Miracle-dz/UniFAR-FTUs huggingface dataset:
Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior: citalopram ineffective in children with autism.

CONTEXT Selective serotonin reuptake inhibitors are widely prescribed for children with autism spectrum disorders. OBJECTIVES To determine the efficacy and safety of citalopram hydrobromide therapy for repetitive behavior in children with autism spectrum disorders. DESIGN National Institutes of Health-sponsored randomized controlled trial. SETTING Six academic centers, including Mount Sinai School of Medicine, North Shore-Long Island Jewish Health System, University of North Carolina at Chapel Hill, University of California at Los Angeles, Yale University, and Dartmouth Medical School. PARTICIPANTS One hundred forty-nine volunteers 5 to 17 years old (mean [SD] age, 9.4 [3.1] years) were randomized to receive citalopram (n = 73) or placebo (n = 76). Participants had autistic spectrum disorders, Asperger disorder, or pervasive developmental disorder, not otherwise specified; had illness severity ratings of at least moderate on the Clinical Global Impressions, Severity of Illness Scale; and scored at least moderate on compulsive behaviors measured with the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders. INTERVENTIONS Twelve weeks of citalopram hydrobromide (10 mg/5 mL) or placebo. The mean (SD) maximum dosage of citalopram hydrobromide was 16.5 (6.5) mg/d by mouth (maximum, 20 mg/d). MAIN OUTCOME MEASURES Positive response was defined by a score of much improved or very much improved on the Clinical Global Impressions, Improvement subscale. An important secondary outcome was the score on the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders. Adverse events were systematically elicited using the Safety Monitoring Uniform Report Form. RESULTS There was no significant difference in the rate of positive response on the Clinical Global Impressions, Improvement subscale between the citalopram-treated group (32.9%) and the placebo group (34.2%) (relative risk, 0.96; 95% confidence interval, 0.61-1.51; P > .99). There was no difference in score reduction on the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders from baseline (mean [SD], -2.0 [3.4] points for the citalopram-treated group and -1.9 [2.5] points for the placebo group; P = .81). Citalopram use was significantly more likely to be associated with adverse events, particularly increased energy level, impulsiveness, decreased concentration, hyperactivity, stereotypy, diarrhea, insomnia, and dry skin or pruritus. CONCLUSION Results of this trial do not support the use of citalopram for the treatment of repetitive behavior in children and adolescents with autism spectrum disorders. Trial Registration clinicaltrials.gov Identifier: NCT00086645.
INTRODUCTION TO PARENTAL ACCEPTANCE-REJECTION THEORY , METHODS , EVIDENCE , AND IMPLICATIONS

Parental acceptance-rejection theory (PARTheory) is an evidence-based theory of socialization and lifespan development that attempts to predict and explain major causes, consequences, and other correlates of interpersonal—especially parental—acceptance and rejection within the United States and worldwide (Rohner, 1986, 2004; Rohner and Rohner, 1980). It attempts to answer five classes of questions divided into three subtheories. These are personality subtheory, coping subtheory, and sociocultural systems subtheory. Personality subtheory asks two general questions. First, is it true, as the subtheory postulates, that children everywhere—in different sociocultural systems, racial or ethnic groups, genders, and the like—respond in essentially the same way when they perceive themselves to be accepted or rejected by their parents or other attachment figures? Second, to what degree do the effects of childhood rejection extend into adulthood and old age?
Systemic Activin signaling independently regulates sugar homeostasis, cellular metabolism, and pH balance in Drosophila melanogaster

