Miracle-dz/UniFAR-FTUs huggingface dataset:
The Implementation Effectiveness of a Freely Available Pediatric Cancer Pain Assessment App: A Pilot Implementation Study

Background Pain Squad is an evidence-based, freely available iOS app designed to assess pain in children with cancer. Once research-based technologies such as Pain Squad are validated, it is important to evaluate their performance in natural settings to optimize their real-world clinical use. Objective The objective of this study was to evaluate the implementation effectiveness of Pain Squad in a natural setting. Methods Parents of 149 children with cancer (aged 8-18 years) were contacted to invite their child to participate. Participating children downloaded Pain Squad on their own iOS devices from the Apple App Store and reported their pain using the app twice daily for 1 week. Participants then emailed their pain reports from the app to the research team and completed an online survey on their experiences. Key implementation outcomes included acceptability, appropriateness, cost, feasibility, fidelity, penetration, and sustainability. Results Of the 149 parents contacted, 16 of their children agreed to participate. More than a third (6/16, 37.5%) of participating children returned their pain reports to the research team. Adherence to the pain assessments was 62.1% (mean 8.7/14 assessments). The 6 children who returned reports rated the app as highly feasible to download and use and rated their overall experience as acceptable. They also reported that they would be willing to sustain their Pain Squad use over several weeks and that they would recommend it to other children with cancer, which suggests that it may have potential for penetration. Conclusions While Pain Squad was well received by the small number of children who completed the study, user uptake, engagement, and adherence were significant barriers to the implementation of Pain Squad in a natural setting. Implementation studies such as this highlight important challenges and opportunities for promoting the use and uptake of evidence-based technologies by the intended end-users.
Genetic Contribution to the Divergence in Type 1 Diabetes Risk Between Children From the General Population and Children From Affected Families

The risk for autoimmunity and subsequently type 1 diabetes is 10-fold higher in children with a first-degree family history of type 1 diabetes (FDR children) than in children in the general population (GP children). We analyzed children with high-risk HLA genotypes (n = 4,573) in the longitudinal TEDDY birth cohort to determine how much of the divergent risk is attributable to genetic enrichment in affected families. Enrichment for susceptible genotypes of multiple type 1 diabetes–associated genes and a novel risk gene, BTNL2, was identified in FDR children compared with GP children. After correction for genetic enrichment, the risks in the FDR and GP children converged but were not identical for multiple islet autoantibodies (hazard ratio [HR] 2.26 [95% CI 1.6–3.02]) and for diabetes (HR 2.92 [95% CI 2.05–4.16]). Convergence varied depending upon the degree of genetic susceptibility. Risks were similar in the highest genetic susceptibility group for multiple islet autoantibodies (14.3% vs .12.7%) and diabetes (4.8% vs. 4.1%) and were up to 5.8-fold divergent for children in the lowest genetic susceptibility group, decreasing incrementally in GP children but not in FDR children. These findings suggest that additional factors enriched within affected families preferentially increase the risk of autoimmunity and type 1 diabetes in lower genetic susceptibility strata.
Algebras, diagrams and decisions in language, logic and computation

This exemplary volume shows how the shared interests of three different research areas can lead to significant and fruitful exchanges: each of six papers very accessibly presents an exciting contribution to the study and uses of algebra, diagrams, and decisions, ranging from indipensable overview papers about shared formal members to inspiring applications of formal tools to specific problems.
Cigarette Smoking and E-Cigarette Use by Pharmacy Students in Serbia

