Miracle-dz/UniFAR-FTUs huggingface dataset:
N160 of Aiolos Determines its DNA‐Binding Activity

Aiolos is a transcription factor of the Ikaros family. It is expressed in lymphocytes and plays a vital role in the development of lymphatic system. Recently, Aiolos has been found to be ectopically expressed in lung cancer cells and promotes cancer metastasis through repression of p66Shc expression. Blocking DNA‐binding activity of Aiolos may benefit cancer patients by preventing further metastasis. However, it is not clear which sequence is essential for its DNA binding. In this study, we found that N160 is a key amino acid to determine the DNA‐binding activity of Aiolos. Mutation of N160A resulted in loss of peripheral heterochromatin localization and dissociation with its target gene. Accordingly, Aiolos with N160A could not change the expression of its target genes. Thus, we identified the amino acid (N160) that is essential for Aiolos binding to DNA. Anat Rec, 302:2014–2019, 2019. © 2019 American Association for Anatomy
Incorporation of a Agent Based approach for Integrated OLAP/OLAM Architecture

The current data mining tools is used to build knowledge based on a huge historical data. At present, businesses are facing with fast growing data that are very valuable in contributing knowledge. Knowledge should be updated regularly in order to ensure its quality and precision thus improve the decision making process. Data mining has shown great potential in extracting valuable knowledge from large databases. However, current data mining algorithms and tools are costly and several are too complex in their operations when dealing with large databases. In recent years, agents have become a popular paradigm in computing, because its autonomous, flexible and provides intelligence. Embedding agents in the current data mining processes and tools are believed to be able to solve the obstacle . Data warehouses are used for information processing, analytical processing, and data mining. An OLAP based data mining is referred to as OLAP mining, or on-line analytical mining (OLAM), which emphasizes the interactive and exploratory nature of OLAP mining. This paper focuses on an agent-based integrated OLAP/OLAM architecture that mainly focuses on data preprocessing. The aims is to provides an auto preprocessing a set of new data, which suite to data mining novice user. The proposed agent based framework consists of eight supporting agents: data cleaning agent, transformation agent, data reduction agent, data integration agent, proxy MDDB agent, input agent, GUI agent and dividing agent. Also we have three co-coordinating agents: DB API agent, MDDB agent and CUBE API agent. This paper is start by introducing the data mining process problem includes data preprocessing which agent can solve data mining problems. By applying agent in data preprocessing, a tool that intelligence yet flexible can be produced
HNRNPA1-mediated 3′ UTR length changes of HN1 contributes to cancer- and senescence-associated phenotypes

Cellular senescence has been regarded as a mechanism of tumor suppression. Studying the regulation of gene expression at various levels in cell senescence will shed light on cancer therapy. Alternative polyadenylation (APA) regulates gene expression by altering 3′ untranslated regions (3′ UTR) and plays important roles in diverse biological processes. However, whether APA of a specific gene functions in both cancer and senescence remains unclear. Here, we discovered that 3′ UTR of HN1 (or JPT1) showed shortening in cancers and lengthening in senescence, correlated well with its high expression in cancer cells and low expression in senescent cells, respectively. HN1 transcripts with longer 3′ UTR were less stable and produced less protein. Down-regulation of HN1 induced senescence-associated phenotypes in both normal and cancer cells. Patients with higher HN1 expression had lower survival rates in various carcinomas. Interestingly, down-regulating the splicing factor HNRNPA1 induced 3′ UTR lengthening of HN1 and senescence-associated phenotypes, which could be partially reversed by overexpressing HN1. Together, we revealed for the first time that HNRNPA1-mediated APA of HN1 contributed to cancer- and senescence-related phenotypes. Given senescence is a cancer prevention mechanism, our discovery indicates the HNRNPA1-HN1 axis as a potential target for cancer treatment.
Population Genetic Divergence and Environment Influence the Gut Microbiome in Oregon Threespine Stickleback

