Miracle-dz/UniFAR-FTUs huggingface dataset:
The Phosphate Binder Ferric Citrate Alters the Gut Microbiome in Rats with Chronic Kidney Disease

In chronic kidney disease (CKD), the gut microbiome is altered and bacterial-derived uremic toxins promote systemic inflammation and cardiovascular disease. Ferric citrate complex is a dietary phosphate binder prescribed for patients with end-stage kidney disease to treat hyperphosphatemia and secondary hyperparathyroidism. Iron is an essential nutrient in both microbes and mammals. This study was undertaken to test the hypothesis that the large iron load administered with ferric citrate in CKD may significantly change the gut microbiome. Male Sprague-Dawley rats underwent 5/6 nephrectomy to induce CKD. Normal control and CKD rats were randomized to regular chow or a 4% ferric citrate diet for 6 weeks. Fecal and cecal microbial DNA was analyzed via 16S ribosomal RNA gene sequencing on the Illumina MiSeq system. CKD rats had lower abundances of Firmicutes and Lactobacillus compared with normal rats and had lower overall gut microbial diversity. CKD rats treated with ferric citrate had improved hemoglobin and creatinine clearance and amelioration of hyperphosphatemia and hypertension. Ferric citrate treatment increased bacterial diversity in CKD rats almost to levels observed in control rats. The tryptophanase-possessing families Verrucomicrobia, Clostridiaceae, and Enterobacteriaceae were increased by ferric citrate treatment. The uremic toxins indoxyl sulfate and p-cresyl sulfate were not increased with ferric citrate treatment. Verrucomicrobia was largely represented by Akkermansia muciniphila, which has important roles in mucin degradation and gut barrier integrity. In summary, ferric citrate therapy in CKD rats was associated with significant changes in the gut microbiome and beneficial kidney and blood pressure parameters.
RPSE: Reification as Paradigm of Software Engineering

The paper introduces RPSE, Reification as a Paradigm of Software Engineering, and enumerates the most important theoretical and practical problems of the development and application of this paradigm. Main thesis: Software engineering is the reification (materialization of ideas) via the transformation of mental models into code executed on computers . Within the proposed paradigm: 1.All basic processes of software engineering are concrete variants (implementations) of the process of constructing chains of mental and material models I1, I2,. In, M1, M2, . Mm. The last most specific model in this chain is, as a rule, program code. 2.The essence of software engineering is the construction of such chains. 3.All main issues of optimizing the development, its cost, and quality can be reduced to the optimization of construction of the corresponding chain of models.
The impact of fibroblast growth factor-23 on the cardiovascular system in chronic kidney disease

Chronic kidney disease is associated with an accelerated risk of cardiovascular (CV) mortality. Seminal work over the last decade has identified abnormal bone metabolism as an important modulator of the increased CV burden in this cohort. In particular, FGF23, a phosphaturic hormone with serum levels found to be markedly elevated in chronic kidney disease, is independently associated with increased risks of all-cause mortality and CV events. This editorial will discuss the proposed mechanisms linking FGF23 to CV disease in chronic kidney disease, namely, direct cardiac myocyte toxicity, endothelial dysfunction and vascular calcification.
Ameliorating deleterious effects of heat stress on growing Muscovy ducklings using feed withdrawal and cold water

&NA; We studied the effect of feed withdrawal and cold water on the growth performance and health status of 180 Muscovy ducklings (28 days old) during the summer season. The experiment used a 3 × 2 factorial design consisting of 3 and 2 feeding and water systems, respectively. The birds were divided into 6 experimental groups of 30 birds each (10/replicate). The 3 feeding systems were ad libitum, full‐feeding (AD); afternoon, feed withdrawn from 8 am to 2 pm daily (AF); and diurnal, feed withdrawn from 2 pm to 8 am daily (DI). The 2 water systems were tap water (TW) or cold water (CW). The results indicated that the different feeding systems with cold water positively affected the growth performance, dressed carcass, liver, gizzard, meat tenderness, juiciness, susceptibility, body temperature, tonic immobility, and blood biochemistry (glucose, aspartate aminotransferase, alanine aminotransferase, total antioxidant capacity, and malondialdehyde) of Muscovy ducklings. However, no differences in percentages of plumage, leg problems, breast blister scores, and most blood parameters were found among all groups. In conclusion, AF feeding of ducklings in combination with CW during hot conditions was more suitable than other feeding methods.
Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage

Some (re)programming notes on cancer Epithelial cancers develop resistance to targeted therapies in a number of different ways. Several cancer types do so by undergoing phenotypic conversion to a highly aggressive cancer called small cell neuroendocrine carcinoma (SCNC). Whether distinct cancer types accomplish this “reprogramming” through the same mechanism has been unclear. Park et al. show that the same set of oncogenic factors transforms both normal lung and normal prostate epithelial cells into SCNCs that resemble clinical samples (see the Perspective by Kareta and Sage). This convergence of molecular pathways could potentially simplify the development of new therapies for SCNC, which is currently untreatable. Science, this issue p. 91; see also p. 30 Prostate and lung cancers convert to a drug-resistant, lethal form of cancer through the same reprogramming mechanism. The use of potent therapies inhibiting critical oncogenic pathways active in epithelial cancers has led to multiple resistance mechanisms, including the development of highly aggressive, small cell neuroendocrine carcinoma (SCNC). SCNC patients have a dismal prognosis due in part to a limited understanding of the molecular mechanisms driving this malignancy and the lack of effective treatments. Here, we demonstrate that a common set of defined oncogenic drivers reproducibly reprograms normal human prostate and lung epithelial cells to small cell prostate cancer (SCPC) and small cell lung cancer (SCLC), respectively. We identify shared active transcription factor binding regions in the reprogrammed prostate and lung SCNCs by integrative analyses of epigenetic and transcriptional landscapes. These results suggest that neuroendocrine cancers arising from distinct epithelial tissues may share common vulnerabilities that could be exploited for the development of drugs targeting SCNCs.
Is renal tubular cadmium toxicity clinically relevant?

ABSTRACT Background Exposure to cadmium (Cd) has been associated with the development of hypertension, especially in women, but the mechanism of such an association is not understood. We hypothesize that Cd exposure alters renal production of 20-hydroxyeicosatetraenoic acid (20-HETE), which plays an indispensable role in renal salt balance and blood pressure control. Methods We examined long-term Cd exposure in relation to urinary 20-HETE excretion levels, tubular dysfunction and blood pressure measures, using data from a population-based, cross-sectional study that included 115 normotensive and 110 hypertensive women, 33–55 years of age, who lived in Cd contamination areas in Thailand. Results The mean [standard deviation (SD)] blood Cd level of the study subjects was 3.57 (3.3) µg/L, while the mean (SD) urinary Cd and urinary 20-HETE levels were 0.58 (0.47) µg/g creatinine and 1651 (4793) pg/mL, respectively. Elevated 20-HETE levels were associated with a 90% increase in prevalence odds of hypertension (P = 0.029), four times greater odds of having higher urinary Cd levels (P = 0.030) and a 53% increase in odds of having higher levels of tubular dysfunction (P = 0.049), evident from an increase in urinary excretion of β2-microglobulin. In normotensive subjects, an increase in urinary 20-HETE levels from tertile 1 to tertile 3 was associated with a systolic blood pressure increase of 6 mmHg (95% confidence interval 0.3–12, P = 0.040). Conclusions This is the first report that links urinary 20-HETE levels to blood pressure increases in Cd-exposed women, thereby providing a plausible mechanism for associated development of hypertension.
The role of education interventions in improving economic rationality

