Miracle-dz/UniFAR-FTUs huggingface dataset:
Slight cognitive impairment and magnetic resonance imaging abnormalities but normal school levels in children treated for acute lymphoblastic leukemia with chemotherapy only.

OBJECTIVES To investigate persistent neuropsychologic late effects in children treated for acute lymphoblastic leukemia at a young age with chemotherapy only by means of serial neuropsychologic assessments (NPAs), magnetic resonance imaging (MRI) of the brain, and evaluation of school levels. STUDY DESIGN Consecutive patients (n = 17) had 2 extensive NPAs (12 psychometric measures) after cessation of therapy. Test results were compared with those of both healthy control subjects and 28 previously treated children who received cranial irradiation. MRI findings were related to test scores. School levels were evaluated in the patients and their healthy siblings. RESULTS Initial participation (n = 17) and availability of the study group after 8 years of follow-up were 100%. Significant group differences between patients who received chemotherapy and healthy control subjects were found for memory and fine-motor functioning. The 17 patients combined showed 16 deficits on various test measures. MRI abnormalities were seen in 6 children, but these did not correlate with cognitive performance. No differences in school levels were seen when the patients who received chemotherapy were compared with their siblings. The current nonirradiated patients demonstrated significantly better test results and significantly fewer learning disabilities and MRI abnormalities than did the previously irradiated group. CONCLUSION Treatment with chemotherapy only may be associated with some cognitive impairment. However, these children attained normal school levels.
Identification of gut-derived metabolites of maslinic acid, a bioactive compound from Olea europaea L.

SCOPE Maslinic acid has been described to exert a chemopreventive activity in colon cancer. Hereby, we determined maslinic acid and its metabolites in the rat intestine previous oral administration as a first step in elucidating whether this triterpene might be used as a nutraceutical. METHODS AND RESULTS Maslinic acid was orally administered at 1, 2, and 5 mg/kg to male Sprague-Dawley for 2 days. At 24 h after the last administration, the content of the duodenum and jejunum, ileum, cecum, and colon was collected and extracted with methanol 80% prior to LC-APCI-MS analysis. The developed method was validated providing suitable sensitivity (LOQ of 5 nM), good recovery (97.8 ± 3.6%), linear correlation, and appropriate precision (< 9%). Maslinic acid was detected in all the segments with higher concentrations in the distal part of the intestine. LC-APCI-LTQ-ORBITRAP-MS allowed the identification of 11 gut-derived metabolites that were formed by mono-, dihydroxylation, and dehydrogenation reactions. CONCLUSION Maslinic acid undergoes phase I reactions resulting in a majority of monohydroxylated metabolites without the presence of phase II derivatives. The high concentration of maslinic acid achieved in the intestine suggests that it could exert a beneficial effect in the prevention of colon cancer.
ANALYSIS OF POWER MARKET STABILITY

Power market makes resources optimally allocating by market mechanism, of which the stability study is significant for regulating the supply and demand of power market. For a kind of dynamic power market models with congestion, this paper provides a series of sufficient conditions to determine the stability of power market. Under those sufficient conditions, the stability of market models can be obtained by less symbolic computation or even without computation. So power market stability can be determined more conveniently and accurately. In addition, the theoretical results in this paper can be used to reasonably explain the unstable phenomena of power market proposed by Alvarado, which also provide a theoretical basis to control the stability of power market.
Targeted Therapy in the Treatment of Metastatic Renal Cell Cancer

The treatment of metastatic renal cell carcinoma (MRCC) has evolved from being predominantly cytokine-based to being grounded in the use of drugs targeting vascular endothelial growth factor, platelet-derived growth factor and mammalian target of rapamycin (mTOR) pathways. New agents including the small-molecule targeted inhibitors sunitinib, sorafenib and temsirolimus and the monoclonal antibody bevacizumab have shown anti-tumor efficacy and have become the standard of care for most patients. Sunitinib and temsirolimus have shown significant improvements in overall survival (OS), in the first-line setting, when compared with interferon. Sorafenib has demonstrated prolonged progression-free survival (PFS) in a phase III study in comparison with placebo in the second-line setting. More recently, two phase III studies have compared bevacizumab and interferon with interferon alone. Both studies showed a statistically significant improvement in PFS for the combination arm but no difference in OS. Everolimus showed prolonged PFS in the second/third-line setting. Pazopanib prolongs PFS in naïve/cytokine refractory patients. Immunotherapy confers a small but significant OS advantage but only for the minority of patients with good prognostic features. The results of these trials and ongoing efforts to improve treatment of MRCC are the focus of this review.
Calcium Antagonists and Renal Failure Progression

