Miracle-dz/UniFAR-FTUs huggingface dataset:
Costs and cost-effectiveness of the meeting centres support programme for people living with dementia and carers in Italy, Poland and the UK: The MEETINGDEM study.

We examined the costs and cost-effectiveness of the Meeting Centre Support Programme (MCSP) implemented and piloted in the UK, Poland and Italy, replicating the Dutch Meeting Centre model. Dutch Meeting Centres combine day services for people with dementia with carer support. Data were collected over 2015-2016 from MCSP and usual care (UC) participants (people with dementia-carer dyads) at baseline and 6 months. We examined participants' health and social care (HSC), and societal costs, including Meeting Centre (MC) attendances. Costs and outcomes in MCSP and UC groups were compared. Primary outcomes: Persons with dementia: quality-adjusted life years (EQ-5D-5L-derived); QOL-AD. DQoL was examined as a secondary outcome. Carers: Short Sense of Competence Questionnaire (SSCQ). Incremental cost-effectiveness ratios (ICER) and cost-effectiveness acceptability curves were obtained by bootstrapping outcome and cost regression estimates. Eighty-three MCSP and 69 UC dyads were analysed. The 6-month cost of providing MCSP was €4,703; participants with dementia attended MC a mean of 45 times and carers 15 times. Including intervention costs, adjusted 6-month HSC costs were €5,941higher in MCSP than in UC. From the HSC perspective: in terms of QALY, the probability of cost-effectiveness was zero over willingness-to-pay (WTP) ranging from €0 to €350,000. On QOL-AD, the probability of cost-effectiveness of MCSP was 50% at WTP of €5,000 for a one-point increase. A one-point gain in the DQoL positive affect subscale had a probability of cost-effectiveness of 99% at WTP over €8,000. On SSCQ, no significant difference was found between MCSP and UC. Evidence for cost-effectiveness of MCSP was mixed but suggests that it may be cost-effective in relation to gains in dementia-specific quality of life measures. MCs offer effective tailored post-diagnostic support services to both people with dementia and carers in a context where few evidence-based alternatives to formal home-based social services may be available.
Synthesis and Biological Activities of Cyclodepsipeptides of Aurilide Family from Marine Origin

Aurilides are a class of depsipeptides occurring mainly in marine cyanobacteria. Members of the aurilide family have shown to exhibit strong cytotoxicity against various cancer cell lines. These compounds bear a pentapeptide, a polyketide, and an α-hydroxy ester subunit in their structure. A large number of remarkable studies on aurilides have emerged since 1996. This comprehensive account summarizes the biological activities and total syntheses of natural compounds of the aurilide family as well as their synthetic analogues.
Wide-Range Measurement of Thermal Preference—A Novel Method for Detecting Analgesics Reducing Thermally-Evoked Pain in Mice

Background: Wide use of oxaliplatin as an antitumor drug is limited by severe neuropathy with pharmacoresistant cold hypersensitivity as the main symptom. Novel analgesics to attenuate cold hyperalgesia and new methods to detect drug candidates are needed. Methods: We developed a method to study thermal preference of oxaliplatin-treated mice and assessed analgesic activity of intraperitoneal duloxetine and pregabalin used at 30 mg/kg. A prototype analgesiameter and a broad range of temperatures (0–45 °C) were used. Advanced methods of image analysis (deep learning and machine learning) enabled us to determine the effectiveness of analgesics. The loss or reversal of thermal preference of oxaliplatin-treated mice was a measure of analgesia. Results: Duloxetine selectively attenuated cold-induced pain at temperatures between 0 and 10 °C. Pregabalin-treated mice showed preference towards a colder plate of the two used at temperatures between 0 and 45 °C. Conclusion: Unlike duloxetine, pregabalin was not selective for temperatures below thermal preferendum. It influenced pain sensation at a much wider range of temperatures applied. Therefore, for the attenuation of cold hypersensitivity duloxetine seems to be a better than pregabalin therapeutic option. We propose wide-range measurements of thermal preference as a novel method for the assessment of analgesic activity in mice.
Epithelial IL-33 appropriates exosome trafficking for secretion in chronic airway disease

