Miracle-dz/UniFAR-FTUs huggingface dataset:
Search for potential gastric cancer markers using miRNA databases and gene expression analysis.

AIM The aim of this study was to identify genes that are differentially expressed in gastric tumors and to analyze the association of their expression level with tumor clinicopathologic features. METHODS In the present research, we used bioinformatic-driven search to identify miRNA that are down-regulated in gastric tumors and to find their potential targets. Then, the expression levels of some of the target mRNAs were investigated using reverse transcription polymerase chain reaction (RT-PCR) analysis. RESULTS As a result of the bioinformatics analysis, fifteen genes were found to be potentially differentially expressed between the tumors and normal gastric tissue. Five of them were chosen for the further analysis (WNT4, FGF12, EFEMP1, CTGF, and HSPG2) due to their important role in cell proliferation and differentiation. Expression levels of these genes were evaluated in our collection of frozen tissue samples of gastric tumor and paired normal stomach epithelia. Increased FGF12 expression was observed in diffuse type of gastric cancer while WNT4 mRNA was found to be down-regulated in intestinal type of gastric cancer. Besides, CTGF gene overexpression was revealed in diffuse type of stomach cancer in comparison with that in intestinal type. Up-regulation of CTGF was also associated with lymph node metastasis. CONCLUSIONS The findings show its expedient to perform further investigations in order to clarify diagnostic and prognostic value of CTGF, FGF12, and WNT4's in stomach cancer as well as the role of these genes in carcinogenesis.
Pediatric Erosive Esophagitis Maintenance: Finally, Some Level 1 Evidence!

In children, as in adults, gastroesophageal reflux disease (GERD), particularly erosive esophagitis, is now believed to be a chronic disease, probably requiring lifelong maintenance therapy. However, this assumption has not received adequate clinical testing, and the provocative article by Boccia et al. in this issue of the Journal challenges it. The strengths of this exceptional pediatric study lie in its prospective, controlled, randomized character, and in its relatively long duration of prospective follow-up. Weaknesses of the study include its limited power and lack of prior validation of outcome measures. The conclusions of the study are applicable only to children without chronic neurologic, respiratory, or congenital esophageal abnormalities, the children for whom chronic proton pump inhibitors (PPIs) are most often required. The study's provocative results might be explained by the fundamental lack of GERD chronicity in otherwise healthy children, combined with absence of the PPI dependence that can be produced when PPIs are used chronically for chronic disease.
Principles and promises in the Convention on the Rights of the Child and the Convention on the Rights of Persons with Disabilities

What are children's basic developmental needs, especially in early childhood? And how can these needs best be addressed to the benefit of all children, including children with specific needs? Which human rights norms provide us with guidance and tools to explore and improve the social and legal position of all young children, including children with disabilities, so as to guarantee to each of them the best possible start in life? These questions are dealt with in two parts. In part one, a general introduction to the theme of basic developmental needs of young children is presented. In part two, a broad and comprehensive approach is proposed towards meeting these needs, for which the acronym SMECC is introduced. SMECC refers to an integrated 'big five' of child rights based child and family laws and policies (viz., School child rights and parenthood education, a legal Minimum standard for competent parenthood, child rights and parenting Education for parents-to-be, Child- and family-friendly social and economic policies, and a high-quality Continuum of care for children and families). In both parts of this contribution, the principles and promises contained in the Convention on the Rights of the Child and the Convention on the Rights of Persons with Disabilities are highlighted, whereby special reference is made to the views of the Committee on the Rights of the Child.
The Diagnosis and Prevalence of Hyperactivity in Chinese Schoolboys

