Miracle-dz/UniFAR-FTUs huggingface dataset:
CNS tumours of childhood/adolescence : outcomes related to disability and identity in adult survivors

Central nervous system (CNS) tumour survivors are at increased risk for adverse health and functional late effects. Results from previous studies from the Swedish LIFE project, of which this licentiate thesis is a part, indicate needs of expanded clinical surveillance, and long-term follow-up in order to reduce late effects and protect quality of survival. The focus of the licentiate thesis is on psychological consequences of illnessand treatment-related late effects in adult survivors of childhood CNS tumours. Particularly, the studies address outcomes associated with identity and self-perception. These factors are usually considered as vital components of mental health and psychological well-being. The aim combined of Study I and II of the licentiate thesis was to examine the long-term impact of childhood CNS tumours and their treatment on self-perception of adult survivors. Study I investigated the extent to which healthand functional status of survivors predicted outcomes in self-confidence related to body image and physical ability, as they appeared in adult age. In Study II survivors and general population individuals were compared as regards self-perception in six domains: body, sports/athletics, peers, work, and family, and as to a global self-esteem index. Data in Study I and Study II covered between 526 to 528 survivors from the entire national cohort of Swedish survivors diagnosed between 1982 and 2001 with a primary CNS tumour. Comparison data in Study II were collected from 995 randomly selected stratified general population individuals. The outcomes were based on quantitative self-report data, including the multidimensional SelfEsteem Questionnaire (SEQ-42) and, in Study I also Health Utilities IndexTM Mark2/3 (HUI2/3), which provides patients’ self-reported outcomes regarding health and functional status. Findings from Study I indicated that self-confidence related to body image and physical ability was negatively affected by health, functional status, and disability in adult survivors. Findings from Study II showed that self-perception of CNS tumour survivors were poorer in all domains (except family) and in the global self-esteem summary measure, compared with the general population. The long-term CNS tumour survivors constitute a high-risk group regarding functional and psychological late effects. The poorer self-perception outcomes of survivors can be interpreted as a likely indirect effect of the cancer diagnosis and treatment. Self-perception and self-esteem are significant elements of mental health and quality of survival. The findings show the importance of paying attention to both medical and psychological care and follow-up needs in early and post-treatment surveillance of CNS tumour survivors.
Dietary compounds and traditional Chinese medicine ameliorate type 2 diabetes by modulating gut microbiota

Abstract Diabetes mellitus (DM) and its complications are major public health concerns which strongly influence the quality of humans’ life. Modification of gut microbiota has been widely used for the management of diabetes. In this review, the relationship between diabetes and gut microbiota, as well as the effects of different dietary components and traditional Chinese medicine (TCM) on gut microflora are summarized. Dietary compounds and TCM possessing bioactive components (fiber and phytochemicals) first change the composition of gut microbiota (inhibiting pathogens and promoting the beneficial bacteria growth) and then influence the production of their metabolites, which would further modify the intestinal environment through inhibiting the production of detrimental compounds (such as lipopolysaccharide, hydrogen sulfide, indol, etc.). Importantly, metabolites (short chain fatty acids and other bioactive components) fermented/degraded by gut microbiota can target multiple pathways in intestine, liver, pancreas, etc., resulting in the improvement of gut health, glycemic control, lipids profile, insulin resistance and inflammation. Furthermore, understanding the interaction between different dietary components and gut microbiota, as well as underlying mechanisms would help design different diet formula for the management of diabetes. Further researches could focus on the combination of different dietary components for preventing and treating diabetes, based on the principle of “multiple components against multiple targets” from the perspective of gut microbiota.
Vegan Nutrition for Mothers and Children: Practical Tools for Healthcare Providers

As the number of subjects choosing vegan diets increases, healthcare providers must be prepared to give the best advice to vegan patients during all stages of life. A completely plant-based diet is suitable during pregnancy, lactation, infancy, and childhood, provided that it is well-planned. Balanced vegan diets meet energy requirements on a wide variety of plant foods and pay attention to some nutrients that may be critical, such as protein, fiber, omega-3 fatty acids, iron, zinc, iodine, calcium, vitamin D, and vitamin B12. This paper contains recommendations made by a panel of experts from the Scientific Society for Vegetarian Nutrition (SSNV) after examining the available literature concerning vegan diets during pregnancy, breastfeeding, infancy, and childhood. All healthcare professionals should follow an approach based on the available evidence in regard to the issue of vegan diets, as failing to do so may compromise the nutritional status of vegan patients in these delicate periods of life.
Aortic stiffness in families with inherited non-syndromic thoracic aortic disease

