Miracle-dz/UniFAR-FTUs huggingface dataset:
What drives phenotypic divergence among coral clonemates of Acropora palmata?

Evolutionary rescue of populations depends on their ability to produce phenotypic variation that is heritable and adaptive. DNA mutations are the best understood mechanisms to create phenotypic variation, but other, less well‐studied mechanisms exist. Marine benthic foundation species provide opportunities to study these mechanisms because many are dominated by isogenic stands produced through asexual reproduction. For example, Caribbean acroporid corals are long lived and reproduce asexually via breakage of branches. Fragmentation is often the dominant mode of local population maintenance. Thus, large genets with many ramets (colonies) are common. Here, we observed phenotypic variation in stress responses within genets following the coral bleaching events in 2014 and 2015 caused by high water temperatures. This was not due to genetic variation in their symbiotic dinoflagellates (Symbiodinium “fitti”) because each genet of this coral species typically harbours a single strain of S. “fitti”. Characterization of the microbiome via 16S tag sequencing correlated the abundance of only two microbiome members (Tepidiphilus, Endozoicomonas) with a bleaching response. Epigenetic changes were significantly correlated with the host's genetic background, the location of the sampled polyps within the colonies (e.g., branch vs. base of colony), and differences in the colonies’ condition during the bleaching event. We conclude that long‐term microenvironmental differences led to changes in the way the ramets methylated their genomes, contributing to the differential bleaching response. However, most of the variation in differential bleaching response among clonemates of Acropora palmata remains unexplained. This research provides novel data and hypotheses to help understand intragenet variability in stress phenotypes of sessile marine species.
Compositional Analysis of Genetically Engineered GR2E “Golden Rice” in Comparison to That of Conventional Rice

Compositional analyses were performed on samples of rice grain, straw, and derived bran obtained from golden rice event GR2E and near-isogenic control PSBRc82 rice grown at four locations in the Philippines during 2015 and 2016. Grain samples were analyzed for key nutritional components, including proximates, fiber, polysaccharides, fatty acids, amino acids, minerals, vitamins, and antinutrients. Samples of straw and bran were analyzed for proximates and minerals. The only biologically meaningful difference between GR2E and control rice was in levels of β-carotene and other provitamin A carotenoids in the grain. Except for β-carotene and related carotenoids, the compositional parameters of GR2E rice were within the range of natural variability of those components in conventional rice varieties with a history of safe consumption. Mean provitamin A concentrations in milled rice of GR2E can contribute up to 89–113% and 57–99% of the estimated average requirement for vitamin A for preschool children in Bangladesh and the Philippines, respectively.
Suppressed immune microenvironment and repertoire in brain metastases from patients with resected non-small cell lung cancer.

BACKGROUND The tumor immune microenvironment (TIME) of lung cancer brain metastasis is largely unexplored. We performed immune profiling and sequencing analysis of paired resected primary tumors and brain metastases of non-small cell lung carcinoma (NSCLC). PATIENTS AND METHODS TIME profiling of archival formalin-fixed and paraffin embedded specimens of paired primary tumors and brain metastases from 39 patients with surgically resected NSCLCs was performed using a 770 immune gene expression panel and by T cell receptor beta repertoire (TCRß) sequencing. Immunohistochemistry was performed for validation. Targeted sequencing was performed to catalog hot spot mutations in cancer genes. RESULTS Somatic hot spot mutations were mostly shared between both tumor sites (28/39 patients; 71%). We identified 161 differentially expressed genes, indicating inhibition of dendritic cell maturation, Th1, and leukocyte extravasation signaling pathways, in brain metastases compared to primary tumors (p < 0.01). The proinflammatory cell adhesion molecule vascular cell adhesion protein 1 was significantly suppressed in brain metastases compared to primary tumors. Brain metastases exhibited lower T cell and elevated macrophage infiltration compared with primary tumors (p < 0.001). T cell clones were expanded in 64% of brain metastases compared with their corresponding primary tumors. Further, while TCR repertoires were largely shared between paired brain metastases and primary tumors, T cell densities were sparse in the metastases. CONCLUSION We present findings that suggest that the TIME in brain metastases from NSCLC is immunosuppressed and comprises immune phenotypes (e.g. immunosuppressive tumor-associated macrophages) that may help guide immunotherapeutic strategies for NSCLC brain metastases.
When is irony influenced by communicative constraints? ERP evidence supporting interactive models

