Miracle-dz/UniFAR-FTUs huggingface dataset:
On some contributions of the cognitive sciences and epistemology to a theory of classification

Intended is first of all a preliminary review of the implications that the new approaches to the theory of classification, mainly from Cognitive Psychology and Epistemology may have for information work and research. As a secondary topic the scientific relations existing among Information Science, Epistemology, and the Cognitive Sciences are discussed. Classification is seen as a central activity in all daily and scientific activities, and, of course, of knowledge organization in information services. There is a mutual implication between classification and conceptualization, as the former moves in a natural way to the latter and the best result elaborated for classification is the concept. Research in concept theory is a need for a Theory of Classification. In this direction it is of outstanding importance to integrate the achievements of natural concept formation theory (NCFT) as an alternative approach to conceptualization different from the traditional one of logicians and problem solving researchers. In clonclusion both approaches are seen as being complementary: the NCFP approach being closer to the user and the logical one being more suitable for experts, including expert systems
Assessment of stationarity horizon of the heart rate

This work presents a new method using time-varying autoregressive modelling for the assessment of heart rate signals stationarity in patients before the onset of ventricular tachyarrhythmias, including comparison with a control group. A general stationarity trend is reported for all subjects, and particularly no significant change is observed before an arrhythmic event. Evaluation of the model fitting performed by a hypothesis test suggests the presence of nonlinearities.
Macrophage-Mediated Subversion of Anti-Tumour Immunity

Despite the incredible clinical benefits obtained by the use of immune checkpoint blockers (ICBs), resistance is still common for many types of cancer. Central for ICBs to work is activation and infiltration of cytotoxic CD8+ T cells following tumour-antigen recognition. However, it is now accepted that even in the case of immunogenic tumours, the effector functions of CD8+ T cells are highly compromised by the presence of an immunosuppressive tumour microenvironment (TME) at the tumour site. Tumour-associated macrophages (TAMs) are among the most abundant non-malignant stromal cell types within the TME and they are crucial drivers of tumour progression, metastasis and resistance to therapy. TAMs are able to regulate either directly or indirectly various aspects of tumour immunity, including T cell recruitment and functions. In this review we discuss the mechanisms by which TAMs subvert CD8+ T cell immune surveillance and how their targeting in combination with ICBs represents a very powerful therapeutic strategy.
Melatonin and (−)-Epigallocatechin-3-Gallate: Partners in Fighting Cancer

We have demonstrated previously that melatonin attenuates hepatotoxicity triggered by high doses of (−)-epigallocatechin-3-gallate (EGCG) in mice. The current work investigated the influence of melatonin on the oncostatic activity of EGCG in two cancer cell lines, wherein melatonin induced an opposite response of p21. In human tongue cancer TCA8113 cells, melatonin-induced p21 and EGCG-mediated formation of quinoproteins were positively associated with the oncostatic effects of melatonin and EGCG. Melatonin-stimulated an increase in p21 which was correlated with a pronounced nuclear translocation of thioredoxin 1 and thioredoxin reductase 1, both of which are known to induce p21 via promoting p53 trans-activation. Melatonin did not influence the EGCG-mediated increase of quinoprotein formation nor did EGCG impair melatonin-induced p21 up-regulation. Co-treatment with both agents enhanced the cell-killing effect as well as the inhibitory activities against cell migration and colony formation. It is known that p21 also plays a powerful anti-apoptotic role in some cancer cells and confers these cells with a survival advantage, making it a target for therapeutic suppression. In human hepatocellular carcinoma HepG2 cells, melatonin suppressed p21 along with the induction of pro-survival proteins, PI3K and COX-2. However, EGCG prevented against melatonin-induced PI3K and COX-2, and melatonin probably sensitized HepG2 cells to EGCG cytotoxicity via down-regulating p21, Moreover, COX-2 and HO-1 were significantly reduced only by the co-treatment, and melatonin aided EGCG to achieve an increased inhibition on Bcl2 and NFκB. These events occurring in the co-treatment collectively resulted in an enhanced cytotoxicity. In addition, the co-treatment also enhanced the inhibitory activities against cell migration and colony formation. Overall, the results gathered from these two cancer cell lines with a divergent p21 response to melatonin show that the various oncostatic activities of melatonin and EGCG together are more robust than each agent alone, suggesting that they may be useful partners in fighting cancer.
Variations of Secondary Metabolites among Natural Populations of Sub-Antarctic Ranunculus Species Suggest Functional Redundancy and Versatility

