Miracle-dz/UniFAR-FTUs huggingface dataset:
Sulfated Glycoaminoglycans and Proteoglycan Syndecan-4 Are Involved in Membrane Fixation of LL-37 and Its Pro-Migratory Effect in Breast Cancer Cells

Initially characterized by its antimicrobial activities, LL-37 has also been shown to significantly contribute to tumor development. On breast cancer cell lines, LL-37 increases intracellular calcium via the TRPV2 channel and their migration via the activation of PI3K/AKT signaling. Its all-d enantiomer d-LL-37 induces similar effects, which excludes a protein-protein interaction of LL-37 in a classic ligand-receptor manner. Its net charge of +6 gave rise to the hypothesis that the peptide uses the negative charges of sulfoglycans or sialic acids to facilitate its attachment to the cell membrane and to induce its activities. Whereas several vegetal lectins, specifically attaching to sialylated or sulfated structures, blocked the activities of LL-37 on both calcium increase and cell migration, several sialidases had no effect. However, the competitive use of free sulfated glycoaminoglycans (GAGs) as chrondroitin and heparin, or treatment of the cell surface with chondroitinase and heparinase resulted in an activity loss of 50–100% for LL-37. Concordant results were obtained by blocking the synthesis of GAGs with 4-Methylumbelliferyl-β-d-xyloside, and by suppression of glycan sulfatation by sodium chlorate. Using a candidate approach by suppressing proteoglycan synthesis using RNA interference, syndecan-4 was shown to be required for the activities of LL-37 and its binding to the cell surface. This leads to the conclusion that syndecan-4, by means of sulfated GAGs, could act as a receptor for LL-37.
Illuminating Smiles and Frowns: Visual-Affective Cueing Influences Viewer Perceptions of Page Layout Images

The present research was motivated by the routine digital media practice of producing page layouts as composite images that include several unrelated pictures. We investigated whether or how visually highlighting affective and positional components of pictures in a viewer’s field of vision might influence viewer perception and evaluation of the composite image. We examined combinations of visual, spatial, and affective features of cues in composite images to learn whether they affected the viewer’s attentional capture of other affective information in the composite image and viewer’s affective evaluations. The manipulation check of the feature combinations (positive/negative affect, presence/absence of highlighted color, central/peripheral position) showed significant effects of these features and their interactions on viewers’ eye movements. On the other hand, we observed only a small effect on viewers’ affective evaluations. Our results suggested that media page layout designers might manipulate the viewer’s attention by visual and positional adjustments of affective components in composite images. Future researchers might use this study’s design to better understand the human perception of real media images.
Healthy Food Labels Tailored to a High-Risk, Minority Population More Effectively Promote Healthy Choices than Generic Labels

The decades-long increase in obesity in the US has led to a number of policies aimed at improving diets, which are thought to play a significant role in obesity. Many of these policies seek to influence individuals’ behaviors. Front-of-package labels providing salient, easily interpretable information to consumers have exhibited promise in helping people identify and choose healthier foods. However, behavioral economics may offer an opportunity to enhance label effectiveness. Tailoring labels to high-risk communities, including minority and rural populations, which have higher rates of diet-related diseases than the overall population, may increase the label’s effectiveness. We conducted a choice experiment with supermarket shoppers on a rural American Indian reservation to test labels tailored to the local population relative to a generic label, which had previously been identified as highly effective in the general population. Results show that while the generic label continues to be quite effective in encouraging healthier choices, the label that is tailored to the local community is more effective, resulting in a marked increase in the premium shoppers were willing to pay for a healthy item. Tailoring healthy food labeling systems using insights from behavioral economics may increase their effectiveness.
Design and Synthesis of Novel 1,3-Thiazole and 2-Hydrazinyl-1,3-Thiazole Derivatives as Anti-Candida Agents: In Vitro Antifungal Screening, Molecular Docking Study, and Spectroscopic Investigation of their Binding Interaction with Bovine Serum Albumin

