Miracle-dz/UniFAR-FTUs huggingface dataset:
IT-based reminders for medication adherence: systematic review, taxonomy, framework and research directions

ABSTRACT IT-based reminders have been one of the most promising interventions to improve medication adherence. Even with considerable research, it is not clear what types of reminders are effective for different patients and diseases and how much improvement in adherence is sustainable over time. To answer this, we conduct a systematic literature review of IT-based reminders. We utilise a six-step process reflecting the systematicity and transparency which is implemented using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Then, we develop a taxonomy of reminders, using Nickerson’s method, including thirteen characteristics categorised in four different dimensions. The findings are used in deciding when and where and how to use reminders with what type of patients for how long in improving medication adherence. The subsequent detailed analysis of the articles brought numerous insights leading to the development of Comprehensive Framework for Medication Reminders (CFMR). The framework can be used by the IS researchers for developing theoretical models to study the effectiveness of interventions for improving medication adherence. The taxonomy can be extended to a multi-level taxonomy using the proposed framework and research directions and can be further evaluated using domain experts.
Elaborating dependent (co)pattern matching: No pattern left behind

In a dependently typed language, we can guarantee correctness of our programmes by providing formal proofs. To check them, the typechecker elaborates these programs and proofs into a lowlevel core language. However, this core language is by nature hard to understand by mere humans, so how can we know we proved the right thing? This question occurs in particular for dependent copattern matching, a powerful language construct for writing programmes and proofs by dependent case analysis and mixed induction/coinduction. A definition by copattern matching consists of a list of clauses that are elaborated to a case tree, which can be further translated to primitive eliminators. In previous work this second step has received a lot of attention, but the first step has been mostly ignored so far. We present an algorithm elaborating definitions by dependent copattern matching to a core language with inductive data types, coinductive record types, an identity type, and constants defined by well-typed case trees. To ensure correctness, we prove that elaboration preserves the firstmatch semantics of the user clauses. Based on this theoretical work, we reimplement the algorithm used by Agda to check left-hand sides of definitions by pattern matching. The new implementation is at the same time more general and less complex, and fixes a number of bugs and usability issues with the old version. Thus, we take another step towards the formally verified implementation of a practical dependently typed language.
Facts only the perpetrator could have known? A study of contamination in mock crime interrogations.

OBJECTIVE This paper examines contamination in interrogations: the process by which an interrogator divulges privileged information to a suspect. HYPOTHESES In Experiment 1, we predicted that mock investigators would communicate critical crime details when they interview mock suspects about a crime-and that innocent and guilty suspects alike would later produce confessions that contained these details. In Experiment 2, we hypothesized that observers who listened only to the confessions would exhibit a greater guilt bias than those who also had exposure to the eliciting interview. METHOD Experiment 1 (N = 59) used student participants in a mock crime scenario to test whether contamination is natural to communication even in the absence of external incentives. In Experiment 2, MTurk participants (N = 499) listened to audio-clips from Experiment 1 to test whether presenting observers with the full interview decreases guilt ratings for false confessors. RESULTS Investigators divulged crime information to both innocent and guilty suspects, and even false confessions later included accurate details. Although Experiment 2 observers exhibited a guilt bias, exposure to the interview (not just the confession) attenuated this effect for innocent confessors. CONCLUSIONS The information disclosure associated with contamination is a normal cognitive process that occurs even without external incentives to secure a confession. Experiment 2 showed that seeing contamination in action may decrease judgments of guilt for innocent suspects. Interrogations should be recorded in their entirety to provide fact finders with an objective record of the source of crime details contained within narrative confessions. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
The safety evaluation of food flavoring substances: the role of genotoxicity studies

