Miracle-dz/UniFAR-FTUs huggingface dataset:
Towards understanding neurocognitive mechanisms of parenting: Maternal behaviors and structural brain network organization in late childhood

A substantial body of knowledge suggests that exposure to adverse family environments – including violence and neglect – influences many aspects of brain development. Relatively less attention has been directed toward the influence of “normative” differences in parenting behaviors. Given the rapid brain reorganization during late childhood, parenting behaviors are particularly likely to impact the structure of the brain during this time. This study investigated associations between maternal parenting behaviors and the organization of structural brain networks in late childhood, as measured by structural covariance. One hundred and forty‐five typically developing 8‐year‐olds and their mothers completed questionnaire measures and two observed interaction tasks; magnetic resonance imaging (MRI) scans were obtained from the children. Measures of maternal negative, positive, and communicative behavior were derived from the interaction tasks. Structural covariance networks based on partial correlations between cortical thickness estimates were constructed and estimates of modularity were obtained using graph theoretical analysis. High levels of negative maternal behavior were associated with low modularity. Minimal support was found for an association between positive maternal behaviors and modularity and between maternal communicative behaviors and modularity. Our findings suggest that variation in negative maternal behavior is associated with the structural organization of brain networks in children.
Successful implementation of telemedicine depends on personal relations between company representatives and healthcare providers: A qualitative study of business models for Danish home telemonitoring

The struggle to transform telemedicine from project level to daily clinical practice is ongoing. An assessment of the business models of telemedicine applications could provide insights into how to facilitate this transition. Our aim was to identify the qualitative characteristics of business models of long-term operational telemedicine providers in Denmark. A structured interview study design was applied to interviews of representatives from seven Danish companies providing home telemonitoring in long-term operation. Data was analysed using Osterwalder’s Business Model Canvas framework. Multiple themes emphasized the importance of strong personal relationships between company representatives and healthcare providers. Personal relations could 1) secure a strong relationship to lead users and clinical ambassadors; 2) facilitate work with healthcare providers to develop, test and revise value propositions; 3) promote user support and education; 4) establish an indirect connection between companies and healthcare managers or decision makers. Thus, a strong personal relationship between company representatives and healthcare providers is of paramount importance when integrating home telemonitoring from project stage into clinical practice. However, this strategy could lack patient involvement, use of data, and business scalability. Additionally, companies with the ability to establish strong personal connections could be favoured over companies which provide strong clinical and economic evidence.
Meiotic chromosome axis remodelling is critical for meiotic recombination in Brassica rapa

Abstract Meiosis generates genetic variation through homologous recombination (HR) that is harnessed during breeding. HR occurs in the context of meiotic chromosome axes and the synaptonemal complex. To study the role of axis remodelling in crossover (CO) formation in a crop species, we characterized mutants of the axis-associated protein ASY1 and the axis-remodelling protein PCH2 in Brassica rapa. asy1 plants form meiotic chromosome axes that fail to synapse. CO formation is almost abolished, and residual chiasmata are proportionally enriched in terminal chromosome regions, particularly in the nucleolar organizing region (NOR)-carrying chromosome arm. pch2 plants show impaired ASY1 loading and remodelling, consequently achieving only partial synapsis, which leads to reduced CO formation and loss of the obligatory CO. PCH2-independent chiasmata are proportionally enriched towards distal chromosome regions. Similarly, in Arabidopsis pch2, COs are increased towards telomeric regions at the expense of (peri-) centromeric COs compared with the wild type. Taken together, in B. rapa, axis formation and remodelling are critical for meiotic fidelity including synapsis and CO formation, and in asy1 and pch2 CO distributions are altered. While asy1 plants are sterile, pch2 plants are semi-sterile and thus PCH2 could be an interesting target for breeding programmes.
Peste des Petits Ruminants Virus-Induced Novel MicroRNA miR-3 Contributes To Inhibit Type I IFN Production by Targeting IRAK1

