Miracle-dz/UniFAR-FTUs huggingface dataset:
Sirtuin‐1/Mitochondrial Ribosomal Protein S5 Axis Enhances the Metabolic Flexibility of Liver Cancer Stem Cells

Metabolic reprogramming endows cancer cells with the ability to adjust metabolic pathways to support heterogeneously biological processes. However, it is not known how the reprogrammed activities are implemented during differentiation of cancer stem cells (CSCs). In this study, we demonstrated that liver CSCs relied on the enhanced mitochondrial function to maintain stemness properties, which is different from aerobic glycolysis playing main roles in the differentiated non‐CSCs. We found that liver CSCs exhibit increased mitochondrial respiratory capacity and that complex‐I of mitochondria was necessary for stemness properties of liver CSCs through regulation of mitochondrial respiration. Bioinformatics analysis reveals that mitochondrial ribosomal protein S5 (MRPS5) is closely related with the function of complex‐I. Further experiments confirmed that MRPS5 promoted the production of nicotinamide adenine dinucleotide (NAD+), which is necessary for enhanced mitochondrial function in liver CSCs. MRPS5 played a critical role for liver CSCs to maintain stemness properties and to participate in tumor progression. Mechanistically, the acetylation status of MRPS5 is directly regulated by NAD+ dependent deacetylase sirtuin‐1 (SIRT1), which is abundant in liver CSCs and decreased during differentiation. Deacetylated MRPS5 locates in mitochondria to promote the function complex‐I and the generation of NAD+ to enhance mitochondrial respiration. Conversely, the acetylated MRPS5 gathered in nuclei leads to increased expression of glycolytic proteins and promotion of the Warburg Effect. Therefore, liver CSCs transform mitochondrial‐dependent energy supply to a Warburg phenotype by the dual function of MRPS5. Clinical analysis of SIRT1 and MRPS5 expression in tumor tissues showed the SIRT1High/Cytoplasmic‐MRPS5High profile was associated with patients with hepatocellular carcinoma with poor prognosis. Conclusion: SIRT1/MRPS5 axis participates in metabolic reprogramming to facilitate tumor progression and may serve as a promising therapeutic target of liver cancer.
Sequential Emergence and Wide Spread of Neutralization Escape Middle East Respiratory Syndrome Coronavirus Mutants, South Korea, 2015

The unexpectedly large outbreak of Middle East respiratory syndrome in South Korea in 2015 was initiated by an infected traveler and amplified by several “superspreading” events. Previously, we reported the emergence and spread of mutant Middle East respiratory syndrome coronavirus bearing spike mutations (I529T or D510G) with reduced affinity to human receptor CD26 during the outbreak. To assess the potential association of spike mutations with superspreading events, we collected virus genetic information reported during the outbreak and systemically analyzed the relationship of spike sequences and epidemiology. We found sequential emergence of the spike mutations in 2 superspreaders. In vivo virulence of the mutant viruses seems to decline in human patients, as assessed by fever duration in affected persons. In addition, neutralizing activity against these 2 mutant viruses in serum samples from mice immunized with wild-type spike antigen were gradually reduced, suggesting emergence and wide spread of neutralization escapers during the outbreak.
International multiphase mixed methods study protocol to develop a cross-cultural patient-reported outcome and experience measure for hand conditions (HAND-Q)

