Miracle-dz/UniFAR-FTUs huggingface dataset:
Ocular pharmacokinetics of bevacizumab in vitrectomized eyes with silicone oil tamponade.

PURPOSE We characterized the ocular pharmacokinetics of bevacizumab in vitrectomized eyes with silicone oil tamponade. METHODS A total of 18 pigmented rabbits underwent vitrectomy and silicone oil tamponade before an intra-silicone oil injection of 1.25 mg bevacizumab. At post-injection days 1, 7, 14, 28, 42, and 56, 3 rabbits were sacrificed and enucleated, and bevacizumab concentrations were measured in various ocular tissues and plasma. RESULTS The bevacizumab peak concentration was reached at day 14 in the aqueous humor (4030.70 ng/mL), retina (42,171.7 ng/g), and choroid (56,243.33 ng/g). In the iris/ciliary body and plasma, the peak concentration was reached at day 7 with 52,648.30 ng/g and 197.70 ng/mL, respectively. The choroid had the maximum exposure to bevacizumab with an area under the curve calculated from time zero to the last observed time (AUC(last)) of 1,151,633.40 ng/day/g and the aqueous humor had the minimum exposure (AUC(last) = 74,611.28 ng/day/g) among the ocular tissues, while the drug exposure to the plasma was the smallest of all tissues studied (AUC(last) = 3795.17 ng/day/g). The terminal half-lives and the mean residence time of bevacizumab in the ocular tissues ranged from 3-5 and 10-13 days, respectively. CONCLUSIONS The peak concentration of bevacizumab in various ocular tissues and plasma was delayed and lower than that found in normal rabbit eyes; however, the terminal half-lives were similar to those found in the eyes with native vitreous following an intravitreal injection. Oil may have impacted the distribution of bevacizumab and led to an altered profile of drug level in the ocular tissues.
Comparison of Composite Indices Tailored for Psoriatic Arthritis Treated with csDMARD and bDMARD: A Cross-sectional Analysis of a Longitudinal Cohort

Objective. In a complex disease such as psoriatic arthritis (PsA), several methods are available to define remission or low disease activity (LDA), including the assessment of different clinical features. The aim of this study was to compare the composite indices tailored for PsA in patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARD) and biological DMARD (bDMARD). Methods. Patients with PsA classified with the ClASsification criteria for Psoriatic ARthritis criteria and with > 6 months followup treated with first csDMARD and bDMARD were consecutively enrolled. To assess disease activity, composite indices tailored for PsA were used, such as the Disease Activity Index for Psoriatic Arthritis (DAPSA), clinical DAPSA (cDAPSA), Psoriatic Arthritis Disease Activity Score (PASDAS), minimal disease activity (MDA) 5/7, and MDA 7/7. DAPSA and cDAPSA score ≤ 4, MDA 7/7, and PASDAS ≤ 1.9 identified remission. MDA 5/7, DAPSA score ≤ 14, cDAPSA score ≤ 13, and PASDAS < 3.2 identified the MDA and LDA criteria. Results. One hundred nine patients with PsA were enrolled: 79 patients were receiving stable treatment with bDMARD and 30 with csDMARD. Overall, 28 (25.6%), 23 (21.1%), 19 (17.4%), and 13 patients (11.9%) were in cDAPSA remission, DAPSA remission, MDA 7/7, and PASDAS ≤ 1.9, respectively. Moreover, 54 (49.5%), 80 (73.3%), 79 (72.3%), and 38 patients (34.8%) were in MDA 5/7, DAPSA LDA, cDAPSA LDA, and PASDAS LDA. Patients treated with bDMARD had significantly lower median DAPSA, cDAPSA, and PASDAS score than patients treated with csDMARD. Conclusion. Patients with PsA receiving bDMARD are more likely to achieve a status of MDA and remission when compared with csDMARD. PASDAS ≤ 1.9 and MDA 7/7 seem to be stringent remission criteria.
Relative Efficiency of the EQ-5D, HUI2, and HUI3 Index Scores in Measuring Health Burden of Chronic Medical Conditions in a Population Health Survey in the United States