Peste des petits ruminants virus (PPRV) induces in the host a transient but severe immunosuppression, which threatens both small livestock and endangered susceptible wildlife populations in many countries. Despite extensive research, the mechanism underlying PPRV immune system evasion remains elusive. ABSTRACT Peste des petits ruminants virus (PPRV) is an important pathogen that seriously influences the productivity of small ruminants worldwide. PPRV has evolved several mechanisms to evade type I interferon (IFN-I) responses. We report that a novel microRNA in goat peripheral blood mononuclear cells (PBMCs) called miR-3 is upregulated by PPRV to facilitate virus infection. Furthermore, PPRV V protein alone was sufficient to induce novel miR-3 expression, and NF-κB and p38 pathways may be involved in the induction of miR-3 during PPRV infection. Importantly, we demonstrated that miR-3 was a potent negative regulator of IFN-α production by targeting interleukin-1 receptor-associated kinase 1 (IRAK1), which resulted in the enhancement of PPRV infection. In addition, we found that PPRV infection can activate interferon-stimulated genes (ISGs) through IFN-independent and IRF3-dependent pathways. Moreover, our data revealed that miR-3-mediated regulation of IFN-α production may be involved in the differential susceptibility between goat and sheep to PPRV. Taken together, our findings identify a new strategy by PPRV to escape IFN-I-mediated antiviral immune responses by engaging cellular microRNA, and thus leads to improved understanding of PPRV pathogenesis. IMPORTANCE Peste des petits ruminants virus (PPRV) induces in the host a transient but severe immunosuppression, which threatens both small livestock and endangered susceptible wildlife populations in many countries. Despite extensive research, the mechanism underlying PPRV immune system evasion remains elusive. Our data provide the first direct evidence that a novel microRNA-3 (miR-3) feedback-inhibits type I IFN signaling when goat PBMCs are infected with PPRV vaccine strain N75/1, thus promoting the infection. In this study, the target of miR-3 was identified as IRAK1, which is important for type I IFN production. Moreover, we identified NF-κB and p38 pathways as possibly involved in miR-3 induction in response to PPRV infection. Taken together, our research has provided new insight into understanding the effects of miRNA on host-virus interactions, and revealed a potential therapeutic target for antiviral intervention.
Vascularized adipocyte organoid model using isolated human microvessel fragments

Tissue organoids are proving valuable for modeling tissue health and disease in a variety of applications. This is due, in part, to the dynamic cell–cell interactions fostered within the 3D tissue-like space. To this end, the more that organoids recapitulate the different cell–cell interactions found in native tissue, such as that between parenchyma and the microvasculature, the better the fidelity of the model. The microvasculature, which is comprised of a spectrum of cell types, provides not only perfusion in its support of tissue health, but also important cellular interactions and biochemical dynamics important in tissue phenotype and function. Here, we incorporate whole, intact human microvessel fragments isolated from adipose tissue into organoids to form both mesenchymal stem cell (MSC) and adipocyte vascularized organoids. Isolated microvessels retain their native structure and cell composition, providing a more complete representation of the microvasculature within the organoids. Microvessels expanded via sprouting angiogenesis within organoids comprised of either MSCs or MSC-derived adipocytes grew out of the organoids when placed in a 3D collagen matrix. In MSC organoids, a ratio of 50 MSCs to 1 microvessel fragment created the optimal vascularization response. We developed a new differentiation protocol that enabled the differentiation of MSCs into adipocytes while simultaneously promoting microvessel angiogenesis. The adipocyte organoids contained vascular networks, were responsive in a lipolysis assay, and expressed the functional adipocyte markers adiponectin and peroxisome proliferator-activated receptor gamma. The presence of microvessels promoted insulin receptor expression by adipocytes and modified interleukin-6 secretion following a tumor necrosis factor alpha challenge. Overall, we demonstrate a robust method for vascularizing high cell-density organoids with potential implications for other tissues as well.
Rapid Identification of Tropilaelaps Mite (Mesostigmata: Laelapidae) Species Using a COI Barcode-HRM