Introduction patient-reported outcome measures (PROMs) are instruments used to measure outcomes and experiences of healthcare from the patient perspective. The specific methodology used to develop a PROM should be communicated to establish the quality of the instrument. This mixed methods protocol describes the development of a cross-cultural, internationally applicable PROM for hand conditions, the HAND-Q. Methods and analysis The multiphase approach used for this study has been previously used with the development of other PROMs by our team (eg, BODY-Q, BREAST-Q, CLEFT-Q, FACE-Q). In Phase I, we establish what important concepts matter to patients with hand conditions. A conceptual framework is developed from a systematic review of existing PROMs in the field and an extensive international qualitative study. Interpretive description is the qualitative approach used. Item generation is based on the qualitative data. The preliminary scales will be created for each theme identified in the conceptual framework. These scales will be refined by cognitive debriefing interviews with participants and expert input. Phase II involves a large international sample of patients with varied hand conditions completing the field-test version of the HAND-Q. The scales will be refined using the modern psychometric approach of Rasch Measurement Theory. Analysis will result in a shortened set of clinically meaningful and scientifically robust HAND-Q scales. Ethics and dissemination This study is coordinated at Flinders University (Adelaide, Australia) where it has ethics board approval for phase I and phase II. Findings will be published in peer-reviewed journals and presented at local, national and international conferences.
Distinguishing underlying and surface variation patterns in speech perception

ABSTRACT This study examines the relationship between patterns of variation and speech perception using two English prefixes: “in-”/“im-” and “un-”. In natural speech, “in-” varies due to an underlying process of phonological assimilation, while “un-” shows a pattern of surface variation, assimilating before labial stems. In a go/no-go lexical decision experiment, subjects were presented a set of “mispronounced” stimuli in which the prefix nasal was altered (replacing [n] with [m], or vice versa), in addition to real words with unaltered prefixes. No significant differences between prefixes were found in responses to unaltered words. In mispronounced items, responses to “un-” forms were faster and more accurate than to “in-” forms, although a significant interaction mitigated this effect in labial contexts. These results suggest the regularity of variation patterns has consequences for the lexical specification of words, and argues against radical underspecification accounts which argue for a maximally sparse lexicon.
Helicase/SUMO-targeted ubiquitin ligase Uls1 interacts with the Holliday junction resolvase Yen1

Resolution of branched DNA structures is pivotal for repair of stalled replication forks and meiotic recombination intermediates. The Yen1 nuclease cleaves both Holliday junctions and replication forks. We show that Yen1 interacts physically with Uls1, a suggested SUMO-targeted ubiquitin ligase that also contains a SWI/SNF-family ATPase-domain. Yen1 is SUMO-modified in its noncatalytic carboxyl terminus and DNA damage induces SUMOylation. SUMO-modification of Yen1 strengthens the interaction to Uls1, and mutations in SUMO interaction motifs in Uls1 weakens the interaction. However, Uls1 does not regulate the steady-state level of SUMO-modified Yen1 or chromatin-associated Yen1. In addition, SUMO-modification of Yen1 does not affect the catalytic activity in vitro. Consistent with a shared function for Uls1 and Yen1, mutations in both genes display similar phenotypes. Both uls1 and yen1 display negative genetic interactions with the alternative HJ-cleaving nuclease Mus81, manifested both in hypersensitivity to DNA damaging agents and in meiotic defects. Point mutations in ULS1 (uls1K975R and uls1C1330S, C1333S) predicted to inactivate the ATPase and ubiquitin ligase activities, respectively, are as defective as the null allele, indicating that both functions of Uls1 are essential. A micrococcal nuclease sequencing experiment showed that Uls1 had minimal effects on global nucleosome positioning/occupancy. Moreover, increased gene dosage of YEN1 partially alleviates the mus81 uls1 sensitivity to DNA damage. We suggest a preliminary model in which Uls1 acts in the same pathway as Yen1 to resolve branched DNA structures.
Fate of preserved bicuspid valves at time of ascending aortic aneurysmectomy

The fate of the spared bicuspid aortic valve in patients undergoing ascending aortic aneurysm surgery is relatively unknown. Our institutional policy has been to replace all aortic valves with significant abnormalities, as evidenced by intraoperative transesophageal echocardiography or direct visual inspection. In this study, we elaborate our experience regarding the long‐term fate of preserved bicuspid aortic valves after ascending aortic aneurysm extirpation.
Effectiveness and Safety of Platelet ADP–P2Y12 Receptor Inhibitors Influenced by Smoking Status: A Systematic Review and Meta‐Analysis