Abstract Background. In families with an inherited form of non-syndromic thoracic aortic disease (TAAD), aortic diameter alone is not a reliable marker for disease occurrence or progression. To identify other parameters of aortic function, we studied aortic stiffness in families with TAAD. We also compared diameter measurements obtained by transthoracic echocardiography (TTE) and magnetic resonance imaging (MRI). Methods. Seven families, including 116 individuals, with non-syndromic TAAD, were studied. The aortic diameter was measured by TTE and MRI. Aortic stiffness was assessed as local distensibility in the ascending aorta and as regional and global pulse wave velocity (PWV). Individuals with a dilated thoracic aorta (n = 21) were compared with those without aortic dilatation (n = 95). Results. Ascending aortic diameter measured by TTE strongly correlated with the diameter measured by MRI (r2 = 0.93). The individuals with dilated aortas were older than those without dilatation (49 vs 37 years old). Ascending aortic diameter increased and distensibility decreased with increasing age; while, PWV increased with age and diameter. Some young subjects without aortic dilatation showed increased aortic stiffness. Individuals with a dilated thoracic aorta had significantly higher PWV and lower distensibility, measured by MRI than individuals without dilatation. Conclusions. Diameters measured with TTE agree with those measured by MRI. Aortic stiffness might be a complementary marker for aortic disease and progression when used with aortic diameter, especially in young individuals.
Monkeys (Sapajus apella and Macaca tonkeana) and great apes (Gorilla gorilla, Pongo abelii, Pan paniscus, and Pan troglodytes) play for the highest bid.

Many studies investigate the decisions made by animals by focusing on their attitudes toward risk, that is, risk-seeking, risk neutrality, or risk aversion. However, little attention has been paid to the extent to which individuals understand the different odds of outcomes. In a previous gambling task involving 18 different lotteries (Pelé, Broihanne, Thierry, Call, & Dufour, 2014), nonhuman primates used probabilities of gains and losses to make their decision. Although the use of complex mathematical calculation for decision-making seemed unlikely, we applied a gradual decrease in the chances to win throughout the experiment. This probably facilitated the extraction of information about odds. Here, we investigated whether individuals would still make efficient decisions if this facilitating factor was removed. To do so, we randomized the order of presentation of the 18 lotteries. Individuals from 4 ape and 2 monkey species were tested. Only capuchin monkeys differed from others, gambling even when there was nothing to win. Randomizing the lottery presentation order leads all species to predominantly use a maximax heuristic. Individuals gamble as soon as there is at least one chance to win more than they already possess, whatever the risk. Most species also gambled more as the frequency of larger rewards increased. These results suggest optimistic behavior. The maximax heuristic is sometimes observed in human managerial and financial decision-making, where risk is ignored for potential gains, however low they may be. This suggests a shared and strong propensity in primates to rely on heuristics whenever complexity in evaluation of outcome odds arises. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
Enhanced population coding for rewarded choices in the medial frontal cortex of the mouse

Instrumental behavior is characterized by the selection of actions based on the degree to which they lead to a desired outcome. However, we lack a detailed understanding of how rewarded actions are reinforced and preferentially implemented. In rodents, the medial frontal cortex is hypothesized to play an important role in this process, based in part on its capacity to encode chosen actions and their outcomes. We therefore asked how neural representations of choice and outcome might interact to facilitate instrumental behavior. To investigate this question, we imaged neural ensemble activity in layer 2/3 of the secondary motor region (M2) while mice engaged in a two-choice auditory discrimination task with probabilistic outcomes. Correct choices could result in one of three reward amounts (single-, double-, or omitted-reward), which allowed us to measure neural and behavioral effects of reward magnitude, as well as its categorical presence or absence. Single-unit and population decoding analyses revealed a consistent influence of outcome on choice signals in M2. Specifically, rewarded choices were more robustly encoded relative to unrewarded choices, with little dependence on the exact magnitude of reinforcement. Our results provide insight into the integration of past choices and outcomes in the rodent brain during instrumental behavior.
Evaluating the safety profile of focused ultrasound and microbubble-mediated treatments to increase blood-brain barrier permeability

ABSTRACT Introduction: Treatment of several diseases of the brain are complicated by the presence of the skull and the blood-brain barrier (BBB). Focused ultrasound (FUS) and microbubble (MB)-mediated BBB treatment is a minimally invasive method to transiently increase the permeability of blood vessels in targeted brain areas. It can be used as a general delivery system to increase the concentration of therapeutic agents in the brain parenchyma. Areas covered: Over the past two decades, the safety of using FUS+MBs to deliver agents across the BBB has been interrogated through various methods of imaging, histology, biochemical assays, and behavior analyses. Here we provide an overview of the factors that affect the safety profile of these treatments, describe methods by which FUS+MB treatments are controlled, and discuss data that have informed the assessment of treatment risks. Expert opinion: There remains a need to assess the risks associated with clinically relevant treatment strategies, specifically repeated FUS+MB treatments, with and without therapeutic agent delivery. Additionally, efforts to develop metrics by which FUS+MB treatments can be easily compared across studies would facilitate a more rapid consensus on the risks associated with this intervention. Trial registration: ClinicalTrials.gov identifier: NCT03321487. Trial registration: ClinicalTrials.gov identifier: NCT03119961. Trial registration: ClinicalTrials.gov identifier: NCT02343991. Trial registration: ClinicalTrials.gov identifier: NCT03608553. Trial registration: ClinicalTrials.gov identifier: NCT03626896. Trial registration: ClinicalTrials.gov identifier: NCT03616860. Trial registration: ClinicalTrials.gov identifier: NCT03671889. Trial registration: ClinicalTrials.gov identifier: NCT03712293.
On-the-road driving performance the morning after bedtime administration of lemborexant in healthy adult and elderly volunteers

