Miracle-dz/UniFAR-FTUs huggingface dataset:
The somal patterning of the AII amacrine cell mosaic in the mouse retina is indistinguishable from random simulations matched for density and constrained by soma size

Abstract The orderly spacing of retinal neurons is commonly regarded as a characteristic feature of retinal nerve cell populations. Exemplars of this property include the horizontal cells and the cholinergic amacrine cells, where individual cells minimize the proximity to like-type neighbors, yielding regularity in the patterning of their somata. Recently, two types of retinal bipolar cells in the mouse retina were shown to exhibit an order in their somal patterning no different from density-matched simulations constrained by soma size but being otherwise randomly distributed. The present study has now extended this finding to a type of retinal amacrine cell, the AII amacrine cell. Voronoi domain analysis revealed the patterning in the population of AII amacrine somata to be no different from density-matched and soma-size-constrained random simulations, while analysis of the density recovery profile showed AII amacrine cells to exhibit a minimal intercellular spacing identical to that for those random simulations: AII amacrine somata were positioned side-by-side as often as chance would predict. Regularity indexes and packing factors (PF) were far lower than those achieved by either the horizontal cells or cholinergic amacrine cells, with PFs also being comparable to those derived from the constrained random simulations. These results extend recent findings that call into question the widespread assumption that all types of retinal neurons are assembled as regular somal arrays, and have implications for the way in which AII amacrine cells must distribute their processes to ensure a uniform coverage of the retinal surface.
[Protective effect of proanthocyanidin on oxidative stress and mRNA expression of Nrf2 and HO-1 of mice cerebellar tissue induced by cypermethrin].

OBJECTIVE To investigate the protective effect of proanthocyanidin on oxidative stress and mRNA expression of Nrf2 and HO-1 of mice cerebellar tissue induced by cypermethrin. METHODS A total of 50 male Kunming mice were randomly divided into five groups by gavage once daily for three consecutive weeks, the control group, CYP group( 10 mg / kg) and PC pretreated group( 50, 100 and 200 mg / kg). The mice were sacrificed and activitie levels of GSH-Px, T-SOD, CAT and MDA were measured, and then used the immunohistochemistry to analyse the expression of Nrf2, semi-quantitative RTPCR detected mRNA expression of Nrf2 and HO-1. RESULTS Compared to the controlgroup, the activity levels of GSH-Px, T-SOD, CAT decreased and MDA increased in CYP group. Nucleus positive cells was higher and mRNA expression of Nrf2 and HO-1 was higher than the control group( P < 0. 05). Compared to the CYP group, the level of GSHPx、T-SOD、CAT increased and MDA decreased in PC pretreated group, the count of nucleus-positive cells and mRNA expression of Nrf2 and HO-1 was lower than the CYP group( P < 0. 05). CONCLUSION s Cypermethrin could increase oxidative stress in cerebellar tissue of mice, induces the nuclear translocation of Nrf2 from the cytoplasm to the nucleus, and upregulating downstream gene of HO-1 expression. Proanthocyanidin could adjust mRNA expression of Nrf2 and HO-1 and ameliorate cypermethrin-induced oxidative stress.
The Schaake Shuffle: A Method for Reconstructing Space–Time Variability in Forecasted Precipitation and Temperature Fields

Abstract A number of statistical methods that are used to provide local-scale ensemble forecasts of precipitation and temperature do not contain realistic spatial covariability between neighboring stations or realistic temporal persistence for subsequent forecast lead times. To demonstrate this point, output from a global-scale numerical weather prediction model is used in a stepwise multiple linear regression approach to downscale precipitation and temperature to individual stations located in and around four study basins in the United States. Output from the forecast model is downscaled for lead times up to 14 days. Residuals in the regression equation are modeled stochastically to provide 100 ensemble forecasts. The precipitation and temperature ensembles from this approach have a poor representation of the spatial variability and temporal persistence. The spatial correlations for downscaled output are considerably lower than observed spatial correlations at short forecast lead times (e.g., less than 5.
Idiopathic intracranial hypertension: consensus guidelines on management

