Miracle-dz/UniFAR-FTUs huggingface dataset:
Challenges for clinical practice and research in family medicine in reducing the risk of chronic diseases. Notes on the EGPRN Spring Conference 2017 in Riga

Abstract Chronic diseases in most cases belong to the category of non-communicable diseases (NCDs), which are the main cause of mortality globally. Cardiovascular diseases, diabetes, chronic obstructive pulmonary disease and cancer are the four NCDs responsible for 82% of NCD deaths. Prevention of NCDs implies health promotion activities that encourage healthy lifestyle and limit the initial onset of chronic diseases. Prevention also includes early detection activities, such as screening at-risk populations, as well as strategies for appropriate management of existing diseases and related complications. Early intervention, reducing morbidity and mortality rates could be an appealing idea for patients, physicians and governmental institutions but could also cause harm. Healthcare is undergoing profound changes, and the role of technology in diagnostics and management of chronic diseases in primary healthcare (PHC) is increasing remarkably. However, studies show that the standards of care for chronic diseases and preventive care are met by less than 50%. We still lack clear standards for patients with multiple chronic diseases. The applicability of a single evidence-based guideline to multimorbid patients is limited and can be problematic. Well-designed PHC studies focusing on the impact of medical interventions on morbidity, mortality and quality of life in the fields of early diagnosis, early treatment and multimorbidity are still needed.
MiR-200c and miR-141 inhibit ZEB1 synergistically and suppress glioma cell growth and migration.

OBJECTIVE This study aimed to investigate the expression of miR-200c and miR-141 in glioma tissues and cell lines and then to study their regulative effect on ZEB1 expression and on glioma cell growth and migration. MATERIALS AND METHODS QRT-PCR analysis was performed to detect miR-200c and miR-141 expression in 10 paired glioma tissues and adjacent normal tissues from patients with glioblastoma multiforme (GBM) and in glioma cell lines. U87 and U251 cells were transfected with miR-200c mimics, miR-141 mimics or ZEB1 siRNA respectively. ZEB1 expression was detected qRT-PCR and Western blot assay. MTT assay, flow cytometry and wound healing assay were performed to examine the tumor suppressive effects of the miR-200c/miR-141-ZEB1 axis on glioma cells. RESULTS Both miR-200c and miR-141 were significantly lower in glioma tissues than in adjacent normal tissues. The glioma cell lines, including U87, U251 and A172 also had significantly decreased miR-200c and miR-141 expression than normal tissues. ZEB1 expression had at least two-fold increase in glioma tissues than in normal tissues. Both miR-200c and miR-141 could significantly induce ZEB1 mRNA degradation and suppress ZEB1 protein expression. ZEB1 siRNA presented similar growth and migration inhibiting and apoptosis inducing effect to miR-200c and miR-141 mimics in U87 cells. CONCLUSIONS MiR-200c and miR-141 are significantly downregulated in glioma tissues and cell lines and can significantly induce ZEB1 mRNA degradation and suppress ZEB1 protein expression in the cells. ZEB1 is a functional downstream target of miR-200c and miR-141 in inhibiting glioma cell growth and migration.
Central fatigue in multiple sclerosis: a review of the literature

Concept: Fatigue is a major concern for patients with multiple sclerosis (MS). A clear definition of MS-related fatigue is a prerequisite for appropriate instruments for fatigue assessment. In turn, accurate assessment of fatigue in MS will enhance exploration of plausible mechanisms underlying this common and distressing symptom. Content/Objectives: To provide an integrative review of the current literature on theoretical models used to study fatigue in MS, instruments used to assess fatigue and other factors that impact fatigue during the various phases of MS. Methods: Data sources: PUBMED, OVID, Ovid Health Star, Ovid MEDINE, CINAHL, Health and Psychosocial Instruments (HaPI), and PsycINFO. Seventeen articles fit the inclusion criteria and were included in the review. Results: Definitions of MS-related fatigue are reviewed. Several studies found a link with neurotransmitter dysfunction, circadian rhythm, and the timing of fatigue. Central fatigue in MS is associated with neurotransmitters disruptions as well as circadian rhythm disorders, but the evidence is not strong. Perceptions of fatigue or fatigability may arise as either a primary or secondary manifestation of disease. Based on findings from the literature review, a theoretical model of fatigue in MS is proposed. Conclusion: Future research on MS-related fatigue may consider a longitudinal design with a carefully selected self-report instrument to advance understanding of the underlying pathological mechanisms.
Cholecalciferol v. ergocalciferol for 25-hydroxyvitamin D (25(OH)D) repletion in chronic kidney disease: a randomised clinical trial

