Miracle-dz/UniFAR-FTUs huggingface dataset:
Developmental Bias and Evolution: A Regulatory Network Perspective

A recurrent theme in evolutionary biology is to contrast natural selection and developmental constraint – two forces pitted against each other as competing explanations for organismal form. Despite its popularity, this juxtaposition is deeply misleading. Phenotypic variation is generated by the processes of development, with some variants arising more readily than others—a phenomenon known as “developmental bias. ” Developmental bias and natural selection have often been portrayed as alternative explanations, but this is a false dichotomy: developmental bias can evolve through natural selection, and bias and selection jointly influence phenotypic evolution. Here, we briefly review the evidence for developmental bias and illustrate how it is studied empirically. We describe recent theory on regulatory networks that explains why the influence of genetic and environmental perturbation on phenotypes is typically not uniform, and may even be biased toward adaptive phenotypic variation. We show how bias produced by developmental processes constitutes an evolving property able to impose direction on adaptive evolution and influence patterns of taxonomic and phenotypic diversity. Taking these considerations together, we argue that it is not sufficient to accommodate developmental bias into evolutionary theory merely as a constraint on evolutionary adaptation. The influence of natural selection in shaping developmental bias, and conversely, the influence of developmental bias in shaping subsequent opportunities for adaptation, requires mechanistic models of development to be expanded and incorporated into evolutionary theory. A regulatory network perspective on phenotypic evolution thus helps to integrate the generation of phenotypic variation with natural selection, leaving evolutionary biology better placed to explain how organisms adapt and diversify.
The effect of curing hepatitis C with direct-acting antiviral treatment on endothelial function

Background Epidemiological data suggest that chronic HCV infection (CHC) is associated with increased cardiovascular risk, but it is unknown if it is associated with endothelial dysfunction. We aimed to assess the effect of antiviral treatment on endothelial function in non-cirrhotic adults with CHC. Methods Self-controlled before and after study. All patients had genotype-1 CHC and were treated with 12 weeks of paritaprevir/ritonavir, ombitasvir and dasabuvir (PrOD), with ribavirin added for those with geno-type-1a infection. Endothelial function was assessed at three time points before antiviral treatment, at treatment weeks 1, 4, 8 and 12, and 12 weeks after the end of treatment. The main assessment tools were reactive hyperaemia peripheral arterial tonometry (RHPAT) and serum concentrations of angiopoietin-2 (Ang-2) and E-selectin. Results A total of 16 patients were enrolled. Mean (sd) age was 51.4 (6.9) years and 11 participants (69%) were male. All 16 patients achieved a sustained virological response. The mean (sd) baseline RHPAT index was 2.05 (0.48), and there was no significant change during treatment (mean within-patient change from baseline to end of treatment =-0.23 [0.45]; P= not significant). There was a significant improvement in both mean Ang-2 (baseline 2.44 [0.79] ng/ml, within-patient change -0.60 [0.44]; P<0.001) and E-selectin (baseline 48.7 [21.5] ng/ml, within-patient change -14.4 [13.0]; P<0.001). Conclusions Removing HCV viraemia is associated with a significant improvement in endothelial function as measured by serum markers, but not in bedside micro-vascular reactivity. Chronic HCV viraemia may be associated with endothelial cell dysfunction and therefore long-term cardiovascular risk.
A quantile regression approach to panel data analysis of health‐care expenditure in Organisation for Economic Co‐operation and Development countries

This paper investigates the variation in the effects of various determinants on the per capita health-care expenditure. A total of 28 Organisation for Economic Co-operation and Development countries are studied over the period 1990-2012, employing an instrumental variable quantile regression method for a dynamic panel model with fixed effects. The results show that the determinants of per capita health-care expenditure growth, involving the growth of lagged health spending, of per capita gross domestic product (GDP), of physician density, of elderly population, of life expectancy, of urbanization, and of female labor force participation, do vary with the conditional distribution of the health-care expenditure growth, while the changing patterns are dissimilar. Moreover, we show that Baumol's model of "unbalanced growth" has a significantly positive effect on per capita health spending growth, and its effect is quite stable over the entire distribution. However, the correlation between the components (wage growth and labor productivity growth) of the "Baumol variable" and health expenditure growth is more varied. As a comparison, only the growth of lagged health spending, per capita GDP, and the Baumol variable (or its components) are found related to health spending growth in conditional mean regressions. The prediction results were also quite different between the quantile regression dynamic panel instrumental variable models and linear panel data models. More attention needs to be paid to the varying influence of determinants in health expenditure study.
Continental‐scale nitrogen pollution is shifting forest mycorrhizal associations and soil carbon stocks