Abstract The Flavor and Extract Manufacturers Association (FEMA) Expert Panel relies on the weight of evidence from all available data in the safety evaluation of flavoring substances. This process includes data from genotoxicity studies designed to assess the potential of a chemical agent to react with DNA or otherwise cause changes to DNA, either in vitro or in vivo. The Panel has reviewed a large number of in vitro and in vivo genotoxicity studies during the course of its ongoing safety evaluations of flavorings. The adherence of genotoxicity studies to standardized protocols and guidelines, the biological relevance of the results from those studies, and the human relevance of these studies are all important considerations in assessing whether the results raise specific concerns for genotoxic potential. The Panel evaluates genotoxicity studies not only for evidence of genotoxicity hazard, but also for the probability of risk to the consumer in the context of exposure from their use as flavoring substances. The majority of flavoring substances have given no indication of genotoxic potential in studies evaluated by the FEMA Expert Panel. Examples illustrating the assessment of genotoxicity data for flavoring substances and the consideration of the factors noted above are provided. The weight of evidence approach adopted by the FEMA Expert Panel leads to a rational assessment of risk associated with consumer intake of flavoring substances under the conditions of use.
Identification and functional characterization of Penicillium marneffei major facilitator superfamily (MFS) transporters

ABSTRACT Penicillium marneffei is a thermally dimorphic fungus that causes penicilliosis, and become the third-most-common opportunistic fungal infection in immunocompromised patients in Southeast Asia. Azoles and amphotericin B have been introduced for the treatment, however, it is important to investigate possible mechanisms of azole resistance for future treatment failure. We identified 177 putative MFS transporters and classified into 17 subfamilies. Among those, members of the Drug:H+ antiporter 1 subfamily are known to confer resistance to antifungals. Out of 39 paralogs, three (encoded by PmMDR1, PmMDR2, and PmMDR3) were heterologously overexpressed in S. cerevisiae AD∆ conferred resistance to various drugs and compounds including azoles, albeit to different degrees. PmMDR1-expressing strain showed resistance to the broadest range of drugs, followed by the PmMDR3, and PmMDR2 conferred weak resistance to a limited range of drugs. We conclude that PmMDR1 and PmMDR3, may be able to serve as multidrug efflux pumps. Graphical abstract Two MSF transporters of Penicillium marneffei, PmMdr1p and PmMdr3p, showed the efflux pump functions to different antifungals.
An investigation of the relationship between identifying as a smoker and urges to smoke among young adult combustible cigarette smokers.

Identifying as a smoker and urges to smoke are 2 predictors of persistent combustible cigarette smoking. We investigated the relationship between them. Specifically, grounded in PRIME Theory (West & Brown, 2013), we investigated whether a smoker identity and urges to smoke predict each other over time independent of their relationships with smoking behavior. At 3 yearly time points, young adult combustible cigarette smokers (N = 286) completed assessments of endorsement and importance of identifying as a smoker as well as smoking behavior; during the subsequent week at the first 2 time points, participants repeatedly completed assessments of momentary smoking urge intensity and current social situation in randomly prompted ecological momentary assessments (EMA). Within time points, greater endorsement of identifying as a smoker predicted more intense momentary urges to smoke, particularly when in the presence of other people than when alone. Across time points, both elevated and elevating levels of smoker identity endorsement predicted increases in average smoking urge intensity; vice versa, both elevated and elevating levels of average smoking urge intensity predicted increases in smoker identity endorsement and importance. All relationships were independent of smoking behavior. These findings add to our understanding of persistent combustible cigarette smoking, as they indicate that a smoker identity and urges to smoke contribute to each other independent of their relationships with smoking behavior. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
Kainate receptor regulation of synaptic inhibition in the hippocampus

Kainate receptors (KARs) are glutamate‐type receptors that mediate both canonical ionotropic currents and non‐canonical metabotropic signalling. While KARs are expressed widely throughout the brain, synaptic KAR currents have only been recorded at a limited set of synapses, and the KAR currents that have been recorded are relatively small and slow, which has led to the question, what is the functional significance of KARs? While the KAR current itself is relatively modest, its impact on inhibition in the hippocampus can be profound. In the CA1 region of the hippocampus, presynaptic KAR activation bidirectionally regulates γ‐aminobutyric acid (GABA) release in a manner that depends on the glutamate concentration; lower levels of glutamate facilitate GABA release via an ionotropic pathway, while higher levels of glutamate depress GABA release via a metabotropic pathway. Postsynaptic interneuron KAR activation increases spike frequency through an ionotropic current, which in turn can strengthen inhibition. In the CA3 region, postsynaptic KAR activation in pyramidal neurons also strengthens inhibition, but in this case through a metabotropic pathway which regulates the neuronal chloride gradient and hyperpolarizes the reversal potential for GABA (EGABA). Taken together, the evidence for KAR‐mediated regulation of the strength of inhibition via pre‐ and postsynaptic mechanisms provides compelling evidence that KARs are ideally positioned to regulate excitation–inhibition balance – through sensing the excitatory tone and concomitantly tuning the strength of inhibition.
Development, characterization, comparative pharmacokinetic and pharmacodynamic studies of iloperidone solid SMEDDS and liquisolid compact