Plants produce a high diversity of metabolites which help them sustain environmental stresses and are involved in local adaptation. However, shaped by both the genome and the environment, the patterns of variation of the metabolome in nature are difficult to decipher. Few studies have explored the relative parts of geographical region versus environment or phenotype in metabolomic variability within species and none have discussed a possible effect of the region on the correlations between metabolites and environments or phenotypes. In three sub-Antarctic Ranunculus species, we examined the role of region in metabolite differences and in the relationship between individual compounds and environmental conditions or phenotypic traits. Populations of three Ranunculus species were sampled across similar environmental gradients in two distinct geographical regions in îles Kerguelen. Two metabolite classes were studied, amines (quantified by high-performance liquid chromatography and fluorescence spectrophotometry) and flavonols (quantified by ultra-high-performance liquid chromatography with triple quadrupole mass spectrometry). Depending on regions, the same environment or the same trait may be related to different metabolites, suggesting metabolite redundancy within species. In several cases, a given metabolite showed different or even opposite relations with the same environmental condition or the same trait across the two regions, suggesting metabolite versatility within species. Our results suggest that metabolites may be functionally redundant and versatile within species, both in their response to environments and in their relation with the phenotype. These findings open new perspectives for understanding evolutionary responses of plants to environmental changes.
Effect of Agave Fructans as Carrier on the Encapsulation of Blue Corn Anthocyanins by Spray Drying

Effects of agave fructans as carrier agents on the encapsulation of blue corn anthocyanins using spray-drying were evaluated. Blue corn extract was mixed with 6%, 8%, 10%, and 12% (w/v) of agave fructans in duplicate and dried at 150 °C. The extract showed good contents of anthocyanins, polyphenols, and antioxidant activity. The increase of agave fructans in the encapsulated powders caused a significant increase (p < 0.05) in the humidity, water activity (aw), pH, bulk density, water solubility index (WSI), and color L* values. On the contrary, the agave fructan addition decreased the hygroscopicity, water absorption index (WAI), antioxidant activity, total anthocyanin, total polyphenol, and individual anthocyanin contents. The encapsulation of blue corn extract with 6% agave fructans (w/v) resulted in good physical, thermal, morphological, and high antioxidant properties. The results suggest that the use of agave fructans as wall material represents advantages in the conservation of anthocyanins and other bioactive compounds from blue corn extract during their encapsulation. The application of blue corn anthocyanin encapsulated powders as a food ingredient is promising for food pigmentation, representing additional advantages for their contribution as a soluble fiber that can benefit the health of consumers.
TAF-ChIP: an ultra-low input approach for genome-wide chromatin immunoprecipitation assay

The authors present a novel method for obtaining chromatin profiles from low cell numbers without prior nuclei isolation. The method is successfully implemented in generating epigenetic profile from 100 cells with high signal-to-noise ratio. Chromatin immunoprecipitation (ChIP) followed by next generation sequencing (ChIP-Seq) is a powerful technique to study transcriptional regulation. However, the requirement of millions of cells to generate results with high signal-to-noise ratio precludes it in the study of small cell populations. Here, we present a tagmentation-assisted fragmentation ChIP (TAF-ChIP) and sequencing method to generate high-quality histone profiles from low cell numbers. The data obtained from the TAF-ChIP approach are amenable to standard tools for ChIP-Seq analysis, owing to its high signal-to-noise ratio. The epigenetic profiles from TAF-ChIP approach showed high agreement with conventional ChIP-Seq datasets, thereby underlining the utility of this approach.
Use of Natural Components Derived from Oil Seed Plants for Treatment of Inflammatory Skin Diseases.

