Miracle-dz/UniFAR-FTUs huggingface dataset:
ARTP statement on pulmonary function testing 2020

The Association for Respiratory Technology & Physiology (ARTP) last produced a statement on the performance of lung function testing in 1994. At that time the focus was on a practical statement for people working in lung function laboratories. Since that time there have been many technological advances and alterations to best practice in the measurement and interpretation of lung function assessments. In light of these advances an update was warranted. ARTP, therefore, have provided within this document, where available, the most up-to-date and evidence-based recommendations for the most common lung function assessments performed in laboratories across the UK. These recommendations set out the requirements and considerations that need to be made in terms of environmental and patient factors that may influence both the performance and interpretation of lung function tests. They also incorporate procedures to ensure quality assured diagnostic investigations that include those associated with equipment, the healthcare professional conducting the assessments and the results achieved by the subject. Each section aims to outline the common parameters provided for each investigation, a brief principle behind the measurements (where applicable), and suggested acceptability and reproducibility criteria.
Pharmacogenomics of Hypertension Treatment

Hypertension is one of the strongest modifiable cardiovascular risk factors, affecting an increasing number of people worldwide. Apart from poor medication adherence, the low efficacy of some therapies could also be related to inter-individual genetic variability. Genetic studies of families revealed that heritability accounts for 30% to 50% of inter-individual variation in blood pressure (BP). Genetic factors not only affect blood pressure (BP) elevation but also contribute to inter-individual variability in response to antihypertensive treatment. This article reviews the recent pharmacogenomics literature concerning the key classes of antihypertensive drugs currently in use (i.e., diuretics, β-blockers, ACE inhibitors, ARB, and CCB). Due to the numerous studies on this topic and the sometimes-contradictory results within them, the presented data are limited to several selected SNPs that alter drug response. Genetic polymorphisms can influence drug responses through genes engaged in the pathogenesis of hypertension that are able to modify the effects of drugs, modifications in drug–gene mechanistic interactions, polymorphisms within drug-metabolizing enzymes, genes related to drug transporters, and genes participating in complex cascades and metabolic reactions. The results of numerous studies confirm that genotype-based antihypertension therapies are the most effective and may help to avoid the occurrence of major adverse events, as well as decrease the costs of treatment. However, the genetic heritability of drug response phenotypes seems to remain hidden in multigenic and multifactorial complex traits. Therefore, further studies are required to analyze all associations and formulate final genome-based treatment recommendations.
Hydroxytyrosol Inhibits Protein Oligomerization and Amyloid Aggregation in Human Insulin

Hydroxytyrosol (HT), one of the main phenolic components of olive oil, has attracted considerable interest for its biological properties, including a remarkable antioxidant and anti-inflammatory power and, recently, for its ability to interfere with the amyloid aggregation underlying several human diseases. We report here a broad biophysical approach and cell biology techniques that allowed us to characterize the molecular mechanisms by which HT affects insulin amyloid aggregation and the related cytotoxicity. Our data show that HT is able to fully inhibit insulin amyloid aggregation and this property seems to be ascribed to the stabilization of the insulin monomeric state. Moreover, HT completely reverses the toxic effect produced by amyloid insulin aggregates in neuroblastoma cell lines by fully inhibiting the production of toxic amyloid species. These findings suggest that the beneficial effects of olive oil polyphenols, including HT, may arise from multifunctional activities and suggest possible a application of this natural compound in the prevention or treatment of amyloid-associated diseases.
The Specific IKKε/TBK1 Inhibitor Amlexanox Suppresses Human Melanoma by the Inhibition of Autophagy, NF-κB and MAP Kinase Pathways

