lifetime was 40 ns. The inhomogeneity was ascribed to the interplay of nonradiative diffusion‐limited recombination at grain boundaries and a bulk lifetime in the crystallite centers. The numerical solution of spatially‐resolved carrier decay rate in the crystallite centers at high injection levels and comparison with experimental data provided a bulk nonradiative recombination time of ∼70 ns. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Rethinking Crop Nutrition in Times of Modern Microbiology: Innovative Biofertilizer Technologies

Global population growth poses a threat to food security in an era of increased ecosystem degradation, climate change, soil erosion, and biodiversity loss. In this context, harnessing naturally-occurring processes such as those provided by soil and plant-associated microorganisms presents a promising strategy to reduce dependency on agrochemicals. Biofertilizers are living microbes that enhance plant nutrition by either by mobilizing or increasing nutrient availability in soils. Various microbial taxa including beneficial bacteria and fungi are currently used as biofertilizers, as they successfully colonize the rhizosphere, rhizoplane or root interior. Despite their great potential to improve soil fertility, biofertilizers have yet to replace conventional chemical fertilizers in commercial agriculture. In the last 10 years, multi-omics studies have made a significant step forward in understanding the drivers, roles, processes, and mechanisms in the plant microbiome. However, translating this knowledge on microbiome functions in order to capitalize on plant nutrition in agroecosystems still remains a challenge. Here, we address the key factors limiting successful field applications of biofertilizers and suggest potential solutions based on emerging strategies for product development. Finally, we discuss the importance of biosafety guidelines and propose new avenues of research for biofertilizer development.
Downregulation of the lncRNA ASB16-AS1 Decreases LARP1 Expression and Promotes Clear Cell Renal Cell Carcinoma Progression via miR-185-5p/miR-214-3p

Clear cell renal cell carcinoma (ccRCC) comprises approximately 75% of renal cell carcinomas, which is one of the most common and lethal urologic cancers, with poor quality of life for patients and is a huge economic burden to health care systems. It is imperative we find novel prognostic and therapeutic targets for ccRCC clinical intervention. In this study, we found that the expression of the long noncoding RNA (lncRNA) ASB16-AS1 was downregulated in ccRCC tissues compared with non-diseased tissues and was also associated with advanced tumor stage and larger tumors. By constructing cell and mouse models, it was found that downregulated lncRNA ASB16-AS1 enhanced cell proliferation, migration, invasion, and promoted tumor growth and metastasis. Furthermore, by performing bioinformatics analysis, biotinylated RNA pull-downs, AGO2-RIP, and luciferase reporter assays, our findings showed that downregulated ASB16-AS1 decreased La-related protein 1 (LARP1) expression by inhibiting miR-185-5p and miR-214-3p. Furthermore, it was found that overexpression of LARP1 reversed the promotive effects of downregulated ASB16-AS1 on ccRCC cellular progression. Our results revealed that downregulated ASB16-AS1 promotes ccRCC progression via a miR-185-5p-miR-214-3p-LARP1 pathway. We suggest that this pathway could be used to monitor prognosis and presents therapeutic targets for ccRCC clinical management.
SE-OnionNet: A Convolution Neural Network for Protein–Ligand Binding Affinity Prediction

Deep learning methods, which can predict the binding affinity of a drug–target protein interaction, reduce the time and cost of drug discovery. In this study, we propose a novel deep convolutional neural network called SE-OnionNet, with two squeeze-and-excitation (SE) modules, to computationally predict the binding affinity of a protein–ligand complex. The OnionNet is used to extract a feature map from the three-dimensional structure of a protein–drug molecular complex. The SE module is added to the second and third convolutional layers to improve the non-linear expression of the network to improve model performance. Three different optimizers, stochastic gradient descent (SGD), Adam, and Adagrad, were also used to improve the performance of the model. A majority of protein–molecule complexes were used for training, and the comparative assessment of scoring functions (CASF-2016) was used as the benchmark. Experimental results show that our model performs better than OnionNet, Pafnucy, and AutoDock Vina. Finally, we chose the macrophage migration inhibitor factor (PDB ID: 6cbg) to test the stability and robustness of the model. We found that the prediction results were not affected by the docking position, and thus, our model is of acceptable robustness.
Sex Differences in Time to Treat and Outcomes for Gliomas