Abstract Iloperidone (ILO) is an anti-psychotic, used in schizophrenia. It has low bioavailability (36%) due to low solubility and first pass effect. Oral solid self microemulsifying drug delivery system (SMEDDS) and liquisolid compact (LSC) of ILO were developed. The hypothesis is to test in vivo performance (PK and PD effects) of these delivery systems, as both systems improve dissolution. Based on solubility Capmul MCM, Labrafac WL 1349 were selected as oils, Lauroglycol 90 and PEG 600 were selected as surfactant and cosurfactant. Syloid XDP was optimized for adsorption of liquid SMEDDS. Syloid XDP and Aerosil 200 were optimized as carrier and coating material in the ratio of 15:1 w/w for liquisolid formulation. SEM and PXRD studies indicated no specific crystallinity due to bulkiness in both formulations, which showed similar flow and release behavior. Pharmacokinetic studies were performed for ILO Coarse suspension (CS), Tablet suspension (TS), optimized solid SMEDDS (A1X) and liquisolid compact (S3) in wistar rats. About 3.80 and 2.19-fold improvements in relative bioavailabilty were found for A1X and S3, respectively, when compared to CS. In comparison to TS, 2.61 and 1.51 fold improvements in bioavailability were found for A1X and S3, respectively. Further, Pharmacodynamic activity was studied by reversal of MK-801 induced hyperlocomotion in rats. A1X and S3 formulations showed maximum reversal after 15 min when compared to CS and found to have similar performance. Thus, in comparison to S3, A1X showed significant difference in pharmacokinetic effects but similar pharmacodynamic effects.
Incidence and Associations of Chronic Kidney Disease in Community Participants With Diabetes: A 5-Year Prospective Analysis of the EXTEND45 Study

OBJECTIVE To determine the incidence of and factors associated with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 in people with diabetes. RESEARCH DESIGN AND METHODS We identified people with diabetes in the EXamining ouTcomEs in chroNic Disease in the 45 and Up Study (EXTEND45), a population-based cohort study (2006–2014) that linked the Sax Institute’s 45 and Up Study cohort to community laboratory and administrative data in New South Wales, Australia. The study outcome was the first eGFR measurement <60 mL/min/1.73 m2 recorded during the follow-up period. Participants with eGFR < 60 mL/min/1.73 m2 at baseline were excluded. We used Poisson regression to estimate the incidence of eGFR <60 mL/min/1.73 m2 and multivariable Cox regression to examine factors associated with the study outcome. RESULTS Of 9,313 participants with diabetes, 2,106 (22.6%) developed incident eGFR <60 mL/min/1.73 m2 over a median follow-up time of 5.7 years (interquartile range, 3.0–5.9 years). The eGFR <60 mL/min/1.73 m2 incidence rate per 100 person-years was 6.0 (95% CI 5.7–6.3) overall, 1.5 (1.3–1.9) in participants aged 45–54 years, 3.7 (3.4–4.0) for 55–64 year olds, 7.6 (7.1–8.1) for 65–74 year olds, 15.0 (13.0–16.0) for 75–84 year olds, and 26.0 (22.0–32.0) for those aged 85 years and over. In a fully adjusted multivariable model incidence was independently associated with age (hazard ratio 1.23 per 5-year increase; 95% CI 1.19–1.26), geography (outer regional and remote versus major city: 1.36; 1.17–1.58), obesity (obese class III versus normal: 1.44; 1.16–1.80), and the presence of hypertension (1.52; 1.33–1.73), coronary heart disease (1.13; 1.02–1.24), cancer (1.30; 1.14–1.50), and depression/anxiety (1.14; 1.01–1.27). CONCLUSIONS In participants with diabetes, the incidence of an eGFR <60 mL/min/1.73 m2 was high. Older age, remoteness of residence, and the presence of various comorbid conditions were associated with higher incidence.
Acid exposure disrupts mucus secretion and impairs mucociliary transport in neonatal piglet airways.

