Miracle-dz/UniFAR-FTUs huggingface dataset:
Most frequent errors in inhalation technique of patients with asthma treated at a tertiary care hospital

ABSTRACT Objective: To demonstrate the most frequent errors in inhalation technique in patients with asthma undergoing treatment at a tertiary care hospital. Methods: A cross-sectional study with a convenience sample of asthma patients aged 18 years or over, treated at a pulmonology outpatient clinic of a tertiary care hospital. The assessment of inhalation technique of users of the dry powder inhalers Aerolizer®, Aerocaps and Diskus®, or metered-dose inhalers was based on the manufacturer's instructions for use of each inhaler device. Patients demonstrated the inhalation technique with empty inhaler devices, and it was considered correct when all stages were performed properly, or when errors probably did not interfere with the treatment outcome. Results: Among 71 participants, 43 (60.5%) performed inhalation technique incorrectly. Among metered-dose inhalers and dry powder inhalers users, inhalation technique errors were found in 84.2% and 51.9%, respectively (p=0.013). Errors were more frequent at the exhalation stage (67.4%), followed by breathing in (58.1%) and apnea (51.2%). In the group using dry powder inhalers, the most common errors occurred during exhalation and, for those using metered-dose inhalers, the most compromised stage was aspiration. Conclusion: Errors were more frequent among those using metered-dose inhalers compared with dry powder inhalers. Misconceptions are more common at the expiration stage among users of dry powder inhalers and in aspiration among those on metered-dose inhalers.
Incorporating Household Spillovers in Cost Utility Analysis: A Case Study Using Behavior Change in COPD

Abstract Objectives It is important to capture all health effects of interventions in cost-utility analyses conducted under a societal or healthcare perspective. However, this is rarely done. Household spillovers (health effects on patients’ other household members) may be particularly likely in the context of technologies and interventions to change behaviors that are interdependent in the household. Our objective was to prospectively collect outcome data from household members and illustrate how these can be included in a cost-utility analysis of a behavior change intervention in chronic obstructive pulmonary disease (COPD). Methods Data were collected from patients’ household members (n = 153) alongside a randomized controlled trial of a COPD self-management intervention. The impact of the intervention on household members’ EQ-5D-5L scores (primary outcome), was evaluated. Analyses were then carried out to estimate household members’ quality-adjusted life-years (QALYs) and assess the impact of including these QALYs on cost-effectiveness. Results The intervention had a negligible spillover on household members’ EQ-5D-5L scores (−0.007; p = .75). There were also no statistically significant spillovers at the 5 percent level in household member secondary outcomes. In the base-case model, the inclusion of household member QALYs in the incremental cost-effectiveness ratio (ICER) denominator marginally increased the ICER from GBP 10,271 (EUR 13,146) to GBP 10,991 (EUR 14,068) per QALY gained. Conclusions This study demonstrates it is feasible to prospectively collect and include household members’ outcome data in cost utility analysis, although the study highlighted several methodological issues. In this case, the intervention did not impact significantly on household members’ health or health behaviors, but inclusion of household spillovers may make a difference in other contexts.
Gene Profiling in Temporal Lobe Epilepsy Tissue and Dysplastic Lesions

