Miracle-dz/UniFAR-FTUs huggingface dataset:
Survival differences of CIMP subtypes integrated with CNA information in human breast cancer

CpG island methylator phenotype of breast cancer is associated with widespread aberrant methylation at specified CpG islands and distinct patient outcomes. However, the influence of copy number contributing to the prognosis of tumors with different CpG island methylator phenotypes is still unclear. We analyzed both genetic (copy number) and epigenetic alterations in 765 breast cancers from The Cancer Genome Atlas data portal and got a panel of 15 biomarkers for copy number and methylation status evaluation. The gene panel identified two groups corresponding to distinct copy number profiles. In status of mere-loss copy number, patients were faced with a greater risk if they presented a higher CpG islands methylation pattern in biomarker panels. But for samples presenting merely-gained copy number, higher methylation level of CpG islands was associated with improved viability. In all, the integration of copy number alteration and methylation information enhanced the classification power on prognosis. Moreover, we found the molecular subtypes of breast cancer presented different distributions in two CpG island methylation phenotypes. Generated by the same set of human methylation 450K data, additional copy number information could provide insights into survival prediction of cancers with less heterogeneity and might help to determine the biomarkers for diagnosis and treatment for breast cancer patients in a more personalized approach.
The statistical analysis plan for the 0 . 9 % Saline vs . Plasma-Lyte 148 ® for Intensive care fluid Therapy ( SPLIT ) study

1 Medical Research Institute of New Zealand, Wellington, New Zealand 2 Intensive Care Unit, Wellington Regional Hospital, Wellington, New Zealand 3 Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, VIC, Australia 4 Department of Intensive Care Medicine, Christchurch Hospital, Christchurch, New Zealand 5 Department of Critical Care Medicine, Auckland City Hospital, Auckland, New Zealand 6 Intensive Care Unit, St George Hospital, Sydney, New South Wales, Australia 7 Critical Care Division, The George Institute for Global Health, Sydney, New South Wales, Australia 8 Cardiac and Vascular Intensive Care Unit, Auckland City Hospital, Auckland, New Zealand 9 Intensive Care Unit, Austin Hospital, Melbourne, VIC, Australia
Imaging , Diagnosis , Prognosis Prognostic Impact of D TAp 73 Isoform Levels and Their Target Genes in Colon Cancer Patients

Purpose: Cumulative data support the role of DTAp73 variants in tumorigenic processes such as drug resistance. We evaluate the impact of TP73 isoforms and their putative target genes ABCB1, HMGB1, and CASP1 on the survival of colon cancer patients and the correlation between their expressions. Experimental Design: We determined in 77 colon cancer patients the expression of DEx2p73, DEx2/ 3p73, DNp73, TAp73, ABCB1, HMGB1, and CASP1 by quantitative real-time reverse transcriptase-PCR. Tumor characteristics, disease-free survival, and overall survival (OS) were examined in each patient. Functional experiments were carried out to check whether ectopic expression of DNp73 modifies the proliferation, drug resistance, migration, and invasion properties of colon tumor cells and the expression of ABCB1, HMGB1, and CASP1. Results: Positive correlations were observed between the expression levels of DTAp73 variants and HMGB1. Furthermore, a trend was observed for ABCB1. Overexpression of DEx2/3p73 and DNp73 isoforms was significantly associated with advanced stages (P 1⁄4 0.04 and P 1⁄4 0.03, respectively) and predicted shortenedOS (P1⁄4 0.04 and P1⁄4 0.05, respectively). High levels of ABCB1 andHMGB1were associated with shorter OS (P 1⁄4 0.04 and P 1⁄4 0.05, respectively). Multivariate analysis showed that, in addition to the tumor stage, ABCB1 and HMGB1 had independent relationships with OS (P 1⁄4 0.008). Ectopic expression of DNp73 was associated with an increase in proliferation and drug resistance. Conclusions: The positive correlation between DTAp73 variants and HMGB1 and ABCB1 expression supports them as TP73 targets. The fact that upregulation of DTAp73 isoforms was associated with shortened OS, increase in proliferation, and drug resistance confirms their oncogenic role and plausible value as prognostic markers. ABCB1 and HMGB1, putative DTAp73 target genes, strongly predict OS in an independent manner, making clear the importance of studying downstream TP73 targets that could predict the outcome of colon cancer patients better than DTAp73 variants themselves do. Clin Cancer Res; 17(18);
An artificial anisotropy WCS-FDTD method