Objective:We sought to compare the ability of the EQ-5D, Health Utilities Index Mark 2 (HUI2), and HUI Mark 3 (HUI3) index scores to discriminate between respondents based on the presence or absence of chronic medical conditions in a population health survey. Methods:Secondary analyses were conducted with data from a probability sample (n = 3480, mean age: 42.5 years, male: 42.4%, Hispanic: 28.6%) of the 2001 noninstitutionalized US general adult population. F-statistic ratios were used to evaluate the relative efficiency of the EQ-5D, HUI2, and HUI3 in differentiating respondents with or without each of 18 chronic medical conditions, and differentiating respondents with low- or high-burden conditions. Results:In comparing respondents with and without chronic medical conditions, the F-statistic values of these 3 indices were not significantly different, except for EQ-5D versus HUI2 [mean F-statistic ratio: 0.79, 95% confidence interval (CI): 0.59–0.98]. In comparing respondents with a low-burden condition with those with a high-burden condition, the F-statistic values of EQ-5D and HUI2 index scores were similar, while those for EQ-5D versus HUI3 (mean: 0.79; 95% CI: 0.66–0.92) and for HUI2 versus HUI3 (mean: 0.83; 95% CI: 0.71–0.95) were significantly less than 1.0. The overall ceiling effects of the EQ-5D, HUI2, and HUI3 index scores were 48.9%, 15.4%, and 15.3%, respectively. Conclusions:Although the EQ-5D seems to be marginally less informative, the EQ-5D, HUI2, and HUI3 index scores were generally comparable in determining health burden of chronic medical conditions in this population health survey data.
Progesterone and ovulation across stages of the transition to menopause

Objective: Detailed characterization of progesterone and ovulation across the menopausal transition provides insight into conception risk and mechanisms of reproductive aging. Methods: Participants (n = 108, aged 25-58 y) collected daily urine specimens for 6-month intervals in each of 5 consecutive years. Specimens were assayed for pregnanediol glucuronide (PDG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estrone glucuronide (E1G). Reproductive stage was determined using cycle length variance. A hierarchical algorithm was used to identify ovulation. Linear mixed-effects models estimated (1) the frequency and day of ovulation by age and stage; (2) differences in FSH, LH, and E1G levels between ovulatory (O) and anovulatory (AO) cycles; and (3) total PDG levels and PDG levels in O cycles by age and stage. Results: The probability of AO cycles increased across the perimenopause (P < 0.0001); reproductive stage was a stronger predictor than age of the probability of anovulation. Most cycles in late perimenopause were AO (>60%), but one quarter of cycles longer than 60 days were O. Average day of ovulation was later in the late perimenopause (mean [SD] cycle day, 27 [25] d) compared with the premenopause. FSH and LH levels were higher and E1G levels were lower in AO than O cycles (P < 0.0001 for each). Total PDG decreased in the late perimenopause, but 95th percentile PDG in O cycles declined steadily across the transition. Conclusions: Exposure to the risk of conception in women experiencing cycles long enough to classify them as late perimenopausal is far from negligible. Reproductive stage is more informative than age about PDG levels and the likelihood of anovulation.
Prevalence of primary cardiac tumor malignancies in retrospective studies over six decades: a systematic review and meta-analysis

The incidence of patients diagnosed with primary malignant cardiac tumors (PMCTs) has increased greatly in the past few decades. Whether this rising prevalence is due to overdiagnosis or an increased malignancy rate of primary cardiac tumors (PCTs) remains unclear. Therefore, we performed a systematic review and meta-analysis of published retrospective studies to determine whether the malignancy rate has been increasing over time. Published studies containing relevant data between 1956 and 2014 were evaluated. Two authors searched for all retrospective studies that included patients diagnosed with PCT and PMCT. Two other investigators independently extracted the data, and discrepancies were resolved by consensus. A random-effects meta-analysis model and cumulative meta-analysis model were used to evaluate the pooled prevalence and trend of dynamic change in PCT malignancies. The effects of time, study period and sample size were studied using a logit-linear regression model with robust error variance and a time variable. Thirty-eight studies involving 5,586 patients were analyzed. The pooled prevalence of PMCT among the patients diagnosed with PCT was 9.9% (95% CI, 8.4% to 11.4%) (I2=70%; P< 0.001), and this prevalence has been stable since around 2003. In the regression model, the malignancy odds ratio remained stable from 1975 onward, and no time effect was observed. Our study confirms that PMCT is uncommon, and the prevalence of PCT malignancies remained stable in the past few decades. The clinically observed increase in incidence is unlikely to reflect a true population-level increase in tumorigenesis. This result strongly suggests that the observed increase in incidence of PMCT most likely reflects increased diagnostic detection over time.
Occurrence and Phylogenetic Diversity of Sphingomonas Strains in Soils Contaminated with Polycyclic Aromatic Hydrocarbons

