CRISPR/Cas9‐HPV‐liposome enhances antitumor immunity and treatment of HPV infection associated cervical cancer

alexandrossfakianakis shared this article with you from Inoreader CRISPR/Cas9‐HPV‐liposome enhances antitumor immunity and treatment of HPV infection associated cervical cancer via Journal of Medical Virology ABSTRACT Increasing evidence shows that human papillomavirus (HPV) E6/E7 deletion in cervical cancer cells may be related to immunosuppressive tumour microenvironment and adverse reactions or resistance to immune checkpoint blockade. Here, we demonstrate that liposome delivery of CRISPR/cas9 can effectively knock out HPV, which in turn induces autophagy and triggers cell death-related immune activation by releasing damage-related molecular patterns. The results of in vivo experiments showed that HPV-targeting gRNA–liposomes could promote CD8+ T cell infiltration in tumour tissues; enhance the expression of pro-inflammatory cytokines, such as interleukin-12, tumour necrosis factor-α and interferon-γ and reduce regulatory T cells and myeloid suppressor cells. The combination of HPV-targeting gRNA–liposomes with immune checkpoint inhibitors and anti-programmed death-1 antibodies produced highly effective antitumour effects. In addition, combination therapy induced immune memory in the cervical cancer model. This article is protected by copyright. All rights reserved. View on Web

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Single‐cell transcriptome atlas reveals protective characteristics of COVID‐19 mRNA vaccine

alexandrossfakianakis shared this article with you from Inoreader Single‐cell transcriptome atlas reveals protective characteristics of COVID‐19 mRNA vaccine via Journal of Medical Virology Abstract mRNA vaccines are promising alternatives to conventional vaccines in many aspects. We previously developed a lipopolyplex (LPP)-based mRNA vaccine (SW0123) that demonstrated robust immunogenicity and strong protective capacity against SARS-CoV-2 infection in mice and rhesus macaques. However, the immune profiles and mechanisms of pulmonary protection induced by SW0123 remain unclear. Through high-resolution single-cell analysis, we found that SW0123 vaccination effectively suppressed SARS-CoV-2-induced inflammatory responses by inhibiting the recruitment of pro-inflammatory macrophages and increasing the frequency of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). In addition, the apoptotic process in both lung epithelial and endothelial cells was significantly inhibited, which was proposed to be one major mechanism contributing to vaccine-induced lung protection. Cell-cell interaction in the lung compartment was also altered by vaccination. These data collectively unravel the mechanisms by which the SW0123 protects against lung damage caused by SARS-CoV-2 infection. This article is protected by copyright. All rights reserved. View on Web

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Prevalence and functional impact of social (pragmatic) communication disorders

alexandrossfakianakis shared this article with you from Inoreader Prevalence and functional impact of social (pragmatic) communication disorders via Journal of Child Psychology and Psychiatry Background The aim of this study was to evaluate the Children's Communication Checklist-2 (CCC-2) for measuring social-pragmatic communication deficits and to ascertain their prevalence and functional impact in a community sample. Methods We used parent and teacher responses to the CCC-2 to approximate inclusion (poor social-pragmatic skills) and exclusion (poor structural language skills or autistic symptomatology) criteria for social (pragmatic) communication disorder (SPCD). We tested the prevalence of social-pragmatic deficits in a population-based sample of children (n = 386) aged 5–6 years old using CCC-2 algorithms. We also investigated the academic and behavioural profiles of children with broadly defined limitations in social-pragmatic competence on the CCC-2. Results Regardless of the diagnostic algorithm used, the resulting prevalence rates for social-pragmatic deficits indicated that very few children had isolated social-communication difficulties (0–1.3%). However, a larger proportion of children (range: 6.1–10.5%) had social-pragmatic skills outside the expected range alongside structural language difficulties and/or autism spectrum symptoms, and this profile was associated with a range of adverse academic and behavioural outcomes. Conclusions A considerable proportion of children in the early years of primary school has social-pragmatic deficits that interfere with behaviour and scholastic activity; however, these rarely occur in isolation. Exclusionary criteria that include structural language may lead to underidentification of individuals with social-pragmatic deficits that may benefit from tailored support and intervention. View on Web

