Miracle-dz/UniFAR-FTUs huggingface dataset:
Chorionic gonadotropin regulates the transcript level of VHL, p53, and HIF‐2α in human granulosa lutein cells

The ovarian corpus luteum plays a critical role in reproduction being the primary source of circulating progesterone. After ovulation the corpus luteum is build by avascular granulosa lutein cells through rapid vascularization regulated by gonadotropic hormones. The present study was performed to investigate whether this process might be influenced by the human chorionic gonadotropin (hCG)‐dependent expression of different tumor suppressor genes and hypoxia dependent transcription factors. RNA was isolated from cultured granulosa lutein cells, transcribed into cDNA, and the transcript level of following genes were determined: RB‐1, VHL, NF‐1, NF‐2, Wt‐1, p53, APC, and hypoxia inducible factor‐1 (HIF‐1), ‐2, and ‐3α. Additionally, the influence of hCG on the expression of VHL, p53, and HIf2α were investigated. We demonstrate that in human granulosa lutein cells the tumor suppressor genes RB‐1, VHL, NF‐1, NF‐2, Wt‐1, p53, and APC and the hypoxia dependent transcription factors HIF‐1α, ‐2α, and ‐3α are expressed. In addition, we showed that hCG regulates the expression of p53, VHL, and HIF‐2α. Our results indicate that hCG may determine the growth and development of the corpus luteum by mediating hypoxic and apoptotic pathways in human granulosa lutein cells. Mol. Reprod. Dev. 69: 397–401, 2004. © 2004 Wiley‐Liss, Inc.
Performance of a self-report measure of the level of response to alcohol in 12- to 13-year-old adolescents.

OBJECTIVE A low level of response (LR) to alcohol characterizes groups at high risk for alcoholism and predicts future heavier drinking and alcohol-related problems. Because LR might change with increasing age and years of drinking, there is a need to measure this phenotype as early as possible in the drinking career. METHOD Data were generated from 1,106 12- to 13-year-old subjects in the Avon Longitudinal Study of Parents and Children (ALSPAC). Information about alcohol and other substance use and problems was obtained using a structured interview, and LR from the Self-Rating of the Effects of Alcohol (SRE) questionnaire. RESULTS Drinking was reported by 80 (7.3% of all subjects) boys and girls. Boys comprised 62.5% of the sample; the mean (SD) age of subjects was 12.9 (0.16) years. Among those 80 drinkers, alcohol had been consumed on an average of 5.4 occasions over the prior 6 months, the average maximum drinks ever imbibed was about 3.3, and 23.8% had any of 26 possible alcohol-related problems. In this group, 36.3% had smoked cigarettes, and 12.5% had used marijuana. The First 5 SRE score among drinkers correlated with the maximum number of drinks consumed at one time at . 61 (p < .001), the number of alcohol problems at . 25 (p < .01) and the frequency of drinking at . 29 (p < .01). When considered along with smoking and marijuana histories, sex and weight, the SRE score contributed significantly to the prediction of maximum drinks per occasion (beta = .60, p < .001) and drinking frequency (beta = .24, p < .05), with a trend (beta = .17, p = .08) for alcohol problems. CONCLUSION These results support the conclusion that a low LR to alcohol correlates well with the maximum number of drinks consumed even early in the drinking career among individuals for whom acquired tolerance or other factors were unlikely to have explained the relationship.
CpG ODN enhance antigen‐specific NKT cell activation via plasmacytoid dendritic cells

Human Vα24+ Vβ11+ natural killer T cells (NKT cells) are “natural memory” T cells that detect glycolipid antigens such as α‐galactosylceramide (α‐GalCer) presented on CD1d. In the present study we found that highly purified Vα24+ NKT cells lack TLR9 mRNA, and thus are not sensitive towards stimulation with CpG oligodeoxynucleotides (ODN). Within PBMC, however, CpG ODN synergistically activated NKT cells stimulated with their cognate antigen α‐GalCer. Depletion of plasmacytoid dendritic cells (PDC) or myeloid dendritic cells (MDC) revealed that both DC subsets were necessary for the synergistic activation of NKT cells by α‐GalCer and CpG ODN. While PDC were responsible for the stimulation of NKT cells with CpG ODN, MDC but not PDC presented α‐GalCer via CD1d. Partial activation of NKT cells was mediated by PDC‐derived IFN‐α, whereas full activation of NKT cells as indicated by IFN−γ production required cell‐to‐cell contact of PDC and NKT cells in addition to IFN‐α; OX40 was involved in this interaction. We conclude that CpG‐activated PDC enhance α‐GalCer‐specific NKT cell activation, and bias activated NKT cells towards a Th1 phenotype. Our results lead to a novel concept of PDC function: to regulate effector activity of antigen‐stimulated T cells in a cell contact‐dependent manner without the need of simultaneous presentation of the cognate T cell antigen.
Clinicopathological and prognostic characteristics of triple- negative breast cancer (TNBC) in Chinese patients: a retrospective study.

