Miracle-dz/UniFAR-FTUs huggingface dataset:
A scientific theory of gist communication and misinformation resistance, with implications for health, education, and policy

A framework is presented for understanding how misinformation shapes decision-making, which has cognitive representations of gist at its core. I discuss how the framework goes beyond prior work, and how it can be implemented so that valid scientific messages are more likely to be effective, remembered, and shared through social media, while misinformation is resisted. The distinction between mental representations of the rote facts of a message—its verbatim representation—and its gist explains several paradoxes, including the frequent disconnect between knowing facts and, yet, making decisions that seem contrary to those facts. Decision makers can falsely remember the gist as seen or heard even when they remember verbatim facts. Indeed, misinformation can be more compelling than information when it provides an interpretation of reality that makes better sense than the facts. Consequently, for many issues, scientific information and misinformation are in a battle for the gist. A fuzzy-processing preference for simple gist explains expectations for antibiotics, the spread of misinformation about vaccination, and responses to messages about global warming, nuclear proliferation, and natural disasters. The gist, which reflects knowledge and experience, induces emotions and brings to mind social values. However, changing mental representations is not sufficient by itself; gist representations must be connected to values. The policy choice is not simply between constraining behavior or persuasion—there is another option. Science communication needs to shift from an emphasis on disseminating rote facts to achieving insight, retaining its integrity but without shying away from emotions and values.
COVID‐19 and the clinical hematology laboratory

The ongoing COVID‐19 pandemic originated in Wuhan, Hubei Province, China, in December 2019. The etiologic agent is a novel coronavirus of presumed zoonotic origin with structural similarity to the viruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Like SARS and MERS, COVID‐19 infection manifests most frequently with lower respiratory symptoms. A minority of patients progress to acute respiratory distress syndrome/ diffuse alveolar damage. In addition to its central role in the diagnosis of COVID‐19 infection, the clinical laboratory provides critical information to clinicians regarding prognosis, disease course, and response to therapy. The purpose of this review is to (a) provide background context about the origins and course of the pandemic, (b) discuss the laboratory's role in the diagnosis of COVID‐19 infection, (c) summarize the current state of biomarker analysis in COVID‐19 infection, with an emphasis on markers derived from the hematology laboratory, (d) comment on the impact of COVID‐19 on hematology laboratory safety, and (e) describe the impact the pandemic has had on organized national and international educational activities worldwide.
Social Neighborhood Graph and Multigraph Fusion Ranking for Multifeature Image Retrieval

A single feature is hard to describe the content of images from an overall perspective, which limits the retrieval performances of single-feature-based methods in image retrieval tasks. To fully describe the properties of images and improve the retrieval performances, multifeature fusion ranking-based methods are proposed. However, the effectiveness of multifeature fusion in image retrieval has not been theoretically explained. This article gives a theoretical proof to illustrate the role of independent features in improving the retrieval results. Based on the theoretical proof, the original ranking list generated with a single feature greatly influences the performances of multifeature fusion ranking. Inspired by the principle of three degrees of influence in social networks, this article proposes a reranking method named $k$ -nearest neighbors’ neighbors’ neighbors’ graph (N3G) to improve the original ranking list by a single feature. Furthermore, a multigraph fusion ranking (MFR) method motivated by the group relation theory in social networks for multifeature ranking is also proposed, which considers the correlations of all images in multiple neighborhood graphs. Evaluation experiments conducted on several representative data sets (e.g., UK-bench, Holiday, Corel-10K, and Cifar-10) validate that N3G and MFR outperform the other state-of-the-art methods.
Stochasticity in microbiology: managing unpredictability to reach the Sustainable Development Goals