Abstract Patients with chronic kidney disease (CKD) demonstrate complex mineral metabolism derangements and a high prevalence of vitamin D deficiency. However, the optimal method of 25-hydroxyvitamin D (25(OH)D) repletion is unknown, and trials analysing the comparative efficacy of cholecalciferol and ergocalciferol in this population are lacking. We conducted a randomised clinical trial of cholecalciferol 1250μg (50 000 IU) weekly v. ergocalciferol 1250μg (50 000 IU) weekly for 12 weeks in forty-four non-dialysis-dependent patients with stage 3–5 CKD. The primary outcome was change in total 25(OH)D from baseline to week 12 (immediately after therapy). Secondary analyses included the change in 1,25-dihydroxyvitamin D (1,25(OH)2D), parathyroid hormone (PTH), D2 and D3 sub-fractions of 25(OH)D and 1,25(OH)2D and total 25(OH)D from baseline to week 18 (6 weeks after therapy). Cholecalciferol therapy yielded a greater change in total 25(OH)D (45·0 (sd 16·5) ng/ml) v. ergocalciferol (30·7 (sd 15·3) ng/ml) from baseline to week 12 (P<0·01); this observation partially resulted from a substantial reduction in the 25(OH)D3 sub-fraction with ergocalciferol. However, following cessation of therapy, no statistical difference was observed for total 25(OH)D change from baseline to week 18 between cholecalciferol and ergocalciferol groups (22·4 (sd 12·7) v. 17·6 (sd 8·9) ng/ml, respectively; P=0·17). We observed no significant difference between these therapies with regard to changes in serum PTH or 1,25(OH)2D. Therapy with cholecalciferol, compared with ergocalciferol, is more effective at raising serum 25(OH)D in non-dialysis-dependent CKD patients while active therapy is ongoing. However, levels of 25(OH)D declined substantially in both arms following cessation of therapy, suggesting the need for maintenance therapy to sustain levels.
Role of TNF and LTA polymorphisms on biological markers of response to oxidative stimuli in coal miners : a model of gene-environment interaction

Introduction Interaction between genetic background and oxidative environmental stimuli in the pathogenesis of human lung disease has been largely unexplored. Methods A prospective epidemiologic study was undertaken in 253 coal miners. Intermediate quantitative phenotypes of response to oxidant exposure, including erythrocyte glutathione peroxidase (GSH-Px) and catalase activities were studied. Oxidant exposures studied were smoking habits and cumulative dust exposure assessed by job history and ambient measures. Disease phenotypes included subclinical computed tomography score at the first survey and X-ray profusion grades twice, 5 years apart, to assess established coal workers’ pneumoconiosis (CWP). Miners were genotyped for common functional polymorphisms in the gene for tumor necrosis factor α (TNF) and lymphotoxin α (LTA), two proinflammatory cytokines that have been implicated in the pathogenesis of chronic lung diseases. Results Regarding gene-environment interaction on intermediate phenotypes, results showed interaction of a promoter polymorphism at the –308 position in TNF with occupational exposure on erythrocyte GSH-Px activity with a significant association in those with high exposure (p = 0.003) whereas no association was observed among those with low exposure (interaction p = 0.06). Regarding gene-intermediate phenotype interaction on clinical outcome, results showed an association of CWP prevalence with a NcoI polymorphism in LTA in those with low catalase activity (p = 0.05) whereas no association was observed in those with high activity (interaction p = 0.03). No other significant association was observed. Conclusion Results suggest that interactions of genetic background with environmental exposure and intermediate response phenotypes are important components in the pathogenesis of CWP.
The role of depression in the insomnia of people with subjective memory impairment, mild cognitive impairment, and dementia in a community sample of elderly individuals in South Korea