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Polygenic risk score and peer victimisation independently predict depressive symptoms in adolescence: results from the Quebec Longitudinal Study of Children Development

alexandrossfakianakis shared this article with you from Inoreader Polygenic risk score and peer victimisation independently predict depressive symptoms in adolescence: results from the Quebec Longitudinal Study of Children Development via Journal of Child Psychology and Psychiatry Background Peer victimisation has been associated with depressive symptoms during adolescence, however not all peer victimised adolescents will exhibit such symptoms. This study tested whether having a genetic predisposition to developing depression increased the risk of experiencing depressive symptoms in peer victimised youth. To date, no study has explored such gene–environment interaction using a polygenic risk score for depression (PRS-depression) in the context of peer victimisation and depressive symptoms in adolescence. Methods The sample included 748 participants born in 1997/98 from the Quebec Longitudinal Study of Child Development with genotype data and prospectively collected information on peer victimisation (12–13 years) obtained from both self- and teacher-reports, as well as self-reported depressive symptoms (15–17 years). The PRS-depression was based on the genome-wide association meta-analysis of broad depression by Howard et al. (2019). Results Self- and teacher-reported peer victimisation in early adolescence were both associated with depressive symptoms in adolescence (β = 0.34, p < .001; β = 0.14, p = .001 respectively), and this association remained significant when accounting for PRS-depression (β = 0.33, p < .001; β = 0.13, p = .002 respectively). PRS-depression was independently associated with depressive symptoms, but there was no significant PRS-depression by peer victimisation interaction (self-reported and teacher-reported). PRS-depression was correlated with self-reported, but not teacher-reported, peer victimisation. Conclusions Our findings suggested that a partial measure of an individual's genetic predisposition to depression, as measured by PRS-depression, and being exposed to peer victimisation (self- and teacher-reported) were independently associated with depressive symptoms in adolescence. Furthermore, PRS-depression did not exacerbate the risk of depressive symptoms among adolescents who had been peer victimised. Lastly, we found evidence of a gene–environment correlation between PRS-depression and self-reported peer victimisation. Future studies are needed to replicate this finding and to further understand the role of genetic predispositions in experiencing depressive symptoms following peer victimisation. View on Web

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Facial reactions to emotional films in young children with conduct problems and varying levels of callous‐unemotional traits

alexandrossfakianakis shared this article with you from Inoreader Facial reactions to emotional films in young children with conduct problems and varying levels of callous‐unemotional traits via Journal of Child Psychology and Psychiatry Background Elevated levels of callous-unemotional (CU) traits have proven useful for identifying a distinct subgroup of children whose conduct problems (CP) are early emerging, severe, persistent, and underpinned by aberrant emotional processing. The early childhood emotional experiences and expressions of CP subtypes are poorly understood, despite their importance to understanding the problematic attachments and atypical social affiliation experienced by children with elevated CU traits. The current study aimed to test for differences in facial emotional reactions to mood-inducing film clips in children with CP and varying levels of CU traits. Method We compared facial emotional reactions during a developmentally appropriate mood induction task in a mixed-sex sample of clinic-referred preschool children (M age = 3.64 years, SD = 0.63, 66.9% male) classified as CP with elevated levels of CU traits (CP + CU; n = 25) versus low CU traits (CP-only; n = 47), and typically developing children (TD; n = 28). Results Relative to TD children, children with clinical CP showed less congruent and more incongruent facial emotional expressions to sad and happy film clips, controlling for child sex, age, and ethnicity. Conclusions Consistent with older samples, young children with CP show atypical facial emotional expressions in response to positive and negative emotional stimuli. Findings have implications for developmental models of childhood antisocial behavior and can inform the development of targeted interventions. View on Web

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Opening a DOOR for pivotal studies: an example for complicated urinary tract infections

alexandrossfakianakis shared this article with you from Inoreader Opening a DOOR for pivotal studies: an example for complicated urinary tract infections via Clinical Infectious Diseases Advance Access View on Web

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Molecular and regulatory mechanisms of oxidative stress adaptation in Streptococcus mutans

alexandrossfakianakis shared this article with you from Inoreader Molecular and regulatory mechanisms of oxidative stress adaptation in Streptococcus mutans via Molecular Oral Microbiology Abstract Dental caries is a chronic progressive disease, which destructs dental hard tissues under the influence of multiple factors, mainly bacteria. Streptococcus mutans (S. mutans) is the main cariogenic bacteria. However, its cariogenic virulence is affected by environmental stress such as oxidative stress, nutrient deficiency and low pH to some extent. Oxidative stress is one of the main stresses that S. mutans faces in oral cavity. But there are a variety of protective molecules to resist oxidative stress in S. mutans, including superoxide dismutase, nicotinamide adenine dinucleotide oxidase, Dps-like peroxide resistance protein, alkyl-hydrogen peroxide reductase, thioredoxin, glutamate-reducing protein system and some metabolic substances. Additionally, some transcriptional regulatory factors (SloR, PerR, Rex, Spx, etc.) and two-component systems are also closely related to oxidative stress adaptation by modulating the expression of protective molecules. This review summarizes the research progress of protective molecules and regulatory mechanisms (mainly transcription factors) of oxidative stress adaptation of S. mutans. This article is protected by copyright. All rights reserved View on Web