Abstract The purpose of this study was to assess the use of e-cigarettes among pharmacy students. In 2016, we conducted a cross-sectional study among pharmacy students enrolled at the University of Kragujevac (Serbia). Overall, 47.0% of pharmacy students reported that they ever smoked cigarettes; 29.7% were former and 17.3% were current smokers. The overall prevalence of e-cigarette use was 9.9%. The final year pharmacy students significantly more frequently smoked tobacco cigarettes (p = .001) and used e-cigarettes (p = .009) compared to younger students. Also, alcohol use was positively related to ever smoking tobacco cigarettes (adjusted OR = 4.57, 95% CI = 2.80–7.43; p < .001) and to ever use of e-cigarettes (adjusted OR = 5.58, 95% CI = 1.58–19.71; p = .008). The pharmacy students who ever used e-cigarettes more frequently reported a history of self-funded study financing (adjusted OR = 14.68, 95% CI = 2.42–89.17; p = .004) and use of psychoactive substances (adjusted OR = 13.63, 95% CI = 2.52–73.69; p = .002). In pharmacy students, a higher overall grade was related to a significantly less frequent ever use of tobacco cigarettes (adjusted OR = 0.43, 95% CI = 0.22–0.84, p = .015). This paper highlights the need for a more effective tobacco control among pharmacy students in Serbia in order to reduce smoking prevalence.
The influence of truncating the carboxy-terminal amino acid residues of streptococcal enolase on its ability to interact with canine plasminogen

The native octameric structure of streptococcal enolase from Streptococcus pyogenes increasingly dissociates as amino acid residues are removed one by one from the carboxy-terminus. These truncations gradually convert native octameric enolase into monomers and oligomers. In this work, we investigated how these truncations influence the interaction between Streptococcal enolase and canine plasminogen. We used dual polarization interferometry (DPI), localized surface plasmon resonance (LSPR), and sedimentation velocity analytical ultracentrifugation (AUC) to study the interaction. The DPI was our first technique, was performed on all the truncations and used one exclusive kind of chip. The LSRP was used to show that the DPI results were not dependent on the type of chip used. The AUC was required to show that our surface results were not the result of selecting a minority population in any given sample; the majority of the protein was responsible for the binding phenomenon we observed. By comparing results from these techniques we identified one detail that is essential for streptococcal enolase to bind plasminogen: In our hands the individual monomers bind plasminogen; dimers, trimers, tetramers may or may not bind, the fully intact, native, octamer does not bind plasminogen. We also evaluated the contribution to the equilibrium constant made by surface binding as well as in solution. On a surface, the association coefficient is about twice that in solution. The difference is probably not significant. Finally, the fully octameric form of the protein that does not contain a hexahis N-terminal peptide does not bind to a silicon oxynitride surface, does not bind to a Au-nanoparticle surface, does not bind to a surface coated with Ni-NTA nor does it bind to a surface coated with DPgn. The likelihood is great that the enolase species on the surface of Streptococcus pyogenes is an x-mer of the native octamer.
SOCK : A calculus for service oriented computing

Service oriented computing is an emerging paradigm for designing distributed applications where service and composition are the main concepts it is based upon. In this paper we propose SOCK, a three-layered calculus equipped with a formal semantics, for addressing all the basic mechanisms of service communication and composition. The main contribute of our work is the development of a formal framework where the service design is decomposed into three fundamental parts: the behaviour, the declaration and the composition where each part can be designed independently of the other ones.
Interleukin-6 and Diabetic Retinopathy: A Systematic Review and Meta-Analysis

ABSTRACT Background: Interleukin-6 (IL-6) is produced by a variety of cells involved in inflammation and acts as local intensification signals in pathological processes associated with chronic eye inflammation. This meta-analysis was performed to provide a better understanding of the relationship between IL-6 and diabetic retinopathy. Methods: The study was started with systematic search for literatures by using the PubMed, Web of Science and Embase online databases. The standard mean difference (SMD) and its 95% confidence intervals (CIs) were was included and then pooled with a random effects model. Results: Thirty-one articles, containing1099 DR patients and 1010 controls, were included in this meta-analysis. The level of IL-6 in the DR group was found to be higher than that in the control group (SMD: 2.12, 95% CI: 1.53−2.70, p < 0.00001). Obvious heterogeneity existed between the studies (p < 0.00001, I2 = 96%). So a subgroup analysis and sensitivity analysis were performed. Removing the sensitivity studies, the stability of the overall treatment effect was good. Subgroup analysis showed that the levels of IL-6 in case group were observed to be higher than those in the control group; and the IL-6 levels in the proliferative diabetic retinopathy (PDR) group were also higher than those in the non-proliferative diabetic retinopathy (NPDR) group. (SMD: 0.78, 95% CI: 0.26–1.31, p= 0.003) Conclusion: The results from this current meta-analysis indicated that increased level of IL-6 generally exist in DR patients. And it may associated with the severity of DR. However, large-scale and high-quality studies in future are required to confirm the present findings.
Molecular Dynamics Simulations of Wild Type and Mutants of SAPAP in Complexed with Shank3

