Miracle-dz/UniFAR-FTUs huggingface dataset:
Prediction of Drug Exposure in Critically Ill Encephalopathic Neonates Treated With Therapeutic Hypothermia Based on a Pooled Population Pharmacokinetic Analysis of Seven Drugs and Five Metabolites

Drug dosing in encephalopathic neonates treated with therapeutic hypothermia is challenging; exposure is dependent on body size and maturation but can also be influenced by factors related to disease and treatment. A better understanding of underlying pharmacokinetic principles is essential to guide drug dosing in this population. The prospective multicenter cohort study PharmaCool was designed to investigate the pharmacokinetics of commonly used drugs in neonatal encephalopathy. In the present study, all data obtained in the PharmaCool study were combined to study the structural system specific effects of body size, maturation, recovery of organ function, and temperature on drug clearance using nonlinear mixed effects modeling. Data collected during the first 5 days of life from 192 neonates treated with therapeutic hypothermia were included. An integrated population pharmacokinetic model of seven drugs (morphine, midazolam, lidocaine, phenobarbital, amoxicillin, gentamicin, and benzylpenicillin) and five metabolites (morphine‐3‐glucuronide, morphine‐6‐glucuronide, 1‐hydroxymidazolam, hydroxymidazolam glucuronide, and monoethylglycylxylidide) was successfully developed based on previously developed models for the individual drugs. For all compounds, body size was related to clearance using allometric relationships and maturation was described with gestational age in a fixed sigmoidal Hill equation. Organ recovery after birth was incorporated using postnatal age. Clearance increased by 1.23%/hours of life (95% confidence interval (CI) 1.03–1.43) and by 0.54%/hours of life (95% CI 0.371–0.750) for high and intermediate clearance compounds, respectively. Therapeutic hypothermia reduced clearance of intermediate clearance compounds only, by 6.83%/°C (95% CI 5.16%/°C–8.34%/°C). This integrated model can be used to facilitate drug dosing and future pharmacokinetic studies in this population.
Factors Responsible for Decreasing Sturdiness of the Lower Part in Lodging of Rice (Oryza sativa L.)

Abstract Here, we propose new improvement targets capable of decreasing loss of the sturdiness of the lower part in the rice plant (Oryza sativa L.), thereby improving lodging resistance. In nine rice cultivars with various plant lengths, we analyzed the factors responsible for sturdiness of the lower part and, thus, for resistance to lodging. The ratio of lodging resistance to sturdiness of the lower part (RLS) was calculated. The difference in pushing resistance between the lower part and the whole plant varied among cultivars. Among the morphological traits, plant length and the weight of the upper part of plant were not correlated with RLS, but the difference between plant length and length from the ground to the ear (DPE), as well as the weight of the lower stem, were positively correlated with RLS. DPE and the weight of the lower stem were not significantly correlated with ear weight. These results suggest that improvements in DPE and in the weight of the lower stem could be primary targets for improving RLS, thus increasing lodging resistance, without affecting yield.
The ENIGMA‐Epilepsy working group: Mapping disease from large data sets

Epilepsy is a common and serious neurological disorder, with many different constituent conditions characterized by their electro clinical, imaging, and genetic features. MRI has been fundamental in advancing our understanding of brain processes in the epilepsies. Smaller‐scale studies have identified many interesting imaging phenomena, with implications both for understanding pathophysiology and improving clinical care. Through the infrastructure and concepts now well‐established by the ENIGMA Consortium, ENIGMA‐Epilepsy was established to strengthen epilepsy neuroscience by greatly increasing sample sizes, leveraging ideas and methods established in other ENIGMA projects, and generating a body of collaborating scientists and clinicians to drive forward robust research. Here we review published, current, and future projects, that include structural MRI, diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI), and that employ advanced methods including structural covariance, and event‐based modeling analysis. We explore age of onset‐ and duration‐related features, as well as phenomena‐specific work focusing on particular epilepsy syndromes or phenotypes, multimodal analyses focused on understanding the biology of disease progression, and deep learning approaches. We encourage groups who may be interested in participating to make contact to further grow and develop ENIGMA‐Epilepsy.
CULTURAL CHARACTERS AS A GUIDE TO THE TAXONOMY AND PHYLOGENY OF THE POLYPORACEAE