Pure (single) cultures of microorganisms and mixed microbial communities (microbiomes) have been important for centuries in providing renewable energy, clean water and food products to human society and will continue to play a crucial role to pursue the Sustainable Development Goals. To use microorganisms effectively, microbial engineered processes require adequate control. Microbial communities are shaped by manageable deterministic processes, but also by stochastic processes, which can promote unforeseeable variations and adaptations. Here, we highlight the impact of stochasticity in single culture and microbiome engineering. First, we discuss the concepts and mechanisms of stochasticity in relation to microbial ecology of single cultures and microbiomes. Second, we discuss the consequences of stochasticity in relation to process performance and human health, which are reflected in key disadvantages and important opportunities. Third, we propose a suitable decision tool to deal with stochasticity in which monitoring of stochasticity and setting the boundaries of stochasticity by regulators are central aspects. Stochasticity may give rise to some risks, such as the presence of pathogens in microbiomes. We argue here that by taking the necessary precautions and through clever monitoring and interpretation, these risks can be mitigated.
Pan‐tissue analysis of allelic alternative polyadenylation suggests widespread functional regulation

Alternative polyadenylation (APA) is a major layer of gene regulation. However, it has recently been argued that most APA represents molecular noise. To clarify their functional relevance and evolution, we quantified allele‐specific APA patterns in multiple tissues from an F1 hybrid mouse. We found a clearly negative correlation between gene expression and APA diversity for the 2,866 genes (24.9%) with a dominant polyadenylation site (PAS) usage above or equal to 90%, suggesting that their other PASs represent molecular errors. Among the remaining genes with multiple PASs, 3,971 genes (34.5%) express two or more isoforms with potentially functional importance. Interestingly, the genes with potentially functional minor PASs specific to neuronal tissues often express two APA isoforms with distinct subcellular localizations. Furthermore, our analysis of cis‐APA divergence shows its pattern across tissues is distinct from that of gene expression. Finally, we demonstrate that the relative usage of alternative PASs is not only affected by their cis‐regulatory elements, but also by potential coupling between transcriptional and APA regulation as well as competition kinetics between alternative sites.
Stimulating effects of vardenafil, tadalafil, and udenafil on vascular endothelial growth factor, angiogenesis, vitamin D3, bone morphogenic proteins in ovariectomized rats

Abstract Objective This study investigated the effect of vardenafil, tadalafil, and udenafil from phosphodiesterase-5 inhibitors (PDE-5Is) on bone morphogenic-protein (BMP)2 and 4 levels, along with angiogenesis in ovariectomized rat’s kidney. Method Rats were randomly divided into five groups (n = 10). Sham: abdomen was opened, and closed. OVX: ovaries were removed. OVX + vardenafil, OVX + tadalafil, and OVX + udenafil groups: ovaries were removed and closed, and after 6 months from postoperative, 10 mg/kg of vardenafil, tadalafil, and udenafil were administrated as daily a single-dose for 60 days, respectively. Histopathologic and immunohistochemical examinations were performed for angiogenesis, and biochemical analysis for vascular endothelial growth-factor (VEGF), VitaminD3, BMP2 and 4 levels in rat’s kidney. Results VEGF, BMP2 and 4, VitaminD3, and angiogenesis were high in the all inhibitor groups compared with the sham and OVX (p < .05). However, BMP4 levels were only high in the OVX + tadalafil group (p < .05). Conclusion The results indicated that vardenafil, udenafil, and especially tadalafil increased VEGF, BMP2, and VitaminD3 levels.
The genomic landscape of undifferentiated embryonal sarcoma of the liver is typified by C19MC structural rearrangement and overexpression combined with TP53 mutation or loss

Undifferentiated embryonal sarcoma of the liver (UESL) is a rare and aggressive malignancy. Though the molecular underpinnings of this cancer have been largely unexplored, recurrent chromosomal breakpoints affecting a noncoding region on chr19q13, which includes the chromosome 19 microRNA cluster (C19MC), have been reported in several cases. We performed comprehensive molecular profiling on samples from 14 patients diagnosed with UESL. Congruent with prior reports, we identified structural variants in chr19q13 in 10 of 13 evaluable tumors. From whole transcriptome sequencing, we observed striking expressional activity of the entire C19MC region. Concordantly, in 7 of 7 samples undergoing miRNAseq, we observed hyperexpression of the miRNAs within this cluster to levels >100 fold compared to matched normal tissue or a non-C19MC amplified cancer cell line. Concurrent TP53 mutation or copy number loss was identified in all evaluable tumors with evidence of C19MC overexpression. We find that C19MC miRNAs exhibit significant negative correlation to TP53 regulatory miRNAs and K-Ras regulatory miRNAs. Using RNA-seq we identified that pathways relevant to cellular differentiation as well as mRNA translation machinery are transcriptionally enriched in UESL. In summary, utilizing a combination of next-generation sequencing and high-density arrays we identify the combination of C19MC hyperexpression via chromosomal structural event with TP53 mutation or loss as highly recurrent genomic features of UESL.
Myocyte-derived Myomaker expression is required for regenerative fusion but exacerbates membrane instability in dystrophic myofibers.