In this letter, we present a three-dimensional (3-D) artificial anisotropy weakly conditional stability finite-difference time-domain (WCS-FDTD) method to achieve better dispersion performance. This artificial anisotropy WCS-FDTD algorithm can minimize the dispersion error for arbitrary incident angles and different time-step sizes. Stability analysis presents that this algorithm is weakly conditionally stable if proper artificial anisotropy parameter values are chosen. Dispersion analysis illustrates the error of the numerical phase velocity can be controlled.
Optimistic initial value analysis in a greedy selection approach to MAB problems

The Multi Arm Bandit (MAB) problem is a well-known decision making problem, where the gambler (operator), seeks the highest value and best choice among arms with different reward distributions. In recent years, many effective strategies have been proposed for the mentioned MAB problem. The strategy's procedure mainly includes attempts on acquiring a better exploitation and efficiency, while also maximizing reliability by effectively exploring the search space. Hence, a suitable tradeoff between exploration and exploitation has been deemed necessary for achieving highest expected rewards. In the presented paper, the effect of assigning initial values has been studied as a deciding factor in the aforementioned tradeoff. In this regard, the initial value has been studied as an implicit exploration agent in greedy based selection strategies. Simulation and comparison of five methods have been presented and evaluated, using a similar exemplary case. Contrary to common belief, the obtained results have illustrated the high efficiency and exploration capability with proper initializing.
Psychiatric Problems and Trauma Exposure in Nondetained Delinquent and Nondelinquent Adolescents

This study examined the prevalence of and associations between specific psychiatric disorders, substance use problems, and trauma exposure in a sample of delinquent and nondelinquent adolescents. A nationally representative sample of adolescents (n = 3,614; M age = 14.5 years, SD = 1.7; 51% male; 71% White, non-Hispanic, 13.3% African American, non-Hispanic, 10.7% Hispanic) was interviewed via telephone about engagement in delinquent acts and their experience of posttraumatic stress disorder, major depressive episode, substance use, interpersonal violence, and other forms of trauma exposure. Delinquent adolescents were more likely than nondelinquent adolescents to experience trauma; they were also more likely to report past-year posttraumatic stress disorder, major depressive episode, alcohol abuse, and nonexperimental drug use. After accounting for the effects of demographics and trauma exposure, delinquency was associated with increased likelihood of posttraumatic stress disorder and problematic substance use in both genders and increased likelihood of major depressive episode in girls. Findings highlight substantial overlap among delinquency, trauma exposure, posttraumatic stress disorder, and major depressive episode in adolescents and the need for interventions that address these varied clinical problems. Future work should examine the factors underlying the development of these relations over time.
Regulation of prostaglandin production by nitric oxide; an in vivo analysis

1 Endotoxin E. Coli lipopolysaccharide (LPS)‐treatment in conscious, restrained rats increased plasma and urinary prostaglandin (PG) and nitric oxide (NO) production. Inducible cyclo‐oxygenase (COX‐2) and nitric oxide synthase (iNOS) expression accounted for the LPS‐induced PG and NO release since the glucocorticoid, dexamethasone inhibited both effects. Thus, LPS (4 mg kg−1) increased the plasma levels of nitrite/nitrate from 14 ± 1 to 84 ± 7 μm within 3 h and this rise was inhibited to 35 ± 1 μm by dexamethasone. Levels of 6‐keto PGF1α in the plasma were below the detection limit of the assay (< 0.2 ng ml−1). However, 3 h after the injection of LPS these levels rose to 2.6 ± 0.2 ng ml−1 and to 0.7 ± 0.01 ng ml−1 after LPS in rats that received dexamethasone.
Development of replication-competent viral vectors for HIV vaccine delivery.