Tenacious mucus produced by tracheal and bronchial submucosal glands is a defining feature of several airway diseases, including cystic fibrosis (CF). Airway acidification as a driving force of CF airway pathology has been controversial. Here we tested the hypothesis that transient airway acidification produces pathologic mucus and impairs mucociliary transport. We studied pigs challenged with intra-airway acid. Acid had a minimal effect on mucus properties under basal conditions. However, cholinergic stimulation in acid-challenged pigs revealed retention of mucin 5B (MUC5B) in the submucosal glands, decreased concentrations of MUC5B in the lung lavage fluid, and airway obstruction. To more closely mimic a CF-like environment, we also examined mucus secretion and transport following cholinergic stimulation under diminished bicarbonate and chloride transport conditions ex vivo. Under these conditions, airways from acid-challenged pigs displayed extensive mucus films and decreased mucociliary transport. Pre-treatment with diminazene aceturate, a small molecule with the ability to inhibit acid detection through blockade of the acid-sensing ion channel (ASIC) at the doses provided, did not prevent acid-induced pathologic mucus or transport defects but did mitigate airway obstruction. These findings suggest that transient airway acidification early in life has significant impacts on mucus secretion and transport properties. Further, they highlight diminazene aceturate as an agent that might be beneficial in alleviating airway obstruction.
Effectiveness of treadmill training on gait function in children with cerebral palsy: meta-analysis

The purpose of this review was to analysis the effects of treadmill training on gait function in children with cerebral palsy. Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Central Register of Controlled Trials, Physiotherapy Evidence Database (PEDro), PubMed and Web of Science were searched. Investigating the effects of treadmill training on gait endurance, gait speed, limb support time, cadence, and step length in children with cerebral palsy. Similar outcomes were pooled by calculating the standardized mean difference. Of the eight studies, 179 participants were included. The average PEDro score was 6.25/10. The results of the sensitivity test for bias evaluation using the duval and tweedie’s trim and fill method showed low publication bias. The test regarding the effect of treadmill training on overall gait function yielded a moderate effect size of 0.53, which was a statistically significant effect as its confidence interval did not include. The overall effect size of gait endurance was 0.85. The overall effect size of gait speed and limb support time were 0.52 and 0.73. The overall effect size of cadence and step length were 0.14 and 0.21, indicating a nonsignificant improvement. These findings suggested that treadmill training on cerebral palsy was effective for gait endurance, gait speed and limb support time than cadence and step length.
Combined Influences of Dementia Exposure and Personality on Self-Reported Memory Problems

The current study investigated whether having a first-degree relative with dementia influenced older adults’ self-reported memory, if personality traits moderated these associations, and whether these associations differed by the type of item asked (ie, frequency of memory problems vs perceived memory decline). Data drawn from the Einstein Aging study included 454 older adults (M age = 76.64, standard deviation = 4.77, 66.96% white, and 63% female). Multilevel modeling analyses showed participants who had a first-degree relative with dementia reported more frequent memory problems and were more likely to report memory decline over the past year. Among participants with a first-degree relative with dementia, higher levels of neuroticism were related to reports of more frequent memory problems at baseline, whereas higher levels of conscientiousness and lower levels of extraversion were related to reports of more frequent memory problems over time. Future research should consider personality traits and family history of dementia as potential contributors to self-reported memory problems.
Mortality of Different Stages of Plodia interpunctella (Lepidoptera: Pyralidae) at Three Temperatures in Controlled Atmosphere of High Nitrogen