Distinct theoretical proposals have described how communicative constraints (contextual biases, speaker identity) impact verbal irony processing. Modular models assume that social and contextual factors have an effect at a late stage of processing. Interactive models claim that contextual biases are considered early on. The constraint‐satisfaction model further assumes that speaker's and context's characteristics can compete at early stages of analysis. The present ERP study teased apart these models by testing the impact of context and speaker features (i.e., speaker accent) on irony analysis. Spanish native speakers were presented with Spanish utterances that were ironic or literal. Each sentence was preceded by a negative or a positive context. Each story was uttered in a native or a foreign accent. Results showed that contextual biases and speaker accent interacted as early as 150 ms during irony processing. Greater N400‐like effects were reported for ironic than literal sentences only with positive contexts and native accent, possibly suggesting semantic difficulties when non‐prototypical irony was produced by natives. A P600 effect of irony was also reported indicating inferential processing costs. The results support the constraint‐satisfaction model and suggest that multiple sources of information are weighted and can interact from the earliest stages of irony analysis.
Automated Flow Cytometric MRD Assessment in Childhood Acute B‐ Lymphoblastic Leukemia Using Supervised Machine Learning

Minimal residual disease (MRD) as measured by multiparameter flow cytometry (FCM) is an independent and strong prognostic factor in B‐cell acute lymphoblastic leukemia (B‐ALL). However, reliable flow cytometric detection of MRD strongly depends on operator skills and expert knowledge. Hence, an objective, automated tool for reliable FCM‐MRD quantification, able to overcome the technical diversity and analytical subjectivity, would be most helpful. We developed a supervised machine learning approach using a combination of multiple Gaussian Mixture Models (GMM) as a parametric density model. The approach was used for finding the weights of a linear combination of multiple GMMs to represent new, “unseen” samples by an interpolation of stored samples. The experimental data set contained FCM‐MRD data of 337 bone marrow samples collected at day 15 of induction therapy in three different laboratories from pediatric patients with B‐ALL for which accurate, expert‐set gates existed. We compared MRD quantification by our proposed GMM approach to operator assessments, its performance on data from different laboratories, as well as to other state‐of‐the‐art automated read‐out methods. Our proposed GMM‐combination approach proved superior over support vector machines, deep neural networks, and a single GMM approach in terms of precision and average F 1‐scores. A high correlation of expert operator‐based and automated MRD assessment was achieved with reliable automated MRD quantification (F 1‐scores >0.5 in more than 95% of samples) in the clinically relevant range. Although best performance was found, if test and training samples were from the same system (i.e., flow cytometer and staining panel; lowest median F 1‐score 0.92), cross‐system performance remained high with a median F 1‐score above 0.85 in all settings. In conclusion, our proposed automated approach could potentially be used to assess FCM‐MRD in B‐ALL in an objective and standardized manner across different laboratories. © 2019 International Society for Advancement of Cytometry
Allowing failure for educational purposes in postgraduate clinical training: A narrative review

Abstract Background: Educational domains such as pedagogy or psychology have embraced the philosophy that “allowing failure” in training and practice is essential to learn. In clinical training, however, allowing learners to fail is not explicitly discussed as a strategy, possibly due to the negative implications for patients. Therefore, we do not know whether clinical supervisors allow trainees to fail for educational purposes and, if so, how this supervisory strategy is used. Methods: To inform research on this topic, we conducted a narrative review to understand what was known about this educational strategy in postgraduate medicine. Results: Analyzing the selected literature, we found no studies directly exploring the question of clinical supervisors allowing failure as an educational strategy. However, related literature on resident errors suggested that trainees perceived their own errors to be highly instructive and that factors such as a sense of responsibility and emotional response influenced the educational impact of these errors. Conclusions: The lack of discussion in the medical education literature regarding allowing failure for learning suggests that we need research into the nature and extent of this supervisory strategy which may hold educational benefits but must be employed in a manner that upholds patient safety and safeguards trainee resilience.
Meta‐analysis of genotype‐phenotype associations in Bardet‐Biedl syndrome uncovers differences among causative genes

