Miracle-dz/UniFAR-FTUs huggingface dataset:
Rating Transitions Forecasting: A filtering Approach

Analyzing the effect of business cycle on rating transitions has been a subject of great interest these last fifteen years, particularly due to the increasing pressure coming from regulators for stress testing. In this paper, we consider that the dynamics of rating migrations is governed by an unobserved latent factor. Under a point process filtering framework, we explain how the current state of the hidden factor can be efficiently inferred from observations of rating histories. We then adapt the classical Baum-Welsh algorithm to our setting and show how to estimate the latent factor parameters. Once calibrated, we may reveal and detect economic changes affecting the dynamics of rating migration, in real-time. To this end we adapt a filtering formula which can then be used for predicting future transition probabilities according to economic regimes without using any external covariates. We propose two filtering frameworks: a discrete and a continuous version. We demonstrate and compare the efficiency of both approaches on fictive data and on a corporate credit rating database. The methods could also be applied to retail credit loans.
Learning Through Structure: Towards Deep Neuromorphic Knowledge Graph Embeddings

Computing latent representations for graph-structured data is an ubiquitous learning task in many industrial and academic applications ranging from molecule synthetization to social network analysis and recommender systems. Knowledge graphs are among the most popular and widely used data representations related to the Semantic Web. Next to structuring factual knowledge in a machine-readable format, knowledge graphs serve as the backbone of many artificial intelligence applications and allow the ingestion of context information into various learning algorithms. Graph neural networks attempt to encode graph structures in low-dimensional vector spaces via a message passing heuristic between neighboring nodes. Over the recent years, a multitude of different graph neural network architectures demonstrated ground-breaking performances in many learning tasks. In this work, we propose a strategy to map deep graph learning architectures for knowledge graph reasoning to neuromorphic architectures. Based on the insight that randomly initialized and untrained (i.e., frozen) graph neural networks are able to preserve local graph structures, we compose a frozen neural network with shallow knowledge graph embedding models. We experimentally show that already on conventional computing hardware, this leads to a significant speedup and memory reduction while maintaining a competitive performance level. Moreover, we extend the frozen architecture to spiking neural networks, introducing a novel, event-based and highly sparse knowledge graph embedding algorithm that is suitable for implementation in neuromorphic hardware.
The causal effects of body mass index (BMI) on childhood symptoms of depression, anxiety disorder, and attention-deficit hyperactivity disorder: a within family Mendelian randomization study

Abstract Objectives: Higher BMI in childhood predicts neurodevelopmental and emotional problems, but it is unclear if these associations are causal. Previous genetic studies imply causal effects of childhood BMI on depression and attention-deficit hyperactivity disorder (ADHD), but these observations might also reflect effects of demography and the family environment. We used within-family Mendelian randomization, which accounts for familial effects by controlling for parental genotype, to investigate the impact of BMI on symptoms of depression, anxiety, and ADHD symptoms at age 8. Methods: This study is based on the Norwegian Mother, Father and Child Cohort Study (MoBa) and uses data from the Medical Birth Registry of Norway (MBRN). Participants were 26,370 8-year-old children (48.7% female) born 1999-2009, together with their parents. We applied multivariable regression, classic Mendelian randomization (classic MR), and within-family Mendelian randomization (within-family MR). We report estimates of the effects of the child's own BMI, mother's BMI, and father's BMI on the child's depressive, anxiety, and ADHD symptoms, reported by mothers when the child was aged 8. Results: In multivariable regression, higher BMI was marginally associated with more depressive and ADHD symptoms, and associated with fewer anxiety symptoms, in 8-year-old children. Classic MR models implied a causal effect of children's higher BMI on higher depressive and ADHD symptoms, and to a lesser degree, lower anxiety symptoms. In within-family MR models, there was less evidence that children's own BMI affected any of these symptoms. For example, a 5kg/m2 increase in BMI was associated with 0.04 standard deviations (SD) higher depressive symptoms (95% CI -0.01 to 0.09) in multivariable regression, with corresponding effect estimates of 0.41 SD (95% CI 0.10 to 0.56) in classic MR and 0.08 SD (95% CI -0.25 to 0.42) in within-family MR. Within-family MR suggested that maternal but not paternal BMI was associated with children's depressive symptoms. Conclusions: The influence of childhood BMI on depressive, anxiety and ADHD symptoms may have been overstated by MR approaches that do not account for parental genotype. Factors correlated with maternal BMI may influence offspring symptoms of depression.
Butyrate and related epigenetic changes link Parkinson's disease to inflammatory bowel disease and depressive symptoms

