Miracle-dz/UniFAR-FTUs huggingface dataset:
Depletion of Perineuronal Nets Enhances Recognition Memory and Long-Term Depression in the Perirhinal Cortex

Perineuronal nets (PNNs) are extracellular matrix structures surrounding cortical neuronal cell bodies and proximal dendrites and are involved in the control of brain plasticity and the closure of critical periods. Expression of the link protein Crtl1/Hapln1 in neurons has recently been identified as the key event triggering the formation of PNNs. Here we show that the genetic attenuation of PNNs in adult brain Crtl1 knock-out mice enhances long-term object recognition memory and facilitates long-term depression in the perirhinal cortex, a neural correlate of object recognition memory. Identical prolongation of memory follows localized digestion of PNNs with chondroitinase ABC, an enzyme that degrades the chondroitin sulfate proteoglycan components of PNNs. The memory-enhancing effect of chondroitinase ABC treatment attenuated over time, suggesting that the regeneration of PNNs gradually restored control plasticity levels. Our findings indicate that PNNs regulate both memory and experience-driven synaptic plasticity in adulthood.
Priming psychic and conjuring abilities of a magic demonstration influences event interpretation and random number generation biases

Magical ideation and belief in the paranormal is considered to represent a trait-like character; people either believe in it or not. Yet, anecdotes indicate that exposure to an anomalous event can turn skeptics into believers. This transformation is likely to be accompanied by altered cognitive functioning such as impaired judgments of event likelihood. Here, we investigated whether the exposure to an anomalous event changes individuals’ explicit traditional (religious) and non-traditional (e.g., paranormal) beliefs as well as cognitive biases that have previously been associated with non-traditional beliefs, e.g., repetition avoidance when producing random numbers in a mental dice task. In a classroom, 91 students saw a magic demonstration after their psychology lecture. Before the demonstration, half of the students were told that the performance was done respectively by a conjuror (magician group) or a psychic (psychic group). The instruction influenced participants’ explanations of the anomalous event. Participants in the magician, as compared to the psychic group, were more likely to explain the event through conjuring abilities while the reverse was true for psychic abilities. Moreover, these explanations correlated positively with their prior traditional and non-traditional beliefs. Finally, we observed that the psychic group showed more repetition avoidance than the magician group, and this effect remained the same regardless of whether assessed before or after the magic demonstration. We conclude that pre-existing beliefs and contextual suggestions both influence people’s interpretations of anomalous events and associated cognitive biases. Beliefs and associated cognitive biases are likely flexible well into adulthood and change with actual life events.
Heat Shock Proteins 60 and 70 Specific Proinflammatory and Cytotoxic Response of CD4+CD28null Cells in Chronic Kidney Disease

Background. CD4+CD28null T cells are expanded in peripheral blood of patients with chronic kidney disease and associated with subclinical atherosclerosis. However, triggers for the oligoclonal expansion and activation of these cells are not clear. Methods. We investigated twenty-five stage V-IV chronic kidney disease (CKD) patients and eight healthy subjects (HC). Peripheral mononuclear cells were isolated and incubated with heat shock protein- (HSP) 60 and 70. CD4+CD28null and CD4+CD28+ cells were sorted by flowcytometry and antigen specific response was assessed by the mRNA and protein expression of interferon (IFN)-γ, perforin, and granzyme B using qRT-PCR and Elispot. Results. The basal mRNA expression of IFN-γ, perforin, and granzyme B in CD4+CD28null cells was higher in subjects with CKD compared to that in HC (P < 0.0001). Subjects with CKD also showed expression of IFN-γ, perforin, and granzyme B in the CD4+CD28+ subset, but this was much weaker than that seen in the CD4+CD28null population (P < 0.0001). We did not note the expression of these molecules at mRNA or protein level in either subset of CD4 cells in HC. After incubation with HSP60 and HSP70, CD4+CD28null cells showed increased expression at mRNA (P < 0.001) and protein level (P < 0.001). CD4+CD28+ cells also showed a weak increase in expression. No antigen-specific response was noted in HC. Conclusion. These data show that CD4+CD28null cells in subjects with CKD react with HSP60 and HSP70 by upregulating the expression of IFN-γ, perforin and granzyme B. Increased circulating level of HSP60 and HSP70 might play a role in initiation and/or progression of atherosclerosis in CKD subjects through perturbation of CD4+CD28null cells.
Efficient Greedy Learning of Gaussian Mixture Models