Background This study was undertaken to examine the validity of different diagnostic definitions of hyperactivity in a Chinese population. Estimates of the prevalence of hyperactivity were made according to these different diagnostic definitions. Method In a two-stage epidemiological study of hyperactivity in Hong Kong, 3069 Chinese schoolboys were screened by questionnaires; and a stratified sample of 611 of them entered a second stage for more detailed diagnostic assessment. Results Children with hyperkinetic disorder (ICD–10) or ADDH (DSM–III) both displayed significant hyperactive symptoms, but with somewhat different external correlates; hyperkinetic disorder tended to show more neurodevelopmental impairments, ADDH more cognitive and educational difficulties. These findings raise the possibility of heterogeneity in the disorders present with hyperactivity. The DSM–III–R category of ADHD was more common, and those extra cases, that did not overlap with ADDH or hyperkinetic disorder, included children with no obvious behavioural, cognitive or neurodevelopmental impairments. Hence ADHD may be an over-inclusive category. Prevalence rates for hyperkinetic disorder, ADDH and ADHD were respectively 0.78%, 6.1% and 8.9%. Conclusions A disorder of hyperactivity does exist in the Chinese culture, displaying the same kinds of symptomatology and external correlates as in the West. The prevalence rates of hyperkinetic disorder and ADDH in Chinese schoolboys are on the low side when compared to those reported in Western studies.
Modulation of Ca2+ channel currents of acutely dissociated rat periaqueductal grey neurons

1 The actions of the neuropeptide nociceptin on the calcium channel currents (IBa) of acutely dissociated rat periaqueductal grey (PAG) neurons were examined using whole‐cell patch clamp techniques. These effects were compared with those of opioid receptor agonists and the GABAB receptor agonist baclofen. 2 Neurons from young adult rats (23 to 56 days old) expressed predominantly ω‐conotoxin GVIA (N‐type)‐ and ω‐agatoxin IVA (P/Q‐type)‐sensitive IBa, together with smaller amounts of nimodipine‐sensitive current and current resistant to all three blockers. There was proportionately more N‐type IBa in neurons from female rats and proportionately more resistant current in neurons from male rats. 3 Nociceptin (EC50, 5 nm) and baclofen (EC50, 0.8 μm) inhibited IBa in all PAG neurons, while the opioid agonist methionine enkephalin (met‐enkephalin; 300 nm‐10 μm) inhibited IBa in 40 % of neurons. The effects of met‐enkephalin were reversed by the μ‐opioid antagonist CTAP, and mimicked by the μ‐opioid agonist DAMGO (300 nm‐3 μm). The δ‐opioid agonists DPDPE and deltorphin II, and the κ‐opioid agonist U69593, did not affect IBa in any neuron. The actions of nociceptin were not mimicked or blocked by the opioid antagonist naloxone or the nociceptin analogue [desPhe1]‐nociceptin. 4 The effects of nociceptin and baclofen on IBa were blocked by pretreatment of the neurons with pertussis toxin (500 ng ml−1, 8 h). 5 Nociceptin predominantly inhibited the N‐type (EC50, 2 nm; maximum inhibition, 50 %) and P/Q‐type (EC50, 7 nm; maximum inhibition, 33 %) IBa while having little effect on the L‐type and R‐type IBa. 6 These results are consistent with the previously described actions of nociceptin, baclofen and μ‐opioids in PAG slices, whereby they couple to increases in an inwardly rectifying K+ conductance. These agonists thus have the potential to modulate the function of PAG neurons via a number of different cellular effectors.
Mucin histochemical analysis of minute gastric differentiated adenocarcinoma

Fifty‐six surgically resected intramucosal differentiated adenocarcinomas (DA) of the stomach with a maximum diameter of less than 5 mm were analyzed by mucin histochemistry. Gastric type phenotypic expression was observed in 41.1% of cases, intestinal type in 28.6% and gastric–intestinal type in 28.6% of all cancers. Gastric type phenotypic expression was the most frequent. As the tumor diameter increased, the incidence of DA with gastric phenotype tended to decrease. Intestinal metaplasia of the cancer’s surrounding mucosa was absent or slight in DA with gastric phenotype, but moderate to severe in DA with gastric–intestinal phenotype and intestinal phenotype. Morphologically and mucin histochemically, intestinal metaplasia surrounding DA with gastric phenotype was immature and incomplete compared with DA with gastric– intestinal phenotype or intestinal phenotype. It is suggested that a large amount of DA with gastric phenotype is histogenetically derived from the gastric gland proper without intestinal metaplasia. However, as the tumor grows and intestinal metaplasia progresses, intestinal type phenotypic expression appears and then DA with gastric phenotype changes into DA with gastric–intestinal phenotype or intestinal phenotype.
Treatment Trends and Outcomes in US Hospital Stays of Children With Empyema