Specific interactions between scaffold protein SH3 and multiple ankyrin repeat domains protein 3 (Shank3) and synapse-associated protein 90/postsynaptic density-95–associated protein (SAPAP) are essential for excitatory synapse development and plasticity. In a bunch of human neurological diseases, mutations on Shank3 or SAPAP are detected. To investigate the dynamical and thermodynamic properties of the specific binding between the N-terminal extended PDZ (Post-synaptic density-95/Discs large/Zonaoccludens-1) domain (N-PDZ) of Shank3 and the extended PDZ binding motif (E-PBM) of SAPAP, molecular dynamics simulation approaches were used to study the complex of N-PDZ with wild type and mutated E-PBM peptides. To compare with the experimental data, 974QTRL977 and 966IEIYI970 of E-PBM peptide were mutated to prolines to obtain the M4P and M5P system, respectively. Conformational analysis shows that the canonical PDZ domain is stable while the βN extension presents high flexibility in all systems, especially for M5P. The high flexibility of βN extension seems to set up a barrier for the non-specific binding in this area and provide the basis for specific molecular recognition between Shank3 and SAPAP. The wild type E-PBM tightly binds to N-PDZ during the simulation while loss of binding is observed in different segments of the mutated E-PBM peptides. Energy decomposition and hydrogen bonds analysis show that M4P mutations only disrupt the interactions with canonical PDZ domain, but the interactions with βN1′ remain. In M5P system, although the interactions with βN1′ are abolished, the binding between peptide and the canonical PDZ domain is not affected. The results indicate that the interactions in the two-binding site, the canonical PDZ domain and the βN1′ extension, contribute to the binding between E-PBM and N-PDZ independently. The binding free energies calculated by MM/GBSA (Molecular Mechanics/Generalized Born Surface Area) are in agreement with the experimental binding affinities. Most of the residues on E-PBM contribute considerably favorable energies to the binding except A963 and D964 in the N-terminal. The study provides information to understand the molecular basis of specific binding between Shank3 and SAPAP, as well as clues for design of peptide inhibitors.
Light-Activated ROS Production Induces Synaptic Autophagy

The regulated turnover of synaptic vesicle (SV) proteins is thought to involve the ubiquitin-dependent tagging and degradation through endo-lysosomal and autophagy pathways. Yet, it remains unclear which of these pathways are used, when they become activated, and whether SVs are cleared en masse together with SV proteins or whether both are degraded selectively. Equally puzzling is how quickly these systems can be activated and whether they function in real-time to support synaptic health. To address these questions, we have developed an imaging-based system that simultaneously tags presynaptic proteins while monitoring autophagy. Moreover, by tagging SV proteins with a light-activated ROS generator, Supernova, it was possible to temporally control the damage to specific SV proteins and assess their consequence to autophagy-mediated clearance mechanisms and synaptic function. Our results show that, in mouse hippocampal neurons of either sex, presynaptic autophagy can be induced in as little as 5–10 min and eliminates primarily the damaged protein rather than the SV en masse. Importantly, we also find that autophagy is essential for synaptic function, as light-activated damage to, for example, Synaptophysin only compromises synaptic function when autophagy is simultaneously blocked. These data support the concept that presynaptic boutons have a robust highly regulated clearance system to maintain not only synapse integrity, but also synaptic function. SIGNIFICANCE STATEMENT The real-time surveillance and clearance of synaptic proteins are thought to be vital to the health, functionality, and integrity of vertebrate synapses and are compromised in neurodegenerative disorders, yet the fundamental mechanisms regulating these systems remain enigmatic. Our analysis reveals that presynaptic autophagy is a critical part of a real-time clearance system at synapses capable of responding to local damage of synaptic vesicle proteins within minutes and to be critical for the ongoing functionality of these synapses. These data indicate that synapse autophagy is not only locally regulated but also crucial for the health and functionality of vertebrate presynaptic boutons.
The influence of β-amyloid on [18F]AV-1451 in semantic variant of primary progressive aphasia