Significance Deciphering the systemic signaling mechanisms that modulate metabolic activity has important implications owing to the central role that metabolism plays in regulating organismal adaptability and survival. Here, we show that loss of Drosophila TGF-β/Activin-like ligand Dawdle (Daw) causes major alterations in larval metabolic activity, including accumulation of tricarboxylic acid cycle intermediates, acidification of hemolymph pH, and misregulation of insulin signaling and nuclear-encoded mitochondrial gene expression. These metabolic defects lead to a food-dependent lethality phenotype, suggesting that Daw likely influences environmental adaptability via its modulation of several central metabolic processes. These observations, coupled with previous findings in mammals and Caenorhabditis elegans, highlight a potentially conserved role for TGF-β/Activin signaling in regulating important metabolic processes across the animal kingdom and may have clinical implications. The ability to maintain cellular and physiological metabolic homeostasis is key for the survival of multicellular organisms in changing environmental conditions. However, our understanding of extracellular signaling pathways that modulate metabolic processes remains limited. In this study we show that the Activin-like ligand Dawdle (Daw) is a major regulator of systemic metabolic homeostasis and cellular metabolism in Drosophila. We find that loss of canonical Smad signaling downstream of Daw leads to defects in sugar and systemic pH homeostasis. Although Daw regulates sugar homeostasis by positively influencing insulin release, we find that the effect of Daw on pH balance is independent of its role in insulin signaling and is caused by accumulation of organic acids that are primarily tricarboxylic acid (TCA) cycle intermediates. RNA sequencing reveals that a number of TCA cycle enzymes and nuclear-encoded mitochondrial genes including genes involved in oxidative phosphorylation and β-oxidation are up-regulated in the daw mutants, indicating either a direct or indirect role of Daw in regulating these genes. These findings establish Activin signaling as a major metabolic regulator and uncover a functional link between TGF-β signaling, insulin signaling, and metabolism in Drosophila.
Very Early Optical Afterglows of Gamma-Ray Bursts: Evidence for Relative Paucity of Detection

Very early observations with the Swift satellite of γ-ray burst (GRB) afterglows reveal that the optical component is not detected in a large number of cases. This is in contrast to the bright optical flashes previously discovered in some GRBs (e.g., GRB 990123 and GRB 021211). Comparisons of the X-ray afterglow flux to the optical afterglow flux and prompt γ-ray fluence is used to quantify the seemingly deficient optical, and in some cases X-ray, light at these early epochs. This comparison reveals that some of these bursts appear to have higher than normal γ-ray efficiencies. We discuss possible mechanisms and their feasibility for explaining the apparent lack of early optical emission. The mechanisms considered include, foreground extinction, circumburst absorption, Lyα blanketing and absorption due to high-redshift, low-density environments, rapid temporal decay, and intrinsic weakness of the reverse shock. Of these, foreground extinction, circumburst absorption, and high redshift provide the best explanations for most of the nondetections in our sample. There is tentative evidence of suppression of the strong reverse shock emission. This could be because of a Poynting flux-dominated flow or a pure nonrelativistic hydrodynamic reverse shock.
Circulating Leptin Concentrations Are Positively Related to Leptin Messenger RNA Expression in the Adipose Tissue of Fetal Sheep in the Pregnant Ewe Fed at or Below Maintenance Energy Requirements During Late Gestation1

Abstract We have investigated the effects of maternal undernutrition during late gestation on maternal and fetal plasma concentrations of leptin and on leptin gene expression in fetal perirenal adipose tissue. Pregnant ewes were randomly assigned at 115 days of gestation (term = 147 ± 3 days [mean ± SEM]) to either a control group (n = 13) or an undernourished group (n = 16) that received ∼50% of the control diet until 144–147 days of gestation. Maternal plasma glucose, but not leptin, concentrations were lower in the undernourished ewes. A significant correlation was found, however, between mean maternal plasma leptin (y) and glucose (x) concentrations (y = 2.9x − 2.4; r = 0.51, P < 0.02) when the control and undernourished groups were combined. Fetal plasma glucose and insulin, but not fetal leptin, concentrations were lower in the undernourished ewes, and no correlation was found between mean fetal leptin concentrations and either mean fetal glucose or insulin concentrations. A positive relationship, however, was found between mean fetal (y) and maternal (x) plasma leptin concentrations (y = 0.18x + 0.45; r = 0.66, P < 0.003). No significant difference was found in the relative abundance of leptin mRNA in fetal perirenal fat between the undernourished (0.60 ± 0.09, n = 10) and control (0.70 ± 0.08, n = 10) groups. Fetal plasma concentrations of leptin (y) and leptin mRNA levels (x) in perirenal adipose tissue were significantly correlated (y = 1.5x ± 0.3; r = 0.69, P < 0.05). In summary, the capacity of leptin to act as a signal of moderate maternal undernutrition may be limited before birth in the sheep.
Changing trends of adult lymphoma in the Kingdom of Saudi Arabia - comparison of data sources.