Background Gliomas are the most common type of primary malignant brain tumor in adults, representing one third of all primary and central nervous system (CNS) tumors and 80% of malignant tumors diagnosed in the Western world. Epidemiological data indicate that the overall incidence and mortality of cancer is higher in males, while females have a better prognosis. The goal of this study is to determine whether there are sex differences in the time to treat and clinical outcomes in patients with glioma Methods Glioblastoma (GB) and Lower Grade Glioma (LGG) patients were defined per the Central Brain Tumor Registry of the United States (CBTRUS) from the National Cancer Database (NCDB) for diagnosis years 2004 to 2016. Associations between sex and time to treatment variables as well as associations between sex and multiple clinical outcomes were assessed using univariable and multivariable models. Results A total of 176,100 patients were used for analysis (124,502 GBM and 51,598 LGG). Males had a statistically significant association with >7 days to surgery (OR = 1.09, CI 1.05–1.13, p < 0.001) but this association was not observed in the multivariable model (OR = 1.05, CI 0.96–1.16, p = 0.25). After adjustment for key variables including time to treat variables, males with GB and LGG had a higher risk of death (HR = 1.11, CI 1.09–1.13, p < 0.001, HR = 1.09, CI 1.03–1.15, p < 0.001; respectfully). Sex differences in 90-day mortality for GBM were not found after adjustment (OR for males = 0.99, CI 0.91–1.08, p = 0.93). For LGG, both the univariable and multivariable logistic regression models showed no sex differences in 90-day mortality (OR for males = 1.03, CI 0.94–1.12, p = 0.45; multivariable OR for males = 0.81, CI 0.62–1.06, p = 0.13). Conclusions Based on NCDB data, there were no statistically significant differences in time to treatment between males and females, however males had a higher proportion of GB and LGG as well as a higher risk of death compared to females.
CircHIPK3 Promotes the Tumorigenesis and Development of Gastric Cancer Through miR-637/AKT1 Pathway

Circular RNA is a kind of RNA with a covalently closed loop, which has a complex ability to modulate genes in the process of tumorigenesis and metastasis. Nevertheless, how circular RNA functions in gastric cancer (GC) remains unclear. The effect of circHIPK3 in vitro was studied here. Quantitative real-time PCR (qRT-PCR) was employed to found that circHIPK3 markedly increased in GC tissues and cell lines. And low expression of circHIPK3 suppressed the GC cells growing and metabolizing. Then the bioinformatics tool predicted the downstream target of circHIPK3, and it was proved by the dual-luciferase report experiment. According to the results of bioinformatics analysis and experimental data, it was clarified that circHIPK3 acted as a sponge of miR-637, releasing its direct target AKT1. The dual-luciferase assay revealed that mir-637 could bind circHIPK3 and AKT1. qRT-PCR data indicated that overexpression circHIPK3 led to the low level of miR-637 and overexpressed miR-637 would reduce AKT1 level. Finally, we demonstrated that the low expression of miR-637 or overexpression of AKT1 could attenuate the anti-proliferative effects of si-circHIPK3. These results suggest that the circHIPK3/miR-637/AKT1 regulatory pathway may be associated with the oncogene and growth of gastric cancer. In short, a new circular RNA circHIPK3 and its function are identified, and the regulatory pathway of circHIPK3/miR-637/AKT1 in the tumorigenesis and development of gastric cancer is discovered.
Biochemical Characterization and Differential Expression of PAL Genes Associated With “Translocated” Peach/Plum Graft-Incompatibility

Grafting is an ancient plant propagation technique widely used in horticultural crops, particularly in fruit trees. However, the involvement of two different species in grafting may lead to lack of affinity and severe disorders between the graft components, known as graft-incompatibility. This complex agronomic trait is traditionally classified into two categories: “localized” (weak graft unions with breaks in cambial and vascular continuity at the graft interface and absence of visual symptoms in scion leaves and shoots) and “translocated” (degeneration of the sieve tubes and phloem companion cells at the graft interface causing translocation problems in neighboring tissues, and reddening/yellowing of scion leaves). Over the decades, more attention has been given to the different mechanisms underlying the “localized” type of graft-incompatibility; whereas the phenylpropanoid-derived compounds and the differential gene expression associated with the “translocated” graft-incompatibility remain unstudied. Therefore, the aim of this study was to shed light on the biochemical and molecular mechanisms involved in the typical “translocated” graft-incompatibility of peach/plum graft-combinations. In this study, the “Summergrand” (SG) nectarine cultivar was budded on two plum rootstocks: “Adara” and “Damas GF 1869”. “Translocated” symptoms of incompatibility were shown and biochemically characterized in the case of “SG/Damas GF 1869” graft-combination, 3 years after grafting. Non-structural carbohydrates (soluble sugars and starch), phenolic compounds and antioxidant activity, were significantly enhanced in the incompatible graft-combination scion. Similarly, the enzymatic activities of the antioxidant enzyme peroxidase, the phenylalanine ammonia-lyase (PAL) and polyphenol oxidase involved in the phenylpropanoid pathway were significantly affected by the incompatible rootstock “Damas GF 1869”, inducing higher activities in the scion than those induced by the compatible rootstock “Adara”. In addition, a positive and strong correlation was obtained between total phenol content, antioxidant capacity and the expression of the key genes involved in the phenylpropanoid pathway, PAL1 and PAL2. Regarding the “SG/Adara” graft-combination, there were neither external symptoms of “translocated” incompatibility nor significant differences in the biochemical and molecular parameters between scion and rootstock, proving it to be a compatible combination. The differential expression of PAL genes together with the biochemical factors cited above could be good markers for the “translocated” peach/plum graft-incompatibility.
Massively Parallel Sequencing for Rare Genetic Disorders: Potential and Pitfalls

