Miracle-dz/UniFAR-FTUs huggingface dataset:
Toward Accurate Visual Reasoning With Dual-Path Neural Module Networks

Visual reasoning is a critical stage in visual question answering (Antol et al., 2015), but most of the state-of-the-art methods categorized the VQA tasks as a classification problem without taking the reasoning process into account. Various approaches are proposed to solve this multi-modal task that requires both abilities of comprehension and reasoning. The recently proposed neural module network (Andreas et al., 2016b), which assembles the model with a few primitive modules, is capable of performing a spatial or arithmetical reasoning over the input image to answer the questions. Nevertheless, its performance is not satisfying especially in the real-world datasets (e.g., VQA 1.0& 2.0) due to its limited primitive modules and suboptimal layout. To address these issues, we propose a novel method of Dual-Path Neural Module Network which can implement complex visual reasoning by forming a more flexible layout regularized by the pairwise loss. Specifically, we first use the region proposal network to generate both visual and spatial information, which helps it perform spatial reasoning. Then, we advocate to process a pair of different images along with the same question simultaneously, named as a “complementary pair,” which encourages the model to learn a more reasonable layout by suppressing the overfitting to the language priors. The model can jointly learn the parameters in the primitive module and the layout generation policy, which is further boosted by introducing a novel pairwise reward. Extensive experiments show that our approach significantly improves the performance of neural module networks especially on the real-world datasets.
Conventional Two-Stage Hepatectomy or Associating Liver Partitioning and Portal Vein Ligation for Staged Hepatectomy for Colorectal Liver Metastases? A Systematic Review and Meta-Analysis

Background: Pushing the surgical limits for initially unresectable colorectal liver metastases (CRLM) are two approaches for sequential liver resection: two-stage hepatectomy (TSH) and associating liver partitioning and portal vein ligation for staged hepatectomy (ALPPS). However, the role of each treatment modality remains ill-defined. The present meta-analysis was designed to compare the safety, efficacy, and oncological benefits between ALPPS and TSH in the management of advanced CRLM. Methods: A systematic literature search was conducted from online databases through to February 2020. Single-arm synthesis and cumulative meta-analysis were performed. Results: Eight studies were included, providing a total of 409 subjects for analysis (ALPPS: N = 161; TSH: N = 248). The completions of the second stage of the hepatectomy [98 vs. 78%, odds ratio (OR) 5.75, p < 0.001] and R0 resection (66 vs. 37%; OR 4.68; p < 0.001) were more frequent in patients receiving ALPPS than in those receiving TSH, and the waiting interval was dramatically shortened in ALPPS (11.6 vs. 45.7 days, weighted mean difference = −35.3 days, p < 0.001). Nevertheless, the rate of minor complications was significantly higher in ALPPS (59 vs. 18%, OR 6.5, p < 0.001) than in TSH. The two treatments were similar in 90-day mortality (7 vs. 5%, p = 0.43), major complications (29 vs. 22%, p = 0.08), posthepatectomy liver failure (PHLF; 9 vs. 9%, p = 0.3), biliary leakage (11 vs. 14%, p = 0.86), length of hospital stay (27.95 vs. 26.88 days, p = 0.8), 1-year overall survival (79 vs. 84%, p = 0.61), 1-year recurrence (49 vs. 39%, p = 0.32), and 1-year disease-free survival (34 vs. 39%, p = 0.66). Cumulative meta-analyses indicated chronological stability for the pooled effect sizes of resection rate, 90-day mortality, major complications, and PHLF. Conclusions: Compared with TSH, ALPPS for advanced CRLM resulted in superior surgical efficacy with comparable perioperative mortality rate and short-term oncological outcomes, while this was at the cost of increased perioperative minor complications.
Equine hyperimmune globulin raised against the SARS-CoV-2 spike glycoprotein has extremely high neutralizing titers