Inhibitor-kappaB kinase epsilon (IKKε) and TANK-binding kinase 1 (TBK1) are non-canonical IκB kinases, both described as contributors to tumor growth and metastasis in different cancer types. Several hints indicate that they are also involved in the pathogenesis of melanoma; however, the impact of their inhibition as a potential therapeutic measure in this “difficult-to-treat” cancer type has not been investigated so far. We assessed IKKε and TBK1 expression in human malignant melanoma cells, primary tumors and the metastasis of melanoma patients. Both kinases were expressed in the primary tumor and in metastasis and showed a significant overexpression in tumor cells in comparison to melanocytes. The pharmacological inhibition of IKKε/TBK1 by the approved drug amlexanox reduced cell proliferation, migration and invasion. Amlexanox did not affect the cell cycle progression nor apoptosis induction but significantly suppressed autophagy in melanoma cells. The analysis of potential functional downstream targets revealed that NF-кB and ERK pathways might be involved in kinase-mediated effects. In an in vivo xenograft model in nude mice, amlexanox treatment significantly reduced tumor growth. In conclusion, amlexanox was able to suppress tumor progression potentially by the inhibition of autophagy as well as NF-кB and MAP kinase pathways and might therefore constitute a promising candidate for melanoma therapy.
Characterization of a Toothpaste Containing Bioactive Hydroxyapatites and In Vitro Evaluation of Its Efficacy to Remineralize Enamel and to Occlude Dentinal Tubules

Demineralization of dental hard tissues is a well-known health issue and the primary mechanism responsible for caries and dentinal hypersensitivity. Remineralizing toothpastes are nowadays available to improve conventional oral care formulations regarding the prevention and repair of demineralization. In this paper, we analyzed the chemical-physical features of a commercial toothpaste (Biosmalto Caries Abrasion and Erosion, Curasept S.p.A., Saronno, Italy), with particular attention paid to the water-insoluble fraction which contains the remineralizing bioactive ingredients. Moreover, the efficacy of the toothpaste to induce enamel remineralization and to occlude dentinal tubules has been qualitatively and semiquantitatively tested in vitro on human dental tissues using scanning electron microscopy and X-ray microanalysis. Our results demonstrated that the water-insoluble fraction contained silica as well as chitosan and poorly crystalline biomimetic hydroxyapatite doped with carbonate, magnesium, strontium, and fluoride ions. The formulation showed excellent ability to restore demineralized enamel into its native structure by epitaxial deposition of a new crystalline phase in continuity with the native one. It was also able to occlude the dentinal tubules exposed completely by acid-etching. Overall, this study demonstrated that the tested toothpaste contained a biomimetic ionic-substituted hydroxyapatite-based active principle and that, within the in vitro conditions analyzed in this study, it was effective in dental hard tissue remineralization.
Identifying multiscale spatio-temporal patterns in human mobility using manifold learning

When, where and how people move is a fundamental part of how human societies organize around every-day needs as well as how people adapt to risks, such as economic scarcity or instability, and natural disasters. Our ability to characterize and predict the diversity of human mobility patterns has been greatly expanded by the availability of Call Detail Records (CDR) from mobile phone cellular networks. The size and richness of these datasets is at the same time a blessing and a curse: while there is great opportunity to extract useful information from these datasets, it remains a challenge to do so in a meaningful way. In particular, human mobility is multiscale, meaning a diversity of patterns of mobility occur simultaneously, which vary according to timing, magnitude and spatial extent. To identify and characterize the main spatio-temporal scales and patterns of human mobility we examined CDR data from the Orange mobile network in Senegal using a new form of spectral graph wavelets, an approach from manifold learning. This unsupervised analysis reduces the dimensionality of the data to reveal seasonal changes in human mobility, as well as mobility patterns associated with large-scale but short-term religious events. The novel insight into human mobility patterns afforded by manifold learning methods like spectral graph wavelets have clear applications for urban planning, infrastructure design as well as hazard risk management, especially as climate change alters the biophysical landscape on which people work and live, leading to new patterns of human migration around the world.
Molecular genetic analysis of siRNA biogenesis and function in Arabidopsis thaliana

