Miracle-dz/UniFAR-FTUs huggingface dataset:
Chromosome territory reorganization in a human disease with altered DNA methylation

Chromosome territory (CT) organization and chromatin condensation have been linked to gene expression. Although individual genes can be transcribed from inside CTs, some regions that have constitutively high expression or are coordinately activated loop out from CTs and decondense. The relationship between epigenetic marks, such as DNA methylation, and higher-order chromatin structures is largely unexplored. DNMT3B mutations in immunodeficiency centromeric instability facial anomalies (ICF) syndrome result in loss of DNA methylation at particular sites, including CpG islands on the inactive X chromosome (Xi). This allows the specific effects of DNA methylation on CTs to be examined. Using fluorescence in situ hybridization, we reveal a differential organization of the human pseudoautosomal region (PAR)2 between the CTs of the X and Y in normal males and the active X (Xa) and the Xi in females. There is also a more condensed chromatin structure on Xi compared with Xa in this region. PAR2 genes are relocalized toward the outside of the Y and Xi CTs in ICF, and on the Xi, we show that this can extend to genes distant from the site of DNA hypomethylation itself. This reorganization is not simply a reflection of the transcriptional activation of the relocalized genes. This report of altered CT organization in a human genetic disease illustrates that DNA hypomethylation at restricted sites in the genome can lead to more extensive changes in nuclear organization away from the original site of epigenetic change.
Effect of Ultrasonic Extraction on Production and Structural Changes of C-Phycocyanin from Marine Spirulina maxima

This work first showed that very high amounts of phycocyanins, such as 11.3 mg/mL C-phycocyanin (C-PC), 3.1 mg/mL allophycocyanin (APC), and 0.8 mg/mL phycoerythrin (PE), can be obtained using an ultrasonic extraction process (UE) with a 60 kHz frequency and 3 h of process time at 25 °C, without any other pretreatments. These yields were higher than those from most conventional water extractions at 4 °C for 24 h (Control condition) or at 25 °C for 24 h (WE), namely, 9.8 and 5.7 mg/mL C-PC, 2.3 and 1.2 mg/mL APC, and 0.7 and 0.3 mg/mL PE, respectively. These yields were also shown to be even higher than yields from other reported data. Structural changes in C-PC in the extracts were also found for the first time, according to extraction conditions, showing that the total concentration of C-PC and of the α-subunit of C-PC in the UE were much higher than in the WE, with little difference in the amount of β-subunit of C-PC in the UE or WE. It was also shown that the structural changes in C-PC in the WE decreased both antioxidant and anti-inflammation activities—29.83% vs. 32.09% of α,α-diphenyl-β-picrylhydrazyl (DPPH) scavenging activity and 8.21 vs. 7.25 µM of NO production for the WE and UE, respectively—while the UE, with similar patterns to standard C-PC, showed very high biological effects, which may suggest that the biologically active part is the α-subunit of C-PC, not the β-subunit.
Opioid Modulation of Recurrent Excitation in the Hippocampal Dentate Gyrus

κ opioid receptor activation inhibits granule cell-mediated excitatory neurotransmission in the hippocampal formation via a decrease in glutamate release from both perforant path and mossy fiber terminals. We now report a third, anatomically and pharmacologically distinct site of such κ opioid inhibition within the hippocampus. Granule cell population responses to selective stimulation of an excitatory hilar pathway were decreased by the κ1 opioid receptor agonist U69,593, an effect blocked by the κ1 antagonist norbinaltorphimine. U69,593 also inhibited hilar path induced long-term potentiation (LTP) of granule cell responses. LTP in this pathway was also blocked by the NMDA receptor antagonist d-2-amino-5-phosphonovalerate, unlike granule cell mossy fiber LTP in CA3. The κ opioid peptide dynorphin is present in hilar mossy fiber collaterals. Ultrastructural analysis of these collaterals demonstrated dynorphin-containing vesicles in asymmetric synapses formed between axon terminals and granule cell dendrites, suggesting direct granule cell–granule cell connections. Evoked release of endogenous dynorphin within the hilus was effective in reducing hilar excitation of granule cells, although this release, in contrast to the release of dynorphin in the dentate molecular layer, was not dependent on L-type calcium channels. No hilar path excitation was observed in the absence of bicuculline, suggesting a strong GABAA-mediated inhibition of this pathway. However, hilar path activity could be seen after LTP, with or without bicuculline. Thus, κ opioids can inhibit granule cell recurrent excitation, likely via effects on excitatory mossy fiber collaterals. Such collaterals are thought to be important in mediating temporal lobe epilepsy.
Number of fragments, margin status and thermal artifacts of conized specimens from LLETZ surgery to treat cervical intraepithelial neoplasia