Although tighter blood pressure control is considered the main mechanism for preventing the progression of chronic renal failure, angiotensin-converting enzyme inhibitors and angiotensin receptors blockers seem to have an additional organ protective role. The effects of calcium antagonists in renal disease are not so clearly defined. Calcium antagonists have pleiotropic effects that might contribute to protect the kidney, such as attenuating mesangial entrapment of macromolecules, countervailing the mitogenic effect of platelet-derived growth factors and platelet-activating factors, and suppressing mesangial cell proliferation. They could also act as free radical scavengers and inhibit the renal effects of endothelin. Some evidence has been accumulated demonstrating that certain new dihydropyridinic calcium antagonists may affect postglomerular as well as preglomerular vessels, resulting in decreased filtration fraction and nephroprotective effect as renin-angiotensin axis-blocking drugs. Though there are few reports on the clinical renal effects of new calcium antagonists, they have rendered promising results. Manidipine does not increase proteinuria as do some classic calcium antagonists, and lercanidipine combined with renin-angiotesin axis-blocking drugs reduce proteinuria. Both drugs have been shown to decrease microalbuminuria when administered alone.
Characteristics of adolescent excessive drinkers compared with consumers and abstainers.

INTRODUCTION AND AIMS This study aimed at comparing adolescent abstainers, consumers and excessive drinkers in terms of family characteristics (structure of family, socioeconomic factors), perceived social support, personality characteristics (extraversion, self-esteem, aggression) and well-being. DESIGN AND METHODS Cross-sectional data were obtained from 3694 elementary school students in the 8th and 9th grades from several cities in Slovakia (mean age 14.5, 49.0% men; response rate 93%). Respondents completed questions on the use of alcohol and on family structure (parental divorce), the socioeconomic position of the family (parents' education and family affluence), perceived social support, extraversion, self-esteem, aggression and psychological well-being. They were split into three groups based on the pattern of alcohol use--abstainers, consumers and excessive drinkers (i.e. being drunk at least once during the past 4 weeks). RESULTS The results showed significant differences between abstainers, consumers and excessive drinkers in almost every characteristic explored. A risky pattern of alcohol consumption occurs more frequently among adolescents who have divorced parents, higher socioeconomic position, higher scores for perceived social support from friends, extraversion, negative self-esteem and aggression, and lower scores for social support from family and for well-being. DISCUSSION AND CONCLUSIONS A risky pattern of alcohol consumption is more likely among relatively easily identifiable groups of adolescents from high socioeconomic position and divorced families. Their personalities and social networks have characteristics that could be accommodated in preventive interventions as well.
Simultaneous and Differential Fronto-orbital and Midface Distraction Osteogenesis for Syndromic Craniosynostosis Using Rigid External Distractor II

Abstract In syndromic craniosynostosis, the relation between the supraorbital area and the frontal bone is not good, and it is not possible to reform this area with 1-block advancement. To avoid this problem, the frontal bone is separated from the fronto-orbital bandeau, each is reshaped and remodeled separately, and then both are reattached. The retrusion of the midface, especially in syndromic craniosynostosis, is usually greater than that of cranial bones, so the technique usually separating the midface from the cranium is Le Fort III osteotomy, which allows differential distraction of each part. In this procedure, the cranial and midfacial bones are advanced simultaneously and differentially, both to the planned extent, in a single-stage operation, using rigid external distractor II, correcting exorbitism, respiratory embarrassment, and cranial structures and avoiding eye complications in the future. This procedure was used, with a follow-up, in 10 patients with syndromic craniosynostosis from 2 to 5 years.
Evaluation of an antiseptic triple‐lumen catheter in an intensive care unit

Objective: To evaluate a decrease in catheter‐related bloodstream infection rate in patients with antiseptic triple‐lumen catheters in an intensive care unit. Data Sources: Retrospective review of surveillance records, patient medical records, laboratory and microbiological reports, and antibiotic administration records. Study Selection: Patients admitted to the intensive care unit with triple‐lumen catheters. Data Extraction: A subset of one entry per patient was extracted from 2 yrs of primary bloodstream infection surveillance data. Data collection included risk factors, laboratory and microbiological data, and insertion sites and dates of all intravascular catheters present during triple‐lumen catheterization. Data Synthesis: The catheter‐related bloodstream infection rate was 5.4 and 11.3 per 1000 catheter days in antiseptic and nonantiseptic triple‐lumen catheter groups, respectively (p = .06). By multivariate analysis using a Cox Proportional Hazards Model, the antiseptic triple‐lumen catheters were associated with a significant reduction in catheter‐related bloodstream infection (p = .03). Model expansion to include intrajugular site was significant by a likelihood ratio test [2(log likelihood diff) = 4.26 p < . 05 χ21] Conclusions: The use of antiseptic triple‐lumen catheters may substantially reduce catheter‐related bloodstream infections in an intensive care population and may be subsequently associated with a decrease in length of stay.
Control of filtering bleb structure through tissue bioengineering: An animal model.

