Miracle-dz/UniFAR-FTUs huggingface dataset:
Developing and Evaluating a Capacity-Building Intervention for Healthcare Providers to Improve Communication Skills and Awareness of Hard of Hearing and D/deaf Populations: Protocol for a Participative Action Research-Based Study

Background: D/deaf and hard of hearing populations are at higher risk for experiencing physical and mental health problems compared to hearing populations. In addition, they commonly encounter barriers to accessing and benefiting from health services, which largely stem from challenges they face in communicating with healthcare providers. Healthcare providers commonly lack tailored communication skills in caring for D/deaf and hard of hearing populations, which lead to difficulties and dissatisfaction for both staff and D/deaf and hard of hearing communities. This research project aims to develop and evaluate a capacity-building intervention for healthcare providers with the goal of increasing their awareness of D/deaf and hard of hearing individuals' experiences with the healthcare system, their distinct needs, and improving their capacity to communicate effectively with this patient population. Methods: This research project features a participative action research design using qualitative and quantitative methods. Consistent with participative action research, the study will actively involve the target populations, key stakeholders and representative associations. The intervention will be developed and tested through iterative phases. The Integrated Model of Training Evaluation and Effectiveness will guide prospective evaluation of the intervention. The latter will involve qualitative and quantitative assessments in participants before and after the intervention and at 6-months follow-up. Discussion: Results will contribute to research aimed at decreasing barriers to accessing and benefiting from healthcare services for D/deaf and hard of hearing individuals. Findings will be presented to representative associations and political authorities, as well as disseminated at research conferences and in peer-reviewed journals.
Longer and Deeper Desaturations Are Associated With the Worsening of Mild Sleep Apnea: The Sleep Heart Health Study

Study Objectives Obesity, older age, and male sex are recognized risk factors for sleep apnea. However, it is unclear whether the severity of hypoxic burden, an essential feature of sleep apnea, is associated with the risk of sleep apnea worsening. Thus, we investigated our hypothesis that the worsening of sleep apnea is expedited in individuals with more severe desaturations. Methods The blood oxygen saturation (SpO2) signals of 805 Sleep Heart Health Study participants with mild sleep apnea [5 ≤ oxygen desaturation index (ODI) < 15] were analyzed at baseline and after a mean follow-up time of 5.2 years. Linear regression analysis, adjusted for relevant covariates, was utilized to study the association between baseline SpO2-derived parameters and change in sleep apnea severity, determined by a change in ODI. SpO2-derived parameters, consisting of ODI, desaturation severity (DesSev), desaturation duration (DesDur), average desaturation area (avg. DesArea), and average desaturation duration (avg. DesDur), were standardized to enable comparisons between the parameters. Results In the group consisting of both men and women, avg. DesDur (β = 1.594, p = 0.001), avg. DesArea (β = 1.316, p = 0.004), DesDur (β = 0.998, p = 0.028), and DesSev (β = 0.928, p = 0.040) were significantly associated with sleep apnea worsening, whereas ODI was not (β = −0.029, p = 0.950). In sex-stratified analysis, avg. DesDur (β = 1.987, p = 0.003), avg. DesArea (β = 1.502, p = 0.024), and DesDur (β = 1.374, p = 0.033) were significantly associated with sleep apnea worsening in men. Conclusion Longer and deeper desaturations are more likely to expose a patient to the worsening of sleep apnea. This information could be useful in the planning of follow-up monitoring or lifestyle counseling in the early stage of the disease.
Central nervous system infusion of TrkB agonist, 7,8-dihydroxyflavone, is ineffective in promoting myelin repair in cuprizone and experimental autoimmune encephalomyelitis mouse models of multiple sclerosis

Small molecular weight functional mimetics of brain-derived neurotrophic factor (BDNF) which act via the TrkB receptor have been developed to overcome the pharmacokinetic limitations of BDNF as a therapeutic agent for neurological disease. Activation of TrkB signalling on oligodendrocytes has been identified as a potential strategy for promoting myelin repair in demyelinating conditions such as Multiple Sclerosis (MS). Here, we tested the efficacy of intracerebroventricular infusion of TrkB agonist 7,8-dihydroxyflavone (DHF) to promote myelin repair in the cuprizone model of de- and remyelination and alter the course of experimental autoimmune encephalomyelitis (EAE), after the onset of clinical signs. In these two distinct, but common mouse models used for the preclinical testing of MS therapeutics, we found that DHF infusion increased the percentage of myelin basic protein and density of oligodendrocyte progenitor cells (OPCs) in the corpus callosum of female C57BL/6 mice after cuprizone demyelination. However, DHF did not alter the percentage of axons myelinated or increase the density of post-mitotic oligodendrocytes in this model. Direct central nervous system infusion of DHF infusion also had no effect on the clinical course of EAE in male and female C57BL/6 mice, and examination of the lumbar spinal cord after 21 days of treatment revealed extensive demyelination, with active phagocytosis of myelin debris by Iba1+ macrophages/microglia. These results indicate that direct central nervous system infusion of DHF is ineffective at promoting myelin repair in toxin-induced and inflammatory models of demyelination.
Identification of heat responsive genes in pea stipules and anthers through transcriptional profiling