This article concerns the greedy learning of gaussian mixtures. In the greedy approach, mixture components are inserted into the mixture one aftertheother.We propose a heuristic for searching for the optimal component to insert. In a randomized manner, a set of candidate new components is generated. For each of these candidates, we find the locally optimal new component and insert it into the existing mixture. The resulting algorithm resolves the sensitivity to initialization of state-of-the-art methods, like expectation maximization, and has running time linear in the number of data points and quadratic in the (final) number of mixture components. Due to its greedy nature, the algorithm can be particularly useful when the optimal number of mixture components is unknown. Experimental results comparing the proposed algorithm to other methods on density estimation and texture segmentation are provided.
Exploring Hessian Regularization in Mixup

Mixup is a data augmentation technique that gener-ates new samples using a convex combination of samples. Despite its remarkable simplicity, this method significantly improves the generalization performance of Deep Neural Networks (DNNs). Various studies have been conducted to understand Mixup, and it has been theoretically shown that Mixup involves Jacobian regularization. Furthermore, a relationship between Mixup and label smoothing has been suggested. However, these studies are limited to cases where the sample generated by Mixup is close to the original sample, and other cases have not yet been analyzed. In this study, we theoretically proved that applying Mixup to logistic regression results in Hessian regularization when the sample generated by Mixup is far from the original sample, a previously unexplored scenario. Additionally, through numerical experiments, we confirmed that a similar tendency holds true for DNNs as well. Our results provide a novel interpretation that Mixup is a method for collectively approximating several regularization methods, including Jacobian regularization, label smoothing, and Hessian regularization.
The effect of socio-demographic variables and dairy use on the intake of essential macro- and micronutrients in 0.5-12-year-old Indonesian children.

BACKGROUND AND OBJECTIVES To study the associations between nutrient intake, dairy intake and socioeconomic variables. METHODS AND STUDY DESIGN Food consumption data using 24 h recall were collected in 3600 children, aged 0.5 to 12 years old in addition to frequency of dairy use and anthropometric and sociodemographic variables. RESULTS Overall height for age Z-score (HAZ) and body mass index for age Z-score (BAZ) values (mean±SE) were -1.40±0.03 and -0.48±0.03 respectively, associated with a high prevalence of stunting and thinness in the population. The overall percentage of children not using any dairy products was 71%, and this percentage increased steadily with age. The overall energy intake from dairy was 99±3 kcal/capita/day and the overall energy intake from dairy in dairy users was 291±7 kcal/day. Dairy use did not differ between boys and girls, but was higher in urban areas, higher if the education of the mother was higher and higher if the mother had a permanent job and if the wealth status of the family was in the upper levels. Nutrient intake after the age of 3 years was inadequate for energy and all nutrients except for protein. The achievement of Recommended Dietary Allowances (RDA) for all nutrients was higher in dairy users compared to non-dairy users, also after correcting for the confounding effect of the higher energy intake (from dairy) and socio-demographic variables. The contribution increased with increasing frequency of dairy use. CONCLUSION Adequate dairy intake can substantially add to the achievement of RDA in Indonesian children.
A Model for Schema Versioning in Temporal Database Systems

The aim of temporal data models is to accommodatethe nature of time naturally and directly and toavoid the ad hoc, one-off extensions commonlyemployed in information systems design. Schemaversioning is one of a number of related areasdealing with the general problem of using multipleschemata for various database related tasks. Inparticular, schema versioning, and its weakercompanion, schema evolution, deal with the need toretain current data and software systemfunctionality in the face of changing databasestructure. This paper brings temporal andevolutionary models together and proposes anextension to temporal data models capable ofaccommodating partial schema versioning.Keywords Schema Evolution, Partial SchemaVersioning, Temporal Data Modelling.
Patient willingness for repeat screening and preference for CT colonography and optical colonoscopy in ACRIN 6664: the National CT Colonography trial