The aim was to capture interdisciplinary expertise from a large group of clinicians, reflecting practice from across the UK and further, to inform subsequent development of a national consensus guidance for optimal management of idiopathic intracranial hypertension (IIH). Methods Between September 2015 and October 2017, a specialist interest group including neurology, neurosurgery, neuroradiology, ophthalmology, nursing, primary care doctors and patient representatives met. An initial UK survey of attitudes and practice in IIH was sent to a wide group of physicians and surgeons who investigate and manage IIH regularly. A comprehensive systematic literature review was performed to assemble the foundations of the statements. An international panel along with four national professional bodies, namely the Association of British Neurologists, British Association for the Study of Headache, the Society of British Neurological Surgeons and the Royal College of Ophthalmologists critically reviewed the statements. Results Over 20 questions were constructed: one based on the diagnostic principles for optimal investigation of papilloedema and 21 for the management of IIH. Three main principles were identified: (1) to treat the underlying disease; (2) to protect the vision; and (3) to minimise the headache morbidity. Statements presented provide insight to uncertainties in IIH where research opportunities exist. Conclusions In collaboration with many different specialists, professions and patient representatives, we have developed guidance statements for the investigation and management of adult IIH.
ER–Mitochondria Microdomains in Cardiac Ischemia–Reperfusion Injury: A Fresh Perspective

The mitochondrial and endoplasmic reticulum (ER) homeostasis is pivotal to the maintenance of an array of physiological processes. The physical contact and association between ER and mitochondria, known as the ER–mitochondria microdomains or mitochondria-associated ER membrane (MAM), temporally and spatially regulates the mitochondria/ER structure and function. More evidence suggests a role for MAMs in energy production, cellular contraction and mobility, and normal extracellular signal transmission. In pathological states, such as cardiac ischemia–reperfusion (I/R injury), this ER–mitochondria microdomains may act to participate in the cellular redox imbalance, ER stress, mitochondrial injury, energy deletion, and programmed cell death. From a therapeutic perspective, a better understanding of the cellular and molecular mechanisms of the pathogenic ER–mitochondria contact should help to identify potential therapeutic target for cardiac I/R injury and other cardiovascular diseases and also pave the road to new treatment modalities pertinent for the treatment of reperfusion damage in clinical practice. This review will mainly focus on the possible signaling pathways involved in the regulation of the ER–mitochondria contact. In particular, we will summarize the downstream signaling modalities influenced by ER–mitochondria microdomains, for example, mitochondrial fission, mitophagy, calcium balance, oxidative stress, and programmed cell death in details.
Cost-effectiveness analysis of internet-mediated cognitive behavioural therapy for depression in the primary care setting: results based on a controlled trial

Objective To perform a cost-effectiveness analysis of a randomised controlled trial of internet-mediated cognitive behavioural therapy (ICBT) compared with treatment as usual (TaU) for patients with mild to moderate depression in the Swedish primary care setting. In particular, the objective was to assess from a healthcare and societal perspective the incremental cost-effectiveness ratio (ICER) of ICBT versus TaU at 12 months follow-up. Design A cost-effectiveness analysis alongside a pragmatic effectiveness trial. Setting Sixteen primary care centres (PCCs) in south-west Sweden. Participants Ninety patients diagnosed with mild to moderate depression at the PCCs. Main outcome measure ICERs calculated as (CostICBT−CostTaU)/(Health outcomeICBT−Health outcomeTaU)=ΔCost/ΔHealth outcomes, the health outcomes being changes in the Beck Depression Inventory-II (BDI-II) score and quality-adjusted life-years (QALYs). Results The total cost per patient for ICBT was 4044 Swedish kronor (SEK) (€426) (healthcare perspective) and SEK47 679 (€5028) (societal perspective). The total cost per patient for TaU was SEK4434 (€468) and SEK50 343 (€5308). In both groups, the largest cost was associated with productivity loss. The differences in cost per patient were not statistically significant. The mean reduction in BDI-II score was 13.4 and 13.8 units in the ICBT and TaU groups, respectively. The mean QALYs per patient was 0.74 and 0.79 in the ICBT and TaU groups, respectively. The differences in BDI-II score reduction and mean QALYs were not statistically significant. The uncertainty of the study estimates when assessed by bootstrapping indicated that no firm conclusion could be drawn as to whether ICBT treatment compared with TaU was the most cost-effective use of resources. Conclusions ICBT was regarded to be as cost-effective as TaU as costs, health outcomes and cost-effectiveness were similar for ICBT and TaU, both from a healthcare and societal perspective. Trial registration number ID NR 30511.
Immunogenicity and safety of a second dose of a measles-mumps-rubella vaccine administered to healthy participants 7 years of age or older: A phase III, randomized study

