Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantitative and Semiquantitative Measures of Regional Pulmonary Microvascular Perfusion by Magnetic Resonance Imaging and Their Relationships to Global Lung Perfusion and Lung Diffusing Capacity: The Multiethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease Study

ObjectivesThe aim of this study was to evaluate the quantitative and semiquantitative measures of regional pulmonary parenchymal perfusion in patients with chronic obstructive pulmonary disease (COPD) in relationship to global lung perfusion (GLP) and lung diffusing capacity (DLCO). Materials and MethodsA total of 143 participants in the Multiethnic Study of Atherosclerosis COPD Study were examined by dynamic contrast-enhanced pulmonary perfusion magnetic resonance imaging (MRI) at 1.5 T. Pulmonary microvascular blood flow (PBF) was calculated on a pixel-by-pixel basis by using a dual-bolus technique and the Fermi function model. Semiquantitative parameters for regional pulmonary microvascular perfusion were calculated from signal intensity-time curves in the lung parenchyma. Intraoberserver and interobserver coefficients of variation (CVs) and correlations between quantitative and semiquantitative MRI parameters and with GLP and DLCO were determined. ResultsQuantitative and semiquantitative parameters of pulmonary microvascular perfusion were reproducible, with CVs for all parameters of less than 10%. Furthermore, these MRI parameters were correlated with GLP and DLCO, and there was good agreement between PBF and GLP. Quantitative and semiquantitative MRI parameters were closely correlated (eg, r = 0.86 for maximum signal increase with PBF). In participants without COPD, the physiological distribution of pulmonary perfusion could be determined by regional MRI measurements. ConclusionRegional pulmonary microvascular perfusion can reliably be quantified from dynamic contrast-enhanced MRI. Magnetic resonance imaging–derived quantitative and semiquantitative perfusion measures correlate with GLP and DLCO.
Prevalence of intestinal complications in inflammatory bowel disease: a comparison between paediatric-onset and adult-onset patients

Introduction Intestinal complications in inflammatory bowel disease indicate active inflammation and typically result in the intensification of therapy. Aim To analyse whether the rates of intestinal complications were associated with age at disease onset. Patients and methods Data from 1506 individuals with Crohn’s disease (CD) and 1201 individuals with ulcerative colitis (UC) were obtained from the Swiss inflammatory bowel disease cohort study database, classified into groups on the basis of age at diagnosis (<10, <17, <40 and >40 years of age), and retrospectively analysed. Results In CD patients, the rates of stricturing (29.1–36.2%), abdominal penetrating disease (11.9–18.2%), resectional surgery (17.9–29.8%) and perianal disease (14.7–34.0%) were correlated with disease duration, but not age at diagnosis. However, paediatric-onset CD was associated with higher rates of multiple, rectal and anal strictures and earlier colon surgery. In addition, perianal disease occurred earlier, required earlier surgical intervention, and was more often combined with stricturing and penetrating disease. Finally, anal fissures were more prevalent among younger patients. In UC patients, the rates of progression or extension of disease (0–25.8%) and colectomy (3.0–8.7%) were dependent on disease duration, but not age at disease onset. Paediatric-onset disease was associated with a higher rate of extensive colitis at diagnosis and earlier progression or extension of disease, and nonsurgically treated patients with the youngest ages at onset more frequently required antitumour necrosis factor-&agr; treatments. Conclusion The higher rates of intestinal complications, including those of the small and large bowel and in the anal region, in paediatric-onset CD patients point towards a level of inflammation that is more difficult to control. Similar findings were also evident in UC patients.
New inhibitors of ABCG2 identified by high-throughput screening