In the context of there being a limited number of clinically approved drugs for the treatment of Candida sp. -based infections, along with the rapid development of resistance to the existing antifungals, two novel series of 4-phenyl-1,3-thiazole and 2-hydrazinyl-4-phenyl-1,3-thiazole derivatives were synthesized and tested in vitro for their anti-Candida potential. Two compounds (7a and 7e) showed promising inhibitory activity against the pathogenic C. albicans strain, exhibiting substantially lower MIC values (7.81 μg/mL and 3.9 μg/mL, respectively) as compared with the reference drug fluconazole (15.62 μg/mL). Their anti-Candida activity is also supported by molecular docking studies, using the fungal lanosterol C14α-demethylase as the target enzyme. The interaction of the most biologically active synthesized compound 7e with bovine serum albumin was investigated through fluorescence spectroscopy, and the obtained data suggested that this molecule might efficiently bind carrier proteins in vivo in order to reach the target site.
Preparation and Application of Bioshell Calcium Oxide (BiSCaO) Nanoparticle-Dispersions with Bactericidal Activity

Scallop-shell powder (SSP) heated at high temperature exhibits high pH and broad antimicrobial activity. Bioshell calcium oxide (BiSCaO) is an SSP composed mainly of calcium oxide. It is poorly water-soluble under alkaline conditions and the generated precipitate can plug spray nozzles. The aim of this study was to establish that BiSCaO dispersion caused no significant CaO loss and plugging of spray nozzles, and to evaluate its deodorization and microbicidal abilities and its ability to reduce the concentrations of NO2− and NO3−. BiSCaO dispersions were prepared by mixing various concentrations of BiSCaO suspension, while phosphate compounds such as Na3PO4, Na2HPO4 or NaH2PO4 and the pH, average diameter, zeta potential, and form of the compounds with cryo-SEM were evaluated. We evaluated deodorization using tainted pork meat and microbicidal efficacy using contaminated suspension with normal bacterial flora. The concentration of NO2− and NO3− after mixing BiSCaO dispersion and pure water containing a high proportion of NO2− and NO3− were measured. BiSCaO dispersion formed with Na2HPO4, whose ratio to BiSCaO was 60%, showed a high pH (>12), a small particle diameter (>181 nm) and was stable for seven days. The BiSCaO dispersion showed higher deodorization and microbicidal activities than SSP-Ca(OH)2, which was mainly composed of Ca(OH)2. BiSCaO, but not SSP-Ca(OH)2, could reduce the concentration of NO2− and NO3− by more than 90% within 15 min. We developed a stable BiSCaO dispersion, and it had high deodorization and microbicidal efficacy. These activities of BiSCaO might result from the high pH caused by CaO hydration and a reduction activity causing active radical species.
The Link of the Prion Protein with Ca2+ Metabolism and ROS Production, and the Possible Implication in Aβ Toxicity

The cellular prion protein (PrPC) is an ubiquitous cell surface protein mostly expressed in neurons, where it localizes to both pre- and post-synaptic membranes. PrPC aberrant conformers are the major components of mammalian prions, the infectious agents responsible for incurable neurodegenerative disorders. PrPC was also proposed to bind aggregated misfolded proteins/peptides, and to mediate their neurotoxic signal. In spite of long-lasting research, a general consensus on the precise pathophysiologic mechanisms of PrPC has not yet been reached. Here we review our recent data, obtained by comparing primary neurons from PrP-expressing and PrP-knockout mice, indicating a central role of PrPC in synaptic transmission and Ca2+ homeostasis. Indeed, by controlling gene expression and signaling cascades, PrPC is able to optimize glutamate secretion and regulate Ca2+ entry via store-operated channels and ionotropic glutamate receptors, thereby protecting neurons from threatening Ca2+ overloads and excitotoxicity. We will also illustrate and discuss past and unpublished results demonstrating that Aβ oligomers perturb Ca2+ homeostasis and cause abnormal mitochondrial accumulation of reactive oxygen species by possibly affecting the PrP-dependent downregulation of Fyn kinase activity.
Lung Cryobiopsy for the Diagnosis of Interstitial Lung Diseases: A Series Contribution to a Debated Procedure