ABSTRACT The introduction of vaccination programs against measles, mumps, and rubella (MMR) led to significant global reduction in morbidity and mortality from these diseases. The currently recommended MMR vaccination schedule in the United States of America comprises 2 vaccine doses typically administered at 12–15 months and 4–6 years, respectively. Considering recent outbreaks in the USA, catch-up vaccination with an additional dose of MMR vaccine could contribute to outbreak control and community protection. This phase III, observer-blind, randomized controlled trial (NCT02058563) assessed the immunogenicity and safety of a dose of the MMR-RIT vaccine (Priorix, GSK) compared to MMR II vaccine (control; M-M-R II, Merck&Co Inc.) in ≥7-year-olds who had received ≥1 previous dose of MMR vaccine. We assessed anti-measles, anti-mumps, and anti-rubella antibody geometric mean concentrations (GMCs; primary endpoint) and seroresponse rates (SRRs) at day 42 post-vaccination. Solicited, unsolicited, and serious adverse events (AEs) were recorded. The according-to-protocol cohort for immunogenicity included 869 participants (MMR-RIT: N = 433; MMR II: N = 436). We observed anti-measles, anti-mumps, and anti-rubella antibody GMCs of 1790.2 mIU/mL, 113.5 EU/mL, and 76.1 IU/mL, respectively, and SRRs of 98.8%, 98.4%, and 99.5%, respectively, after a dose of MMR-RIT; non-inferiority compared to MMR II was demonstrated. Both vaccines showed comparable reactogenicity profiles; the most common solicited AEs were injection site redness and pain, and fever (MMR-RIT: 12.2%, 11.8%, and 3.0%; MMR II: 11.7%, 11.5%, and 5.2%, respectively). The dose of MMR-RIT induced robust immune responses that were not inferior to those of MMR II, and was well tolerated.
Investigation of raphe function in the bicuspid aortic valve and its influence on clinical criteria—A patient‐specific finite element study

The aortic valve is normally composed of 3 cusps. In one common lesion, 2 cusps are fused together. The conjoined area of the fused cusps is termed raphe. Occurring in 1% to 2% of the population, the bicuspid aortic valve (BAV) is the most common congenital cardiac malformation. The majority of BAV patients eventually require surgery. There is a lack in the literature regarding modeling of the raphe (geometry and material properties), its role and its influence on BAV function. The present study aims to propose improvements on these aspects. Three patient‐specific finite element models of BAVs were created based on 3D trans‐esophageal echocardiography measurements, and assuming age‐dependent material properties. The raphe was initially given the same material properties as its underlying cusps. Two levels of validation were performed; one based on the anatomical validation of the pressurized geometry in diastole (involving 7 anatomical measures), as simulated starting from the unpressurized geometry, and the other based on a functional assessment using clinical measurements in both systole and diastole (involving 16 functional measures). The pathology was successfully reproduced in the FE models of all 3 patients. To further investigate the role of the raphe, 2 additional scenarios were considered; (1) the raphe was considered as almost rigid, (2) the raphe was totally removed. The results confirmed the interpretation of the raphe as added stiffness in the fused cusp's rotation with respect to the aortic wall, as well as added support for stress distribution from the fused cusps to the aortic wall.
Sample Entropy of the Heart Rate Reflects Properties of the System Organization of Behaviour