Abstract Tropilaelaps mite (Mesostigmata: Laelapidae) is an ectoparasite of bees present, to date, only on the Asian continent. In the context of the threat of Tropilaelaps's introduction into new regions, accurate, rapid, and sensitive detection of the Tropilaelaps spp. is essential. In the present study, we developed a novel molecular method for bee mite's identification, which consists of a new real-time PCR method. A high-resolution melting analysis (HRM) was then performed on the amplified products to differentiate the species. PCR amplification was applied on the cytochrome c oxidase subunit I gene (580 bp). Short fragments from the most variable regions of this gene were identified in silico to amplify and discriminate among the four Tropilaelaps species. Four reference plasmids were synthesized to characterize species by well-distinguished melting curves. The method was then validated in terms of its specificity and sensitivity using a panel of 12 specimens. The results showed that an HRM method can be applied for the intended objective: for rapid and simultaneous identification of Tropilaelaps species. To our knowledge, this study reports the first direct HRM assay developed for the genome of a bee mite, specific for Tropilaelaps species. This COI barcode-HRM technique could be a promising tool for mite species identification.
Succinylation of H3K122 destabilizes nucleosomes and enhances transcription

Histone post‐translational modifications (PTMs) are key players in chromatin regulation. The identification of novel histone acylations raises important questions regarding their role in transcription. In this study, we characterize the role of an acylation on the lateral surface of the histone octamer, H3K122 succinylation (H3K122succ), in chromatin function and transcription. Using chromatin succinylated at H3K122 in in vitro transcription assays, we show that the presence of H3K122succ is sufficient to stimulate transcription. In line with this, we found in our ChIP assays H3K122succ enriched on promoters of active genes and H3K122succ enrichment scaling with gene expression levels. Furthermore, we show that the co‐activators p300/CBP can succinylate H3K122 and identify sirtuin 5 (SIRT5) as a new desuccinylase. By applying single molecule FRET assays, we demonstrate a direct effect of H3K122succ on nucleosome stability, indicating an important role for histone succinylation in modulating chromatin dynamics. Together, these data provide the first insights into the mechanisms underlying transcriptional regulation by H3K122succ.
Extemporaneous compounding and administration of tretinoin slurry for acute promyelocytic leukemia

Introduction Acute promyelocytic leukemia (APL) is a potentially curable malignancy with 4-year overall survival rates >90%. Early complications from the disease or its treatment may result in a loss of oral access and require alternative administration of medications. Tretinoin has been the backbone of APL therapy since the late 1990s and is only available as a liquid filled capsule. Case report Two patients with high-risk APL were unable to safely swallow tretinoin capsules due to complications of their disease. Management & outcome We prepared a tretinoin slurry using tretinoin 10 mg capsules, sterile water, and mineral oil at a ratio of 1 capsule to 2.75 mL sterile water to 1.25 mL mineral oil. This was successfully administered to both patients and no doses of tretinoin slurry were missed by either patient. In the patient who has long-term follow up available, a complete remission was achieved. Discussion Due to tretinoin’s known teratogenicity, this capsule should not be crushed, cut, or open, which limits its use in patients without oral access. Alternative routes of administration, such as via a nasogastric tube or sublingually, have not been safe and effective. By preparing a tretinoin slurry in our hazardous extemporaneous compounding area, we were able to safely and effectively prepare a tretinoin slurry that was successfully administered to two patients. This alternative preparation did not alter long-term outcomes and represents a viable option for patients who do not have oral access.
Greenland and Svalbard glaciers host unknown basidiomycetes: the yeast Camptobasidium arcticum sp. nov. and the dimorphic Psychromyces glacialis gen. and sp. nov.

Sampling campaigns in Greenland and Svalbard were executed to explore fungal diversity in cold habitats. Three very abundant groups of strains were discovered, consisting either of recently described or of yet-undescribed psychrophilic and oligotrophic yeasts and dimorphic fungi, accounting for around 50 % of the total cultivable diversity of basidiomycetes in our studies. The occurrence of these taxa has also been demonstrated by culture-independent methods. Based on phylogenetic analyses of ribosomal gene cluster sequences (D1/D2 domains of 28S (LSU), 18S (SSU), ITS with 5.8S rDNA) and sequences of protein-coding genes for elongation factor one alpha (TEF), cytochrome b (CYTB) and two subunits of the RNA polymerase II (RPB1 and RPB2) obtained from pure cultures, the isolated taxa presented in this study belong to Basidiomycota, subphylum Pucciniomycotina, class Microbotryomycetes, family Camptobasidiaceae. The dataset of the sequences supported the recognition of three species: Camptobasidium gelus, Camptobasidium arcticum sp. nov. (ex-type strain EXF-12713) and Psychromyces glacialis gen. and sp. nov. (ex-type strain EXF-13111). Camptobasidium gelus was found in the Svalbard and Greenland samples, while representatives of the here proposed new species, C. arcticum, were found only in the Greenland Ice Sheet. Psychromyces gen. nov. was erected for the dimorphic/filamentous isolates found in Svalbard and Greenland glacial environments. The taxon, for which the invalid name ‘Rhodotorula svalbardensis’ has been used, belongs to this genus. Based on ribosomal genes, Camptobasidium arcticum and Psychromyces glacialis are related, phylogenetically most closely related to the genera Glaciozyma and Cryolevonia. Seven genes phylogeny restricted to taxa with available sequences, supported the placement of Psychromyces to Camptobasidiaceae.
Segmental adsorption energies for polymers on silica and alumina.