Abstract Study Objectives To assess potential effects of lemborexant on next-morning driving performance in adult and elderly healthy volunteers. Methods Randomized, double-blind, double-dummy, placebo and active-controlled, four period incomplete crossover study in 48 healthy volunteers (22 females), 23–78 years old. Participants were treated at bedtime for eight consecutive nights with two of three dose levels of lemborexant (2.5, 5, or 10 mg), zopiclone 7.5 mg (on the first and last night with placebo on intervening nights), or placebo. Driving performance was assessed in the morning on days 2 and 9 using a standardized highway driving test in normal traffic, measuring standard deviation of lateral position (SDLP). Drug–placebo differences in SDLP >2.4 cm were considered to reflect clinically meaningful driving impairment. Results Mean drug–placebo differences in SDLP following lemborexant 2.5, 5, and 10 mg on days 2 and 9 were 0.74 cm or less. The upper bound of the 95% confidence intervals (CIs) for lemborexant treatment groups were all below 2.4 cm and the 95% CIs included zero, indicating that the effects were neither clinically meaningful nor statistically significant. Symmetry analysis further supported the lack of clinically meaningful impairment with lemborexant. Conclusions When assessed starting ~9 h after lemborexant administration at bedtime the previous night, there was no statistically significant or clinically meaningful effect on driving performance in healthy adults and elderly, as assessed by either mean differences in SDLP relative to placebo or symmetry analysis. In this study, lemborexant at doses up to 10 mg was well-tolerated. Clinical Trial Registration clinicaltrials.gov, NCT02583451. https://clinicaltrials.gov/ct2/show/NCT02583451.
Association of early disease progression and very poor survival in the GALLIUM study in follicular lymphoma: benefit of obinutuzumab in reducing the rate of early progression

We evaluated early disease progression and its impact on overall survival (OS) in previously untreated follicular lymphoma patients in GALLIUM (clinicaltrials.gov identifier: 01332968), and investigated the effect on early disease progression of the two randomization arms: obinutuzumab-based versus rituximab-based immunochemotherapy. Cause-specific Cox regression was used to estimate the effect of treatment on the risk of disease progression or death due to disease progression within 24 months of randomization and to analyze OS in patients with or without disease progression after 24 months. Mortality in both groups was analyzed 6, 12, and 18 months post randomization (median follow up, 41 months). Fewer early disease progression events occurred in obinutuzumab (57 out of 601) versus rituximab (98 out of 601) immunochemotherapy patients, with an average risk reduction of 46.0% (95%CI: 25.0-61.1%; cumulative incidence rate 10.1% vs. 17.4%). At a median post-progression follow up of 22.6 months, risk of mortality increased markedly following a progression event [HR of time-varying progression status, 25.5 (95%CI: 16.2-40.3)]. Mortality risk was higher the earlier patients progressed within the first 24 months. Age-adjusted HR for OS after 24 months in surviving patients with disease progression versus those without was 12.2 (95%CI: 5.6-26.5). Post-progression survival was similar by treatment arm. In conclusion, obinutuzumab plus chemotherapy was associated with a marked reduction in the rate of early disease progression events relative to rituximab plus chemotherapy. Early disease progression in patients with follicular lymphoma was associated with poor prognosis, with mortality risk higher after earlier progression. Survival post progression did not seem to be influenced by treatment arm.
Caracterización de los aspectos metodológicos empleados en la enseñanza de la materia de Educación Física en los centros públicos de secundaria con sección bilingüe en inglés de Castilla y León

