Miracle-dz/UniFAR-FTUs huggingface dataset:
Lactic Acidosis Triggers Starvation Response with Paradoxical Induction of TXNIP through MondoA

Although lactic acidosis is a prominent feature of solid tumors, we still have limited understanding of the mechanisms by which lactic acidosis influences metabolic phenotypes of cancer cells. We compared global transcriptional responses of breast cancer cells in response to three distinct tumor microenvironmental stresses: lactic acidosis, glucose deprivation, and hypoxia. We found that lactic acidosis and glucose deprivation trigger highly similar transcriptional responses, each inducing features of starvation response. In contrast to their comparable effects on gene expression, lactic acidosis and glucose deprivation have opposing effects on glucose uptake. This divergence of metabolic responses in the context of highly similar transcriptional responses allows the identification of a small subset of genes that are regulated in opposite directions by these two conditions. Among these selected genes, TXNIP and its paralogue ARRDC4 are both induced under lactic acidosis and repressed with glucose deprivation. This induction of TXNIP under lactic acidosis is caused by the activation of the glucose-sensing helix-loop-helix transcriptional complex MondoA:Mlx, which is usually triggered upon glucose exposure. Therefore, the upregulation of TXNIP significantly contributes to inhibition of tumor glycolytic phenotypes under lactic acidosis. Expression levels of TXNIP and ARRDC4 in human cancers are also highly correlated with predicted lactic acidosis pathway activities and associated with favorable clinical outcomes. Lactic acidosis triggers features of starvation response while activating the glucose-sensing MondoA-TXNIP pathways and contributing to the “anti-Warburg” metabolic effects and anti-tumor properties of cancer cells. These results stem from integrative analysis of transcriptome and metabolic response data under various tumor microenvironmental stresses and open new paths to explore how these stresses influence phenotypic and metabolic adaptations in human cancers.
Population health management guiding principles to stimulate collaboration and improve pharmaceutical care

Purpose A range of strategies to improve pharmaceutical care has been implemented by population health management (PHM) initiatives. However, which strategies generate the desired outcomes is largely unknown. The purpose of this paper is to identify guiding principles underlying collaborative strategies to improve pharmaceutical care and the contextual factors and mechanisms through which these principles operate. Design/methodology/approach The evaluation was informed by a realist methodology examining the links between PHM strategies, their outcomes and the contexts and mechanisms by which these strategies operate. Guiding principles were identified by grouping context-specific strategies with specific outcomes. Findings In total, ten guiding principles were identified: create agreement and commitment based on a long-term vision; foster cooperation and representation at the board level; use layered governance structures; create awareness at all levels; enable interpersonal links at all levels; create learning environments; organize shared responsibility; adjust financial strategies to market contexts; organize mutual gains; and align regional agreements with national policies and regulations. Contextual factors such as shared savings influenced the effectiveness of the guiding principles. Mechanisms by which these guiding principles operate were, for instance, fostering trust and creating a shared sense of the problem. Practical implications The guiding principles highlight how collaboration can be stimulated to improve pharmaceutical care while taking into account local constraints and possibilities. The interdependency of these principles necessitates effectuating them together in order to realize the best possible improvements and outcomes. Originality/value This is the first study using a realist approach to understand the guiding principles underlying collaboration to improve pharmaceutical care.
Comparison of Vector Stacking, Multi-SVMs Fuzzy Output, and Multi-SVMs Voting Methods for Multiscale VHR Urban Mapping