AIMS To determine the clinical, pathological and prognostic features associated with triple-negative breast cancer (TNBC). METHODS Clinical and histologic data of 21,749 breast cancer patients who were treated at Tianjin Medical University Cancer Institute and Hospital between July 2002 and December 2011 were collected. Patients were divided into two groups: those with TNBC and those with other types of breast cancer. Patients and tumor characteristics were compared between the two groups using the Chi-square test. The prognostic results of 9,823 patients in the study population were also analyzed to determine long-term survival rates in the two groups of breast cancer patients. RESULTS Among the breast cancer patients treated in our hospital between 2003 and 2011, 10.4%-13.5% of them had triple-negative breast cancers. Data analyses revealed significant differences in disease onset age, family history of breast cancer, tumor size, tumor histologic grade, lymph note positivity and metastatic status between TNBC and non-TNBC patients. There were also significant differences in 5-year, 7-year and 9-year disease-free and 7-year and 9-year overall survival probability between the groups. CONCLUSIONS TNBC are associated with younger disease onset age, larger tumor size, higher rate of axillary lymph node positivity, and higher tumor histologic grade. TNBC is also related to family history of breast cancer, increased metastatic risk and poor prognosis.
The International Commonality of Idiosyncratic Variances

We document strong global commonality in firm-level and aggregate idiosyncratic return variances across 23 developed markets, and develop a rational pricing model to explain the empirical pattern. We find that the global common factor of idiosyncratic return variances is highly correlated with that of idiosyncratic cash flow variances, and is also significantly related to variables capturing aggregate discount rate variation and growth opportunities. We further document that the aggregate idiosyncratic return and cash flow variances are mostly but not always countercyclical. These findings are mostly inconsistent with extant theories regarding the time variation in idiosyncratic return variances.
Association of Ureaplasma urealyticum (Biovar 2) With Nongonococcal Urethritis

Background The tiny (T)-strain mycoplasmas, designated in 1974 as Ureaplasma urealyticum, have been divided into 2 species, Ureaplasma parvum (biovar 1) and U. urealyticum (biovar 2), but association of each of these species with nongonococcal urethritis (NGU) remains unclear. Goal The goal of this study was to determine whether U. parvum (biovar 1) or U. urealyticum (biovar 2) is associated with NGU. Study Design The prevalences of U. parvum (biovar 1) and U. urealyticum (biovar 2) in 572 patients with urethritis were compared with those in 141 men without urethritis. Results The prevalence of U. urealyticum (biovar 2) in men with NGU (15.8%) or with nonchlamydial NGU (18.0%) was significantly higher than that in men without urethritis (7.8%). The prevalence of U. parvum (biovar 1) in men with NGU (8.5%) or with nonchlamydial NGU (11.1%) did not differ significantly from that in men without urethritis (13.5%). Conclusion Our results showed a significant association between U. urealyticum (biovar 2) and NGU. They also suggest that the presence of U. parvum (biovar 1) in the male urethra might be the result of colonization.
Once-daily insulin glargine compared with twice-daily NPH insulin in patients with type 1 diabetes.