A study of the cultures of 252 species of the Polyporaceae provides evidence that the family is composed of two major groups: a primitive group consisting of species that produce no extracellular oxidase and, if heterothallic, show the bipolar type of interfertility; and a more advanced group made up of species that produce extracellular oxidase and, if heterothallic, show the tetrapolar type of interfertility in species whose hyphae are regularly nodose-septate or simple-septate, and the bipolar type of interfertility in species with hyphae simple-septate in the advancing zone and nodose-septate elsewhere. Within these major groups, groups of species, alike in hyphal and basidiospore characters, appear to be related and may represent taxa of generic or higher rank. An annotated key is presented, in which these groups of species are segregated in order of the increasing complexity of their hyphal components. The evaluation of the groups as taxonomic entities and of their arrangement in the key as a system.
Group Selection by Selective Emigration: The Effects of Migration and Kin Structure

Group selection may operate through selective emigration, as Sewall Wright envisioned, as well as through selective extinction. The discrete-generation model of selective emigration developed here yields the following conclusions. 1. The fitness benefit of altruism, bp̄, depends on the frequency of altruists. Consequently, selective emigration is more likely than kin selection or selective extinction to lead to polymorphic equilibria. 2. In contrast to selective extinction, selective emigration is facilitated (weakly) by high levels of mobility between groups. 3. Like selective extinction, selective emigration is facilitated (weakly) by kinstructured migration and by isolation by distance, particularly where the dimensionality of the migration pattern is low. 4. The only factor with any great effect on the strength of selective emigration is the size of the social group within which altruistic interactions occur. 5. Wright emphasized that selective emigration requires a delicate balance between the migration rate and population size, but this balance appears to be less delicate than Wright thought. For any conceivable migration pattern, migration rate, number of groups, and level of kin structure, an allele for altruism is favored only if its benefit-to-cost ratio exceeds a number of the same order as group size.
Natural Cyanobacterial Polymer-Based Coating as a Preventive Strategy to Avoid Catheter-Associated Urinary Tract Infections

Catheter-associated urinary tract infections (CAUTIs) represent about 40% of all healthcare-associated infections. Herein, the authors report the further development of an infection preventive anti-adhesive coating (CyanoCoating) meant for urinary catheters, and based on a natural polymer released by a marine cyanobacterium. CyanoCoating performance was assessed against relevant CAUTI etiological agents, namely Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, methicillin resistant Staphylococcus aureus (MRSA), and Candida albicans in the presence of culture medium or artificial urine, and under biofilm promoting settings. CyanoCoating displayed a broad anti-adhesive efficiency against all the uropathogens tested (68–95%), even in the presence of artificial urine (58–100%) with exception of P. mirabilis in the latter condition. Under biofilm-promoting settings, CyanoCoating reduced biofilm formation by E. coli, P. mirabilis, and C. albicans (30–60%). In addition, CyanoCoating prevented large crystals encrustation, and its sterilization with ethylene oxide did not impact the coating stability. Therefore, CyanoCoating constitutes a step forward for the implementation of antibiotic-free alternative strategies to fight CAUTIs.
The Relationship Between Health-Related Quality of Life and Saliva C-Reactive Protein and Diurnal Cortisol Rhythm in Latina Breast Cancer Survivors and Their Informal Caregivers: A Pilot Study

Introduction: To date, no study has explored associations between objective stress-related biomarkers (i.e., inflammatory markers, diurnal rhythm of cortisol) and health-related quality of life (HRQOL) in Latina breast cancer survivors and their informal caregivers (i.e., family, friends). Method: This cross-sectional feasibility study assessed saliva C-reactive protein, saliva diurnal cortisol rhythm (cortisol slope), and self-reported HRQOL (psychological, physical, and social domains) in 22 Latina survivor–caregiver dyads. Feasibility was defined as ≥85% samples collected over 2 days (on waking, in afternoon, and in evening). Associations between biomarkers and HRQOL were examined with correlational analyses. Results: Collection of saliva was feasible. Strongest associations were observed between survivor evening cortisol (as well as cortisol slope) and fatigue, a component of physical HRQOL. Discussion: Associations presented may help promote investigations of mechanisms linking stress-related biomarkers and HRQOL in Latina breast cancer survivor–caregiver dyads, which will facilitate development of culturally congruent interventions for this underserved group.
Glandular Trichomes of Artemisia campestris (ssp. Maritima): Ontogeny and Histochemistry of the Secretory Product

