Miracle-dz/UniFAR-FTUs huggingface dataset:
Hot and cool executive function in children and adolescents with autism spectrum disorder: Cross-sectional developmental trajectories

ABSTRACT The development of executive function (EF) in autism spectrum disorder (ASD) has only been investigated using “cool”-cognitive-EF tasks. Little is known about the development of “hot”-affective-EF and whether it follows a similar developmental pathway. This study employed a cross-sectional developmental trajectories approach to examine the developmental changes in cool (working memory, inhibition, and planning) and hot EF (delay discounting and affective decision-making) of ASD participants (n = 79) and controls (n = 91) relative to age and IQ, shedding more light on the hot–cool EF organization. The developmental trajectories of some aspects of cool EF (working memory and planning) differed significantly as a function of age in ASD participants relative to controls. For both hot EFs, no significant age-related changes were found in either group. These findings extend our understanding regarding the maturation of EF from childhood through adolescence in ASD.
Eating-disordered behavior in Australian and Singaporean women: a comparative study.

OBJECTIVE AND METHOD We used the Eating Disorder Examination Questionnaire (EDE-Q) to compare the specific eating disorder psychopathology of young adult women in Australia (n = 339) and Singapore (n = 164). All participants completed a brief questionnaire that included the EDE-Q, basic socio-demographic information, and self-reported height and weight. RESULTS Overall levels of eating disorder psychopathology, as measured by the EDE-Q global score, were very similar. There were also no differences between groups on the EDE-Q subscales. However, analysis at the item level indicated that Singaporean women were more fearful of losing control over their eating, more fearful of gaining weight or becoming fat, and more anxious at the prospect of regularly weighing themselves, than Australian women. Singaporean women were also more likely to report binge eating and laxative misuse, whereas excessive exercise was more common among Australian women. The findings were unaltered when between-group differences in body weight were statistically controlled. DISCUSSION The findings provide further evidence that levels of eating disorder psychopathology in some Asian countries may be as high as, if not higher than, those of Western nations. Potentially important differences between different cultural groups may be obscured when the assessment of eating disorder psychopathology is confined to summary-type measures.
Ephrin-B1 Reverse Signaling Activates JNK through a Novel Mechanism That Is Independent of Tyrosine Phosphorylation*

Eph receptors and their cognate ligand ephrins play important roles in various biological processes such as cell migration, axon guidance, and synaptic plasticity. One characteristic feature of the Eph-ephrin signal transduction is that, upon interaction with the receptor, the transmembrane B-class ephrins become tyrosine-phosphorylated and transduce intracellular signals that lead to reorganization of the cytoskeleton. Although in vitro and genetic studies have demonstrated unequivocally the significance of this reverse signaling, the underlying mechanism remains unclear. We report here that transfection of ephrin-B1 into 293 cells resulted in robust increase in JNK activity, whereas expression of truncated ephrin-B1 lacking the cytoplasmic domain had a negligible effect, indicating that the induction of JNK activity was attributed mainly to the reverse signaling. The ephrin-B1-mediated JNK activation was reduced significantly by dominant-negative TAK1, MKK4, or MKK7. Ephrin-B1 over-expressing 293 cells became rounded in morphology. Surprisingly, ephrin-B1 that lacked all six intracellular tyrosine residues still triggered JNK activation and rounding morphology of the transfected cells. Consistent with these observations, activation of JNK and the resulting morphological changes mediated by ephrin-B1 could be abolished by the JNK inhibitor SP600125 but not the Src inhibitor PP2. Taken together, our findings have identified a novel reverse signaling pathway transduced by ephrin-B1, which is independent of tyrosine phosphorylation but involves the activation of JNK through TAK1 and MKK4/MKK7 and leads to changes in cell morphology.
Replicative fitness in vivo of HIV‐1 variants with multiple drug resistance‐associated mutations

