Miracle-dz/UniFAR-FTUs huggingface dataset:
Biotin, coenzyme Q10, and their combination ameliorate aluminium chloride‐induced Alzheimer's disease via attenuating neuroinflammation and improving brain insulin signaling

Insulin is important for brain function and neuronal survival. Insulin signaling is initiated by the phosphorylation of insulin receptor substrate‐1 (IRS‐1) at tyrosine (pTyr) residue. However, IRS‐1 is inhibited by phosphorylation at serine (pSer). In Alzheimer's disease (AD), oxidative stress and accumulation of amyloid beta (Aβ) induce neuroinflammation, which augments pSer‐IRS‐1 and reduces pTyr‐IRS‐1 disturbing insulin signaling pathway. Coenzyme Q10 (CoQ10) and biotin possess antioxidant and anti‐inflammatory properties, and, in this study, their impact on insulin signaling is investigated in an aluminium chloride (AlCl3) model of AD. AD was induced by oral administration of AlCl3 (75 mg/kg) for 60 days. Biotin (2 mg/kg), CoQ10 (10 mg/kg), and their combination were supplemented concomitantly with AlCl3 for 60 days. Memory test and histological examination were performed. Brain levels of lipid peroxides, antioxidants (reduced glutathione and superoxide dismutase), inflammatory markers (tumor necrosis factor‐α, interleukin‐6 [IL‐6], IL‐1, and nuclear factor κB), and phosphorylated Akt (survival kinase) as well as protein levels of Aβ, IRS‐1 (pTyr and pSer), and caspase‐3 (apoptotic marker) were determined. AlCl3 resulted in impaired memory, significant increase in Aβ, lipid peroxides, inflammatory markers, caspase‐3, and pSer‐IRS‐1, with significant reduction of the antioxidants, pTyr‐IRS‐1, and p‐Akt reflecting Aβ‐induced inflammation and defective insulin signaling. Histological examination revealed focal aggregations of inflammatory cells and neuronal degeneration. The biochemical deviations and histological changes were attenuated by the concomitant treatment with biotin and, to greater extent, with CoQ10 and the combination. In conclusion, biotin and CoQ10 could protect against AD via attenuating inflammatory response and enhancing insulin signaling.
Long‐term effects of temperature on the wood production of Pinus sylvestris L. and Picea abies (L.) Karst. In old provenance experiments

Old provenance experiments with Scots pine and Norway spruce in Finland were used for assessing the long‐term effects of the projected climatic change on forest trees. The northernmost origins showed an increase in wood production when transferred southwards into a climate with an annual mean effective temperature sum close to that which is expected in northern areas as a result of the projected climatic change. A model is constructed with the estimated changes in wood production as a function of the annual mean temperature sum at the original location and the change in the annual mean temperature sum caused by the geographical transfer. The major changes in wood production are expected to occur in the northernmost areas of tree growth.
Evaluation of the optical and biomechanical properties of bioengineered human skin generated with fibrin-agarose biomaterials

Abstract. Significance: Recent generation of bioengineered human skin allowed the efficient treatment of patients with severe skin defects. However, the optical and biomechanical properties of these models are not known. Aim: Three models of bioengineered human skin based on fibrin-agarose biomaterials (acellular, dermal skin substitutes, and complete dermoepidermal skin substitutes) were generated and analyzed. Approach: Optical and biomechanical properties of these artificial human skin substitutes were investigated using the inverse adding-doubling method and tensile tests, respectively. Results: The analysis of the optical properties revealed that the model that most resembled the optical behavior of the native human skin in terms of absorption and scattering properties was the dermoepidermal human skin substitutes after 7 to 14 days in culture. The time-course evaluation of the biomechanical parameters showed that the dermoepidermal substitutes displayed significant higher values than acellular and dermal skin substitutes for all parameters analyzed and did not differ from the control skin for traction deformation, stress, and strain at fracture break. Conclusions: We demonstrate the crucial role of the cells from a physical point of view, confirming that a bioengineered dermoepidermal human skin substitute based on fibrin-agarose biomaterials is able to fulfill the minimal requirements for skin transplants for future clinical use at early stages of in vitro development.
Anatomical and dosimetric assessment of the prostate apex: A pilot comparison of image‐guided transperineal ultrasound to conventional computed tomography simulation

