Miracle-dz/UniFAR-FTUs huggingface dataset:
Brain functional magnetic resonance imaging response to glucose and fructose infusions in humans

Aims: In animals, intracerebroventricular glucose and fructose have opposing effects on appetite and weight regulation. In humans, functional brain magnetic resonance imaging (fMRI) studies during glucose ingestion or infusion have demonstrated suppression of hypothalamic signalling, but no studies have compared the effects of glucose and fructose. We therefore sought to determine if the brain response differed to glucose vs. fructose in humans independently of the ingestive process.
Validation of a prognostic model and the impact of mutations in patients with lower-risk myelodysplastic syndromes.

PURPOSE A subset of patients with myelodysplastic syndromes (MDS) who are predicted to have lower-risk disease as defined by the International Prognostic Scoring System (IPSS) demonstrate more aggressive disease and shorter overall survival than expected. The identification of patients with greater-than-predicted prognostic risk could influence the selection of therapy and improve the care of patients with lower-risk MDS. PATIENTS AND METHODS We performed an independent validation of the MD Anderson Lower-Risk Prognostic Scoring System (LR-PSS) in a cohort of 288 patients with low- or intermediate-1 IPSS risk MDS and examined bone marrow samples from these patients for mutations in 22 genes, including SF3B1, SRSF2, U2AF1, and DNMT3A. RESULTS The LR-PSS successfully stratified patients with lower-risk MDS into three risk categories with significant differences in overall survival (20% in category 1 with median of 5.19 years [95% CI, 3.01 to 10.34 years], 56% in category 2 with median of 2.65 years [95% CI, 2.18 to 3.30 years], and 25% in category 3 with median of 1.11 years [95% CI, 0.82 to 1.51 years]), thus validating this prognostic model. Mutations were identified in 71% of all samples, and mutations associated with a poor prognosis were enriched in the highest-risk LR-PSS category. Mutations of EZH2, RUNX1, TP53, and ASXL1 were associated with shorter overall survival independent of the LR-PSS. Only EZH2 mutations retained prognostic significance in a multivariable model that included LR-PSS and other mutations (hazard ratio, 2.90; 95% CI, 1.85 to 4.52). CONCLUSION Combining the LR-PSS and EZH2 mutation status identifies 29% of patients with lower-risk MDS with a worse-than-expected prognosis. These patients may benefit from earlier initiation of disease-modifying therapy.
Transfer alignment of SINS based on quaternion algorithm

In this paper a new algorithm for missile transfer alignment is supposed. The quaternion algorithm based on the specific force output and angular rate output of the master inertial navigation system and the slave inertial navigation system is deduced too. According to the motion relations between the master INS and the slave INS, the velocity relation and the acceleration relation are derived too. The computing simulation showed the performance of the new algorithm under the noise-disturbance. The new algorithm can be used prior to the more extractive alignment as it can provide smaller misalignment angle by which we can obtain the linear dynamic error model. As we know the linear dynamic error model is more simple for the transfer alignment, so the algorithm of this paper has engineering sense.
Reduction of cephalic arteriovenous shunting by ergotamine is not mediated by 5‐HT1‐like or 5‐HT2 receptors

1 The potent, antimigraine drug ergotamine has affinity for both 5‐HT1 and 5‐HT2 binding sites and constricts arteriovenous anastomoses. Since 5‐HT also constricts arteriovenous anastomoses (mainly via 5‐HT1‐like receptors), this study investigates the involvement of 5‐HT receptors in the ergotamine‐induced reduction of arteriovenous shunting in the carotid circulation of the cat and pig. 2 In the cat, ergotamine (3, 10 and 30 μg kg−1, i.v.) reduced carotid blood flow, predominantly by a reduction in arteriovenous anastomotic blood flow. Pretreatment with ketanserin (0.5 mg kg−1, i.v.) or methiothepin (1 mg kg−1, i.v.) did not antagonize the effects of ergotamine. 3 In the pig, ergotamine (2.5, 5, 10 and 20 μg kg−1, i.v.) also reduced carotid blood flow and arteriovenous shunting, which was not affected by pretreatment with methiothepin (1 mg kg−1, i.v.). 4 These results suggest that the reduction by ergotamine in the shunting of carotid arterial blood via cephalic arteriovenous anastomoses is not mediated by 5‐HT1‐like or 5‐HT2 receptors.
Vom Schmerz zur somatoformen Ausweitung