PURPOSE To devise a means of providing controlled resistance between the anterior chamber and the subconjunctival space after trabeculectomy by implantation of a biodegradable, porous collagen matrix. METHODS Matrices were implanted in the right eyes of 17 rabbits after trabeculectomy, while left eyes served as surgical controls. The scleral flap was sutured loosely, and the implant provided pressure on the scleral flap to reduce overfiltration. Trabeculectomy in the control eyes was performed with tight sutures using standard methodology. Intraocular pressure (IOP) was measured before surgery and on days 3, 7, 14, 21, and 28 after surgery. Masson trichrome and alpha-smooth muscle actin stains were used for histologic study of the filtering blebs. RESULTS The initial postoperative IOP reduction was approximately equal, at 14% to 16%, for both groups. In the implanted group, the IOP continued to decrease to 55% below baseline at day 28 as the implant gradually degraded. In the control group, IOP had returned to the preoperative level by day 21. Histologic examination with Masson trichrome and alpha-smooth muscle actin stains showed a prominent bleb in the implanted group compared with scar formation and limited bleb formation in the control group. CONCLUSIONS Implantation of a biodegradable, porous collagen matrix in the subconjunctival space offers the potential for a new means of avoiding early scar formation and maintaining long-term IOP control by creating a loosely structured filtering bleb.
The sex ratios of offspring of diabetic parents

Journal compilation © 2006 Diabetes UK. Diabetic Medicine , 23 , 1042–1044 and only individuals with two values diagnostic of diabetes on separate days ( n = 22) were classified as having diabetes in accordance with the recommendation from WHO [1]. As generally seen with other diagnostic tests, full agreement between two test procedures was not obtained. A total of 18 people had confirmed diabetes by BG values; of these, four had at least one PG value in the diabetic range and 14 had confirmed diabetes by PG. Thus the concordance between the two methods is higher than the concordance rate of 14/18 would indicate. In our study we also evaluated cardiovascular risk in individuals with confirmed vs. unconfirmed diabetes measured by PG or BG. The distribution of individual risk factors as well as the 10-year cardiovascular risk score [3] were comparable between the groups. In conclusion, we find that diagnostic tests for diabetes can be made correctly and safely in general practice, based either on high-quality ‘bed side’ equipment for measuring capillary blood glucose or on measuring plasma glucose by separating plasma and sending it for analysis at a central laboratory. The first method may be less time consuming, does not include centrifuging blood and provides an immediate answer to the patient and may thus be preferred by the doctor and the patient as, even in a small country such as Denmark, the distance to a laboratory may be a barrier to making the diagnosis.
Golgi stress response reprograms cysteine metabolism to confer cytoprotection in Huntington’s disease

Significance Golgi stress response is emerging as a major stress response pathway although molecular players in the process have not been identified. We show that Golgi stress response induced by the ionophore monensin is mediated by the PERK-ATF4 pathway. We further show that subtoxic levels of monensin precondition cells to respond to future damaging insults. Monensin stimulates the reverse transsulfuration pathway via cystathionine γ-lyase, the biosynthetic enzyme for cysteine, important for redox homeostasis. We have harnessed this pathway to mitigate toxicity associated with cysteine deprivation in Huntington’s disease (HD). These findings are relevant to not only HD, but also other diseases involving redox imbalance. Targeting the molecular controls for restoration of cysteine balance may offer more robust therapeutic avenues for disease management. Golgi stress response is emerging as a physiologic process of comparable importance to endoplasmic reticulum (ER) and mitochondrial stress responses. However, unlike ER stress, the identity of the signal transduction pathway involved in the Golgi stress response has been elusive. We show that the Golgi stressor monensin acts via the PKR-like ER kinase/Activating Transcription Factor 4 pathway. ATF4 is the master regulator of amino acid metabolism, which is induced during amino acid depletion and other forms of stress. One of the genes regulated by ATF4 is the biosynthetic enzyme for cysteine, cystathionine γ-lyase (CSE), which also plays central roles in maintenance of redox homeostasis. Huntington’s disease (HD), a neurodegenerative disorder, is associated with disrupted cysteine metabolism caused by depletion of CSE leading to abnormal redox balance and stress response. Thus, restoring CSE function and cysteine disposition may be beneficial in HD. Accordingly, we harnessed the monensin-ATF4–signaling cascade to stimulate CSE expression by preconditioning cells with monensin, which restores cysteine metabolism and an optimal stress response in HD. These findings have implications for treatment of HD and other diseases associated with redox imbalance and dysregulated ATF4 signaling.
What Drives Financial Complexity? A Look into the Retail Market for Structured Products

By focusing on the highly innovative retail market for structured products, we investigate the drivers of financial complexity. We perform a lexicographic analysis of the term sheets of 55,000 retail structured products issued in Europe since 2002. We observe that financial complexity has been steadily increasing, even after the recent financial crisis, and that financial complexity is more prevalent among distributors with a less sophisticated investor base. Complex products exhibit higher markups and lower ex post performance than simpler products. Using issuance level data spanning 15 countries over the period 2002-2010, we find that financial complexity increases when competition intensifies. These findings are consistent with financial institutions strategically using complexity to mitigate competition.
Prefrontal cortex and the regulation of food intake in the rat.

