Miracle-dz/UniFAR-FTUs huggingface dataset:
Short- versus long-term Dual AntiPlatelet Therapy for Stent-Assisted treatment of CErebral aneurysm (DAPTS ACE): a multicenter, open-label, randomized clinical trial

Background The optimal duration of dual antiplatelet therapy (DAPT) after stent-assisted coil embolization (SACE) for cerebral aneurysm remains uncertain. This randomized trial of short- versus long-term Dual AntiPlatelet Therapy for Stent-Assisted treatment of CErebral aneurysm (DAPTS ACE) aimed to clarify whether long-term DAPT can reduce the occurrence of ischemic stroke in patients with cerebral aneurysms treated by SACE compared with short-term DAPT. Methods Patients treated for cerebral aneurysm with SACE were enrolled from 17 hospitals in Japan. Patients were enrolled within 30 days after SACE and assigned in a 1:1 ratio to receive long-term (12 months) or short-term (3 months) DAPT with aspirin and clopidogrel. Randomization was performed centrally through a web-based system. The primary outcome was the time to ischemic stroke event during 3 to 12 months after SACE. This trial was registered with the Japan Registry of Clinical Trials (jRCTs051180141). Results A total of 142 patients were recruited from November 4, 2016 to January 7, 2019. Among them, 65 and 68 patients assigned to the long- and short-term DAPT groups, respectively, were included in the full analysis set. Ischemic stroke occurred in no patients in the long-term DAPT group and in one patient in the short-term DAPT group. The incidence rate did not differ between the groups (0.0 vs 2.1/100 person-years; log rank test, P=0.33). Conclusions In this multicenter randomized controlled trial, there was not a statistically significant difference in the rate of ischemic strokes between long- and short-term DAPT.
Negotiating pre-service EFL teachers’ identity orientations through telecollaboration

ABSTRACT Purpose Telecollaboration has become a dynamic subfield of CALL studies with the increasing availability of multimodal platforms in language learning and teaching. Although current studies mostly have focused on bilingual and bicultural exchanges, affordances of multi-faceted teacher identity have not received considerable attention. To address this gap, 57 teacher candidates took part in an eight-week telecollaboration project with four instructors from European universities. Method Drawing on [Deardorff, D. K. 2006. “Identification and Assessment of Intercultural Competence as a Student Outcome of Internationalization. ” Journal of Studies in International Education 10 (3): 241–266. ] process orientation and [Bennett, M. J. 1993. “Towards Eethnorelativism: A Developmental Model of Iintercultural Sensitivity. ” In Education for the Intercultural Experience, edited by R. Michael Paige, 21–71. Yarmouth, ME: Intercultural Press] developmental models, teacher candidates’ identity negotiations were analysed through the data generated on (a)synchronous modes. Findings and Originality Findings suggest that dynamics resulting from multicultural and multilingual identity contribute to higher intercultural communicative competence, and teacher candidates’ intercultural development is manifested through their (a) intercultural adjustment, (b) culture-specific identity orientations, (c) gender socialisation and (d) culture and technology interplay. This study provides several implications for EFL practitioners to foster intercultural communicative competence in language classes and utilise telecollaboration as a valuable asset with concrete outcomes for upcoming studies.
Exploring How Workspace Awareness Cues Affect Distributed Meeting Outcome

Abstract Nowadays, using the online whiteboard to share knowledge in distributed meetings has become a common practice. Existing studies and practices have attempted to visualize attendees’ interactive activities in whiteboard tools to support the virtual team’s workspace awareness (WA). However, the impact of such visual cues on meeting success remains unclear. For this purpose, we primarily explore whether and to what extent WA cues are conducive to meeting outcome. This study applies activity theory to guide our prototype design and research analysis. A customized web-based whiteboard interface is implemented under two conditions. We conduct a study with 42 subjects in a distributed meeting scenario via a controlled experiment. Also, we analyze the system affordance via user experience. The results demonstrate that the benefits of WA cues to meeting outcome are especially embodied in goal attainment and quality of contributions, but not effectively supported in productivity and user satisfaction. Moreover, subjects report that they do not feel distracted by the system’s visual cues because they do not notice those cues most of the time and use them only when needed. Drawing upon findings from our trial work, we provide several implications for designing a collaborative knowledge-sharing environment to assist the visual support of WA in distributed meetings.
Disciplinary mobility and women’s empowerment: a complicated connection