Background: Recently published practice guidelines continue to reflect uncertainty about the comparative effectiveness of various treatments for empyema in children. We describe treatment trends and outcomes in pediatric empyema using the most current nationally representative data. Methods: Using survey methods and Kids’ Inpatient Databases from 1997 to 2009, we evaluated hospital stays in children 0–18 years of age. We used 2009 data to compare transfer-out rates and lengths of stay across various types of treatment, after adjusting for patient and hospital factors. Results: From 1997 to 2009, empyema discharges steadily increased from 3.1 to 6.0 per 100,000 children (P < 0.001 for trend) and also were increasingly likely (P < 0.01) to be coded for: (1) at least 1 pleural drainage procedure (76.4–83.2%), (2) multiple drainage procedures (36.0–41.6%) and (3) home health care (8.7–15.0%). By 2009, video-assisted thoracoscopic surgery was more commonly coded than chest tube drainage and was associated with a lower transfer-out rate (0.6% vs. 10.1%, adjusted P < 0.001) but no reduction in mean length of stay [11.2 vs. 13.4 days, adjusted incidence rate ratio 0.95 (95% confidence interval: 0.88–1.04)] for children neither admitted nor discharged by transfer. Conclusions: US hospital stays for empyema in children not only continued to increase through 2009 but were also characterized by more intense procedural management. Outcomes results in this population-based study are consistent with practice guidelines and recommendations that recently endorsed chest tube drainage as an acceptable first treatment option for most children with empyema.
Intergenerational transmission of role reversal between parent and child: Dyadic and family systems internal working models

The current study examined the intergenerational transmission of role reversal within a developmental psychopathology framework. Role reversal is a relationship disturbance in which a parent looks to a child to meet the parent's need for comfort, parenting, intimacy, or play, and the child attempts to meet these needs. In a normative sample, n = 138, fathers and mothers reported on childhood role reversal with their mothers as part of the Adult Attachment Interview, AAI (George, Kaplan, & Main, 1984). Mother – child role reversal was then assessed in an observational paradigm when children were 2 years of age. Based on theories of dyadic and family systems internal working models we hypothesized gender specific replications of role reversal in the next generation. Indeed, mothers who reported role reversal with their mothers during the AAI tended to engage in higher levels of role reversal with their toddler-aged daughters. Furthermore, when fathers reported role reversal with their mothers during the AAI, mothers tended to engage in higher levels of role reversal with their toddler-aged sons. The importance of the inclusion of fathers in family research, the relationship between role reversal and attachment, and implications for preventive interventions are discussed.
Knockdown of ALR (MLL2) Reveals ALR Target Genes and Leads to Alterations in Cell Adhesion and Growth

ABSTRACT ALR (MLL2) is a member of the human MLL family, which belongs to a larger SET1 family of histone methyltransferases. We found that ALR is present within a stable multiprotein complex containing a cohort of proteins shared with other SET1 family complexes and several unique components, such as PTIP and the jumonji family member UTX. Like other complexes formed by SET1 family members, the ALR complex exhibited strong H3K4 methyltransferase activity, conferred by the ALR SET domain. By generating ALR knockdown cell lines and comparing their expression profiles to that of control cells, we identified a set of genes whose expression is activated by ALR. Some of these genes were identified by chromatin immunoprecipitation as direct ALR targets. The ALR complex was found to associate in an ALR-dependent fashion with promoters and transcription initiation sites of target genes and to induce H3K4 trimethylation. The most characteristic features of the ALR knockdown cells were changes in the dynamics and mode of cell spreading/polarization, reduced migration capacity, impaired anchorage-dependent and -independent growth, and decreased tumorigenicity in mice. Taken together, our results suggest that ALR is a transcriptional activator that induces the transcription of target genes by covalent histone modification. ALR appears to be involved in the regulation of adhesion-related cytoskeletal events, which might affect cell growth and survival.
A Phase I Single-Agent Study of Twice-Weekly Consecutive-Day Dosing of the Proteasome Inhibitor Carfilzomib in Patients with Relapsed or Refractory Multiple Myeloma or Lymphoma