ABSTRACT CONTEXT AND OBJECTIVE: Large loop excision of the transformation zone (LLETZ) is a nontraumatic cut and coagulation method with several advantages, but it induces thermal artifacts in the cut region. The aim here was to assess the correlations of age, number of fragments, lesion grade and degree of thermal artifacts with margin quality in conized specimens from LLETZ for cervical intraepithelial neoplasia (CIN). DESIGN AND SETTING: Cross-sectional study at Universidade Federal de São Paulo (Unifesp). METHODS: The records and histopathology findings of 118 women who underwent LLETZ between 1999 and 2007 were reviewed. Age, number of fragments, lesion grade, degree of thermal artifacts and margin quality were assessed. RESULTS: The patients’ mean age was 27.14 years; 63.6% had been diagnosed with CIN II and 36.4% with CIN III. The lesion was removed as a single fragment in 79.6% of the cases. The margins were free from intraepithelial neoplasia in 85.6% and compromised in the endocervical margin in 6.8%. Fragment damage due to artifacts occurred in 2.5%. Severe artifacts occurred in 22.8%. Women aged 30 years or over presented more cases of CIN III (P < 0.0004). Neoplastic compromising of surgical margins and severe artifacts occurred more often in cases in which two or more fragments were removed, and in patients aged 30 years or over. CONCLUSION: CIN III in women aged 30 or over, when removed in two or more fragments during LLETZ, presented a greater number of compromised margins and greater severity of thermal artifacts.
Paediatric otitis media surgery in Norway

Conclusions: In Norway there are large, regional differences in the incidence of surgery and combinations of surgery for otitis media. Objectives: A descriptive study of complete national administrative data on frequency of surgery for otitis media in 2002. Materials and methods: This study analysed anonymous patient data from the Norwegian patient registry for 2002 and measured rates of tympanostomy tube insertions, myringotomy and the combinations of adenoidectomies and tympanostomy tubes and myringotomy, respectively. Surgical rates were assessed by region and variations within the country were evaluated. Results: The peak age for surgical treatment of otitis media was 5 years. Tympanostomy tubes were inserted in more than half of the children treated and the analysis showed considerable regional variation in the rates and in choice of surgical treatment.
Reduced Capacity in a Dichotic Memory Test for Adult Patients With ADHD

Objective: To evaluate whether a dichotic memory test would reveal deficits in short-term working-memory recall and long-term memory recall in a group of adult patients with ADHD. Methods: A dichotic memory test with ipsilateral backward speech distraction in an adult ADHD group (n = 69) and a control group (n = 66) is used to compare performance between the groups and inside the subgroups of ADHD diagnosed with DSM-IV. Results: The ADHD participants showed significant impairment in the dichotic memory test compared with control participants when controlled for age, sex, and education. Study findings reveal that there is no difference in subdivision in the three ADHD subgroups of DSM-IV. A discriminant analysis shows an overall classification rate of 78% and specific in ADHD 80%. Conclusions: The results indicate that the dichotic test is measuring one of the important ADHD deficits. (J. of Att. Dis. 2010; 13(6) 677-683)
Cancer treatment-induced bone loss in breast and prostate cancer.