BACKGROUND Lymphoma is one of the most common malignancies affecting the young Saudi population. This disease has diversified pathologies and clinical stages that necessitate well optimized clinical management. Regular updates of epidemiological behavior of lymphoma from various parts of the world are available but studies from the Kingdom of Saudi Arabia (KSA) in this field are not consistent. OBJECTIVES The aim of this study was to investigate the current trends in presentation and distribution of lymphoma with special reference to incidence and mortality, gender, age, histopathological subtypes, and clinical stages at King Faisal Specialist Hospital and Research Centre (KFSH and RC). MATERIALS AND METHODS Our study included lymphoma data from Saudi Cancer Registry, and relative comparison against KFSH and RC tumor registry data, Gulf country data and International Agency for Research on Cancer data. RESULTS Common tumors in the West (lung, colon, and prostate) were found to be much less frequent in KSA while leukemia, lymphoma and thyroid cancers were more common. Non-Hodgkin Lymphoma (NHL) ranked 3rd most common cancer with age-adjusted incidence of 6/100,000. Estimated age adjusted mortality was 4/100,000 in KSA. There was a peak rise in incidence of lymphoma in 1997-2007. Most common NHL was diffuse large B cell lymphoma at KFSH and RC. A total of 434 cases were diagnosed in 5 years with 55% of them at advanced stage and 35% demonstrating bulky disease and high risk. KFSH and RC registered 35% of Hodgkins and 21% of total NHL identified in entire Saudi Cancer Registry, 2009. CONCLUSIONS Results of this study are very unique, and reveal diverse trends. The findings provide valuable insights in the understanding of current epidemiological features of lymphoma in this part of the world.
Expression of the urokinase plasminogen activator receptor (uPAR) and its ligand (uPA) in brain tissues of human immunodeficiency virus patients with opportunistic cerebral diseases

The urokinase plasminogen activator receptor (uPAR) and its ligand (uPA) play an important role in cell migration and extracellular proteolysis. We previously described uPAR/uPA overexpression in the cerebrospinal fluid (CSF) and brain tissues of patients with human immunodeficiency virus (HIV)-related cerebral diseases. In this study, we examined uPAR/uPA expression by immunohistochemistry (IHC) in brains of HIV patients with opportunistic cerebral lesions and in HIV-positive/negative controls. uPAR was found in macrophages/microglia with the highest levels in cytomegalo-virus (CMV) encephalitis, toxoplasmosis, and lymphomas; in cryptococcosis and progressive multifocal leukoencephalopathy (PML) cases, only a few positive cells were found and no positivity was observed in controls. uPA expression was demonstrated only in a few macrophages/microglia and lymphocytes in all the cases and HIV-positive controls without different pattern of distribution; no uPA immunostaining was found in cryptococcosis and HIV-negative controls. The higher expression of uPAR/uPA in most of the opportunistic cerebral lesions supports their role in these diseases, suggesting their contribution to tissue injury.
On the Inversion Complexity of a System of Functions

1. Let n be a natural number different from zero. We will call the alphabet {0, 1, xl , . , xn, &, V, l, ( , )} an alphabet of a formula in n variables. We will denote this alphabet by ~ . We will call the letters Xl, • • • , x. of the alphabet • ~ variables and the letters 0, 1 constants. We will denote by formulas in n variables words in the alphabet ,I)~ which are defined by the following generating rules. F1. Single-lettered words
Alternative dystrophin gene transcripts in golden retriever muscular dystrophy

Golden retriever muscular dystrophy (GRMD), the canine model of Duchenne muscular dystrophy (DMD), is caused by a splice site mutation in the dystrophin gene. This mutation predicts a premature termination codon in exon 8 and a peptide that is 5% the size of normal dystrophin. Western blot analysis of skeletal muscle from GRMD dogs reveals a slightly truncated 390‐kD protein that is approximately 91% the size of normal dystrophin. This 390‐kD dystrophin suggests that GRMD dogs, like some DMD patients, employ a mechanism to overcome their predicted frameshift. Reverse‐transcriptase polymerase chain reaction on GRMD muscle has revealed two in‐frame dystrophin transcripts which lack either exons 3–9 or exons 5–12. Both transcripts could be translated into a dystrophin protein of approximately 390 kD. An understanding of how truncated dystrophin is produced in GRMD may allow this mechanism to be manipulated toward a potential therapy for DMD. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:991–998, 1998.
REDUCTION OF VITREOUS PROSTAGLANDIN E2 LEVELS AFTER TOPICAL ADMINISTRATION OF INDOMETHACIN 0.5%, BROMFENAC 0.09%, AND NEPAFENAC 0.1%