Inaccuracies in prostate apex contour delineation based on simulation computed tomography (CT) imaging can impact treatment outcomes and toxicity profiles for prostate cancer radiotherapy. Transperineal ultrasound (TPUS) is a non‐invasive imaging modality that can improve delineation of prostate volumes. We performed a pilot analysis to assess for differences in anatomical position between conventional CT and a TPUS delineated prostate apex and determined whether these translated into a clinically significant difference in apical point dose.
Characterization of a Novel GT-box Binding Protein from Arabidopsis.

We isolated a cDNA encoding a novel GT-box binding protein from Arabidopsis, designated GT-4. The predicted open reading frame encodes a protein of 372 amino acids and the predicted protein sequence revealed the presence of a putative DNA-binding domain with 80% homology to the trihelix region of previously described light-responsive element binding protein, GT-1. Reverse transcription-PCR analysis showed that GT-4 transcripts are present in all tissues tested in light-grown plants, but light-regulated expression of GT-4 mRNA was observed only in etiolated seedlings. Electro-mobility shift assay using recombinant protein revealed that the GT-box-binding specificity of GT-4 is almost identical to that of GT-1. Transient expression of GT-4::GFP fusion protein in onion epidermal cells revealed the presence of a nuclear localization signal within the GT-4 protein. These results suggest the possibility that GT-4 is involved in GT-box-mediated gene expression by recognizing target sequences closely related to GT-1 binding sites.
Influences of Fermentable Carbohydrates on Shifting Nitrogen Excretion and Reducing Ammonia Emission of Pigs

There is increasing evidence that nitrogen (N) excretion is shifted from urea in urine to bacterial protein in feces when fibrous feedstuffs are included in the diet. Carbohydrates also beneficially affect the host by selectively stimulating the growth and activity of one or a limited number of bacterial species that are already resident in the cecum and colon of pigs and are known to extend health-promoting properties. Ammonia emissions were reduced significantly in monogastric animal manure by adding a variety of carbohydrate sources to the basal diet, although certain fractions of carbohydrates are not involved or are less involved in reducing these emissions. When sucrose thermal oligosacchride caramel (STOP) was added to the basal diet of pigs at 2%, both stored manure and fresh manure had reductions of 62 and 37%, respectively, in NH3-N, while total Kjeldahl nitrogen (TKN) in the stored manure and fresh manure declined by 55 and 35%, respectively. The addition of cellulose at 5% to the pigs basal diet resulted in NH3-N reductions of 73 and 68% in stored and fresh manure, respectively. TKN levels were reduced by 35 and 61%, respectively, in stored manure and fresh manure. The addition of paper products at 2.5 to 5.0% reduced ammonia emission by 29 to 47%. Soybean hulls added at 10% reduced emissions 21 to 41%. When sugar beets were added at 6.1% of the diet, ammonia reduction was 45%. A 0.15% addition of lactosucrose resulted in a 50% reduction in ammonia emissions from the cecal contents of chicks. Lactosucrose when supplemented at 1.5 g/day to the dog and 0.175 g/day to the cat resulted in ammonia reductions of 53% and 47%, respectively, in their feces. The inclusion of fermentable carbohydrates in pig diets can be a practical method for ammonia emission control and reducing nitrogen excretion. However, these effects on ammonia emission and nitrogen excretion need to be verified in practical situations. Primary odor-causing compounds evolve from excess degradable proteins and lack of specific fermentable carbohydrates during microbial fermentation. Continued research to incorporate protein degradation with fermentable carbohydrates in the lower gastrointestinal tracts of pigs will further control odors and N excretion from swine manure.
Health Equity and the Social Determinants: Putting Newborn Health in Context