IL-33 is a key mediator of chronic airway disease driven by type 2 immune pathways, yet the nonclassical secretory mechanism for this cytokine remains undefined. We performed a comprehensive analysis in human airway epithelial cells, which revealed that tonic IL-33 secretion is dependent on the ceramide biosynthetic enzyme neutral sphingomyelinase 2 (nSMase2). IL-33 is cosecreted with exosomes by the nSMase2-regulated multivesicular endosome (MVE) pathway as surface-bound cargo. In support of these findings, human chronic obstructive pulmonary disease (COPD) specimens exhibited increased epithelial expression of the abundantly secreted IL33Δ34 isoform and augmented nSMase2 expression compared with non-COPD specimens. Using an Alternaria-induced airway disease model, we found that the nSMase2 inhibitor GW4869 abrogated both IL-33 and exosome secretion as well as downstream inflammatory pathways. This work elucidates a potentially novel aspect of IL-33 biology that may be targeted for therapeutic benefit in chronic airway diseases driven by type 2 inflammation.
Two new 2,5-diketopiperazine derivatives from mangrove-derived endophytic fungus Nigrospora camelliae-sinensis S30

Abstract Two new 2,5-diketopiperazines derivatives (1-2), together with eight known analogs (3-10), were isolated from a culture broth of an endophytic fungus Nigrospora camelliae-sinensis S30, derived from mangrove Lumnitzera littorea. Their complete structures were determined by a detailed analysis of spectroscopic data and ECD calculations. The antimicrobial activity and neuroprotective activity of these isolated compounds were also evaluated. Graphical Abstract
Antimicrobial and antioxidant activity of the Ephedra sarcocarpa growing in Iran

The antimicrobial capacity of the methanolic extracts of Ephedra sarcocarpa growing in Iran is screened against Gram-positive and Gram-negative bacteria and fungi. The extract inhibited the growth of Gram-negative bacteria, being Pseudomonas aeroginosa the most susceptible one with MIC of 16 μg/mL for the extract. The antioxidant activities are evaluated using ferric reducing antioxidant power (FRAP) and 2, 2 diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assays. FRAP values 2.1 mmol eq quercetin/g extracts and IC50values in the DPPH assay 4.6 mg/mL. This plant had shown the high antioxidant activities. FRAP and DPPH assay results were shown good correlations with the total phenolic contents of the plants, measured by the Folin-ciocalteau assay: (r2 = 0.920 and 0.893, respectively, p < 0.0001). Key words: Antioxidant(s), ferric reducing antioxidant power (FRAP), 2, 2 diphenyl-1-picrylhydrazyl (DPPH), total phenol, antimicrobial.
Sialidase of Glaesserella parasuis Augments Inflammatory Response via Desialylation and Abrogation of Negative Regulation of Siglec-5

Siglecs are sialic acid-binding immunoglobulin-like lectins that play an important role in tissue homeostasis, immune response, and pathogen infection. Bacterial sialidases act on natural ligands of Siglecs, interfering with the Siglec-mediated immune response. Glaesserella parasuis is a porcine bacterial pathogen that secretes sialidase. ABSTRACT Siglecs are sialic acid-binding immunoglobulin-like lectins that play an important role in tissue homeostasis, immune response, and pathogen infection. Bacterial sialidases act on natural ligands of Siglecs, interfering with the Siglec-mediated immune response. Glaesserella parasuis is a porcine bacterial pathogen that secretes sialidase. However, little is known about the sialidase of G. parasuis and its impact on immune regulation. Here, we used wild-type G. parasuis, a sialidase-deficient mutant, and complementary strains to investigate the role of sialidase in porcine alveolar macrophage infection. Sialidase induced the release of proinflammatory cytokines, such as interleukin-1α (IL-1α), IL-6, and tumor necrosis factor alpha, from porcine alveolar macrophages. Moreover, sialidase desialylated the surface of porcine alveolar macrophages and altered the expression of Siglecs (the expression of Siglec-5 was reduced). Furthermore, sialidase led to a reduction in endogenous SH2 domain-containing protein tyrosine phosphatase (SHP-2) recruitment to Siglec-5 and simultaneously activated the inflammatory response via the mitogen-activated protein kinase and nuclear factor kappa light chain enhancer of activated B cell signaling pathways. This desialylation occurred before the release of proinflammatory cytokines, suggesting that the sialidase-induced inflammatory response was followed by reduced recruitment of SHP-2 to Siglec-5. Thus, this study is the first to demonstrate the role of sialidase in the inflammatory response of G. parasuis. This role resulted from the abrogation of negative regulation of Siglec-5 on proinflammatory cytokine release. This study helps to understand the molecular mechanism underlying the inflammatory response induced by sialidase secreted by G. parasuis and the acute inflammation caused by G. parasuis.
The Effect of Mobile Learning on Student Success and Anxiety in Teaching Genital System Anatomy