Objective To compare [18F]AV-1451 uptake in the semantic variant of primary progressive aphasia (svPPA) to Alzheimer dementia, and determine whether increased uptake in svPPA is associated with the presence of β-amyloid (Aβ). Methods Thirty-one participants with svPPA underwent MRI and Pittsburgh compound B–PET scanning, and 17 of these also underwent [18F]AV-1451 tau-PET. A global Pittsburgh compound B standardized uptake value ratio was calculated for all participants, with a cutoff of 1.42 used to define Aβ(+) participants. We assessed region and voxel-level [18F]AV-1451 uptake in the whole svPPA cohort and separately in Aβ(+) and Aβ(−) svPPA groups, compared to 12 Aβ(+) participants with Alzheimer dementia and 170 cognitively normal, Aβ(−) controls. Results Of the entire cohort of participants with svPPA, 26% were Aβ(+). The Aβ(+) participants were older at scan compared to the Aβ(−) participants. svPPA showed elevated [18F]AV-1451 uptake in anteromedial temporal regions but the degree of uptake was lower than in Alzheimer dementia. After controlling for age, Aβ(+) status in svPPA was associated with significantly higher uptake in all anteromedial and inferior/middle lateral temporal regions, but uptake was still lower than in Alzheimer dementia. Conclusion Although [18F]AV-1451 uptake is focally elevated in svPPA, the level of uptake is much less than what occurs in Alzheimer dementia and appears to be at least partially related to Aβ. Therefore, it is possible that some of the increased uptake of [18F]AV-1451 in svPPA is related to binding paired helical filament tau.
Greater risk for more money: the economics of negotiating condom use amongst sex workers in South Africa

ABSTRACT The economics of sex work and the effect on safe sex practices remain understudied. This research contributes to a better understanding of how economic opportunity and vulnerability place sex workers (SWs) at an increased risk of STI infection. Using quantitative and qualitative methods, we investigated the role of economic incentives in determining condom use among SWs. The data reveals that SWs are on average, nearly doubling their rates for condomless sex. Our findings that SWs are engaging in condomless sex to increase their earnings, illustrates the point that the context in which they operate influences condom negotiation and consequently, increases risky sexual behaviour.
Exploring a new structured professional judgment measure (impulsivity measure related to violence) after an average follow‐up of 10 years: A study of Finnish offenders

Abstract Background Identification of the risk factors underlying impulsivity related to violent acts is an essential component of risk assessment and management to reduce violent offending. Aims Our aim was to develop a clinically useful measure for assessing impulsivity related to violence. Our research questions were which items in the newly developed measure are associated with later violent recidivism and what is the measure's predictive validity? Methods A new scale, the impulsivity measure related to violence (IMP‐V), was studied by completing the scale, blind to outcome, from information in the forensic psychiatric examination reports of 63 of a 1‐year referral cohort of 181 Finnish offenders. Data on reoffending for up to 15 years after release were collected from official criminal records. Results The predictive accuracy of the IMP‐V continuous ratings was 78% and for the categorical summary risk ratings 77%. Univariate analyses of categorical summary risk ratings of the risk factors revealed that, with two exceptions, each additional score on the IMP‐V was associated with a significant increase in violence recidivism. Conclusions These preliminary results indicate that the IMP‐V is a promising decision‐enhancing guide for assessing the risk of violence in impulsive people and that the measure is worth developing for use with impulsivity‐prone offenders and forensic psychiatric patients. The IMP‐V organises information on the nature of impulsivity in violence‐prone persons and thus also creates opportunities for more effective risk management.
The weekend effect in status epilepticus: a national cohort study