Bardet‐Biedl syndrome (BBS) is a recessive genetic disease causing multiple organ anomalies. Most patients carry mutations in genes encoding for the subunits of the BBSome, an octameric ciliary transport complex, or accessory proteins involved in the BBSome assembly or function. BBS proteins have been extensively studied using in vitro, cellular, and animal models. However, the molecular functions of particular BBS proteins and the etiology of the BBS symptoms are still largely elusive. In this study, we applied a meta‐analysis approach to study the genotype‐phenotype association in humans using our database of all reported BBS patients. The analysis revealed that the identity of the causative gene and the character of the mutation partially predict the clinical outcome of the disease. Besides their potential use for clinical prognosis, our analysis revealed functional differences of particular BBS genes in humans. Core BBSome subunits BBS2, BBS7, and BBS9 manifest as more critical for the function and development of kidneys than peripheral subunits BBS1, BBS4, and BBS8/TTC8, suggesting that incomplete BBSome retains residual function at least in the kidney.
Z-palatopharyngoplasty combined with 70-degree endoscopy-assisted coblator partial medial glossectomy on severe obstructive sleep apnea

Abstract Background: Patients with severe obstructive sleep apnea (OSA) require safe and effective surgical treatment. Objectives: To evaluate the effectiveness of combined Z-palatopharyngoplasty (ZPPP) and partial glossectomy via 70-degree endoscopy-assisted coblation (Eco-TBR) on severe OSA. Materials and methods: Twenty-two consecutive patients with severe OSA were enrolled between September 2014 and July 2016. The lingual artery was evaluated by contrasted computed tomography (CT). Drug-induced sleep endoscopy (DISE) was performed to determine the necessity of multilevel surgery. Combined ZPPP and Eco-TBR were performed. Polysomnographic parameters were collected pre-operatively and 6 months post-operatively. Results: No adverse events were observed postoperatively. The short-term ( < 12 months) rate of total surgical effectiveness was 63.6% (14/22), with Friedman classifications as follows: I (1/1), Friedman II (6/10) and Friedman III (7/11). There were no differences between Friedman classification groups. The differences in AHI, apnea index (AI), mean blood oxygen, and percentage of cumulative time with oxygen saturation < 90% (CT 90%) were different compared to preoperative levels. Tonsil size was also significantly larger in the multi-level surgery group (2.14 ± 1.03) compared with the control group (1.13 ± 0.64). Conclusions and significance: Combined ZPPP and Eco-TB is safe and effective, with good surgical effectiveness for the treatment of severe OSA patients. Trial registration: Chinese Clinical Trial Registry identifier: ChiCTR-CCC-13003415.
Effect of SEGUE-based communication education on nursing simulation practice: a quasi-experimental design

Background: Effective educational approaches are required to enhance nursing students’ communication competency. Objectives: To evaluate the effectiveness of SEGUE (‘set the stage,’ ‘elicit information,’ ‘give information,’ ‘understand the patient's perspective,’ and ‘end the encounter’)-based communication education. Design: A non-equivalent control group pretest–posttest design. Methods: Students were randomized into the control group (n = 41) and experimental group (n = 57). Communication competency and efficacy were measured via a self-report questionnaire and via ratings of the students from professor and standardized patient. Results: Scores by students (self-evaluations; p < .001), professor (p < .001), and standardized patient (p < .042) showed higher communication competency in the experimental group. Compared with the control group, the pre–post difference in communication efficacy in the experimental group was increased (p = .004). Conclusions: Simulation practice to reflect the various clinical situation is recommended to improve students’ communication. Impact statement: SEGUE-based communication education in nursing simulation practice with the standardized patient was an effective strategy for improving nursing students’ communication.
TxtH is a key component of the thaxtomin biosynthetic machinery in the potato common scab pathogen Streptomyces scabies

