bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypersilencing of SRRM4 suppresses basal microexon inclusion and promotes tumor growth across cancers
Authors: Head Sarah A. , Hernandez-Alias Xavier , Yang Jae-Seong , Beltran-Sastre Violeta , Torres-Méndez Antonio , Irimia Manuel , Schaefer Martin H. , Serrano Luis 
Published: March 2020

AbstractRNA splicing is widely dysregulated in cancer, frequently due to altered expression or activity of splicing factors. Microexons are extremely small exons (3-27 nucleotides long) that are highly evolutionarily conserved and play critical roles in promoting neuronal differentiation and development. Inclusion of microexons in mRNA transcripts is mediated by the splicing factor SRRM4, whose expression is largely restricted to neural tissues. However, microexons have been largely overlooked in prior analyses of splicing in cancer, as their small size necessitates specialized computational approaches for their detection. Here we demonstrate that despite having low expression in normal non-neural tissues, SRRM4 is hypersilenced in tumors, resulting in the suppression of basal microexon inclusion. Remarkably, SRRM4 is the most consistently silenced splicing factor across all tumor types analyzed, implying a general advantage of microexon downregulation in cancer independent of its tissue of origin. We show that this silencing is favorable for tumor growth, as decreased SRRM4 expression in tumors is correlated with an increase in mitotic gene expression, and upregulation of SRRM4 in cancer cell lines dose-dependently inhibits proliferationin vitroand in a mouse xenograft model. Further, this proliferation inhibition is accompanied by induction of neural-like expression and splicing patterns in cancer cells, suggesting that SRRM4 expression shifts the cell state away from proliferation and towards differentiation. We therefore conclude that SRRM4 acts as a proliferation brake, and tumors gain a selective advantage by cutting off this brake.SignificanceMicroexons are extremely small exons enriched in the brain that play important roles in neural development. Their inclusion is mediated by the splicing factor SRRM4, also predominantly expressed in the brain. Surprisingly, we find that low expression of SRRM4 outside of the brain is further decreased in tumors, and in fact SRRM4 is the most consistently silenced splicing factor in tumors across tissue types. We demonstrate that SRRM4 inhibits cancer cell proliferationin vitroandin vivoby inducing a neuronal differentiation program. Our findings add a new element to the overall picture of splicing dysregulation in cancer, reveal an antiproliferative function for SRRM4 and microexons outside of the brain, and may present a common therapeutic intervention point across cancer types.
The glycolysis regulator PFKFB4 interacts with ICMT and activates RAS/AKT signaling-dependent cell migration in melanoma
Authors: Sittewelle Méghane , Kappès Vincent , Lécuyer Déborah , Monsoro-Burq Anne H. 
Published: March 2020

AbstractCell migration is a complex process, tightly regulated during embryonic development and abnormally activated during cancer metastasis. RAS-dependent signaling is a major nexus controlling essential cell parameters including proliferation, survival and migration, utilizing downstream effectors such as the PI3K/AKT signaling pathway. In melanoma, oncogenic mutations frequently enhance RAS, PI3K/AKT or MAP kinase signaling, and trigger other cancer hallmarks among which the activation of metabolism regulators. PFKFB4 is one of these critical regulators of glycolysis and of the Warburg effect. Here however, we explore a novel function of PFKFB4 in melanoma cell migration. We find that PFKFB4 interacts with ICMT, a post-translational modifier of RAS. PFKFB4 promotes ICMT/RAS interaction, controls RAS localization at the plasma membrane, activates AKT signaling and enhances cell migration. We thus provide evidence of a novel and glycolysis-independent function of PFKFB4 in human cancer cells. This unconventional activity links the metabolic regulator PFKFB4 to RAS-AKT signaling and impacts melanoma cell migration.Highlights-PFKFB4, a known regulator of glycolysis, also displays an unconventional role in melanoma cell migration.-PFKFB4 interacts with ICMT and promotes RAS localization at the plasma membrane.-PFKFB4 and ICMT cooperation modulates AKT signaling and controls melanoma cell migration.
Benchmarking accuracy and precision of intensity-based absolute quantification of protein abundances inSaccharomyces cerevisiae
Authors: Sánchez Benjamín J. , Lahtvee Petri-Jaan , Campbell Kate , Kasvandik Sergo , Yu Rosemary , Domenzain Iván , Zelezniak Aleksej , Nielsen Jens 
Published: March 2020

