Miracle-dz/UniFAR-FTUs huggingface dataset:
Affective E-Learning System: Analysis of Learners' State

Learning systems provide adaptation to the learners’ preferences without taking under consideration the learners’ current status. The more a learning system exchanges relevant fragments of information about the learner’s affective status the more it adapts to it. Following this direction, we propose an integrated learning system taking under consideration learners’ emotional state in order to provide a personalized e-learning system. An extended version of the IEEE Reference Model (WG) LTSA (IEEE 2003) is used for this purpose. The proposed approach is based on the automatic analysis of the learners’ emotional state providing different learners’ profiles which are built and maintained by “observing” each learner behavior. As a learner is strongly positively affected to the learning procedure in the presence of an agent, the proposed system has adopted an expressive ECA (Embodied Conversational Agent) which is adapted to the learner’s emotional states in the duration of the learning procedure. DOI: 10.4018/978-1-60566-940-3.ch015
Accelerating the domestication of a bioenergy crop: identifying and modelling morphological targets for sustainable yield increase in Miscanthus

To accelerate domestication of Miscanthus, an important energy crop, 244 replicated genotypes, including two different species and their hybrids, were analysed for morphological traits and biomass yield over three growing seasons following an establishment phase of 2 years in the largest Miscanthus diversity trial described to date. Stem and leaf traits were selected that contributed both directly and indirectly to total harvested biomass yield, and there was variation in all traits measured. Morphological diversity within the population was correlated with dry matter yield (DMY) both as individual traits and in combination, in order to determine the respective contributions of the traits to biomass accumulation and to identify breeding targets for yield improvement. Predictive morphometric analysis was possible at year 3 within Miscanthus sinensis genotypes but not between M. sinensis, Miscanthus sacchariflorus, and interspecific hybrids. Yield is a complex trait, and no single simple trait explained more than 33% of DMY, which varied from 1 to 5297g among genotypes within this trial. Associating simple traits increased the power of the morphological data to predict yield to 60%. Trait variety, in combination, enabled multiple ideotypes, thereby increasing the potential diversity of the crop for multiple growth locations and end uses. Both triploids and interspecific hybrids produced the highest mature yields, indicating that there is significant heterosis to be exploited within Miscanthus that might be overlooked in early selection screens within years 1–3. The potential for optimizing biomass yield by selecting on the basis of morphology is discussed.
Iterative weighted k-NN for constructing missing feature values in Wisconsin breast cancer dataset

This paper presents a new approach for constructing missing feature values based on iterative nearest neighbors and distance metrics. The proposed approach employs weighted k nearest neighbors' algorithm and propagating the classification accuracy to a certain threshold. The proposed method showed improvement of classification accuracy of 0.005 in the constructed dataset than the original dataset which contain some missing feature values. The maximum classification accuracy was 0.9698 on k=1. This work is a component from a research for an automated diagnosing for breast cancer. The main aim of the current paper is to prepare the dataset for mining process. Future work includes applying the proposed method on more datasets.
Epidemiology and burden of osteoarthritis.

BACKGROUND Osteoarthritis (OA) is a degenerative joint disease involving the cartilage and many of its surrounding tissues. Disease progression is usually slow but can ultimately lead to joint failure with pain and disability. OA of the hips and knees tends to cause the greatest burden to the population as pain and stiffness in these large weight-bearing joints often leads to significant disability requiring surgical intervention. SOURCES OF DATA The article reviews the existing data on epidemiology of osteoarthritis and the burden of the disease. AREAS OF AGREEMENT Symptoms and radiographic changes are poorly correlated in OA. Established risk factors include obesity, local trauma and occupation. The burden of OA is physical, psychological and socioeconomic. AREAS OF CONTROVERSY Available data does not allow definite conclusion regarding the roles of nutrition, smoking and sarcopenia as risk factors for developing OA. GROWING POINTS Variable methods of diagnosing osteoarthritis have significantly influenced the comparability of the available literature. AREAS TIMELY FOR DEVELOPING RESEARCH Further research is required to fully understand how OA affects an individual physically and psychologically, and to determine their healthcare need.
Proteins Involved in the Trafficking and Functional Synaptic Expression of AMPA and KA Receptors