OBJECTIVE To present the findings in a randomized, parallel-group study, comparing once-daily insulin glargine with twice-daily NPH insulin in patients with type 1 diabetes previously treated with multiple daily injections of basal and regular insulin. METHODS Of 394 patients with type 1 diabetes treated for up to 28 weeks, 195 received insulin glargine and 199 received NPH insulin, in addition to preprandial regular insulin. Glycemic control and hypoglycemic episodes were assessed. RESULTS A greater mean decrease in fasting blood glucose (FBG) was achieved at endpoint with insulin glargine than with NPH insulin (-21 mg/dL versus -10 mg/dL [-1.17 mmol/L versus -0.56 mmol/L]; P = 0.015), and a greater percentage of patients treated with insulin glargine reached the target FBG (32.6% versus 21.3%; P = 0.015). Similar percentages of patients in both treatment groups achieved glycosylated hemoglobin values of 7.0% or less at endpoint (insulin glargine, 35.8%; NPH insulin, 35.4%). After the 1-month titration phase, the percentage of patients who reported at least one symptomatic hypoglycemic event confirmed by a blood glucose value of less than 50 mg/dL (2.8 mmol/L) was significantly lower with insulin glargine than with NPH insulin (73.3% versus 81.7%; P = 0.021). Furthermore, the percentage of patients who reported at least one symptomatic hypoglycemic event confirmed by a blood glucose value of less than 36 mg/dL (2.0 mmol/L) was significantly lower with insulin glargine than with NPH insulin (36.6% versus 46.2%; P = 0.033). CONCLUSION Once-daily insulin glargine was at least as effective as twice-daily NPH insulin in improving fasting glycemic control and resulted in fewer reported symptomatic hypoglycemic events.
The Reproductive Transition in an Indigenous Population of Northern Argentina

Latin America has been registering a fast decrease in fertility rates since the mid-twentieth century. This change can be linked to the modernization process these populations have been undergoing. However, research with Latin American indigenous populations, which are undergoing relatively similar lifestyle changes, shows very different trends in fertility. The aim of this study was to analyze fertility patterns in the indigenous Toba community of Cacique Sombrero Negro, which is experiencing a rapid process of economic and social Westernization. Fertility patterns were analyzed between 1981 and 1999, the period for which the most accurate records were found. Results showed an overall increase in fertility rates and changes in the age of peak fertility across time periods. It is hypothesized that the lifestyle transition this population is experiencing leads to better access to resources that, in the absence of contraception, allow for a higher number of offspring. Nevertheless, this higher resource availability would be differential, affecting mostly the fertility of younger mothers.
What are ventilation defects in asthma?

Background Hyperpolarised 3He MRI provides a way to visualise regional pulmonary functional abnormalities that in asthma are thought to be related to airway morphological abnormalities. However, the exact aetiology of ventilation defects in asthma is not well understood. Objective To better understand the determinants of ventilation defects in asthma, we evaluated well-established clinical as well as 3He MRI and X-ray CT airway measurements in healthy subjects and subjects with asthma. Methods Thirty-four subjects (n=26 subjects with asthma, n=8 healthy volunteers) underwent MRI, spirometry, plethysmography, fraction of exhaled nitric oxide analysis, methacholine challenge and CT for a region-of-interest proximal to ventilation defects. For subjects who consented to CT (n=18 subjects with asthma, n=5 healthy volunteers), we evaluated 3rd to 5th generation airway wall area and wall thickness per cent and lumen area. Results Seventeen subjects with asthma (17/26=65%) had visually obvious evidence of 3He ventilation defects prior to bronchoprovocation and nine subjects with asthma had no ventilation defects prior to bronchoprovocation (9/26=35%). Subjects with asthma with defects were older (p=0.01) with worse forced expiratory volume in 1 s (FEV1)/forced vital capacity (p=0.0003), airways resistance (p=0.004), fraction of exhaled nitric oxide (p=0.03), greater bronchoprovocation concentration of methacholine that reduced FEV1 by 20% (p=0.008) and wall thickness per cent (p=0.02) compared with subjects with asthma without defects. There was a moderate correlation for wall area per cent with ventilation defect per cent (r=0.43, p=0.04). Conclusions Subjects with asthma with 3He ventilation defects were older with significantly worse airway hyper-responsiveness, inflammation and airway remodelling but similar FEV1 as subjects with asthma without defects; hyperpolarised 3He ventilation abnormalities were spatially and quantitatively related to abnormally remodelled airways.
Transcriptional regulation of scar gene expression in primary astrocytes