The objective of this letter is to integrate multiscale information for urban mapping using very high resolution (VHR) imagery. Three multiscale fusion methods were presented: 1) vector stacking (VS); 2) multiple support vector machines (multi-SVMs) fuzzy output; and 3) multi-SVMs voting. Two kinds of spatial features were used to obtain multiscale representations of VHR images: morphological structural features and object-based approaches. In experiments, the Reflective Optics System Imaging Spectrometer-03 Pavia Center and University, the Hyperspectral Digital Imagery Collection Experiment Washington DC Mall, and the Quickbird Beijing data sets were used for algorithm validation. The experimental results revealed that, in most cases, the VS fusion outperformed other methods because it was able to create a new high-dimensional multiscale feature space and enhance the class separability. It was also shown that the multi-SVMs fuzzy fusion could optimize and reorganize the multiscale information effectively. Furthermore, multi-SVMs fuzzy output was better than multi-SVMs voting because the former was able to exploit the probabilistic output, while the latter only considered the crisp classification label. In addition, it is suggested that VS fusion is suitable for morphological features; however, for the object-based classification, the multiscale fusion methods do not necessarily yield better results than the single-scale classification in terms of accuracies.
HIV-specific CD4+ T cells may contribute to viral persistence in HIV controllers.

BACKGROUND Human immunodeficiency virus (HIV)--infected individuals maintaining plasma HIV RNA levels <75 copies/mL in the absence of therapy ("HIV controllers") often maintain high HIV-specific T cell responses, which likely contribute to the control of viral replication. Despite robust immune responses, these individuals never eradicate HIV infection. We hypothesized that HIV-specific CD4(+) T cells might serve as target cells for HIV, contributing to viral persistence in this setting. METHODS We measured frequencies of activated (CD38(+) HLA-DR(+)) and HIV Gag-specific CD4(+) and CD8(+) T cells and plasma- and cell-associated levels of HIV RNA and DNA in a cohort of 38 HIV controllers. RESULTS Although there was no evidence of a relationship between the extent of low-level viremia and the frequency of either activated or HIV-specific CD4(+) T cells, controllers with higher HIV-specific CD4(+) T cell frequencies had higher cell-associated HIV DNA levels (ρ = 0.53; P = .019). Higher activated CD4+ T cell frequencies were also associated with higher levels of cell-associated DNA (P = .027) and RNA (P = .0096). However, there was no evidence of a relationship between cell-associated HIV RNA or DNA levels and HIV-specific CD8(+) T cell frequencies. CONCLUSIONS These data support a model in which strong HIV-specific CD4(+) T cell responses in HIV controllers, while contributing to a potent adaptive immune response, may also contribute to viral persistence, preventing the natural eradication of HIV infection.
LncRNAs as an intermediate in HPV16 promoting myeloid-derived suppressor cell recruitment of head and neck squamous cell carcinoma

The emerging evidence showed that long noncoding RNAs (lncRNAs) are involved in cell growth and apoptosis as well as cancer progression and metastasis of malignant tumor, however, limited data are available on the role of lncRNAs in human papillomavirus (HPV)-associated Head and neck squamous cell carcinomas (HNSCC). Here, we demonstrated that 23.98% of 196 HNSCC cases in Southwest China could be classified as HPV16 infection. The number of MDSCs in HPV-positive HNSCC was significantly higher than normal control, indicating that HPV infection may promote MDSCs aggregation. Then, we applied an array-based approach to monitor the lncRNA expression between HPV-positive HNSCC, HPV-negative HNSCC and normal oral mucous, and obtained 132 different lncRNAs in different HPV infected states of HNSCC. HOTAIR, PROM1, CCAT1, and MUC19 mRNA levels, determined by qRT-PCR were inversely correlated with MDSCs collection of HPV-associated HNSCC in 2 independent patient cohorts. The results may provide a rationale for the further evaluation of lncRNAs as a molecular target to elucidate the molecular mechanism of HPV promoting MDSCs collection of HNSCC.
Analysis and Design of Hollow Helical Springs for Shape Memory Actuators