COVID-19 pandemic caused approximately 750,000 deaths and over 20 million confirmed cases of infection by SARS-CoV-2 within 8 months since the emergence of the virus. While there are no vaccines approved and considering the difficulty in meeting the large vaccination demand worldwide, the potential use of passive immunization should be considered based on existing successful therapies against many diseases. Here we demonstrate that hyperimmune globulin preparations raised in horses against the recombinant trimeric spike (S) glycoprotein of SARS-CoV-2 in the prefusion conformation provide very high ELISA titers as well as highly potent neutralizing activity against SARS-CoV-2. Five horses were subcutaneously inoculated for 6 weeks with the recombinant S protein (ectodomain, residues 1-1208). Four out of the 5 horses presented a strong immune response. Considering the average of all 5 horses, ELISA titers above 1:1,000,000 and neutralizing titers (PRNT90) reaching 1:14,604 were observed. When compared with the plasma of three convalescent COVID-19 patients, sera of immunized horses displayed approximately 140-fold higher neutralizing titers measured as PRNT90. To prevent eventual side effects caused by horse antiserum, IgG was digested with pepsin and purified by fractional salt precipitation to eliminate Fc fragments, a process that is industrially used for the production of passive immunization F(ab9)2 concentrates against rabies, tetanus and snake venoms. The high neutralizing titers against SARS-CoV-2 obtained for the unprocessed sera were confirmed for the F(ab9)2 fragments and were 150-fold higher than the PRNT90 neutralizing titers of plasma of three COVID-19 convalescent patients. The great advantage of using the recombinant trimeric S glycoprotein is that it is safe and provides quick adaptive immunity in horses. Our data show the perspective of using hyperimmune anti-SARS-CoV-2 F(ab9)2 preparations as a passive immunization therapy in humans, similar to therapies that have been safely used for decades against rabies, tetanus and snake venoms.
Histone demethylase complexes KDM3A and KDM3B cooperate with OCT4/SOX2 to construct pluripotency gene regulatory network

The pluripotency gene regulatory network of porcine-induced pluripotent stem cells (piPSCs), especially in epigenetics, remains elusive. To determine this biological function of epigenetics, we cultured piPSCs in different culture conditions. We found that activation of pluripotent gene- and pluripotency-related pathways requires the erasure of H3K9 methylation modification which was further influenced by mouse embryonic fibroblast (MEF) served feeder. By dissecting the dynamic change of H3K9 methylation during loss of pluripotency, we demonstrated that the H3K9 demethylases KDM3A and KDM3B regulated global H3K9me2/me3 level and that their co-depletion led to the collapse of the pluripotency gene regulatory network. Immunoprecipitation-mass spectrometry (IP-MS) provided evidence that KDM3A and KDM3B formed a complex to perform H3K9 demethylation. The genome-wide regulation analysis revealed that OCT4 (O) and SOX2 (S), the core pluripotency transcriptional activators, maintained the pluripotent state of piPSCs depending on the H3K9 hypomethylation. Further investigation revealed that O/S cooperating with histone demethylase complex containing KDM3A and KDM3B promoted pluripotency genes expression to maintain the pluripotent state of piPSCs. Together, these data offer a unique insight into the epigenetic pluripotency network of piPSCs. Summary Erasure of H3K9 methylation in porcine pluripotent stem cells depends on the complex of transcription factors OCT4/SOX2 and histone demethylase KDM3A/KDM3B.
Prospects for Future Methodological Development and Application of Magnetoencephalography Devices in Psychiatry

Magnetoencephalography (MEG) is a functional neuroimaging tool that can record activity from the entire cortex on the order of milliseconds. MEG has been used to investigate numerous psychiatric disorders, such as schizophrenia, bipolar disorder, major depression, dementia, and autism spectrum disorder. Although several review papers on the subject have been published, perspectives and opinions regarding the use of MEG in psychiatric research have primarily been discussed from a psychiatric research point of view. Owing to a newly developed MEG sensor, the use of MEG devices will soon enter a critical period, and now is a good time to discuss the future of MEG use in psychiatric research. In this paper, we will discuss MEG devices from a methodological point of view. We will first introduce the utilization of MEG in psychiatric research and the development of its technology. Then, we will describe the principle theory of MEG and common algorithms, which are useful for applying MEG tools to psychiatric research. Next, we will consider three topics—child psychiatry, resting-state networks, and cortico-subcortical networks—and address the future use of MEG in psychiatry from a broader perspective. Finally, we will introduce the newly developed device, the optically-pumped magnetometer, and discuss its future use in MEG systems in psychiatric research from a methodological point of view. We believe that state-of-the-art electrophysiological tools, such as this new MEG system, will further contribute to our understanding of the core pathology in various psychiatric disorders and translational research.
Fruit Development in Ficus carica L.: Morphological and Genetic Approaches to Fig Buds for an Evolution From Monoecy Toward Dioecy