Summary Streptomyces scabies causes potato common scab disease, which reduces the quality and market value of affected tubers. The predominant pathogenicity determinant produced by S. scabies is the thaxtomin A phytotoxin, which is essential for common scab disease development. Production of thaxtomin A involves the nonribosomal peptide synthetases (NRPSs) TxtA and TxtB, both of which contain an adenylation (A‐) domain for selecting and activating the appropriate amino acid during thaxtomin biosynthesis. The genome of S. scabies 87.22 contains three small MbtH‐like protein (MLP)‐coding genes, one of which (txtH) is present in the thaxtomin biosynthesis gene cluster. MLP family members are typically required for the proper folding of NRPS A‐domains and/or stimulating their activities. This study investigated the importance of TxtH during thaxtomin biosynthesis in S. scabies. Biochemical studies showed that TxtH is required for promoting the soluble expression of both the TxtA and TxtB A‐domains in Escherichia coli, and amino acid residues essential for this activity were identified. Deletion of txtH in S. scabies significantly reduced thaxtomin A production, and deletion of one of the two additional MLP homologues in S. scabies completely abolished production. Engineered expression of all three S. scabies MLPs could restore thaxtomin A production in a triple MLP‐deficient strain, while engineered expression of MLPs from other Streptomyces spp. could not. Furthermore, the constructed MLP mutants were reduced in virulence compared to wild‐type S. scabies. The results of our study confirm that TxtH plays a key role in thaxtomin A biosynthesis and plant pathogenicity in S. scabies.
Immunohistochemical Expression of CD133 and LGR5 in Ulcerative Colitis-associated Colorectal Cancer and Dysplasia

Background/Aim: Cluster of differentiation 133 (CD133) and leu cine-rich orphan G-protein-coupled receptor 5 (LGR5) are the most putative stem cell markers for colorectal cancer (CRC), and are associated with poor prognosis of patients with CRC. However, the role of CD133 and LGR5 in the inflammation–dysplasia–carcinoma sequence has not been fully elucidated. We examined the expression of CD133 and LGR5 in ulcerative colitis-associated CRC (UC-CRC; n=20) and UC-associated colorectal dysplasia (n=16) by immunohistochemistry. Results: The rate of CD133-positive cases in UC-CRC was significantly higher than that in dysplasia (p=0.026), but that of LGR5 expression was not. Moreover, LGR5 expression was significantly positively associated with p53 expression (p=0.03), whereas CD133 expression positively correlated with p53 expression, but not significantly (p=0.10). Conclusion: CD133 may play an important role in tumor development in the context of the inflammation–dysplasia–carcinoma sequence. LGR5-positive cancer stem cells may play a critical role in the development of UC-CRC, particularly upon loss of p53 function.
Single‐dose etoposide is an effective and safe protocol for stem cell mobilization in patients with multiple myeloma

Single‐dose etoposide was used an outpatient‐based protocol for mobilization in patients with multiple myeloma (MM) for autologous stem cell transplantation (ASCT). Thus, we retrospectively analyzed the efficacy and safety of our one‐day protocol in comparison with that of previous methods.
Collaborative Methods for Real-Time Localization in Urban Centers

This article presents an effective solution for the localization of a vehicle in dense urban areas where GNSS-based methods fail because of poor satellite visibility. It advocates the use of a visual-based method processing georeferenced landmarks obtained after a learning path and stored in a new layer of the geographical information system (GIS) used for navigation. Real-time localization gives, with few failures, accurate results in the areas covered by the GIS. The integrity of the localization is obtained by running another algorithm in parallel, processing odometric data combined with the geometric model of the drivable area and, when available, GNSS data in tight coupling. An ellipsoidal confidence domain is updated by using both extended Kalman filtering (EKF) and set-membership estimation. Although less accurate, this estimation is reliable and, when the visual method fails, the availability of a confidence domain enables us to speed up the restart of the visual method while navigating cautiously. A large-scale experiment (>4 km) was conducted in the centre of Paris. We compare the absolute localization results with the ground truth obtained by combining RTK-GPS and a high-end inertial measurement unit (IMU).
(Pro)renin receptor accelerates development of sarcopenia via activation of Wnt/YAP signaling axis