Shape memory alloys (SMAs) can be exploited successfully to reduce the complexity and the weight of actuators, but the main drawbacks that limit the use of SMAs are the low bandwidth, poor energetic efficiency, and unsatisfactory stroke. This article contributes to enhancing the mechanical, thermal, and electric performances of SMA actuators by providing analysis and design equations for helical springs with hollow round section. By emptying the inefficient material from its center, the hollow section features a lower mass, lower cooling time, and lower heating energy than its solid counterpart for given strength, stiffness, and deflection. The advantages of the hollow construction over solid springs are presented and discussed by means of dimensionless functions. A step-by-step procedure leading to the optimal design of hollow springs with minimum energy consumption is finally proposed.
Physical Activity in End-Stage Renal Disease Patients: The Effects of Starting Dialysis in the First 6 Months after the Transition Period

Objectives: Physical inactivity in end-stage renal disease (ESRD) patients is associated with increased mortality, and might be related to abnormalities in body composition (BC) and physical performance. It is uncertain to what extent starting dialysis influences the effects of ESRD on physical activity (PA). This study aimed to compare PA and physical performance between stage 5 chronic kidney disease (CKD-5) non-dialysis and dialysis patients, and healthy controls, to assess alterations in PA during the transition from CKD-5 non-dialysis to dialysis, and to relate PA to BC. Methods: For the cross-sectional analyses 44 CKD-5 non-dialysis patients, 29 dialysis patients, and 20 healthy controls were included. PA was measured by the SenseWear™ pro3. Also, the walking speed and handgrip strength (HGS) were measured. BC was measured by the Body Composition Monitor©. Longitudinally, these parameters were assessed in 42 CKD-5 non-dialysis patients (who were also part of the cross-sectional analysis), before the start of dialysis and 6 months thereafter. Results: PA was significantly lower in CKD-5 non-dialysis patients as compared to that in healthy controls but not as compared to that in dialysis patients. HGS was significantly lower in dialysis patients as compared to that in healthy controls. Walking speed was significantly lower in CKD-5 non-dialysis patients as compared to that in healthy controls but not as compared to that in dialysis patients. Six months after starting dialysis, activity related energy expenditure (AEE) and walking speed significantly increased. Conclusions: PA is already lower in CKD-5 non-dialysis patients as compared to that in healthy controls and does not differ from that of dialysis patients. However, the transition phase from CKD-5 non-dialysis to dialysis is associated only with a modest improvement in AEE.
Three-dimensional cardiovascular imaging-genetics: a mass univariate framework

Abstract Motivation Left ventricular (LV) hypertrophy is a strong predictor of cardiovascular outcomes, but its genetic regulation remains largely unexplained. Conventional phenotyping relies on manual calculation of LV mass and wall thickness, but advanced cardiac image analysis presents an opportunity for high-throughput mapping of genotype-phenotype associations in three dimensions (3D). Results High-resolution cardiac magnetic resonance images were automatically segmented in 1124 healthy volunteers to create a 3D shape model of the heart. Mass univariate regression was used to plot a 3D effect-size map for the association between wall thickness and a set of predictors at each vertex in the mesh. The vertices where a significant effect exists were determined by applying threshold-free cluster enhancement to boost areas of signal with spatial contiguity. Experiments on simulated phenotypic signals and SNP replication show that this approach offers a substantial gain in statistical power for cardiac genotype-phenotype associations while providing good control of the false discovery rate. This framework models the effects of genetic variation throughout the heart and can be automatically applied to large population cohorts. Availability and implementation The proposed approach has been coded in an R package freely available at https://doi.org/10.5281/zenodo.834610 together with the clinical data used in this work. Supplementary information Supplementary data are available at Bioinformatics online.
Infrared Spectra of Asphalts

A procedure for preparing thin films of airblown asphalts and a spectroscopic study of such films throughout the infrared region of 2.5 to 15 microns are described. The relationship of transmittance of several absorption bands with the durability of the asphalt is discussed. Exposure to ultraviolet radiation produced changes in transmittance at four wavelengths which, in a series of asphalts studied, showed statistically significant correlations with durability.
CMOS-compatible contact technology for Si photonics