The mechanism behind the bud evolution towards breba or main crop in Ficus carica L. is uncertain. Anatomical and genetic studies may put a light on the possible similarities/differences between the two types of fruits. For this reason, we collected complimentary data from anatomical, X-ray imaging, and genetic techniques. The RNA seq together with structural genome annotation allowed the prediction of 34,629 known genes and 938 novel protein-coding genes. Transcriptome analysis of genes during bud differentiation revealed differentially expressed genes in two fig varieties (Dottato and Petrelli) and in breba and main crop. We chose Dottato and Petrelli because the first variety does not require pollination to set main crop and the latter does; moreover, Petrelli yields many brebas whereas Dottato few. Of the 1,615 and 1,904 loci expressed in Dottato and Petrelli, specifically in breba or main crop, respectively, only 256 genes appeared to be transcripts in both varieties. The buds of the two fig varieties were observed under optical microscope and using 3D X-ray tomography, highlighting differences mainly related to the stage of development. The X-ray images of buds showed a great structural similarity between breba and main crop during the initial stages of development. Analysis at the microscope indicated that inflorescence differentiation of breba was split in two seasons whereas that of main crop started at the end of winter of season 2 and was completed within 2 to 3 months. The higher expression of floral homeotic protein AGAMOUS in breba with respect to main crop, since this protein is required for normal development of stamens and carpels in the flower, may indicate an original role of these fruits for staminate flowers production for pollination of the main crop, as profichi in the caprifig. Several genes related to auxin (auxin efflux carrier, auxin response factor, auxin binding protein, auxin responsive protein) and to GA synthesis (GA20ox) were highly expressed in brebas with respect to main crop for the development of this parthenocarpic fruit.
Microbiome-Aware Ecotoxicology of Organisms: Relevance, Pitfalls, and Challenges

Over the last 15 years, the advent of high-throughput “omics” techniques has revealed the multiple roles and interactions occurring among hosts, their microbial partners and their environment. This microbiome revolution has radically changed our views of biology, evolution, and individuality. Sitting at the interface between a host and its environment, the microbiome is a relevant yet understudied compartment for ecotoxicology research. Various recent works confirm that the microbiome reacts to and interacts with contaminants, with consequences for hosts and ecosystems. In this paper, we thus advocate for the development of a “microbiome-aware ecotoxicology” of organisms. We emphasize its relevance and discuss important conceptual and technical pitfalls associated with study design and interpretation. We identify topics such as functionality, quantification, temporality, resilience, interactions, and prediction as major challenges and promising venues for microbiome research applied to ecotoxicology.
Microarray Analysis of lncRNA and mRNA Reveals Enhanced Lipolysis Along With Metabolic Remodeling in Mice Infected With Larval Echinococcus granulosus

Parasitic infection improves metabolic homeostasis in “western diet”-induced obesity through the regulation of adipogenesis. However, the underlying mechanism is not yet fully understood. Using microarray analysis, this study investigated the long non-coding RNA (lncRNA) and messenger RNA (mRNA) profiles of subcutaneous adipose tissues from mice infected with Echinococcus granulosus protoscoleces. A total of 1052 mRNA (541 upregulated, 511 downregulated) and 220 lncRNA (126 upregulated, 94 downregulated) transcripts were differentially expressed (fold change ≥2, P < 0.05) in the infected subcutaneous adipose tissues. When compared with the control group, the infected mice showed a decrease in adipose tissue mass and a reduction in adipocyte size. Indirect calorimetry revealed the change in the energy metabolism after infection, characterized by a lower CO2 production and O2 consumption, a sharp decline in carbohydrate oxidation, and a slight increase in fat oxidation. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that the parasitic infection reprogrammed a complex metabolic network. Notably, “lipoxygenase” and “arginine and proline metabolism” pathways were significantly upregulated while “glycolysis,” “tricarboxylic acid cycle,” “de novo lipogenesis,” and “lipid droplet” pathways were dramatically downregulated. In addition, several key lncRNAs were associated with insulin resistance and adipocyte differentiation. Overall, the present study suggested that E. granulosus infection could enhance lipolysis. Thus, our findings provide novel insights into parasite-mediated metabolic homeostasis, and into the mechanism of hypertrophic adipocytes in obesity.
Regularization of Linear Ill-posed Problems in Two Steps: Combination of Data Smoothing and Reconstruction Methods