Muscle progenitor cell fusion is required for the formation and regeneration of multinucleated skeletal muscle fibers. Chronic muscle regeneration in Duchenne muscular dystrophy (DMD) is characterized by ongoing fusion of satellite cell (SC) progeny, but the effects of fusion on disease and the mechanisms by which fusion is accomplished in this setting are not fully understood. Using the mdx mouse model of DMD, we deleted the fusogenic protein Myomaker in SCs or myofibers. Following deletion in SCs, mice displayed a complete lack of myocyte fusion, resulting in severe muscle loss, enhanced fibrosis, and significant functional decline. Reduction of Myomaker in mature myofibers in mdx mice, however, led to minimal alterations in fusion dynamics. Unexpectedly, myofiber-specific deletion of myomaker resulted in improvement of disease phenotype, with enhanced function and decreased muscle damage. Our data indicate that Myomaker has divergent effects on dystrophic disease severity depending upon its compartment of expression. These findings show that myocyte fusion is absolutely required for effective regeneration in DMD, but persistent Myomaker expression in myofibers due to ongoing fusion may have unintended deleterious consequences for muscle integrity. Thus, sustained activation of a component of the myogenic program in dystrophic myofibers exacerbates disease.
Contribution of STAT1 to innate and adaptive immunity during type I interferon-mediated lethal virus infection

Signal transducers and activators of transcription (STAT) 1 is critical for cellular responses to type I interferons (IFN-Is), with the capacity to determine the outcome of viral infection. We previously showed that while wildtype (WT) mice develop mild disease and survive infection with lymphocytic choriomeningitis virus (LCMV), LCMV infection of STAT1-deficient mice results in a lethal wasting disease that is dependent on IFN-I and CD4+ cells. IFN-Is are considered to act as a bridge between innate and adaptive immunity. Here, we determined the relative contribution of STAT1 on innate and adaptive immunity during LCMV infection. We show that STAT1 deficiency results in a biphasic disease following LCMV infection. The initial, innate immunity-driven phase of disease was characterized by rapid weight loss, thrombocytopenia, systemic cytokine and chemokine responses and leukocyte infiltration of infected organs. In the absence of an adaptive immune response, this first phase of disease largely resolved resulting in survival of the infected host. However, in the presence of adaptive immunity, the disease progressed into a second phase with continued cytokine and chemokine production, persistent leukocyte extravasation into infected tissues and ultimately, host death. Overall, our findings demonstrate the key contribution of STAT1 in modulating innate and adaptive immunity during type I interferon-mediated lethal virus infection.
Preconcentration and Analytical Methods for Determination of Methyl Tert-Butyl Ether and Other Fuel Oxygenates and Their Degradation Products in Environment: A Review

Abstract Fuel oxygenates (FOs) are mainly ethers or alcohols which are added to gasoline either to boost the octane number or to make the fuel burning process more “cleaner” with increasing the oxygen content, or to obtain a combination of both effects. FOs are water soluble with high mobility in the environment which presence even at very low concentrations lower the quality of water making it unsafe or unpleasant due to their objectionable taste and/or odor. Thus, their determination at trace in environmental samples is of high importance because of their sparingly biodegradability and their biological hazards. Instruments such as gas chromatography, Fourier transform infrared spectroscopy and ion mobility spectrometry are mainly used for the determination of FOs. However, the main challenge for determination of such oxygenates relates to proper sample preparation. Dilute or complex samples often demand a specific treatment to ensure effective enrichment of FOs before their detection. The main techniques used for this purpose are purge and trap, membrane extraction, and solid phase microextraction. This review presents a comprehensive evaluation of extraction/preconcentration techniques and analytical methods for determination of FOs in environmental samples. Advantages and disadvantages of each method are discussed in details along with critical evaluation of currently available methods.
Image‐guided mathematical modeling for pharmacological evaluation of nanomaterials and monoclonal antibodies

