Miracle-dz/UniFAR-FTUs huggingface dataset:
Loss of CX3CR1 increases accumulation of inflammatory monocytes and promotes gliomagenesis

The most abundant populations of non-neoplastic cells in the glioblastoma (GBM) microenvironment are resident microglia, macrophages and infiltrating monocytes from the blood circulation. The mechanisms by which monocytes infiltrate into GBM, their fate following infiltration, and their role in GBM growth are not known. Here we tested the hypothesis that loss of the fractalkine receptor CX3CR1 in microglia and monocytes would affect gliomagenesis. Deletion of Cx3cr1 from the microenvironment resulted in increased tumor incidence and shorter survival times in glioma-bearing mice. Loss of Cx3cr1 did not affect accumulation of microglia/macrophages in peri-tumoral areas, but instead indirectly promoted the trafficking of CD11b+CD45hiCX3CR1lowLy-6ChiLy-6G−F4/80−/low circulating inflammatory monocytes into the CNS, resulting in their increased accumulation in the perivascular area. Cx3cr1-deficient microglia/macrophages and monocytes demonstrated upregulation of IL1β expression that was inversely proportional to Cx3cr1 gene dosage. The Proneural subgroup of the TCGA GBM patient dataset with high IL1β expression showed shorter survival compared to patients with low IL1β. IL1β promoted tumor growth and increased the cancer stem cell phenotype in murine and human Proneural glioma stem cells (GSCs). IL1β activated the p38 MAPK signaling pathway and expression of monocyte chemoattractant protein (MCP-1/CCL2) by tumor cells. Loss of Cx3cr1 in microglia in a monocyte-free environment had no impact on tumor growth and did not alter microglial migration. These data suggest that enhancing signaling to CX3CR1 or inhibiting IL1β signaling in intra-tumoral macrophages can be considered as potential strategies to decrease the tumor-promoting effects of monocytes in Proneural GBM.
Eighteen-month-olds’ memory interference and distraction in a modified A-not-B task is not associated with their anticipatory looking in a false-belief task

Infants’ performance in non-verbal false-belief tasks is often interpreted as if they have understood false beliefs. This view has been questioned by a recent account that explains infants’ performance in non-verbal false-belief tasks as the result of susceptibility to memory interference and distraction. We tested this alternative account by investigating the relationship between infants’ false-belief understanding, susceptibility to memory interference and distraction, and general cognitive development in 18-month-old infants (N = 22). False-belief understanding was tested in an anticipatory looking paradigm of a standard false-belief task. Susceptibility to memory interference and distraction was tested in a modified A-not-B task. Cognitive development was measured via the Mental Scale of the Bayley Scales of Infant Development. We did not find any relationship between infants’ performance in the false-belief task and the A-not-B task, even after controlling for cognitive development. This study shows that there is no ubiquitous relation between susceptibility to memory interference and distraction and performance in a false-belief task in infancy.
Dissecting out the Complex Ca2+-Mediated Phenylephrine-Induced Contractions of Mouse Aortic Segments

L-type Ca2+ channel (VGCC) mediated Ca2+ influx in vascular smooth muscle cells (VSMC) contributes to the functional properties of large arteries in arterial stiffening and central blood pressure regulation. How this influx relates to steady-state contractions elicited by α1-adrenoreceptor stimulation and how it is modulated by small variations in resting membrane potential (Vm) of VSMC is not clear yet. Here, we show that α1-adrenoreceptor stimulation of aortic segments of C57Bl6 mice with phenylephrine (PE) causes phasic and tonic contractions. By studying the relationship between Ca2+ mobilisation and isometric tension, it was found that the phasic contraction was due to intracellular Ca2+ release and the tonic contraction determined by Ca2+ influx. The latter component involves both Ca2+ influx via VGCC and via non-selective cation channels (NSCC). Influx via VGCC occurs only within the window voltage range of the channel. Modulation of this window Ca2+ influx by small variations of the VSMC Vm causes substantial effects on the contractile performance of aortic segments. The relative contribution of VGCC and NSCC to the contraction by α1-adrenoceptor stimulation could be manipulated by increasing intracellular Ca2+ release from non-contractile sarcoplasmic reticulum Ca2+ stores. Results of this study point to a complex interactions between α1-adrenoceptor-mediated VSMC contractile performance and Ca2+ release form contractile or non-contractile Ca2+ stores with concomitant Ca2+ influx. Given the importance of VGCC and their blockers in arterial stiffening and hypertension, they further point toward an additional role of NSCC (and NSCC blockers) herein.
The Long-Term Follow-Up Results of External Dacryocystorhinostomy Skin Incision Scar with “W Incision”

