Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation and function of actin nucleators Dia and FMNL in the early Drosophila embryo

The formation of the subapical domain during cellularization in Drosophila embryogenesis is mediated by a pathway including the proteins Rap1, Canoe and their downstream effectors Bazooka and Armadillo. The cortical domain at the subapical position gives rise to the zonula adherens with adherens junctions after cellularization. The timing of the subapical domain formation remained unclear. It is possible that the introduction happens gradually with ongoing cellularization or that the domain is introduced at the beginning of cellularization. The localization of Bazooka leads to the first hypothesis as it gets enriched gradually at the subapical domain over the course of cellularization. However, I could show that Bazookas upstream factor Canoe localizes to the subapical domain already during early cellularization. Furthermore, I could show by live imaging with CanoeYFP and the basal marker CherrySlam, that the segregation of subapical and basal domains happens during the first minutes of cellularization. The upstream factor of Canoe Rap1 localizes to all cortical domains without an enrichment at the subapical domain and the factor activating the GTPase locally remained unclear. I could show that the unconventional Rap1 GEF ELMO-Sponge localizes to the subapical domain and that the formation of this domain is perturbed in ELMO and sponge mutants. This led to the hypothesis, that ELMO-Sponge locally activates Rap1 leading to the formation of the subapical domain. ELMO-Sponge both localize to actin caps before cellularization in a disc-like fashion, labeling the whole cap. This localization changes with onset of cellularization to a more ring-like pattern defining the position for the formation of the subapical domain. I further could show, that the introduction of the subapical domain depends on midblastula transition and with this onset of zygotic gene expression. In embryos in which zygotic gene expression was repressed by injection of the drug α-amanitin, cellularization was blocked and subapical Canoe localization was lost.
Diagnostic performance of congestion score index evaluated from chest radiography for acute heart failure in the emergency department: A retrospective analysis from the PARADISE cohort

Background Congestion score index (CSI), a semiquantitative evaluation of congestion on chest radiography (CXR), is associated with outcome in patients with heart failure (HF). However, its diagnostic value in patients admitted for acute dyspnea has yet to be evaluated. Methods and findings The diagnostic value of CSI for acute HF (AHF; adjudicated from patients’ discharge files) was studied in the Pathway of dyspneic patients in Emergency (PARADISE) cohort, including patients aged 18 years or older admitted for acute dyspnea in the emergency department (ED) of the Nancy University Hospital (France) between January 1, 2015 and December 31, 2015. CSI (ranging from 0 to 3) was evaluated using a semiquantitative method on CXR in consecutive patients admitted for acute dyspnea in the ED. Results were validated in independent cohorts (N = 224). Of 1,333 patients, mean (standard deviation [SD]) age was 72.0 (18.5) years, 686 (51.5%) were men, and mean (SD) CSI was 1.42 (0.79). Patients with higher CSI had more cardiovascular comorbidities, more severe congestion, higher b-type natriuretic peptide (BNP), poorer renal function, and more respiratory acidosis. AHF was diagnosed in 289 (21.7%) patients. CSI was significantly associated with AHF diagnosis (adjusted odds ratio [OR] for 0.1 unit CSI increase 1.19, 95% CI 1.16–1.22, p < 0.001) after adjustment for clinical-based diagnostic score including age, comorbidity burden, dyspnea, and clinical congestion. The diagnostic accuracy of CSI for AHF was >0.80, whether alone (area under the receiver operating characteristic curve [AUROC] 0.84, 95% CI 0.82–0.86) or in addition to the clinical model (AUROC 0.87, 95% CI 0.85–0.90). CSI improved diagnostic accuracy on top of clinical variables (net reclassification improvement [NRI] = 94.9%) and clinical variables plus BNP (NRI = 55.0%). Similar diagnostic accuracy was observed in the validation cohorts (AUROC 0.75, 95% CI 0.68–0.82). The key limitation of our derivation cohort was its single-center and retrospective nature, which was counterbalanced by the validation in the independent cohorts. Conclusions In this study, we observed that a systematic semiquantified assessment of radiographic pulmonary congestion showed high diagnostic value for AHF in dyspneic patients. Better use of CXR may provide an inexpensive, widely, and readily available method for AHF triage in the ED.
Posterior medial frontal cortex and threat-enhanced religious belief: a replication and extension