Cardiac activity is involved in the processes of organization of goal-directed behaviour. Each behavioural act is aimed at achieving an adaptive outcome and it is subserved by the actualization of functional systems consisting of elements distributed across the brain and the rest of the body. This paper proposes a system-evolutionary view on the activity of the heart and its variability. We have compared the irregularity of the heart rate, as measured by sample entropy (SampEn), in behaviours that are subserved by functional systems formed at different stages of individual development, which implement organism-environment interactions with different degrees of differentiation. The results have shown that SampEn of the heart rate was higher during performing tasks that included later acquired knowledge (foreign language vs. native language; mathematical vocabulary vs. general vocabulary) and decreased in the stress and alcohol conditions, as well as at the beginning of learning. These results are in line with the hypothesis that irregularity of the heart rate reflects the properties of a set of functional systems subserving current behaviour, with higher irregularity corresponding to later acquired and more complex behaviour.
How to Use Security Analysis to Improve Portfolio Selection

It has been argued convincingly in a series of papers on the Capital Asset Pricing Model that, in the absence of insight generating expectations different from the market consensus, the investor should hold a replica of the market portfolio. ' A number of empirical papers have demonstrated that portfolios of more than 50-100 randomly selected securities tend to correlate very highly with the market portfolio, so that, as a practical matter, replicas are relatively easy to obtain. If the investor has no special insights, therefore, he has no need of the elaborate balancing algorithms of Markowitz and Sharpe.2 On the other hand if he has special insights, he will get little, if any, help from the portfolio-balancing literature on how to translate these insights into the expected returns, variances, and covariances the algorithms require as inputs. What was needed, it seemed to us, was exploration of the link between conventional subjective, judgmental, work of the security analyst, on one hand-rough cut and not very quantitative-and the essentially objective, statistical approach to portfolio selection of Markowitz and his successors, on the other. The void between these two bodies of ideas was made manifest by our inability to answer to our own satisfaction the following kinds of questions: Where practical is it desirable to so balance a portfolio between long positions in securities considered underpriced and short positions in securities considered overpriced that market risk is completely eliminated (i.e., hedged)? Or should one strive to diversify a portfolio so completely that only market risk remains? As this implies, in the highly diversified portfolio market sensitivity in individual securities seems to contribute directly to market sensitivity in the overall portfolio, whereas other sources of return variability in individual securities seem to average out. Does this mean that the latter sources
Understanding the Rate‐Limiting Step of Glycogenolysis by Using QM/MM Calculations on Human Glycogen Phosphorylase

Liver glycogen phosphorylase (GP) is a key enzyme for human health, as its increased activity is associated with type 2 diabetes. The GP catalytic mechanism has been explored by quantum mechanics/molecular mechanics (QM/MM) methods. Herein, we propose a mechanism that proceeds by three steps: 1) it begins with transfer of a hydrogen atom from the phosphate group of the pyridoxal 5′‐phosphate (HPO42−‐PLP) cofactor to the phosphate substrate; 2) the glycosidic linkage is then cleaved through protonation of the glycosidic oxygen atom by a hydroxy group of the inorganic phosphate group; and 3) an oxygen atom of the phosphate performs a nucleophilic attack on the anomeric carbon atom of glucose, concomitant with the return of a proton from phosphate to PO43−‐PLP, which finally leads to formation of the glucose‐1‐phosphate product and recovers the initial state of the PLP cofactor. The glycosidic bond cleavage and nucleophilic attack from the phosphate group to the glycosyl molecule have the highest activation free energies. The structural properties of the hereby characterized transition states could be very useful in structure‐based drug design studies against liver GP.
Biomechanical Properties of Bruch's Membrane-Choroid Complex and Their Influence on Optic Nerve Head Biomechanics.