Abstract While plasma concentration kinetics has traditionally been the predictor of drug pharmacological effects, it can occasionally fail to represent kinetics at the site of action, particularly for solid tumors. This is especially true in the case of delivery of therapeutic macromolecules (drug‐loaded nanomaterials or monoclonal antibodies), which can experience challenges to effective delivery due to particle size‐dependent diffusion barriers at the target site. As a result, disparity between therapeutic plasma kinetics and kinetics at the site of action may exist, highlighting the importance of target site concentration kinetics in determining the pharmacodynamic effects of macromolecular therapeutic agents. Assessment of concentration kinetics at the target site has been facilitated by non‐invasive in vivo imaging modalities. This allows for visualization and quantification of the whole‐body disposition behavior of therapeutics that is essential for a comprehensive understanding of their pharmacokinetics and pharmacodynamics. Quantitative non‐invasive imaging can also help guide the development and parameterization of mathematical models for descriptive and predictive purposes. Here, we present a review of the application of state‐of‐the‐art imaging modalities for quantitative pharmacological evaluation of therapeutic nanoparticles and monoclonal antibodies, with a focus on their integration with mathematical models, and identify challenges and opportunities. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Diagnostic Tools > in vivo Nanodiagnostics and Imaging Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Target base editing in soybean using a modified CRISPR/Cas9 system

In recent years, the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat)/Cas9 (CRISPR-associated 9) system has revolutionized functional genomic research and crop improvement, owing to its advantages of simplicity, efficiency, cost-effectiveness, and versatility (Chen et al., 2019). There have been abundant reports in plants showing that a small amount of base insertions/deletions (indels) at the intended target site through non-homologous end joining (NHEJ) are typically used to disrupt gene function by frameshift mutations (Chen et al., 2019).
Variations of Flavonoid Composition and Antioxidant Properties among Different Cultivars, Fruit Tissues and Developmental Stages of Citrus Fruits

A large number of biologically active compounds are present in ripe citrus fruits. However, few studies have been focused on the changes in flavonoids and the evolution of antioxidant activity during citrus fruit growth. In this study, fruits of five citrus cultivars cultivated in China were sampled at 60–210 days post‐anthesis (DPA) at intervals of 30 days. The amounts of main flavonoids in the peel and pulp were analyzed by HPLC and their activities were studied by DPPH, ABTS and FRAP. The results showed that the contents of hesperidin, diosmin, eriodictyol, rutin and nobiletin increased before 90 DPA and then decreased with the growth and development of fruits, but an opposite tendency was observed for naringin and narirutin. The antioxidant activities in citrus peel and pulp were found to be significantly correlated with some flavonoids. The results may be of guiding values in citrus production and utilization of citrus fruit by‐products.
Identification of a RAS-activating TMEM87A–RASGRF1 Fusion in an Exceptional Responder to Sunitinib with Non–Small Cell Lung Cancer

Purpose: We pursued genomic analysis of an exceptional responder with non–small cell lung cancer (NSCLC) through a multi-platform effort to discover novel oncogenic targets. Experimental Design: In this open-label, single-arm phase II study (NCT01829217), an enriched cohort of patients with advanced NSCLC was treated with the multi-kinase inhibitor sunitinib. The primary endpoint was objective response rate. Tissue was collected for multi-platform genomic analysis of responders, and a candidate oncogene was validated using in vitro models edited by CRISPR-Cas9. Results: Of 13 patients enrolled, 1 patient (8%), a never smoker, had a partial response lasting 33 months. Genomic analysis of the responder identified no oncogenic variant using multi-platform DNA analysis including hotspot allelotyping, massively parallel hybrid-capture next-generation sequencing, and whole-exome sequencing. However, bulk RNA-sequencing (RNA-seq) revealed a novel fusion, TMEM87A–RASGRF1, with high overexpression of the fusion partners. RASGRF1 encodes a guanine exchange factor which activates RAS from GDP-RAS to GTP-RAS. Oncogenicity was demonstrated in NIH/3T3 models with intrinsic TMEM87A–RASGRF1 fusion. In addition, activation of MAPK was shown in PC9 models edited to express this fusion, although sensitivity to MAPK inhibition was seen without apparent sensitivity to sunitinib. Conclusions: Sunitinib exhibited limited activity in this enriched cohort of patients with advanced NSCLC. Nonetheless, we find that RNA-seq of exceptional responders represents a potentially underutilized opportunity to identify novel oncogenic targets including oncogenic activation of RASGRF1.
Favorable retention rates and safety of conventional anti-rheumatic drugs in older patients with rheumatoid arthritis