Abstract Objective: To determine the effect of “W incision” instead of classical vertical incision at external DCR on scar formation. Materials and Methods: Patients with acquired nasolacrimal duct obstruction (NLDO) who were treated with external DCR with classical vertical incision, and patients who were treated with external DCR with “W incision” were included in the study. The first 39 eyes were operated with a vertical incision, and the remaining 37 eyes were operated with a “W incision”. All the skin incision scars of the patients were assessed and scored by at least the 6th month. The assessment was made by both the patients themselves, and by an ophthalmologist other than the surgeon himself, each scored the incision scar separately (single-masked study). Scores for both groups were compared, and statistical analyses were performed. Results: Self-assessment scores for the incision scar were Grade 2.28 ± 0.94 in the Vertical incision group, and Grade 1.68 ± 0.57 in the “W incision” group (p < 0.01). The “W incision” scar formation was significantly less noticable than the Vertical incision scar formation. Similarly, the assessment scores of the ophthalmologist other than the surgeon himself were significantly lower for the “W incision” group than for the Vertical incision group. The mean scar assessment scores were Grade 2.13 ± 0.95 in the Vertical incision group, and Grade 1.57 ± 0.68 in the “W incision” group (p < 0.01). Conclusion: Skin scar tissue was found to be significantly reduced with a “W incision” in external DCR operations.
Apolipoprotein A-I Promotes the Formation of Phosphatidylcholine Core Aldehydes That Are Hydrolyzed by Paraoxonase (PON-1) during High Density Lipoprotein Oxidation with a Peroxynitrite Donor*

High density lipoprotein (HDL) is rich in polyunsaturated phospholipids that are sensitive to oxidation. However, the effect of apolipoprotein A-I and paraoxonase-1 (PON-1) on phosphatidylcholine oxidation products has not been identified. We subjected native HDL, trypsinized HDL, and HDL lipid suspensions to oxidation by the peroxynitrite donor, 3-morpholinosydnonimine. HDL had a basal level of phosphatidylcholine mono- and di-hydroperoxides that increased to a greater extent in HDL, compared with either trypsinized HDL or HDL lipid alone. Phosphatidylcholine core aldehydes, which were present in small amounts, increased 10-fold during oxidation of native HDL, compared with trypsinized HDL (p = 0.004), and 4-fold compared with HDL lipid suspensions (p = 0.0021). In addition, the content of lysophosphatidylcholine increased 300% during oxidation of native HDL, but only 80 and 25%, respectively, during oxidation of trypsinized HDL and HDL lipid suspensions. Phosphatidylcholine isoprostanes accumulated in comparable amounts during the oxidation of all three preparations. Incubation of apolipoprotein A-I with 1-palmitoyl-2-linoleoyl glycerophosphocholine proteoliposomes in the presence of 3-morpholinosydnonimine or apoAI with phosphatidylcholine hydroperoxides resulted in a significant increase in phosphatidylcholine core aldehydes with no formation of lysophosphatidylcholine. We propose that apolipoprotein A-I catalyzes a one-electron oxidation of alkoxyl radicals. Purified PON-1 hydrolyzed phosphatidylcholine core aldehydes to lysophosphatidylcholine. We conclude that, upon HDL oxidation with peroxynitrite, apolipoprotein AI increases the formation of phosphatidylcholine core aldehydes that are subsequently hydrolyzed by PON1.
A sub-0.9V logic-compatible embedded DRAM with boosted 3T gain cell, regulated bit-line write scheme and PVT-tracking read reference bias

Circuit techniques for enabling a sub-0.9V logic-compatible embedded DRAM (eDRAM) are presented. A boosted 3T gain cell increases read margin, enhances read speed and improves data retention time. A regulated bit-line write scheme and a read reference bias generator are proposed to cope with write disturbance issues and PVT variations. Measurement results from a 64kb eDRAM test chip implemented in a 65nm low-leakage CMOS process demonstrate the effectiveness of the proposed techniques.
Doxorubicin versus doxorubicin and cisplatin in endometrial carcinoma: definitive results of a randomised study (55872) by the EORTC Gynaecological Cancer Group.