Field pea (Pisum sativum L.), a cool-season legume crop, is known for poor heat tolerance. Our previous work identified PR11-2 and PR11-90 as heat tolerant and susceptible lines in a recombinant inbred population. CDC Amarillo, a Canadian elite pea variety, was considered as another heat tolerant variety based on its similar field performance as PR11-2. This study aimed to characterize the differential transcription. Plants of these three varieties were stressed for 3h at 38°C prior to self-pollination, and RNAs from heat stressed anthers and stipules on the same flowering node were extracted and sequenced via the Illumina NovaSeq platform for the characterization of heat responsive genes. In silico results were further validated by qPCR assay. Differentially expressed genes (DEGs) were identified at log2 fold change, the three varieties shared 588 DEGs which were up-regulated and 220 genes which were down-regulated in anthers when subjected to heat treatment. In stipules, 879 DEGs (463/416 upregulation/downregulation) were consistent among varieties. The above heat-induced genes of the two plant organs were related to several biological processes i.e., response to heat, protein folding and DNA templated transcription. Ten gene ontology (GO) terms were over-represented in the consistently down-regulated DEGs of the two organs, and these terms were mainly related to cell wall macromolecule metabolism, lipid transport, lipid localization, and lipid metabolic processes. GO enrichment analysis on distinct DEGs of individual pea varieties suggested that heat affected biological processes were dynamic, and variety distinct responses provide insight into molecular mechanisms of heat-tolerance response. Several biological processes, e.g., cellular response to DNA damage stimulus in stipule, electron transport chain in anther that were only observed in heat induced PR11-2 and CDC Amarillo, and their relevance to field pea heat tolerance is worth further validation.
Outer membrane vesicles produced by pathogenic strains of Escherichia coli block autophagic flux and exacerbate inflammasome activation

Escherichia coli strains are responsible for a majority of human extra-intestinal infections, resulting in huge direct medical and social costs. We had previously shown that HlyF encoded by a large virulence plasmid harbored by pathogenic E. coli is not a hemolysin but a cytoplasmic enzyme leading to the overproduction of outer membrane vesicles (OMVs). Here, we show that these specific OMVs inhibit the autophagic flux by impairing the autophagosome – lysosome fusion, thus preventing the formation of acidic autophagolysosome and autophagosome clearance. Furthermore, HlyF-associated OMVs are more prone to activate the non-canonical inflammasome pathway. Since autophagy and inflammation are crucial in the host’s response to infection especially during sepsis, our findings reveal an unsuspected role of OMVs in the crosstalk between bacteria and their host, highlighting the fact that these extracellular vesicles have exacerbated pathogenic properties.
Evolutionary transcriptomics implicates new genes and pathways in human pregnancy and adverse pregnancy outcomes

Evolutionary changes in the anatomy and physiology of the female reproductive system underlie the origins and diversification of pregnancy in Eutherian (“Placental”) mammals. This developmental and evolutionary history constrains normal physiological functions and biases the ways in which dysfunction contributes to reproductive trait diseases and adverse pregnancy outcomes. Here, we show that gene expression changes in the human endometrium during pregnancy are associated with the evolution of human-specific traits and pathologies of pregnancy. We found that hundreds of genes gained or lost endometrial expression in the human lineage. Among these are genes that may contribute to human-specific maternal-fetal communication (HTR2B) and maternal-fetal immunotolerance (PDCD1LG2) systems, as well as vascular remodeling and deep placental invasion (CORIN). These data suggest that explicit evolutionary studies of anatomical systems complement traditional methods for characterizing the genetic architecture of disease. We also anticipate our results will advance the emerging synthesis of evolution and medicine (“evolutionary medicine”) and be a starting point for more sophisticated studies of the maternal-fetal interface. Furthermore, the gene expression changes we identified may contribute to the development of diagnostics and interventions for adverse pregnancy outcomes.
Antibiotic Breakdown by Susceptible Bacteria Enhances the Establishment of β-Lactam Resistant Mutants

