Miracle-dz/UniFAR-FTUs huggingface dataset:
Synergy Between Pseudomonas aeruginosa Filtrates And Voriconazole Against Aspergillus fumigatus Biofilm Is Less for Mucoid Isolates From Persons With Cystic Fibrosis

Persons with cystic fibrosis (CF) frequently suffer from Pseudomonas aeruginosa and Aspergillus fumigatus co-infections. There is evidence that co-infections with these interacting pathogens cause airway inflammation and aggravate deterioration of lung function. We recently showed that P. aeruginosa laboratory isolates synergistically interact with the anti-fungal azole voriconazole (VCZ), inhibiting biofilm metabolism of several A. fumigatus laboratory strains. Interaction was usually mediated via pyoverdine, but also via pyocyanin or pyochelin. Here we used planktonic filtrates of 7 mucoid and 9 non-mucoid P. aeruginosa isolates from CF patients, as well as 8 isolates without CF origin, and found that all of these isolates interacted with VCZ synergistically at their IC50 as well as higher dilutions. CF mucoid isolates showed the weakest interactive effects. Four non-mucoid P. aeruginosa CF isolates produced no or very low levels of pyoverdine and did not reach an IC50 against forming A. fumigatus biofilm; interaction with VCZ still was synergistic. A VCZ-resistant A. fumigatus strain showed the same level of susceptibility for P. aeruginosa anti-fungal activity as a VCZ-susceptible reference strain. Filtrates of most Pseudomonas isolates were able to increase anti-fungal activity of VCZ on a susceptible A. fumigatus strain. This was also possible for the VCZ-resistant strain. In summary these data show that clinical P. aeruginosa isolates, at varying degrees, synergistically interact with VCZ, and that pyoverdine is not the only molecule responsible. These data also strengthen the idea that during co-infections of A. fumigatus and P. aeruginosa lower concentrations of VCZ might be sufficient to control fungal growth.
Biannual and Quarterly Comparison Analysis of Agglutinating Antibody Kinetics on a Subcohort of Individuals Exposed to Leptospira interrogans in Salvador, Brazil

Introduction Leptospirosis is a zoonosis with a worldwide spread that leads to clinical manifestations ranging from asymptomatic infection to a life-threatening disease. The immune response is predominantly humoral mediated limited to the infecting serovar. Individuals living in an area endemic for leptospirosis are often exposed to an environment contaminated with leptospires and there is a paucity of information on naturally acquired immunity. In the present study, we evaluated the kinetics of agglutinating antibodies in individuals from an endemic area for leptospirosis in Salvador, Brazil comparing two different intersample collection times. Methods Between 2017–2018, we carried out a biannual prospective cohort with 2,086 individuals living in an endemic area for leptospirosis in Salvador, Brazil. To compare agglutinating antibody kinetics using microscopic agglutination test (MAT) with different collection times, a subcohort of 72 individuals with quarterly follow-up was carried out in parallel. Results The results revealed that using a shorter time for intersample collection led to the detection of a higher number of infections and reinfection events. Furthermore, we observed a higher rate of titer decay indicating partial and short protection. However, there was no indication of major changes in risk factors for the disease. Conclusions We evaluated antibody kinetics among residents of an endemic area for leptospirosis comparing two sample collection times. The constant exposure to the contaminated environment increases the risk for leptospirosis infection with reinfection events being more common than expected. This indicates that the burden of leptospirosis might be underestimated by serological surveys, and further studies are necessary to better characterize the humoral response after infection.
Predictive Modeling of Mental Illness Onset Using Wearable Devices and Medical Examination Data: Machine Learning Approach