Zusammenfassung Aufgrund der neuronalen Verbindungen der nozizeptiven Impulsübertragung werden bestimmte Hirnstrukturen aktiviert. Davon ausgehend kann es zu Störungen kommen, die Funktionen betreffen, die von diesen Hirnarealen reguliert werden. In erster Linie können Schlafstörungen auftreten und Störungen der Hypothalamus-Hypophysen-Nebennieren-Achse. Infolge dieser Störungen bzw. einer negativen gegenseitigen Beeinflussung kann es zu umfassenden Störungen der physischen, psychischen und kognitiven Funk-tionen kommen. Diese Störungen können einen wesentlichen Einfluss auf die kognitive (gedankliche, imaginierte, mit eigenen Überzeugungen übereinstimmende) und schließlich emotionale Verarbeitung haben. Daraus ergeben sich Probleme in der Bewältigung, zumal wenn aufgrund der Veranlagung oder der aktuellen Lebensbedingungen eine Neigung zu negativen Kognitionen und Emotionen und zur Katastrophisierung besteht. Es handelt sich um eine prozesshafte Entwicklung, die durch Ergebnisse der empirischen Studien belegt wird und in vieler Hinsicht Symptomverstärkung und -ausweitung erklären kann. Ausgehend davon muss in der Behandlung der chronischen Schmerzen der Fokus weg vom nozizeptiven Impuls hin zu einer umfassenden therapeutischen Beeinflussung der be-einträchtigten Funktionen verlegt werden. Dabei ist eine angemessene Information des Patienten bezüglich der komplexen Zusammenhänge beim chronischen Schmerz eine wichtige Voraussetzung.
Automatische Konfiguration der Bewegungssteuerung von Industrierobotern

Robotersteuerungen erfordern sehr lange Entwicklungszeiten und hohe Entwicklungskosten. Die Software wird sehr aufwandig von Hand entwickelt und implementiert. Die automatische, schnelle und zuverlassige Konfiguration der Bewegungssteuerung von beliebigen Robotertypen ist neuartig. Hierfur wurde in dieser Arbeit ein System zur automatisierten Konfiguration komponentenbasierter Software auf Basis einer Beschreibung der mechanischen Struktur und Eigenschaften von Industrierobotern entwickelt.
Cutting Edge: TGF-β Inhibits Th Type 2 Development Through Inhibition of GATA-3 Expression

TGF-β is an important immunomodulatory cytokine that can inhibit differentiation of effector T cells. In this report, we address the molecular mechanisms through which TGF-β inhibits differentiation of CD4+ cells into Th type 2 cells. We demonstrate that TGF-β inhibits GATA-3 expression in developing Th cells. We also show that inhibition of GATA-3 expression by TGF-β is a major mechanism of inhibition of Th2 differentiation by TGF-β as ectopic expression of GATA-3 in developing T cells overcomes the ability of TGF-β to inhibit Th2 differentiation. TGF-β likely inhibits GATA-3 expression at the transcriptional level and does so without interfering with IL-4 signaling.
Post-Stroke Mania Late in Life Involving the Left Hemisphere

Objective: Although post-stroke depression is well recognised, post-stroke mania has rarely been reported and researched. Most reported cases have involved lesions of the non-dominant hemisphere. We report a case of late-onset mania following stroke with a lesion in the dominant hemisphere. Clinical picture: A 78-year-old, right-handed man developed sudden cognitive deficits and manic symptoms. Investigations revealed lesions in the dominant hemisphere. Treatment: Pharmacological intervention was complicated by side effects. Outcome: His symptoms resolved gradually over 2 months and he was back to normal in 4 months. Conclusions: We would encourage further study in the area of post-stroke mania and especially in relation to the site of the lesion in the brain.
Efficacy of Venlafaxine ER in patients with social anxiety disorder: a double‐blind, placebo‐controlled, parallel‐group comparison with paroxetine