Purpose The purpose of this study was to measure the rupture pressure and the biomechanical properties of porcine Bruch's membrane (BM)-choroid complex (BMCC) and the influences of BM on optic nerve head (ONH) tissues. Methods The biomechanical properties of BMCC were extracted through uniaxial tensile tests of 10 BMCC specimens from 10 porcine eyes; the rupture pressures of BMCC were measured through burst tests of 20 porcine eyes; and the influence of BM on IOP-induced ONH deformations were investigated using finite element (FE) analysis. Results Uniaxial experimental results showed that the average elastic (tangent) moduli of BMCC samples at 0% and 5% strain were 1.60 ± 0.81 and 2.44 ± 1.02 MPa, respectively. Burst tests showed that, on average, BMCC could sustain an IOP of 82 mm Hg before rupture. FE simulation results predicted that, under elevated IOP, prelamina tissue strains increased with increasing BM stiffness. On the contrary, lamina cribrosa strains showed an opposite trend but the effects were small. Conclusions BMCC stiffness is comparable or higher than those of other ocular tissues and can sustain a relatively high pressure before rupture. Additionally, BM may have a nonnegligible influence on IOP-induced ONH deformations.
Multiple Nonsense-Mediated mRNA Processes Require Smg5 in Drosophila

The nonsense-mediated messenger RNA (mRNA) decay (NMD) pathway is a cellular quality control and post-transcriptional gene regulatory mechanism and is essential for viability in most multicellular organisms . A complex of proteins has been identified to be required for NMD function to occur; however, there is an incomplete understanding of the individual contributions of each of these factors to the NMD process. Central to the NMD process are three proteins, Upf1 (SMG-2), Upf2 (SMG-3), and Upf3 (SMG-4), which are found in all eukaryotes, with Upf1 and Upf2 being absolutely required for NMD in all organisms in which their functions have been examined. The other known NMD factors, Smg1, Smg5, Smg6, and Smg7, are more variable in their presence in different orders of organisms and are thought to have a more regulatory role. Here we present the first genetic analysis of the NMD factor Smg5 in Drosophila. Surprisingly, we find that unlike the other analyzed Smg genes in this organism, Smg5 is essential for NMD activity. We found this is due in part to a requirement for Smg5 in both the activity of Smg6-dependent endonucleolytic cleavage, as well as an additional Smg6-independent mechanism. Redundancy between these degradation pathways explains why some Drosophila NMD genes are not required for all NMD-pathway activity. We also found that while the NMD component Smg1 has only a minimal role in Drosophila NMD during normal conditions, it becomes essential when NMD activity is compromised by partial loss of Smg5 function. Our findings suggest that not all NMD complex components are required for NMD function at all times, but instead are utilized in a context-dependent manner in vivo.
Mesenchymal stromal cells from amniotic fluid are less prone to senescence compared to those obtained from bone marrow: An in vitro study

Mesenchymal stromal cells (MSCs) are considered to be an excellent source in regenerative medicine. They contain several cell subtypes, including multipotent stem cells. MSCs are of particular interest as they are currently being tested using cell and gene therapies for a number of human diseases. They represent a rare population in tissues; for this reason, they require, before being transplanted, an in vitro amplification. This process may induce replicative senescence, thus affecting differentiation and proliferative capacities. Increasing evidence suggests that MSCs from fetal tissues are significantly more plastic and grow faster than MSCs from bone marrow. Here, we compare amniotic fluid mesenchymal stromal cells (AF‐MSCs) and bone marrow mesenchymal stromal cells (BM‐MSCs) in terms of cell proliferation, surface markers, multidifferentiation potential, senescence, and DNA repair capacity. Our study shows that AF‐MSCs are less prone to senescence with respect to BM‐MSCs. Moreover, both cell models activate the same repair system after DNA damage, but AF‐MSCs are able to return to the basal condition more efficiently with respect to BM‐MSCs. Indeed, AF‐MSCs are better able to cope with genotoxic stress that may occur either during in vitro cultivation or following transplantation in patients. Our findings suggest that AF‐MSCs may represent a valid alternative to BM‐MSCs in regenerative medicine, and, of great relevance, the investigation of the mechanisms involved in DNA repair capacity of both AF‐MSCs and BM‐MSCs may pave the way to their rational use in the medical field.