The prevention and treatment of mental illness is a serious social issue. Prediction and intervention, however, have been difficult because of lack of objective biomarkers for mental illness. The objective of this study was to use biometric data acquired from wearable devices as well as medical examination data to build a predictive model that can contribute to the prevention of the onset of mental illness. This was an observational study of 4,612 subjects from the health database of society-managed health insurance in Japan provided by JMDC Inc. The inputs to the predictive model were 3-months of continuous wearable data and medical examinations within and near that period; the output was the presence or absence of mental illness over the following month, as defined by insurance claims data. The features relating to the wearable data were sleep, activity, and resting heart rate, measured by a consumer-grade wearable device (specifically, Fitbit). The predictive model was built using the XGBoost algorithm and presented an area-under-the-receiver-operating-characteristic curve of 0.712 (SD = 0.02, a repeated stratified group 10-fold cross validation). The top-ranking feature importance measure was wearable data, and its importance was higher than the blood-test values from medical examinations. Detailed verification of the model showed that predictions were made based on disrupted sleep rhythms, mild physical activity duration, alcohol use, and medical examination data on disrupted eating habits as risk factors. In summary, the predictive model showed useful accuracy for grouping the risk of mental illness onset, suggesting the potential of predictive detection, and preventive intervention using wearable devices. Sleep abnormalities in particular were detected as wearable data 3 months prior to mental illness onset, and the possibility of early intervention targeting the stabilization of sleep as an effective measure for mental illness onset was shown.
Novel Opioid Analgesics for the Development of Transdermal Opioid Patches That Possess Morphine-Like Pharmacological Profiles Rather Than Fentanyl: Possible Opioid Switching Alternatives Among Patch Formula

BACKGROUND: Transdermal fentanyl is widely used in the treatment of severe pain because of convenience, safety, and stable blood concentrations. Nevertheless, patients often develop tolerance to fentanyl, necessitating the use of other opioids; transdermal buprenorphine patch is widely used as an analgesic agent, though available formulation does not provide comparable analgesic effect as transdermal fentanyl patch. Opioids bind to the opioid receptor (OR) to activate both G protein–mediated and β-arrestin–mediated pathways. We synthesized morphine-related compounds with high transdermal absorbability (N1 and N2) and evaluated their OR activities pharmacologically in comparison with fentanyl and morphine. METHODS: In cells stably expressing μ-opioid receptor (MOR), δ-opioid receptor (DOR), and κ-opioid receptor (KOR), G protein–mediated pathways were assessed using the CellKey and an intracellular cyclic adenosine monophosphate (cAMP) assay, while β-arrestin–mediated pathways were analyzed with β-arrestin recruitment and receptor internalization assays. Furthermore, analgesic effects were evaluated using a tail-flick test in mice, and the analgesic effect on fentanyl-tolerant mice was evaluated. RESULTS: In the CellKey and cAMP assays, both N1 and N2 showed the highest affinity for MOR and acted as full agonists as well as partial agonists for DOR and KOR. In the β-arrestin and internalization assays, only fentanyl acted as a full agonist; N1 and N2 acted as partial agonists of MOR. In the mouse tail-flick test, N1 and N2 showed analgesic effects equivalent to those of fentanyl and morphine. In fentanyl-tolerant mice, fentanyl showed a diminished analgesic effect, whereas N1 and N2 as well as morphine retained their analgesic effects. CONCLUSIONS: While N1 and N2 have higher transdermal absorbability than fentanyl, they also have analgesic effects comparable to those of morphine, suggesting that they may be attractive compounds for the development of novel opioid patches for transitioning from fentanyl patches.
The Relationship Between Design Outcomes and Mental States During Ideation

Using electroencephalography (EEG) to predict design outcomes could be used in many applications as it facilitates the correlation of engagement and cognitive workload with ideation effectiveness. It also establishes a basis for the connection between EEG measurements and common constructs in engineering design research. In this paper, we propose a support vector machine (SVM)-based prediction model for design outcomes using EEG metrics and some demographic factors as predictors. We trained and validated the model with more than 100 concepts, and then evaluated the relationship between EEG data and concept-level measures of novelty, quality, and elaboration. The results characterize the combination of engagement and workload that is correlated with good design outcomes. Findings also suggest that EEG technologies can be used to partially replace or augment traditional ideation metrics and to improve the efficacy of ideation research. [DOI: 10.1115/1.4036131]
Fishing grounds footprint and economic freedom indexes: Evidence from Asia-Pacific