This thesis is a contribution to the field of ill-posed inverse problems. This field has been in the focus of mathematical research for the past four decades. During the last ten years a new development has taken place: Besides operator-adapted methods for the solution of inverse problems also methods adjusted to smoothness properties of functions are studied. The thesis at hand is linked to this development. Its intention is to present and analyze two-step methods for the solution of linear ill-posed problems. It is the fundamental idea of a two-step method to perform first a data estimation step of probably noisy data and then to perform a reconstruction step to solve the inverse problem using the data estimate. Besides the general description of two-step methods two realizations are analyzed. On the one hand classical regularization methods like the ones proposed by Tikhonov or Landweber are interpreted as two-step methods. It is well-known that solving inverse problems by classical regularization methods generally results in an oversmoothing. This effect is explained by the two-step approach. Furthermore the classical methods are modified such that a parameter allows to control the amount of smoothing. For a certain range of this parameter the modified method is order optimal. On the other hand the combination of wavelet shrinkage and classical regularization methods is analyzed. This yields an order optimal method which is, by the use of wavelet shrinkage, adapted to smoothness properties of functions in Sobolev and Besov spaces and, by the use of the singular system, adapted to the operator under consideration. In addition it is shown that the combination of wavelet shrinkage and the modified classical methods – with a greater parameter range – is order optimal. The combination of wavelet shrinkage and Tikhonov regularization is applied to a problem from medical imaging.
MicroRNAs in Alzheimer’s Disease: Function and Potential Applications as Diagnostic Biomarkers

Alzheimer’s disease (AD) is the most common form of dementia. Although the incidence of AD is high, the rates of diagnosis and treatment are relatively low. Moreover, effective means for the diagnosis and treatment of AD are still lacking. MicroRNAs (miRNAs, miRs) are non-coding RNAs that play regulatory roles by targeting mRNAs. The expression of miRNAs is conserved, temporal, and tissue-specific. Impairment of microRNA function is closely related to AD pathogenesis, including the beta-amyloid and tau hallmarks of AD, and there is evidence that the expression of some microRNAs differs significantly between healthy people and AD patients. These properties of miRNAs endow them with potential diagnostic and therapeutic value in the treatment of this debilitating disease. This review provides comprehensive information about the regulatory function of miRNAs in AD, as well as potential applications as diagnostic biomarkers.
The Contribution of Plasma and Brain Vitamin C on Age and Gender-Related Cognitive Differences: A Mini-Review of the Literature

There is increasing evidence that sex differences in the brain may contribute to gender-related behavioral differences, including cognitive function. Literature has revealed gender dimorphisms in cognitive function between males and females. Additionally, several risk factors associated with cognitive decline depend on chronological age. It is well recognized that the process of aging is associated with a decline in cognitive ability and brain function. Various explanations may account for these gender-related cognitive differences and age-associated cognitive changes. Recent investigations have highlighted the importance of vitamin C in maintaining brain health and its association with cognitive function in both cognitively intact and impaired cohorts. The present review explores previous literature that has evaluated differences in plasma/brain vitamin C between genders and during aging. It then assesses whether these age and gender-related differences may affect the relationship between plasma/brain vitamin C and cognition. The purpose of this review was to examine the evidence for a link between plasma/brain vitamin C and cognition and the impact of gender and age on this relationship. Epidemiological studies have frequently shown higher vitamin C plasma concentrations in women. Similarly, aging has been systematically associated with reductions in plasma vitamin C levels. A range of animal studies has demonstrated potential gender and age-related differences in vitamin C brain distribution and utilization. The reviewed literature suggests that gender differences in plasma and brain vitamin C may potentially contribute to differences in gender-associated cognitive ability, particularly while females are pre-menopausal. Additionally, we can propose that age-associated differences in plasma and brain vitamin C may be potentially linked to age-associated cognitive differences, with older cohorts appearing more vulnerable to experience declines in plasma vitamin C concentrations alongside compromised vitamin C brain regulation. This review encourages future investigations to take into account both gender and age when assessing the link between plasma vitamin C concentrations and cognitive function. Further large scale investigations are required to assess whether differences in cognitive function between genders and age groups may be causally attributed to plasma vitamin C status and brain distribution and utilization.
PHF6 Interacts with LMO2 During Normal Haematopoiesis and in Leukaemia and Regulates Gene Expression and Genome Integrity

