Miracle-dz/UniFAR-FTUs huggingface dataset:
Prestige centrality-based functional outlier detection in gene expression analysis

MOTIVATION Traditional gene expression analysis techniques capture an average gene expression state across sample replicates. However, the average signal across replicates will not capture activated gene networks in different states across replicates. For example, if a particular gene expression network is activated within a subset or all sample replicates, yet the activation state across the sample replicates differs by the specific genes activated in each replicate, the activation of this network will be washed out by averaging across replicates. This situation is likely to occur in single cell gene expression experiments or in noisy experimental settings where a small sub-population of cells contributes to the gene expression signature of interest. RESULTS AND IMPLEMENTATION In this light, we developed a novel network-based approach which considers gene expression within each replicate across its entire gene expression profile, and identifies outliers across replicates. The power of this method is demonstrated by its ability to enrich for distant metastasis related genes derived from noisy expression data of CD44+CD24-/low tumor initiating cells.
The Role of Domain Content in Understanding Identity Development Processes

The current studies examined the importance of domain content in the processes of identity development using two approaches – narrative and status. We examined personal narratives for identity domain content, the co-occurrence of different contents, and the relations between content and processes, using two approaches to identity – status and narrative. Across two studies, 762 participants (average age = 19 years), and 2214 narratives, traditional ideological and interpersonal status domains were present, but so was a novel domain: existential concerns. Narrative identity processes were more frequent in narratives with multiple contents, and relations between identity statuses processes and narrative processes were modest. We discuss theoretical implications, the importance of examining content, and the utility of narrative approaches for doing so.
Vasculopathy in sickle cell disease: Biology, pathophysiology, genetics, translational medicine, and new research directions

Sickle cell disease has been very well characterized as a single amino acid molecular disorder of hemoglobin leading to its pathological polymerization, with resulting red cell rigidity that causes poor microvascular blood flow, with consequent tissue ischemia and infarction. More recently, an independent spectrum of pathophysiology of blood vessel function has been demonstrated, involving abnormal vascular tone and activated, adhesive endothelium. These vasculopathic abnormalities are attributable to pathways involving hemolysis-associated defects in nitric oxide bioavailability, oxidative stress, ischemia-reperfusion injury, hemostatic activation, leukocytes and platelets. Vasculopathy of sickle cell disease has been implicated in the development of pulmonary hypertension, stroke, leg ulceration and priapism, particularly associated with hemolytic severity, and reported also in other severe hemolytic disorders. This vasculopathy might also play a role in other chronic organ dysfunction in patients with sickle cell disease. These pathways present novel targets for pharmacologic intervention, and several clinical trials are already under way. The authors present their perspectives of a workshop held at the National Institutes of Health in August 2008 on vasculopathy in sickle cell disease, along with meritorious future scientific questions on the topic of vascular complications of sickle cell disease.
The paradox of invasion: Reeves' muntjac deer invade the British Isles from a limited number of founding females

High levels of genetic diversity and high propagule pressure are favoured by conservation biologists as the basis for successful reintroductions and ensuring the persistence of populations. However, invasion ecologists recognize the ‘paradox of invasion’, as successful species introductions may often be characterized by limited numbers of individuals and associated genetic bottlenecks. In the present study, we used a combination of high-resolution nuclear and mitochondrial genetic markers to investigate the invasion history of Reeves' muntjac deer in the British Isles. This invasion has caused severe economic and ecological damage, with secondary spread currently a concern throughout Europe and potentially globally. Microsatellite analysis based on eight loci grouped all 176 introduced individuals studied from across the species' range in the UK into one genetic cluster, and seven mitochondrial D-loop haplotypes were recovered, two of which were present at very low frequency and were related to more common haplotypes. Our results indicate that the entire invasion can be traced to a single founding event involving a low number of females. These findings highlight the fact that even small releases of species may, if ignored, result in irreversible and costly invasion, regardless of initial genetic diversity or continual genetic influx.
Emerging adenosine receptor agonists

Adenosine receptors (ARs) are a four-member subfamily of G protein-coupled receptors and are major targets of caffeine and theophylline. There are four subtypes of ARs, designated as A1, A2A, A2B and A3. Selective agonists are now available for all four subtypes. Over a dozen of these selective agonists are now in clinical trials for various conditions, although none has received regulatory approval except for the endogenous AR agonist adenosine itself. A1AR agonists are in clinical trials for cardiac arrhythmias and neuropathic pain. A2AAR agonists are now in trials for myocardial perfusion imaging and as anti-inflammatory agents. A2BAR agonists are under preclinical scrutiny for potential treatment of cardiac ischemia. A3AR agonists are in clinical trials for the treatment of rheumatoid arthritis and colorectal cancer. The present review will mainly cover the agonists that are presently in clinical trials for various conditions and only a brief introduction will be given to major chemical classes of AR agonists presently under investigation.
Atypical Memory B Cells Are Greatly Expanded in Individuals Living in a Malaria-Endemic Area1