In order to identify novel inhibitors of the ATP-binding cassette transporter, ABCG2, a high-throughput assay measuring the accumulation of the ABCG2 substrate pheophorbide a in ABCG2-overexpressing NCI-H460 MX20 cells was used to screen libraries of compounds. Out of a library of 7,325 natural products and synthetic compounds from the National Cancer Institute/Developmental Therapeutics Program collection, 18 were found to inhibit ABCG2 at 10 μmol/L. After eliminating flavonoids and compounds of limited availability from the 18 original compounds, 10 of the 11 remaining compounds reversed mitoxantrone resistance in NCI-H460/MX20 cells and prevented ABCG2-mediated BODIPY-prazosin transport in ABCG2-transfected HEK293 cells, confirming an interaction with ABCG2. Based on the activity profiles and the availability of materials, five inhibitors were examined for their ability to compete with [125I]iodoarylazidoprazosin labeling of ABCG2, increase binding of the anti-ABCG2 antibody 5D3, and prevent P-glycoprotein or multidrug resistance protein 1–mediated transport. At a concentration of 20 μmol/L, all of the compounds reduced iodoarylazidoprazosin labeling by 50% to 80% compared with controls. All five compounds also increased 5D3 labeling of ABCG2, indicating that these compounds are inhibitors but not substrates of ABCG2. None of the compounds affected P-glycoprotein–mediated rhodamine 123 transport, whereas three affected multidrug resistance protein-1–mediated calcein transport at 25 μmol/L, suggesting that the compounds are relatively specific for ABCG2. These five novel inhibitors of ABCG2 activity may provide a basis for further investigation of ABCG2 function and its relevance in multidrug resistance. [Mol Cancer Ther 2007;6(12):3271–8]
Study on the developmental disparities of adolescents' core self-evaluation and its relationship with multidimensional life satisfaction

【Objective】 To explore the disparities of adolescents' core self-evaluation and its relationship with multidimensional life satisfaction. 【Method】 A stratified random sample of 300 adolescent students completed the Core Self-evaluation Scale(CSES),Multidimensional Students' Life Satisfaction Scale(MSLSS) and basic circumstance questionnaire. 【Results】 The averages of CSES and MSLSS were both significantly higher than theoretical mid-value(P0.001). There were no significant differences in adolescents' core self-evaluation score in respect to different grade,sex,area and being only-child or not(P0.05). CSES predicted 24.6% of total variances of MSLSS,and predictive powers to each subscale of MSLSS were between 10.5% to 19.9%. 【Conclusion】 Core self-evaluation is an important factor to preserve adolescents' multidimensional life satisfaction.
International patterns and trends in testicular cancer incidence, overall and by histologic subtype, 1973–2007

Incidence rates of testicular cancer in Northern European and North American countries have been widely reported, whereas rates in other populations, such as Eastern Europe, Central/South America, Asia, and Africa, have been less frequently evaluated. We examined testicular cancer incidence rates overall and by histologic type by calendar time and birth cohort for selected global populations 1973–2007. Age‐standardized incidence rates over succeeding 5‐year periods were calculated from volumes 4–9 of Cancer Incidence in Five Continents electronic database (CI5plus) and the newly released CI5X (volume 10) database. Annual percent change over the 35‐year period was calculated using weighted least squares regression. Age‐period‐cohort analyses were performed and observed rates and fitted rate ratios presented by birth cohort. Incidence rates of testicular cancer increased between 1973–1977 and 2003–2007 in most populations evaluated worldwide. Of note, incidence rates in Eastern European countries rose rapidly and approached rates in Northern European countries. Rates in Central and South America also increased and are now intermediate to the high rates among men of European ancestry and low rates among men of Asian or African descent. Some heterogeneity in the trends in seminoma and nonseminoma were observed in Denmark, the United Kingdom, and among US whites, particularly in recent generations, with rapid and uniform increases in the incidence of both histologic types in Slovakia. Reasons for the rising incidence rates among European and American populations remain unexplained; however, changing distributions in the prevalence of risk factors for testicular cancer cannot be ruled out.
Patients with schizophrenia show increased aversion to angry faces in an associative learning task

Background We were interested in examining the relationship between socially relevant stimuli and decision processes in patients with schizophrenia. Method We tested patients with schizophrenia and healthy controls on a stochastically rewarded associative learning task. Participants had to determine, through trial and error, which of two faces was associated with a higher chance of reward: one face was angry, the other happy. Results Both patients and healthy controls were able to perform the task at above-chance accuracy, and there was no significant difference in overall accuracy between the groups. Both groups also reliably preferred the happy face, such that they selected it more often than the angry face on the basis of the same amount of positive versus negative feedback. However, patients were significantly more averse to the angry face, such that they chose it less often than control participants when the reward feedback strongly supported the angry face as the best choice. Conclusions Patients show an increased aversion to angry faces, in a task in which they must learn to associate rewards with expressions.
Nelfinavir, A Lead HIV Protease Inhibitor, Is a Broad-Spectrum, Anticancer Agent that Induces Endoplasmic Reticulum Stress, Autophagy, and Apoptosis In vitro and In vivo