Epilepsies are among the most frequent CNS disorders, affecting approximately 1% of the population in the world. In pharmacoresistant patients with focal epilepsies, surgical removal of the epileptogenic focus allows access to human tissue for neuropathologic and molecular biologic analyses. Ammon’s horn sclerosis (AHS) of the hippocampal formation in temporal lobe epilepsy (TLE), highly differentiated glioneuronal malformations, and tumors such as gangliogliomas constitute frequent neuropathologic findings in biopsy specimens. The multifactorial pathogenesis of the epilepsies includes molecular mechanisms of compromised neurodevelopment, neuronal plasticity, and aberrant cellular excitability, as well as neuronal cell degeneration in affected CNS areas. The complex pathology of focal epilepsies (including those with glioneuronal lesions) renders them a particular challenge—and opportunity—for functional genomics investigations. A comprehensive analysis of transcriptional commands, as well as tissueand cell-specific expression profiles, may provide insights into underlying mechanisms, despite the large number of expressed genes in normal and diseased brain tissue and the possibilities of dynamic epigenetic modifications. The recent development in microarray and gene-expression profiling technologies allows transcriptional studies of large numbers of genes, by using minute amounts of tissue (or even single cells). In combination, laser-microdissection approaches and powerful mRNA amplification strategies [e.g., quantitative reverse transcription–polymerase chain reaction (RT-PCR) technologies] facilitate large-scale expression analysis in well-defined tissue specimens or cellular subpopulations. The integration and interpretation of large amounts of array data, from different epilepsy models and disease states, are ongoing challenges. These data may
Cardio-Metabolic Disorders in Non-Alcoholic Fatty Liver Disease

With the progressive epidemics of obesity, non-alcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease in adults and children. The increasing prevalence and incidence of NAFLD with advanced fibrosis is concerning because patients appear to experience higher non-liver-related morbidity and mortality than the general population. Recent clinical evidence suggests that NAFLD is directly associated with an increased risk of cardio-metabolic disorders. This mini review describes briefly the current understanding of the pathogenesis of NAFLD, summarizing the link between NAFLD and cardio-metabolic complications, focusing mainly upon ischemic stroke, type 2 diabetes mellitus (DM), hypertension, chronic kidney disease (CKD) and cardiac arrhythmias. In addition, it describes briefly the current understanding of the pathogenesis of NAFLD.
Infection outcomes are robust to thermal variability in a bumble bee host-parasite system.

Climate change-related increases in thermal variability and rapid temperature shifts will affect organisms in multiple ways, including imposing physiological stress. Furthermore, the effects of temperature may alter the outcome of biotic interactions, including those with pathogens and parasites. In the context of host-parasite interactions, the beneficial acclimation hypothesis posits that shifts away from acclimation or optimum performance temperatures will impose physiological stress on hosts and will affect their ability to resist parasite infection. We investigated the beneficial acclimation hypothesis in a bumble bee-trypanosome parasite system. Freshly emerged adult worker bumble bees, Bombus impatiens, were acclimated to 21 °C, 26 °C or 29 °C. They were subsequently experimentally exposed to the parasite, Crithidia bombi, and placed in a performance temperature that was the same as the acclimation temperature (constant) or one of the other temperatures (mismatched). Prevalence of parasite transmission was checked four and six days post-parasite exposure, and infection intensity in the gut was quantified at eight days post-exposure. Parasite strain, host colony, and host size had significant effects on transmission prevalence and infection load. However, neither transmission nor infection intensity were significantly different between constant and mismatched thermal regimes. Furthermore, acclimation temperature, performance temperature, and the interaction of acclimation and performance temperatures had no significant effects on infection outcomes. These results, counter to predictions of the beneficial acclimation hypothesis, suggest that infection outcomes in this host-parasite system are robust to thermal variation within typically experienced ranges. This could be a consequence of adaptation to commonly experienced natural thermal regimes or a result of individual and colony level heterothermy in bumble bees. However, thermal variability may still have a detrimental effect on more sensitive stages or species, or when extreme climatic events push temperatures outside of the normally experienced range.
Multiparty Differential Privacy via Aggregation of Locally Trained Classifiers

As increasing amounts of sensitive personal information finds its way into data repositories, it is important to develop analysis mechanisms that can derive aggregate information from these repositories without revealing information about individual data instances. Though the differential privacy model provides a framework to analyze such mechanisms for databases belonging to a single party, this framework has not yet been considered in a multi-party setting. In this paper, we propose a privacy-preserving protocol for composing a differentially private aggregate classifier using classifiers trained locally by separate mutually untrusting parties. The protocol allows these parties to interact with an untrusted curator to construct additive shares of a perturbed aggregate classifier. We also present a detailed theoretical analysis containing a proof of differential privacy of the perturbed aggregate classifier and a bound on the excess risk introduced by the perturbation. We verify the bound with an experimental evaluation on a real dataset.
Thermal effects in stretching of Go‐like models of titin and secondary structures