PURPOSE Bone loss resulting from the treatment of breast and prostate cancer is an emerging problem. Bisphosphonates have a potential role in the prevention of this cancer treatment-induced bone loss (CTIBL). METHODS Studies evaluating the incidence and prevalence of CTIBL in early breast and prostate cancer patients and trials evaluating the preventative role of bisphosphonates were identified by a search of the PubMed and Cochrane Library databases through the end of March 2008. Reference lists from retrieved articles were cross referenced, and further information was obtained from relevant scientific meetings. RESULTS Several therapies commonly used in the treatment of women and men with breast and prostate cancers, in particular the aromatase inhibitors (AIs) for breast cancer and androgen deprivation therapy (ADT) for prostate cancer, are associated with significant bone loss and with an increase in fracture risk. The use of bisphosphonates seems to attenuate the bone loss, although the long-term impact remains unclear because of insufficient follow-up. CONCLUSION Adjuvant endocrine therapy with an AI or androgen deprivation can be considered a risk factor for the development of osteopenia, osteoporosis, and bone fracture, which can be mitigated by appropriate bisphosphonate therapy. Clear identification of risk factors for osteoporosis in individual patients should aid treatment decisions about whether to use bisphosphonates when starting or switching to an AI or ADT. Patients need to be educated about this risk and other measures to avoid this complication, including lifestyle modifications that may benefit their general and bone health.
A polyphenol extract modifies quantity but not quality of liver fatty acid content in high-fat–high-sucrose diet-fed rats: possible implication of the sirtuin pathway

High-fat or high-fat–high-sucrose diets are known to induce non-alcoholic fatty liver disease and this is emerging as one of the most common liver diseases worldwide. Some polyphenols have been reported to decrease rat hepatic lipid accumulation, in particular those extracted from red grapes such as resveratrol. The present study was designed to determine whether a polyphenol extract (PPE), from red grapes, modulates liver fatty acid composition and desaturase activity indexes in rats fed a high-fat–high-sucrose (HFHS) diet, and to explore whether sirtuin-1 deacetylase activation was implicated in the effect of the PPE against liver steatosis. The effect of this PPE on mitochondriogenesis and mitochondrial activity was also explored. The PPE decreased liver TAG content in HFHS+PPE diet-fed rats in comparison with HFHS diet-fed rats. The PPE had no effect on liver fatty acid composition, desaturase activity indexes and stearoyl-CoA desaturase 1 (SCD1) gene expression. Sirtuin-1 deacetylase protein expression was significantly increased with the PPE; AMP kinase protein expression was higher with the PPE in comparison with the HFHS rats, but no modification of phosphorylated AMP kinase was observed. Protein expression of phospho-acetyl-CoA carboxylase was decreased in HFHS rats and returned to basal values with the PPE. Finally, the PPE modulated PPARγ coactivator-1α (PGC-1α) but did not modify mitochondriogenesis and mitochondrial activity. In conclusion, the PPE partially prevented the accumulation of TAG in the liver by regulating acetyl-CoA carboxylase phosphorylation, a key enzyme in lipid metabolism, probably via sirtuin-1 deacetylase activation. However, the PPE had no effect on the qualitative composition of liver fatty acids.
Aprotinin reduces red blood cell transfusion in orthotopic liver transplantation: A prospective, randomized, double‐blind study

The effect of an aprotinin infusion on blood and blood product transfusion during adult primary orthotopic liver transplantation (OLT) was investigated in a prospective, randomized, double‐blind study. Sixty‐three patients were enrolled; 33 patients were administered an aprotinin regimen of a 1,000,000‐KIU loading dose, followed by a 250,000‐KIU/h infusion during surgery, and 30 patients were administered equivalent volumes of normal saline. Red blood cell (RBC) and blood product transfusion intraoperatively and for the first 24 hours postoperatively was by protocol. Intraoperative coagulation testing and thromboelastography (TEG; Hemoscope Corp, Skokie, IL) were performed. Intraoperative RBC transfusion was significantly less in the aprotinin group versus controls: median, 5 units (interquartile range [IQR], 3 to 9 units) versus 7 units (IQR, 5 to 16 units; P = .0016). No significant differences were found for intraoperative blood product transfusion or transfusion of RBCs or blood products in the 24‐hour postoperative period. No significant differences were observed in intraoperative coagulation testing or TEG parameters. We conclude that aprotinin infusion reduces RBC transfusion requirements in OLT.
Did I Get the Best Discount? Counterfactual Thinking of Tourism Products

