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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Tracheostomy dependence following “organ preservation” (chemo)radiation protocol for laryngeal and hypopharyngeal cancers

alexandrossfakianakis shared this article with you from Inoreader Tracheostomy dependence following "organ preservation" (chemo)radiation protocol for laryngeal and hypopharyngeal cancers via Head & Neck Abstract Background Patients receiving primary (chemo)radiotherapy for laryngeal or hypopharyngeal cancer risk developing severe laryngeal dysfunction and becoming tracheostomy dependent, detracting from the benefits of organ preservation. We aim to describe the airway outcomes for this cohort and identify risk factors for developing tracheostomy dependence. Methods Patients with laryngeal or hypopharyngeal cancer who were recommended for and underwent primary (chemo)radiotherapy over a 6-year period were identified from a tertiary hospital Head and Neck cancer database. Patient, tumor, and treatment details were collected and analyzed. Results Of 166 patients, 18.7% (N = 31) required tracheostomy insertion. Advanced tumor classification was the only significant predictor (p < 0.00001). Successful decannulation was observed in 12.9% (N = 4). Decannulation was observably less successful with advanced tumors, bilateral vocal cord immobility, tracheostomies inserted under emergency conditions. Conclusion We quantified tracheostomy insertion rates and dependence in patients undergoing "organ-preserving" (chemo)radiotherapy, to assist in the pre-treatment counseling of patients opting for this approach. View on Web

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Developmental pathways linking early behavioral inhibition to later anxiety

alexandrossfakianakis shared this article with you from Inoreader Annual Research Review: Developmental pathways linking early behavioral inhibition to later anxiety via Journal of Child Psychology and Psychiatry Behavioral Inhibition is a temperament identified in the first years of life that enhances the risk for development of anxiety during late childhood and adolescence. Amongst children characterized with this temperament, only around 40 percent go on to develop anxiety disorders, meaning that more than half of these children do not. Over the past 20 years, research has documented within-child and socio-contextual factors that support differing developmental pathways. This review provides a historical perspective on the research documenting the origins of this temperament, its biological correlates, and the factors that enhance or mitigate risk for development of anxiety. We review as well, research findings from two longitudinal cohorts that have identified moderators of behavioral inhibition in understanding pathways to anxiety. Research on these moderators has led us to develop the Detection and Dual Control (DDC) framework to understand differing developm ental trajectories among behaviorally inhibited children. In this review, we use this framework to explain why and how specific cognitive and socio-contextual factors influence differential pathways to anxiety versus resilience. 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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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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Use of Cold-Stored Whole Blood is Associated With Improved Mortality in Hemostatic Resuscitation of Major Bleeding: A Multicenter Study

alexandrossfakianakis shared this article with you from Inoreader Use of Cold-Stored Whole Blood is Associated With Improved Mortality in Hemostatic Resuscitation of Major Bleeding: A Multicenter Study via Annals of Surgery - Most Popular Articles Objective: The aim of this study was to identify a mortality benefit with the use of whole blood (WB) as part of the resuscitation of bleeding trauma patients. Background: Blood component therapy (BCT) is the current standard for resuscitating trauma patients, with WB emerging as the blood product of choice. We hypothesized that the use of WB versus BCT alone would result in decreased mortality. Methods: We performed a 14-center, prospective observational study of trauma patients who received WB versus BCT during their resuscitation. We applied a generalized linear mixed-effects model with a random effect and controlled for age, sex, mechanism of injury (MOI), and injury severity score. All patients who received blood as part of their initial resuscitation were included. Primary outcome was mortality and secondary outcomes included acute kidney injury, deep vein thrombosis/pulmonary embolism, pulmonary complications, and bleeding complications. Results: A total of 1623 [WB: 1180 (74%), BCT: 443(27%)] patients who sustained penetrating (53%) or blunt (47%) injury were included. Patients who received WB had a higher shock index (0.98 vs 0.83), more comorbidities, and more blunt MOI (all P View on Web

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