* Abbreviations: IVH — : intraventricular hemorrhage RRS — : residential racial segregation In this issue of Pediatrics , Murosko et al1 explore the impact of residential racial segregation (RRS) on risk for intraventricular hemorrhage (IVH) in preterm infants. Using propensity score matching to reduce bias from confounding, they found a modest increase in the risk ratio for any grade of IVH among infants whose mothers lived in areas with high levels compared with low levels of racial segregation. In a stratified analysis, the effect of segregation was only significant for African American infants and not for white infants. This methodologically rigorous study was motivated by the observation that African American infants have higher rates of IVH compared with their white peers, and African American women have higher rates of pregnancy-related complications associated with neonatal IVH compared with white women. The authors note that “…RRS accounts for some of the residual disparities between African American and white infants in infant mortality, preterm birth rates, and low birth weight” and aimed to interrogate the role of segregation as a driver of racial disparities in neonatal morbidities. It has long been clear that social forces act in … Address correspondence to Jonathan S. Litt, MD, MPH, ScD, Department of Neonatology, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Rose 3, Boston, MA 02215. E-mail: jlitt{at}bidmc.harvard. edu
Pharmacological treatment of psoriatic arthritis: a systematic literature research for the 2019 update of the EULAR recommendations for the management of psoriatic arthritis

Objective To perform an update of a review of the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) in psoriatic arthritis (PsA). Methods This is a systematic literature research of 2015–2018 publications on all DMARDs in patients with PsA, searching Medline, Embase and the Cochrane Library. Efficacy was assessed in randomised controlled trials. For safety, cohort studies, case–control studies and long-term extensions (LTEs) were analysed. Results 56 publications (efficacy: n=33; safety n=23) were analysed. The articles were on tumour necrosis factor (TNF) inhibitors (n=6; golimumab, etanercept and biosimilars), interleukin (IL)-17A inhibitors (n=10; ixekizumab, secukinumab), IL-23-p19 inhibitors (n=2; guselkumab, risankizumab), clazakizumab (IL-6 inhibitor), abatacept (CD80/86 inhibitor) and ABT-122 (anti-TNF/IL-17A), respectively. One study compared ustekinumab (IL-12/23i) with TNF inhibitor therapy in patients with entheseal disease. Three articles investigated DMARD tapering. Trials on targeted synthetic DMARDs investigated apremilast (phosphodiesterase-4 inhibitor) and Janus kinase inhibitors (JAKi; tofacitinib, filgotinib). Biosimilar comparison with bio-originator showed non-inferiority. Safety was evaluated in 13 LTEs, 9 cohort studies and 1 case–control study investigating malignancies, infections, infusion reactions, multiple sclerosis and major cardiovascular events, as well as efficacy and safety of vaccination. No new safety signals were identified; however, warnings on the risk of venous thromboembolic events including pulmonary embolism when using JAKi were issued by regulators based on other studies. Conclusion Many drugs in PsA are available and have demonstrated efficacy against placebo. Efficacy varies across PsA manifestations. Safety must also be taken into account. This review informed the development of the European League Against Rheumatism 2019 updated PsA management recommendations.
Genetic risk scores for coronary artery disease and its traditional risk factors: Their role in the progression of coronary artery calcification—Results of the Heinz Nixdorf Recall study

