Evidence for membrane affinity of the C-terminal domain of bovine milk PP3 component

AbstractComponent PP3 is a phosphoglycoprotein isolated from bovine milk with unknown biological function, which displays in its C-terminal region a basic amphipathic α-helix, a feature often involved in membrane association. According to that, the behaviour of PP3 and of a synthetic peptide from the C-terminal domain (residues 113–135) was investigated in lipid environment. Conductance measurements indicated that the peptide was able to associate and form channels in planar lipid bilayers composed of neutral or charged phospholipids. Electrostatic interactions seemed to promote voltage-dependant channel formation but this was not absolutely required since the pore-forming ability of the 113–135 C-terminal peptide was also detected with the zwitterionic lipid bilayer. Additionally, a spectroscopic study using circular dichroism argues that the peptide adopts an α-helical conformation in interaction with neutral or charged micelles. Thus, the conducting aggregates in bilayers might be composed of a bundle of peptides in helical conformation. Besides, similar conductance measurements performed with the whole PP3 protein did not induce any channel fluctuations. However, with the latter, an early breakdown of the bilayers occurred, a finding that can be tentatively explained by a massive incorporation of PP3. In the light of the present results, it could be inferred that PP3 membrane attachment may be achieved by oligomerization of the C-terminal amphipathic helical region

Stable interpolation with exponential-polynomial splines and node selection via greedy algorithms

In this work we extend some ideas about greedy algorithms, which are well-established tools for, e.g., kernel bases, and exponential-polynomial splines whose main drawback consists in possible overfitting and consequent oscillations of the approximant. To partially overcome this issue, we develop some results on theoretically optimal interpolation points. Moreover, we introduce two algorithms which perform an adaptive selection of the spline interpolation points based on the minimization either of the sample residuals (f-greedy), or of an upper bound for the approximation error based on the spline Lebesgue function (λ-greedy). Both methods allow us to obtain an adaptive selection of the sampling points, i.e., the spline nodes. While the f-greedy selection is tailored to one specific target function, the λ-greedy algorithm enables us to define target-data-independent interpolation nodes

High GADA titer increases the risk of insulin requirement in LADA patients: a 7-year follow-up (NIRAD study 7).

The aim of this study was to determine whether glutamic acid decarboxylase antibody (GADA) titer and other clinical parameters could define the risk of progression to insulin therapy in latent autoimmune diabetes in adults (LADA) patients during a 7-year follow-up. This study involved 220 LADA and 430 type 2 diabetes subjects followed up for 7 years from the time of GADA screening to evaluate their progression toward insulin therapy. Kaplan-Meier curves and multivariate logistic regression analysis were performed to identify the markers capable of influencing this progression. RESULTS: During the follow-up, the drop out was 4% in both groups. A total of 119 (56.1%) out of 212 LADA patients required insulin during the 7 years of follow-up. The Kaplan-Meier plots showed that 74/104 (71.1%) of high GADA titer required insulin compared with 45/108 (41.6%) of low GADA titer and with 86/412 (20.9%) of type 2 diabetes (P<0.0001 for both). A BMI of ???25???kg/m2 and IA-2IC and zinc transporter 8 (ZnT8) positivity were also shown as the markers of faster progression (P<0.0001 for both). The proportion of LADA patients requiring insulin was significantly higher in the group of subjects treated also with sulfonylurea in the first year from diagnosis compared with those treated with diet and/or insulin sensitizers (P<0.001). The multivariate analysis confirmed that the presence of high GADA titer was a significant predictor of insulin requirement (P<0.0001, OR=6.95). CONCLUSIONS: High GADA titer, BMI ??? 25, ZnT8 and IA-2IC positivity and sulfonylurea treatment, in the first year from diagnosis, significantly increase the progression toward insulin requirement in LADA patients

Schema2QA: High-Quality and Low-Cost Q&A Agents for the Structured Web

Building a question-answering agent currently requires large annotated datasets, which are prohibitively expensive. This paper proposes Schema2QA, an open-source toolkit that can generate a Q&A system from a database schema augmented with a few annotations for each field. The key concept is to cover the space of possible compound queries on the database with a large number of in-domain questions synthesized with the help of a corpus of generic query templates. The synthesized data and a small paraphrase set are used to train a novel neural network based on the BERT pretrained model. We use Schema2QA to generate Q&A systems for five Schema.org domains, restaurants, people, movies, books and music, and obtain an overall accuracy between 64% and 75% on crowdsourced questions for these domains. Once annotations and paraphrases are obtained for a Schema.org schema, no additional manual effort is needed to create a Q&A agent for any website that uses the same schema. Furthermore, we demonstrate that learning can be transferred from the restaurant to the hotel domain, obtaining a 64% accuracy on crowdsourced questions with no manual effort. Schema2QA achieves an accuracy of 60% on popular restaurant questions that can be answered using Schema.org. Its performance is comparable to Google Assistant, 7% lower than Siri, and 15% higher than Alexa. It outperforms all these assistants by at least 18% on more complex, long-tail questions