α-Amino-3-hydroxy-5-methylisoxazolepropionate receptors (AMPARs) mediate the majority of fast synaptic transmission in the mammalian central nervous system, play a central role in synapse stabilisation and plasticity, and their prolonged activation is potently neurotoxic. The functional roles of kainate receptors (KARs) are less well defined but they play a role in some forms of synaptic plasticity. Both receptor types have been shown to be highly developmentally and activity-dependently regulated and their functional synaptic expression is under tight cellular regulation. The molecular and cellular mechanisms that regulate the synaptic localisation and functional expression of AMPARs and KARs are objects of concerted research. There has been significant progress towards elucidating some of the processes involved with the discovery of an array of proteins that selectively interact with individual AMPAR and KAR subunits. These proteins have been implicated in, among other things, the regulation of post-translational modification, targeting and trafficking, surface expression, and anchoring. The aim of this review is to present an overview of the major interacting proteins and suggest how they may fit into the hierarchical series of events controlling the trafficking of AMPARs and KARs.
Young‐onset Alzheimer dementia: a comparison of Brazilian and Norwegian carers' experiences and needs for assistance

Although dementia typically occurs in older people, it can also emerge in people aged younger than 65 years in the form of young‐onset dementia, the most common type of which is Alzheimer's disease (AD). However, few studies have examined the needs of persons with young‐onset AD (YO‐AD) and their families, and cross‐cultural research on the topic is even scarcer. In response, we investigated the situations, experiences and needs for assistance of carers of persons with YO‐AD in Brazil and Norway.
Control of the thymic medulla and its influence on αβT‐cell development

The thymus is a primary lymphoid tissue that supports the generation of αβT cells. In this review, we describe the processes that give rise to the thymus medulla, a site that nurtures self‐tolerant T‐cell generation following positive selection events that take place in the cortex. To summarize the developmental pathways that generate medullary thymic epithelial cells (mTEC) from their immature progenitors, we describe work on both the initial emergence of the medulla during embryogenesis, and the maintenance of the medulla during postnatal stages. We also investigate the varying roles that receptors belonging to the tumor necrosis factor receptor superfamily have on thymus medulla development and formation, and highlight the impact that T‐cell development has on thymus medulla formation. Finally, we examine the evidence that the thymic medulla plays an important role during the intrathymic generation of distinct αβT‐cell subtypes. Collectively, these studies provide new insight into the development and functional importance of medullary microenvironments during self‐tolerant T‐cell production in the thymus.
Effectiveness and cost-effectiveness of a stepped care intervention for alcohol use disorders in primary care: pilot study.

BACKGROUND Screening for alcohol use disorders identifies a wide range of needs, varying from hazardous and harmful drinking to alcohol dependence. Stepped care offers a potentially resource-efficient way of meeting these needs, but requires evaluation in a randomised controlled trial. AIMS To evaluate the feasibility, effectiveness and cost-effectiveness of opportunistic screening and a stepped care intervention in primary care. METHOD A total of 1794 male primary care attendees at six practices in South Wales were screened using the Alcohol Use Disorders Identification Test (AUDIT). Of these, 112 participants who scored 8 or more on the AUDIT and who consented to enter the study were randomised to receive either 5 minutes of minimal intervention delivered by a practice nurse (control group) or stepped care intervention consisting of three successive steps (intervention group): a single session of behaviour change counselling delivered by a practice nurse; four 50-minute sessions of motivational enhancement therapy delivered by a trained alcohol counsellor; and referral to a community alcohol treatment agency. RESULTS Both groups reduced alcohol consumption 6 months after randomisation with a greater, although not significant, improvement for the stepped care intervention. Motivation to change was greater following the stepped care intervention. The stepped care intervention resulted in greater cost savings compared with the minimal intervention. CONCLUSIONS Stepped care was feasible to implement in the primary care setting and resulted in greater cost savings compared with minimal intervention.
The Lower Limit of Cerebral Blood Flow Autoregulation Is Increased with Elevated Intracranial Pressure