Background As reports on the influence of cigarette smoking, an important cardiovascular risk factor, on platelet ADP–P2Y12 receptor inhibitors lack consistency, we aimed to assess the effectiveness and safety of platelet ADP–P2Y12 receptor inhibitors influenced by smoking status. Methods and Results PubMed, Web of Science, EMBASE, Clinical Trials, and the Cochrane Library were searched from inception until June 2018. Among the 5076 citations retrieved, 22 studies, including 163 011 patients with or without percutaneous coronary intervention, were included for meta‐analysis. Compared with nonsmokers within the first year of follow‐up, the reductions of stroke and major adverse cardiovascular event rate were 18% (P=0.008) and 26% (P=0.02), respectively. A 20% reduction in stroke (P=0.02) and a 34% reduction in major adverse cardiovascular event (P=0.0001) rates were observed in smoking patients without percutaneous coronary intervention. No significant difference was observed in clinical outcome rates among prasugrel, ticagrelor, and clopidogrel in different smoking status. No significant difference was found in myocardial infarction and bleeding event incidence between current smokers and nonsmokers. Conclusions We concluded that current smokers had a lower incidence of major adverse cardiovascular events and stroke events than did nonsmokers, particularly in the early period (1 year) and among patients without percutaneous coronary intervention. However, because of the lack of original adjusted data, smoker's paradox still needs to consider the impact of age and other covariates. Thus, a differential risk‐benefit evaluation should be considered, according to different smoking status, patient conditions, and therapy time points.
The use of social media in the B2B sales process: a meta synthesis

Purpose The purpose of this study is to understand how business-to-business organizations use social media during the sales process. Design/methodology/approach The meta-synthesis steps methodology (Hoon, 2013) was applied. Findings This study presents a theoretical framework and contributes to improved understanding of how business can use social media in the sales process stages. The results allow identifying stages, discussing the integration between marketing and sales and generating benefits for the organization. Originality/value The proposed framework helps in understanding the previously performed fragmented studies. This study shows that social media use not only influences the sales process stages and increases the benefits to the business but also works as a mediator in the relation between sales process stages and identified benefits.
Performance of Three Scoring Systems in Predicting Massive Transfusion in Patients with Unstable Upper Gastrointestinal Hemorrhage

Purpose After trauma and surgery, upper gastrointestinal bleeding (UGIB) is the most common condition that can require massive transfusion (MT). The present study aimed to analyze and compare the prognostic performance of the Glasgow-Blatchford (GB), pre-endoscopy Rockall (PER), and modified early warning (MEW) scores for predicting MT in patients with unstable UGIB. Materials and Methods This retrospective observational study included patients with UGIB from March 2016 to February 2018. Receiver operating characteristics analysis was performed to examine the prognostic performance of the GB, PER, and MEW scoring systems. Logistic regression analysis was used to identify independent risk factors for MT, after adjusting for relevant covariates. The primary outcome was MT. Results Of the 484 included patients with unstable UGIB, 19 (3.9%) received an MT. The areas under the curves (AUCs) of the GB, PER, and MEW scores for MT were 0.577 [95% confidence interval (CI), 0.531–0.621], 0.570 (95% CI, 0.525–0.615), and 0.767 (95% CI, 0.727–0.804), respectively. The AUC of the MEW score was significantly different from those of the GB and PER scores. In multivariate analysis, MEW score was independently associated with MT in patients with unstable UGIB (odds ratio, 1.495; 95% CI, 1.100–2.033; p=0.010). Conclusion In unstable UGIB patients, MEW score had the best prognostic performance for MT among three scoring systems.
The Role of Entrepreneurship Learning Program for Encouraging the Students Entrepreneurial Motivation

