Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of cocaine addiction-like behavior in heterogeneous stock rats

Twin studies suggest that approximately 50% of the vulnerability to cocaine use disorder is determined by genetic factors, but genome-wide association studies (GWAS) in humans have only begun to identify specific genes that confer this risk. The identification of a set of single nucleotide polymorphisms (SNPs) associated with increased vulnerability to develop compulsive cocaine use represents a major goal for understanding of the genetic risk factors to cocaine use disorder and facilitating the identification of novel druggable targets. Here we characterized addiction-like behaviors in heterogeneous stock (HS) rats, a unique outbred strain of rats characterized by high genetic variability that has been developed to mimic genetic variability in humans. HS rats were allowed to self-administer cocaine 6h/daily for 14 days. Animals were also screened for compulsive cocaine use, using progressive-ratio (PR) and responding despite adverse consequences (contingent foot shocks). To minimize cohort-specific effects, we used large cohorts (n = 46-60) and normalized the level of responding within cohorts using a Z-score. To take advantage of the three behaviors related to compulsive intake and further identify subjects that are consistently vulnerable vs. resilient to compulsive cocaine use we computed an Addiction index by averaging normalized responding (Z-scores) for the three behavioral tests. Results showed high individual variability between vulnerable and resilient rats that is likely to facilitate detection of gene variants associated with vulnerable vs. resilient individuals. Such data will have considerable translational value for designing pharmacogenetic studies in humans.
Pectin remodeling belongs to a homeostatic system and triggers transcriptomic and hormonal modulations

Here, we focused on the biological modifications arisen from a strong and transient variation of the pectin methylesterification status during the seed-to-seedling transition. A reverse genetic approach was used to trigger specific reduction of pectin de-methylesterification during the seed maturation stage and the related physiological effects were assessed using a combination of biochemical, transcriptomic and microscopic analyses. Arabidopsis PME36 is required to implement the characteristic pattern of de-methylesterified pectin in the mature seed. While this pattern is strongly impaired in pme36-1 and pme36-2 mature seed, no phenotypical effect is observed in the knockout mutant during seed germination. By analyzing hormone homeostasis and gene expression regulation, we show a strong and dynamic physiological disorder in the mutant, which reveals the existence of a complex compensatory mechanism overcoming the defect in pectin de-methylesterification. Our results reveal that pectin methylesterification status acts as upstream modulator involved in an undescribed homeostatic system in which pectin remodeling, hormone signaling and transcriptomic regulations interact to ensure the maintenance of a normal seed-to-seedling developmental program.
Automated identification of piglet brain tissue from MRI images using Region-based Convolutional Neural Networks

Magnetic Resonance Imaging is an important tool for characterizing volumetric changes of the piglet brain during development. Typically, an early step of an imaging analysis pipeline is brain extraction, or skull stripping. Brain extractions are usually performed manually; however, this approach is time-intensive and can lead to variation between brain extractions when multiple raters are used. Automated brain extractions are important for reducing the time required for analyses and improving the uniformity of the extractions. Here we demonstrate the use of Mask R-CNN, a Region-based Convolutional Neural Network (R-CNN), for automated brain extractions of piglet brains. We validate our approach using Nested Cross-Validation on six sets of training/validation data drawn from 32 pigs. Visual inspection of the extractions shows acceptable accuracy, Dice coefficients are in the range of 0.95-0.97, and Hausdorff Distance values in the range of 4.1-8.3 voxels. These results demonstrate that R-CNNs provide a viable tool for skull stripping of piglet brains.
European stakeholder perspectives on challenges to rare disease drug development – a qualitative study

ABSTRACT Background The multifaceted challenges of rare disease research remain, leaving a large proportion of rare disease patients without treatment options. This study aims to identify the challenges of rare disease drug development. Research design & methods Ten semi-structured interviews were carried out with a range of stakeholders. Thematic analysis was conducted to identify common and important themes. Results Four overarching themes of stakeholder engagement, regulatory structure, data, and patient support were identified, encompassing fifteen subthemes. Conclusion The presence of an active patient group is a significant factor in reducing barriers to rare diseases treatment development. Effective collaboration between the various stakeholders of rare disease research is crucial.
Why Can’t I Stop Using Social Media Problematically? The Impact of Norm and Neutralization from the Regulatory Focus Perspective

