Notes

Platelet activating-factor acetylhydrolase II: Associated with phospholipase A2 family members that hydrolyzes oxidized phospholipids.
Proteins are engines involved in almost all functions of life. They have specific spatial structures formed by twisting and folding of one or more polypeptide chains composed of amino acids. Protein sites are protein structure microenvironments that can be identified by three-dimensional locations and local neighborhoods in which the structure or function exists. Understanding the amino acid environment affinity is essential for additional protein structural or functional studies, such as mutation analysis and functional site detection. In this study, an amino acid environment affinity model based on the graph attention network was developed. Initially, we constructed a protein graph according to the distance between amino acid pairs. Then, we extracted a set of structural features for each node. Finally, the protein graph and the associated node feature set were set to input the graph attention network model and to obtain the amino acid affinities. Numerical results show that our proposed method significantly outperforms a recent 3DCNN-based method by almost 30%.Participatory modelling seeks to foster stakeholder engagement to better attune models to their decision-making and policy contexts. Such approaches are increasingly advocated for use in the field of health. We review the instrumental and epistemological claims made in support of participatory modelling approaches. These accentuate participatory models as offering a better evidence-base for health policy decisions. By drawing attention to recent modelling experiments in a sector outside of health, that of water management, we outline a different way of thinking about participation and modelling. Here, the participatory model is configured in relation to matters of 'knowledge controversy', with modelling constituted as an 'evidence-making intervention' in relation to the making of science and expertise. Rather than presenting participatory models as an improved technical solution to addressing given policy problems within an evidence-based intervention approach, models are alternatively potentiated as sites for the redistribution of expertise among actor networks as they seek to engage politically in a matter of concern. This leads us to consider possible new directions for participatory modelling in the field of health.This paper illuminates how the psychoanalytic work of Winnicott and Wittgenstein's philosophy on language complement each other in elucidating a "psychoanalytic language game". The paper takes a close look at the grammar and linguistic mechanisms which underlie psychoanalytic work. Wittgenstein's linguistic turn from positivism is discussed; his ideas like 'family resemblance', 'aspect seeing' and 'language games' are examined in order to shed light on the paradoxical communication at play in Winnicott's potential space. The paper looks at the potentiality central to therapeutic work, arguing that it accords with what Wittgenstein calls the grammatical optative mode, as Freud already indicated in his theory of dreaming.Infants express emotional distress through whining, crying, flailing, silence, etc., which can be viewed as communications that also afflict the caregiver(s). One expressive mode, subtle and often unnoticed except by the parents, is infant gaze avoidance. It often elicits parental feelings of rejection, shame and despair, and may be a reason for seeking parent-infant psychotherapy. In therapy, the symptom often discloses a disturbance in the dyad's emotional interaction. Therapy can bring about relief in the symptom and the relational disorder. Sometimes, the therapist discovers that the infant is avoiding the therapist's, rather than the parents', eyes. This challenges the therapist's expertise in establishing contact with the baby and in perceiving and processing emotional reactions to what may be experienced as the baby's dismissal. Gaze avoidance elicits theoretical questions approached in a previous publication what does the child seem to avoid in the adult's eyes, and how can we conceptualize the psychodynamics behind the symptom? It also evokes technical questions how can the therapist make contact with an infant who avoids the mother's or the therapist's eyes? How can the clinician exploit their emotional reactions, the countertransference, to understand and further the dyad's emotional communication? Two case vignettes are provided.The effects of violence exposure on the risk of self-harming behaviors of youth in low- and middle-income countries is not well-understood. Using household survey data from one nationally representative sample and one sample from conflict-affected areas, we examined violence exposure and self-harm among Colombian youth aged 13-24. Survey-weighted prevalence ratios comparing self-harming behaviors by exposure to violence were estimated with Poisson log-linear models, controlling for age, sex, education and food insecurity. Compared to unexposed youth, those exposed to violence in both home and community settings were 7.97 (95% confidence interval [CI]2.72-23.36) times more likely in the conflict-affected sample, and 21.05 (95% CI 8.80-50.34) times more likely in the national sample to report having attempted suicide. Among Colombian youth, exposure to violence as either witness or victim was associated with greater prevalence of self-harming behaviors. Youth suicide prevention programs can address exposures to violence as a risk factor for self-harm.For safety studies, two types of hypothesis testing are often considered detecting a safety signal and ruling out a safety concern. Under the detecting framework, statistical non-significance is often confused with the conclusion that there is no safety concern. Such a conclusion, in the presence of low study power or large variability, is problematic. To overcome the interpretation issue with non-significant results from a