Current trends in the tourism industry indicate that most potential travelers purchase tourism products from online travel agents that provide price promotions. Even though the range of price promotions often varies, the tourism literature does not address potential travelers’ perceptions after purchasing products at various discount rates. This study examined the relationships among different discount rates, temporal distance, and counterfactual thinking—a mental undoing of existing outcomes. Results showed that the relationship between discount rate and counterfactual thinking had a U-shaped curve. Furthermore, the shape differed by temporal distance. The optimal discount rate for minimizing counterfactual thinking was 29.62% when the reservation was made 15 days prior to departure but rose to 33.33% when the reservation was made three months prior to departure. This study suggested that counterfactual thinking mediates the relationship between discount rate and perceived regret.
Favorable prognostic impact of NPM1 mutations in older patients with cytogenetically normal de novo acute myeloid leukemia and associated gene- and microRNA-expression signatures: a Cancer and Leukemia Group B study.

PURPOSE To analyze the prognostic significance of NPM1 mutations, and the associated gene- and microRNA-expression signatures in older patients with de novo, cytogenetically normal acute myeloid leukemia (CN-AML) treated with intensive chemotherapy. PATIENTS AND METHODS One hundred forty-eight adults age >or= 60 years with de novo CN-AML, enrolled onto Cancer and Leukemia Group B protocols 9720 and 10201, were studied at diagnosis for NPM1, FLT3, CEBPA, and WT1 mutations, and gene- and microRNA-expression profiles. RESULTS Patients with NPM1 mutations (56%) had higher complete remission (CR) rates (84% v 48%; P < .001) and longer disease-free survival (DFS; P = .047; 3-year rates, 23% v 10%) and overall survival (OS; P < .001; 3-year rates, 35% v 8%) than NPM1 wild-type patients. In multivariable analyses, NPM1 mutations remained independent predictors for higher CR rates (P < .001) and longer DFS (P = .004) and OS (P < .001), after adjustment for other prognostic clinical and molecular variables. Unexpectedly, the prognostic impact of NPM1 mutations was mainly observed in patients >or= 70 years. Gene- and microRNA-expression profiles associated with NPM1 mutations were similar across older patient age groups and similar to those in younger (< 60 years) patients with CN-AML. These profiles were characterized by upregulation of HOX genes and their embedded microRNAs and downregulation of the prognostically adverse MN1, BAALC, and ERG genes. CONCLUSION NPM1 mutations have favorable prognostic impact in older patients with CN-AML, especially those age >or= 70 years. The gene- and microRNA-expression profiles suggest that NPM1 mutations constitute a marker defining a biologically homogeneous entity in CN-AML that might be treated with specific and/or targeted therapies across age groups.
Market Integration and Global Crashes

We develop an equilibrium model of real and financial market integration in which real firms and financial investors independently decide on their investment into different locations (countries). We show that, in the presence financial frictions, firms' real investment choices become strategic complements, leading to multiple, self-fulfilling equilibria. This fragility may lead to a global crash in which severe underinvestment into countries with under-developed financial markets spills over to countries connected to them by real investment linkages. We show that such global crashes are particularly severe when frictions are sufficiently symmetric across countries. By contrast, with enough asymmetry, the economy is likely to end up in a local crash equilibrium in which countries with low real investment barriers suffer the most.
Elevated methylation of HPV16 DNA is associated with the development of high grade cervical intraepithelial neoplasia