Environmental challenges are as wide as the universe so that its different dimensions can be the subject of diverse studies. In this research, using 17 data from Asia-Pacific during the period 2000 to 2017, an attempt has been made to investigate the economic factors responsible for the ecological footprint in the fishing sector. The main contribution of the present study is to investigate the effects of nine economic freedom indicators along with other control variables on environmental pressure on the status of fishery resources. Based on the results, the Kuznets curve hypothesis was confirmed in the fishing grounds footprint, so that the growth of GDP per capita shows a positive and significant effect, while its squared form coefficient is negative. Other control variables including natural resource rents, urbanization, and energy intensity, do not show significant effects on the fishing footprint. The different components of economic freedom show different effects, while their cumulative effects in the form of the total economic freedom index have a positive effect on the footprint of fishing and lead to increased extraction from fishing resources. The results show that the Government Integrity, Tax Burden, Business Freedom, Monetary Freedom indices increase the fishing footprint, while the indices of trade freedom and investment freedom, by revealing the negative effects on the fishing footprint, have beneficial environmental effects in reducing the pressure on the aquatic resources of countries. The results of the present study reveal the need to examine how the various dimensions of economic freedom affect to provide the proper management of fishery resources.
Morphology of foveal hypoplasia: Hyporeflective zones in the Henle fiber layer of eyes with high-grade foveal hypoplasia

Background Foveal hypoplasia is characterized by the persistance of inner retinal layers at the macular center. We evaluated using spectral-domain optical coherence tomography (SD-OCT) morphological parameters of the macular center of eyes with foveal hypoplasia and describe the presence of hyporeflective zones in the Henle fiber layer (HFL) of eyes with high-grade foveal hypoplasia. Methods Eyes with foveal hypoplasia were classified into two groups: high-grade foveal hypoplasia with thick inner retinal layers at the macular center (thickness above 100 μm; 16 eyes of 9 subjects) and low-grade foveal hypoplasia with thinner inner retinal layers at the macular center (thickness below 100 μm; 25 eyes of 13 subjects). As comparison, SD-OCT images of normal control eyes (n = 75) were investigated. Results Eyes with foveal hypoplasia displayed shorter central photoreceptor outer segments (POS), a thinner central myoid zone, and a thicker central HFL compared to control eyes. Eyes with high-grade foveal hypoplasia also displayed a thinner central outer nuclear layer (ONL) compared to eyes with low-grade foveal hypoplasia and control eyes. There was a negative correlation between the thicknesses of the central ONL and HFL in eyes with foveal hypoplasia; however, the total thickness of both ONL and HFL was similar in all eye populations investigated. Visual acuity of subjects with foveal hypoplasia was negatively correlated to the thickness of the central inner retinal layers and positively correlated to the length of central POS. In contrast to central POS, the length of paracentral POS (0.5 and 1.0 mm nasal from the macular center) was not different between the three eye populations investigated. The paracentral ONL was thickest in eyes with high-grade foveal hypoplasia and thinnest in control eyes. Hyporeflective zones in the HFL were observed on SD-OCT images of eyes with high-grade foveal hypoplasia, but not of eyes with low-grade foveal hypoplasia and control eyes. OCT angiography images recorded at the level of the HFL of eyes with high-grade foveal hypoplasia showed concentric rings of different reflectivity around the macular center; such rings were not observed on images of eyes with low-grade foveal hypoplasia and control eyes. Conclusions It is suggested that the hyporeflective zones in the HFL of eyes with high-grade foveal hypoplasia represent cystoid spaces which are surrounded by Henle fiber bundles. Cystoid spaces are likely formed because there are fewer Henle fibers and a thinner central ONL despite an unchanged thickness of both ONL and HFL. Cystoid spaces may cause the concentric rings of different reflectivity around the macular center in the HFL of eyes with high-grade foveal hypoplasia.
Distracted driving: so what's the big picture?