The incidence of inflammatory skin diseases is increasing, so the search for relevant therapeutics is of major concern. Plants are rich in phytochemicals which can alleviate many symptoms. In this review we concentrate on compounds found in the seeds of widely cultivated plants, regularly used for oil production. The oils from these plants are often used to alleviate the symptoms of inflammatory diseases through synergetic action of unsaturated fatty acids and other phytochemicals most commonly derived from the terpenoid pathway. The knowledge of the chemical composition of oil seeds and the understanding of the mechanisms of action of single components should allow for a more tailored approach to treatment for many diseases. In many cases these seeds could serve as an efficient material for the isolation of pure phytochemicals. Here we present the content of phytochemicals, assumed to be responsible for healing properties of plant oils, in widely cultivated oil seed plants and review the proposed mechanism of action for fatty acids, selected mono-, sesqui-, di- and triterpenes, carotenoids, tocopherol and polyphenols.
Perceived burdensomeness, bullying, and suicidal ideation in suicidal military personnel.

OBJECTIVE Suicide is a major public health concern among military servicemembers and previous research has demonstrated an association between bullying and suicide. This study evaluated the association between workplace bullying and suicidal ideation via perceived burdensomeness and thwarted belongingness which were hypothesized to mediate this association. METHOD Four hundred and seventy-one suicidal Army Soldiers and U.S. Marines completed self-report measures of suicidal ideation, thwarted belongingness, perceived burdensomeness, and bullying. A series of regressions were used to test the hypothesized mediation model using the baseline data from a larger clinical trial. RESULTS Perceived burdensomeness was a significant mediator of the association between bullying and the level of suicidal ideation, but thwarted belongingness was not a significant mediator. CONCLUSIONS Perceived burdensomeness may represent a malleable target for intervention to prevent suicide among military service members, and should be evaluated further as an intervening variable with regard to suicidality in the setting of bullying victimization.
The Role of a “Treat-to-Target” Approach in the Long-Term Renal Outcomes of Patients with Gout

Background: Although gout is accompanied by the substantial burden of kidney disease, there are limited data to assess renal function as a therapeutic target. This study evaluated the importance of implementing a “treat-to-target” approach in relation to renal outcomes. Methods: Patients with gout who underwent continuous urate-lowering therapy (ULT) for at least 12 months were included. The effect of ULT on renal function was investigated by means of a sequential comparison of the estimated glomerular filtration rate (eGFR). Results: Improvement in renal function was only demonstrated in subjects in whom the serum urate target of <6 mg/dL was achieved (76.40 ± 18.81 mL/min/1.73 m2 vs. 80.30 ± 20.41 mL/min/1.73 m2, p < 0.001). A significant difference in the mean change in eGFR with respect to serum urate target achievement was shown in individuals with chronic kidney disease stage 3 (−0.35 ± 3.87 mL/min/1.73 m2 vs. 5.33 ± 11.64 mL/min/1.73 m2, p = 0.019). Multivariable analysis predicted that patients ≥65 years old had a decreased likelihood of improvement (OR 0.31, 95% CI 0.13–0.75, p = 0.009). Conclusions: The “treat-to-target” approach in the long-term management of gout is associated with better renal outcomes, with a greater impact on those with impaired renal function.
Opioid Use among Individuals with Traumatic Brain Injury: A Perfect Storm?

As the opioid epidemic continues to unfold and efforts to address the crisis are expanded, identifying subgroups at elevated risk for opioid use disorder (OUD) and its devastating consequences is of critical importance. Growing evidence suggests that individuals with traumatic brain injury (TBI) may be at elevated risk for OUD by virtue of a confluence of factors that converge for this population. Opioids are commonly prescribed for pain during acute care, and high rates of chronic pain after TBI set the stage for long-term use. Even as state and federal regulations attempt to curb prescribing practices, rates of prescription opioid use remain elevated among individuals with disabilities. Pre-injury substance use is not uncommon among people who have incurred a TBI, and can increase susceptibility to misuse of highly addictive medications. Some of the most common sequelae of TBI, including changes in cognition and mood, may confer additional vulnerability for medication mismanagement and misuse. Long-term use of opioids is associated with changes in health and cognition that can further exacerbate TBI-related sequelae. Access to substance abuse treatment is an ongoing challenge for people who have had a TBI, and the efficacy of OUD treatment practices in this population is unknown. The convergence of multiple risk and perpetuating factors in this population creates a perfect storm such that persons with TBI may be uniquely vulnerable to opioid misuse and its devastating consequences. Research is urgently needed to quantify and characterize the population of individuals with TBI and OUD, and to identify opportunities for prevention and tailored interventions.
Vitamin D Alleviates Rotavirus Infection through a Microrna-155-5p Mediated Regulation of the TBK1/IRF3 Signaling Pathway In Vivo and In Vitro