The relative fitness of HIV‐1 viral variants containing a broad range of drug resistance‐associated mutations has been little studied in vivo. Understanding the relative fitness associated with viruses containing mutations may aid future therapeutic management. The aim of this study was to investigate the relative fitness of mutant viruses by assessing a cohort of patients who had developed resistance to many drugs and subsequently stopped all therapy. Eleven patients were assessed for drug resistance associated mutations in the protease (PR) and reverse transcriptase (RT) genes before and, at multiple time points, after stopping therapy. Relative fitness was calculated as a function of the rate of disappearance of mutant viruses when therapy was stopped. The least fit viruses were associated with the RT mutation M184I/V (11.6% less fit) and the PR mutations D30N (12.4% less fit) and M46I/L (21% less fit). Mutations at these codons were associated with significant reductions in fitness levels compared to wild‐type viruses. Mutations at codons 10, 20, 36, and 63 in the PR gene remained fairly constant when therapy was stopped and may not significantly reduce viral fitness. The rapid re‐population of wild‐type viruses may allow the recycling of antiretroviral drugs prescribed previously. J. Med. Virol. 65:218–224, 2001. © 2001 Wiley‐Liss, Inc.
Adjuvant Therapy for Melanoma

AbstractEstimates from the U.S. Surveillance, Epidemiology, and End Results registry suggest that melanoma incidence will reach 70,230 cases in 2011, of whom 8790 will die. The rising incidence and predilection for young individuals makes this tumor a leading source of lost productive years in the society.High-dose interferon-&agr;-2b is the only agent approved for adjuvant therapy for melanoma; the improvement in relapse-free survival has been observed across nearly all published studies and meta-analyses. However, toxicity affects compliance, and current research is focusing on biomarkers that may allow selection of patients with greater likelihood of response and exploring new agents either singly or in combination that may improve on the benefit of interferon.In this article, we review the data for the adjuvant therapy for malignant melanoma—focusing on the results obtained with various regimens testing the several formulations of interferon-&agr;2 and the adjuvant studies of vaccines and radiotherapy. Recent advances in the treatment of metastatic disease have established a role for CTLA-4 blockade and BRAF-inhibition, raising hopes that these agents may have a role in the adjuvant setting. At present, several trials investigating combinations of novel agents with existing immunomodulators are underway.
Glucosepane Is a Major Protein Cross-link of the Senescent Human Extracellular Matrix

The extracellular matrix in most tissues is characterized by progressive age-related stiffening and loss of proteolytic digestibility that are accelerated in diabetes and can be duplicated by the nonenzymatic reaction of reducing sugars and extracellular matrix proteins. However, most cross-links of the Maillard reaction described so far are present in quantities too low to account for these changes. Here we have determined in human skin and glomerular basement membrane (GBM) collagen the levels of the recently discovered lysine-arginine cross-links derived from glucose, methylglyoxal, glyoxal, and 3-deoxyglucosone, i.e. glucosepane, MODIC, GODIC, and DOGDIC, respectively. Insoluble preparations of skin collagen (n = 110) and glomerular basement membrane (GBM, n = 28) were enzymatically digested, and levels were measured by isotope dilution technique using liquid chromatography/mass spectrometry. In skin, all cross-links increased with age (p < 0.0001) except DOGDIC (p = 0.34). In nondiabetic controls, levels at 90 years were 2000, 30, and 15 pmol/mg for glucosepane, MODIC, and GODIC, respectively. Diabetes, but not renal failure, increased glucosepane to 5000 pmol/mg (p < 0.0001), and for all others, increased it to <60 pmol/mg (p < 0.01). In GBMs, glucosepane reached up to 500 pmol/mg of collagen and was increased in diabetes (p < 0.0001) but not old age. In conclusion, glucosepane is the single major cross-link of the senescent extracellular matrix discovered so far, accounting for up to >120 mole% of triple helical collagen modification in diabetes. Its presence in high quantities may contribute to a number of structural and cell matrix dysfunctions observed in aging and diabetes.
Prolactin and Pituitary‐Gonadal Function in Cigarette Smoking Infertile Patients

Summary: Serum prolactin (PRL) was significantly lower in smokers, compared with non‐smokers in 233 males and 250 females referred to our infertility clinics. In subjects smoking 10 cigarettes or more per day, the mean serum PRL was 22% and 20% lower in men and women, respectively. In cigarette smoking men serum testosterone was significantly higher and semen volume lower, while neither serum luteinizing hormone (LH) or follicle stimulating hormone (FSH), sperm density, motility of morphology differed between smokers and non‐smokers. It is possible that the higher serum testosterone levels in smokers are due to their lower bodyweight, and that the lower semen volume may be due to an effect of nicotine on the contractility of the deferental ducts. Cigarette smoking may increase central dopaminergic tonus and reduce PRL levels, but it is unknown whether or not this is of biological significance in relation to reproductive function.
The Absorption and Retention of Magnesium, Zinc, and Copper by Low Birth Weight Infants Fed Pasteurized Human Breast Milk