The glandular trichomes of Artemisia campestris (ssp. maritima) originate from a single protodermal cell and develop through an anticlinal and several periclinal divisions. These multicellular and biseriate trichomes have a secretory head with three pairs of cells, two stalk cells, and two basal cells. The number of glandular trichomes is established early during leaf differentiation; thus, gland density decreases with leaf development. Oleoresin production begins as soon as the glandular trichomes are fully developed. The main components of the oleoresin are terpenoids (mono- and sesquiterpenes and probably steroids), fatty acids, flavonoids as free aglycones, hydroxycoumarins, and alkaloids. The oleoresin accumulates in the subcuticular space and is released over the leaf blade by rupture of the cuticle.
Adherent-Invasive E. coli: Update on the Lifestyle of a Troublemaker in Crohn’s Disease

Besides genetic polymorphisms and environmental factors, the intestinal microbiota is an important factor in the etiology of Crohn’s disease (CD). Among microbiota alterations, a particular pathotype of Escherichia coli involved in the pathogenesis of CD abnormally colonizes the intestinal mucosa of patients: the adherent-invasive Escherichia coli (AIEC) pathobiont bacteria, which have the abilities to adhere to and to invade intestinal epithelial cells (IECs), as well as to survive and replicate within macrophages. AIEC have been the subject of many studies in recent years to unveil some genes linked to AIEC virulence and to understand the impact of AIEC infection on the gut and consequently their involvement in CD. In this review, we describe the lifestyle of AIEC bacteria within the intestine, from the interaction with intestinal epithelial and immune cells with an emphasis on environmental and genetic factors favoring their implantation, to their lifestyle in the intestinal lumen. Finally, we discuss AIEC-targeting strategies such as the use of FimH antagonists, bacteriophages, or antibiotics, which could constitute therapeutic options to prevent and limit AIEC colonization in CD patients.
Measurement of Protein Content in Fruit Juices, Wine and Plant Extracts in the Presence of Endogenous Organic Compounds

Abstract Measurement of soluble protein in wines, fruit juices and enzyme extracts by the standard Coomassie blue assay gave results that did not agree with protein content calculated from samples and standards on silver-stained SDS-PAGE gels. A simple one-step change has improved the quantitative measurement of protein The acidic pH of wines and fruit juices, and acidic to neutral pH of vegetable extracts favour hydrogen bonding of some organic compounds to protein. In a modified Coomassie blue assay the samples were made alkaline to reduce hydrogen bonding of protein to phenolics, fats and their breakdown products. Electrostatic binding to the positively charged guanidino group of arginine, the amino acid responsible for the colour change when protein interacts with Coomassie blue dye, was also reduced. On addition of Coomassie blue dye (pH 0.70) there may be competition for binding to protein by organic compounds and dye, rather than a strengthening of the already hydrogen-bound compounds to protein. Protein content measured by the standard Coomassie blue assay and by alkaline treatment of the samples differed significantly. Results from the ‘alkali assay’ agreed quantitatively with protein estimates from silver-stained SDS-PAGE gels.
Respiratory Diseases, Malaria and Leishmaniasis: Temporal and Spatial Association with Fire Occurrences from Knowledge Discovery and Data Mining