The effect of temperature on mechanical unfolding of proteins is studied using a Go‐like model with a realistic contact map and Lennard–Jones contact interactions. The behavior of the I27 domain of titin and its serial repeats is contrasted to that of simple secondary structures. In all cases, thermal fluctuations accelerate the unraveling process, decreasing the unfolding force nearly linearly at low temperatures. However, differences in bonding geometry lead to different sensitivity to temperature and different changes in the unfolding pattern. Due to its special native‐state geometry, titin is much more thermally and elastically stable than the secondary structures. At low temperatures, serial repeats of titin show a parallel unfolding of all domains to an intermediate state, followed by serial unfolding of the domains. At high temperatures, all domains unfold simultaneously, and the unfolding distance decreases monotonically with the contact order, that is, the sequence distance between the amino acids that form the native contact. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Granule-Dependent Natural Killer Cell Cytotoxicity to Fungal Pathogens

Natural killer (NK) cells kill or inhibit the growth of a number of fungi including Cryptococcus, Candida, Aspergillus, Rhizopus, and Paracoccidioides. Although many fungi are not dangerous, invasive fungal pathogens, such as Cryptococcus neoformans, cause life-threatening disease in individuals with impaired cell-mediated immunity. While there are similarities to cell-mediated killing of tumor cells, there are also important differences. Similar to tumor killing, NK cells directly kill fungi in a receptor-mediated and cytotoxic granule-dependent manner. Unlike tumor cell killing where multiple NK cell-activating receptors cooperate and signal events that mediate cytotoxicity, only the NKp30 receptor has been described to mediate signaling events that trigger the NK cell to mobilize its cytolytic payload to the site of interaction with C. neoformans and Candida albicans, subsequently leading to granule exocytosis and fungal killing. More recently, the NKp46 receptor was reported to bind Candida glabrata adhesins Epa1, 6, and 7 and directly mediate fungal clearance. A number of unanswered questions remain. For example, is only one NK cell-activating receptor sufficient for signaling leading to fungal killing? Are the signaling pathways activated by fungi similar to those activated by tumor cells during NK cell killing? How do the cytolytic granules traffic to the site of interaction with fungi, and how does this process compare with tumor killing? Recent insights into receptor use, intracellular signaling and cytolytic granule trafficking during NK cell-mediated fungal killing will be compared to tumor killing, and the implications for therapeutic approaches will be discussed.
Effects of 5/6 nephrectomy on renal function and blood pressure in mice.

BACKGROUND/AIMS The rat has been the most used experimental animal for studies of cardiovascular and kidney diseases. However, it is notable that there is increasing importance placed on the use of the mouse model to increase understanding of these pathophysiologies. The aim of the present study was to induce chronic kidney disease in a mouse model and to evaluate the resulting changes in blood pressure (BP) and in renal morphology and function. METHODS Adult male C57BL/6 mice underwent 5/6 nephrectomy (5/6 Nx) or a sham operation (Sham). Two weeks later, conscious animals were subjected to a 24-hour urine collection and to a direct measurement of BP. RESULTS Compared to Sham animals, 5/6 Nx mice showed reduced creatinine clearance (3-fold, p<0.01), proteinuria (1.5-fold, p<0.01) and uremia (4-fold, p<0.01), as well as high blood pressure (~20%, p<0.01). 5/6 Nx animals showed increases in the 24 h urine excretion of Na(+) (2-fold, p<005), K(+) (~2-fold, <0.01) and Ca(2+) (~12-fold). Kidney histology of 5/6 Nx mice also demonstrated glomerular hypertrophy (1.5-fold, p<0.05), mesangial expansion (~40%, p<0.01) and increased glomerular collagen deposition (~30%, p<0.05). CONCLUSION Induction of 5/6 nephrectomy in mice for two weeks leads to systemic arterial hypertension and to functional and morphological damage of the remnant kidney, which are considered the main characteristics of chronic kidney disease.
Both the mirror and the affordance systems might be impaired in adults with high autistic traits. Evidence from EEG mu and beta rhythms