Abstract The intersections between gender, mobility and power have been well established. While research has examined the inequity of (im)mobility, the role of restricted mobility as a form of domestic violence and the connection between freedom of movement and feminism, hardly any attention has been given to the relationship between physical mobility and women’s empowerment programming. By drawing on the literature on ‘disciplined’ mobility and feminist understandings of space and violence, this research argues that mobility and empowerment are complicatedly entwined. Through qualitative field research in West Bengal, India, this article illustrates that empowerment programming is limited in what it can achieve due to the disciplining of mobility. Women’s mobility is disciplined through patriarchal control, evident in three key domains: first, through actively restricting women’s mobility; second, through surveillance and monitoring; and third, through women self-regulating their own behaviour. Through showing the difficulty of improving women’s wellbeing via empowerment programs, this research illustrates the pervasive violence of disciplined mobility.
Optimal HLA imputation of admixed population with dimension reduction

Human genomics has quickly evolved, powering genome-wide association studies (GWASs). SNP-based GWASs cannot capture the intense polymorphism of HLA genes, highly associated with disease susceptibility. There are methods to statistically impute HLA genotypes from SNP-genotypes data, but lack of diversity in reference panels hinders their performance. We evaluated the accuracy of the 1,000 Genomes data as a reference panel for imputing HLA from admixed individuals of African and European ancestries, focusing on (a) the full dataset, (b) 10 replications from 6 populations, (c) 19 conditions for the custom reference panels. The full dataset outperformed smaller models, with a good F1-score of 0.66 for HLA-B. However, custom models outperformed the multiethnic or population models of similar size (F1-scores up to 0.53, against up to 0.42). We demonstrated the importance of using genetically specific models for imputing admixed populations, which are currently underrepresented in public datasets, opening the door to HLA imputation for every genetic population.
Identification of differentially recognized T cell epitopes in the spectrum of Mtb infection

Tuberculosis caused by Mycobacterium tuberculosis is one of the leading causes of death from a single infectious agent. Identifying dominant epitopes and comparing their reactivity in different tuberculosis (TB) infection states can help design diagnostics and vaccines. We performed a proteome-wide screen of 20,610 Mtb derived peptides in 21 Active TB (ATB) patients 3-4 months post-diagnosis of pulmonary TB (mid-treatment) using an IFNγ and IL-17 Fluorospot assay. Responses were mediated exclusively by IFNγ and identified a total of 137 unique epitopes, with each patient recognizing, on average, 8 individual epitopes and 22 epitopes (16%) recognized by 2 or more participants. Responses were predominantly directed against antigens part of the cell wall and cell processes category. Testing 517 peptides spanning TB vaccine candidates and ESAT- 6 and CFP10 antigens also revealed differential recognition between ATB participants mid-treatment and healthy IGRA+ participants of several vaccine antigens. An ATB-specific peptide pool consisting of epitopes exclusively recognized by participants mid-treatment, allowed distinguishing participants with active pulmonary TB from healthy interferon-gamma release assay (IGRA)+/- participants from diverse geographical locations. Analysis of longitudinal samples indicated decreased reactivity during treatment for pulmonary TB. Together, these results show that a proteome-wide screen of T cell reactivity identifies epitopes and antigens that are differentially recognized depending on the Mtb infection stage. These have potential use in developing diagnostics and vaccine candidates and measuring correlates of protection.
A maturation defective HIV-1 activates cGAS