AbstractProtein quantification via label-free mass spectrometry (MS) has become an increasingly popular method for determining genome-wide absolute protein abundances. A known caveat of this approach is the poor technical reproducibility, i.e. how consistent the estimations are when the same sample is measured repeatedly. Here, we measured proteomics data forSaccharomyces cerevisiaewith both biological and inter-batch technical triplicates, to analyze both accuracy and precision of protein quantification via MS. Moreover, we analyzed how these metrics vary when applying different methods for converting MS intensities to absolute protein abundances. We found that a simple normalization and rescaling approach performs as accurately yet more precisely than methods that rely on external standards. Additionally, we show that inter-batch reproducibility is worse than biological reproducibility for all evaluated methods. These results subsequently serve as a benchmark for assessing MS data quality for protein quantification, whilst also underscoring current limitations in this approach.
The impact of characteristics of intra-organizational environment on entrepreneurial marketing intensity and performance in Egypt
Authors: Mahrous Abeer , Genedy Mohamed Ashraf , Kalliny Morris 
Published: March 2020

Purpose
The purpose of this paper is to contribute to the entrepreneurial marketing (EM) paradigm by empirically investigating the relationship between intra-organizational environment, EM intensity (EMI) and organizational performance in an emerging market context. Specifically, the paper identifies the elements of the intra-organizational environment that enhances EMI and also examines the impact of EMI on organizational performance.

Design/methodology/approach
The data were collected from large-sized companies in Egypt. Data were analyzed by using path analysis on Smart-PLS.

Findings
The findings suggest that the characteristics of the intra-organizational environment that support developing and increasing EMI in large-sized companies in emerging markets are cooperative competency, deep locus of planning and institutional support. Also, it was found that the long planning horizon hinders EMI. Finally, it was found that EMI is positively related to organizational performance and competitive advantage.

Practical implications
The study provides guidelines for managers of large-sized organizations, especially in emerging economies, on how to develop the intra-organizational environment to enhance EMI.

Originality/value
The study of EMI received little or no attention in previous research. Also, there is a paucity of empirical research on the impact of the intra-organizational environment on EMI and also on the impact of EMI on the organizational performance of large-sized companies in emerging markets. Therefore, the results of this research are a step toward filling these gaps.
Islamic financial institutions: conduits for money laundering?
Authors: Jabbar Siti Faridah Abdul 
Published: March 2020

PurposeThe purpose of this paper is to discuss various situations in the Islamic financial services industry that are asserted to facilitate money laundering and the counter-arguments to the assertions.Design/methodology/approachThe approach adopted by this paper is a review of literature and of several practices of Islamic financial institutions in a number of countries.FindingsThere is no evidence to support the contentions that Islamic financial institutions facilitate money laundering. Further, Islamic financial institutions are not any more susceptible to money laundering than conventional financial institutions are.Originality/valueThis paper demonstrates that Islamic financial institutions are not conduits for money laundering.
Genome‐resolved metagenomics to study co‐occurrence patterns and intraspecific heterogeneity among plant pathogen metapopulations
Authors: Newberry Eric , Bhandari Rishi , Kemble Joseph , Sikora Edward , Potnis Neha 
Published: March 2020

SummaryAssessment of pathogen diversity in agricultural fields is essential for informing management decisions and the development of resistant plant varieties. However, many population genomic studies have relied on culture‐based approaches that do not provide quantitative assessment of pathogen populations at the field‐level or the associated host microbiome. Here, we applied whole‐genome shotgun sequencing of microbial DNA extracted directly from the washings of pooled leaf samples, collected from individual tomato and pepper fields in Alabama that displayed the classical symptoms of bacterial spot disease caused by Xanthomonas spp. Our results revealed that while the occurrence of both X. perforans and X. euvesicatoria within fields was limited, evidence of co‐occurrence of up to three distinct X. perforans genotypes was obtained in 7 of 10 tomato fields sampled. These population dynamics were accompanied by the corresponding type 3 secreted effector repertoires associated with the co‐occurring X. perforans genotypes, indicating that metapopulation structure within fields should be considered when assessing the adaptive potential of X. perforans. Finally, analysis of microbial community composition revealed that co‐occurrence of the bacterial spot pathogens Pseudomonas cichorii and Xanthomonas spp. is common in Alabama fields and provided evidence for the non‐random association of several other human and plant opportunists.
ASERNIP‐S: unusual acronym, outstanding results
Authors: Maddern Guy J. , Babidge Wendy J. , Faulkner Kingsley W. 
Published: March 2020