Purpose: The development of new cancer drugs is slow and costly. HIV protease inhibitors are Food and Drug Administration approved for HIV patients. Because these drugs cause toxicities that can be associated with inhibition of Akt, an emerging target in cancer, we assessed the potential of HIV protease inhibitors as anticancer agents. Experimental Design: HIV protease inhibitors were screened in vitro using assays that measure cellular proliferation, apoptotic and nonapoptotic cell death, endoplasmic reticulum (ER) stress, autophagy, and activation of Akt. Nelfinavir was tested in non–small cell lung carcinoma (NSCLC) xenografts with biomarker assessment. Results: Three of six HIV protease inhibitors, nelfinavir, ritonavir, and saquinavir, inhibited proliferation of NSCLC cells, as well as every cell line in the NCI60 cell line panel. Nelfinavir was most potent with a mean 50% growth inhibition of 5.2 μmol/L, a concentration achievable in HIV patients. Nelfinavir caused two types of cell death, caspase-dependent apoptosis and caspase-independent death that was characterized by induction of ER stress and autophagy. Autophagy was protective because an inhibitor of autophagy increased nelfinavir-induced death. Akt was variably inhibited by HIV protease inhibitors, but nelfinavir caused the greatest inhibition of endogenous and growth factor–induced Akt activation. Nelfinavir decreased the viability of a panel of drug-resistant breast cancer cell lines and inhibited the growth of NSCLC xenografts that was associated with induction of ER stress, autophagy, and apoptosis. Conclusions: Nelfinavir is a lead HIV protease inhibitor with pleiotropic effects in cancer cells. Given its wide spectrum of activity, oral availability, and familiarity of administration, nelfinavir is a Food and Drug Administration–approved drug that could be repositioned as a cancer therapeutic.
Polymorphisms of Genes in the Lipid Metabolism Pathway and Risk of Biliary Tract Cancers and Stones: A Population-Based Case-Control Study in Shanghai, China

Biliary tract cancers, encompassing the gallbladder, extrahepatic bile duct, and ampulla of Vater, are uncommon yet highly fatal malignancies. Gallstones, the primary risk factor for biliary cancers, are linked with hyperlipidemia. We examined the associations of 12 single nucleotide polymorphisms of five genes in the lipid metabolism pathway with the risks of biliary cancers and stones in a population-based case-control study in Shanghai, China. We included 235 gallbladder, 125 extrahepatic bile duct, and 46 ampulla of Vater cancer cases, 880 biliary stone cases, and 779 population controls. Subjects completed an in-person interview and gave blood. Genotyping was conducted by TaqMan assay using DNA from buffy coats. The effects of APOE IVS1+69 (rs440446) and APOB IVS6+360C>T (rs520354) markers were limited to men. Men carrying the G allele of APOE IVS1+69 had a 1.7-fold risk of stones [95% confidence interval (95% CI), 1.2-2.4], a 1.8-fold risk of gallbladder cancer (95% CI, 1.0-3.3), a 3.7-fold risk of bile duct cancer (95% CI, 2.0-7.0), and a 4-fold risk of ampullary cancer (95% CI, 1.4-12.4). Male carriers of the T allele of APOB IVS6+360C>T had a 2-fold risk of bile duct cancer (95% CI, 1.2-3.4). The APOB T-T haplotype (APOB IVS6+360C>T, EX4+56C>T) was associated with a 1.6-fold risk of bile duct cancer (95% CI, 1.1-2.3). Male and female carriers of the T allele of LDLR IVS9-30C>T (rs1003723) had a 1.5-fold risk of bile duct cancer. Our findings suggest that gene variants in the lipid metabolism pathway contribute to the risk of biliary tract stones and cancers, particularly of the bile duct. (Cancer Epidemiol Biomarkers Prev 2008;17(3):525–34)
Evidence for the Role of Mast Cells in Cystitis-Associated Lower Urinary Tract Dysfunction: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Animal Model Study