In diverse eukaryotes, small RNA products of Dicer-like (DCL) proteins regulate mRNA stability or translation, and direct chromatin modifications to genomic regions, phenomena collectively known as RNA silencing. In plants, different types of small RNAs generated from double-stranded RNA, called short interfering RNAs (siRNAs), mediate RNA-directed DNA methylation (RdDM) to endogenous repeats and defense against viruses. Here, I studied the biogenesis and function of siRNAs from two types of tandem repeat: the 180 bp and 5S rDNA arrays of Arabidopsis thaliana. Furthermore, I analyzed siRNAs derived from two DNA viruses -- Cabbage Leaf Curl Virus (CaLCuV) and Cauliflower Mosaic Virus (CaMV) -- in Arabidopsis. Using a reverse genetics approach, I found that accumulation of specific size classes of ~20-24 nt siRNAs depends on particular Arabidopsis DCLs and also HEN1, which methylates siRNA 3’-ends. Upstream of these steps, biogenesis of tandem repeat-derived siRNAs required the RNA polymerase IV (Pol IV) pathway, known to include NRPD1a and RDR2. 5S rDNA methylation was reduced in mutants deficient for NRPD1a, RDR2 or the chromatin remodeling factor DDM1, but not in strains deficient for four Arabidopsis DCLs. Genetic crosses showed that DDM1 and the Pol IV pathway play distinct but intertwined roles in 5S rDNA methylation: analysis of a strain deficient for both DDM1 and DCL3 suggests that siRNA function in cytosine methylation is most crucial when CpG-methylation maintenance is impaired. Integrating my data with reports on 5S rRNA gene regulation, I propose a dynamic model to describe RdDM affecting the 5S rDNA arrays. A similar mechanism might regulate genes that impact growth in Arabidopsis, since double mutants deficient for DDM1 and the Pol IV pathway showed reduced fresh weight. Unlike endogenous siRNAs, viral siRNA accumulation did not require upstream components of known RNA silencing pathways, such as RDR2 or RDR6. However, RDR-independent mechanisms leading to viral siRNA biogenesis may include: (i) overlapping sense / antisense transcription about the circular viral DNA, and (ii) folding of the CaMV 35S RNA transcript leader. Supporting the latter hypothesis, CaMV-infected plants accumulate siRNA from three “hotspots”, all matching the structured leader. Furthermore, DCL1 -- thought to excise microRNAs from stem-loop hairpin precursors -- appears to mediate production of ~21 nt siRNAs from the leader or related dsRNA. In general, my results are consistent with a “branched” pathway model for siRNA biogenesis, in which substrates from various sources can be funneled through the same DCL and HEN1 steps, before the siRNA products are incorporated into specialized effectors.
Light sheet microscopy of the gerbil cochlea

Light sheet fluorescence microscopy (LSFM) provides a rapid and complete three‐dimensional image of the cochlea. The method retains anatomical relationships—on a micrometer scale—between internal structures such as hair cells, basilar membrane (BM), and modiolus with external surface structures such as the round and oval windows. Immunolabeled hair cells were used to visualize the spiraling BM in the intact cochlea without time intensive dissections or additional histological processing; yet material prepared for LSFM could be rehydrated, the BM dissected out and reimaged at higher resolution with the confocal microscope. In immersion‐fixed material, details of the cochlear vasculature were seen throughout the cochlea. Hair cell counts (both inner and outer) as well as frequency maps of the BM were comparable to those obtained by other methods, but with the added dimension of depth. The material provided measures of angular, linear, and vector distance between characteristic frequency regions along the BM. Thus, LSFM provides a unique ability to rapidly image the entire cochlea in a manner applicable to model and interpret physiological results. Furthermore, the three‐dimensional organization of the cochlea can be studied at the organ and cellular level with LSFM, and this same material can be taken to the confocal microscope for detailed analysis at the subcellular level.
Prey selection by a reintroduced lion population in the Greater Makalali Conservancy, South Africa