espanolLa presente tesis doctoral tiene como objetivo caracterizar la metodologia empleada en la ensenanza integrada de Educacion Fisica (EF) e ingles en la Comunidad de Castilla y Leon (CyL). En el estudio participan la totalidad de centros publicos de Secundaria de CyL donde la EF es una de las materias que se imparten en ingles dentro de su seccion bilingue, es decir 26 centros educativos. Se emplea una metodologia mixta que estructura la investigacion en dos fases: una primera cuantitativa y una segunda cualitativa. Entre los resultados obtenidos se encuentra que los profesores de EF tienen una percepcion positiva sobre las posibilidades que la materia puede ofrecer en el aprendizaje del ingles. Se concluye que las destrezas de comprension y expresion oral en ingles son las mas utilizadas en EF. Finalmente, se ratifica que la organizacion de grupos en modalidades bilingue y no bilingue coincide con la obtencion de mejores y peores resultados academicos respectivamente EnglishThis dissertation aims to characterize the methodology used in PE teaching in the community of Castilla y Leon. The study is carried out with all public secondary schools in Castilla y Leon where PE was one of the subjects taught in English, i.e. 26 schools are participating in the study. This study uses a mixed methodology beginning with quantitative analyses and followed with qualitative analyses. Evidences show that teachers have a positive perception about possibilities of PE in English learning. It is concluded that comprehension and oral expression skills are more used than comprehension and written expression in PE. The organization of groups in not bilingual and bilingual coincides with best and worst academic results respectively
Gastric cancer trends in Estonia 1995–2014 by age, subsite, morphology and stage

Abstract Background: Gastric cancer (GC) is among the most common cancers and one of the leading causes of cancer deaths globally. In general, the incidence of GC has declined and survival improved in Europe. Nevertheless, previous analysis has shown that survival of GC patients in Estonia is still significantly lower compared to some European countries. Therefore, to improve patient outcomes, better overview of GC epidemiology is needed. The aim of this study was to describe the incidence and survival of GC in Estonia 1995–2014 in relation to age, subsite, morphology, and the extent of disease. Material and methods: We used data from the population-based Estonian Cancer Registry on all incident cases of GC diagnosed in 1995–2014. Incidence rates and relative survival were calculated. Joinpoint regression modeling was used to estimate annual percentage change for incidence trends. Data were analyzed by age, sex, subsite, morphology, and the extent of disease. Changes between 1995–1999 and 2010–2014 were assessed. Results: The overall incidence of GC in Estonia decreased in 1995–2014. The age-standardized (world) incidence declined significantly for both sexes, for patients below 70 years of age, adenocarcinomas, NOS and other morphologies, non-cardia and unspecified cases, and for all known stages. Approximately 40% of GC cases were diagnosed with distant metastasis. Overall age-standardized 5-year relative survival of GC patients increased from 20% to 28%. Survival improved the most in age group 50–69 years. A large survival gain was also seen for localized (from 55% to 70%) and locally/regionally spread disease (from 23% to 37%). Conclusions: In Estonia, the incidence of GC has declined and relative survival increased. However, special emphasis needs to be put on improving survival among men, elderly and in patients with metastatic disease.
Iterated function systems that contract on average

Consider an iterated function system (IFS) that does not necessarily contract uniformly, but instead contracts on average after a finite number of iterations. Under some technical assumptions, previous work by Barnsley, Demko, Elton and Geronimo has shown that such an IFS has a unique invariant probability measure, whilst many (such as Peign�, Hennion and Herv�, Guivarc'h and le Page, Santos and Walkden) have shown that (for different function spaces) the transfer operator associated with the IFS is quasi-compact. A result due to Keller and Liverani allows one to deduce whether the transfer operator remains quasi-compact under suitable, small perturbations.The first part of this thesis proves a large deviations result for IFSs that contract on average using skew product transfer operators, a technique used by Broise to prove a similar result for dynamical systems.The remaining chapters introduce a notion of `coupled IFSs', an analogue of the traditional coupled map lattices where the base, unperturbed behaviour is determined by an underlying dynamical system. We use transfer operators and Keller and Liverani's theorem to prove that quasi-compactness of the transfer operator is preserved for `product IFSs' under small perturbations and for coupled IFSs. This allows us to prove a central limit theorem with a rate of convergence for the coupled IFS.
Transcriptional Programs and Regeneration Enhancers Underlying Heart Regeneration

The heart plays the vital role of propelling blood to the entire body, which is essential to life. While maintaining heart function is critical, adult mammalian hearts poorly regenerate damaged cardiac tissue upon injury and form scar tissue instead. Unlike adult mammals, adult zebrafish can regenerate injured hearts with no sign of scarring, making zebrafish an ideal model system with which to study the molecular mechanisms underlying heart regeneration. Investigation of heart regeneration in zebrafish together with mice has revealed multiple cardiac regeneration genes that are induced by injury to facilitate heart regeneration. Altered expression of these regeneration genes in adult mammals is one of the main causes of heart regeneration failure. Previous studies have focused on the roles of these regeneration genes, yet the regulatory mechanisms by which the expression of cardiac regeneration genes is precisely controlled are largely unknown. In this review, we will discuss the importance of differential gene expression for heart regeneration, the recent discovery of cardiac injury or regeneration enhancers, and their impact on heart regeneration.