Background Current American Cancer Society recommendations for colon cancer screening include optical colonoscopy every 10 years or computed tomography colonography (CTC) every 5 years. Bowel preparation (BP) is currently required for both screening modalities. Purpose To compare ACRIN 6664: the National CT Colonography Trial (NCTCT) participant experiences with CTC and optical colonoscopy (OC), procedure preference, and willingness to return for each procedure. Materials and methods Participants from fifteen NCTCT sites, who underwent CTC followed by OC under sedation, were invited to complete questionnaires 2 weeks postexam, asking about procedure preference, physical discomfort, and embarrassment experienced and whether that discomfort and embarrassment was better or worse than expected during BP, CTC, and OC, as well as willingness to return for repeat CTC and OC at different time intervals. Results A total of 2,310 of 2,600 patients (89%) returned their questionnaires. Of patients reporting a preference, 1,058 (46.6%) preferred CTC, 569 (25.0%) preferred OC, and 626 (27.6%) reported no preference. Participant-reported discomfort worse than expected differed significantly between CTC (32.9%) and OC (5.0%) (P<0.001). About 79.3% were willing to be screened again with CTC in 5 years, and 96.6% with OC in 10 years. Discomfort and embarrassment worse than expected with OC were associated with increased intention to adhere with CTC in the future. Conversely, embarrassment experienced during CTC and discomfort worse than expected on CTC were associated with increased intention to adhere with OC in the future. Conclusion While a larger proportion of participants indicated that they preferred CTC to OC, willingness to undergo repeat CTC compared to OC was limited by unanticipated exam discomfort and embarrassment and CTC’s shorter screening interval.
Evaluation of the Use of Static and Dynamic Models to Predict Drug-Drug Interaction and Its Associated Variability: Impact on Drug Discovery and Early Development

Simcyp, a population-based simulator, is widely used for evaluating drug-drug interaction (DDI) risks in healthy and disease populations. We compare the prediction performance of Simcyp with that of mechanistic static models using different types of inhibitor concentrations, with the aim of understanding their strengths/weaknesses and recommending the optimal use of tools in drug discovery/early development. The inclusion of an additional term in static equations to consider the contribution of hepatic first pass to DDIs (AUCRhfp) has also been examined. A second objective was to assess Simcyp's estimation of variability associated with DDIs. The data set used for the analysis comprises 19 clinical interactions from 11 proprietary compounds. Except for gut interaction parameters, all other input data were identical for Simcyp and static models. Static equations using an unbound average steady-state systemic inhibitor concentration (Isys) and a fixed fraction of gut extraction and neglecting gut extraction in the case of induction interactions performed better than Simcyp (84% compared with 58% of the interactions predicted within 2-fold). Differences in the prediction outcomes between the static and dynamic models are attributable to differences in first-pass contribution to DDI. The inclusion of AUCRhfp in static equations leads to systematic overprediction of interaction, suggesting a limited role for hepatic first pass in determining inhibition-based DDIs for our data set. Our analysis supports the use of static models when elimination routes of the victim compound and the role of gut extraction for the victim and/or inhibitor in humans are not well defined. A fixed variability of 40% of predicted mean area under the concentration-time curve ratio is recommended.
The cytoplasmic domain mediates localization of furin to the trans- Golgi network en route to the endosomal/lysosomal system