For a better understanding of the evolution of antibiotic resistance, it is imperative to study the factors that determine the initial establishment of mutant resistance alleles. In addition to the antibiotic concentration, the establishment of resistance alleles may be affected by interactions with the surrounding susceptible cells from which they derive, for instance via the release of nutrients or removal of the antibiotic. Here, we investigate the effects of social interactions with surrounding susceptible cells on the establishment of Escherichia coli mutants with increasing β-lactamase activity (i.e. the capacity to hydrolyze β-lactam antibiotics) from single cells under the exposure of the antibiotic cefotaxime on agar plates. We find that mutant establishment probability is increased in the presence of susceptible cells due to the active breakdown of the antibiotic, but the rate of breakdown by the susceptible strain is much higher than expected based on its low enzymatic activity. A detailed theoretical model suggests that this observation can be explained by cell filamentation causing delayed lysis. While susceptible cells may hamper the spread of higher-resistant β-lactamase mutants at relatively high frequencies, our findings show that they could promote establishment during their emergence.
Wolbachia cifB induces cytoplasmic incompatibility in the malaria mosquito vector

Wolbachia, a maternally inherited intracellular bacterial species, can manipulate host insect reproduction by cytoplasmic incompatibility (CI), which results in embryo lethality in crosses between infected males and uninfected females. CI is encoded by two prophage genes, cifA and cifB. Wolbachia, coupled with the sterile insect technique, has been used in field trials to control populations of the dengue vector Aedes albopictus, but CI-inducing strains are not known to infect the malaria vector Anopheles gambiae. Here we show that cifA and cifB can induce conditional sterility in the malaria vector An. gambiae. We used transgenic expression of these Wolbachia-derived genes in the An. gambiae germline to show that cifB is sufficient to cause embryonic lethality and that cifB-induced sterility is rescued by cifA expression in females. When we co-expressed cifA and cifB in male mosquitoes, the CI phenotype was attenuated. In female mosquitoes, cifB impaired fertility, which was overcome by co-expression of cifA. Our findings pave the way towards using CI to control malaria mosquito vectors. Wolbachia cifB expression in Anopheles gambiae males is sufficient to induce cytoplasmic incompatibility that is sensitive to the expression level of the factors involved.
Restriction of Wolbachia bacteria in early embryogenesis of neotropical Drosophila species via ER-mediated autophagy

Wolbachia bacteria are maternally transmitted intracellular microbes that are not only restricted to the reproductive organs but also found in various somatic tissues of their native hosts. The abundance of the endosymbiont in somatic tissues, usually a dead end for vertically transmitted bacteria, causes a multitude of effects on life history traits of their hosts, which are still not well understood. Thus, deciphering the host-symbiont interactions on a cellular level throughout a host’s lifecycle is of great importance to understand their homeostatic nature, persistence and spreading success. Using fluorescent and transmission electron microscopy, we conducted a comprehensive analysis of Wolbachia tropism in somatic and reproductive tissues of six Drosophila species at the intracellular level during host development. Our data uncovered diagnostic patterns of infections to embryonic primordial germ cells and to particular cells of somatic tissues in three different neotropical Drosophila species of the willistoni and saltans groups that have apparently evolved in both independently. We further found that restricted patterns of Wolbachia tropism are already determined in early fly embryogenesis. This is achieved via selective autophagy, and the restriction of infection is preserved through larval hatching and metamorphosis. We further uncovered tight interactions of Wolbachia with membranes of the endoplasmic reticulum, which might play a scaffolding role for autophagosome formation and subsequent elimination of the endosymbiont. Finally, by analyzing D. simulans lines transinfected with non-native Wolbachia, we uncovered that the host genetic background regulates tissue tropism of infection. Our data demonstrate a peculiar and novel mechanism to limit and spatially restrict bacterial infection in somatic tissues during a very early stage of host development.
A billion years arms-race between viruses, virophages, and eukaryotes

Bamfordviruses are arguably the most diverse group of viruses infecting eukaryotes. They include the Nucleocytoplasmic Large DNA viruses (NCLDVs), virophages, adenoviruses, Mavericks and Polinton-like viruses. Two main hypotheses for their origins have been proposed: the “nuclear-escape” and “virophage-first” hypotheses. The “nuclear-escape” hypothesis proposes an endogenous, Maverick-like ancestor which escaped from the nucleus and gave rise to adenoviruses and NCLDVs. In contrast, the “virophage-first” hypothesis proposes that NCLDVs coevolved with protovirophages; Mavericks then evolved from virophages that became endogenous, with adenoviruses escaping from the nucleus at a later stage. Here, we test the predictions made by both models and consider alternative evolutionary scenarios. We use a data set of the four core virion proteins sampled across the diversity of the lineage, together with Bayesian and maximum-likelihood hypothesis-testing methods, and estimate rooted phylogenies. We find strong evidence that adenoviruses and NCLDVs are not sister groups, and that Mavericks and Mavirus acquired the rve-integrase independently. We also found strong support for a monophyletic group of virophages (family Lavidaviridae) and a most likely root placed between virophages and the other lineages. Our observations support alternatives to the nuclear-escape scenario and a billion years evolutionary arms-race between virophages and NCLDVs.
The Babytwins Study Sweden (BATSS): A Multi-Method Infant Twin Study of Genetic and Environmental Factors Influencing Infant Brain and Behavioral Development