This study aims to determine the differences in entrepreneurial motivation in students who take part in the Management Entrepreneur Day (MED) program, including both implicit and explicit motivation in Management Department, Faculty of Economics and Business, Brawijaya University. This type of research is quantitative research with a method of collecting data in the form of probability sampling. The collected data was analyzed by applying SPSS analysis with a different test based on Analysis of Variance (ANOVA). The results of this study indicate that implicit motivation including motives for achievement (need for achievement) and motives for affiliation (need for affiliation) provides no difference in motivation (for entrepreneurship) in students who take MED. However, implicit motivation for controlling (need for power) presents a significant difference in the personal value among the students before (pre) and after (post) participating the MED activities. Whereas, explicit motivation including motives for achievement, depics a significant difference in students who take the MED program. Explicit motivation for affiliation (need for affiliation) and explicit motivation for controlling (need for power) indicates no difference in both before (pre) and after (post) participating in MED. From these results, the researchers concluded that the entrepreneurship program did not provide a significant change in entrepreneurial motivation among the participating students.
Compact high-isolation self-diplexing antenna based on SIW for C-band applications

ABSTRACT This paper presents a novel compact high-isolation cavity-backed inverted U-shaped slot antenna using substrate-integrated waveguide (SIW) for C-band applications. The SIW cavity is loaded by an inverted U-shaped slot that produces two fictitious aperture for radiation at two distinct frequency bands and to exhibit self-diplexing antenna (SDA) characteristics. Two orthogonal microstrip feed lines are applied for excitation of fundamental mode () and two degenerated modes ( and ). The perturbation of these modes due to slot loading allows to achieve size miniaturization. Compared with conventional SIW cavity without slot, the proposed SDA allows a size reduction of 56%. High isolation is achieved due to the transmission zeros produced by these modes and orthogonal feed lines. This isolation is further improved (>40.5 and >32.8 dB) due to off-centered input ports that creates very weak cross-coupling path between them. The resonating frequencies of the proposed SDA can be designed individually. Finally, an SDA working at 4.29 and 7.52 GHz is fabricated for validation of simulated performances. The measured gains of the fabricated SDA are 5.38 and 5.82 dBi at the resonating frequencies of 4.29 and 7.52 GHz, respectively. A good consistency is found between measured and simulated results.
Edinburgh Research Explorer Association between APOE e4 and white matter hyperintensity volume, but not total brain volume or white matter integrity

Apolipoprotein ( APOE ) e4 genotype is an accepted risk factor for accelerated cognitive aging and dementia, though its neurostructural substrates are unclear. The deleterious effects of this genotype on brain structure may increase in magnitude into older age. This study aimed to investigate in UK Biobank the association between APOE e4 allele presence vs. absence and brain imaging variables that have been associated with worse cognitive abilities; and whether this association varies by cross-sectional age. We used brain magnetic resonance imaging (MRI) and genetic data from a general-population cohort: the UK Biobank ( N = 8395 after exclusions). We adjusted for the covariates of age in years, sex, Townsend social deprivation scores, smoking history and cardiometabolic diseases. There was a statistically significant association between APOE e4 genotype and increased (i.e. worse) white matter (WM) hyperintensity volumes (standardised beta = 0.088, 95% confidence intervals = 0.036 to 0.139, P = 0.001), a marker of poorer cerebrovascular health. There were no associations with left or right hippocampal, total grey matter (GM) or WM volumes, or WM tract integrity indexed by fractional anisotropy (FA) and mean diffusivity (MD). There were no statistically significant interactions with age. Future research in UK Biobank utilising intermediate phenotypes and longitudinal imaging hold significant promise for this area, particularly pertaining to APOE e4 ’ s potential link with cerebrovascular contributions to cognitive aging.
One bout of neonatal inflammation impairs adult respiratory motor plasticity in male and female rats