Background Detection of viruses by host pattern recognition receptors induces the expression of type I interferon (IFN) and IFN-stimulated genes (ISGs), which suppress viral replication. Retroviruses such as HIV-1 are subject to sensing by both RNA and DNA sensors, and whether there are any particular features of the viral genome or reverse transcripts that facilitate or enhance this sensing is currently unknown. Results Whilst investigating the determinants of innate detection of HIV-1 we noticed that infection of THP-1 cells or primary macrophages with a virus expressing Gag fused to a reporter gene (luciferase or GFP) induced a robust IFN and ISG response that was not observed with an equivalent virus with similar genome length and composition, but expressing wild-type Gag. Innate immune activation by Gag-fusion HIV-1 was dependent on reverse transcription and DNA sensor cGAS, suggesting activation of an IFN response by viral DNA. Further investigation of the Gag-fusion viral particles revealed maturation defects, as evidenced by incomplete Gag cleavage and a diminished capacity to saturate restriction factor TRIM5α, likely due to aberrant particle formation. We propose that expression of the Gag fusion protein disturbs the correct cleavage and maturation of wild-type Gag, yielding viral particles that are unable to effectively shield viral DNA from detection by innate sensors including cGAS. Conclusions These data highlight the crucial role of capsid in innate evasion and support growing literature that disruption of Gag cleavage and capsid formation induces a viral DNA- and cGAS-dependent innate immune response. Together these data demonstrate a protective role for capsid and suggest that antiviral activity of capsid-targeting antivirals may benefit from enhanced innate and adaptive immunity in vivo.
Inverse Eigenvalue Problem with Non-simple Eigenvalues for Damped Vibration Systems ?

In this paper, we will present a general form of real and symmetric $n\times n$ matrices $M$, $C$ and $K$ for a quadratic inverse eigenvalue problem QIEP: $Q(\lambda) \equiv (\lambda^{2}M +\lambda C+K) x=0$, so that $Q(\lambda)$ has a prescribed set of $k$ eigenvalues with algebraic multiplicity $n_{i}$, $i=1,\cdots,k$ which $2n_{1}+2n_{2}+\cdots+2n_{l} +n_{l+1}+\cdots+n_{k}=2n)$. This paper generalizes the method of inverse problem for self-adjoint linear pencils, to self-adjoint quadratic pencils $Q(\lambda)$. It is shown that this inverse problem involves certain free parameters. Via appropriate choice of free variables in the general form of QIEP, we solve a QIEP.
MUSSEL: Enhanced Bayesian Polygenic Risk Prediction Leveraging Information across Multiple Ancestry Groups

Polygenic risk scores (PRS) are now showing promising predictive performance on a wide variety of complex traits and diseases, but there exists a substantial performance gap across different populations. We propose MUSSEL, a method for ancestry-specific polygenic prediction that borrows information in the summary statistics from genome-wide association studies (GWAS) across multiple ancestry groups. MUSSEL conducts Bayesian hierarchical modeling under a MUltivariate Spike-and-Slab model for effect-size distribution and incorporates an Ensemble Learning step using super learner to combine information across different tuning parameter settings and ancestry groups. In our simulation studies and data analyses of 16 traits across four distinct studies, totaling 5.7 million participants with a substantial ancestral diversity, MUSSEL shows promising performance compared to alternatives. The method, for example, has an average gain in prediction R2 across 11 continuous traits of 40.2% and 49.3% compared to PRS-CSx and CT-SLEB, respectively, in the African Ancestry population. The best-performing method, however, varies by GWAS sample size, target ancestry, underlying trait architecture, and the choice of reference samples for LD estimation, and thus ultimately, a combination of methods may be needed to generate the most robust PRS across diverse populations.
Zn2+ is essential for Ca2+ oscillations in mouse eggs