PURPOSE OF REVIEW To briefly describe some of the replication-competent vectors being investigated for development of candidate HIV vaccines focusing primarily on technologies that have advanced to testing in macaques or have entered clinical trials. RECENT FINDINGS Replication-competent viral vectors have advanced to the stage at which decisions can be made regarding the future development of HIV vaccines. The viruses being used as replication-competent vector platforms vary considerably, and their unique attributes make it possible to test multiple vaccine design concepts and also mimic various aspects of an HIV infection. Replication-competent viral vectors encoding simian immunodeficiency virus or HIV proteins can be used to safely immunize macaques, and in some cases, there is evidence of significant vaccine efficacy in challenge protection studies. Several live HIV vaccine vectors are in clinical trials to evaluate immunogenicity, safety, the effect of mucosal delivery, and potential effects of preexisting immunity. SUMMARY A variety of DNA and RNA viruses are being used to develop replication-competent viral vectors for HIV vaccine delivery. Multiple viral vector platforms have proven to be well tolerated and immunogenic with evidence of efficacy in macaques. Some of the more advanced HIV vaccine prototypes based on vesicular stomatitis virus, vaccinia virus, measles virus, and Sendai virus are in clinical trials.
p16(Ink4a) and senescence-associated β-galactosidase can be induced in macrophages as part of a reversible response to physiological stimuli

Constitutive p16Ink4a expression, along with senescence-associated β-galactosidase (SAβG), are commonly accepted biomarkers of senescent cells (SCs). Recent reports attributed improvement of the healthspan of aged mice following p16Ink4a-positive cell killing to the eradication of accumulated SCs. However, detection of p16Ink4a/SAβG-positive macrophages in the adipose tissue of old mice and in the peritoneal cavity of young animals following injection of alginate-encapsulated SCs has raised concerns about the exclusivity of these markers for SCs. Here we report that expression of p16Ink4a and SAβG in macrophages is acquired as part of a physiological response to immune stimuli rather than through senescence, consistent with reports that p16Ink4a plays a role in macrophage polarization and response. Unlike SCs, p16Ink4a/SAβG-positive macrophages can be induced in p53-null mice. Macrophages, but not mesenchymal SCs, lose both markers in response to M1- [LPS, IFN-α, Poly(I:C)] and increase their expression in response to M2-inducing stimuli (IL-4, IL-13). Moreover, interferon-inducing agent Poly(I:C) dramatically reduced p16Ink4a expression in vivo in our alginate bead model and in the adipose tissue of aged mice. These observations suggest that the antiaging effects following eradication of p16Ink4a-positive cells may not be solely attributed to SCs but also to non-senescent p16Ink4a/SAβG-positive macrophages.
Multicolor Staining of Globin Subtypes Reveals Impaired Globin Switching During Erythropoiesis in Human Pluripotent Stem Cells

Adult hemoglobin composed of α‐ and β‐globin reflects a change from expression of embryonic ε‐ and fetal γ‐globin to adult β‐globin in human erythroid cells, so‐called globin switching. Human pluripotent stem cells (hPSCs) are a potential source for in vitro erythrocyte production, but they show prominent expression of γ‐globin with little β‐globin expression, which indicates incomplete globin switching. To examine the mechanism of this impaired globin switching, we optimized multicolor flow cytometry to simultaneously follow expression of different globin subtypes using different immunofluorescent probes. This enabled us to detect upregulation of β‐globin and the corresponding silencing of γ‐globin at the single‐cell level during cord blood CD34+ cell‐derived erythropoiesis, examined as an endogenous control. Using this approach, we initially characterized the heterogeneous β‐globin expression in erythroblasts from several hPSC clones and confirmed the predominant expression of γ‐globin. These hPSC‐derived erythroid cells also displayed reduced expression of BCL11A‐L. However, doxycycline‐induced overexpression of BCL11A‐L in selected hPSCs promoted γ‐globin silencing. These results strongly suggest that impaired γ‐globin silencing is associated with downregulated BCL11A‐L in hPSC‐derived erythroblasts and that multicolor staining of globin subtypes is an effective approach to studying globin switching in vitro.
Detection of enteroviruses in groundwater with the polymerase chain reaction