ABSTRACT Problematic social media use has increasingly become an issue in schools and companies. Individuals often attempt to reduce their problematic use, but some may not be successful. This implies that there are both impeding and maintaining factors influencing problematic use and that different individuals may follow different mechanisms during problematic use. Drawing on cognitive dissonance theory and regulatory focus theory, our study develops a theoretical model to describe how impeding factors (here, injunctive norms) and maintaining factors (neutralization) influence individuals’ intention to reduce problematic use through guilt, as well as how the effects of these factors are moderated by individuals’ regulatory focus. The results provide strong support for our model. While injunctive norms have a stronger effect on prevention-focused users, the effect of neutralization is stronger on promotion-focused users. Our study highlights the importance of regulatory focus to our understanding of the differential impact of injunctive norms and neutralization and suggests that future studies further examine how individuals experience cognitive dissonance following different mechanisms. Our results suggest that when trying to reduce students’ problematic social media use, teachers need to follow different approaches for individuals with different types of regulatory focus.
An (un)happy marriage: child psychotherapy with children who are medicated for ADHD

ABSTRACT Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common psychiatric diagnoses given in childhood. The recommended treatment is medication in combination with behavioural intervention, and psychoanalytic treatments are rarely recommended or sought. However, in recent decades, there has been an increase in psychoanalytic interest in ADHD, conceptualising it as a complex, biopsychosocial phenomenon requiring a multimodal approach, and suggesting that psychoanalytic psychotherapy can be helpfully and effectively combined with medication in treatment. This study aimed to empirically investigate this practice, by interviewing psychoanalytic child psychotherapists about their experiences of treating children medicated for ADHD. Semi-structured interviews were carried out with six child psychotherapists. The data were analysed qualitatively, using thematic analysis and discourse analysis. Participants presented psychotherapy and medication as theoretically compatible and complementary, but expressed uncertainty about and resistance to the use of medication alongside psychotherapy in practice. Interviewees adopted positions of compliance, avoidance and resistance to the practice of combining medication and psychotherapy, understood as negotiations of the powerful medical discourse of ADHD. While the literature emphasises the potential for psychopharmacological and psychoanalytic approaches to be mutually enriching, this study highlights the challenges of adopting a multi-perspective approach in this contested field.
Hydrogen Atom and Molecule Adsorptions on FeCrAl (100) Surface: A First-Principle Study

FeCrAl alloys are promising accident-tolerant fuel (ATF) cladding materials for applications in light water reactors (LWRs). Despite the excellent mechanical and antioxidation properties, this series of iron-based alloys has poor hydrogen embrittlement (HE) resistance due to the strong hydrogen uptaking ability. The hydrogen embrittlement effect can cause the degradation and premature failure of the material, and this effect can be enhanced by the high-temperature/high-pressure/high-irradiation environment in reactors. So, the potential danger should be taken seriously. In this paper, we have studied the hydrogen atom and molecule adsorptions on both Fe (100) and FeCrAl (100) surfaces to discover how the hydrogen atom and molecule (H/H2) interact with the Fe and FeCrAl (100) surface in the first place. The results show that there are strong element effects on the FeCrAl surface. The Al atom itself has no interaction with hydrogen. When the Al atom is beside the Fe atom, this Fe atom has a slightly lower interaction with hydrogen. However, the Al atom beside the Cr atom will enhance the hydrogen interaction with this Cr atom. On the other hand, when the Cr atom is beside the Fe atom, these two atoms (Fe–Cr bridge site) can reduce the interactions with H. In addition, when two Cr and two Fe atoms together make a four-fold site (FF site), the two Cr atoms can increase the interaction of the two Fe atoms with H. The element effects discovered can be a good guide for making hydrogen prevention coatings.
Jordanian Men's Experience of Emotional Abuse in Marital Relationships: The Role of Marriage Length and Motivation