Summary: Using serial metabolic balance techniques, the absorption and retention of magnesium, copper, and zinc have been measured in six preterm infants (mean gestation 29 weeks), and two term small for gestational age infants (< 1.5 kg birth weight). The amounts of the minerals retained were compared with the amounts retained by a fetus of equivalent gestational age in utero.The preterm infants absorbed 5.3 ± 3.5 mg/kg · day magnesium (43% of intake, range 1–74%) and retained 2.8 ± 1.3 mg/kg · day (25% of intake, range −15 to +48%). The mean postnatal retention over the whole study period, as a percentage of intrauterine accumulation by a fetus of equivalent maturity, was 41% (range 17–66%). The light for dates infants absorbed 5.7 mg/kg · day, range 4.0–7.2 (81% of intake, range 51–95%) and retained 5.4 mg/kg · day, range 3.3–6.6 (76% of intake, range 41–88%). In the preterm infants balance for zinc was negative on average until the 60th day of life. The most negative balance averaged −0.611 ± 0.432 mg/kg · day (n = 6) on days 20–22. All the preterm infants experienced a net loss of body zinc over the period of study (mean −18.1 mg, range −4.2 to −37 mg). In contrast the light for dates infants were in positive balance and they absorbed 0.44 mg/kg · day range −0.06 to +0.75 (56% of intake, range −35 to +86%) and retained 0.42 mg/kg · day, range −0.08 to +0.73 (52% of intake, range −46 to +82%). In the preterm infants balance for copper was negative on average until the 35th day of life, and the most negative balance was-0.035 ± 0.061 mg/kg · day on days 10–12. Three of the six preterm infants, during the period of study, experienced a net loss of body copper which averaged 0.73 mg (range −1.3 to −0.3 mg); the other three retained on average 1.74 mg (range 0.12 to 3.2 mg). The light for dates infants absorbed and retained 0.045 mg/kg · day, range 0.004 to 0.079 (57% of intake, range 12–88%). It is concluded that breast milk supplies enough magnesium but insufficient copper and zinc for preterm infants, with the result that their body stores of copper and zinc cannot develop normally.Speculation: Because of the depletion of body stores of copper and zinc a deficiency of these substances is likely to occur in some preterm infants during later infancy.
Prevalence of deleterious germline variants in risk genes including BRCA1/2 in consecutive ovarian cancer patients (AGO-TR-1)

Background Identification of families at risk for ovarian cancer offers the opportunity to consider prophylactic surgery thus reducing ovarian cancer mortality. So far, identification of potentially affected families in Germany was solely performed via family history and numbers of affected family members with breast or ovarian cancer. However, neither the prevalence of deleterious variants in BRCA1/2 in ovarian cancer in Germany nor the reliability of family history as trigger for genetic counselling has ever been evaluated. Methods Prospective counseling and germline testing of consecutive patients with primary diagnosis or with platinum-sensitive relapse of an invasive epithelial ovarian cancer. Testing included 25 candidate and established risk genes. Among these 25 genes, 16 genes (ATM, BRCA1, BRCA2, CDH1, CHEK2, MLH1, MSH2, MSH6, NBN, PMS2, PTEN, PALB2, RAD51C, RAD51D, STK11, TP53) were defined as established cancer risk genes. A positive family history was defined as at least one relative with breast cancer or ovarian cancer or breast cancer in personal history. Results In total, we analyzed 523 patients: 281 patients with primary diagnosis of ovarian cancer and 242 patients with relapsed disease. Median age at primary diagnosis was 58 years (range 16–93) and 406 patients (77.6%) had a high-grade serous ovarian cancer. In total, 27.9% of the patients showed at least one deleterious variant in all 25 investigated genes and 26.4% in the defined 16 risk genes. Deleterious variants were most prevalent in the BRCA1 (15.5%), BRCA2 (5.5%), RAD51C (2.5%) and PALB2 (1.1%) genes. The prevalence of deleterious variants did not differ significantly between patients at primary diagnosis and relapse. The prevalence of deleterious variants in BRCA1/2 (and in all 16 risk genes) in patients <60 years was 30.2% (33.2%) versus 10.6% (18.9%) in patients ≥60 years. Family history was positive in 43% of all patients. Patients with a positive family history had a prevalence of deleterious variants of 31.6% (36.0%) versus 11.4% (17.6%) and histologic subtype of high grade serous ovarian cancer versus other showed a prevalence of deleterious variants of 23.2% (29.1%) and 10.2% (14.8%), respectively. Testing only for BRCA1/2 would miss in our series more than 5% of the patients with a deleterious variant in established risk genes. Conclusions 26.4% of all patients harbor at least one deleterious variant in established risk genes. The threshold of 10% mutation rate which is accepted for reimbursement by health care providers in Germany was observed in all subgroups analyzed and neither age at primary diagnosis nor histo-type or family history sufficiently enough could identify a subgroup not eligible for genetic counselling and testing. Genetic testing should therefore be offered to every patient with invasive epithelial ovarian cancer and limiting testing to BRCA1/2 seems to be not sufficient.
State‐by‐state variation in emergency versus elective colon resections: Room for improvement