Purpose: Carfilzomib is a next-generation, selective, proteasome inhibitor with clinical activity in relapsed and/or refractory multiple myeloma. The objectives of this phase I study were to establish the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of escalating doses of carfilzomib in patients with relapsed or refractory hematologic malignancies. Experimental design: Carfilzomib (doses ranging from 1.2–27 mg/m2) was administered i.v. on 2 consecutive days for 3 weeks of a 4-week cycle. Single-agent dose escalation (n = 37) was followed by a dose-expansion phase (n = 11) that comprised 2 cohorts (carfilzomib or carfilzomib + dexamethasone). During dose expansion, carfilzomib was administered starting with 20 mg/m2 during the first week (days 1, 2) and then escalated to 27 mg/m2 thereafter. Results: A maximum tolerated dose (MTD) was not reached during dose escalation. Dosing in the expansion cohort was well tolerated. Adverse events were manageable and primarily of grade I or II. The main hematologic adverse events of ≥ grade III were anemia and thrombocytopenia. Notably, there were no observations of grade III or more peripheral neuropathy. Carfilzomib was cleared rapidly with an elimination half-life of less than 30 minutes but still induced dose-dependent inhibition of the 20S chymotrypsin-like proteasome activity. At doses of 15 to 27 mg/m2, there was evidence of activity among patients with multiple myeloma and with non-Hodgkin lymphoma. Conclusions: Escalated dosing of carfilzomib on a schedule of 2 consecutive days for 3 weeks of a 4-week cycle was tolerable and showed promising activity. This dose regimen has been selected for ongoing and future clinical studies, including PX-171-003A1 and the pivotal trial ASPIRE. Clin Cancer Res; 18(17); 4830–40. ©2012 AACR.
Enhancement of the HIV‐1 inhibitory activity of RANTES by modification of the N‐terminal region: dissociation from CCR5 activation

Although selected chemokines act as natural inhibitors of human immunodeficiency virus (HIV) infection, their inherent proinflammatory activity may limit a therapeutic use. To elucidate whether the antiviral and signaling functions of RANTES can be dissociated, several recombinant analogues mutated at the N terminus were generated and functionally compared with the wild‐type (WT) molecule, as well as with three previously described mutants. Substitution of selected residues within the N‐terminal region caused a marked loss of antiviral potency. By contrast, two unique analogues (C1.C5‐RANTES and L‐RANTES) exhibited an increased antiviral activity against different CXCR4‐negative HIV‐1 isolates grown in primary mononuclear cells or in macrophages. This enhanced HIV‐blocking activity was associated with an increased binding affinity for CCR5. Both C1.C5‐RANTES and L‐RANTES showed a dramatically reduced ability to trigger intracellular calcium mobilization via CCR3 or CCR5, while potently antagonizing the action of the WT chemokine. By contrast, two previously described analogues (RANTES3–68 and AOP‐RANTES) maintained a WT ability to trigger CCR5‐mediated signaling, while a third one (RANTES9–68) showed a dramatic loss of antiviral activity. These data demonstrate that the antiviral and signaling functions of RANTES can be uncoupled, opening new perspectives for the development of chemokine‐based therapeutic approaches for HIV infection.
Hypothalamic‐pituitary‐adrenal axis suppression in asthmatic children on inhaled corticosteroids: Part 1. Which test should be used?

The effect of inhaled corticosteroids (ICS) on the hypothalamic‐pituitary‐adrenal axis (HPA) has been regarded as a ‘benign physiological response’. A recent survey suggests that adrenal crisis might be more common in asthmatic children on ICS than previously thought. The clinical features of adrenal insufficiency are non‐specific and can easily be missed. Accurate biochemical assessment of the axis is therefore mandatory. A review of the literature determined that all basal adrenal function tests, including plasma cortisol profiles, cannot identify which children can respond to stress. There is no evidence to suggests that the degree of the physiological adjustment of the HPA to ICS predicts clinically significant HPA suppression. Only gold standard adrenal function tests can assess the integrity of the whole axis. Of the two available tests, the correctly performed overnight metyrapone test (with ACTH levels) is safe and better by far. The use of cortisol profiles should only be used to demonstrate differences in systemic activity of various ICS and delivery devices. Regulatory bodies should insist on trials that evaluate the HPA with a gold standard adrenal function test before it is declared safe and allowed to be marketed. A re‐analysis of studies that have utilized gold standard adrenal function tests only might identify the lowest safe dose and duration of ICS.
PriA supports two distinct pathways for replication restart in UV‐irradiated Escherichia coli cells