BACKGROUND Combination chemotherapy yields better response rates which do not always lead to a survival advantage. The aim of this study was to investigate whether the reported differences in the efficacy and toxicity of monotherapy with doxorubicin (DOX) versus combination therapy with cisplatin (CDDP) in endometrial adenocarcinoma lead to significant advantage in favour of the combination. PATIENTS AND METHODS Eligible patients had histologically-proven advanced and/or recurrent endometrial adenocarcinoma and were chemo-naïve. Treatment consisted of either DOX 60 mg/m(2) alone or CDDP 50 mg/m2 added to DOX 60 mg/m2, every 4 weeks. RESULTS A total of 177 patients were entered and median follow-up is 7.1 years. The combination DOX-CDDP was more toxic than DOX alone. Haematological toxicity consisted mainly of white blood cell toxicity grade 3 and 4 (55% versus 30%). Non-haematological toxicity consisted mainly of grade 3 and 4 alopecia (72% versus 65%) and nausea/vomiting (36 % versus 12%). The combination DOX-CDDP provided a significantly higher response rate than single agent DOX (P <0.001). Thirty-nine patients (43%) responded on DOX-CDDP [13 complete responses (CRs) and 26 partial responses (PRs)], versus 15 patients (17%) on DOX alone (8 CR and 7 PR). The median overall survival (OS) was 9 months in the DOX-CDDP arm versus 7 months in the DOX alone arm (Wilcoxon P = 0.0654). Regression analysis showed that WHO performance status was statistically significant as a prognostic factor for survival, and stratifying for this factor, treatment effect reaches significance (hazard ratio = 1.46, 95% confidence interval 1.05-2.03, P = 0.024). CONCLUSIONS In comparison to single agent DOX, the combination of DOX-CDDP results in higher but acceptable toxicity. The response rate produced is significantly higher, and a modest survival benefit is achieved with this combination regimen, especially in patients with a good performance status.
Effects of an Elementary Dual Language Immersion School Program on Junior High Achievement.

The purpose of this study was to analyze the effects of a twoway immersion elementary school program on academic achievement at the end of the elementary school and the end of the first year of junior high school. Longitudinal high stakes test data in reading, writing, and mathematics were collected on native English speakers and native Spanish speakers from the two-way immersion program and on matched controls through the use of an ex post facto quasiexperimental design. Findings suggest consistent support for the twoway immersion program over matched control students across all three achievement areas. It appears the greatest effect for native English speakers may be in reading, while native Spanish speakers may benefit more in writing and mathematics. Limitations to generalizability and causal inferences due to the small sample sizes and inherent weaknesses of the research design are noted. 2 Effects of an Elementary MGRJ Vol.1 (1)
High von Willebrand Factor Levels Increase the Risk of First Ischemic Stroke: Influence of ADAMTS13, Inflammation, and Genetic Variability

Background and Purpose— Elevated von Willebrand factor (vWF) concentrations are associated with an increased risk of ischemic heart disease. Several factors influence vWF antigen levels and activity, including blood group, genetic variability, acute-phase response, and proteolysis by A Disintegrin and Metalloprotease with ThromboSpondin motif (ADAMTS13), a determinant of proteolytic cleavage of vWF. We assessed how these factors affect the relation between vWF and the occurrence of stroke to understand the underlying mechanism. Methods— In a case-control study of 124 first-ever ischemic stroke patients and 125 age- and sex-matched controls, we studied vWF antigen (vWF:Ag), vWF ristocetin cofactor activity (vWF:RCo), ADAMTS13 activity, the −1793C/G polymorphism in the vWF gene, and C-reactive protein. Results— vWF antigen and activity levels were significantly higher in cases than in controls. The relative risk of ischemic stroke was highest in individuals in the upper quartile of vWF:Ag (odds ratio, 3.2; 95% CI, 1.4 to 7.5) and vWF:RCo (odds ratio, 2.1; 95% CI, 0.9 to 4.8) compared with individuals in the lowest quartiles. In individuals with ADAMTS13 in the lowest quartile, the relative risk of stroke was 1.7 (95% CI, 0.7 to 3.9) compared with the highest quartile. C-reactive protein, ADAMTS13, and genetic variation did not affect the association between vWF and the relative risk of stroke, whereas blood group did affect the association. Conclusions— vWF antigen and activity are associated with the occurrence of acute ischemic stroke. This relation is unaffected by the severity of the acute-phase response or by genetic variation or degradation.
Clinical Cancer esearch ing , Diagnosis , Prognosis omparison of PAM 50 Intrinsic Subtyping with unohistochemistry and Clinical Prognostic Factors in oxifen-Treated Estrogen Receptor – Positive R ast Cancer