Abstract Research indicates that the posterior medial frontal cortex (pMFC) functions as a ‘neural alarm’ complex broadly involved in registering threats and helping to muster relevant responses. Holbrook and colleagues investigated whether pMFC similarly mediates ideological threat responses, finding that downregulating pMFC via transcranial magnetic stimulation (TMS) caused (i) less avowed religious belief despite being reminded of death and (ii) less group bias despite encountering a sharp critique of the national in-group. While suggestive, these findings were limited by the absence of a non-threat comparison condition and reliance on sham rather than control TMS. Here, in a pre-registered replication and extension, we downregulated pMFC or a control region (MT/V5) and then primed participants with either a reminder of death or a threat-neutral topic. As mentioned previously, participants reminded of death reported less religious belief when pMFC was downregulated. No such effect of pMFC downregulation was observed in the neutral condition, consistent with construing pMFC as monitoring for salient threats (e.g. death) and helping to recruit ideological responses (e.g. enhanced religious belief). However, no effect of downregulating pMFC on group bias was observed, possibly due to reliance on a collegiate in-group framing rather than a national framing as in the prior study.
Combining transcriptomic and fitness data reveals adaptive and additive plastic responses of gene expression to multiple stressors in Tribolium castaneum

Gene expression is known to be highly responsive to the environment and important for adjustment of metabolism but there is also growing evidence that differences in gene regulation contribute to species divergence and differences among locally adapted populations. However, most studies so far investigated populations when divergence already occurred. Not much is known about the evolutionary processes acting on expression levels when populations first encounter environmental change. Understanding the mechanisms is further complicated by the fact that environmental change is often multivariate, meaning that organisms are exposed to multiple stressors simultaneously, with interactive effects, which can constrain adaptation when multiple responses cannot be optimized at the same time. Here we use a novel approach by combining fitness and whole-transcriptome data in a large-scale experiment to investigate responses to drought, heat and their combination in Tribolium castaneum. We found that fitness was reduced by both stressors and their combined effect was almost additive. Expression data showed that both stressors were acting independently and did not interfere physiologically. Since we measured expression and fitness within the same individuals, we were able to estimate selection on single gene expression levels. We found that variation in fitness can be attributed to gene expression variation and that dependent on the environment different selection pressures are acting, which were opposite between control and stress conditions. We could further show that plastic responses of expression are largely adaptive, meaning they changed in the direction that should increase fitness.
Circulating whole genome miRNA expression corresponds to progressive right ventricle enlargement and systolic dysfunction in adults with tetralogy of Fallot

Introduction The adult congenital heart disease population with repaired tetralogy of Fallot (TOF) is subject to chronic volume and pressure loading leading to a 40% probability of right ventricular (RV) failure by the 3rd decade of life. We sought to identify a non-invasive signature of adverse RV remodeling using peripheral blood microRNA (miRNA) profiling to better understand the mechanisms of RV failure. Methods Demographic, clinical data, and blood samples were collected from adults with repaired TOF (N = 20). RNA was isolated from the buffy coat of peripheral blood and whole genome miRNA expression was profiled using Agilent’s global miRNA microarray platform. Fold change, pathway analysis, and unbiased hierarchical clustering of miRNA expression was performed and correlated to RV size and function assessed by echocardiography performed at or near the time of blood collection. Results MiRNA expression was profiled in the following groups: 1. normal RV size (N = 4), 2. mild/moderate RV enlargement (N = 11) and 3. severe RV enlargement (N = 5). 267 miRNAs were downregulated, and 66 were upregulated across the three groups (fold change >2.0, FDR corrected p<0.05) as RV enlargement increased and systolic function decreased. qPCR validation of a subset of these miRNAs identified increasing expression of miRNA 28-3p, 433-3p, and 371b-3p to be associated with increasing RV size and decreasing RV systolic function. Unbiased hierarchical clustering of all patients based on miRNA expression demonstrates three distinct patient clusters that largely coincide with progressive RV enlargement. Pathway analysis of dysregulated miRNAs demonstrates up and downregulation of cell cycle pathways, extracellular matrix proteins and fatty acid synthesis. HIF 1α signaling was downregulated while p53 signaling was predicted to be upregulated. Conclusion Adults with TOF have a distinct miRNA profile with progressive RV enlargement and dysfunction implicating cell cycle dysregulation and upregulation in extracellular matrix and fatty acid metabolism. These data suggest peripheral blood miRNA can provide insight into the mechanisms of RV failure and can potentially be used for monitoring disease progression and to develop RV specific therapeutics to prevent RV failure in TOF.
Hypomethylation of GDNF family receptor alpha 1 promotes epithelial-mesenchymal transition and predicts metastasis of colorectal cancer