ABSTRACT Background: This study investigates the relationship between insomnia and cognitive dysfunctions including, subjective memory impairment (SMI), mild cognitive impairment (MCI), and dementia, by considering depression in a community sample of elderly individuals. Methods: Data for 1,740 elderly individuals aged 65 years and over were obtained from a nationwide dementia epidemiological study conducted in South Korea. Cognitive functional status was assessed by the Mini-Mental State Examination and the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet Clinical Assessment Battery. Insomnia was defined as the presence of at least one of the four sleep complaints (difficulty in initiating sleep, difficulty in maintaining sleep, early morning awakening, and non-restorative sleep), accompanied by moderate to severe daytime consequences. Depression was evaluated using the Geriatric Depression Scale. Results: The prevalence of insomnia in the patients with SMI, MCI, and dementia was found to be 23.2%, 19.6%, and 31.0%, respectively. The patients with SMI, MCI, and dementia were significantly more likely to have insomnia and the four sleep complaints than the normal comparison patients. After adjusting for sociodemographic factors, the significant relationships between cognitive dysfunctional status and insomnia remained. However, after adjusting for sociodemographic factors and depression, no significant relationships with any of the sleep complaints or insomnia remained. Conclusion: Insomnia is a very common complaint in the elderly with SMI, MCI, and dementia. Depression might play an important factor in the relationship between insomnia and cognitive dysfunctional status in the elderly.
Dedicated population genomics for the silent world: the specific questions of marine population genetics

The life cycle of most marine species is characterized by high fecundity, dispersal during a planktonic larval phase and a sessile or sedentary adult phase with large census population size (Figure 1). Many articles on marine population genetics start by recalling these main characteristics and ensuing expectations, namely: high genetic diversity within population, low genetic differentiation between populations, high influx of effectively selected advantageous and deleterious mutations, and a high migration load opposing local adaptation. Most of the time, this reminder serves to better emphasize the paradox that observations deviate from these expectations, the most popular being genetic differentiation despite larval dispersal, challenging the idea that marine populations are open and well connected, just followed by pervasive local adaptation, challenging the idea that high migration rates prevent the establishment of locally adapted alleles in the sea, and finally low effective population size ( N e) despite large census size ( N ). The list of such counterexamples became so long that what was initially thought paradoxical finally became a shift to a new paradigm (Hauser and Carvalho 2008): (1) larval dispersal would be less effective than expected to homogenize allele frequencies between populations with high rates of self-recruitment, as, for example, in coral reef fishes (Palumbi and Warner 2003; Jones et al. 2005), (2) selection would be rampant in genomes and easy to identify with genome scans, as, for example, adaptation to brackish waters of the Baltic Sea that would target nothing less than ∼500 loci homogeneously distributed in the herring genome (Lamichhaney et al. 2012; Martinez Barrio et al. 2016), and (3) genetic drift would be stronger than thought owing to a very low proportion of individuals effectively contributing to the following generation, as, for example, in exploited fish and shellfish stocks (Hauser et al. 2002; Ovenden et al. …
Selective Genotyping and Phenotyping Strategies in a Complex Trait Context

Selective genotyping and phenotyping strategies are used to lower the cost of quantitative trait locus studies. Their efficiency has been studied primarily in simplified contexts—when a single locus contributes to the phenotype, and when the residual error (phenotype conditional on the genotype) is normally distributed. It is unclear how these strategies will perform in the context of complex traits where multiple loci, possibly linked or epistatic, may contribute to the trait. We also do not know what genotyping strategies should be used for nonnormally distributed phenotypes. For time-to-event phenotypes there is the additional question of choosing follow-up time duration. We use an information perspective to examine these experimental design issues in the broader context of complex traits and make recommendations on their use.
Motivation and volition in the course of action