Higher mortality following admission to hospital at the weekend has been reported for several conditions. It is unclear whether this variation is due to differences in patients or their care. Status epilepticus mandates hospital admission and usually critical care: its study might provide new insights into the nature of any weekend effect. We studied 20,922 adults admitted to UK critical care with status epilepticus from 2010 to 2015. We used multiple logistic regression to evaluate the association between weekend admission and in‐hospital mortality, comparing university hospitals with other hospitals. There were 2462 in‐hospital deaths (12%). There was no difference in mortality after weekend admission to university hospitals, adjusted odds ratio (95%CI) 0.99 (0.84–1.16), p = 0.89. Mortality was less after weekend admission than after admissions Monday to Friday in hospitals not associated with a university, adjusted odds ratio (95%CI) 0.74 (0.64–0.87), p = 0.0001. There is no evidence that adults admitted to UK critical care at the weekend in status epilepticus are more likely to die than similar patients admitted during the week.
Antimicrobial potential of haloalkaliphilic Nocardiopsis sp. AJ1 isolated from solar salterns in India

Antagonistic haloalkaliphilic Nocardiopsis sp. AJ1 (GenBank JX575136.1), isolated and identified from the saline soil of Kovalam solar salterns was able to produce antimicrobial secondary metabolites and effectively suppressed several bacterial and fungal pathogens. The metabolite extracted from ethyl acetate precipitation suppressed the bacterial and fungal pathogens to the range between 2.14 and 20.14 mm and also controlled the shrimp killer virus WSSV by 83% than the control and significantly (p < 0.05) differed. GC‐MS analysis revealed that, the ethyl acetate precipitation contains pyrrolo (1,2‐A(pyrazine‐1,4‐dione, hexahydro‐3‐(2‐methylpropyl)‐) and actinomycin C2. Non ribosomal peptide synthetase (NRPS) was amplified by PCR with the amplicon size of 750‐800 bp length and further predicted the secondary structure by Iterative Threading Assembly Refinement (I‐TASSER) bioinformatics approach. I‐TASSER prediction helped to find out the secondary, 3‐D structure, and ligand binding sites. The top ten modelling concluded that, the NRPS gene is closely similar to surfactin synthesizing gene, surfactin A synthetase C (SRFA‐C). The findings revealed that, the active compounds from the secondary metabolites effectively suppressed the pathogenic bacteria, fungi, and virus and useful to develop antimicrobials.
Temporal dynamics of the pharmacological MRI response to subanaesthetic ketamine in healthy volunteers: A simultaneous EEG/fMRI study

Background: Pharmacological magnetic resonance imaging has been used to investigate the neural effects of subanaesthetic ketamine in healthy volunteers. However, the effect of ketamine has been modelled with a single time course and without consideration of physiological noise. Aims: This study aimed to investigate ketamine-induced alterations in resting neural activity using conventional pharmacological magnetic resonance imaging analysis techniques with physiological noise correction, and a novel analysis utilising simultaneously recorded electroencephalography data. Methods: Simultaneous electroencephalography/functional magnetic resonance imaging and physiological data were collected from 30 healthy male participants before and during a subanaesthetic intravenous ketamine infusion. Results: Consistent with previous literature, we show widespread cortical blood-oxygen-level dependent signal increases and decreased blood-oxygen-level dependent signals in the subgenual anterior cingulate cortex following ketamine. However, the latter effect was attenuated by the inclusion of motion regressors and physiological correction in the model. In a novel analysis, we modelled the pharmacological magnetic resonance imaging response with the power time series of seven electroencephalography frequency bands. This showed evidence for distinct temporal time courses of neural responses to ketamine. No electroencephalography power time series correlated with decreased blood-oxygen-level dependent signal in the subgenual anterior cingulate cortex. Conclusions: We suggest the decrease in blood-oxygen-level dependent signals in the subgenual anterior cingulate cortex typically seen in the literature is the result of physiological noise, in particular cardiac pulsatility. Furthermore, modelling the pharmacological magnetic resonance imaging response with a single temporal model does not completely capture the full spectrum of neuronal dynamics. The use of electroencephalography regressors to model the response can increase confidence that the pharmacological magnetic resonance imaging is directly related to underlying neural activity.