Tumor metastasis is the major cause of poor prognosis and mortality in colorectal cancer (CRC). However, early diagnosis of highly metastatic CRC is currently difficult. In the present study, we screened for a novel biomarker, GDNF family receptor alpha 1 (GFRA1) based on the expression and methylation data in CRC patients from The Cancer Genome Altlas (TCGA), followed by further analysis of the correlation between the GFRA1 expression, methylation, and prognosis of patients. Our results show DNA hypomethylation-mediated upregulation of GFRA1 in invasive CRC, and it was found to be correlated with poor prognosis of CRC patients. Furthermore, GFRA1 methylation-modified sequences were found to have potential as methylation diagnostic markers of highly metastatic CRC. The targeted demethylation of GFRA1 by dCas9-TET1CD and gRNA promoted CRC metastasis in vivo and in vitro. Mechanistically, demethylation of GFRA1 induces epithelial-mesenchymal transition (EMT) by promoting AKT phosphorylation and increasing c-Jun expression in CRC cells. Collectively, our findings indicate that GFRA1 hypomethylation can promote CRC invasion via inducing EMT, and thus, GFRA1 methylation can be used as a biomarker for the early diagnosis of highly metastasis CRC.
Transitions from One Electronic Health Record to Another: Challenges, Pitfalls, and Recommendations

Abstract Objective We address the challenges of transitioning from one electronic health record (EHR) to another—a near ubiquitous phenomenon in health care. We offer mitigating strategies to reduce unintended consequences, maximize patient safety, and enhance health care delivery. Methods We searched PubMed and other sources to identify articles describing EHR-to-EHR transitions. We combined these references with the authors' extensive experience to construct a conceptual schema and to offer recommendations to facilitate transitions. Results Our PubMed query retrieved 1,351 citations: 43 were relevant for full paper review and 18 met the inclusion criterion of focus on EHR-to-EHR transitions. An additional PubMed search yielded 1,014 citations, for which we reviewed 74 full papers and included 5. We supplemented with additional citations for a total of 70 cited. We distinguished 10 domains in the literature that overlap yet present unique and salient opportunities for successful transitions and for problem mitigation. Discussion There is scant literature concerning EHR-to-EHR transitions. Identified challenges include financial burdens, personnel resources, patient safety threats from limited access to legacy records, data integrity during migration, cybersecurity, and semantic interoperability. Transition teams must overcome inadequate human infrastructure, technical challenges, security gaps, unrealistic providers' expectations, workflow changes, and insufficient training and support—all factors affecting potential clinician burnout. Conclusion EHR transitions are remarkably expensive, laborious, personnel devouring, and time consuming. The paucity of references in comparison to the topic's salience reinforces the necessity for this type of review and analysis. Prudent planning may streamline EHR transitions and reduce expenses. Mitigating strategies, such as preservation of legacy data, managing expectations, and hiring short-term specialty consultants can overcome some of the greatest hurdles. A new medical subject headings (MeSH) term for EHR transitions would facilitate further research on this topic.
Putative Involvement of Endocrine Disruptors in the Alzheimer's Disease Via the Insulin-Regulated Aminopeptidase/GLUT4 Pathway