Changes in the intracellular concentration of free calcium (Ca2+) underpin egg activation and initiation of development in animals and plants. In mammals, the Ca2+ release is periodical, known as Ca2+ oscillations, and mediated by the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1). Another divalent cation, zinc (Zn2+), increases exponentially during oocyte maturation and is vital for meiotic transitions, arrests, and polyspermy prevention. It is unknown if these pivotal cations interplay during fertilization. Here, using mouse eggs, we showed that basal concentrations of labile Zn2+ are indispensable for sperm-initiated Ca2+ oscillations because Zn2+-deficient conditions induced by cell-permeable chelators abrogated Ca2+ responses evoked by fertilization and other physiological and pharmacological agonists. We also found that chemically or genetically generated eggs with lower levels of labile Zn2+ displayed reduced IP3R1 sensitivity and diminished ER Ca2+ leak despite the stable content of the stores and IP3R1 mass. Resupplying Zn2+ restarted Ca2+ oscillations, but excessive Zn2+ prevented and terminated them, hindering IP3R1 responsiveness. The findings suggest that a window of Zn2+ concentrations is required for Ca2+ responses and IP3R1 function in eggs, ensuring optimal response to fertilization and egg activation.
Myosin inhibitor reverses hypertrophic cardiomyopathy in pediatric iPSC-cardiomyocytes to mirror variant correction

Hypertrophic cardiomyopathy (HCM) is mainly caused by sarcomere gene variants in MYH7 and MYBPC3. Targeted drugs like myosin ATPase inhibitors have shown efficacy in adult HCM but have not been evaluated in children. We generated iPSC-cardiomyocytes (CMs) from four children with HCM harboring variants in MYH7 (V606M; R453C) or MYBPC3 (G148R; P955fs and TNNI3_A157P), variant-corrected controls, and a healthy individual. All CMs showed hypertrophy and sarcomere disorganization. All 3 single variant CMs showed higher contractility, slower relaxation, higher calcium transients and higher ATPase activity. Only MYH7 variant CMs showed stronger myosin-actinin binding. Targeted myosin ATPase inhibitor showed complete rescue of the phenotype in affected CMs and in cardiac Biowires to mirror isogenic controls. The response was stronger compared to verapamil or metoprolol, highlighting the need for clinical trials of myosin targeted therapy in pediatric HCM patients. The phenotype and response to drug therapy are influenced by the underlying genotype.
RBP-J regulates homeostasis and function of circulating Ly6Clo monocytes

Notch-RBP-J signaling plays an essential role in maintenance of myeloid homeostasis. However, its role in monocyte cell fate decisions is not fully understood. Here we showed that conditional deletion of transcription factor RBP-J in myeloid cells resulted in marked accumulation of blood Ly6Clo monocytes that highly expressed chemokine receptor CCR2. Bone marrow transplantation and parabiosis experiments revealed a cell intrinsic requirement of RBP-J for controlling blood Ly6CloCCR2hi monocytes. RBP-J-deficient Ly6Clo monocytes exhibited enhanced capacity competing with wildtype counterparts in blood circulation. In accordance with alterations of circulating monocytes, RBP-J deficiency led to markedly increased population of lung tissues with Ly6Clo monocytes and CD16.2+ interstitial macrophages. Furthermore, RBP-J deficiency-associated phenotypes could be genetically corrected by further deleting Ccr2 in myeloid cells. These results demonstrate that RBP-J functions as a crucial regulator of blood Ly6Clo monocytes and thus derived lung-resident myeloid populations, at least in part through regulation of CCR2.
Differentiating Bacillus subtilis incorporates valine and methionine carbon into the backbone of specific fatty acids

Summary Sporulation in Bacillus subtilis has long been a model of cellular differentiation, many aspects of which are well understood. The early stage of this process is of particular interest, especially the interrelationship of regulatory processes with metabolism in response to environmental changes. We analyzed cellular fatty acids as their methyl esters using capillary gas chromatography coupled to mass spectrometry during the transition from vegetative growth to early sporulation phase. Measurement of changes in the content of heavy fatty acid analogs in cultures supplemented with deuterium-labeled valine or methionine, or 13C-labeld valine, showed that label was incorporated into the backbone of 12-methyltridecanoic and 14-methylpentadecanoic acid, in both sporulating and Δspo0A cultures. These fatty acids were formed starting with isobutyryl-CoA apparently originating only from L-valine-d8 in cultures so supplemented. Our observations indicate that following vegetative growth a pathway exists from certain amino acids into fatty acid methylene groups, evidently passing through propionyl-CoA. This finding has the potential to deepen understanding of the metabolic basis of cellular differentiation and identify new targets for antibiotics. We also observed a significant, continuous increase in the proportion of 13-methyltetradecanoic acid in fatty acids during the same period in which the pre-spore membrane would be formed. Graphical abstract: Abbreviated Summary Early in at least some Bacillus subtilis differentiation scenarios, a straight-chain metabolite derived from propionyl-CoA is incorporated into fatty acids primed with isobutyryl-CoA possibly derived from cellular protein valine. Concurrently a leucine related fatty acid increases significantly, potentially comprising the predominant pre-spore septum fatty acid component. These processes occur in conjunction with the onset of fatty acid β-oxidation and bulk protein turnover.
Human visual cortex and deep convolutional neural network care deeply about object background