Though emotional abuse is one of the worst and most common types of intimate partner violence, it has not been investigated in Arabic literature. Thus, this study explored the prevalence of emotional abuse among married Jordanian men. Furthermore, the moderating roles of marriage length, marriage motivation, age, and area in the path to emotional abuse were investigated. An online survey was conducted using a random sample of Jordanian married men in Amman. A total of 1,003 participants with an average age of 42.51 and a marital relationship duration ranging from 1 to 53 years were selected. The results revealed that isolation was the most prevalent emotional abuse domain, followed by degradation, property damage, and sexual coercion. However, all emotional abuse domains were more prevalent among rural rather than urban men, in both traditional and love marriages. Emotional abuse was higher among men who married for love. Younger men reported experiencing higher emotional abuse levels, which declined with age and increasing marriage length. Further research is required to explore the nature of emotional abuse forms and their underlying reasons among married men, as differences in sociodemographic characteristics could affect the identification and understanding of emotional abuse and contribute to developing an intellectual framework capable of finding solutions for abusive marital relations in the Jordanian context.
Administration of All-Trans Retinoic Acid to Pregnant Sows Alters Gut Bacterial Community of Neonatal Piglets With Different Hoxa1 Genotypes

Administration of all-trans retinoic acid (ATRA) to pregnant sows improves developmental defects of Hoxa1–/– fetal pigs, and this study aimed to explore the influence of maternal ATRA administration during pregnancy on gut microbiota of neonatal piglets. Samples of jejunal and ileal meconium of neonatal piglets before suckling were collected including 5 Hoxa1–/– and 20 non-Hoxa1–/– (Hoxa1+/+ and Hoxa1+/−) neonatal piglets from the control group and 5 Hoxa1–/– and 7 non-Hoxa1–/– neonatal piglets from the experimental group. Results indicated that Hoxa1 mutation shaped the bacterial composition of the jejunum and ileum of neonatal piglets and Hoxa1–/– neonatal piglets had significantly higher diversity and species richness, higher relative abundance of phylum Bacteroidetes, lower relative abundances of phylum Firmicutes and genus Lactobacillus, and lower ratio of Firmicutes to Bacteroidetes than non-Hoxa1–/– neonatal piglets. After maternal ATRA administration, Hoxa1–/– neonatal piglets had significantly higher diversity and species richness, higher relative abundances of two bacterial phyla (Bacteroidetes and Proteobacteria), and lower relative abundances of phylum Firmicutes and genus Lactobacillus in the jejunum than non-Hoxa1–/– neonatal piglets. Hoxa1–/– neonatal piglets delivered by sows with maternal ATRA administration had lower diversity and species richness and higher relative abundance of phylum Firmicutes in the jejunum than Hoxa1–/– neonatal piglets born by sows with no maternal ATRA administration. Non-Hoxa1–/– neonatal piglets delivered by sows with maternal ATRA administration had higher diversity and species richness and significantly lower relative abundances of phyla Firmicutes and Actinobacteria and genus Lactobacillus in the ileum than non-Hoxa1–/– neonatal piglets born by sows with no maternal ATRA administration. Hoxa1 mutation decreased the expression of bacterial genes involved in ABC transporters, purine metabolism, and aminoacyl-tRNA biosynthesis and increased the expression of bacterial genes involved in two-component system, starch and sucrose metabolism, and arginine and proline metabolism. Maternal ATRA administration decreased the expression of bacterial genes involved in arginine and proline metabolism, peptidoglycan biosynthesis, and fatty acid biosynthesis. Hoxa1 mutation resulted in bacterial dysbiosis of the small intestine of Hoaxa1–/– neonatal piglets, and maternal ATRA administration restored the bacterial dysbiosis of Hoxa1–/– neonatal piglets and altered the bacterial composition of the small intestine of non-Hoxa1–/– neonatal piglets.
Effects of Brain Atlases and Machine Learning Methods on the Discrimination of Schizophrenia Patients: A Multimodal MRI Study