It has been well established that there is a connection between type II diabetes (DMTII) and Alzheimer's disease (AD). In fact, the increase in AD incidence may be an emerging complication of DMTII. Both pathologies are related to estradiol (E2) exposure; on the one hand, estrogen receptors (ER) are emerging as important modulators of glucose homeostasis through ß-pancreatic cell function; on the other hand, brain bioenergetic and cognitive deficits have been related to the down regulation of brain ERs, contributing to women ageing and AD susceptibility, both related to the reduction in estradiol levels and the deficits in brain metabolism. Here we discuss that environmental contaminants with estrogenic capacity such as bisphenol A (BPA) could develop pharmacological effects similar to those of E2, which could affect ß-pancreatic cell function by increasing the biosynthesis of glucose-induced insulin after extranuclear ER binding. BPA-induced hyperinsulinemia would promote the translocation of glucose transporter 4 (GLUT4), which is located next to insulin-regulated aminopeptidase (IRAP) in intracellular vesicles. In insulin-responsive tissues, IRAP and GLUT 4 are routed together to the cell surface after insulin stimulation. IRAP is also the angiotensin IV (AngIV) receptor, and AngIV associates the brain renin-angiotensin system (bRAS) with AD, since AngIV is related to learning, memory, emotional responses, and processing of sensory information not only through its inhibitory effect on IRAP but also through the stimulation of glucose uptake by increasing the presence of IRAP/GLUT4 at the cell surface. Thus, the IRAP/GLUT4 pathway is an emerging target for pharmacological intervention against AD.
Primer and Historical Review on Rapid Cardiac CINE MRI

Acceleration is an important consideration when imaging moving organs such as the heart. Not only does acceleration enable motion‐free scans but, more importantly, it lies at the heart of capturing the dynamics of cardiac motion. For over three decades, various ingenious approaches have been devised and implemented for rapid CINE MRI suitable for dynamic cardiac imaging. Virtually all techniques relied on acquiring less data to reduce acquisition times. Parallel imaging was among the first of these innovations, using multiple receiver coils and mathematical algorithms for reconstruction; acceleration factors of 2 to 3 were readily achieved in clinical practice. However, in the context of imaging dynamic events, further decreases in scan time beyond those provided by parallel imaging were possible by exploiting temporal coherencies. This recognition ushered in the era of k‐t accelerated MRI, which utilized predominantly statistical methods for image reconstruction from highly undersampled k‐space. Despite the successes of k‐t acceleration methods, however, the accuracy of reconstruction was not always guaranteed. To address this gap, MR physicists and mathematicians applied compressed sensing theory to ensure reconstruction accuracy. Reconstruction was, indeed, more robust, but it required optimizing regularization parameters and long reconstruction times. To solve the limitations of all previous methods, researchers have turned to artificial intelligence and deep neural networks for the better part of the past decade, with recent results showing rapid, robust reconstruction. This review provides a comprehensive overview of key developments in the history of CINE MRI acceleration, and offers a unique and intuitive explanation behind the techniques and underlying mathematics.Level of Evidence: 5Technical Efficacy Stage: 1
Training using a simulation-based workshop reduces inaccuracies in estimations of testicular volume

Abstract Objectives Measuring testicular volume (TV) by orchidometer is routine in the clinic when staging male puberty. We have developed a simulation model for TV estimation and investigated whether training medical students, using a workshop with simulation models, could improve the accuracy and reliability of TV estimation. Methods All participating medical students watched a video representing standard undergraduate training in male pubertal assessment. Volunteers were then randomised directly to assessment or to attend a workshop consisting of a further video and four stations contextualising and practising the skills required for TV estimation, prior to assessment. Three child mannequins displaying testes of 3 mL, 4 mL (twice), 5, 10 and 20 mL were used for assessment. Participants were asked to return a fortnight later for repeat assessment to assess intra-observer reliability, the effect of repeated examinations on accuracy and time on skill retention. Results Ninety students participated (55F), 46 attended the workshop and were considered “trained”. There was no difference between the groups in numbers of correct estimations (29% trained, 27% untrained, p=0.593). However, the trained group’s estimations were closer to the true volume, with more from the trained group one bead away (p=0.002) and fewer more than three beads away from the true volume (p<0.001), compared to the untrained group. Trained participants were more accurate at the second assessment (n=80) (p<0.001) and had greater intra-observer reliability (p=0.004). Conclusions Overall TV estimation accuracy was poor. Workshop-style training improved accuracy, reliability and retention of skill acquisition and could be considered as a useful learning tool.
Molecular characterization of canine astrovirus, vesivirus and circovirus, isolated from diarrheic dogs in Turkey.