Purpose: To assess vitreous concentrations of nonsteroidal anti-inflammatory drugs (NSAIDs) and prostaglandin E2 (PGE2) in patients treated with NSAIDs before vitrectomy for macular pucker. Methods: A prospective, investigator-masked, randomized study was performed in 64 patients scheduled to undergo vitrectomy. The patients were randomized 1:1:1:1 to receive indomethacin 0.5%, bromfenac 0.09%, nepafenac 0.1%, or placebo three times a day. NSAIDs and PGE2 levels were evaluated in vitreous samples collected at the beginning of surgery. Results: Mean (SD) vitreous concentrations of the study drugs were 503.13 (241.1) pg/mL for indomethacin, 302.5 (91.03) pg/mL for bromfenac, and 284.38 (128.2) pg/mL for nepafenac. Mean (SD) vitreous PGE2 levels were 247.9 (140.9) pg/mL for indomethacin, 322.12 (228.1) pg/mL for bromfenac, 448.8 (261.1) pg/mL for nepafenac, and 1,133 (323.9) pg/mL for placebo. All three NSAIDs reduced vitreous PGE2 levels to a statistically significant extent, without a significant difference among them. Conclusion: All assessed NSAIDs penetrated the vitreous and lowered basal PGE2 levels. A greater penetration was associated with pseudophakic eyes. The important inhibition of prostaglandins in the retina may have a clinical effect on the management of inflammatory retina diseases.
Hairy is a cell context signal controlling Notch activity

Notch signaling regulates cell fate determination and many developmental processes. Here we report that lateral inhibition, a major mechanism for Notch activity, is modulated by Hairy, a bHLH‐WRPW protein. In Xenopus, Notch can have from inhibitory, permissive to enhancing roles in muscle or neural differentiation. These cell context‐dependent effects correlate with Hairy expression levels from high to low, respectively, in the cells. Moreover, Notch effects can be altered upon manipulation of Hairy expression. We propose that Hairy provides a cell context in which a cell can interpret Notch and other extrinsic signals by controlling responsiveness of its target genes; this mode of Hairy–Notch interaction may apply in other systems.
Pigment Epithelium-Derived Factor: A Not So Sympathetic Regulator of Insulin Resistance?

Pigment epithelium-derived factor (PEDF), an adipokine, is a regulator of oxidative stress, inflammation, angiogenesis, and insulin sensitivity. Contrary to animal and cell culture data, inhibition of the sympathoadrenal system does not affect serum PEDF in humans. However, during acute beta-adrenergic receptor stimulation serum PEDF concentration is decreased. PEDF may be involved in cross talk between adipose tissue and skeletal muscle.
Higher Risk of Common Mental Disorders After Experiencing Physical Violence in Rio De Janeiro, Brazil: the Pró-Saúde Study

Background: In Brazil, violence is a major public health problem. However, up until now, the extent to which violence acts as a risk factor for mental disorders has not been investigated prospectively. Aims: We determined the risk of common mental disorders (CMD) associated with personal experience with physical violence (PV). Methods: A cohort of 3253 public employees in Rio de Janeiro completed questionnaires that measured CMD (GHQ-12), experience with PV and stressful life events (SLE). Results: After adjusting for age, income and SLE, those who experienced PV in either 1999 or 2001 and those who experienced PV in both years had, respectively, 1.2-fold (95% CI; 1.0—1.4) and 2.1-fold (1.6—2.6) increased risks of CMD. Conclusion: Direct exposure to violence may act cumulatively on the risk of developing CMD. The absence of association for reporting CMD both in 1999 and 2001 suggests that other determinants may be more relevant for chronic mental disorders.
Response to glucocorticoids and toxicity in childhood acute lymphoblastic leukemia: Role of polymorphisms of genes involved in glucocorticoid response