The knowledge source for safe driving In the past five years distracted driving has garnered growing media attention and rapidly emerged as one of the most high-profile, talked-about issues in road safety today. In fact, Webster’s Dictionary named “distracted driving” as its word of the year in 2009 (Webster’s 2009). Governments, industry, safety advocates, researchers and the public have all weighed in on the issue and what needs to be done to address it. This has resulted in an unprecedented level of national and global commitment, legislation, and policy – all designed with the intention of making roads safer. Education and enforcement activities, however, have been much less pronounced.
next The effect of cryopreservation on the genome of gametes and embryos: Principles of embryos by genome of embryo

Preimplantation genetic testing (PGT) encompasses methods that allow embryos to be tested 55 for severe inherited conditions or for chromosome abnormalities, relevant to embryo health 56 and viability. In order to obtain embryonic genetic material for analysis, a biopsy is required, involving the removal of one or more cells. This invasive procedure greatly increases the costs of PGT and there have been concerns that embryo viability could be compromised in some cases. The recent discovery of DNA within the blastocoele fluid (BF) of blastocysts, and in spent embryo culture media (SCM), has led to interest in the development of non-invasive 61 methods of PGT (NI-PGT). This review evaluates the current scientific evidence regarding non-invasive genetic assessment of preimplantation embryos. The success of different PGT methodologies in collecting and analyzing extra-embryonic DNA is evaluated, and consideration is given to the potential biological and technical hindrances to obtaining a reliable clinical diagnosis.
A systematic review of research into the management of manufacturing capabilities

Abstract Our study aims to explore the past and present knowledge related to the management of manufacturing capabilities and to assess the extent to which our knowledge of this field has developed. It places specific emphasis on the philosophical foundations of the field, while also providing a set of directions for future research. A systematic review is applied, covering 104 articles. The authors unfold a strong dominance of the positivist paradigm and call for a more balanced and informed approach in philosophical and, more specifically, methodological selection by scholars. In terms of the research content, a strong bias exists towards measuring the impact that certain manufacturing capabilities and various configurations of these may have on key performance indicators, such as cost. Our review warns on the dangers of following a dominant paradigmatic stance and on the limitations of researching a limited area of the complex and dynamic manufacturing capabilities arena.
Unique Metabolic Profiles in South Asian Women Characterizes Gestational Diabetes in Low and High-Risk Women

Background: Gestational Diabetes Mellitus (GDM) is the most common pregnancy complication to occur worldwide, however prevalence varies substantially between ethnicities with South Asians experiencing up to 3-times the risk of the disease compared to white Europeans (WEs). Factors driving this discrepancy in prevalence and the pathogenesis of GDM are unclear, although the metabolome is of great importance due to the metabolic dysregulation characterised GDM. Objective: To characterise and distinguish the metabolic profiles of GDM in two distinct ethnic populations at < 28 weeks gestation. Design: 146 fasting serum metabolite values, quantified by nuclear magnetic resonance, from 2668 pregnant WE and 2671 pregnant Pakistani (PK) women from the Born in Bradford (BIB) cohort, were analysed using partial least squares discriminatory analyses (PLSDA). The presence of a linear relationships between metabolite values and post-oral glucose tolerance test measures of dysglycemia (fasting glucose and 2- hour post glucose) were also examined. Results: Seven metabolites were associated with GDM status in both ethnicities, while 6 additional metabolites associated with GDM only in WE women. Unique metabolic profiles were observed in healthy weight women who later developed GDM, with distinct metabolite patterns identified by ethnicity and BMI status. Of the 146 metabolite values analysed in relation to dysglycemia, quantities of lactate, histidine, apolipoprotein A1, HDL cholesterol, HDL2 cholesterol, and DHA, as well as the diameter of very low density lipoprotein particles (nm) were associated with dysglycemia in WE women; while in PK women albumin alone associated with dysglycemia. Conclusion: This is the first study to show that the metabolic risk profile for GDM differs between ethnicities and highlights a need for ethnically appropriate GDM prevention strategies.
Association between Endocrine Disorders and Severe COVID-19 Disease in Pediatric Patients