The Rubicon model of behavioral phases distinguishes between four phases: weighing, planning, acting, and evaluating. Each phase instigates different mental states which are conducive to successfully completing the tasks each of them requires. This chapter first provides an overview of the previously studied effects of these mental states during the phases of weighing and planning on cognition and behavior. Subsequently, the chapter will discuss intention theory, differentiating between two types of intentions: goal intentions vs. implementation intentions. Goal intentions represent states or standards an individual wishes to accomplish, while implementation intentions specify the required steps for the realization of the desired goal. The chapter discusses the processes which are initiated when people set these two kinds of intentions as well as empirically documented effects on goal striving. The chapter closes with future perspectives for research on motivation and volition throughout the behavioral phases.
Passive Restraint Reduces Visually Induced Motion Sickness in Older Adults

Virtual environments such as those used in video games and driving/flight simulators are used for entertainment and training, but are often associated with visually induced motion sickness (VIMS). In this study, we asked whether passive restraint of the head and torso could reduce VIMS in younger and older adults. Twenty-one younger (18–35 years) and 16 older (65 + years) healthy adults engaged in a simulated driving task using a console video game while seated. On different days, participants completed 2 conditions: (a) in the unrestrained condition, participants were seated in a chair without a backrest and were free to move and (b) in the restrained condition, participants’ head and torso were passively restrained to the backrest and headrest of the seat using tense elastic strips. Before and after exposure to the driving game, we measured standing postural sway with eyes closed. VIMS severity was quantified using the Fast Motion Sickness Scale and the Simulator Sickness Questionnaire. Results showed that older (but not younger) participants who became sick in the unrestrained condition reported significantly less VIMS when they were passively restrained. The present findings suggest that passive restraint may be useful to reduce, but not fully prevent, VIMS, particularly in older adults.
Convolutional neural network for earthquake detection and location

ConvNetQuake is the first neural network for detection and location of earthquakes from seismograms. The recent evolution of induced seismicity in Central United States calls for exhaustive catalogs to improve seismic hazard assessment. Over the last decades, the volume of seismic data has increased exponentially, creating a need for efficient algorithms to reliably detect and locate earthquakes. Today’s most elaborate methods scan through the plethora of continuous seismic records, searching for repeating seismic signals. We leverage the recent advances in artificial intelligence and present ConvNetQuake, a highly scalable convolutional neural network for earthquake detection and location from a single waveform. We apply our technique to study the induced seismicity in Oklahoma, USA. We detect more than 17 times more earthquakes than previously cataloged by the Oklahoma Geological Survey. Our algorithm is orders of magnitude faster than established methods.
Distribution of triclosan-resistant genes in major pathogenic microorganisms revealed by metagenome and genome-wide analysis

The substantial use of triclosan (TCS) has been aimed to kill pathogenic bacteria, but TCS resistance seems to be prevalent in microbial species and limited knowledge exists about TCS resistance determinants in a majority of pathogenic bacteria. We aimed to evaluate the distribution of TCS resistance determinants in major pathogenic bacteria (N = 231) and to assess the enrichment of potentially pathogenic genera in TCS contaminated environments. A TCS-resistant gene (TRG) database was constructed and experimentally validated to predict TCS resistance in major pathogenic bacteria. Genome-wide in silico analysis was performed to define the distribution of TCS-resistant determinants in major pathogens. Microbiome analysis of TCS contaminated soil samples was also performed to investigate the abundance of TCS-resistant pathogens. We experimentally confirmed that TCS resistance could be accurately predicted using genome-wide in silico analysis against TRG database. Predicted TCS resistant phenotypes were observed in all of the tested bacterial strains (N = 17), and heterologous expression of selected TCS resistant genes from those strains conferred expected levels of TCS resistance in an alternative host Escherichia coli. Moreover, genome-wide analysis revealed that potential TCS resistance determinants were abundant among the majority of human-associated pathogens (79%) and soil-borne plant pathogenic bacteria (98%). These included a variety of enoyl-acyl carrier protein reductase (ENRs) homologues, AcrB efflux pumps, and ENR substitutions. FabI ENR, which is the only known effective target for TCS, was either co-localized with other TCS resistance determinants or had TCS resistance-associated substitutions. Furthermore, microbiome analysis revealed that pathogenic genera with intrinsic TCS-resistant determinants exist in TCS contaminated environments. We conclude that TCS may not be as effective against the majority of bacterial pathogens as previously presumed. Further, the excessive use of this biocide in natural environments may selectively enrich for not only TCS-resistant bacterial pathogens, but possibly for additional resistance to multiple antibiotics.
Evolution of the Solar Nebula. VIII. Spatial and Temporal Heterogeneity of Short-lived Radioisotopes and Stable Oxygen Isotopes