Glucocorticoids (GCs) play a fundamental role in the treatment of pediatric acute lymphoblastic leukemia (ALL), but therapy with these agents often results in a number of severe side effects. The aim of our study was to evaluate the association between polymorphisms of genes encoding for proteins involved in the pharmacokinetics/pharmacodynamics of these drugs and the occurrence of side effects, in particular infections, in a small population of ALL children.
Chapter 10. Language contact and variation in Cape Verde and São Tomé and Príncipe

Both Cape Verdean Portuguese (CVP) and Santomean Portuguese (STP) are in contact with Portuguese-related Creole languages formed during the 15 th and 16 th centuries: Capeverdean, in Cape Verde, and Santome, Angolar and Lung’Ie, in São Tomé and Príncipe. Despite this, Portuguese is the only official language of the two archipelagos. The goal of this chapter is twofold. First, we aim to compare and discuss corpora data from CVP and STP underlining the impact of sociohistorical factors in some morphosyntactic aspects of these Portuguese varieties’ grammars. Second, we will show that the convergence and divergence observed is not only driven by the language contact situation but also by internal change mechanisms.
Abnormalities of glucocorticoid metabolism and the renin-angiotensin system: a four-corners approach to the identification of genetic determinants of blood pressure.

AIM To assess the feasibility and utility of a new method to identify factors associated with increased predisposition to high blood pressure in young people. SUBJECTS Eight hundred and sixty-four people aged 16-24 years and their parents. SETTING Ladywell Medical Centre, Edinburgh, Scotland, UK. METHOD Blood pressure was measured in 864 young adults and in both of their parents. Four groups of approximately 50 offspring were selected from the corners of a scatter diagram, with offspring blood pressure scores on one axis and combined parental blood pressure scores on the other. Blood and urine samples were taken for biochemical and genetic analyses. RESULTS Two groups of offspring had parents with high blood pressure and two groups had parents with low blood pressure. When parental blood pressure was low, comparison of offspring with high and low blood pressure revealed significantly higher mean body mass index in offspring with high blood pressure, but no significant elevation of biochemical or hormonal variables. When parental blood pressure was high, comparison of offspring with high and low blood pressure also revealed a significant difference in body mass index, but in addition, offspring with high blood pressure and high parental blood pressure had higher levels of angiotensinogen, cortisol and 18-OH corticosterone. Restriction fragment length polymorphism analysis revealed that 27% of offspring at the greatest genetic risk (high personal and parental blood pressure) were homozygous for the larger allele of the glucocorticoid receptor gene compared with only 9% of those at lowest genetic risk (low personal and parental blood pressure). CONCLUSION The combined biochemical and genetic findings suggest that abnormalities of glucocorticoid metabolism and the renin-angiotensin system may help to explain genetic predisposition to high blood pressure. The new sampling method is practicable and could be applied to the investigation of other continuously distributed variables which show familial aggregation.
Role of inflammatory mechanisms in pathogenesis of type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is characterized by progressive β‐cell dysfunctioning and insulin resistance. This article reviews recent literature with special focus on inflammatory mechanisms that provoke the pathogenesis of T2DM. We have focused on the recent advances in progression of T2DM including various inflammatory mechanisms that might induce inflammation, insulin resistance, decrease insulin secretion from pancreatic islets and dysfunctioning of β‐cells. Here we have also summarized the role of various pro‐inflammatory mediators involved in inflammatory mechanisms, which may further alter the normal structure of β‐cells by inducing pancreatic islet's apoptosis. In conclusion, it is suggested that the role of inflammation in pathogenesis of T2DM is crucial and cannot be neglected. Moreover, the insight of inflammatory responses in T2DM may provide a new gateway for the better treatment of diabetes mellitus. J. Cell. Biochem. 114: 525–531, 2013. © 2012 Wiley Periodicals, Inc.
Middle Paleolithic Shell Beads in Israel and Algeria

Perforated marine gastropod shells at the western Asian site of Skhul and the North African site of Oued Djebbana indicate the early use of beads by modern humans in these regions. The remoteness of these sites from the seashore and a comparison of the shells to natural shell assemblages indicate deliberate selection and transport by humans for symbolic use. Elemental and chemical analyses of sediment matrix adhered to one Nassarius gibbosulus from Skhul indicate that the shell bead comes from a layer containing 10 human fossils and dating to 100,000 to 135,000 years ago, about 25,000 years earlier than previous evidence for personal decoration by modern humans in South Africa.