Background Canine astrovirus (CAstV) has been considered the primary cause of gastroenteritis in young animals worldwide, while canine vesivirus (CVeV) and canine circovirus (CCiV) are occasionally reported. Aims This study aimed to investigate the existence and molecular characteristics for these three viruses in Turkey. Methods: Faecal samples from 150 shelter dogs with gastrointestinal problems (127 adults and 23 puppies) were collected and examined by reverse transcription-polymerase chain reaction (RT-PCR) analysis based on the partial sequence of RdRp gene (ORF1b) for CAstV, ORF2 gene of CVeV and capsid protein (Cap) and replication associated protein (Rep) gene of CCiV. Randomly selected positive samples were submitted to sequencing and molecular analyses were conducted based on partial sequences. Results It was found that 66% (99/150) of diarrhoeic dogs were positive for CAstV, 3.33% (5/150) for CVeV, and 6% (9/150) for CCiV. Four sub-genotypes for CAstV and two sub-genotypes for CVeV were suggested according to molecular analyses. The phylogenetic relationship of CCiV with other strains obtained from various areas was further demonstrated. Conclusion This study emphasizes the importance of emerging viruses for canids, classification of them and their proportional contribution in gastroenteritis cases. We concluded that astrovirus infection must be considered as the major cause of diarrhea in dogs; However, the prevalences of vesivirus and circovirus were relatively low in cases makes them less important in Turkey.
Experimental investigation of vacuum ultraviolet emissions in microwave argon plasmas: dependence on microwave power and discharge pressure

Vacuum ultraviolet emission from argon wave driven microwave (2.45GHz) plasmas operating at low pressures (0.2 – 1 mbar) has been investigated. The emitted spectra show the presence of argon atomic and ionic lines in the range 80 – 110 nm. The relative emission intensities of excited Ar atoms (at 104.8 nm and 106.6 nm) and ions (at 92.0 nm and 93.2 nm) were investigated as a function of the microwave power and pressure of the discharge. Both atomic and ionic emission lines increased linearly in intensity as the power was raised. Concerning the dependence on pressure, experimental results show that atomic and ionic lines decreased linearly in intensity as the pressure was increased. The plasma electron density was estimated to be in the order of 10 cm.
An experimental comparison of Value at Risk estimates based on elliptical and hierarchical Archimedean copulas

In this paper, we estimate Value at Risk for a selected portfolio using elliptical and hierarchical Archimedean copulas, where the latter is based on a recent approach to estimation of hierarchical Archimedean copulas based on the Kendall correlation matrix. The estimates are compared using the Kupiec's test for three periods of time: a period of significant movements of index prices, a period of relative calm in the stock market and a long term period which includes the both situation in the stock market. Our experimental results show that the estimates based on elliptical copulas are more accurate in the periods of relative calm in the stock market, whereas the estimates based on hierarchical Archimedean copulas are more accurate in the period of significant movements in the stock market.
Palm Vein Recognition Based on Centerline

The palm vein recognition is one of the biometric systems that use for identification and verification processes since each person have unique characteristics for the veins. In this paper we can improvement palm vein recognition system have been made. The system based on centerline extraction of veins, and employs the concept of Difference-of Gaussian (DoG) Function to construct features vector. The tests results on our database showed that the identification rate is 100 % with the minimum error rate was 0.333.