Background The gut microbiome and its metabolites can impact brain health and are altered in Parkinson's disease (PD) patients. It has been recently demonstrated that PD patients have reduced fecal levels of the potent epigenetic modulator butyrate and its bacterial producers. Here, we investigate whether the changes in the gut microbiome and associated metabolites are linked to PD symptoms and epigenetic markers in leucocytes and neurons. Methods Stool, whole blood samples, and clinical data were collected from 55 PD patients and 55 controls. We performed DNA methylation analysis on whole blood samples and analyzed the results in relation to fecal short-chain fatty acid concentrations and microbiota composition. In another cohort, prefrontal cortex neurons were isolated from control and PD brains. We identified the genome-wide DNA methylation by targeted bisulfite sequencing. Results We show that lower fecal butyrate and reduced Roseburia, Romboutsia, and Prevotella counts are linked to depressive symptoms in PD patients. Genes containing butyrate-associated methylation sites include PD risk genes and significantly overlap with sites epigenetically altered in PD blood leucocytes, predominantly neutrophils, and in brain neurons, relative to controls. Moreover, butyrate-associated methylated-DNA (mDNA) regions in PD overlap with those altered in gastrointestinal, autoimmune, and psychiatric diseases.
High Resolution Three-Dimensional Tracking of Motor Proteins with Optical Tweezers

Optical tweezers are high resolution position and force transducers used in biology and physics. The instrument’s ability to trap microscopic objects and measure their displacements with high precision on the nanometre scale allows to track single molecules and to exert forces in the piconewton range. In this work, I used optical tweezers to investigate the three-dimensional motion of cytoskeletal molecular machines, so-called kinesin motor proteins. The exact path of kinesin’s motion on its track, the microtubule, is crucial for its biological function. I implemented an assay in which the three-dimensional motion of kinesin motors can be tracked using optical tweezers with high resolution. This approach, I applied to different kinesins. For the microtubule-depolymerising kinesin-8 Kip3, I found that it showed sideward motion to the left and right, in addition to its forward motion. This sideward motion could be asymmetrically biased by applying sideward forces with the optical tweezers. The sideward motion of Kip3 might be an important part of its motility mechanism as it provides a simple way to bypass obstacles on its track. For another kinesin, kinesin-1, I observed no sideward motion but only forward motion. This unidirectional motion could be used to investigate the structure of the microtubules. The developed threedimensional experimental assay can be used to track the motion of other molecular motors with high resolution in the future.
Role of Dicer-Dependent RNA Interference in Regulating Mycoparasitic Interactions