The transcriptional mediator LIM domain only 2 (LMO2) forms a large multi-protein complex together with TAL1/LYL1, HEB/E2A, LDB1 and GATA. This complex regulates transcription from the onset of haematopoietic development and during differentiation. Chromosomal re-arrangements involving LMO and other members of the complex are causative for T-cell lymphoblastic leukaemia (T-ALL). We have identified Plant Homeodomain (PHD)-like Finger 6 (PHF6) as a new LMO2 interacting factor. Somatic mutations in PHF6 have been found to occur in several types of leukaemia. We show that PHF6 interacts with LMO2 during the initial stages of the haematopoietic development, myeloid differentiation and in T-ALL. The LMO2/PHF6 complex binds the DNA and regulates linage-specific gene expression. Additionally, a loss or reduction of LMO2 and PHF6 leads to chromosomal instability. PHF6 and LMO2 are required for maintaining levels of γH2AX and 53BP1, where PHF6 is important for γH2AX accumulation and LMO2 has a role in recruiting 53BP1 to γH2AX foci.
Dynamical Wilson twisted mass fermions: a scaling analysis

This talk is based on reference [1] and is one of four contributions about N f = 2 dynamical twisted mass fermions which are summarized in ref. [2]. This common contribution covers three different gauge actions, namely the standard Wilson plaquette gauge action investigated here, the DBW2 [2,3] and the tree-level improved Symanzik [4] gauge action. In addition, first results are compared to next-to-leading order chiral perturbation theory formulae.
States of power: Ronan Paddison, Space and Polity

ABSTRACT In this article, I record some thoughts on Ronan Paddison’s accomplishments as an intellectual leader-scholar-citizen who made substantive and consequential contributions to the advancement of the systematic branch of Political Geography. I first consider that portion of Ronan’s body of published research which tackles political geographical themes, commenting in particular upon his scholarship on state power, before exploring in greater detail the meaning and implications of his role as founder and Editor in Chief of the journal Space and Polity. Against the backdrop of the neoliberalising academy, Ronan Paddison’s service to Political Geography serves as a lighthouse for those who survive him: it gestures to the kinds of academic subjectivities which enable privilege to be used wisely and reminds us of the indispensable work the protean scholar performs so that academic communities might prosper.
How does self-image congruity affect tourists’ environmentally responsible behavior?

Abstract Tourists’ environmentally responsible behavior (TERB) is crucial to the destination’s natural environment. Drawing on self-congruity theory, this study extends the existing literature on the underlying mechanism of TERB from the perspective of self-image congruity. Specifically, this study investigates the effects of actual and ideal self-image congruity on TERB by addressing the mediating role of destination psychological ownership (DPO) and the moderating role of endorsement of the New Ecological Paradigm (NEP). With 424 valid questionnaires collected from domestic tourists visiting Xiamen in China, this study finds that DPO fully mediates the positive effect of actual self-image congruity on TERB, whereas partially mediates the positive effect of ideal self-image congruity on TERB. Furthermore, the findings of this study suggest that endorsement of the NEP moderates the effects of actual and ideal self-image congruity and DPO on TERB, such that the relationships are stronger when endorsement of the NEP is high rather than low. Theoretically, this study makes a valuable addition to the TERB literature by empirically examining the roles of self-image congruity, DPO, and endorsement of the NEP. Practically, some helpful implications are proposed to stimulate TERB.