ABSTRACT Bacterial strains of the genus Sphingomonas are often isolated from contaminated soils for their ability to use polycyclic aromatic hydrocarbons (PAH) as the sole source of carbon and energy. The direct detection of Sphingomonas strains in contaminated soils, either indigenous or inoculated, is, as such, of interest for bioremediation purposes. In this study, a culture-independent PCR-based detection method using specific primers targeting the Sphingomonas 16S rRNA gene combined with denaturing gradient gel electrophoresis (DGGE) was developed to assess Sphingomonas diversity in PAH-contaminated soils. PCR using the new primer pair on a set of template DNAs of different bacterial genera showed that the method was selective for bacteria belonging to the family Sphingomonadaceae. Single-band DGGE profiles were obtained for most Sphingomonas strains tested. Strains belonging to the same species had identical DGGE fingerprints, and in most cases, these fingerprints were typical for one species. Inoculated strains could be detected at a cell concentration of 104 CFU g of soil−1. The analysis of Sphingomonas population structures of several PAH-contaminated soils by the new PCR-DGGE method revealed that soils containing the highest phenanthrene concentrations showed the lowest Sphingomonas diversity. Sequence analysis of cloned PCR products amplified from soil DNA revealed new 16S rRNA gene Sphingomonas sequences significantly different from sequences from known cultivated isolates (i.e., sequences from environmental clones grouped phylogenetically with other environmental clone sequences available on the web and that possibly originated from several potential new species). In conclusion, the newly designed Sphingomonas-specific PCR-DGGE detection technique successfully analyzed the Sphingomonas communities from polluted soils at the species level and revealed different Sphingomonas members not previously detected by culture-dependent detection techniques.
Heterozygosity in the glutathione synthesis gene Gclm increases sensitivity to diesel exhaust particulate induced lung inflammation in mice

Context: Inhalation of ambient fine particulate matter (PM2.5) is associated with adverse respiratory and cardiovascular effects. A major fraction of PM2.5 in urban settings is diesel exhaust particulate (DEP), and DEP-induced lung inflammation is likely a critical event mediating many of its adverse health effects. Oxidative stress has been proposed to be an important factor in PM2.5-induced lung inflammation, and the balance between pro- and antioxidants is an important regulator of this inflammation. An important intracellular antioxidant is the tripeptide thiol glutathione (GSH). Glutamate cysteine ligase (GCL) carries out the first step in GSH synthesis. In humans, relatively common genetic polymorphisms in both the catalytic (Gclc) and modifier (Gclm) subunits of GCL have been associated with increased risk for lung and cardiovascular diseases. Objective: This study was aimed to determine the effects of Gclm expression on lung inflammation following DEP exposure in mice. Materials and methods: We exposed Gclm wild type, heterozygous, and null mice to DEP via intranasal instillation and assessed lung inflammation as determined by neutrophils and inflammatory cytokines in lung lavage, inflammatory cytokine mRNA levels in lung tissue, as well as total lung GSH, Gclc, and Gclm protein levels. Results: The Gclm heterozygosity was associated with a significant increase in DEP-induced lung inflammation when compared to that of wild type mice. Discussion and conclusion: This finding indicates that GSH synthesis can mediate DEP-induced lung inflammation and suggests that polymorphisms in Gclm may be an important factor in determining adverse health outcomes in humans following inhalation of PM2.5.
Is Discretionary Fiscal Policy in Japan Effective

