Miracle-dz/UniFAR-FTUs huggingface dataset:
The flaws in the detail of an observational study on transcatheter aortic valve implantation versus surgical aortic valve replacement in intermediate-risks patients

The PARTNER group recently published a comparison between the latest generation SAPIEN 3 transcatheter aortic valve implantation (TAVI) system (Edwards Lifesciences, Irvine, CA, USA) and surgical aortic valve replacement (SAVR) in intermediate-risk patients, apparently demonstrating superiority of the TAVI and suggesting that TAVI might be the preferred treatment method in this risk class of patients. Nonetheless, assessment of the non-randomized methodology used in this comparison reveals challenges that should be addressed in order to elucidate the validity of the results. The study by Thourani and colleagues showed several major methodological concerns: suboptimal methods in propensity score analysis with evident misspecification of the propensity scores (PS; no adjustment for the most significantly different covariates: left ventricular ejection fraction, moderate-severe mitral regurgitation and associated procedures); use of PS quintiles rather than matching; inference on not-adjusted Kaplan-Meier curves, although the authors correctly claimed for the need of balancing score adjusting for confounding factors in order to have unbiased estimates of the treatment effect; evidence of poor fit; lack of data on valve-related death.These methodological flaws invalidate direct comparison between treatments and cannot support authors' conclusions that TAVI with SAPIEN 3 in intermediate-risk patients is superior to surgery and might be the preferred treatment alternative to surgery.
Assessment of nasal resistance using computational fluid dynamics

Abstract Anterior rhinomanometry is the current gold standard for the objective assessment of nasal breathing by determining the nasal resistance. However, computational fluid dynamics would allow spatially and temporally well- resolved investigation of additional flow parameters. In this study, measured values of nasal resistance are compared with measured values. An unclear discrepancy between the two methods was found, suggesting further investigation.
Inside Out: Two Jointly Predictive Models for Word Representations and Phrase Representations

Distributional hypothesis lies in the root of most existing word representation models by inferring word meaning from its external contexts. However, distributional models cannot handle rare and morphologically complex words very well and fail to identify some fine-grained linguistic regularity as they are ignoring the word forms. On the contrary, morphology points out that words are built from some basic units, i.e., morphemes. Therefore, the meaning and function of such rare words can be inferred from the words sharing the same morphemes, and many syntactic relations can be directly identified based on the word forms. However, the limitation of morphology is that it cannot infer the relationship between two words that do not share any morphemes. Considering the advantages and limitations of both approaches, we propose two novel models to build better word representations by modeling both external contexts and internal morphemes in a jointly predictive way, called BEING and SEING. These two models can also be extended to learn phrase representations according to the distributed morphology theory. We evaluate the proposed models on similarity tasks and analogy tasks. The results demonstrate that the proposed models can outperform state-of-the-art models significantly on both word and phrase representation learning.
Phytoremediation Potential of Tomato (Lycopersicon Esculentum Mill) in Artificially Contaminated Soils

This study investigated the uptake and distribution of heavy metals in tomato (Lycopersicon esculentum Mill) in artificially contaminated soil. The seeds were germinated in trays filled with typical farm soil and at its third truly leaf, transplanted in soil pots contaminated with low and high levels of copper, iron, cadmium and nickel. The elemental distributions of the heavy metals in the plant organs were determined after harvesting stage. The uptake and distribution of the three heavy metals Fe, Cd and Ni were accumulated in the different organs of tomato in decreasing pattern of root>stem>leaf>fruit, while Cu has root>fruit>stem>leaf order were observed. This pattern of distribution in the plant organ exhibit the typical pattern of an excluder plant with higher concentration of metals accumulated in the roots than in the shoots. The decreasing pattern of the bioconcentration factor (BCF) showed that the ability of tomato to accumulate heavy metals was reduced as the level of contamination is increased.
Low back pain and gastroesophageal reflux in patients with COPD: the disease in the breath