This study evaluated the anxiolytic efficacy, safety and tolerability of a flexible dose of venlafaxine extended release (ER) compared with placebo and paroxetine in the short‐term treatment of generalized social anxiety disorder (SAD). Adult outpatients with generalized SAD (n = 434) were randomized to receive capsules of venlafaxine ER 75 mg to 225 mg/day, paroxetine 20 mg to 50 mg/day, or placebo for 12 weeks. The primary efficacy variable was the Liebowitz social anxiety scale total score. Secondary efficacy variables included the patient‐rated social phobia inventory and the proportion of responders in each group (a responder was defined as having a clinical global impression‐improvement score of 1 or 2). Treatment with venlafaxine ER was associated with significantly greater improvement than treatment with placebo for all primary and secondary efficacy variables (p < 0.05). No significant differences in primary or secondary efficacy variables were observed between the venlafaxine ER and paroxetine groups. The week 12 response rates were 69%, 66% and 36% for the venlafaxine ER, paroxetine and placebo groups, respectively. Both active treatments were generally well tolerated and were associated with a similar incidence of adverse events. This study shows that venlafaxine ER is an effective, safe and well‐tolerated drug treatment for SAD. Copyright © 2004 John Wiley & Sons, Ltd.
Aldose Reductase Inhibition Increases CNTF-Like Bioactivity and Protein in Sciatic Nerves From Galactose-Fed and Normal Rats

The impact of exaggerated polyol pathway flux on ciliary neurotrophic factor (CNTF)-like bioactivity and expression of CNTF in rat sciatic nerve was examined after 2 months of galactose intoxication. Polyol content was elevated (P < 0.001) and motor nerve conduction velocity reduced (P < 0.05) in galactose-fed rats compared with control animals or control and galactose-fed rats treated with the aldose reductase inhibitor (ARI) Ponalrestat. CNTF-like bioactivity in the galactose-fed group was reduced to 30% of that assayed in the control group (P < 0.001). ARI treatment significantly increased CNTF-like bioactivity by 60% compared with the untreated galactose group (P < 0.05) but did not restore it to control levels. Unexpectedly, bioactivity in ARI-treated control animals was increased by nearly 250% compared with untreated controls (P < 0.005). In addition to the deficit in CNTF bioactivity in untreated galactose rats, the expression of protein, but not of mRNA, was reduced (P < 0.05). In ARI-treated control and galactose-fed rats, the expression of CNTF peptide was significantly enhanced above control levels (both P < 0.05). Concomitant with the reduction in CNTF levels, there was a shift in the axonal size-frequency distribution of myelinated fibers toward smaller axons in galactose-fed rats that was prevented by ARI treatment. Since galactose feeding has little impact on levels of CNTF mRNA, these observations suggest that deficits in CNTF-like bioactivity may result from a posttranscriptional modification of neurotrophic protein expression or turnover. Unlike other functional and structural disorders in galactose neuropathy, factors other than polyol accumulation may contribute to the deficit in CNTF-like bioactivity.
Long-term Follow-up of 414 HIV-Infected Romanian Children and Adolescents Receiving Lopinavir/Ritonavir-Containing Highly Active Antiretroviral Therapy

BACKGROUND. There are no published reports of the long-term safety and effectiveness of highly active antiretroviral therapy for children and adolescents living in resource-limited settings or of large cohorts of HIV-infected children and adolescents treated long-term (>48 weeks) with lopinavir/ritonavir-containing highly active antiretroviral therapy. OBJECTIVES. The purpose of this work was to evaluate the long-term outcomes of treatment of HIV-infected children and adolescents with lopinavir/ritonavir-containing highly active antiretroviral therapy in a resource-limited setting. METHODS. We studied an inception cohort of 414 HIV-infected children receiving lopinavir/ritonavir-containing highly active antiretroviral therapy between November 2001 and August 2006 at the Romanian-American Children's Center in Constanta, Romania. The center provides comprehensive primary and HIV specialty care and treatment to all known HIV-infected children and adolescents living in Constanta. We measured safety and effectiveness by the percentage of children remaining on treatment, rates of mortality, and changes in plasma HIV RNA concentrations and CD4+ lymphocyte counts. RESULTS. The study population consisted predominantly of antiretroviral drug–experienced older children and adolescents with advanced HIV disease. Treatment was well tolerated, with 337 children (81%) remaining on therapy after a median duration of >4 years. Thirty-seven deaths occurred; the death rate compared favorably to prospectively collected historical data. The most recent on-treatment plasma HIV RNA concentration was <400 copies per milliliter in 192 of 265 children tested. The mean baseline CD4+ lymphocyte count was 292 cells per microliter (n = 299); the mean change from baseline was +266 (n = 284), +317 (n = 260), +343 (n = 176), and +270 cells per microliter (n = 121) after 1, 2, 3, and 4 years of treatment, respectively. CONCLUSIONS. Highly active antiretroviral therapy can be administered safely and effectively to children and adolescents in resource-limited settings. Lopinavir/ritonavir-containing highly active antiretroviral therapy is a safe, effective, and durable treatment option for antiretroviral drug–experienced older children and adolescents with advanced HIV disease.
ART-123 Asahi Kasei.