The relationship between the fires occurrences and diseases is an essential issue for making public health policy and environment protecting strategy. Thanks to the Internet, today, we have a huge amount of health data and fire occurrence reports at our disposal. The challenge, therefore, is how to deal with 4 Vs (volume, variety, velocity and veracity) associated with these data. To overcome this problem, in this paper, we propose a method that combines techniques based on Data Mining and Knowledge Discovery from Databases (KDD) to discover spatial and temporal association between diseases and the fire occurrences. Here, the case study was addressed to Malaria, Leishmaniasis and respiratory diseases in Brazil. Instead of losing a lot of time verifying the consistency of the database, the proposed method uses Decision Tree, a machine learning-based supervised classification, to perform a fast management and extract only relevant and strategic information, with the knowledge of how reliable the database is. Namely, States, Biomes and period of the year (months) with the highest rate of fires could be identified with great success rates and in few seconds. Then, the K-means, an unsupervised learning algorithms that solves the well-known clustering problem, is employed to identify the groups of cities where the fire occurrences is more expressive. Finally, the steps associated with KDD is perfomed to extract useful information from mined data. In that case, Spearman’s rank correlation coefficient, a nonparametric measure of rank correlation, is computed to infer the statistical dependence between fire occurrences and those diseases. Moreover, maps are also generated to represent the distribution of the mined data. From the results, it was possible to identify that each region showed a susceptible behaviour to some disease as well as some degree of correlation with fire outbreak, mainly in the drought period.
The Thermodynamic Origin of Ecosystems

A general theory of the origin of ecosystems in thermodynamic terms is developed. Regular fluctuations in the availablility of energy give rise to dissipative structures in systems where the boundary constraints preclude the development of the equilibrium state. Dissipative structures are patterns in the energy flow that cease to exist when the energy flow ceases; when in the vicinity of their equilibrium position, they tend to a state of least entropy production. The ecodeme, or group of like individuals interacting equally within the constraints of the niche boundaries, exhibits the characteristics of a dissipative structure. The characteristics of a dissipative structure demand that it actively acquire and conserve energy, and that it exhibit organization. Organization implies the existence of order and a goal or end point; order is represented by uniformity of individuals in the ecodeme, the goal is represented by the state of least entropy production. Within the ecosystem ecodemes interact so that th.
Long-Term Rupture Risk in Patients with Unruptured Intracranial Aneurysms Treated with Endovascular Therapy: A Systematic Review and Meta-Analysis

BACKGROUND: Surveillance imaging of previously unruptured, coiled aneurysms remains routine even though reports of rupture of these aneurysms are extremely rare. PURPOSE: We performed meta-analysis to examine long-term rupture risk over ≥1-year follow-up duration in patients with unruptured intracranial aneurysm who underwent endovascular therapy. DATA SOURCES: Multiple databases were searched for relevant publications between 1995 and 2018. STUDY SELECTION: Studies reporting outcome of long-term rupture risk over ≥1-year follow-up in treated patients with unruptured intracranial aneurysms were included. DATA ANALYSIS: Random effects meta-analysis was used, and results were expressed as long-term rupture rate per 100 patient-year with respective 95% CIs. For ruptured aneurysms during follow-up, data were collected on size and completeness of initial Treatment. DATA SYNTHESIS: Twenty-four studies were identified. Among 4842 patients with a mean follow-up duration of 3.2 years, a total of 12 patients (0.25%) experienced rupture of previous unruptured intracranial aneurysms after endovascular treatment. Nine of these 12 patients harbored aneurysms that were large, incompletely treated, or both. A total of 2 anterior circulation, small, completely coiled aneurysms subsequently ruptured. The long-term rupture rate per 100 patient-year for unruptured intracranial aneurysms treated with endovascular therapy was 0.48 (95% CI, 0.45–0.51). Retreatment was carried out in 236 (4.9%) of these 4842 patients. LIMITATIONS: A limitation of the study is that a lack of systematic nature of follow-up and mean follow-up duration of 3.2 years are not sufficient to make general recommendations about aneurysm followup paradigms. CONCLUSIONS: Given a 5% retreatment rate, postcoil embolization spontaneous rupture of previously unruptured, small- and medium-sized, well-treated aneurysms is exceedingly rare.
Cigarette smoke-induced lung inflammation in COPD mediated via CCR1/JAK/STAT /NF-κB pathway