The Escherichia coli PriA protein loads the DnaB replicative helicase at branched DNA structures independently of the replication initiator protein, DnaA, and thereby facilitates assembly of functional replisomes at sites removed from oriC. It is therefore a critical factor in the rescue of replication forks stalled at DNA lesions. It is also a DNA helicase. We describe insertions near the 3′ end of priA that interfere with PriA activity. These insertions and the previously described priA300 encoding helicase‐defective PriA K230R are shown to be effective suppressors of the DNA repair defect in recG strains, but substantially reduce the ability of ruv mutants to survive DNA damage. The data presented suggest that PriA helicase in conjunction with RecG can promote direct rescue of stalled forks independently of the recombinational pathway promoted by the combined activities of the RuvABC, RecBCD and RecA proteins, which requires only the primosome assembly activity of PriA to load DnaB at D loops. In cells lacking the helicase activity of PriA, we propose that stalled forks can be redirected to the recombination pathway via a Holliday junction intermediate common to both pathways, thus explaining the resistance of these cells to DNA damage.
Contour Interaction in the Preschool Child

ABSTRACT Preschool children show poorer visual acuity when tested with multiple optotypes than when tested with isolated optotypes. This difference in performance could be the result of contour interaction or the greater distractions imposed by a multiple optotype display, which may be beyond a young child's ability. To differentiate between these alternatives, isolated and surrounded visual acuity were measured in children aged 2 to 7 years by pairing a Landolt C with an O. The surrounded optotypes were identical to the isolated optotypes with the exception of the flanking bars located at 2.5 times the minimum angle of resolution (MAR) of the optotype. A two‐alternative forced choice interleaved paradigm was used to measure surrounded and isolated visual acuity defined as 75% correct. When the test demands were equated by measuring isolated and surrounded acuity using a single optotype, poorer visual acuity was obtained with surrounded optotypes. This suggests that preschool children, like adults, show contour interaction.
Reduced Insulin-like Growth Factor I Receptor and Altered Insulin Receptor Isoform mRNAs in Normal Mucosa Predict Colorectal Adenoma Risk

Background: Hyperinsulinemia resulting from obesity and insulin resistance is associated with increased risk of many cancers, but the biology underlying this risk is unclear. We hypothesized that increased mRNA levels of the insulin-like growth factor I receptor (IGFIR) versus the insulin receptor (IR) or elevated ratio of IR-A:IR-B isoforms in normal rectal mucosa would predict adenoma risk, particularly in individuals with high body mass index (BMI) or plasma insulin. Methods: Biopsies from normal rectal mucosa were obtained from consenting patients undergoing routine colonoscopy at University of North Carolina Hospitals (Chapel Hill, NC). Subjects with colorectal adenomas were classified as cases (n = 100) and were matched to adenoma-free controls (n = 98) based on age, sex, and BMI. IGFIR and IR mRNA levels were assessed by qRT-PCR, and IR-A:IR-B mRNA ratios by standard PCR. Plasma insulin and crypt apoptosis were measured by ELISA and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), respectively. Logistic regression models examined relationships between receptor mRNAs, BMI, plasma insulin, and adenoma risk. Results: Unexpectedly, cases were significantly more likely to have lower IGFIR mRNA levels than controls. No overall differences in total IR mRNA or IR-A:IR-B ratios were observed between cases and controls. Interestingly, in patients with high plasma insulin, increased IR-A:IR-B ratio was associated with increased likelihood of having adenomas. Conclusions: Our work shows novel findings that reduced IGFIR mRNA and, during high plasma insulin, increased IR-A:IR-B ratios in normal rectal mucosa are associated with colorectal adenoma risk. Impact: Our work provides evidence supporting a link between IGFIR and IR isoform expression levels and colorectal adenoma risk. Cancer Epidemiol Biomarkers Prev; 23(10); 2093–100. ©2014 AACR.