There have been two major eras in the history of gene discovery. The first was the era of linkage analysis, with approximately 1,300 disease-related genes identified by positional cloning by the turn of the millennium. The second era has been powered by two major breakthroughs: the publication of the human genome and the development of massively parallel sequencing (MPS). MPS has greatly accelerated disease gene identification, such that disease genes that would have taken years to map previously can now be determined in a matter of weeks. Additionally, the number of affected families needed to map a causative gene and the size of such families have fallen: de novo mutations, previously intractable by linkage analysis, can be identified through sequencing of the parent–child trio, and genes for recessive disease can be identified through MPS even of a single affected individual. MPS technologies include whole exome sequencing (WES), whole genome sequencing (WGS), and panel sequencing, each with their strengths. While WES has been responsible for most gene discoveries through MPS, WGS is superior in detecting copy number variants, chromosomal rearrangements, and repeat-rich regions. Panels are commonly used for diagnostic purposes as they are extremely cost-effective and generate manageable quantities of data, with no risk of unexpected findings. However, in instances of diagnostic uncertainty, it can be challenging to choose the right panel, and in these circumstances WES has a higher diagnostic yield. MPS has ethical, social, and legal implications, many of which are common to genetic testing generally but amplified due to the magnitude of data (e.g., relationship misattribution, identification of variants of uncertain significance, and genetic discrimination); others are unique to WES and WGS technologies (e.g., incidental or secondary findings). Nonetheless, MPS is rapidly translating into clinical practice as an extremely useful part of the clinical armamentarium.
Reactions of Peroxynitrite with Phenolic and Carbonyl Compounds: Flavonoids are not Scavengers of Peroxynitrite

Peroxynitrite (ONOO−, oxoperoxonitrate(1−)), an isomer of nitrate that oxidizes and nitrates biomolecules, is likely to be formed in vivo from the reaction of superoxide with nitrogen monoxide. To determine whether flavonoids scavenge peroxynitrite as postulated in the literature, we studied the reactions of peroxynitrite with phenol, hydroquinone, catechol, and the flavonoid monoHER. These reactions are first-order with respect to peroxynitrous acid and zero-order with respect to the organic compounds, and proceed as fast as the isomerization of peroxynitrous acid to nitrate. In vivo, a large fraction of all peroxynitrite is likely to react with carbon dioxide to form an unstable adduct, the 1-carboxylato-2-nitrosodioxidane anion (ONOOCO). The presence of phenolic compounds did not influence the rate of disappearance of this adduct, which was ca. 4×102 s−1. On the basis of these kinetic studies, it can be concluded that flavonoids are not scavengers of peroxynitrite. The products from the reaction of peroxynitrite with hydroquinone (benzene-1,4-diol) and catechol (benzene-1,2-diol) are para-benzoquinone and ortho-benzoquinone, respectively; no nitrated products were found. In a subsequent reaction, ortho-quinone reacted with nitrite, a common contaminant of peroxynitrite preparations to form 1,2-dihydroxy-4-nitrobenzene. We also investigated whether carbonyl compounds could redirect the reactivity of peroxynitrite toward nitration, as carbon dioxide does. The reaction with acetone is first-order with respect to peroxynitrite and first-order with respect to the carbonyl compound. The rate constant is 1.8 M−1s−1 at neutral pH and 20°; peroxynitrite does not react with the carbonyl compounds dimethyl acetamide, L-alanylalanine, or methyl acetate. It is not likely that the carbonyl compounds or the mono-, di-, or polyphenolic compounds can scavenge peroxynitrite in vivo.