AbstractIn the late 1990s, concerns regarding the introduction of new surgical procedures arose following the rapid uptake of some minimally invasive procedures. At that time, the evidence was not clear on the safety and effectiveness of these new procedures, and it was recommended that data be collected to look at both short‐ and long‐term outcomes. Based on a UK group, ‘the Safety and Efficacy Register of New Interventional Procedures (SERNIP)’, the Australian SERNIP was born under the auspices of the Royal Australasian College of Surgeons, with ‘‐S’ added to the acronym to highlight the focus on surgery. ASERNIP‐S was established to review the evidence on new interventional procedures before their introduction into the Australian healthcare system. The programme operated with initial national government funding for 7 years. Following establishment of the Medical Services Advisory Committee, ASERNIP‐S became a contractor and remains so today. ASERNIP‐S was an also an early adopter of Horizon Scanning, a key activity informing of new procedures/technologies on the verge of introduction into our healthcare system. A strong international reputation of ASERNIP‐S is recognised, both by lead roles of international networks and in working relationships with overseas agencies. In recent years the remit of ASERNIP‐S has expanded to include research and evaluation services across the Royal Australasian College of Surgeons (including committees) and for Specialty Surgical Societies. Externally funded work is growing, including for the Federal Office of Public Health in Switzerland and the Ludwig Boltzmann Institute in Austria. It is unknown what the future will be for this unusually titled programme, but its long history in promoting and supporting surgical evidence and innovation is clear.
Does early surgery imply a critical risk for patients with Grade III acute cholecystitis?
Authors: Kohga Atsushi , Okumura Takuya , Yamashita Kimihiro , Isogaki Jun , Kawabe Akihiro , Kimura Taizo 
Published: March 2020

AbstractBackgroundFor patients with Grade III acute cholecystitis (AC), several factors have been proposed in the 2018 Tokyo guidelines as caution signs in performing early surgery. However, these factors have not been externally validated in detail.MethodsThis retrospective study examined 35 patients who had been diagnosed with Grade III AC and treated with laparoscopic cholecystectomy between January 2008 and July 2019. The patients were allocated into an early group (patients who underwent surgery within 7 days of admission, n = 28) and a delayed group (patients who underwent surgery at least 8 days after admission, n = 7). Comparisons were made between these groups.ResultsNo patients died. Significantly more patients required a conversion to open surgery (0% vs 28.5%, P = .003) or conversion to subtotal cholecystectomy (25.0% vs 71.4%, P = .020) in the delayed group than in the early group, and the total length of postoperative stay was significantly longer in the delayed group (11.4 vs 27.2 days, P = .001). The presence of negative predictive factors or risk factors listed in the 2018 Tokyo guidelines was not associated with death or postoperative complications.ConclusionsEarly surgery was considered appropriate and feasible for select patients who had Grade III AC and preoperative risk factors.
Effects of dietary dihydroartemisinin supplementation on growth performance, hepatic inflammation, and lipid metabolism in weaned piglets with intrauterine growth retardation
Authors: Zhao Yongwei , Niu Yu , He Jintian , Gan Zhending , Ji Shuli , Zhang Lili , Wang Chao , Wang Tian 
Published: March 2020