Inflammation is an important cause of chronic obstructive pulmonary disease (COPD) and its acute exacerbation. However, the critical role of C-C chemokine receptor (CCR)1 in progression of cigarette smoke-induced chronic inflammation remains unclear. We studied CCR1 expression using immunohistochemistry, immunofluorescence, and real-time polymerase chain reaction (RT-PCR) in COPD patients and controls. Cytokine levels in peripheral blood were measured by enzyme-linked immunosorbent assay (ELISA). In vitro, we investigated Janus kinase/signal transducers and activators of transcription (JAK/STAT)/nuclear factor-κB (NF-κB) signaling in cigarette smoke extract-induced or CCR1 deficiency/overexpressed mouse macrophage cell line MH-S by RT-PCR and western blot, and measured the cytokine levels in the supernatant with ELISA. We found that CCR1 expression was upregulated in COPD patients and there was a negative correlation between CCR1 mRNA levels and predicted % forced expiratory volume in 1 min. Inflammatory cytokine levels in the peripheral blood were higher in COPD patients than controls, and these were positively correlated with CCR1 levels. CCR1 was shown to play a critical role in regulating smoke-induced inflammation via JAK/STAT3/NF-κB signaling in vitro. CCR1 may play a critical role in airway inflammation in COPD. Additionally, understanding the molecular mechanism may help develop novel methods for the treatment of COPD.
About Berrigan and Charnov's life-history puzzle

In a recent and stimulating Forum paper, Berrigan and Charnov (1994) address the important life-history point that the slope of the reaction norm for size-to-age at maturity in ectotherms depends on whether changes in growth are due to food or to temperature. If growth is affected by temperature, then both age and size at maturity usually respond in the same way, thus resulting in a positive slope of the reaction norm (Fig. lb). By contrast, if changes are due to food availability, then these traits usually respond in opposite ways, thus resulting in a negative slope of the reaction norm (Fig. la). Berrigan and Charnov (see also Atkinson 1994, Sibly and Atkinson 1994) report enough empirical data to show how widespread this pattern seems to be among ectotherms.
Studies on the Mechanisms of Anti-Inflammatory Activity of Heparin- and Hyaluronan-Containing Multilayer Coatings—Targeting NF-κB Signalling Pathway

The use of implants can be hampered by chronic inflammatory reactions, which may result in failure of the implanted device. To prevent such an outcome, the present study examines the anti-inflammatory properties of surface coatings made of either hyaluronic acid (HA) or heparin (Hep) in combination with chitosan (Chi) prepared as multilayers through the layer-by-layer (LbL) technique. The properties of glycosaminoglycan (GAG)-modified surfaces were characterized in terms of surface topography, thickness and wettability. Results showed a higher thickness and hydrophilicity after multilayer formation compared to poly (ethylene imine) control samples. Moreover, multilayers containing either HA or Hep dampened the inflammatory response visible by reduced adhesion, formation of multinucleated giant cells (MNGCs) and IL-1β release, which was studied using THP-1 derived macrophages. Furthermore, investigations regarding the mechanism of anti-inflammatory activity of GAG were focused on nuclear transcription factor-кB (NF-κB)-related signal transduction. Immunofluorescence staining of the p65 subunit of NF-κB and immunoblotting were performed that showed a significant decrease in NF-κB level in macrophages on GAG-based multilayers. Additionally, the association of FITC-labelled GAG was evaluated by confocal laser scanning microscopy and flow cytometry showing that macrophages were able to associate with and take up HA and Hep. Overall, the Hep-based multilayers demonstrated the most suppressive effect making this system most promising to control macrophage activation after implantation of medical devices. The results provide an insight on the anti-inflammatory effects of GAG not only based on their physicochemical properties, but also related to their mechanism of action toward NF-κB signal transduction.
Immune response of blue mussels (Mytilus edulis) in spawning period following exposure to metals

Mytilus edulis are sensitive to environmental contamination like metals, such as silver (Ag), lead (Pb), cadmium (Cd) and mercury (Hg), which are bioavailable for this species.1-3 It is well documented that these metals can disrupt the immune responses in bivalves.4-6 During spawning, important physiological systems are involved, such as serotonin and dopamine,7-11 which in turn could modulate the immune system.12,13 Indeed, bivalves reduce their metabolic activity after spawning which is reflected by a decrease of the phagocytosis activity.14-18 It is expected that during the period of reduced immune activity (i.e., after spawning) mussels are more vulnerable to contaminations and diseases.14-16,18,19 The aim of this pilot study was to determine if spawning modulates immune responses of Mytilus edulis exposed to metals (Ag, Cd, Hg and Pb).