Lion prey selection was studied on the Greater Makalali Conservancy (140 km2), Limpopo Province, South Africa, in order to assist with management strategies. Monitoring was carried out between February 1998 and December 2001. Lion killed 15 species, with warthog, blue wildebeest, Burchell’s zebra, kudu and waterbuck constituting approximately 75% of their diet. Between 2.2% and 3.1% of the available prey biomass was killed yearly, while each female equivalent unit (FEQ) killed between 3 kg and 3.2 kg daily. Lion predation was greater for warthog, wildebeest and waterbuck and less for impala than expected. When male lion were present, a greater number of warthog and giraffe were killed, while number of females had a significant effect on medium sized prey species and total prey species killed. Significantly more warthog, wildebeest and kudu were killed in winter than summer. More prey than expected was killed in open habitats and less than expected in thickets. Managers of small, enclosed reserves need to constantly monitor prey populations, especially medium sized prey and may be able to reduce predation on large prey species by manipulating male lion numbers. Reserves also need to contain adequate open habitats for lion to make use of these areas for hunting.
An Eye Tracking Approach to Understanding Misinformation and Correction Strategies on Social Media: The Mediating Role of Attention and Credibility to Reduce HPV Vaccine Misperceptions

ABSTRACT This study uses an unobtrusive eye tracking approach to examine understudied psychological mechanisms – message attention and credibility – when people are exposed to misinformation and correction on social media. We contrast humor versus non-humor correction strategies that point out rhetorical flaws in misinformation regarding the HPV vaccine, which was selected for its relevance and impact on public health. We randomly assigned participants to one of two experimental conditions: humor correction versus non-humor correction. Our analyses revealed that the humor correction increased attention to the image portion of the correction tweet, and this attention indirectly lowered HPV misperceptions by reducing the credibility of the misinformation tweet. The study also found that the non-humor correction outperformed the humor correction in reducing misperceptions via its higher credibility ratings. Practical implications for correcting misinformation on social media are discussed.
A Descriptive Quantitative Analysis on the Extent of Polypharmacy in Recipients of Ontario Primary Care Team Pharmacist-Led Medication Reviews

Pharmacist-led medication reviews have been shown to improve medication management, reducing the adverse effects of polypharmacy among older adults. This paper quantitatively examines the medications, medication discrepancies and drug therapy problems of recipients in primary care. A convenience sample of 16 primary care team pharmacists in Ontario, Canada contributed data for patients with whom they conducted a medication review over a prior four-week period. Data were uploaded using electronic data capture forms and descriptive analyses were completed. Two hundred and thirty-seven patients (on average, 67.9 years old) were included in the study, taking an average of 9.2 prescription medications (±4.7). Majority of these patients (83.5%) were categorized as polypharmacy patients taking at least five or more prescribed drugs per day. Just over half of the patients were classified as having a low level of medication complexity (52.3%). Pharmacists identified 2.1 medication discrepancies (±3.9) and 3.6 drug therapy problems per patient (±2.8). Half these patients had more than one medication discrepancy and almost every patient had a drug therapy problem identified. Medication reviews conducted by pharmacists in primary care teams minimized medication discrepancies and addressed drug therapy problems to improve medication management and reduce adverse events that may result from polypharmacy.
Low-impact (compliant) flooring and staff injuries

Abstract Introduction Low impact flooring (LIF) has shown potential for reducing fall-related injuries for older people in residential care or hospital environments. However, the increased rolling resistance when moving equipment on these floors has raised concerns that staff injuries may increase. Methods LIF was trialled on one Older Persons Health ward for 2.5 years. Reported staff injuries were monitored during and following the trial. Numbers of staff injured on the LIF ward were compared with three other similar and adjacent OPH wards without LIF for the duration of the trial (‘concurrent control’ evaluation). At the trial conclusion the LIF ward moved to a different hospital that had standard flooring. This enabled a further ‘during and after’ evaluation where numbers of staff injured from the LIF ward during the trial were compared with those reported afterwards by the same ward staff without LIF. Results There was no difference in the numbers of staff injured in the LIF ward compared with the concurrent control wards (28 LIF vs 30 control; p = 0.44). The number of staff with injuries in the LIF ward also did not significantly alter when those staff moved to a new ward without LIF (45 after vs 28 before; p = 0.11). Conclusion There was no change in the numbers of staff with injuries during the LIF trial in an Older Persons Health ward. This small study suggests LIF appears safe for both patients and staff. Implications for rehabilitation Falls in hospital are common with patient injuries occurring in approximately 20-30% of falls. Low impact (compliant) flooring may reduce fall-related injuries in hospitals and residential care. Low impact flooring has an increased rolling resistance, which has the potential to increase staff injuries when moving equipment. This study found no change in the number of staff injured during a low impact flooring trial providing some reassurance that these floors are safe for staff.
Assessing frost hardiness of Pinus bungeana shoots and needles by electrical impedance spectroscopy with and without freezing tests