Epidemiological observations in malaria endemic areas have long suggested a deficiency in the generation and maintenance of B cell memory to Plasmodium falciparum (Pf) in individuals chronically reinfected with the parasite. Recently, a functionally and phenotypically distinct population of FCRL4+ hyporesponsive memory B cells (MBCs) was reported to be expanded in HIV-infected individuals with high viral loads. In this study, we provide evidence that a phenotypically similar atypical MBC population is significantly expanded in Pf-exposed Malian adults and children as young as 2 years of age as compared with healthy U.S. adult controls. The number of these atypical MBCs was higher in children with chronic asymptomatic Pf infections compared with uninfected children, suggesting that the chronic presence of the parasite may drive expansion of these distinct MBCs. This is the first description of an atypical MBC phenotype associated with malaria. Understanding the origin and function of these MBCs could be important in informing the design of malaria vaccines.
Limitations of Using a Single Postdose Midazolam Concentration to Predict CYP3A‐Mediated Drug Interactions

Midazolam is a common probe used to predict CYP3A activity, but multiple blood samples are necessary to determine midazolam's area under the concentration‐time curve (AUC). As such, single sampling strategies have been examined. The purpose of this study was to assess the ability of single midazolam concentrations to predict midazolam AUC in the presence and absence of CYP3A modulation by Ginkgo biloba extract (GBE). Subjects received oral midazolam 8 mg before and after 28 days of GBE administration. Postdose blood samples were collected during both study periods and midazolam AUC determined. Linear regression was used to generate measures of predictive performance for each midazolam concentration. The geometric mean ratio (90% confidence intervals) of midazolam AUC0‐∞ post‐GBE/AUC0‐∞ pre‐GBE was 0.66 (0.49–0.84) (P = .03). Before and after GBE administration, optimal midazolam sampling times were identified at 3.5 to 5 hours and 2 to 3 hours, respectively. Single midazolam concentrations between 2 and 5 hours correctly predicted the reduction in midazolam AUC following GBE exposure, but confidence intervals were generally wide. Intersubject variability in CYP3A activity (either inherent or from drug administration) alters the prediction of optimal midazolam sampling times; therefore, midazolam AUC is preferred for assessing CYP3A activity in drug‐drug interaction studies.
Two Pilot Randomized Trials To Examine Feasibility and Impact of Treated Parents as Peer Interventionists in Family-Based Pediatric Weight Management.

BACKGROUND To examine feasibility and initial efficacy of having previously treated parents serve as peer interventionists in family-based behavioral weight management treatment (FBT). METHODS Children aged 7-11 years with overweight/obesity and parents (n = 59 families) were enrolled in one of two pilot trials, the EPICH (Engaging Parents in Child Health) randomized trial comparing professional versus peer FBT delivery or the Parent Partnership trial, which provided professionally delivered FBT to families (first generation) and then randomly assigned first generation parents to either be or not be peer interventionists for subsequent families (second generation). Efficacy (child zBMI change), feasibility, and costs for delivering FBT, and impacts of being a peer interventionist were examined. RESULTS In EPICH, families receiving professional versus peer intervention had similar decreases in child zBMI and parent BMI, with markedly lower costs for peer versus professional delivery. In Parent Partnership, families receiving peer intervention significantly decreased weight status, with very preliminary evidence suggesting better maintenance of child zBMI changes if parents served as peer interventionists. Previously treated parents were willing, highly confident, and able to serve as peer interventionists in FBT. CONCLUSIONS Two pilot randomized clinical trials suggest parents-as-peer interventionists in FBT may be feasible, efficacious, and delivered at lower costs, with perhaps some additional benefits to serving as a peer interventionist. More robust investigation is warranted of peer treatment delivery models for pediatric weight management.
Identification and characterization of the intercellular adhesion molecule-2 gene as a novel p 53 target