Most tree roots on Earth form a symbiosis with either ecto‐ or arbuscular mycorrhizal fungi. Nitrogen fertilization is hypothesized to favor arbuscular mycorrhizal tree species at the expense of ectomycorrhizal species due to differences in fungal nitrogen acquisition strategies, and this may alter soil carbon balance, as differences in forest mycorrhizal associations are linked to differences in soil carbon pools. Combining nitrogen deposition data with continental‐scale US forest data, we show that nitrogen pollution is spatially associated with a decline in ectomycorrhizal vs. arbuscular mycorrhizal trees. Furthermore, nitrogen deposition has contrasting effects on arbuscular vs. ectomycorrhizal demographic processes, favoring arbuscular mycorrhizal trees at the expense of ectomycorrhizal trees, and is spatially correlated with reduced soil carbon stocks. This implies future changes in nitrogen deposition may alter the capacity of forests to sequester carbon and offset climate change via interactions with the forest microbiome.
Changes in Health- Related Quality of Life and Psychosocial Well-being of Breast Cancer Survivors: Findings from a Group- Based Intervention Program in Malaysia

Background There is a lack of evidence on the effectiveness of multifaceted group-based interventions to improve psychological well-being and health-related quality of life (HRQOL) of breast cancer (BCa) survivors in Malaysia. This study is aimed at assessing the effectiveness of such intervention program among the BCa survivors. Materials and Methods This was a group-based intervention program with pre- and post-test design, carried out among BCa survivors (n=37) who were members of Breast Cancer Support Group Centre, Johor Bahru. A validated self-administered questionnaire was used to assess the impact of the program on psychosocial well-being and HRQOL of the participants. Results The mean age of BCa survivors was 58.1 years (SD=9.7), with mean age at diagnosis of 49.9 years (SD=9.6). Majority of them were of Chinese ethnicity, married and had secondary level education, but were unemployed. More than 86% of them were diagnosed to have early BCa diagnosis and have since completed the treatment. There were significant decreases in median depression (p=0.001), anxiety (p<0.001) and stress (p<0.001) scores at post-intervention. More than 85% of the participants rated themselves to have a good or very good QOL at post-intervention, as opposed to 75.9% at pre-intervention. Significant improvements in several HR-QOL domain scores were seen, with psychological score improving the most (p<0.001), followed by social relationship (p=0.002) and physical health (p=0.004). Conclusions Group-based multifaceted intervention can be a viable solution to improve psychosocial well-being of BCa survivors.
The Small Yeast GTPase Rho5 and Its Dimeric GEF Dck1/Lmo1 Respond to Glucose Starvation

Rho5 is a small GTPase of Saccharomyces cerevisiae and a homolog of mammalian Rac1. The latter regulates glucose metabolism and actin cytoskeleton dynamics, and its misregulation causes cancer and a variety of other diseases. In yeast, Rho5 has been implicated in different signal transduction pathways, governing cell wall integrity and the responses to high medium osmolarity and oxidative stress. It has also been proposed to affect mitophagy and apoptosis. Here, we demonstrate that Rho5 rapidly relocates from the plasma membrane to mitochondria upon glucose starvation, mediated by its dimeric GDP/GTP exchange factor (GEF) Dck1/Lmo1. A function in response to glucose availability is also suggested by synthetic genetic phenotypes of a rho5 deletion with gpr1, gpa2, and sch9 null mutants. On the other hand, the role of mammalian Rac1 in regulating the action cytoskeleton does not seem to be strongly conserved in S. cerevisiae Rho5. We propose that Rho5 serves as a central hub in integrating various stress conditions, including a crosstalk with the cAMP/PKA (cyclic AMP activating protein kinase A) and Sch9 branches of glucose signaling pathways.
Bidirectional associations between psychological distress and hearing problems: an 18-year longitudinal analysis of the British Household Panel Survey