Much of animal-associated microbiome research has been conducted in species for which little is known of their natural ecology and evolution. Microbiome studies that combine population genetic, environment, and geographic data for wild organisms can be very informative, especially in situations where host genetic variation and the environment both influence microbiome variation. The few studies that have related population genetic and microbiome variation in wild populations have been constrained by observation-based kinship data or incomplete genomic information. Here we integrate population genomic and microbiome analyses in wild threespine stickleback fish distributed throughout western Oregon, USA. We found that gut microbiome diversity and composition partitioned more among than within wild host populations and was better explained by host population genetic divergence than by environment and geography. We also identified gut microbial taxa that were most differentially abundant across environments and across genetically divergent populations. Our findings highlight the benefits of studies that investigate host-associated microbiomes in wild organisms.
Predictive value of combining the SYNTAX score with reactive hyperemia index in patients with acute coronary syndrome undergoing percutaneous coronary intervention

To investigate the predictive value of SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score (SS) combined with reactive hyperemia index (RHI) in predicting 2‐year major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).
KNAT2/6b, a class I KNOX gene, impedes xylem differentiation by regulating NAC domain transcription factors in poplar.

Wood formation is the terminal differentiation of xylem mother cells derived from cambial initials, and negative regulators play important roles in xylem differentiation. The molecular mechanism of the negative regulator of xylem differentiation PagKNAT2/6b was investigated. PagKNAT2/6b is an ortholog of Arabidopsis KNAT2 and KNAT6 that is highly expressed in phloem and xylem. Compared to non-transgenic control plants, transgenic poplar plants overexpressing PagKNAT2/6b present with altered vascular patterns, characterized by decreased secondary xylem with thin cell walls containing less cellulose, xylose, and lignin. RNA sequencing analyses revealed that differentially expressed genes are enriched in xylem differentiation and secondary wall synthesis functions. Expression of NAM/ATAF/CUC (NAC) domain genes including PagSND1-A1, PagSND1-A2, PagSND1-B2, and PagVND6-C1 is downregulated by PagKNAT2/6b, while PagXND1a is directly upregulated. Accordingly, the dominant repression form of PagKNAT2/6b leads to increased xylem width per stem diameter through downregulation of PagXND1a. PagKNAT2/6b can inhibit cell differentiation and secondary wall deposition during wood formation in poplar by modulating the expression of NAC domain transcription factors. Direct activation of PagXND1a by PagKNAT2/6b is a key node in the negative regulatory network of xylem differentiation by KNOXs. This article is protected by copyright. All rights reserved.
The translational neural circuitry of anxiety

Anxiety is an adaptive response that promotes harm avoidance, but at the same time excessive anxiety constitutes the most common psychiatric complaint. Moreover, current treatments for anxiety—both psychological and pharmacological—hover at around 50% recovery rates. Improving treatment outcomes is nevertheless difficult, in part because contemporary interventions were developed without an understanding of the underlying neurobiological mechanisms that they modulate. Recent advances in experimental models of anxiety in humans, such as threat of unpredictable shock, have, however, enabled us to start translating the wealth of mechanistic animal work on defensive behaviour into humans. In this article, we discuss the distinction between fear and anxiety, before reviewing translational research on the neural circuitry of anxiety in animal models and how it relates to human neuroimaging studies across both healthy and clinical populations. We highlight the roles of subcortical regions (and their subunits) such as the bed nucleus of the stria terminalis, the amgydala, and the hippocampus, as well as their connectivity to cortical regions such as dorsal medial and lateral prefrontal/cingulate cortex and insula in maintaining anxiety responding. We discuss how this circuitry might be modulated by current treatments before finally highlighting areas for future research that might ultimately improve treatment outcomes for this common and debilitating transdiagnostic symptom.
The evolving (epi)genetic landscape of pancreatic neuroendocrine tumours.