The p53 tumor suppressor inhibits cell growth through the activation of both cell cycle arrest and apoptosis, which maintain genome stability and prevent cancer development. Here, we report that intercellular adhesion molecule-2 (ICAM2) is transcriptionally activated by p53. Specifically, ICAM2 is induced by the p53 family and DNA damage in a p53-dependent manner. We identified a p53 binding sequence located within the ICAM2 gene that is responsive to wild-type p53, TAp73, and TAp63. In terms of function, we found that the ectopic expression of ICAM2 inhibited cancer cell migration and invasion. In addition, we demonstrated that silencing endogenous ICAM2 in cancer cells caused a marked increase in extracellular signal-regulated kinase (ERK) phosphorylation levels, suggesting that ICAM2 inhibits migration and invasion of cancer cells by suppressing ERK signaling. Moreover, ICAM2 is underexpressed in human cancer tissues containing mutant p53 as compared to those with wild-type p53. Notably, the decreased expression of ICAM2 is associated with poor survival in patients with various cancers. Our findings demonstrate that ICAM2 induction by p53 has a key role in inhibiting migration and invasion.
Ribonucleotide triggered DNA damage and RNA-DNA damage responses

Research indicates that the transient contamination of DNA with ribonucleotides exceeds all other known types of DNA damage combined. The consequences of ribose incorporation into DNA, and the identity of protein factors operating in this RNA-DNA realm to protect genomic integrity from RNA-triggered events are emerging. Left unrepaired, the presence of ribonucleotides in genomic DNA impacts cellular proliferation and is associated with chromosome instability, gross chromosomal rearrangements, mutagenesis, and production of previously unrecognized forms of ribonucleotide-triggered DNA damage. Here, we highlight recent findings on the nature and structure of DNA damage arising from ribonucleotides in DNA, and the identification of cellular factors acting in an RNA-DNA damage response (RDDR) to counter RNA-triggered DNA damage.
Caudal-like PAL-1 directly activates the bodywall muscle module regulator hlh-1 in C. elegans to initiate the embryonic muscle gene regulatory network

Previous work in C. elegans has shown that posterior embryonic bodywall muscle lineages are regulated through a genetically defined transcriptional cascade that includes PAL-1/Caudal-mediated activation of muscle-specific transcription factors, including HLH-1/MRF and UNC-120/SRF, which together orchestrate specification and differentiation. Using chromatin immunoprecipitation (ChIP) in embryos, we now demonstrate direct binding of PAL-1 in vivo to an hlh-1 enhancer element. Through mutational analysis of the evolutionarily conserved sequences within this enhancer, we identify two cis-acting elements and their associated transacting factors (PAL-1 and HLH-1) that are crucial for the temporal-spatial expression of hlh-1 and proper myogenesis. Our data demonstrate that hlh-1 is indeed a direct target of PAL-1 in the posterior embryonic C. elegans muscle lineages, defining a novel in vivo binding site for this crucial developmental regulator. We find that the same enhancer element is also a target of HLH-1 positive auto regulation, underlying (at least in part) the sustained high levels of CeMyoD in bodywall muscle throughout development. Together, these results provide a molecular framework for the gene regulatory network activating the muscle module during embryogenesis.
Can Medicaid Claims Validly Ascertain Foster Care Status?

Medicaid claims have been used to identify populations of children in foster care in the current literature; however, the ability of such an approach to validly ascertain a foster care population is unknown. This study linked children in the National Survey of Child and Adolescent Well-Being-I to their Medicaid claims from 36 states using their Social Security numbers. Using this match, we examined discordance between caregiver report of foster care placement and the foster care eligibility code contained in the child’s Medicaid claims. Only 73% of youth placed in foster care for at least a year displayed a Medicaid code for foster care eligibility. Half of all youth coming into contact with child welfare displayed discordance between caregiver report and Medicaid claims. Children with emergency department utilization, and those in primary care case management health insurance arrangements, had the highest odds of accurate ascertainment. The use of Medicaid claims to identify a cohort of children in foster care results in high rates of underascertainment. Supplementing administrative data with survey data is one way to enhance validity of ascertainment.
Variation and context of yawns in captive chimpanzees (Pan troglodytes)

Primate yawns are usually categorized according to context (e.g. as a threat, anxious, or rest yawn), but there has been little consideration of whether these yawns are best regarded as a unitary behavior that only differs with respect to the context in which it is observed. This study examined the context and precise morphology of yawns in a group of 11 captive chimpanzees. Focal video sampling was used to describe the morphology and intensity of 124 yawns using ChimpFACS, a system for coding facial movements. Two distinct forms of yawn were identified, a full yawn and a yawn which is modified by additional actions that reduce the mouth aperture. These modified yawns may indicate some degree of voluntary control over facial movement in chimpanzees and, consequently, multiple functions of yawning according to context. To assess context effects, mean activity levels (resting, locomotion, and grooming) and scratching rates were compared one minute before and after each yawn. Locomotion was significantly increased following both types of yawn, whereas scratching rates significantly increased following modified yawns but decreased following full yawns. In terms of individual differences, males did not yawn more than females, although male yawns were of higher intensity, both in the degree of mouth opening and in the amount of associated head movement. These data indicate that yawning is associated with a change in activity levels in chimpanzees, but only modified yawns may be related to increased arousal. Different types of yawn can therefore be differentiated at the morphological level as well as context level. Am. J. Primatol. 72:262–269, 2010. © 2009 Wiley‐Liss, Inc.
Downregulation of Filamin A Interacting Protein 1-Like is Associated with Promoter Methylation and Induces an Invasive Phenotype in Ovarian Cancer