We explored the association of human papillomavirus type 16 (HPV16) DNA methylation with age, viral load, viral persistence and risk of incident and prevalent high grade CIN (CIN2+) in serially collected specimens from the Guanacaste, Costa Rica cohort. 273 exfoliated cervical cell specimens (diagnostic and pre‐diagnostic) were selected: (1) 92 with HPV16 DNA clearance (controls), (2) 72 with HPV16 DNA persistence (without CIN2+) and (3) 109 with CIN2+. DNA was extracted, bisulfite converted and methylation was quantified using pyrosequencing assays at 66 CpGs across the HPV genome. The Kruskal‐Wallis test was used to determine significant differences among groups, and receiver operating characteristic curve analyses were used to evaluate how well methylation identified women with CIN2+. In diagnostic specimens, 88% of CpG sites had significantly higher methylation levels in CIN2+ after correction for multiple tests compared with controls. The highest area under the ROC curve (AUC) was 0.82 for CpG site 6457 in L1, and a diagnostic sensitivity of 91% corresponded to a specificity of 60% for CIN2+. Prospectively, 17% of CpG sites had significantly higher methylation in pre‐diagnostic CIN2+ specimens (median time of 3 years before diagnosis) versus controls. The strongest pre‐diagnostic CpG site was 6367 in L1 with an AUC of 0.76. Age‐stratified analyses suggested that women older than the median age of 28 years have an increased risk of precancer associated with high methylation. Higher methylation in CIN2+ cases was not explained by higher viral load. We conclude that elevated levels of HPV16 DNA methylation may be useful to predict concurrently diagnosed as well as future CIN2+.
The impact of perioperative factors on subsequent intelligence quotient deficits in children treated for medulloblastoma/posterior fossa primitive neuroectodermal tumors

Background. Despite success in treating children with medulloblastoma/posterior fossa primitive neuroectodermal tumor (PF PNET), some children survive with significant neurocognitive sequelae. This study was performed to understand better the significance of perioperative factors on subsequent full scale intelligence quotient (FSIQ) deterioration in these children.
Predatory-Prey Decision Making During Market Bubbles—Preliminary Evidence from a Neurobiological Study

ABSTRACT The present paper examines decision making during market bubbles. In the context of high market volatility, high speculation and inappropriate regulation (e.g., as such was the case in the years prior to the 2008 subprime crisis), market agents adopt either a predator or prey position. By way of a neurobiological study, it is shown that market-agent-turned preys benefit from moderate stress when it enhances their level of vigilance; however, past a certain stress threshold, their efforts at wealth maximization are considerably reduced. This may explain some of the cognitive causes of failures found by various authors in their description of the market bubble phenomenon. The paper emphasizes the importance of setting up proper regulations aimed at preventing the emergence of predatory behaviors (such as those that prevailed with the establishment of predatory mortgages during the year 2000 in the United States) and better educating average investors.
Infectious burden and risk of stroke: the northern Manhattan study.

OBJECTIVE To determine the association between a composite measure of serological test results for common infections (Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpes simplex virus 1 and 2) and stroke risk in a prospective cohort study. DESIGN Prospective cohort followed up longitudinally for median 8 years. SETTING Northern Manhattan Study. Patients Randomly selected stroke-free participants from a multiethnic urban community. Main Outcome Measure Incident stroke and other vascular events. RESULTS All 5 infectious serological results were available from baseline samples in 1625 participants (mean [SD] age, 68.4 [10.1] years; 64.9% women). Cox proportional hazards models were used to estimate associations of each positive serological test result with stroke. Individual parameter estimates were then combined into a weighted index of infectious burden and used to calculate hazard ratios and confidence intervals for association with risk of stroke and other outcomes, adjusted for risk factors. Each individual infection was positively, though not significantly, associated with stroke risk after adjusting for other risk factors. The infectious burden index was associated with an increased risk of all strokes (adjusted hazard ratio per standard deviation, 1.39; 95% confidence interval, 1.02-1.90) after adjusting for demographics and risk factors. Results were similar after excluding those with coronary disease (adjusted hazard ratio, 1.50; 95% confidence interval, 1.05-2.13) and adjusting for inflammatory biomarkers. CONCLUSIONS A quantitative weighted index of infectious burden was associated with risk of first stroke in this cohort. Future studies are needed to confirm these findings and to further define optimal measures of infectious burden as a stroke risk factor.