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Transition Metals and Enterococcus faecalis: Homeostasis, Virulence and Perspectives

alexandrossfakianakis shared this article with you from Inoreader Transition Metals and Enterococcus faecalis: Homeostasis, Virulence and Perspectives via Molecular Oral Microbiology Abstract Enterococcus faecalis, a Gram-positive bacterium is known to be a key player in several chronic infections as well as nosocomial, heart valve, urinary tract, surgical wound and dental root canal infections. The capability to sense different transition metal levels and tune its response accordingly endows it with the potential to thrive and cause infections in several host niches. Over the past decade, our knowledge of how transition metals play a critical role in maintaining homeostasis of E. faecalis has improved significantly. The aim of this review is to elucidate the roles of metals such as iron, manganese, zinc and copper in the physiology, metabolism, and pathogenicity of E. faecalis. These essential micronutrients contribute to energy production, redox stress response, expression of virulence determinants, and cooperation in polymicrobial communities. The review also highlights metal homeostasis systems in E. faecalis, which respond to fluctuatio ns in extracellular metal levels, and regulate the intracellular metal content. Regulation of intracellular metallome secures the tolerance of E. faecalis to oxidative stress and host-mediated metal sequestration strategies. Therapeutic interventions which deprive E. faecalis of its essential metal requirements or disrupt its homeostatic control have been proposed to combat E. faecalis infections. This article is protected by copyright. All rights reserved View on Web

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Transfer effects from language processing to visual attention dynamics: The impact of orthographic transparency

alexandrossfakianakis shared this article with you from Inoreader Transfer effects from language processing to visual attention dynamics: The impact of orthographic transparency via British Journal of Psychology Abstract The consistency between letters and sounds varies across languages. These differences have been proposed to be associated with different reading mechanisms (lexical vs. phonological), processing grain sizes (coarse vs. fine) and attentional windows (whole words vs. individual letters). This study aimed to extend this idea to writing to dictation. For that purpose, we evaluated whether the use of different types of processing has a differential impact on local windowing attention: phonological (local) processing in a transparent language (Spanish) and lexical (global) processing of an opaque language (English). Spanish and English monolinguals (Experiment 1) and Spanish–English bilinguals (Experiment 2) performed a writing to dictation task followed by a global–local task. The first key performance showed a critical dissociation between languages: the response times (RTs) from the Spanish writing to dictation task was modulated by word length, whereas the RTs from the English w riting to dictation task was modulated by word frequency and age of acquisition, as evidence that language transparency biases processing towards phonological or lexical strategies. In addition, after a Spanish task, participants more efficiently processed local information, which resulted in both the benefit of global congruent information and the reduced cost of incongruent global information. Additionally, the results showed that bilinguals adapt their attentional processing depending on the orthographic transparency. View on Web

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The problem with picking: Permittance, escape and shame in problematic skin picking

alexandrossfakianakis shared this article with you from Inoreader The problem with picking: Permittance, escape and shame in problematic skin picking via Psychology and Psychotherapy: Theory, Research and Practice Abstract Objectives Problematic skin picking (SP) is a poorly understood experience characterised by a drive to pick the skin and related psychosocial impact. In the DSM-5, problematic SP is classified as 'excoriation (skin picking) disorder'. The aim of this article is to present a rare qualitative perspective on the lived experience of problematic SP, prioritising participants' voices and sense-making. Design An in-depth qualitative study of individuals who self-identified as picking their skin problematically and experienced related distress. Methods Seventeen UK-based participants were recruited online and interviewed about their SP. Participants were given choice of interview modality, including instant messenger platforms, telephone, email and Skype, to maximise comfort and improve the accessibility of the study. Transcripts were analysed using thematic analysis. Results Three themes offering novel insight into the phenomenology of participants' SP are highlighted and explored: (1) how cognitions and circumstances drove and permitted SP, (2) how participants 'zoned out' while SP and the escape or relief that this attentional experience offered and (3) participants' feelings of shame and distress in how they felt their SP may appear to others. Conclusions This study contributes in-depth and novel ideas to the understanding of SP phenomenology and identifies how environmental factors, cognitions, contextual distress and shame may be considerations in therapeutic intervention. It presents the complexity of SP sense-making and demonstrates the need for individual formulation. View on Web

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