Standard methods for the detection of enteroviruses in environmental samples involve the use of cell culture, which is expensive and time-consuming. The polymerase chain reaction (PCR) is an attractive method for the detection of enteroviruses in water because primary cell culture is not needed and the increased sensitivity of PCR allows detection of the low numbers of target DNAs and RNAs usually found in environmental samples. However, environmental samples often contain substances that inhibit PCR amplification of target DNA and RNA. Procedures that remove substances that interfere with the amplification process need to be developed if PCR is to be successfully applied to environmental samples. An RNA-PCR assay for the detection of enteroviruses in water was developed and used to test a variety of groundwater concentrates and humic acid solutions seeded with poliovirus type 1. The groundwater samples and humic acid solutions were treated with Sephadex G-50, Sephadex G-100, Sephadex G-200, Chelex-100 resin, and a mixed bed resin to remove PCR-inhibitory material from the samples. Sephadex G-100 in combination with Chelex-100 was found to be very effective in removing inhibitory factors for the detection of enteroviruses in groundwater concentrates by PCR. Viruses were detected in two of the groundwater concentrates by the RNA-PCR assay after treatment with Sephadex G-100 plus Chelex-100. This was confirmed by tissue culture, suggesting that the treatment protocol and, subsequently, the RNA-PCR assay are applicable for the detection of enteroviruses in environmental samples.
Official Japanese reports significantly underestimate prevalence of overweight in school children: Inappropriate definition of standard weight and calculation of excess weight

Background: The obesity epidemic in Japan continues to increase. However, the prevalence and trends of obesity have not explicitly been determined in Japanese children. Aim: The study estimated the trend and prevalence of overweight in Japanese school children, 1980–2001. Subjects and methods: The 2001 cross-sectional national survey on 334,939 boys and 335,204 girls, 5–18 years of age was studied, using the 1978–1981 references. Main outcome measures were proportion of children with BMI ≥95th centile and those with ≥ + 20% excess body weight. Results: The prevalence of overweight increased 2.6 times (5.0% to 12.9%) in Japanese boys and 2.5 times (5.0% to 12.5%) in Japanese girls during the last two decades as assessed by using BMI, whereas the Japanese Ministry of Education, Culture, Sports and Science and Technology reported a much smaller increment in prevalence (5.8% to 9.2% in boys, 5.6% to 8.0% in girls, respectively) using the same data but based on a cut-off value of ≥ + 20% excess body weight. Conclusion: Official governmental reports significantly underestimate the current epidemic of obesity in Japan.
PROMOTING SUSTAINABLE PRACTICES: THE IMPORTANCE OF BUILDING LEADERSHIP CAPACITY

This paper highlights the importance of building leadership capacity in organisations that are seeking to promote more sustainable resource management practices. It also provides a review of the literature on environmental leadership and provides practical guidance on strategies to build leadership capacity. The paper s content is primarily derived from an international literature review conducted as part of research on emergent leaders who promote more sustainable forms of urban water management. The target audience for this paper is leadermanagers who are seeking to promote sustainable practices, have the power to implement leadership development initiatives in their organisations, and support the principle that leaders grow leaders .
Effect of imperceptible vibratory noise applied to wrist skin on fingertip touch evoked potentials – an EEG study

Random vibration applied to skin can change the sense of touch. Specifically, low amplitude white‐noise vibration can improve fingertip touch perception. In fact, fingertip touch sensation can improve even when imperceptible random vibration is applied to other remote upper extremity areas such as wrist, dorsum of the hand, or forearm. As such, vibration can be used to manipulate sensory feedback and improve dexterity, particularly during neurological rehabilitation. Nonetheless, the neurological bases for remote vibration enhanced sensory feedback are yet poorly understood. This study examined how imperceptible random vibration applied to the wrist changes cortical activity for fingertip sensation. We measured somatosensory evoked potentials to assess peak‐to‐peak response to light touch of the index fingertip with applied wrist vibration versus without. We observed increased peak‐to‐peak somatosensory evoked potentials with wrist vibration, especially with increased amplitude of the later component for the somatosensory, motor, and premotor cortex with wrist vibration. These findings corroborate an enhanced cortical‐level sensory response motivated by vibration. It is possible that the cortical modulation observed here is the result of the establishment of transient networks for improved perception.
Draft Genome Sequence of Pseudomonas sp. Strain JMM, a Sediment-Hosted Environmental Isolate