Educating for economic rationality The hypothesis that education enhances economic decision-making has been surprisingly underexplored. Kim et al. studied this question using a randomized control trial in a sample of 2812 girls in secondary schools in Malawi. Four years after providing financial support for a year's schooling, they presented the subjects with a set of decision problems (for example, allocating funds to immediate versus future expenses) that test economic rationality. The education intervention enhanced both educational outcomes and economic rationality as measured by consistency with utility maximization in the long run. Science, this issue p. 83 An experiment with secondary school students shows that education enhances economic rationality measured with decision problems. Schooling rewards people with labor market returns and nonpecuniary benefits in other realms of life. However, there is no experimental evidence showing that education interventions improve individual economic rationality. We examine this hypothesis by studying a randomized 1-year financial support program for education in Malawi that reduced absence and dropout rates and increased scores on a qualification exam of female secondary school students. We measure economic rationality 4 years after the intervention by using lab-in-the-field experiments to create scores of consistency with utility maximization that are derived from revealed preference theory. We find that students assigned to the intervention had higher scores of rationality. The results remain robust after controlling for changes in cognitive and noncognitive skills. Our results suggest that education enhances the quality of economic decision-making.
Improving High Contention OLTP Performance via Transaction Scheduling

Research in transaction processing has made significant progress in improving the performance of multi-core in-memory transactional systems. However, the focus has mainly been on low-contention workloads. Modern transactional systems perform poorly on workloads with transactions accessing a few highly contended data items. We observe that most transactional workloads, including those with high contention, can be divided into clusters of data conflict-free transactions and a small set of residuals. In this paper, we introduce a new concurrency control protocol called Strife that leverages the above observation. Strife executes transactions in batches, where each batch is partitioned into clusters of conflict-free transactions and a small set of residual transactions. The conflict-free clusters are executed in parallel without any concurrency control, followed by executing the residual cluster either serially or with concurrency control. We present a low-overhead algorithm that partitions a batch of transactions into clusters that do not have cross-cluster conflicts and a small residual cluster. We evaluate Strife against the optimistic concurrency control protocol and several variants of two-phase locking, where the latter is known to perform better than other concurrency protocols under high contention, and show that Strife can improve transactional throughput by up to 2x. We also perform an in-depth micro-benchmark analysis to empirically characterize the performance and quality of our clustering algorithm
JAK VYSOKÉ JE KORPORÁTNÍ DAŇOVÉ ZATÍŽENÍ

The acticle is focused on corporate income tax. The aim of the article is to determine tax rates for comparing corporate tax burden as several methods and rates can be used for comparison of corporate tax burden. Statutory corporate income tax rates are not the right indicator for the comparison of the real economic tax burden so effective corporate tax rate are often used for these purpose. Effective corporate income tax rates can be based on three different methods: macro backward looking, micro backward looking or micro forward looking. Differences between the approaches are used due to differences in data and varying degrees of data aggregation. Following tax rates are mostly used for decisions about asset allocation: average tax rate, effective marginal tax rate EMTR or average effective tax rate EATR. EATR seems to be the most accurate rate for compaing the corporate tax burden due to its complexity. Úvod S pokračující globalizací se kapitál stává stále mobilnějším mezi zeměmi. Daňový systém a výše korporátního daňového zatížení trvale zůstává jedním z rozhodujících faktorů při rozhodování podnikového managementu o alokaci investic. Členské státy Evropské unie (EU) mají v zásadě samostatné daňové systémy a uplatňují samostatné daňové politiky. Uspořádání těchto systémů vychází z rozdílných ekonomických, sociologických, historických a dalších faktorů. Evropský hospodářský a sociální výbor (2006) zmiňuje, že OECD v roce 1990 uvedla, že 60 % světového obchodu probíhá v rámci obchodních skupin. Existence 1 Tento článek vznikl za podpory grantu GAČR 402/08/0067 – Finanční integrace nových členských zemí EU
Immunoregulatory effects of indole-3-carbinol on monocyte-derived macrophages in systemic lupus erythematosus: A crucial role for aryl hydrocarbon receptor