Aims Nursery and forest operations require that frost hardiness results be produced faster than can be provided by controlled freezing tests. There is a great challenge to develop a rapid method for predicting frost hardiness that might not necessitate controlled freezing tests. The aim of this study was to examine the assessment of the frost hardiness of shoots and needles of Pinus bungeana by electrical impedance spectroscopy (EIS) with and without controlled exposure to freezing. Methods The frost hardiness of current-year shoots and needles of P. bungeana in an 8-year-old provenance field trial was measured at Shisanlin Nursery in Beijing, China, from September 2006 to January 2007 by means of EIS and conventional electrolyte leakage (EL). In the same plants, but without controlled freezing test, were monitored the EIS parameters in current-year shoots and needles. Important Findings The results showed that (i) after controlled freezing tests, the frost hardiness estimated by EIS parameters (extracellular resistance, re, and membrane time constant, sm) was significantly correlated with the frost hardiness assessed by EL method (r = 0.95) and (ii) for the samples not exposed to controlled freezing treatment, the relaxation time s1 for shoots and b for needles had greater correlations with the frost hardiness estimated by EL after controlled freezing tests relative to the other parameters (r = � 0.90 for shoots and r = 0.84 for needles, respectively). The parameters re of shoots and needles and sm of needles might be applied for measuring frost hardiness of samples after exposed to controlled freezing tests. The frost hardiness results can be obtained within 48 h. The parameters s1 of shoots and b of needles could be used for estimating the frost hardiness of samples without using a controlled freezing test. The frost hardiness results can be obtained within 24 h.
IDENTIFYING FAVORABLE RESPONSES TO DROUGHT STRESS IN DIVERSE GENOTYPES OF MAIZE (ZEA MAYS L.)

Of the many potential abiotic stresses, insufficient water supply is the major limiting physiological constraint for crop production in many regions of the world. Because yield is a product of many phenotypic components, plant breeders experience difficulties when selecting lines for higher yield under drought conditions. The use of other measurable traits, such as reproductive timing or concentrations of stress hormones, can reveal information regarding changes in plant behavior during low water availability. The purpose of this project is to further decipher the signaling behind the drought response of maize and identify which physiological responses might characterize drought-resistant genotypes. Eight tropical inbred maize genotypes, previously shown to have varying behavior under drought conditions, were surveyed for physiological response during water stress. Water stress was imposed once plants reached the flowering period. During a ten-day treatment period, transpiration, ear growth and silk length were calculated daily for each plant. Upon tissue harvest (after ten days of treatment), ear size and leaf water potential were measured. Leaf and ear tissue sampled in the greenhouse were analyzed for non-structural carbohydrates, abscisic acid (ABA), cytokinin, and invertase. Physiological differences in genotypic response to water stress were apparent. Of the eight lines examined, the P1 genotype appeared to respond best to low water availability. Under water stress, P1 maintained low ear and leaf ABA concentrations, higher sucrose levels in the leaves, more starch in the ear tissue, and exhibited little change in ovary invertase activity. When comparing measured traits among all genotypes, leaf and ear ABA was negatively correlated with reproductive growth. Leaf carbohydrate levels were positively correlated with ear growth, and negatively associated with ABA levels in the leaves and ears. In general, cytokinin levels in the ear tissue increased under water stress. Invertase activity decreased in water-stressed ear tissue compared to control plants, and cell wall invertase activity was higher than soluble invertase. Carbohydrate partitioning appears to be an important indicator of reproductive growth under water stress, and identifying the differences in invertase behavior and their relationship to yield performance in several genotypes would be a crucial next step in assessing drought tolerance.