Ovarian cancer is the most lethal gynecologic malignancy with a five-year survival rate below 25% for patients with stages III and IV disease. Identifying key mediators of ovarian cancer invasion and metastasis is critical to the development of more effective therapeutic interventions. We previously identified Filamin A interacting protein 1-like (FILIP1L) as an important mediator of cell proliferation and migration. In addition, targeted expression of FILIP1L in tumors inhibited tumor growth in vivo. In our present study, we confirmed that both mRNA and protein expression of FILIP1L were downregulated in ovarian cancer cells compared with normal ovarian epithelial cells. FILIP1L expression was inversely correlated with the invasive potential of ovarian cancer cell lines and clinical ovarian cancer specimens. We also provide evidence that DNA methylation is a mechanism by which FILIP1L is downregulated in ovarian cancer. The CpG island in the FILIP1L promoter was heavily methylated in ovarian cancer cells. Methylation status of the FILIP1L promoter was inversely correlated with FILIP1L expression in ovarian cell lines and clinical ovarian specimens. Reduced methylation in the FILIP1L promoter following treatment with a DNA demethylating agent was associated with restoration of FILIP1L expression in ovarian cancer cells. A transcription activator, cAMP-responsive element binding protein (CREB) was shown to bind to the CREB/ATF site in the CpG island of the FILIP1L promoter. Overall, these findings suggest that downregulation of FILIP1L associated with DNA methylation is related with the invasive phenotype in ovarian cancer and that modulation of FILIP1L expression has the potential to be a target for ovarian cancer therapy. Mol Cancer Res; 9(8); 1126–38. ©2011 AACR.
Comparing the Effects of Elementary Music and Visual Arts Lessons on Standardized Mathematics Test Scores.

The purpose of this quantitative, causal-comparative study was to compare the effect elementary music and visual arts lessons had on third through sixth grade standardized mathematics test scores. Inferential statistics were used to compare the differences between test scores of students who took in-school, elementary, music instruction during the same semester state standardized mathematics tests were administered and those who took in-school, elementary visual arts instruction during the same semester standardized mathematics tests were administered. The students attended seven elementary schools in the same North Alabama school district. The research questions were: (a) Does participation in elementary school music lessons have a greater positive effect on the proportion of third through sixth grade students who score Level III and Level IV on the ARMT mathematics test compared to third through sixth grade students participating in elementary school visual arts lessons? and (b) Does participation in elementary school music lessons have a greater positive effect on the mean SAT-10 mathematics test scores of third through sixth grade students compared to third through sixth grade students participating in elementary school visual arts lessons? There results indicated there was not a statistically significant difference in the analysis of the ARMT scores; however, the analysis did reveal that on average a greater proportion of students scored higher on the mathematics section of the ARMT when taking school music lessons compared to visual arts lessons. The analysis results of the SAT-10 scores did yield a statistically significant difference.
Low serum lycopene concentration is associated with an excess incidence of acute coronary events and stroke: the Kuopio Ischaemic Heart Disease Risk Factor Study

A number of epidemiological studies have shown an association between β-carotene and the risk of cardiovascular diseases, whereas only a few studies are available concerning the association of lycopene with the risk of coronary events, and no studies have been undertaken concerning lycopene and stroke. Thus, we tested the hypothesis that low serum levels of lycopene are associated with increased risk of acute coronary events and stroke in middle-aged men previously free of CHD and stroke. The subjects were 725 men aged 46–64 years examined in 1991–3 in the Kuopio Ischaemic Heart Disease Risk Factor Study. Forty-one men had either a fatal or a non-fatal acute coronary event or a stroke by December 1997. In a Cox' proportional hazard's model adjusting for examination years, age, systolic blood pressure and three nutritional factors (serum folate, β-carotene and plasma vitamin C), men in the lowest quarter of serum lycopene levels (≤0·07 μmol/l) had a 3·3-fold (95 % CI 1.7, 6.4, P < 0·001) risk of acute coronary events or stroke compared with the others. Our study suggests that a low serum level of lycopene is associated with an increased risk of atherosclerotic vascular events in middle-aged men previously free of CHD and stroke.