Segmental adsorption energies for polymers on inorganic solids were determined from adsorption/desorption transitions in binary solvent mixtures which were measured by thin layer chromatography. Polystyrene, poly(methyl methacrylate), poly(butyl methacrylate), poly(tetrahydrofuran) and poly(ethylene oxide) were classified according to their adsorption strength on silica and alumina. A consistent trend with respect to the adsorption energy was observed for both substrates.
Pharmacokinetics of Nitrate and Nitrite Following Beetroot Juice Drink Consumption

Background: Nitrate (NO3−)-rich beetroot (BR) juice supplementation has been shown to improve cardiovascular function via reduction to nitrite (NO2−) and then to the bioactive molecule nitric oxide (NO). However, limited research exists for the role of inorganic NO2− that is contained naturally within BR. Objective: As BR juice can naturally contain both NO3− and NO2− the objective of this study was to evaluate the individual effects of NO3− and NO2− consumed from BR on plasma [NO3−]/[NO2−] and their subsequent effects on various cardiovascular measures. Design: In four separate treatments, 11 healthy adults consumed 250 mL of BR containing one of the following: (i) high NO3−, low NO2− (HL; 572 mg NO3−, 32 mg NO2−); (ii) medium NO3−, medium NO2− (MM; 280 mg NO3−, 237 mg NO2−); (iii) low NO3−, medium NO2− (LM; 43 mg NO3−, 262 mg NO2−); (iv) placebo (PL; low NO3−, low NO2−: 8 mg NO3−, 5.8 mg NO2−). Plasma [NO3−]/[NO2−], blood pressure, heart rate, mean arterial pressure (MAP), cardiac output and stroke volume were measured at baseline and every hour or second hour for 6 h post-BR consumption. Outcomes: Ingestion of the HL and MM BR increased plasma [NO2−] and [NO3−] after 2 h, with both remaining elevated after 6 h (p < 0.05). LM increased plasma [NO3−] (p < 0.05) but did not increase plasma [NO2−] compared to PL (p = 0.177). MAP was lower following the consumption of HL at 4 h and LM at 6 h (p < 0.05). Conclusion: Inorganic NO3− consumption is the critical factor in elevating plasma [NO3−] and [NO2−]; however, both NO2− and NO3− show potential to reduce MAP. The known reduction of systolic blood pressure (SBP)/diastolic blood pressure (DBP) following NO3− supplementation was not observed, making it unclear if NO2− contributes to a reduction in SBP/DBP alongside NO3−.
The association between medical students' motivation with learning environment, perceived academic rank, and burnout