COPD is a worsening condition that leads to a pathologic degeneration of the respiratory system. It represents one of the most important causes of mortality and morbidity in the world, and it is characterized by the presence of associated comorbidity. This article analyzes gastroesophageal reflux disease (GERD) and low back pain (LBP) in patients with COPD and tries to produce anatomo-clinical considerations on the reasons of the presence of these comorbidities. The considerations of the authors are based on the anatomic functions and characteristics of the respiratory diaphragm that are not always considered, from which elements useful to comprehend the symptomatic status of the patient can be deduced, finally improving the therapeutic approach. The information contained in the article can be of help to the clinician and for physiotherapy, and to all health professionals who gravitate around the patient’s care, improving the approach to the diaphragm muscle.
A novel acetyltransferase p300 inhibitor ameliorates hypertension-associated cardio-renal fibrosis

ABSTRACT Hypertension-associated end-organ damage commonly leads to cardiac and renal fibrosis. As no effective anti-fibrotic therapy currently exists, the unchecked progression of fibrogenesis manifests as cardio-renal failure and early death. We have previously shown that FATp300—p300 with intrinsic factor acetyltransferase activity—is an essential epigenetic regulator of fibrogenesis, and is elevated in several fibrotic tissues. In this report, we investigate the therapeutic efficacy of a novel FATp300 inhibitor, L002, in a murine model of hypertensive cardio-renal fibrosis. Additionally, we examine the effects of L002 on cellular pro-fibrogenic processes and provide mechanistic insights into its antifibrogenic action. Utilizing cardiac fibroblasts, podocytes, and mesangial cells, we demonstrate that L002 blunts FATp300-mediated acetylation of specific histones. Further, incubating cells with L002 suppresses several pro-fibrogenic processes including cellular proliferation, migration, myofibroblast differentiation and collagen synthesis. Importantly, systemic administration of L002 in mice reduces hypertension-associated pathological hypertrophy, cardiac fibrosis and renal fibrosis. The anti-hypertrophic and anti-fibrotic effects of L002 were independent of blood pressure regulation. Our work solidifies the role of epigenetic regulator FATp300 in fibrogenesis and establishes it as a pharmacological target for reducing pathological matrix remodeling and associated pathologies. Additionally, we discover a new therapeutic role of L002, as it ameliorates hypertension-induced cardio-renal fibrosis and antagonizes pro-fibrogenic responses in fibroblasts, podocytes and mesangial cells.
Predicting Summer Site Occupancy for an Invasive Species, the Common Brushtail Possum (Trichosurus vulpecula), in an Urban Environment

Invasive species are often favoured in fragmented, highly-modified, human-dominated landscapes such as urban areas. Because successful invasive urban adapters can occupy habitat that is quite different from that in their original range, effective management programmes for invasive species in urban areas require an understanding of distribution, habitat and resource requirements at a local scale that is tailored to the fine-scale heterogeneity typical of urban landscapes. The common brushtail possum (Trichosurus vulpecula) is one of New Zealand’s most destructive invasive pest species. As brushtail possums traditionally occupy forest habitat, control in New Zealand has focussed on rural and forest habitats, and forest fragments in cities. However, as successful urban adapters, possums may be occupying a wider range of habitats. Here we use site occupancy methods to determine the distribution of brushtail possums across five distinguishable urban habitat types during summer, which is when possums have the greatest impacts on breeding birds. We collected data on possum presence/absence and habitat characteristics, including possible sources of supplementary food (fruit trees, vegetable gardens, compost heaps), and the availability of forest fragments from 150 survey locations. Predictive distribution models constructed using the programme PRESENCE revealed that while occupancy rates were highest in forest fragments, possums were still present across a large proportion of residential habitat with occupancy decreasing as housing density increased and green cover decreased. The presence of supplementary food sources was important in predicting possum occupancy, which may reflect the high nutritional value of these food types. Additionally, occupancy decreased as the proportion of forest fragment decreased, indicating the importance of forest fragments in determining possum distribution. Control operations to protect native birds from possum predation in cities should include well-vegetated residential areas; these modified habitats not only support possums but provide a source for reinvasion of fragments.
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of dietary fatty acids. The expression of genes involved in several lipid metabolic processes, as well as fish health and immune response, in both liver and anterior intestine were altered in fish fed the GM-derived oils. This showed a similar pattern to that observed in WCO-fed fish reflecting the hybrid fatty acid profile of the new oils. Overall the data indicated that the GM-derived oils could be suitable alternatives to dietary FO in sea bream. Omega-3 (n-3) long-chain
Robust three-factor remote user authentication scheme with key agreement for multimedia systems