Introduction: Transbronchial cryobiopsy is an alternative to surgical biopsy for the diagnosis of fibrosing interstitial lung diseases, although the role of this relatively new method is rather controversial. Aim of this study is to evaluate the diagnostic performance and the safety of transbronchial cryobiopsy in patients with fibrosing interstitial lung disease. Materials and methods: The population in this study included patients with interstitial lung diseases who underwent cryobiopsy from May 2015 to May 2018 at the Division of Pneumology of San Giuseppe Hospital in Milan and who were retrospectively studied. All cryobiopsy procedures were performed under fluoroscopic guidance using a flexible video bronchoscope and an endobronchial blocking system in the operating room with patients under general anaesthesia. The diagnostic performance and safety of the procedure were assessed. The main complications evaluated were endobronchial bleeding and pneumothorax. All cases were studied with a multidisciplinary approach, before and after cryobiopsy. Results: Seventy-three patients were admitted to this study. A specific diagnosis was reached in 64 cases, with a diagnostic sensitivity of 88%; 5 cases (7%) were considered inadequate, 4 cases (5%) were found to be non-diagnostic. Only one major bleeding event occurred (1.4%), while 14 patients (19%) experienced mild/moderate bleeding events while undergoing bronchoscopy; 8 cases of pneumothorax (10.9%) were reported, of which 2 (2.7%) required surgical drainage. Conclusions: When performed under safe conditions and in an experienced center, cryobiopsy is a procedure with limited complications having a high diagnostic yield in fibrotic interstitial lung disease.
Inhibitory effect of edaravone on systemic inflammation and local damage in skeletal muscles following long-term ischemia to murine hind limb

Purpose: The purpose of this study was to evaluate local and systemic pathology in a murine model of ischemia–reperfusion (I/R) injury induced by long-term application of a tourniquet on the hind limbs and to assess the protective effects of edaravone, a potent systemic scavenger of free radicals, using this model. Methods: Sixty C57BL6 mice were divided in two groups, with one group receiving a 3 mg/kg intraperitoneal injection of edaravone and the other group receiving an identical amount of saline 30 min before ischemia under deep anesthesia. The left thigh of each animal was constricted for 4 h with a 4.5-oz. orthodontic rubber band to induce ischemia; 4 h was the critical duration for skeletal muscles. After ischemia, specimens of skeletal muscles, both kidneys, and plasma were collected at 0, 2, 12, 24, 48, and 72 h. Injury to the skeletal muscles and vacuolar degeneration of the kidneys were histologically assessed. Additionally, apoptosis of skeletal muscle cells was assessed by analysis of caspase 3/7 activity and TUNEL staining. Plasma tumor necrosis factor (TNF)-α levels were measured using an enzyme-linked immunosorbent assay kit. Results: Skeletal muscles exhibited prominent injury of myofibers at 12 h after I/R injury, with clear upregulation of plasma TNF-α expression and histologic evidence of tubular dysfunction of the kidneys. Plasma TNF-α levels declined and histologic renal damage was ameliorated in edaravone-treated mice, but treatment did not protect skeletal muscle following ischemia for 4 h. Nonetheless, compared with group S, expression of the apoptosis marker caspase 3/7 was significantly inhibited in the skeletal hind limb muscles of Ed-group mice affected by reperfusion injury following ischemia for 4 h. Conclusion: The present study demonstrated that edaravone is a potentially useful drug for systemic or local treatment of reperfusion injury resulting from long-term ischemia.
Assessment of cognitive instrumental activities of daily living: a systematic review