AbstractThe aims of this study were to investigate the effects of dietary supplementation with dihydroartemisinin (DHA) on growth performance, hepatic inflammation, and lipid metabolism in intrauterine growth retardation (IUGR)‐affected weaned piglets. Eight piglets with normal birth weight (NBW) and 16 IUGR‐affected piglets were selected and fed either a basal diet (NBW and IUGR groups) or the basal diet supplemented with 80 mg/kg DHA (IUGR‐DHA group) from 21 to 49 day of age. Blood and liver samples were collected on day 49. DHA supplementation significantly alleviated the compromised growth performance and liver damage in IUGR‐affected piglets. Additionally, DHA supplementation decreased the activities of alanine aminotransferase and aspartate aminotransferase, as well as the serum levels of non‐esterified fatty acids (NEFA), very‐low‐density lipoprotein, and total cholesterol. In the liver, the concentrations of interleukin 1 beta, interleukin 6, tumor necrosis factor alpha, triglycerides, and NEFA were decreased. Fatty acid synthesis was decreased by DHA supplementation, whereas the activities of lipoprotein lipase, hepatic lipase, and total lipase were increased. Dietary DHA supplementation led to upregulation of the expression of AMPK/SIRT1 signaling pathway‐related genes, whereas that of inflammatory factor‐related genes were downregulated. In conclusion, dietary inclusion of 80 mg/kg DHA can alleviate IUGR‐induced impairments in piglets.
Effect of probiotics during vonoprazan‐containing triple therapy on gut microbiota in Helicobacter pylori infection: A randomized controlled trial
Authors: Kakiuchi Toshihiko , Mizoe Akihiko , Yamamoto Kentaroh , Imamura Ichiro , Hashiguchi Kazutoshi , Kawakubo Hiroharu , Yamaguchi Daisuke , Fujioka Yasuhiko , Nakayama Aiko , Okuda Masumi , Matsuo Muneaki 
Published: March 2020

AbstractBackgroundProbiotics are beneficial to patients with Helicobacter pylori infections by modulating the gut microbiota. Biofermin‐R (BFR) is a multiple antibiotic‐resistant lactic acid bacteria preparation of Enterococcus faecium 129 BIO 3B‐R and is effective in normalizing the gut microbiota when used in combination with antibiotics. This study aimed to determine the effect of BFR in combination with vonoprazan (VPZ)‐based therapy on gut microbiota.MethodsPatients with positive urinary anti‐H pylori antibody test (primary test) and fecal H pylori antigen test (secondary test) were examined. Patients in group 1 (BFR−) received VPZ (20 mg twice daily), amoxicillin (750 mg twice daily), and clarithromycin (400 mg twice daily) for 7 days. Patients in group 2 (BFR+) received BFR (3 tablets/day) for 7 days, in addition to the aforementioned treatments. Following treatment, the relative abundance, α‐diversity, and β‐diversity of gut microbiota were assessed.ResultsSupplementation with BFR prevented the decrease in a‐diversity after eradication therapy (Day 7). β‐diversity was similar between groups. The incidence rate of diarrhea was non‐significantly higher in the BFR− than in the BFR+ group (73.1% vs 56.5%; P = .361). Stool consistency was comparable in the BFR+ group on Days 7 and 1 (3.86 ± 0.95 vs 3.86 ± 1.46; P = .415).ConclusionBiofermin‐R combined with VPZ‐based therapy resulted in higher microbial α‐strain diversity and suppressed stool softening during H pylori eradication therapy.
Rethinking student participation in the college classroom: Can commitment and self‐affirmation enhance oral participation?
Authors: Sereno Ken , Walter Nathan , Brooks John J. 
Published: March 2020

AbstractThe literature suggests that in‐class oral participation is associated with various positive outcomes that directly contribute to academic success. The goal of the current study was to investigate the role played by psychological barriers to oral participation, focusing on commitment and self‐affirmation as methods to bypass barriers to participation. The results of the semester‐long experiment (N = 157) demonstrate that committed individuals who had an opportunity to self‐affirm outperformed both committed students and affirmed students, as well as members of the control group. Interestingly, the interplay between self‐affirmation and commitment increased oral participation, irrespective of whether students had high or low self‐esteem and high or low self‐efficacy. The current results offer some room for cautious optimism, as they highlight the importance of self‐affirmation and commitment as a route to academic success.
Effectiveness of a guided online mindfulness-focused intervention in a student population: Study protocol for a randomised control trial
Authors: Schultchen Dana , Küchler Ann-Marie , Schillings Christine , Weineck Felicitas , Karabatsiakis Alexander , Ebert David D. , Baumeister Harald , Pollatos Olga 
Published: March 2020