The failure of the adult injured spinal cord to support axonal regeneration is in part attributed to the glial scar. Reactive astrocytes constitute a major cellular component of the glial scar and are heterogeneous with respect to the extracellular matrix proteins that they secrete. Astrocytes may produce antiregenerative molecules such as chondroitin sulphate proteoglycans (CSPGs) or proregenerative molecules such as laminin and fibronectin. While many different CSPGs are expressed after spinal cord injury (SCI) they all rely on the same enzymes, xylosyltransferase‐I and ‐II (XT‐I, XT‐II) and chondroitin 4‐sulfotransferase (C4ST) to add the repulsive chondroitin sulfate side chains to their core proteins. We show that XT‐I, XT‐II, and C4ST are part of a CSPG biosynthetic gene (CBG) battery. Using primary astrocyte cultures and quantitative PCR we demonstrate that TGFβ2, PDGF, and IL‐6 induce the expression of CBGs, laminin and fibronectin by several‐fold. We further show that over‐expression of the transcription factor SOX9 also strongly induces the expression of CBGs but does not increase the expression of laminin or fibronectin. Correspondingly, SOX9 knock‐down in primary astrocytes causes a decrease in CBG and an increase in laminin and fibronectin mRNA levels. Finally, we show that the in vivo expression profiles of TGFβ2, PDGF, IL‐6, and SOX9 are consistent with their potential roles in differentially regulating CBGs, laminin and fibronectin gene expression in the injured spinal cord. This work suggests that SOX9 levels may be pivotal in determining the balance of pro‐ and anti‐regenerative extracellular matrix molecules produced by astrocytes. © 2007 Wiley‐Liss, Inc.
A Transient Elevated Irisin Blood Concentration in Response to Prolonged, Moderate Aerobic Exercise in Young Men and Women

Abstract Irisin, a newly discovered, PGC-1α dependent myokine, has recently been shown to increase in circulation in response to sprint exercise. This study examined the effect of prolonged exercise on irisin concentrations in young men (n=7) as well as in young women (n=5) during different stages of the menstrual cycle. Seven young men completed 90 min of treadmill exercise at 60% of VO2max and a resting control trial. Five women completed the same exercise protocol in two different trials: during the early follicular phase and mid-luteal phase of the menstrual cycle. Blood samples were collected and analyzed for irisin concentrations immediately before exercise, at 54 and 90 min of exercise, and at 20 min of recovery (R20). Findings revealed that by 54 min of a 90 min treadmill exercise protocol at 60% of VO2max, irisin concentrations significantly increased 20.4% in young men and 20.3% as well as 24.6% in young women during the early follicular and mid-luteal phases of the menstrual cycle, respectively. However, by 90 min of exercise as well as R20, irisin concentrations were no longer elevated. Stage of the menstrual cycle did not affect responses in young women. Findings indicate that prolonged aerobic exercise produces a transient increase in irisin concentrations during the first hour of exercise for both genders and suggest that this form of moderate exercise may be helpful in improving fat metabolism.
Adaptation and World Market Effects of Climate Change on Forestry and Forestry Products

We use a computable general equilibrium model to study the impacts of climate change on forestry over time. The model is constructed around the GTAP v5 database, with nine regions and eleven production sectors. The model also includes a forestry module, with data of the standing mass and growth rates of the regional forests. The production in the forestry sector is subject to changes in the productivity of “land”, which gives rise to a Ricardian rent on forests. The rent depends partly on the natural prerequisites for growth of the bio-mass, which relate to climatic conditions, but also the infrastructure investments required to gain access to the forests. The forestry sector is impacted by different dimensions of climatic change, such as combinations of changes in temperature and precipitation. For a possible future climate change scenario, we assess the consequences on the world market for forestry and derived products.
Lung Dendritic Cells Rapidly Mediate Anthrax Spore Entry through the Pulmonary Route1

Inhalational anthrax is a life-threatening infectious disease of considerable concern, especially because anthrax is an emerging bioterrorism agent. The exact mechanisms leading to a severe clinical form through the inhalational route are still unclear, particularly how immobile spores are captured in the alveoli and transported to the lymph nodes in the early steps of infection. We investigated the roles of alveolar macrophages and lung dendritic cells (LDC) in spore migration. We demonstrate that alveolar macrophages are the first cells to phagocytose alveolar spores, and do so within 10 min. However, interstitial LDCs capture spores present in the alveoli within 30 min without crossing the epithelial barrier suggesting a specific mechanism for rapid alveolus sampling by transepithelial extension. We show that interstitial LDCs constitute the cell population that transports spores into the thoracic lymph nodes from within 30 min to 72 h after intranasal infection. Our results demonstrate that LDCs are central to spore transport immediately after infection. The rapid kinetics of pathogen transport may contribute to the clinical features of inhalational anthrax.
Simple and accurate assessment of forward cardiac output by use of 1-(11)C-acetate PET verified in a pig model.