The widespread use of smartphones has led to the emergence of new mobile learning tools. The aim of this study was to compare traditional methods to mobile learning applications, and their effect on the academic achievement and anxiety levels of students learning genital system anatomy. This research study was a randomized controlled study conducted with students who took anatomy between November and December 2018. The cohort consisted of 63 students who met the sampling criteria. Groups (control = 31, experimental = 32) were randomly selected using a simple number table. The mobile application developed for the experimental group was installed on the students' mobile devices with the extension “genitalsystem.apk. ” The anatomy of the genital system was taught to the control group using the standard curriculum and to the experimental group using the mobile application. After teaching the anatomy of the genital system, the state anxiety levels of the students in the control group were determined to be higher at 45.6 (±8.7) than the experimental group at 40.4 (±8.3) as measured by the 20–80 point STAI scale. The posttest examination average of the control group was 8.9 (±6.9) out of 22 or 40.4 (±6.9)% and the posttest average of the experimental group using mobile application was 14.9 (±5.5) or 67.7 (±5.5)%. State anxiety levels and examination grades showed a highly significant difference in favor of the experimental group. These results indicate that using mobile applications when teaching anatomy may be an effective method to enhance learning and reduce anxiety levels when compared to the traditional teaching methods.
Efficacy of topical acidified aliphatic ester for treatment of axillary osmidrosis by rebalancing skin microecology

This study investigated the mechanism and efficacy of topical acidified aliphatic ester for treatment of axillary osmidrosis (AO). A total of 32 AO patients were enrolled in this study. In the initial pilot study, 20 patients were double‐blindly, randomly divided into acidified aliphatic ester or aliphatic ester treatment groups, followed by efficacy evaluation after 4 weeks. Then, all patients (n = 32) were treated with topical acidified aliphatic ester for 16 weeks. Efficacy was evaluated at every 4 weeks, and at 3‐ and 6‐month follow‐ups. Changes of pH values and microecology at targeting sites were analyzed. In the first cohort (n = 20) of pilot study, acidified aliphatic ester showed significantly higher curative rate (60% vs 10%, P < .05) and effective rate (90% vs 30%; P < .05) than aliphatic ester. For the next 16 weeks, 25 of 32 cases completed treatment. Curative rate showed gradual and significant increases from 64% to 96% during the treatment courses (P = .001); it slightly but insignificantly decreased at 3‐ and 6‐ month follow‐ups. Abundance of Corynebacterium and Anaerobic bacteria decreased while Staphylococcus increased after treatments. Axillary pH values negatively correlated with Staphylococcus abundance (r = −.40, P = .01) and positively with Corynebacterium abundance (r = .64, P = .01). We concluded that topical acidified aliphatic ester could effectively alleviate conditions of AO patients by reducing value of axillary pH and rebalancing axillary microecology.
A dietary ketone ester mitigates histological outcomes of NAFLD and markers of fibrosis in high-fat diet fed mice.