Isotopic abundances of short-lived radionuclides such as 26Al provide the most precise chronometers of events in the early solar system, provided that they were initially homogeneously distributed. On the other hand, the abundances of the three stable isotopes of oxygen in primitive meteorites show a mass-independent fractionation that survived homogenization in the solar nebula. As a result of this and other cosmochemical evidence, the degree of spatial heterogeneity of isotopes in the solar nebula has long been a puzzle. We show here that based on hydrodynamic models of the mixing and transport of isotopic anomalies formed at, or injected onto, the surface of the solar nebula, initially high levels of isotopic spatial heterogeneity are expected to fall to steady state levels (~10%) low enough to validate the use of 26Al for chronometry, but high enough to preserve the evidence for mass-independent fractionation of oxygen isotopes. The solution to this puzzle relies on the mixing being accomplished by the chaotic fluid motions in a marginally gravitationally unstable disk, as seems to be required for the formation of gas giant planets, and by the inability of alternative physical processes to drive large-scale mixing and transport in the planet-forming midplane of the solar nebula. Such a disk is also capable of large-scale outward transport of the thermally annealed dust grains found in comets, and of driving the shock fronts that appear to be responsible for much of the thermal processing of the components of primitive meteorites, creating a self-consistent picture of the basic physical processes shaping the early solar nebula.
ACC/AHA guidelines superior to ESC/EAS guidelines for primary prevention with statins in non-diabetic Europeans: the Copenhagen General Population Study

Abstract Aim We compared the 2013 American College of Cardiology/American Heart Association (ACC/AHA) and the 2016 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines on prevention of atherosclerotic cardiovascular disease (ASCVD) using different risk prediction models [US Pooled Cohort Equations (US-PCE for any ASCVD) and European Systematic COronary Risk Evaluation system (European-SCORE for fatal ASCVD)] and different statin eligibility criteria. Methods and results We examined 44 889 individuals aged 40–75 recruited in 2003–09 in the Copenhagen General Population Study, all free of ASCVD, diabetes, and statin use at baseline. We detected 2217 any ASCVD events and 199 fatal ASCVD events through 2014. The predicted-to-observed event ratio was 1.2 using US-PCE for any ASCVD and 5.0 using European-SCORE for fatal ASCVD. The US-PCE, but not the European-SCORE, was well-calibrated around decision thresholds for statin therapy. For a Class I recommendation, 42% of individuals qualified for statins using the ACC/AHA guidelines vs. 6% with the ESC/EAS guidelines. Using ACC/AHA- vs. ESC/EAS-defined statin eligibility led to a substantial gain in sensitivity (+62% for any ASCVD and +76% for fatal ASCVD) with a smaller loss in specificity (−35% for any ASCVD and −36% for fatal ASCVD). Similar differences between the ACC/AHA and ESC/EAS guidelines were found for men and women separately, and for Class IIa recommendations. The sensitivity and specificity of a US-PCE risk of 5% were similar to those of a European-SCORE risk of 1.4%, whereas a US-PCE risk of 7.5% was similar to a European-SCORE risk of 2.4%. Conclusions The ACC/AHA guidelines were superior to the ESC/EAS guidelines for primary prevention of ASCVD, that is, for accurately assigning statin therapy to those who would benefit.