BACKGROUND: The cerebral perfusion pressure that denotes the lower limit of cerebral blood flow autoregulation (LLA) is generally considered to be equivalent for reductions in arterial blood pressure (ABP) or increases in intracranial pressure (ICP). However, the effect of decreasing ABP at different levels of ICP has not been well studied. Our objective in the present study was to determine if the LLA during arterial hypotension was invariant with ICP. METHODS: Using continuous ventricular fluid infusion, anesthetized piglets were assigned to 1 of 3 groups: naïve ICP (n = 10), moderately elevated ICP (20 mm Hg; n = 11), or severely elevated ICP (40 mm Hg; n = 9). Gradual hypotension was induced by inflation of a balloon catheter in the inferior vena cava. The LLA was determined by monitoring cortical laser-Doppler flux. RESULTS: The naïve ICP group had an average CPP at the LLA (LLACPP) of 29.8 mm Hg (95% CI: 26.5–33.0 mm Hg). However, the moderately elevated ICP group had a mean LLACPP of 37.6 mm Hg (95% CI: 32.0–43.2 mm Hg), and the severely elevated ICP group had a mean LLACPP of 51.4 mm Hg (95% CI: 41.2–61.7 mm Hg). The LLA significantly differed among groups, and the increase in LLA correlated with the increase in ICP. CONCLUSIONS: In this atraumatic, elevated ICP model in piglets, the LLA had a positive correlation with ICP, which suggests that compensating for an acute increase in ICP with an equal increase in ABP may not be sufficient to prevent cerebral ischemia.
Age and SPARC Change the Extracellular Matrix Composition of the Left Ventricle

Secreted protein acidic and rich in cysteine (SPARC), a collagen-binding matricellular protein, has been implicated in procollagen processing and deposition. The aim of this study was to investigate age- and SPARC-dependent changes in protein composition of the cardiac extracellular matrix (ECM). We studied 6 groups of mice (n = 4/group): young (4-5 months old), middle-aged (11-12 m.o.), and old (18–29 m.o.) C57BL/6J wild type (WT) and SPARC null. The left ventricle (LV) was decellularized to enrich for ECM proteins. Protein extracts were separated by SDS-PAGE, digested in-gel, and analyzed by HPLC-ESI-MS/MS. Relative quantification was performed by spectral counting, and changes in specific proteins were validated by immunoblotting. We identified 321 proteins, of which 44 proteins were extracellular proteins. Of these proteins, collagen III levels were lower in the old null mice compared to WT, suggestive of a role for SPARC in collagen deposition. Additionally, fibrillin showed a significant increase in the null middle-aged group, suggestive of increased microfibril deposition in the absence of SPARC. Collagen VI increased with age in both genotypes (>3-fold), while collagen IV showed increased age-associated levels only in the WT animals (4-fold, P < 0.05). These changes may explain the previously reported age-associated increases in LV stiffness. In summary, our data suggest SPARC is a possible therapeutic target for aging induced LV dysfunction.
Effect of experimental stress on the small bowel and colon in healthy humans

Symptoms of irritable bowel syndrome (IBS) are frequently reported to be exacerbated by stress. Animal studies suggest that corticotrophin releasing hormone (CRH) mediates the effect of stress on the bowel. We have shown that stressed IBS patients with diarrhea have constricted small bowels. We hypothesized that we could mimic this effect by applying experimental stress in the form of either hand immersion in ice water or CRH injection in healthy volunteers (HV).
The incidence and risk factors for new onset atrial fibrillation in the PROSPER study.