Background Atherosclerosis is the primary cause of coronary artery disease (CAD). Several observational studies have examined the association of traditional CAD risk factors with the progression of coronary artery calcification (CAC). In our study we investigated the effect of 11 different genetic risk scores associated with CAD and CAD risk factors on the progression of CAC. Methods and results We included 3097 participants from the Heinz Nixdorf Recall study who had available CAC measurements at baseline (CACb) and at the 5-year follow-up (CAC5y). A weighted genetic risk score for CAD and each of the CAD-associated risk factors was constructed. Multiple regression analyses were applied to i) the difference between the observed log(CAC5y+1) (log(obs)) and expected log(CAC5y+1) (log(exp)) at the 5-year follow-up following the individual’s log(CACb+1) percentile for the time between scans (log(obs)–log(exp)) and ii) the 5-year CAC progression, defined as 5*(log(CAC5y+1)–log(CACb+1))/time between the scans, adjusted for age, sex, and log(CACb+1) as well as for risk factors. The median percent deviation from the expected (CAC5y+1) and the 5-year progression of (CAC+1) in our study were 0 (first quartile: Q1; third quartile: Q3: -0.32; 0.48) and 45.4% (0%; 171.0%) respectively. In the age-, sex- and log(CACb+1)-adjusted model, the per-standard deviation (SD) increase in CAD genetic risk score was associated with the percent deviation from the expected (CAC5y+1) (9.7% (95% confidence interval: 5.2%; 14.5%), p = 1.6x10-5) and the 5-year progression of CAC (7.1% (3.0%; 11.4%), p = 0.0005). The CAD genetic risk score explains an additional 0.6% of the observed phenotypic variance for “log(obs)–log(exp)” and 0.4% for 5-year progression of CAC. Additionally, the per-SD increase in the CAC genetic risk score was associated with the percent deviation from the expected (CAC5y+1) (6.2% (1.9%; 10.8%, p = 0.005)) explaining an additional 0.2% of the observed phenotypic variance. However, the per-SD increase in the CAC genetic risk score was not associated with the 5-year progression of CAC (4.4% (0.4%; 8.5%), p = 0.03) after multiple testing. Adjusting for risk factors did not change the results. None of the other genetic risk scores showed an association with the percent deviation from the expected (CAC5y+1) or with the 5-year progression of CAC. Conclusions The association of the CAC genetic risk score and the CAD genetic risk score provides evidence that genetic determinants for CAC and CAD influence the progression of CAC.
Spatio‐phylogenetic multispecies distribution models

Ecologists increasingly consider phylogenetic relatedness in both community composition and spatial arrangements in communities. Here we considered both the phylogenetic correlation between multiple species and the spatial correlation induced by unobserved spatial heterogeneity on multiple plots. For this analysis, we introduced phylogenetic spatial generalised linear mixed models (PSGLMMs), which are an extension of phylogenetic generalised linear mixed models (PGLMMs). We used the framework of generalised linear array models to simultaneously model species and plot dimension. Such models have the potential to explain the correlation of the phylogenetic relationship of the observed species and of the spatial proximity of the plots, or both. We proposed model selection strategies based on proper scores and empirically evaluated them in a case study using bird count data. In our analysis, we focused on two special cases: the community composition model and the environmental sensitivity model. Our simulation study indicated that it might be difficult to correctly identify phylogenetic signals when the phylogenetic correlation is rather low and when studying presence‐absence or count data of rare or pervasive species.
Education and the new imperialism

The aim of the article is to discuss the role of education in relation to the new imperialism. The article begins by explaining what is meant by the term the ‘new imperialism’ and how it differs from older forms of European imperialism characterized by colonial rule. The new imperialism is presented as having material and discursive aspects although it is the discursive basis of western rule and how this affects education that forms the major focus for the article. Using Foucault's theory of governmentality, the new imperialism is presented as the incorporation of low‐income countries and regions that were previously subject to older forms of European imperialism into a new regime of global governance which serves to secure the interests of the USA, its western allies and of global capitalism more generally. The article then analyses the concept of ‘development’ which has provided the principal means by which the West has come to understand and hence control the non‐West. The article then turns to a consideration of education as a key policy area for the multilateral development agencies and an important disciplinary institution in relation to the development project. The article concludes by briefly setting out a possible role for education in a new anti‐imperial politics.
Are There Benefits from the Use of Fish Oil Supplements in Athletes? A Systematic Review.

Despite almost 25 y of fish oil supplementation (FS) research in athletes and widespread use by the athletic community, no systematic reviews of FS in athletes have been conducted. The objectives of this systematic review are to: 1) provide a summary of the effect of FS on the athlete's physiology, health, and performance; 2) report on the quality of the evidence; 3) document any side effects as reported in the athlete research; 4) discuss any risks associated with FS use; and 5) provide guidance for FS use and highlight gaps for future research. Electronic databases (PubMed, Embase, Web of Science, Google Scholar) were searched up until April 2019. Only randomized placebo-controlled trials (RCTs) in athletes, assessing the effect of FS on a health, physiological/biochemical, or performance variable were included. Of the 137 papers identified through searches, 32 met inclusion criteria for final analysis. Athletes varied in classification from recreational to elite, and from Olympic to professional sports. Mean age for participants was 24.9 ± 4.5 y, with 70% of RCTs in males. We report consistent effects for FS on reaction time, mood, cardiovascular dynamics in cyclists, skeletal muscle recovery, the proinflammatory cytokine TNF-α, and postexercise NO responses. No clear effects on endurance performance, lung function, muscle force, or training adaptation were evident. Methodological quality, applying the Physiotherapy Evidence Database (PEDro) scale, ranged from 6 to a maximum of 11, with only 4 RCTs reporting effect sizes. Few negative outcomes were reported. We report various effects for FS on the athlete's physiology; the most consistent findings were on the central nervous system, cardiovascular system, proinflammatory cytokines, and skeletal muscle. We provide recommendations for future research and discuss the potential risks with FS use.
Network-based strategies in metabolomics data analysis and interpretation: from molecular networking to biological interpretation