The postoperative regulation of food and water intake was studied in rats with aspiration lesions to either the medial frontal or orbital frontal projection fields of thalamic nucleus medialis dorsalis (prefrontal cortex). These projection fields proved functionally dissociable in that orbital frontal lesions impaired immediate postoperative regulation of food and water intake for up to 2 wk. , while medial frontal lesions produced finickiness. Neither lesion affected response to cellular dehydration or recovery from extended deprivation. These data are consistent with data from rhesus monkeys with prefrontal lesions and differ from animals with lateral hypothalamic lesions.
Systematic searches for molecular synapomorphies in model metazoan genomes give some support for Ecdysozoa after accounting for the idiosyncrasies of Caenorhabditis elegans

Summary There has been broad acceptance among evolutionary biologists of the Ecdysozoa hypothesis that, based principally on molecular phylogenetic studies of small and large subunit ribosomal RNA sequences, postulates a close relationship between molting taxa such as arthropods and nematodes. On the other hand, recent studies of as many as 100 additional genes do not support the Ecdysozoa hypothesis and instead favor the older Coelomata hypothesis that groups the coelomate arthropods with the coelomate vertebrates to the exclusion of the nematodes. Here, exploiting completely sequenced genomes, we examined this question using cladistic analyses of the phylogenetic distribution of 1712 orthologous genes and 2906 protein domain combinations; we found stronger support for the Coelomata hypothesis than for the Ecdysozoa hypothesis. However, although arrived at by considering very large data sets, we show that this conclusion is unreliable, biased toward grouping arthropods with chordates by systematic high rate of character loss in the nematode. When we addressed this problem, we found slightly more support for Ecdysozoa than for Coelomata. Our identification of this systematic bias even when using entire genomes has important implications for future phylogenetic studies. We conclude that the results from the intensively sampled ribosomal RNA genes supporting the Ecdysozoa hypothesis provide the most credible current estimates of metazoan phylogeny.
Can ESG Add Alpha? An Analysis of ESG Tilt and Momentum Strategies

Do institutional investors sacrifice risk-adjusted returns by incorporating environmental, social, and corporate governance (ESG) considerations? The authors analyze two relatively hightracking-error global strategies constructed using ESG data—a tilt strategy and a momentum strategy and find that both model portfolios outperformed the MSCI World Index over the past eight years, while also improving the ESG profile of the portfolios. These backtested model portfolios provide an example of how institutional investors with the tolerance to take some active risk, while at the same time looking to improve the ESG profile of their portfolios on a systematic basis, can incorporate such strategies in their investment processes.
The Contribution of Immune Regulatory and Thyroid Specific Genes to the Etiology of Graves' and Hashimoto's Diseases

The autoimmune thyroid diseases (AITD) are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility in combination with external factors (e.g. dietary iodine) are believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been employed to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions) that are linked with AITD, and in some of these loci putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD) and Hashimoto's thyroiditis (HT) and some are common to both diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4) and thyroid specific genes (e.g. TSHR, Tg). Most likely these loci interact and their interactions may influence disease phenotype and severity.
Niacin‐mediated Tace activation ameliorates CMT neuropathies with focal hypermyelination

Charcot–Marie–Tooth (CMT) neuropathies are highly heterogeneous disorders caused by mutations in more than 70 genes, with no available treatment. Thus, it is difficult to envisage a single suitable treatment for all pathogenetic mechanisms. Axonal Neuregulin 1 (Nrg1) type III drives Schwann cell myelination and determines myelin thickness by ErbB2/B3‐PI3K–Akt signaling pathway activation. Nrg1 type III is inhibited by the α‐secretase Tace, which negatively regulates PNS myelination. We hypothesized that modulation of Nrg1 levels and/or secretase activity may constitute a unifying treatment strategy for CMT neuropathies with focal hypermyelination as it could restore normal levels of myelination. Here we show that in vivo delivery of Niaspan, a FDA‐approved drug known to enhance TACE activity, efficiently rescues myelination in the Mtmr2−/− mouse, a model of CMT4B1 with myelin outfoldings, and in the Pmp22+/− mouse, which reproduces HNPP (hereditary neuropathy with liability to pressure palsies) with tomacula. Importantly, we also found that Niaspan reduces hypermyelination of Vim (vimentin)−/− mice, characterized by increased Nrg1 type III and Akt activation, thus corroborating the hypothesis that Niaspan treatment downregulates Nrg1 type III signaling.