Abstract Objective: Hearing problems are a significant public health concern. It has been suggested that psychological distress may represent both a cause and a consequence of hearing problems. Prospective data that allow testing such potential bi-directionality have thus far been lacking. The present study aimed to address this knowledge gap. Random (RE) and fixed effects (FE) panel regression models estimated the association of psychological distress (GHQ-12) and participant-reported hearing problems. Data from 18 annual waves of the British Household Panel Survey were used (n = 10,008). Psychological distress was prospectively associated with self-reported hearing problems in women (multivariable odds ratios (ORs) ≥1.44; one-year time lag ≥ 1.16) and men (ORs ≥ 1.15; time lag ≥ 1.17). Conversely, self-reported hearing problems were associated with increases in psychological distress in both sexes (OR ≥ 1.26; time lag ≥ 1.08). These associations were independent of the analytical strategy and of adjustment for sociodemographic variables, lifestyle factors, and measurement period. We present first evidence of a bidirectional association between psychological distress and self-reported hearing problems. These findings suggest that stress management interventions may contribute to the prevention of self-reported hearing problems, and, in turn, alleviating self-reported hearing problems may reduce psychological distress.
Living With Rheumatoid Arthritis in Spain: A Qualitative Study of Patient Experience and the Role of Health Professionals

The aim of this study was to explore the experience of Spanish people living with rheumatoid arthritis (RA) and the support these people received from health professionals, particularly nurses. Nineteen patients with >1 year diagnosis, disease activity moderate or severe (DAS28 > 3.2), and already treated with disease-modifying antirheumatic drugs (DMARDs) were interviewed. A thematic analysis was performed to interpret the discourses. The difficulties of symptom management; the need for home-adaptations, the difficulties of living with a deteriorating self-image; and the reluctant reliance on medication to control their disease were the main themes that emerged from the discourse analysis of this study. Nurses appeared to have a limited role in RA patients care, and focused primarily on giving information and training for biological therapies. RA patients in Spain would benefit from having contact with specialist nurses who could empower them to self-manage their disease, as happens in other countries.
Effect of synthetic and natural polymers on reducing bauxite residue dust pollution

ABSTRACT Dust emission from the bauxite residue drying areas is of great concern for its serious environmental and health impacts. The application of polymer stabilizers is a promising approach to mitigate such issues. However, limited studies have been done on their application on red sand and the investigation of the effect of polymers on penetration resistance, which is a key mechanical property closely related to the dust control performance. Stabilizers reduce the dust emission potential by forming a crust on the surface of treated material. This paper investigates the relationship of crust properties and dust control performance by applying synthetic (polyacrylamide) and natural (xanthan gum and guar gum) polymers. Results illustrated that the water retention property of treated sand is greatly improved after the application of stabilizers. The thickness of the formed crust decreases with stabilizer concentration. Results from wind tunnel simulation illustrated that the polymer stabilizer offers nearly 8 times longer protective period than water when used as a stabilizing agent. Cationic PAM performed the best, and cationic guar gum outperformed anionic xanthan gum. The penetration resistance is proved in this study to be a primary index for predicting dust control performance of polymer stabilizers. GRAPHICAL ABSTRACT
Lung nodules assessment in ultra-low-dose CT with iterative reconstruction compared to conventional dose CT.