Download pose: To compare clinical, immunohistochemical (IHC), and gene expression models of prognosis able to formalin-fixed, paraffin-embedded blocks in a large series of estrogen receptor (ER)–positive cancers from patients uniformly treated with adjuvant tamoxifen. erimental Design: Quantitative real-time reverse transcription-PCR (qRT-PCR) assays for 50 genes fying intrinsic breast cancer subtypes were completed on 786 specimens linked to clinical (median -up, 11.7 years) and IHC [ER, progesterone receptor (PR), HER2, and Ki67] data. Performance of fined intrinsic subtype and risk-of-relapse scores was assessed using multivariable Cox models and n-Meier analysis. Harrell's C-index was used to compare fixed models trained in independent data ncluding proliferation signatures. ults: Despite clinical ER positivity, 10% of cases were assigned to nonluminal subtypes. qRT-PCR ures for proliferation genes gave more prognostic information than clinical assays for hormone res or Ki67. In Cox models incorporating standard prognostic variables, hazard ratios for breast cansease-specific survival over the first 5 years of follow-up, relative to the most common luminal A e, are 1.99 [95% confidence interval (CI), 1.09-3.64] for luminal B, 3.65 (95% CI, 1.64-8.16) for -enriched subtype, and 17.71 (95% CI, 1.71-183.33) for the basal-like subtype. For node-negative e, PAM50 qRT-PCR–based risk assignment weighted for tumor size and proliferation identifies a with >95% 10-year survival without chemotherapy. In node-positive disease, PAM50-based progmodels were also superior. clusion: The PAM50 gene expression test for intrinsic biological subtype can be applied to large Con series of formalin-fixed, paraffin-embedded breast cancers, and gives more prognostic information than clinical factors and IHC using standard cut points. Clin Cancer Res; 16(21); 5222–32. ©2010 AACR.
A Panic Attack on Unit Roots and Cointegration

This paper develops a new methodology that makes use of the factor structure of large dimensional panels to understand the nature of non-stationarity in the data We refer to it as PANIC - a 'Panel Analysis of Non-stationarity in Idiosyncratic and Common components' PANIC consists of univariate and panel tests with a number of novel features It can detect whether the nonstationarity is pervasive or variable-specific or both It tests the components of the data instead of the observed series Inference is therefore more accurate when the components have different orders of integration PANIC also permits the construction of valid panel tests even when cross-section correlation invalidates pooling of statistics constructed using the observed data The key to PANIC is consistent estimation of the components even when the regressions are individually spurious We provide a rigorous theory for estimation and inference In Monte Carlo simulations the tests have very good size and power PANIC is applied to a panel of inflation series
Molecular Gas in the Powerful Radio Nucleus of the Ultraluminous Infrared Galaxy PKS 1345+12

Millimeter CO (1 → 0) interferometry and high-resolution, Hubble Space Telescope 1.1, 1.6, and 2.2 μm imaging of the radio compact galaxy PKS 1345+12 are presented. With an infrared luminosity of ~2 × 1012 L☉, PKS 1345+12 is a prime candidate for studying the link between the ultraluminous infrared galaxy phenomenon and radio galaxies. These new observations probe the molecular gas distribution and obscured nuclear regions of PKS 1345+12 and provide morphological support for the idea that the radio activity in powerful radio galaxies is triggered by the merger of gas-rich galaxies. Two nuclei separated by 2'' (4.0 kpc) are observed in the near-infrared; the extended southeastern nucleus has colors consistent with reddened starlight, and the compact northwestern nucleus has extremely red colors indicative of an optical quasar with a warm dust component. Further, the molecular gas, 3 mm continuum, and radio emission are coincident with the redder nucleus, confirming that the northwestern nucleus is the site of the active galactic nucleus and that the molecular gas is the likely fuel source.
Phylogeography, phylogeny and hybridization in trichechid sirenians: implications for manatee conservation