Abstract Physicians are challenged by the recognition and treatment of older patients with rheumatoid arthritis (RA). The aim of this case-control study was to evaluate the retention and safety of conventional disease-modifying anti-rheumatic drugs in older patients with RA. In this observational case-control study, we assessed older patients with RA (≥65 years) who were diagnosed in 3 different rheumatology centers from Turkey. Patients were divided as to those aged ≥65 years (elderly rheumatoid arthritis [ERA]) and those aged <65 years (young rheumatoid arthritis [YRA]) at the time of conventional DMARD treatment initiation. The Mann-Whitney U test was used for the comparison of 2 non-normally distributed groups. The Chi-square (χ2) test was used for categorical variables. Survival analysis were performed using the Kaplan-Meier method. Four hundred eighteen patients with RA (296 females [71%]) were included from January 2010 to January 2018. The age of treatment onset of 190 (47%) patients was in the elderly period and they were included in the ERA group. In the analysis of drug retention rates, there was no significant difference between the ERA and YRA groups for each conventional DMARD (methotrexate 71.2% in ERA, 62.7% in YRA, P = .817; hydroxychloroquine 82.9% in ERA, 78.8% in YRA, P = .899; leflunomide 81.4% in ERA, 84.4% in YRA, P = .205; sulfasalazine 37.5% in ERA, 40.9% in YRA, P = .380). The adverse event data were also similar in both groups. The drug retention and adverse effect rates in older patients with RA using conventional DMARDS are similar to the rates in young patients with RA.
Ropivacaine inhibits proliferation, invasion, migration and promotes apoptosis of papillary thyroid cancer cells via regulating ITGA2 expression

The present study aimed to investigate the roles of Ropivacaine in papillary thyroid cancer (PTC) and identify the possible mechanisms. The expression of integrin alpha‐2 (ITGA2) in TC cell lines was tested using Western blotting and RT‐qPCR. Subsequently, the level of ITGA2 in human PTC cell line (TPC‐1) was measured following intervention with a series of concentrations of Ropivacaine. Then, cell counting kit‐8 (CCK‐8) assay and colony formation assay were executed for detecting proliferation of cells after transfection with ITGA2 pcDNA3.1. The expression of proliferation‐related protein was determined by Western blotting. Additionally, the abilities of TPC‐1 cell invasion and migration were examined using Transwell assay and scratch wound healing assay. Apoptosis of TPC‐1 cells was analyzed using TUNEL assay and the expressions of apoptosis‐related proteins were tested via West blotting. The results suggested that ITGA2 was highly expressed in TC cell lines, especially in TPC‐1 cells. Ropivacaine decreased the expression of ITGA2 in a dose‐dependent manner. Moreover, after treatment with Ropivacaine, cell proliferation was inhibited accompanied by changes of proliferation‐related protein expressions, which was reversed following co‐transfection with ITGA2 pcDNA3.1. Furthermore, Ropivacaine concentration‐dependently suppressed invasion and migration of TPC‐1 cells, whereas these inhibitory effects were attenuated after ITGA2 overexpression. Furthermore, apoptosis was promoted, coupled with a decrease of Bcl‐2 expression and increases of Bax, cleaved caspase‐3 and cleaved caspase‐9 expression, in Ropivacaine‐treated TPC‐1 cells, which was restored following ITGA2 overexpression. These findings demonstrated that Ropivacaine could suppress proliferation, invasion, migration, and accelerate apoptosis of PTC cells via regulating ITGA2 expression.