Nutritional ketosis as a therapeutic tool has extended to the treatment of metabolic diseases including - obesity, type 2 diabetes and nonalcoholic fatty liver disease. The purpose of this study was to determine whether dietary administration of the ketone ester (KE), R,S-1,3-butanediol diacetoacetate (BD-AcAc2), attenuates markers of hepatic stellate cell (HSC) activation and hepatic fibrosis in the context of high fat diet (HFD)-induced obesity. Six-week-old male C57BL/6J mice were placed on a 10-week ad libitum HFD (45% FAT, 32% CHO, 23% PRO). Mice were then randomized to 1 of 3 groups (n = 10 per group) for an additional 12 weeks: 1) control (CON), continuous HFD, 2) pair-fed (PF) to KE; and 3) KE (HFD+30% energy from BD-AcAc2, KE). KE feeding significantly reduced histological steatosis, inflammation and total NAFLD activity score vs CON, beyond improvements observed for calorie restriction alone (PF). Dietary KE supplementation also reduced the protein content and gene expression of pro-fibrotic markers (α-SMA, Col1a1, PDGF-β, MMP9) vs CON (p<0.05), beyond reductions observed for PF vs CON. Furthermore, KE feeding increased hepatic markers of anti-inflammatory M2 macrophages (CD163) and also reduced pro-inflammatory markers (TRAIL and CCN1) vs CON and PF (p ≤ 0.05), in the absence of changes in markers of total hepatic macrophage content (F4/80 and CD68; p > 0.05). These data highlight that the dietary ketone ester, BD-AcAc2, ameliorates histological NAFLD and inflammation and reduces pro-fibrotic and pro-inflammatory markers. Future studies to further explore potential mechanisms are warranted.
Intracellular Bacteria in Plants: Elucidation of Abundant and Diverse Cytoplasmic Bacteria in Healthy Plant Cells Using In Vitro Cell and Callus Cultures

This study was initiated to assess whether the supposedly axenic plant cell cultures harbored any cultivation-recalcitrant endophytic bacteria (CREB). Adopting live-cell imaging with bright-field, fluorescent and confocal microscopy and bacterial 16S-rRNA gene taxonomic profiling, we report the cytoplasmic association of abundant and diverse CREBs in long-term actively maintained callus and cell suspension cultures of different plant species. Preliminary bright-field live-cell imaging on grape cell cultures showed abundant intracellular motile micro-particles resembling bacteria, which proved uncultivable on enriched media. Bacterial probing employing DNA stains, transmission electron microscopy, and Eubacterial FISH indicated abundant and diverse cytoplasmic bacteria. Observations on long-term maintained/freshly established callus stocks of different plant species—grapevine, barley, tobacco, Arabidopsis, and medicinal species—indicated intracellular bacteria as a common phenomenon apparently originating from field shoot tissues.Cultivation-independent 16S rRNA gene V3/V3–V4 amplicon profiling on 40-year-old grape cell/callus tissues revealed a high bacterial diversity (>250 genera), predominantly Proteobacteria, succeeded by Firmicutes, Actinobacteria, Bacteriodetes, Planctomycetes, and 20 other phyla, including several candidate phyla. PICRUSt analysis revealed diverse functional roles for the bacterial microbiome, majorly metabolic pathways. Thus, we unearth the widespread association of cultivation-recalcitrant intracellular bacteria “Cytobacts” inhabiting healthy plant cells, sharing a dynamic mutualistic association with cell hosts.
Coronary Artery Calcium and Cognitive Function in Dutch Adults: Cross‐Sectional Results of the Population‐Based ImaLife Study

Background The aim of this study was to investigate whether increased severity of coronary artery calcium (CAC), an imaging biomarker of subclinical coronary atherosclerosis, is associated with worse cognitive function independent of cardiovascular risk factors in a large population‐based Dutch cohort with broad age range. Methods and Results A cross‐sectional analysis was performed in 4988 ImaLife participants (aged 45–91 years, 58.3% women) without history of cardiovascular disease. CAC scores were obtained using nonenhanced cardiac computed tomography scanning. The CogState Brief Battery was used to assess 4 cognitive domains: processing speed, attention, working memory, and visual learning based on detection task, identification task, 1‐back task, and 1‐card‐learning task, respectively. Differences in mean scores of each cognitive domain were compared among 4 CAC categories (0, 1–99, 100–399, ≥400) using analysis of covariates to adjust for classical cardiovascular risk factors. Age‐stratified analysis (45–54, 55–64, and ≥65 years) was performed to assess whether the association of CAC severity with cognitive function differed by age. Overall, higher CAC was associated with worse performance on 1‐back task after adjusting for classical cardiovascular risk factors, but CAC was not associated with the other cognitive tasks. Age‐stratified analyses revealed that the association of CAC severity with working memory persisted in participants aged 45 to 54 years, while in the elderly this association lost significance. Conclusions In this Dutch population of ≥45 years, increased CAC severity was associated with worse performance of working memory, independent of classical cardiovascular risk factors. The inverse relationship of CAC score categories with working memory was strongest in participants aged 45 to 54 years.
A cross-cultural examination of pleasant events and depressive symptoms.