The three living species of manatees, West Indian (Trichechus manatus), Amazonian (Trichechus inunguis) and West African (Trichechus senegalensis), are distributed across the shallow tropical and subtropical waters of America and the western coast of Africa. We have sequenced the mitochondrial DNA control region in 330 Trichechus to compare their phylogeographic patterns. In T. manatus we observed a marked population structure with the identification of three haplotype clusters showing a distinct spatial distribution. A geographic barrier represented by the continuity of the Lesser Antilles to Trinidad Island, near the mouth of the Orinoco River in Venezuela, appears to have restricted the gene flow historically in T. manatus. However, for T. inunguis we observed a single expanding population cluster, with a high diversity of very closely related haplotypes. A marked geographic population structure is likely present in T. senegalensis with at least two distinct clusters. Phylogenetic analyses with the mtDNA cytochrome b gene suggest a clade of the marine Trichechus species, with T. inunguis as the most basal trichechid. This is in agreement with previous morphological analyses. Mitochondrial DNA, autosomal microsatellites and cytogenetic analyses revealed the presence of hybrids between the T. manatus and T. inunguis species at the mouth of the Amazon River in Brazil, extending to the Guyanas and probably as far as the mouth of the Orinoco River. Future conservation strategies should consider the distinct population structure of manatee species, as well as the historical barriers to gene flow and the likely occurrence of interspecific hybridization.
Vaccination with DNA Encoding an Immunodominant Myelin Basic Protein Peptide Targeted to Fc of Immunoglobulin G Suppresses Experimental Autoimmune Encephalomyelitis

We explore here if vaccination with DNA encoding an autoantigenic peptide can suppress autoimmune disease. For this purpose we used experimental autoimmune encephalomyelitis (EAE), which is an autoaggressive disease in the central nervous system and an animal model for multiple sclerosis. Lewis rats were vaccinated with DNA encoding an encephalitogenic T cell epitope, guinea pig myelin basic protein peptide 68–85 (MBP68–85), before induction of EAE with MBP68–85 in complete Freund's adjuvant. Compared to vaccination with a control DNA construct, the vaccination suppressed clinical and histopathological signs of EAE, and reduced the interferon γ production after challenge with MBP68–85. Targeting of the gene product to Fc of IgG was essential for this effect. There were no signs of a Th2 cytokine bias. Our data suggest that DNA vaccines encoding autoantigenic peptides may be useful tools in controlling autoimmune disease.
The changing epidemiology of upper gastrointestinal cancers in Israel: clinical and screening implications

Western countries and now developing countries have noted a decreasing incidence of upper gastrointestinal (UGI) (esophageal and gastric) cancers, but increasing distal esophageal adenocarcinoma and a shift to fundal-sited gastric cancer. We examined these trends in Israeli Jewish and nonJewish populations, drawing conclusions on the need to promote prevention and/or screening. Israel Cancer Registry UGI cancer data were computed by ethnicity, immigration after 1990, sex, sites and histology, examining age-standardized rates (ASR)/105 for 2000–2005 and incidence trends during 1980–2005. In Jews, male esophageal cancer incidence has increased (P<0.01) and is highest in European-American-born males (ASR/105, 1.98), but decreasing in the upper two-thirds of esophagus so that in men 89% now occur in the lower one-third. In both sexes this was associated with decreasing squamous cell carcinoma (P<0.01) but increased adenocarcinoma to cause 72.6% of esophageal cancers in men. Gastric cancer incidence is highest in European-American-born males (ASR/105, 11.75); there is a decreasing incidence in both sexes (P<0.01) and gastric site trends are stable. In nonJews, esophageal cancer incidence is three times higher in men (ASR/105, 0.82); they are only squamous cell cancers and incidence trends are stable. Gastric cancer incidence is twice as high in men (ASR/105, 8.45) and gastric site trends are stable. UGI cancer incidence in Jews and nonJews, men and women, is low as compared with most developing countries. The important findings are the low but prominent incidence of distal esophageal and gastric adenocarcinoma in male immigrants. This requires attention to possible preventive measures in at-risk groups.