In this paper, we present a short overview of the CMOS-compatible contact technology developed in our group on n-InP and p-InGaAs for Si photonic applications. Obtained results cover a wide spectrum: from surface preparation and solid-state reaction to electrical results and laser integration. The metallurgy of several systems including Ni / InGaAs, Ni / InP, Ti / InGaAs and Ti / InP has been studied. Most of the metallizations studied provide efficient solutions for contacting n-InP and p-InGaAs. Finally, guidelines for integrating low resistivity contacts are proposed.
Independent Transitions between Monsoonal and Arid Biomes Revealed by Systematic Revison of a Complex of Australian Geckos (Diplodactylus; Diplodactylidae)

How the widespread expansion and intensification of aridity through the Neogene has shaped the Austral biota is a major question in Antipodean biogeography. Lineages distributed across wide aridity gradients provide opportunities to examine the timing, frequency, and direction of transitions between arid and mesic regions. Here, we use molecular genetics and morphological data to investigate the systematics and biogeography of a nominal Australian gecko species (Diplodactylus conspicillatus sensu lato) with a wide distribution spanning most of the Australian Arid Zone (AAZ) and Monsoonal Tropics (AMT). Our data support a minimum of seven genetically distinct and morphologically diagnosable taxa; we thus redefine the type species, ressurrect three names from synonymy, and describe three new species. Our inferred phylogeny suggests the history and diversification of lineages in the AAZ and AMT are intimately linked, with evidence of multiple independent interchanges since the late Miocene. However, despite this shared history, related lineages in these two regions also show evidence of broadly contrasting intra-regional responses to aridification; vicarance and speciation in older and increasingly attenuated mesic regions, versus a more dynamic history including independent colonisations and recent range expansions in the younger AAZ.
Avoiding Toxic Levels of Essential Minerals: A Forgotten Factor in Deer Diet Preferences

Ungulates select diets with high energy, protein, and sodium contents. However, it is scarcely known the influence of essential minerals other than Na in diet preferences. Moreover, almost no information is available about the possible influence of toxic levels of essential minerals on avoidance of certain plant species. The aim of this research was to test the relative importance of mineral content of plants in diet selection by red deer (Cervus elaphus) in an annual basis. We determined mineral, protein and ash content in 35 common Mediterranean plant species (the most common ones in the study area). These plant species were previously classified as preferred and non-preferred. We found that deer preferred plants with low contents of Ca, Mg, K, P, S, Cu, Sr and Zn. The model obtained was greatly accurate identifying the preferred plant species (91.3% of correct assignments). After a detailed analysis of these minerals (considering deficiencies and toxicity levels both in preferred and non-preferred plants) we suggest that the avoidance of excessive sulphur in diet (i.e., selection for plants with low sulphur content) seems to override the maximization for other nutrients. Low sulphur content seems to be a forgotten factor with certain relevance for explaining diet selection in deer. Recent studies in livestock support this conclusion, which is highlighted here for the first time in diet selection by a wild large herbivore. Our results suggest that future studies should also take into account the toxicity levels of minerals as potential drivers of preferences.
White matter changes after stroke in type 2 diabetic rats measured by diffusion magnetic resonance imaging

Diffusion-related magnetic resonance imaging parametric maps may be employed to characterize white matter of brain. We hypothesize that entropy of diffusion anisotropy may be most effective for detecting therapeutic effects of bone marrow stromal cell treatment of ischemia in type 2 diabetes mellitus rats. Type 2 diabetes mellitus was induced in adult male Wistar rats. These rats were then subjected to 2 h of middle cerebral artery occlusion, and received bone marrow stromal cell (5 × 106, n = 8) or an equal volume of saline (n = 8) via tail vein injection at three days after middle cerebral artery occlusion. Magnetic resonance imaging was performed on day one and then weekly for five weeks post middle cerebral artery occlusion. The diffusion metrics complementarily permitted characterization of axons and axonal myelination. All six magnetic resonance imaging diffusion metrics, confirmed by histological measures, demonstrated that bone marrow stromal cell treatment significantly (p < 0.05) improved magnetic resonance imaging diffusion indices of white matter in type 2 diabetes mellitus rats after middle cerebral artery occlusion compared with the saline-treated rats. Superior to the fractional anisotropy metric that provided measures related to organization of neuronal fiber bundles, the entropy metric can also identify microstructures and low-density axonal fibers of cerebral tissue after stroke in type 2 diabetes mellitus rats.
PPARα activation alleviates damage to the cytoskeleton during acute myocardial ischemia/reperfusion in rats