To investigate the mechanisms of membrane protein localization to the Golgi complex, we have examined the intracellular trafficking of epitope-tagged forms of the mammalian endopeptidase, furin, in stably transformed rat basophilic leukemia cells. Our studies show that furin is predominantly localized to the trans-Golgi network (TGN) at steady state, with smaller amounts present in intracellular vesicles. Biochemical and morphological analyses reveal that furin is progressively delivered to a lysosomal compartment, where it is degraded. Analyses of furin deletion mutants and chimeric proteins show that the cytoplasmic domain is both necessary and sufficient for localization to the TGN in various cell types. Interestingly, deletion of most of the cytoplasmic domain of furin results in a molecule that is predominantly localized to intracellular vesicles, some of which display characteristics of lysosomes. To a lesser extent, the cytoplasmically deleted molecule is also localized to the plasma membrane. These observations suggest the existence of an additional determinant for targeting to the endosomal/lysosomal system within the lumenal and/or transmembrane domains of furin. Thus, the overall pattern of trafficking and steady state localization of furin are determined by targeting information contained within more than one region of the molecule.
Improved RT-PCR Amplification for Molecular Analyses with Long-term Preserved Formalin-fixed, Paraffin-embedded Tissue Specimens

Recently, in addition to DNA, RNA extracted from archival tissue specimens has become an invaluable source of material for molecular biological analysis. Successful amplification with PCR/RT-PCR is problematic when using amplicons of short size due to degradation of DNA or RNA. We established an improved method for efficient RT-PCR amplification of RNA extracted from archival formalin-fixed, paraffin-embedded tissue by the elimination of RNA modification and the restoration of RNA template activity. Namely, the preheating in citrate buffer (pH 4.0) of RNA extracted from long-term preserved tissue specimens resulted in significantly increased efficiency of RT-PCR.
Prevention and Epidemiology a Randomized Trial of Dietary Intervention for Breast Cancer Prevention

Epidemiologic data and animal experiments suggest that dietary fat may influence risk of breast cancer. To determine whether intervention with a low-fat, high-carbohydrate diet would reduce breast cancer incidence in women at increased risk of the disease, we carried out a randomized controlled trial in Canada. We recruited 4,690 women with extensive mammographic density and randomized them to an intervention group or a comparison group. The intervention group received intensive dietary counseling to reduce fat intake to a target of 15% of calories and increase carbohydrate to 65% of calories. Dietary intakes were assessed throughout using food records. Subjects were followed for at least 7 years and for an average of 10 years. The main outcome was invasive breast cancer. Percentage of calories from fat in the intervention group decreased from 30% at baseline to 20% after randomization and remained 9% to 10% lower than the comparison group throughout. There were 118 invasive breast cancers in the intervention group and 102 in the comparison group [adjusted hazard ratio ¼ 1.19 (95% CI: 0.91–1.55)]. Analysis of food records showed that fat intake at baseline and after randomization was not associated with total breast cancer incidence. Greater weight and lower carbohydrate intake at baseline and after randomization were associated with an increased risk of estrogen receptor (ER)-positive breast cancer. Our findings suggest that a sustained reduction in dietary fat intake did not reduce risk of breast cancer in women with extensive mammographic density. Weight and carbohydrate intakes were associated with risk of ER-positive breast cancer.
Influence of slow oscillation on hippocampal activity and ripples through cortico-hippocampal synaptic interactions, analyzed by a cortical-CA3-CA1 network model

Hippocampal sharp wave-ripple complexes (SWRs) involve the synchronous discharge of thousands of cells throughout the CA3-CA1-subiculum-entorhinal cortex axis. Their strong transient output affects cortical targets, rendering SWRs a possible means for memory transfer from the hippocampus to the neocortex for long-term storage. Neurophysiological observations of hippocampal activity modulation by the cortical slow oscillation (SO) during deep sleep and anesthesia, and correlations between ripples and UP states, support the role of SWRs in memory consolidation through a cortico-hippocampal feedback loop. We couple a cortical network exhibiting SO with a hippocampal CA3-CA1 computational network model exhibiting SWRs, in order to model such cortico-hippocampal correlations and uncover important parameters and coupling mechanisms controlling them. The cortical oscillatory output entrains the CA3 network via connections representing the mossy fiber input, and the CA1 network via the temporoammonic pathway (TA). The spiking activity in CA3 and CA1 is shown to depend on the excitation-to-inhibition ratio, induced by combining the two hippocampal inputs, with mossy fiber input controlling the UP-state correlation of CA3 population bursts and corresponding SWRs, whereas the temporoammonic input affects the overall CA1 spiking activity. Ripple characteristics and pyramidal spiking participation to SWRs are shaped by the strength of the Schaffer collateral drive. A set of in vivo recordings from the rat hippocampus confirms a model-predicted segregation of pyramidal cells into subgroups according to the SO state where they preferentially fire and their response to SWRs. These groups can potentially play distinct functional roles in the replay of spike sequences.
Acceleration of a CNN-based Heart Sound Segmenter: Implementation on Different Platforms Targeting a Wearable Device