Small RNAs mediated RNA interference (RNAi) known to regulate several biological processes. Dicer-like endoribonucleases (DCLs) play a vital role in the RNAi pathway by generating sRNAs. ABSTRACT Dicer-like proteins (DCLs) play a vital role in RNA interference (RNAi), by cleaving RNA filament into small RNAs. Although DCL-mediated RNAi can regulate interspecific communication between pathogenic/mutualistic organisms and their hosts, its role in mycoparasitic interactions is yet to be investigated. In this study, we deleted dcl genes in the mycoparasitic fungus Clonostachys rosea and characterize the functions of DCL-dependent RNAi in mycoparasitism. Deletion of dcl2 resulted in a mutant with reduced secondary metabolite production, antagonism toward the plant-pathogenic fungus Botrytis cinerea, and reduced ability to control Fusarium foot rot disease on wheat, caused by Fusarium graminearum. Transcriptome sequencing of the in vitro interaction between the C. rosea Δdcl2 strain and B. cinerea or F. graminearum identified the downregulation of genes coding for transcription factors, membrane transporters, hydrolytic enzymes, and secondary metabolites biosynthesis enzymes putatively involved in antagonistic interactions, in comparison with the C. rosea wild-type interaction. A total of 61 putative novel microRNA-like RNAs (milRNAs) were identified in C. rosea, and 11 were downregulated in the Δdcl2 mutant. In addition to putative endogenous gene targets, these milRNAs were predicted to target B. cinerea and F. graminearum virulence factor genes, which showed an increased expression during interaction with the Δdcl2 mutant incapable of producing the targeting milRNAs. In summary, this study constitutes the first step in elucidating the role of RNAi in mycoparasitic interactions, with important implications for biological control of plant diseases, and poses the base for future studies focusing on the role of cross-species RNAi regulating mycoparasitic interactions. IMPORTANCE Small RNAs mediated RNA interference (RNAi) known to regulate several biological processes. Dicer-like endoribonucleases (DCLs) play a vital role in the RNAi pathway by generating sRNAs. In this study, we investigated a role of DCL-mediated RNAi in interference interactions between mycoparasitic fungus Clonostachys rosea and the two fungal pathogens Botrytis cinerea and Fusarium graminearum (here called mycohosts). We found that the dcl mutants were not able to produce 11 sRNAs predicted to finetune the regulatory network of genes known to be involved in production of hydrolytic enzymes, antifungal compounds, and membrane transporters needed for antagonistic action of C. rosea. We also found C. rosea sRNAs putatively targeting known virulence factors in the mycohosts, indicating RNAi-mediated cross-species communication. Our study expanded the understanding of underlying mechanisms of cross-species communication during interference interactions and poses a base for future works studying the role of DCL-based cross-species RNAi in fungal interactions.
Prevalence of Child Sexual Abuse in Spain: A Representative Sample Study

The prevalence of child sexual abuse (CSA) is difficult to assess, and rates vary widely across studies due to methodological and sample differences. In Spain, prevalence data from representative samples are lacking. The objective of this study was to determine the prevalence of different CSA experiences in a sample that was representative of the Spanish population in terms of gender, age, and region. The sample comprised 1,071 (539 male and 532 female) Spanish adults (Mage = 45.37; SD = 14.84). Participants completed an anonymous online survey about different types of CSA and were asked whether they had disclosed the experience at the time. Prevalence was analyzed as a function of gender and generation. Results indicated prevalence rates ranging from 2.8% to 18.5%, depending on the type of experience. The most common experience suffered during childhood was being shown pornographic material, while that with the lowest prevalence was being forced to perform a sexual act involving penetration. Prevalence was higher in females than males for eight of the ten experiences considered. Young adults from Generation Z were the most likely to report having suffered three of the CSA experiences, two of them related to technology. Only 27.5% of respondents said that they had told someone about the abuse at the time, mainly their mother (more common among females) or a friend/peer (more frequent among males). The results suggest that CSA is prevalent in Spain, with considerable rates for several types of abusive experience, especially among females and the youngest generation. The implications of the results are discussed. The findings may inform social policy and the development of effective prevention programs.
Neuroanatomical correlates of reality monitoring in patients with schizophrenia and auditory hallucinations

Abstract Background Reality-monitoring process enables to discriminate memories of internally generated information from memories of externally derived information. Studies have reported impaired reality-monitoring abilities in schizophrenia patients with auditory hallucinations (AHs), specifically with an exacerbated externalization bias, as well as alterations in neural activity within frontotemporoparietal areas. In healthy subjects, impaired reality-monitoring abilities have been associated with reduction of the paracingulate sulcus (PCS). The current study aimed to identify neuroanatomical correlates of reality monitoring in patients with schizophrenia. Methods Thirty-five patients with schizophrenia and AHs underwent a reality-monitoring task and a 3D anatomical MRI scan at 1.5 T. PCS lengths were measured separately for each hemisphere, and whole-brain voxel-based morphometry analyses were performed using the Computational Anatomy Toolbox (version 12.6) to evaluate the gray-matter volume (GMV). Partial correlation analyses were used to investigate the relationship between reality-monitoring and neuroanatomical outcomes (PCS length and GMV), with age and intracranial volume as covariates. Results The right PCS length was positively correlated with reality-monitoring accuracy (Spearman’s ρ = 0.431, p = 0.012) and negatively with the externalization bias (Spearman’s ρ = −0.379, p = 0.029). Reality-monitoring accuracy was positively correlated with GMV in the right angular gyrus, whereas externalization bias was negatively correlated with GMV in the left supramarginal gyrus/superior temporal gyrus, in the right lingual gyrus and in the bilateral inferior temporal/fusiform gyri (voxel-level p < 0.001 and cluster-level p < 0.05, FDR-corrected). Conclusions Reduced reality-monitoring abilities were significantly associated with shorter right PCS and reduced GMV in temporal and parietal regions of the reality-monitoring network in schizophrenia patients with AHs.
Should Pertrochanteric and Subtrochanteric Fractures Be Treated with a Short or Long Intramedullary Nail?