As the fast growth of multimedia information, the security of multimedia systems is becoming a rather important topic nowadays. Multimedia systems are often suffering attacks when users access the information and online services. Because of the excellent features of the biometric, many biometric-based three-factor remote user authentication schemes have been proposed to provide high level of security for different network-based application systems. Recently, An pointed out the weaknesses of Das's three-factor remote user authentication scheme and proposed an improved biometric-based three-factor remote user authentication scheme. An's scheme improves the security problems of previous schemes while keeping the efficiency. However, after detailed analysis, we find that An's scheme exists some weaknesses such as vulnerable to denial-of-service attack and forgery attack, cannot detect unauthorized login quickly, and does not provide session key agreement. In order to provide high level of security for multimedia systems, we design a robust three-factor remote user authentication scheme with key agreement using elliptic curve cryptosystem. Copyright © 2014 John Wiley & Sons, Ltd.
Higher-order concurrent programs with finite communication topology (extended abstract)

Concurrent ML (CML) is an extension of the functional language Standard ML(SML) with primitives for the dynamic creation of processes and channels and for the communication of values over channels. Because of the powerful abstraction mechanisms the communication topology of a given program may be very complex and therefore an efficient implementation may be facilitated by knowledge of the topology. This paper presents an analysis for determining when a bounded number of processes and channels will be generated. The analysis proceeds in two stages. First we extend a polymorphic type system for SML to deduce not only the type of CML programs but also their communication behaviour expressed as terms in a new process algebra. Next we develop an analysis that given the communication behaviour predicts the number of processes and channels required during the execution of the CML program. The correctness of the analysis is proved using a subject reduction property for the type system.
The formation and evolution of frost flowers and related phenomena

Frost flowers are hoarfrost–like clusters of ice crystals that are typically found on young sea ice. Their presence on the ice surface can dramatically alter surface albedo. Their high surface area and salinity have been linked to increased levels of the ozone depleting chemical, bromine monoxide (BrO), in polar regions. In this thesis, I investigate the growth of frost flowers and related phenomena mathematically, and describe a new experimental approach for the reliable growth of frost flowers in the laboratory. First I investigate the dynamics of surface–melted films on ice. These are microscopic liquid films that exist in equilibrium between bulk solid and gas phases at temperatures close to the melting point. Ice has been shown to surface melt against air. I derive the equations of motion for the evolution of the interface and apply them to the case of a grain–boundary groove between two ice crystals. I demonstrate that the equations reduce to Mullins’ equation for the evolution of a grain–boundary groove (see Mullins, 1957), but with an explicit transport parameter. Next, I describe a model for evaporation or condensation of a solid (or liquid) in contact with a gas phase consisting of vapour and an inert gas. I derive a new regime diagram that describes the vapour properties at the interface in terms of relative humidity and temperature. A regime exists where supersaturation exists directly above the interface even though the solid is evaporating. I hypothesise that natural frost flowers normally grow in this regime. The stability of the interface is investigated by linear and nonlinear stability analyses. I show that in these calculations the interface is stable due to the high thermal conductivity of the solid relative to that of air. I also show nonlinearly that this does not rule out the possibility of surface instability. Experiments are conducted and show good agreement with theory. I describe an outline for a model of the areal coverage of frost flowers as a function of time. Growth velocity and nucleation rate are shown to be important parameters. Finally I derive a model for an instability observed in evaporatively grown salt trees by Du & Stone (1996). The instability wavelength is shown to be relatively independent of the thickness of the salty film covering the crystal, taking a value 18±2μm. However, the growth rate of the instability reduces as the film thins, owing to the presence of the evaporating liquid interface near the salt–liquid interface. Results are applicable to growth of brine covered frost flowers.
A Mechanism‐Based Pharmacokinetic/Pharmacodynamic Model for Bococizumab, a Humanized Monoclonal Antibody Against Proprotein Convertase Subtilisin/Kexin Type 9, and Its Application in Early Clinical Development