The association of autism spectrum disorder (ASD) with an altered mirror neuron system is still controversial. At the same time, the processing of object affordances by persons with ASD is a neglected issue. In this electroencephalographic study, adults differing in their autism quotient (AQ) scores were selected. We found anomalous modulation of mu and beta rhythms in high‐AQ, compared to low‐AQ persons, while they watched a set of goal‐directed manual actions. This confirms that observing actions involving implicit intentions most clearly reveals the impairment of the mirror neurons system (MNS). The high‐AQ group also showed anomalous mu and beta modulation when they looked at pictures of manipulable objects, indicating a deficit in processing motor affordances. We conclude that high‐AQ adults have neural impairment of both the MNS and the affordance systems, which could underlie their relational problems with both people and objects. Autism Res 2019, 12: 1032–1042. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.
Assessing Distraction Potential of Augmented Reality Head-Up Displays for Vehicle Drivers

Objective: To develop a framework for quantifying the visual and cognitive distraction potential of augmented reality (AR) head-up displays (HUDs). Background: AR HUDs promise to be less distractive than traditional in-vehicle displays because they project information onto the driver’s forward-looking view of the road. However, AR graphics may direct the driver’s attention away from critical road elements. Moreover, current in-vehicle device assessment methods, which are based on eyes-off-road time measures, cannot capture this unique challenge. Method: This article proposes a new method for the assessment of AR HUDs by measuring driver gaze behavior, situation awareness, confidence, and workload. An experimental user study (n = 24) was conducted in a driving simulator to apply the proposed method for the assessment of two AR pedestrian collision warning (PCW) design alternatives. Results: Only one of the two tested AR interfaces improved driver awareness of pedestrians without visually and cognitively distracting drivers from other road elements that were not augmented by the display but still critical for safe driving. Conclusion: Our initial human-subject experiment demonstrated the potential of the proposed method in quantifying both positive and negative consequences of AR HUDs on driver cognitive processes. More importantly, the study suggests that AR interfaces can be informative or distractive depending on the perceptual forms of graphical elements presented on the displays. Application: The proposed methods can be applied by designers of in-vehicle AR HUD interfaces and be leveraged by designers of AR user interfaces in general.
For a Change, May the Hare Defeat the Tortoise.

In this issue of Indian Pediatrics, Modi and coworkers [1] have published an interesting openlabel randomized controlled trial in which they compared an early aggressive enteral feeding strategy with a conservative enteral feeding strategy among neonates weighing 750-1250 grams at birth, for its effect on all-cause mortality during hospital stay. The authors initiated and advanced feeds at 15 or 20 mL/kg/ day in the conservative arm; and initiated and advanced feeds at 30 or 40 mL/kg/day in the aggressive arm. They did not detect statistically significant differences between the two groups with respect to all-cause mortality, culture-positive sepsis, survival without major morbidity, feed intolerance, or average daily weight gain during hospital stay. However, the aggressive feeding regimen group reached full feeds significantly earlier than the conservative feeding group.
Sperm FISH studies in seven male carriers of Robertsonian translocation t(13;14)(q10;q10).