ABSTRACT Pseudomonas sp. strain JMM was isolated from the sediments of a natural water reservoir (pH, 6 to 7) located at Chambyal village in Samba district of Jammu and Kashmir, India. Here we report the annotated draft genome sequence of strain JMM having 52 contigs with 5,884 genes and an average G+C content of 66.5%.
Y RNA functions at the initiation step of mammalian chromosomal DNA replication

Non-coding Y RNAs have recently been identified as essential novel factors for chromosomal DNA replication in mammalian cell nuclei, but mechanistic details of their function have not been defined. Here, we identify the execution point for Y RNA function during chromosomal DNA replication in a mammalian cell-free system. We determined the effect of degradation of Y3 RNA on replication origin activation and on fork progression rates at single-molecule resolution by DNA combing and nascent-strand analysis. Degradation of Y3 RNA inhibits the establishment of new DNA replication forks at the G1- to S-phase transition and during S phase. This inhibition is negated by addition of exogenous Y1 RNA. By contrast, progression rates of DNA replication forks are not affected by degradation of Y3 RNA or supplementation with exogenous Y1 RNA. These data indicate that Y RNAs are required for the establishment, but not for the elongation, of chromosomal DNA replication forks in mammalian cell nuclei. We conclude that the execution point for non-coding Y RNA function is the activation of chromosomal DNA replication origins.
Relationship of the human immunodeficiency virus type 1 gp120 third variable loop to a component of the CD4 binding site in the fourth conserved region

Neutralizing antibodies that recognize the human immunodeficiency virus gp120 exterior envelope glycoprotein and are directed against either the third variable (V3) loop or conserved, discontinuous epitopes overlapping the CD4 binding region have been described. Here we report several observations that suggest a structural relationship between the V3 loop and amino acids in the fourth conserved (C4) gp120 region that constitute part of the CD4 binding site and the conserved neutralization epitopes. Treatment of the gp120 glycoprotein with ionic detergents resulted in a V3 loop-dependent masking of both linear C4 epitopes and discontinuous neutralization epitopes overlapping the CD4 binding site. Increased recognition of the native gp120 glycoprotein by an anti-V3 loop monoclonal antibody, 9284, resulted from from single amino acid changes either in the base of the V3 loop or in the gp120 C4 region. These amino acid changes also resulted in increased exposure of conserved epitopes overlapping the CD4 binding region. The replication-competent subset of these mutants exhibited increased sensitivity to neutralization by antibody 9284 and anti-CD4 binding site antibodies. The implied relationship of the V3 loop, which mediates post-receptor binding steps in virus entry, and components of the CD4 binding region may be important for the interaction of these functional gp120 domains and for the observed cooperativity of neutralizing antibodies directed against these regions.
Ventilation/perfusion distributions revisited

Purpose of review A major cause of hypoxemia in anesthesia is ventilation-perfusion (VA/Q) mismatch. With more advanced surgery and an aging population, monitoring of VA/Q is of increasing importance. Recent findings The classic multiple inert gas elimination technique has been simplified with a new approach based on mass spectrometry. VA/Q distributions can also be measured, at the bedside, by varying inspired oxygen concentration. MRI, 3-dimensional single photon emission computed tomography, positron emission tomography, and electrical impedance tomography enable imaging of perfusion and ventilation, and in some of the techniques also the distribution of inflammation. One-lung ventilation with thoracoscopy and capnothorax require careful monitoring of VA/Q, made possible bedside by electrical impedance tomography. Carbon dioxide, but not air, for pneumoperitoneum enhances shift of perfusion to ventilated regions. Ventilatory support during cardiopulmonary resuscitation causes less VA/Q mismatch when inspired oxygen concentrations are lower. Mechanisms of redistribution of lung blood flow by inhaled nitric oxide include endothelin-mediated vasoconstriction in collapsed lung regions. Summary Methods are continuously developing to simplify measurement of VA/Q and also to relate VA/Q to inflammation. The recording of VA/Q has helped to explain important aspects of gas exchange in thoracic anesthesiology and in intensive care medicine.