Asahi Kasei is developing a recombinant thrombomodulin (ART-123), a human protein with both thrombin inhibiting and protein C stimulating activities, for the potential treatment of thromboembolism and blood clotting disorders, such as disseminated intravascular thromboembolism [169907]. By September 2000, it had entered phase III trials [383525]. A patent, US-05916874, claiming a method for treating liver injury and whose composition comprises a thrombomodulin, was published in 1999 by the company.
Exploring Relationships of Psychopathology in Hypersexual Patients Using the MMPI-2

This article reports the findings of a study investigating relationships among Minnesota Multiphasic Personality Inventory-2 (MMPI-2) scales as they pertain to a group of individuals seeking help for hypersexual behavior (N = 152). A number of MMPI-2 scale elevations were prevalent with this group, suggesting that some of these patients experience symptoms associated with psychopathology and interference or impairment in important areas of personal and interpersonal functioning. We failed to find any evidence in our data supporting the notion that hypersexual patients experience addictive tendencies. For a significant portion of the group, however, there were few-to-minimal elevations, reflecting normal psychological profiles. An overall important finding in our data suggests that patients presenting with hypersexual behavior are a diverse group, sufficiently so that studying subsamples of this group may lead to a clearer understanding of this behavior. Models that promote a homogenous conceptualization and treatment of hypersexuality likely miss important differences that provide valuable insight when working with this population.
Assessing the Reliability and Validity of a Shorter Walk Test Compared With the 10-Meter Walk Test for Measurements of Gait Speed in Healthy, Older Adults

Background and Purpose:Walking speed is associated with several health-related outcomes. Research examining how differences in test walking distance affect walking speed reliability and validity is limited. The primary purpose of this study was to examine the reliability and concurrent validity of gait speed measurements obtained from a 4-Meter Walk Test compared with the commonly used 10-Meter Walk Test. A second objective was to similarly examine 2 different timing methods: stopwatch and automatic timers. Methods:Forty-three healthy, older adults (mean age = 84.3 ± 6.9 years) performed 3 consecutive walking trials on the 4- and 10-Meter Walk Tests at their self-selected walking speed. Results:Gait speed measurements for both tests were shown to have excellent test-retest reliability (ICC values of 0.96–0.98), with similar results for stopwatch and automatic timer assessments (ICC values of 0.99–1.00). Standard error of the measurement (SEM) values were small (0.004–0.008 m/s) across measurement methods. While the ICC value for gait speed measurements between the 2 walk tests was 0.93, the Bland-Altman analysis revealed a discrepancy of ±0.15 to ±0.17 m/s between measurement methods. Discussion:Both 4- and 10-m gait speed assessments had excellent test-retest reliability with similar SEM and minimal detectable change values. There was little difference in SEM values between the 2 timing methods. While the mean difference in gait speed between the 4- and 10-Meter Walk Tests was small, the range of the measurement differences was large enough to potentially mask meaningful changes in gait speed over time if both methods were used interchangeably. Conclusions:While the reliability of both walking tests is excellent, the 4-Meter Walk Test does not exhibit a high enough degree of concurrent validity with the 10-Meter Walk Test to be used interchangeably for gait speed assessments in healthy, older adults. We therefore recommend using the 10-Meter Walk Test to obtain the most valid clinical assessment of walking speed when using it as a 1-time indicator of health status.
CircRNAs in the brain