Bladder inflammation frequently causes cystitis pain and lower urinary tract dysfunction (LUTD) such as urinary frequency and urgency. Although mast cells have been identified to play a critical role in bladder inflammation and pain, the role of mast cells in cystitis-associated LUTD has not been demonstrated. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating inflammatory condition of the urinary bladder characterized by the hallmark symptoms of pelvic pain and LUTD. In this study we investigated the role of mast cells in LUTD using a transgenic autoimmune cystitis model (URO-OVA) that reproduces many clinical correlates of IC/BPS. URO-OVA mice express the membrane form of the model antigen ovalbumin (OVA) as a self-antigen on the urothelium and develop bladder inflammation upon introduction of OVA-specific T cells. To investigate the role of mast cells, we crossed URO-OVA mice with mast cell-deficient KitW-sh mice to generate URO-OVA/KitW-sh mice that retained urothelial OVA expression but lacked endogenous mast cells. We compared URO-OVA mice with URO-OVA/KitW-sh mice with and without mast cell reconstitution in response to cystitis induction. URO-OVA mice developed profound bladder inflammation with increased mast cell counts and LUTD, including increased total number of voids, decreased mean volume voided per micturition, and decreased maximum volume voided per micturition, after cystitis induction. In contrast, similarly cystitis-induced URO-OVA/KitW-sh mice developed reduced bladder inflammation with no mast cells and LUTD detected. However, after mast cell reconstitution URO-OVA/KitW-sh mice restored the ability to develop bladder inflammation and LUTD following cystitis induction. We further treated URO-OVA mice with cromolyn, a mast cell membrane stabilizer, and found that cromolyn treatment reversed bladder inflammation and LUTD in the animal model. Our results provide direct evidence for the role of mast cells in cystitis-associated LUTD, supporting the use of mast cell inhibitors for treatment of certain forms of IC/BPS.
Longitudinal changes in polysyllable maturity of preschool children with phonologically-based speech sound disorders

ABSTRACT Children’s polysyllables were investigated for changes in (1) consonant and vowel accuracy, (2) error frequency and (3) polysyllable maturity over time. Participants were 80 children (4;0-5;4) with phonologically-based speech sound disorders who participated in the Sound Start Study and completed the Polysyllable Preschool Test (Baker, 2013) three times. Polysyllable errors were categorised using the Word-level Analysis of Polysyllables (WAP, Masso, 2016a) and the Framework of Polysyllable Maturity (Framework, Masso, 2016b), which represents five maturity levels (Levels A-E). Participants demonstrated increased polysyllable accuracy over time as measured by consonant and vowel accuracy, and error frequency. Children in Level A, the lowest level of maturity, had frequent deletion errors, alterations of phonotactics and alterations of timing. Participants in Level B were 8.62 times more likely to improve than children in Level A at Time 1. Children who present with frequent deletion errors may be less likely to improve their polysyllable accuracy.
Surface plasmon driven scalable low-loss negative-index metamaterial in the visible spectrum

We demonstrate that surface plasmons of a thin metal film interacting with a periodic array of nano-structures around it can be utilized to make bulk negative index metamaterials at visible spectrum with simultaneously negative permittivity and permeability. These surface plasmon driven metamaterials have high figure of merit and can be tuned arbitrarily to operate at any wavelength in the visible spectrum and possibly at ultraviolet spectrum. We numerically demonstrate the idea by a metamaterial structure which exhibits a strong magnetic response resulting in a negative index of refraction in the green region of the electromagnetic spectrum at 536nm with a figure of merit of 3.67. We also demonstrate by simply changing the constituent material only, hence by modifying the underlying surface plasmon dispersion, that the operating wavelength of the structure can be blue-shifted to the violet region at 406nm with a figure of merit of 2.27. In contrast to the fishnet-structure based approaches for visible metamaterials, our proposed approach offers a more frequency scalable way of achieving negative index of refraction in the visible and possibly at ultraviolet wavelengths with high figure of merit.
Bankruptcy Spillovers