Neuroendocrine neoplasms are a relatively rare group of heterogeneous tumours originating from neuroendocrine cells found throughout the body. Pancreatic NENs (PanNENs) are the second most common pancreatic malignancy accounting for 1-3% of all neoplasms developing in the pancreas. Despite having a low background mutation rate, driver mutations in MEN1, DAXX/ATRX and mTOR pathway genes (PTEN, TSC1/2) are implicated in disease development and progression. Their increased incidence coupled with advances in sequencing technologies, has re-ignited the interest in PanNEN research and has accelerated the acquisition of molecular data. Studies utilising such technological advances have further enriched our knowledge of PanNENs' biology through novel findings, including higher-than-expected presence of germline mutations in 17% of sporadic tumours of no familial background, identification of novel mutational signatures and complex chromosomal re-arrangements and a dysregulated epigenetic machinery. Integrated genomic studies have progressed the field by identifying the synergistic action between different molecular mechanisms, while holding the promise for deciphering disease heterogeneity. Although our understanding is far from being complete, these novel findings have provided the optimism of shaping the future of PanNEN research, ultimately leading to an era of precision medicine for NETs. Here, we recapitulate the existing knowledge on PanNENs and discuss how recent, novel findings have furthered our understanding of these complex tumours.
Comparison of the Efficacy of Nilotinib and Imatinib in the Treatment of Chronic Myeloid Leukemia.

OBJECTIVE To compare the efficacy of nilotinib and imatinib in the treatment of chronic myeloid leukemia (CML). STUDY DESIGN Analytical study. PLACE AND DURATION OF STUDY Department of Hematology, Chongqing Three Gorges Central Hospital, China, from January 2016 to January 2018. METHODOLOGY Eighty patients with CML were randomly divided into the nilotinib group (treated with nilotinib) and the imatinib group (treated with imatinib), 40 patients in each group. The therapeutic effects of the two groups of patients were compared. RESULTS After months of treatment, the neutrophilic granulocytes and neutrophilic metamyelocyte, serum interleukin (IL)-6 and IL-8 and α1-acid glycoprotein (AGP) levels in nilotinib group were lower than those in imatinib group (p=0.002, p<0.001, p=0.027, p=<0.001 and p=0.001, respectively); the proportion of patients with BCR-ABLIS <10% in nilotinib group and the proportion of patients with BCR-ABLIS <0.0032% were higher than those in imatinib group (p=0.032 and 0.043, respectively). During treatment period, there was no significant difference in the incidence of adverse reactions such as mild liver damage, nausea and vomiting, rash, musculoskeletal pain and edema between two groups (p = 0.556, 0.396, 0.576, 0.775 and 0.390, respectively). CONCLUSION Nilotinib is superior to imatinib in the treatment of CML. There is no significant difference in the safety of the two drugs, and the adverse reactions can be tolerated.
Evolution and Interspecies Transmission of Canine Distemper Virus—An Outlook of the Diverse Evolutionary Landscapes of a Multi-Host Virus