Bococizumab (RN316/PF‐04950615), a humanized monoclonal antibody, binds to secreted proprotein convertase subtilisin/kexin type 9 (PCSK9) and prevents its downregulation of low‐density lipoprotein receptor, leading to improved clearance and reduction of low‐density lipoprotein cholesterol (LDL‐C) in plasma. A mechanism‐based drug‐target binding model was developed, accounting for bococizumab, PCSK9, and LDL‐C concentrations and the effects of concomitant administration of statins. This model was utilized to better understand the pharmacokinetic/pharmacodynamic (PK/PD) data obtained from 3 phase 1 and 2 phase 2a clinical studies. First, simulations performed with this model demonstrated that the conventional method of the area‐under‐the‐curve ratio for bioavailability determination underestimated the subcutaneous bioavailability of bococizumab due to its target‐mediated disposition. Second, a covariate model component for statin effects on bococizumab PK/PD was characterized, including a description of the decreased baseline LDL‐C, increased baseline PCSK9, and increased LDL‐C lowering with concomitant use of statins. Last, the impact of the dosing regimens with and without a dose holiday on bococizumab's LDL‐C–lowering effectiveness was shown to be predictable due to the well‐characterized PK‐PD relationship.
Monaural Voiced Speech Segregation Based on Dynamic Harmonic Function

Correlogram is an important representation for periodic signals. It is widely used in pitch estimation and source separation. For these applications, major problems of correlogram are its low resolution and redundant information. This paper proposes a voiced speech segregation system based on a newly introduced concept called dynamic harmonic function (DHF). In the proposed system, conventional correlograms are further processed by replacing the autocorrelation function (ACF) with DHF. The advantages of DHF are: 1) peak's width is adjustable by controlling the variance of the Gaussian function and 2) the invalid peaks of ACF, not at the pitch period, tend to be suppressed. Based on DHF, pitch detection and effective source segregation algorithms are proposed. Our system is systematically evaluated and compared with the correlogram-based system. Both the signal-to-noise ratio results and the perceptual evaluation of speech quality scores show that the proposed system yields substantially better performance.
Glioma cells promote angiogenesis through the release of exosomes containing long non-coding RNA POU3F3.