Abstract Twin studies can help us understand the relative contributions of genes and environment to phenotypic trait variation, including attentional and brain activation measures. In terms of applying methodologies such as electroencephalography (EEG) and eye tracking, which are key methods in developmental neuroscience, infant twin studies are almost nonexistent. Here, we describe the Babytwins Study Sweden (BATSS), a multi-method longitudinal twin study of 177 MZ and 134 DZ twin pairs (i.e., 622 individual infants) covering the 5−36 month time period. The study includes EEG, eye tracking and genetics, together with more traditional measures based on in-person testing, direct observation and questionnaires. The results show that interest in participation in research among twin parents is high, despite the comprehensive protocol. DNA analysis from saliva samples was possible in virtually all participants, allowing for both zygosity confirmation and polygenic score analyses. Combining a longitudinal twin design with advanced technologies in developmental cognitive neuroscience and genomics, BATSS represents a new approach in infancy research, which we hope to have impact across multiple disciplines in the coming years.
Immune cell networks uncover candidate biomarkers of cancer immunotherapy response

Therapeutic activation of antitumour immunity by immune checkpoint inhibitors (ICIs) is a significant advance in cancer medicine, not least due to the prospect of long-term remission. However, many patients are unresponsive to ICI therapy and may experience serious side effects; companion biomarkers are urgently needed to help inform ICI prescribing decisions. We present the IMMUNETS networks of gene coregulation in five key immune cell types, and application to interrogate control of nivolumab response in advanced melanoma cohorts. Results evidence a role for each of the IMMUNETS cell types in ICI response and in driving tumour clearance with independent cohorts from TCGA. As expected, ‘immune hot’ status, including T cell proliferation, confers good response to first line ICI therapy. Genes regulated in NK, dendritic and B cells are the most prominent discriminators of nivolumab response in patients that had previously progressed on another ICI. Multivariate analysis controlling for tumour stage and age highlights B cell genes as candidate prognostic biomarkers. IMMUNETS provide a resource for network biology, enabling context-specific analysis of immune components in orthogonal datasets. Overall, our results illuminate the relationship between the tumour microenvironment and clinical trajectories, with potential implications for precision medicine.
The Impact of a Dynamic Working Environment on Human Gut Microbiota

Gut microbiota dysbiosis is associated with a variety of diseases, such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), metabolic diseases, allergic diseases, neurodevelopmental disorders and cancer. The human gut microbiota can be influenced by a variety of factors, including geography, dietary habits, living environment, age and altered lifestyle etc. This study was conducted to explore the gut microbiota compositions in officials who are in a stable working environment and train drivers who are in a dynamic working environment. Microbiota communities in the feces of 80 officials and 88 train drivers were analyzed using Illumina MiSeq sequencing targeting the V3-V4 region of 16S ribosomal RNA (rRNA) gene and ITS1 region of fungi. There were significant differences between the two groups in diversity and richness of gut microbiota, while the microbial community compositions of the two groups were similar. The relationship between gut microbiota and clinical characteristics was investigated. We found that more bacteria and fungi were positively correlated with clinical characteristics. Functional prediction analysis of the gut microbiota between the two groups by PICRUSt2 revealed significant differences between the official group and the train driver group. Elucidating these differences of the microbiome between the two groups will provide a foundation understanding of the impact of a dynamic environment on gut microbiota.
Single-molecule imaging of chromatin remodelers reveals role of ATPase in promoting fast kinetics of target search and dissociation from chromatin

Conserved ATP-dependent chromatin remodelers establish and maintain genome-wide chromatin architectures of regulatory DNA during cellular lifespan, but the temporal interactions between remodelers and chromatin targets have been obscure. We performed live-cell single-molecule tracking for RSC, SWI/SNF, CHD1, ISW1, ISW2, and INO80 remodeling complexes in budding yeast and detected hyperkinetic behaviors for chromatin-bound molecules that frequently transition to the free state for all complexes. Chromatin-bound remodelers display notably higher diffusion than nucleosomal histones, and strikingly fast dissociation kinetics with 4-7 s mean residence times. These enhanced dynamics require ATP binding or hydrolysis by the catalytic ATPase, uncovering an additional function to its established role in nucleosome remodeling. Kinetic simulations show that multiple remodelers can repeatedly occupy the same promoter region on a timescale of minutes, implicating an unending ‘tug-of-war’ that controls a temporally shifting window of accessibility for the transcription initiation machinery.