To extend life expectancy and ensure healthy aging, it is crucial to prevent and minimize age‐induced skeletal muscle atrophy, also known as sarcopenia. However, the disease's molecular mechanism remains unclear. The age‐related Wnt/β‐catenin signaling pathway has been recently shown to be activated by the (pro)renin receptor ((P)RR). We report here that (P)RR expression was increased in the atrophied skeletal muscles of aged mice and humans. Therefore, we developed a gain‐of‐function model of age‐related sarcopenia via transgenic expression of (P)RR under control of the CAG promoter. Consistent with our hypothesis, (P)RR‐Tg mice died early and exhibited muscle atrophy with histological features of sarcopenia. Moreover, Wnt/β‐catenin signaling was activated and the regenerative capacity of muscle progenitor cells after cardiotoxin injury was impaired due to cell fusion failure in (P)RR‐Tg mice. In vitro forced expression of (P)RR protein in C2C12 myoblast cells suppressed myotube formation by activating Wnt/β‐catenin signaling. Administration of Dickkopf‐related protein 1, an inhibitor of Wnt/β‐catenin signaling, and anti‐(P)RR neutralizing antibody, which inhibits binding of (P)RR to the Wnt receptor, significantly improved sarcopenia in (P)RR‐Tg mice. Furthermore, the use of anti‐(P)RR neutralizing antibodies significantly improved the regenerative ability of skeletal muscle in aged mice. Finally, we show that Yes‐associated protein (YAP) signaling, which is coordinately regulated by Wnt/β‐catenin, contributed to the development of (P)RR‐induced sarcopenia. The present study demonstrates the use of (P)RR‐Tg mice as a novel sarcopenia model, and shows that (P)RR‐Wnt‐YAP signaling plays a pivotal role in the pathogenesis of this disease.
Neutral Shadowing Force Effect on Structural Properties and Oscillations of Dust Particles in Cryogenic Environment

Recently, it was shown that the neutral shadowing interaction can be significantly stronger in the cryogenic complex plasma than in the plasma with neutrals at room temperature. Here, we present the results of the investigation—by molecular dynamics (MD) simulations—of the impact of the neutral shadowing interaction on the radial pair distribution function and the velocity autocorrelation function (VAF) of the charged dust particles in a 2-D layer. The spectrum of VAF was computed to estimate the influence of the neutral shadowing force on the oscillations of dust particles. We found that the neutral shadowing interaction can significantly affect the structural properties and the characteristic longitudinal oscillation frequency of dust particles if the characteristic radius of the neutral shadowing interaction exceeds a mean interdust particle distance. The latter case corresponds to low pressures, $p < 1$ Pa, and cryogenic temperatures less than 10 K. In addition, the dust acoustic wave taking into account that the neutral shadowing force was derived. It is found that the neutral shadowing force leads to the increase of the sound speed of the dust acoustic wave.
Web traffic modeling exploiting TCP connections' temporal clustering through HTML-REDUCE

This article presents a measurement analysis methodology that, starting from packet-level traces, identifies some statistics useful to characterize Web traffic, such as page size, page request frequency, and the user's think time between the download of pages. The methodology was implemented in a tool named HTML-REDUCE and applied on traces collected in CSELT's corporate network. For each identified statistic the analytic expression best approximating its empirical distribution is searched. A simplified model for bandwidth dimensioning in the server-to-client direction is then presented and validated through comparison with full protocol stack simulations. The model only requires the page request frequency of an aggregate of clients and the first two moments of page size distribution.