OBJECTIVES To examine the associations between pleasant or reinforcing activities (as they relate to the behavioral theory of depression) and depressive symptoms across cultures. METHODS We tested for differences in the strength of association between pleasant events and depressive symptoms in probability samples of adults from the United States (N = 619) and Japan (N = 232). RESULTS Results indicate that frequency, enjoyment, and obtained pleasure from pleasant events were significantly and negatively associated with depressive symptoms for both American and Japanese adults, and these associations were significantly greater in magnitude for American adults relative to Japanese adults. CONCLUSIONS Findings suggest that there is a cross-sectional association between pleasant events and depressive symptoms in both the United States and Japan, and that this association is stronger in the United States.
Evaluation of potential feedstock for biogas production via anaerobic digestion in Malaysia: kinetic studies and economics analysis

ABSTRACT As the population increases, energy demands continue to rise rapidly. In order to satisfy this increasing energy demand, biogas offers a potential alternative. Biogas is economically viable to be produced through anaerobic digestion (AD) from various biomass feedstocks that are readily available in Malaysia, such as food waste (FW), palm oil mill effluent (POME), garden waste (GW), landfill, sewage sludge (SS) and animal manure. This paper aims to determine the potential feedstocks for biogas production via AD based on their characteristics, methane yield, kinetic studies and economic analysis. POME and FW show the highest methane yield with biogas yields up to 0.50 L/g VS while the lowest is 0.12 L/g VS by landfill leachate. Kinetic study shows that modified Gompertz model fits most of the feedstock with R 2 up to 1 indicating that this model can be used for estimating treatment efficiencies of full-scale reactors and performing scale-up analysis. The economic analysis shows that POME has the shortest payback period (PBP), highest internal rate of return (IRR) and net present value (NPV). However, it has already been well explored, with 93% of biogas plants in Malaysia using POME as feedstock. The FW generation rate in Malaysia is approximately 15,000 tonnes per day, at the same time FW as the second place shows potential to have a PBP of 5.4 years and 13.3% IRR, which is close to the results achieved with POME. This makes FW suitable to be used as the feedstock for biogas production. GRAPHICAL ABSTRACT
Lights and Shadows: A Comprehensive Survey on Cooperative and Precoding Schemes to Overcome LOS Blockage and Interference in Indoor VLC

Visible light communications (VLC) have received significant attention as a way of moving part of the saturated indoor wireless traffic to the wide and unregulated visible optical spectrum. Nowadays, VLC are considered as a suitable technology, for several applications such as high-rate data transmission, supporting internet of things communications or positioning. The signal processing originally derived from radio-frequency (RF) systems such as cooperative or precoding schemes can be applied to VLC. However, its implementation is not straightforward. Furthermore, unlike RF transmission, VLC present a predominant line-of-sight link, although a weak non-LoS component may appear due to the reflection of the light on walls, floor, ceiling and nearby objects. Blocking effects may compromise the performance of the aforementioned transmission schemes. There exist several surveys in the literature focused on VLC and its applications, but the management of the shadowing and interference in VLC requires a comprehensive study. To fill this gap, this work introduces the implementation of cooperative and precoding schemes to VLC, while remarking their benefits and drawbacks for overcoming the shadowing effects. After that, the combination of both cooperative and precoding schemes is analyzed as a way of providing resilient VLC networks. Finally, we propose several open issues that the cooperative and precoding schemes must face in order to provide satisfactory VLC performance in indoor scenarios.
Temporal dissociation of neural activity underlying synesthetic and perceptual colors

Grapheme-color synesthetes experience color when seeing achromatic symbols. We examined whether similar neural mechanisms underlie color perception and synesthetic colors using magnetoencephalography. Classification models trained on neural activity from viewing colored stimuli could distinguish synesthetic color evoked by achromatic symbols after a delay of ∼100 ms. Our results provide an objective neural signature for synesthetic experience and temporal evidence consistent with higher-level processing in synesthesia.