OBJECTIVE Angiogenesis is a key event in the progression of gliomas, and emerging evidence suggests that exosomes are signaling extracellular organelles that modulate the tumor microenvironment and promote angiogenesis and tumor progression. This study aimed to explore the mechanism by which glioma-derived exosomes affect angiogenesis. MATERIALS AND METHODS qRT-PCR was used to determine the expression level of linc-POU3F3 in glioma tissue as well as glioma cell lines. Ultrafiltration combined with a purification method was used to isolate exosomes derived from A172 cells (A172-Exo) and linc-POU3F3 shRNA-treated A172 cells (shA172-Exo). Transmission electron microscopy, Western blot and tunable resistive pulse sensing (TRPS) were used to identify exosomes. In vitro migration, proliferation, and tube formation experiments, as well as in vivo CAM assays, were used to analyze the pro-angiogenesis ability of exosomes. qRT-PCR and Western blot were used to identify expression levels of angiogenesis-related genes and proteins in human brain microvascular endothelial cells (HBMECs) after being cultured with exosomes. RESULTS The levels of linc-POU3F3 were upregulated in glioma tissue and significantly correlated with the advanced tumor stage. A172 cells exhibited the highest expression level. A172-Exo was similar to shA172-Exo (50-100 nm in diameter) and expressed Alix, Tsg101 and CD9, while the expression level of linc-POU3F3 in A172-Exo was significantly higher than that in shA172-Exo. HBMECs rapidly internalized A172-Exo and shA172-Exo, and the linc-POU3F3 expression level in HBMECs treated with A172-Exo was significantly higher than the level in HBMECs treated with shA172-Exo. A172-Exo exhibited better function in promoting HBMECs migration, proliferation, tubular-like structure formation in vitro and arteriole formation in vivo. The gene and protein expression level of bFGF, bFGFR, VEGFA, and Angio in HBMECs treated with A172-Exo was much higher than that of HBMECs treated with shA172-Exo. CONCLUSIONS These results indicated that gliomas can induce angiogenesis by secreting exosomes enriched in linc-POU3F3. Exosomes and lncRNA-POU3F3 may, therefore, function as a putative therapeutic target in glioma.
Metformin attenuates susceptibility to inflammation-induced preterm birth in mice with higher endocannabinoid levels†

Abstract Premature decidual senescence is a contributing factor to preterm birth. Fatty acid amide hydrolase mutant females (Faah−/−) with higher endocannabinoid levels are also more susceptible to preterm birth upon lipopolysaccharide (LPS) challenge due to enhanced decidual senescence; this is associated with mitogen-activated protein kinase p38 activation. Previous studies have shown that mechanistic target of rapamycin complex 1 (mTORC1) contributes to decidual senescence and promotes the incidence of preterm birth. In this study, we sought to attenuate premature decidual aging in Faah−/− females by targeting mTORC1 and p38 signaling pathways. Because metformin is known to inhibit mTOR and p38 signaling pathways, Faah−/− females were treated with metformin. These mice had a significantly lower preterm birth incidence with a higher rate of live birth after an LPS challenge on day 16 of pregnancy; metformin treatment did not affect placentation or neonatal birth weight. These results were associated with decreased levels of p38, as well as pS6, a downstream mediator of mTORC1 activity, in day 16 Faah−/− decidual tissues. Since metformin treatment attenuates premature decidual senescence with limited side effects during pregnancy, careful use of this drug may be effective in ameliorating specific adverse pregnancy events. Summary Sentence Metformin treatment attenuates premature decidual senescence caused by higher endocannabinoid levels and susceptibility to inflammation-induced preterm birth in mice.
Repair of UVB-induced DNA damage is reduced in melanoma due to low XPC and global genome repair

UVB exposure leads to DNA damage, which when unrepaired induces C>T transitions. These mutations are found throughout the melanoma genome, particularly in non-transcribed regions. The global genome repair (GGR) branch of nucleotide excision repair (NER) is responsible for repairing UV-induced DNA damage across non-transcribed and silent regions of the genome. This study aimed to examine the relationship between UVB and GGR in melanoma. DNA repair capacity and relative expression of NER in melanocytes and melanoma cell lines before and after treatment with UVB was quantified. Transcript expression from 196 melanomas was compared to clinical parameters including solar elastosis and whole transcriptome data collected. Melanoma cell lines showed significantly reduced DNA repair when compared to melanocytes, most significantly in the S phase of the cell cycle. Expression of GGR components XPC, DDB1 and DDB2 was significantly lower in melanoma after UVB. In the melanoma tumours, XPC expression correlated with age of diagnosis and low XPC conferred significantly poorer survival. The same trend was seen in the TCGA melanoma dataset. Reduced GGR in melanoma may contribute to the UV mutation spectrum of the melanoma genome and adds further to the growing evidence of the link between UV, NER and melanoma.