ABSTRACT Introduction Metabolomics has become a crucial part of systems biology; however, data analysis is still often undertaken in a reductionist way focusing on changes in individual metabolites. Whilst such approaches indeed provide relevant insights into the metabolic phenotype of an organism, the intricate nature of metabolic relationships may be better explored when considering the whole system. Areas covered This review highlights multiple network strategies that can be applied for metabolomics data analysis from different perspectives including: association networks based on quantitative information, mass spectra similarity networks to assist metabolite annotation and biochemical networks for systematic data interpretation. We also highlight some relevant insights into metabolic organization obtained through the exploration of such approaches. Expert opinion Network based analysis is an established method that allows the identification of non-intuitive metabolic relationships as well as the identification of unknown compounds in mass spectrometry. Additionally, the representation of data from metabolomics within the context of metabolic networks is intuitive and allows for the use of statistical analysis that can better summarize relevant metabolic changes from a systematic perspective.
Mashes to Mashes, Crust to Crust. Presenting a novel microstructural marker for malting in the archaeological record

The detection of direct archaeological remains of alcoholic beverages and their production is still a challenge to archaeological science, as most of the markers known up to now are either not durable or diagnostic enough to be used as secure proof. The current study addresses this question by experimental work reproducing the malting processes and subsequent charring of the resulting products under laboratory conditions in order to simulate their preservation (by charring) in archaeological contexts and to explore the preservation of microstructural alterations of the cereal grains. The experimentally germinated and charred grains showed clearly degraded (thinned) aleurone cell walls. The histological alterations of the cereal grains were observed and quantified using reflected light and scanning electron microscopy and supported using morphometric and statistical analyses. In order to verify the experimental observations of histological alterations, amorphous charred objects (ACO) containing cereal remains originating from five archaeological sites dating to the 4th millennium BCE were considered: two sites were archaeologically recognisable brewing installations from Predynastic Egypt, while the three broadly contemporary central European lakeshore settlements lack specific contexts for their cereal-based food remains. The aleurone cell wall thinning known from food technological research and observed in our own experimental material was indeed also recorded in the archaeological finds. The Egyptian materials derive from beer production with certainty, supported by ample contextual and artefactual data. The Neolithic lakeshore settlement finds currently represent the oldest traces of malting in central Europe, while a bowl-shaped bread-like object from Hornstaad–Hörnle possibly even points towards early beer production in central Europe. One major further implication of our study is that the cell wall breakdown in the grain’s aleurone layer can be used as a general marker for malting processes with relevance to a wide range of charred archaeological finds of cereal products.
Herbivory by reef fishes and the production of dimethyl sulfide and acrylic acid

The content of dimethylsulfoniopropionate (DMSP) in selected marine reef macrophytes was examined and related to levels of DMSP and one of its decomposition products, dimethylsulfide (DMS), in guts of herbivorous fish. Concentrations of short-chain fatty acids and acrylic acid (ACR), another decomposition product of DMSP, were also measured in gut contents. The fatty acid data provide evidence for bacterial fermentation within fish intestines. Unlike previous observations of gut microflora, the concentrations of ACR in these guts did not support a role for ACR as an inhibitor of the gut microflora. DMSP also appears to concentrate in the tissues of certain fish, but not in others. These results illustrate the complex trophic interactions which determine the dynamics of DMSP in the marine food web.