Canine distemper virus (CDV) is a worldwide distributed virus which belongs to the genus Morbillivirus within the Paramyxoviridae family. CDV spreads through the lymphatic, epithelial, and nervous systems of domestic dogs and wildlife, in at least six orders and over 20 families of mammals. Due to the high morbidity and mortality rates and broad host range, understanding the epidemiology of CDV is not only important for its control in domestic animals, but also for the development of reliable wildlife conservation strategies. The present review aims to give an outlook of the multiple evolutionary landscapes and factors involved in the transmission of CDV by including epidemiological data from multiple species in urban, wild and peri-urban settings, not only in domestic animal populations but at the wildlife interface. It is clear that different epidemiological scenarios can lead to the presence of CDV in wildlife even in the absence of infection in domestic populations, highlighting the role of CDV in different domestic or wild species without clinical signs of disease mainly acting as reservoirs (peridomestic and mesocarnivores) that are often found in peridomestic habits triggering CDV epidemics. Another scenario is driven by mutations, which generate genetic variation on which random drift and natural selection can act, shaping the genetic structure of CDV populations leading to some fitness compensations between hosts and driving the evolution of specialist and generalist traits in CDV populations. In this scenario, the highly variable protein hemagglutinin (H) determines the cellular and host tropism by binding to signaling lymphocytic activation molecule (SLAM) and nectin-4 receptors of the host; however, the multiple evolutionary events that may have facilitated CDV adaptation to different hosts must be evaluated by complete genome sequencing. This review is focused on the study of CDV interspecies transmission by examining molecular and epidemiological reports based on sequences of the hemagglutinin gene and the growing body of studies of the complete genome; emphasizing the importance of long-term multidisciplinary research that tracks CDV in the presence or absence of clinical signs in wild species, and helping to implement strategies to mitigate the infection. Integrated research incorporating the experience of wildlife managers, behavioral and conservation biologists, veterinarians, virologists, and immunologists (among other scientific areas) and the inclusion of several wild and domestic species is essential for understanding the intricate epidemiological dynamics of CDV in its multiple host infections.
Bisphenol A co-exposure effects: a key factor in understanding BPA’s complex mechanism and health outcomes

Abstract Bisphenol A (BPA) is an environmental endocrine disrupting chemical widely used in the production of consumer products, such as polycarbonate plastics, epoxies, and thermal receipt paper. Human exposure to BPA is ubiquitous due to its high-volume production and use. BPA exposure has been associated with obesity, diabetes, reproductive disorders, and cancer. Yet, the molecular mechanisms or modes of action underlying these disease outcomes are poorly understood due to the pleiotropic effects induced by BPA. A further confounding factor in understanding BPA’s impact on human health is that co-exposure of BPA with endogenous and exogenous agents occurs during the course of daily life. Studies investigating BPA exposure effects and their relationship to adverse health outcomes often ignore interactions between BPA and other chemicals present in the environment. This review examines BPA co-exposure studies to highlight potentially unexplored mechanisms of action and their possible associations with the adverse health effects attributed to BPA. Importantly, both adverse and beneficial co-exposure effects are observed between BPA and natural chemicals or environmental stressors in in vitro and in vivo models. These interactions clearly influence cellular responses and impact endpoint measures and need to be considered when evaluating BPA exposures and their health effects.
Fermented soybean meal ameliorates Salmonella Typhimurium infection in young broiler chickens.

The present study was designed to investigate the effectiveness of dietary fermented soybean meal (FSBM) in comparison with prebiotic (Xylooligosaccharide; XOS) and probiotic (Lactic acid bacteria-based probiotic; LAC) for prevention of Salmonella Typhimurium (ST) infection in young broiler chickens from 1 to 24 d. The in vitro study revealed that soybean meal (SBM) fermentation increased the number of lactic acid bacteria (LAB) and lactic acid content and inhibited the growth of enterobacteria such as coliforms in SBM. A total of 450 day-old Ross 308 broiler chicks were placed in 30 pens (15 birds/pen) and allocated to 5 experimental treatments that consisted an un-supplemented basal diet and not infected (NC) or infected with ST (IC); IC plus 2 g XOS/kg; IC plus 0.2 g LAC/kg; and IC containing a complete replacement of SBM with FSBM. All birds (except NC) were orally administered with 0.5 mL of the ST solution (1 × 106 CFU/mL) at d 3 post-hatch. The ST challenge decreased body weight gain and feed intake (P < 0.05). The impairment of feed conversion ratio was alleviated by the addition of XOS, LAC, and FSBM in broiler diets compared with IC birds (P < 0.05). The ST infection reduced duodenum and jejunum villus height and increased Salmonella colonization throughout the gut as well as internal organ invasion compared with NC birds (P < 0.05). However, ST-infected broilers fed the XOS, LAC, and FSBM-containing diets showed a significant decrease in gut Salmonella colonization, and internal organ invasion, an increase in LAB counts, and improvement in intestinal mucosa morphology (P < 0.05). The tested feed additives or FSBM reduced heterophil to lymphocyte ratio compared with the IC group (P < 0.05). The results suggest that XOS, LAC, and FSBM improve growth performance, lower Salmonella colonization, and improve intestinal characteristics and immune response in ST-challenged broiler chicks. Therefore, fermented feeds due to having functional ingredients can be considered as an effective strategy to lessen the colonization of gut pathogens in broiler chickens.
Cardiac rehabilitation delivery in low/middle-income countries