Neonatal inflammation is common and has lasting consequences for adult health. We investigated the lasting effects of a single bout of neonatal inflammation on adult respiratory control in the form of respiratory motor plasticity induced by acute intermittent hypoxia, which likely compensates and stabilizes breathing during injury or disease and has significant therapeutic potential. Lipopolysaccharide-induced inflammation at postnatal day four induced lasting impairments in two distinct pathways to adult respiratory plasticity in male and female rats. Despite a lack of adult pro-inflammatory gene expression or alterations in glial morphology, one mechanistic pathway to plasticity was restored by acute, adult anti-inflammatory treatment, suggesting ongoing inflammatory signaling after neonatal inflammation. An alternative pathway to plasticity was not restored by anti-inflammatory treatment, but was evoked by exogenous adenosine receptor agonism, suggesting upstream impairment, likely astrocytic-dependent. Thus, the respiratory control network is vulnerable to early-life inflammation, limiting respiratory compensation to adult disease or injury.
Loss of oral self-care ability results in a higher risk of pneumonia in older inpatients: A prospective cohort study in a Japanese rural hospital.

OBJECTIVES To identify significant risk factors associated with incidence of mortality and pneumonia in whole-community-based older inpatients resident in Japanese rural region. METHODS Patients older than 65 years admitted between 1 April and 15 April 2010 to a core hospital located in a rural region were exhaustively recruited, and incidence of mortality and pneumonia during the 32-month follow-up period were evaluated. Independent variables at baseline measurement included age, gender, body mass index, Charlson comorbidity index, functional dependency, oral self-care ability index, number of remaining teeth, hyposalivation and nutritional status. Dependent variables were incidence of mortality and pneumonia. Survival and non-pneumonia curves were drawn using Kaplan-Meier analysis. Cox proportional hazards analysis was performed to identify the risk factors related to incidence of mortality and pneumonia. RESULTS The survival rate of 46 patients (male/female: 11/35; mean age: 83.8 ± 6.8 years) was 52.1%, and the incidence of pneumonia was 60.9%. Malnutrition and gender (male) were identified as significant risk factors for mortality (odds ratio [OR]: 8.18 and 4.90; 95% confidence interval [CI]: 1.77-37.3 and 1.50-16.0; P < 0.01 and <0.01, respectively). Loss of oral self-care ability and gender (male) were identified as significant risk factors for incidence of pneumonia (OR: 8.97 and 4.58; 95% CI: 1.70-47.4 and 1.50-14.0; P = 0.01 and <0.01, respectively). CONCLUSIONS Malnutrition and loss of oral self-care ability were significant risk factors for incidence of mortality and pneumonia, respectively. In response, supplying nutrition with appropriate diet and personalised oral care might contribute to reduction in mortality and prevention of pneumonia.
An Ultra-Dense Haploid Genetic Map for Evaluating the Highly Fragmented Genome Assembly of Norway Spruce (Picea abies)

Norway spruce (Picea abies (L.) Karst. ) is a conifer species of substanital economic and ecological importance. In common with most conifers, the P. abies genome is very large (∼20 Gbp) and contains a high fraction of repetitive DNA. The current P. abies genome assembly (v1.0) covers approximately 60% of the total genome size but is highly fragmented, consisting of >10 million scaffolds. The genome annotation contains 66,632 gene models that are at least partially validated (www.congenie.org), however, the fragmented nature of the assembly means that there is currently little information available on how these genes are physically distributed over the 12 P. abies chromosomes. By creating an ultra-dense genetic linkage map, we anchored and ordered scaffolds into linkage groups, which complements the fine-scale information available in assembly contigs. Our ultra-dense haploid consensus genetic map consists of 21,056 markers derived from 14,336 scaffolds that contain 17,079 gene models (25.6% of the validated gene models) that we have anchored to the 12 linkage groups. We used data from three independent component maps, as well as comparisons with previously published Picea maps to evaluate the accuracy and marker ordering of the linkage groups. We demonstrate that approximately 3.8% of the anchored scaffolds and 1.6% of the gene models covered by the consensus map have likely assembly errors as they contain genetic markers that map to different regions within or between linkage groups. We further evaluate the utility of the genetic map for the conifer research community by using an independent data set of unrelated individuals to assess genome-wide variation in genetic diversity using the genomic regions anchored to linkage groups. The results show that our map is sufficiently dense to enable detailed evolutionary analyses across the P. abies genome.