AIMS Atrial fibrillation/flutter (AF) is the most common arrhythmia in older people. It associates with reduced exercise capacity, increased risk of stroke, and mortality. We aimed to determine retrospectively whether pravastatin reduces the incidence of AF and whether any electrocardiographic measures or clinical conditions might be risk factors for its development. METHODS AND RESULTS The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) was a randomized, double-blind controlled trial that recruited 5804 individuals aged 70-82 years with a history of, or risk factors for, vascular disease. A total of 2891 were allocated to pravastatin and 2913 to placebo; mean follow-up was 3.2 years. Electrocardiograms (ECGs), which were recorded at baseline, annually thereafter, and at run-out, were processed by computer and reviewed manually. In all, 264 of 2912 (9.1%) of the placebo group and 283 of 2888 (9.8%) of the pravastatin-treated group developed AF [hazard ratio 1.08 (0.92,1.28), P= 0.35)]. Multivariate analysis showed that PR and QTc intervals, age, left ventricular hypertrophy, and ST-T abnormalities were related to development of AF after adjustment for many variables including alcohol consumption, which itself was univariately predictive of developing AF. Previous myocardial infarction on the ECG was not a risk factor. A history of vascular disease was strongly linked with developing AF but not diabetes and hypertension. CONCLUSION Pravastatin does not reduce the incidence of AF in older people at risk of vascular disease, at least in the short-medium term. Risk factors for AF include older age, prolongation of PR or QTc intervals, left ventricular hypertrophy, and ST-T abnormalities on the ECG.
Vaccination with a Shigella DNA Vaccine Vector Induces Antigen-Specific CD8+ T Cells and Antiviral Protective Immunity

ABSTRACT A prototype Shigella human immunodeficiency virus type 1 (HIV-1) gp120 DNA vaccine vector was constructed and evaluated for immunogenicity in a murine model. For comparative purposes, mice were also vaccinated with a vaccinia virus-env(vaccinia-env) vector or the gp120 DNA vaccine alone. Enumeration of the CD8+-T-cell responses to gp120 after vaccination using a gamma interferon enzyme-linked spot assay revealed that a single intranasal dose of the Shigella HIV-1 gp120 DNA vaccine vector elicited a CD8+ T-cell response to gp120, the magnitude of which was comparable to the sizes of the analogous responses to gp120 that developed in mice vaccinated intraperitoneally with the vaccinia-env vector or intramuscularly with the gp120 DNA vaccine. In addition, a single dose of the Shigella gp120 DNA vaccine vector afforded significant protection against a vaccinia-env challenge. Moreover, the number of vaccinia-env PFU recovered in mice vaccinated intranasally with the Shigella vector was about fivefold less than the number recovered from mice vaccinated intramuscularly with the gp120 DNA vaccine. Since theShigella vector did not express detectable levels of gp120, this report confirms that Shigella vectors are capable of delivering passenger DNA vaccines to host cells and inducing robust CD8+ T-cell responses to antigens expressed by the DNA vaccines. Furthermore, to our knowledge, this is the first documentation of antiviral protective immunity following vaccination with a live Shigella DNA vaccine vector.
Mediterranean diet as the diet of choice for patients with chronic kidney disease

Traditional dietary management of chronic kidney disease (CKD) focuses on the quantity within the diet of energy and protein, and the restriction of single micronutrients, with little mention of dietary quality. Dietary patterns that are more plant-based, lower in meat (including processed meat), sodium and refined sugar, and have a higher content of grains and fibres are now included in multiple clinical guidelines for chronic disease prevention. The Mediterranean diet (MD) has been associated with reduced cardiovascular disease incidence in both observational and interventional studies. A wealth of evidence links MD with other beneficial effects on chronic diseases such as diabetes, obesity or cognitive health. This review examines each constituent of the classical MD and evaluates their suitability for the management of patients with CKD. We also evaluate the potential hyperkalaemia risk of increasing fruit and vegetable intake. Overall, a decrease in net endogenous acid production and increase in fibre may lead to a better control of metabolic acidosis. This, together with other putative favourable effects of MD on endothelial function, inflammation, lipid profile and blood pressure, provide mechanistic pathways to explain the observed reduced renal function decline and improved survival in CKD patients adhering to an MD.
Comprehensive characterisation of hypertensive heart disease left ventricular phenotypes