Background: The purpose of the present multicenter cohort study was to compare the rates of reoperation in elderly patients with pertrochanteric and subtrochanteric fractures that had been treated with a short or long intramedullary nail. Methods: Eleven orthopaedic departments across Denmark delivered data that had been obtained from the Danish Multidisciplinary Hip Fracture Registry (DMHFR) and a review of health-care records. With use of surgical procedure codes for pertrochanteric and subtrochanteric fractures that had been treated with an intramedullary nail, the DMRHF was searched to identify patients who had been ≥65 years of age between 2008 and 2013. The health-care records for patients who had had major reoperations, defined as any reoperation with the exclusion of simple hardware removal, were retrieved from the DMHFR, were reviewed for the type of intramedullary nail and missed reoperations, including peri-implant fractures, within 2 years of follow-up. Crude logistic regression analysis with adjustment for age, sex, and comorbidity was performed, yielding odds ratios (ORs) with 95% confidence intervals (CIs). Results: Of 2,245 pertrochanteric fractures, 1,867 were treated with a short intramedullary nail and 378 were treated with a long intramedullary nail. The rate of major reoperations was 4.0% in the short intramedullary nail group and 6.3% in the long intramedullary nail group. This yielded a crude OR of 1.61 (1.01 to 2.60) and an adjusted OR of 1.67 (1.04 to 2.70). Of 909 subtrochanteric fractures, 308 were treated with a short intramedullary nail and 601 were treated with a long intramedullary nail. The rate of major reoperations was 8.4% in the short intramedullary nail group and 4.0% in the long intramedullary nail group, yielding a crude OR of 0.45 (0.25 to 0.80) and an adjusted OR of 0.45 (0.25 to 0.81). Conclusions: This is the first study confirming the theory that, for subtrochanteric fractures, a long intramedullary nail has a lower rate of major reoperations compared with a short intramedullary nail. In contrast, a short intramedullary nail has a lower rate of major reoperations compared with a long intramedullary nail for pertrochanteric fractures but with a lower absolute risk reduction compared with the results for subtrochanteric intramedullary nailing. There is a need for validation of these results in other large studies, especially for pertrochanteric fractures. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Role of Glucose-6-Phosphate in Metabolic Adaptation of Staphylococcus aureus in Diabetes