The role peer responses to adolescent expression of emotions plays in their emotion regulation : A systematic literature review

Introduction Peer responses to adolescents’ emotional expressions (PREE), are thought to influence the continued development of emotion regulation (ER). Unsupportive (e.g., dismissive) PREE, for example, are expected to be associated with greater maladaptive ER. Poor ER is known to place adolescents at risk of psychopathology. The aim of this systematic review was to collate and synthesize the emerging evidence exploring the role that peer emotion socialization, specifically PREE, plays in adolescent ER and identify future directions. Methods In adherence with PRISMA guidelines, PsychINFO, Medline Complete, CINAHL Complete, Scopus and Web of Science were searched on April 20th, 2021, May 28th, 2022, and April 12th, 2023 for English language reports published after 1998. To be included, studies needed to report on PREE and its relation to adolescent ER. Results A total of eight studies, one qualitative and seven quantitative, met inclusion criteria and had a combined N of 785 participants (aged 10–18 years). Studies were primarily undertaken in the US and mostly included males and females, with one study only including female participants. Conclusions Although only eight studies were identified, the review identified preliminary evidence for an association between PREE and ER in adolescents. This association appeared to vary depending on adolescent gender, age, the closeness of the friendship and the PREE. Several limitations were identified, and suggestions are made for future research in this emerging area

Quality improvement interventions to prevent the use of hospital services among nursing home residents: protocol for a systematic review and meta-analysis

Introduction: Quality improvement interventions are a promising strategy for reducing hospital services use among nursing home residents. However, evidence for their effectiveness is limited. It is unclear which characteristics of the quality improvement intervention and activities planned to facilitate implementation may promote fidelity to organisational and system changes. This systematic review and meta-analysis will assess the effectiveness of quality improvement interventions and implementation strategies aimed at reducing hospital services use among nursing home residents. Methods and analysis: The MEDLINE, CINAHL, Cochrane Library, Embase and Web of Science databases will be comprehensively searched in September 2023. The eligible studies should focus on the implementation of a quality improvement intervention defined as the systematic, continuous approach that designs, tests and implements changes using real-time measurement to reduce hospitalisations or emergency department visits among long-stay nursing home residents. Quality improvement details and implementation strategies will be deductively categorised into effective practice and organisation of care taxonomy domains for delivery arrangements and implementation strategies. Quality and bias assessments will be completed using the Quality Improvement Minimum Quality Criteria Set and the Joanna Briggs Institute Critical Appraisal Tools.The results will be pooled in a meta-analysis, by combining the natural logarithms of the rate ratios across the studies or by calculating the rate ratio using the generic inverse-variance method. Heterogeneity will be assessed using the I2 or H2 statistics if the number of included studies will be less than 10. Raw data will be requested from the authors, as required. Ethics and dissemination: Ethical approval is not required. The results will be published in a peer-review journal and presented at (inter)national conferences. Prospero registration number: CRD42022364195

effect of a nicotine free inhalator as part of a smoking cessation programme

Smoking-cessation drugs are inadequate at addressing the behavioural component of tobacco dependence. Nicotine-free inhalators are plastic devices that may provide a coping mechanism for conditioned smoking by replacing some of the rituals associated with smoking gestures. This study assessed the effect of using a nicotine-free inhalator to improve success in a cessation programme. At baseline, 120 smokers attending a smoking-cessation programme were assessed for their sociodemographic factors, smoking history, depression, physical and behavioural dependence, and motivation. Participants were randomly assigned to two groups, nicotine-free inhalator group (PAIPO; Echos Srl, Milan, Italy) versus reference group. For the whole sample, no significant difference was found in quit rates at 24 weeks between the PAIPO group and the reference group. However, the quit rate in the PAIPO group (66.7%) was more than three-fold higher than the reference group (19.2%) for those individuals with high Glover–Nilsson Smoking Behavioural Questionnaire (GN-SBQ) scores at baseline. The results of the logistic model analysis indicate that a high GN-SBQ score is a strong independent predictor for successful quitting at 24 weeks (OR 8.88; 95% CI 2.08–37.94) in the PAIPO group. Nicotine-free inhalators may be beneficial when used in the context of smoking-cessation interventions, particularly for those smokers for whom handling and manipulation of their cigarettes plays an important part in the ritual of smoking