Abstract Macrophages are versatile phagocytic cells in immune system with immunoregulatory functions. However, the removal of apoptotic cells by macrophages is disturbed in systemic lupus erythematosus (SLE). Aryl hydrocarbon receptor (AhR) is a ligand-activated cytoplasmic receptor and transcription factor with diverse effects on immune response. Indole-3-carbinol (I3C) is an AhR agonist which has been implicated as a beneficial factor in regulating inflammation and cytokine expression in murine models of SLE. However, the molecular mechanisms are not thoroughly studied. Here, we aimed to investigate the ex vivo effects of I3C on polarization of monocyte-derived macrophages (MDMs) in SLE patients and the expression of regulatory cytokines upon AhR activation. MDMs from 15 newly diagnosed SLE patients and 10 normal subjects were induced by Jurkat apoptotic bodies (JABs) and treated with I3C. I3C enhanced the nuclear accumulation of AhR among MDMs of SLE patients and altered the expression of AhR target genes including CYP1A1, IL1- β, IDO-1 and MRC-1. The imbalanced expression of pro- and anti- inflammatory cytokines (IL-10, IL-12, TGFβ1, TNFα, IL-23, IL-6 and IFN-γ) was compensated in response to I3C. AhR activation was also associated with the overexpression of M2 markers (CD163) and downregulation of M1 markers (CD86). Thus, macrophages are activated alternatively in response to I3C. The obtained data indicate that I3C-mediated AhR activation possess immunoregulatory effects on macrophages of SLE patients by exerting an obvious downregulation in the expression of pro-inflammatory and overexpression of anti-inflammatory cytokines. Therefore, AhR could be targeted and further investigated as a choice of anti-inflammatory therapies for autoimmune disorders such as SLE.
Dual practice of public hospital physicians in Vietnam

Although many public hospital physicians in Vietnam offer private service on the side, little is known about the magnitude and nature of the phenomenon so-called dual practice, let alone the dynamics between the public and private health sectors. This study investigates how and to what degree public hospital physicians engage in private practice. It also examines the commitment of dual practitioners to the public sector. The analysis is based on a hospital-based survey of 483 physicians at 10 public hospitals in four provinces of Vietnam. Nearly half of the participants in the study sample reported themselves as dual practitioners. Various types of private practice were mentioned. Private practice at health facilities owned by the private sector was the most prevalent, followed by private practice delivered at health facilities owned by the dual practitioners themselves. Private practice inside public hospitals was also noted. Dual practitioners were likely to be senior and hold management positions inside their public hospitals. Substantial income differences were found between dual practitioners and those physicians practicing exclusively in the public sector. The majority of dual practitioners, however, reported the willingness to give up private practice if certain conditions were met, such as a basic salary increase or non-pecuniary benefits. The main reasons dual practitioners gave for not leaving the public sector included a sense of public responsibility and opportunities to gain a broader professional network and more training. This study reiterates the significant challenges associated with dual practice, including its financial implications and possible effects on health care quality and access. The need for a high-quality workforce committed to the public sector is particularly critical, given the possibility of universal insurance coverage. Future research should address the need to improve data collection on physicians' dual practice and incorporate the topic in policy debates on health reform.
CIRCOAST: a statistical hypothesis test for cellular colocalization with network structures

Motivation: Colocalization of structures in biomedical images can lead to insights into biological behaviors. One class of colocalization problems is examining an annular structure (disk-shaped such as a cell, vesicle, or molecule) interacting with a network structure (vascular, neuronal, cytoskeletal, organellar). Examining colocalization events across conditions is often complicated by changes in density of both structure types, confounding traditional statistical approaches since colocalization cannot be normalized to the density of both structure types simultaneously. We have developed a technique to measure colocalization independent of structure density and applied it to characterizing intercellular colocation with blood vessel networks. This technique could be used to analyze colocalization of any annular structure with an arbitrarily shaped network structure. Results: We present the circular colocalization affinity with network structures test (CIRCOAST), a novel statistical hypothesis test to probe for enriched network colocalization in 2D z-projected multichannel images by using agent-based Monte Carlo modeling and image processing to generate the pseudo-null distribution of random cell placement unique to each image. This hypothesis test was validated by confirming that adipose-derived stem cells (ASCs) exhibit enriched colocalization with endothelial cells forming arborized networks in culture and then applied to show that locally-delivered ASCs have enriched colocalization with murine retinal microvasculature in a model of diabetic retinopathy. We demonstrate that the CIRCOAST test provides superior power and type I error rates in characterizing intercellular colocalization compared to generic approaches that are confounded by changes in cell or vessel density. Availability: CIRCOAST source code available at: https://github.com/uva-peirce-cottler-lab/ARCAS. Contact: bac7wj@virginia.edu Supplementary information: Supplementary data are available at Bioinformatics online.
Dual Convolutional Neural Network for Graph of Graphs Link Prediction