Objective Myocardial intracellular/extracellular structure and aortic function were assessed among hypertensive left ventricular (LV) phenotypes using cardiovascular magnetic resonance (CMR). Methods An observational study from consecutive tertiary hypertension clinic patients referred for CMR (1.5 T) was performed. Four LV phenotypes were defined: (1) normal with normal indexed LV mass (LVM) and LVM to volume ratio (M/V), (2) concentric remodelling with normal LVM but elevated M/V, (3) concentric LV hypertrophy (LVH) with elevated LVM but normal indexed end-diastolic volume (EDV) or (4) eccentric LVH with elevated LVM and EDV. Extracellular volume fraction was measured using T1-mapping. Circumferential strain was calculated by voxel-tracking. Aortic distensibility was derived from high-resolution aortic cines and contemporaneous blood pressure measurements. Results 88 hypertensive patients (49±14 years, 57% men, systolic blood pressure (SBP): 167±30 mm Hg, diastolic blood pressure (DBP): 96±14 mm Hg) were compared with 29 age-matched/sex-matched controls (47±14 years, 59% men, SBP: 128±12 mm Hg, DBP: 79±10 mm Hg). LVH resulted from increased myocardial cell volume (eccentric LVH: 78±19 mL/m2 vs concentric LVH: 73±15 mL/m2 vs concentric remodelling: 55±9 mL/m2, p<0.05, respectively) and interstitial fibrosis (eccentric LVH: 33±10 mL/m2 vs concentric LVH: 30±10 mL/m2 vs concentricremodelling: 19±2 mL/m2, p<0.05, respectively). LVH had worst circumferential impairment (eccentric LVH: −12.8±4.6% vs concentric LVH: −15.5±3.1% vs concentric remodelling: –17.1±3.2%, p<0.05, respectively). Concentric remodelling was associated with reduced aortic distensibility, but not with large intracellular/interstitial expansion or myocardial dysfunction versus controls. Conclusions Myocardial interstitial fibrosis varies across hypertensive LV phenotypes with functional consequences. Eccentric LVH has the most fibrosis and systolic impairment. Concentric remodelling is only associated with abnormal aortic function. Understanding these differences may help tailor future antihypertensive treatments.
Seven Year Itch: Pan-Assay Interference Compounds (PAINS) in 2017—Utility and Limitations

Pan-Assay Interference Compounds (PAINS) are very familiar to medicinal chemists who have spent time fruitlessly trying to optimize these nonprogressible compounds. Electronic filters formulated to recognize PAINS can process hundreds and thousands of compounds in seconds and are in widespread current use to identify PAINS in order to exclude them from further analysis. However, this practice is fraught with danger because such black box treatment is simplistic. Here, we outline for the first time all necessary considerations for the appropriate use of PAINS filters.
Tertiary siRNAs Mediate Paramutation in C. elegans

In the nematode Caenorhabditis elegans, different small RNA-dependent gene silencing mechanisms act in the germline to initiate transgenerational gene silencing. Piwi-interacting RNAs (piRNAs) can initiate transposon and gene silencing by acting upstream of endogenous short interfering RNAs (siRNAs), which engage a nuclear RNA interference (RNAi) pathway to trigger transcriptional gene silencing. Once gene silencing has been established, it can be stably maintained over multiple generations without the requirement of the initial trigger and is also referred to as RNAe or paramutation. This heritable silencing depends on the integrity of the nuclear RNAi pathway. However, the exact mechanism by which silencing is maintained across generations is not understood. Here we demonstrate that silencing of piRNA targets involves the production of two distinct classes of small RNAs with different genetic requirements. The first class, secondary siRNAs, are localized close to the direct target site for piRNAs. Nuclear import of the secondary siRNAs by the Argonaute HRDE-1 leads to the production of a distinct class of small RNAs that map throughout the transcript, which we term tertiary siRNAs. Both classes of small RNAs are necessary for full repression of the target gene and can be maintained independently of the initial piRNA trigger. Consistently, we observed a form of paramutation associated with tertiary siRNAs. Once paramutated, a tertiary siRNA generating allele confers dominant silencing in the progeny regardless of its own transmission, suggesting germline-transmitted siRNAs are sufficient for multigenerational silencing. This work uncovers a multi-step siRNA amplification pathway that promotes germline integrity via epigenetic silencing of endogenous and invading genetic elements. In addition, the same pathway can be engaged in environmentally induced heritable gene silencing and could therefore promote the inheritance of acquired traits.