The cytoskeleton serves an important role in maintaining cellular morphology and function, and it is a substrate of calpain during myocardial ischemia/reperfusion (I/R) injury (MIRI). Calpain may be activated by endoplasmic reticulum (ER) stress during MIRI. The activation of peroxisome proliferator-activated receptor α (PPARα) may inhibit ischemia/reperfusion damage by regulating stress reactions. The present study aimed to determine whether the activation of PPARα protects against MIRI-induced cytoskeletal degradation, and investigated the underlying mechanism involved. Wistar rats were pretreated with or without fenofibrate and subjected to left anterior descending coronary artery ligation for 45 min, followed by 120 min of reperfusion. Calpain activity and the expression of PPARα, desmin and ER stress parameters were evaluated. Electrocardiography was performed and cardiac function was evaluated. The ultrastructure was observed under transmission electron microscopy. I/R significantly induced damage to the cytoskeleton in cardiomyocytes and cardiac dysfunction, all of which were improved by PPARα activation. In addition, I/R increased ER stress and calpain activity, which were significantly decreased in fenofibrate-pretreated rat heart tissue. The results suggested that PPARα activation may exert a protective effect against I/R in the myocardium, at least in part via ER stress inhibition. Suppression of ER stress may be an effective therapeutic target for protecting the I/R myocardium.
Myocardial Structure, Function, and Scar in Patients With Type 1 Diabetes Mellitus

Background— We report relationships between cardiovascular disease risk factors and myocardial structure, function, and scar in patients with type 1 diabetes mellitus in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. Methods and Results— Cardiac magnetic resonance was obtained in 1017 patients with type 1 diabetes mellitus. Gadolinium cardiac magnetic resonance was also obtained in 741 patients. The mean age was 49±7 years; 52% were men; and mean duration of diabetes mellitus was 28±5 years. Associations of cardiovascular disease risk factors with cardiac magnetic resonance parameters were examined with linear and logistic regression models. History of macroalbuminuria was positively associated with left ventricular mass (by 14.8 g), leading to a significantly higher ratio of left ventricular mass to end-diastolic volume (by 8%). Mean hemoglobin A1c levels over the preceding 22 years were inversely associated with end-diastolic volume (−3.0 mL per unit mean hemoglobin A1c percent) and stroke volume (−2.3 mL per unit mean hemoglobin A1c percent) and positively related to the ratio of elevated left ventricular mass to end-diastolic volume (0.02 g/mL per unit). The overall prevalence of myocardial scar was 4.3% by cardiac magnetic resonance and 1.4% by clinical adjudication of myocardial infarction. Both mean hemoglobin A1c (odds ratio, 1.5 [95% confidence interval, 1.0–2.2] per unit) and macroalbuminuria (odds ratio, 3.5 [95% confidence interval, 1.2–9.9]) were significantly associated with myocardial scar and traditional cardiovascular disease risk factors. Conclusions— In addition to traditional cardiovascular disease risk factors, elevated mean hemoglobin A1c and macroalbuminuria were significantly associated with alterations in left ventricular structure and function. The prevalence of myocardial scar was 4.3% in this subcohort of DCCT/EDIC participants with relatively preserved renal function. Clinical Trial Registration— URL: http://www.clinicaltrials. gov. Unique identifiers: NCT00360893 and NCT00360815.