ABSTRACT Circular RNAs (circRNAs) are highly abundant and evolutionarily conserved non-coding RNAs produced by circularization of specific exons. Since their re-discovery as potential regulators of gene expression, thousands of circRNAs were detected in different tissues and cell types across most organisms. Accumulating data suggest key roles for them in the central nervous system. Neuronal-expressed RNAs are diverted to yield highly enriched CircRNAs in human, mouse, pig and flies, with many of them enriched in neuronal tissues. CircRNA levels are dynamically modulated in neurons, both during differentiation and following bursts of electrical activity, and accumulate with age, and many of them are enriched in synapses. Together, available data suggest that circRNAs have important roles in synaptic plasticity and neuronal function. This review covers current advances in the field and lays out hypotheses regarding functions of circRNAs in the brain as well as their putative involvement in initiation and progression of neurodegenerative processes.
Index of central obesity as a parameter to replace waist circumference for the definition of metabolic syndrome in predicting cardiovascular disease

Objective To compare the suitability of metabolic syndrome definitions in predicting cardiovascular disease (CVD) risk. Methods We analyzed data from a population-based prospective cohort of 3598 participants from Jiangsu, China. Waist circumference was replaced with central obesity [index of central obesity (ICO), a ratio of waist circumference and height] in Cholesterol Education Program Adult Treatment Panel III (ICO-replaced ATPIII) and International Diabetes Federation (ICO-replaced IDF), respectively. Cox proportional-hazards regression model and the receiver operating characteristic curve (ROC curve) was used to evaluate the suitability of ATPIII, IDF, ICO-replaced IDF and ICO-replaced ATPIII in predicting CVD risk. Results ICO was a better parameter in predicting CVD risk by ROC curve analysis. The ROC curve analysis also showed that although ICO-replaced IDF and IDF had the higher degree of specificity, lower sensitivity, longer ROC curve distance, less area under the curve to identify CVD than ATPIII and ICO-replaced ATPIII, therefore ICO-replaced IDF and IDF seemed to be undesirable. However, there was no significant difference in area under the curve between ATPIII and ICO-replaced ATPIII in predicting CVD risk. But it seems that odds ratios for abnormal triglyceride and high-density lipoprotein levels increase slightly when using ICO, but decrease for hyperglycemia and hypertension when using ICO. Conclusion ICO was a better predictor of abnormal triglyceride and high-density lipoprotein levels than waist circumference, but waist circumference was a better predictor of hyperglycemia and hypertension than ICO. However, we failed to support ICO as a better parameter for metabolic syndrome definition in predicting CVD risk compared with waist circumference.
Markers of chronic obstructive pulmonary disease are associated with mortality in people living with HIV

Objective: Aging people living with HIV (PLWH) face an increased burden of comorbidities, including chronic obstructive pulmonary disease (COPD). The impact of COPD on mortality in HIV remains unclear. We examined associations between markers of COPD and mortality among PLWH and uninfected study participants. Design: Longitudinal analysis of the Examinations of HIV-Associated Lung Emphysema (EXHALE) cohort study. Methods: EXHALE includes 196 PLWH and 165 uninfected smoking-matched study participants who underwent pulmonary function testing and computed tomography (CT) to define COPD and were followed. We determined associations between markers of COPD with mortality using multivariable Cox regression models, adjusted for smoking and the Veterans Aging Cohort Study (VACS) Index, a validated predictor of mortality in HIV. Results: Median follow-up time was 6.9 years; the mortality rate was 2.7/100 person-years among PLWH and 1.7/100 person-years among uninfected study participants (P = 0.11). The VACS Index was associated with mortality in both PLWH and uninfected study participants. In multivariable models, pulmonary function and CT characteristics defining COPD were associated with mortality in PLWH: those with airflow obstruction (forced expiratory volume in 1 s/ forced vital capacity <0.7) had 3.1 times the risk of death [hazard ratio 3.1 (95% confidence interval 1.4–7.1)], compared with those without; those with emphysema (>10% burden) had 2.4 times the risk of death [hazard ratio 2.4 (95% confidence interval 1.1–5.5)] compared with those with ⩽ 10% emphysema. In uninfected subjects, pulmonary variables were not significantly associated with mortality, which may reflect fewer deaths limiting power. Conclusion: Markers of COPD were associated with greater mortality in PWLH, independent of the VACS Index. COPD is likely an important contributor to mortality in contemporary PLWH.