How do different bankruptcy approaches affect the local economy? Using U.S. Census microdata at the establishment level, we explore the spillover effects of reorganization and liquidation on geographically proximate firms. We exploit the random assignment of bankruptcy judges as a source of exogenous variation in the probability of liquidation. We find that within a five-year period, employment declines substantially in the immediate neighborhood of the liquidated establishments, relative to reorganized establishments. Most of the decline is due to lower growth of existing establishments and, to a lesser extent, reduced entry into the area. The spillover effects are highly localized and concentrate in the non-tradable and service sectors, particularly when the bankrupt firm operates in the same sector. These results suggest that liquidation leads to a reduction in consumer traffic to the local area and to a decline in knowledge spillovers between firms. The evidence is inconsistent with the notion that liquidation leads to creative destruction, as the removal of bankrupt businesses does not lead to increased entry nor the revitalization of the area.
First trimester thyroid stimulating hormone as an independent risk factor for adverse pregnancy outcome

Abstract Purpose: Maternal thyroid gland dysfunction may adversely affect pregnancy outcome. We aimed to examine the association between subclinical thyroid dysfunction, both hypothyroidism and hyperthyroidism, to adverse pregnancy outcome. Materials and methods: Retrospective cohort study of all women with an available first trimester thyroid function testing and known pregnancy outcome, categorized to subclinical hypothyroidism, or hyperthyroidism and evaluated for complication during gestation and delivery. Results: Four thousand five hundred and four women were included in the final analysis – 3231 were euthyroid, 73 (1.6%) were categorized as subclinical hyperthyroidism and 1200 (26.6%) had subclinical hypothyroidism. Low thyroid-stimulating hormone (TSH) levels, i.e. subclinical hyperthyroidism, correlates with higher rates of placental abruption and extremely low birth weight, below 1500 g. Also, the risk for preterm delivery prior to 34 gestational weeks is higher among women with subclinical hypothyroidism, with greater risk among those with a higher TSH level. (OR 1.81, 95% CI 1.0–3.28 for TSH 2.5–4.0 mIU/L and OR 2.33, 95% CI 1.11–4.42 for those with TSH > 4 4.0 mIU/L). Conclusions: Subclinical hypothyroidism is associated with an increased risk for preterm delivery prior to 34 gestational weeks. Additionally, subclinical hyperthyroidism may also have a role in adverse pregnancy outcome – low birth weight and placental abruption – although this needs to be further explored.
Systolic blood pressure levels among adults with hypertension and incident cardiovascular events: the atherosclerosis risk in communities study.

IMPORTANCE Studies document a progressive increase in heart disease risk as systolic blood pressure (SBP) rises above 115 mm Hg, but it is unknown whether an SBP lower than 120 mm Hg among adults with hypertension (HTN) lowers heart failure, stroke, and myocardial infarction risk. OBJECTIVE To examine the risk of incident cardiovascular (CV) events among adults with HTN according to 3 SBP levels: 140 mm Hg or higher; 120 to 139 mm Hg; and a reference level of lower than 120 mm Hg. DESIGN, SETTING, AND PARTICIPANTS A total of 4480 participants with HTN but without prevalent CV disease at baseline (years 1987-1989) from the Atherosclerosis Risk in Communities Study were included. Measurements of SBP were taken at baseline and at 3 triennial visits; SBP was treated as a time-dependent variable and categorized as elevated (≥140 mm Hg), standard (120-139 mm Hg), and low (<120 mm Hg). Multivariable Cox regression models included baseline age, sex, diabetes status, BMI, high cholesterol level, smoking status, and alcohol intake. MAIN OUTCOMES AND MEASURES Incident composite CV events (heart failure, ischemic stroke, myocardial infarction, or death related to coronary heart disease). RESULTS After a median follow-up of 21.8 years, a total of 1622 incident CV events had occurred. Participants with elevated SBP developed incident CV events at a significantly higher rate than those in the low BP group (adjusted hazard ratio [HR], 1.46; 95% CI, 1.26-1.69). However, there was no difference in incident CV event-free survival among those in the standard vs low SBP group (adjusted HR, 1.00; 95% CI, 0.85-1.17). Further adjustment for BP medication use or diastolic BP did not significantly affect the results. CONCLUSIONS AND RELEVANCE Among patients with HTN, having an elevated SBP carries the highest risk for cardiovascular events, but in this categorical analysis, once SBP was below 140 mm Hg, an SBP lower than 120 mm Hg did not appear to lessen the risk of incident CV events.