BACKGROUND Robertsonian translocation t(13;14) is one of the most common structural reorganization in humans, but meiotic segregation studies in these carriers are still limited. The segregation pattern of the chromosomes involved, the possible influence of the translocated chromosomes on the synapsis and disjunction of other chromosome pairs [interchromosomal effects (ICE)] and the rates of unbalanced spermatozoa produced still deserve attention, not only to obtain a better characterization of the meiotic behaviour of this reorganization, but also to offer carrier couples accurate genetic counselling. METHODS Multicolour fluorescence in-situ hybridization was used to analyse the segregation of chromosomes 13 and 14 and the possible occurrence of ICE (on chromosomes 18, 21, 22, X and Y) in seven male carriers of a t(13;14)(q10;q10). RESULTS AND CONCLUSIONS The individuals analysed showed a homogeneous segregation pattern, with a clear predominance of alternate segregations resulting in the production of normal/balanced spermatozoa (83-88.23%). A significant increase in the disomy rates for the sex chromosomes, which could be considered as a positive ICE, was observed in two of the carriers analysed.
Apparent diffusion coefficient and tumor volume measurements help stratify progression-free survival of bevacizumab-treated patients with recurrent glioblastoma multiforme

Background The aim of this study was to determine whether apparent diffusion coefficient (ADC) bi-component curve-fitting histogram analysis and volume percentage change (VPC) prior to bevacizumab treatment can stratify progression-free survival (PFS) and overall survival (OS) in patients with glioblastoma multiforme (GBM) on first recurrence. Methods We retrospectively evaluated 17 patients with recurrent GBM who received bevacizumab and fotemustine (n = 13) or only bevacizumab (n = 4) on first recurrence at our institution between December 2009 and July 2015. Both T2/FLAIR abnormalities and enhancing tumor on T1 images were mapped to the ADC images. ADC-L and ADC-M values were obtained trough bi-Gaussian curve fitting histogram analysis. Furthermore, the study population was dichotomized into two subgroups: patients displaying a reduction in enhancing tumor volume of either >55% or <55% between the mean value calculated at baseline and first follow-up. Subsequently, a second dichotomization was performed according to a reduction in the T2 / FLAIR volume >41% or <41% at first check after treatment. OS and PFS were assessed using volume parameters in a Cox regression model adjusted for significant clinical parameters. Results In univariate analysis, contrast-enhanced (CE)-ADC-L was significantly predictive of PFS (p = 0.01) and OS (p = 0.03). When we dichotomized our sample using the 55% cut-off for enhancing tumor volume, CE-VPC was able to predict PFS (p = 0.01) but not OS (p = 0.08). In multivariate analysis, only the CE-ADC-L was predictive of PFS (p = 0.01), albeit not predictive of OS (p = 0.14). CE-ADC-M, T2/FLAIR-ADC-L, T2/FLAIR-ADC, and T2/FLAIR VPC were not significantly predictive of PFS and OS (p > 0.05) in both univariate and multivariate analysis. Conclusions CE-ADC and CE-VPC can stratify PFS for patients with recurrent glioblastoma prior to bevacizumab treatment.
Phylogenomics of Aplacophora (Mollusca, Aculifera) and a solenogaster without a foot

Recent molecular phylogenetic investigations strongly supported the placement of the shell-less, worm-shaped aplacophoran molluscs (Solenogastres and Caudofoveata) and chitons (Polyplacophora) in a clade called Aculifera, which is the sister taxon of all other molluscs. Thus, understanding the evolutionary history of aculiferan molluscs is important for understanding early molluscan evolution. In particular, fundamental questions about evolutionary relationships within Aplacophora have long been unanswered. Here, we supplemented the paucity of available data with transcriptomes from 25 aculiferans and conducted phylogenomic analyses on datasets with up to 525 genes and 75 914 amino acid positions. Our results indicate that aplacophoran taxonomy requires revision as several traditionally recognized groups are non-monophyletic. Most notably, Cavibelonia, the solenogaster taxon defined by hollow sclerites, is polyphyletic, suggesting parallel evolution of hollow sclerites in multiple lineages. Moreover, we describe Apodomenia enigmatica sp. nov., a bizarre new species that appears to be a morphological intermediate between Solenogastres and Caudofoveata. This animal is not a missing link, however; molecular and morphological studies show that it is a derived solenogaster that lacks a foot, mantle cavity and radula. Taken together, these results shed light on the evolutionary history of Aplacophora and reveal a surprising degree of morphological plasticity within the group.