Background To retrospectively assess whether the low-voltage lung CT scan coupled with iterative reconstruction algorithms can be an optimal scanning method for measuring the size and density of lung nodules in cancer patients. Methods Eighty two cancer patients receiving both chest scan with low-voltage (80 kV) and abdomen CT scan with standard voltage (120 kV) were enrolled in this study. Lung nodules were measured manually and semi-automatically by two different computer-aided diagnosis (CAD) systems. The nodules were then divided into large-, medium- and small-size groups based on their largest diameter. Additionally, the nodules were categorized into three different groups according to their density: calcified, solid and partial-solid nodules. The 3D volumes, average diameter and CT value of lung nodules were measured using the two CAD semi-automated systems, and the CT values were compared with regards to the different tube voltages. Furthermore, the accuracy and reliability of CAD systems were validated in the large nodules. Results The scores of subjective evaluation indicated that the quality of lung nodule images yielded optimal clinical diagnostic value for both 80 kV (2.35±0.054) and 120 kV (2.51±0.053) scanning methods, with a strong inter-observer consistency (Kappa =0.848 and 0.829, respectively). Intraclass correlation coefficient (ICC) and Bland-Altman plot revealed that two CAD systems produced the consistent results. Mean CT values of large nodules (n=18) were significantly different between 80 and 120 kV (-28.11±47.39 vs. -39.61±43.32 HU, P<0.05). Notably, the CT value of 80 kV was 33.96% higher than that of 120 kV. Moreover, the volumes of 66 solid lung nodules demonstrated a statistically significant difference (1.68%) between 80 kV group (740.89±156.97 mm3) and 120 kV group (753.48±157.92 mm3, P<0.05). Furthermore, significant differences were observed in the CT values of large nodules between 80 and 120 kV groups (25.64±12.67 vs. 13.89±9.78 HU, P<0.05), but not the maximum diameters (12.08±1.56 vs. 12.13±1.56 mm, P>0.05). Conclusions Our study suggests that detection of lung nodules with ultra-low-dose CT can yield an excellent image quality and optimal diagnostic values as compared to the standard dose CT. Therefore, CT scan with low voltage of 80 kV CT scan can be leveraged to improve the diagnosis and surveillance of lung nodules measured less than 30 mm in diameter. Further investigation with a larger sample size is warranted to confirm our findings, particularly the increased CT values of large nodules and the greater volume of solid nodules after exposure to low-dose CT scan.
Lectins modulate the microbiota of social amoebae

Sticky bacteria tolerated as future food Dictyostelium discoideum amoebae consume bacteria until the supply is exhausted. Then the amoeba cells clump together into a “slug” and initiate a complex multicellular reproductive phase. Specialized cells within aggregates rid the slug of any extracellular bacteria. However, some strains of amoeba tolerate live, intracellular bacteria. Dinh et al. discovered that these carrier strains bear surface lectins that bind Klebsiella bacteria, promote cell entry, and prevent the bacteria from being immediately digested. These bacteria then provide a future food source. Moreover, the internalized bacteria transfer DNA into the amoeba nucleus, resulting in transient genetic transformation. Science, this issue p. 402 Lectins facilitate bacterial uptake by eukaryotic cells through specific receptor recognition. The social amoeba Dictyostelium discoideum maintains a microbiome during multicellular development; bacteria are carried in migrating slugs and as endosymbionts within amoebae and spores. Bacterial carriage and endosymbiosis are induced by the secreted lectin discoidin I that binds bacteria, protects them from extracellular killing, and alters their retention within amoebae. This altered handling of bacteria also occurs with bacteria coated by plant lectins and leads to DNA transfer from bacteria to amoebae. Thus, lectins alter the cellular response of D. discoideum to bacteria to establish the amoebae’s microbiome. Mammalian cells can also maintain intracellular bacteria when presented with bacteria coated with lectins, so heterologous lectins may induce endosymbiosis in animals. Our results suggest that endogenous or environmental lectins may influence microbiome homeostasis across eukaryotic phylogeny.
A robust deconvolution method to disentangle multiple water pools in diffusion MRI

The diffusion‐weighted magnetic resonance imaging (dMRI) signal measured in vivo arises from multiple diffusion domains, including hindered and restricted water pools, free water and blood pseudo‐diffusion. Not accounting for the correct number of components can bias metrics obtained from model fitting because of partial volume effects that are present in, for instance, diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI). Approaches that aim to overcome this shortcoming generally make assumptions about the number of considered components, which are not likely to hold for all voxels. The spectral analysis of the dMRI signal has been proposed to relax assumptions on the number of components. However, it currently requires a clinically challenging signal‐to‐noise ratio (SNR) and accounts only for two diffusion processes defined by hard thresholds. In this work, we developed a method to automatically identify the number of components in the spectral analysis, and enforced its robustness to noise, including outlier rejection and a data‐driven regularization term. Furthermore, we showed how this method can be used to take into account partial volume effects in DTI and DKI fitting. The proof of concept and performance of the method were evaluated through numerical simulations and in vivo MRI data acquired at 3 T. With simulations our method reliably decomposed three diffusion components from SNR = 30. Biases in metrics derived from DTI and DKI were considerably reduced when components beyond hindered diffusion were taken into account. With the in vivo data our method determined three macro‐compartments, which were consistent with hindered diffusion, free water and pseudo‐diffusion. Taking free water and pseudo‐diffusion into account in DKI resulted in lower mean diffusivity and higher fractional anisotropy values in both gray and white matter. In conclusion, the proposed method allows one to determine co‐existing diffusion compartments without prior assumptions on their number, and to account for undesired signal contaminations within clinically achievable SNR levels.
Evaluation of Serum Vitamin D Levels in Patients with Systemic Sclerosis and Healthy Controls: Results of a Pilot Study