Introduction: Though severe illness due to COVID-19 is uncommon in children, there is an urgent need to better determine the risk factors for disease severity in youth. This study aims to determine the impact a preexisting endocrine diagnosis has on severity of COVID-19 presentation in youth. Methods: The cross-sectional chart review study included all patients less than 25 years old with a positive SARS-CoV-2 PCR at St. Louis Children’s Hospital between March 2020 and February 2021. Electronic medical record data for analysis included patient demographics, BMI percentile, inpatient hospitalization or admission to the pediatric intensive care unit (PICU), and the presence of a preexisting endocrine diagnosis such as diabetes mellitus (type 1 and type 2), adrenal insufficiency, and hypothyroidism. Two outcome measures were analyzed in multivariate analysis: inpatient admission and PICU admission. Adjusted odds ratios with a 95% CI were calculated using binary logistic regression, along with p values after Wald χ2 analysis. Results: 390 patients were included in the study. Mean age was 123.1 (±82.2) months old. 50.3% of patients were hospitalized, and 12.1% of patients were admitted to intensive care. Preexisting diagnoses of diabetes mellitus, obesity, and hypothyroidism were associated with an increased risk of hospital and ICU admission, independent of socioeconomic status. Discussion/Conclusion: This study provides evidence that unvaccinated youth with a preexisting diagnosis of obesity, hypothyroidism, or diabetes mellitus infected with COVID-19 are more likely to have a more severe clinical presentation requiring inpatient hospital admission and/or intensive care.
Differences in Power Distribution in the Subsystems of the Human – Anti-Vibration Glove – Tool System

The article continues the analysis presented in the article „Power distribution in anti-vibration gloves” [6], which described the approach adopted to construct an energy model of the Human – Glove – Tool system (H – G – T). The outcome of the analysis was the power distribution calculated only for the anti-vibration glove. This article continues the energy analysis for another subsystem of the H – G – T system – the human physical model. The energy method was also used to calculate the power distribution in its dynamic structure in order to account for interactions between the elements of the H – G – T system. The results obtained in the study indicate that the power distribution in the human physical model and in the glove model is completely different.
Evaluation of P57, P53 and Ki67 Expression in Meningiomas

Objective We conducted this study with the aim of predicting the biological behavior of meningiomas, and determining the benefits of associating histological subtype and grade with the expression of proliferative markers and tumor suppressor proteins. Methods The study included 29 patients with primary intracranial and intraspinal meningioma diagnosed in the pathology laboratory of Konya City Hospital between January 2014 and December 2020. Clinicopathological characteristics of the patients including parameters such as age and gender were obtained from the hospital records. Histopathological findings were obtained by re-evaluating the preparations stained with Hematoxylin-Eosin, which were extracted from the archive, and by evaluating new sections obtained from paraffin blocks of patients stained with Ki67, p53, and p57 immunohistochemical stains. Results A moderate correlation was found between tumor size and Ki67 proliferation index (PI) (p=0.003, r=0.530). There was no significant difference between grade I and grade II tumors in terms of p53 (p=0.184) and p57 (p=0.487) expressions. There were higher levels of Ki67 PI in grade II tumors. The histological subtypes of the tumor had no significant difference with Ki67 PI (p=0.018), p53 (p=0.662), and p57 (p=0.368) expressions. Conclusion In order to obtain more definitive results, there is a need for studies, which are conducted with a greater number of patients and in multiple centers, and in which a long prospective follow-up is planned. The combination of histological, surgical, and imaging markers could make a more sensitive tool for predicting recurrence, and this could also be tested in future studies.
Method Comparison of β-Hydroxybutyrate Using a Point-of-Care Device and Dry Chemistry Analyzer in Three Sea Turtle Species

Abstract: The ketone β-hydroxybutyrate (BHB) serves as an energy source when bodily energy stores are low. Concentrations of this blood analyte are often determined by spectrophotometric quantitative assays with a dry chemistry analyzer; however, rapid assessment with point-of-care devices have the potential to improve assessment of animals in the field or in clinical settings. We measured BHB concentrations in whole blood samples from 54 leatherback (Dermochelys coriacea), 27 loggerhead (Caretta caretta), and 14 green (Chelonia mydas) sea turtles in Florida, US with a point-of-care device and validated its use with corresponding plasma samples and dry chemistry analyzer as the gold standard. Concentrations of BHB highly correlated between the two methods for all three species, with loggerheads showing the best agreement and lowest bias. Therefore, the point-of-care device used for this study (Lucidplus β-ketone monitoring system) is probably appropriate for sea turtle BHB measurements.