Objective Cardiac rehabilitation (CR) availability, programme characteristics and barriers are not well-known in low/middle-income countries (LMICs). In this study, they were compared with high-income countries (HICs) and by CR funding source. Methods A cross-sectional online survey was administered to CR programmes globally. Need for CR was computed using incident ischaemic heart disease (IHD) estimates from the Global Burden of Disease study. General linear mixed models were performed. Results CR was identified in 55/138 (39.9%) LMICs; 47/55 (85.5% country response rate) countries participated and 335 (53.5% programme response) surveys were initiated. There was one CR spot for every 66 IHD patients in LMICs (vs 3.4 in HICs). CR was most often paid by patients in LMICs (n=212, 65.0%) versus government in HICs (n=444, 60.2%; p<0.001). Over 85% of programmes accepted guideline-indicated patients. Cardiologists (n=266, 89.3%), nurses (n=234, 79.6%; vs 544, 91.7% in HICs, p=0.001) and physiotherapists (n=233, 78.7%) were the most common providers on CR teams (mean=5.8±2.8/programme). Programmes offered 7.3±1.8/10 core components (vs 7.9±1.7 in HICs, p<0.01) over 33.7±30.7 sessions (significantly greater in publicly funded programmes; p<0.001). Publicly funded programmes were more likely to have social workers and psychologists on staff, and to offer tobacco cessation and psychosocial counselling. Conclusion CR is only available in 40% of LMICs, but where offered is fairly consistent with guidelines. Governments should enact policies to reimburse CR so patients do not pay out-of-pocket.
A Three-Way Optimization Technique for Noise Robust Moving Object Detection Using Tensor Low-Rank Approximation, l1/2, and TTV Regularizations

The rising demand for surveillance systems naturally necessitates more efficient and noise robust moving object detection (MOD) systems from the captured video streams. Inspired by the challenges in MOD which are yet to be addressed properly, this paper proposes a new MOD scheme using <inline-formula> <tex-math notation="LaTeX">$l_{1/2}$ </tex-math></inline-formula> regularization in the tensor framework. It takes advantage of the special features of tensor singular value decomposition (<inline-formula> <tex-math notation="LaTeX">${t}$ </tex-math></inline-formula>-SVD) along with regularizations using <inline-formula> <tex-math notation="LaTeX">$l_{1/2}$ </tex-math></inline-formula>-norm with half thresholding operation and tensor total variation (TTV) to develop a noise robust MOD system with improved detection accuracy. While <inline-formula> <tex-math notation="LaTeX">${t}$ </tex-math></inline-formula>-SVD exploits the spatio-temporal correlation of the video background, <inline-formula> <tex-math notation="LaTeX">$l_{1/2}$ </tex-math></inline-formula> regularization provides noise robustness besides removing the sparser but discontinuous dynamic elements in the spatio-temporal direction. Moreover, TTV enhances the spatio-temporal continuity and fills up the gaps due to the lingering objects and thereby extracting the foreground precisely. The proposed three-way optimization method is designed to address both static and dynamic background cases of MOD separately with the intention to reduce the misclassifications due to moving/cluttered background. The brilliance of this method is confirmed by the impressive visual quality of the background/foreground separation, noise robustness, reduced computational complexity, and rapid response. The quantitative evaluation discloses the predominance of the proposed method with respect to the state-of-the-art techniques.