detecting hypothesis, we propose a Two-Stage Decision-Making (TSDM) approach for safety studies. It is basically a ruling-out design allowing an interim analysis that applies both detecting and ruling-out criteria at the interim and final stages with a pre-specified alpha spending function. The proposed TSDM approach incorporates both detecting a safety signal and ruling out safety concerns into a single study design to increase the probability of making a definite decision. It is based on the ruling-out framework that utilizes both directions of the confidence interval to make a decision for ruling out unacceptable risk or detecting safety signal at each analysis stage. We assess the proposed TSDM approach by investigating properties such as operational type I error rate, overall study power based on analytical approximations, overall probability of making a decision, and required sample sizes. selleckchem We conduct Monte Carlo simulations to evaluate such properties regarding various outcome types of confidence intervals and summarize the statistical interpretations and the implications on study design.Ribosomes are essential nanomachines responsible for all protein production in cells. Ribosome biogenesis and function are energy costly processes, they are tightly regulated to match cellular needs. In cancer, major pathways that control ribosome biogenesis and function are often deregulated to ensure cell survival and to accommodate the continuous proliferation of tumour cells. Ribosomal RNAs (rRNAs) are abundantly modified with 2'-O-methylation (Nm, ribomethylation) being one of the most common modifications. In eukaryotic ribosomes, ribomethylation is performed by the methyltransferase Fibrillarin guided by box C/D small nucleolar RNAs (snoRNAs). Accumulating evidences indicate that snoRNA expression and ribosome methylation profiles are altered in cancer. Here we review our current knowledge on differential snoRNA expression and rRNA 2'-O methylation in the context of human malignancies, and discuss the consequences and opportunities for cancer diagnostics, prognostics, and therapeutics.Many implementation efforts experience interruptions, especially in settings with developing health systems. Approaches for evaluating interruptions are needed to inform re-implementation strategies. We sought to devise an approach for evaluating interruptions by exploring the sustainability of a programme that implemented diabetes mellitus (DM) screening within tuberculosis clinics in Uganda in 2017. In 2019, we conducted nine interviews with clinic staff and observed clinic visits to determine their views and practices on providing integrated care. We mapped themes to a social ecological model with three levels derived from the Consolidated Framework for Implementation Research (CFIR) outer setting (i.e. community), inner setting (i.e. clinic), and individuals (i.e. clinicians). Respondents explained that DM screening ceased due to disruptions in the national supply chain for glucose test strips, which had cascading effects on clinics and clinicians. Lack of screening supplies in clinics limited clinicians' opportunities to perform DM screening, which contributed to diminished self-efficacy. However, culture, compatibility and clinicians' beliefs about DM screening sustained throughout the interruption. We propose an approach for evaluating interruptions using the CFIR and social ecological model; other programmes can adapt this approach to identify cascading effects of interruptions and target them for re-implementation.ABSTRACTEmotion dysregulation (ED) is a transdiagnostic risk factor for several forms of psychopathology. One established, integrative conceptualisation of ED that has informed our understanding of psychopathology (Gratz, K. L., & Roemer, L. (2004). Multidimensional assessment of emotion regulation and dysregulation  development, factor structure, and initial validation of the difficulties in emotion regulation scale. Journal of Psychopathology and Behavioral Assessment, 26(1), 41-54) was recently extended to account for state-level and specifically physiological aspects of ED. As such, the goal of the current study was to assess the degree to which this conceptualisation could be captured using a physiological, state-level index (i.e. the late positive potential; LPP). Participants (N=41; Mage=27.5 years, SD=11.0) completed a trait-based rating scale measure of the extended conceptualisation of ED and viewed a series of images that ranged in valence (i.e. unpleasant, pleasant, and neutral). Multilevel modelling indicated some points of convergence between rating scale scores and the LPP, and other points of divergence. Findings underscore the utility of a multi-method approach to improve understanding of key transdiagnostic characteristics across levels of analysis. Further, results are novel evidence supporting validity of the extended conceptualisation of ED.The gut-brain axis hypothesis suggests that interactions in the intestinal milieu are critically involved in regulating brain function. Several studies point to a gut-microbiota-brain connection linking an impaired intestinal barrier and altered gut microbiota composition to neurological disorders involving neuroinflammation. Increased gut permeability allows luminal antigens to cross the gut epithelium, and via the blood stream and an impaired blood-brain barrier (BBB) enters the brain impacting its function. Pre-haptoglobin 2 (pHP2), the precursor protein to mature HP2, is the first characterized member of the zonulin family of structurally related proteins. pHP 2 has been identified in humans as the thus far only endogenous regulator of epithelial and endothelial tight junctions (TJs). We have leveraged the Zonulin-transgenic mouse (Ztm) that expresses a murine pHP2 (zonulin) to determine the role of increased gut permeability and its synergy with a dysbiotic intestinal microbiota on brain function and behavior.
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