Graphs are general and powerful data representations which can model complex real-world phenomena, ranging from chemical compounds to social networks; however, effective feature extraction from graphs is not a trivial task, and much work has been done in the field of machine learning and data mining. The recent advances in graph neural networks have made automatic and flexible feature extraction from graphs possible and have improved the predictive performance significantly. In this paper, we go further with this line of research and address a more general problem of learning with a graph of graphs (GoG) consisting of an external graph and internal graphs, where each node in the external graph has an internal graph structure. We propose a dual convolutional neural network that extracts node representations by combining the external and internal graph structures in an end-to-end manner. Experiments on link prediction tasks using several chemical network datasets demonstrate the effectiveness of the proposed method.
Abordagem preventiva da doença periodontal no paciente diabético: revisão da literatura

Periodontal disease has several phases with different evolution patterns and clinical manifestations. The etiological factor is always the dental biofilm, but it is modulated by the different alteration of susceptible host. The gingivitis and periodontitis are manifestations of periodontal health/disease process. The diabetes mellitus acts as an important factor of risk to the development and progression of the periodontal disease, because the diabetics have larger susceptibility to the infection. The aim of this study is to emphasize the relationship among diabetes mellitus and periodontal disease and to describe the adequate treatment and the prevention of the disease periodontal in diabetic patients. descriptors: Diabetes mellitus Periodontitis Gingivitis Madeiro AT, Passos IA, Figueiredo CRLV. Abordagem preventiva da doença periodontal no paciente diabético: Revisão da literatura Revista de Odontologia da Universidade Cidade de São Paulo 2008 jan-abr; 20(1):76-81
Doxorubicin-loaded dextran-based nano-carriers for highly efficient inhibition of lymphoma cell growth and synchronous reduction of cardiac toxicity

Purpose Cardiac side effects of doxorubicin (Dox) have limited its clinical application. The aim of this study was to explore new Dox-loaded dextran-based nano-carriers (NCs) in efficiently targeting tumor growth with less cardiac toxicity. Methods Inspired by recent reports that polymeric NCs could function as sustained, controlled and targeted drug delivery systems, we developed Dox-loaded NCs which displayed a 2-fold release ratio of Dox in the mimic tumor site condition (pH 5.0 with 10 mM glutathione, GSH) as much as that in systemic circulation condition (pH 7.4). Results Lymphoma cells treated with Dox-NCs had significantly higher intracellular Dox concentrations and more apoptotic induction, with lower P-gp expression, when compared with those treated with Dox alone. The identified mechanism of action, apoptosis, was triggered through survivin reduction and caspase-3 activation. Even in the Dox-resistant cells, Dox-NCs could significantly inhibit cell growth and induce apoptosis. In murine lymphoma xenograft models, Dox-NCs also remarkably significantly retarded tumor growth, assessed by murine weight, and demonstrated less cytotoxicity. Noticeably, apoptotic myocardial cells were decreased in the Dox-NCs-treated group, when compared with the control group, which was consistent with low intracellular Dox concentration in the cardiac cell line H9C2. Conclusion Dox-NCs showed an anti-lymphoma effect with reduced cardiac toxicity in both in vivo and in vitro models and, therefore, could be a potential therapeutic agent in the treatment of lymphoma.