BACKGROUND: Compared with elective surgical procedures, emergency procedures are associated with higher cost, morbidity, and mortality. This study seeks to investigate potential state‐by‐state variations in the incidence of emergent versus elective colon resections. METHODS: A retrospective analysis of all adult patients (aged >=18 years) included in the Nationwide Inpatient Sample from 2005 to 2009 who underwent hemicolectomy (right or left) or sigmoidectomy was conducted. Discharge‐level weights were applied, and generalized linear models were used to assess the odds of a patient undergoing emergent versus elective colon surgery nationally and for each state after adjusting for patient and hospital factors. Odds ratios (ORs) were estimated with the national average as the reference. RESULTS: The final study cohort included 203,050 observations composed of 83,090 emergent and 119,960 elective colectomies. The state with the highest unadjusted proportion of emergent procedures was Nevada (53.6%), whereas Texas had the lowest (2.8%). Compared with the national average, the adjusted odds of undergoing emergency colectomy remained highest in Nevada (OR, 1.70; 95% confidence interval, 1.54–1.87) and lowest in Texas (OR, 0.43; 95% confidence interval, 0.36–0.51). CONCLUSION: Substantial state variations exist in rates of emergency colon surgery within the United States. Identification of these differences suggests significant variations in practice and a potential to decrease the number of emergent colon operations. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level III.
Requirement of functional ryanodine receptor type 3 for astrocyte migration

Astrocyte motility plays an important role in the response of the brain to injury and during regeneration. We used two in vitro assays, a wound‐healing model and a chemotaxis assay, to study mechanisms that control astrocyte motility. Ryanodine receptors (RyR), intracellular calcium‐release channels, modulate intracellular Ca2+ levels, and also motility: 1) blocking RyR with antagonizing concentration of ryanodine (200 μM) strongly attenuated motility and 2) motility of astrocytes cultured from homozygous RyR type 3 knockout mice was impaired strongly compared with wild‐type. In contrast, MIP‐1α‐induced chemotaxis was neither impaired in the presence of ryanodine nor in the cells from the knockout animals. Reverse transcription‐polymerase chain reaction (RT‐PCR) analysis combined with Western blotting and immunocytochemistry confirmed the expression of RyR type 3, but not type 1 or 2 in cultured and acutely isolated astrocytes. RyR in astrocytes are linked to Ca2+ signaling because the RyR agonist 4‐chloro‐m‐cresol induced a release of Ca2+ from intracellular stores. These results indicate that astrocytes express only RyR type 3 and that this receptor is important for controlling astrocyte motility.
A Novel Partial Fatty Acid Oxidation Inhibitor Decreases Myocardial Oxygen Consumption and Improves Cardiac Efficiency in Demand-induced Ischemic Heart