Abstract The lethal exposure time to controlled atmospheres of high nitrogen at stored grain temperatures is an important information for control of stored-product insects. The mortality of 1-d-old egg, 1-wk-old (first or second instar) larva, 3-wk-old (fourth or fifth instar) larva, and 1-d-old pupa of Plodia interpunctella (Hübner) was determined at 18 ± 1, 23 ± 1, and 28 ± 1°C in 98% N2 mixed with air. At 18°C, the lethal exposure times to achieve 100% mortality were 12.7 ± 0.7, 16.3 ± 0.3, 19.7 ± 0.7, and 14.7 ± 0.7 d for 1-d-old egg, 1-wk-old larva, 3-wk-old larva, and 1-d-old pupa, respectively. Temperature had significant effect on the lethal exposure time, and increase of the temperature significantly decreased the lethal exposure time. The order of the insect stages from the highest to lowest for LT50 values was follows: 3-wk-old larva > 1-wk-old larva > 1-d-old pupa ≥ 1-d-old egg. The minimum lethal exposure times required to kill all stages of P. interpunctella were about 20, 16, and 12 d at 18, 23, and 28°C, respectively.
Effect of tadalafil on penile nitric oxide synthase and corporal smooth muscle in rats under dutasteride treatment

Abstract Aim: To investigate the effect of tadalafil in rats administered with daily dutasteride. Methods: Twenty-four Sprague–Dawley male rats were allocated to three groups as control (group C), dutasteride (group D) and dutasteride plus tadalafil (group D + T). After a month of treatment, serum samples were obtained from rats to measure dihydrotestosterone and total testosterone. Nitric oxide (NO) synthase (NOS) immunoreactivity and levels of NOS enzyme isoforms, NO and cyclic guanosine monophosphate (cGMP) were evaluated in the harvested penile tissues. Also, corporal smooth muscle and collagen were examined. Results: Staining intensities of neuronal NOS and endothelial NOS were significantly lower in group D (p < .05). They were similar between group C and group D + T. Immunoreactivity of inducible NOS was observed higher in group D than group C (p = .01) whereas group D + T had the highest iNOS (p<.001). ELISA revealed similar outcomes in terms of NOS enzyme isoform levels. The mean of smooth muscle to collagen ratio was the lowest in group D (p < .001) and it was similar among group C and group D + T (p = .072). Group D had the lowest cGMP and NO levels (p < .05) and they did not differ between group C and group D + T (p>.05). Group D and group D + T had significantly decreased dihydrotestosterone and increased testosterone, compared to group C (p < .001). They were similar between group D and group D + T. Conclusion: Daily treatment with tadalafil improves dutasteride-induced changes in rat penis.
Use of Lipid Lowering Medications in Youth

The treatment of youth with lipid lowering medications presents some unique challenges and consideration. As demonstrated by the 2011 NHLBI's guidelines, available information regarding the treatment of youth with lipid disorders has greatly expanded. HMG-CoA reductase inhibitors, or statins, are now considered first-line pharmacologic treatment for children and adolescents with severe dyslipidemia who fail treatment with diet and exercise alone, although statins are only FDA approved for youth with familial hypercholesterolemia. Despite their ability to effectively reduced cholesterol levels, use of bile acid sequestrants continue to pose challenges for pediatric patients due to their unpalatability and are typically utilized as adjunctive therapy or for patients not able to tolerate statins. Fibric acid derivatives, as a class of medications, not only lack an FDA approved agent, but also continue to lack significant pediatric safety and efficacy data. Niacin lacks FDA approval for pediatric patients and is plagued by significant adverse effects, making it an unlikely therapeutic option for youth. Ezetimibe provides clinicians with an alternative adjunct therapy option when synergistically paired with an HMG-CoA reductase inhibitor or used as monotherapy for patients intolerant to statins and bile acid sequestrants. Despite several marketed formulations, omega-3 fish oils currently lack FDA approval in pediatric patients and have failed to demonstrate statistically significant lipid lowering in pediatric and adolescent patients. Finally, PCSK9 inhibitors present an emerging adjunctive treatment option with more studies in the pediatric and adolescent population expected. Regular monitoring for adverse events and side effects of therapy is essential as youth will have a greater lifetime exposure compared to adults and long-term data is generally limited. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT. ORG.