(1) Background: Vitamin D (VD) plays a vital role in anti-viral innate immunity. However, the role of VD in anti-rotavirus and its mechanism is still unclear. The present study was performed to investigate whether VD alleviates rotavirus (RV) infection through a microRNA-155-5p (miR-155-5p)-mediated regulation of TANK-binding kinase 1 (TBK1)/interferon regulatory factors 3 (IRF3) signaling pathway in vivo and in vitro. (2) Methods: The efficacy of VD treatment was evaluated in DLY pig and IPEC-J2. Dual-luciferase reporter activity assay was performed to verify the role of miR-155-5p in 1α,25-dihydroxy-VD3 (1,25D3) mediating the regulation of the TBK1/IRF3 signaling pathway. (3) Results: A 5000 IU·kg–1 dietary VD3 supplementation attenuated RV-induced the decrease of the villus height and crypt depth (p < 0.05), and up-regulated TBK1, IRF3, and IFN-β mRNA expressions in the jejunum (p < 0.05). Incubation with 1,25D3 significantly decreased the RV mRNA expression and the RV antigen concentration, and increased the TBK1 mRNA and protein levels, and the phosphoprotein IRF3 (p-IRF3) level (p < 0.05). The expression of miR-155-5p was up-regulated in response to an RV infection in vivo and in vitro (p < 0.05). 1,25D3 significantly repressed the up-regulation of miR-155-5p in vivo and in vitro (p < 0.05). Overexpression of miR-155-5p remarkably suppressed the mRNA and protein levels of TBK1 and p-IRF3 (p < 0.01), while the inhibition of miR-155-5p had an opposite effect. Luciferase activity assays confirmed that miR-155-5p regulated RV replication by directly targeting TBK1, and miR-155-5p suppressed the TBK1 protein level (p < 0.01). (4) Conclusions: These results indicate that miR-155-5p is involved in 1,25D3 mediating the regulation of the TBK1/IRF3 signaling pathway by directly targeting TBK1.
Differential Signaling Mediated by ApoE2, ApoE3, and ApoE4 in Human Neurons Parallels Alzheimer's Disease Risk

In blood, apolipoprotein E (ApoE) is a component of circulating lipoproteins and mediates the clearance of these lipoproteins from blood by binding to ApoE receptors. Humans express three genetic ApoE variants, ApoE2, ApoE3, and ApoE4, which exhibit distinct ApoE receptor-binding properties and differentially affect Alzheimer's disease (AD), such that ApoE2 protects against, and ApoE4 predisposes to AD. In brain, ApoE-containing lipoproteins are secreted by activated astrocytes and microglia, but their functions and role in AD pathogenesis are largely unknown. Ample evidence suggests that ApoE4 induces microglial dysregulation and impedes Aβ clearance in AD, but the direct neuronal effects of ApoE variants are poorly studied. Extending previous studies, we here demonstrate that the three ApoE variants differentially activate multiple neuronal signaling pathways and regulate synaptogenesis. Specifically, using human neurons (male embryonic stem cell-derived) cultured in the absence of glia to exclude indirect glial mechanisms, we show that ApoE broadly stimulates signal transduction cascades. Among others, such stimulation enhances APP synthesis and synapse formation with an ApoE4>ApoE3>ApoE2 potency rank order, paralleling the relative risk for AD conferred by these ApoE variants. Unlike the previously described induction of APP transcription, however, ApoE-induced synaptogenesis involves CREB activation rather than cFos activation. We thus propose that in brain, ApoE acts as a glia-secreted signal that activates neuronal signaling pathways. The parallel potency rank order of ApoE4>ApoE3>ApoE2 in AD risk and neuronal signaling suggests that ApoE4 may in an apparent paradox promote AD pathogenesis by causing a chronic increase in signaling, possibly via enhancing APP expression. SIGNIFICANCE STATEMENT Humans express three genetic variants of apolipoprotein E (ApoE), ApoE2, ApoE3, and ApoE4. ApoE4 constitutes the most important genetic risk factor for Alzheimer's disease (AD), whereas ApoE2 protects against AD. Significant evidence suggests that ApoE4 impairs microglial function and impedes astrocytic Aβ clearance in brain, but the direct neuronal effects of ApoE are poorly understood, and the differences between ApoE variants in these effects are unclear. Here, we report that ApoE acts on neurons as a glia-secreted signaling molecule that, among others, enhances synapse formation. In activating neuronal signaling, the three ApoE variants exhibit a differential potency of ApoE4>ApoE3>ApoE2, which mirrors their relative effects on AD risk, suggesting that differential signaling by ApoE variants may contribute to AD pathogenesis.
A 9-Step Theory- and Evidence-Based Postgraduate Medical Digital Education Development Model: Empirical Development and Validation