Objectives To assess the correlations between extrinsic and intrinsic motivation, personal growth and quality of life with learning environment perceptions, perceived academic rank and burnout among medical students. Methods Cross-sectional questionnaires were administered to medical students at three medical schools in Israel, Malaysia, and China, at the end of one academic year. Surveys included demographic data, students' perceived academic rank, two learning environment perceptions scales, and scales for personal growth, goal orientation, burnout and quality of life. Comparative analyses were made to determine the significance of relationships between the outcome measures and control variables, using a series of t-tests. Pearson correlation coefficients were used to test the hypothesis. Results Sixty-four percent (400/622) of the students responded. Significant correlations were found between: intrinsic motivation (r(398) =. 37, p<. 001); personal growth (r(398)=. 62, p<. 001); and quality of life (r(398)= . 48, p <. 001) with higher learning environment perceptions, intrinsic motivation (r(398)= . 21, p<. 001); personal growth (r(398) =. 21, p< . 001); and quality of life (r(398)=. 18, p<. 001) with perceived academic rank, and negative correlation between personal growth (r(398) =-. 38, p<. 001); and quality of life (r(398) =-. 42, p<. 001) with burnout. Conclusions Intrinsic motivation, personal growth and quality of life are correlated with higher learning environment perceptions and perceived academic rank. Burnout is influenced by personal growth and quality of life. We suggest focusing on motivation profiles before acceptance to medical school and during studies.
Sex-Stratified Gene Regulatory Networks Reveal Female Key-Driver Genes of Atherosclerosis Involved in Smooth Muscle Cell Phenotype Switching.

Background: While sex differences in coronary artery disease (CAD) are widely accepted with women developing more stable atherosclerosis than men, the underlying pathobiology of such differences remains largely unknown. In CAD, recent integrative systems biological studies have inferred gene regulatory networks (GRNs). Within these GRNs, key driver genes have shown great promises but have thus far been unidentified in females. Methods: We generated sex-specific GRNs of the atherosclerotic arterial wall in 160 females and age-matched males in the Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task (STARNET) study. We integrated the female GRNs with single-cell RNA-sequencing data of the human atherosclerotic plaque and single-cell RNA-sequencing of advanced atherosclerotic lesions from wildtype and Klf4 knock-out atherosclerotic SMC lineage tracing mice. Results: By comparing sex-specific GRNs, we observed clear sex differences in network activity within the atherosclerotic tissues. Genes more active in females were associated with mesenchymal cells and endothelial cells, whereas genes more active in males were associated with the immune system. We determined that key drivers of GRNs active in female CAD were predominantly found in smooth muscle cells (SMCs) by single-cell sequencing of the human atherosclerotic plaques, as well as higher expressed in female plaque SMCs. To study the functions of these female SMC key drivers in atherosclerosis, we examined single-cell RNA-sequencing of advanced atherosclerotic lesions from wildtype and Klf4 knock-out atherosclerotic SMC lineage tracing mice. The female key drivers were found to be expressed by phenotypically modulated SMCs and affected by Klf4, suggesting that sex differences in atherosclerosis involves phenotypic switching of plaque SMCs. Conclusions: Our systems approach provides novel insights into molecular mechanisms that underlie sex differences in atherosclerosis. To discover sex-specific therapeutic targets for atherosclerosis, an increased emphasis on sex-stratified approaches in the analysis of multi-omics datasets is warranted.
Replacement of potatoes with other vegetables and risk of myocardial infarction in the Danish Diet, Cancer and Health cohort

Abstract Intake of vegetables is recommended for the prevention of myocardial infarction (MI). However, vegetables make up a heterogeneous group, and subgroups of vegetables may be differentially associated with MI. The aim of this study was to examine replacement of potatoes with other vegetables or subgroups of other vegetables and the risk of MI. Substitutions between subgroups of other vegetables and risk of MI were also investigated. We followed 29 142 women and 26 029 men aged 50–64 years in the Danish Diet, Cancer and Health cohort. Diet was assessed at baseline by using a detailed validated FFQ. Hazard ratios (HR) with 95 % CI for the incidence of MI were calculated using Cox proportional hazards regression. During 13·6 years of follow-up, 656 female and 1694 male cases were identified. Among women, the adjusted HR for MI was 1·02 (95 % CI 0·93, 1·13) per 500 g/week replacement of potatoes with other vegetables. For vegetable subgroups, the HR was 0·93 (95 % CI 0·77, 1·13) for replacement of potatoes with fruiting vegetables and 0·91 (95 % CI 0·77, 1·07) for replacement of potatoes with other root vegetables. A higher intake of cabbage replacing other vegetable subgroups was associated with a statistically non-significant higher risk of MI. A similar pattern of associations was found when intake was expressed in kcal/week. Among men, the pattern of associations was overall found to be similar to that for women. This study supports food-based dietary guidelines recommending to consume a variety of vegetables from all subgroups.