Abstract Purpose Cognitive instrumental activities of daily living are particularly related to executive functions, such as scheduling appointments, monthly payments, managing the household economy, shopping or taking the bus. The aim of this systematic review was to determine the available tests for the assessment of executive functions with ecological validity to predict individuals’ functioning. Materials and methods An electronic search was conducted in MEDLINE, Cochrane Central, PsyCInfo and IEEE Xplore until May 2019, in addition to a manual search. The PRISMA criteria and the Covidence platform were used to select articles and extract data. Results After applying the search selection criteria, 76 studies were identified. They referred to 110 tools to assess instrumental activities of daily living. Those that have received most attention are related to menu preparation and shopping. Performance-based measures are the most widely used traditional methods. Most tests were aimed at the adult population with acquired brain damage, cognitive impairment or dementia. There was a predominance of tests based on the Multiple Errands Test paradigm. Conclusions In recent years, it has increased the number of tools that assess the instrumental activities of daily living based on technologies such as personal or environmental sensors and serious games. IMPLICATIONS FOR REHABILITATION Assessment of Instrumental Activities of Daily Living through performance-based measures is especially useful for the early detection of dysfunctions or preclinical disability. Difficulties in performing instrumental activities of daily living are closely associated with deficits in executive functions and prospective memory. Activities of Daily Living can be understood as multitasks. The use of virtual reality-based tests was shown to be sensitive to the detection of cognitive deficits in Activities of Daily Living. An advantage of using virtual reality in assessments is that it can help to predict the level of personal autonomy in patients who are in an institutional environment and could be a first approximation to the real environment.
MicroRNA‐210 Promotes Bile Acid–Induced Cholestatic Liver Injury by Targeting Mixed‐Lineage Leukemia‐4 Methyltransferase in Mice

Bile acids (BAs) are important regulators of metabolism and energy balance, but excess BAs cause cholestatic liver injury. The histone methyltransferase mixed‐lineage leukemia‐4 (MLL4) is a transcriptional coactivator of the BA‐sensing nuclear receptor farnesoid X receptor (FXR) and epigenetically up‐regulates FXR targets important for the regulation of BA levels, small heterodimer partner (SHP), and bile salt export pump (BSEP). MLL4 expression is aberrantly down‐regulated and BA homeostasis is disrupted in cholestatic mice, but the underlying mechanisms are unclear.
Preventing Metachronous Gastric Cancer after the Endoscopic Resection of Gastric Epithelial Neoplasia: Roles of Helicobacter pylori Eradication and Aspirin

Whether Helicobacter pylori eradication actually reduces the risk of metachronous gastric cancer (MGC) development remains a controversial question. In this review, we addressed this topic by reviewing the results of clinical investigations and molecular pathological analyses of the roles of H. pylori eradication and aspirin administration in the prevention of MGC. In regard to the clinical studies, the results of meta-analyses and randomized control trials differ from those of retrospective studies: the former trials show that H. pylori eradication has a preventive effect on MGC, while the latter studies do not. This discrepancy may be at least partly attributable to differences in the follow-up periods: H. pylori eradication is more likely to prevent MGC over a long-term follow-up period (≥5 years) than over a short-term follow-up period. In addition, many studies have shown that aspirin may have an additive effect on MGC-risk reduction after H. pylori eradication has been achieved. Both H. pylori eradication and aspirin use induce molecular alterations in the atrophic gastritis mucosa but not in the intestinal metaplasia. Unfortunately, the molecular pathological analyses of these interventions have been limited by short follow-up periods. Therefore, a long-term prospective cohort is needed to clarify the changes in molecular events caused by these interventions.
Identification and selection of food safety‐related risk factors to be included in the Canadian Food Inspection Agency’s Establishment‐based Risk Assessment model for Hatcheries

Towards the continuous improvement of its inspection system, the Canadian Food Inspection Agency (CFIA) is developing an Establishment‐based Risk Assessment model for Hatcheries to allocate inspection resources based on the food safety risk associated with the Canadian hatcheries falling under its jurisdiction. The objectives of the current study were to identify and select critical food safety‐related risk factors that would be included in this model, with a main focus on Salmonella. A literature review was used to develop a comprehensive list of risk factors that could potentially contribute to the food safety risk attributed to Canadian hatcheries operating in all production streams (breeders, layers, broilers, turkeys, waterfowl and game birds). The development of this list used a selection process that was conducted according to the availability of data sources, the clarity of definition and the measurability of the selected risk factors. A panel of experts reviewed and adjusted the identified risk factors. A final list of 29 risk factors was generated; 20 originated from the scientific literature and nine from the expert panel. Risk factors were grouped in three clusters according to whether they pertained to the inherent risk (nine factors identified), risk mitigation (nine factors identified) or compliance of a hatchery with its preventive control plan and regulatory requirements (11 factors identified). Criteria for assessing each risk factor were defined based on common practices used in the Canadian hatchery industry. This comprehensive list of risk factors and criteria represents useful information to support the design and implementation of a Canadian risk assessment model for hatcheries, but could also be used by like‐minded food safety authorities.
What have recent advances in therapy taught us about severe asthma disease mechanisms?