UNLABELLED Dynamic 1-(11)C-acetate PET (AC-PET) allows quantification of myocardial blood flow and oxidative metabolism. We wanted to determine the accuracy of AC-PET in measuring cardiac output (CO) using first-pass analysis and the indicator dilution principle. Further, we wanted to investigate the pulmonary uptake of acetate in relation to left atrial filling pressures and ventricular function. METHODS Twenty-four steady-state experiments were performed in 5 domestic pigs. Pulmonary capillary wedge pressure (PCWP) and CO by thermodilution (CO(thermo)) were recorded invasively simultaneous with AC-PET scans at baseline (n = 9), dobutamine infusion (n = 6), high-dose metoprolol and morphine (n = 6), and angiotensinamide infusion (n = 3). 1-(11)C-Acetate was injected as a rapid manual bolus. Regions of interest (ROIs) were placed in the right (RV) and left (LV) heart cavities. Time-activity curves were constructed and the area under the curve (AUC) was integrated from beginning the scan to the time of visually determined recirculation by simple arithmetic. CO by PET (CO(PET)) was calculated as injected dose/AUC. Image handling and curve analysis were repeated by a blinded observer. Total pulmonary extravascular retention of (11)C, expressed as percentage of injected dose (lung-uptake %ID), was measured using a combination of transmission, (15)O-carbon monoxide, and AC-PET scans. RESULTS CO(thermo) ranged from 2.1 to 8.2 L/min. CO(PET) determined from both LV and RV was linearly related to CO(thermo) with slopes close to 1 (LV, r = 0.98; RV, r = 0.96; both P < 0.001). Interobserver reproducibility was r = 0.98, P < 0.001. The PCWP range was 6-14 mm Hg and the lung-uptake %ID was 2.7-8.5 %ID. When normalized to baseline, lung-uptake %ID was correlated with PCWP (r = 0.56, P = 0.01) and linearly correlated with LV input resistance (PCWP divided by CO(thermo); r = 0.91, P < 0.001). When both lung-uptake %ID and stroke volume were normalized to baseline, a piecewise linear relation was found (r = 0.95, P < 0.001). CONCLUSION Our results suggest that measurements of CO by AC-PET are feasible and accurate. Using RV ROIs might favor CO measurements by any injectable PET tracer. The lung-uptake %ID might be useful in evaluation of pulmonary congestion, but further studies are needed.
A systematic review and quantitative appraisal of fMRI studies of verbal fluency: Role of the left inferior frontal gyrus

The left inferior frontal gyrus (LIFG) has consistently been associated with both phonologic and semantic operations in functional neuroimaging studies. Two main theories have proposed a different functional organization in the LIFG for these processes. One theory suggests an anatomic parcellation of phonologic and semantic operations within the LIFG. An alternative theory proposes that both processes are encompassed within a supramodal executive function in a single region in the LIFG. To test these theories, we carried out a systematic review of functional magnetic resonance imaging studies employing phonologic and semantic verbal fluency tasks. Seventeen articles meeting our pre‐established criteria were found, consisting of 22 relevant experiments with 197 healthy subjects and a total of 41 peak activations in the LIFG. We determined 95% confidence intervals of the mean location (x, y, and z coordinates) of peaks of blood oxygenation level‐dependent (BOLD) responses from published phonologic and semantic verbal fluency studies using the nonparametric technique of bootstrap analysis. Significant differences were revealed in dorsal–ventral (z‐coordinate) localizations of the peak BOLD response: phonologic verbal fluency peak BOLD response was significantly more dorsal to the peak associated with semantic verbal fluency (confidence interval of difference: 1.9–17.4 mm). No significant differences were evident in antero–posterior (x‐coordinate) or medial–lateral (y‐coordinate) positions. The results support distinct dorsal–ventral locations for phonologic and semantic processes within the LIFG. Current limitations to meta‐analytic integration of published functional neuroimaging studies are discussed. Hum Brain Mapp, 2006. © 2006 Wiley‐Liss, Inc.
Mycosis fungoides associated with unusual epidermal hyperplasia

A 58‐year‐old white woman presented with widespread pruritic brownish plaques and hyperpigmented flexural lesions with a velvety appearance. On histopathological examination, the macules were diagnostic of mycosis fungoides, plaque stage, and the flexural lesions showed epidermal hyperplasia with a seborrhoeic keratosis‐like appearance. There was intense mucin deposition and marked reduction of elastic fibres in the papillary dermis, as well as a moderately dense dermal lymphoid infiltrate composed of GD4+ T cells with occasional atypia and focal epidermotropism.