Recently, machine learning techniques have been widely applied in discriminative studies of schizophrenia (SZ) patients with multimodal magnetic resonance imaging (MRI); however, the effects of brain atlases and machine learning methods remain largely unknown. In this study, we collected MRI data for 61 first-episode SZ patients (FESZ), 79 chronic SZ patients (CSZ) and 205 normal controls (NC) and calculated 4 MRI measurements, including regional gray matter volume (GMV), regional homogeneity (ReHo), amplitude of low-frequency fluctuation and degree centrality. We systematically analyzed the performance of two classifications (SZ vs NC; FESZ vs CSZ) based on the combinations of three brain atlases, five classifiers, two cross validation methods and 3 dimensionality reduction algorithms. Our results showed that the groupwise whole-brain atlas with 268 ROIs outperformed the other two brain atlases. In addition, the leave-one-out cross validation was the best cross validation method to select the best hyperparameter set, but the classification performances by different classifiers and dimensionality reduction algorithms were quite similar. Importantly, the contributions of input features to both classifications were higher with the GMV and ReHo features of brain regions in the prefrontal and temporal gyri. Furthermore, an ensemble learning method was performed to establish an integrated model, in which classification performance was improved. Taken together, these findings indicated the effects of these factors in constructing effective classifiers for psychiatric diseases and showed that the integrated model has the potential to improve the clinical diagnosis and treatment evaluation of SZ.
Adherence to Traditional Chinese Postpartum Practices and Postpartum Depression: A Cross-Sectional Study in Hunan, China

Background: The relationship between adherence to traditional Chinese postpartum practices (known as “doing-the-month”) and postpartum depression (PPD) remains unknown. Practices including restrictions on diet, housework and social activity, personal hygiene, and cold contact, could introduce biological, psychological, and socio-environmental changes during postpartum. Methods: The cross-sectional study included 955 postpartum women in obstetric clinics in Hunan Province of China between September 2018 to June 2019. Thirty postpartum practices were collected by a self-report online structured questionnaire. Postpartum depression symptoms were assessed by the Chinese version of the Edinburgh Postnatal Depression Scale (EPDS). Multivariable linear regression was used to estimate the differences in EPDS scores according to adherence to postpartum practices. Firth's bias-reduced logistic regression was employed to analyze the binary classification of having PPD symptoms (EPDS ≥ 10). Results: Overall, both moderate and low adherence to postpartum practices appeared to be associated with higher EPDS scores (adjusted difference 1.07, 95% CI 0.20, 1.94 for overall moderate adherence; and adjusted difference 1.72, 95% CI 0.84, 2.60 for overall low adherence). In analyses by practice domain, low adherence to housework-related and social activity restrictions was associated with having PPD symptoms compared with high adherence (OR 1.61, 95% CI 1.07, 2.43). Conclusions: Low adherence to traditional Chinese postpartum practices was associated with higher EPDS scores indicating PPD symptoms, especially in the domain of housework-related and social activity restrictions. Psychosocial stress and unsatisfactory practical support related to low adherence to postpartum practices might contribute to PPD. Longitudinal study and clinical assessment would be needed to confirm these findings.
Iberian Protected Areas Capture Regional Functional, Phylogenetic and Taxonomic Diversity of Most Tetrapod Groups

Protected areas (PAs) have been created with the purpose of preserving biodiversity, acting as refuges from anthropogenic pressures. Traditionally, PAs have been designed and managed to represent mainly taxonomic diversity, ignoring other diversity facets such as its functional and phylogenetic components. Yet, functional and phylogenetic diversity are, respectively, connected with species’ roles on ecosystems and evolutionary history held within communities. Here, we focused on the amphibian, reptile, resident breeding bird, and non-flying mammal faunas of the national and natural parks of the Iberian Peninsula, to evaluate whether these PAs are adequately representing regional functional, phylogenetic, and taxonomic diversity of each group. Specifically, we computed functional and phylogenetic diversity within each PA, and then compared those values to the ones obtained from a random assembly of species from the regional pool, that was defined as the region encompassing the PA and a neighboring area of 50 km beyond its boundary. We also calculated the proportion of species in each regional pool that were present within the PAs. In general, the functional and phylogenetic diversity of amphibians, reptiles and non-flying mammals found within PAs did not differ significantly from random expectations generated from the species pertaining to the regional pool, although a few PAs showed a higher diversity. In contrast, resident breeding birds presented lower functional and phylogenetic diversity than expected by chance in many of the PAs, which could relate to climatic variables and the habitat specificity of some species. The proportion of species from the regional pools that are present in the PAs was high for amphibians, reptiles and mammals, and slightly lower for birds. These results suggest that the Iberian natural and national parks are effectively capturing the functional, phylogenetic and taxonomic diversity of most tetrapod assemblages present at the regional level. Future studies should identify priority areas to expand the representation of these biodiversity components, and assess potential effects of climate and land-use changes on current patterns.
Congenital Deficiency of Conventional Dendritic Cells Promotes the Development of Atopic Dermatitis-Like Inflammation