The benefits of inhibition of fatty acid oxidation (FOX) and stimulation of glucose oxidation (GOX) in ischemia are controversial. The objective of this study was to evaluate the effect of the FOX inhibitor CVT-4325 on the rates of FOX, GOX, myocardial oxygen consumption (MVO2), and cardiac efficiency in the absence and presence of palmitate during demand-induced ischemia of the rodent isolated hearts. Palmitate concentration-dependently increased FOX, decreased GOX, and increased MVO2. CVT-4325 inhibited FOX and increased GOX in the presence (but not the absence) of 1.2 mM palmitate, with EC50 values of 0.9 and 5.8 μM, respectively. The potency for CVT-4325 to inhibit FOX was 10-fold greater (0.9 versus 9.7 μM) in the presence of 1.2 mM compared with 0.4 mM palmitate. The increase in MVO2 caused by 1.2 mM palmitate was significantly reduced by 3 to 10 μM CVT-4325 in guinea pig hearts. In the presence of 1.2 mM palmitate, an increase in pacing rate of the guinea pig heart from 3.5 to 6.5 Hz caused a significant 50% increase in MVO2, a decrease in cardiac efficiency, and an increase in lactate concentration in the cardiac effluent from 0.04 ± 0.01 to 0.10 ± 0.02 mM (P < 0.01). CVT-4325 (3 μM) attenuated the increase (P < 0.05) in MVO2 while maintaining cardiac contractility, and decreased the lactate production to 0.05 ± 0.01 mM (P < 0.01). Thus, the FOX inhibitor CVT-4325 decreased MVO2 and increased myocardial efficiency during demand-(pacing)-induced ischemia in the presence of palmitate in the rodent isolated hearts.
Evaluating the efficacy of endoscopic thoracic sympathectomy for generalized social anxiety disorder with blushing complaints: a comparison with sertraline and no treatment-santiago de chile 2003-2009.

OBJECTIVE No study has yet compared the efficacy of endoscopic thoracic sympathectomy for treating facial blushing with other treatment or no treatment. We conducted a prospective, observational, open-label, clinical study to compare endoscopic thoracic sympathectomy for blushing with generalized social anxiety disorder versus sertraline treatment and no treatment. METHOD Three-hundred and thirty consecutive patients seeking treatment for their blushing were assessed by psychiatric interview and patient-rated scales. The Brief Social Phobia Scale was the primary outcome measure. Patients meeting Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition criteria for generalized social anxiety disorder, scoring 20 points or more in the Brief Social Phobia Scale and 19 points or more in the Social Phobia Inventory were considered eligible and followed up for a mean of 11 months (range 1-64) after endoscopic thoracic sympathectomy or initiation of sertraline. RESULTS At baseline, 97 percent of the endoscopic thoracic sympathectomy-treated group, 87 percent of the sertraline-treated group, and 78 percent of the nontreated group rated their blushing as being "severe" or "extreme. " At follow up, 16 percent of endoscopic thoracic sympathectomy-treated patients, 32 percent of sertraline-treated patients, and 57 percent of untreated patients reported this degree of blushing. At endpoint, Brief Social Phobia Scale total scores exhibited a greater decline with either treatment than with no treatment. Nonetheless, in comparison to no treatment, only the results obtained with endoscopic thoracic sympathectomy achieved statistical significance (p=0.003). Compensatory sweating occurred in 99 percent of patients who underwent endoscopic thoracic sympathectomy. High degrees of satisfaction with treatment were reported by 89 percent of patients undergoing endoscopic thoracic sympathectomy and by 59 percent of patients taking medication. CONCLUSION Endoscopic thoracic sympathectomy was associated to a greater reduction of blushing and Brief Social Phobia Scale scores, and higher degrees of satisfaction with treatment, in comparison to sertraline and no treatment.
Dissection of complex adult traits in a mouse synthetic population

Finding the causative genetic variations that underlie complex adult traits is a significant experimental challenge. The unbiased search strategy of genome-wide association (GWAS) has been used extensively in recent human population studies. These efforts, however, typically find only a minor fraction of the genetic loci that are predicted to affect variation. As an experimental model for the analysis of adult polygenic traits, we measured a mouse population for multiple phenotypes and conducted a genome-wide search for effector loci. Complex adult phenotypes, related to body size and bone structure, were measured as component phenotypes, and each subphenotype was associated with a genomic spectrum of candidate effector loci. The strategy successfully detected several loci for the phenotypes, at genome-wide significance, using a single, modest-sized population (N = 505). The effector loci each explain 2%–10% of the measured trait variation and, taken together, the loci can account for over 25% of a trait's total population variation. A replicate population (N = 378) was used to confirm initially observed loci for one trait (femur length), and, when the two groups were merged, the combined population demonstrated increased power to detect loci. In contrast to human population studies, our mouse genome-wide searches find loci that individually explain a larger fraction of the observed variation. Also, the additive effects of our detected mouse loci more closely match the predicted genetic component of variation. The genetic loci discovered are logical candidates for components of the genetic networks having evolutionary conservation with human biology.