Background: The anti-inflammatory, immunomodulatory, and anti-proliferative effects of vitamin D in pathogenesis of autoimmune diseases have been highlighted in recent years but implications of vitamin D deficiency in systemic sclerosis (SSc) remain understudied. Objectives: To evaluate serum vitamin D levels in SSc patients and matched controls. Materials and Methods: Serum vitamin D levels were estimated in 38 (M:F 5:33) patients aged 23–70 years of untreated SSc and age and gender matched healthy controls. Clinical and investigative evaluation for skin sclerosis by modified Rodnan skin score (mRSS), presence of digital ulcers, Raynaud's phenomenon, type of auto-antibodies, systemic involvement, and serum vitamin D levels were performed. Serum vitamin D levels were defined as normal (30–100 ng/ml), insufficient (10–30 ng/ml), and deficient (<10 ng/ml). Results: Serum vitamin D levels (median ± IQR) were 19.5 ± 77.8 ng/ml in 38 patients and 100 ± 31.3 ng/ml in controls each. Vitamin D deficiency in 13 (34.2%) and insufficiency in 10 (26.3%) patients were identified. Only 2 (5.3%) controls had vitamin D insufficiency and the difference was statistically significant (P = 0.001). An inverse relationship was observed between mRSS and serum vitamin D levels. Conclusions: Patients with SSc have significantly lower serum vitamin D levels than healthy controls. Serum vitamin D levels do not correlate well with age, gender, disease duration or its variants, type of auto antibodies, presence of digital ulceration, or systemic involvement but has inverse correlation with skin sclerosis. Better-designed studies will perhaps resolve issues of potential benefits of vitamin D supplementation in modification of disease activity or severity in SSc.
Autophagic cell death associated to Sorafenib in renal cell carcinoma is mediated through Akt inhibition in an ERK1/2 independent fashion

Objectives To fully clarify the role of Mitogen Activated Protein Kinase in the therapeutic response to Sorafenib in Renal Cell Carcinoma as well as the cell death mechanism associated to this kinase inhibitor, we have evaluated the implication of several Mitogen Activated Protein Kinases in Renal Cell Carcinoma-derived cell lines. Materials and methods An experimental model of Renal Cell Carcinoma-derived cell lines (ACHN and 786-O cells) was evaluated in terms of viability by MTT assay, induction of apoptosis by caspase 3/7 activity, autophagy induction by LC3 lipidation, and p62 degradation and kinase activity using phospho-targeted antibodies. Knock down of ATG5 and ERK5 was performed using lentiviral vector coding specific shRNA Results Our data discard Extracellular Regulated Kinase 1/2 and 5 as well as p38 Mitogen Activated Protein Kinase pathways as mediators of Sorafenib toxic effect but instead indicate that the inhibitory effect is exerted through the PI3K/Akt signalling pathway. Furthermore, we demonstrate that inhibition of Akt mediates cell death associated to Sorafenib without caspase activation, and this is consistent with the induction of autophagy, as indicated by the use of pharmacological and genetic approaches. Conclusion The present report demonstrates that Sorafenib exerts its toxic effect through the induction of autophagy in an Akt-dependent fashion without the implication of Mitogen Activated Protein Kinase. Therefore, our data discard the use of inhibitors of the RAF-MEK-ERK1/2 signalling pathway in RCC and support the use of pro-autophagic compounds, opening new therapeutic opportunities for Renal Cell Carcinoma.