Sugars are essential nutrients for S. aureus to survive and proliferate within the host. Because elevated serum glucose levels are a hallmark of diabetes, most studies have focused on the effect of glucose metabolism, and very little is known regarding the effects of metabolism of other sugars on the pathogenesis of S. aureus in diabetes. ABSTRACT Diabetic foot ulcer (DFU) is the most common and costly sequela of diabetes mellitus, often leading to lower-extremity amputation with poor 5-year survival rates. Staphylococcus aureus is the most prevalent pathogen isolated from DFU, suggesting adaptation of S. aureus to the unique metabolic conditions of diabetes. Diabetes is a complex metabolic disorder with increases not only in serum glucose levels but also in levels of other sugars, including fructose, mannose, and glucose-6-phosphate (G6P). However, the effect of metabolism of these sugars on the pathogenesis of S. aureus is not fully understood. In this study, we demonstrated that metabolism of G6P, fructose, and mannose induced greater expression of staphylococcal virulence factors than did glucose metabolism, but only G6P effects were independent of glucose-mediated carbon catabolite repression, suggesting a physiologically relevant role in diabetes. Our in vivo studies further demonstrated that G6P was highly present in skin adipose tissues of diabetic TALLYHO/JngJ mice, and subcutaneous infection with S. aureus caused significantly greater tissue necrosis and bacterial burden, compared to nondiabetic SWR/J mice. Finally, enhanced pathogenesis of S. aureus in diabetic TALLYHO/JngJ mice was significantly attenuated by deletion of the hexose phosphate transport (HPT) system. These results suggest that G6P is an important metabolic signal for S. aureus, enhancing the virulence in diabetes. A better understanding of how G6P metabolism is linked to the virulence of S. aureus will lead to the development of novel alternative therapeutics. IMPORTANCE Sugars are essential nutrients for S. aureus to survive and proliferate within the host. Because elevated serum glucose levels are a hallmark of diabetes, most studies have focused on the effect of glucose metabolism, and very little is known regarding the effects of metabolism of other sugars on the pathogenesis of S. aureus in diabetes. In this study, we demonstrated that G6P, which is highly present in diabetes, can induce expression of staphylococcal virulence factors that cause severe tissue necrosis and bacterial burden in skin infections. Our results highlight the importance of nutritional control of blood sugar levels, not only glucose but also other highly metabolizable sugars such as G6P. A better understanding of how activation of the HPT system is linked to the virulence of S. aureus will guide development of novel alternative therapeutics.
Retinal Astrocytes and Microglia Activation in Diabetic Retinopathy Rhesus Monkey Models

ABSTRACT Purpose To assess the retinal neurodegeneration in type-1 diabetes mellitus (T1DM) and type-2 diabetes mellitus (T2DM) rhesus monkeys, and to investigate whether alterations of glial cells occur in the early stage of diabetic retinopathy (DR). Materials and methods T1DM rhesus monkeys were established by daily intravenous injections of streptozotocin (STZ, 25 mg/kg body weight) in citrate buffer (pH 4.5) for 5 days, while T2DM rhesus monkeys were induced by feeding with high-fat diet. The period of DR in rhesus monkeys was evaluated by fundoscopy and optical coherence tomography (OCT). Afterward, the morphological changes of inner neurons and glial cells in the retina were detected by immunofluorescence (IF). Results When compared with the control groups, no difference was observed in both T1DM and T2DM by fundus photographs, while slight exudation and effusion in the blood vessels of retina of rhesus monkeys were found by OCT in DM rhesus monkeys. In addition, the expression of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule (Iba1) were significantly increased in both T1DM (P < .01) and T2DM (P < .05) rhesus monkeys. Moreover, the positive expression of PKC-α, parvalbumin, and NeuN were significantly decreased, while the positive expression of calbindin showed no difference in T1DM group. However, only the expression cells of PKC-α were reduced in T2DM group when compared with that of the control group. Conclusion Astrocytes activation, reactive gliosis, and neurodegeneration were observed in both T1DM and T2DM rhesus monkey models at the early stage of DR.
U2af1 is a haplo-essential gene required for hematopoietic cancer cell survival in mice.

Somatic mutations in the spliceosome gene U2AF1 are common in patients with myelodysplastic syndromes. U2AF1 mutations that code for the most common amino acid substitutions are always heterozygous, and the retained wild-type allele is expressed, suggesting that mutant hematopoietic cells may require the residual wild-type allele to be viable. We show that hematopoiesis and RNA splicing in U2af1 heterozygous knock-out mice was similar to control mice, but that deletion of the wild-type allele in U2AF1(S34F) heterozygous mutant expressing hematopoietic cells (i.e., hemizygous mutant) was lethal. These results confirm that U2AF1 mutant hematopoietic cells are dependent on the expression of wild-type U2AF1 for survival in vivo and that U2AF1 is a haplo-essential cancer gene. Mutant U2AF1 (S34F) expressing cells were also more sensitive to reduced expression of wild-type U2AF1 than non-mutant cells. Furthermore, mice transplanted with leukemia cells expressing mutant U2AF1 had significantly reduced tumor burden and improved survival after the wild-type U2af1 allele was deleted compared to when it was not deleted. These results suggest that selectively targeting the wild-type U2AF1 allele in heterozygous mutant cells could induce cancer cell death and be a therapeutic strategy for patients harboring U2AF1 mutations.