ABSTRACT Introduction: Severe asthma still represents a worldwide challenge. The need for further treatment options has stimulated basic and pharmacological research to focus on the immune and inflammatory background of asthma. The new biologic drugs express the considerable advances in the field and besides providing a revolutionary treatment option for severe asthma, contribute themselves to better understand the pathophysiologic mechanisms they address, paving the way to new potential targets. Areas covered: A selective search on PubMed and Medline was performed, including the evidence on immunology of severe asthma published up to May 2019 by focusing on the immunological effects of biologic drugs underlying their clinical outcomes. Expert opinion: The recent pharmacological research in the field of biologics has represented an exceptional opportunity for exploring severe asthma mechanisms. However, some points deserve to be addressed by further investigation. Although in the absence of safety warnings so far, interfering with the immune system may raise some safety concerns, especially in the long-term use. Particularly when interacting with epithelial and innate immunity the selection of candidates probably deserves special caution. Also, whether biologics exert a true disease-modifying effect is not completely clear. As a direct practical implication, the optimal treatment duration is still controversial.
Oxytocin augmentation: poison a potion in the mutipara: review

Oxytocin is one of the most commonly used drugs in obstetric practice but it is also the drug associated with the most preventable adverse events in childbirth. In this review we look at the use of oxytocin augmentation in the multigravida. We look at the concept of whether the multigravida is different to the primigravida. We provide a differential diagnosis for poor progress in the multigravida and look at the use of the partogram. Oxytocin recommended regimens are discussed and we look at how one can measure the effects of oxytocin. We summarize the evidence for the use of oxytocin in augmentation of the multigravida and then provide strategies to avoid problems if oxytocin is used in the multigravid patient. We conclude that the multigravida is very different to the primigravida and that use of oxytocin for augmentation in the multigravida should be strongly discouraged. If used, one should seriously consider the risks associated with oxytocin augmentation in the multigravida which includes uterine rupture. Use needs to be decided on a senior consultant level and it should only be used with continuous fetal monitoring, intrauterine pressure monitoring and only after all other causes of poor progress in the multigravida have been excluded. Consent, with explanation of all the risks associated with augmentation, should be obtained from the mother before augmentation is initiated. If oxytocin is going to be used for augmentation in the multigravida there must be a standardized protocol, there must be a doctor on site who is able to perform emergency caesarean section and who is available to respond to all emergencies. A low-dose, low-frequency dosing regimen should be used with weaning to the lowest dose necessary to maintain contractions.
High-throughput Monitoring of Multiclass Syrup Adulterants in Honey Based on the Oligosaccharide and Polysaccharide Profiles by MALDI Mass Spectrometry.

Honey is a natural product that could be easily adulterated with various cheaper sweeteners. In the present study, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) was applied for the detection of honey adulteration based on oligosaccharide and polysaccharide profiles. MS-based strategy could reveal the presence of polysaccharides with higher degree of polymerization (DP ≥ 13) and abnormal trends of saccharides in adulterated honey samples, which could be used as indicators for the identification of honey adulteration with high-fructose corn syrup and corn syrup. MS/MS-based strategy was proposed to characterize the difference in the composition of oligosaccharide isomers between honey samples and adulterated ones with corn syrup or invert syrup, in which the [M+Cl]- of disaccharides, trisaccharides and tetrasaccharides were fragmented to give diagnostic product ion pairs. The method is effective and robust for the high-throughput monitoring of honey adulteration, and provides a new perspective for the identification of other high-carbohydrate foods.