Atopic dermatitis (AD) is a common pruritic inflammatory skin disease characterized by impaired epidermal barrier function and dysregulation of Thelper-2 (TH2)-biased immune responses. While the lineage of conventional dendritic cells (cDCs) are implicated to play decisive roles in T-cell immune responses, their requirement for the development of AD remains elusive. Here, we describe the impact of the constitutive loss of cDCs on the progression of AD-like inflammation by using binary transgenic (Tg) mice that constitutively lacked CD11chi cDCs. Unexpectedly, the congenital deficiency of cDCs not only exacerbates the pathogenesis of AD-like inflammation but also elicits immune abnormalities with the increased composition and function of granulocytes and group 2 innate lymphoid cells (ILC2) as well as B cells possibly mediated through the breakdown of the Fms-related tyrosine kinase 3 ligand (Flt3L)-mediated homeostatic feedback loop. Furthermore, the constitutive loss of cDCs accelerates skin colonization of Staphylococcus aureus (S. aureus), that associated with disease flare. Thus, cDCs maintains immune homeostasis to prevent the occurrence of immune abnormalities to maintain the functional skin barrier for mitigating AD flare.
Antibody Mediated Immunity to SARS-CoV-2 and Human Coronaviruses: Multiplex Beads Assay and Volumetric Absorptive Microsampling to Generate Immune Repertoire Cartography

The COVID-19 pandemic is caused by SARS-CoV-2, a novel zoonotic coronavirus. Emerging evidence indicates that preexisting humoral immunity against other seasonal human coronaviruses (HCoVs) plays a critical role in the specific antibody response to SARS-CoV-2. However, current work to assess the effects of preexisting and cross-reactive anti-HCoVs antibodies has been limited. To address this issue, we have adapted our previously reported multiplex assay to simultaneously and quantitatively measure anti-HCoV antibodies. The full mPlex-CoV panel covers the spike (S) and nucleocapsid (N) proteins of three highly pathogenic HCoVs (SARS-CoV-1, SARS-CoV-2, MERS) and four human seasonal strains (OC43, HKU1, NL63, 229E). Combining this assay with volumetric absorptive microsampling (VAMS), we measured the anti-HCoV IgG, IgA, and IgM antibodies in fingerstick blood samples. The results demonstrate that the mPlex-CoV assay has high specificity and sensitivity. It can detect strain-specific anti-HCoV antibodies down to 0.1 ng/ml with 4 log assay range and with low intra- and inter-assay coefficients of variation (%CV). We also estimate multiple strain HCoVs IgG, IgA and IgM concentration in VAMS samples in three categories of subjects: pre-COVID-19 (n=21), post-COVID-19 convalescents (n=19), and COVID-19 vaccine recipients (n=14). Using metric multidimensional scaling (MDS) analysis, HCoVs IgG concentrations in fingerstick blood samples were well separated between the pre-COVID-19, post-COVID-19 convalescents, and COVID-19 vaccine recipients. In addition, we demonstrate how multi-dimensional scaling analysis can be used to visualize IgG mediated antibody immunity against multiple human coronaviruses. We conclude that the combination of VAMS and the mPlex-Cov assay is well suited to performing remote study sample collection under pandemic conditions to monitor HCoVs antibody responses in population studies.