This paper uses a novel time-varying factor model to examine the dynamic effects of fiscal policy in Japan over the last three decades. This paper shows that despite Japan's high debt levels and long-term budgetary difficulties there is little evidence of any substantial Ricardian offset in the short-run, with private consumption and investment rising in response to discretionary government spending. Estimates drawn in the aftermath of the recent financial crisis report a potential multiplier value of around 1.2. The estimates imply that there is still scope for counter-cyclical fiscal policy despite Japan's long-term budgetary difficulties.
Impact of Frequency of Multi-Vitamin/Multi-Mineral Supplement Intake on Nutritional Adequacy and Nutrient Deficiencies in U.S. Adults

Although >50% of U.S. adults use dietary supplements, little information is available on the impact of supplement use frequency on nutrient intakes and deficiencies. Based on nationally representative data in 10,698 adults from the National Health and Nutrition Examination Surveys (NHANES) 2009 to 2012, assessments were made of intakes from food alone versus food plus multi-vitamin/multi-mineral supplements (MVMS) of 17 nutrients with an Estimated Average Requirement (EAR) and a Tolerable Upper Intake Level (UL), and of the status of five nutrients with recognized biomarkers of deficiency. Compared to food alone, MVMS use at any frequency was associated with a lower prevalence of inadequacy (p < 0.01) for 15/17 nutrients examined and an increased prevalence of intakes >UL for 7 nutrients, but the latter was ≤4% for any nutrient. Except for calcium, magnesium, and vitamin D, most frequent MVMS use (≥21 days/30 days) virtually eliminated inadequacies of the nutrients examined, and was associated with significantly lower odds ratios of deficiency for the examined nutrient biomarkers except for iron. In conclusion, among U.S. adults, MVMS use is associated with decreased micronutrient inadequacies, intakes slightly exceeding the UL for a few nutrients, and a lower risk of nutrient deficiencies.
Do Parents Blame or Doubt their Child More When Sexually Abused by Adolescents Versus Adults?

Although the importance of parental support for child sexual abuse victims is well documented, the nature of parental support for victims sexually abused by adolescents is less understood. In this exploratory study, we examine whether parents differ in their levels of blame or doubt for their child when sexually abused by adolescents versus adults. Data included 161 reports of child sexual abuse. Parental blame toward their child was higher when sexually abused by an adolescent versus an adult suspect. In the bivariate and multivariate analysis, parental blame was significantly higher as victim age increased, for Black, non-Hispanic children, and when there was an adolescent suspect. Practitioners need to recognize that high levels of blame and doubt could exist for adolescent victims of sexual abuse and when children are sexually abused by adolescents.
Role of retinal input on the development of striate–extrastriate patterns of connections in the rat

Previous studies have shown that retinal input plays an important role in the development of interhemispheric callosal connections, but little is known about the role retinal input plays on the development of ipsilateral striate–extrastriate connections and the interplay that might exist between developing ipsilateral and callosal pathways. We analyzed the effects of bilateral enucleation performed at different ages on both the distribution of extrastriate projections originating from restricted loci in medial, acallosal striate cortex, and the overall pattern of callosal connections revealed following multiple tracer injections. As in normal rats, striate–extrastriate projections in rats enucleated at birth consisted of multiple, well‐defined fields that were largely confined to acallosal regions throughout extrastriate cortex. However, these projections were highly irregular and variable, and they tended to occupy correspondingly anomalous and variable acallosal regions. Moreover, area 17, but not area 18a, was smaller in enucleates compared to controls, resulting in an increase in the divergence of striate projections. Anomalies in patterns of striate–extrastriate projections were not observed in rats enucleated at postnatal day (P)6, although the size of area 17 was still reduced in these rats. These results indicate that the critical period during which the eyes influence the development of striate–extrastriate, but not the size of striate cortex, ends by P6. Finally, enucleation did not change the time course and definition of the initial invasion of axons into gray matter, suggesting that highly variable striate projections patterns do not result from anomalous pruning of exuberant distributions of 17–18a fibers in gray matter. J. Comp. Neurol. , 520:3256–3276, 2012. © 2012 Wiley Periodicals, Inc.
The Playing Field : Findings for Evaluating Hypotheses About WM Capacity