Cardiovascular diseases (CVDs) are currently one of the leading causes of death worldwide. Being able to detect their symptoms at early stages, even the most hidden ones, is crucial to shorten the diagnosis time and facilitate an early treatment. Currently, the use of continuous tracking systems, mainly based on wearable devices that analyze data using artificial intelligence (AI) algorithms, is being explored to automatically identify, in real time, CVDs symptoms. This could be especially relevant in lowincome countries where there is a shortage of specialized doctors. Therefore, this work focuses on analyzing the real-time execution of the state-of-the-art convolutional neural network (CNN) for heart sound segmentation (HSS) on platforms such as traditional CPU/GPU and the Fraunhofer IMS © AIRISC Core Complex (a RISC-V processor developed for AI). Results revealed that, while all implementations exploiting the CPU/GPU platform proved to be useful in real-time diagnosis from a fixed location, the AIRISC demonstrated its goodness, as a system on a chip (SoC) for a real-time wearable application, when executing a quantized version of the CNN.
YB-1 expression promotes epithelial-to-mesenchymal transition in prostate cancer that is inhibited by a small molecule fisetin

Epithelial-to-mesenchymal transition (EMT) plays an important role in prostate cancer (PCa) metastasis. The transcription/translation regulatory Y-box binding protein-1 (YB-1) is known to be associated with cancer metastasis. We observed that YB-1 expression increased with tumor grade and showed an inverse relationship with E-cadherin in a human PCa tissue array. Forced YB-1 expression induced a mesenchymal morphology that was associated with down regulation of epithelial markers. Silencing of YB-1 reversed mesenchymal features and decreased cell proliferation, migration and invasion in PCa cells. YB-1 is activated directly via Akt mediated phosphorylation at Ser102 within the cold shock domain (CSD). We next identified fisetin as an inhibitor of YB-1 activation. Computational docking and molecular dynamics suggested that fisetin binds on the residues from β1 - β4 strands of CSD, hindering Akt's interaction with YB-1. Calculated free binding energy ranged from −11.9845 to −9.6273 kcal/mol. Plasmon Surface Resonance studies showed that fisetin binds to YB-1 with an affinity of approximately 35 μM, with both slow association and dissociation. Fisetin also inhibited EGF induced YB-1 phosphorylation and markers of EMT both in vitro and in vivo. Collectively our data suggest that YB-1 induces EMT in PCa and identify fisetin as an inhibitor of its activation.
Mechanics regulates ATP-stimulated collective calcium response in fibroblast cells

Cells constantly sense their chemical and mechanical environments. We study the effect of mechanics on the ATP-induced collective calcium response of fibroblast cells in experiments that mimic various tissue environments. We find that closely packed two-dimensional cell cultures on a soft polyacrylamide gel (Young's modulus E = 690 Pa) contain more cells exhibiting calcium oscillations than cultures on a rigid substrate (E = 36 000 Pa). Calcium responses of cells on soft substrates show a slower decay of calcium level relative to those on rigid substrates. Actin enhancement and disruption experiments for the cell cultures allow us to conclude that actin filaments determine the collective Ca2+ oscillatory behaviour in the culture. Inhibition of gap junctions results in a decrease of the oscillation period and reduced correlation of calcium responses, which suggests additional complexity of signalling upon cell–cell contact. Moreover, the frequency of calcium oscillations is independent of the rigidity of the substrate but depends on ATP concentration. We compare our results with those from similar experiments on individual cells. Overall, our observations show that collective chemical signalling in cell cultures via calcium depends critically on the mechanical environment.