BackgroundPrevious studies show that university students experience higher psychological stress than the general population, resulting in increased vulnerability for mental disorders for the student population. Online mindfulness interventions will be delivered to students as a potentially promising and more flexible approach compared to face-to-face interventions with the aim of improving their mental health. This study purposes to investigate the effectiveness of a guided online mindfulness-focused intervention for university students by using both self-reported and psychobiological measures.Methods and analysesIn this multicentre, two-armed randomised controlled trial with a parallel design, a guided version of the online mindfulness-focused intervention ‘StudiCare Mindfulness’ will be compared with a waitlist control group. In total, 120 participants will be recruited at different universities (of Applied Sciences) in (Neu-) Ulm. Data will be assessed prior to randomisation, after eight weeks (post-intervention) and six months after randomisation (follow-up). The primary outcome measure is mindfulness. The secondary outcome measures include depression, anxiety and stress levels, well-being, interoceptive sensibility, emotion regulation and alexithymia. Psychobiological parameters comprise interoceptive accuracy, hair cortisol and FKBP5 genotype. Sociodemographic variables, treatment expectations, side and adverse side effects, as well as intervention satisfaction and adherence will be assessed. All data analyses will be conducted according to the intention-to-treat principle.Ethics and disseminationAll study procedures have been approved by the Ethics Committee of Ulm University (application No. 48/18). The findings will be disseminated widely through peer-reviewed publications and conference presentations.Trial registration numberDRKS00014701.
Discontinuation of nucleos(t)ide analogues is not associated with a higher risk of HBsAg seroreversion after antiviral-induced HBsAg seroclearance: a nationwide multicentre study
Authors: Kim Minseok Albert , Kim Seung Up , Sinn Dong Hyun , Jang Jeong Won , Lim Young-Suk , Ahn Sang Hoon , Shim Jae-Jun , Seo Yeon Seok , Baek Yang Hyun , Kim Sang Gyune , Kim Young Seok , Kim Ji Hoon , Choe Won Hyeok , Yim Hyung Joon , Lee Hyun Woong , Kwon Jung Hyun , Lee Sung Won , Jang Jae Young , Kim Hwi Young , Park Yewan , Kim Gi-Ae , Yang Hyun , Lee Han Ah , Koh Myeongseok , Lee Young-Sun , Kim Minkoo , Chang Young , Kim Yoon Jun , Yoon Jung-Hwan , Zoulim Fabien , Lee Jeong-Hoon 
Published: March 2020

ObjectiveDirect comparison of the clinical outcomes between nucleos(t)ide analogue (NA) discontinuation versus NA continuation has not been performed in patients with chronic hepatitis B who achieved HBsAg-seroclearance. Whether NA discontinuation was as safe as NA continuation after NA-induced surface antigen of HBV (HBsAg) seroclearance was investigated in the present study.DesignsThis multicentre study included 276 patients from 16 hospitals in Korea who achieved NA-induced HBsAg seroclearance: 131 (47.5%) discontinued NA treatment within 6 months after HBsAg seroclearance (NA discontinuation group) and 145 (52.5%) continued NA treatment (NA continuation group). Primary endpoint was HBsAg reversion and secondary endpoints included serum HBV DNA redetection and development of hepatocellular carcinoma (HCC).ResultsDuring follow-up (median=26.9 months, IQR=12.2–49.2 months), 10 patients (3.6%) experienced HBsAg reversion, 6 (2.2%) showed HBV DNA redetection and 8 (2.9%) developed HCC. Compared with NA continuation, NA discontinuation was not associated with HBsAg reversion in both univariable (HR=0.45, 95% CI=0.12 to 1.76, log-rank p=0.24) and multivariable analyses (adjusted HR=0.65, 95% CI=0.16 to 2.59, p=0.54). The cumulative probabilities of HBsAg reversion at 1, 3 and 5 years were 0.8%, 2.3% and 5.0% in the NA discontinuation group, and 1.5%, 6.3% and 8.4% in the NA continuation group, respectively. NA discontinuation was not associated with higher risk of either HBV redetection (HR=0.83, 95% CI=0.16 to 4.16, log-rank p=0.82) or HCC development (HR=0.53, 95% CI=0.12 to 2.23, log-rank p=0.38).ConclusionThe discontinuation of NA was not associated with a higher risk of either HBsAg reversion, serum HBV DNA redetection or HCC development compared with NA continuation among patients who achieved HBsAg seroclearance with NA.