Deep convolutional neural networks (DCNNs) are able to predict brain activity during object categorization tasks, but factors contributing to this predictive power are not fully understood. Our study aimed to investigate the factors contributing to the predictive power of DCNNs in object categorization tasks. We compared the activity of four DCNN architectures with electroencephalography (EEG) recordings obtained from 62 human subjects during an object categorization task. Previous physiological studies on object categorization have highlighted the importance of figure-ground segregation - the ability to distinguish objects from their backgrounds. Therefore, we set out to investigate if figure-ground segregation could explain DCNNs predictive power. Using a stimuli set consisting of identical target objects embedded in different backgrounds, we examined the influence of object background versus object category on both EEG and DCNN activity. Crucially, the recombination of naturalistic objects and experimentally-controlled backgrounds creates a sufficiently challenging and naturalistic task, while allowing us to retain experimental control. Our results showed that early EEG activity (<100ms) and early DCNN layers represent object background rather than object category. We also found that the predictive power of DCNNs on EEG activity is related to processing of object backgrounds, rather than categories. We provided evidence from both trained and untrained (i.e. random weights) DCNNs, showing figure-ground segregation to be a crucial step prior to the learning of object features. These findings suggest that both human visual cortex and DCNNs rely on the segregation of object backgrounds and target objects in order to perform object categorization. Altogether, our study provides new insights into the mechanisms underlying object categorization as we demonstrated that both human visual cortex and DCNNs care deeply about object background. Author summary Our study aimed to investigate the factors contributing to the predictive power of deep convolutional neural networks (DCNNs) on EEG activity in object recognition tasks. We compared the activity of four DCNN architectures with human neural recordings during an object categorization task. We used a stimuli set consisting of identical target objects embedded in different phase-scrambled backgrounds. The distinction between object backgrounds and object categories allows us to investigate the influence of either factor for human subjects and DCNNs. Surprisingly, we found that both human visual processing and early DCNNs layers dedicate a large proportion of activity to processing object backgrounds instead of object category. Furthermore, this shared ability to make object backgrounds (and not just object category) invariant is largely the reason why DCNNs are predictive of brain dynamics in our experiment. We posit this shared ability to be an important solution for object categorization. Finally, we conclude that DCNNs, like humans, care deeply about object backgrounds.
GTP signaling links metabolism, DNA repair, and responses to genotoxic stress

How cell metabolism regulates DNA repair is incompletely understood. Here, we define a GTP-mediated signaling cascade that links metabolism to DNA repair and has significant therapeutic implications. GTP, but not other nucleotides, regulates the activity of Rac1, a G protein, that promotes the dephosphorylation of serine 323 on Abl-interactor 1 (Abi-1) by protein phosphatase 5 (PP5). Dephosphorylated Abi-1, a protein previously not known to activate DNA repair, promotes non-homologous end joining. In patients and mouse models of glioblastoma, Rac1 and dephosphorylated Abi-1 mediate DNA repair and resistance to standard of care genotoxic treatments. The GTP-Rac1-PP5-Abi-1 signaling axis is not limited to brain cancer, as GTP supplementation promotes DNA repair and Abi-1-S323 dephosphorylation in non-malignant cells and protects mouse tissues from genotoxic insult. This unexpected ability of GTP to regulate DNA repair independently of deoxynucleotide pools has important implications for normal physiology and cancer treatment.