We review the evidence for the 3 principal theoretical contenders that vie to explain why and how working memory (WM) capacity is limited. We examine the possibility that capacity limitations arise from temporal decay; we examine whether they might reflect a limitation in cognitive resources; and we ask whether capacity might be limited because of mutual interference of representations in WM. We evaluate each hypothesis against a common set of findings reflecting the capacity limit: The set-size effect and its modulation by domain-specificity and heterogeneity of the memory set; the effects of unfilled retention intervals and of distractor processing in the retention interval; and the pattern of correlates of WM tests. We conclude that—at least for verbal memoranda—a decay explanation is untenable. A resource-based view remains tenable but has difficulty accommodating several findings. The interference approach has its own set of difficulties but accounts best for the set of findings, and therefore, appears to present the most promising approach for future development.
Persistence, Perseveration and Perfectionism in the Eating Disorders

Background: Perseveration, persistence and perfectionism are traits that have been suggested to be relevant to the eating disorders. This study explored the levels and correlates of these three traits in the eating disorders and control groups. Method: A measure of these three elements (the Persistence, Perseveration and Perfectionism Questionnaire - PPPQ-22) was administered to 99 women with eating disorders, 25 women with other psychiatric disorders, and 91 non-clinical women. Differences in PPPQ-22 scores across groups were measured, as were the associations between PPPQ-22 scores and eating attitudes. Results: The eating disordered groups showed lower levels of persistence (the drive towards goal achievement) than the non-clinical group, but did not show higher levels of perseveration (the following of rules, without considering whether goals are achieved). Both women with eating disorders and non-clinical controls showed correlations between eating disorder symptoms and perseveration. Conclusions: The current study, using a relatively new measure, suggests that low levels of persistence, rather than high levels of perseveration, may be implicated in the eating disorders. It was less clear that perfectionism per se was a useful construct in understanding eating pathology. If confirmed by future research, persistence should be considered in treatment of these complex and challenging conditions.
Hepatitis B Reactivation: The Controversies Continue

Hepatitis B virus (HBV) reactivation is a serious but largely avoidable complication of immunosuppressive therapy. The consequences of reactivation range from subclinical increases in HBV DNA to fulminant liver failure, which can be prevented with the appropriate use of prophylactic antiviral therapy. However, which patients need to be screened and whether all patients who test positive for any serological test require antiviral therapy are issues that still remain unclear. Additional issues such as the choice of antiviral and the duration of treatment also need clarification. Some of the confusion comes from the use of varying definitions in the literature to define outcomes. In this review, areas of controversy from definitions of reactivation to management of patients who are hepatitis B surface antigen and lone anti-core antibody positive in different clinical settings are discussed. The recently recognized issue of reactivation in the setting of hepatitis C antiviral therapy is also addressed as well as some recommendations for areas of future research to help clarify best practices.
Family resources as predictors of positive family-to-work spillover

The purpose of this study was to predict the family resources that influence positive family-to-work spillover for women who are engaged in parent, partner, and paid employee roles. While much research examines the construct of work-family conflict, little examines the positive benefits for women participating in multiple roles. A conceptual framework for the study was obtained from Voydanoff’s (2002) work applying ecological systems theory to the work-family interface. Several factors were hypothesized to predict positive family-to-work spillover for multiple role women, including: spousal support; perceived fairness in the division of housework and childcare; relative share of childcare and housework; and paid assistance with housework. Data for this study was collected in a survey designed for a larger assessment of work, family, gender, and health in the Saskatoon area. The current study utilized data collected from women who met the following criteria: 1) spoke fluent English; 2) fell between the ages of 25 54 years; 3) were employed full-time or part-time; and 4) were the parent of at least one child under the age of 20 years. The dependent variable was a measure of positive family-to-work spillover. Independent variables included: spousal support; perceived fairness of the division of childcare; perceived fairness of the division of housework; relative of share of housework for respondents compared to ones partner; and paid assistance with housework. Control variables included: income, presence of preschool children, number of children, educational attainment, and hours of paid employment. A sequential multiple regression was performed to predict positive family-to-work spillover from the independent variables. The final regression model predicting positive family-to-work spillover included three independent variables: 1) spousal support; 2) the perception of division of childcare as unfair to one’s partner; and 3) relative share of housework for the respondent. Implications and limitations of these findings are discussed.