Background Digital education tools (e-learning, technology-enhanced learning) can be defined as any educational intervention that is electronically mediated. Decveloping and applying such tools and interventions for postgraduate medical professionals who work and learn after graduation can be called postgraduate medical digital education (PGMDE), which is increasingly being used and evaluated. However, evaluation has focused mainly on reaching the learning goals and little on the design. Design models for digital education (instructional design models) help educators create a digital education curriculum, but none have been aimed at PGMDE. Studies show the need for efficient, motivating, useful, and satisfactory digital education. Objective Our objective was (1) to create an empirical instructional design model for PGMDE founded in evidence and theory, with postgraduate medical professionals who work and learn after graduation as the target audience, and (2) to compare our model with existing models used to evaluate and create PGMDE. Methods Previously we performed an integrative literature review, focus group discussions, and a Delphi procedure to determine which building blocks for such a model would be relevant according to experts and users. This resulted in 37 relevant items. We then used those 37 items and arranged them into chronological steps. After we created the initial 9-step plan, we compared these steps with other models reported in the literature. Results The final 9 steps were (1) describe who, why, what, (2) select educational strategies, (3) translate to the real world, (4) choose the technology, (5) complete the team, (6) plan the budget, (7) plan the timing and timeline, (8) implement the project, and (9) evaluate continuously. On comparing this 9-step model with other models, we found that no other was as complete, nor were any of the other models aimed at PGMDE. Conclusions Our 9-step model is the first, to our knowledge, to be based on evidence and theory building blocks aimed at PGMDE. We have described a complete set of evidence-based steps, expanding a 3-domain model (motivate, learn, and apply) to an instructional design model that can help every educator in creating efficient, motivating, useful, and satisfactory PGMDE. Although certain steps are more robust and have a deeper theoretical background in current research (such as education), others (such as budget) have been barely touched upon and should be investigated more thoroughly in order that proper guidelines may also be provided for them.
A 13-Channel 1.53-mW 11.28-mm2 Electrical Impedance Tomography SoC Based on Frequency Division Multiplexing for Lung Physiological Imaging

An electrical impedance tomography (EIT) system based on frequency division multiplexing (FDM) is proposed for real-time lung physiological imaging. The FDM technique allows the integration of 13 dedicated voltage sensing channels by combining data on-chip and sharing of ADC to alleviate area penalty caused by multi-channel. The EIT system-on-chip (SoC) is of the following features. 1) Early I/Q demodulation to relax the bandwidth requirement of analog front end and minimize the impact of motion artifacts and dc electrode offset. 2) Eliminates the need of adaptive gain control with constant inverted “U-shape” gain configuration to compensate amplitude variations across all channels. 3) FDM to combine 13 pairs of I/Q signals into two data streams for quantization using only two ΔΣ modulators. 4) Batch data recovery by Blackman window corrected fast Fourier transform without any digital filtering involved. 5) Lowest power consumption and smallest area occupation per channel reported to date. The EIT SoC occupies an area of 11.28 mm2 in 130-nm CMOS technology with a total power consumption of 1.53 mW under 1-V power supply. As a result, it generates lung EIT images at up to five frames per second.